Acute severe thrombocytopenia induced by rivaroxaban in a patient with atrial fibrillation: a case report

Acute severe thrombocytopenia induced by rivaroxaban in a patient with atrial fibrillation: 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 Acute severe thrombocytopenia induced by rivaroxaban in a patient with atrial fibrillation: a case report zhiwei ai, xia liu, xing she, zhixin zhu, cheng wang, gang yang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9393668/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Rivaroxaban, a novel oral direct factor Xa inhibitor, is widely used for preventing thromboembolic complications in patients with non-valvular atrial fibrillation (AF). Bleeding is its most common adverse reaction, while acute severe thrombocytopenia is extremely rare. We report a case of rivaroxaban-induced acute severe thrombocytopenia in an elderly AF patient with multiple comorbidities, aiming to highlight the need for close monitoring of platelet counts during initial anticoagulation and provide clinical insights for managing such rare adverse events. Case Presentation An 82-year-old male with persistent AF and chronic heart failure (NYHA class IV) was admitted to our hospital on January 13, 2025. His medical history included chronic kidney disease (CKD) stage 3, benign prostatic hyperplasia, and pulmonary hypertension. After admission, rivaroxaban 15mg once daily (qd) was initiated for anticoagulation. On the second night of hospitalization, the patient developed sudden epistaxis (≈ 50mL blood loss) and extensive ecchymoses on the limbs and trunk. Emergency complete blood count (CBC) revealed a platelet count of 2×10⁹/L, which dropped to 1×10⁹/L on repeat testing. Rivaroxaban was discontinued immediately, and the patient received platelet transfusion plus thrombopoietic therapy. Comprehensive differential evaluations excluded immune disorders, infections, hematologic diseases, and other etiologies. The platelet count gradually normalized to 95×10⁹/L within 2 weeks, and no bleeding recurrence was observed during 6-month follow-up. Discussion Rivaroxaban-induced thrombocytopenia is a rare adverse reaction with an unclear mechanism, possibly involving immune-mediated platelet destruction or inhibition of thrombin production. This case is consistent with previously reported cases where thrombocytopenia developed shortly after rivaroxaban initiation and resolved promptly upon drug discontinuation. Elderly patients with multiple comorbidities (e.g., CKD) may be at higher risk due to impaired drug metabolism and reduced hematopoietic reserve. Conclusion This case emphasizes that acute severe thrombocytopenia can occur as a rare adverse reaction to rivaroxaban. Clinicians should be vigilant about platelet count changes and bleeding symptoms in elderly AF patients with comorbidities receiving rivaroxaban, especially during the initial treatment phase. Prompt discontinuation of the suspected drug and targeted therapy can lead to favorable outcomes. Rivaroxaban Atrial fibrillation Acute severe thrombocytopenia Adverse drug reaction Anticoagulant therapy Figures Figure 1 Background Atrial fibrillation (AF) is the most common persistent arrhythmia worldwide, with thromboembolic complications representing a major cause of morbidity and mortality [ 1 ]. Novel oral anticoagulants (NOACs), including rivaroxaban-a selective direct factor Xa inhibitor-have become first-line agents for thromboembolism prevention in non-valvular AF due to their high oral bioavailability, rapid onset of action, and no need for routine coagulation monitoring [ 2 ]. Bleeding is the most prevalent adverse reaction to rivaroxaban, while thrombocytopenia is extremely rare, with an estimated incidence of approximately 0.2% [ 3 ]. To date, only a few cases of rivaroxaban-induced thrombocytopenia have been reported in the literature [ 4 – 6 ]. Elderly patients with multiple comorbidities (e.g., chronic kidney disease [CKD]) may face increased risks of adverse drug reactions due to altered drug metabolism and reduced physiological reserve [ 7 ]. Herein, we report a case of acute severe thrombocytopenia in an 82-year-old AF patient with CKD stage 3 shortly after initiating rivaroxaban, aiming to raise clinical awareness of this rare adverse event and provide guidance for safe anticoagulation management. Case Presentation Clinical History An 82-year-old male was admitted to our hospital on January 13, 2025, with the chief complaint of "recurrent dyspnea and palpitations for 8 years, aggravated over 1 month." Eight years prior to admission, the patient developed exertional dyspnea (triggered by brisk walking, slope climbing, or stair ascent) that relieved after 5–10 minutes of rest. Symptoms progressively worsened, with declining exercise tolerance and persistent bilateral lower limb edema. Previous coronary angiography at our hospital showed no abnormalities in the coronary arteries, leading to a diagnosis of: (1) acute exacerbation of chronic heart failure; (2) persistent AF with occasional ventricular premature beats; (3) gastritis; (4) CKD stage 3; (5) benign prostatic hyperplasia (BPH);(6) pulmonary hypertension; (7) pericardial effusion; (8) pleural effusion;(9) pulmonary infection; (10) hypokalemia; and (11) moderate anemia. The patient refused anticoagulant therapy and maintained long-term treatment with aspirin enteric-coated tablets 100mg qd, atorvastatin calcium tablets 20mg qd, furosemide tablets 20mg qd, and spironolactone 20mg qd. One month before admission, the patient experienced unexplained worsening dyspnea and palpitations, which occurred with minimal bed activity. He preferred a high-pillow position, with partial relief after prolonged rest. Associated symptoms included cough with difficult-to-expectorate sputum, chest tightness, poor appetite, fatigue, dizziness, reduced urine output, and