Venous Thrombo_Embolism .pdf

thrombus composed of cellular material (red and white blood cells, platelets) Deep vein thrombosis (DVT) Intro: factors IXa, Xa, XIIa, thrombin (IIa). It is the common cardiovascular disease which results from: bound together with fibrin strands in the veins. clot formation in the venous circula...

thrombus composed of cellular material (red and white blood cells, platelets) Deep vein thrombosis (DVT) Intro: factors IXa, Xa, XIIa, thrombin (IIa). It is the common cardiovascular disease which results from: bound together with fibrin strands in the veins. clot formation in the venous circulation and is manifested as Pulmonary embolism (PE). is mediated through UFH-antithrombin complex inhibiting the activity of thrombus that arises from the systemic circulation in the pulmonary blood vessels, causing complete or partial obstruction of pulmonary blood flow. MOA: factor V It also inhibits thrombininduced activation of factor VIII. ➢ hypersensitivity to the drug ➢ active bleeding, hemophilia ➢ severe liver disease with elevated prothrombin time (PT) Must not give heparin Since can induce bleeding ➢ severe thrombocytopenia C/I: Due to less thrombin Higher contractions = higher blood flow Unfractionated heparin (UFH): ➢ malignant hypertension = higher risk of internal bleeding ➢ inability to supervise and monitor treatment Severe headache joint pain chest pain Symptoms of bleeding are common and may include: abdominal pain swelling, tarry stools hematuria, or the passing of bright red blood through the rectum. A/E: Venous circulation: IV protamine sulfate If major bleeding occurs, discontinue therapy immediately and start by slow IV infusion over 10 minutes. Age after 50 It is the slowed blood flow in the deep veins of the legs resulting from damage to venous valves, vessel obstruction, prolonged periods of immobility (3 Days or more), or increased blood viscosity. (After stopping the use of Heparin) (1) more predictable anticoagulation dose response (2) improved SC bioavailability Increase or decrease in dose? = no change in Cl – Major medical illness (e.g.,heart failure, myocardial infarction) Venous Stasis: (3) dose-independent clearance – Majorsurgery Advantages of LMWHs over UFH include: – Paralysis (e.g., stroke, spinal cord injury) Conditions associated with venous stasis include: (4) longer biologic half-life (5) lower incidence of thrombocytopenia – Polycythemia vera (in which the bone marrow makes too many red blood cells. Low-molecular-weight heparins (LMWHs): (6) less need for routine laboratory monitoring It may also result in the overproduction of white blood cells and platelets) – Obesity Enoxaparin – Immobility for ≥3 days during hospital admission Dalteparin Examples: – Malignancy Tinzaparin – Activated protein C resistance prevents thrombus generation Risk factors: and clot formation by indirectly inhibiting factor Xa activities. – Deficiency of protein C, protein S, or anti-thrombin Hypercoagulable states: Fondaparinux sodium: – Excess of factor VIII or XI Pharmacological therapy: Similar to UFH and the LMWHs, it binds to antithrombin, greatly accelerating its activity – Anti-phospholipid antibodies selective inhibitors of both free and clot-bound factor Xa – Pregnancy/postpartum and other situations. Rivaroxaban & apixaban: - Major orthopedic surgery (e.g., knee and hip replacement) that do not require antithrombin to exert their anticoagulant effect. factors II (prothrombin), VII, IX, and X, proteins C and S. Vitamin K–dependent coagulation: Vitamin K–dependent anticoagulant: Vascular injury: Warfarin exerts its anticoagulant effect by inhibiting production of the: - Trauma (especially fractures of the pelvis, hip , or leg) - Indwelling venous catheters. Estrogen-containing oral contraceptive pills ➢ Warfarin is FDA approved for prevention and treatment of VTE. Estrogen replacement therapy Drug Therapy: Although very effective, warfarin has a narrow therapeutic index, requiring frequent dose adjustments and careful patient monitoring SERMs Warfarin: Chemotherapy ➢ Warfarin has no direct effect on previously circulating clotting factors or previously formed thrombi. It is the normal response of the blood vessels to injury Hemostasis: Warfarin therapy (5-10 mg) is monitored by the INR (target: 2 to 3 for DVT or PE). Intracranial hemorrhage (often results in permanent disability and death). by forming a clot to arrest of bleeding following vascular injury. It is the formation of clot that results when hemostasis is excessively activated Adverse reactions: Purple toe syndrome and skin necrosis. Thrombosis: Warfarin Therapy: in the absence of bleeding. active bleeding, hemorrhagic tendencies, pregnancy, Contraindications: Venous ThromboEmbolism history of warfarin-induced skin necrosis enhance the conversion of plasminogen to plasmin, which subsequently degrades the fibrin matrix. Thrombolytic agents are proteolytic enzymes that: ➢ Streptokinase ➢ Urokinase ➢ Alteplase Three thrombolytic agents and regimens are available for treatment of DVT and/or PE: Thrombolytic agents: Note: = Activate Plasmin Full-dose anticoagulation therapy is essential during the entire operative and postoperative period. Visuals: dynamic interplay between thrombogenic (activating) Homeostasis & Thrombosis When the vessels is injured: and antithrombotic (inhibiting) forces result in the local formation of a hemostatic plug that seals the vessel wall and prevents further blood loss. ❖ inhibit platelet adherence Under normal circumstances, the endothelial cells that line the inside of blood vessels maintain blood flow by producing a number of substances that: ❖ prevent the activation of the coagulation cascade ❖ facilitate fibrinolysis By tissue plasminogen activator Evaluation and prevention of VTE: Visuals: 1- the production of fibrin Thrombin plays a key role in the coagulation cascade. It is responsible for: 2- the activation of factors V and VIII 3- enhances platelet aggregation Swelling of the leg Pain or tenderness in the leg; DVT: the pain is usually in 1 leg and may only be present when standing or walking Skin warmth Red or discolored skin Unexplained shortness of breath Chest pain and/or palpitations Symptoms of DVT and PE PE: Anxiety and/or sweating Coughing Fatigue and/or fainting Note: Not all people with DVT have signs or symptoms