Heparin-Associated Thrombocytopenia

Cines, Douglas B.; Kaywin, Paul; Bina, Mahin; Tomaski, Ann; Schreiber, Alan D.

doi:10.1056/nejm198010023031404

Cited by 254 publications

(82 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The differences in the reported frequencies of anti-H/PF4 antibodies may be due in part to the spontaneous disappearance of these antibodies, as described in previous series [19,20]. In a series of 243 patients, heparin-induced antibody titers fell below the detection threshold within a median of 50 days if a platelet serotonin-release assay was used and within 85 days if an antigen assay was used [21].…”

Section: Discussionmentioning

confidence: 81%

A prospective study of the prevalence of heparin‐induced antibodies and other associated thromboembolic risk factors in pediatric patients undergoing hemodialysis

et al. 2006

View full text Add to dashboard Cite

Heparin, which is used at high doses in hemodialysis patients, may induce antibodies favoring thromboembolic complications. We prospectively investigated the prevalence of heparininduced platelet-reactive antibodies in a cohort of 38 pediatric hemodialysis patients, by means of heparin/platelet factor 4 (H/PF4) ELISA and heparin-induced platelet activation assay (HIPA). We also assessed other acquired and congenital hypercoagulable states. Heparin-induced antibodies were detected in 13 and 21% of patients with HIPA and ELISA, respectively. Anti-H/PF4 antibodies were negatively correlated with the number of hemodialysis sessions. These antibodies disappeared after a median time of 6 months despite continuing heparin treatment. The prevalence of antiphospholipid antibodies was 21% (anticardiolipin 10.5%, anti-b2GPI 13%, and lupus anticoagulant 5%). Blood levels of homocysteine, factor VIII, and fibrinogen were significantly higher and factor II levels were significantly lower in hemodialysis patients than in controls, whereas factor VII, factor IX, and natural coagulation inhibitor levels were similar in patients and controls. Overall, 26 of 38 patients had at least one biomarker of hypercoagulability, but only 1 patient, without anti-H/PF4 antibodies, presented with thrombosis. In conclusion, heparin induces the transient production of anti-H/PF4 antibodies in children undergoing hemodialysis, but other abnormalities probably contribute to hypercoagulability. These findings may help to improve the diagnosis and management of thrombotic events in hemodialysis patients. Am. J. Hematol. 81:328-334, 2006. V V C 2006 Wiley-Liss, Inc.

show abstract

Section: Discussionmentioning

confidence: 81%

A prospective study of the prevalence of heparin‐induced antibodies and other associated thromboembolic risk factors in pediatric patients undergoing hemodialysis

et al. 2006

View full text Add to dashboard Cite

show abstract

“…30 KKO activates platelets via the Fc␥RIIA receptor in the presence of heparin as demonstrated by 14 C-serotonin release. 33 RTO, a mouse monoclonal antibody, has antigenic specificity for hPF4 but not the PF4/heparin complex.…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

“…[10][11][12] Antibodies to the PF4/heparin complex have been shown to activate human platelets in vitro via the platelet Fc receptor (FcR) for immunoglobuin (Ig)-G, Fc␥RIIA. [13][14][15][16] The binding of HIT antibodies to activated platelets probably promotes microparticle release as well as platelet-platelet and platelet-vessel wall interactions, predisposing to thrombosis. 15,17 However, the mechanism by which HIT antibodies activate platelets and promote thrombosis is uncertain.…”

mentioning

confidence: 99%

Heparin-induced thrombocytopenia/thrombosis in a transgenic mouse model requires human platelet factor 4 and platelet activation through FcγRIIA

