1. Vanderbilt Pediatric Hematology Anticoagulation Guidance Protocol Robert F. Sidonio, Jr. MD, MSc. 4/11/12 Enoxaparin Dosing Goal anti-Xa levels are 0.6 – 1 units/mL. Certain patient populations (i.e. pregnancy, Berlin heart, etc.) may require higher anti-Xa levels. The pharmacist should be contacted if higher anti-Xa levels are needed in these patients. Doses to achieve therapeutic anticoagulation are highest in infants because of altered heparin pharmacokinetics, larger volume of distribution and physiologically low antithrombin activity. Consider additional monitoring at least once during acute illness requiring hospitalization, all inpatient cardiac patients and any acute renal impairment. Monitoring once at admission and again weekly is a reasonable monitoring plan while hospitalized for illness. Enoxaparin Dosing Monitoring and Considerations Administration is via injection into subcutaneous tissue. Consider topical lidocaine or EMLA cream 20 minutes prior to dosing to reduce discomfort in children. Monitoring should begin after the second dose is administered. Check an anti-Factor Xa level 4-5 hours after an AM dose. Dosing will be given at 0800/2000 while inpatient to ensure appropriate lab turnaround time. Please consult the Pharmacy Enoxaparin monitoring service for help in dosage adjustment while inpatient. Pharmacy enoxaparin monitoring service will be paged when new orders for enoxaparin are ordered in WIZ/HEO. The anticoagulation dashboard will also be utilized. If patient is sent home on enoxaparin then consult Pediatric Hematology thrombosis nurse for parent education in administration. If patient is transitioned to generic enoxaparin, patients will have anti-Xa level drawn initially to ensure no deviation. Levels will then be followed via nomogram. Administration with an Insuflon catheter should be avoided since difficult to obtain outpatient Dosage titration nomogram For patients < 10 kg, all doses will be rounded to the nearest 0.5 milligram to aid in ease of dosing administration upon discharge. For patients ≥ 10 kg, doses will be rounded to the nearest whole milligram. Conversion from UFH to Enoxaparin Give 1 st dose of Enoxparin at the same time the UFH drip is stopped. Conversion from Enoxaparin to UFH If > 12 hours since last enoxaparin dose, give standard bolus followed by maintenance continuous UFH drip. If 8-12 hours since last enoxaparin dose, give only the standard maintenance continuous UFH drip, skipping the bolus. Procedures For cardiac catheterization hold only the AM dose prior to procedure. For invasive or surgical procedures hold a total of two doses thus the PM dose and the AM dose. Restarting enoxaparin is per discretion of the surgeon or cardiologist, typically within 12-24 hours. Enoxaparin Dosing Goal anti-Xa levels are 0.6 – 1 units/mL. Certain patient populations (i.e. pregnancy, Berlin heart, etc.) may require higher anti-Xa levels. The pharmacist should be contacted if higher anti-Xa levels are needed in these patients. Doses to achieve therapeutic anticoagulation are highest in infants because of altered heparin pharmacokinetics, larger volume of distribution and physiologically low antithrombin activity. Consider additional monitoring at least once during acute illness requiring hospitalization, all inpatient cardiac patients and any acute renal impairment. Monitoring once at admission and again weekly is a reasonable monitoring plan while hospitalized for illness. Enoxaparin Dosing Monitoring and Considerations Administration is via injection into subcutaneous tissue. Consider topical lidocaine or EMLA cream 20 minutes prior to dosing to reduce discomfort in children. Monitoring should begin after the second dose is administered. Check an anti-Factor Xa level 4-5 hours after an AM dose. Dosing will be given at 0800/2000 while inpatient to ensure appropriate lab turnaround time. Please consult the Pharmacy Enoxaparin monitoring service for help in dosage adjustment while inpatient. Pharmacy enoxaparin monitoring service will be paged when new orders for enoxaparin are ordered in WIZ/HEO. The anticoagulation dashboard will also be utilized. If patient is sent home on enoxaparin then consult Pediatric Hematology thrombosis nurse for parent education in administration. If patient is transitioned to generic enoxaparin, patients will have anti-Xa level drawn initially to ensure no deviation. Levels will then be followed via nomogram. Administration with an Insuflon catheter should be avoided since difficult to obtain outpatient Dosage titration nomogram For patients < 10 kg, all doses will be rounded to the nearest 0.5 milligram to aid in ease of dosing administration upon discharge. For patients ≥ 10 kg, doses will be rounded to the nearest whole milligram. Conversion from UFH to Enoxaparin Give 1 st dose of Enoxparin at the same time the UFH drip is stopped. Conversion from Enoxaparin to UFH If > 12 hours since last enoxaparin dose, give standard bolus followed by maintenance continuous UFH drip. If 8-12 hours since last enoxaparin dose, give only the standard maintenance continuous UFH drip, skipping the bolus. Procedures For cardiac catheterization hold only the AM dose prior to procedure. For invasive or surgical procedures hold a total of two doses thus the PM dose and the AM dose. Restarting enoxaparin is per discretion of the surgeon or cardiologist, typically within 12-24 hours. Heparin Dosing and monitoring Obtain a baseline CBC, PT, aPTT, Fibrinogen and correct coagulopathies as needed. Initial Loading dose: 75 Units/kg over 10 minutes (Maximum 5000 units) Initial Maintenance dose Infusion begins after initial bolus is complete < 1 year: 28 units/kg/hr ≥ 1 year: 20 units/kg/hr (Maximum initial rate 1000 units/hour) Obtain blood for aPTT 4 hours after loading dose and adjust based on nomogram below. Follow adjustment guidelines below to maintain aPTT between 65 – 100 seconds (assuming this reflects anti-factor Xa of 0.35 – 0.7 units/mL) Patients with prolonged baseline aPTT, infants, perceived difficulty managing therapeutic aPTT, excessive bleeding with therapeutic aPTT, or progression of thrombus with therapeutic aPTT may be monitored predominantly with anti-Factor Xa levels but encourage daily PTT (drawn at same time as anti-FXa) surveillance. Please discuss with hematology service. Please page the clinical pharmacist on the patient’s service when planning transition to enoxaparin or warfarin. Obtain blood for aPTT/anti-FXa 4 hours after each dose adjustment and readjust as needed. Maintain fibrinogen >100 mg/dL and platelet count >50k while on UFH. When aPTT/anti-FXa is therapeutic on 2 consecutive samples, obtain blood for CBC, aPTT and anti-FXa level daily x 5 days. Thereafter can check CBC every other day or twice a week if limited blood draws are needed. Discrepancies may arise between anti-FXa and aPTT. Use clinical judgement, would recommend utilizing anti-FXa as it correlates more closely with Heparin levels. Reversal of Enoxaparin There is no proven method for neutralizing LMWH and protamine leads to incomplete reversal. Consultation with hematology is recommended prior to administration. Protamine is rarely indicated as the preferred strategy over observation. If LMWH was given within 8 hours, protamine sulfate should be administered in a dose of 1 mg per 100 anti-Xa units of LMWH (maximum dose 50 mg). 1 mg enoxaparin equals approximately 100 anti-Xa units. A second dose of 0.5 mg protamine sulfate per 100 anti-Xa units should be administered if bleeding continues.