Thromboembolism and pulmonary hypertension after splenectomy in thalassemia: a case report

Thromboembolism and pulmonary hypertension after splenectomy in thalassemia: a case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Thromboembolism and pulmonary hypertension after splenectomy in thalassemia: a case report Qun Hu, Kaige Wang, Gang Wang, Bojiang Chen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8315474/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 18 You are reading this latest preprint version Abstract Background: Pulmonary embolism (PE) and pulmonary hypertension (PH) are common respiratory diseases that require a thorough etiological workup. However, the pathophysiology of PE and PH in thalassemia patient post-splenectomy can be easily overlooked by both hematologists and pulmonologists. Case presentation: A 38-year-old man, who had diagnosed with α-thalassemia at 7 months of age, and subsequently underwent splenectomy nine years ago due to severe anemia, developed chest tightness and shortness of breath, and progressed to dyspnea at rest accompanied by dizziness and abdominal pain. Chest and abdomen enhanced CT scan revealed extensive venous thrombosis including pulmonary artery, portal vein, mesenteric vein, hepatic vein and possibly cerebral thrombosis. Cardiac echocardiography demonstrated severe PH (tricuspid-valve regurgitant jet velocity was 4.2 m/s). Further accessory examination containing tumor markers, immunological indicators, thrombophilia screen and genetic testing could not elucidate potential provoking factors and pathogeny. Management consisted of curative anticoagulation, antibiotherapy, diuretics and hyperosmotic dehydration, leading to clinical improvement and subsequent stability on follow-up. Conclusion: The understanding of PE and PH following splenectomy in patients with thalassemia are often suboptimal, let alone the early management and treatment. It necessitates an integrated, multidisciplinary strategy involving hematology and pulmonology specialists. Pulmonary embolism Pulmonary hypertension Splenectomy Thalassemia Case report Figures Figure 1 Figure 2 Figure 3 Background Venous thromboembolism (VTE) includes deep vein thrombosis (DVT) and pulmonary embolism (PE). DVT most often occurs in the leg vein but can also develop in the abdominal, cerebral, and arm veins. Afflicting worldwide nearly 10 million people per year, VTE is a significant contributor to the global burden of disease. 1 Once VTE diagnosed, especially PE, contributing triggers are commonly needed to be underlined. Frequent clinical provoking risk factors for VTE include prolonged immobility, recent major surgery, active cancer, chronic inflammatory disorders, and antiphospholipid syndrom. 2 However, splenectomy for thalassemia as a possible trigger is rare and not widely recognized in clinical respiratory practice. Pulmonary hypertension (PH) is life-threatening condition characterized by a mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg at rest. Clinical classification of PH with multiple pathophysiological mechanisms can be divided into five subgroups. Suspected PH is initially evaluated by echocardiography and ultimately diagnosed through right heart catheterisation (RHC). Early diagnosis and specialized management for PH is highly required. 3 PE and PH are common conditions in clinical pulmonology that often necessitate further investigation to elucidate their etiology. Herein, we present a representative case to advance the pathophysiological understanding of PE and PH in splenectomized thalassemia patients, highlighting the need for collaborative attention from hematologists and pulmonologists. Case presentation This patient was a 38-year-old man who was admitted to the emergency department (ED) due to chest tightness and shortness of breath on exertion for two weeks, which progressed to dyspnea at rest accompanied by dizziness and abdominal pain over the past 10 days. He who had been maintained on deferasirox, was diagnosed with α-thalassemia at 7 months of age, and subsequently underwent splenectomy nine years ago due to severe anemia. His social/family history is unremarkable. He was unmarried and had no children. Diagnostic workup in the ED revealed systemic multiple thromboses, including PE. Following management with anticoagulation and diuresis, the patient was admitted to the department of respiratory medicine. Vital signs were normal and he exhibited an anemic complexion. Chest and abdomen enhanced CT revealed the following main findings: 1) Lungs: bilateral patchy opacities, consistent with pneumonia. 2) Pulmonary arteries: dilation of the main and bilateral main pulmonary arteries (Fig. 1 A). Multiple filling defects are present in the bilateral lower lobe arteries (Fig. 1 B, C). 3) Heart and pericardium: significant cardiomegaly with a small pericardial effusion (Fig. 1 B). 4) Abdominal vasculature: filling defects are noted in the superior mesenteric vein, the main portal vein (including left and right branches), and the right hepatic vein, highly suggestive of thrombosis (Fig. 1 D, E). 5) Liver and Spleen: marked hepatomegaly with imaging features of cirrhosis and portal hypertension. The spleen is not visualized (Fig. 1 F). Arterial and venous color doppler ultrasound of the extremities revealed no evidence of thrombosis. Cardiac echocardiography demonstrated right heart enlargement, right ventricular hypertrophy, severe pulmonary hypertension (tricuspid-valve regurgitant jet velocity was 4.2 m/s, and the peak gradient (PG) was 73 mmHg, yielding an estimated pulmonary artery systolic pressure (PASP) of 76 mmHg). The laboratory findings were as follows: hemoglobin 85 g/L (normal range: 130–175 g/L), platelet count 381 × 10⁹/L (normal range: 100–300 × 10⁹/L), white blood cell count (WBC) 9.94 × 10⁹/L (normal range: 3.5–9.5 × 10⁹/L), neutrophils (segmented) 48.0% (normal range: 40–75%). Biochemical tests: total bilirubin (TB) 55.0 µmol/L (normal range: 3.2–20.5 µmol/L), direct bilirubin (DB) 35.0 µmol/L (normal < 6.8 µmol/L), alanine aminotransferase (ALT) 168 U/L (normal range: 9–50 U/L), aspartate aminotransferase (AST) 127 U/L (normal range: 15–40 U/L). Coagulation profile: fibrin/fibrinogen degradation products (FDP) 31.1 mg/L (normal < 5 mg/L), d-dimer 12.16 mg/L FEU (normal < 0.55 mg/l FEU). Cardiac Markers: N-terminal pro-B-type natriuretic peptide (NT-proBNP) 5313 ng/L (normal < 91 ng/L), high-sensitivity troponin T (hs-TnT) was measured at 35.2 ng/L (normal < 14 ng/L). To investigate the underlying etiology of the patient's pulmonary embolism, a series of diagnostic tests including tumor marker assays, a comprehensive immunological panel, and a thrombophilia screen were conducted. Test of serum tumor markers showed carbohydrate antigen (CA) 125 261.00 U/mL (normal < 24.00 U/mL). Other tumor markers including carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin 19 fragment (CYFRA21–1), CA 15 − 3 and CA 19 − 9 were negative. The immunological panel including anti-nuclear antibody (ANA), extractable nuclear antigen antibody profile (ENA), anti-dsDNA, antineutrophil cytoplasmic antibodies (ANCA) was negative. Testing for anticardiolipin antibodies, lupus anticoagulant, protein C and protein S was in the normal range. In addition, externally tested genetic panels for thrombophilia detected no pathogenic variants. The etiology of the patient's systemic multiple thromboses remained elusive. Thus, the whole-body fluorodeoxyglucose positron emission tomography / computed tomography (PET/CT) imaging was obtained to rule out large vessel vasculitis. The PET/CT revealed decreased bone density throughout the skeletal system, with mildly increased glucose metabolism in the axial skeleton and bilateral femurs (Fig. 2). The nature of these PET/CT findings is indeterminate, with reactive changes or hematologic malignancies considered as potential etiologies. Based on the diagnostic