ISTH Abstract

R. Pombal 1 ; L. Vieira 2 ; S. Lopes 2 ; R. Neto 2 ; J. Ribeiro 2 ; H. Gomes 2 ; M. Figueiredo 3 1 Centro Hospitalar Vila Nova de Gaia/Espinho EPE, Portugal, Vila Nova de Gaia, Porto, Portugal; 2 Centre of Thrombosis and Hemostasis and Department of Transfusion Medicine, Centro Hospitalar Vila Nova de Gaia/Espinho, E.P.E., Portugal, Vila Nova de Gaia, Porto, Portugal; 3 Centro Hospitalar Centro Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Porto, Portugal Background : Bleeding abnormalities are commonly found in critically ill patients and may have a major impact on the outcome. Aims : Description of a bleeding disorder in a critically ill patient. Methods : Collection of clinical data in SClínico® application. Results : Man, 56‐years‐old, with chronic coronary disease and multiple cardiovascular risk factors, presented on January 2022 with cardiorespiratory arrest due to acute myocardial infarction. After successful resuscitation and coronary angioplasty, he progressed to cardiogenic shock requiring veno‐arterial extracorporeal membrane oxygenation (ECMO) and mechanical ventilation. He started unfractionated heparin (UHF) titration to maintain the aPTT in the target range (1.5–2 times normal aPTT). On the fourth day a hepatogastric hematoma (7.6 × 2.5 × 1.7 cm) was identified and associated with the resuscitation maneuvers, so UHF was maintained. On the same day sepsis diagnosis arose. On the sixth day, with aPTT in the target range, hemoptysis set in, with hemodynamic repercussion and UHF was stopped even though he was on ECMO. Even without UHF bleeding persisted. Bronchoscopy revealed a large bronchial clot and bronchial mucosa hemorrhage. Analytical findings showed: aPTT 34.8 s; INR 1.2; D‐dimer 19.96 μg/ml; Fibrinogen 739 mg/dl; Hemoglobin 8.8 g/dl; Platelets 78,000 cells/mm 3 . We do not have access to von Willebrand functional tests at our institution. Despite local hemostatic procedures, platelets transfusion and 1 g tranexamic acid nebulization, bleeding persisted. The patient deceased two days later with multiple organ dysfunction. Conclusion(s) : Management of bleeding in critical patients should be directed at the underlying condition, but often presents as a challenging multifactorial clinical setting. Our patient did not respond to the treatment of sepsis and organ dysfunction. Also we could not exclude acquired von Willebrand syndrome ECMO‐associated, characterized by loss of von Willebrand factor large multimers. All these aspects contributed to the outcome. With this case we intend to highlight a situation that was difficult to manage and for which we felt powerless.

C. Câmara 1 ; M. Deveza 1 ; C. Peixoto 2 ; F. Pires 1 ; M. Galvão 3 ; Á. Beleza 3 1 CHULN, Santa Maria's Hospital ‐ Portugal, Lisbon, Lisboa, Lisboa, Portugal; 2 Centro Hospitalar Universitário Lisboa Norte ‐ Hospital Santa Maria, Lisbon, Portugal, Lisboa, Lisboa, Portugal; 3 Centro Hospitalar Universitário Lisboa Norte ‐ Hospital Santa Maria, Lisboa, Lisboa, Portugal Background : Aplastic anemia (AA) is a syndrome of bone marrow failure characterized by peripheral pancytopenia and marrow hypoplasia. Anemia, bleeding, and infection are usually presenting symptoms. Intracranial hemorrhage (IH) is a life‐threatening complication of AA. Aims : We aim to examine laboratory and radiological findings in two patients with intracranial hemorrhage associated with AA and their therapeutic approach. Methods : A 12‐year‐old boy with a diagnosis of severe acquired AA was admitted to our hospital. After multiple bleeding episodes and febrile neutropenia he developed a bulky, spontaneous hematoma without surgical indication. The course of treatment was medical: eltrombopag, immunoglobulin plus methylprednisolone, platelet transfusion and FVII, FXIII and fibrinogen administration as needed. A 70‐year‐old woman with severe acquired AA and prior hypertension, atrial fibrillation and multiple bleeding events was admitted to our hospital after reporting a strong progressive headache, nausea and generalized lack of strength. CT scan brain imaging reveal an intracranial bleeding (several cerebral micro‐bleeding sites and a hemorrhage on the right cerebellar hemisphere). The course of treatment was medical: immunoglobulin plus dexamethasone, eltrombopag, fibrinogen correction and platelet transfusion. Results : Three months later the boy's hematoma reabsorbed and he was refered for allogenic transplantation with hematopoietic progenitor cells. On the other hand, despite the severity of the intracranial hemorrhage, an optimized medical treatment allowed the woman to have medical release to ambulatory follow‐up two weeks later. Conclusion(s) : IH is a serious complication of pancytopenia in AA, potentially lethal and should be treated as soon as the diagnosis is made. A detailed patient history and physical examination as well as laboratory and radiological monitoring are crucial to the management of intracranial bleeding in this context. In some cases, conservative treatment can be effective by correcting the thrombocytopenia and clotting factor levels.

E. Shchegov Petrozavodsk State University, Petrozavodsk, Karelia, Russia Background : We use anticoagulants widely now. But we must remember, that these drugs can lead to very dangerous bleeding, including gastroduodenal one. Aims : To estimate the gastroduodenal bleeding risk in the group of patients with VTE, receiving anticoagulants and to work out the safe algorithm for their application and primary and secondary prevention tactics. Methods : 731 patients with VTE were treated. Venous ultrasonography was made in all cases. D‐dimer was done according to indications. 722 patients underwent gastro‐duodenoscopy before treatment. Results : There were no signs of gastric problems in 84 patients. This group received anticoagulants. The second group 538 patients had gastric problems, but without signs of bleeding. The third group (86 patients) had gastric or duodenal bleeding during the investigation, but it was stopped using coagulation with stable hemostasis. Anticoagulants together with proton pump inhibitor (omeprazol or esomeprazol) were administrated. The fourth group had gastric or duodenal bleeding which was stopped during the gastro‐duodenoscopy, but the hemostasis was unstable. Proton pump inhibitor was administrated initially. After second gastro‐duodenoscopy anticoagulants were administrated if the bleeding was not continued. Conclusion(s) : The use of proton pump inhibitor together with anticoagulant drug can prevent the bleeding. The use of gastro‐duodenoscopy and adequate treatment make the use of anticoagulant drug safety.

T. Saralidze ; T. Svanidze; I. Mamatsashvili; M. Noniashvili Tbilisi State Medical University, Tbilisi, Shida Kartli, Georgia Background : Thromboembolism is challenging problem in patients with atrial fibrillation (AF). Aims : Our aim was prevention of secondary cardiogenic arterial thromboembolism. Methods : A 77 year‐old woman presented with paroxysmal‐recurrent AF, acute heart failure (HF), bilateral hydrothorax, moderate anemia, chronic kidney disease‐IVstage, chronic encephalopathy. 2.5 months ago patient had acute myocardial infarction with bilateral pneumonia and paroxysmal AF (NSTEMI, Killip class III; Coronarography revealed 95% stenosis of ADCA, 95% stenosis of I diagonal branch, 75% stenosis of circumflex CA. 3 stents were implanted in LAD and CCA.). Besides usual treatment she recieved aspirin and rivaroxaban, but last 10 days she quitted medication and became orthopneic. W‐68 kg, H‐165 cm, BMI 26.5. Skin pale, cyanosis. Edema on lower extremities, oliguria. P‐98′, irregular. Cor: dull sounds, systolic murmur on apex. TA‐160/90 mmHg. Pulmo: R‐28′, SpO 2 ‐88%. Crackles in lower lobes bilaterally. CBC: WBC‐6.6 × 103/μl; RBC‐2.43 × 106/μl; Hb‐8.2 g/dl; X‐ray: Lungs‐marked prominence of interstitial lines and hila bilaterally, fluid accumulation in pleural cavity. Cor‐enlarged transverse size. Echoscopy revealed 11 cm separation in right and 7 cm separation in left pleura. Cor: Enlarged left and right atria, left ventricular hypertrophy, scarring on inferio‐lateral and apical walls. Not floating thrombus attached at apex (1.6 cm, Figure 1). Ejection fraction (EF)‐40%; Moderate pulmonary artery hypertension. Moderate calcinosis and regurgitation of aortic and mitral valves. AF. Patient had serum albumin‐28.52 g/L, low GFR‐26.2 ml/min/1.73 m 2 , proteinuria – 30 mg/dl and hematuria–25‐28 Er/HPF. Results : She was treated routinely plus albumin, heparin‐i/v, rivaroxaban. 2 thoracentesis was made, 900 ml transudate (according to lab.data) was removed. Patient improved, signs of acute HF disappeared, heart regained sinus rhythm though irregular with frequent atrial premature beats. By echocardiography thrombus was resolved, EF raised up to 44%. Conclusion(s) : Use of rivaroxaban is reasonable not only for treatment of intracardial thrombus, but also to prevent blood clots from forming in patients with congestive HF and AF, especially with previous MI for long‐term anticoagulation therapy. FIGURE 1 Thrombus at apex in left ventricle. Secondary prevention of cardiogenic arterial thromboembolism .

E. Shorikov ; D. Shorikova; P. Shorikov; A. Esmaeil Bukovinian State Medical University, Chernivtsi, Chernivets'ka Oblast', Ukraine Background : It is important to inherit the tendency to thrombosis, which in the combined course of hypertension and diabetes 2 may be one of the factors in the development of atherothrombotic complications. One of the identified genetic risk factors for increased thrombosis is the existence of MTHFR polymorphism (C677T, Ala222Val). Aims : To investigate the phenotype of coagulation and fibrinolysis in patients with hypertension with diabetes type 2 depending on MTHFR C677T polymorphism. Methods : The study included of 100 patients with hypertension with concomitant diabetes mellitus 2, which determined the carrier of alleles and genotypes of polymorphic locus MTHFR C677T. The fibrinogen and factor XIII, protein C (PrC) and antithrombin III (AT III) activity, potential plasminogen activity (PAP), enzymatic fibrinolytic activity (EFA) were studied. Results : Analysis of AT III and PrC activity depending on MT67FR C677T polymorphism revealed changes in AT III level, and the absence of changes in PrC ( p  > 0.05). The pecularity of this was that the carrier of the protective allele C had a higher ATIII activity (98.30 ± 11.13% (CC) and 101.24 ± 12.29% (CT) against 90.50 ± 12.12% (TT)) ( p   0.05). The changes of factor XIII were specific: the level reliably increased only in two “risk” alleles TT carriers ( p  < 0.05). Association between EFA and C677T of MTHFR depended on “protective” allele C: in CC and CT activity was higher versus TT‐ 0.71 ± 0.08 ( p   0.05). Conclusion(s) : Under conditions of carriers of “risk” genotypes in MTHFR C677T polymorphism there are prerequisites for more frequent atherothrombosis, given the existing imbalance in the factor XIII level and enzymatic fibrinolysis.

H. Khachatryan 1 ; N. Sargsyan 2 ; A. Harutyunyan 3 ; I. Karapetyan 4 ; Y. Hovhannisyan 5 ; G. Tamamyan 6 1 Hematology Center after Prof. R.H. Yeolyan, Yerevan, Armenia, Yerevan, Yerevan, Armenia; 2 Hematology center after prof. R.H.Yeloyan Armenian Hemophilia and Thrombosis Center Yerevan State Medical University, Department of Pediatric Oncology and Hematology, Yerevan, Yerevan, Armenia; 3 Yerevan State Medical University, Depatment of Obstetrics and Gynecology, Yerevan, Yerevan, Armenia; 4 Yerevan State Medical University, Department of Obstetrics and Gynecology, Yerevan, Yerevan, Armenia; 5 HeratsiN1 University Clinic, YSMU, Yerevan, Armenia, Yerevan, Yerevan, Armenia; 6 Pediatric Cancer and Blood Disorders Center of Armenia, Hematology Center after Prof. R.H. Yeolyan, Yerevan, Armenia, Department of Pediatric Oncology and Hematology, Yerevan State Medical University, Yerevan, Armenia, Yerevan, Yerevan, Armenia Background : Up to 23–25% of patients experience a second stroke within the first 5 years after the first episode despite prophylaxis. Aims : Our aim is to discuss the risk factors of recurrent ischemic stroke and the efficiency of anticoagulation therapy. Methods : A report of a 50‐year‐old female patient who presented with a medical history of migraine, hypertension, 3 episodes of ischemic stroke within 12 years (the last one occurring 2 months ago), right hemiplegia, 2 miscarriages and multiple surgeries: appendectomy, myomectomy, hysterectomy due to adenomyosis, cataract surgery, cervical polypectomy, oophorectomy, meniscectomy after trauma. Results : Thrombophilia testing revealed heterozygous mutations of F13A1, ITGA2 and PAI1 genes. Antiphospholipid antibodies were within normal ranges. She received treatment with Rivaroxaban 20 mg/daily 1 month, B‐Complex vitamins, after which Clopidogrel 75 mg was prescribed. But the next ischemic stroke with hemorrhagic transformation occurred within 6 months. Type 2 diabetes was diagnosed 1 year later and Metformin hydrochloride was initiated. She underwent cholecystectomy due to benign tumors of the gallbladder and received treatment for Helicobacter pylori after which fifth episode of ischemic stroke happened. One year later she complained of headache, dizziness, unsteady gait, memory impairment, syncope and convulsions. Electroencephalography and echocardiography findings were not remarkable, ultrasound revealed multinodular goiter (TIRADS 2). COVID‐19 PCR test and anti‐SARS‐CoV‐2 IgG/IgM antibodies were negative. Labs showed 40.9% lymphocytes, prolonged APTT (45.4 s, reference range 30–40 s), slightly elevated ALT (34.9 U/L, reference range < 33). Urinalysis detected 0.03 g/L albumin and 1.13 HPF mucus. Two weeks later the sixth episode of ischemic stroke occurred despite receiving antiaggregation with Acetylsalicylic acid. Double testing for antiphospholipid antibodies, Protein C and S, homocysteine were normal, antithrombin III was 123.0%. Conclusion(s) : Although low‐risk thrombophilia mutations, type 2 diabetes, hypertension, overweight and multiple surgeries are the risk factors of 6 thrombotic events, cancer should be excluded taking into account her anamnesis.

