Research Article

Incidence and features of heparin-induced thrombocytopenia in mechanical heart valves and immunologic cardiac diseases

Manzoor H Mangi*, Ulrich Stock, Kanval Ali, Eftychia Galiatsou, Visuvanathan Jeyakumar, Ana Hurtado Doce, Paul Harris and Sunil K Bhudia

Published: 05 January, 2022 | Volume 6 - Issue 1 | Pages: 001-008

Background: Heparin-induced thrombocytopenia/thrombosis (HIT/T) is characterized by a fall in platelet count 5-10days after starting heparin therapy and is diagnosed with specific 4-T clinical features and laboratory tests. This complication is relatively common in Cardiothoracic surgery patients. 
Objective: To evaluate the positive and negative predictive value of various HIT laboratory tests and assess any correlation between HIT, the underlying diagnosis, underlying procedure, and mechanical cardiac devices. 
Patients and methods: The patient’s medical records were correlated with two laboratories HIT diagnostic tests, the pan-specific screening test with IgG, IgA, and IgM antibodies, followed by HIT specific IgG ELISA. 
Results: Total n = 80 patients were assessed, 48% (n = 38) were HIT screen pan-specific negative and 50% (n = 40) were HIT pan-specific positive and 2 cases were inconclusive. 17% 
(n = 14) were both pan-specific and specific HIT IgG ELISA positive. There were 5 atypical cases. One patient had Eosinophilic myocarditis and was HIT ELISA IgG neg. Argatroban was given on clinical grounds with successful recovery. One patient with Sarcoidosis had an aggressive course and received IV Immunoglobulin (IVIG) but succumbed secondary to liver failure. One patient progressed to gut ischemia and had surgical intervention but succumbed. Two patients with mechanical heart valves were on Argatroban but relapsed and responded to IVIG therapy. 
Conclusion: Our study indicates that 9/16 (> 50%) HIT-positive patients had valve replacement or cardiac devices suggesting that like knee arthroplasty there is a high incidence of HIT in patients with mechanical heart valves and cardiac devices and this warrants further prospective study. 

Read Full Article HTML DOI: 10.29328/journal.ach.1001028 Cite this Article Read Full Article PDF


Heparin Induced Thrombocytopenia (HIT); Thrombosis; Cardiothoracic surgery; Mechanical heart valves (MVR); Immune Thrombocytopenia (ITP)


