Venous Thromboembolism (VTE) Part II PDF

Venous Thromboembolism (VTE) DR. RACHEL ZAREMBA, PHARMD, BCPS ASSISTANT PROFESSOR OF PHARMACY PRACTICE 1 OBJECTIVES Differentiate between the different the etiologies of venous thromboembolism (VTE). Calculate, interpret, and apply a Well’s score...

Venous Thromboembolism (VTE) DR. RACHEL ZAREMBA, PHARMD, BCPS ASSISTANT PROFESSOR OF PHARMACY PRACTICE 1 OBJECTIVES Differentiate between the different the etiologies of venous thromboembolism (VTE). Calculate, interpret, and apply a Well’s score (DVT or PE) and 4T score. Evaluate a patient for heparin induced thrombocytopenia and develop a plan regarding treatment moving forward. Compare and contrast the different options for VTE prophylaxis and treatment options for VTE. 2  OBJECTIVES Educate a patient on how to give subcutaneous anticoagulation injections (e.g. enoxaparin). Educate a patient on warfarin dosing, drug interactions (e.g. drug-diet, drug-drug), and monitoring. Given a patient case, develop an initial warfarin plan and an adjustment regimen based on follow-up monitoring. Given a patient case, develop both a nonpharmacologic and pharmacologic plan, monitoring plan, and follow-up plan for VTE prophylaxis and to treat a patient with a VTE. 3 VTE Prevention BACKGROUND VTEs are major risks for hospitalized patients ~50% of VTEs are secondary to hospital admission or surgery Appropriate prophylaxis can help prevent up to 70% Consider risk of VTE and bleeding 5 Patient Care Process: Prevention of VTE Collect Patient characteristics History Current medications Objective data: Vitals Labs 6 Patient Care Process: Prevention of VTE Assess Plan Presence of VTE risk factors Pharmacotherapy regimen Active bleeding Consideration for reversal Contraindications for agents anticoagulation Monitoring parameters Medications increasing risk of VTE Safety considerations Ability to self-inject parental Patient education therapy Self- monitoring Affordability When to seek emergency Ability to obtain monitoring medical attentipon 7 Patient Care Process: Prevention of VTE Implement Follow-Up: Monitor & Evaluate Appropriate VTE prevention VTE symptoms Patient specific factors Adverse Drug reactions Bleeding risk Heparin-induced thrombocytopenia Education INR results Motivational Interviewing Adherence Schedule follow-up Is patient ambulatory? 8 Nonpharmacologic Options: Prevention Graduated Intermittent pneumatic Compression Socks compression (IPC) Orthopedic surgery General surgery Cardiac surgery Orthopedic surgery Gynecologic surgery Neurosurgery Neurosurgery Both can be used together 9 Nonpharmacologic Options: Prevention Inferior Vena Cava (IVC) filters Block embolization of thrombus formed below filter Short-term protection for PE Utilize in very high-risk patients Routine use is not recommended IVC should be removed 10 Pharmacotherapy Options: Prevention Pharmacologic therapy is preferred over mechanical Medical Patients Surgical patients Total hip or knee arthroplasty 11 UNFRACTIONATED HEPARIN Medically Ill: 5,000 units subcut every 8-12 hours Sub q injections dont affect aPTT Orthopedic surgeries: 5,000 units subcut every 8-12 hours Pregnancy (subcut) First trimester: 5,000-7,500 units every 12 hours Second trimester: 7,500-10,000 units every 12 hours Third trimester: 10,000 units every 12 hours 12 ENOXAPARIN (LOVENOX) 40 mg subcut every 24 hours Renal impairment CrCl < 30 mL/min: 30 mg subcut daily Dialysis: not recommended Obesity: BMI > 40 kg/m^2: 40 mg subcut every 12 hours BMI > 50 kg/m^2: 60 mg subcut every 12 hours 13 ENOXAPARIN (LOVENOX) Total hip or knee arthroplasty 40 mg subcut daily OR 30 mg subcut every 12 hours Administer > 12 hours pre- or postoperatively Duration: minimum 10-14 days; may 35 days Bariatric Surgery BMI < 50 kg/m^2: 40 mg subcut every 12 hours at least 2 hours prior to surgery BMI > 50 kg/m^2: 60 mg subcut every 12 hours at least 