Heparin-induced thrombocytopenia overview


 * Associate Editor(s)-In-Chief: Priyamvada Singh, M.B.B.S. [mailto:psingh@perfuse.org]

Overview
Heparin-induced thrombocytopenia is diagnosed when the platelet count falls by > 50% typically after 5-10 days of heparin therapy. The development of mild to moderate thrombocytopenia (platelet counts of 50-70,000) in the context of heparin exposure is suggestive of a possible diagnosis of HIT while severe thrombocytopenia and platelet counts less than 20,000 are quite unusual for the syndrome. Given the nadirs in the platelet count, clinically significant bleeding associated with the thrombocoytopenia is quite rare. On the contrary, heparin induced thrombocytopenia is primarily a thrombotic disorder, with very high rates of thrombosis, in the arteries with or without venous complications.

Epidemiology and Demographics
It has been found to occur with increased frequencies in females, white population and patients over age of 60 years. An episode of Heparin-induced thrombocytopenia increases risks for other future thrombo-embolic events.

Pathophysiology
It is caused by antibodies to complexes between heparin and platelet factor 4 (PF4). These antibody complexes stimulates the procoagulant pathways due to activation of platelet and endothelium.

Classification
There are two types of HIT, type I and type II. Type I HIT patients characteristically have a transient decrease in platelet count (rarely <100,000) without any further symptoms and can recover even if heparin is continued to be administered. It occurs in 10-20% of all patients on heparin and is not due to an immune reaction and antibodies are not found upon investigation. HIT-1 is due to heparin-induced platelet clumping; it is innocuous. Type II is due to an autoimmune reaction with antibodies formed against platelet factor 4 (PF4), neutrophil-activating peptide 2 (NAP-2) and interleukin 8 (IL8) which form complexes with heparin.

Causes
Heparin-induced thrombocytopenia (HIT) with or without thrombosis (HITT) is thrombocytopenia (low platelet counts) due to the administration of heparin. While it is mainly associated with unfractionated heparin (UFH), it can also occur with exposure to low-molecular weight heparin (LMWH), but at significantly lower rates.

History and symptoms
HIT typically develops 4-14 days after the administration of heparin. The onset of thrombocytopenia in less than 4-5 days after the initiation of heparin treatment is extremely rare due to the time required for antibody production, and alternative explanations should be sought for the development of thrombocytopenia this early in therapy. The primary exception to this is in the case of recent heparin exposures (<100 days) where the patient may have pre-existing antibodies against the heparin-PF4 complex.

Lab tests
The four commonest diagnostic tests used for heparin-induced thrombocytopenia (HIT) are Serotonin release assay, heparin-induced platelet aggregation assay, solid phase immunoassay (enzyme-linked immunosorbent assay), and particle gel immunoassay.

Treatment
Treatment is by prompt withdrawal of heparin and replacement with a suitable alternative anticoagulant. Lepirudin, fondaparinux, bivalirudin, argatroban, danaparoid or other direct thrombin inhibitors are used to treat the thrombotic state. Out of these lepirudin and argatroban are available for use in USA.

Prevention
Patients with HIT should be treated with Bivalirudin, a direct thrombin inhibitor to support future procedures.