challenges, we consulted related references and found the correlation between the patient's extensive venous thrombosis and his history of thalassemia with splenectomy. Thalassemia itself predisposes individuals to a hypercoagulable state and heightened hemostatic activation, effects that are potentiated by splenectomy. Furthermore, the intermittent visual disturbances were likely related to transient cerebral microthromboembolism, and thus the transient ischemic attack, which would explain the absence of abnormalities on cerebral contrast-enhanced sequences and MRV. Upon clinical stabilization, the patient was discharged on oral rivaroxaban for continued anticoagulation. Relevant examinations would be re-evaluated after three months. At the one-month follow-up, the patient remained clinically stable, and rivaroxaban was sustained. Discussion This case typically illustrates the development of thrombosis and severe PH in association with a history of splenectomy for thalassemia. However, we did not perform RHC on this patient and instead initiated anticoagulation therapy due to the coexistence of these two complications. Thalassemia is a heterogeneous inherited hemoglobinopathy characterized by an imbalance in the ratio of α- and β-globin chains. 4 The estimated global prevalence for α-thalassemia and β-thalassemia is 5–20% and approximately 1.5%, respectively. 5 A series of conditions, including ineffective erythropoiesis, chronic anemia, extramedullary hematopoiesis, and iron overload are developed in these patients, regardless of the type of thalassemia. Ineffective erythropoiesis results as chronic anemia, without an adequate mature red blood cells in the peripheral blood. Compensatory hematopoietic proliferation affect both within and outside the bone marrow, associated with medullary expansion and hepatosplenomegaly. 4 , 5 Iron overload arises from transfusions and increased intestinal iron absorption due to ineffective erythropoiesis and reduced hepcidin production 6 , 7 . The treatment includes long-term blood transfusions, splenectomy, and iron chelation therapy. Transfusion therapy is the basic management for thalassemia, and the frequency and magnitude indirectly reflects the underlying severity of the disease 8 , 9 . Splenectomy is common when splenomegaly that results in excessive filtration of blood components, thus provoking severe anemia, leukopenia, or thrombocytopenia 10 , 11 . While significantly reducing transfusion requirement and improve haematologic profile, splenectomy is associated with an increased risk of venous thromboembolism, pulmonary hypertension, high-output failure, and silent cerebral infarcts. 12 – 18 Iron chelation therapy has dramatically improved survival of patients with thalassemia. Ineffective erythropoiesis and red cell transfusions in thalassemia lead to excess iron, overloading in the liver, heart, and pancreas. Reports had showed that iron overload plays a role in the pathogenesis of hepatic cirrhosis, pulmonary hypertension, thrombosis, and malignant transformation. 6 , 19 , 20 Thalassemia patients face an elevated risk of VTE, ranging from lower extremity DVT, PE, portal vein thrombosis (PVT) and cerebral thrombosis. Transfusion-independent patients showed a prevalence of thromboembolic events with 29% and regularly transfused patients with 2% 13 . An overall prevalence of thromboembolic events in 8860 patients with beta-thalassaemia is 1.65%. 14 The main independent risk factors for thrombotic events are splenectomy, age > 35 years, serum ferritin level ≥ 1000 ng/mL, and a hemoglobin level < 9 g/dL. 13,15 Additionally, thromboembolic complications following splenectomy itself for hematologic diseases (including thalassaemia) occur in up to 10% of patients. 21 And the median time to thrombosis following splenectomy was 8 years. 15 Our patient underwent splenectomy nine years ago. But the extensive systemic venous thrombosis may have developed prior to this event, with diagnosis only being established recently. The thrombophilic status in thalassemia patients is multifaceted, involving hemostatic changes and activation of the coagulation cascade. The thrombocytosis and the spontaneous platelet activation and aggregation, which contributes to a procoagulant state, endothelial cell stimulation, and increased pulmonary in situ thrombosis, remain an attractive pathophysiological factor, particularly after splenectomy. The absence of spleen can enhance hypercoagulability and cause frequent thrombotic events, which is triggered by membrane phosphatidylserine exposure and procoagulant activity of circulating damaged red blood cells. 14 , 22 , 23 Moreover, splenectomised thalassaemia patients have increased levels of microparticles or medium extra-cellular vesicles, which are associated with vascular dysfunction, increased coagulation activity and platelet activation and aggregation 24 . Our patient was also complicated by severe PH. Ineffective erythropoiesis and iron overload are basically implicated in the pathogenesis of PH. 25 Risk factors for PH in this patient population include advanced age, a previous history of thromboembolism, and splenectomy. 16 , 26 Because of high cardiac output and pulmonary microvasculature emboli, thalassemia patients with splenectomy can develop PH with histopathological changes similar to those with WHO Group 1 pulmonary arterial hypertension (PAH) and WHO Group 4 chronic thromboembolic pulmonary hypertension (CTEPH). 27 – 29 Autopsy findings from 58 patients with thalassemia showed pulmonary vascular changes indicative of microthromboemboli in 54% splenectomized patients compared to 16% of those who had not had splenectomy. 28 Hemodynamic changes and raised vascular resistance from platelet activation, coagulopathy caused by platelet turnover and endothelial functions predispose PH in splenectomized thalassemia patients. 30 , 31 Conversely, PH has also been attributed to the presence of a pulmonary thromboembolism, with evident autopsy findings of pulmonary thrombotic lesions inpatients with biventricular heart failure. 28 The screening and management of PH in thalassemia patients is important. multidiscipline collaboration including haematology and respiratory medicine are needed to get early detection and intervention. Findings indicate a significant correlation of older age with presence and severity of PH, suggesting a need for closer monitoring of right heart pressure, particularly in those over 15–20 years old. 17 The positive predictive value for the tricuspid-valve regurgitant jet velocity ≥ 3.2 m/s threshold for the diagnosis of PH was 93.9%. Symptomatic patients with a tricuspid-valve regurgitant jet velocity > 2.5 m/s are likely to have pulmonary hypertension and should undergo confirmatory right heart catheterization. 