2 hours prior to surgery 14 APIXABAN (ELIQUIS) Indefinite anticoagulation: Elevated risk of recurrent VTE after > 6 months therapeutic anticoagulation 2.5 mg by mouth twice daily Total hip or knee arthroplasty: 2.5 mg by mouth twice daily 12-24 hours post-op Duration: minimum of 10-14 days; up to 35 days 15 RIVAROXABAN (XARELTO) Indefinite anticoagulation: 10 mg by mouth daily- without food 15 mg or greater - taken with food Acutely ill medical patients: 10 mg by mouth daily for 31-39 days Total hip/knee arthroplasty: 10 mg by mouth daily initiated > 6 to 10 hours after surgery or once hemostasis achieved Duration: minimum of 10-14 days; up to 35 days 16  PATIENT CASE A patient is returning to their room on your floor after completion of their total knee arthroplasty. The doctor calls and asks what options they can consider for VTE prophylaxis in this patient. What option(s) do you recommend? -Eliquis 2.5 mg by mouth twice daily -Rivaroxaban 10 mg PO QD -Enoaparin 40 mg subcut daily OR 30 mg subcut every 12 hours Administer > 12 hours pre- or postoperatively -Sub Q 5000 units every 8-12 hours 17 PATIENT CASE What is the recommended duration of prophylaxis for this patient? 18  PATIENT CASE You are reviewing the following patients on your unit for VTE prophylaxis. What medications would you recommend for each patient? 26-year-old female that is 26 weeks 4 days pregnant. She presented with a urinary tract infection that required intravenous antibiotics. Sub q unfractionated heparin First trimester: 5,000-7,500 units every 12 hours Second trimester: 7,500-10,000 units every 12 hours Third trimester: 10,000 units every 12 hours 74-year-old male admitted to the hospital with complaints of a migraine. Stroke is ruled out. His BMI is 28 kg/m^2 and his renal function is 26 mL/min. 48-year-old patient with a BMI of 62.7 kg/m^2. 19 VTE Treatment Patient Care Process: Treatment of VTE Collect Patient characteristics History Current medications Objective data: Vitals Labs Objective confirmation Do NOT order hypercoaguability tests 21 Patient Care Process: Treatment of VTE Assess Plan Hemodynamic instability Pharmacotherapy regimen (PE) Reversal Agent? Active bleeding Monitoring parameters Provoking factors Safety considerations Ability to self-inject Patient education parenteral options Self- monitoring Ability to pay for options When to seek emergency Ability to obtain labs medical attention Emotional status Refer out 22 Patient Care Process: Treatment of VTE Implement Education Motivational Interviewing Schedule follow-up Follow-Up: Monitor & Evaluate Resolution of signs and symptoms Adverse Drug reactions INR results Adherence Duration of therapy >90 days 23  2016 CHEST GUIDELINE VTE RECOMMENDATIONS “Direct oral anticoagulants are preferred over warfarin for VTE without cancer diagnosis (Grade 2B).” “Warfarin is recommended over low molecular weight heparin (Grade 2C).” “For VTE and cancer, we suggest LMWH over VKA (Grade 2B), dabigatran (Grade 2C), rivaroxaban (Grade 2C), apixaban (Grade 2C), or edoxaban (Grade 2C). ” “For patients with recurrent VTE while treated with a non-LMWH anticoagulant, the guideline recommends changing to LMWH therapy (Grade 2C).” “If patients suffer a recurrent VTE while on LMWH treatment, the guideline recommends increasing the LMWH dose (Grade 2C).” 24 Chest. 2016;149(2):315-352.  2021 CHEST GUIDELINE VTE RECOMMENDATIONS “Initial anticoagulation setting: Outpatient treatment is recommended over hospitalization in patients with low-risk PE, if access to medications and outpatient care is available. (Strong recommendation, low-certainty evidence)” “Treatment-phase anticoagulants: DOACs are recommended over warfarin. (Strong recommendation, moderate-certainty evidence)” “Patients with cancer-associated VTE: Direct-acting oral anticoagulants (DOACs; i.e., apixaban, edoxaban, or rivaroxaban) should be used for the treatment phase of therapy (strong recommendation, moderate-certainty evidence).” 