Womens & Childrens Services SDMS ID: P2010/0307-001 Policy August 2006 Policy 3.

7-07WACS Title: Description: Target Audience: Key Words: Policy Supported:

Purpose: This Procedure dictates the measures to be taken to minimise the incidence of venous thromboembolism (VTE) in postnatal women.

POSTNATAL THROMBOPROPHYLAXIS Postpartum Thromboprophylaxis All Obstetric Medical Staff, Anaesthetists, Midwives, Pharmacy Postnatal Thromboprophylaxis LGH Womens & Childrens Services Clinical Protocol

The procedure does not deal with 1. 2. 3. 4. postnatal prophylaxis for women already on antenatal prophylaxis therapy of established VTE antenatal prophylaxis diagnosis of VTE

Background: Pregnant women have a 5 to 10-fold increase in VTE compared with non-pregnant women giving an incidence of clinical VTE of about 1 per 1000 (Doyle 2004, RCOG 2004). Few figures are available for the rate of subclinical VTE in pregnant women. While there is an equal distribution of VTE throughout pregnancy, the daily risk is greatest in the few weeks following delivery. VTE is the commonest cause of maternal death in Australia with an incidence, in the last reported triennium (1994-6) of 9 deaths 8 with VTE as major cause, 1 with VTE as contributory cause (ectopic). This is a rate of VTE deaths to total pregnancies of just over 1 per 100,000. Of these 9 deaths, six were postpartum, two were in the first trimester and one was at 33 weeks. The risk after caesarean is considerably increased. Only 20% of women were delivered by caesarean (C/S) in the above report, but 4 of the 6 postpartum deaths from VTE occurred in women whod had a caesarean birth. The reason for the caesarean e.g. severe preeclampsia, is often a contributing factor but surgery itself greatly increases VTE.

POSTNATAL THROMBOPROPHYLAXIS (TP) THERAPIES

1. All postnatal women Adequate hydration Early mobilisation 2. High-risk postnatal women defined as:a. All caesarean (CS) deliveries or extended pelvic surgery e.g. hysterectomy for PPH b. Vaginal deliveries with 4 or more risk factors: i. General Risk Factors 1. Age > 35 years 2. Booking BMI > 30kg / m2 * 3. Para 4 or more 4. Major intercurrent illness 5. Major current infection 6. Gross varicose veins 7. Heterozygous Factor V Leiden or Prothrombin Gene Mutation 8. Family history of VTE in first degree relative Pregnancy-related Risk Factors 1. Pre-eclampsia 2. Immobility 4 days or longer 3. Labour >12 hours 4. Forceps/ventouse delivery 5. Major blood loss morbidly obese women (Booking BMI >40) should have postnatal TP even if no other risk factors are present High risk women are to be given Low Molecular Weight Heparin (LMWH) Enoxaparine (Clexane):40mg s.c. on a once-daily basis the first dose should be given within 4 hours of delivery, usually on return to the ward or delivery suite HDU, unless there are specific written instructions in the operation report and medication chart that it is to be withheld or delayed. subsequent doses should be given nocte from the first post-operative day administration should be away from wound site (alternating lateral upper thigh suitable after CS) at least 2 hours must elapse between insertion or removal of epidural / spinal and subsequent Clexane administration i.e. wait 2 hours after insertion/removal of epidural/spinal before giving Clexane At least 12 hours must elapse between last prophylactic dose of Clexane and subsequent insertion or removal of an epidural / spinal (24 hours if therapeutic doses) i.e. wait 12 hours after Clexane before inserting or removing epidural / spinal. Liaise with the Anaesthetic Service is advisable. administration should be continued daily until discharge or until Day 5 if mobilising well by serum platelet levels usually do not need to be checked (see below) Very High Risk postnatal women defined as:a. Paralysis of lower limbs b. Homozygous Sickle Cell Disease (HbSS) c. Previous spontaneous VTE (i.e. no probably cause) d. Previous provoked VTE with any thrombophilia e. Lupus anticoagulant or high-titre anticardiolipin antibody f. AT III, Protein C, Protein S deficiency (on non-pregnant serum sample) g. Homozygous Factor V Leiden or Prothrombin Gene Mutation, or double heterozygote

