Heparin-induced thrombocytopenia: In vitro studies on the interaction of dabigatran, rivaroxaban, and low-sulfated heparin, with platelet factor 4 and anti-PF4/heparin antibodies

Blood

Volumn 119, Issue 5, 2012, Pages 1248-1255

  Krauel, Krystin ^a   Hackbarth, Christine ^a   Fürll, Birgitt ^a   Greinacher, Andreas ^a  

^a UNIVERSITY MEDICINE GREIFSWALD   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBODY; ARGATROBAN; DABIGATRAN; DABIGATRAN ETEXILATE; DANAPAROID; HEPARIN; IMMUNOGLOBULIN G ANTIBODY; LEPIRUDIN; RIVAROXABAN; THROMBOCYTE FACTOR 4;

ANTICOAGULATION; ARTICLE; CELL SURFACE; COMPLEX FORMATION; CONTROLLED STUDY; HEPARIN INDUCED THROMBOCYTOPENIA; HUMAN; HUMAN CELL; IMMUNOGENICITY; IN VITRO STUDY; NORMAL HUMAN; PRIORITY JOURNAL; RISK REDUCTION; THROMBOCYTE ACTIVATION;

EID: 84856600313     PISSN: 00064971     EISSN: 15280020     Source Type: Journal    
DOI: 10.1182/blood-2011-05-353391     Document Type: Article

References (36)