25 Chest. 2024;166(2):388-404.  2021 CHEST GUIDELINE VTE RECOMMENDATIONS “Extended-phase therapy (beyond 3 months) for VTE: Extended anticoagulation should be offered to patients with unprovoked VTE — i.e., with no major or minor transient risk factors. Risk for recurrent VTE, risk for bleeding, and patients' values and preferences should be considered in decisions about extended anticoagulation therapy. (Strong recommendation, moderate- certainty evidence)” Low-dose apixaban or rivaroxaban is recommended over full doses of these agents. (Weak recommendation, very low-certainty evidence) Aspirin is recommended for patients who are stopping anticoagulation. (Weak recommendation, low-certainty evidence) 26 Chest. 2024;166(2):388-404. UNFRACTIONATED HEPARIN Intravenous Bolus: 80 units/kg/hr followed by Continuous Infusion: 18 units/kg Titrated based on aPTT or Anti-Xa levels Requires baseline labs prior to starting Subcutaneous (outpatient) 333 units/kg x1 followed by 250 units/kg twice daily Do not need to monitor aPTT 27 UNFRACTIONATED HEPARIN Intravenous infusion aPTT therapeutic range: 1.5-2.3 x mean normal control (usually 24-36 seconds) Anti-Xa therapeutic range: 0.3-0.7 units/mL Check aPTT 6 hours after start of infusion Check aPTT every 6 hours during first 24 hours Adjust per nomogram If therapeutic x24 hours, monitor every 24 hours 28 EXAMPLE NOMOGRAM: 29  PATIENT CASE – UNFRACTIONATED HEPARIN The team wants to start a patient on a heparin drip for VTE treatment. What baseline labs do you want to collect? -aPTT -Platelets -INR -Hemoglobin 30 PATIENT CASE – UNFRACTIONATED HEPARIN What initial dose do you recommend? (Weight = 87 kg) Round to the nearest 100 units. 80 units x 87 kg -6,960 or 7,000 units/hr bolus dose 18 units x 87 kg 1566 or 1600 units/hr coninuous infusion 31  PATIENT CASE – UNFRACTIONATED HEPARIN What lab do you recommend the team monitor? When should it be obtained? 32 ENOXAPARIN (LOVENOX) 1 mg/kg subcut every 12 hours OR 1.5 mg/kg subcut every 24 hours Renal impairment CrCl < 30 mL/min: 1 mg/kg subcut daily Dialysis: not recommended Overlap consideration: Warfarin, dabigatran, edoxaban **Dosed based on actual body weight** 33 DALTEPARIN (FRAGMIN) 200 units/kg subcut every 24 hours OR 100 units/kg subcut every 12 hours No renal dose adjustments Monitoring: Consider Anti-Xa level 4 hours after dose 34 DIRECT ORAL ANTICOAGULANTS Medication Dose Dabigatran (Pradaxa) After 5 days of parenteral anticoagulant: avoid in elderly/bleeding 150 mg by mouth twice daily Apixaban (Eliquis) 10 mg by mouth twice daily for 7 days followed by 5 mg twice daily Rivaroxaban (Xarelto) 15 mg by mouth twice daily with food for 21 days followed by 20 mg daily with food Edoxaban (Savaysa) After 5 days of parenteral anticoagulant: Weight > 60 kg: 60 mg by mouth daily Weight < 60 kg: 30 mg by mouth daily Consider alternative if CrCl > 95 mL/min 35 WARFARIN (COUMADIN) DVT/PE Goal INR range 2-3 Overlap with parenteral anticoagulant for at least 5 days AND at least 2 therapeutic INRs (value of 2-3) See dosing in “warfarin management section” 36 SUMMARY OF TREATMENT OPTIONS 37 MONITORING – PARENTERAL AGENTS Coagulation studies Baseline CBC Serum creatinine Ongoing Signs and symptoms of bleeding IV UFH: aPTT or anti-Xa Every 1-3 CBC days 38 SPECIFIC REVERSAL AGENTS Heparin & LMWH Protamine Dabigatran (Pradaxa) Idarucizumab (Praxbind) Apixaban (Eliquis) & Andexanet Alfa (Andexxa) Rivaroxaban (Xarelto) Warfarin Vitamin K 39 NONSPECIFIC REVERSAL AGENTS Fresh frozen plasma Prothrombin Complex Concentrate PCC4 (Kcentra) Recombinant Factor VII 40 Discharging Patients DISCHARGING OPTIONS FROM IV HEPARIN start within 2 hour LMWH, apixaban IV Heparin of discontinuing IV or rivaroxaban heparin Start within give parenteral dabigatran 2 hours of IV Heparin therapy for 5-10 or edoxaban discontinuin