Clinical guideline Lw Mlecular Weight Heparin Prescribing and Administratin (Adults) The Natinal Patient Safety Agency issued guidance n ways f reducing dsing errrs when prescribing lw mlecular weight heparins (LMWH) in July 2010. The main issues highlighted include 1 : Lack f cnsideratin f patients accurate weight befre dsing The dse f LMWH may still be miscalculated based n the knwn weight LMWH dses and frequencies are smetimes used utside guideline recmmendatins fr the required clinical indicatin r ther predispsing factrs such as renal failure. Limited infrmatin is cmmunicated during transfer f care i.e. indicatin, dsage, intended duratin f treatment and the patient s weight. This guideline is t prvide infrmatin t supprt the safe and apprpriate use f LMWHs acrss bth secndary and primary care. Chice f LMWH The chice f lw mlecular weight heparin used at Wirral University Teaching Hspital (WUTH) depends n the indicatin f treatment and the patient s renal functin. Indicatin Renal functin Chice f LMWH Venus thrmbemblism (VTE) prphylaxis and treatment all areas (except trauma and rthpaedics) VTE prphylaxis trauma and rthpaedics Acute crnary syndrme (ACS) alne (i.e. n ther indicatins requiring full anticagulatin) Irrespective f renal functin CrCl 15ml/min CrCl <15ml/min) CrCl 20ml/min CrCl <20ml/min Enxaparin Apixaban Enxaparin *Fndaparinux Enxaparin ACS plus ther indicatins requiring full anticagulatin (e.g. mechanical prsthetic valves, treatment f VTE r atrial fibrillatin requiring high level anticagulatin) Irrespective f renal functin Enxaparin *Fndaparinux is a synthetic pentasaccharide that inhibits factr Xa. CrCl = Creatinine Clearance Page 1 f 10
Dsing cnsideratins Renal functin A patient s renal functin shuld be cnsidered befre prescribing a LMWH as this may affect the chice and the dse f LMWH. Hwever, this shuld nt delay initiatin f treatment but every effrt must be made t calculate subsequent dse based n this infrmatin. Renal functin shuld be checked befre starting treatment and then at apprpriate intervals if cntinuing n LMWH (i.e. rutinely every 3 mnths r sner if the patient s cnditin changes in a way that might affect renal functin). A patient s estimated creatinine clearance can be calculated using Cckcrft and Gault s equatin. Cckcrft and Gault equatin fr creatinine clearance Creatinine clearance (ml/min) = Y x (140-age) x weight Where Y = 1.23 fr males and 1.04 fr females Serum creatinine uml/l Fr bese patients, adjusted bdy weight shuld be used Adjusted bdy weight = ideal bdy weight + 0.4 x (actual bdy weight ideal bdy weight) Ideal bdy weight (IBW) shuld be used t calculate the creatinine clearance unless patients are underweight. IBW can be calculated using the fllwing equatin: IBW Females = [45.5kg + (2.3 x every inch ver 5ft)] kg IBW Males = [50kg + (2.3 x every inch ver 5ft)] kg Fr underweight patients use actual bdy weight. An nline creatinine clearance calculatr is available at: http://bnf.rg/bnf/extra/current/450019.htm N.B: Renal functin may be reprted as estimated Glmerular Filtratin Rate (egfr) (in ml/min/1.73m 2 ) which is nt equivalent t the estimates f creatinine clearance described abve (reprted in ml/min). Since egfr estimates have nt yet been validated fr drug dsing, dse adjustment fr renal impairment cntinues t be based n estimates f creatinine clearance (e.g. calculated frm the Cckcrft and Gault equatin r frm a 24-hur urine cllectin) Weight Treatment dses f LMWHs are calculated based n the patient s weight. Therefre, where pssible, an accurate weight (in kg) shuld be btained using validated weighing equipment by persnnel trained in using the weighing equipment. In