E. Lourenco ; A. Jakhi; N. Thomas; A. Pandey; D. Sheikh; D. Kriplani; D. Antia Breach Candy Hospital Trust, Mumbai, Maharashtra, India Background : Coronavirus disease 2019 (COVID‐19) is a deadly respiratory disease caused by severe acute respiratory syndrome Coronavirus 2 (SARS‐CoV‐2).This virus may predispose patients to venous thromboembolic [VTE] complications. Venous Thromboembolic Disease i.e. DVT and PE are distinct clinical entities but manifestation of the same disease. Pulmonary embolism is a complication of DVT. Coagulopathy include haemostatic abnormalities with increased levels of D‐dimers. D‐dimers are fibrinolytic products produced at the site of venous thrombosis. Aims : Our aim was to study the presence or absence of D‐dimers in the blood of a patient with suspected Covid 19 diseases which could help in confirming or refuting the diagnosis. Methods : Study done at tertiary hospital, Mumbai, India, 400 patients sample tested for D‐Dimer, admitted with fever, RT‐PCR positive and some also had other underlying clinical history. By using STA‐Liatest D‐D plus kit analyzed quantitative on Stago Compact Max Instrument using latex enhanced immunoturbidimetric assay. Results : N: 50 Normal [12.5%] D‐dimer normal. Covid test negative, all tested lab parameters normal. N: 340 true positive [85%] D‐dimer positive. Covid positive patients N: 08: false positive [2%] D‐Dimer False Positive. Patient Covid negative N: 02 false negative [0.5%]‐D‐Dimer false negative. Patient Covid positive Sensitivity: 99.42%, Specificity: 86.21% [Normal Range of D‐DIMER: < or = 500 ng/ml]. Conclusion(s) : D‐Dimer is increased in thrombotic events indicating fibrinolysis. D‐Dimer quantification with persistent elevation of D‐Dimer gives clue of presence of DVT which can avail in diagnosing VTE Key message:. Early diagnosis and prompt treatment can prevent patients from critical complication of VTE disease Chest CT to be considered in all patients suspected of having COVID‐19 who have an indication for hospital admission Prophylactic‐dose low‐molecular‐weight heparin to be initiated in all hospitalized patients with proven or suspected COVID‐19.

T. Pertseva 1 ; L. Konopkina 2 ; K. Bielosludtseva 3 ; N. Habshydze 2 1 Dnipropetrovsk Medical Academy, Dnipro, Dnipropetrovs'ka Oblast', Ukraine; 2 Dnipro State Medical University, Dnipro, Dnipropetrovs'ka Oblast', Ukraine; 3 Dnipropetrovsk State Medical Academy, Dnipro, Dnipropetrovs'ka Oblast', Ukraine Background : There is an increased risk of thrombotic events in patients with COVID‐19, while thrombosis in patients who recovered from COVID‐19 is less investigated. Aims : To investigate thrombotic events in patients who recovered from COVID‐19; to establish risk factors for thrombosis development. Methods : We reviewed 32 patients who recovered from COVID‐19 (M/F:13/19, median age: 57 [49–67] years). Group 1 included 16 patients who had had a thrombotic event, whereas 16 patients from group 2 had not. Statistical analysis was performed by non‐parametric methods (median (Me), 95% confidence interval (95% CI), Mann–Whitney U test). We used odds ratio and relative risk to measure the association between risk factors and outcome. Results : 15 patients from group 1 had pulmonary embolism, 1 patient had ischemic stroke. The median term of thrombotic events was 45 (32–60) days. 2 patients had thrombophilia, 2 were hospitalized when the outcome occurred. 5 patients had BMI 30 or more, 7 did not have any risk factors. There was no statistically significant difference between two groups regarding age, weight, hospitalization duration, respiratory failure degree and its duration. Comorbidity, hospitalization requirement or oxigenotherapy during COVID‐19 did not affect the outcome. The only one association found was increased risk of thrombosis in patients who had not received anticoagulation RR 2.829 (95% CI 1279; 6255); OR 9.533 (95% CI 1.847; 49.206). Risk was also significantly elevated in case of antiplatelet agent use RR – 2.250 (95% CI 0.898; 5.636); OR – 4.333 (95% CI 0.742; 25.295). Conclusion(s) : Anticoagulant therapy was the only intervention decreased thrombosis probability in survivors after COVID‐19. Absence of anticoagulation treatment increases the risk of thrombosis during post‐covid period in 9 times.

B. Diaz Jordan ; V. Yepez Espinales Hospital General de Valdepenas, Valdepenas, Castilla‐La Mancha, Spain Background : Immune thrombocytopenia (IT) is a complication described within COVID‐19, probably secondary to the “immunological storm” produced during the acute infection. It usually responds to first‐line treatment (corticosteroids, immunoglobulins), with the use of thrombopoietin (TPO) agonists being somewhat infrequent. Aims : The objective is to present these cases of eltrombopag‐dependent immune thrombocytopenia secondary to severe COVID‐19 infection within a probable context of “persistent COVID syndrome”. Methods : Unicentric, descriptive study that describes our experience with two patients who presented severe forms of COVID‐19 (need to stay in intensive care) during the first wave (March 2020) and who to date have depended on eltrombopag to maintain hematological response. Results : Two patients (women aged 67 and 65 years) with no relevant medical history, diagnosed in March and April 2020, respectively, with bibasal pneumonia secondary to severe COVID‐19. On discharge they had severe IT associated with skin bleeding events, initially treated with oral prednisone mg/kg/day plus unspecific IVIg g/kg/day (no hematologic response in both cases) and dexamethasone 40 mg for 4 days plus unspecific IVIg g/kg/day every 15 days (3 cycles), without response. Second‐line treatment was started with TPO analogues (oral eltrombopag 50 mg/day, with dose escalation to 75 mg/day), obtaining hematological response on day +7 of start and complete remission on day +21 of treatment. After 18 months of treatment at high doses, it was decided to de‐escalate the dose, with loss of symptomatic hematological response, for which it was decided to return to the previous dose in both patients, with platelet count recovery 5–14 days later. Conclusion(s) : The fact that IT is refractory to corticosteroids and, furthermore, dependent on high doses of eltrombopag (with no possibility of reduction) after almost two years of treatment, gives us an idea that the process of immune dysregulation secondary to COVID ‐19 persists in time, as well as its long‐term consequences.

N. Vorobyeva 1 ; A. Barteneva 2 1 Federal State Budgetary Institution “National Medical Research Center for Hematology” (Northern branch) Ministry of Health of Ru, Arckhangelsk, Arkhangelsk, Russia; 2 Federal State Budgetary Institution Northern State Medical University Ministry of Health of Russia, Arkhangelsk, Arckhangelsk, Arkhangelsk, Russia Background : TGA is a sensitive and specific method for diagnosing thrombin formation and one of the best methods correlating with bleeding or thrombotic events. TGA provides information about the total clotting potential, because thrombin generation does not stop after the formation of fibrin clots. Aims : To evaluate the parameters of the thrombin generation test in patients with Covid‐19. Methods : A retrospective study on the basis of the regional center for antithrombotic therapy of SBHI CCH “1 City Hospital named after E.E.Volosevich”. Patients with confirmed Covid‐19 ( n  = 100). Blood sampling to determine the parameters of the thrombin generation (kinetics) test (TGA) was performed on the 1st day of the study. The automatic formulation of the TGA method is carried out on an open‐type coagulometer — Ceveron® alpha TGA. Genetic methods ‐ Real‐time PCR, Litech Company (Russia): Hemostasis system genes: FII G20210A, FGB G455A, PAI‐1675 5G/4G. Results : It was found that Tlag (min) and tPeak (min) significantly decreased in patients on the 1st day of hospitalization. Correlation analysis of Tlag (min) with the genotype of F I (fibrinogen) rS = − 0.3 ( p  = 0.02), confirming that heterozygous polymorphism of the FI gene is associated with a decrease in Tlag (min). The presence of polymorphism in the PAI‐1 gene is associated with a decrease in tPeak (min), i.e. in patients with polymorphism in PAI‐1, the peak of thrombin is achieved faster (rS = 0.5; p  = 0.03). The presence of polymorphism in the F I gene is associated with an increase in Peak (nmol/l), which is significantly higher in contrast to patients without polymorphism. The presence of polymorphisms in the PAI‐1 and F I genes is associated with an increase in EPT (nmol/min: rS = 0.3; p  = 0.04 and rS = 0.6; p  = 0.02). Conclusion(s) : The results of TGA in our study reflect data on an increase in the procoagulant potential of blood in patients with COVID‐19.

t. Kim 1 ; S. Namgoong 2 ; M. Choi 2 ; H. Kim 3 , S. Jang 4 1 Department of Laboratory Medicine, Asan Medical Center, Seoul, Seoul‐t'ukpyolsi, Republic of Korea; 2 Department of Laboratory Medicine, Asan Medical Center, Seoul, Seoul‐t'ukpyolsi, Republic of Korea; 3 Seoul National University Bundang Hospital, Seoul Seongnam, Kyonggi‐do, Republic of Korea; 4 Asan Medical Center, Seoul, Seoul‐t'ukpyolsi, Republic of Korea Background : As COVID‐19 is associated with a prothrombotic condition and some critically ill patients may even undergo extracorporeal oxygenation treatment, heparin is the essential for treatment in these situations. The prevalence of anti‐platelet factor 4 (PF4)/heparin antibodies associated with thrombotic tendency may be present in patients hospitalized for COVID‐19 without heparin therapy. Lupus anticoagulant (LA) included in the diagnostic criteria for antiphospholipid syndrome, which is one of the common causes of thrombophilia, is also commonly detected during SARS‐CoV‐2 infection. Most patients hospitalized for COVID‐19 showed elevated D‐dimer and prolonged activated partial thromboplastin time (aPTT), However, there were no studies on the association of SARS‐CoV‐2 infection with LA and anti‐PF4/heparin antibodies. Aims : The purpose of this study was to analyze the expression of LA and anti‐PF4/heparin antibodies associated with thrombotic tendency in COVID‐19 patients. Methods : We performed LA test (Instrumentation Laboratory, Bedford, MA) and LIFECODES PF4 IgG assay (Immucor, Norcross, GA) on 46 COVID‐19 patients admitted to Asan Medical Center and analyzed their frequency. Results : Of a total of 46 COVID‐19 patients, 26 patients (56.5%) were positive for LA test, 3 patients (6.5%) for anti‐PF4/heparin antibodies. In particular, anti‐PF4/heparin antibodies was detected only in LA‐negative patients and showed low optical density values (3 out of 20 LA‐negative patients, 15.0%). All three patients positive for anti‐PF4/heparin antibodies had no history of heparin treatment. Conclusion(s) : In COVID‐19‐patients, anti‐PF4/heparin antibody test does not predict clinically relevant HIT antibodies. Anti‐PF4/heparin antibodies appear in LA‐negative COVID‐19 patients, so they are carefully expected to serve as LA‐independent indicators.

K. Chasakova 1 ; M. Bílý 2 ; M. Paprota 2 ; J. Konečný 2 1 Hospital in Havirov, Havirov, Moravskoslezsky Kraj, Czech Republic; 2 General Hospital Havířov, Havířov, Moravskoslezsky Kraj, Czech Republic Background : COVID‐19 infection may be associated with coagulopathy, both thrombotic as well as haemorrhagic events. Bleeding manifestations are rather rare. Our case describes a possible association between acquired hemophilia A (AHA) and COVID‐19 infection. This causality has been described only in several cases. Aims : A 78‐year‐old male was admitted to hospital for ecchymoses, appearing just over past several days, located on the right breast and the left upper limb, with no history of recent injury. No previous personal or family history of any bleeding symptoms. Concurrently COVID‐19 infection was confirmed. During the hospital stay, the skin bruises have further spontaneously extended, covering both the pectoral areas, the abdomen and all extremities. Methods : Basic laboratory sampling was performed. The isolated presence of striking prolongation of aPTT was discovered (aPTT ratio 4.28, normal range 0.8–1.2). Investigations on prolonged aPTT have been initiated. Results : Extremely low activity of factor VIII (0.4%) was found. Further studies have subsequently identified a specific factor VIII inhibitor (24 Bethesda units). During the investigations of the condition no malignancy, autoimmune disorders or drug interactions were disclosed. A 30% COVID pneumonia was discovered by CT imagining. Conclusion(s) : The diagnosis of AHA was made, most likely due to an acute onset COVID‐19 infection. This association can only be speculated for the time being, however, COVID‐19 infection induced autoantibody production and influence on coagulation system is described by a number of studies. We therefore recommend a frequent coagulation monitoring including aPTT in patients admitted with acute COVID‐19 infection and the specific/non‐specific inhibitor search in cases with otherwise unexplained onset or worsening of haemorrhagic episodes and/or an aPTT prolongation.

R. Gupta Stony Brook University, Kolkata, West Bengal, India Background : Hypofibrinolysis, is the underlying reason behind hypercoagulability in severe COVID‐19. Hypertension, cardiovascular diseases and diabetes are the prime comorbidities. Blood clotting, maintained by regulatory balance between procoagulants and anticoagulants, lead to equilibrium between coagulation and fibrinolysis. Fibrin clots made of meshwork of polymerized fibrin threads, generated by proteolysis of fibrinogen by thrombin, play a cardinal role in thrombosis. RBC, WBC and platelets get embroiled in the meshwork of fibrin thread to form “clot”. Clots made up thin, highly branched fibrin fibers with smaller pores are less susceptible to fibrinolysis, on the contrary clots with thick fibers, less branched with larger pores are prone to lysis. Factor VIIIa crosslinks to fibrin, also crosslinks α2‐antiplasmin, TAFI, and PAI‐2 to fibrin, to increase resistance to fibrinolysis and enhancing thrombosis risk. Aims : How COVID‐19 comorbidities escalate hypofibrinolysis? Methods : Methods are from published literatures. Results : Fibrinogen levels are found to be enhanced in diabetes, with fibrin clots denser and resistant to fibrinolysis. Glycation of fibrinogen attributes to increased fibrin polymerization and crosslinkings, ensuing in abnormal clots. Altered fibrin structures, resistant to fibrinolysis are also observed in patients with coronary artery diseases and peripheral arterial diseases. Hypertension has also contributed to altered fibrin structures, with antihypertensive treatment increasing the clot susceptibility to lysis. Interestingly, platelet derived polyphosphate has been known to induce higher mass‐length ratio of fibrin threads making it fibrinolysis resistant. More so, thromboembolic COVID‐19 patients reported of elevated factor VIII, in comparison to patients without thromboembolisms. Severe COVID‐19 patients also reported of elevated anticoagulant proteins as SERPINS, PAI‐1, α2‐antiplasmin and TAFI, reflective of impaired fibrinolysis. Supportively, expression of PAI‐1 and TAFI are known to be enhanced in comorbidities. Conclusion(s) : Altered fibrin structures coupled with enhanced anticoagulant production, can lead to hypofibrinolysis, which predisposes to thromboembolisms in some severe COVID‐19 patients with comorbidities.

