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ESSAY 140 - VTE IN PREGNANCY

Posted by narmin B.
Thromboembolic diseases are the leading cause of maternal mortality in the last report of confidential enquiry into maternal death in the UK. There are steps hat can be taken to minimise this risk.
There should be agreed protocols and guidelines for prophylactic measures for VTE in each unit. These should be based on the RCOG and other nationally agreed guide lines.

Although pregnancy is a hypercoagulable state and the risk of VTE is higher compared to non pregnant state, but the presence of certain risk factors increase the risk of VTE considerably. Early in the antenatal period, women should be assessed for the risk of developing VTE and they should be categorised into mild, moderate and high risk group .However this division should be reviewed whenever there were changes in the patient,s circumstances, such as intercurrent disease or hospitalisation.

In mild form, women have an uncomplicated pregnancy and there are no other risk factors. Taking measures such as early mobilisation and adequate hydration reduce the risk of VTE.

Women who have medical diseases such as heart or lung diseases , inflammatory bowel disease, age over 35, parity above 4, obesity and prolonged immobility, they have moderate risk for developing VTE. Intrapartum and postnatal thromboprophlaxis, with low molecular weight heparin and thromboembolic deterrent stockings (TEDS) should be offered. Some women may have combination of these factors such as in obese women who need prolonged hospitalisation, antenatal thromboprophlaxis also should be given.

Women with thrombosis in current pregnancy or recurrent thrombosis, certain forms of inherited thrombophlia such as antithrombin III and homozygosity for factor V leiden and antiphospholipid syndrome are at high risk of developing VTE and antenatal and intrapartum and postnatal thromboprophylaxis in the form of low molecular weight heparin and TEDS should be offered. Postnatal prophylaxis should be continuied for 6 weeks. This reduces the risk of VTE significantly but anticoagulation has side effects like thrombocytopenia and osteoporosis, although these are uncommon with low molecular weight heparin. Regular platelet count is required. Monitoring for osteoporosis is not recommended during pregnancy. Osteoporosis due to heparin is reversible after discontinuation of the treatment. delivery. Also inconvenience with injections is another problem. Although warfarin tablets can be given postnataly for prophylaxis, but it is contraindicated in antenatal period due to its teratogenesity (except in certain conditions such as prosthetic heart valves).

Reviewing the plan of prophylaxis by a haematologist may be required to ensure correct dose and duration of thromboprophylaxis and also in cases where there is a doubt whether prophylaxis is necessary or not.

Another step in reducing the risk of VTE is prevention of immobilisation and dehydration during pregnancy. Both these conditions significantly increase the risk of VTE. In cases such as hyper emesis gravidarum where there may be severe dehydration, low molecular weight heparin during hospitalisation should be considered. TEDS and adequate hydration are also necessary.

As the risk of VTE is increased in air travels, especially the long haul one, appropriate measures should be taken to reduce the risk of VTE. These women should be advised to move in the cabin during travel and avoid drinking alcohol and coffee. TEDS also can be used. If there were additional risk factors, apart from the above measures, low dose aspirin three days before and after travel or low molecular weight heparin on the day of travel and the following day should be offered.

Combined oral contraceptive pill should be avoided in the first 3 months post partum in women who are at high risk of developing VTE.