exceptinal circumstances, when a patient cannt be weighed, bdy weight infrmatin can be btained frm the patient r carer. Hwever, if this infrmatin cannt be btained, as a last resrt, the weight may be estimated by the prescriber. The patient s weight shuld be dcumented in the clinical ntes (medical r nursing ntes r GP clinical system) AND the hspital prescribing system (when in use) r the cmmunity patient medicatin administratin chart (PMAC) at the start f the treatment. The patient s weight shuld be added t the FP10 prescriptin. This is required by the cmmunity pharmacist when assessing the dse. It shuld then be rechecked at apprpriate intervals, at least every 3 mnths r sner if the patient s clinical cnditin changes in a way that might affect their bdy weight. Every effrt shuld be made t ensure an accurate weight (in kg) is btained prir t a LMWH being prescribed but this shuld nt delay treatment. If it is nt pssible t weigh the patient, r an estimated weight is used t calculate the dse f LMWH, this shuld be made clear in the patient s clinical ntes and re-assessed at a later date if apprpriate. Page 2 f 10
Preventin f venus thrmbemblism Duratin LMWH shuld cntinue t be administered fr as lng as the patient remains at risk f venus thrmbemblism (VTE). Calculating the right dse ALL patients wh are admitted t hspital MUST have their risk f develping a venus thrmbemblism (VTE) assessed n admissin, reassessed within 24 hurs f admissin and whenever the clinical situatin changes 2. PCIS will prvide guidance n the chice f LMWH and dse depending n the patient s renal functin (and patient s weight if their CrCl <30ml/min). Fr areas that d nt use PCIS, please refer t Table 1 fr dsing infrmatin. Table 1 Dses f enxaparin fr prphylaxis against VTE Indicatin LMWH Dse fr patients with a creatinine clearance 30mL/min Dse fr patients with creatinine clearance <30ml/min Medical thrmbprphylaxis 40mg sc nce daily 20mg sc nce daily Surgical thrmbprphylaxis*- Mderate risk Enxaparin 20mg sc nce daily 20mg sc nce daily Surgical thrmbprphylaxis*- High risk 40mg sc nce daily *Fr VTE prphylaxis in rthpaedic patients please refer t Trauma and Orthpaedic Venthrmbemblic (VTE) Prphylaxis Guidelines n the intranet. http://nww.wirralhealth.nhs.uk/clinical_guidance/trauma_and_rthpaedics.html VTE prphylaxis in pregnancy Fr prphylaxis f VTE in pregnancy please refer t Wirral Wmen and Children s Guideline n 33: Venus Thrmbemblism Prphylaxis and Treatment. Page 3 f 10
Treatment f VTE Duratin Fr the initial treatment f VTE, a LMWH shuld be cntinued fr at least 6 days AND until an ral anticagulant (if used) is established i.e. until the patient s INR is in the specified therapeutic range. Shrt term therapy with LMWH Althugh ral anticagulatin is preferred fr the treatment f VTE, LMWHs shuld be cnsidered fr up t 6 weeks fr the small subgrup f patients: And With very lw risk VTE ( i.e. thse wh suffered a belw knee DVT fr which there were likely precipitating factrs) Fr whm ral anticagulatin appears unjustified r inapprpriate, 3 such as thse with: (list nt exhaustive) - Pr cmpliance, cgnitive impairment, chatic lifestyle* r recreatinal drug misuse* - Increased bleeding risk (e.g. due t falls, peptic ulcer disease) - Liver dysfunctin (indicated by elevated INR >1.2) NOTE: This will be a very small subgrup f patients *Fr patients with chatic lifestyle r recreatinal drug misuse, the risks in treating these patients with LMWH shuld be cnsidered e.g. safe sharps dispsal Extended (>6weeks) r lng term (indefinite) LMWH therapy A LMWH may be cnsidered fr lnger perids in patients wh are at higher risk f VTE than the very lw risk VTE grup described