pitting edema in both lower extremities. His medical history included BPH (4 years, managed with tamsulosin sustained-release capsules 1 capsule qd and finasteride tablets 1 tablet qd) and CKD (2 years, treated with Uremic Clearance Granules: 1 sachet at 6:00, 12:00, and 18:00; 2 sachets at 22:00). Physical Examination On admission, vital signs were as follows: Temperature 36.5℃, pulse 78 beats/min, respiratory rate 20 breaths/min, blood pressure 130/85 mmHg. The patient was alert and oriented, with mild cyanosis of the lips. Bilateral lung auscultation revealed fine crackles at the lung bases. Cardiac examination showed an irregular rhythm (atrial fibrillation), with a heart rate of 85 beats/min; the first heart sound was of variable intensity, and a grade 2/6 systolic murmur was heard at the mitral valve area. Abdominal examination was unremarkable. Bilateral lower limbs showed pitting edema (grade 2). Diagnostic Findings Baseline Laboratory Investigations Upon admission, the following tests were performed: (1) Complete blood count (CBC): White blood cell count 3.66×10⁹/L, neutrophil percentage 71.3%, red blood cell count 3.11×10¹²/L, hemoglobin 84g/L, platelet count 109×10⁹/L;(2)Renal function: Urea 18.41mmol/L, creatinine 225.01µmol/L, uric acid 569.9µmol/L (estimated glomerular filtration rate [eGFR] 28 mL/min/1.73m², consistent with CKD stage 3); (3)Urinalysis: Proteinuria (1+); fecal occult blood (+); (4)Inflammatory markers: High-sensitivity C-reactive protein (Hs-CRP) 12.69ng/L, procalcitonin (PCT) 4.41ng/mL;(5)Liver function, lipid profile, blood gas analysis, electrolytes, cardiac enzymes, coagulation panel + D-dimer, stool routine, and thyroid function were unremarkable. Imaging and Special Examinations (1) Electrocardiogram (ECG): Atrial fibrillation with slow ventricular rate, ST-T segment changes, right axis deviation, and poor R-wave progression; (2) Echocardiography: Mild mitral valve thickening with anterior leaflet prolapse and moderate regurgitation; left atrial enlargement (42mm); right ventricular enlargement (44mm); severe tricuspid regurgitation (regurgitant pressure gradient 41mmHg, consistent with pulmonary hypertension); mild pulmonary and aortic valve regurgitation; pericardial effusion (posterior pericardial space ≈3mm, right atrial roof space ≈ 11mm); enhanced left ventricular systolic function (fractional shortening [FS] 49%, ejection fraction [EF] 51%) with reduced diastolic function; (3) Chest CT: Mild bilateral pulmonary inflammation; minimal fibrous proliferative lesions in the right lung apex; cardiac enlargement; widened pulmonary trunk; minimal pericardial effusion; aortic and coronary artery wall calcification; mild bilateral pleural effusion with right oblique fissure effusion; (4) Renal ultrasound: Bilateral renal cysts, right perirenal effusion, and increased resistance in both renal arteries. Treatment Course Considering the patient’s persistent AF complicated by heart failure, oral anticoagulation with rivaroxaban 15mg qd was initiated (adjusted for CKD stage 3). On the second night of hospitalization (January 14, 2025), the patient developed sudden epistaxis (≈ 50mL blood loss) and extensive cyanotic ecchymoses on the limbs and trunk. Nasal packing was performed urgently, and an emergency CBC revealed a platelet count of 2×10⁹/L (other parameters: White blood cell count 3.25×10⁹/L, neutrophil percentage 73%, red blood cell count 3.44×10¹²/L, hemoglobin 94g/L). Coagulation profile: Prothrombin time (PT) 25.8s, international normalized ratio (INR) 2.38, activated partial thromboplastin time (APTT) 35.1s, fibrinogen 2.79g/L, thrombin time (TT) 17s, D-dimer 1.88µg/mL. To rule out laboratory error, a repeat CBC was performed immediately, confirming a platelet count of 1×10⁹/L. Rivaroxaban was discontinued immediately, and emergency management was initiated: (1) Administration of 3 therapeutic units of platelet transfusion; (2) Thrombopoiesis-enhancing therapy: (i) Subcutaneous injection of Recombinant Human Thrombopoietin Injection at a dose of 15,000 IU, administered once; (ii) Oral administration of Eltrombopag Olamine Tablets at 25 mg once daily for 1 day, with the dosage increased to 50 mg once daily for the subsequent 12 days. Comprehensive differential evaluations were conducted to identify the cause of thrombocytopenia: (1)Platelet function tests: Arachidonic acid (AA)-induced maximum aggregation rate 9.2%, mean aggregation rate 7.4%, maximum aggregation time 413s, adhesion function 3.1%, effective inhibition rate 90.8%, mean inhibition rate 92.6%; (2)Hematologic cell morphology, viral serology (hepatitis B, hepatitis C, HIV, syphilis), and tumor markers (carcinoembryonic antigen [CEA], alpha-fetoprotein [AFP]) were unremarkable;(3)Flow cytometry: No immune phenotypic abnormalities suggestive of acute leukemia or high-risk myelodysplastic syndrome (MDS); relative proportion of nucleated red blood cells was significantly increased; (3)Abdominal, cervical, axillary, and inguinal ultrasound: Normal spleen size; no deep tissue/organ hematomas, masses, or lymphadenopathy; (4)Autoantibody panel (antinuclear antibody [ANA], anti-double-stranded DNA [dsDNA] antibody, anti-platelet antibody): Negative, excluding immune-mediated thrombocytopenia. Follow-up On day 4 after rivaroxaban discontinuation and initiation of targeted therapy, the patient’s platelet count increased to 41×10⁹/L; by day 8, it reached 81×10⁹/L, with gradual resolution of bleeding symptoms (Fig. 1 ). Within 2 weeks, the platelet count normalized to 95×10⁹/L. At the 3-month follow-up, the patient remained free of bleeding, and platelet counts were stably within the normal range (198 ×10⁹/L). Discussion This case reports an 82-year-old AF patient with CKD stage 3 who developed acute severe thrombocytopenia (minimum count 1×10⁹/L) shortly after initiating rivaroxaban. The diagnosis of