Y. Tsegay 1 ; M. Bitew 2 1 Armauer Hansen Research Insutitute, Addis Ababa, Adis Abeba, Ethiopia; 2 EBTI, Addis Ababa, Adis Abeba, Ethiopia Background : Coagulopathy and thromboembolic events are among the complications of Corona Virus disease 2019 (COVID‐19). Abnormal coagulation parameters in COVID‐19 patients are important prognostic factors of disease severity. Aims : To analyze coagulation profiles of hospitalized COVID‐19 patients in Addis Ababa, Ethiopia, the Horn of Africa. Methods : This prospective cross‐sectional study was conducted among 455 Covid‐19 patients admitted at Millennium COVID 19 care and treatment center, Addis Ababa, Ethiopia from July 1‐October 23, 2020. Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) and International normalized ratio (INR) were determined on HUMACLOTDUEPLUS® coagulation analyzer (Wiesbaden, Germany). In all statistical analysis of results, p  < 0.05 was defined as statistically significant. Results : A prolonged prothrombin time was found in 46.8% of study participants with COVID‐19 and a prolonged prothrombin time and elevated INR in 53.3% of study subjects with severe and 51% of critically COVID patients.Thrombocytopenia was detected in 22.1% of COVID‐19 patients. 50.5% and 51.3% of COVID‐19 patients older than 55 years had thrombocytopenia and prolonged APTT respectively. Conclusion(s) : Inthisstudy, prolonged prothrombin time and elevated INR were detected in morethan 50% of severe and critical COVID‐19 patients.Thrombocytopenia and prolonged APTT were dominant in COVID‐19 patients olderthan 55 years.Thus, were commendemphasis to be given for monitoring of platelet count, PT, APTT and INR in hospitalized and admitted COVID‐19 patients.

F. Alayoubi 1 ; G. Elgohary 2 1 KSUMC, Riyadh, Ar Riyad, Saudi Arabia; 2 King Saud Univesrty, Ryidh, Ar Riyad, Saudi Arabia Background : This pandemic has impacted health and the economy worldwide on an unprecedented scale. It has important systemic effects including the cardiovascular and immune systems. Aims : Discuss the links between COVID‐19 clinical features and complications and its hematological findings and coagulopathy. This link may shed light on our prognostic view to patients with COVID‐19 and will have significant therapeutic implications. One of these important implications is the use of mesenchymal stem cells (MSCs) to treat COVID‐19 patients. Methods : Review done to Autopsy findings support the concept that the pathogenesis of severe COVID‐19 involves direct viral‐induced injury of multiple organs, including heart and lungs, coupled with the consequences of a procoagulant state with coagulopathy. Mesenchymal stem cells as a potential therapy for COVID‐19 INFECTION. Results : Mesenchymal stem cells (MSCs) can be isolated from different adult tissues, and neonatal birth‐associated tissues, including placenta (PL), umbilical cord (UC), Warton jelly (WJ), amniotic fluid (AF), and cord blood (CB), and then stored for future possible applications. Differentiation potential, powerful immunoregulation, and endogenous repair mechanisms. Support to potential use of MSCs in treating patients came from observations that MSCs have been identified to efficiently cure ALI/ARDS from both infectious and noninfectious causes, mediated primarily by paracrine mechanisms based on the released extracellular vesicles (EVs). The immune‐regulation of MSCs depends mainly on modulating activation and effector function of immune cells, suppressing lung‐infiltrated cells, and enhancing the resolution of pulmonary edema [35]. Conclusion(s) : COVID‐19 is associated with distinct hematological changes, rise in serum inflammatory markers, and coagulopathy. Most of these changes were related to the patients' prognosis and mortality, particularly in those with severe disease. There are links between COVID‐19 clinical features and complications and its hematological findings and coagulopathy. COVID‐19 patients seems to be a promising approach. Further studies are needed to clarify more clinic‐pathologic links in COVID‐19 that might improve outcomes.

G. Gonen‐Yaacovi; O. Segurado ASC Therapeutics, Milpitas, California, United States Background : Allogeneic cell therapies require screening and monitoring biomarkers to ensure a precision medicine approach that personalizes treatment. The standard procedure of stem cell transplantation imposes toxicity and immune‐related concerns, which are evidenced by the development of acute graft‐versus‐host disease (aGVHD). The availability of live human placenta‐derived as a source of Decidua Stromal Cells (DSCs) has shown encouraging efficacy and safety profiles in many diseases, including aGVHD. Aims : A limitation of using DSCs in aGVHD is a lack of understanding of how the cells behave in the body and how they affect the immune system of the host. ASC Therapeutics has developed ASC930, an allogeneic cell therapy consisting of DSCs for the treatment of patients with Steroid Refractory aGVHD (SR‐aGVHD) and concomitant biomarkers to profile therapeutic screening and monitoring. Methods : In the prospective study ( NCT04883918 ), the safety and efficacy of ASC930 is being evaluated. Disease response will be assessed using surrogate safety and efficacy endpoints. To better understand the relationship between established biomarkers and DSCs, the study will include quantification of donor‐derived cell‐free DNA and flow cytometry to measure the immune response. In addition, two biomarkers of endothelial dysfunction, predicting long‐term outcomes, will be evaluated: suppressor of tumorigenicity‐2 (ST2) and regenerating islet‐derived protein 3‐α (REG3α), which have been identified in high concentrations in the blood of patients with aGVHD and are predictors of increased mortality. Results : Preliminary clinical work using labeled DSCs showed that the cells travel to the lungs, then to the spleen and liver (Erkers 2015). These results are being assessed in vivo with the methodology described above, focusing on DSC pharmacokinetics and pharmacodynamics, as well as immune and therapeutic response. Conclusion(s) : The introduction of selective biomarkers of cellular, immune, and disease response to DSCs can help select the right patient, the right treatment, and the right monitoring in the treatment of aGVHD.

J. Dahlen 1 ; A. Wu 2 ; K. Bliden 3 ; C. Ong 2 ; P. Gurbel 4 ; U. Tantry 5 1 Hikari Dx, San Diego, California, United States; 2 University of California at San Francisco, San Francisco, California, United States; 3 SInai Center for Thrombosis Research and Drug Development, Baltimore, Maryland, United States; 4 Sinai Center for Thrombosis Research and Drug Development, Baltimore, MD, Maryland, United States; 5 Platelet and Thrombosis Research, Baltimore, Maryland, United States Background : The T‐TAS 01 AR assay is a novel in vitro diagnostic system that measures total thrombogenicity in whole blood samples using a flow chamber model of vascular injury. Citrated whole blood is recalcified and spiked with corn trypsin inhibitor to inhibit the intrinsic coagulation pathway and passed at large vessel arterial shear rates through a thrombogenic path coated with collagen and tissue thromboplastin to produce platelet‐rich thrombus formation. Flow pressure increases inside the chip proportionally as the thrombus forms and impedes flow. Results are reported as occlusion time (OT; sec), which is the time at which flow has stopped due to thrombus formation. Aims : To establish a preliminary T‐TAS 01 AR assay reference range from healthy donors and to evaluate the repeatability of the assay. Methods : Healthy subjects were enrolled according to an IRB‐approved protocol at two investigational sites. Blood samples were collected into evacuated tubes containing 3.2% sodium citrate. Subjects were screened for possible primary or secondary hemostasis defects using standard laboratory methods. T‐TAS 01 AR measurements were performed between 30–120 min after blood collection. Reference ranges were calculated as the central 90% distribution using the quantile method and the average replicate CV was calculated from the overall mean OT and mean variance. Results : 49 subjects who had no evidence of primary or secondary hemostasis defects were included in the analysis. The study population was 65% female, aged 20–68 years. The OT reference range was 357–729 s. The overall CV for the replicates was 11.9%. Conclusion(s) : The T‐TAS 01 AR assay reference range in healthy donors was 357–729, and the average CV between replicates of 11.9% demonstrated good reproducibility. Establishment of the T‐TAS 01 AR assay reference range will be helpful for the interpretation of results as normal or abnormal, and abnormal results can be further categorized as hyperthrombotic or hypothrombotic.

K. Cabolis 1 ; T. Richards 2 ; K. Smith 1 ; M. Sajic 1 1 University College London, London, United Kingdom; 2 The University of Western Australia, Perth, Western Australia, Australia Background : Iron deficiency (ID) is common and, even in the absence of anemia is associated with fatigue and exhaustion. Given the central role of iron in the mitochondrial energy production, iron loss from energy demanding tissue, such as muscle, may lead to a deficit in mitochondrial metabolism, which may exasperate the symptom manifestation in ID and anemia. Aims : We aimed to assess the effects of ID and intravenous iron repletion on the function of skeletal muscle mitochondria in mice. Methods : Mice were fed either iron‐depleted (2–6 ppm total iron, n  = 25) or control diets (50–58 ppm total iron, n  = 13). [Hb] was measured weekly and fatigue was examined behaviourally by training mice to run to exhaustion on a treadmill. After seven weeks, a group of iron‐depleted fed mice received an intravenous iron injection (ferric carboxymaltose) thus becoming the iron‐repleted (IR, n  = 10) group. The soleus muscle was dissected 72 h post‐injections and using high‐resolution respirometry (Oroboros), we assessed mitochondrial respiration. Results : The [Hb] levels of control diet fed mice remained healthy throughout the experiment. At weeks six and seven, mice fed the iron‐depleted diet had significantly lower [Hb] levels compared with the control mice ( p  < 0.05). The respirometry data demonstrated that maximum coupled respiration was reduced by 63% in muscle of ID mice compared with control ( p  < 0.05). However, this was rescued following repletion, whereby maximum coupled respiration increased by 3.5‐fold compared with the ID group ( p  < 0.05). Furthermore, compared with the ID group, repletion induced a significant increase in complex II and complex IV activity ( p  < 0.05). Conclusion(s) : ID negatively affects the ability of mitochondria to produce energy in the muscle; however, intravenous iron can rapidly restore this. Overall, our results suggest that ID induced muscle fatigue may arise due to an impairment in the ability of mitochondria to produce energy through oxidative phosphorylation.

Y. Xu ; R. Zhou Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China (People's Republic) Background : The cytopenic diseases such as aplastic anemia (AA), myelodysplastic syndrome (MDS) and primary immune thrombocytopenia (ITP) sometimes have similar clinical and laboratory manifestation, which bring difficulties to clinical differential diagnosis. Therefore, it is necessary to explore new reference indicators conductive to differential diagnosis. Aims : To explore the value of neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), and platelet to lymphocyte ratio (PLR) in the differential diagnosis of cytopenic diseases. Methods : The clinical and laboratory data of 105 patients with AA, MDS and ITP from 2017 to 2020 were retrospectively analyzed. Results : The means of NLR level in AA, MDS and ITP groups were 0.631 ± 0.414、1.285 ± 1.165、3.527 ± 2.033, respectively, the difference was statistically significant (F = 35.82, p  < 0.001). The three groups were sequentially compared in pairs, and the differences within the groups were statistically significant ( p  < 0.001). The NLR level of hypoplastic MDS (hypo‐MDS) group was lower than that of non‐hypo‐MDS group, although there was no significant difference between these two groups, the NLR level of hypo‐MDS group was closer to AA group ( p  > 0.05). The MLR levels of these three groups were 0.114 ± 0.099, 0.316 ± 0.297 and 0.275 ± 0.136, respectively (F = 6.584, p  = 0.002). The MLR level of AA group was significantly lower than that of both MDS group and ITP group ( p   0.05). Similarly, the MLR level of hypo‐MDS group was lower than that of non‐hypo‐MDS group, while the former was closer to AA group. The PLR levels of these three groups were 16.718 ± 23.322, 87.628 ± 155.335 and 10.972 ± 18.697, respectively (F = 5.689, p  = 0.001). The PLR level of MDS group was significantly higher than that of both AA group and ITP group ( p  < 0.05). Conclusion(s) : There are differences in NLR, MLR and PLR levels among AA, MDS and ITP patients, which may have certain reference value for differential diagnosis of the three diseases. Compared to ITP group，aP＜0.05；Compared to AA group，bP＜0.05 TABLE 1 Data of different groups. Hemophilia and Rare Bleeding Disorders

N. Vorobyeva 1 ; A. Vorobyeva 2 1 Federal State Budgetary Institution “National Medical Research Center for Hematology” (Northern branch) Ministry of Health of Ru, Arckhangelsk, Arkhangelsk, Russia; 2 Federal State Budgetary Institution Northern State Medical University Ministry of Health of Russia, Arkhangelsk, Архангельск, Arkhangelsk, Russia Background : In comorbid and elderly patients taking DOACs, it is important to maintain adherence to both antithrombotic therapy itself and to concomitant pharmacotherapy, as otherwise it may lead to progression pathology, fatal complications, naturally, to an increase in mortality, an increase health care costs in general. Aims : The article is to evaluate adherence to therapy with direct factor Xa inhibitors in clinical practice. Methods : An study included patients receiving a antithrombotic therapy with factor Xa inhibitors ( n  = 50), who were observed at the Regional Center for Antithrombotic Therapy of the City Clinical Hospital, Arkhangelsk. To confirm the fact of taking DOAC and compliance with the therapy, the study determined peak concentration of DOAC in blood plasma and analyzed whether a patient had completed training at the DOAC School. To assess the patient compliance with the antithrombotic therapy, laboratory monitoring of the peak concentration of DOAC was carried out, depending on the fact of training at the School. Results : The study showed no statistically significant difdrug and did not attendferences in the concentration of rivaroxaban and apixaban in patients who were trained at the DOAC School and did not attend the class. Laboratory monitoring of the peak concentration of DOACs in 10% patients showed they had no DOAC in blood plasma. This indicated that the drug was not being taken. It is important to note that 5 patients concealed from the doctor the fact that they did not take the School. Prescription of potentially non‐recommended drugs according to «STOPP» criteria (2015 ed.) was identified in 4% of patients. Conclusion(s) : Events clarifying the importance of antithrombotic therapy are advisable to increase patient compliance and, accordingly, the effectiveness and safety of this type of drug therapy. In some cases, to determine the peak concentration of the drug is recommended to assess compliance with the DOAC therapy.

T. Kim 1 ; S. Namgoong 2 ; M. Choi 2 ; S. Jang 3 1 Department of Laboratory Medicine, Asan Medical Center, Seoul, Seoul‐t'ukpyolsi, Republic of Korea; 2 Department of Laboratory Medicine, Asan Medical Center, Seoul, Seoul‐t'ukpyolsi, Republic of Korea; 3 Asan medical center, Seoul, Seoul‐t'ukpyolsi, Republic of Korea Background : Activated clotting time (ACT) is a point‐of‐care coagulation test monitored an unfractionated heparin (UFH) in whole blood of patients receiving heparin therapy. The target value of the ACT should be changed according to the devices type. Aims : The purpose of this study was to set up the target value ACT of i‐STAT on cardiopulmonary bypass (CPB) patient. Methods : We perfomed precision tests, which used quality control materials to reproducibility, and comparison tests with 42 samples. We performed target setup tests with CPB patient samples (310 samples/74 patients) to reflect clinically meaningful UFH concentrations. Hemochron Response (Instrumentation Laboratory, USA; HR) was tested in a non‐preheat method (FTCA510 tube). i‐STATs (Abbott, USA; i‐STAT1, i‐STAT2) was tested in a preheat method (ACT Celite® cartridge). Results : Precision test did not exceed the manufacturer's acceptable range (HR‐level 1: 1.81, level 2: 0.75, i‐STAT1‐Level 1: 2.70, Level 2: 2.08, i‐STAT2‐Level 1: 2.18, Level 2: 3.08). The difference between the hemocron response and the i‐STAT devices in the comparative test was as follows (R i‐STAT1: 0.9053, i‐STAT2: 0.9074, mean difference i‐STAT1: −10.2%, i‐STAT2: −12.0%). i‐STAT1 and 2 showed a good correlation and the mean difference showed similar results (R 2 : 0.9769, mean difference: −2.0%). The R value of the target setup tests was 0.8543. Conclusion(s) : HR is known to have a linearity of 80 to 600 s and, i‐STAT is known 50 to 1000 s. Their results were different due to differences in slope, but the same UFH concentration was reflected because the same specimen was performed at the same time. The setting of the target value used medical decision point (MDP) analysis because the R was 0.8543. Based on 480 s, the minimum was 363.6 s, the maximum was 393.8 s, and the mean was 378.7 s. We decided that the target vlaue of i‐STAT is 380 s.

