We studied the possibility that immune injury to endothelial cells may have a role in the development of thrombosis in some patients with heparin-associated thrombocytopenia. Serum samples from each of 27 patients who had this clinical diagnosis contained heparin-dependent platelet antibodies and deposited more than normal amounts of IgG, IgA, or IgM on endothelial cells, stimulating the production of tissue factor. Binding of immunoglobulins to endothelial cells was no longer detected when the patients were studied after heparin was withdrawn, but reappeared within several days upon reexposure to heparin in a patient who experienced a clinical recurrence. Binding of immunoglobulin to endothelial cells was partially reduced by the preadsorption of serum samples with heparin or heparan sulfate bound to Sepharose or by enzymatic cleavage of cell-bound heparan sulfate, and was augmented by the addition of heparan sulfate. Thus, serum from some patients with heparin-associated thrombocytopenia may contain antibodies that react with heparin bound to endothelial cells or with heparan sulfate synthesized by endothelial cells. Immune injury to both platelets and endothelial cells may play a part in the development of thrombosis in some patients after heparin therapy.
This article has been cited by other articles:
Kelton, J. G., Warkentin, T. E.
(2008). Heparin-induced thrombocytopenia: a historical perspective. Blood
112: 2607-2616
[Full Text]
Xiao, Z., Visentin, G. P., Dayananda, K. M., Neelamegham, S.
(2008). Immune complexes formed following the binding of anti-platelet factor 4 (CXCL4) antibodies to CXCL4 stimulate human neutrophil activation and cell adhesion. Blood
112: 1091-1100
[Abstract][Full Text]
Tardy, B., Lecompte, T., Boelhen, F., Tardy-Poncet, B., Elalamy, I., Morange, P., Gruel, Y., Wolf, M., Francois, D., Racadot, E., Camarasa, P., Blouch, M. T., Nguyen, F., Doubine, S., Dutrillaux, F., Alhenc-Gelas, M., Martin-Toutain, I., Bauters, A., Ffrench, P., de Maistre, E., Grunebaum, L., Mouton, C., Huisse, M. G., Gouault-Heilmann, M., Lucke, V., for the GEHT-HIT study group,
(2006). Predictive factors for thrombosis and major bleeding in an observational study in 181 patients with heparin-induced thrombocytopenia treated with lepirudin. Blood
108: 1492-1496
[Abstract][Full Text]
(2006). ASHP Therapeutic Position Statement on the Institutional Use of 0.9% Sodium Chloride Injection To Maintain Patency of Peripheral Indwelling Intermittent Infusion Devices.. Am J Health Syst Pharm
63: 1273-1275
[Full Text]
Davenport, A.
(2006). Sudden collapse during haemodialysis due to immune-mediated heparin-induced thrombocytopaenia. Nephrol Dial Transplant
21: 1721-1724
[Full Text]
de Maistre, E., Gruel, Y., Lasne, D.
(2006). Diagnosis and management of heparin-induced thrombocytopenia: [Le diagnostic et le traitement de la thrombopenie induite par l'heparine].. Canadian J. Anesthesia
53: S123-S134
[Abstract][Full Text]
Rauova, L., Zhai, L., Kowalska, M. A., Arepally, G. M., Cines, D. B., Poncz, M.
(2006). Role of platelet surface PF4 antigenic complexes in heparin-induced thrombocytopenia pathogenesis: diagnostic and therapeutic implications. Blood
107: 2346-2353
[Abstract][Full Text]
Jang, I.-K., Hursting, M. J.
(2005). When Heparins Promote Thrombosis: Review of Heparin-Induced Thrombocytopenia. Circulation
111: 2671-2683
[Full Text]
Kelton, J. G.
(2005). The Pathophysiology of Heparin-Induced Thrombocytopenia: Biological Basis for Treatment. Chest
127: 9S-20S
[Full Text]
Lubenow, N., Eichler, P., Lietz, T., Farner, B., Greinacher, A.
(2004). Lepirudin for prophylaxis of thrombosis in patients with acute isolated heparin-induced thrombocytopenia: an analysis of 3 prospective studies. Blood
104: 3072-3077
[Abstract][Full Text]
Suzuki, S., Sakamoto, S., Okada, T., Matsuo, M., Saitoh, A., Matsuo, T.
(2003). Acute Myocardial Infarction Caused by Delayed Heparin-Induced Thrombocytopenia and Acute Immunoreaction due to Re-exposure to Heparin in a Systemic Lupus Erythematosus Patient with HIT Antibodies. CLIN APPL THROMB HEMOST
9: 341-346
[Abstract]
Lewis, B. E., Wallis, D. E., Leya, F., Hursting, M. J., Kelton, J. G.
(2003). Argatroban Anticoagulation in Patients With Heparin-Induced Thrombocytopenia. Arch Intern Med
163: 1849-1856
[Abstract][Full Text]
Sachais, B. S., Kuo, A., Nassar, T., Morgan, J., Kariko, K., Williams, K. J., Feldman, M., Aviram, M., Shah, N., Jarett, L., Poncz, M., Cines, D. B., Higazi, A. A.-R.