abve and fr whm ral anticagulant may be unsuitable (as utlined abve). It may als be cnsidered fr patients with an active malignancy (within 6 mnths f malignancy diagnsis r treatment) r t prevent r treat a VTE in pregnant wmen. NOTE: The use f LMWHs fr lnger than 6 weeks is nt licensed Any decisin t ffer a LMWH n discharge shuld be made by a cnsultant and will be made mst frequently by the cnsultant acute physician r cnsultant n-call fr the acute take. The n-call cnsultant haematlgist is als available t discuss cmplex cases. Fr patients being discharged n extended (>6weeks) r lng term (indefinite) LMWH due t pr cmpliance, this decisin MUST be made by the cnsultant r ther senir medical staff and this shuld be clearly dcumented in the patients medical ntes. If this is nt clearly dcumented in the patient s medical ntes, then it will be queried by the pharmacist n discharge. It shuld be nted that GPs may ffer useful cmments n patients scial factrs. In mst instances, patients receiving LMWH therapy beynd 3 mnths shuld be under the care f a cnsultant haematlgist fr cnsideratin f anti-factr Xa mnitring, bne densitmetry and steprsis prphylaxis. Calculating the right dse At WUTH, PCIS prvides guidance n the chice f LMWH and dse depending n the patient s indicatin, weight and renal functin. Fr areas that d nt use PCIS, refer t Table 2a/2b (verleaf) fr dsing infrmatin. Page 4 f 10
1. If the patient s creatinine clearance is 30mL/min Enxaparin 1.5mg/kg, by SC injectin, nce daily. There are different size graduated syringes. Select the mst apprpriate size t give the required dse. Table 2a. Dses f enxaparin fr the initial treatment f DVT/PE if CrCl 30ml/min Bdy weight (kg) Daily dse (mg) Syringe Type 40-49 60 60mg/0.6ml (ne range syringe) 50-59 80 80mg/0.8ml (ne brwn syringe) 60-74 100 100mg/1ml (ne grey syringe) 75-89 120 120mg/0.8ml (ne lilac syringe) 90-99 140 100mg/1ml (ne grey syringe) AND 40mg/0.4ml (ne yellw syringe) 100-109 150 150mg/1ml (ne blue syringe) 110-114 160 100mg/1ml (ne grey syringe) AND 60mg/0.6ml (ne range syringe) 115-120 180 100mg/1ml (ne grey syringe) AND 80mg/0.8ml (ne brwn syringe) 121-135 200* 100mg/1ml (Tw grey syringes) 136-150 220* 100mg/1ml (ne grey syringe) AND 120mg/0.8ml (ne lilac syringe) * Antifactr Xa levels need t be taken after the 3 rd r 4 th dse and dses adjusted accrdingly after discussin with haematlgy when required. Page 5 f 10
2. If the patient s creatinine clearance is <30mL/min Enxaparin 1mg/kg, by SC injectin, nce daily. There are different size graduated syringes. Select the mst apprpriate size t give the required dse. Table 2b. Dses f enxaparin fr the initial treatment f DVT/PE if CrCl <30ml/min Syringe size Bdy weight Daily dse Injectin vlume 40mg/0.4ml 40kg 40mg 0.4ml 60mg/0.6ml 50kg 50mg 0.5ml 60kg 60mg 0.6ml 80mg/0.8ml 70kg 70mg 0.7ml 80kg 80mg 0.8ml 100mg/1ml 90kg 90mg 0.9ml Cmbinatin f abve syringes 100kg 100mg 1ml 110kg 110mg 1.1ml 120kg 120mg 1.2ml 130kg 130mg 1.3ml 140kg 140mg 1.4ml 150kg 150mg 1.5ml Weight runded t nearest 10kg and 0.1ml VTE treatment in pregnancy Fr prphylaxis and treatment f VTE in pregnancy please refer t Wirral Wmen and Children s Guideline n 33: Venus Thrmbemblism Prphylaxis and Treatment Page 6 f 10