R. Santoja Rubio 1 ; A. Tugues 2 ; E. Vicente 2 ; C. Marzo 3 ; P. Monteagudo 4 ; L. Amuh 4 ; C. Chávez 5 ; M. Teixidó 4 ; A. Garcia 5 ; A. Luaña 4 ; A. Ferrero 4 ; A. Ruiz 5 ; T. Garcia 4 1 Hospital Universitario Arnau de Vilanova, Lleida, Catalonia, Spain; 2 Hospital Universitari Arnau de Vilanova de Lleida, Departamento de Trombosis y Hemostasia, Servicio de Hematología y Hemoterapia, Lleida, Catalonia, Spain; 3 Hospital Universitari Arnau de Vilanova de Lleida, Departamento de Trombosis y Hemostasia, Servicio de Hematología y Hemoterapia, Lérida, Catalonia, Spain; 4 Hospital Universitari Arnau de Vilanova de Lleida, Departamento de Trombosis y Hemostasia, Servicio de Hematología y Hemoterapia, lleida, Catalonia, Spain; 5 Hospital Universitari Arnau de Vilanova de Lleida, Servicio de Hematología y Hemoterapia, lleida, Catalonia, Spain Background : Acquired hemophilia is a rare bleeding disorder with an underestimated incidence due to the complexity of diagnosis. It's characterized by the presence of autoantibodies against coagulation Factor VIII, which can trigger bleeding episodes. Most cases are of idiopathic etiology. It has a high morbi‐mortality, hence the importance of establishing an early diagnosis and treatment. Aims : Establish, according to current guidelines, individualized therapeutic management, hemostatic, immunosuppressive and immunomodulatory treatment, as well as its monitoring and follow‐up of the case studied. Methods : Clinical case study of a 71‐year‐old patient with active bleeding, factor VIII level less than 1% and inhibitor titer greater than 40 Bethesda Units (UB) at the time of diagnosis. Results : Given the absence of hemorrhagic symptoms, treatment with corticosteroids mg/kg was started after diagnosis. The etiological study did not identify cause. After 24 h, the patient presented significant subcutaneous hematomas requiring transfusion of packed red blood cells (HHCC) and the addition of activated recombinant Factor VII (arFVII). Also, immunosuppressive treatment with immunoglobulins and Rituximab was started. After one week, due to new onset of bruising and progressive anemia despite HHCC transfusion, with persistence of FVIII 40 UB, cyclophosphamide was added to the therapeutic regimen and arFVII was changed to activated prothrombin complex. After three weeks of intensive treatment, the evolution was satisfactory with cessation of hemorrhagic symptoms, presenting figures of FVIII 7% and inhibitor of 9 UB. Conclusion(s) : Despite being a rare entity, it is important to know the differential diagnosis in a patient with bleeding diathesis and alteration in coagulation tests due to its high morbidity and mortality. It requires close monitoring in addition to intensive treatment, with the aim of controlling possible bleeding complications and reducing the autoantibody titer through different therapeutic schemes, trying to control the disease and achieve remission. TABLE 1 Evolution of rPTTA, FVIII and inhibitor concentration. FIGURE 1 Clinical picture of patient bleeding.

A. Sarmento 1 ; C. Almeida 1 ; M. Mendes 2 ; L. Borges 2 1 Centro Hospitalar Baixo Vouga, Aveiro, Aveiro, Aveiro, Portugal; 2 Centro Hospitalar do Baixo Vouga, Aveiro, Aveiro, Aveiro, Portugal Background : Acquired hemophilia A (AHA) is a rare but clinically significant bleeding disorder resulting from circulating autoantibodies that target and inhibit coagulation factor VIII (FVIII). It is well‐established that underlying condition such as autoimmune diseases, malignancies and post‐partum status have a clear association with AHA. However, about half of the cases are considered idiopathic. Aims : We describe the case of a 40‐year‐old Caucasian woman diagnosed with AHA with a possible autoimmune disease as an underlying cause. Methods : Collected data was obtained from patient record. Results : The patient was being followed recently by our Rheumatology department due to polyarthralgia. The initial coagulation assessment revealed a prolonged activated partial thromboplastin time (aPTT) with a normal prothrombin time, which was initially explained by the presence of a lupus anticoagulant. However, a positive history for spontaneous and prolonged bleeds in the previous year, namely multiple unexplained ecchymosis and several episodes of gross hematuria, prompted the study of a possible bleeding disorder. The aPTT mixing study failed to correct the prolonged aPTT. The intrinsic pathway coagulation factors activities were measured and FVIII activity was 4%. We tested for the presence of a FVIII inhibitor using the Bethesda assay, which determined a titer of 7.90 Bethesda Units. The diagnosis of AHA was then established. Our patient initiated treatment with prednisolone 1 mg/Kg daily PO. After 3 weeks, FVIII activity was normal and inhibitor testing was negative. Furthermore, bleeding symptoms had ceased and corticosteroid tapering was begun. Our patient remains in monthly follow‐up. Conclusion(s) : The onset of bleeding symptoms should grant a laboratory investigation with an assessment of routine coagulation assays. An isolated prolonged aPTT should cause caution about this diagnosis. Bleeding can be often severe. Fast diagnosis is critical, as well as early strategies to bleeding control. Inhibitor eradication with immunosuppressive agent is the cornerstone of AHA treatment.

T. Talako 1 ; D. Tsvirko 2 ; K. Kabaeva 3 ; Y. Statsenko 4 ; I. Iskrov 2 1 Belarusian Medical Academy of Postgraduate Education, Minsk, Minskaya Voblasts', Belarus; 2 Belorusian Medical Academy of Postgraduate Education, Minsk, Minskaya Voblasts', Belarus; 3 Belorusian Medical Academy of Postgraduate Education, MInsk, Minskaya Voblasts', Belarus; 4 United Arab Emirates University, Al Ain, Abu Dhabi, United Arab Emirates Background : Natural anticoagulants deficiency and hyperfibrinolysis are among the main features of DIC. Aims : To present successful management of 3 cases of patients with full‐blown DIC. Methods : Full blood count, hematological tests, thromboelastogram (TEG) were done. Results : Case 1: 28‐year‐old lady after hysterectomy presented DIC with massive bleeding on skin and mucous membranes with bloody drains discharge. Laboratory tests: platelets ‐ 28 × 109/L, activated partial thromboplastine time (APTT) ‐ 124 s, Quick prothrombin test (QPT) ‐ 22%, fibrinogen ‐ 0.7 g/L, D‐dimers ‐ 5200 μg/L, antithrombin (AT) III ‐ 43%. The clot wasn't formed at TEG. Prothrombin complex concentrate 30 IU/kg intravenously (iv), donor platelets, fresh frozen plasma (FFP) 15 ml/kg/day iv, cryoprecipitate iv were used. Bleeding stopped in a day, platelets stabilized at >100 × 109/L, fibrinogen ‐ at >1.5 g/L, normocoagulation was achieved. Case 2: 30‐year‐old woman after abortion at 12 weeks of gestation with sepsis developed DIC without bleeding. Her platelets were 81 × 109/L, APTT ‐ 54 s, QPT ‐ 56%, fibrinogen ‐ 1.2 g/L, D‐dimers ‐ 1400 μg/L, AT III ‐ 68%. Treatment included FFP 15 ml/kg/day. Normalization of APTT and QPT was achieved in a day. Case 3: 30 years old man with APL had DIC with fibrinolytic phenotype after chemotherapy with massive skin and mucous bleeding. Tests showed platelets ‐ 31 × 109/L, APTT ‐ 64 s, QPT‐ 52%, fibrinogen −1.2 g/L, D‐dimers ‐ 4800 μg/L, AT III ‐ 53%, the clot was lysed by 30 min at TEG. Donor platelets, FFP 15 ml/kg/day, tranexamic acid 25 mg/kg iv were used in treatment. Bleeding stopped in 2 days, normalization of APTT and QPT, TEG and fibrinogen >1.5 g/L was achieved. Conclusion(s) : Pathogenic therapy of DIC is based on the assessment of hemostasis along with clinical manifestations and includes use of blood components and fibrinolysis inhibitors.

C. Ursu 1 ; M. Serban 1 ; C. Vlad 2 ; A. Traila 3 ; E. Boeriu 4 ; C. Jinca 4 ; E. Boia 5 ; M. Negru 5 ; T. Arghirescu 4 1 Romanian Academy of Medical Sciences, Onco‐Hematology Research Unit, Children Emergency Hospital “Louis Turcanu”, European Hemophilia Treatment Center, Timisoara, Romania, Timisoara, Timis, Romania; 2 Pediatric Orthopedic Department, Children's Clinical Hospital ″Doctor Victor Gomoiu″ Bucharest, Bucharest, Bucuresti, Romania; 3 Medical Centre for Evaluation Therapy, Medical Education and Rehabilitation of Children and Young Adults, European Hemophilia Treatment Centre, Buzias, Romania, Buzias, Timis, Romania; 4 Department of Pediatrics, Division of Onco‐Hematology, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania, Timisoara, Timis, Romania; 5 Department of Pediatric Surgery, Victor Babes University of Medicine and Pharmacy, Timisoara, Romania, Timisoara, Timis, Romania Background : Non‐severe hemophilia (NSH) is a possible subject of delayed, under‐or misdiagnosis, which can sometimes develop challenging dangerous events with risky outcomes. Aims : Our present objective is to give some insights into the challenging NSH field, presenting an evocative case, with a real diagnostic pitfall and unexpected outcome. Methods : Case presentation. Results : A 5‐year‐old male patient, with no personal history of bleedings or family history of hemophilia, was incidentally diagnosed with moderate hemophilia B due to a post‐traumatic hepatic injury with intraabdominal bleeding and severe anemia. Surgical hepatic capsular suture, plasma‐derived FIX (pdFIX) replacement, and blood transfusion assured a good clinical evolution. After two years of bleeding‐free time, the patient is addressed to our clinic for a spontaneously occurred limp, mild pain localized to the right hip joint, described as radiating to the inguinal area and with limited motion. Ultrasonography excluded the presence of haemarthrosis, but the native pelvic MRI revealed idiopathic avascular necrosis changes of the right femoral head, with incomplete subchondral linear fracture. After ~12 months of continuous pdFIX prophylaxis and immobilization, the clinical and radiological evolution was unfavorable, with the involvement of more than 50% of the right proximal femoral epiphysis. This challenging worse evolution urged a surgical decision for that challenging Perthes disease. Under prophylactic treatment with an extended half‐life (EHL) FIX product, a right proximal femoral varus osteotomy with a triple pelvic osteotomy for femoral head coverage and containment was undertaken. The evolution was slowly favorable, under a rigorous rehabilitation program with physical therapy and prophylactic EHL‐FIX replacement. Conclusion(s) : This case with challenging late diagnosis, challenging rare complication, challenging unfavorable evolution, requiring a challenging surgical solution highlighted the importance of a comprehensive approach, in order to avoid unpredictable diagnosis and subsequent risks.

L. Stanciakova 1 ; P. Holly 2 ; M. Dobrotova 3 ; M. Brunclikova 3 ; M. Samos 4 ; T. Bolek 4 ; P. Kubisz 3 ; J. Stasko 3 1 National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Martin University Hospital, Martin, Slovak Republic, Martin, Zilina, Slovakia; 2 Comenius University, The Jessenius Faculty of Medicine in Martin, Martin, Zilina, Slovakia; 3 National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, Slovakia, Martin, Zilina, Slovakia; 4 Department of Internal Medicine I, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Martin University Hospital, Martin, Slovak Republic, Martin, Zilina, Slovakia Background : Hemophilia A is a X‐linked recessive bleeding disorder caused by defective synthesis of coagulation factor VIII (FVIII). Anyway, it does not protect from thromboembolic events. Cardiovascular complications develop even earlier and significantly more frequently in individuals with hemophilia A than in control group. Aims : The authors report the case of the patient with hemophilia A with repeated thrombotic episodes. Methods : The 60‐year‐old man with moderate hemophilia A (FVIII 2.3–2.6%), treated initially with on demand FVIII concentrate (weight 60 kg) is presented. Written informed consent was obtained and the study was approved by the Ethics committee of the Jessenius Faculty of Medicine. Study complies with the Declaration of Helsinki. The authors do not have any conflict of interest. Results : At first, the patient reported the dull pain in epi‐ and mesogastrium irradiating to the back. The computed tomography confirmed the presence of the irregular thrombus almost in whole part of the abdominal aorta. Combination of antithrombotic agents led to disappearance of these symptoms. In 4‐years time, he was admitted to the hospital with dyspnea, bilateral rattling sounds in the lungs. This time, he was diagnosed with acute myocardial infarction with ST‐segment elevation of the inferior wall, unilateral pneumonia and pleural effusion. Despite the treatment, breathlessness was still present. Finally, bronchial carcinoma with lung metastases was found. Conclusion(s) : The management of cardiovascular events in hemophiliacs is challenging especially in the situations when antithrombotic treatment or invasive procedure is planned. Thus, the optimalization of the concomitant antithrombotic and substitution therapy in patients with the coexistence of opposing disorders of hemostasis is needed. Acknowledgement: The authors thank the support of projects of the Agency for the Support of Research and Development (APVV) APVV‐16‐0020 and Scientific Grant Agency (Vega) 1/0549/19.

