VTE lecture slides_IDM2 Fall 2021-Student slides - 1pp color.pdf

Venous Thromboembolism: Lesson Overview Jennifer Steinberg, PharmD, BCPS Assistant Professor NSU College of Pharmacy  Learning objectives Compare and contrast anticoagulant agents in terms of efficacy, safety, laboratory monitoring, and precautions Apply pharmacokinetic and pharmacogenomic...

Venous Thromboembolism: Lesson Overview Jennifer Steinberg, PharmD, BCPS Assistant Professor NSU College of Pharmacy  Learning objectives Compare and contrast anticoagulant agents in terms of efficacy, safety, laboratory monitoring, and precautions Apply pharmacokinetic and pharmacogenomic principles to appropriately initiate, adjust, and monitor anticoagulant therapy Recommend non-pharmacologic and pharmacologic therapy for the prevention of VTE in a given patient, including appropriate dosing, therapeutic range, and duration of therapy Recommend anticoagulant therapy for the treatment of VTE in a given patient, including appropriate dosing, therapeutic range, and duration of therapy Monitor anticoagulant therapy and recommend appropriate dosage adjustments on the basis of laboratory results and/or clinical presentation List the most common and significant interactions with warfarin Counsel a patient on anticoagulation therapy, including parenteral administration Recognize the presentation of heparin induced thrombocytopenia (HIT) Recommend appropriate management strategies in the setting of HIT  Abbreviations VKA: vitamin K antagonist TWD: total weekly dose ▫ e.g. warfarin FFP: fresh frozen plasma LMWH: low molecular weight PCC: prothrombin complex heparin concentrate ▫ e.g. enoxaparin (Lovenox®) CVA: cerebrovascular attack UFH: unfractionated heparin stroke VTE: venous thromboembolism TIA: transient ischemic attack ▫ DVT: deep vein thrombosis AF: atrial fibrillation ▫ PE: pulmonary embolism LVD: Left ventricular dysfunction DOAC: Direct Oral Anticoagulants AVR: aortic valve replacement MVR: mitral valve replacement Guidelines Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl) Parenteral Anticoagulants: e24S-e43S. Oral Anticoagulant Therapy: e44S-e88S. Prevention of VTE in Nonsurgical Patients: e195S-e226S. Prevention of VTE in Nonorthopedic Surgery Patients: e227S-e277S. Prevention of VTE in Orthopedic Surgery Patients: e278S-e325S. Antithrombotic Therapy for VTE: e419S-e494S. Treatment of HIT: e495S-e530S. Guidelines VTE Chapter updates: Antithrombotic Therapy for VTE Disease, CHEST Guideline and Expert Panel Report. Chest. 2016;149(2):315-352 !"#$#%&'()'#$*+,%-&./0+1'&+2,3+4$5-.5-6+7-*'"8+9/8.#-+'1+ #%-+:;37,+$"-+."8+3?/-&#+@."->+A-/'&#B+:%-5#B+CDCEB+ @=)>$5%-8+'">$"-B+https://doi.org/10.1016/j.chest.2021.07.055 Guidelines American Society of Hematology guidelines for the management of venous thromboembolism Multiple individual documents (e.g. diagnosis, HIT, anticoagulation therapy, etc) available at http://www.hematology.org/Clinicians/Guideline s-Quality/8743.aspx Vascular disease IHD Veins VTE ACS Coronary Stroke Cerebral Vascular disease Arteries TIA Peripheral Renal Lymphatic Mesenteric system Aorta Pathophysiology of clots Arterial Venous “White clots” “Red clots” High pressure Low pressure Platelet rich Red blood cells Antiplatelet agents Anticoagulant agents Pharmacist's Letter/Prescriber's Letter 2009;25(9):250901. VTE Lesson Components Introduction Acute treatment (parenteral agents) Outpatient treatment (oral agents) Prophylaxis Heparin Induced Thrombocytopenia Live session active learning activities  Venous Thromboembolism: Introduction Jennifer Steinberg, PharmD, BCPS Assistant Professor NSU College of Pharmacy Venous Thromboembolism (VTE) Venous thrombosis – clot in the venous system, usually the deep veins of the legs (DVT) Pulmonary embolism (PE) – clot in the lung, usually resulting from DVT Risk Factors for VTE Immobility Malignancy Surgery Trauma Estrogen use Heart disease Inherited coagulation disorders Virchow’s Triad Venous stasis Vessel wall injury Hypercoagulability Coagulation Cascade UFH LMWH dabigatran argatroban lepirudin UFH LMWH fondaparinux rivaroxaban apixaban Presentation & Evaluation Medications Medical Physical History Exam Risk Factors Presentation Symptoms ▫ Often asymptomatic ▫ Non-specific ▫ Resembles other disease states Objective testing required to confirm diagnosis Presentation: DVT Unilateral swelling Warmth Discoloration Pain Tenderness + Homan’s sign Presentation: PE Shortness of breath Cough Chest pain Anxiety Tachycardia Tachypnea Diagnosis: DVT Doppler ultrasound Venography Diagnosis: PE ECG Chest X-ray Arterial blood gas CT