Lect 26

• Hemostasis is the prevention or control of hemorrhage.
• Physiological control systems work to secure fluidity of blood.
• Opposing systems promote the coagulation when the circulatory system is invaded.
• The basic process of hemostasis can be separated into vascular, platelet, and coagulation phases.
• Once activated, these zymogen coagulation factors activate other factors in a sequence until thrombin is generated.
• Calcium ions (clotting factor IV) are required for all coagulation reactions, except the first two steps in the intrinsic pathway.
• Collagen is a blood coagulation factor.
• The clotting cascade consists of a sequence of events involving the activation of zymogens.
• Each phase of hemostasis must remain in equilibrium to maintain a normal state of hemostasis.
• Vascular and platelet phase is composed of vascular wall contraction and platelet adherence.
• Both phases of vascular and platelet phase are closely associated with the vascular endothelium.
• Nitric oxide (NO), prostacyclin (PGI2), and ADPase are released by vascular endothelial cells.
• Adenosine diphosphate (ADP) is a potent stimulator of platelet activation.
• After a blood vessel is injured and the subendothelium exposed, tissue factor (TF) and von Willebrand factor (vWF) are exposed.
• Enoxaparin’s inhibition ratio is 3.3 and 5.3/1 against anti-factor Xa/anti-factor IIa (thrombin) ratio.
• PK properties in horses are similar to humans.
• Enoxaparin is used in dogs and cats with a dose of 0.8 mg/Kg q 6h SC.
• Protamine sulfate (1 - 2% solution) is a low-molecular-weight protein (strongly basic) used as an antagonist against heparin induced hemorrhages (also in vitro) and has some anticoagulant properties.
• Enoxaparin is characterized by a molecular weight of approx 5,000.
• Dalteparin is excreted by renal clearance in animals, and if renal disease is present, elimination will be prolonged.
• Enoxaparin is excreted by renal clearance in animals, and if renal disease is present, elimination will be prolonged.
• Dalteparin’s inhibition ratio is 2.7/1 against anti-factor Xa/anti-factor IIa (thrombin) ratio.
• 200 units/Kg/IV, followed by 100 - 300 units/Kg q 6 - 8h SC
• Dalteparin is used in dogs and cats with a dose of 150 units/Kg SC, followed by 125 units/Kg SC q 8 - 12h.
• Dalteparin (Fragmin®) is characterized by a molecular weight of approx 5,000.
• Dalteparin has a shorter half-life in dogs and cats than in humans, with a half-life of 2h in dogs and 1.5h in cats.
• Rebound hypercoagulability may occur after discontinuation of heparin treatment, and the dose should be tapered slowly when discontinuing treatment.
• LMWHs produce their effect by binding to antithrombin (AT).
• Enoxaparin has a shorter half-life in dogs and cats than in humans, with a half-life of 5h in dogs and 1.9h in cats.
• Tissue factor (TF) and von Willebrand factor (vWF) exposure attracts platelets to the injured endothelium.
• Platelets have specialized receptors for TF and vWF.
• Animals deficient in vWF may have bleeding disorders and need to be treated by medications that stimulate it.
• Endothelial cells are involved in activation of platelets.
• Substances involved in activation of platelets include ADP, ATP, serotonin (5-HT), platelet factor 3 and 4, thromboxane A2 (TXA2), and platelet-derived growth factor.
• Once adhesion has occurred, the platelets undergo changes at the damage site that triggers their degranulation and release of diverse substances that recruit more platelets to the clot.
• The dose of 1 mg protamine is used to neutralize 80 – 100 units of UFH, with a dose of 1 – 1.5 mg to antagonize 1 mg heparin.
• Protamine interferes with the action of thrombin and fibrinogen.
• Warfarin is not in vitro active, and its anticoagulant activity is not affected by other drugs.
• Protamine is administered slowly intravenously, with a dose of 50 mg over a 10-minute period.
• Warfarin is administered orally, and there are no laboratory control tests for it.