rivaroxaban-induced thrombocytopenia was confirmed based on: (1) temporal correlation between drug initiation and adverse reaction onset (symptoms developed 1 day after rivaroxaban administration); (2) rapid resolution of thrombocytopenia after drug discontinuation and targeted therapy; (3) exclusion of alternative etiologies (immune disorders, infections, hematologic diseases, etc.). Rivaroxaban-induced thrombocytopenia is extremely rare, with only 5 cases reported in the literature to date [ 4 – 8 ]. Mima et al. first reported a 75-year-old male with paroxysmal AF who developed thrombocytopenia (37×10⁹/L) after switching from warfarin to rivaroxaban, with rapid recovery after drug discontinuation [ 4 ]. Pop et al. described a 66-year-old male with AF who developed melena and rash due to rivaroxaban-induced thrombocytopenia, which responded well to intravenous immunoglobulin (IVIG) and steroid therapy [ 5 ]. Consistent with these reports, our patient’s thrombocytopenia developed acutely after rivaroxaban initiation and resolved promptly upon drug withdrawal, supporting a drug-related etiology. The mechanism of rivaroxaban-induced thrombocytopenia remains incompletely understood. Two potential pathways have been proposed: (1) Immune-mediated platelet destruction: Rivaroxaban may act as a hapten to induce antibody production against platelets, leading to immune complex formation and platelet clearance [ 9 ]. However, anti-platelet antibodies were negative in our patient, which may be due to the transient nature of antibody production or limitations of the detection assay. (2) Inhibition of thrombin production: Rivaroxaban inhibits factor Xa, which blocks thrombin burst and reduces platelet aggregation [ 10 ]. Thrombin plays a key role in platelet activation and aggregation, and its inhibition may indirectly affect platelet function and survival. Additionally, rivaroxaban may have direct toxic effects on bone marrow megakaryocytes, though this is not supported by previous studies [ 11 ]. Elderly patients with comorbidities (e.g., CKD) are at increased risk of adverse drug reactions. In our case, the patient had CKD stage 3 (eGFR 28 mL/min/1.73m²), which may have impaired rivaroxaban metabolism (approximately 35% of rivaroxaban is excreted via the kidneys) [ 12 ]. Accumulation of the drug may enhance its potential to induce thrombocytopenia. Furthermore, elderly patients often have reduced hematopoietic reserve, making them more susceptible to drug-induced myelosuppression [ 7 ]. This case has important clinical implications. First, clinicians should be vigilant about platelet count changes and bleeding symptoms (e.g., epistaxis, ecchymoses, gastrointestinal bleeding) in elderly AF patients with comorbidities during the initial 1–2 weeks of rivaroxaban therapy. Routine platelet count monitoring is recommended, especially for patients with CKD, anemia, or a history of hematologic disorders. Second, if acute thrombocytopenia or bleeding occurs, rivaroxaban should be discontinued immediately, and comprehensive differential evaluations should be performed to exclude other etiologies. Targeted therapy (e.g., platelet transfusion, rhTPO) should be initiated promptly to prevent life-threatening bleeding. Third, alternative anticoagulants (e.g., dabigatran etexilate, edoxaban) may be considered after resolution of thrombocytopenia, though close monitoring is still required as cross-reactivity cannot be excluded [ 13 ]. Conclusion Acute severe thrombocytopenia is a rare but potentially life-threatening adverse reaction to rivaroxaban. Elderly AF patients with comorbidities (e.g., CKD) are at increased risk and require close monitoring of platelet counts and bleeding signs during initial anticoagulation. Prompt discontinuation of rivaroxaban and targeted therapy can lead to favorable outcomes. Clinicians should be aware of this rare adverse event to ensure safe and effective anticoagulation management. Abbreviations AF Atrial fibrillation NOACs Novel oral anticoagulants CKD Chronic kidney disease CBC Complete blood count eGFR Estimated glomerular filtration rate NYHA New York Heart Association ECG Electrocardiogram CT Computed tomography PT Prothrombin time INR International normalized ratio APTT Activated partial thromboplastin time TT Thrombin time rhTPO Recombinant human thrombopoietin IVIG Intravenous immunoglobulin MDS Myelodysplastic syndrome ANA Antinuclear antibody dsDNA Anti-double-stranded DNA PLT Platelet count BPH Benign prostatic hyperplasia Declarations Ethics approval and consent to participate This case report was approved by the Medical Ethics Committee of Jiangsu Province Hospital Chongqing Hospital. Written informed consent was obtained from the patient for participation in this study. Consent for publication Written informed consent was obtained from the patient for publication of this case report and accompanying clinical data. Competing interests The authors declare that they have no competing interests. Funding The authors declare that no funding was received for this study. Data availability No datasets were generated or analysed during the current study. Author contributions Zhiwei Ai and Gang Yang conceived and designed the study. Zhiwei Ai, Xia Liu, Xing She, Zhixin Zhu and Cheng Wang collected the clinical data and followed up the patient. Zhiwei Ai drafted the manuscript. All authors revised the manuscript and approved the final version for submission. Acknowledgements The authors thank the patient for providing informed consent to publish this case report. We also appreciate the support from the Department of Cardiology and the Clinical Laboratory of Jiangsu Province Hospital Chongqing Hospital for clinical data collection and laboratory testing. References Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22:983–8. Ansell J, Hirsh J, Hylek E et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:160S-198S. Tığlıoğlu M, Akyol P, Sağlam B, et al. Thrombocytopenia due to rivaroxaban: A rare adverse effect. Transfus Apher Sci. 2020;59:102718. Mima Y, Sangatsuda Y, Yasaka M, et al. Acute thrombocytopenia after initiating anticoagulation with rivaroxaban. Intern Med. 2014;53:2649–53. Pop MK, Farokhi F, Iduna L. Drug-induced thrombocytopenia after anticoagulation with rivaroxaban. Am J Emerg Med. 2018;36:e17–8. He X-Y, Bai Y. Acute thrombocytopenia after anticoagulation with rivaroxaban: A case report. World J Clin Cases. 