These women are to be given Low Molecular Weight Heparin (LMWH) Enoxaparine (Clexane) as above but continuing for 8 weeks post-partum. Consultation with haematologists is advisable. Serum platelet levels will need to be checked (see below). MONITORING TESTING SERUM PLATELET LEVELS POSTNATALLY No previous LMWH received in previous three months:o Women having LMWH for 5 days or less do not need platelets checked o Women still on LMWH on Day 6 should have platelets tested. Further testing should occur second-daily until Day 14 (or until woman ceases LMWH if less that 14 days) o If platelets normal and patient remains on LMWH, thereafter check platelet levels monthly o Cease LMWH if platelets drop below 50% of pre-treatment level or below 100 x 10 9/L. Seek urgent haematological review. LMWH received in previous three months, then discontinued, now recommenced *:o Begin testing platelet levels on Day 2 o Test second-daily until Day 14 o If platelets normal and patient remains on LMWH, thereafter check platelet levels monthly o Cease LMWH if platelets drop below 50% of pre-treatment level of 100 x 109 / L. Seek urgent haematological review *This does not apply to women who have been on LMWH in the antenatal period who are continuing it without a break into the postnatal period who only require platelet testing once a month. CONTRA-INDICATIONS TO THROMBOPROPHYLAXIS WITH CLEXANE 1. Major antepartum or postpartum blood loss which is not yet stable. 2. Blood epidural/spinal 3. Renal Impairment: a. Clexane should be used in caution in women with impaired renal function. b. Standard Heparin S/C may be used as an alternative in such patients (5000u b.d. or t.d.s) c. Alternatively Clexane dosage should be modified according to the hospital protocol for Clexane in the presence of renal failure. (Appendix 2). OTHER THERAPIES 1. Intermittent Pneumatic Compression (IPC) In Addition to Clexane) a. All pregnant women should have IPC used intra-operatively b. Postnatal women nursed in the delivery suite HDU for severe pre-eclampsia or other serious medical conditions are a particularly high-risk group and should have IPC commenced intraoperatively and continued without interruption (except for showering and ambulation) for 5 days or until full mobilisation / discharge. 2. Intermittent Pneumatic Compression (IPC) In Lieu of Clexane a. Occasional women will not be suitable for Clexane e.g. major antepartum or postpartum blood loss which is not yet stable or particularly bloody epidural / spinal. Such women should have IPC commenced intraoperatively and continued without interruption (except for showering and ambulation) for 5 days or until full mobilisation / discharge. Clexane should be started when considered safe. 3. Graduated Compression Stockings (GCS) a. Well-fitted BCS are effective in VTE prophylaxis in non-pregnant women but have not been adequately studied in pregnant women. b. GCS are probably less effective in thromboprophylaxis than LMWH and prolonged IPC. c. GCS have little to add to TP in patients already on LMWH or prolonged IPC and therefore have only limited place in the postnatal woman. In general, women using prolonged IPC do not also need GCS.

d. GCS may have a place in antenatal women on prolonged bed rest. 4. Warfarin Women who may require prolonged postpartum TP may be switched to Warfarin in the postnatal period. When no contra-indications exists (eg: active bleeding) Warfarin may be commenced 24 hours postpartum with the Clexane continuing until therapeutic Warfarin levels are achieved. Breastfeeding is not contra-indicated with Clexane or Warfarin. ANTENATAL PROPHYLAXIS While full consideration of antenatal TP is outside the scope of this postnatal procedure, the following should be noted: High-risk women with significant thrombophilia or previous VTE will often require antenatal anticoagulation with LMWH in either prophylactic or therapeutic doses. Such women should be managed on a case by case basis, usually in consultation with the haematology department. Low-risk women on bed rest (placenta praevia, PPROM, short cervix) have a significantly increased tendency to VTE. Consideration should be given to the use of well-fitting belowknee GCS in such women.

Attachment 1. Attachment 2. Attachment 3.