Women who are at high risk group should be made aware of the symptoms of VTE such as calf pain, leg swelling ro redness. It may be necessary to give written information in addition to verbal advice. They should be seen whenever there are symptoms and investigation and appropriate treatment should be instituted as soon as possible to prevent maternal mortality and morbidity.
Posted by uma M.
CEMD of the last triennium(2000-2003) reports that VTE is the leading direct cause of maternal deaths.It has highlighted that substandard care -failure to identify risk factors, failure to institute
thromboprophylaxis were responsible for 80% of fatal PE.Implementing prophylaxis after caesarean has shown
to reduce incidence of VTE afterc.section.However fatal PE still ocurr in antepartum period and after normal delivery.
Pregnancy is assossated with increased risk ofVTE ,by 10 fold due to its thrombogenic state.This risk is even more in certain group of women with additional risk factors.
To minimise the risk of VTE in pregnant women prepregnancy evaluation is ideal. this should include
assessment for existing risk factors.Women\'s medical history including h/oVTE -provoked ,unprovoked,related to use of OCP\'s,h/o thrombophilia -congenital/acquired noted.Note her BMI. extreme obesity,parity>4, age>35yrs, gross varicose veins, paraplegia, sicklecelldisease, IBD, myeloproliferative disorders,etc
are assosiated with increased risk of VTE.women should be screened for thrombophilias if she gives history of VTE.
Assess if she is already on anti coagulation,in which case she might have to change to LMWH.
Ante natally if not seen in prepregnancy period assess risk ofVTE by noting preexisting risk factors.Preform thrombophilia
screen if not done and gives if h/oVTE.
As a general measure against VTE women should be advised against dehydration,prolonged immobility.
Haematologist advice should be sought for prophylaxis in high risk group or if obstetrician is uncertain regarding thromboprophylaxis.Risk assessment should be ongoing,as she might develop new risk factors as pregnancy advances. this should happen when ever she is admitted during AN period.These risk factors include hyperemesis, long haul travel, Preeclampsia, dehydration, surgical procedures in pregnant state,
OHSS, severe infection like acute pyelonephritis, immobility.The risk of VTE explained to women and reasons for recommendations explained.
AN thromboprophylaxis is recommended for CERTAIN WOMEN LIKE-women with h/o recurrent VTE,single
episode but with family h/oVTE, H/OVTE at unusual site(axillary vein), women with h/oVTE and known thrombophilia.
In addition women with no h/o VTE but known thrombophilias should be managed according to there defect. women with
AT IIIdef, combined defects, homozygous defects, require AN thromboprophylaxis
APS wih h/o VTE merit prophylaxis WITH LMWH, but if there is no h/oVTE then she can be started on lowdose aspirin for
managing obstetric manifestations. In Women without h/oVTE or thrombophilia clinical judgement is essential to deceide on need for prophylaxis. >_3 preexisting risk factors warrant AN prophylaxis.But in certain cicumstances like extreme obesity,immobility, OHSS, hyperemesis presence of even 1 risk factor warrants Prophylaxis.
Duration of such treatment depends on risk. temporary in situations like OHSS, HYPEREMESIS, air travel.

ANTEPARTUM PROPHYLAXIS SHOULD BE STARTED AS EARLY AS POssible as risk of VTE is present from early gestation.
These should be continued through out pregnancy.Once the women is in labour she should stop further doses and report immediately. further doses will be administered by staff after assessing .
caution for placement of EPidural catheter. Inform senior anaesthetist.

Among all drugs LMWH is used for AN PROPHYLAXIS .it is safe,as effective as UFH,less heparin induced thrombocytopenia
,osteoporosis compared to UFH.Single dailydosing is of advantage.Monitor platelets 1/week. No need to monitor
Factor xa if normal RFT.Commonly used agens include Enoxaparine40mg/day.deltaparin 50000u/day.How ever these doses vary with body weight ,kind of thrombophilia. Always involve haematologist if in doubt about dose required.
Low dose aspirin can be used if risk of VTE exists but not high to warrant use of LMWH. 75 mg.day reduse risk by 35%
Warfarin use is contraindicated in preganancy due to risk of embryopathy(5%).
Dextrans are not used as it carries risk of fatal anaphylaxis & uterine hypertonus.
TED stocking can be used in conjunction with other agents like LMWH.

In a unit ,protocol should exist based on guidelines available.Regular audit should take place so that
incidence & mortality due to VTE be avoided.Risk management in the event of adverse outcome.

