Analgesia, Anaesthesia and Pregnancy. 4th Ed. Róisín Monteiro

Chapter 105. Thrombophilia

Thrombophilia has been defined as a familial or acquired abnormality of haemostasis likely to predispose to thrombosis. Up to 30-50% of patients with a history of venous thromboembolism may have a congenital thrombophilia, and others may have a detectable phospholipid autoantibody. This is a developing area, which may yet demonstrate further congenital or acquired factors explaining a propensity to thrombosis.

Problems and special considerations

Pregnancy is associated with a physiological hypercoagulable state. When a pre-existing thrombophilia is present, thrombosis may occur within the uterus causing failure of implantation; within the placenta causing fetal loss, abruption, pre-eclampsia, fetal growth restriction and fetal distress in labour; or in the systemic circulation. Patients with thrombophilia may thus present with subfertility, with a personal or family history of venous and arterial thromboses, or with thromboses in pregnancy or in the puerperium.

Diagnosis is difficult in pregnancy because of the changes in clotting-factor profile associated with pregnancy.

The usual treatment of thrombophilia complicating pregnancy is prophylactic subcutaneous low-molecular-weight heparin combined with low-dose aspirin. This has implications for the timing of regional analgesia and anaesthesia (see Chapter 106, Coagulopathy).

Thrombophilias can be classified into congenital and acquired.

Congenital thrombophilias

These deficiencies are heterogeneous; factors may be reduced quantitatively or qualitatively, underlying the importance of haematological input in their management. Subtle, subclinical deficiencies of these factors are very much more common than the figures quoted below (around 1 in 200):

• Activated protein C resistance (APCR). The circulating anticoagulant protein C, when activated by thrombin, inactivates factors V and VIII. APCR occurs normally in pregnancy, associated with an increase in factor VIII. This makes diagnosis in pregnancy difficult. In congenital APCR, factor V is more resistant to cleavage by protein C. Factor V Leiden occurs in about 5-7% of the European population and is associated with a rate of thrombosis in pregnancy of about 1 in 400-500. Factor V Leiden is much more sinister when in the homozygous form or when combined with another thrombophilia. In the absence of other risk factors such patients should not need thromboprophylaxis in pregnancy.

 Antithrombin III (ATIII) deficiency. This is a rare defect occurring in 1 in 5000 women, but it may account for up to 12% of thromboembolic events in pregnancy.

In untreated affected women, 55-68% of pregnancies are complicated by venous thromboembolism. Anticoagulant prophylaxis may be required throughout pregnancy and for at least 3 months postpartum. Discontinuation of heparin at the time of delivery and administration of ATIII concentrate has been advocated by some authors, but this is controversial.

 Protein C or protein S deficiency. This occurs in 1 in 15,000 pregnancies and is associated with a rate of venous thrombosis of up to 25% (protein S is a cofactor for protein C). Treatment with heparin throughout pregnancy and the puerperium is controversial. The risk of thrombosis is greatest postpartum in both protein C and S deficiencies, and several authors suggest thromboprophylaxis for this period only.

 Other causes. These include hyperhomocystinaemia and mutations of the prothrombin gene.

Acquired thrombophilia

The antiphospholipid syndrome is the most common cause of acquired thrombophilia. Autoantibodies against cell membrane phospholipids, including lupus anticoagulant and anticardiolipin antibodies, may lead to intravascular thrombosis which may lead to fetal loss. There is some evidence that other as yet unidentified autoantibodies may also cause thrombosis and miscarriage.

The lupus anticoagulant is so called because it causes a prolongation of the activated partial thromboplastin time even when diluted (because the autoantibody binds to phospholipid in the assay). However, it is associated with a thrombotic tendency. It may occur on its own (hence antiphospholipid syndrome) but may also occur as part of various autoimmune diseases such as systemic lupus erythematosus. Anticardiolipin antibodies are detected by using an immunoassay.

Of women with recurrent miscarriage (three or more), 15% have persistently positive results for phospholipid antibodies. If untreated, 90% will have spontaneous abortions or stillbirths in subsequent pregnancies. Lupus anticoagulant is detected in ~30% of cases and anticardiolipin antibodies in ~70%. Clinical features of the antiphospholipid syndrome are recurrent fetal loss, thrombosis (arterial and venous), thrombocytopenia, haemolytic anaemia, hypertension, pulmonary hypertension and livedo reticularis. Antiphospholipid syndrome is associated with a 5% incidence of thromboembolism or cerebrovascular accident in pregnancy. Rarely, a severe generalised thrombotic state may lead to multi-organ failure.

Management options

Women with a strong personal or family history of thrombosis and a poor obstetric history should be screened for known causes of thrombophilia.

Patients are at high risk of obstetric intervention in labour and may benefit from epidural analgesia and regional anaesthesia for delivery and caesarean section. The decision to site an epidural should be based on the dose and interval after heparin administration and the potential benefit to the patient. Ideally, women who are likely to be receiving heparin at the time of delivery should discuss a management plan with an anaesthetist in an assessment clinic. In the majority of cases the benefits of regional analgesia and anaesthesia far outweigh the risk of epidural haematoma.

Key points

 Thrombophilias are a significant cause of fetal loss in pregnancy.

 The adverse effects on maternal and fetal health are treatable.

 The risks and benefits of regional analgesia and anaesthesia should be considered antenatally if possible.

Further reading

Bates SM, Greer IA, Middeldorp S, et al. VTE, thrombophilia, antithrombotic therapy, and pregnancy: antithrombotic therapy and prevention of thrombosis, 9th edn: American College of Chest Physicians Evidence-based Clinical Practice Guidelines. Chest 2012; 141 (2 Suppl): e691S-736S.

Danza A, Ruiz-Irastorza G, Khamashta M. Antiphospholipid syndrome in obstetrics. Best Pract Res Clin Obstet Gynaecol 2012; 26: 65-76.

Gray G, Nelson-Piercy C. Thromboembolic disorders in obstetrics. Best Pract Res Clin Obstet Gynaecol 2012; 26: 53-64.

Royal College of Obstetricians and Gynaecologists. Reducing the Risk of Thromboembolism During Pregnancy and the Puerperium. Green-top Guideline 37a. London: RCOG, 2015. www.rcog.org.uk/ en/guidelines-research-services/guidelines/gtg37a (accessed December 2018).



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