Abbreviations Clinical Notes References

Signature:

Dr A Dennis _____________________ Co-Director- Medical WACS

Sue McBeath _____________________ Co-Director Nursing WACS

Date: _______________________

ATTACHMENT 1. Abbreviations: BMI CS DVT GCS IPC LMWH PE PPH PPROM TP UH V/Q SCAN VTE Body Mass Index measured as kg / m 2 Caesarean Section Deep Vein Thrombosis Graduated Compression Stockings (previously known as TEDS) Intermittent Pneumatic Compression (calf compressors) Low Molecular Weight Heparin Pulmonary Embolus / Embolism Postpartum Haemorrhage Premature Preterm Rupture of Membranes Thromboprophylaxis Unfractionated heparin Ventilation Perfusion Lung Scan looking for evidence of PE Venous Thromboembolism

ATTACHMENT 2.
Some pregnant women have an even higher risk but there currently exists little data to allow quantification of the magnitude of each risk factor. Little data exists regarding efficacy of VTE prophylaxis in pregnant women (Gates 2002) The risk after caesarean can be significantly modified by thromboprophylaxis. Following the 1995 introduction of post-caesarean TP in the UK, the VTE deaths after CS dropped from 15 (1994-6) to 4 (1997-9). In the recently released 2000-2002 Report, the deaths after CS had jumped back up to 10 out of 17 postnatal deaths, often because indicated TP was inadequately provided. VTE is common after spontaneous vaginal delivery as well, with over 90% of the vaginal deliveries which resulted in fatal VTE being spontaneous rather than instrumental (9 of 10 in 1997-9 RCOP Report; 7 of 7 in 2000-2 RCOG Report). Most of these women were either >35 years and/ or obese. Of the 17 postnatal VTE deaths in the latest 2000-2 UK report, 16 had clearly identifiable risk factors, many of which were not recognised. Age is a major risk factor. A woman aged 40 years has sixty times the rate of VTE of a woman aged 25 years (RCOG 1995). In non-pregnant women, the rate of VTE for a 15 y.o. is < 5 per 1000,000 while the rate for an 80y.o. is 500 per 100,000 (White 2003) Obesity is a major risk factor for VTE. A linear relationship exists between BMI and risk of VTE. While this Procedure only deals with postpartum TP, the increased thrombotic risk exists from the beginning of the first trimester. About three-quarters of antenatal deaths occur in the first trimester. (8 of 13 in RCOG Report 1997-9, 7 of 8 in RCOG Report 2000-2, 2 of 3 in 1994-6 Australian Report). Hyperemesis, haemorrhage, surgery, ectopic and

hyperstimulation after fertility treatment are major risk factors. Two LMWHs are widely used in pregnant women enoxaparine (Clexane) and dalteparine (Fragmin). Clexane has been chosen in this Procedure since it is the favoured LMWH for post-operative. Low dose unfractionated heparin (UH) and LMWH are equally effective in TP but LMWH has the advantages of :Longer half-life allowing once-daily administration Less bleeding problems Less thrombocytopenia Less osteoporosis if used long-term The risk of heparin-induced thrombocytopenia is extremely low with LMWH and has never been reported in pregnancy (RCOG 2004). Current guidelines still recommend checking platelet levels.

Caesarean wound haematoma is about 2% with both LMWH and unfractionated heparin (Greer 2001). Misdiagnosis of VTE is extremely common all pregnant women with leg and / or chest symptoms need to be considered as possibly having VTE. A normal D-dimer result has a high negative predictive value, while an elevated result can be due to pregnancy alone and therefore has a lower positive predictive value c.f. the nonpregnant woman. None of the following is contraindicated in pregnancy chest xray V/Q scan limited venogram IPC can be made available for prolonged antenatal or postnatal use by contacting B6a. Below-knee IPC is thought to be as effective as full length IPC (Vanek 1998, Morris 2004) The data supporting IPC in significant prevention of VTE relate only to use commenced intraoperative and continued without a break for at least several (about 5) days postoperatively (Clarke-Pearson 1993) There is little or no data supporting efficacy of IPC used only intraoperative or even continued for 24 hours post-op (Clarke-Pearson 1984). However, many thrombi are known to begin intraoperative and IPC has rare or no morbidity. It should therefore be used intraoperative in all pregnant women. GCS exert gradually diminishing pressure up the leg, with the commonly available brands exerting approximately 10-18 mmHg at the ankle, 8-14mmHg at the calf and 6-12mmHg at the thigh. This is to be distinguished from the higher pressure gradients found in the considerably more expensive compression stockings used by patients with venous / valve insufficiency. There is conflicting evidence as to whether GCS enhance the effectiveness of IPC. Until the matter is clarified, women under our care will not usually be given both. While there is little comparative data (Byrne 2001, Amarigiri 2004), below knee GCS are probably as effective as thigh-length. They are certainly more comfortable, less likely to wrinkle / band, and less likely to become soiled. As a result, compliance is greater.