(2002). Platelet factor 4 binds to low-density lipoprotein receptors and disrupts the endocytic itinerary, resulting in retention of low-density lipoprotein on the cell surface. Blood
99: 3613-3622
[Abstract][Full Text]
Mureebe, L., Silver, D.
(2002). Heparin-Induced Thrombocytopenia: Pathophysiology and Management. VASC ENDOVASCULAR SURG
36: 163-170
[Abstract]
Li, Z. Q., Liu, W., Park, K. S., Sachais, B. S., Arepally, G. M., Cines, D. B., Poncz, M.
(2002). Defining a second epitope for heparin-induced thrombocytopenia/thrombosis antibodies using KKO, a murine HIT-like monoclonal antibody. Blood
99: 1230-1236
[Abstract][Full Text]
Blank, M., Shoenfeld, Y., Tavor, S., Praprotnik, S., Boffa, M. C., Weksler, B., Walenga, M. J., Amiral, J., Eldor, A.
(2002). Anti-platelet factor 4/heparin antibodies from patients with heparin-induced thrombocytopenia provoke direct activation of microvascular endothelial cells. Int Immunol
14: 121-129
[Abstract][Full Text]
Warkentin, T. E.
(2001). Venous Limb Gangrene during Warfarin Treatment of Cancer-Associated Deep Venous Thrombosis. ANN INTERN MED
135: 589-593
[Abstract][Full Text]
Arepally, G. M., Mayer, I. M.
(2001). Antibodies from patients with heparin-induced thrombocytopenia stimulate monocytic cells to express tissue factor and secrete interleukin-8. Blood
98: 1252-1254
[Abstract][Full Text]
Pouplard, C., Iochmann, S., Renard, B., Herault, O., Colombat, P., Amiral, J., Gruel, Y.
(2001). Induction of monocyte tissue factor expression by antibodies to heparin-platelet factor 4 complexes developed in heparin-induced thrombocytopenia. Blood
97: 3300-3302
[Abstract][Full Text]
Baglin, T P
(2001). Heparin induced thrombocytopenia thrombosis (HIT/T) syndrome: diagnosis and treatment. J. Clin. Pathol.
54: 272-274
[Abstract][Full Text]
Greinacher, A., Lubenow, N.
(2001). Recombinant Hirudin in Clinical Practice : Focus on Lepirudin. Circulation
103: 1479-1484
[Abstract][Full Text]
McCrae, K. R., Bussel, J. B., Mannucci, P. M., Remuzzi, G., Cines, D. B.
(2001). Platelets: An Update on Diagnosis and Management of Thrombocytopenic Disorders. ASH Education Book
2001: 282-305
[Abstract][Full Text]
Hyers, T. M., Agnelli, G., Hull, R. D., Morris, T. A., Samama, M., Tapson, V., Weg, J. G.
(2001). Antithrombotic Therapy for Venous Thromboembolic Disease. Chest
119: 176S-193S
[Full Text]
Eichler, P., Friesen, H.-J., Lubenow, N., Jaeger, B., Greinacher, A.
(2000). Antihirudin antibodies in patients with heparin-induced thrombocytopenia treated with lepirudin: incidence, effects on aPTT, and clinical relevance. Blood
96: 2373-2378
[Abstract][Full Text]
Pohl, C., Harbrecht, U., Greinacher, A., Theuerkauf, I., Biniek, R., Hanfland, P., Klockgether, T.
(2000). Neurologic complications in immune-mediated heparin-induced thrombocytopenia. Neurology
54: 1240-1245
[Abstract][Full Text]
Wallis, D. E., Quintos, R., Wehrmacher, W., Messmore, H.
(1999). Safety of Warfarin Anticoagulation in Patients With Heparin-Induced Thrombocytopenia. Chest
116: 1333-1338
[Abstract][Full Text]
Wallis, D. E., Lewis, B. E., Messmore, H. L., Pifarre, R., Walenga, J. M.
(1999). Inadequacy of Current Prevention Strategies for Heparin-Induced Thrombocytopenia. CLIN APPL THROMB HEMOST
5: S16-S20
[Abstract]
Fareed, J., Walenga, J. M., Hoppensteadt, D. A., Jeske, W. P., Ahmad, S., Lietz, H., McKenna, R., Messmore, H. L., Haas, S.
(1999). Soluble Adhesion Molecules in the HIT Syndrome: Pathophysiologic Role and Therapeutic Modulation. CLIN APPL THROMB HEMOST
5: S38-S44
[Abstract]
Walenga, J. M., Michal, K., Hoppensteadt, D., Wood, J. J., Robinson, J. A., Bick, R. L.
(1999). Vascular Damage Correlates Between Heparin-Induced Thrombocytopenia and the Antiphospholipid Syndrome. CLIN APPL THROMB HEMOST
5: S76-S84
[Abstract]
Greinacher, A., Volpel, H., Janssens, U., Hach-Wunderle, V., Kemkes-Matthes, B., Eichler, P., Mueller-Velten, H. G., Potzsch, B.