Reilly

Taylor

Hartman

et al. 2001

Blood

Self Cite

200

196

View full text Add to dashboard Cite

Heparin-induced thrombocytopenia/thrombosis (HIT/HITT) is a severe, life-threatening complication that occurs in 1% to 3% of patients exposed to heparin. Interactions between heparin, human platelet factor 4 (hPF4), antibodies to the hPF4/heparin complex, and the platelet Fc receptor (FcR) for immunoglobulin G, Fc␥RIIA, are the proposed primary determinants of the disease on the basis of in vitro studies. The goal of this study was to create a mouse model that recapitulates the disease process in humans in order to understand the factors that predispose some patients to develop thrombocytopenia and thrombosis and to investigate new therapeutic approaches. Mice that express both human platelet Fc␥RIIA and hPF4 were generated. The Fc␥RIIA/hPF4 mice and controls, transgenic for either Fc␥RIIA or hPF4, were injected with KKO, a mouse monoclonal antibody specific for hPF4/heparin complexes, and then received heparin (20 U/d). Nadir platelet counts for KKO/heparin-treated Fc␥RIIA/hPF4 mice were 80% below baseline values, significantly different (P < .001) from similarly treated controls. Fc␥RIIA/hPF4 mice injected with KKO IntroductionHeparin is one of the most widely used anticoagulants during invasive vascular procedures and to treat thromboembolic diseases. Among patients who receive therapeutic courses of heparin, 1% to 3% will develop an antibody-mediated thrombocytopenia, 1-3 and 30% to 70% of these patients will develop potentially lifethreatening thrombosis. There is abundant evidence that more than 95% of patients with heparin-induced thrombocytopenia (HIT) alone and those with thrombocytopenia and thrombosis (HITT) develop antibodies that recognize complexes between platelet factor 4 (PF4) and heparin. 4-7 PF4, a major component of platelet ␣-granules, is released when platelets are activated. 8,9 It is currently believed that complexes between PF4 and heparin form on the surface of activated platelets, where they are positioned to be recognized by anti-PF4/heparin antibodies. [10][11][12] Antibodies to the PF4/heparin complex have been shown to activate human platelets in vitro via the platelet Fc receptor (FcR) for immunoglobuin (Ig)-G, Fc␥RIIA. [13][14][15][16] The binding of HIT antibodies to activated platelets probably promotes microparticle release as well as platelet-platelet and platelet-vessel wall interactions, predisposing to thrombosis. 15,17 However, the mechanism by which HIT antibodies activate platelets and promote thrombosis is uncertain. It has been proposed that HIT antibodies bind to cell-surface-associated PF4/heparin complexes via the Fab end of the molecule, providing an opportunity to transduce platelet-activating signals through the interaction between the Fc portion of the bound IgG and Fc␥RIIA. 12,13 Fc␥RIIA, the sole Fc␥ receptor expressed on platelets, 18 has been shown to transduce signals without the requirement for another transmembrane partner. 19 A monoclonal antibody to Fc␥RIIA blocks platelet aggregation and secretion induced by HIT antibodies. 12,13 Although increased...

show abstract

“…The diagnosis of thrombocytopenia induced by abciximab required a decrease in platelet count to Ͻ100ϫ10 9 cells/L, with a fall Ͼ25% from baseline and the exclusion of pseudothrombocytopenia and heparin-induced thrombocytopenia as the cause. A diagnosis of heparin-induced thrombocytopenia was entertained in cases meeting the criteria of Pouplard and colleagues, 13 if heparin-dependent platelet-reactive antibodies were demonstrated using the C-serotonin release assay, 14 or if increased levels of anti-heparin/PF4 antibodies were found by ELISA assay. 15 …”

Section: Adjudication Of Thrombocytopeniamentioning

confidence: 99%

Abciximab Readministration

et al. 2001

Self Cite

View full text Add to dashboard Cite

Background-Platelet glycoprotein IIb/IIIa blockade with abciximab (ReoPro) improves the clinical outcomes of percutaneous coronary intervention. This registry was conducted to characterize the effects of repeated administration of abciximab during intervention. Methods and Results-We recruited 500 consecutive patients at 22 centers in the United States who were receiving abciximab for at least a second time during percutaneous coronary intervention. Safety was measured as the incidence of hypersensitivity reactions, major bleeding, and thrombocytopenia. Efficacy was assessed as event-free clinical success. Human antichimeric antibody (HACA) responses were also characterized. There were no cases of hypersensitivity (95% upper confidence bound, 0.3%), major bleeding, or death. Clinical success was 94.4%. Thrombocytopenia occurred in 23 patients (4.6%; 95% CI, 2.8% to 6.4%), including 12 (2.4%; 95% CI, 1.1% to 3.7%) who developed profound thrombocytopenia (Ͻ20ϫ10 9 cells/L). In 2 patients (0.4%), profound thrombocytopenia did not develop until after hospital discharge; in 4 (0.8%), profound thrombocytopenia recurred despite platelet transfusion. Before a first readministration, a positive HACA titer was present in 22 of 454 patients (4.8%); after a first readministration, an additional 82 of 432 (19.0%) became HACA-positive. HACA did not neutralize the in vitro inhibition of platelet aggregation by abciximab or correlate with clinical events. Conclusions-The results, including overall rates of thrombocytopenia, were consistent with randomized clinical trials of first abciximab treatment. However, there was a shift from mild to profound thrombocytopenia, and cases of delayed presentation and of recurrent thrombocytopenia were seen. These findings suggest that indications and guidelines for first-time use apply to retreatment, particularly the systematic monitoring for thrombocytopenia.

show abstract

Heparin-Associated Thrombocytopenia

Cited by 254 publications

References 35 publications

A prospective study of the prevalence of heparin‐induced antibodies and other associated thromboembolic risk factors in pediatric patients undergoing hemodialysis

A prospective study of the prevalence of heparin‐induced antibodies and other associated thromboembolic risk factors in pediatric patients undergoing hemodialysis

Heparin-induced thrombocytopenia/thrombosis in a transgenic mouse model requires human platelet factor 4 and platelet activation through FcγRIIA

Abciximab Readministration

Contact Info

Product

Resources

About