Posted by Rani M.
Q:Evaluate critically the steps which should be taken to minimise the risk of VTE in a pregnant woman.
Pulmonary embolism is the most common direct cause of maternal death in U.K. the risk of pulmonary embolism and venous thromboembolism can be minimised by adequate thromboprophylaxis in women at risk ( primary prevention) and by early diagnosis and prompt treatment of thromboembolic diseases ( secondary prevention)during pregnancy.
.
All woman should undergo an assessment of risk factors for VTE in early pregnancy or before pregnancy. This assessment should be repeated if she is admitted to hospital or develops other intercurrent problems.
Since all women dying from VTE following vaginal delivery in the last confidential enquiry were either overweight or above 35 years; B.M.I.must be calculated for all woman at the time of booking and other risk factors are looked for i.e. parity more than 4, history of thromboembolism in the past or in the family, any inherited or acquired thrombophilias, gross varicose veins.,sickle cell disease, inflammatory disorders or any associated medical disorders like nephrotic syndrome.Many risk factors will develop later in gestation or in labour such as proonged labour,dehydration, preeclampsia, undergoing surgery,or midcavity instrumental delivery. henceforth an ongoing individual risk assessment in important.
An attemt is made to categorise woman into high, moderate or low risk group. all woman in high risk group should undergo prepregnanacy counselling and a management plan is formulated.
Presence of any single risk factor will not cause thrombosis in itself unless virchow\'s triad is satisfied.. it is the combination of factors which is responsible for thrmbosis. Presence of 3 or more risk factors,or previous history of recurrent thromboembolism, previous thromboembolism at an unusual site like axillary vein, previous thromboembolism plus thrombophilia, or antiphospholipid antibody; antithrombin deficiency, homozygous defects or combined defects of factor 5 leiden. or prothrombin gene defect. categorise woman into high risk group. they should be given antenatal prophylaxis with heparin, intrapartum prophylaxis and postpartum continue thromboprophylaxis till 6 weks.
Woman with 2 risk factors may be given low dose aspirin antenatally and intrapartm thromboprophylaxis which continues postpartum for 5 days.
during pregnaancy if there is clinical susician of VTE, treatment with heparin should be started and prompt investigations are undertaken to make an objective diagnosis( as history and clinical examination during pregnancy may be unreliable.).
if the index of suspician is high treatment should be started without waiting for the results of objective tests.
Intrapartum epidural analgesia can be given 10-12 hours after the last dose of heparin. woman should be instructed to skip morning dose of heparin when they go in labour. heparin can be restarted as soon as after delivery or 3-4 hours after epidural analgesia.
Postpartum combined oral contraceptive pills should not be prescribed for 3 months after delivery in high risk woman.
Posted by vijaya L.
VTE is still the leading cause for maternal mortality. Pregnancy is a highly thrombogenic condition (60/100000 vs 5/100000)) where in, all the three predisposing factors (coagulation factors, venous stasis and vascular injury) are increased.

Though postpartum is generally considered to be at a high risk for VTE the absolute risk is more antepartum than postpartum (0.8/1000 vs 0.5/1000).

Preconceptionally women with age greater than 35, obesity, personal or family history of VTE, personal or family history of thrombophilia and artificial heart valves are identified and offered counseling. They should be advised to reduce weight and stop smoking and women with a history of VTE should be offered thrombophilia screening.

Pregnant women should be advised to take short walks or wear TED stockings during air travel and prolonged car journeys.

Routine antepartum thromboprophylaxis has not shown any benefit in women with personal history of VTE not associated with thrombophilia, but this group should be offered prophylaxis at onset of labour and continued for 6 weeks postpartum. When these women test positive for thrombophilia antepartum thromboprophylaxis is also offered as the benefits outweigh the risks.
Thromboprophylaxis in pregnant women with congenital thrombophilia depends on the type of the defect. Anti thrombin III with a 50% chance of thrombosis by the age of 30 years should be offered antepartum and postpartum heparin prophylaxis, where as factor V leiden mutation the commonest variety (5% of UK population) would require general advice and low dose Aspirin can be offered as the side effects are minimal followed by peripartum and postpartum heparin prophylaxis.

Low molecular weight heparin is associated with lower incidence of osteoporosis, thrombocytopeania, and bleeding tendencies than unfractioned heparin and experience of its use in pregnancy is accumulating.
The dose of heparin used for prophylaxis is higher than in non-pregnant women (10,000 units bid of UH and 40 mg of enoxaparin) because of increased plasma volume and increased base line risk. APTT is not reliable in monitoring the heparin therapy even when unfractioned one is used, baseline might be low, and anti Xa levels are better.
Warfarin is safe to be substituted during postpartum prophylaxis.

Warfarin has been the preferred method for women with artificial heart valves as the risk of thrombosis outweighs that of embryopathy (6%), but LMWH heparin when used in higher and adjusted provides good antithrombosis while reducing the embryopathy. This would require regular monitoring with anti Xa levels.

Prompt correction of dehydration and electrolyte imbalance decreases the risk VTE in hyperemesis gravidarum.