2020;8:5694–700. van den Bemt PMLA, Meyboom RHB, Egberts ACG. Drug-induced immune thrombocytopenia. Drug Saf. 2004;27:1019–32. Tucker M, Padarti A. Thrombocytopenia Due to Direct Oral Anticoagulation and Low-Molecular-Weight Heparin. Cureus. 2021;13:e17562. Carey PJ. Drug-induced myelosuppression: diagnosis and management. Drug Saf. 2003;26:589–602. Kubitza D, Becka M, Wensing G, et al. Safety, pharmacodynamics, and pharmacokinetics of BAY 59-7939–an oral, direct Factor Xa inhibitor–after multiple dosing in healthy male subjects. Eur J Clin Pharmacol. 2005;61:873–80. Kvasnicka T, Malikova I, Zenahlikova Z, et al. Rivaroxaban - Metabolism, Pharmacologic Properties and Drug Interactions. Curr Drug Metab. 2017;18:743–54. Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981–92. Farasatinasab M, Zarei B, Moghtadaei M, et al. Rivaroxaban as an Alternative Agent for Heparin-Induced Thrombocytopenia. J Clin Pharmacol. 2020;60:1464–72. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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-9393668","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":633792868,"identity":"7be44ea6-90f5-43fe-bcaa-eaaeaf346e5c","order_by":0,"name":"zhiwei ai","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA50lEQVRIiWNgGAWjYBACNvb2479/VPyXs79/sPFBQkUNYS18PGcSpBnOMBsz3GA+bPDgzDHCWuQkEgykGVuYExtusKVJPmxhJsJhPAcSjAsb2BIbZ/eYVSQ2sDHwt3cnEPBL44HkmTt4jJtlzpjdSNwhwyBx5uwGgrYc4D0jIdvGkAPUcoaNwUAil4AWiQTDBt42A8YeoJaCxDZmorQYM/O2JSjOkEhLYyBOC8+ZNMYZZw4YG/AcPiyRcOYYD0G/yLe3H2P4UHFAzoC9sfHjj4oaOf72XvxaMAAPacpHwSgYBaNgFGAFABsQTSFn1pHpAAAAAElFTkSuQmCC","orcid":"","institution":"江苏省人民医院重庆医院（重庆市綦江区人民医院）","correspondingAuthor":true,"prefix":"","firstName":"zhiwei","middleName":"","lastName":"ai","suffix":""},{"id":633792869,"identity":"633d2d57-a1e1-4e84-8401-9978da233eae","order_by":1,"name":"xia liu","email":"","orcid":"","institution":"江苏省人民医院重庆医院（重庆市綦江区人民医院）","correspondingAuthor":false,"prefix":"","firstName":"xia","middleName":"","lastName":"liu","suffix":""},{"id":633792870,"identity":"143e7f36-d6a6-40f8-8b68-88a626e14efe","order_by":2,"name":"xing she","email":"","orcid":"","institution":"江苏省人民医院重庆医院（重庆市綦江区人民医院）","correspondingAuthor":false,"prefix":"","firstName":"xing","middleName":"","lastName":"she","suffix":""},{"id":633792875,"identity":"d8dbe0b7-dafa-4360-b39f-297851209bcc","order_by":3,"name":"zhixin zhu","email":"","orcid":"","institution":"江苏省人民医院重庆医院（重庆市綦江区人民医院）","correspondingAuthor":false,"prefix":"","firstName":"zhixin","middleName":"","lastName":"zhu","suffix":""},{"id":633792876,"identity":"6aaaea3c-940c-40fd-9fb2-a773d87fcf03","order_by":4,"name":"cheng wang","email":"","orcid":"","institution":"江苏省人民医院重庆医院（重庆市綦江区人民医院）","correspondingAuthor":false,"prefix":"","firstName":"cheng","middleName":"","lastName":"wang","suffix":""},{"id":633792877,"identity":"25fc46f2-ff6d-48ad-b7ee-6a344c889ff7","order_by":5,"name":"gang yang","email":"","orcid":"","institution":"江苏省人民医院重庆医院（重庆市綦江区人民医院）","correspondingAuthor":false,"prefix":"","firstName":"gang","middleName":"","lastName":"yang","suffix":""}],"badges":[],"createdAt":"2026-04-12 11:08:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9393668/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9393668/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108822467,"identity":"88c106aa-3062-41c3-b31e-ee30dfe42836","added_by":"auto","created_at":"2026-05-08 16:48:49","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":267298,"visible":true,"origin":"","legend":"\u003cp\u003eTimeline of clinical course and platelet count changes\u003c/p\u003e\n\u003cp\u003eFigure 1 illustrates the clinical course of an 82-year-old patient who developed acute severe thrombocytopenia after initiation of rivaroxaban. Rivaroxaban was started on Day 1 for anticoagulation in the setting of atrial fibrillation. On Day 2, the patient developed epistaxis and generalized ecchymoses, with a platelet nadir of 1 × 10⁹/L. Rivaroxaban was immediately discontinued, and platelet transfusion with thrombopoietic therapy was administered. Platelet counts gradually recovered over the subsequent days and normalized within two weeks. No recurrence of thrombocytopenia or bleeding was observed during 6 months of follow-up.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-9393668/v1/01bb0d4e30ce4a3529dad0c7.png"},{"id":108823012,"identity":"756fb6bd-e208-41e3-ad1a-04603d0f4bb4","added_by":"auto","created_at":"2026-05-08 16:51:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":411786,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9393668/v1/0a584699-8e6a-47f5-ad38-0b5c45507d54.