Hereditary and Acquired Hypercoagulability Questions & Answers

1. Rosendaal FR. Venous thrombosis: a multicausal disease. Lancet. 1999 Apr 3. 353(9159):1167-73. [QxMD MEDLINE Link].

2. Ataga KI. Hypercoagulability and thrombotic complications in hemolytic anemias. Haematologica. 2009 Nov. 94 (11):1481-4. [QxMD MEDLINE Link]. [Full Text].

3. Naik RP, Streiff MB, Haywood C Jr, Nelson JA, Lanzkron S. Venous thromboembolism in adults with sickle cell disease: a serious and under-recognized complication. Am J Med. 2013 May. 126 (5):443-9. [QxMD MEDLINE Link].

4. Iba T, Levy JH, Levi M, Thachil J. Coagulopathy in COVID-19. J Thromb Haemost. 2020 Sep. 18 (9):2103-2109. [QxMD MEDLINE Link]. [Full Text].

5. Kichloo A, Dettloff K, Aljadah M, Albosta M, Jamal S, Singh J, et al. COVID-19 and Hypercoagulability: A Review. Clin Appl Thromb Hemost. 2020 Jan-Dec. 26:1076029620962853. [QxMD MEDLINE Link]. [Full Text].

6. Ranucci M, Ballotta A, Di Dedda U, Bayshnikova E, Dei Poli M, Resta M, et al. The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome. J Thromb Haemost. 2020 Jul. 18 (7):1747-1751. [QxMD MEDLINE Link]. [Full Text].

7. Panigada M, Bottino N, Tagliabue P, Grasselli G, Novembrino C, Chantarangkul V, et al. Hypercoagulability of COVID-19 patients in intensive care unit: A report of thromboelastography findings and other parameters of hemostasis. J Thromb Haemost. 2020 Jul. 18 (7):1738-1742. [QxMD MEDLINE Link]. [Full Text].

8. INSPIRATION Investigators; Parham Sadeghipour et al. Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial. JAMA. 2021 Apr 27. 325 (16):1620-1630. [QxMD MEDLINE Link]. [Full Text].

9. Lopes RD et al. Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial. Lancet. 2021 Jun 12. 397 (10291):2253-2263. [QxMD MEDLINE Link]. [Full Text].

10. [Guideline] ASH Guidelines on Use of Anticoagulation in Patients with COVID-19. American Society of Hematology. July 8, 2021; Accessed: July 11, 2021.

11. Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S. Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination. N Engl J Med. 2021 Jun 3. 384 (22):2092-2101. [QxMD MEDLINE Link]. [Full Text].

12. Kate-Lynn Muir, Avyakta Kallam, Scott A Koepsell, Krishna Gundabolu. Thrombotic Thrombocytopenia after Ad26.COV2.S Vaccination. N Engl J Med. May 20 2021. 384(2):1964-1965. [QxMD MEDLINE Link]. [Full Text].

13. AstraZeneca’s COVID-19 vaccine: EMA finds possible link to very rare cases of unusual blood clots with low blood platelets. European Medicines Agency. 07/04/2021. Available at https://www.ema.europa.eu/en/news/astrazenecas-covid-19-vaccine-ema-finds-possible-link-very-rare-cases-unusual-blood-clots-low-blood.

14. Shimabukuri T, Advisory Committee on Immunization Practices. Update: Thrombosis with thrombocytopenia syndrome (TTS) following COVID-19 vaccination. CDC. Available at https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-05-12/07-COVID-Shimabukuro-508.pdf. May 12, 2021; Accessed: July 11, 2021.

15. Hillarp A, Dahlback B, Zoller B. Activated protein C resistance: from phenotype to genotype and clinical practice. Blood Rev. 1995 Dec. 9(4):201-12. [QxMD MEDLINE Link].

16. Wu KK, Thiagarajan P. Role of endothelium in thrombosis and hemostasis. Annu Rev Med. 1996. 47:315-31. [QxMD MEDLINE Link].

17. Colman-Brochu S. Deep vein thrombosis in pregnancy. MCN Am J Matern Child Nurs. 2004 May-Jun. 29(3):186-92. [QxMD MEDLINE Link].

18. [Guideline] Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb. 141 (2 Suppl):e691S-e736S. [QxMD MEDLINE Link]. [Full Text].