(1999). Recombinant Hirudin (Lepirudin) Provides Safe and Effective Anticoagulation in Patients With Heparin-Induced Thrombocytopenia : A Prospective Study. Circulation
99: 73-80
[Abstract][Full Text]
Ziporen, L., Li, Z.Q., Park, K.S., Sabnekar, P., Liu, W.Y., Arepally, G., Shoenfeld, Y., Kieber-Emmons, T., Cines, D.B., Poncz, M.
(1998). Defining an Antigenic Epitope on Platelet Factor 4 Associated With Heparin-Induced Thrombocytopenia. Blood
92: 3250-3259
[Abstract][Full Text]
Carlsson, L. E., Santoso, S., Baurichter, G., Kroll, H., Papenberg, S., Eichler, P., Westerdaal, N. A.C., Kiefel, V., van de Winkel, J. G.J., Greinacher, A.
(1998). Heparin-Induced Thrombocytopenia: New Insights Into the Impact of the Fcgamma RIIa-R-H131 Polymorphism. Blood
92: 1526-1531
[Abstract][Full Text]
Wallis, D. E., Lewis, B. E., Messmore, H., Wehrmacher, W. H.
(1998). State-of-the-Art Review : Heparin-induced Thrombocytopenia and Thrombosis Syndrome. CLIN APPL THROMB HEMOST
4: 160-163
Krause, I, Blumenfeld, Z, Malchinsky, M, Cohen, S, Blank, M, Eldor, A, Weksler, B, Schweitzer, K, Shoenfeld, Y
(1998). Anti-endothelial cell antibodies in the sera of hyperprolactinemic women. Lupus
7: 377-382
[Abstract]
Cines, D. B., Pollak, E. S., Buck, C. A., Loscalzo, J., Zimmerman, G. A., McEver, R. P., Pober, J. S., Wick, T. M., Konkle, B. A., Schwartz, B. S., Barnathan, E. S., McCrae, K. R., Hug, B. A., Schmidt, A.-M., Stern, D. M.
(1998). Endothelial Cells in Physiology and in the Pathophysiology of Vascular Disorders. Blood
91: 3527-3561
[Full Text]
Harper, L, Savage, C.
(1998). Anti-heparin antibodies: part of the repertoire of anti-endothelial cell antibodies (AECA). Lupus
7: 68-72
Renaudineau, Y, Revelen, R, Bordron, A, Mottier, D, Youinou, P, Le Corre, R
(1998). Two populations of endothelial cell antibodies cross-react with heparin. Lupus
7: 86-94
[Abstract]
Bauer, T. L., Arepally, G., Konkle, B. A., Mestichelli, B., Shapiro, S. S., Cines, D. B., Poncz, M., McNulty, S., Amiral, J., Hauck, W. W., Edie, R. N., Mannion, J. D.
(1997). Prevalence of Heparin-Associated Antibodies Without Thrombosis in Patients Undergoing Cardiopulmonary Bypass Surgery. Circulation
95: 1242-1246
[Abstract][Full Text]
Arepally, G., McKenzie, S. E., Jiang, X.-M., Poncz, M., Cines, D. B.
(1997). Fcgamma RIIA H/R131 Polymorphism, Subclass-Specific IgG Anti-Heparin/Platelet Factor 4 Antibodies and Clinical Course in Patients With Heparin-Induced Thrombocytopenia and Thrombosis. Blood
89: 370-375
[Abstract][Full Text]
Hirsh, J., Hoak, J.
(1996). Management of Deep Vein Thrombosis and Pulmonary Embolism : A Statement for Healthcare Professionals From the Council on Thrombosis (in Consultation With the Council on Cardiovascular Radiology), American Heart Association. Circulation
93: 2212-2245
[Full Text]
Wilhelm, M. J., Schmid, C., Kececioglu, D., Mollhoff, T., Ostermann, H., Scheld, H. H.
(1996). Cardiopulmonary Bypass in Patients With Heparin-Induced Thrombocytopenia Using Org 10172. Ann. Thorac. Surg.
61: 920-924
[Abstract][Full Text]
Kalangos, A., Relland, J. Y. M., Altes, A., Martino, R., Gari, M., Camara, M. L., Garin, R., Casas, J.-I., Fontcuberta, J.
(1995). Therapeutic Implications for Heparin-Induced Thrombocytopenia and Thrombosis. Ann. Thorac. Surg.
60: 1159-1160
[Full Text]
Dzik, W. H., Duncan, L. M.
(1994). Case 35-1994- A 55-Year-Old Woman with a Skin Rash and Hemiparesis after Staphylococcal Protein A Column Therapy. NEJM
331: 792-800
[Full Text]
Adler, Y., Salozhin, K., Le Tonqueze, M., Shoenfeld, Y., Youinou, P.
(1994). Review: Anti-Endothelial Cell Antibodies: a Need for Standardization. Lupus
3: 77-84
[Abstract]
Brent Kerns, D., Frymoyer, P. A., Kopecky, R. T., Tice, D., Fillinger, M. F., Bruch, D., Schwartz, R. A.
(1992). Is Heparin-Induced Platelet Activation an Unrecognized Cause of Thrombosis in Chronic Dialysis Patients?. VASC ENDOVASCULAR SURG
26: 487-493
[Abstract]
Previous