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Acute severe thrombocytopenia induced by rivaroxaban in a patient with atrial fibrillation: a case report","fulltext":[{"header":"Background","content":"\u003cp\u003eAtrial fibrillation (AF) is the most common persistent arrhythmia worldwide, with thromboembolic complications representing a major cause of morbidity and mortality [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Novel oral anticoagulants (NOACs), including rivaroxaban-a selective direct factor Xa inhibitor-have become first-line agents for thromboembolism prevention in non-valvular AF due to their high oral bioavailability, rapid onset of action, and no need for routine coagulation monitoring [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBleeding is the most prevalent adverse reaction to rivaroxaban, while thrombocytopenia is extremely rare, with an estimated incidence of approximately 0.2% [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. To date, only a few cases of rivaroxaban-induced thrombocytopenia have been reported in the literature [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Elderly patients with multiple comorbidities (e.g., chronic kidney disease [CKD]) may face increased risks of adverse drug reactions due to altered drug metabolism and reduced physiological reserve [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Herein, we report a case of acute severe thrombocytopenia in an 82-year-old AF patient with CKD stage 3 shortly after initiating rivaroxaban, aiming to raise clinical awareness of this rare adverse event and provide guidance for safe anticoagulation management.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eClinical History\u003c/p\u003e \u003cp\u003eAn 82-year-old male was admitted to our hospital on January 13, 2025, with the chief complaint of \"recurrent dyspnea and palpitations for 8 years, aggravated over 1 month.\"\u003c/p\u003e \u003cp\u003eEight years prior to admission, the patient developed exertional dyspnea (triggered by brisk walking, slope climbing, or stair ascent) that relieved after 5\u0026ndash;10 minutes of rest. Symptoms progressively worsened, with declining exercise tolerance and persistent bilateral lower limb edema. Previous coronary angiography at our hospital showed no abnormalities in the coronary arteries, leading to a diagnosis of: (1) acute exacerbation of chronic heart failure; (2) persistent AF with occasional ventricular premature beats; (3) gastritis; (4) CKD stage 3; (5) benign prostatic hyperplasia (BPH);(6) pulmonary hypertension; (7) pericardial effusion; (8) pleural effusion;(9) pulmonary infection; (10) hypokalemia; and (11) moderate anemia. The patient refused anticoagulant therapy and maintained long-term treatment with aspirin enteric-coated tablets 100mg qd, atorvastatin calcium tablets 20mg qd, furosemide tablets 20mg qd, and spironolactone 20mg qd.\u003c/p\u003e \u003cp\u003eOne month before admission, the patient experienced unexplained worsening dyspnea and palpitations, which occurred with minimal bed activity. He preferred a high-pillow position, with partial relief after prolonged rest. Associated symptoms included cough with difficult-to-expectorate sputum, chest tightness, poor appetite, fatigue, dizziness, reduced urine output, and pitting edema in both lower extremities. His medical history included BPH (4 years, managed with tamsulosin sustained-release capsules 1 capsule qd and finasteride tablets 1 tablet qd) and CKD (2 years, treated with Uremic Clearance Granules: 1 sachet at 6:00, 12:00, and 18:00; 2 sachets at 22:00).\u003c/p\u003e \u003cp\u003ePhysical Examination\u003c/p\u003e \u003cp\u003eOn admission, vital signs were as follows: Temperature 36.5℃, pulse 78 beats/min, respiratory rate 20 breaths/min, blood pressure 130/85 mmHg. The patient was alert and oriented, with mild cyanosis of the lips. Bilateral lung auscultation revealed fine crackles at the lung bases. Cardiac examination showed an irregular rhythm (atrial fibrillation), with a heart rate of 85 beats/min; the first heart sound was of variable intensity, and a grade 2/6 systolic murmur was heard at the mitral valve area. Abdominal examination was unremarkable. Bilateral lower limbs showed pitting edema (grade 2).\u003c/p\u003e \u003cp\u003eDiagnostic Findings\u003c/p\u003e \u003cp\u003eBaseline Laboratory Investigations\u003c/p\u003e \u003cp\u003eUpon admission, the following tests were performed: (1) Complete blood count (CBC): White blood cell count 3.66\u0026times;10⁹/L, neutrophil percentage 71.3%, red blood cell count 3.11\u0026times;10\u0026sup1;\u0026sup2;/L, hemoglobin 84g/L, platelet count 109\u0026times;10⁹/L;(2)Renal function: Urea 18.41mmol/L, creatinine 225.01\u0026micro;mol/L, uric acid 569.9\u0026micro;mol/L (estimated glomerular filtration rate [eGFR] 28 mL/min/1.73m\u0026sup2;, consistent with CKD stage 3); (3)Urinalysis: Proteinuria (1+); fecal occult blood (+); (4)Inflammatory markers: High-sensitivity C-reactive protein (Hs-CRP) 12.69ng/L, procalcitonin (PCT) 4.41ng/mL;(5)Liver function, lipid profile, blood gas analysis, electrolytes, cardiac enzymes, coagulation panel\u0026thinsp;+\u0026thinsp;D-dimer, stool routine, and thyroid function were unremarkable.\u003c/p\u003e \u003cp\u003eImaging and Special Examinations\u003c/p\u003e \u003cp\u003e(1) Electrocardiogram (ECG): Atrial fibrillation with slow ventricular rate, ST-T segment changes, right axis deviation, and poor R-wave progression;\u003c/p\u003e \u003cp\u003e(2) Echocardiography: Mild mitral valve thickening with anterior leaflet prolapse and moderate regurgitation; left atrial enlargement (42mm); right ventricular enlargement (44mm); severe tricuspid regurgitation (regurgitant pressure gradient 41mmHg, consistent with pulmonary hypertension); mild pulmonary and aortic valve regurgitation; pericardial effusion (posterior pericardial space \u0026asymp;3mm, right atrial roof space \u0026asymp;\u0026thinsp;11mm); enhanced left ventricular systolic function (fractional shortening [FS] 49%, ejection fraction [EF] 51%) with reduced diastolic function;\u003c/p\u003e \u003cp\u003e(3) Chest CT: Mild bilateral pulmonary inflammation; minimal fibrous proliferative lesions in the right lung apex; cardiac enlargement; widened pulmonary trunk; minimal pericardial effusion; aortic and coronary artery wall calcification; mild bilateral pleural effusion with right oblique fissure effusion;\u003c/p\u003e \u003cp\u003e(4) Renal ultrasound: Bilateral renal cysts, right perirenal effusion, and increased resistance in both renal arteries.