26 It is currently recommended to treat thrombotic events as per general standard guidelines. Notably, aspirin therapy may benefit for splenectomized thalassaemia patients with a platelet count ≥ 500 × 109/L. 8,22 Emerging curative approaches such as stem cell therapy is the most promising strategy for achieving a long-term cure. Treatment for PH includes chelation therapy to lessen the iron load and possible vascular problems, 29 transfusion therapy in high-risk groups and splenectomized patients, and Hydroxyurea by suppressing ineffective erythropoiesis and reducing hypercoagulability 12 , 25 . Balloon pulmonary angioplasty is a promising option in thalassemic patients with inoperable CTEPH 32 . Riociguat, a soluble guanylate cyclase stimulator approved for CTEPH, may be recommended in patients developing PH in the setting of pulmonary thromboembolic events 29 . Our patient had never undergone thrombosis screening or echocardiographic monitoring since the diagnosis of thalassemia, which means an absent assessment of relative complications in such a medication condition, let alone any intervention or treatment. But the oversight could potentially have fatal consequences. Overall, the management of thromboembolism and PH in thalassemia patients is important but not enough, and should call an action to hematologists and pulmonary hypertension specialists. Conclusion The pathophysiological mechanisms underlying PE and PH in patients post splenectomy for thalassemia are not recognized by both hematology and respiratory specialists, leading to suboptimal management and treatment. It necessitates an integrated, multidisciplinary strategy for this medical condition. Abbreviations ALT: alanine aminotransferase; AST: aspartate aminotransferase; ANA: anti-nuclear antibody; ANCA: antineutrophil cytoplasmic antibodies; CTEPH: chronic thromboembolic pulmonary hypertension; DB: direct bilirubin; DVT: deep vein thrombosis; ED: emergency department; ENA: extractable nuclear antigen antibody profile; FDP: fibrin/fibrinogen degradation products; hs-TnT: high-sensitivity troponin T; ICP: increased intracranial pressure; mPAP: mean pulmonary arterial pressure; MRI: magnetic resonance imaging; MRV: magnetic resonance venography; NT-proBNP: N-terminal pro-B-type natriuretic peptide; PAH: pulmonary arterial hypertension; PASP: pulmonary artery systolic pressure; PE: Pulmonary embolism; PET/CT: positron emission tomography / computed tomography; PG: peak gradient; PH: pulmonary hypertension; PVT: portal vein thrombosis; RHC: right heart catheterisation; TB: total bilirubin; VTE: venous thromboembolism; WBC: white blood cell count. Declarations Ethics approval and consent to participate Written informed consent was obtained from the patient. This work is a case report, not a clinical trial, which describes the clinical course and management conducted under our hospital's standardized care protocols. Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding Not applicable. Authors’ contributions H. Q. performed frontline clinical care, drafted the initial manuscript and revised subsequently. W.K. and W.G. provided the medical case in charge of the overall clinical care. C.B. critically reviewed and revise the manuscript, and supervised the study. All authors significantly contributed to the work and approved the final manuscript as submitted. Acknowledgements None Authors and Affiliations Department of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China Qun Hu, Kaige Wang, Gang Wang, Bojiang Chen Precision Medicine Center, West China Hospital, Sichuan University, Chengdu, China Bojiang Chen Corresponding author Correspondence to Bojiang Chen References Raskob GE, Angchaisuksiri P, Blanco AN, Buller H, Gallus A, Hunt BJ, et al. Thrombosis: a major contributor to global disease burden. Arterioscler Thromb Vasc Biol. 2014;34(11):2363–71. Khan F, Tritschler T, Kahn SR, Rodger MA. Venous thromboembolism. Lancet (London England). 2021;398(10294):64–77. Kovacs G, Bartolome S, Denton CP, Gatzoulis MA, Gu S, Khanna D et al. Definition, classification and diagnosis of pulmonary hypertension. Eur Respir J 2024;64(4). Mufarrij A, Hodroj MH, Charbel N, El Khoury S, Arabi S, Taher A. Beyond the blood: A practical guide to thalassemia care in the emergency department. Blood Rev 2025:101327. Musallam KM, Cappellini MD, Coates TD, Kuo KHM, Al-Samkari H, Sheth S, et al. Αlpha-thalassemia: A practical overview. Blood Rev. 2024;64:101165. Pinto VM, Forni GL. Management of Iron Overload in Beta-Thalassemia Patients: Clinical Practice Update Based on Case Series. International journal of molecular sciences. 2020;21(22). Taher AT, Weatherall DJ, Cappellini MD, Thalassaemia. Lancet (London England). 2018;391(10116):155–67. Taher A, Vichinsky E, Musallam K, Cappellini MD, Viprakasit V. Guidelines for the Management of Non Transfusion Dependent Thalassaemia (NTDT). Nicosia (Cyprus): Thalassaemia International Federation . 2013. Cappellini MD, Cohen A, Porter J, Taher A, Viprakasit V. Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT). Nicosia (CY): Thalassaemia International Federation . 2014. Godeau B. Is splenectomy a good strategy for refractory immune thrombocytopenia in adults? Br J Haematol. 2023;203(1):86–95. Capecchi M, Ciavarella A, Artoni A, Abbattista M, Martinelli I. Thrombotic Complications in Patients with Immune-Mediated Hemolysis. J Clin Med 2021;10(8). Taher AT, Musallam KM, Karimi M, El-Beshlawy A, Belhoul K, Daar S, et al. Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: the OPTIMAL CARE study. Blood. 2010;115(10):1886–92. Cappellini MD, Robbiolo L, Bottasso BM, Coppola R, Fiorelli G, Mannucci AP. Venous thromboembolism and hypercoagulability in splenectomized patients with thalassaemia intermedia. Br J Haematol. 2000;111(2):467–73. Taher A, Isma'eel H, Mehio G, Bignamini D, Kattamis A, Rachmilewitz EA, et al. Prevalence of thromboembolic events among 8,860 patients with thalassaemia major and intermedia in the Mediterranean area and Iran. Thromb Haemost. 2006;96(4):488–91. Taher AT, Musallam KM, Karimi M, El-Beshlawy A, Belhoul K, Daar S, et al. Splenectomy and thrombosis: the case of thalassemia intermedia. J Thromb haemostasis: JTH. 2010;8(10):2152–8. Karimi M, Musallam KM, Cappellini MD, Daar S, El-Beshlawy A, Belhoul K, et al. Risk factors for pulmonary hypertension in patients with β thalassemia intermedia. Eur J Intern Med. 2011;22(6):607–10. Singer ST, Kuypers FA, Styles L, Vichinsky EP, Foote D, Rosenfeld H. Pulmonary hypertension in thalassemia: association with platelet activation and hypercoagulable state. Am J Hematol. 2006;81(9):670–5. Phrommintikul A, Sukonthasarn A, Kanjanavanit R, Nawarawong W. Splenectomy: a strong risk factor for pulmonary hypertension in patients with thalassaemia. Heart. 2006;92(10):1467–72. Musallam KM, Motta I, Salvatori M, Fraquelli M, Marcon A, Taher AT, et al. Longitudinal changes in serum ferritin levels correlate with measures of hepatic stiffness in transfusion-independent patients with β-thalassemia intermedia. Blood Cells Mol Dis. 2012;49(3–4):136–9. Saliba AN, Taher AT. Morbidities in non-transfusion-dependent thalassemia. Ann N Y Acad Sci. 2016;1368(1):82–94. Mohren M, Markmann I, Dworschak U, Franke A, Maas C, Mewes S, et al. Thromboembolic complications after splenectomy for hematologic diseases. Am J Hematol. 2004;76(2):143–7. Cappellini MD, Grespi E, Cassinerio E, Bignamini D, Fiorelli G. Coagulation and splenectomy: an overview. Ann N Y Acad Sci. 2005;1054:317–24. Bou-Fakhredin R, Cappellini MD, Taher AT, De Franceschi L. Hypercoagulability in hemoglobinopathies: Decoding the thrombotic threat. Am J Hematol. 2025;100(1):103–15. Phongpao K, Pholngam N, Chokchaichamnankit D, Nuamsee K, Praneetponkang R, Ounjai P, et al. Proteomic profiling of circulating β-thalassaemia/haemoglobin E extra-cellular vesicles reveals that association with immunoglobulin induces membrane vesiculation. Br J Haematol. 2024;204(5):2025–39. Wood JC. Pulmonary hypertension in thalassemia: a call to action. Blood. 2022;139(13):1937–8. Derchi G, Galanello R, Bina P, Cappellini MD, Piga A, Lai ME, et al. Prevalence and risk factors for pulmonary arterial hypertension in a large group of β-thalassemia patients using right heart catheterization: a Webthal study. Circulation. 2014;129(3):338–45. Palkar AV, Agrawal A, Verma S, Iftikhar A, Miller EJ, Talwar A. Post splenectomy related pulmonary hypertension. World J Respirol. 2015;5(2):69–77. Sumiyoshi A, Thakerngpol K, Sonakul D. Pulmonary microthromboemboli in thalassemic cases. Southeast Asian J Trop Med Public Health. 1992;23(Suppl 2):29–31. Marie G, Bonaguro A, Walsh C, Omer Leghari M, Dia M, Laroy V, Macaluso GP, et al. A CASE OF POST-SPLENECTOMY PULMONARY HYPERTENSION. Chest. 