Venous Thromboembolism in

PregnancySiti Nurul Afiqah binti Johari

10-6-95Siti Suhaila Mohaad Sariff

10-6-91

Venous Thromboembolism (VTE)

IntroductionOne of the many early physiological adaptations of pregnancy involves changes in the coagulation system, which promote coagulation and impair fibrinolysis. The physiological goal is to prepare for the haemostatic challenge of delivery. A ‘side effect’ of this change is an increased risk of thrombosis. All pregnant women are therefore at risk of thrombosis, compared with non-pregnant women. This risk is manifest from early in the first trimester until 4−6 weeks post partum.

Why pregnancy has a greater risk?

PHYSIOLOGICAL CHANGES IN THE COAGULATION SYSTEM DURING PREGNANCY

These changes, which may not completely return to baseline until more than 8 weeks post partum, begin at conception.

RISK FACTORS FOR VTE IN PREGNANCY

In some women the risks are increased further because they have one or more additional risk factors.So pregnant women should have a risk assessment for VTE to include the risk factor as listed. This risk is not static and should be reconsidered in any case. A careful hx should be taken from the woman of any prior or family hx of thromboembolic events.

Pregnancy itself is a risk factor

Clinical PresentationType Signs and Symptoms

Pulmonary embolism • Dyspnea• Palpitations• Pleuritic chest pain• Hemoptysis• Cyanosis/hypoxia in massive PE• Tachycardia• Tachypnea• Hypotension• Collapse• +/- symptoms or signs of DVT

Deep vein thrombosis • DVT in pregnancy usually proximal• Unilateral leg pain/tenderness• Swelling in an extremity• Increase calf/thigh circumference• Increased temperature• Prominent superficial veins• Pitting edema

Differential Diagnosis

• DVT: swelling and lower leg discomfort are not unusual in a normal pregnancy. Other possibilities include muscle strain, a ruptured Baker’s cyst, cellulitis, superficial thrombophlebitis, ruptured plantaris tendon and trauma.

• PE: potentially extensive but specifically rule out chest infection and an intra-abdominal bleed (look for abdominal signs, shoulder tip pain from diaphragmatic irritation and a low JVP).

Management

Massive life treatening PE

• Management by an experienced multidisciplinary team involving senior obstetrician,physicians and radiologist for collapsed,shock patient.

• An urgent portable echocardiogram should be arranged within one hour presentation.

• Immediate thrombolysis should be considered when massive PE is confirmed or extensive circumstance occur.

• IV unfractionated heparin.

General points• In a woman with a past history of VTE or with a known inherited

thrombophilia, it is best to refer her prior to a planned pregnancy for optimum prophylaxis throughout the pregnancy.

• Medical anticoagulation is the treatment of choice for acute VTE. Subsequently, surgical interventions may be considered

• Anticoagulation is by far the most common treatment option. Heparin is the most frequently used drug, being non-toxic to the fetus (it does not cross the placental barrier). However, its main disadvantages are that it has to be parentally administered and, in the long-term, may give rise to heparin-induced osteoporosis and thrombocytopenia. In some patients, it can also provoke a painful, localized allergic reaction on administration.

• Warfarin is the other treatment option in the postnatal patient but it must be avoided antenatally, as it is teratogenic and can also cause placental abruption and fetal/neonatal hemorrhage.

• In clinically suspected DVT or PE, treatment with unfractionated heparin or LMWH should be given until the diagnosis is excluded.

Initiating treatment

There are several different types of heparin to choose from:• LMWH: this is the drug of choice. It has been shown to be more

effective than unfractionated heparin with lower mortality and fewer hemorrhagic complications in the initial treatment of DVT in non-pregnant subjects.

• Intravenous unfractionated heparin: this is an extensively used drug in the acute management of VTE, particularly massive PE with cardiovascular compromise

• Subcutaneous unfractionated heparin: this has been shown to be as effective as the intravenous form.

• Additionally, the leg should be elevated and a graduated elastic compression stocking applied to reduce edema. Mobilization with graduated elastic compression stockings should be encouraged.

Maintenance therapy

Pregnancy• Heparins are the maintenance treatment of choice. • Subcutaneous LMWH appears to have advantages over aPTT-monitored

unfractionated heparin in the maintenance treatment of VTE in pregnancy. Women should be taught to self-inject and can then be managed as outpatients until delivery.

• If unfractionated heparin is used, monitor the platelet count at least every other day for the first 14 days or until treatment is stopped (whichever comes first).