\u003c/p\u003e \u003cp\u003eTreatment Course\u003c/p\u003e \u003cp\u003eConsidering the patient\u0026rsquo;s persistent AF complicated by heart failure, oral anticoagulation with rivaroxaban 15mg qd was initiated (adjusted for CKD stage 3). On the second night of hospitalization (January 14, 2025), the patient developed sudden epistaxis (\u0026asymp;\u0026thinsp;50mL blood loss) and extensive cyanotic ecchymoses on the limbs and trunk. Nasal packing was performed urgently, and an emergency CBC revealed a platelet count of 2\u0026times;10⁹/L (other parameters: White blood cell count 3.25\u0026times;10⁹/L, neutrophil percentage 73%, red blood cell count 3.44\u0026times;10\u0026sup1;\u0026sup2;/L, hemoglobin 94g/L). Coagulation profile: Prothrombin time (PT) 25.8s, international normalized ratio (INR) 2.38, activated partial thromboplastin time (APTT) 35.1s, fibrinogen 2.79g/L, thrombin time (TT) 17s, D-dimer 1.88\u0026micro;g/mL. To rule out laboratory error, a repeat CBC was performed immediately, confirming a platelet count of 1\u0026times;10⁹/L.\u003c/p\u003e \u003cp\u003eRivaroxaban was discontinued immediately, and emergency management was initiated: (1) Administration of 3 therapeutic units of platelet transfusion; (2) Thrombopoiesis-enhancing therapy: (i) Subcutaneous injection of Recombinant Human Thrombopoietin Injection at a dose of 15,000 IU, administered once; (ii) Oral administration of Eltrombopag Olamine Tablets at 25 mg once daily for 1 day, with the dosage increased to 50 mg once daily for the subsequent 12 days.\u003c/p\u003e \u003cp\u003eComprehensive differential evaluations were conducted to identify the cause of thrombocytopenia: (1)Platelet function tests: Arachidonic acid (AA)-induced maximum aggregation rate 9.2%, mean aggregation rate 7.4%, maximum aggregation time 413s, adhesion function 3.1%, effective inhibition rate 90.8%, mean inhibition rate 92.6%; (2)Hematologic cell morphology, viral serology (hepatitis B, hepatitis C, HIV, syphilis), and tumor markers (carcinoembryonic antigen [CEA], alpha-fetoprotein [AFP]) were unremarkable;(3)Flow cytometry: No immune phenotypic abnormalities suggestive of acute leukemia or high-risk myelodysplastic syndrome (MDS); relative proportion of nucleated red blood cells was significantly increased; (3)Abdominal, cervical, axillary, and inguinal ultrasound: Normal spleen size; no deep tissue/organ hematomas, masses, or lymphadenopathy; (4)Autoantibody panel (antinuclear antibody [ANA], anti-double-stranded DNA [dsDNA] antibody, anti-platelet antibody): Negative, excluding immune-mediated thrombocytopenia.\u003c/p\u003e \u003cp\u003eFollow-up\u003c/p\u003e \u003cp\u003eOn day 4 after rivaroxaban discontinuation and initiation of targeted therapy, the patient\u0026rsquo;s platelet count increased to 41\u0026times;10⁹/L; by day 8, it reached 81\u0026times;10⁹/L, with gradual resolution of bleeding symptoms (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Within 2 weeks, the platelet count normalized to 95\u0026times;10⁹/L. At the 3-month follow-up, the patient remained free of bleeding, and platelet counts were stably within the normal range (198 \u0026times;10⁹/L).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case reports an 82-year-old AF patient with CKD stage 3 who developed acute severe thrombocytopenia (minimum count 1\u0026times;10⁹/L) shortly after initiating rivaroxaban. The diagnosis of rivaroxaban-induced thrombocytopenia was confirmed based on: (1) temporal correlation between drug initiation and adverse reaction onset (symptoms developed 1 day after rivaroxaban administration); (2) rapid resolution of thrombocytopenia after drug discontinuation and targeted therapy; (3) exclusion of alternative etiologies (immune disorders, infections, hematologic diseases, etc.).\u003c/p\u003e \u003cp\u003eRivaroxaban-induced thrombocytopenia is extremely rare, with only 5 cases reported in the literature to date [\u003cspan additionalcitationids=\"CR5 CR6 CR7\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Mima et al. first reported a 75-year-old male with paroxysmal AF who developed thrombocytopenia (37\u0026times;10⁹/L) after switching from warfarin to rivaroxaban, with rapid recovery after drug discontinuation [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Pop et al. described a 66-year-old male with AF who developed melena and rash due to rivaroxaban-induced thrombocytopenia, which responded well to intravenous immunoglobulin (IVIG) and steroid therapy [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Consistent with these reports, our patient\u0026rsquo;s thrombocytopenia developed acutely after rivaroxaban initiation and resolved promptly upon drug withdrawal, supporting a drug-related etiology.\u003c/p\u003e \u003cp\u003eThe mechanism of rivaroxaban-induced thrombocytopenia remains incompletely understood. Two potential pathways have been proposed: (1) Immune-mediated platelet destruction: Rivaroxaban may act as a hapten to induce antibody production against platelets, leading to immune complex formation and platelet clearance [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, anti-platelet antibodies were negative in our patient, which may be due to the transient nature of antibody production or limitations of the detection assay. (2) Inhibition of thrombin production: Rivaroxaban inhibits factor Xa, which blocks thrombin burst and reduces platelet aggregation [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Thrombin plays a key role in platelet activation and aggregation, and its inhibition may indirectly affect platelet function and survival. Additionally, rivaroxaban may have direct toxic effects on bone marrow megakaryocytes, though this is not supported by previous studies [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eElderly patients with comorbidities (e.g., CKD) are