The process which causes the bleeding to stop. Maintains blood fluidity and prevents blood from leaving the vascular compartments
1. Cell membrane 2. Platelets 3. Coagulation cascade
Abnormal function of hemostasis: thrombosis (inappropriate clotting) or bleeding/hemorrhaging *insufficient clotting)
Blood Testing for Coagulability
PT- Prothrombin time
Tests extrinsic and common pathway. Looking at time to clot. Used to monitor warfarin. Normal is 11-13 seconds. PT is increased with warfarin
PTT- Partial thromboplastic time
Tests intrinsic pathway. Used to monitor heparin. Normal range is 30-50 seconds.
Hypercoagulability (increased platelet function)
Hypercoagulability results in platelet adhesion and formation of clots which leads to disruption of blood flow.
Increased Clotting Activity
Genetics. Mutations in factor V and prothrombin genes. Results in inability of factor Va to be deactivated by protein C. Examples: Factor V Leiden disorder where clotting persists and predisposes to DVT. Other disorders are inherited deficiencies of antithrombin III, protein C/S.
Acquired. Stasis due to bed rest (slows normal blood flow and allows accumulation of clotting factors)cancer, birth control, smoking and obesity, MI.
AKA Hughes syndrome. Autoimmune hypercoagulable state caused by antiphospholipid antibodies. Provokes blood clots in arteries in veins. Can be primary or secondary (due to lupus).
normal range: 150,000- 400,000/ml. Signs of disorders include:
Petechia, purpura, ecchmyosis, bleeding from mucous membrane
Low circulating platelets. Due to decreased production by bone marrow (aplastic anemia, leukemia, HIV) or increased pooling of platelets in the spleen, or decreased platelet survival or nutritional deficiencies (B12, iron, folic acid),
Types: idiopathic, thrombotic or hemolytic uremia syndromes or heparin induced.
Decreased platelet function:
Caused by asprin, uremia (increased urea in blood coats the platelets causing glycoproteins not to function) or genetic disorders
Genetic disorders: Bernard Soulier- GpIIb disorder so vWf has nowhere to bind, Von Willebrand Disease-no vWF to bind platelets. Leads to decreased platelet adhesion *Vasopressin can stimulate release of vWF for tx. Glanzmann thrombocytopenia- GpIIb-IIIa so platelets cant bind together
Coagulation Cascade Disorders:
Deficiencies or impairments of one or more coagulation factors due to defective synthesis, inherited disease or increased consumption. Prevents fibrinogen from converting to fibrin. Will see bleeding in deep tissues like hematomas. Elevated PTT and PT.
Hemophilia A- Factor VIII deficiency: X-linked recessive disorder, affects mostly males. Soft tissue bleeding of GI, hip, knee, elbow and ankle joints. Can lead to joint fibrosis and contractures. Tx is factor VIII replacement therapy. Only affects intrinsic pathway.
Vitamin K antagonist. Blocks epoxidase reductase, leads to depletion of reduced vit K (which is essential for synthese of factors II, VII,IX,X, protein c/s)
Uses: Prevention of thrombosis in predisposed patients. AE- bleeding
Heparin(IV)/ LMW Heparin (lovenox):
Induces a conformational change in antithrombin III making it more accessible to proteases -> increase inactivation of thrombin
Uses: Prophylaxis and tx of thromboembolic diseases, unfractionated (IV heparin) used with antiplatelet agents for tx of acute coronary syndromes. Lovenox is an efficient catalyzation of factor Xa inactivation.
AE: bleeding and heparin induced thrombocytopenia
Novel Oral Anticoagulants
Apixaban (Eliquis), Rivaroxaban (Xarelto):
Direct inhibitor of free and clot-bound factor Xa which prevents the conversion of prothrombin to thrombin. Prevents clot formation.
Uses: A- reduces stroke and systemic embolism, prophylaxis of DVT/PE after hip or knee surgery. R- same but prophylaxis of venous thromboembolic events for hip/knee surgery pts.
AE: easy bruising, bleeding, back or muscle pain, hypotension.
Direct thrombin inhibitor which prevents conversion of fibrinogen to fibrin.
Uses: Prevents thromboembolism in pts with AF, DVT, PE
Cofactor-independent direct inhibitor of factor Xa.
Uses: prophylaxis of VTE in moderate to severe restricted mobility patients.
Rivaroxaban interacts with Aspirin.
All drugs will have bleeding as a side effect!
Inhibition of Anticoagulation
Antagonist of heparin.
Uses: IV administration if there is life threatening hemorrhage/heparin excess
Forms a stable complex with plasminogen which then cleaves other plasminogen molecules into plasmin
Uses: PE, STEMI, arterial thrombosis, DVT. AE:systemic fibrinolysis, hemorrhage
Recombinant Tissue Plasminogen Activator:
Binds to newly formed thrombi and makes it a potent activator of plasminogen. Cleaves plasminogen into plasmin which then cleaves fibrin into fibrin degradation products
Uses: PE,STEMI, Acute ischemia stroke. AE: bleeding
Non selective COX inhibitor. Irreversible inhibition of COX-1= inhibits platelet aggregation for 10 days. Stops conversion of arachidonic acid to thromboxane A2 (potent platelet aggregation inducer).
Uses: Pain/inflammation/fever, reduces risk of MI/unstable angina, prevents strokes due to blood clots
AE: hemorrhagic stroke, GI bleeding
Antiplatelet and vasodilator. Inhibitors phosphodiesterase II -> suppresses cAMP degradation -> increases cAMP in platelets and blood vessels -> inhibition of platelet aggregation and vasodilation
Uses: Intermittent claudication symptoms (by widening the vessels in teh legs which helps with blood flow).
AE, DI: heart failure, tachycardia, interacts with NSAIDs and aspirin.
Inhibits erythrocyte phosphodiesterase -> increases cAMP activity, decreases blood viscosity by reducing plasma fibrinogen concentrations and increasing fibrinolytic activity
Uses: Intermittent claudication, chronic occlusive arterial disease
AE: muscle aches, headaches, GI discomfort
ADP Receptor Pathway Inhibitor
Irreversibly binds to P2Y12 which prevents the binding of ADP receptors on platelets which prevents GPIIb-IIIa activation -> inhibits platelets aggregation
Uses: reduces risk of MI/stroke, better than aspirin in decreasing CV outcomes
AE, DI: upper RTI, joint, chest pain, depression, bleeding. DI- Ibuprofen
Binds to intact platelet GPIIb/IIIa receptor and blocks access of large molecules to receptor through steric hinderance or conformational change. Prevents cell adhesion
Uses: prevents cardiac ischemic complications in vascular surgeries or pts w/ unstable angina, intended for use with aspirin and heparin
AE: N&V, hypotension, vision changes, back pain