Scan Ventilation/perfusion scan (V/Q scan) Pulmonary angiography D-dimer Degradation product of fibrin clot Sensitive à elevated in patients with acute thrombosis Not specific à can be elevated due to other causes ▫ Trauma, pregnancy, cancer, surgery, infection, inflammation Case MJ is a 58 YO female. She presents to the ED with recent onset unilateral swelling of the right calf. Patient reports no SOB, no CP, no trauma. She states had a hysterectomy last month with a difficult recovery. Wt: 130 lbs; Ht: 5’5” PMHx: S/P Hysterectomy (1 month ago) Osteoarthritis 141 101 18 Hypertension 123 4.1 28 1.1 Meds: Naproxen 500mg Q12H prn APAP 650mg Q6H prn 13 HCTZ 25mg PO qAM 303 11 36  Venous Thromboembolism: Acute Treatment [parenteral agents] Jennifer Steinberg, PharmD, BCPS Assistant Professor NSU College of Pharmacy Pharmacologic Agents for VTE Unfractionated heparin (UFH) Low molecular weight heparin (LMWH) Parenteral Fondaparinux Warfarin Rivaroxaban Dabigatran Apixaban Target specific oral anticoagulants (DOAC) Edoxaban Betrixaban Thrombolytics Acute VTE Management options Parenteral agent with bridging to warfarin Parenteral agent alone Parenteral agent for 5-10 days then initiating dabigatran (Pradaxa) or edoxaban (Savaysa) Apixaban (Eliquis) or Rivaroxaban (Xarelto) Unfractionated Heparin (UFH) Mixture of mucopolysaccharides of variable length & pharmacologic profiles Accelerates anticoagulant activity of antithrombin III ▫ Inactivation of several clotting factors ▫ Factors IIa (thrombin) and Xa are most sensitive (1:1) Halts extension of existing thrombus  Unfractionated Heparin (UFH) Antithrombin Factor Xa Factor Xa Antithrombin Antithrombin Heparin Antithrombin Pentasaccharide sequence Thrombin Thrombin (IIa) Pharmacokinetics: Heparin Immediate anticoagulation effect Elimination ▫ Saturable enzymatic inactivation ▫ Non-saturable renal clearance T½ 30 – 150 minutes Adverse Effects: Heparin Bleeding ▫ Antidote: protamine sulfate Thrombocytopenia Osteoporosis Treatment of VTE: Heparin Various dosing strategies Sample weight based heparin ▫ 80 units/kg bolus IV ▫ 18 units/kg/hour continuous infusion – Dose adjusted based on aPTT monitoring – Adjustment protocols are institution specific Sample subcutaneous regimens ▫ ~5000 units bolus then 250 units/kg q12hrs ▫ 333 units/kg bolus then 250 units/kg q12hrs aPTT Monitoring: Heparin Reflects changes in intrinsic pathway Variations by lab/reagent/instrumentation à local institution ranges should be established Therapeutic goal: 1.5-2.5 times control ▫ Baseline aPTT ▫ aPTT 6 hours after initiation of therapy ▫ aPTT 6 hours after dose adjustment ▫ aPTT every 24 hours once therapeutic (two consecutive levels in therapeutic range) Sample IV Heparin Protocol (aPTT) aPTT Rate Change Other actions Repeat aPTT (sec) Units/kg/hr 90 -3 Hold infusion 1hr 6 hrs Adapted from: Hyers TM, et al. Chest 2001;114(suppl):179S. Anti-factor Xa Monitoring Monitoring of drugs with activity against factor Xa with varying degrees of applicability Therapeutic goal varies based on medication and indication ▫ UFH treatment: 0.3 – 0.7 anti-factor Xa units/mL Goal Timing of measurement ▫ UFH continuous infusion: random level ▫ LMWH: 4 hours after subQ dose administration Sample IV Heparin Protocol (anti-Xa) Anti-Xa Rate Change Repeat Other actions (IU/mL) Units/kg/hr levels < 0.1 +3 Rebolus 40 units/kg 6 hrs 0.1- 0.19 +2 Rebolus 20 units/kg 6 hrs 0.2- 0.29 +1 None 6 hrs 0.3- 0.7 No change **Therapeutic Range** 6 hrs / daily 0.71- 0.8 -1 None 6 hrs 0.81- 1.7 -2 Hold infusion 1hr 6 hrs >1.7 -3 Hold infusion 1.5 hrs 6 hrs Monitoring: Heparin Baseline H/H, platelets, PT, aPTT Routine H/H, platelet monitoring Routine aPTT/Anti-Xa monitoring Clinical safety and efficacy Low Molecular Weight Heparin Fragments of UFH Accelerates anticoagulant activity of antithrombin III Inactivates clotting factors ▫ Factor Xa > IIa (3:1) Halts extension of thrombus  LMWH Antithrombin Factor Xa Factor Xa Antithrombin Antithrombin LMWH Antithrombin Thrombin Pentasaccharide sequence Thrombin (IIa) Pharmacokinetics: LMWH More predictable response ▫ Good bioavailability ▫ Low protein binding Longer t½ Renal excretion ▫ Clearance reduced in severe renal impairment Adverse Effects: LMWH Bleeding ▫ Lower incidence than UFH? ▫ Incomplete inactivation by protamine sulfate Thrombocytopenia Black box warning – epidural or spinal puncture Treatment for VTE: LMWH Enoxaparin (Lovenox®) ▫ Treatment – DVT/PE – 1 mg/kg SubQ every 12hrs (or) 1.5 mg/kg SubQ every 24hrs ▫ Renal Adjustment– CrCl 100 kg: 10 mg SubQ daily Contraindicated in severe renal impairment (CrCl