at increased risk of adverse drug reactions. In our case, the patient had CKD stage 3 (eGFR 28 mL/min/1.73m\u0026sup2;), which may have impaired rivaroxaban metabolism (approximately 35% of rivaroxaban is excreted via the kidneys) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Accumulation of the drug may enhance its potential to induce thrombocytopenia. Furthermore, elderly patients often have reduced hematopoietic reserve, making them more susceptible to drug-induced myelosuppression [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis case has important clinical implications. First, clinicians should be vigilant about platelet count changes and bleeding symptoms (e.g., epistaxis, ecchymoses, gastrointestinal bleeding) in elderly AF patients with comorbidities during the initial 1\u0026ndash;2 weeks of rivaroxaban therapy. Routine platelet count monitoring is recommended, especially for patients with CKD, anemia, or a history of hematologic disorders. Second, if acute thrombocytopenia or bleeding occurs, rivaroxaban should be discontinued immediately, and comprehensive differential evaluations should be performed to exclude other etiologies. Targeted therapy (e.g., platelet transfusion, rhTPO) should be initiated promptly to prevent life-threatening bleeding. Third, alternative anticoagulants (e.g., dabigatran etexilate, edoxaban) may be considered after resolution of thrombocytopenia, though close monitoring is still required as cross-reactivity cannot be excluded [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAcute severe thrombocytopenia is a rare but potentially life-threatening adverse reaction to rivaroxaban. Elderly AF patients with comorbidities (e.g., CKD) are at increased risk and require close monitoring of platelet counts and bleeding signs during initial anticoagulation. Prompt discontinuation of rivaroxaban and targeted therapy can lead to favorable outcomes. Clinicians should be aware of this rare adverse event to ensure safe and effective anticoagulation management.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAtrial fibrillation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNOACs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNovel oral anticoagulants\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCKD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eChronic kidney disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCBC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eComplete blood count\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eeGFR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEstimated glomerular filtration rate\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNYHA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNew York Heart Association\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eECG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eElectrocardiogram\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eComputed tomography\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eProthrombin time\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eINR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInternational normalized ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAPTT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eActivated partial thromboplastin time\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eThrombin time\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003erhTPO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRecombinant human thrombopoietin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIVIG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eIntravenous immunoglobulin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMDS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMyelodysplastic syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eANA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAntinuclear antibody\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003edsDNA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAnti-double-stranded DNA\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePLT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePlatelet count\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBPH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBenign prostatic hyperplasia\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThis case report was approved by the Medical Ethics Committee of Jiangsu Province Hospital Chongqing Hospital. Written informed consent was obtained from the patient for participation in this study.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and accompanying clinical data.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funding was received for this study.\u003c/p\u003e\n\u003cp\u003eData availability\u003c/p\u003e\n\u003cp\u003eNo datasets were generated or analysed during the current study.\u003c/p\u003e\n\u003cp\u003eAuthor contributions\u003c/p\u003e\n\u003cp\u003eZhiwei Ai and Gang Yang conceived and designed the study. Zhiwei Ai, Xia Liu, Xing She, Zhixin Zhu and Cheng Wang collected the clinical data and followed up the patient. Zhiwei Ai drafted the manuscript. All authors revised the manuscript and approved the final version for submission.\u003c/p\u003e\n\u003cp\u003eAcknowledgements\u003c/p\u003e\n\u003cp\u003eThe authors thank the patient for providing informed consent to publish this case report. We also appreciate the support from the Department of Cardiology and the Clinical Laboratory of Jiangsu Province Hospital Chongqing Hospital for clinical data collection and laboratory testing.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk factor for stroke: the Framingham Study. Stroke. 1991;22:983\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAnsell J, Hirsh J, Hylek E et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:160S-198S.