days g IV heparin At least 5 days and IV Heparin warfarin 2 therapeutic INRs 42 DISCHARGING OPTIONS FROM LMWH start at next Apixaban or LMWH rivaroxaban dosing interval Give Start at next Dabigatran parenteral LMWH or edoxaban therapy for dosing interval 5-10 days At least 5 days and 2 LMWH warfarin therapeutic INRs 43 PATIENT CASE ▪ We are discharging our pregnant patient home after experiencing a PE. She has been on parenteral anticoagulation for 3 days and the team is ready to discharge her home. Which of the following is the most appropriate anticoagulation to discharge the patient on? A) Apixaban B) Warfarin C) Rivaroxaban D) Dabigatran E) Enoxaparin 44 Warfarin Management CLINICAL MONITORING INR TTR Frequent monitoring Time in therapeutic Testing Options: range Point of care Calculated from INRs Venipuncture Overview of INR Home/self-testing control Goal VTE: 2-3 Not expected to be 100% INTERPRETING INR Subtherapeutic below goal range Therapeutic within goal range Supratherapeutic above goal range 47  INITIAL DOSING CHEST guidelines recommend 10 mg by mouth daily for 2 days in healthy patients treated outpatient Other experts recommend lower doses such as 5 mg daily. Consider lower dose of 2.5 mg daily if: Renal dysfunction Interacting medications Liver disease High bleeding risk Older age 48 ADJUSTMENT OF WARFARIN DURING INITIATION Frequent INR checks Inpatient: daily Outpatient: every 2-3 days INR should steadily increase Large jumps may require holding or decreasing dose Example: Normal INR = 1; Day 3 INR = 1.9 Slow response will require increased dosing Example: Normal INR = 1; Day 3 INR = 1.2 49 ADJUSTMENT OF WARFARIN DURING INITIATION Inpatient Likely utilize a protocol May have a nomogram Outpatient Consider gradually increase time between INR checks if patient maintains a therapeutic INR 50 ASSESSMENT OF MAINTENANCE PHASE WARFARIN S/Sx of Medication INR bleeding/VTE changes Dietary Missed/Extra Health changes Doses changes 51 ADJUSTMENT OF WARFARIN DOSING Assess weekly dose Do not include: Boost: extra dose(s) Holds: skipping dose(s) Examples: 5 mg daily = 35 mg/week 5 mg MWF and 2.5 mg all other days = 25 mg/week 52 ADJUSTMENT OF WARFARIN DOSING Assess weekly dose 5 mg daily = 35 mg/week 5 mg MWF and 2.5 mg all other days = 25 mg/week Do not include: Boost: extra dose(s) Holds: skipping dose(s) 5-10% dose changes are generally used 53 ADJUSTMENT OF WARFARIN DOSING If INR previously stable with one out of range INR: Consider continuing current regimen Retest INR in 1-2 weeks If there is clear reason for INR change that will continue, dose change is required. If temporary change impacted INR, change may be considered but is not required. 54  WARFARIN NOMOGRAM EXAMPLE INR Recommendation Subtherapeutic Boost x 0-1 days Increase dose by 5-10% Therapeutic Continue same dose Supratherapeutic Hold x 0-1 days Decrease dose by 5-10% Hold x 1 day if INR 0.5 or more above goal If significantly above range (e.g. 1.0 or more above goal) consider holding until rechecked INR is therapeutic before restarting at a lower dose Oral vitamin K if INR > 10 (see reversal section) 55 WARFARIN DOSING CLINICAL PEARLS Patient specific dosing Utilize a single strength tablet Example: Use 5 mg tablets Give 5 mg MWF and 2.5 mg all other days; 25 mg/week Stick with 5-10% changes based on weekly dose Consider holding warfarin if INR > 0.5 above goal – hold x1 dose INR > 1 above goal, hold until INR decreases 56 MONITORING RECOMMENDATIONS After dose change, recheck INR in 1-2 weeks. After 1 therapeutic INR on stable dose, recheck in 2 weeks. After 2 therapeutic INRs on stable dose, recheck in 4 weeks Ideally, continue to check monthly If stable for extended time frame (e.g. months), can consider increasing time in between INRs up to 12 weeks 57 WARFARIN REVERSAL Vitamin K (phytonadione – Mephyton) 5 mg scored tablets Injectable given as slow intravenous infusion