Preeclampsia further increases the RISK of VTE due to underlying vascular pathology, constricted intravascular volume and prolonged hospitalization, hence benefit from peripartum thromboprophylaxis.
Women who suffer from VTE during the index pregnancy need to be confirmed objectively and prophylaxis continued through out the pregnancy and till 6 weeks postpartum

Epidural analgesia or anaesthesia can pose problem for women on thromboprophylaxis the general guideline followed is that epidural should not be sited till 8 hrs after the heparin injection and should not be removed within 4 hrs of heparin injection. And these women should be followed up for the development of cord compression.
Women with operative vaginal delivery, prolonged labour and infection are at a higher risk of VTE and early ambulation with or without TEDs should be recommended.
Women undergoing cesarean section is at a higher risk of VTE than vaginal delivery more so when it is done on an emergency basis. These women should undergo risk stratification before caesarean section to decide on the mode of thromboprophylaxis. In the absence of high risk factors early ambulation, avoiding dehydration are adequate measures. In the presence of one or more risk factors like obesity, high parity, pre-eclampsia, should receive TED stockings as well and heparin considered. In the presence of thrombophilia and when three or more risk factors are present heparin prophylaxis should be recommended.
Posted by Nibedita R.


As VTE is a multicausal condition and the leading cause of maternal death in UK, individualised risk assessment should start before pregnancy if possible or in the antenatal booking visit. This assessment should be repeated if woman is admitted or develop intercurrent illness such as hyperemesis and preeclamsia. Woman with a positive family or personal history of VTE should be offered screening for hereditary (Antithrombin III deficiency, Protein C and Protein S deficiency, homozygous for factor V leiden mutation) or acquired thrombophilia (anti phospholipid syndrome).

Women would be classed as high, moderate or low risk categories according to presence or absence of risk factors. Moderate risk factors are: age>35, BMI>30kg/m2, para 4 or more, emergency caesarean section in labour, gross varicose veins, sickle cell disease and inflammatory bowel disease. High risk factors are: personal history of recurrent thromboembolism, hereditary or acquired thrombophilia, or presence of three or more moderate risk factors.

All obstetric units should follow local guidelines or protocol based on national guidelines, and should be audited regularly to improve obstetric outcome.

Avoidance of immobilisation and dehydration are preventive measures for all pregnant women irrespective of risk factors. Isometric calf exercises and TED stockings are effective measures against thromboembolism in moderate to high risk women.

Antenatal thromboprophylaxis should begin as early in pregnancy as possible. Post partum prophylaxis should begin as soon as possible after delivery. Those women on thromboprophylaxis prior to pregnancy have to be reviewed for dose adjustment or change in the regimen with consultation with haematologist
.
Low molecular weight heparin (LMWH) is the agent of choice and is as effective as unfractionated heparin (UH) for thromboprophylaxis with additional advantage of once daily administration with better side effect profile (allergy, osteoporosis, thrombocytopenia) as well as being safer. Since neither UH or LMWH crosses the placenta, there is no risk of teratogenesis or foetal haemorrhage.

High risk women with no previous VTE should receive thrombophylaxis for at least six weeks postpartum.
LMWH antenatally and for 3-5 days post partum should be considered for those with three or more moderate risk factors. Those with two moderate risk factors should receive LMWH for 3-5 days post partum. Women with single moderate risk factors like obesity (BMI>30) or conditions like ovarian hyperstimulation syndrome should receive LMWH during hospital admission.
Women with previous VTE and no other risk factors or those with thrombophilia but no history of VTE should get LMWH for six weeks post partum.

Women with antiphospholipid syndrome are at higher risk of VTE and low dose aspirin throughout pregnancy has been shown to improve outcome.

Regional anaesthesia can be used with careful attention to the timing of heparin injection to avoid haematoma. Delay of injection for at least four hours after insertion or removal of epidural catheter would reduce complications. First dose can be given after insertion but before removal of catheter.

Warfarin is contraindicated for use during pregnancy, as it is associated with increased risk of embryopathy, miscarriage, faetal and maternal haemorrhage, neurological abnormalities and stillbirth. The only indication for warfarin use in pregnancy is for women with metallic prosthetic valve who require a full anticoagulation in pregnancy. They require close monitoring with INR and frequent visits to anticoagulant clinic.

All pregnant women should be aware with the signs and symptoms of VTE (pleuritic chest pain, red swollen leg, SOB and haemoptysis). Identification and early reporting with prompt initiation of treatment with heparin if high index of suspicion until objective testing would improve outcome.

