HEPARIN-INDUCED
THROMBOCYTOPENIA (HIT): Management of
heparin-induced
thrombocytopenia (HIT) and treatment options have significantly changed recently.
Heparin may induce two types of
thrombocytopenia. Type I, occurring earlier with a much higher rate of incidence (5-30%), is characterized by mild
thrombocytopenia without significant clinical manifestations. Type II, is less frequent (0.5-2%), life threatening immune type, develops following a period of minimum 5-7 days upon introduction of
heparin therapy (patients earlier treated with
heparin are excluded). Type II
heparin-induced
thrombocytopenia with severely reduced platelet count may be clinically manifested by
thrombosis in 20-50% cases within the period of 30 days. HIT is suspected in persons resistant to
heparin with relatively reduced platelet count, though HIT is described in person with normal platelet counts, as well. None of available assays used for HIT detection is completely reliable. Sensitivity of a highly specific platelet aggregation assay is only 36%, sensitivity and specificity of 14C-serotonin release assays amounts to 95%, while ELISA using a
heparin/platelet factor-4 target has a sensitivity of 85%. Thus, it is sometimes necessary to combine functional and
antigen assays. Furthermore, new classes of
antigen assays, like antibody detection tests of complexes between
heparin and
neutrophil-activating peptide-2 as well as those between
heparin and
interleukin-8, have been used. CURRENT
THERAPY OPTIONS: Current
therapy options exclude formerly applied low-molecular-weight heparins due to the existing cross-reactivity of 80-100%.
Danaparoid sodium exhibits in vitro cross-reactivity of 10-61%, clinically manifested in less than 5% of patients. Two drugs are drugs of choice in HIT type II treatment:
lepirudin, especially in patients without
renal failure, and
argatroban, particularly in patients with
renal failure. The following procedures and agents are also efficient: asmapheresis in the first four days, high-dose intravenous gammaglobulin, antiaggregans, especially
ADP antagonists,
aspirin, dipirydamole,
dextran,
prostacyclin analagoues,
thrombolytic therapy as well as thromboembolectomy. Oral
anticoagulants are not administered in active HIT type II, in
deep vein thrombosis with high international normalized ratio (INR) and
thrombin-
antithrombin complexes, and low
protein C levels to avoid the possibility of venous limb
gangrene development. They can be administered in a stable phase, when the
thrombin generation is controlled by previous administration of one of the above-mentioned alternative
anticoagulants.