Heparin is an anticoagulant (blood thinner) used mainly in the prevention and treatment of deep vein thrombosis, pulmonary embolism, arterial thromboembolism, heart attacks and unstable angina. A common side effect of heparin use is bleeding. A more serous complication is Heparin Induced Thrombocytopaenia (HIT). HIT is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 (PF4 – a positively charged platelet protein stored in platelet α-granules and released in high quantities at sites of platelet activation) and heparin – Anti-PF4/heparin antibodies. Pathogenic antibodies to PF4/heparin bind and activate cellular FcγRIIA on platelets to propagate a hypercoagulable state which can lead to life-threatening thrombosis.
The development of anti-PF4/heparin antibodies is common (8% to 50%), however, clinical complications of thrombocytopenia and thrombosis are far less frequent, affecting approximately 0.2%-3% of patients exposed to the drug. Once antibodies develop, some patients experience a profound thrombocytopenia and progress to life-threatening complications of thrombosis. The principal cellular targets for HIT antibodies are platelets, which express FcγRIIa receptors. Binding of HIT antibodies to platelet FcγRIIA elicits platelet activation via intracellular signalling involving the spleen tyrosine kinase and release of procoagulant microparticles. Platelet activation accompanied by intense thrombin generation.
Diagnosis of HIT requires demonstration of thrombocytopenia (platelet count < 150 x 109/L) and/or thrombosis at around the time of heparin therapy while excluding other causes of thrombocytopenia. In heparin-naïve individuals, Anti-PF4/heparin antibodies become detectable at a median of 4 days from start of heparin treatment. Thrombocytopenia and/or thrombosis develop 5 to 14 days after initial heparin therapy and on average, approximately 2 days (range 1-5 days) after antibody detection.
The H&I laboratory can contribute to the diagnosis of HIT through functional assays as well as immunoassays. Test for both HIT and PTP. If HIT is confirmed then stop PTP investigation. Functional assays include platelet activation assays such as measuring release of radio-labelled serotonin from target platelets exposed to patient serum and a low concentration of heparin and platelet aggregation assays. These assays are highly specific for HIT but tend to be complex to perform and not highly sensitive.
Immunoassays on the other hand are relatively easy to perform. They detect the presence of anti-PF4/heparin antibodies using a variety of antibody capture platforms, including enzyme-linked immunosorbent assay and particle gel.
Treatment for HIT involves discontinuation of all sources of heparin and administration of one of the alternative agents such as Danaparoid or Bivalirudin.
Heparin antibodies should be Neg after 100 days.