2023;164(4):A6092–3. Caocci G, Mulas O, Barella S, Orecchia V, Mola B, Costa A et al. Long-Term Health-Related Quality of Life and Clinical Outcomes in Patients with β-Thalassemia after Splenectomy. J Clin Med 2023;12(7). McPhetridge JB, Lynch AM, Webster CRL, McCobb E, de Laforcade AM, O'Toole TE. Pre-operative Hemostatic Status in Dogs Undergoing Splenectomy for Splenic Masses. Front veterinary Sci. 2022;9:686225. Karyofyllis P, Tsiapras D, Papadopoulou V, Diamantidis MD, Fotiou P, Demerouti E, et al. Balloon pulmonary angioplasty is a promising option in thalassemic patients with inoperable chronic thromboembolic pulmonary hypertension. J Thromb Thrombolysis. 2018;46(4):516–20. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 21 Apr, 2026 Reviews received at journal 09 Feb, 2026 Reviews received at journal 08 Feb, 2026 Reviews received at journal 28 Jan, 2026 Reviewers agreed at journal 26 Jan, 2026 Reviews received at journal 24 Jan, 2026 Reviewers agreed at journal 21 Jan, 2026 Reviews received at journal 21 Jan, 2026 Reviewers agreed at journal 20 Jan, 2026 Reviews received at journal 16 Jan, 2026 Reviewers agreed at journal 15 Jan, 2026 Reviewers agreed at journal 15 Jan, 2026 Reviewers agreed at journal 14 Jan, 2026 Reviewers invited by journal 13 Jan, 2026 Editor assigned by journal 13 Jan, 2026 Editor invited by journal 16 Dec, 2025 Submission checks completed at journal 16 Dec, 2025 First submitted to journal 16 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8315474","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":575259997,"identity":"7a6b896b-a342-42ed-9627-792be5d64619","order_by":0,"name":"Qun Hu","email":"","orcid":"","institution":"Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Qun","middleName":"","lastName":"Hu","suffix":""},{"id":575259998,"identity":"7d5a7aff-ab47-499b-9b21-26675950a0b1","order_by":1,"name":"Kaige Wang","email":"","orcid":"","institution":"Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Kaige","middleName":"","lastName":"Wang","suffix":""},{"id":575259999,"identity":"85db7d69-6632-40dc-a2d7-a8bb4126e3f8","order_by":2,"name":"Gang Wang","email":"","orcid":"","institution":"Sichuan University","correspondingAuthor":false,"prefix":"","firstName":"Gang","middleName":"","lastName":"Wang","suffix":""},{"id":575260000,"identity":"36995790-1dfd-4ac1-bfb1-ba4113bed09b","order_by":3,"name":"Bojiang Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAw0lEQVRIiWNgGAWjYFCCMwzMDDw2QAZzAwPDAeK1pDEwsDESrYUHqIXhMAla+BvPHvxcIHNezuB+Y+ODD2cY5PnFCOiTOHAuWXoGz21jg2OMzYYzbjAYzpydgF+LAcMZM2YentuJG44xtknzfGBIMLhNnJZzpGs5ANVygwgtEgfOGAP9kmwseSwR6JczEoT9wj/jjOHnwh47Ob7Dhw8++HDMRp5fmoAWoDUMDIw9CC4B5WBrGoDEDyIUjoJRMApGwcgFAAanRQqZFGRDAAAAAElFTkSuQmCC","orcid":"","institution":"Sichuan University","correspondingAuthor":true,"prefix":"","firstName":"Bojiang","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2025-12-09 09:08:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8315474/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8315474/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":100595201,"identity":"806916dd-796e-455e-91ba-82d5d5cc8ea7","added_by":"auto","created_at":"2026-01-19 13:47:51","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1137814,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscriptrevised2.docx","url":"https://assets-eu.researchsquare.com/files/rs-8315474/v1/14fdef202ba9b02a78de429d.docx"},{"id":100565721,"identity":"78fcd31a-a130-4c84-bd7a-237f233a26c7","added_by":"auto","created_at":"2026-01-19 09:06:06","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":5889,"visible":true,"origin":"","legend":"","description":"","filename":"505015f62a0a4b869a89cc5e3f47f7ef.json","url":"https://assets-eu.researchsquare.com/files/rs-8315474/v1/5e890d93b0709b84056afe49.json"},{"id":100594876,"identity":"e3c2bfc5-828b-4344-9a4e-84939ef947c3","added_by":"auto","created_at":"2026-01-19 13:45:56","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":77866,"visible":true,"origin":"","legend":"","description":"","filename":"505015f62a0a4b869a89cc5e3f47f7ef1enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-8315474/v1/548e5aa4db9730aaba9af50d.xml"},{"id":100595255,"identity":"06acdaff-ac82-4564-a5e6-831e966c983e","added_by":"auto","created_at":"2026-01-19 13:48:03","extension":"png","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":561015,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8315474/v1/4ee437936fd6bf8f791fb0b9.png"},{"id":100565732,"identity":"0ec7f656-4cd1-4e63-8b6f-1cc8f0f078ce","added_by":"auto","created_at":"2026-01-19 09:06:07","extension":"jpeg","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":602112,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8315474/v1/7dd9d6e7f1b6911cfe981237.jpeg"},{"id":100594781,"identity":"89b5d279-4534-4db5-abdd-7b9262023ad1","added_by":"auto","created_at":"2026-01-19 13:44:57","extension":"png","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":141654,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8315474/v1/9669c91466ad401fc6ee1e70.png"},{"id":100565730,"identity":"7f5b5013-0f73-4258-be7e-29b3d102e933","added_by":"auto","created_at":"2026-01-19 09:06:07","extension":"png","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":147899,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8315474/v1/24e06ba4507779ac1623934c.png"},{"id":100595598,"identity":"8e02c013-1c63-467d-8753-f76726e834f7","added_by":"auto","created_at":"2026-01-19 13:48:53","extension":"xml","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":76553,"visible":true,"origin":"","legend":"","description":"","filename":"505015f62a0a4b869a89cc5e3f47f7ef1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8315474/v1/8fc710cc713aad0bc378419e.xml"},{"id":100565724,"identity":"fc3d36f5-ac33-44f9-9310-e08e2855b4c6","added_by":"auto","created_at":"2026-01-19 09:06:06","extension":"html","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":83993,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8315474/v1/62d3ebb0160c15f5e11ccca0.html"},{"id":100594838,"identity":"fe93b187-7301-4692-8898-0a2770b087b0","added_by":"auto","created_at":"2026-01-19 13:45:32","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":103356,"visible":true,"origin":"","legend":"\u003cp\u003eFindings on contrast-enhanced computed tomography (CT) of the chest and abdomen. (A) The main pulmonary artery and the bilateral main pulmonary arteries were dilated, indicated by the red asterisk. (B) Chest CT revealed cardiomegaly, with prominent dilation of the right atrium and right ventricle. Filling defects were observed in the right lower lobe pulmonary arteries, indicated by the red arrow. (C) Filling defects were observed in the left lower lobe pulmonary arteries, indicated by the red arrow. (D) Filling defects are noted in the main portal vein and its right branch. the yellow arrow indicates the main portal vein, while the red arrow denoted the right main portal vein. (E) Filling defects are noted in the left main portal vein. (F) Significant hepatomegaly is evident, and spleen is absent.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8315474/v1/449f73f77e9236abbdf213b0.jpg"},{"id":100565727,"identity":"1e94dd51-5c15-4fda-bfb8-10cacfdf7740","added_by":"auto","created_at":"2026-01-19 09:06:07","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":11120,"visible":true,"origin":"","legend":"\u003cp\u003eThe whole-body fluorodeoxyglucose (FDG) positron emission tomography / computed tomography (PET/CT) imaging showed mild metabolic elevation in the axial skeleton and bilateral femurs.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8315474/v1/6b1d1473f2b6b0db816d5eb8.jpg"},{"id":100565728,"identity":"d3bafcfa-0894-43f0-9bb8-3d7e591703ed","added_by":"auto","created_at":"2026-01-19 09:06:07","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":36477,"visible":true,"origin":"","legend":"\u003cp\u003eMagnetic resonance (MR) imaging and MR venography of the head showed no significant abnormalities. (A) T2-weighted imaging. (B) T1-weighted-based MR venography.