Heparin Associated Thrombocytopenia

Pathophysiology

Due to a lack of standard diagnostic criteria and lab tests, the incidence of HAT has been variably reported in the literature (1.1-30%). More recent estimates puts the incidence at 3.0%. HAT is increased with prior exposure to heparin and the type of heparin.

Platelet Factor 4 (PF4) is a heparin binding protein stored in platelets and released into plasma following platelet activation. Heparin/PF4 complexes normally do not have adverse sequelae. Specific antibodies to Heparin/PF4 complexes generate IgG complexes (Heparin associated Platelet Aggregating Factor) that activate platelets. Platelets are activated by the Fc portion of IgG and Heparin/PF4 in the immune complex may bind to adjacent platelets or to the same platelet. These activated platelets release procoagulant microparticles that provide a phos-pholipid surface to accelerate thrombin generation. This leads to platelet activation and thrombosis or their removal by the spleen and thrombocytopenia.

There are two distinct types of HAT distinguishable clinically, but not with diagnostic tests (Table 13.1).

The diagnosis of HAT is based on:

• thrombocytopenia during heparin therapy (> 50% decrease)

• absence of other causes of thrombocytopenia

• resolution of thrombocytopenia after discontinuation of heparin

• confirmation of heparin dependent platelet antibody by in vitro testing

Heparin Associated Thrombocytopenia and Thrombosis (HATT) presents clinically as

• Arterial thromboses, most often involving major vessels of extremities, less frequently cerebral and mesenteric vasculature and implicated in myocardial, kidney and adrenal infarction.

Table 13.1. Comparison HAT I and HAT II

HAT I

HAT II

Thrombocytopenia mild seldom < 100,000 Onset after heparin 1-2 days Symptoms none, mild severe, often < 60,000

4-14 days (sooner if repeat exposure)

may lead to thrombosis, bleeding uncommon nonrecovery of platelet count recovery of platelet count 5-7 days stop heparin

• Venous thrombosis including deep venous thrombosis (DVT), pulmonary embolism (PE) and warfarin associated venous limb gangrene.

• Skin lesions at heparin injection sites.

• Overall 30% mortality and 20% risk of limb amputation.

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