Intrinsic pathway Extrinsic pathway Common pathway thombosis Thomboembolus

Intrinsic pathway Extrinsic pathway Common pathway

thombosis �Thomboembolus : thomboembolism DVT : deep vein thrombosis PE : pulmonary embolism Cardioembolic stroke

ยาตานการแขงตวของเลอด (Anticoagulants) ชนด ฉด Unfractionated heparin (UFH) Low molecular weight heparins (LMWH) ชนด กน Vitamin K antagonists: warfarin

การตรวจผลทางหองปฏบตการ �Activated partial thromboplastin Time (a. PTT) �Prothrombin Time (PT) �International Normalized Ratio (INR) �Heparin Anti-factor Xa Level

Unfractionated Heparin (UFH) �Heterogeneous mixture of polysaccharide �chains (40 -45 chains) �MW ~ 3, 000 -30, 000 daltons �มความเปนประจลบบนโมเลกลสง �Pentasaccharide is present in only 1/3 of heparin molecules

Pentasaccharide (5 units) irreversible ยบยง Xa > 18 units factor

1/2

Limitations of UFH �Nonspecific binding to proteins and cells �Poor bioavailability at low doses �Marked variability in its anticoagulant response �Short plasma half-life �Need frequent monitoring of activated Partial Thromboplastin Time (a. PTT) �Heparin-induced thrombocytopenia (HIT)

LMHN �Obtained through chemical or enzymatic depolymerization of heparin �Approximately 1/3 of the size of heparin (average MW = 5, 000 d) �More selective and more potent in inactivating factor Xa but have little effect on thrombin

Monitoring of Therapy Efficacy a. PTT for UFH, None for LMWH Safety CBC Renal function Liver function Signs/symptoms of bleeding

Dosing of LMWH �Enoxaparin 1 mg/kg SQ q 12 hr (1 mg = 100 IU) 1 mg/kg SQ OD if Cr. Cl < 30 ml/min

Reversal of Heparin �Protamine: basic protein derived from fish sperm, binds to heparin, form a stable salt. � 1 mg of protamine neutralize 100 U UFH. �A patient who bleeds immediately following an IV bolus of 5, 000 U UFH, use 50 mg protamine. �a patient receiving a continuous IV infusion of 1, 250 U per hour will require approximately 30 mg protamine.

warfarin

Half-life of clotting factors �Factor VII (proconvertin) �Factor IX (Christmas factor) �Factor X (Stuart factor) �Factor II (Prothrombin) �Protein C = 6 hr = 24 hr = 40 hr = 60 hr = 8 hr

ปจจยทมผลตอคา �อาย �Drug adherence �Alcoholic drink �Disease states �Drug interaction INR Increase INR hyperthyroids CHF liver disease fever diarrhea

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