19. Rand JH, Wolgast LR. Antiphospholipid Syndrome. In: Hoffman R, Benz EJ Jr, Silberstein LE, Heslop H, Weitz J, Anastasi J, eds. Hemostasis and Thrombosis. 6th ed. Philadelphia, PA: Elsevier/Saunders; 2013. 2025-38.

20. Ortel TL. Thrombosis and the antiphospholipid syndrome. Hematology Am Soc Hematol Educ Program. 2005. 462-8. [QxMD MEDLINE Link]. [Full Text].

21. Triplett DA. Antiphospholipid antibodies. Clin Adv Hematol Oncol. 2003 Dec. 1(12):726-30. [QxMD MEDLINE Link].

22. Franchini M, Mannucci PM. ABO blood group and thrombotic vascular disease. Thromb Haemost. 2014 Dec. 112 (6):1103-9. [QxMD MEDLINE Link].

23. Heit JA, Cunningham JM, Petterson TM, et al. Genetic variation within the anticoagulant, procoagulant, fibrinolytic and innate immunity pathways as risk factors for venous thromboembolism. J Thromb Haemost. 2011 Jun. 9(6):1133-42. [QxMD MEDLINE Link]. [Full Text].

24. Di Micco P, Scudiero O, Lombardo B, Lodigiani C. Idiopathic Hypereosinophilia and Venous Thromboembolism: Is There a Pathophysiological or Clinical Link? Description of an Intriguing Clinical Case. J Blood Med. 2020. 11:73-76. [QxMD MEDLINE Link]. [Full Text].

25. Eroglu A, Egin Y, Cam R, Akar N. The 19-bp deletion of dihydrofolate reductase (DHFR), methylenetetrahydrofolate reductase (MTHFR) C677T, Factor V Leiden, prothrombin G20210A polymorphisms in cancer patients with and without thrombosis. Ann Hematol. 2009 Jan. 88(1):73-6. [QxMD MEDLINE Link].

26. Mayo Clinic. Activated Protein C Resistance V (APCRV). Mayo Medical Laboratories. Available at http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/81967. Accessed: March 22, 2020.

27. Heit JA. Thrombophilia: common questions on laboratory assessment and management. Hematology Am Soc Hematol Educ Program. 2007. 127-35. [QxMD MEDLINE Link]. [Full Text].

28. Couturaud F, Leroyer C, Julian JA, et al. Factors that predict risk of thrombosis in relatives of patients with unprovoked venous thromboembolism. Chest. 2009 Jul 10. epub ahead of print. [QxMD MEDLINE Link].

29. Lijfering WM, Veeger NJ, Middeldorp S, et al. A lower risk of recurrent venous thrombosis in women compared with men is explained by sex-specific risk factors at time of first venous thrombosis in thrombophilic families. Blood. 2009 Sep 3. 114(10):2031-6. [QxMD MEDLINE Link]. [Full Text].

30. Roberts LN, Patel RK, Arya R. Venous thromboembolism and ethnicity. Br J Haematol. 2009 Aug. 146(4):369-83. [QxMD MEDLINE Link].

31. Hong SN, Yun HC, Yoo JH, Lee SH. Association Between Hypercoagulability and Severe Obstructive Sleep Apnea. JAMA Otolaryngol Head Neck Surg. 2017 Oct 1. 143 (10):996-1002. [QxMD MEDLINE Link].

32. Cushman M. Inherited risk factors for venous thrombosis. Hematology Am Soc Hematol Educ Program. 2005. 452-7. [QxMD MEDLINE Link]. [Full Text].

33. Aiach M, Emmerrich J. Thrombophilia genetics. Colman RW, Marder VJ, Clowes AW, et al, eds. Hemostasis and Thrombosis. 5th ed. Philadelphia, Pa: Lippincott, Williams and Wilkins; 2006. 779-93.

34. Colucci G, Tsakiris DA. Thrombophilia Screening. Clin Appl Thromb Hemost. 2017 Jan 1. 1076029616683803. [QxMD MEDLINE Link].

35. Pruthi RK. Optimal utilization of thrombophilia testing. Int J Lab Hematol. 2017 May. 39 Suppl 1:104-110. [QxMD MEDLINE Link].

36. van Ommen CH, Nowak-Göttl U. Inherited Thrombophilia in Pediatric Venous Thromboembolic Disease: Why and Who to Test. Front Pediatr. 2017. 5:50. [QxMD MEDLINE Link]. [Full Text].

