Unfractionated heparin compared with low-molecular-weight heparin as related to heparin-induced thrombocytopenia

Current Opinion in Pulmonary Medicine

Volumn 11, Issue 5, 2005, Pages 385-391

  Walenga, Jeanine M ^a   Prechel, Margaret ^a   Jeske, Walter P ^a   Bakhos, Mamdouh ^a  

^a LOYOLA UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Antibody; Heparin; Heparin induced thrombocytopenia; Low molecular weight heparin; Platelets

Indexed keywords

HEPARIN; IMMUNOGLOBULIN A; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M; LOW MOLECULAR WEIGHT HEPARIN; THROMBOCYTE FACTOR 4;

ANTIBODY PRODUCTION; COMPARATIVE STUDY; DISEASE COURSE; DISEASE SEVERITY; HUMAN; HYPERCOAGULABILITY; IMMUNE RESPONSE; INFLAMMATION; PATHOPHYSIOLOGY; REVIEW; RISK FACTOR; SENSITIZATION; THROMBOCYTE COUNT; THROMBOCYTOPENIA;

EID: 24744442783     PISSN: 10705287     EISSN: 15316971     Source Type: Journal    
DOI: 10.1097/01.mcp.0000174232.78219.03     Document Type: Review

References (73)

1. Amiral J, Bridey F, Dreyfus M, et al. PF4 complexed to heparin is the target for antibodies generated in heparin-induced thrombocytopenia. Thromb Haemost 1992; 68:95-96.
2. Kelton JG, Smith JW, Warkentin TE, et al. Immunoglobulin G from patients with heparin-induced thrombocytopenia binds to a complex of heparin and platelet factor 4. Blood 1994; 83:3232-3239.
3. Greinacher A, Pötzsch B, Amiral J, et al. Heparin-associated thrombocytopenia: isolation of the antibody and characterization of a multimolecular PF4-heparin complex as the major antigen. Thromb Haemost 1994; 71:247-251.
4. Amiral J, Wolf M, Fischer A-M, et al. Pathogenicity of IgA and/or IgM antibodies to heparin-PF4 complexes in patients with heparin-associated thrombocytopenia. Br J Haematol 1996; 92:954.
5. Kelton JG, Sheridan D, Santos A, et al. Heparin-induced thrombocytopenia: laboratory studies. Blood 1988; 72:925-930.
6. Jeske WP, Walenga JM, Szatkowski E, et al. Effect of glycoprotein IIb/IIIa antagonists on the HIT serum induced activation of platelets. Thromb Res 1997; 88:271-281.
7. Newman PM, Chong B. Heparin-induced thrombocytopenia: new evidence for the dynamic binding of purified anti-PF4-heparin antibodies to platelets and the resultant platelet activation. Blood 2000; 96:182-187.
8. Warkentin TE, Hayward CPM, Boshkov LK, et al. Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia. Blood 1994; 84:3691-3699.
9. Jeske WP, Vasaiwala S, Schlenker R, et al. Leukocytes activation in heparin-induced thrombocytopenia. Blood 2000; 96:29b.
10. Pouplard C, Lochmann S, Renard B, et al. Induction of monocyte tissue factor expression by antibodies to heparin-platelet factor 4 complexes developed in heparin-induced thrombocytopenia. Blood 2001; 97:3300-3302.
11. Blank M, Shoenfeld Y, Tavor S, et al. Anti-platelet factor 4/heparin antibodies from patients with heparin-induced thrombocytopenia provoke direct activation of microvascular endothelial cells. Int Immunol 2002; 14:121-129.
12. Walenga JM, Jeske WP, Prechel MM, Bakhos M. Newer insights on the mechanism of heparin-induced thrombocytopenia. Semin Thromb Hemost 2004; 30(Suppl 1):57-67. This paper reviews the mechanisms of heparin-induced thrombocytopenia.
13. Herbert JM, Savi P, Jeske WP, Walenga JM. Effect of SR121566A, a potent GPIIb/IIIa antagonist, on the HIT serum/heparin-induced platelet mediated activation of human endothelial cells. Thromb Haemost 1998; 80:326-331.
14. Walenga JM, Michal K, Hoppensteadt D, et al. Vascular damage correlates between heparin-induced thrombocytopenia and the antiphospholipid syndrome. Clin Appl Thromb Hemost 1999; (Suppl 1):S56-S62.
15. Fareed J, Walenga JM, Hoppensteadt DA, et al. Selectins in the HIT syndrome: pathophysiologic role and therapeutic modulation. Semin Thromb Hemost 1999; 25(Suppl 1):37-42.
