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Anti-Thrombotic Agents (Fibrinolytics (IV administration) (Streptokinase…

- - - - has a pentasaccharide sequence that binds to antithrombin 3, activates antithrombin 3 so that it can bind to coagulation factor Xa and thrombin (Factor 2a) to inhibit it. Hence fibrin clot cannot be formed
        
        Enhance AT‐III to inhibit factors 2a, 9a, 10a
        Stimulates Tissue Factor Pathway Inhibitor (TFPI) release from endothelium, inhibiting factor 10a
        
        Sources: Porcine Intestines/Bovine Lungs
        ROA: IV (Infusion Pump) & Subcutaneous
        On‐Set: Immediate (IV); 20‐60 min (SQ)
        DOES NOT Cross Placenta
        Used In Pregnant Women At Risk of Thrombosis
        
        Side Effects of Heparin
        Bleeding (8‐10%) [aPTT monitoring]
        Allergy leading to Heparin‐Induced Thrombocytopenia (HIT) due to antibodies against the porcine/bovine heparin
        (Paradoxical Thromboembolism)
        Platelet Counts Should Be Performed
        Long term side effects:
        Osteoporosis/Spontaneous Fractures
        Transient Reversible Alopecia
        Mineralocorticoid Deficiency
    - - has a pentasaccharide sequence that binds to antithrombin 3, activates antithrombin 3 and only binds to factor Xa which is smaller than thrombin, Inhibits More On Factor Xa & Less On Factor IIa, Subcutaneous administration only, less side effects than UFH
  - - - Inhibit synthesis of factors 2,7,9,10, protein C/S
        
        How?
        
        Gla residues of factors 2,7,9,10, protein C/S are non-functional, they need to be gamma carboxylated to be functional
        
        Gamma carboxylase needs Vitamin K to be a cofactor. VitK is converted to an epoxide. In order to replenish the pool of VitK, the oxidised product/epoxide is converted back to active Vit K via Vitamin K Epoxide Reductase (VKOR). Warfarin inhibits VKOR, reducing the pool of active Vit K
      - Factor 5a and 8a inhibited by protein C. Warfarin lowers level of protein C, causing factors 5a and 8a to increase
    - - Why cutaneous necrosis and infarction?
        Warfarin reduces protein C level, protein C supposed to inhibit factor 5a, 8a. Hence, hypercoagulable state leads to blood clots. The blood clots interrupt the blood supply to the skin, causing necrosis
- - - - Decrease TXA2 from platelets
        Decrease PGI2 from endothelium
        Block more TXA2 than PGI2
        
        TXA2 increases platelet aggregation
        PGI2 inhibits platelet activation