X. Feng 1 ; S. Zheng 2 ; J. Sun 3 ; Z. Wang 4 ; H. Li 5 ; Z. Chen 6 ; Q. Li 7 ; J. Lai 8 ; J. Du 5 1 Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (People's Republic); 2 Cardiothoracic Surgery, Nanfang Hospital, Souther Medical University, Guangzhou, Guangdong, China (People's Republic); 3 Hematology, Nanfang Hospital, Southern Medical University, Guanghzou, Guangdong, China (People's Republic); 4 Cardiothoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (People's Republic); 5 Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (People's Republic); 6 Beijing Children's Hospital, Beijing, Beijing, China (People's Republic); 7 Clinical Laboratory, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China (People's Republic); 8 Guangzhou Zhili medical laboratory, Guangzhou, Guangdong, China (People's Republic) Background : Prevention of bleeding during major surgery in patients with high titer inhibitors is a great challenge. Emicizumab or rhFVII is possible valid options. Aims : To explore the efficacy of Emicizumab combined with rhFVII in preventing hemorrhage in children with high titer inhibitors during the perioperative period of major surgery. Methods : Method:The patient was 2 years old boy, 13 kg, diagnosed severe hemophilia A with ventricular septal defect (massive left‐to‐right shunt), accompanied by severe pulmonary hypertension. After the 20th exposure days, he was found to combine inhibitor around 27‐ 35 BU/ml.He received a total of 4 doses of Emicizumab (30 mg, IH, 1/W)for prophylactic application. The operation of ventricular septal repair and mitral valvuloplasty under cardiopulmonary bypass were performed after systemic heparinization. Arteries were blocked for 69 min. In the perioperative period, rhFVII 1–2 mg/dose was used, q2h‐q12h, and continued to used Emicizumab 30 mg/W for 2 weeks after surgery. Laboratory data such as PT, D‐Dimmer, FVII level, CAT and clinical bleeding were monitored. Results : RESULTS: After 3 doses of Emicizumab, the equivalent FVIII levels reached 9.8%–15.7%, respectively. Intraoperative bleeding was about 60 ml. However, there was persistent pericardial oozing blood after operation. He was given rhFVII 2 mg/dose, q2h IV, infusion of RBC and fresh frozen plasma for supportive treatment, and then the bleeding gradually decreased. The dose of rFVII was gradually tappered. One week after the operation, the inhibitor titer was 14.3 BU/ml. The drainage tube was removed 5 days after the operation, and the patient recovered well. CAT and plasma FVII levels are shown in Figures 1 and 2. Conclusion(s) : Discussion:For the cardiac surgery under cardiopulmonary bypass after heparinization in children with high titer inhibitors, the use of Emicizumab combined with rFVII to prevent perioperative bleeding, still requires high‐dose of rhFVII in the early postoperative period, and overall effective prevention bleeding can be achieved. FIGURE 1 CAT in the day after operation (D1). FIGURE 2 FVII level after operation.

G. Maestrini 1 ; E. Baldacci 2 ; A. Ferretti 1 ; M. Chavez Orellana 1 ; M. Mormile 2 ; F. Barone 1 ; S. Olivieri 3 ; A. Pallotta 3 ; A. Serrao 4 ; F. Viola 1 ; A. Chistolini 1 ; C. Santoro 2 1 Hematology, Sapienza University of Rome, Rome, Lazio, Italy; 2 Hematology, University Hospital Policlinico Umberto I, Rome, Rome, Lazio, Italy; 3 Hematology, University Hospital Policlinico Umberto I, Rome, Italy, Rome, Lazio, Italy; 4 Hematology, Sapienza University, Rome, Italy, Rome, Lazio, Italy Background : The use of emicizumab as prophylaxis for severe HA with or without inhibitor, is increasing in routine clinical practice. Aims : To describe our center experience with emicizumab prophylaxis in severe hemophilia A (HA) patients without and with inhibitors. Methods : All the participants signed an informed consent; data were collected from clinical charts. Results : 10 severe HA patients received emicizumab prophylaxis (table 1). We observed 1 drug‐related adverse event, a relapsing orticarioid reaction at the injection site. Non‐inhibitor patients: 6, 4 on rFVIII prophylaxis, 1 on demand therapy, 1 never treated. Reason for starting emicizumab: need to facilitate the therapy administration in young children. Just one traumatic tongue lesion occurred which was treated with one dose of rFVIII. None surgical or invasive procedures were performed. Inhibitor patients: 4. Before switching to emicizumab: 3 on bypassing agents on demand; one patient on rFVIII prophylaxis developed a high titer inhibitor. Two patients received ITI. All patients switched to emicizumab for a better control of the disease. No spontaneous bleeding were reported. A traumatic fracture of the homerus occurred, treated with 4 doses of rFVIIa (90 μg/kg/dose) without any complication. One patient underwent a colonoscopy without additional prophylaxis (no biopsies performed). Two patients underwent dental extraction: just one received prophylaxis with tranexamic acid; no hemorrhagic complications were observed. Conclusion(s) : We confirm the efficacy and safety of emicizumab prophylaxis. No spontaneous bleedings occurred. Two traumatic bleedings were easily managed with rFVIIa or FVIII concentrate. Dental extractions in inhibitor patients were performed without rFVIIa therapy. No serious adverse events observed. The different median age and follow‐up between inhibitor and non‐inhibitor patients depends on timelines of regulatory indications for prescription and previous participation in clinical studies. We observed an improvement in quality of life of patients and their families. TABLE 1 Patients characteristics.

C. Albayrak 1 ; D. Albayrak 2 1 Ondokuz Mayıs University Medical Faculty Haed of Pediatric Bone Marrow Unit, Samsun, Samsun, Turkey; 2 Samsun Medicalpark Hospital, Samsun, Samsun, Turkey Background : In patients who can use high doses of prophylactic factors, the moment of application may not be very important. However, in order to obtain an effective prophylaxis with a limited amount of factors, it is very important that the prophylaxis be administered just before active life. Aims : Turkey is gradually improving hemophilia care. Most of our severe hemophilia patients use 4500 IU factor VIII or IX weekly as a prophylactic. Depending on body weight and bleeding frequency, the dose can be increased to 6000 IU weekly. This factor is paid by the social security institution for all patients. Our patients frequently infuse 1500 IU of factor 3 days a week. Patients who do the infusion or their family members cannot find time for the infusion due to the rush to get to work and school in the mornings. They mostly apply the infusion in the evening hours. For this reason, they are actively engaged in daily work during the hours when factor levels are the lowest. During the hours when the factor level is the highest, they are at rest or asleep. Methods : In order to correct this situation, we planned a competition in order to apply prophylactic factor applications at the beginning of the day in the morning. Results : In order to develop this habit, we, as the 19 May Hemophilia Association, organized a contest for our patients called “I make my factor in the morning, I start the day healthy”. We asked our patients to take photos with own slogans while doing their prophylaxis infusions in the morning and share them with us on social media. Fifty‐five of our patients participated in this campaign. Conclusion(s) : In patients receiving prophylaxis with a limited amount of factor, the application time in the morning maximizes the effectiveness.

R. Pombal 1 ; L. Vieira 2 ; S. Lopes 3 ; R. Neto 1 ; D. Ferreira 1 ; M. Figueiredo 3 1 Centro Hospitalar Centro Vila Nova de Gaia/Espinho, Porto, Porto, Portugal; 2 Centro Hospitalar Vila Nova de Gaia/Espinho, Porto, Portugal; 3 Centro Hospitalar Centro Vila Nova de Gaia/Espinho, Vila Nova de Gaia, Porto, Portugal Background : Hemophilia A is an X‐linked coagulopathy, characterized by FVIII deficiency. Although usually inherited, sporadic cases are common. In Portugal, there is a referral network for congenital coagulopathies that ensures follow‐up of these patients in centers with specialized healthcare professionals. Aims : Description of two cases of sporadic hemophilia, diagnosed in a Portuguese hospital that is not a reference center for follow‐up/treatment of congenital coagulopathies. Methods : Collection of clinical data in SClínico® application. Results : Patient 1 is a male newborn who presented, after instrumented delivery, a large median parieto‐occipital cephalohematoma. A cranial CT scan revealed a mild subarachnoid hemorrhage. Hemoglobin decreased to 6.3 g/dl, without evidence of hemolytic disease of newborn. Transfusion of 60 ml of packed red blood cells was performed (body‐weight: 3690 g). The patient presented a favorable clinical evolution and was discharged. At 15 months, due to frequent extensive ecchymoses since he started walking, a coagulation study was requested, revealing a prolonged aPTT (60.8 s; age‐adjusted normal range: 28.6–35.8 s) and a decreased factor VIIIc (2%), compatible with moderate hemophilia A. Patient 2 is a 21‐month‐old male child admitted to the emergency department with ecchymosis, pain and claudication in the right leg, without history of trauma/fall. His mother mentioned easy bruising in minor trauma situations, previously reported to assistant clinician. Coagulation study showed a prolonged aPTT (76.3 s; age‐adjusted normal as above) and a decreased factor VIIIc (<1%), compatible with severe hemophilia A. Family history of diagnosed/suspected coagulopathy was absent in both cases. Conclusion(s) : Individuals with inherited coagulopathies are often already identified, allowing early evaluation/follow‐up of their offspring. In hemophilia A, 55% of severe cases and 30% of mild/moderate cases are, however, sporadic. These diagnoses were established 2 years‐apart, in a hospital without experience in coagulopathies management, highlighting the importance of a comprehensive/standardized assessment of bleeding signs/symptoms by all clinicians, even in the absence of suggestive family setting.

G. Sargsyan 1 ; G. Tamamyan 1 ; N. Sargsyan 2 ; S. Danelyan 3 ; L. Sahakyan 3 ; A. Voskanyan 4 ; A. Ter‐Grigoryan 5 ; H. Khachatryan 4 1 Pediatric Cancer and Blood Disorders Center of Armenia, Hematology Center after Prof. R.H. Yeolyan, Yerevan, Armenia; Department of Pediatric Oncology and Hematology, Yerevan State Medical University, Yerevan, Armenia, Yerevan, Yerevan, Armenia; 2 Hematology center after prof. R.H.Yeloyan Armenian Hemophilia and Thrombosis Center Yerevan State Medical University, Department of Pediatric Oncology and Hematology, Yerevan, Yerevan, Armenia; 3 Hematology center after prof. R.H.Yeloyan, Yerevan, Armenia, Yerevan, Yerevan, Armenia; 4 Hematology Center after Prof. R.H. Yeolyan, Yerevan, Armenia, Yerevan, Yerevan, Armenia; 5 Armenian Hemophilia and Thrombosis Center Yerevan State Medical University, Department of Pediatric Oncology and Hematology, Yerevan, Yerevan, Armenia Background : Hemophilia treatment center reports a case of a 38‐year‐old male with the second degree of disability without history of previous disease. He was diagnosed with hemophilia in December 1985. Aims : This was the first time we had a case of such complexity in our hospital. The case report summarizes the successful treatment of a patient with hemophilia A and major bleeding, and also it became clear that having several patients with such severe bleeding could deplete the blood bank reserves. Methods : A retrospective review of the patient's medical history was performed. Results : As a result of clinical diagnosis, he was diagnosed with Hemophilia A inhibitor version, which was accompanied by acute mucosal bleeding. The patient had acute nasal bleeding, gastrointestinal bleeding and two episodes of tamponade, arterial embolization and coagulation with endoscopic intervention in the posterior nasal cavity. Among the complications he had 2 episodes of endoscopic coagulation, hematoma of the palate and the nasal cavity, erosive surfaces. He had HCV infection, chronic ulcer disease, obesity, encephalopathy, arterial hypertension from concomitant diseases. The patient was hospitalized on December 11 and discharged on the 30th, thus spending 19 bed days in the clinic. The subsequent tests revealed low factor VIII and high inhibitor levels (VIII 3% and inhibitor titer 5.5 BE Units/ml). The patient weighed 130 kg. Management relies on a rapid and accurate diagnosis, control of bleeding episodes. Appropriate treatment was prescribed, the patient was managed with medications resulting in normalization of factor VIII levels. Conclusion(s) : All medical resources have been used for the prevention and treatment of bleeding in one patient. The bottom line is that on average, hemophiliacs are the most vulnerable group, especially in the presence of hepatitis, especially in the presence of overweight, especially in countries where the drug problem has not been resolved.

A. Aribandi 1 ; C. Ranjith 2 ; K. Ashok 1 ; R. Gottipati 3 1 American Oncology Institute, Hyderabad, Telangana, India; 2 Amerian Oncology Institute, Hyderabad, Telangana, India; 3 American Oncology Insttute, Vijayawada, Andhra Pradesh, India Background : The mortality risk in hypocoagulation disorders is reported to be about 30–40%. Without a multidisciplinary approach, there is high risk for morbidity and mortality. With increased bleeding the patients are at risk for transfusion associated complications too. Accurate diagnosis and early intervention would reduce both morbidity and mortality. In the developing countries, availability of laboratories capable of making an accurate diagnosis, resources for identifying the source of bleeding and managing the patient comprehensively is much more challenging. Here we are presenting our data relating to such complex bleeds and a multimodality approach for control of the bleeding. Aims : Managing complex bleeds in hypo coagulation disorders using a multidisciplinary approach will reduce both morbidity and mortality. Methods : Here we present the data from 3 patients that were admitted with major bleeding manifestations and how a multimodality approach for identification and control of the bleeding was made. Data was collected from HIMS. Results : Among the cases presented, 2 had severe, Type III von Williebrand disease and 1 had Factor XIII deficiency. Presenting complaints were severe uterine bleeding in one, upper GI bleeding in one and epistaxis in another. All three cases received multiple transfusion support. The profile of the patients is depicted in the table below. Conclusion(s) : Complex bleeds in hypocoagulation are difficult to manage, which need both supportive care to maintain hemoglobin and hemodynamic stability and factor replacement, in parallel with finding the source and controlling it. Massive transfusion associated issues need to be keep in mind when managing such bleeds. Complex bleeds need multidisciplinary approach as presented above or else mortality in these patients is high. TABLE 1 Patients profile.

M. Sterankova 1 ; T. Simurda 2 ; J. Zolkova 3 ; M. Brunclikova 3 ; J. Stasko 3 ; I. Skornova 3 ; Z. Cibula 4 ; L. Nečas 5 1 Comenius University, The Jessenius Faculty of Medicine in Martin, Martin, Zilina, Slovakia; 2 Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, University Hospital Martin, Martin, Zilina, Slovakia; 3 National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, Slovakia, Martin, Zilina, Slovakia; 4 Jessenius Faculty of Medicine, University Hospital in Martin, Matin, Zilina, Slovakia; 5 Jessenius Faculty of Medicine, University Hospital in Martin, Martin, Zilina, Slovakia Background : Severe joint degeneration is a common complication in patients suffering from inherited bleeding disorders. Rotational thromboelastometry (ROTEM) allows to monitor hemostatic treatment with the possibility of specific treatment intervention. Aims : To highlight the importance of ROTEM. Methods : We are reporting the perioperative management in 21‐ and 22‐year old patients with von Willebrand disease type 3 (vWD) and severe hemophilia A (HemA) during ankle arthrodesis. Standard laboratory tests and ROTEM‐guided therapy were used. Results : To the patient with vWD there was preoperatively administered 30 IU/kg FVIII/vWF concentrate. The basal levels before substitution were: FVIII: 34%, vWF activity: 16%, vWF antigen: 30%, aPTT: 32.4 s and clotting time (CT) of INTEM: 178 s. After the surgery these levels were normalized: FVIII: 103.5%, vWF activity: 84%, VWF antigen: 138% and aPTT: 29.2 s. During the first 48 h after the surgery, the patient was administered 20 IU/kg FVIII/vWF every 8 h. The patient was discharged home after 96 h with aPTT 26.8 s and control CT of INTEM 148 s. To the patient with severe HemA there was preoperatively administered rFVIII 50 IU/kg. After the surgery, FVIII level was 78% and CT of INTEM was 255 s. During the first 24 h after the surgery, the patient was administered rFVIII 30 IU/kg every 8 h. The FVIII level was maintained 89 ± 1% and CT of INTEM 200 ± 5 s. On the 1st postoperative day, the rFVIII dose was changed to 35 IU/kg every 12 h. FVIII level achieved 76–66% and CT of INTEM 174–181 s. Based on the CT of INTEM and FVIII level, the rFVIII dose was reduced to 20 IU/kg every 12 h. On the 7th postoperative day, the patient was discharged home with a FVIII level 52% and CT of INTEM 82 s. Bleeding symptoms were not observed in both patients. Conclusion(s) : Combination of standard coagulation testing and ROTEM represents adequate method for designing perioperative management in patients with inherited bleeding disorders.

