Heparin-Induced Thrombocytopenia: Frequency and Pathogenesis

Greinacher, Andreas

doi:10.1159/000093542

Cited by 30 publications

(31 citation statements)

References 84 publications

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“…Heparin-induced thrombocytopenia (HIT) is a prothrombotic, immune-mediated adverse reaction that occurs after exposure to unfractionated heparin (UFH), low molecular weight heparin (LMWH), or other polyanions such as hypersulfated chondroitin sulfate [Greinacher, 2006;Warkentin et al 2008b]. The in vivo formation of highly immunizing multimolecular complexes consisting of the negatively charged polyanions and the cationic protein platelet factor 4 (PF4) results in antibody formation in many heparinexposed patients [Amiral et al 1992;Greinacher et al 1994].…”

Section: Introductionmentioning

confidence: 99%

“…The in vivo formation of highly immunizing multimolecular complexes consisting of the negatively charged polyanions and the cationic protein platelet factor 4 (PF4) results in antibody formation in many heparinexposed patients [Amiral et al 1992;Greinacher et al 1994]. Only a minority of these patients, however, develop HIT characterized by a fall in platelet count beginning after 5-10 days of heparin therapy with or without thromboembolic events [Greinacher, 2006;Warkentin, 2003]. The risk of immunization depends on the type of heparin (UFH >> LMWH) [Warkentin, 2003], length of heparin administration (>5 days >> 1-4 days), underlying disease (major surgery > minor surgery > medical patients) [Lubenow et al 2010;Prandoni et al 2005aPrandoni et al , 2005b, and gender (female > male) .…”

Section: Introductionmentioning

confidence: 99%

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Recent advances in the diagnosis and treatment of heparin-induced thrombocytopenia

Bakchoul

Greinacher

2012

Therapeutic Advances in Hematology

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Heparin-induced thrombocytopenia (HIT) is a drug-mediated, prothrombotic disorder caused by immunization against platelet factor 4 (PF4) after complex formation with heparin or other polyanions. After their binding to PF4/heparin complexes on the platelet surface, HIT antibodies are capable of intravascular platelet activation by cross-linking Fcγ receptor IIA leading to a platelet count decrease and/or thrombosis. Diagnosis of HIT is often difficult. This, and the low specificity of the commercially available immunoassays, leads currently to substantial overdiagnosis of HIT. Timing of onset, the moderate nature of thrombocytopenia, and the common concurrence of thrombosis are very important factors, which help to differentiate HIT from other potential causes of thrombocytopenia. A combination of a clinical pretest scoring system and laboratory investigation is usually necessary to diagnose HIT. Although HIT is considered to be a rare complication of heparin treatment, the very high number of hospital inpatients, and increasingly also hospital outpatients receiving heparin, still result in a considerable number of patients developing HIT. If HIT occurs, potentially devastating complications such as life-threatening thrombosis make it one of the most serious adverse drug reactions. If HIT is strongly suspected, all heparin must be stopped and an alternative nonheparin anticoagulant started at a therapeutic dose to prevent thromboembolic complications. However, the nonheparin alternative anticoagulants bear a considerable bleeding risk, especially if given to patients with thrombocytopenia due to other reasons than HIT. While established drugs for HIT are disappearing from the market (lepirudin, danaparoid), bivalirudin, fondaparinux and potentially the new anticoagulants such as dabigatran, rivaroxaban and apixaban provide new treatment options.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Recent advances in the diagnosis and treatment of heparin-induced thrombocytopenia

Bakchoul

Greinacher

2012

Therapeutic Advances in Hematology

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“…This early onset of IgG production strongly indicates that patients have been pre-immunized against PF4/polyanion complexes, and we have shown recently that this probably occurs via PF4-coated bacteria. 6,7 In fact, in vitro data and a mouse model suggest that PF4 might have a role in bacterial host defense mechanisms. 7 The risk of developing anti-PF4/H Abs is influenced by patient related factors; for example, it is strongly increased when heparin is given within the context of trauma or inflammation.…”

Section: Introductionmentioning

confidence: 99%

“…7 The risk of developing anti-PF4/H Abs is influenced by patient related factors; for example, it is strongly increased when heparin is given within the context of trauma or inflammation. 6,8 Trauma and inflammation might provide additional "danger signals" facilitating activation of the involved B cells.…”

Section: Introductionmentioning

confidence: 99%

Heparin-induced thrombocytopenia: further evidence for a unique immune response

Pötschke

Selleng

Bröker

et al. 2012

Blood

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Cardiopulmonary bypass surgery (CPB) is associated with a high incidence of IgG Abs against platelet factor 4/heparin (PF4/H) complexes by day 6 after surgery. These Abs are associated with an immune-mediated adverse drug reaction, heparin-induced thrombocytopenia. Although the early onset of the anti-PF4/H IgG response is compatible with a secondary immune response, the rapid decline of Ab titers thereafter is not. To shed light on the origin of these Abs, in the present study, we prospectively compared the kinetics of these Abs with that of Abs against 2 recall Ags and to that of autoantibodies in 166 CPB patients over 4 months. Surgery induced strong inflammation, as shown by an increase in mean C-reactive protein levels. Consistent with previous studies, anti-PF4/H IgG optical density transiently increased between baseline and day 10 (P < .001; not associated with C-reactive protein levels), followed by a decrease over the next months. In con-

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“…First cases of HIT have been described 1958 [7], further recognition and knowledge of this phenomenon emerged later [8][9][10]. If unrecognized, HIT may result in life-threatening complications like pulmonary embolism, deep vein thrombosis, limb ischemia, stroke, myocardial infarction or cerebral vein thrombosis [11,12]. It has a kind of contradictory character regarding the fact that application of an anticoagulant like heparin is able to induce an immune mediated thromboembolic state.…”

Section: Introductionmentioning

confidence: 99%

Anticoagulation in Patients with Heparin-Induced Thrombocytopenia undergoing Percutaneous Coronary Angiography and Interventions

Joost

Kurowski²,

Radke³

2008

CPD

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The administration of heparins (unfractionated or fractionated) represents the current standard as anticoagulant treatment during percutaneous coronary intervention in different clinical settings (elective cases and acute coronary syndrome). Since the incidence of heparin-induced thrombocytopenia (HIT) is expected to range between 0.1 and 5%, the application of an appropriate anticoagulant agent has become a mandatory issue. This review will provide current pathophysiological insights of HIT as well as contemporary alternative anticoagulant strategies during PCI in patients with or at risk of HIT.

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Heparin-Induced Thrombocytopenia: Frequency and Pathogenesis

Cited by 30 publications

References 84 publications

Recent advances in the diagnosis and treatment of heparin-induced thrombocytopenia

Recent advances in the diagnosis and treatment of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia: further evidence for a unique immune response

Anticoagulation in Patients with Heparin-Induced Thrombocytopenia undergoing Percutaneous Coronary Angiography and Interventions

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