Pediatric Anticoagulation Discuss high-risk pediatric populations - PDF document

Pharmacist Objectives • Compare and contrast differences between adult and pediatric anticoagulation management Pediatric Anticoagulation • Discuss high-risk pediatric populations and indications for anticoagulation Emily S. Waite, PharmD, BCOP Pediatric Hematology-Oncology Pharmacist • Evaluate available anticoagulant agents and use of them in the pediatric population • Given a patient case, select a treatment regimen and monitoring plan Technician Objectives Disclosure • Identify anticoagulants commonly used in • I have nothing to disclose related to the content pediatric patients of this presentation. • Discuss different dosing of anticoagulants in pediatrics compared to adults • Recognize available dosage forms and available strengths of anticoagulants used in pediatrics Patient Case Patient Case Continued… • HG is a 14 year old caucasian female who • Past Medical History: presents to the emergency room with chief ▫ Diagnosed with Polycystic Ovarian Syndrome complaint of lower leg pain and swelling. (PCOS) at age 12 ▫ NKDAs • She denies any leg injury, shortness of breath or ▫ Immunizations: up to date chest pain. • Current medications: • You are an inpatient clinical pharmacist ▫ Ethinyl estradiol 0.03 mg/desogestrol 0.15 mg responsible for providing recommendations to daily (Started approximately 2 years ago) the inpatient medical team for comprehensive • Prescription Insurance patient medication management. ▫ Blue Cross Blue Shield of Alabama

Patient Case Continued… Patient Case Continued… • Family History: • Review of Systems: ▫ Maternal grandfather – hypertension, dyslipidemia ▫ General: (+) fatigue, (-) fever ▫ Paternal grandfather – type 2 diabetes mellitus ▫ CV/Pulm: (-) shortness of breath, chest pain (T2DM), prostate cancer ▫ Ext: (+) tenderness, (+) LLE swelling, (-) discoloration ▫ Mother – hypertension, dyslipidemia • Physical Exam: ▫ Father – T2DM, dyslipidemia ▫ RR 18 resp/min, HR 122 bpm, BP 150/95 mm Hg, ▫ No known clotting disorders Temp 99.1 ⁰ F, O 2 sat 98% RA • Social History ▫ 8 th grader ▫ 80 kg, 160 cm, BMI 32 kg/m 2 ▫ Left calf warm to touch and tender, LLE with warmth ▫ Lives with mother, father, and brother (11) and swelling, normal ROM and pulses ▫ Denies smoking, alcohol and recreational drug use Question 1 Patient Case Continued… Based on HG’s symptoms and confirmed DVT via ultrasound, she is admitted to begin anticoagulation. • CBC: WNL Which of the following would be considered • SCr: 0.8 mg/dL appropriate for initial treatment of HG’s DVT? • Doppler ultrasound: Acute deep vein thrombosis (DVT) of left popliteal vein. a. Warfarin • PT/INR: 10.9 sec / 1.1 b. Enoxaparin c. Rivaroxaban d. Dabigatran Question 1 Treatment of Venous Thromboemobolism (VTE) in Children Based on HG’s symptoms and confirmed DVT via • CHEST Guidelines ultrasound, she is admitted to begin anticoagulation. Which of the following would be considered ▫ Standards primarily derived from adult literature appropriate for initial treatment of HG’s DVT? ▫ Majority of recommendations graded as “weak” • Acute therapy (At least 5 days) a. Warfarin ▫ Unfractionated heparin (UFH) b. Enoxaparin ▫ Low molecular weight heparin (LMWH) c. Rivaroxaban • Ongoing therapy d. Dabigatran ▫ Vitamin K antagonists Monagle PM et al. Chest 2012; 141 (2 Suppl):e-737S-e801S