COCPS should be avoided in the first three months postpartum in high risk women.
Posted by Vaijayanti R.
Measures to reduce the risk of VTE in pregnancy should begin prepregnancy or atleast at the booking visit , with the identification of risk factors and categorization of the woman in high, medium or low risk.
A detailed history and examination will reveal risk factors ? age > 35 years, multiparity, sickle cell disease, prior VTE, thrombophilias, chronic inflmatory conditions ( inflamatory bowel disease),pelvic or abdominal surgery, preeclampsia, obesity ( BMI >30), gross varicose veins etc.
This initial assessment is accurate in identifying those at risk, but is of no use in predicting VTE in women with no apparent risk factors. Also, the risk assessment has to be redone if the woman is hopitalized or develops any complication ( hyperemesis and dehydration would raise her risk of VTE)
Counselling regarding the signs/ symptoms of VTE is given ( DVT ? pain swelling warmth of affected leg, PTE ? chest pain dyspnoea, hemoptysis) with advise to avoid prolonged immobilization and dehydration. She is advised to report is she is planning long haul or air travel or any elective surgery.
Early identification of any episode of VTE will help in reducing the morbidity / mortality associated by instituting anticoagulation and conduction appropriate investiagations.Ensuring mobilization will reduce the risk of raising her risk category for VTE. Appropriate measures can be advised if she is undergoing surgery or travel ( early ambulation after surgery)The disadvantages include unnecessary intervention and psychological sequelae ( fear / depression of developing VTE)
Screening for Thrombophilias to all women with prior VTE is offered.This obviously does not identify the women with Thrombophilias who have not had an episode of VTE in the past, and many conditions at high risk for Vte may be missed ( antithrombin 3 deficiency associated with 30% risk of VTE). However it is not cost effective to screen all pregnant women for thrombophilias.
Multidisciplinary care is advised. This is especially advantageous in high risk women or if there is a doubt regarding the dosage of anticoagulants to be used.But it may involve additional visits to the hospital to meet the hematologist.
Thromboprophylaxis is the mainstay of prevention of VTE in pregnancy ? anticoagulants, thromboembolic deterrent stockings, pneumatic calf pumps are some of the modalities.
Low Molecular Weight Heparin is the drug of choice for antenatal, intrapartum and post partum prophylaxis.It is safe , effective and associated with a lower risk of thrombocytopenia and osteoporosis when compared to unfractionated heparin. It also has the advantage of a single daily dose which can be adminstered by the patient herself, and requires minimal monitoring.It is safe in lactation. If there is any bleeding while on LMWH, a specialists opinion has to be sought ; protamine sulphate is ineffective.
Warfarin is preferably not used during pregnancy because of its effects on the fetus ( embryopathy, CNS defects, bleeding disorders.). It can however be used for postpartum prophylaxis.
Low dose Aspirin ? efficacy in preventing VTE is not proven ; may have a role when the risk for VTE is not high enough to warrant heparinazation.
Regional anesthesia/ analgesia while on anticoagulants must be given carefully with appropriate precautions , by a senior anesthetist.; main risk is that of the developmant of epidural hematoma.
Thromboembolic deterrent stockings and pneumatic compression stockings are physical methods especially useful during labour / surgery. Though not very effective individually, their efficacy increases when combied with anticoagulation. Below knee stockings are advised to prevent post thrombotic syndrome after an episode of DVT.

Combined oral contraceptive pills are avoided for atleast 3 monnths post delivery




Posted by uma M.
Dear paul,
Thank you for correcting my answer.It appeared you wamted regarding prophylaxis after c.section,postpartum. But RCOG guideline (no37) was given a heading\" Thromboprophylaxis during pregnancy,labour and after vaginal delivery\" giving a meanining that they should be addressed as different enteties . When you asked a specific question on minimizing risk of VTE in pregnancy wouldn\'t my answer be reasonable.
Posted by Vaijayanti R.
Dr Paul
could you please give feed back on my answer too !!
thnx
Posted by Rani M.
thanks for marking my answer. Catherine Nelson Piercy writes in her handbook of obstetric medicine--- Intrapartum thromboprophylaxis.Heparin in low/ prophylactic doses does not interfere with activation of normal haemostatic mechanism. heparin should not be discontinued during labour for longer than is necessary to allow safe regional anaesthesia or analgesia. for those low risk women starting prophylaxis with heparin intrapartum, the first dose should be administered ideally prior to delivery.