Emphasis on the Role of PF4 in the Incidence, Pathophysiology and Treatment of Heparin Induced Thrombocytopenia

Prechel, Margaret; Walenga, Jeanine M.

doi:10.1186/1477-9560-11-7

Cited by 42 publications

(42 citation statements)

References 138 publications

(167 reference statements)

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“…Additionally, Roy and associates have shown similar results in DM patients [18]. A possible explanation for the risk of HPF4 formation that extends beyond the duration or frequency of heparin exposure in DM is that persistent heparin exposure may not be necessary for antibody formation to occur against the excess PF4 that exists surface bound to mucopolysaccharides or glycosaminoglycans on the platelet surface [13,19].…”

Section: Discussionmentioning

confidence: 78%

Elevated Heparin Induced Antibodies are More Common in Diabetic Patients With Vascular Disease

Patel

Street

Haydar

et al. 2013

Journal of Surgical Research

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Section: Discussionmentioning

confidence: 78%

Elevated Heparin Induced Antibodies are More Common in Diabetic Patients With Vascular Disease

Patel

Street

Haydar

et al. 2013

Journal of Surgical Research

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“…HIT is associated with the generation of IgG antibodies directed against the complex formed by the binding of a negatively charged heparin molecule to platelet factor 4 (PF4) [7][8]10]. Extremely few complexes that form with heparin, PF4 and the antibodies of the other immunoglobulin classes are clinically irrelevant and usually do not induce HIT [4, 5, 7−9].…”

Section: Pathophysiologymentioning

confidence: 99%

“…Extremely few complexes that form with heparin, PF4 and the antibodies of the other immunoglobulin classes are clinically irrelevant and usually do not induce HIT [4, 5, 7−9]. IgG/PF4/heparin complexes bind to platelet Fc receptors, activate the receptors and lead to thrombocytopenia [10]. Immune complexes can also activate thrombin, resulting in arterial and venous prothrombotic activity, which is defined as HIT with thrombosis (HITT) [7−9].…”

Section: Pathophysiologymentioning

confidence: 99%

Małopłytkowość poheparynowa

Krzych

Nowacka²,

Knapik³

2015

Anaesthesiol Intensive Ther

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Heparin-induced thrombocytopenia (HIT) is a clinical immune-mediated syndrome; symptoms of HIT result from the development of arterial and venous thrombosis and are correlated with the severity of the thrombocytopenia. In all patients receiving heparin preparations in intensive care units, platelet counts should be monitored every 2−3 days throughout therapy, particularly during days 4−14 when HIT is most likely to develop. The major screening tests should always involve a clinical assessment of HIT probability (4Ts or HEP scoring systems) and enzymatic immunoassays (IgG antibodies) for patients with a moderate to high risk of HIT. The full possibilities of such advanced diagnostic procedures are limited in Poland because functional tests are still not widely available. If the diagnosis is questionable, all heparin preparations should be withdrawn and an alternative method of anticoagulation instituted until HIT has been conclusively excluded. The use of new-generation anticoagulants (direct thrombin or Xa factor inhibitors) is currently considered the treatment of choice. Old-generation anticoagulants should not be administered (vitamin K antagonists) as they can aggravate thrombosis. If administered, their action should be reversed by vitamin K once HIT is confirmed. Antithrombotic therapy with "new" anticoagulants should be carried out at least until platelet counts return to the baseline values; the recommended duration of therapy is 4 weeks in patients with isolated thrombocytopenia or 4 months in those with thrombotic complications. Vitamin K antagonists should not be applied until the normal platelet count is restored (usually > 150 G L -1 ). When the therapy with vitamin K antagonists is reintroduced, "old" antagonists should be administered simultaneously with a "new" anticoagulant for at least 5 days due to an initial decrease in protein C concentration concentration, provided that the therapeutic value of INR is maintained (> 2) for at least 2 days.

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“…For example, the gold-standard assays for HIT, the serotonin release assay and the Hep-induced washed platelet activation test, rely on ‘good/highly reactive’ healthy donor platelets, the characteristics of which have been empirical [34]. Rollin et al .…”

Section: Pathophysiologymentioning

confidence: 99%

“…Importantly, as the molar ratio of PF4 to GAG is important for the extent of complex formation and antibody recognition, empiric adjustment of dosing will be required to find the optimal dose at which the correct ratio will be achieved in vivo . A recent lucid summary of PF4 bioavailability in HIT was published, with implications for use of ODSH [34]. …”

Section: Therapeuticsmentioning

confidence: 99%

Advances in the pathophysiology and treatment of heparin-induced thrombocytopenia

McKenzie

Sachais²

2014

Current Opinion in Hematology

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Purpose of review To review the recent developments in understanding the pathophysiology of heparin-induced thrombocytopenia (HIT) and in applying this knowledge to the treatment of patients with suspected and proven HIT. Recent findings HIT pathophysiology is dynamic and complex. HIT pathophysiology is initiated by four essential components – heparin (Hep), platelet factor 4 (PF4), IgG antibodies against the Hep–PF4 complex, and platelet FcγRIIa. HIT is propagated by activated platelets, monocytes, endothelial cells, and coagulation proteins. Insights into the unique HIT antibody response continue to emerge, but without consensus as to the relative roles of B cells, T cells, and antigen-presenting cells. Platelet activation via FcγRIIa, the sine qua non of HIT, has become much better appreciated. Therapy remains challenging for several reasons. Suspected HIT is more frequent than proven HIT, because of the widespread use of Hep and the inadequacies of current diagnostic tests and scoring systems. In proven HIT, approved treatments reduce but do not eliminate thrombosis, and have substantial bleeding risk. Rational novel therapeutic strategies, directed at the initiating steps in HIT pathophysiology and with potential combinations staged over time, are in various phases of development. Summary Progress continues in understanding the breadth of molecular and cellular players in HIT. Translation to improved diagnosis and treatment is needed.

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Emphasis on the Role of PF4 in the Incidence, Pathophysiology and Treatment of Heparin Induced Thrombocytopenia

Cited by 42 publications

References 138 publications

Elevated Heparin Induced Antibodies are More Common in Diabetic Patients With Vascular Disease

Elevated Heparin Induced Antibodies are More Common in Diabetic Patients With Vascular Disease

Małopłytkowość poheparynowa

Advances in the pathophysiology and treatment of heparin-induced thrombocytopenia

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