Heparin induced thrombocytopenia syndrome (HIT I and HIT II)

Heparin induced thrombocytopenia syndrome (HIT I and HIT II)

Heparin induced thrombocytopenia (HIT) was described as two types – HIT I and HIT II (HIT 1 and 2). HIT 1 is a self limiting disease and a non-immune mediated response to heparin which occurs within 1 – 4 days of exposure to heparin. It is not associated with thrombosis and is unlikely to worsen with continued use of heparin. HIT 1 is mediated by a direct interaction between heparin and circulating platelets. This interaction causes clumping or sequestration of platelets. Thrombocytopenia is usually mild and transient and often returns to normal within 4 days of withdrawal of heparin [1].

HIT 2 or HITTS (Heparin Induced Thrombocytopenia and Thrombosis Syndrome) is a more dangerous form in which IgG antibodies against heparin-platelet factor 4 complex are formed. The IgG antibody binds to heparin-platelet factor 4 complex, leading to platelet activation, platelet consumption and thrombocytopenia [2]. The IgG antibodies are known as HIT antibodies or HIT IgG. The antigen antibody complexes can cause production of tissue factor by their interaction with monocytes. Antibody mediated endothelial injury can also occur. These in turn can further activate the coagulation cascade.

There is also a suggestion that HIT 1 be renamed as non‐immune heparin associated thrombocytopenia and HIT 2 as just HIT. Many publications refer to HIT 2 as just HIT.

HIT 2 occurs within 5 to 14 days of exposure to heparin and is associated with thrombotic events [3]. In those who have been previously exposed to heparin recently, the onset is earlier and can occur within hours. HIT is unlikely to be a cause for thrombocytopenia within 5 days of heparin initiation in those who have not received heparin within the previous 3 months [4].

Direct thrombin inhibitors like bivalirudin is the drug of choice in HITTS/HIT 2. Though the chance of developing HITTS with low molecular weight heparin is lower than that with conventional heparin, low molecular weight heparin cannot be used after the onset of HITTS.

Routine monitoring of platelet count in those receiving heparin is recommended for early detection of HIT [3]. Higher risk patients who are receiving therapeutic doses of unfractionated heparin need at least alternate day platelet count estimation.

When warfarin has to be started for conditions like deep vein thrombosis in those with HITTS, it should be delayed till platelet count has fully recovered. Warfarin is started at the expected maintenance dose. Loading dose of warfarin is not given. Parenteral anticoagulation is overlapped for at least 5 days until target international normalized ratio (INR) level has been maintained for 2 days.

References

1. Ahmed I, Majeed A, Powell R. Heparin induced thrombocytopenia: diagnosis and management update. Postgrad Med J. 2007 Sep;83(983):575-82.
2. Kelton JG, Smith JW, Warkentin TE, Hayward CP, Denomme GA, Horsewood P. Immunoglobulin G from patients with heparin-induced thrombocytopenia binds to a complex of heparin and platelet factor 4. Blood. 1994 Jun 1;83(11):3232-9.
3. Warkentin TE, Greinacher A. Heparin-induced thrombocytopenia: recognition, treatment, and prevention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):311S-337S.
4. Lubenow N, Kempf R, Eichner A, Eichler P, Carlsson LE, Greinacher A. Heparin-induced thrombocytopenia: temporal pattern of thrombocytopenia in relation to initial use or reexposure to heparin. Chest. 2002 Jul;122(1):37-42.