Cntraindicatins/Cautins t LMWH 4 D nt prescribe r administer LMWHs t patients wh have: Knwn hypersensitivity t active ingredients Current r previus histry f heparin-induced thrmbcytpenia. Hypersensitivity t benzyl alchl Generalised r lcal haemrrhagic tendency, including: uncntrlled severe hypertensin (i.e. BP >220/120mmHg as per British Hypertensin Sciety definitin) 5. The decisin n whether t use LMWH shuld be cnsidered n the balance f risk versus benefit. severe liver insufficiency active peptic ulcer acute r subacute septic endcarditis intracranial haemrrhage, r injuries peratins n the central nervus system, eyes and ears, and in wmen with abrtus imminens Patients shuld nt have an epidural inserted r remved r spinal inserted until at least 10 hurs have elapsed since the last dse f prphylactic LMWH. Prphylactic LMWH shuld nt be given within 2 hurs f epidural insertin r catheter remval. If insertin was difficult r bldy then prphylactic LMWH shuld nt be given within 4 hurs f insertin r remval. Treatment dses f LMWH must nt be given t patients wh have an epidural catheter in situ. Remve the epidural catheter and nly start the treatment dse f LMWH 4 hurs after the catheter has been remved. If the patient has had a spinal anaesthetic, d nt start treatment dses f LMWH until 4 hurs after the spinal was perfrmed. (see Acute Pain Guidelines). Prphylactic LMWH therapy is nt required if patients are already receiving therapeutic anticagulatin. Mnitring Fr patients receiving a LMWH fr lnger than 5 days, the fllwing shuld be mnitred: Platelets this is due t the risk f antibdy-mediated heparin-induced thrmbcytpenia (HIT). Mnitr platelets apprximately 7 t 10 days after initiatin and then 3 mnthly whilst LMWH treatment cntinues. Treatment shuld be stpped immediately in thse wh develp thrmbcytpenia. Signs f heparin-induced thrmbcytpenia include a 50% reductin f platelet cunt, thrmbsis r skin allergy. 6 Fr further infrmatin n diagnsis and management f HIT, see Heparin-induced Thrmbcytpenia (HIT): Diagnsis and management (adults). Ptassium LMWHs can cause hyperkalaemia due t suppressin f aldsterne secretin. Patients at higher risk f this include thse with diabetes mellitus, chrnic renal failure, pre-existing metablic acidsis, raised plasma ptassium r thse taking ptassium-sparing drugs. Mnitr ptassium apprximately 7 t 10 days after initiatin and then 3 mnthly thereafter whilst LMWH treatment cntinues (r sner if clinically indicated). Page 7 f 10
Administratin f LMWHs In hspital Nursing staff shuld ensure that an accurate weight in kg is dcumented in the medical r nursing ntes r hspital prescribing system t enable an apprpriate LMWH dse t be calculated. Where pssible, the nursing staff shuld ensure that the dse f LMWH has been verified by a pharmacist (indicated by a v n the current drugs list) befre it is given. If the weight, renal functin r pharmacist verificatin is nt available immediately, this shuld nt delay the initiatin f treatment but effrts shuld be made t ensure these are btained as sn as pssible. Fr discharge If the patient is required t self administer a LMWH, apprpriate training must be given prir t discharge. The patient needs t be deemed cmpetent by the nurse befre discharge. If the patient is unable t self-administer, a referral must be sent t the district nurse t cntinue administratin at hme after discharge. In this circumstance, a PMAC must als be filled in clearly by the prescriber befre discharge and clinically checked by pharmacist. Clinical requirements fr discharge It is the respnsibility f the ward prescriber AND cnsultant t ensure the indicatin, dse, duratin f treatment, patient s weight and renal functin is dcumented n the discharge letter. When clinically checking the discharge prescriptin, at minimum, the ward pharmacist must ensure that the abve infrmatin has been cmpleted by the prescriber and is available n the discharge letter. The ward pharmacist shuld then cmplete the checklist belw and endrse IDDA n the discharge prescriptin t indicate that the abve checks are cmplete befre any supplies f LMWH will be made n discharge. Up t 2 weeks supply f LMWH will be made by the hspital at discharge and then this shuld be cntinued by the patient s GP. Apprpriate Indicatin (if n extended duratin f LMWH due t pr cmpliance, must state in the ntes that the decisin has been apprved by the senir medical staff) Dse apprpriate fr the patient s renal functin and weight Duratin Apprpriately trained persn t Administer the LMWH in the cmmunity if the patient is unable t self-administer. Page 8 f 10