37. Straczek C, Oger E, Yon de Jonage-Canonico MB, et al. Prothrombotic mutations, hormone therapy, and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration. Circulation. 2005 Nov 29. 112(22):3495-500. [QxMD MEDLINE Link]. [Full Text].

38. Urbanus RT, de Groot PG. Antiphospholipid antibodies--we are not quite there yet. Blood Rev. 2011 Mar. 25(2):97-106. [QxMD MEDLINE Link].

39. Bates SM. Management of pregnant women with thrombophilia or a history of venous thromboembolism. Hematology Am Soc Hematol Educ Program. 2007. 143-50. [QxMD MEDLINE Link]. [Full Text].

40. Connors JM. Thrombophilia Testing and Venous Thrombosis. N Engl J Med. 2017 Dec 7. 377 (23):2298. [QxMD MEDLINE Link]. [Full Text].

41. Douketis J, Tosetto A, Marcucci M, et al. Risk of recurrence after venous thromboembolism in men and women: patient level meta-analysis. BMJ. 2011 Feb 24. 342:d813. [QxMD MEDLINE Link]. [Full Text].

42. Kearon C, Julian JA, Kovacs MJ, et al. Influence of thrombophilia on risk of recurrent venous thromboembolism while on warfarin: results from a randomized trial. Blood. 2008 Dec 1. 112(12):4432-6. [QxMD MEDLINE Link]. [Full Text].

43. Hirsh J, Raschke R. Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep. 126(3 suppl):188S-203S. [QxMD MEDLINE Link]. [Full Text].

44. Rühle F, Stoll M. Advances in predicting venous thromboembolism risk in children. Br J Haematol. 2017 Dec 19. 82 (1):25-6. [QxMD MEDLINE Link].

45. Warkentin TE. Agents for the treatment of heparin-induced thrombocytopenia. Hematol Oncol Clin North Am. 2010 Aug. 24(4):755-75, ix. [QxMD MEDLINE Link].

46. Robert D McBane 2nd 1 2 3, Waldemar E Wysokinski 1 2 3, Jennifer G Le-Rademacher 4, Tyler Zemla 4, Aneel Ashrani 1 2, Alfonso Tafur 5, et al. Apixaban and dalteparin in active malignancy-associated venous thromboembolism: The ADAM VTE trial. J Thromb Haemost . Feb 20 2020. 18(2):411-421. [QxMD MEDLINE Link]. [Full Text].

47. Young AM, Marshall A, Thirlwall J, Chapman O, Lokare A, Hill C, et al. Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D). J Clin Oncol. 2018 Jul 10. 36 (20):2017-2023. [QxMD MEDLINE Link]. [Full Text].

48. Raskob GE, van Es N, Verhamme P, Carrier M, Di Nisio M, Garcia D, et al. Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism. N Engl J Med. 2018 Feb 15. 378 (7):615-624. [QxMD MEDLINE Link]. [Full Text].

49. Adam SS, McDuffie JR, Lachiewicz PF, Ortel TL, Williams JW. Comparative Effectiveness of Newer Oral Anticoagulants and Standard Anticoagulant Regimens for Thromboprophylaxis in Patients Undergoing Total Hip or Knee Replacement [Internet]. VA Evidence-based Synthesis Program Reports. 2012 Dec. [QxMD MEDLINE Link].

50. Perez A, Merli GJ. Novel Anticoagulant Use for Venous Thromboembolism: A 2013 Update. Curr Treat Options Cardiovasc Med. 2013 Feb 6. [QxMD MEDLINE Link].

51. Dobesh PP, Oestreich JH. Novel Direct-Acting Anticoagulants for Risk Reduction in ACS. J Pharm Pract. 2012 Nov 19. [QxMD MEDLINE Link].

52. Merli GJ. The new oral anticoagulants: a challenge for hospital formularies. Hosp Pract (Minneap). 2012 Aug. 40(3):126-8. [QxMD MEDLINE Link].

53. Komócsi A, Vorobcsuk A, Kehl D, Aradi D. Use of new-generation oral anticoagulant agents in patients receiving antiplatelet therapy after an acute coronary syndrome: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. 2012 Nov 12. 172(20):1537-45. [QxMD MEDLINE Link].

54. Kar S, Bhatt DL. Anticoagulants for the treatment of acute coronary syndrome in the era of new oral agents. Coron Artery Dis. 2012 Sep. 23(6):380-90. [QxMD MEDLINE Link].