Prothrombin complex concentrate (PCC) KCENTRA - Pretreatment INR 2 - 6 Dose of Kcentra (units of Factor IX/kg body weight) 25 35 50 Maximum Dose (units of Factor IX) < 2500 < 3500 < 5000 Other Options: Fresh frozen plasmA recombinant Factor VII 58 REVERSAL - SUPRATHERAPEUTIC INR INR 4.5 – 10 and no clinical signs of bleeding No vitamin K indicated Hold warfarin INR > 10 and no clinical signs of bleeding Oral vitamin K indicated Hold warfarin; give vitamin K 2.5-5 mg by mouth Repeat in 24-48 hours if INR not significantly decreased Supratherapeutic INR with serious or life-threatening bleeding Intravenous Vitamin K indicated Hold warfarin; give vitamin K 5-10 mg by SLOW IV infusion Consider additional reversal options 59 Duration of Therapy TERMINOLOGY Long-term first 3 months Extended no scheduled stop date Surgery or non-surgical trigger Provoked VTE Trauma, injury, estrogen, pregnancy, recent hospitalization 65 years old Cancer Previous bleeding Renal failure Liver failure Antiplatelet Anemia Thrombocytopenia Previous Stroke Diabetes therapy Poor anticoagulation Recent surgery Frequent falls Alcohol Abuse NSAID use control 64 ASSESSING BLEEDING RISK Category Number of Risk Factors Low None Medium 1 High >2 65  DURATIONS Scenario Specifics Duration Provoked Surgery or non- 3 months then stop surgical trigger First-event, Distal/calf DVT 3 months then stop unprovoked Proximal DVT > 3 months, then consider extended therapy or PE Low-moderate bleeding risk: extended therapy High bleeding risk: 3 months then stop Recurrent > 1 event > 3 months, then consider extended therapy VTE Low-moderate bleeding risk: extended therapy High bleeding risk: 3 months then stop VTE & Cancer Active cancer Extended therapy 66 CHEST 2016;149:315-52. Education ENOXAPARIN https://www.lovenox.com/patient-self-injection-video 68 ENOXAPARIN EDUCATION – CLINICAL PEARLS Inject exact dose prescribed Inject at the same time(s) every day Hold skin fold throughout the injection Do not rub the area after injection Rotate sites NEVER inject into the muscle! 69  WARFARIN EDUCATION What is Warfarin? Helps prevent clotting and for patients with previous stoke form having another one What is the reason for taking warfarin? Prevents new clots from forming How do I take this medication? Take at same time each day and do not skip doses 70  WARFARIN EDUCATION How do you monitor this medication? INR checks to see if it's therapeutic What are the side effects of this medication? -Bruising/bleeding -Skin necrosis or purple toe syndrome 71  WARFARIN EDUCATION What are signs and symptoms of minor bleeding? Major bleeding? Minor bleeding Signs of major bleeding Gums bleeding Dark brown or red urine Knicks when shaving Black tarry stools Nosebleeds Vomit that is bright red or Bruising looks like coffee grounds Excessive menstrual flow Situations that require medical attention Bleeding that lasts > 10 minutes; If a patient falls/ hits their head 72 WARFARIN EDUCATION - DIET Primary concern is vitamin K intake Counsel to remain consistent with Vitamin K intake Brussel Collard Kale Spinach Sprouts Greens Asparagus Avocado Soybeans Prunes 73  WARFARIN EDUCATION - DDI know the first 3 agents that increase INR Fluconazole (Azoles) * Increase INR Amiodarone * Rifampin Bactrim (Sulfonamides) * Barbiturates Flagyl * Carbamazepine Decrease INR Fluoroquinolones Phenytoin Thyroid hormones Cholestyramine Cholesterol lowering agents St. John’s Wort Steroids Vitamin K Macrolides **DO NOT TAKE WITH MORE THAN 2 GRAMS OF TYLENOL** 74 WARFARIN EDUCATION - DDI Increase INR Acute alcohol Chronic consumption alcohol Cannabis Use consumption Decrease INR Tobacco Use 75 WARFARIN EDUCATION - DDI OVER THE COUNTER PRODUCTS THAT INCREASE INR Gingko Garlic Ginger biloba Green Ginseng Tea 76 WARFARIN EDUCATION - OTHER Alert other providers of your prescription Teratogenicity – Not safe for pregnancy Other health changes? 77