Unit 4- Blood Flashcards
Vein Thrombosis
Red thrombi of RBC embedded in fibrin, treat with anticoagulants
Coronary Artery Thrombosis
White thrombi of platelets embedded in fibrin, treat with antiplatelets
Phases of Hemostasis
Vascular spasm where blood vessel is damaged, clotting factors cleave prothrombin into thrombin, platelet plug forms, thrombin IIa cleaves fibrinogen into insoluble fibrin, coagulation occurs
Platelet Pathway
NO, prostacyclin, or ADPase activate platelets that produce TXA2 and ADP, activating more platelets, activated platelets aggregate due to clotting factors, fibrin deposits and it becomes a clot
The Clotting Cascade
Vascular injury releases tissue factor, factor VIIa is produced, factor X is activated, activating factor II prothrombin to factor IIa thrombin, that cleaves fibrinogen into fibrin
Zymogens
Precursor proteins, most clotting factors
Factor IV
Ca++, cofactor for thrombin activation and fibrinogen to fibrin
Blood Coagulation
Activation of prothrombin activators, thrombin activation, and fibrin formation, 12 zymogen factors work together
Antithrombin III
AT, inhibits coagulation through fibrinolysis
Conditions Requiring Anticoagulant
Thrombosis, coronary syndrome, arterial fibrillation, stroke, ischemic heart disease, thromboembolic disease in IMHA, antithrombotic prophylaxis
Anticoagulatns
Modify the coagulation cascade, heparin and LMWHs, warfarin and coumarin derivatives, thrombin inhibitors, and factor Xa inhibitors
Heparin
Binds AT and enhances inhibitory effects, inactivating IIa and Xa, found in mast cells
Heparin Use
Excessive clotting or risk of clotting, thromboembolic disease, venous thrombosis, disseminated intravascular coagulopathy, pulmonary thromboembolism, laminitis, endotoxic shock, burns
Unfractionated Heparin
Inactivates thrombin and factor Xa
Low Molecular Weight Heparin
Inactivates factor Xa, dalteparin and enoxaparin
Heparin Dosing
AT levels affect efficacy, variable PK, activated partial thromboplastin time test
Heparin Adverse Effects
Bleeding problems, thrombocytopenia, overdose causes excessive anticoagulation and bleeding
Heparin Overdose Reversal
Protamine sulfate binds acidic heparin to create inactive salt
LMWH Advantages
Greater activity and safety, predictable PK
Dalteparin
LMWH, binds AT to increase AT mediated inhibition of synthesis and activity of factor Xa
Dalteparin Adverse Effects
Bleeding, hematoma from IM admin, prolonged elimination from renal disease, drug interactions
Enoxaparin
LMWH, binds AT to increase AT mediated inhibition of synthesis and activity of factor Xa
Enoxaparin Adverse Effects
Bleeding, hematoma from IM, prolonged elimination from renal disease, drug interactions
Vitamin K
Essential for hepatic synthesis of prothrombin factors II, VII, IX, and X
Coumarin Derivatives
Anticoagulants, warfarin, dicumarol, acenocoumarol, reduce production of vitamin K dependent factors by inhibiting vitamin K regeneration
Coumarin Derivative Uses
Decrease thrombosis tendency in dogs, treat clots in vein or artery, reduce risk of stroke or heart attack
Coumarin Derivative Adverse Effects
Decreased blood clotting, spontaneous bleeding, excessive bleeding, drug interactions with aspirin and clopidogrel
Vitamin K Deficiency
Excessive bleeding due to failure of fibrin clot formation, poisoning by warfarin, treat with menadione
Heparin Characteristics
Accelerates antithrombin activity, immediate onset, short duration, parenteral admin, treat overdose with protamine, test with clotting time
Warfarin Characteristics
Inhibits hepatic synthesis of vitamin K dependent clotting factors, delayed onset, long duration, oral admin, treat overdose with vitamin K, test with prothrombin time
Factor Xa Inhibitors
Rivaroxaban and apixaban, predictable PK, no monitoring needed, less affected by diet, short half life and unable to be reversed
Thrombin Inhibitors
Dabigatran, less drug interaction, reversed with Idarucizumab, can cause bleeding and GI problems
Hemophilia
Inherited deficiency of clotting factors, diagnosed by blood test and coagulation time test
Hemophilia Treatment
Blood transfusion, cryoprecipitate from blood, factor VIII
Hemophilia A
Lack of factor VIII, X linked and common in males, spontaneous bleeding into muscle, joints, or under skin, hemorrhage in chest or abdomen, excessive bleeding after surgery
Hemophilia A Diagnosis
