Subscribe to RSS
DOI: 10.1055/s-0037-1614218
Factor V Leiden and Thrombotic Complications in Heparin-induced Thrombocytopenia
Publication History
Received
11 March 1997
Accepted after resubmission
29 August 1997
Publication Date:
08 December 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/199801/lookinside/thumbnails/10-1055-s-0037-1614218-1.jpg)
Summary
To determine whether factor V Leiden is associated with thrombotic events in patients with heparin-induced thrombocytopenia (HIT), we evaluated 165 patients with serologically confirmed HIT for the presence of factor V Leiden and determined the incidence of venous or arterial thrombosis during the period of HIT. Factor V Leiden was detected in 16 of 165 HIT patients (9.7%). HIT-associated venous thrombosis occurred in 11 of 16 factor V Leiden positive subjects and 94 of 149 factor V Leiden negative subjects (69% vs. 63%; p = 0.79). Arterial thrombosis occurred in 1 of 16 factor V Leiden positive subjects and 21 of 149 factor V Leiden negative subjects (6% vs. 14%; p = 0.70). There was no difference in the incidence of proximal limb DVT, pulmonary embolism, venous limb gangrene, local skin reactions, hemorrhagic adrenal infarction, stroke, or myocardial infarction between the groups. No difference in the severity of venous thrombosis between Leiden positive and negative subjects was detected. Our data suggest that in the acute prothrombotic milieu of HIT, heterozygous factor V Leiden is not an important additional risk factor for thrombosis.
-
References
- 1 Warkentin TE, Kelton JG. Interaction of heparin with platelets, including heparin-induced thrombocytopenia.. In: Low-molecular-weight heparins in prophylaxis and therapy of thromboembolic diseases.. Bounameaux H. ed. Marcel Dekker; New York,: 1994. pp 75-127.
- 2 Warkentin TE, Kelton JG. Heparin-induced thrombocytopenia.. Progr Hemost Thromb 1991; 10: 1-34.
- 3 Warkentin TE, Levine MN, Hirsh J, Horsewood P, Roberts RS, Gent M, Kelton JG. Heparin-induced thrombocytopenia in patients treated with low molecular-weight heparin or unfractionated heparin.. N Eng J Med 1995; 332: 1330-5.
- 4 Warkentin TE, Kelton JG. A 14 year study of heparin-induced thrombocytopenia.. Am J Med 1996; 101: 502-7.
- 5 Boshkov LK, Warkentin TE, Hayward CPM, Andrew M, Kelton JG. Heparin-induced thrombocytopenia and thrombosis: clinical and laboratory studies.. Br J Haematol 1993; 84: 322-8.
- 6 Bertina RM, Koeleman BPC, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, van der Velden PA, Reitsma PH. Mutation in blood coagulation factor V associated with resistance to activated protein C.. Nature 1994; 369: 64-7.
- 7 Voorberg J, Roelse J, Koopman R, Büller H, Berends F, ten Cate JW, Mertens K, van Mourik JA. Assocation of idiopathic thromboembolism with single point-mutation at Arg506 of factor V.. Lancet 1994; 343: 1535-6.
- 8 Zöller B, Dahlbäck B. Linkage between inherited resistance to activated protein C and factor V gene mutation in venous thrombosis.. Lancet 1994; 343: 1536-8.
- 9 Zöller B, Svensson PJ, He X, Dahlbäck B. Identification of the same factor V gene mutation in 47 out of 50 thrombosis-prone families with inherited resistance to activated protein C.. J Clin Invest 1994; 94: 2521-4.
- 10 Heeb M, Kojima Y, Greengard J, Griffin JH. Activated protein C resistance: molecular mechanisms based on studies using purified Gln506-factor V.. Blood 1995; 85: 3405-11.
- 11 Koster T, Rosendaal FR, de Ronde H, Briët E, Vanderbrouke JP, Bertina R. Venous thrombosis due to anticoagulant response to activated protein C: Leiden Thrombophilia Study.. Lancet 1993; 342: 1503-6.
- 12 Griffin JH, Evatt B, Wideman C, Fernández JA. Anticoagulant protein C pathway defective in majority of thrombophilic patients.. Blood 1993; 82: 1989-93.
- 13 Svensson PJ, Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis.. N Eng J Med 1994; 330: 517-22.
- 14 Lee DH, Henderson PA, Blajchman MA. Prevalence of factor V Leiden in a Canadian blood donor population.. Can Med Assoc J 1996; 155: 285-9.
- 15 Ridker PM, Hennekens CH, Lindpaintner K, Stampfer MJ, Eisenberg PR, Miletich JP. Mutation in the gene coding for coagulation factor V and the risk of myocardial infarction, stroke, and venous thrombosis in apparently healthy men.. N Engl J Med 1995; 332: 912-7.