Prescribing LMWHs in the cmmunity Patients prescribed LMWHs in the cmmunity shuld have their weight and renal functin checked every 3 mnths (r sner if clinically indicated) and dcumented in their medical ntes. Prescribers must check the patient s weight and renal functin befre prescribing. Prescribers shuld use the dse calculatin tables 2a (see page 5) and 2b (see page 6) when calculating dses f enxaparin. If a patient medicatin administratin chart (PMAC) is required fr cmmunity nurse administratin, this must include the patient s weight and renal functin and be cmpleted in full by the prescriber. All prescriptins in the cmmunity shuld include the patient s weight. A prmpt will be added t Scriptswitch t facilitate this. Patients receiving a LMWH in the cmmunity fr >3mnths will usually be under the supervisin f a haematlgist. The patient s weight, renal functin and anti factr Xa level shuld be checked apprximately 3 mnthly t ensure the dse f LMWH is still apprpriate. The haematlgist will advise n any ptential dse change. The weight and renal functin shuld be reprted in the hspital crrespndence frm the Cnsultant Haematlgist t the GP. Requirements f cmmunity pharmacy Cmmunity pharmacists shuld check the fllwing befre dispensing a LMWH: Indicatin whether prphylaxis r treatment Duratin f treatment Weight f patient Renal functin Strength f syringe required Vlume f syringe required Dse in internatinal units and in millilitres Rute and frequency f administratin Requirements f cmmunity nurses Cmmunity nurses shuld check the fllwing befre administering a dse f LMWH Indicatin whether prphylaxis r treatment Duratin f treatment Weight f patient Renal functin Strength f syringe required Vlume f syringe required Dse in internatinal units and in millilitres Rute and frequency f administratin Page 9 f 10
References 1. Natinal Patient Safety Agency. Rapid Respnse Reprt. Reducing Treatment Dse Errrs with Lw Mlecular Weight Heparins. July 2010. 2. Department f Health. Venus thrmbemblism risk assessment guidance (March 2010) http://www.dh.gv.uk/en/publicatinsandstatistics/publicatins/publicatinsplicyandguida nce/dh_088215 Accessed <08/01/11> 3. P Lmas, SC Smith, NM Butt. A retrspective audit f extended lw mlecular weight heparin (LMWH) therapy in patients deemed unsuitable fr warfarin at a large district general hspital. British Jurnal f Haematlgy, 149, (Suppl 1), 37. 4. Summary f Prduct Characteristics. Innhep. Le Pharma. and http://www.medicines.rg.uk/emc/medicine/5176/spc/innhep+20%2c000+iu+ml+an d+innhep+syringe+20%2c000+iu+ml/#contraindications (20,000units/ml strength) and http://www.medicines.rg.uk/emc/medicine/2623/spc/innhep+10%2c000+iu+ml+an d+innhep+syringe+10%2c000+iu+ml/ (10,000units/ml) <accessed 06/01/11> 5. B Williams, NR Pulter, et al. British Hypertensin Sciety Guidelines. Guidelines fr management f hypertensin: reprt f the furth wrking party f the British Hypertensin Sciety, 2004 BHS IV. Jurnal f Human Hypertensin (2004) 18, p139-185 6. British Natinal Frmulary nline. 60 th editin. Accessed <08/01/11> Wrking grup: Gareth Malsn, Medicines Management Pharmacist, WUTH Dr R. Dasgupta, Cnsultant Haematlgist, WUTH Page 10 f 10