BNF for Children 2011-2012

118 2.8.2 Oral anticoagulants BNFC 2011–20122 Cardiovascular systemChild 1 month–16 years initially 30 units/kg(max. 1250 units if body-weight under 55 kg,2500 units if over 55 kg) by intravenous injectionthen by continuous intravenous infusion 1.2–2 units/kg/hour adjusted according to coagulationactivityChild 16–18 years initially 2500 units (1250 unitsif body-weight under 55 kg, 3750 units if over90 kg) by intravenous injection then by continuousintravenous infusion 400 units/hour for 2 hours,then 300 units/hour for 2 hours, then 200 units/hour for 5 days adjusted according to coagulationactivityAdministration for intravenous infusion, dilute withGlucose 5% or Sodium Chloride 0.9%Orgaran c (Organon) AInjection, danaparoid sodium 1250 units/mL, netprice 0.6-mL amp (750 units) = £26.68Heparin flushesThe use of heparin flushes should be kept to a minimum.For maintaining patency of peripheral venous catheters,sodium chloride 0.9% injection is as effective as heparinflushes. The role of heparin flushes in maintainingpatency of arterial and central venous catheters isunclear.Heparin Sodium (Non-proprietary) ASolution, heparin sodium 10 units/mL, net price 5-mL amp = £1.00; 100 units/mL, 2-mL amp = £1.05Excipients may include benzyl alcohol (avoid in neonates, see Excipients,p. 2)EpoprostenolEpoprostenol (prostacyclin) can be given to inhibitplatelet aggregation during renal dialysis when heparinsare unsuitable or contra-indicated. For its use in pulmonaryhypertension, see section 2.5.1.2. It is a potentvasodilator and therefore its side-effects include flushing,headache, and hypotension.2.8.2 Oral anticoagulantsOral anticoagulants antagonise the effects of vitamin Kand take at least 48 to 72 hours for the anticoagulanteffect to develop fully; if an immediate effect is required,unfractionated or low molecular weight heparin must begiven concomitantly.Uses Warfarin is the drug of choice for the treatment ofsystemic thromboembolism in children (not neonates)after initial heparinisation. It may also be used occasionallyfor the treatment of intravascular or intracardiacthrombi. Warfarin is used prophylactically in those withchronic atrial fibrillation, dilated cardiomyopathy, certainforms of reconstructive heart surgery, mechanicalprosthetic heart valves, and some forms of hereditarythrombophilia (e.g. homozygous protein C deficiency).Unfractionated or a low molecular weight heparin (section2.8.1) is usually preferred for the prophylaxis ofvenous thromboembolism in children undergoing surgery;alternatively warfarin can be continued in selectedchildren currently taking warfarin and who are at a highrisk of thromboembolism (seek expert advice).Dose The base-line prothrombin time should be determinedbut the initial dose should not be delayed whilstawaiting the result.An induction dose is usually given over 4 days (seeunder Warfarin Sodium below). The subsequent maintenancedose depends on the prothrombin time,reported as INR (international normalised ratio) andshould be taken at the same time each day. The followingindications and target INRs 1 for adults take intoaccount recommendations of the British Society forHaematology 2 ;. INR 2.5 for treatment of deep-vein thrombosis andpulmonary embolism (including those associatedwith antiphospholipid syndrome or for recurrencein patients no longer receiving warfarin), for atrialfibrillation, cardioversion (higher target values, suchas an INR of 3, can be used for up to 4 weeks beforethe procedure to avoid cancellations due to lowINR; anticoagulation should continue for at least 4weeks following the procedure), dilated cardiomyopathy,mural thrombus, symptomatic inheritedthrombophilia, coronary artery thrombosis (if anticoagulated),and paroxysmal nocturnal haemoglobinuria;. INR 3.5 for recurrent deep-vein thrombosis andpulmonary embolism (in patients currently receivingwarfarin with INR above 2);. For mechanical prosthetic heart valves, the recommendedtarget INR depends on the type and locationof the valve. Generally, a target INR of 3 isrecommended for mechanical aortic valves, and 3.5for mechanical mitral valves.Monitoring It is essential that the INR be determineddaily or on alternate days in early days of treatment,then at longer intervals (depending on response 3 ) thenup to every 12 weeks.Haemorrhage The main adverse effect of all oralanticoagulants is haemorrhage. Checking the INR andomitting doses when appropriate is essential; if theanticoagulant is stopped but not reversed, the INRshould be measured 2–3 days later to ensure that it isfalling. The following recommendations are based onthe result of the INR and whether there is major orminor bleeding; the recommendations apply to adultstaking warfarin:. Major bleeding—stop warfarin; give phytomenadione(vitamin K 1 ) 5–10 mg by slow intravenousinjection; give dried prothrombin complex (factorsII, VII, IX, and X—section 2.11) 30–50 units/kg (if1. An INR which is within 0.5 units of the target value isgenerally satisfactory; larger deviations require dosageadjustment. Target values (rather than ranges) are nowrecommended.2. Guidelines on Oral Anticoagulation (warfarin): thirdedition—2005 update. Br J Haematol 2005; 132: 277–285.3. Change in child’s clinical condition, particularly associatedwith liver disease, intercurrent illness, or drug administration,necessitates more frequent testing. See also interactions,Appendix 1 (warfarin). Major changes in diet(especially involving salads and vegetables) and in alcoholconsumption may also affect warfarin control.