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8315474/v1/e1e3674eb46bfa84cbdfb225.jpg"},{"id":100597318,"identity":"90aa8993-6a85-4926-ad0c-72f0e7e30db8","added_by":"auto","created_at":"2026-01-19 14:16:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":579930,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8315474/v1/26251840-647c-406c-8d57-0cab6644730a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Thromboembolism and pulmonary hypertension after splenectomy in thalassemia: a case report","fulltext":[{"header":"Background","content":"\u003cp\u003eVenous thromboembolism (VTE) includes deep vein thrombosis (DVT) and pulmonary embolism (PE). DVT most often occurs in the leg vein but can also develop in the abdominal, cerebral, and arm veins. Afflicting worldwide nearly 10\u0026nbsp;million people per year, VTE is a significant contributor to the global burden of disease.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOnce VTE diagnosed, especially PE, contributing triggers are commonly needed to be underlined. Frequent clinical provoking risk factors for VTE include prolonged immobility, recent major surgery, active cancer, chronic inflammatory disorders, and antiphospholipid syndrom.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e However, splenectomy for thalassemia as a possible trigger is rare and not widely recognized in clinical respiratory practice.\u003c/p\u003e \u003cp\u003ePulmonary hypertension (PH) is life-threatening condition characterized by a mean pulmonary arterial pressure (mPAP)\u0026thinsp;\u0026ge;\u0026thinsp;25 mmHg at rest. Clinical classification of PH with multiple pathophysiological mechanisms can be divided into five subgroups. Suspected PH is initially evaluated by echocardiography and ultimately diagnosed through right heart catheterisation (RHC). Early diagnosis and specialized management for PH is highly required.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003ePE and PH are common conditions in clinical pulmonology that often necessitate further investigation to elucidate their etiology. Herein, we present a representative case to advance the pathophysiological understanding of PE and PH in splenectomized thalassemia patients, highlighting the need for collaborative attention from hematologists and pulmonologists.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eThis patient was a 38-year-old man who was admitted to the emergency department (ED) due to chest tightness and shortness of breath on exertion for two weeks, which progressed to dyspnea at rest accompanied by dizziness and abdominal pain over the past 10 days.\u003c/p\u003e \u003cp\u003eHe who had been maintained on deferasirox, was diagnosed with α-thalassemia at 7 months of age, and subsequently underwent splenectomy nine years ago due to severe anemia. His social/family history is unremarkable. He was unmarried and had no children.\u003c/p\u003e \u003cp\u003eDiagnostic workup in the ED revealed systemic multiple thromboses, including PE. Following management with anticoagulation and diuresis, the patient was admitted to the department of respiratory medicine. Vital signs were normal and he exhibited an anemic complexion.\u003c/p\u003e \u003cp\u003eChest and abdomen enhanced CT revealed the following main findings: 1) Lungs: bilateral patchy opacities, consistent with pneumonia. 2) Pulmonary arteries: dilation of the main and bilateral main pulmonary arteries (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). Multiple filling defects are present in the bilateral lower lobe arteries (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB, C). 3) Heart and pericardium: significant cardiomegaly with a small pericardial effusion (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). 4) Abdominal vasculature: filling defects are noted in the superior mesenteric vein, the main portal vein (including left and right branches), and the right hepatic vein, highly suggestive of thrombosis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eD, E). 5) Liver and Spleen: marked hepatomegaly with imaging features of cirrhosis and portal hypertension. The spleen is not visualized (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eF). Arterial and venous color doppler ultrasound of the extremities revealed no evidence of thrombosis. Cardiac echocardiography demonstrated right heart enlargement, right ventricular hypertrophy, severe pulmonary hypertension (tricuspid-valve regurgitant jet velocity was 4.2 m/s, and the peak gradient (PG) was 73 mmHg, yielding an estimated pulmonary artery systolic pressure (PASP) of 76 mmHg).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe laboratory findings were as follows: hemoglobin 85 g/L (normal range: 130\u0026ndash;175 g/L), platelet count 381 \u0026times; 10⁹/L (normal range: 100\u0026ndash;300 \u0026times; 10⁹/L), white blood cell count (WBC) 9.94 \u0026times; 10⁹/L (normal range: 3.5\u0026ndash;9.5 \u0026times; 10⁹/L), neutrophils (segmented) 48.0% (normal range: 40\u0026ndash;75%). Biochemical tests: total bilirubin (TB) 55.0 \u0026micro;mol/L (normal range: 3.2\u0026ndash;20.5 \u0026micro;mol/L), direct bilirubin (DB) 35.0 \u0026micro;mol/L (normal\u0026thinsp;\u0026lt;\u0026thinsp;6.8 \u0026micro;mol/L), alanine aminotransferase (ALT) 168 U/L (normal range: 9\u0026ndash;50 U/L), aspartate aminotransferase (AST) 127 U/L (normal range: 15\u0026ndash;40 U/L). Coagulation profile: fibrin/fibrinogen degradation products (FDP) 31.1 mg/L (normal\u0026thinsp;\u0026lt;\u0026thinsp;5 mg/L), d-dimer 12.16 mg/L FEU (normal\u0026thinsp;\u0026lt;\u0026thinsp;0.55 mg/l FEU). Cardiac Markers: N-terminal pro-B-type natriuretic peptide (NT-proBNP) 5313 ng/L (normal\u0026thinsp;\u0026lt;\u0026thinsp;91 ng/L), high-sensitivity troponin T (hs-TnT) was measured at 35.2 ng/L (normal\u0026thinsp;\u0026lt;\u0026thinsp;14 ng/L).\u003c/p\u003e \u003cp\u003eTo investigate the underlying etiology of the patient's pulmonary embolism, a series of diagnostic tests including tumor marker assays, a comprehensive immunological panel, and a thrombophilia screen were conducted. Test of serum tumor markers showed carbohydrate antigen (CA) 125 261.00 U/mL (normal\u0026thinsp;\u0026lt;\u0026thinsp;24.00 U/mL). Other tumor markers including carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin 19 fragment (CYFRA21\u0026ndash;1), CA 15\u0026thinsp;\u0026minus;\u0026thinsp;3 and CA 19\u0026thinsp;\u0026minus;\u0026thinsp;9 were negative. The immunological panel including anti-nuclear antibody (ANA), extractable nuclear antigen antibody profile (ENA), anti-dsDNA, antineutrophil cytoplasmic antibodies (ANCA) was negative. Testing for anticardiolipin antibodies, lupus anticoagulant, protein C and protein S was in the normal range. In addition, externally tested genetic panels for thrombophilia detected no pathogenic variants.\u003c/p\u003e \u003cp\u003eThe etiology of the patient's systemic multiple thromboses remained elusive. Thus, the whole-body fluorodeoxyglucose positron emission tomography / computed tomography (PET/CT) imaging was obtained to rule out large vessel vasculitis. The PET/CT revealed decreased bone density throughout the skeletal system, with mildly increased glucose metabolism in the axial skeleton and bilateral femurs (Fig.\u0026nbsp;2). The nature of these PET/CT findings is indeterminate, with reactive changes or hematologic malignancies considered as potential etiologies.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBased on the diagnostic challenges, we consulted related references and found the correlation between the patient's extensive venous thrombosis and his history of thalassemia with splenectomy. Thalassemia itself predisposes individuals to a hypercoagulable state and heightened hemostatic activation, effects that are potentiated by splenectomy. Furthermore, the intermittent visual disturbances were likely related to transient cerebral microthromboembolism, and thus the transient ischemic attack, which would explain the absence of abnormalities on cerebral contrast-enhanced sequences and MRV.