  1. Greinacher A. Heparin-Induced Thrombocytopenia. N Engl J Med. 2015; 373: 1883-1884. PubMed: https://pubmed.ncbi.nlm.nih.gov/26535525/
  2. Linkins LA, Dans AL, Moores LK, Bona R, Davidson BL, et al. Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012; 141: e495S–530S. PubMed: https://pubmed.ncbi.nlm.nih.gov/22315270/
  3. Cuker A, Gowthami MA, Chong BH, Cines DB, Greinacher A, et al. American Society of Hematology guidelines for management of venous thromboembolism: Heparin-induced thrombocytopenia. Blood Adv. 2018; 2: 3360–3392. PubMed: https://pubmed.ncbi.nlm.nih.gov/30482768/
  4. Warkentin TE, Greinacher A. Heparin-Induced Thrombocytopenia and Cardiac Surgery. Ann Thorac Surg. 2003; 76: 2121–2131. PubMed: https://pubmed.ncbi.nlm.nih.gov/14667668/
  5. Everett BM, Yeh R, Foo SY, Criss D, Van Cott EM, et al. Prevalence of Heparin/Platelet Factor 4 Antibodies. Before and After Cardiac Surgery. Ann Thorac Surg. 2007; 83: 592–597. PubMed: https://pubmed.ncbi.nlm.nih.gov/17257993/
  6. Squiccimarro E, Jiritano F, Serraino GF, ten Cate H, Paparella D, et al. Quantitative and Qualitative Platelet Derangements in Cardiac Surgery and Extracorporeal Life Support. J Clin Med. 2021; 10: 615. PubMed: https://pubmed.ncbi.nlm.nih.gov/33561947/
  7. Husseinzadeh HD, Gimotty PA, Pishko AM, Buckley M, Warkentin TE, et al. Diagnostic accuracy of IgG-specific versus poly-specific enzyme-linked immunoassays in heparin-induced thrombocytopenia: a systematic review and meta-analysis. J Thromb Haemost. 2017; 15: 1203-1212. PubMed: https://pubmed.ncbi.nlm.nih.gov/28374939/
  8. Sahu KK, Jindal V, Anderson J, Siddiqui AD, Jaiyesimi IA. Current Perspectives on Diagnostic Assays and Anti-PF4 Antibodies for the Diagnosis of Heparin-Induced Thrombocytopenia. J Blood Med. 2020; 11: 267–277. PubMed: https://pubmed.ncbi.nlm.nih.gov/32884385/
  9. Cines DB, Bussell JB. SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia. N Engl J Med. 2021; 384: 2254-2256.PubMed: https://pubmed.ncbi.nlm.nih.gov/33861524/
  10. Pandya KA, Johnson EG, Davis GA, Padmanabhan A. Serotonin release assay (SRA) negative HIT: a newly recognized entity: implications for diagnosis and management. Thromb Res. 2018; 172: 169‐PubMed: https://pubmed.ncbi.nlm.nih.gov/30419472/
  11. Warkentin TE. Laboratory diagnosis of heparin‐induced thrombocytopenia. Int J Lab Hematol. 2019; 41: 15-25.PubMed: https://pubmed.ncbi.nlm.nih.gov/31069988/
  12. Padmanabhan A, Jones CG, Curtis BR, Bougie DW, Sullivan MJ, et al. A novel PF4‐dependent platelet activation assay identifies patients likely to have heparin‐induced thrombocytopenia/ thrombosis. Chest. 2016; 150: 506‐PubMed: https://pubmed.ncbi.nlm.nih.gov/26905366/
  13. Vayne C, Guery EA, Kizlik-Masson C, Rollin J, Bauters A, et al. Beneficial effect of exogenous platelet factor 4 for detecting pathogenic heparin-induced thrombocytopenia antibodies. Br J Haematol. 2017; 179: 811-819. PubMed: https://pubmed.ncbi.nlm.nih.gov/29048130/
  14. Vayne C, Rollin J, Gruel Y, Pouplard C, Galinat H, et al. PF4 Immunoassays in Vaccine-Induced Thrombotic Thrombocytopenia. N Engl J Med. 385: 376-378.PubMed: https://pubmed.ncbi.nlm.nih.gov/34010527/
  15. Halsall DJ, Mangi, Soos M, Fahie-Wilson MN, Wark G, et al. Hypoglycemia due to an Insulin Binding Antibody in a Patient with an IgA-Myeloma. J Clin Endocrinol Metab. 2007; 92: 2013–2016. PubMed: https://pubmed.ncbi.nlm.nih.gov/17405845/
  16. Poulsen LK, Jensen BM, Esteban V, Garvey LH. Beyond IgE—When Do IgE-Crosslinking and Effector Cell Activation Lead to Clinical Anaphylaxis? Front Immunol. 2017; 8: 871. PubMed: https://pubmed.ncbi.nlm.nih.gov/28848540/