55. Rajasekhar A, Beyth R, Crowther MA. Newer anticoagulants in critically ill patients. Crit Care Clin. 2012 Jul. 28(3):427-51, vii. [QxMD MEDLINE Link].

56. Lee AY. Treatment of established thrombotic events in patients with cancer. Thromb Res. 2012 Apr. 129 Suppl 1:S146-53. [QxMD MEDLINE Link].

57. Cohen AT, Gurwith MM, Dobromirski M. Thromboprophylaxis in non-surgical cancer patients. Thromb Res. 2012 Apr. 129 Suppl 1:S137-45. [QxMD MEDLINE Link].

58. Vande Griend JP, Marcum ZA, Linnebur SA. A year in review: new drugs for older adults in 2011. Am J Geriatr Pharmacother. 2012 Aug. 10(4):258-63. [QxMD MEDLINE Link].

59. Burke DA, Warraich HJ, Pinto DS. Which antithrombin for whom? Identifying the patient population that benefits most from novel antithrombin agents. Curr Cardiol Rep. 2012 Aug. 14(4):493-501. [QxMD MEDLINE Link].

60. Di Nisio M, Middeldorp S, Büller HR. Direct thrombin inhibitors. N Engl J Med. 2005 Sep 8. 353 (10):1028-40. [QxMD MEDLINE Link].

61. Baglin T, Barrowcliffe TW, Cohen A, Greaves M. Guidelines on the use and monitoring of heparin. Br J Haematol. 2006 Apr. 133(1):19-34. [QxMD MEDLINE Link]. [Full Text].

62. Harenberg J. Is laboratory monitoring of low-molecular-weight heparin therapy necessary? Yes. J Thromb Haemost. 2004 Apr. 2(4):547-50. [QxMD MEDLINE Link]. [Full Text].

63. Bounameaux H, de Moerloose P. Is laboratory monitoring of low-molecular-weight heparin therapy necessary? No. J Thromb Haemost. 2004 Apr. 2(4):551-4. [QxMD MEDLINE Link]. [Full Text].

64. [Guideline] Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb. 141 (2 Suppl):e419S-94S. [QxMD MEDLINE Link]. [Full Text].

65. [Guideline] Kitchen S, Gray E, Mackie I, Baglin T, Makris M, BCSH committee. Measurement of non-coumarin anticoagulants and their effects on tests of Haemostasis: Guidance from the British Committee for Standards in Haematology. Br J Haematol. 2014 Sep. 166 (6):830-41. [QxMD MEDLINE Link]. [Full Text].

66. Cho L, Kottke-Marchant K, Lincoff AM, et al. Correlation of point-of-care ecarin clotting time versus activated clotting time with bivalirudin concentrations. Am J Cardiol. 2003 May 1. 91(9):1110-3. [QxMD MEDLINE Link].

67. Welsby IJ, McDonnell E, El-Moalem H, Stafford-Smith M, Toffaletti JG. Activated clotting time systems vary in precision and bias and are not interchangeable when following heparin management protocols during cardiopulmonary bypass. J Clin Monit Comput. 2002 Jul. 17(5):287-92. [QxMD MEDLINE Link].

68. Chang LC, Lee HF, Yang Z, Yang VC. Low molecular weight protamine (LMWP) as nontoxic heparin/low molecular weight heparin antidote (I): preparation and characterization. AAPS PharmSci. 2001. 3(3):E17. [QxMD MEDLINE Link].

69. Schick BP, Maslow D, Moshinski A, San Antonio JD. Novel concatameric heparin-binding peptides reverse heparin and low-molecular-weight heparin anticoagulant activities in patient plasma in vitro and in rats in vivo. Blood. 2004 Feb 15. 103(4):1356-63. [QxMD MEDLINE Link]. [Full Text].

70. Pollack CV Jr, Reilly PA, van Ryn J, Eikelboom JW, Glund S, Bernstein RA, et al. Idarucizumab for Dabigatran Reversal - Full Cohort Analysis. N Engl J Med. 2017 Aug 3. 377 (5):431-441. [QxMD MEDLINE Link]. [Full Text].

71. Momin JH, Candidate P, Hughes GJ. Andexanet Alfa (Andexxa^®) for the Reversal of Direct Oral Anticoagulants. P T. 2019 Sep. 44 (9):530-549. [QxMD MEDLINE Link]. [Full Text].