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTığlıoğlu M, Akyol P, Sağlam B, et al. Thrombocytopenia due to rivaroxaban: A rare adverse effect. Transfus Apher Sci. 2020;59:102718.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMima Y, Sangatsuda Y, Yasaka M, et al. Acute thrombocytopenia after initiating anticoagulation with rivaroxaban. Intern Med. 2014;53:2649\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePop MK, Farokhi F, Iduna L. Drug-induced thrombocytopenia after anticoagulation with rivaroxaban. Am J Emerg Med. 2018;36:e17\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHe X-Y, Bai Y. Acute thrombocytopenia after anticoagulation with rivaroxaban: A case report. World J Clin Cases. 2020;8:5694\u0026ndash;700.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan den Bemt PMLA, Meyboom RHB, Egberts ACG. Drug-induced immune thrombocytopenia. Drug Saf. 2004;27:1019\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTucker M, Padarti A. Thrombocytopenia Due to Direct Oral Anticoagulation and Low-Molecular-Weight Heparin. Cureus. 2021;13:e17562.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCarey PJ. Drug-induced myelosuppression: diagnosis and management. Drug Saf. 2003;26:589\u0026ndash;602.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKubitza D, Becka M, Wensing G, et al. Safety, pharmacodynamics, and pharmacokinetics of BAY 59-7939\u0026ndash;an oral, direct Factor Xa inhibitor\u0026ndash;after multiple dosing in healthy male subjects. Eur J Clin Pharmacol. 2005;61:873\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKvasnicka T, Malikova I, Zenahlikova Z, et al. Rivaroxaban - Metabolism, Pharmacologic Properties and Drug Interactions. Curr Drug Metab. 2017;18:743\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGranger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFarasatinasab M, Zarei B, Moghtadaei M, et al. Rivaroxaban as an Alternative Agent for Heparin-Induced Thrombocytopenia. J Clin Pharmacol. 2020;60:1464\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Rivaroxaban, Atrial fibrillation, Acute severe thrombocytopenia, Adverse drug reaction, Anticoagulant therapy","lastPublishedDoi":"10.21203/rs.3.rs-9393668/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9393668/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eRivaroxaban, a novel oral direct factor Xa inhibitor, is widely used for preventing thromboembolic complications in patients with non-valvular atrial fibrillation (AF). Bleeding is its most common adverse reaction, while acute severe thrombocytopenia is extremely rare. We report a case of rivaroxaban-induced acute severe thrombocytopenia in an elderly AF patient with multiple comorbidities, aiming to highlight the need for close monitoring of platelet counts during initial anticoagulation and provide clinical insights for managing such rare adverse events.\u003c/p\u003e\u003ch2\u003eCase Presentation\u003c/h2\u003e \u003cp\u003eAn 82-year-old male with persistent AF and chronic heart failure (NYHA class IV) was admitted to our hospital on January 13, 2025. His medical history included chronic kidney disease (CKD) stage 3, benign prostatic hyperplasia, and pulmonary hypertension. After admission, rivaroxaban 15mg once daily (qd) was initiated for anticoagulation. On the second night of hospitalization, the patient developed sudden epistaxis (\u0026asymp;\u0026thinsp;50mL blood loss) and extensive ecchymoses on the limbs and trunk. Emergency complete blood count (CBC) revealed a platelet count of 2\u0026times;10⁹/L, which dropped to 1\u0026times;10⁹/L on repeat testing. Rivaroxaban was discontinued immediately, and the patient received platelet transfusion plus thrombopoietic therapy. Comprehensive differential evaluations excluded immune disorders, infections, hematologic diseases, and other etiologies. The platelet count gradually normalized to 95\u0026times;10⁹/L within 2 weeks, and no bleeding recurrence was observed during 6-month follow-up.\u003c/p\u003e\u003ch2\u003eDiscussion\u003c/h2\u003e \u003cp\u003eRivaroxaban-induced thrombocytopenia is a rare adverse reaction with an unclear mechanism, possibly involving immune-mediated platelet destruction or inhibition of thrombin production. This case is consistent with previously reported cases where thrombocytopenia developed shortly after rivaroxaban initiation and resolved promptly upon drug discontinuation. Elderly patients with multiple comorbidities (e.g., CKD) may be at higher risk due to impaired drug metabolism and reduced hematopoietic reserve.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis case emphasizes that acute severe thrombocytopenia can occur as a rare adverse reaction to rivaroxaban. Clinicians should be vigilant about platelet count changes and bleeding symptoms in elderly AF patients with comorbidities receiving rivaroxaban, especially during the initial treatment phase. Prompt discontinuation of the suspected drug and targeted therapy can lead to favorable outcomes.\u003c/p\u003e","manuscriptTitle":"Acute severe thrombocytopenia induced by rivaroxaban in a patient with atrial fibrillation: a case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-08 16:24:31","doi":"10.21203/rs.3.rs-9393668/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5b8b8da5-4c56-4ba1-b8a4-f52c059c6c5c","owner":[],"postedDate":"May 8th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Rejected","date":"2026-05-07T09:07:15+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-06T18:30:14+00:00","index":50,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-08T16:38:08+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-08 16:24:31","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9393668","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9393668","identity":"rs-9393668","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}