• Seek specialist advice if the patient develops heparin-induced thrombocytopenia or a heparin allergy and requires continuing anticoagulant therapy. She should be managed with the heparinoid, danaparoid sodium or fondaparinux, under specialist supervision.

Labour• When the patient thinks she is going into labour, she should stop injecting and get in

touch with the delivery ward staff that will manage the anticoagulation throughout labour and immediately post-delivery. Alternatively, planned elective induction of labour or caesarean section at least 12 hours after prophylactic-dose LMWH or 24 hours after therapeutic-dose LMWH can be considered. As these patients are at high risk of hemorrhage, they will be managed with intravenous unfractionated heparin throughout this time. Regional anaesthetic or analgesic techniques should not be undertaken until at least 24 hours after the last dose of therapeutic LMWH.

Postpartum • Depending on the patient's individual circumstances, she may be managed with ongoing

heparin treatment or warfarin postpartum. If she opts for warfarin, this needs to be avoided until at least day three postpartum with an INR check at day two of warfarin treatment: aim for an INR between 2 and 3. Continue heparin treatment until there have been two successive readings of an INR >2. Although these drugs are detectable in breast milk, all are safe for use during breast-feeding because warfarin metabolites are inactive and heparin is not absorbed through the gastrointestinal tract.

• Postnatal review for women who develop VTE during pregnancy or the puerperium should, whenever possible, be at an obstetric medicine clinic or a joint obstetric hematology clinic.

Stopping treatment

• In theory, therapy should be continued for six months as would be the case for non-pregnant patients. However, the postpartum state is a period of physiological fluctuation of coagulation factors. Therefore, current advice is to continue therapy for at least 6-12 weeks postpartum or until at least three months of therapy have been completed. At that point, the patient should be assessed for the presence of ongoing risk factors for a VTE prior to making the decision to stop anticoagulation therapy.

Prevention: prophylaxisGuidance from the Royal College of Obstetricians and Gynecologists’

suggests:Antenatally• Regardless of their VTE risk, dehydration and immobilization of the patient should be avoided

throughout pregnancy.• Women at high risk of VTE in pregnancy should be offered pre-pregnancy counseling and a

prospective management plan for thromboprophylaxis in pregnancy. Those who become pregnant before receiving such counseling should be referred to a nominated expert early in pregnancy.

• All women with previous VTE should receive postpartum prophylaxis, as this is the time of highest risk.

• In addition, women whose original VTE was unprovoked, idiopathic or related to estrogen, or who have other risk factors, a family history of VTE in a first-degree relative or a documented thrombophilia require LMWH antenatally and for six weeks postpartum.

• Women with recurrent VTE may already be on warfarin. They should be advised to stop warfarin and change to LMWH as soon as pregnancy is confirmed, ideally within two weeks of the missed period and before the sixth week of pregnancy. Women not on warfarin should be advised to start LMWH as soon as they have a positive pregnancy test.

• Women with asymptomatic inherited or acquired thrombophilia only, may be managed with close surveillance antenatally and be considered for LMWH for at least seven days postpartum. Exceptions are women with antithrombin deficiency, those with more than one thrombophilic defect (including homozygosity for factor V Leiden) or those with additional risk factors where antenatal prophylaxis should be considered.

Intrapartum• Women taking LMWH should be advised that, if they bleed vaginally or

contractions begin, they should not inject any further doses. They should be assessed in hospital and further doses be prescribed by medical staff.

Postpartum• All women with obesity (BMI greater than 40 kg/m2) should be considered

for prophylactic LMWH for seven days after delivery. Other postnatal risks include prolonged labour, immobility, infection, hemorrhage and blood transfusion.

• All women who have had an emergency Caesarean section should be considered for LMWH for seven days after delivery. All women who have had an elective caesarean section who have one or more additional risk factors should be considered for LMWH for seven days after delivery.

• In addition, properly applied graduated compression stockings are recommended for women travelling long-distance for more than four hours, women who are still outpatients but have prior VTE (usually combined with LMWH), women who are hospitalized and have a contra-indication to LMWH and those who are hospitalized post-caesarean section (combined with LMWH) and considered to be at particularly high risk of VTE.

References:

1.http://www.aafp.org/afp/2008/0615/p1709.html2.http://atvb.ahajournals.org/content/29/3/326.full3.http://patient.info/doctor/venous-thromboembolism-in-pregnancy#ref-3