\u003c/p\u003e \u003cp\u003eUpon clinical stabilization, the patient was discharged on oral rivaroxaban for continued anticoagulation. Relevant examinations would be re-evaluated after three months. At the one-month follow-up, the patient remained clinically stable, and rivaroxaban was sustained.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case typically illustrates the development of thrombosis and severe PH in association with a history of splenectomy for thalassemia. However, we did not perform RHC on this patient and instead initiated anticoagulation therapy due to the coexistence of these two complications.\u003c/p\u003e \u003cp\u003eThalassemia is a heterogeneous inherited hemoglobinopathy characterized by an imbalance in the ratio of α- and β-globin chains.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e The estimated global prevalence for α-thalassemia and β-thalassemia is 5\u0026ndash;20% and approximately 1.5%, respectively.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e A series of conditions, including ineffective erythropoiesis, chronic anemia, extramedullary hematopoiesis, and iron overload are developed in these patients, regardless of the type of thalassemia.\u003c/p\u003e \u003cp\u003eIneffective erythropoiesis results as chronic anemia, without an adequate mature red blood cells in the peripheral blood. Compensatory hematopoietic proliferation affect both within and outside the bone marrow, associated with medullary expansion and hepatosplenomegaly.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Iron overload arises from transfusions and increased intestinal iron absorption due to ineffective erythropoiesis and reduced hepcidin production\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. The treatment includes long-term blood transfusions, splenectomy, and iron chelation therapy.\u003c/p\u003e \u003cp\u003eTransfusion therapy is the basic management for thalassemia, and the frequency and magnitude indirectly reflects the underlying severity of the disease\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. Splenectomy is common when splenomegaly that results in excessive filtration of blood components, thus provoking severe anemia, leukopenia, or thrombocytopenia\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e. While significantly reducing transfusion requirement and improve haematologic profile, splenectomy is associated with an increased risk of venous thromboembolism, pulmonary hypertension, high-output failure, and silent cerebral infarcts.\u003csup\u003e\u003cspan additionalcitationids=\"CR13 CR14 CR15 CR16 CR17\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIron chelation therapy has dramatically improved survival of patients with thalassemia. Ineffective erythropoiesis and red cell transfusions in thalassemia lead to excess iron, overloading in the liver, heart, and pancreas. Reports had showed that iron overload plays a role in the pathogenesis of hepatic cirrhosis, pulmonary hypertension, thrombosis, and malignant transformation.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThalassemia patients face an elevated risk of VTE, ranging from lower extremity DVT, PE, portal vein thrombosis (PVT) and cerebral thrombosis. Transfusion-independent patients showed a prevalence of thromboembolic events with 29% and regularly transfused patients with 2%\u003csup\u003e13\u003c/sup\u003e. An overall prevalence of thromboembolic events in 8860 patients with beta-thalassaemia is 1.65%.\u003csup\u003e14\u003c/sup\u003e The main independent risk factors for thrombotic events are splenectomy, age\u0026thinsp;\u0026gt;\u0026thinsp;35 years, serum ferritin level\u0026thinsp;\u0026ge;\u0026thinsp;1000 ng/mL, and a hemoglobin level\u0026thinsp;\u0026lt;\u0026thinsp;9 g/dL.\u003csup\u003e13,15\u003c/sup\u003e Additionally, thromboembolic complications following splenectomy itself for hematologic diseases (including thalassaemia) occur in up to 10% of patients.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e And the median time to thrombosis following splenectomy was 8 years.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e Our patient underwent splenectomy nine years ago. But the extensive systemic venous thrombosis may have developed prior to this event, with diagnosis only being established recently.\u003c/p\u003e \u003cp\u003eThe thrombophilic status in thalassemia patients is multifaceted, involving hemostatic changes and activation of the coagulation cascade. The thrombocytosis and the spontaneous platelet activation and aggregation, which contributes to a procoagulant state, endothelial cell stimulation, and increased pulmonary in situ thrombosis, remain an attractive pathophysiological factor, particularly after splenectomy. The absence of spleen can enhance hypercoagulability and cause frequent thrombotic events, which is triggered by membrane phosphatidylserine exposure and procoagulant activity of circulating damaged red blood cells.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e Moreover, splenectomised thalassaemia patients have increased levels of microparticles or medium extra-cellular vesicles, which are associated with vascular dysfunction, increased coagulation activity and platelet activation and aggregation\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOur patient was also complicated by severe PH. Ineffective erythropoiesis and iron overload are basically implicated in the pathogenesis of PH.\u003csup\u003e25\u003c/sup\u003e Risk factors for PH in this patient population include advanced age, a previous history of thromboembolism, and splenectomy.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e Because of high cardiac output and pulmonary microvasculature emboli, thalassemia patients with splenectomy can develop PH with histopathological changes similar to those with WHO Group 1 pulmonary arterial hypertension (PAH) and WHO Group 4 chronic thromboembolic pulmonary hypertension (CTEPH).\u003csup\u003e\u003cspan additionalcitationids=\"CR28\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e Autopsy findings from 58 patients with thalassemia showed pulmonary vascular changes indicative of microthromboemboli in 54% splenectomized patients compared to 16% of those who had not had splenectomy.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e Hemodynamic changes and raised vascular resistance from platelet activation, coagulopathy caused by platelet turnover and endothelial functions predispose PH in splenectomized thalassemia patients.\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e Conversely, PH has also been attributed to the presence of a pulmonary thromboembolism, with evident autopsy findings of pulmonary thrombotic lesions inpatients with biventricular heart failure.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe screening and management of PH in thalassemia patients is important. multidiscipline collaboration including haematology and respiratory medicine are needed to get early detection and intervention. Findings indicate a significant correlation of older age with presence and severity of PH, suggesting a need for closer monitoring of right heart pressure, particularly in those over 15\u0026ndash;20 years old. \u003csup\u003e17\u003c/sup\u003e The positive predictive value for the tricuspid-valve regurgitant jet velocity\u0026thinsp;\u0026ge;\u0026thinsp;3.2 m/s threshold for the diagnosis of PH was 93.9%. Symptomatic patients with a tricuspid-valve regurgitant jet velocity\u0026thinsp;\u0026gt;\u0026thinsp;2.5 m/s are likely to have pulmonary hypertension and should undergo confirmatory right heart catheterization.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIt is currently recommended to treat thrombotic events as per general standard guidelines. Notably, aspirin therapy may benefit for splenectomized thalassaemia patients with a platelet count\u0026thinsp;\u0026ge;\u0026thinsp;500 \u0026times; 109/L.