A. Amireche ; H. Brouk Faculty of Medicine, University of Badji Mokhtar of Annaba, Annaba, Annaba, Algeria Background : Congenital factor XIII deficiency is a rare hereditary bleeding disorder, due to reduced levels and activity of factor XIII (FXIII) and characterized by hemorrhagic diathesis ranging from life‐threatening bleeding to skin bleeding. It occurs at a frequency of approximately 1 in 1–5 millions. Over 200 cases of congenital factor XIII deficiency have been described in the literature over the previous four decades. Aims : To describe a rare case of hemorrhage due to factor XIII deficiency in an infant. Methods : We report the case of a 17‐month‐old boy admitted to pediatrics for a left buttock hematoma. His history of bleeding began in early childhood, when he bled profusely from the umbilical stump. Large superficial ecchymosis had previously appeared in various areas of the body at various times. He had no family history of a bleeding disorder. Results : Investigations revealed hemoglobin of 10.4 g/dl, total leukocyte count of 10.3 G/L and platelet count of 159 G/L. His coagulation profile revealed prothrombin time of 12 s (International Normalized Ratio, INR 1) and activated partial thromboplastin time of 28 s. A prior history of newborn umbilical hemorrhage (almost pathognomonic) and frequent ecchymosis with a normal coagulation profile are highly suspicious of factor XIII deficiency. We proceeded to test FXIII levels and found markedly reduced plasma FXIII activity levels (<0.10 IU/ml; normal reference range 0.73–1.60 IU/ml). As a result, the patient was diagnosed to have congenital factor XIII deficiency. Conclusion(s) : Factor XIII deficiency is a rare condition that can cause severe and sometimes fatal bleeding. In case of bleeding disorder with normal coagulation screening tests, this deficit should be explored. For the treatment of bleeding or during surgery, factor replacement, fresh frozen plasma or cryoprecipitate are used.

I. Berger Head of the Scientific Laboratory of Hemostasis Pathology, Tashkent, Toshkent, Uzbekistan Background : In a retrospective study of pre‐thrombotic conditions in hematological patients who are hospitalized at the Hematology Center (Uzbekistan) for 2018–2021, it turned out that they occur in such pathologies as: chronic myeloid leukemia (250 patients), polycythemia vera (68 patients), subleukemic myelosis (49 patients), myeloma (413 patients), Waldenström's disease (30 patients), chronic megakaryocytic leukemia (23 patients), as well as vasculitis (69 patients). In total, 902 patients with these pathologies were registered for 2021, which is significantly more than in 2020 (850) and 2019 (835 patients). Aims : The goal is to determine the readiness for thrombosis in patients undergoing polychemotherapy. Methods : Hematological analyzer HemaLite “Dixon” (Russia), Nephelometric optical coagulometer “CA‐660” “Sysmex” (Japan), Laser aggregometer “Chrono‐Log” (USA). Results : For the examined group 1 (with signs of thrombosis in anamnesis), shortening of the activated partially thromboplastin time is characteristic compared to the control −33.7 ± 2.5, ( p  < 0.05), and in group 2 with acute thrombosis (30 0.2 ± 1.9 s; P2 < K < 0.05 and P3 < 1–2 < 0.5). The indicators of the prothrombin index (PTI) were within the normal range ( p  ≥ 0.05), which made it possible to exclude a defect in phase II blood coagulation factors in all patients. As for fibrinogen, as a marker of any inflammatory reaction, a high level of fibrinogen was found in patients with acute thrombosis, relative to group 1 (P3 < 1–2 < 0.05). Conclusion(s) : The data obtained in the course of the study indicate that during chemotherapy, the activation of the blood coagulation system occurs, which can lead to acute recurrent rethrombosis, and therefore an early start of prophylaxis with anticoagulants is necessary. TABLE 1 Indicators of violations of coagulation and platelet hemostasis in patients with hemoblastoses.

J. Zhang Beijing Children's Hospital, BeiJing, Beijing, China (People's Republic) Background : Adapted Guideline for the Diagnosis and Treatment of Primary Immune Thrombocytopenia in Children in China (2021 Edition) is the first pediatric primary immune thrombocytopenia (ITP) guideline in the framework of GRADE in China. The guideline panels met two recommendation consensus, finalized 24 recommendations. Aims : The aim of the current study was to assess the property of recommendations and further revise them. Methods : We commissioned the external review of recommendations by questionnaire onilne. Physicians were investigated for appreciations, clarity and feasibility of 24 recommendations as well as other suggestions about the guideline. The guideline panels discussed the result of external review and revised recommendations based on it. Results : 57 physicians from 14 hospitals and 3 guardians of patients participated in the external review. The overall appreciation, clarity and feasibility degree of recommendations was 90.42%, 97.29% and 87.36%. Among them, appreciations, clarity and feasibility degree of all recommendations were over than 50%. 99 subjective suggestions were received. After review of the results, the guideline panels completed 25 recommendations and completed the full article. Conclusion(s) : The external review was participated by ITP‐related clinical staff and guardians of patients, which improved the clarity and feasibility of the recommendations and provided a reference for the formulation of follow‐up guidelines in China.

M. Atfy Zagazig University ‐Pediatrics Department‐Hematology/Onology Unit, Zagazig, Ash Sharqiyah, Egypt Background : Management of neonatal gangrene is usually conservative, Aims : To report controversy of the fate of neonatal gangrene &its management. In this paper, a newborn with reversible toes gangrene is reported without any triggering factor and cured before started with anticoagulants therapy. Methods : Full term male newborn was admitted to neonatal intensive care at birth, was noted to have bluish discoloration of left second toe. The distal pulsations were felt equally on both lower limbs. The general condition and vital signs of the baby within normal. No signs of sepsis, organomegaly, or a history of umbilical catheter. Purpuric eruption was found all over the body. We considered all the differential diagnosis in the investigations. Urgent Doppler ultra sound was done to save the baby toes. Laboratory investigations (CBC, sepsis workup, Coagulation profile, Ddimer, Protein S, proteinC). The mother was 28 years old neither diabetic or hypertensive. No history autoimmune diseases or blood or coagulopathy disorders, no history of previous abortion or still birth. Mother s CBC before delivery was completely normal. She suffered from postpartum hemorrhage that need frequent blood transfusion. Informed assent was obtained. Results :. Normal Duplex of both lower limb arterial &venous system no evidence of significant stenosis or occlusion Or DVT. Also free cranio ultrasonography CBC:revealed Anemia/Hb;11.6 g/dl, thrombocytopenia:20,000/μl Normal coagulation profile, D‐dimer 5.2 Ug/ml. The infant was transfused by platelets as life saving and gamma globulin 1 g/kg. The surprising response within two days by gradual fading of the gangrene and continuous rising of the platelets number. Thrombophilia gene screening revealed that the patient has heterozygous mutation of MTHFR C6771, A1298C.now the patient start prophylaxis anticoagulant therapy. Free protein S&C assay is 45% &21%. Conclusion(s) : Sometime decisions in critical situations are needed. Gangrene may be reversible in neonatal intensive care unit. FIGURE 1 Gangrene of left second toe. FIGURE 2 Toes are completely free within 48 h.

W. Ahn 1 ; S. Hahn 2 ; J. Han 3 ; C. Lyu 3 1 Yonsei Cancer Center, Seoul, Seoul‐t'ukpyolsi, Republic of Korea; 2 Department of Pediatrics, Yonsei University College of Medicine, Seoul, Seoul‐t'ukpyolsi, Republic of Korea; 3 Department of Pediatrics, Yonsei University College of Medicine, seoul, Seoul‐t'ukpyolsi, Republic of Korea Background : Thrombophilia is a group of diseases in which blood clots well, and may occur due to congenital or acquired conditions. Inherited thrombophilia should be suspected when thrombosis occurs repeatedly or in unusual places or situations, and it is necessary to differentiate it from the secondary causes. Recently differentiation is becoming possible through the next‐generation sequencing panel. Aims : The purpose of this study was to compare the thrombosis according to the characteristics and level of inherited thrombophilia patients. Methods : Inherited thrombophilia patients who were diagnosed or treated between the years 2005 and 2021 in Severance Hospital were enrolled in this study. They were classified according to diagnosis and first thrombosis event. In addition, among patients who had a recurrent pregnancy loss, cases with suspicion of inherited thrombophilia were analyzed. Results : 65 patients with inherited thrombophilia disorder were diagnosed or treated. 27.7% ( n  = 18) of them had protein‐C deficiency, 53.8% ( n  = 35) had protein‐S deficiency, 15.4% ( n  = 10) had an antithrombin‐III deficiency, followed by factor V Leiden and prothrombin mutation. The most common symptoms are pain or swelling of low extremity (27.8%) for protein‐C, and recurrent pregnancy loss (37.1%) for protein‐S deficiency. Genetic studies were performed on 49.2%, and genetic variation was confirmed in 78.1%. Median concentrations were 35%, 30%, and 45% in protein‐C deficiency, protein S deficiency, and antithrombin‐III deficiency, respectively. And there were 5 patients with severe protein‐C deficiency and 1 with antithrombin‐III deficiency, they had more hospitalized conditions. Inherited thrombophilia patients with recurrent pregnancy loss were almost protein s deficiency (92.8%) and the concentrations were 36% (28–40%), and they were treated with LMWH and aspirin during pregnancy. Conclusion(s) : Patients with low levels experience thrombosis at younger ages, require early intervention. But the others did not know until adults and developed deep vein thrombosis or recurrent pregnancy loss. And patients with family history and genetic confirmation alone often did not require treatment.

T. Kuhn 1 ; J. Pavlíček 2 1 University Hospital Ostrava, Czech Republic, Ostrava ‐ Poruba, Moravskoslezsky Kraj, Czech Republic; 2 University Hospital Ostrava, Ostrava ‐ Poruba, Guatemala, Czech Republic Background : Pregnancy and the puerperium are well‐established risk factors for venous thromboembolism (VTE), a disease that includes pulmonary embolism (PE) and deep venous thrombosis (DVT). Pregnant women are 4 to 5 times more likely to develop venous thromboembolism than women who are not. Approximately 30% of apparently isolated episodes of PE are associated with silent DVT and in patients presenting with symptoms of DVT, the incidence of silent PE ranges from 40–50%. Aims : PE is the leading cause of maternal death in the developed world. Besides death, venous thromboembolism can cause significant acute and chronic morbidity. Delayed diagnosis, delayed or inadequate treatment and inadequate thromboprophylaxis account for many of these deaths. This presentation aims to raise awareness of increased risk of VTE during the postpartum period even in adolescent women. Methods : Presentation of a case report of a 17 years old woman with a pulmonary embolism. Review of the literature with estimation of frequency of adolescent women with postpartum venous thrombotic event. Results : A 17‐year‐old young woman admitted 27 days after delivery of her first child for 10 days of progressive dyspnea, cough and hemoptysis. Laboratory testing proved high inflammatory values, anemia, thrombocytosis, antithrombin deficiency, increased levels of factor VIII and homocysteine. Angio CT confirmed bilateral embolization and dilatation of the right heart and bilateral pleural effusion. Cardiac examination proved with signs of mild pulmonary hypertension. Anticoagulant treatment of LMWH was introduced, which was later changed to dabigatran. Thrombolytic treatment was not indicated. Molecular genetic testing of antithrombin deficiency is underway. Conclusion(s) : Among pregnant women, the highest risk period for venous thromboembolism and pulmonary embolism in particular is during the postpartum period. Any prophylaxis against these events should be particularly targeted to postpartum women.

F. Alayoubi 1 ; G. Elgohary 2 1 KSUMC, Riyadh, Ar Riyad, Saudi Arabia; 2 King Saud Univesrty, ryidh, Ar Riyad, Saudi Arabia . Background : ATTR‐CM is a rare and progressive disease due to the buildup of amyloid fibrils in the heart, causing the heart muscle to become stiff, eventually resulting in heart failure. Aims : To proper diagnose from the two sub‐types of ATTR‐CM: hereditary, also known as variant, which is caused by a mutation in the transthyretin gene and can occur in people as early as their 50s and 60s or with no mutation and associated with aging. Often the disease is diagnosed only after symptoms have become severe. Methods : A density identified in the left atrium commonly leads to the presumptive diagnosis of an atrial myxoma. However, other pathologies, such as atrial thrombi, can mimic in clinical presentation and appearance to a myxoma. Clinically, these pathologies may lead to obstructive symptoms such as syncope, palpitations, or sudden cardiac death. At present, echocardiography, magnetic resonance imaging, or computed tomography can be used to identify such masses, but fall short of identifying the primary cause. Results : Currently, there are no definitive guidelines on the anticoagulation needed or the duration required for the resolution of cardiac thrombi secondary to amyloidosis. However, there have been several studies on treatment modalities. It is possible that early detection of amyloidosis, vigilant screening for intracardiac thrombosis with early anticoagulation might improve the prognosis. Effective anticoagulation might reduce thromboembolism, which is a significant contributor to mortality in cardiac amyloid patients. Conclusion(s) : This case explores the challenges in the diagnosis and management of intra‐atrial thrombi with cardiac amyloidosis, commonly seen in the elderly population. Densities found on echocardiograms may presumptively be diagnosed as myxomas; however, other pathologies may mimic their clinical presentations, such as atrial thrombi. In conclusion, in agreement with the previous case reports, our case confirms the need for prospective studies addressing the management of cardiac amyloidosis in patients with a thrombotic presentation.

F. Marhoume 1 ; Y. Naasse 1 ; B. Ma 2 ; E. Rajae 1 ; B. Anas 3 1 Center of Regenerative Medicine, Laboratory of Cellular Therapy, Mohammed VI University Hospital, Marrakesh, Morocco, Marrakech, Marrakech‐Tensift‐Al Haouz, Morocco; 2 Trauma and Orthopedics Department, Mohammed VI University Hospital, Marrakesh, Morocco, Marrakech, Marrakech‐Tensift‐Al Haouz, Morocco; 3 Center of Regenerative Medicine, Laboratory of Cellular Therapy, Mohammed VI University Hospital, Marrakesh, Morocco, Marrakech, Marrakech‐Tensift‐Al Haouz, Morocco Background : Several systemic disorders are related to calcaneal enthesophytes, including psoriatic arthritis, rheumatoid arthritis and diffuse idiopathic skeletal hyperostosis. However, enthesophytes may also develop in response to local mechanical stresses and could be associated with significant pain and disability. Aims : Currently, regenerative medicine encompasses a new area of medical science that involves the functional restoration of tissues or organs. Indeed, there are two competitive technologies that can repair and restore damaged tissue: platelet‐rich plasma (PRP) and mesenchymal stem cell (MSC) based therapies Currently, regenerative medicine encompasses a new area of medical science that involves the functional restoration of tissues or organs. Indeed, there are two competitive technologies that can repair and restore damaged tissue: platelet‐rich plasma (PRP) and mesenchymal stem cell (MSC) based therapies. The ability of MSCs to differentiate along a mesodermal cell line and secrete various regenerative and anti‐inflammatory bioactive molecules has led to their consideration as a future repair therapy. On the other hand, PRP is a blood component that contains higher than normal platelet concentrations and includes platelet‐related growth factors and plasma‐derived fibrinogen. Preclinical trials with MSCs and PRP have shown promising positive functional and structural results in various connective tissue disorders. Methods : A 37 years old patient, presents with a clinical history of calcaneal enthesophytes. Subsequent formal X‐rays showed evidence of mechanical irritation between the heel bone and the Achilles tendon. The patient underwent intracalcanous autologous platelets‐rich plasma in combination with adipose‐derived MSC therapy. Results : Following treatment, the patient reported a clear functional improvement with disappearance of pain. Repeat X‐ray showed successful regeneration of the heel bone‐like tissue. Conclusion(s) : Following treatment, the patient reported a clear functional improvement with disappearance of pain. Repeat X‐ray showed successful regeneration of the heel bone‐like tissue.