16. Visentin GP, Ford SE, Scott PJ, Aster RH. Antibodies from patients with heparin-induced thrombocytopenia/thrombosis are specific for platelet factor 4 complexed with heparin or bound to endothelial cells. J Clin Invest 1994; 93:81-88.
17. Suh JS, Aster RH, Visentin GP. Antibodies from patients with heparin-induced thrombocytopenia/thrombosis recognize different epitopes on heparin:platelet factor 4 complexes. Blood 1998; 91:916-922.
18. Walenga JM, Jeske WP, Messmore HL. Mechanisms of venous and arterial thrombosis in heparin-induced thrombocytopenia. J Thromb Thrombolysis 2000; 10:S13-S20.
19. Amiral J, Marfaing-Koka A, Wolf M, et al. Presence of auto-antibodies to interleukin-8 or neutrophil-activating peptide-2 in patients with heparin-associated-thrombocytopenia. Blood 1996; 88:410-416.
20. Regnault V, de Maistre E, Gruel Y, et al. Platelet activation induced by human antibodies to interleukin-8. Blood 2003; 101:1419-1421.
21. Carlsson LE, Santoso S, Baurichter G, et al. Heparin-induced thrombocytopenia: new insights into the impact of the FcγRIIa-R-H131 polymorphism. Blood 1998; 95:1526-1531.
22. Gruel Y, Pouplard C, Lasne D, et al. The homozygous FcγRIIIa-158V genotype is a risk factor for heparin-induced thrombocytopenia in patients with antibodies to heparin-platelet factor 4 complexes. Blood 2004; 104:2791-2793.
23. Horne MK III, Hutchison KJ. Simultaneous binding of heparin and platelet factor-4 to platelets: further insights into the mechanism of heparin-induced thrombocytopenia. Am J Hematol 1998; 58:24-30.
24. Loscalzo J, Melnick B, Handin RI. The interaction of platelet factor 4 and glycosaminoglycans. Arch Biochem Biophys 1985; 240:446-455.
25. Maccarana M, Linbahl U. Model of interaction between platelet factor 4 and heparin. Glycobiology 1993; 3:271-277.
26. Mayo KH, Ilyina E, Roongta V, et al. Heparin binding to platelet factor-4: an NMR and site-directed mutagenesis study: arginine residues are crucial for binding. Biochem J 1995; 312:357-365.
27. Amiral J, Pouplard C, Vissac AM, et al. Affinity purification of heparin-dependent antibodies to platelet factor 4 developed in heparin-induced thrombocytopenia: biological characteristics and effects on platelet activation. Br J Haematol 2000; 109:336-341.
28. Ahmad S, Walenga JM, Jeske WP, et al. Functional heterogeneity of antiheparin-platelet factor 4 antibodies: implications in the pathogenesis of the HIT syndrome. Clin Appl Thromb Hemost 1999; 5(Suppl 1):S32-S37.
29. Horsewood P, Warkentin TE, Hayward CPM, Kelton JG. The epitope specificity of heparin-induced thrombocytopenia. Br J Haematol 1996; 95:161-167.
30. Greinacher A, Michels I, Mueller-Eckert C. Heparin-associated thrombocytopenia: the antibody is not heparin specific. Thromb Haemost 1992; 67:545-549.
31. Greinacher A, Alban S, Dummel V, et al. Characterization of the structural requirements for a carbohydrate based anticoagulant with a reduced risk of inducing the immunological type of heparin-associated thrombocytopenia. Thromb Haemost 1995; 74:886-892.
32. Mikhailov D, Young JC, Linhardt RJ, Mayo KH. Heparin dodecasaccharide binding to platelet factor-4 and growth related protein-α: induction of a partially folded state and implications for heparin-induced thrombocytopenia. J Biol Chem 1999; 274:25317-25329.
33. Suh JS, Aster RH, Visentin GP. Antibodies from patients with heparin-induced thrombocytopenia recognize different epitopes on heparin:platelet factor 4. Blood 1998; 91:916-922.
34. Horne MK III, Chao ES. The effect of molecular weight on heparin binding to platelets. Br J Haematol 1990; 74:306-312.
35. Lane DA, Denton J, Flynn AM, et al. Anticoagulant activities of heparin oligosaccharides and their neutralization by platelet factor 4. Biochem J 1984; 218:725-732.