  17. Thi-Huong, Nguyen TH. Not Only Heparin but Also Antibody Induces thrombocytopenia. Book Chapter 3. 2018.
  18. Ahmed M, Habis S, Samotwoka M, Mahmoud A, Chin M. Mesenteric Ischemia Caused by Heparin-induced Thrombocytopenia: A Case Report. Cureus. 2019; 11: e3900. PubMed: https://pubmed.ncbi.nlm.nih.gov/30911456/
  19. Greinacher A. Me or not me? The danger of spontaneity. Blood. 2014; 123: 3536-3538.
  20. Warkentin TE. Knee replacement and HIT without heparin: Blood. 2016; 127: 961–962.
  21. Bito S, Miyata S, Migita K, Nakamura M, Shinohara K, et al. Mechanical prophylaxis is a heparin-independent risk for antiplatelet factor 4/heparin antibody formation after orthopedic surgery. Blood. 2016; 127: 1036-1043. PubMed: https://pubmed.ncbi.nlm.nih.gov/26659923/
  22. Burch M, Cooper B. Fondaparinux-associated heparin-induced thrombocytopenia. Proc (Bayl Univ Med Cent). 2012; 25: 13–15. PubMed: https://pubmed.ncbi.nlm.nih.gov/22275775/
  23. Olevsky O, Rosove MH. Spontaneous Heparin-Induced Thrombocytopenia and Thrombosis After Total Knee Arthroplasty: A Report of 2 Cases. Arthroplasty Today. 2021; 9: 50-52. PubMed: https://pubmed.ncbi.nlm.nih.gov/34026990/
  24. Swarup S, Kopel J, Yendala R, Thirumala S, Quick DP. Spontaneous Heparin-Induced Thrombocytopenia HIT following curettage and bone graft of femur in a patient with monostatic fibrous dysplasia. J Thrombosis Res. 2020; 196: 75-77. PubMed: https://pubmed.ncbi.nlm.nih.gov/32853979/
  25. Warkentin TE, Kelton JG. Delayed‐onset heparin‐induced thrombocytopenia and thrombosis. Ann Intern Med. 2001; 135: 502‐PubMed: https://pubmed.ncbi.nlm.nih.gov/11578153/
  26. Kopolovic I, Warkentin TE. Progressive thrombocytopenia after cardiac surgery in a 67‐year‐old man. CMAJ. 2014; 186: 929‐PubMed: https://pubmed.ncbi.nlm.nih.gov/24756626/
  27. Padmanabhan A, Jones CG, Pechauer SM, Curtis BR, Bougie DW, et al. IVIg for treatment of severe refractory heparin‐induced thrombocytopenia. Chest. 2017; 152: 478‐PubMed: https://pubmed.ncbi.nlm.nih.gov/28427966/
  28. Warkentin TE, Anderson JAM. How I treat patients with a history of heparin-induced thrombocytopenia. Blood. 2016; 128: 348-359. PubMed: https://pubmed.ncbi.nlm.nih.gov/27114458/
  29. Warkentin TE, Greinacher A. Spontaneous HIT syndrome: Knee replacement, infection, and parallels with vaccine-induced immune thrombotic thrombocytopenia. Thromb Res. 2021; 204: 40–51. PubMed: https://pubmed.ncbi.nlm.nih.gov/34144250/
  30. Ali K, PalomoLopez N, Jeyakumar V, Hurtado Doce A, Mangi M. Unusual laboratory features and clinical course of Heparin induced thrombocytopenia in cardiothoracic patients. EHA 2021 virtual congress 9-17 June 2021, abstract presentation. Hemasphere. 2021; S52: 543-a.
  31. Bucke D, Alizadeh K, Hallam S. COVID-19 complicated by immune thrombocytopaenic purpura and internal jugular vein thrombosis. BMJ Case Rep. 2021; 14: e243680. PubMed: https://pubmed.ncbi.nlm.nih.gov/34285032/
  32. Thrombosis with Thrombocytopenia Syndrome (also termed Vaccine-induced Thrombotic Thrombocytopenia).2021. https://www.hematology.org/covid-19/vaccine-induced-immune-thrombotic-thrombocytopenia  
  33. Pibarot P, Dumesnil JG.Prosthetic Heart Valves Selection of the Optimal Prosthesis and Long-Term Management. Circulation 2009; 119: 1034-1048. PubMed: https://pubmed.ncbi.nlm.nih.gov/19237674/
  34. https://idataresearch.com/over-182000-heart-valve-replacements-per-year-in-the-united-states/
  35. Hogan M, Berger SJ. Heparin-induced thrombocytopenia (HIT): Review of incidence, diagnosis, and management. Vascu Med. 2020; 25: 160–173. PubMed: https://pubmed.ncbi.nlm.nih.gov/32195628/


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