A. Calonge Arribas 1 ; A. Goyache Moreno 2 ; A. Castiella 2 1 Hospital Universitario de Navarra, Pamplona, Navarra, Spain; 2 University Hospital of Navarra, Pamplona, Navarra, Spain Background : Castatrophic Antiphospholipid Syndrome (CAPS) is a rare form of APS (less than 1% of all cases) with a high mortality, which was around 50% in early series but has been reduced to 20–25% in more recent series with the use of more intensive therapies. Aims : The aim of the study was to present an interesting case of CAPS. Methods : Descriptive study of a clinical case of CAPS in a young woman. Results : We present the case of a 32‐year‐old woman with a first episode of deep vein thrombosis in the right lower limb with correctable risk factors for thrombosis (smoking and contraceptive use) and a positive antiphospholipid antibody test (positive lupus anticoagulant, anti‐cardiolipin IgG 103 and anti‐β2 glycoprotein I IgG 36 U/ml). She was started on anticoagulation with enoxaparin 60 mg/12 h and was referred to our clinic for follow‐up and assessment of long‐term treatment. Anamnesis and physical examination revealed no signs or symptoms of systemic lupus erythematosus (SLE). Blood and urine tests were anodyne with normal complement and negative autoimmunity for SLE. Antiphospholipid antibodies were confirmed to be persistently positive. The diagnosis was primary APS with first venous thrombotic event in a patient with correctable risk factors for thrombosis. Oral anticoagulation with acenocoumarol was started and the patient stopped smoking and oral contraceptives. Months later, the patient was admitted to the Intensive Care Unit for pulmonary thromboembolism, jugular thrombosis and small vessel thrombosis of the fingers. She also presented proteinuria and active sediment, with complement consumption. CAPS was suspected. Combined treatment was started with anticoagulation with heparin, glucocorticoid pulses, plasmapheresis and sequenced immunoglobulins and cyclophosphamide as supportive treatment. The patient had a good clinical course and continued on acenocoumarol indefinitely. Conclusion(s) : Although CAPS has a low prevalence, it's important to be aware of it and to start combination therapy early to reduce mortality. FIGURE 1

L. Del Carpio‐Orantes 1 ; S. García‐Méndez 2 ; J. Sánchez‐Díaz 3 ; A. Rosas‐Lozano 3 1 Instituto Mexicano del Seguro Social, Veracruz, Veracruz‐Llave, Mexico; 2 Hospital Regional de Alta Especialidad de Oaxaca, Veracruz, Veracruz‐Llave, Mexico; 3 Instituto Mexicano del Seguro Social, Veracruz, Veracruz‐Llave, Mexico Background : The antiphospholipid syndrome is an autoimmune, prothrombotic and systemic disorder characterized by arterial and/or venous thrombosis, recurrent fetal loss and persistently elevated antiphospholipid antibody titers. Aims : To identify the various forms of manifestation of antiphospholipid syndrome. Methods : A retrospective, longitudinal and descriptive study in which the cases of arterial and venous thrombosis associated with thrombophilia type antiphospholipid syndrome presented during the period from 2016 to 2018 in a Hospital of Veracruz, Mexico were analyzed. Results : We found 7 patients with venous and arterial thrombotic symptoms that were studied antiphospholipid syndrome, the most affected gender was the female and the predominant age group was 21–30 years. The thrombotic event with the highest incidence was in the deep venous system of the pelvic extremities in 5 patients, in one case it was observed as a complication associated with pulmonary thromboembolism and in another case acute cerebral infarction. The antiphospholipid syndrome was primary in 6 cases and one associated with systemic lupus erythematosus. Conclusion(s) : The clinical spectrum of antiphospholipid syndrome is diverse and must be taken into account in order to establish an effective diagnosis and treatment. TABLE 1 Diverse cases of SAF.

E. Sundarita 1 ; M. Syahrir 2 ; Y. Andayani 2 ; L. Legiran 2 ; N. Djamaludin 2 1 Internal Medicine Department, Mohammad Hoesin General Hospital, Palembang, Sumatera Selatan, Indonesia; 2 Universitas Sriwijaya, Palembang, Sumatera Selatan, Indonesia Background : Colorectal cancer is the third most common type of cancer with the fourth‐highest mortality rate in Indonesia. Early diagnosis and prompt treatment are the keys to effective management. Colorectal cancer also causes an increased risk of hypercoagulation, one of which can be evaluated through the D‐Dimer value. Treatment with systemic chemotherapy that targets angiogenesis via the VEGF pathway is often unsuccessful, despite the low evaluation of tumor biomarkers (CEA) at the end of therapy. Given the possibility of a colorectal cancer population with negative CEA, other tumor markers are needed that can predict the clinical outcome of colorectal cancer patients that are independent of the effect of VEGF. The prognostic marker that is believed to have this ability is D‐dimer which can be detected in the serum of colorectal cancer patients. Aims : To evaluate prognostic value of D‐dimer in colorectal cancer. Methods : This study was conducted at the Medical Oncology Hematology Polyclinic and the inpatient ward of the Internal Medicine Division of RSMH Palembang from November 2020 to March 2021. Data processing and analysis using SPSS version 26.0 for Windows. Results : From 70 subjects were followed during the study period and had received six times complete and timely systemic chemotherapy. After assessing the clinical outcome in the form of response to chemotherapy treatment, the subjects were divided into a non‐responder group of 52 people (74.3%) and a group of 18 respondents (25.7%). By using the Chi‐Square test, the p ‐value = 0.017 (multivariate analysis), OR 0.017 (95% CI 0.02–0.67). Conclusion(s) : D‐dimer has good prognostic value in predicting colorectal cancer treatment response.

A. Fioretti 1 ; T. Leopizzi 2 ; M. Porcelli 3 ; V. Fazio 4 ; G. Ranieri 4 ; G. Luzzi 5 ; C. Gadaleta 3 ; S. Oliva 6 1 Cardio‐Oncology Unit, IRCCS Istituto Tumori “Giovanni Paolo II”, Bari, Italy, Bari, Puglia, Italy; 2 Cardiology and Intensive Care Unit, Ospedale SS. Annunziata Taranto, Italy, Taranto, Puglia, Italy; 3 Interventional and Medical Oncology Unit, IRCCS Istituto Tumori Giovanni Paolo II, Bari, Italy, Bari, Puglia, Italy; 4 Interventional and Medical Oncology Unit, IRCCS Istituto Tumori Giovanni Paolo II, Bari, taly, Bari, Puglia, Italy; 5 Cardiology and Intensive Care Unit, Ospedale SS. Annunziata, Taranto, Italy, Bari, Puglia, Italy; 6 Cardio‐Oncology Unit, IRCCS Istituto Tumori Giovanni Paolo II, Bari, Italy, Bari, Puglia, Italy Background : Venous thromboembolism is the second leading cause of death in cancer patients. Anticoagulant management is challenging for intervening comorbidities and ipercoagulable burden. Aims : We underscore the ease of use, efficacy and safety of direct oral anticoagulants (DOACs) compared to low‐molecular‐weight heparins (LMWH). Methods : 41 y‐o woman with breast cancer (pT2N1aMx, G3, ER:70%, PgR:30%, HER‐2/NEU:2+, Ki67:60%) was treated (2010) with adjuvant antracyclines, taxanes and hormonal therapy. Developed (2012) bone lesions treated with radiotherapy and hepatic metastases (2016) treated with iv bevacizumab and taxanes. Started (2017) chemoembolization (CE), due to further liver severe progression configuring a main hepatic disease. Started LIVER ARTERIAL INFUSION CHEMOTHERAPY (LAIC) with 5Fluorouracil and iv chemotherapy (CT) with taxanes and bevacizumab. Developed (2020) arterial catheter‐related thrombosis (ACRT) (Figure 1) recurrent after urokinase, clopidogrel and enoxaparin, in spite of aspirin/clopidogrel prohylaxis. LAIC was discontinued and CT with iv taxanes and trastuzumab was continued. Jugular deep vein thrombosis (DVT) (Figure 2) occurred (2021), treated for 8 months with LMWH: firstly enoxaparin 100 IU/kg twice/die and secondly, because of lack of efficacy and patient's request for a more manageable therapy, parnaparin 6400 IU/die. After 8 months she refused injectable drugs, asking for oral ones. LMWH were replaced by DOAC, edoxaban 30 mg/die (weight: 43 kg). Results : After 3 months of edoxaban, duplex ultrasound: DVT regression; neither bleedings nor drug–drug interactions with the ongoing CT were detected. Instead, the 3 months follow‐up CT‐scan: ACRT persistence, despite of edoxaban. Conclusion(s) : Hypercoagulable burden is common to both venous and arterial thrombosis and sometimes they occur simultaneously. In this case, a young woman with advanced breast cancer treated with CE and LAIC developed both DVT and ACRT. According to inefficacy and patient's preference, we replaced LMWH with edoxaban. DVT was solved, but ACRT was still persistent. Therefore, DOACs is a valuable anticoagulant choice in cancer‐associated thrombosis, but sometimes prothrombotic melieu prevails. FIGURE 1 Liver arterial catheter related thrombosis. FIGURE 2 Jugular vein thrombosis CUS (compression ultrasound maneuver).

V. Musteata 1 ; S. Pinzari 2 ; M. Popescu 3 ; L. Musteata 3 ; V. Tomacinschii 3 ; O. Privalova 2 1 State University of Medicine and Pharmacy “N. Testemitanu”, Institute of Oncology, Chisinau, Chisinau, Moldova; 2 Institute of Oncology, Chisinau, Chisinau, Moldova; 3 State University of Medicine and Pharmacy “N. Testemitanu”, Chisinau, Chisinau, Moldova Background : The thrombotic and thromboembolic events may complicate the evolution of oncological diseases, increase the rates of morbidity and mortality, being considered as an actual issues of oncology and public health. Aims : The aim of the study was to evaluate the evolution patterns and the results of treatment of thrombotic and thromboembolic complications in patients with non‐Hodgkin lymphomas (NHL) and breast cancer (BC). Methods : We performed an analytical and prospective study of 2 patients with NHL and 1 patient with BC, who were treated at the Institute of Oncology from Moldova between 2019–2021. All patients were females of 38, 45 and 46 years old, with comorbidities: Obesity. Hyperglycemia. Internal hemorrhoids. The diagnosis was proved by the standard histopathological, immunohistochemical examinations and staging procedures, including computed tomography. Results : The patient with stage T2N1M0 BC and ECOG‐WHO performance status (PS) 3 was treated with corticosteroids for immune thrombocytopenia and developed left‐sided pulmonary thromboembolism (Figures 1 and 2). She failed to respond to the antiplatelet and anticoagulant therapy. The patient with the relapse of stage IVB marginal zone B‐cell NHL in the ilioinguinal lymph nodes, shin soft tissues and ECOG‐WHO PS 3 received CHOP regimen and obtained the unstable partial response. She developed the thrombophlebitis of the left shin and was managed with antiplatelet and anticoagulant therapy. The patient with stage IIA diffuse large B‐cell NHL and ECOG‐WHO PS 2 was treated with 3 cycles of R‐CHOP chemotherapy, followed by the radiotherapy (RT) on the residual ilioinguinal lymphadenopathy, with complete response. The RT was temporarily stopped due to the acute femoral bilateral grade II phlebothrombosis, which regressed under the antiplatelet and anticoagulant therapy. Conclusion(s) : The progression of NHL and BC may be associated with thrombotic complications, especially if associated with metabolic and vessels disorders. The monitored prophylactic oral antiplatelet and anticoagulant therapy should be administered during the remission induction. FIGURE 1 Onset of the left‐sided pulmonary thromboembolism. FIGURE 2 Left‐sided pulmonary thromboembolism.

R. Messaoudi 1 ; M. Amine 2 1 University Hospital Center of Oran, Oran, Oran, Algeria, 2 University Hospital Oran, Oran, Oran, Algeria Background : the deficiency in coagulation inhibitors (protein C, S, Z, and anti‐thrombin III) predispose to thrombosis, multiple and serious locations in young patients, its prevalence is 1/500,000 inhabitants. Aims : clinical presentation of congenital thrombophilias in the university hospital center of Oran in Algeria. Methods : We identified all patients with congenital thrombophilia followed at the Hematology department of the University Hospital of Oran. We studied the history, hematematric parameters, as well as the balance sheet of thrombophilia with deficiencies in coagulation inhibitor (protein C, S and Anti‐thrombin III). Results : among the 12 patients; 09 female and 03 male, sex ratio 0.33, the average age is 32 years with extremes between 6 and 57 years. Half of the patients have an asymptomatic deficit discovered during family screening, 02 patients have a portal thrombosis, 02 have a pulmonary embolism, 1 patient has a thrombosis of the popliteal vein and another presenting a cerebrovascular accident, we did not note any abortion. Average hemoglobin is 12.5 g/dl (11–13), platelet count 230,000/mm 3 (47000–404,000), white blood cell count 5500/mm 3 (1500–145,000). The thrombophilia assessment found a protein S deficiency in 08 patients, the protein S level between 24 and 46% and 04 patients with a protein C deficiency (27–37%). Conclusion(s) : Female predominance of congenital thrombophilias, although some forms are asymptomatic. There are serious forms of these coagulation inhibitor deficiencies, such as pulmonary embolisms. The degree of the deficit is not predictive of thrombotic risk, but the existence of a chronic inflammatory state increases the incidence of thrombosis.