COST- EFFECTIVENESS OF PROCEDURE There are no data available on the cost-effectiveness of TP in pregnant women, but there is extensive data that confirms the cost-effectiveness of TP in surgical and critical-care patients. Since the maternal death rate is only just over 1 per 1000,000 pregnancies, and since at least 25% of postnatal women will require prophylaxis, the dollar and time-cost of saving one life is likely to be considerable. On the other hand, the rate of non-fatal clinical VTE is about 1 per 1000 pregnant women with subclinical VTE likely to be considerably more common.

As

well,

the

maternal

death

rate

from

VTE

currently

exceeds

that

from

hypertension/eclampsia and yet much greater resources are devoted to managing the latter. The consequences of VTE include not only fatal PE, but also:o o o o o o Delayed discharge from hospital or requiring readmission Costly diagnostic testing Complications from anti-coagulant therapy Recurrent VTE Pulmonary hypertension in 5% after PE Long-term morbidity from post-thrombotic syndrome with persistent occlusion of valvular/venous incompetence developing in 80% after DVT (severe in 10%) causing: Chronic leg swelling Leg ulcers Pain Loss of mobility Loss of income

(Berquist 1990, Kearon 2003, Geerts 2004) COSTS o o o Clexane GCS IPC sleeves = $4.50 per preloaded 40mg syringe = $5.70 per pair = $60 per pair average (range $50 - $105).

ATTACHMENT 3. References:Amaragiri SV, Lees TA. Elastic compression stockings for prevention of DVT. Cochrane Review. The Cochrane Library 2004, Issue 2. Bergqvist A. Late symptoms after pregnancy-related deep vein thrombosis BJOG 1990; 97:338-341 Byrne B. DVT prophylaxis: the effectiveness and implications of using below-knee or thighlength graduated compression stockings. Heart And Lung July-August 2001; 30(4):277284

Clarke-Pearson DL, Creasman WT et al. Perioperative external pneumatic calf compression as thromboembolism prophylaxis in gynecology: report of randomised controlled trial. Gynecol Oncol 1984; 18: 226-32 Clarke-Pearson DL et al. A randomised trial of low-dose heparin and intermittent pneumatic calf compression for the prevention of DVT after gynaecologic oncology surgery. AmJOG April 1993;168(4):1146-54 Doyle NM, Monga M. Thromboembolic disease in pregnancy. O & G Clinics N.Am 2004;31:319-344. Gates S, Brocklehurst P, Davis LJ. Prophylaxis for VTE in pregnancy and early postnatal period. Cochrane Review. The Cochrane Library 2004, Issue 2. Geerts WH et al. Prevention of venous thromboembolism: the seventh American College of Chest Physicians conference on antithrombotic and thrombolytic therapy. Chest September 2004;126:338S-400S.

Greer IA. The acute management of venous thromboembolism in pregnancy. CurrOpO&G Dec 2001; 13(6):569-575 Kearon D. Natural history of VTE. Circulation June 17 2003;107(23) Supplement:I-22 to I30 Maternal Mortality UK 1997-9. Why mothers die. (www.cemach.org.uk/publications) Maternal Mortality UK 2000-2. Why mothers die. (www.cemach.org.uk/publications) Maternal Mortality Australia 1994-6. (www.nhmrc.gov.au/publications) Morris, RJ. Evidence-based compression: prevention of stasis and deep vein thrombosis. Annals Of Surgery February 2004;239(2):162-171 RCOG 2004, January. Thromboprophylaxis during pregnancy, labour and after vaginal delivery Guideline No. 37 (www.rcog.org.uk) RCOG 2001, April. Thromboembolic disease in pregnancy and the puerperium: acute management. Clinical Green Top Guideline (www.rcog.org.uk) 9

RCOG 1995. Report of working party on prophylaxis against VTE in O & G. (Obtained via RCOG library from Elaine Garrett egarrett@rcog.org.uk) Vanek VW. Meta-analysis of effectiveness of intermittent pneumatic compression devices with a comparison of thigh-high to knee-high sleeves AmSurg 1998;64(11):1050-8. White RH. The epidemiology of VTE. Circulation June 17, 2003;107(23) Supplement. I-4 to I-8.

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