Heparin Induced Thrombocytopenia

 Heparin induced thrombocytopenia(HIT) is a clinical pathological syndrome that occurs when Heparin dependent IgG antibodies bind to heparin /PLATELET factor  4  complexes to activate platelets and produce a hypercoagulable state

BACKGROUND

There are two types of HIT.Type 1 HIT is a non immune disorder that typically occurs in 2 days after exposure to HEPARIN,and the platelet count normalizes with continued Heparin therapyType 1 HIT is a non immune disorder that results from the direct affect of heparin on platelet activation

Type 2 HIT is an immune mediated disorder that typically occurs in 4-10 days after exposure to Heparin and has life threatening thrombotic complications

HIT must be suspected when a patient who is receiving heparin has a decrease in the platelet count , particularly if the fall is over 50% of the baseline count, even if the platelet count nadir remains above ,Clinically HIT may manifest as skin lesions at heparin injection sites or by acute systemic reaction ( eg;chills, fever, dyspnea, chest pain) after IV infusion of Heparin.

unlike other forms of thrombocytopenia , HIT is generally not marked by bleeding ,instead of venous thromboembolism, (DVT or Pulmonary Embolism) is the most common complication.less often arterial thrombosis can occur, for that reason,the disorder is sometimes termed Heparin induced thrombocytopenia  and thrombosis (HITT)

Pathogenesis

HIT is a prothrombotic disorder is caused by antibodies to complexes of PLATELET FACTOR 4 (PF4) and heparin

the antibodies binds to the PF4 heparin complexes on the platelet surface and induce platelet activation by cross linking Fcy2a receptors . The activated platelets increase the release and surface expression of PF4 , creating a positive loop in which further release of PF4 promotes platelet activation.

alternatively  HIT antibodies may recognize PF4 bound to platelet Chondroitin sulfate, these antibodies activate platelets even the absence of Heparin, These antibodies activate platelets even in the absence of 

heparin. Thus explaining delayed onset HIT , persistent HIT [recovery take several weeks) or spontaneous HIT syndrome  and Fondaparinux associated HIT.

ETIOLOGY

Prolong use of Heparin is a main etiological factor, HIT is more frequently encountered with unfractionated heparin than with low molecular weight heparin.

the risk of HIT is highest is highest with prolong use of heparin for postoperative thrombophylaxis.and fondaparinux may be associated with formation of anti PF4 /heparin antibodies but in contrast low molecular weight heparin (LMWH) is unlikely to cause HIT because of the poor reactivity of anti bodies  against PF4 /fondaparinux

Diagnosis

diagnosis of HIT is based on the combination of clinical findings, thrombocytopenia characteristics and laboratory findings of HIT anti bodies, 

Treatment

Treatment of HIT begins with discontinuation of all Heparin products( including heparin flushes of IV catheters) ,so patient should then be started on an alternative anticoagulant .