Thrombosis_Thromboembolism_ATE.pptx

THROMBOSIS/ THROMBOEMBOLISM VCS 84610 Small Animal Medicine III Thrombosis Risk THROMBOSIS THROMBOLYSIS Stagnant flow Reduced clotting factors Endothelial injury Reduced platelet function Excessive clotting factors ¯ regulation of clotting factors Enhanced thrombolysis Reduced thrombolysis What Type...

THROMBOSIS/ THROMBOEMBOLISM VCS 84610 Small Animal Medicine III Thrombosis Risk THROMBOSIS THROMBOLYSIS Stagnant flow Reduced clotting factors Endothelial injury Reduced platelet function Excessive clotting factors ¯ regulation of clotting factors Enhanced thrombolysis Reduced thrombolysis What Type of Thrombosis Arterial Thrombosis (AT) Arterial Thromboembolism (ATE) Thrombus at site of vascular disruption Thrombus at distant site; embolus obstructs normal vessel High-shear flow Stagnant flow Platelet-rich thrombus Fibrin-rich/platelet-poor embolus What Type of Thrombosis Venous Thrombosis (DVT) Venous Thromboembolism (VTE/PE) Thrombus may form at site of vascular injury Embolus originates from DVT Stagnant flow Stagnant flow Fibrin-rich/platelet-poor thrombus Fibrin-rich/platelet-poor thrombus Physiology of Thrombosis Virchow’s Triangle – Blood stasis – Endothelial injury – Hypercoagulability Cumulative Thrombotic Risk ENDOTHELIUM HYPERCOAGULABILITY Cumulative Thrombotic Risk EN TH DO M IU EL ENDOTHELIUM HYPERCOAGULABILITY HYPERCOAGULABILITY Cumulative Thrombotic Risk HYPERCOAGULABILITY IUM M IU EL TH DO EN END OTH EL HYPERCOAGULABILITY Cumulative Thrombotic Risk EN D HYPERCOAGULABILITY M IU EL TH DO EN O TH EL IU M HYPERCOAGULABILITY Hypercoagulability Humans Animals Fx (II, V, VIII) ???? ↓Fx/prod (ATIII, prot C/S) ↓ATIII, prot C Platelet hyperreactivity Coagulation factor activity homocystein, Lp(a), PAI-1, TAFI VIII, fibrinogen Neoplasia Platelet hyperreactivity Neoplasia Clinical Conditions Associated with Thrombosis Cats – Cardiac disease – Neoplasia Dogs – IMHA – Protein-losing “opathies” – Neoplasia – Hyperadrenocorticism Hypercoagulability; Cats Breed RR – Ragdoll 8.23 – Birman 5.08 – Tonkinese 2.28 – Abyssinian 2.12 – Maine Coon 1.21 How Do We Identify Hypercoagulability PT/PTT TEG Platelet aggregation MA + Activator MA + Inhibitor MA Prevention Primary vs. secondary Correct underlying prothrombotic condition Treat underlying prothrombotic condition Antithrombotics Prevention-Antithrombotics Antiplatelet drugs – – – – Endothelial injury Inflammatory conditions Known hyperreactive platelets Vascular effects Anticoagulant drugs – Stagnant blood flow – Known coagulation factor abnormality – Thrombosis treatment – Secondary prevention Prevention- Humans First time CTES with non-valvular AF – Placebo- 6%-20% per year – ASA- 1.6%-5.5% per year – Warfarin- 0.41%-2% per year Recurrent CTES with non-valvular AF – Warfarin-1.3%-3.5% per year Primary Prevention- Cats and Dogs Cats with cardiac disease – LA/Ao > 1.7 – LADs > 2.0 cm – Presence of spontaneous contrast “smoke” in LA – Breed predisposition Dogs – Not well established – Severe hypoproteinemia, inflammation Antiplatelet- Aspirin Inhibits cyclo-oxygenase, ↓ thrombroxane A2 Monitor with AA-induced platelet aggregation Inhibits dog platelets – 0.5 mg PO q 24-12 hr Questionable inhibition of cat platelets – 81 mg PO q 72 hr Antiplatelet- Clopidogrel ADP-receptor antagonist Vasomodulating effects Monitor with ADP-induced platelet aggregation Inhibits dog and cat platelets – Dogs – Cats 1-2 mg/kg PO q 24 hr 18.75 mg/cat PO q 24 hr Anticoagulant- Warfarin Vitamin K antagonist – ↓ II, VII, IX, X High variability in pharmacodynamic response – Bleeding – Thrombosis Monitor with PT/INR Seldom used Anticoagulant- Low MolecularWeight Heparins (LMWH) Primarily inhibit Xa through ATIII – Little effect on thrombin (IIa) Better PK profile than unfractionated heparin Monitoring not necessary and currently confusing Dalteparin 100-150 IU/Kg SQ q 24 hr Enoxaparin 1 mg/kg SQ q 24 hr LMWH- Monitoring TEG – No effect due to minimal anti-IIa Anti-Xa activity – Not used for therapeutic monitoring in humans – Shown not correlate to antithrombotic effect in humans and cats Anticoagulant- Xa Inhibitors Anti-Xa monitoring not necessary Rivaroxaban – Direct Xa inhibitor – Dog 0.5 mg/kg PO q 24 hr – Cat 2.5/cat mg PO q 24 hr Fondaparinux – Through ATIII – PK/PD known in cats Apixaban – Not used – Direct Xa inhibitor – Some research experience in dogs Secondary Prevention- Cats and Dogs Preferred – Clopidogrel + anti-Xa OR LMWH If fearful of bleeding complications – Anti-Xa OR LMWH At a minimum – Clopidogrel Thrombosis Treatment Antiplatelet drugs are associated therapy Anticoagulants are principle – Warfarin – LMWH Given q 12 hr – Xa inhibitors Given q 12 hr – Monitoring anti-Xa levels could be considered Feline Arterial Thromboembolism (FATE)/Cardiogenic Embolism/Saddle Thrombus Maturation of thrombus – aged, lamellar edges Embolization of thrombus particles – Point at which embolus size exceeds vessel diameter Cardiogenic Embolism; Prevalence 12%-16% from retrospective HCM literature 6% of cats with cardiac disease – HCM (6%) – DCM (5%) – RCM (6%) – Not specified (7%) A o r t i c t r i f u r c Cardiogenic Embolism; Site of embolization Cardiogenic Embolism; Sequelae Aortic trifurcation (Saddle thrombus) – Ischemic neuromyopathy – Pelvic limb paresis/paralysis (LMN) – Cold, pulses limbs (can be asymmetric) – Firm, painful musculature B r a c h i a l –I s c h e m i c Cardiogenic Embolism; Sequelae Cardiogenic Embolism; Sequelae Renal – Azotemia – Hematuria/renal pain – Oliguric renal failure Cardiogenic Embolism; Sequelae Cerebral – Seizures, coma, cranial nerves, etc Cardiogenic Embolism; Sequelae Splanchnic – Abdominal pain – Vomiting – Diarrhea Cardiogenic Embolism; Sequelae Dogs – Aortic trifurcation Less severe clinical signs – Renal – Splanchnic Pulmonary embolism – Non-cardiogenic Cardiogenic Embolism; ischemic neuromyopathy Peracute in onset Loss of blood flow – Aortic- Not significant by itself – Collateral- Vertebral and epaxial circulation Lost due to platelets, serotonin, thromboxane Cardiogenic Embolism; ischemic neuromyopathy Usually remain relatively stagnant over several days to 3 weeks 50% improve by 4-6 weeks Can be chronic complications Cardiogenic Embolism; ischemic neuromyopathy Reperfusion Injury – Sudden resumption in blood flow to ischemic tissues Re-establishment of aortic/collateral flow – Complete, bilateral, prolonged infarction Worse Px 66% non-survival rate – Majority of cats should be given 72 hrs Cardiogenic Embolism; Acute Management Reduce continued thrombus formation Improve blood flow Pain management Treat concurrent congestive heart failure, if present Supportive care Cardiogenic Embolism; Acute Management Reduce continued thrombus formation – Anticoagulants Heparin – 250-375 IU/kg IV, then 150-250 IU/kg SQ q 6-8 hrs – aPTT prolonged by 1.5-2.0 LMWH – Dalteparin- 100 IU/kg SQ q 12-24 hrs – Enoxaparin- 1.0-1.5 mg/kg SQ q 12-24 hrs Cardiogenic Embolism; Acute Management Reduce continued thrombus formation – Antiplatelets Clopidogrel- 75 mg PO once, 18.75 mg PO q 24 hrs – Dogs: 10 mg/kg PO at presentation, 1-2 mg/kg PO q 24 hr Cardiogenic Embolism; Acute Management Improve Blood Flow – Increase Arterial Flow Thrombolytic therapy – t-PA- 0.25-1.0 mg/kg/hr, 1.0-10.0 mg/kg total dose – Increase Collateral Flow Antiplatelet therapy – Clopidogrel- 75 mg PO on admission Vasodilators do not appear to help Cardiogenic Embolism; Acute Management Pain management – Should be considered in all cats Butorphenol- 0.2-0.4 mg/kg SQ, IM, IV q 1-4 hrs Hydromorphone- 0.08-0.3 mg/kg SQ, IM, IV q 2-6 hrs Buprenorphine- 0.005-0.01 mg/kg SQ, IM, IV q 6-12 hrs Oxymorphone- 0.05-0.1 mg/kg SQ, IM, IV q 1-3 hrs Fentanyl- 4-10 μg/kg IV bolus followed by 4-10 μg/kg/hr infusion Cardiogenic Embolism; Acute Management Treatment of CHF – Reported in up to 60% of cats, much less common in my experience Furosemide- 0.5-1.0 mg/kg IV q 1-8 hrs PRN Oxygen Nitroglycerine 2% ointment- 1/8-1/4” q 8-12 hrs Thoracocentesis, if pleural effusion Cardiogenic Embolism; Acute Management Supportive care – Nutritional support – Comfortable environment – Cautious use of IV fluids, if necessary – Physical therapy to reduce risk for contracture Cardiogenic Embolism; Acute Management Survival – Reported at 33% – 50% of deaths due to euthanasia – Greatest risk in acute period is reperfusion injury – Majority of cats should be given 72 hrs Secondary Prevention- Cats and Dogs Preferred – Clopidogrel + anti-Xa OR LMWH If fearful of bleeding complications – Anti-Xa OR LMWH At a minimum – Clopidogrel