72. Welsby IJ, Stafford-Smith M. Monitoring direct thrombin inhibitors: time for standardization. Anesthesiology. 2004 Oct. 101(4):1048-9. [QxMD MEDLINE Link].

73. Weitz JI. New anticoagulants for treatment of venous thromboembolism. Circulation. 2004 Aug 31. 110(9 suppl 1):I19-26. [QxMD MEDLINE Link]. [Full Text].

74. Connors JM. Antidote for Factor Xa Anticoagulants. N Engl J Med. 2015 Dec 17. 373 (25):2471-2. [QxMD MEDLINE Link]. [Full Text].

75. Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet. 2010 Mar 6. 375(9717):807-15. [QxMD MEDLINE Link].

76. Romualdi E, Ageno W. Oral Xa inhibitors. Hematol Oncol Clin North Am. 2010 Aug. 24(4):727-37, viii-ix. [QxMD MEDLINE Link].

77. Medi C, Hankey GJ, Freedman SB. Stroke risk and antithrombotic strategies in atrial fibrillation. Stroke. 2010 Nov. 41(11):2705-13. [QxMD MEDLINE Link].

78. Becattini C, Lignani A, Agnelli G. New anticoagulants for the prevention of venous thromboembolism. Drug Des Devel Ther. 2010. 4:49-60. [QxMD MEDLINE Link].

79. Desai SS, Massad MG, DiDomenico RJ, et al. Recent developments in antithrombotic therapy: will sodium warfarin be a drug of the past?. Recent Pat Cardiovasc Drug Discov. 2006 Nov. 1(3):307-16. [QxMD MEDLINE Link].

80. Hanley JP. Warfarin reversal. J Clin Pathol. 2004 Nov. 57(11):1132-9. [QxMD MEDLINE Link]. [Full Text].

81. Keeney M, Allan DS, Lohmann RC, Yee IH. Effect of activated recombinant human factor 7 (Niastase) on laboratory testing of inhibitors of factors VIII and IX. Lab Hematol. 2005. 11(2):118-23. [QxMD MEDLINE Link].

82. Malherbe S, Tsui BC, Stobart K, Koller J. Argatroban as anticoagulant in cardiopulmonary bypass in an infant and attempted reversal with recombinant activated factor VII. Anesthesiology. 2004 Feb. 100(2):443-5. [QxMD MEDLINE Link].

83. Powner DJ, Hartwell EA, Hoots WK. Counteracting the effects of anticoagulants and antiplatelet agents during neurosurgical emergencies. Neurosurgery. 2005 Nov. 57(5):823-31; discussion 823-31. [QxMD MEDLINE Link].

Manojna Konda, MD Fellow in Hematology and Oncology, University of Arkansas for Medical Sciences College of Medicine

Manojna Konda, MD is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Paulette Mehta, MD, MPH Professor, Division of Hematology/Oncology and Palliative Care and Hospice Medicine, Department of Internal Medicine, University Arkansas for Medical Sciences College of Medicine and Central Arkansas Veterans Hospital System

Paulette Mehta, MD, MPH is a member of the following medical societies: American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, Association of VA Hematology/Oncology, National Cancer Institute

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ronald A Sacher, MD, FRCPC, DTM&H Professor Emeritus of Internal Medicine and Hematology/Oncology, Emeritus Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MD, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Srikanth Nagalla, MD, MS, FACP Chief of Benign Hematology, Miami Cancer Institute, Baptist Health South Florida; Clinical Professor of Medicine, Florida International University, Herbert Wertheim College of Medicine

Srikanth Nagalla, MD, MS, FACP is a member of the following medical societies: American Society of Hematology, Association of Specialty Professors

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Alexion; Alnylam; Kedrion; Sanofi; Dova; Apellis; Pharmacosmos<br/>Serve(d) as a speaker or a member of a speakers bureau for: Sobi; Sanofi; Rigel.

Paul Schick, MD † Emeritus Professor, Department of Internal Medicine, Jefferson Medical College of Thomas Jefferson University; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital

Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology

Disclosure: Nothing to disclose.

Pradyumna D Phatak, MBBS, MD Chair, Division of Hematology and Medical Oncology, Rochester General Hospital; Clinical Professor of Oncology, Roswell Park Cancer Institute

Pradyumna D Phatak, MBBS, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching.

Barbara P Schick, PhD 

Disclosure: Nothing to disclose.

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