Lect 27

• Coagulopathy is treated with Desmopressin acetate, a synthetic analog of vasopressin that transiently increases the level of vWF via V2 receptors, releasing stored vWF from endothelial cells.
• The recommended dosages for dogs for von Willebrand disease (vWD) treatment are 1 mcg/Kg (0.01 ml/Kg) SC diluted in 20 ml of saline and administered over 10 minutes IV.
• The response to Desmopressin acetate occurs 1 to 2 hours after treatment, with effects lasting 2 hours after administration.
• The effect of Desmopressin acetate is reduced if the drug is given repeatedly.
• Desmopressin acetate increases the level of vWF sufficient to provide improved coagulation activity in animals (dogs) suffering from von Willebrand disease (vWD) that undergo surgery.
• Aspirin (acetylsalicylic acid) is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits the activity of cyclooxygenase type-1 (COX-1), causing irreversible inhibition of platelet cyclooxygenase even at low doses.
• Aspirin acetylates COX-1 and blocks the synthesis of TXA2, a vasoconstrictor and stimulator of platelet aggregation.
• Aspirin is absorbed into the portal vein and most acetylation in platelets occurs in the portal circulation where aspirin levels are the highest.
• At low aspirin doses there is a selective inhibition of COX-1 over COX-2, but at high doses the selectivity is diminished.
• Aspirin inhibits platelet aggregation and is localized in the vascular endothelium.
• Dosage recommendations for platelet inhibition vary widely, with cats responding to 25 mg/kg twice weekly and dogs responding to 0.5 mg/Kg twice daily.
• Clopidogrel (Plavix®) is a prodrug whose active metabolite is 2-oxo-clopidogrel, an ADP antagonist on P2Y12 receptors.
• Hemolytic anemias can be classified as extravascular hemolysis where RBCs are phagocytosed by the mononuclear-phagocytic system in the spleen, liver, and bone marrow, or intravascular hemolysis where lysis of RBCs by antibodies that activate complement occurs.
• Nonregenerative anemia occurs when the bone marrow is unable to produce sufficient new RBCs, resulting in a reduction in the total number of RBCs circulating in the blood and consequently reduced oxygen delivery to the tissues.
• Clinical signs of anemia include pale gums and mucous membranes, weakness, lethargy, exercise intolerance, loss of appetite, weight loss, recumbency, seizures, syncope, or coma.
• Bone marrow is producing RBC normally in regenerative anemias.
• Nonregenerative anemias can be caused by Anemia of chronic disease (ACD) which develops secondary to a variety of chronic inflammatory, degenerative, or neoplastic conditions, bone marrow disorders (paucity or absence of erythroid precursors (hypoplasia or aplasia, respectively)), Anemia of renal disease (erythropoietin is responsible for stimulating RBC production in bone marrow), Vitamin B 12 deficiency (megaloblastic anemia), iron (Fe 2+) deficiency anemia (IDA), folic acid deficiency, Feline leukemia virus (FeLV), feline immunodeficiency virus (FIV).
• Pharmacologic therapy for anemia is oriented toward providing components needed for RBC production including hemoglobin synthesis.
• Chronic diseases suppressing RBC production, infectious diseases (virus infection), excessive bleeding (acute blood loss), medications that interfere with the production of RBC, poisons or toxins, tumors, poor nutrition, bone marrow disease, kidney disease, parasites, and immune-mediated disease can cause anemia.
• Morphology of the erythrocytes, Hb content in the erythrocytes, regeneration ability of the bone marrow can be classified as microcytic, macrocytic, normocytic, hypochromic, hyperchromic, normochromic, regenerative, or non-regenerative.
• Hemolytic anemia occurs when a considerable number of RBCs must be destroyed before anemia develops.
• Vitamin B 12 is essential for DNA synthesis.
• Pharmacological acceleration of fibrinolysis involves drugs that enhance the conversion of the inactive precursor plasminogen to the active enzyme plasmin.
• The use of clopidogrel in veterinary medicine has increased.
• Effects of clopidogrel in cats persisted for 3 days after administration (2 or 4 mg/Kg/day).
• Clopidogrel has been safely administered to different animals.
• The active metabolite of clopidogrel binds irreversibly to the receptors, preventing ADP from exerting its strong aggregating actions.
• 0.5 or 1 mg/Kg/day PO of clopidogrel decreased ADP-induced platelet aggregation for 3 – 7 days after discontinuation of drug administration.
• Fibrin-bound gel-phase plasminogen can be activated locally with selective fibrinolysis.
• Clopidogrel does not cause GI ulceration, but vomiting may occur in some cats, which appears to be ameliorated by giving the drug with food.
• Streptokinase converts both existing phases of plasminogen.
• Clopidogrel is used as an antiplatelet drug for patients with heart disease, thromboembolic disorders, heart worm disease, immune-mediated hemolytic anemia, and cardiogenic arterial thromboembolism.
• In dogs, cats, and horses, oral administration of clopidogrel has produced significant inhibitors effects on platelets, superior to aspirin.
• Plasminogen exists in two phases: the plasma (soluble phase) found in the circulating blood and the gel phase bound to fibrin in the formed clot.
• Thrombolytic therapy is not commonly performed in veterinary medicine due to its expense and lack of evidence that the benefits outweigh the risks and expense.
• The presence of plasmin in peripheral blood indicates a pathological fibrinolytic state.
• Streptokinase is a stable, vacuum-dried powder containing enzymes produced by β-hemolytic Streptococcus.
• The effect of clopidogrel on the platelets appears to be irreversible.
• At 2 mg/Kg q 24 h PO, clopidogrel suppressed platelet activity in horses, which persisted for 6 days after the last dose.
• Anemia: The capacity of blood to transport O 2 is reduced.