36. Horne MK III. Heparin binding to normal and abnormal platelets. Thromb Res 1988; 51:135-144.
37. Walenga JM, Jeske WP, Prechel MM, et al. Decreased prevalence of heparin-induced thrombocytopenia with low-molecular-weight heparin and related drugs. Semin Thromb Hemost 2004; 30(Suppl 1):69-80.
38. Walenga JM, Koza MJ, Lewis BE, Pifarré R. Relative heparin-induced thrombocytopenic potential of low molecular weight heparins and new antithrombotic agents. Clin Appl Thromb Hemost 1996; 2(Suppl 1):S21-S27.
39. Jeske WP, Jay AM, Haas S, Walenga JM. Heparin-induced thrombocytopenic potential of GAG and non-GAG based antithrombotic agents. Clin Appl Thromb Hemost 1999; 5(Suppl 1):S56-S62.
40. Haas S, Walenga JM, Jeske WP, Fareed J. Heparin-induced thrombocytopenia: clinical considerations of alternative anticoagulation with various glycosaminoglycans and thrombin inhibitors. Clin Appl Thromb Hemost 1999; 5:52-59.
41. Ahmad S, Jeske WP, Walenga JM, et al. Synthetic pentasaccharides do not cause platelet activation by antiheparin-platelet factor 4 antibodies. Clin Appl Thromb Hemost 1999; 5:259-266.
42. Prechel M, Jeske WP, Walenga JM. Laboratory methods for heparin-induced thrombocytopenia. In: Mousa SA, editor. Anticoagulants, antiplatelets, and thrombolytics: methods in molecular medicine. Totowa, NJ: Humana Press; 2004; 93:83-93.
43. Visentin GP, Ford SE, Scott PJ, Aster RH. Antibodies from patients with heparin-induced thrombocytopenia/thrombosis are specific for platelet factor 4 complexed with heparin or bound to endothelial cells. J Clin Invest 1994; 93:81-88.
44. Visentin GP. Heparin-induced thrombocytopenia: molecular pathogenesis. Thromb Haemost 1999; 82:448-456.
45. Amiral J, Bridey F, Wolf M. Antibodies to macromolecular platelet factor 4 heparin complexes in heparin-induced thrombocytopenia: a study of 44 cases. Thromb Haemost 1995; 73:21-28.
46. Ahmad S, Haas S, Hoppensteadt DA, et al. Differential effects of clivarin and heparin in patients undergoing hip and knee surgery for the generation of antiheparin-platelet factor 4 antibodies. Thromb Res 2003; 108:49-55.
47. Lindhoff-Last E, Eichler P, Stein M, et al. A prospective study on the incidence and clinical relevance of heparin-induced antibodies in patients after vascular surgery. Thromb Res 2000; 97:387-393.
48. Lindhoff-Last E, Nakov R, Misselwitz F, et al. Incidence and clinical relevance of heparin-induced antibodies in patients with deep vein thrombosis treated with unfractionated or low-molecular-weight heparin. Br J Haematol 2002; 118:1137-1142.
49. Pouplard C, May MA, Iochmann S, et al. Antibodies to platelet factor 4-heparin after cardiopulmonary bypass in patients anticoagulated with unfractionated heparin or a low molecular weight heparin: clinical implications for HIT. Circulation 1999; 99:2530-2536.
50. Ahmad S, Untch B, Haas S, et al. Differential prevalence of anti-heparin-PF4 immunoglobulin subtypes in patients treated with clivarin and heparin: implications in the HIT pathogenesis. Mol Cell Biochem 2004; 258:163-170. The finding of the difference in type of HIT antibodies generated with LMWH and UFH treatment supports the clinical evidence of the lower frequency of clinical HIT development associated with LMWH.
51. Gruel Y, Pouplard C, Nguyen P, et al. the French Heparin-induced Thrombocytopenia Study Group. Biological and clinical features of low-molecular-weight heparin-induced thrombocytopenia. Br J Haematol 2003; 121:786-792.
52. Ahmad S, Bacher P, Lassen MR, et al. Investigations of the immunoglobulin subtype transformation of anti-heparin-platelet factor 4 antibodies during treatment with a low-molecular-weight heparin (Clivarin) in orthopedic patients. Arch Pathol Lab Med 2003; 127:584-588.