\u003csup\u003e8,22\u003c/sup\u003e Emerging curative approaches such as stem cell therapy is the most promising strategy for achieving a long-term cure.\u003c/p\u003e \u003cp\u003eTreatment for PH includes chelation therapy to lessen the iron load and possible vascular problems,\u003csup\u003e29\u003c/sup\u003e transfusion therapy in high-risk groups and splenectomized patients, and Hydroxyurea by suppressing ineffective erythropoiesis and reducing hypercoagulability\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Balloon pulmonary angioplasty is a promising option in thalassemic patients with inoperable CTEPH\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e. Riociguat, a soluble guanylate cyclase stimulator approved for CTEPH, may be recommended in patients developing PH in the setting of pulmonary thromboembolic events\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOur patient had never undergone thrombosis screening or echocardiographic monitoring since the diagnosis of thalassemia, which means an absent assessment of relative complications in such a medication condition, let alone any intervention or treatment. But the oversight could potentially have fatal consequences. Overall, the management of thromboembolism and PH in thalassemia patients is important but not enough, and should call an action to hematologists and pulmonary hypertension specialists.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe pathophysiological mechanisms underlying PE and PH in patients post splenectomy for thalassemia are not recognized by both hematology and respiratory specialists, leading to suboptimal management and treatment. It necessitates an integrated, multidisciplinary strategy for this medical condition.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eALT: alanine aminotransferase; AST: aspartate aminotransferase; ANA: anti-nuclear antibody; ANCA: antineutrophil cytoplasmic antibodies; CTEPH: chronic thromboembolic pulmonary hypertension; DB: direct bilirubin; DVT: deep vein thrombosis; ED: emergency department; ENA: extractable nuclear antigen antibody profile; FDP: fibrin/fibrinogen degradation products; hs-TnT: high-sensitivity troponin T; ICP: increased intracranial pressure; mPAP: mean pulmonary arterial pressure; MRI: magnetic resonance imaging; MRV: magnetic resonance venography; NT-proBNP: N-terminal pro-B-type natriuretic peptide; PAH: pulmonary arterial hypertension; PASP: pulmonary artery systolic pressure; PE: Pulmonary embolism; PET/CT: positron emission tomography / computed tomography; PG: peak gradient; PH: pulmonary hypertension; PVT: portal vein thrombosis; RHC: right heart catheterisation; TB: total bilirubin; VTE: venous thromboembolism; WBC: white blood cell count.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient. This work is a case report, not a clinical trial, which describes the clinical course and management conducted under our hospital\u0026apos;s standardized care protocols.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and any accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eH. Q. performed frontline clinical care, drafted the initial manuscript and revised subsequently. W.K. and W.G. provided the medical case in charge of the overall clinical care. C.B. critically reviewed and revise the manuscript, and supervised the study. All authors significantly contributed to the work and approved the final manuscript as submitted.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors and Affiliations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDepartment of\u0026nbsp;Pulmonary\u0026nbsp;and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eQun Hu, Kaige Wang, Gang Wang, Bojiang Chen\u003c/p\u003e\n\u003cp\u003ePrecision Medicine Center, West China Hospital, Sichuan University, Chengdu, China\u003c/p\u003e\n\u003cp\u003eBojiang Chen\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorresponding author\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCorrespondence to Bojiang Chen\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRaskob GE, Angchaisuksiri P, Blanco AN, Buller H, Gallus A, Hunt BJ, et al. Thrombosis: a major contributor to global disease burden. Arterioscler Thromb Vasc Biol. 2014;34(11):2363\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKhan F, Tritschler T, Kahn SR, Rodger MA. Venous thromboembolism. Lancet (London England). 2021;398(10294):64\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKovacs G, Bartolome S, Denton CP, Gatzoulis MA, Gu S, Khanna D et al. Definition, classification and diagnosis of pulmonary hypertension. Eur Respir J 2024;64(4).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMufarrij A, Hodroj MH, Charbel N, El Khoury S, Arabi S, Taher A. Beyond the blood: A practical guide to thalassemia care in the emergency department. Blood Rev 2025:101327.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMusallam KM, Cappellini MD, Coates TD, Kuo KHM, Al-Samkari H, Sheth S, et al. Αlpha-thalassemia: A practical overview. Blood Rev. 2024;64:101165.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePinto VM, Forni GL. Management of Iron Overload in Beta-Thalassemia Patients: Clinical Practice Update Based on Case Series. \u003cem\u003eInternational journal of molecular sciences.\u003c/em\u003e 2020;21(22).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTaher AT, Weatherall DJ, Cappellini MD, Thalassaemia. Lancet (London England). 2018;391(10116):155\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTaher A, Vichinsky E, Musallam K, Cappellini MD, Viprakasit V. Guidelines for the Management of Non Transfusion Dependent Thalassaemia (NTDT). \u003cem\u003eNicosia (Cyprus): Thalassaemia International Federation\u003c/em\u003e. 2013.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCappellini MD, Cohen A, Porter J, Taher A, Viprakasit V. Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT). \u003cem\u003eNicosia (CY): Thalassaemia International Federation\u003c/em\u003e. 2014.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGodeau B. Is splenectomy a good strategy for refractory immune thrombocytopenia in adults? Br J Haematol. 2023;203(1):86\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCapecchi M, Ciavarella A, Artoni A, Abbattista M, Martinelli I. Thrombotic Complications in Patients with Immune-Mediated Hemolysis. J Clin Med 2021;10(8).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTaher AT, Musallam KM, Karimi M, El-Beshlawy A, Belhoul K, Daar S, et al. Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: the OPTIMAL CARE study. Blood. 2010;115(10):1886\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCappellini MD, Robbiolo L, Bottasso BM, Coppola R, Fiorelli G, Mannucci AP. Venous thromboembolism and hypercoagulability in splenectomized patients with thalassaemia intermedia. Br J Haematol. 2000;111(2):467\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTaher A, Isma'eel H, Mehio G, Bignamini D, Kattamis A, Rachmilewitz EA, et al. Prevalence of thromboembolic events among 8,860 patients with thalassaemia major and intermedia in the Mediterranean area and Iran. Thromb Haemost. 2006;96(4):488\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTaher AT, Musallam KM, Karimi M, El-Beshlawy A, Belhoul K, Daar S, et al. Splenectomy and thrombosis: the case of thalassemia intermedia. J Thromb haemostasis: JTH. 2010;8(10):2152\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKarimi M, Musallam KM, Cappellini MD, Daar S, El-Beshlawy A, Belhoul K, et al. Risk factors for pulmonary hypertension in patients with β thalassemia intermedia. Eur J Intern Med. 2011;22(6):607\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSinger ST, Kuypers FA, Styles L, Vichinsky EP, Foote D, Rosenfeld H. Pulmonary hypertension in thalassemia: association with platelet activation and hypercoagulable state. Am J Hematol. 