Occurrence and clinical significance of pseudothrombocytopenia during abciximab therapy

Sane, David C.; Damaraju, Lakshmi; Topol, Eric J.; Cabot, Catherine F.; Mascelli, Mary Ann; Harrington, Robert A.; Simoons, Maarten L.; Califf, Robert M.

doi:10.1016/s0735-1097(00)00688-4

Cited by 102 publications

(68 citation statements)

References 21 publications

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“…"Thrombocytopenia" following abciximab treatment can be artifactual (pseudothrombocytopenia), being the result of clumping of platelets in blood collected in ethylenediaminetetraacetic acid anticoagulant through mechanisms not yet fully understood. 28,29 However, pseudothrombocytopenia rarely leads to platelet counts as low as the ones observed in the subjects of this report. Moreover, it is not generally associated with bleeding, whereas the patients we studied had extensive petechial hemorrhages (all patients), bleeding from venipuncture sites (patients no.…”

Section: Discussionmentioning

confidence: 48%

Thrombocytopenia after second exposure to abciximab is caused by antibodies that recognize abciximab-coated platelets

Curtis

Swyers

Divgi

et al. 2002

Blood

119

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Thrombocytopenia, often severe, occurs in 1% to 2% of patients given the fibrinogen receptor antagonist abciximab, a chimeric Fab fragment containing murine specificity-determining and human framework sequences. The cause of this complication has not yet been defined. Studies of 9 patients who developed profound thrombocytopenia (platelets <10 ؋ 10 9 /L [10 000/L]) within a few hours of being given abciximab a second time showed that each had a strong immunoglobulin G (IgG) antibody that recognized platelets sensitized with abciximab. Five patients also had IgM antibodies. IgG antibodies reactive with abciximab-coated platelets were also found in 77 (74%) of 104 healthy subjects. However, the patient antibodies could be distinguished from "normal" ones in 2 ways: (1) only the patient antibodies reacted preferentially with platelets sensitized with the intact monoclonal antibody 7E3 from which the murine sequences in abciximab are derived; and (2) the "normal" antibodies could be inhibited by Fab fragments derived from normal human IgG, whereas the patient antibodies were relatively resistant to this treatment. The findings suggest that antibodies from the patients are specific for murine sequences in abciximab and are capable of causing life-threatening thrombocytopenia upon injection of this drug. The antibodies commonly found in healthy subjects are specific for the papain cleavage site of any Fab fragments and, although they react with abciximabcoated platelets, appear not to cause significant thrombocytopenia. It may be possible to identify patients at risk for developing thrombocytopenia if given abciximab by screening for antibodies that recognize 7E3-coated platelets. (Blood.

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Section: Discussionmentioning

confidence: 48%

Thrombocytopenia after second exposure to abciximab is caused by antibodies that recognize abciximab-coated platelets

Curtis

Swyers

Divgi

et al. 2002

Blood

119

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“…1,[3][4][5][6][7][8][9][10][11][12] However, the present study demonstrates by a number of independent methods that neither abciximab (the GP IIb/IIIa antagonist primarily studied by Peter et al), 2 nor tirofiban, nor eptifibatide (the other two FDA-approved GP IIb/IIIa antagonists), nor SC-54701 (the active metabolite of the oral GP IIb/IIIa antagonist xemilofiban) induce stable fibrinogen binding or platelet aggregation under physiological conditions. Furthermore, the findings of Peter et al 2 in experiments with unfixed platelets are probably accounted for by artifactual thrombin generation.…”

Section: Discussionmentioning

confidence: 91%

“…However, the apparently paradoxical results of Peter et al 2 1,[3][4][5]7,9,11,12 (2) the recently reported disappointing results of abciximab in the GUSTO-IV trial of unstable angina, 1 and, (3) abciximab-induced pseudothrombocytopenia. 10 Therefore, in the present study, we reexamined the findings of Peter et al 2 by using a number of independent methods.…”

mentioning

confidence: 98%

Dissociation of Glycoprotein IIb/IIIa Antagonists From Platelets Does Not Result in Fibrinogen Binding or Platelet Aggregation

et al. 2001

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Background-The primary mechanism of action of glycoprotein (GP) IIb/IIIa antagonists is inhibition of the final common pathway of platelet aggregation: fibrinogen binding to the GP IIb/IIIa complex. However, it has been reported that induction of fibrinogen binding and platelet aggregation is an intrinsic prothrombotic property of low-dose GP IIb/IIIa antagonists. These apparently paradoxical results have been extensively referenced in the cardiology literature. Methods and Results-By platelet aggregation and flow cytometry, we demonstrate that (1) dissociation of GP IIb/IIIa antagonists (abciximab, tirofiban, eptifibatide, or xemilofiban) from platelets does not result in platelet aggregation; (2) tirofiban and eptifibatide can induce a fibrinogen-binding-competent conformation of the GP IIb/IIIa receptor, but stable fibrinogen binding does not occur without fixation; (3) the slow off-rate of abciximab exposes only a small proportion of unblocked GP IIb/IIIa receptors at any time, and these also fail to stably bind fibrinogen; and (4)

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“…prednisone 1-2 mg/kg/day for 2-4 agulants, by platelet clumping on a blood smear weeks) may be administered as the diagnosis may be made from anticoagulated blood or by obtaining a difficult to distinguish from idiopathic thrombonormal platelet count on a blood smear made from cytopenic purpura in which corticosteroids are of nonanticoagulated blood. [8] proven benefit. [5,6,75] For the same reason, intrave-…”

Section: General Laboratory Investigationmentioning

confidence: 99%

“…(EDTA) instead of citrate. [8] However, pseuIn table I these 108 articles are categorised by dothrombocytopenia may also occur in anticoagu-type of publication. lants such as heparin and citrate.…”

mentioning

confidence: 99%

Drug-Induced Immune Thrombocytopenia

2004

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Occurrence and clinical significance of pseudothrombocytopenia during abciximab therapy

Cited by 102 publications

References 21 publications

Thrombocytopenia after second exposure to abciximab is caused by antibodies that recognize abciximab-coated platelets

Thrombocytopenia after second exposure to abciximab is caused by antibodies that recognize abciximab-coated platelets

Dissociation of Glycoprotein IIb/IIIa Antagonists From Platelets Does Not Result in Fibrinogen Binding or Platelet Aggregation

Drug-Induced Immune Thrombocytopenia

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