1. Arepally GM, Ortel TL. Clinical practice. Heparin-induced thrombocytopenia. N Engl J Med. 2006; 355(8):809-817.
2. Warkentin TE, Chong BH, Greinacher A. Heparin-induced thrombocytopenia: towards consensus. Thromb Haemost. 1998;79(1):1-7. (Pubitemid 28037046)
3. Greinacher A, Potzsch B, Amiral J, Dummel V, Eichner A, Mueller-Eckhardt C. Heparin-associated thrombocytopenia: isolation of the antibody and characterization of a multimolecular PF4-heparin complex as the major antigen. Thromb Haemost. 1994; 71(2):247-251. (Pubitemid 24047336)
4. Kelton JG, Smith JW, Warkentin TE, Hayward CP, Denomme GA, Horsewood P. Immunoglobulin G from patients with heparin-induced thrombocytopenia binds to a complex of heparin and platelet factor 4. Blood. 1994;83(11):3232-3239. (Pubitemid 24158468)
5. Visentin GP, Ford SE, Scott JP, 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(1):81-88. (Pubitemid 24030823)
6. Chong BH, Fawaz I, Chesterman CN, Berndt MC. Heparin-induced thrombocytopenia: mechanism of interaction of the heparin-dependent antibody with platelets. Br J Haematol. 1989;73(2):235- 240.
7. Kelton JG, Sheridan D, Santos A, et al. Heparin-induced thrombocytopenia: laboratory studies. Blood. 1988;72(3):925-930.
8. Reilly MP, Taylor SM, Hartman NK, et al. Heparin-induced thrombocytopenia/thrombosis in a transgenic mouse model requires human platelet factor 4 and platelet activation through FcgammaRIIA. Blood. 2001;98(8):2442-2447.
9. Warkentin TE. Heparin-induced thrombocytopenia. Hematol Oncol Clin North Am. 2007;21(4): 589-607, v. (Pubitemid 47102555)
10. Mavrakanas T, Bounameaux H. The potential role of new oral anticoagulants in the prevention and treatment of thromboembolism. Pharmacol Ther. 2011;130(1):46-58.
11. Alban S. Pharmacology of heparins and direct anticoagulants. Hamostaseologie. 2008;28(5): 400-420.
12. Walenga JM, Prechel M, Jeske WP, et al. Rivaroxaban-an oral, direct factor Xa inhibitor-has potential for the management of patients with heparin-induced thrombocytopenia. Br J Haematol. 2008;143(1):92-99.
13. Rao NV, Argyle B, Xu X, et al. Low anticoagulant heparin targets multiple sites of inflammation, suppresses heparin-induced thrombocytopenia, and inhibits interaction of RAGE with its ligands. Am J Physiol Cell Physiol. 2010;299(1):C97- C110.
14. Fryer A, Huang YC, Rao G, et al. Selective O-desulfation produces nonanticoagulant heparin that retains pharmacological activity in the lung. J Pharmacol Exp Ther. 1997;282(1):208-219. (Pubitemid 27425543)
15. Wang L, Brown JR, Varki A, Esko JD. Heparin's anti-inflammatory effects require glucosamine 6-O-sulfation and are mediated by blockade of L-and P-selectins. J Clin Invest. 2002;110(1):127- 136.
16. Lasagni L, Grepin R, Mazzinghi B, et al. PF-4/ CXCL4 and CXCL4L1 exhibit distinct subcellular localization and a differentially regulated mechanism of secretion. Blood. 2007;109(10):4127- 4134.
17. Juhl D, Eichler P, Lubenow N, Strobel U,Wessel A, Greinacher A. Incidence and clinical significance of anti-PF4/heparin antibodies of the IgG, IgM, and IgA class in 755 consecutive patient samples referred for diagnostic testing for heparin-induced thrombocytopenia. Eur J Haematol. 2006;76(5):420-426.
18. Warkentin TE, Greinacher A. Laboratory testing for heparin-induced thrombocytopenia. In: Warkentin TE, Greinacher A, eds. Heparin- Induced Thrombocytopenia. New York, NY: Informa Healthcare; 2007:227-238.
19. Greinacher A, Feigl M, Mueller-Eckhardt C. Crossreactivity studies between sera of patients with heparin associated thrombocytopenia and a new low molecular weight heparin, reviparin. Thromb Haemost. 1994;72(4):644-645. (Pubitemid 24305665)
20. Lasagni L, Francalanci M, Annunziato F, et al. An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4. J Exp Med. 2003; 197(11):1537-1549. (Pubitemid 36682550)
21. Schaffner A, Rhyn P, Schoedon G, Schaer DJ. Regulated expression of platelet factor 4 in human monocytes-role of PARs as a quantitatively important monocyte activation pathway. J Leukoc Biol. 2005;78(1):202-209. (Pubitemid 40979959)
22. Greinacher A, Warkentin TE. The direct thrombin inhibitor hirudin. Thromb Haemost. 2008;99(5): 819-829. (Pubitemid 351705298)
23. Lewis BE, Hurstings MJ. Argatroban therapy in heparin-induced thrombocytopenia. In:Warkentin TE, Greinacher A, eds. Heparin-Induced Thrombocytopenia. New York, NY: Informa Healthcare; 2007:379-408.
24. Krauel K, Furll B, Warkentin TE, et al. Heparin-induced thrombocytopenia-therapeutic concentrations of danaparoid, unlike fondaparinux and direct thrombin inhibitors, inhibit formation of platelet factor 4-heparin complexes. J Thromb Haemost. 2008;6(12):2160-2167.
25. Hankey GJ, Eikelboom JW. Dabigatran etexilate: a new oral thrombin inhibitor. Circulation. 2011; 123(13):1436-1450.
26. Harbrecht U. Old and new anticoagulants. Hamostaseologie. 2011;31(1):21-27.
27. Steffel J, Braunwald E. Novel oral anticoagulants: focus on stroke prevention and treatment of venous thrombo-embolism. Eur Heart J. 2011:
28. Kubitza D, Becka M, Wensing G, Voith B, Zuehlsdorf M. 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(12):873-880. (Pubitemid 41803696)
29. van Ryn J, Stangier J, Haertter S, et al. Dabigatran etexilate-a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost. 2010;103(6):1116-1127.
30. Chong BH, Magnani HN. Danaparoid for the treatment of heparin-induced thrombocytopenia. In: Warkentin TE, Greinacher A, eds. Heparin- Induced Thrombocytopenia. New York, NY: Informa Healthcare; 2007:319-343.
31. Rauova L, Arepally G, McKenzie SE, Konkle BA, Cines DB, Poncz M. Platelet and monocyte antigenic complexes in the pathogenesis of heparin-induced thrombocytopenia (HIT). J Thromb Haemost. 2009;7(suppl 1):249-252.
32. Greinacher A, Michels I, Liebenhoff U, Presek P, Mueller-Eckhardt C. Heparin-associated thrombocytopenia: immune complexes are attached to the platelet membrane by the negative charge of highly sulphated oligosaccharides. Br J Haematol. 1993;84(4):711-716. (Pubitemid 23248066)
33. Rauova L, Zhai L, Kowalska MA, Arepally GM, Cines DB, Poncz M. Role of platelet surface PF4 antigenic complexes in heparin-induced thrombocytopenia pathogenesis: diagnostic and therapeutic implications. Blood. 2006;107(6):2346- 2353.
34. Handin RI, Cohen HJ. Purification and binding properties of human platelet factor four. J Biol Chem. 1976;251(14):4273-4282.
35. Greinacher A, Gopinadhan M, Gunther JU, et al. Close approximation of two platelet factor 4 tetramers by charge neutralization forms the antigens recognized by HIT antibodies. Arterioscler Thromb Vasc Biol. 2006;26(10):2386-2393. (Pubitemid 44465738)
36. Greinacher A, Michels I, Mueller-Eckhardt C. Heparin-associated thrombocytopenia: the antibody is not heparin specific. Thromb Haemost. 1992;67(5):545-549.