2006;81(9):670\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePhrommintikul A, Sukonthasarn A, Kanjanavanit R, Nawarawong W. Splenectomy: a strong risk factor for pulmonary hypertension in patients with thalassaemia. Heart. 2006;92(10):1467\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMusallam KM, Motta I, Salvatori M, Fraquelli M, Marcon A, Taher AT, et al. Longitudinal changes in serum ferritin levels correlate with measures of hepatic stiffness in transfusion-independent patients with β-thalassemia intermedia. Blood Cells Mol Dis. 2012;49(3\u0026ndash;4):136\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaliba AN, Taher AT. Morbidities in non-transfusion-dependent thalassemia. Ann N Y Acad Sci. 2016;1368(1):82\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMohren M, Markmann I, Dworschak U, Franke A, Maas C, Mewes S, et al. Thromboembolic complications after splenectomy for hematologic diseases. Am J Hematol. 2004;76(2):143\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCappellini MD, Grespi E, Cassinerio E, Bignamini D, Fiorelli G. Coagulation and splenectomy: an overview. Ann N Y Acad Sci. 2005;1054:317\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBou-Fakhredin R, Cappellini MD, Taher AT, De Franceschi L. Hypercoagulability in hemoglobinopathies: Decoding the thrombotic threat. Am J Hematol. 2025;100(1):103\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePhongpao K, Pholngam N, Chokchaichamnankit D, Nuamsee K, Praneetponkang R, Ounjai P, et al. Proteomic profiling of circulating β-thalassaemia/haemoglobin E extra-cellular vesicles reveals that association with immunoglobulin induces membrane vesiculation. Br J Haematol. 2024;204(5):2025\u0026ndash;39.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWood JC. Pulmonary hypertension in thalassemia: a call to action. Blood. 2022;139(13):1937\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDerchi G, Galanello R, Bina P, Cappellini MD, Piga A, Lai ME, et al. Prevalence and risk factors for pulmonary arterial hypertension in a large group of β-thalassemia patients using right heart catheterization: a Webthal study. Circulation. 2014;129(3):338\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePalkar AV, Agrawal A, Verma S, Iftikhar A, Miller EJ, Talwar A. Post splenectomy related pulmonary hypertension. World J Respirol. 2015;5(2):69\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSumiyoshi A, Thakerngpol K, Sonakul D. Pulmonary microthromboemboli in thalassemic cases. Southeast Asian J Trop Med Public Health. 1992;23(Suppl 2):29\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarie G, Bonaguro A, Walsh C, Omer Leghari M, Dia M, Laroy V, Macaluso GP, et al. A CASE OF POST-SPLENECTOMY PULMONARY HYPERTENSION. Chest. 2023;164(4):A6092\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCaocci G, Mulas O, Barella S, Orecchia V, Mola B, Costa A et al. Long-Term Health-Related Quality of Life and Clinical Outcomes in Patients with β-Thalassemia after Splenectomy. J Clin Med 2023;12(7).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcPhetridge JB, Lynch AM, Webster CRL, McCobb E, de Laforcade AM, O'Toole TE. Pre-operative Hemostatic Status in Dogs Undergoing Splenectomy for Splenic Masses. Front veterinary Sci. 2022;9:686225.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaryofyllis P, Tsiapras D, Papadopoulou V, Diamantidis MD, Fotiou P, Demerouti E, et al. Balloon pulmonary angioplasty is a promising option in thalassemic patients with inoperable chronic thromboembolic pulmonary hypertension. J Thromb Thrombolysis. 2018;46(4):516\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Pulmonary embolism, Pulmonary hypertension, Splenectomy, Thalassemia, Case report","lastPublishedDoi":"10.21203/rs.3.rs-8315474/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8315474/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003ePulmonary embolism (PE) and pulmonary hypertension (PH) are common respiratory diseases that require a thorough etiological workup. However, the pathophysiology of PE and PH in thalassemia patient post-splenectomy can be easily overlooked by both hematologists and pulmonologists.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation: \u003c/strong\u003eA 38-year-old man, who had diagnosed with α-thalassemia at 7 months of age, and subsequently underwent splenectomy nine years ago due to severe anemia, developed chest tightness and shortness of breath, and progressed to dyspnea at rest accompanied by dizziness and abdominal pain. Chest and abdomen enhanced CT scan revealed extensive venous thrombosis including pulmonary artery, portal vein, mesenteric vein, hepatic vein and possibly cerebral thrombosis.\u003cstrong\u003e \u003c/strong\u003eCardiac echocardiography demonstrated severe PH (tricuspid-valve regurgitant jet velocity was 4.2 m/s). Further accessory examination containing tumor markers, immunological indicators, thrombophilia screen and genetic testing could not elucidate potential provoking factors and pathogeny. Management consisted of curative anticoagulation, antibiotherapy, diuretics and hyperosmotic dehydration, leading to clinical improvement and subsequent stability on follow-up.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThe understanding of PE and PH following splenectomy in patients with thalassemia are often suboptimal, let alone the early management and treatment. It necessitates an integrated, multidisciplinary strategy involving hematology and pulmonology specialists.\u003c/p\u003e","manuscriptTitle":"Thromboembolism and pulmonary hypertension after splenectomy in thalassemia: a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-19 09:06:02","doi":"10.21203/rs.3.rs-8315474/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-21T12:21:45+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-10T02:27:07+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-08T20:07:18+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-28T14:30:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"264357940843615005319892125542252507535","date":"2026-01-26T09:16:13+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-24T16:51:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"294893042093784613888169080905262876641","date":"2026-01-21T22:34:54+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-21T05:45:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"29371143330171923441604397372672020340","date":"2026-01-20T13:57:30+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-16T14:02:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"290836982207530518516299431046972047073","date":"2026-01-15T19:58:57+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"72770938234352275940594492534328645147","date":"2026-01-15T16:42:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"316355507523843590935897613676135839395","date":"2026-01-14T09:52:45+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-13T16:30:12+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-13T05:01:01+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-12-17T03:29:08+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-16T09:09:58+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pulmonary Medicine","date":"2025-12-16T08:57:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pulmonary-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pulm","sideBox":"Learn more about [BMC Pulmonary Medicine](http://bmcpulmmed.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/pulm/default.aspx","title":"BMC Pulmonary Medicine","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"bd232034-6e46-49b0-be94-90e62c1bbf88","owner":[],"postedDate":"January 19th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-05-18T12:39:55+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-19 09:06:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8315474","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8315474","identity":"rs-8315474","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}