Unfractionated Heparin (UFH) UFH Pharmacokinetics in Pediatrics • Loading dose • Increased volume of distribution ▫ Neonates and children: 75 units/kg • Increased clearance • Maintenance dose ▫ Less than 1 year old: 28 units/kg/hr • Lower percentage of anti-thrombin ▫ 1-12 years old: 20 units/kg/hr ▫ Greater than 12 years old: 18 units/kg/hr • Reduced capacity to generate thrombin • Prophylaxis dose ▫ 10 units/kg/hr Monagle PM et al. Chest 2012; 141 (2 Suppl):e-737S-e801S UFH Therapeutic Monitoring UFH Dosage Adj ustment by aPTT aPT T(se c onds) R e c omme nde d Dosage Adjustme nt • Activated partial thromboplastin time (aPTT) L e ss than 50 Bo lus 50 units/ kg I nc re ase drip by 10% ▫ Range that correlates with protamine titration 50 – 59 I nc re ase drip by 10% range of 0.2 to 0.4 unit/mL 60 – 85 No c hange 86 – 95 De c re ase drip by 10% • Anti-Xa 96 – 120 Ho ld drip fo r 30 minute s + ▫ Therapeutic goal = 0.35 to 0.7 units/mL* De c re ase drip by 10% Gre ate r than 120 Ho ld drip fo r 1 ho ur + De c re ase drip by 15% Obtain 4 hours after loading dose administration and 4 hours after any infusion rate change Monagle PM et al. Chest 2012; 141 (2 Suppl):e-737S-e801S Ro ac h. Stro ke . 2008; 2644-91 Question 2 UFH Dosage Adj ustment by Anti-Xa The inpatient team decides to begin therapy with enoxaparin and asks for guidance in dosing. Which Anti Xa L e ve l (units/ mL ) R e c omme nde d Dosage Adjustme nt would be the most appropriate recommendation? L e ss than 0.2 Bo lus 75 units/ kg I nc re ase drip by 4 units/ kg/ hr 0.2 - 0.29 Bo lus 40 units/ kg a. 40 mg twice daily I nc re ase drip by 2 units/ kg/ hr 0.3 – 0.7 No c hange b. 80 mg once daily 0.71 – 0.8 De c re ase drip by 2 units/ kg/ hr c. 120 mg once daily 0.81 – 0.99 Ho ld drip fo r 1 ho ur d. 80 mg twice daily + De c re ase drip by 2 units/ kg/ hr Gre ate r than o r e qual to 1 Ho ld drip fo r 1 ho ur + De c re ase drip by 3 units/ kg/ hr

Question 2 Low Molecular Weight Heparin (LMWH) The inpatient team decides to begin therapy with Enoxaparin Prophylaxis enoxaparin and asks for guidance in dosing. Which Age Enoxaparin Treatm ent Premature less would be the most appropriate recommendation? 2mg/kg/dose subQ every 12 hours 0.75mg/kg/dose subQ every 12 hours than 1 month: Full term less 1.7mg/kg/dose subQ every 12 hours 0.75mg/kg/dose subQ every 12 hours than 1 month a. 40 mg twice daily 1 to 2 months: 1.5mg/kg/dose subQ every 12 hours 0.75mg/kg/dose subQ every 12 hours b. 80 mg once daily 2 months to less 1mg/kg/dose subQ every 12 hours 0.5mg/kg/dose subQ every 12 hours c. 120 mg once daily than 14 years: (Max: 150mg/dose) 1mg/kg/dose (Max: 150mg/dose) 0.5mg/kg/dose (Max: 30mg/dose) d. 8 0 m g twice daily subcutaneous every 12 hours subcutaneous every 12 hours Greater than or - or- - or- equal to 14 years: 1.5mg/kg/dose (Max: 225mg/dose) 40mg subcutaneous every 24 hours subcutaneous every 24 hours (*May increase by 30% in obese patients) Question 3 LMWH Therapeutic Monitoring After beginning enoxaparin therapy, which of the following is the most appropriate recommendation Anti-Xa Treatm ent Range Prophylactic Range in regards to monitoring anti-Xa levels for HG? 0 .5 to 1 units/ m L 0 .1 to 0 .3 units/ m L a. Draw anti-Xa 4 hours post first dose b. Draw anti-Xa 4 hours post third dose • Anti-Xa level should be obtained 4-6 hours after c. Draw anti-Xa 8 hours post third dose steady state injection d. Anti-Xa levels are not indicated per guidelines Monagle PM et al. Chest 2012; 141 (2 Suppl):e-737S-e801S. Question 3 Question 4 After beginning enoxaparin therapy, which of the HG is terrified of having to receive enoxaparin following is the most appropriate recommendation injections, so the team asks your advice on initiating in regards to monitoring anti-Xa levels for HG? bridge therapy with warfarin. Which would be the best recommendation for HG’s warfarin? a. Draw anti-Xa 4 hours post first dose a. Begin 5 mg daily following 5 days of enoxaparin b. Draw anti-Xa 4 hours post third dose c. Draw anti-Xa 8 hours post third dose b. Begin 5 mg daily on Day 1 of enoxaparin d. Anti-Xa levels are not indicated per guidelines c. Begin 10 mg daily following 5 days of enoxaparin d. Begin 10 mg daily on Day 1 of enoxaparin