Heparin Induced Thrombocytopenia,A clinical-pathological syndrome

Heparin is an anticoagulant indicated for different clinical situations like prophylaxis and treatment of venous thromboembolism, peripheral arterial embolism, thromboembolic complications from atrial fibrillation, prevention of clotting prior to cardiac surgery as well as several other indications. Heparin induced thrombocytopenia (HIT) is an adverse drug reaction of heparin therapy that is potentially life threating. HIT is caused by platelet activating IgG anti-bodies that recognize complexes of platelet factor 4 (PF4) and heparin. These immune complexes can bind to platelets (Fcγ RIIa) and monocyte (Fcγ RI). Cross linking between these Fcγ receptors can lead to platelet activation and subsequently thrombin generation; these events can resulting in arterial and/or venous thrombotic reactions and increased risk of morbidity and mortality. Immediate diagnosis of HIT is necessary and if diagnosis be confirmed, administration of heparin should be stopped and alternative anticoagulants , like Hirudin or Argatroban should be replaced.Because HIT is a clinicopathological syndrome, attention to clinical events and laboratory findings is necessary for diagnosis of HIT. 4TScore is commonly used assertion system for clinical evaluation of HIT and assigns a score (0,1, or 2; maximum total score 8) for the following symptoms:1) Degree of Thrombocytopenia,2) Time of platelet count decrease after exposure to heparin,3) Occurrence of clinical events like Thrombosis, skin necrosis and so on,4) And excluding other causes of thrombocytopeniaA 4Tscore 0f 6-8 is consistent with high pretest probability of HIT, a score 4-5 is consistent with intermediate probability of HIT and score 0-3 is consistent with low probability of HIT. 4Tscore has excellent negative predictive value (NPV) with 4Tscore<3 and so further laboratory examinations are not necessary. On the other hand, intermediate (4-5) and high(6-8) scores , poorly predict the disease and should be confirmed and followed by diagnostic laboratory tests.In general, two types of laboratory assays are available:1- Immunoassays: Immunoassay are technically simple with high sensitivity (> 97%) but poor specificity (30-70%) for diagnosis of HIT. Check the anti-PF4-heparin antibodies using enzyme-linked immunosorbent assay is one of the most popular immunoassays, however, ELISA results are available once daily at most because determination is time-consuming. Recently several rapid immunoassays (RIA) have been developed to overcome this limitation, with the possibility of less than 30 minutes giving the results with high sensitivity and reasonable specificity. The available RIAs are particle gel immunoassay (PaGIA) , lateral flow immunoassay , latex immunoturbidimetric assay , and chemiluminescent immunoassay .Functional assays: like serotonin releasing assay (SRA) and heparin induced platelet activation test (HIPA) are considered as gold standard for diagnosis of HIT and can detect the subset of anti PF4/heparin antibodies which are able to active platelets an