Heparin Induced Thrombocytopenia (HIT) PDF

Heparin Induced Thrombocytopenia PM Dr Zariyantey Abd Hamid prothrombin inhibit thrombin activity cheaper ↓ - Thrombin (X) ↳> Fibrinogen...

Heparin Induced Thrombocytopenia PM Dr Zariyantey Abd Hamid prothrombin inhibit thrombin activity cheaper ↓ - Thrombin (X) ↳> Fibrinogen HEPARIN Y univers al > - Fibrin 1. An anticoagulant with antithrombin property 2. Activate antithrombin III – inactivates thrombin, factor Xa and other proteases- inhibit fibrinogen conversion to fibrin – inhibit clot = anti-clotting effect Side Effects 1. Bleeding 2. Heparin induced thrombocytopenia (HIT) 3. To stop these side effects, replacement of heparin with other anticoagulant is required.  MOA HEPARIN Heparin : synthetically made : Grade-purity i nactivation Inhibition * thrombin activity inhibit Fibrinogen ↓ Fibrin (X)  WHAT IS HIT?? HEPARIN-INDUCED THROMBOCYTOPENIA ANTI- DECREASED NUMBER of COAGULANT = THROMBOCYTES (Platelets) Prevent blood clots HIT : complication caused by heparin that causes decreased platelets in the blood  WHAT IS HIT?? HEPARIN is typically used to treat thrombotic event such as in pulmonary embolism, myocardial infarction and stroke With HIT, instead of working as anti-coagulant, heparin becomes pro-coagulant Thus thrombus getting bigger in patient with thrombotic event  SO WHAT IS HIT ? 1. Instead of functioning as anticoagulant, heparin becomes procoagulant. 2. Everyone receives heparin is at risk for HIT, so platelet counts is important measurement following administration of heparin. 3. It 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 remains above 150 x 109/L. (Normal Range 150 - 400 x 109 per liter)  HIT : From Exposure to Treatment EXPOSURE PATHOPHYSIOLOGY SYMPTOMS DIAGNOSIS Trombocytopenia Clinical Scoring IMMUNE-MEDIATED Venous / Arterial HEPARIN Heparin-PF4-IGg Complex Platelet Count Thrombosis Platelet Activation Serology Test Serotonin release assay TREATMENT 1. STOP HEPARIN 2. ALTERNATIVE ANTICOAGULANT 3. PLATELET TRANSFUSION  HIT 1. Heparin-induced thrombocytopenia (HIT) is a life-threatening complication of exposure to heparin that occurs in patients exposed, regardless of the dose, schedule, or route of administration. how purity 2. Heparin is administered as unfractionated heparin (UFH) or low molecular weight [LMW] heparin. High purity ( 3. HIT is more common in UFH exposure than LMWH due to greater immunogenic property and greater cross-reactivity with PF4  Type of HIT HIT type I (HIT I) Temporary (nonimmunes - 1. is a mild, transient drop in platelet count that typically occurs within the first two days of heparin exposure. 2. The platelet count typically returns to normal with discontinued heparin administration. 3. Direct effect of heparin on platelets by non-immune-mediated platelet aggregation. 4. Not clinically significant.  Type of HIT HIT type II (HIT II) immune-mediated - 1. An immune-mediated disorder that typically occurs 5-14 days after exposure to heparin. 2. Has life-and limb-threatening thrombotic complications.  HIT TYPE 2 Rapid, Typical, and Delayed Typical HIT: The onset of HIT occurs 5-14 days after starting heparin therapy. Rapid-onset HIT: This can occur in some patients who have had heparin pre exposure within the last 100 days, in which the platelet count falls within 24 = hours of starting heparin. ↳ Thrombocytopenia develop Delayed-onset HIT: Patients develop HIT and present with thrombosis and unexplained thrombocytopenia up to 3 weeks after the end of their heparin therapy.  Initiate immune Platelet-factor 4 response on platelet Recognize as foreign cell + pF4  PATHOPHYSIOLOGY OF HIT Heparin binds to platelet factor 4 (PF4) exposes a previously masked immune epitope, formation of heparin-PF4 complex Trigger production of Pre-mature thrombocyte clearance immunoglobulin (Ig) G antibodies lead to thrombocytopenia Binding of Antibodies to heparin-PF4 complex Platelet activation – platelet aggregation - thrombosis- hypercoagulability state Form circulating immune complex (CIC) Platelet activation also leads to Further stimulation of the Binding CIC on FC-receptor on platelet additional PF4 release immunoreaction.  CLINICAL ASPECTS Clinical manifestation 1. Hypercoagulable state 2. Thrombocytopenia Complication 1. Deep venous thrombosis (most common) 2. Pulmonary embolism (most common) 3. Myocardial infarction 4. Occlusion of limb arteries (possibly resulting in amputation) 5. Transient ischemic attack and stroke 6. Skin necrosis 7. End-organ damage (eg, adrenal, bowel, spleen, gallbladder, or hepatic infarction; renal failure) 8. Death DIAGNOSIS CLINICAL SCORING (4T SCORE)  DIAGNOSIS : DIAGNOSTIC ASSAY 1. The anti-PF4 test: an immunologic, enzyme-linked immunosorbent assay (ELISA) that detects IgG antibodies against the platelet factor 4 (PF4)/heparin complex. sensitive but not spesific can defect but specifically what antigen - X 2. The Serotonin Release Assay test -more definite functional assay that measures heparin-dependent platelet activation. confirmatory test better predictor of thrombosis than anti-PF4 assay