Heparin-induced thrombocytopenia classification


 * Associate Editor-In-Chief:, Aric C. Hall, M.D., [mailto:achall@bidmc.harvard.edu]

Overview
Heparin-induced thrombocytopenia is diagnosed when the platelet count falls by > 50% typically after 5-10 days of heparin therapy. There are two forms of HIT. Type II HIT is the main adverse effect of heparin use.

Classification
There are two forms of HIT. Type II HIT is the main adverse effect of heparin use.

Type I

 * In this form patients characteristically have a transient decrease in platelet count (rarely <100,000) without any further symptoms.
 * This thrombocytopenia recovers even if heparin is continued to be administered.
 * It occurs in 10-20% of all patients on heparin.
 * It 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

 * This form 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.
 * The most common form is to the heparin-PF4 complex.
 * Heparin binding to platelet factor 4 causes a conformational change in the protein, rendering it antigenic.
 * Antibodies bind to these complexes, activate the surrounding platelets and generate thrombin.
 * The antibodies found are most commonly are of the IgG class with or without IgM and IgA class antibodies.
 * IgM and IgA are rarely found without IgG antibodies.
 * Type II HIT develops in about 3% of all patients on UFH and in 0.1% of patients on LMWH, and causes thrombosis in 30% to 40% of these patients.
 * The other patients are able to compensate for the activation of hemostasis that leads to thrombosis.
 * Clot formation is mainly arterial
 * Most thrombotic events are in the lower limbs, skin lesions and necrosis may also occur at the site of the heparin infusion.
 * Rapid-onset HIT can result in life-threatening acute systemic reactions (eg rigors, fever, hypertension, tachycardia) and cardiopulmonary collapse.
 * Single or trivial doses of heparin, such as catheter flushes, can cause HIT.
 * In HIT2 the onset of thrombocytopenia is independent of the type of heparin, dose and route of administration.
 * HIT antibodies can persist for 4-6 weeks but disappear after 3 months.
 * The presence of HIT antibodies, even at higher titer, doesn't predict an increase in complications.
 * An increase in the titers of the antibodies do, however, give an increase in the in-vitro activaton of the coagulation system.
 * The ELISA test, though not ideal, is the best predictive diagnostic test of HIT2. It has been suggested that HIT2 only occurs with high  antibody titers and after persistent exposure to heparin; also it suggests that antigens different from the H-PF4 complex can be involved.  There may be a HIT antibody active in a non-heparin dependent manner.  Data exists suggesting that there are "superactive" HIT antibodies capable of activating platelets without heparin.