53. Warkentin TE, Levine MN, Hirsh J, et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 1995; 332:1330-1335.
54. Amiral J, Peynaud-Debayle E, Wolf M, et al. Generation of antibodies to heparin-PF4 complexes without thrombocytopenia in patients treated with unfractionated or low-molecular-weight heparin. Am J Hematol 1996; 52:90-95.
55. Warkentin TE, Kelton JG. A 14-year study of heparin-induced thrombocytopenia. Am J Med 1996; 101:502-507.
56. Wallis DE, Workman DL, Lewis BE, et al. Failure of early heparin cessation as a treatment for heparin-induced thrombocytopenia. Am J Med 1999; 106:629-635.
57. Warkentin TE, Greinacher A. Heparin-induced thrombocytopenia: recognition, treatment, and prevention. Chest 2004; 126:311S-337S. This paper provides a useful summary of the risk of HIT in different patient populations and the recommended frequency of platelet count monitoring by population.
58. Gerdisch M, Wallis DE, Birger-Botkin S, et al. Pre-operative platelet count as baseline is not predictive of heparin-induced thrombocytopenia following cardiac surgery, the HITME (heparin-induced thrombocytopenia multicenter evaluation) trial. Blood 2002; 100:688a.
59. Elalamy I, Potevin F, Lecrubier C, et al. A fatal low-molecular-weight heparin-associated thrombocytopenia after hip surgery: possible usefulness of PF4-heparin ELISA test. Blood Coagul Fibrinolysis 1996; 7:665-671.
60. Lecompte T. Thrombocytopenia associated with low-molecular-weight heparin. Lancet 1991; 338:1217 (letter).
61. Tardy B. Thrombocytopenia associated with low-molecular-weight heparin. Lancet 1991; 338:1217 (letter).
62. Horellou MH, Conard J, Lecrubier C, et al. Persistent heparin-induced thrombocytopenia despite therapy with low molecular weight heparin. Thromb Haemost 1984; 51:134.
63. Dager WE, White RH. Low-molecular-weight heparin-induced thrombocytopenia in a child. Ann Pharmacother 2004; 38:247-250.
64. de Raucourt E, Vinsonneau C, Juvin K, et al. Heparin-induced thrombocytopenia with thrombotic complications during prophylactic treatment with low-molecular-weight heparin. Blood Coagul Fibrinolysis 1996; 7:786-788.
65. Wenzl ME, Hasse W, Seide K, Wolter D. Prevention of thromboembolism with low-molecular-weight heparin in orthopedic surgery: a 5-year experience. Clin Appl Thromb Hemost 2004; 10:1-4.
66. Ageno W, Crotti S, Turpie AG. The safety of antithrombotic therapy during pregnancy. Expert Opin Drug Saf 2004; 3:113-118.
67. Lewis BE, Wallis DE, Berkowitz SD, et al. for the ARG-911 Study Investigators. Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia. Circulation 2001; 103:1838-1843.
68. Greinacher A, Eichler P, Lubenow N, et al. Heparin-induced thrombocytopenia with thromboembolic complications: meta-analysis of 2 prospective trials to assess the value of parenteral treatment with lepirudin and its therapeutic aPTT range. Blood 2000; 96:846-851.
69. Walenga JM, Jeske WP, Bara L, et al. State-of-the-art article. Biochemical and pharmacologie rationale for the development of a heparin pentasaccharide. Thromb Res 1997; 86:1-36.
70. Parody R, Oliver A, Souto JC, Fontcuberta J. Fondaparinux (Arixtra) as an alternative anti-thrombotic prophylaxis when there is hypersensitivity to low molecular weight and unfractionated heparins. Haematologica 2003; ECR32.
71. D'Amico EA, Villaca PR, Gualandro SF, et al. Successful use of Arixtra in a patient with paroxysmal nocturnal hemoglobinuria, Budd-Chiari syndrome and heparin-induced thrombocytopenia. J Thromb Haemost 2003; 1:2452-2453.
72. Bradner J, Hallisey RK, Kuter DJ. Fondaparinux in the treatment of heparin-induced thrombocytopenia. Blood 2004; 104:Abstract 1775.
73. Weismann RE, Tobin RW. Arterial embolism ocurring during systemic heparin therapy. Arch Surg 1958; 76:219-227.