During surgery, in young animals with excessive bleeding, bleeding of gums, may be stillborn or die as neonate
Factor VIII
Cofactor of factor IX to activate factor X
Hemophilia B
Lack of factor IX, milder than hemophilia A, spontaneous bleeding, not noticed until emergency
Hemophilia C
Extremely rare factor XI deficiency, bleeding induced by trauma or surgery and can be delayed
Von Willibrand Disease
Most common inherited clotting disease, lack of vWB factor important for platelet adhesion
Predisposition to Thrombosis
Injury to vessel wall, altered blood flow, abnormal coagulation
Arterial Thrombus
Atherosclerosis, can cause ischemia, carotid emboli can cause stroke
Venous Thrombus
Forms an embolus, venous emboli can go to pulmonary artery and cause pulmonary embolism
Embolism
Thrombus that has traveled far from where it formed
Thromboembolic Diseases
Feline cardiomyopathy, pulmonary endarteritis from heartworms, membranous glomerulonephritis, mild disseminated intravascular coagulopathy, pulmonary thromboembolism, vasculitis, laminitis, navicular disease
Aspirin
Binds COX-1 preventing TXA2 synthesis that activates platelets, metabolized in liver, cats require less dosage, excreted by kidney
Aspirin MOA
Binds platelet COX1 preventing TXA2 formation and preventing vasoconstriction at low doses, binds COX2 preventing prostaglandin production and causing analgesia at high doses
Clopidogrel
Prodrug, metabolite blocks platelet aggregation, used with aspirin but preferred in vet med
Clopidogrel Adverse Effects
Vomiting, anorexia, diarrhea
Clopidogrel MOA
Active metabolite irreversibly binds P2Y12 ADP receptors on platelets, blocking platelet aggregation
Ticlopidine
P2Y12 receptor inhibitor, rarely used in animals, causes adverse effects in cats
Abciximab
Antibody to anti-glycoprotein IIb/IIIa receptor preventing thrombosis during percutaneous coronary intervention
Abciximab MOA
Reversibly binds platelet IIb/IIIa receptor that binds fibrinogen, vWB factor, and other adhesive platelet molecules
Fibrinolysis
Antithrombin III breaks down fibrin in blood clots, tPA and factor XIa and XIIa activate plasminogen to plasmin that degrades fibrin
Streptokinase
Plasminogen activator, thrombolytic medication, combines with plasminogen to form activator complexes that convert plasminogen to plasmin
Streptokinase Therapeutic Effects
Lysis of thrombi in cat heart attack, lysis of pulmonary embolism in dog, deep venous thrombosis in dog
Streptokinase Adverse Effects
Systemic fibrinolysis, coagulopathy, serious hemorrhage, metabolic acidosis, bleeding, death
Recombinant Tissue Plasminogen Activator
rt-PA, protease with specificity for fibrin within thrombi, causes less systemic bleeding problems, high mortality in cats
Antifibrinolytics
Promote hemostasis, aminocaproic acid and tranexamic acid, lysine compounds that bind to fibrin to decrease fibrinolysis
Regenerative Anemia
Bone marrow produces normal RBC but blood loss occurs
Immune Mediated Hemolytic Anemia
Breakdown of RBC
Nonregenerative Anemia
Deficiency of blood cell production
Erythropoietin
Produced by kidneys, stimulates RBC production in bone marrow
Iron Deficiency Anemia
Hemoglobin contains iron to bind to O2, most common in dogs and piglets after chronic blood loss
Sickle Cell Anemia
Mutation in hemoglobin gene causes malformation of subunit, deformity of RBC restricts O2 carrying capacity
Oxbryta
Inhibits hemoglobin beta polymerization and RBC sickling
Vitamin B12 Anemia
Cobalamin creates heme portion, deficiency results in low RBC and hematological and neuro problems
Ferdex B12
Injectable B12 for treatment of iron deficient anemia
Azathioprine
Immune suppressant, decreases purine metabolism, treats IMHA and immune mediated thrombocytopenia
Azathioprine Adverse Effects
Bone marrow suppression, CI toxicity, liver toxicity, pancreatitis in dogs
Cyclophosphamide
Immunosuppressant with cytotoxic effects on lymphocytes
Cyclophosphamide Adverse Effects
Bone marrow suppression and sterile hemorrhagic cystitis in dogs
Cyclosporine
Inhibits T cell signal transduction, suppresses IL2, blocks T cell activation, treats IMHA and immune mediated thrombocytopenia
Erythropoietin Stimulating Agents
Epoetin alpha and darbepoetin, stimulate erythropoiesis to treat anemia
Chronic Non Regenerative Anemia
Common in cats, decreased erythropoietin production, treat with darbepoetin