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Drug Induced Immune Thrombocytopenia (HIT) (Epidimiology (Patients exposed…
Drug Induced Immune Thrombocytopenia (HIT)
Etiology
HIT 1
Antibody is present, but not clinically significant
HIT 2
Antibody is present and clinically significant
Autoimmune HIT
Rare, usually occurs after major surgery
Pathogenesis
Activated Platelet (d/t surgery or infection) release of PF4 from alpha granule
-PF4/Heparin polyanion complex is formed
-PF4/Bacteria polyanion complex is formed
Activation of B cell and production of IgG against PF4
IgG ab-PF4/polyanion complex
-Platelet activation and more platelet activation (causing increased thrombosis)
-Monocytes activated (causes thrombosis)
-Platelets bound with anti PF4 antibodies are removed by splenic macrophages
Thrombosis and splenic clearing (causes thrombocytopenia)
Epidimiology
Patients exposed to heparin
0.1% - 5% (varies according to several host and drug related factors)
Postoperative & trauma patients who receive heparin
1% - 5% (highest incidence)
Medical patients who received prophylactic heparin
< 1% (very rare)
Obstetric patients
< 0.1% (extremely rare)
Women vs men
1.5 - 2 fold increased incidence
Greater incidence in unfractionated heparin use vs low molecular weight heparin
Diagnosis
Enzyme Linked Immunosorbent Assay (ELISA)
Optical density test for quantification (if ELISA is positive)
Serotonin Release Assay (SRA)
(gold standard for diagnosis, negative SRA does not exclude HIT)
4T scoring system
Treatment
Direct Thrombin Inhibitor
-Lepirudin (FDA approved)
-Argatroban (FDA approved)
-Bivalidurdin (off label use)
Continue treatment until platelet count is >150,000 for 2 consecutive days
Avoid Warfarin
Clinical Manifestations
4T's
Acute Thrombocytopenia
-Usually > 20,000
-10% have platelet count decrease of 30-50%
Timing of onset
-Typically takes 5 days for antibody production
-Exception of if patient was on heparin in the near past
-Rapid onset (within 30 min)
-Delayed onset (up to 3 weeks after)
New Thrombosis
VTE occurs in 50% of confirmed HIT
Other causes of thrombocytopenia
-DIC
-Drugs