- 16 Beauchamp NJ, Martina ED, Hampton KK, Cooper PC, Preston FE, Peake IR. High prevalence of a mutation in the factor V gene within the U.K. population: relationship to activated protein C resistance and familial thrombosis.. Br J Haematol 1994; 88: 219-2.
- 17 Vandenbroucke JP, Koster T, Brïet E, Reitsma PH, Bertina RM, Rosendaal FR. Increased risk of venous thrombosis in oral contraceptive users who are carriers of factor V Leiden mutation.. Lancet 1994; 344: 1453-7.
- 18 Bertina RM, Reitsma PH, Rosendaal FR, Vandenbrouke JP. Resistance to activated protein C and factor V Leiden as risk factors for venous thrombosis.. Thromb Haemost 1995; 74: 449-53.
- 19 Ryan DH, Nuccie BL, Maize B, Arvan DA, Francis CW. Amplification and genotyping of coagulation factor V genomic sequence from stored frozen plasma. (manuscript submitted).
- 20 Warkentin TE. Heparin-induced skin lesions.. Br J Haematol 1996; 92: 494-7.
- 21 Warketin TE, Elavathil LJ, Hayward CPM, Johnston MA, Russett JI, Kelton JG. The pathogenesis of venous limb gangrene associated with heparin-induced thrombocytopenia.. Ann Intern Med 1997; 127: 804-12.
- 22 Warkentin TE, Soutar RL, Panju A, Ginsberg JS. Acute systemic reactions to intravenous bolus heparin therapy: characterization and relationship to heparin-induced thrombocytopenia (abstract).. Blood 1992; 80 (Suppl. 01) 160a.
- 23 Fletcher RH, Fletcher SW, Wagner EH. Clinical Epidemiology.. Williams and Wilkins; Baltimore, MD: 1988
- 24 Makhoul RG, Greenberg CS, McCann RL. Heparin-associated thrombocytopenia and thrombosis: a serious clinical problem and possible solution.. J Vasc Surg 1986; 4: 522-8.
- 25 Bauer KA. Management of patients with hereditary defects predisposing to thrombosis including pregnant women.. Thromb Haemost 1995; 74: 94-100.
- 26 Lane DA, Mannucci PM, Bauer KA, Bertina RM, Bochkov NP, Boulyjenkov V, Chandy M, Dahlbäck B, Ginter EK, Miletich JP, Rosendaal FR, Seligsohn U. Inherited thrombophilia: part 2.. Thromb Haemost 1996; 76: 824-34.
- 27 Warkentin TE. Hemostasis and atherosclerosis.. Can J Cardiol 1995; 11 Suppl C 29C-34C.
- 28 Desmarais S, de Moerloose P, Reber G, Minazio A, Bounameaux H. Resistance to activated protein C in an unselected population of patients with pulmonary embolism.. Lancet 1996; 347: 1374-5.
- 29 Manten B, Westendorp RGJ, Koster T, Reitsma PH, Rosendaal FR. Risk for profiles in patients with different clinical manifestations of venous thromboembolism: A focus on the factor V Leiden mutation.. Thromb Haemost 1996; 76: 510-3.
- 30 Martinelli I, Catteneo M, Panzeri D, Mannucci PM. Low prevalence of factor V:Q506 in patients with isolated pulmonary embolism (abstract).. Blood 1996; 88 (Suppl. 01) 172a.
- 31 Vandenbroucke JP, Koster T, Brïet E, Reitsma PH, Bertina RM, Rosendaal FR. Increased risk of venous thrombosis in oral contraceptive users who are carriers of factor V Leiden mutation.. Lancet 1994; 344: 1453-7.
- 32 Hellgren M, Svensson PJ, Dählback B. Resistance to activated protein C as a basis for venous thromboembolism associated with pregnancy and oral contraceptives.. Am J Obstet Gynecol 1995; 173: 210-3.
- 33 Koeleman BPC, Reitsma PH, Allart CF, Bertina RM. Activated protein C resistance as an additional risk factor for thrombosis in protein C-deficient families.. Blood 1994; 84: 1031-5.
- 34 Ryan DH, Crowther MA, Ginsberg JS, Francis C. Relationship of factor V Leiden genotype to risk of acute deep vein thrombosis following joint replacement therapy.. Ann Intern Med. 1997 in press.
- 35 Donaldson MC, Belkin M, Whittemore AD, Mannick JA, Longtine JA, Dorfman DM. Impact of activated protein C resistance on general vascular surgical patients.. J Vasc Surg 1997; 25: 1054-60.