S. Schulman ; G. Eagle McMaster University, Hamilton, Ontario, Canada Background : The natural course of elevated factor VIII (FVIII) in patients with venous thromboembolism (VTE) and with or without inflammatory bowel disease (IBD) is not well described. Furthermore, the data on effectiveness and safety of extended anticoagulation in these patients are limited. Aims : We aimed in this study to compare outcomes in patients with VTE and elevated FVIII with or without IBD in regards to trajectories of FVIII, recurrence of thromboembolic events and effectiveness of anticoagulant treatment. Methods : We performed a retrospective chart review of all patients with VTE, who had an elevated FVIII level (>1.5 IU/ml) during a period of 16 years. FVIII levels, duration of anticoagulation, recurrent thromboembolic events and bleeding requiring hospitalization were captured. Results : Fourteen patients with IBD and 66 without IBD were followed for 8.0 years (standard deviation [SD] ±3.5) and 5.6 years (SD ±5.1), respectively. Among the 41 patients with repeat levels, FVIII remained elevated in most patients. None of the IBD patients had thromboembolic events or major bleeding during a mean of 5.6 years (SD ±5.1) of anticoagulation. Three of 5 IBD patients that stopped anticoagulation had thromboembolic events at a median of 9 months after stopping – observed event rate 12 per 100 patient‐years. For the 66 non‐IBD patients the event rates of thromboembolism on and off anticoagulation were 1.6 and 7.2 per 100 patient‐years, respectively, and of major bleeding on anticoagulation 0.8 per 100 patient‐years. Conclusion(s) : Elevated FVIII in patients with VTE is often a persistent risk factor. The cohort with VTE and elevated FVIII that we analyzed appeared to have a favorable benefit/risk ratio of extended anticoagulation. TABLE 1 Follow‐up of patients with high F VIII.

D. Stambolieva 1 ; V. Gjorgjevska 2 ; S. Ortakovska 3 1 Institute of Transfusion Medicine Skopje, Department Strumica, Strumica, Strumica, Macedonia; 2 Institute of Transfusion Medicine Skopje, Department Strumica, Delcevo, Delcevo, Macedonia; 3 Institute of Transfusion Medicine Skopje, Department Strumica, Gevgelija, Gevgelija, Macedonia Background : Any immobilization, in any way and in any place, especially Gypsum immobilization, in particular, significantly increases the risk of thromboembolic complications. Aims : A case of a 47‐year‐old patient with Dg.Typical loco radii fracture, and gypsum immobilization of the forearm, which she wore for a month and as thromboprophylaxis she was given acetylsalicylic acid in a dose of 100 mg once a day In our clinic, he came with a referral from a specialist orthopedist, who did an extirpation of the Gypsum after a month and according to the patient ‐ he did NOT like the appearance of the forearm. From the anamnesis, we received information that this is a patient who has not had a menstrual cycle for 3 years, does not drink, does not smoke, does not take any medications, EXCEPT ANALGETICS FOR HAND PAIN. Methods : On clinical examination, we have a swollen forearm, especially the wrist and fingers that cannot bend at all due to swelling, red, hot and swollen forearm and wrist, sore spontaneously, to the touch even more In our laboratory, dimmers were made and they were 1200 mg / ml, after which a venous ultrasound was made immediately and a thrombus in the right radial vein was visualized. Results : The patient was placed on oral anticoagulant therapy for 3 months, on the control Doppler, the affected vein was completely recanalized, without traces of thrombotic masses in it. After that, the patient was referred to physical therapy. Conclusion(s) : The question remains whether such immobilizations require thromboprophylaxis or not, in what dose, for how long ‐ how in our clinics we would not face the side effects of its non‐use and how the physical rehabilitation of patients would not be delayed for so long.

C. Poserio ; J. Calibuso; H. Warren Notre Dame De Chartres Hospital, Baguio, Benguet, Philippines Background : Catastrophic antiphospholipid antibody syndrome (APS) is an autoimmune disorder and an important cause of acquired thrombophilia. APS causes an increased risk for vascular thrombosis. It is common in the fourth decade of life and in females. Its most severe form is Catastrophic Antiphospholipid syndrome. The case highlights a rare presentation of multiple thrombosis at three different sites in a 28‐year‐old male diagnosed with catastrophic antiphospholipid syndrome, and underwent lifesaving surgery with pulmonary thromboendarterectomy. The case also stresses the importance of recognizing a hypercoagulable state as the cause of thrombosis and the important implication on the therapeutic management. Aims : This report highlights the importance of prompt recognition and diagnosis, and therapeutic implications to prevent irreversible complications related to its devastating prognosis. Methods : Results : Conclusion(s) : The case highlights the importance of recognizing CAPS in a young male presenting with VTE ‐ emphasizing auto‐immune disease as a cause of hypercoagulable state in pulmonary embolism because of its high mortality rate and its implication on therapeutic management. FIGURE 1 Catastrophic Antiphospholipid syndrome in a 28 year old male presenting with multiple thrombi at three different sites. TABLE 1 Catastrophic Antiphospholipid syndrome in a 28 year old male presenting with multiple thrombi at three different sites with persistently elevated antiphospholipid antibodies.

R. Ben Salah 1 ; A. Ben Mefteh 2 ; C. Dammak 3 ; F. Frikha 4 ; Z. Bahloul 5 1 Hedi Chaker Hospital, Sfax, Sfax, Tunisia; 2 Sfax University Tunisia, sfax, Sfax, Tunisia; 3 Departement of Internal Medicine, Hédi Chaker Hospital, SFAX, Sfax, Tunisia; 4 Departement of Internal Medicine, Hédi Chaker Hospital, Sfax, Sfax, Tunisia; 5 University of Sfax, SFAX, Sfax, Tunisia Background : Rendu‐Osler‐Weber syndrome is a rare systemic fibrovascular dysplasia, recognized by mucocutaneous telangiectasias, arteriovenous malformations, epistaxis and family history. Aims : Venous thromboembolic disease is a poor prognostic factor in this disease given the risk of increased bleeding caused by anticoagulant therapy. Methods : We report a new case of a 56‐year‐old patient with Osler disease who developed recurrent thromboembolic venous disease. Results : A 56‐year‐old patient was hospitalized in June 2016 for treatment of deep vein thrombosis of the lower limb complicated by bilateral proximal pulmonary embolism. There was no notion of sedentarity or trauma. The patient reported the notion of recurrent epistaxis from a young age. He did not report any notion of hemoptysis or digestive bleeding. On clinical examination, telangiectasias were observed on the face, the inner sides of the cheeks and on the hands. These lesions bled at the slightest touch. On biology, the blood count, hemostasis, renal, hepatic assessments were without notable abnormality. The dosage of coagulation proteins and Circulating anticoagulants and anticardiolipin antibodies without abnormalities. The diagnosis of Rendu Osler disease was made by the association of recurrent epistaxis and multiple telangiectasias. There was no similar case in the family. There were no other associated visceral lesions. The thoraco‐abdominal CT angiography as well as the echocardiography were without abnormalities. The genetic study was not practiced given the unavailability in our hospital. Under anticoagulant treatment “acenocoumarol”, the patient reported a worsening of epistaxis. This anticoagulant treatment was then stopped after 6 months. Two months later, the patient presented with a recurrence of DVT complicated by pulmonary embolism which required a resumption of anticoagulant treatment for a prolonged period given the recurrent nature of the venous thromboembolic disease. Conclusion(s) : According to a review of the literature, this association does not appear to be fortuitous and is a factor of disease severity.

F. Alayoubi 1 ; G. Elgohary 2 ; S. Dasuqi 3 ; A. Hayajneh 1 ; S. Alayoubi 1 1 KSUMC, Riyadh, Ar Riyad, Saudi Arabia; 2 King Saud Univesrty, Ryidh, Ar Riyad, Saudi Arabia; 3 KSUMC, Liverpool, England, United Kingdom Background : Direct Oral anticoagulants (DOACs) have been approved for stroke prevention in non‐valvular atrial fibrillation (AF). The outcomes achieved by clinical trials depend on pharmacokinetics and pharmacodynamics of these drugs which are used orally in regular doses once or twice. During our practice we need to evaluate the safety profile as well as the efficacy of Rivaroxaban in our cardiac center. Real world data is required in different part in the world, No enough information are available in matter of patient on Rivaroxaban a direct factor Xa inhibitor specially in Saudi population. Aims : This study will be the first in Saudi Arabia to give an idea about current practice being used at anticoagulant clinic and criteria used to choose patients were switched to Rivaroxaban, to evaluate the safety & efficacy also. Evaluate the effectiveness and safety of DOACs which is Rivaroxaban for stroke prevention in Non‐Valvular atrial fibrillation. Methods : An observational retrospective study in university tertiary hospital in Saudi Arabia, 326 patient's non‐valvular atrial fibrillation on DOACs Rivaroxaban (2015–2021) Laboratory 1 year follow ups for each patient who was on Rivaroxaban Follow up any thrombotic or bleeding events during their treatment plans. CRF form has been validated by the Team. Results : No significant deferent in the stroke and bleeding events between our data and the global data. as the pharmacokinetics and pharmacodynamic of Rivaroxaban in Saudi patients almost similar to the global ones and so the real world data show's similarity in this part. Conclusion(s) : The data shows that the DOAC Rivaroxaban are effective and safe to be used for Non‐Valvular atrial fibrillation regardless the dose of anticoagulant, Further studies are needed to support these findings in other cardiac centers.

J. Sokol 1 ; F. Nehaj 1 ; M. Mokan 1 ; J. Zolkova 2 ; L. Linekova 1 ; A. Antosikova 1 ; J. Stasko 2 1 Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Martin, Zilina, Slovakia; 2 National Centre of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, Slovakia, Martin, Zilina, Slovakia Background : Dabigatran is a direct thrombin inhibitor belonging to direct oral anticoagulants (DOACs), which are rapidly replacing warfarin as oral anticoagulants in nonvalvular atrial fibrillation (NVAF) or venous thromboembolism. One major advantage with dabigatran compared to warfarin is that no routine testing is required. Nevertheless, the degree of anticoagulation should be determined in cases of severe bleeding or urgent surgery. Routine coagulation tests have proven to be inadequate for sensitive determination of the anticoagulant effect of dabigatran. Rotation thromboelastometry (ROTEM) is a new viscoelastometric point‐of‐care‐test for the complex evaluation of changes in hemostasis introduced to clinical practice. This assay allows quick complex testing of hemostasis in one blood sample. Aims : The aim of this study was to study the anticoagulant effects of dabigatran in patients with atrial fibrillation (AF) as assessed by the whole blood assays ROTEM, and how data from these methods correlate to plasma dabigatran concentrations measured by Hemoclot. Methods : ROTEM was performed with ROTEM Gamma (Pentapharm GmbH, Munich, Germany). Plasma dabigatran concentrations were determined by hemoclot thrombin inhibitor assay (Hyphen BioMed, France) at trough and post‐dose in patients on dabigatran 150 mg BID. Results : Median plasma dabigatran concentrations at trough were 74 ng/ml (11.2–250) and post‐dose (2 h after ingestion) 120 ng/ml (31–282). The ROTEM clotting time (CT) and maximum clot firmnes (MCF) correlated strongly with dabigatran concentrations when activated with the reagents Ex‐tem ( p  < 0.0001) and In‐tem ( p  < 0.0001). Conclusion(s) : In summary, in our study, we have found that the ROTEM variable CT and MCF, when activated with triggers Ex‐tem and In‐tem, has a strong and highly significant correlation with the plasma dabigatran concentration in a real‐life population of AF‐patients and could thereby be an alternative to estimate dabigatran concentration in emergency situations. However, additional studies are needed to further validate these findings. The study was supported by grants VEGA 1/0250/22.

T. Bucci 1 ; D. Pastori 2 ; D. Menichelli 2 ; F. Violi 3 ; J. Harenberg 4 ; P. Pignatelli 5 1 Sapienza Universy, Rome, Lazio, Italy; 2 Sapienza University, Rome, Lazio, Italy; 3 Thrombosis and Hemostasis journal, Berlin, Berlin, Germany; 4 Faculty of Medicine Mannheim and Clinic Mannheim, Heidelberg, Baden‐Wurttemberg, Germany; 5 Sapienza University, Rome, Lazio, Italy Background : In obese patients the drug distribution and plasma concentrations of direct anticoagulants (DOAC) may be unpaired, potentially exposing the patients to a greater risk of both thrombotic and hemorrhagic events. DOAC Dipstick in urine samples of anticoagulated normal weight patients showed a high accuracy at plasma threshold concentrations of 30 ng/ml, suggesting a possible future role in DOAC clinical management. However, no study has been performed to investigate the validity of this rapid test in anticoagulated obese patients. Aims : The primary end point of this study is to evaluate the accuracy of DOAC Dipstick in detecting therapeutical plasma concentration of DOACs in obese anticoagulated patients. A further sub‐analysis will be performed to evaluate the accuracy of DOAC Dipstick in patients with mild, moderate, and severe obesity. Methods : This is the protocol description for a cross sectional single center study in obese patients treated with DOACs. Results : According to the WHO classification, obesity is defined as: mild if body mass index (BMI) is comprised between 30 and 35, moderate if BMI is between 35 and 40, severe if BMI is higher than 40. The DOAC Dipstick contains two separate specific pads for testing DXI and DTI. DOAC Dipstick results will be compared visually with the reference scale. Plasma DOAC concentration will be assessed by Liquid Chromatography‐Mass Spectrometry. Dipstick test results for DXI or DTI will be compared with plasma concentration at a threshold of 30 ng/ml to analyze the true positive and true negative rate. Conclusion(s) : This is the protocol for the first study aimed to investigate the role of DOAC Dipstick in detecting therapeutic DOAC concentration in obese patients. The demonstration of a good accuracy of DOAC Dipstick in obese populations could ameliorate body weight adjusted DOAC management in clinical routine to accelerate medical decision making and for assure adherence to therapy.

A. Markovsky Chita State Medical Academy, Russia, Chita, Zabaykalsky, Russia Background : Currently, most scientific studies argue that a hereditary predisposition to thrombus formation has long been possible to distinguish as an independent group of etiological factors among the causes of miscarriage and other diseases in obstetric and gynecological practice. The most important genetic markers of thrombophilia are allelic variants of the hemostasis and folate metabolism genes. Aims : The purpose of this study is to analyze the frequency of occurrence of gene polymorphisms of the hemostasis system and folate metabolism based on the results of patients in Transbaikalia. Methods : PCR analysis of polymorphism of 12 genes associated with thrombophilia in 1800 women aged 20 to 60 years with complications of reproductive health was carried out. Results : The most frequent genes in the study group were polymorphic variants of the genes PAI‐1*5G/675/4G (5G/4G‐49.6% and 4G/4G‐32.4%) and ITGA2*C807T (C/T‐48.2% and T/T‐13.2%), as well as MTRR*A66G (A/G‐54.3% and G/G‐22.6%) and MTHFR*A1298C (A/C‐43.4% and C/C‐9.7%). It is also important to note the prevalence of combined defects as compared to single ones among all detected cases of mutation carriage, both in the hemostasis system and in folate metabolism ‐ which amounted to 88% and 81.4%, respectively, namely, double and triple combinations of polymorphic variants. This significantly increases the risk of developing thrombosis. The Leiden mutation FV*G1691A (4.0%) and prothrombin FII*G20210A (2.4%) were much less common. Conclusion(s) : When studying the frequencies of genetic polymorphism of the hemostasis system and the main proteins of the folate cycle in Transbaikalia in women with complications of reproductive health and/or a burdened family thrombotic history, a rather high prevalence of mutant genotypes of polymorphism of genes of the hemostasis and folate system was revealed associated with the risk of thrombophilia, including the highest risk FII and FV.