Thrombosis in Pregnancy
THROMBOLYSIS
Fetal as well as maternal survival is dependent on adequate maternal perfusion and oxygenation. The risk of death from PE is significant, with a cross-sectional study of 58 patients with acute, massive PE showing a 55% mortality rate.56 Thus, pregnancy is not an absolute contraindication to mechanical or systemic (recombinant tissue plasminogen activator or streptokinase) thrombolysis in an unstable patient at high risk for death.57–59 There are no major studies of this approach, although a small review of 13 cases using systemic thrombolysis showed no increased risk of maternal mortality.58 Thrombolysis should be considered for appropriate indications in pregnant patients as it would be in nonpregnant patients. However, caution is required when drawing conclusions regarding maternal and fetal safety, given the lack of controlled clinical trials including pregnant women.
SURGICAL PULMONARY EMBOLECTOMY
Surgical pulmonary embolectomy is an important therapeutic and potentially life-saving option in women presenting with massive PE in the immediate postpartum period. Because of the risk of massive uterine bleeding immediately postpartum, thrombolytic therapy should not be used.60
INFERIOR VENA CAVA FILTER
Placement of an inferior vena cava (IVC) filter is indicated in patients who have an acute VTE with absolute contraindications for anticoagulation. In addition, it can be considered in patients with extensive ileofemoral venous thrombosis within 2 weeks prior to expected delivery.61 In a systematic review of 44 studies of IVC filters placed in pregnant patients, the IVC filter complication rate was 8.87% and the failure-to-retrieve rate was 11.25%.62 The complication rate is similar to that found in the nonpregnant population. Thus, IVC filters may be used when appropriately indicated and should be removed as soon as clinically feasible.
,RECURRENT THROMBOSIS AND THROMBOPHILIAS
CASE PRESENTATION 2
A 34-year-old pregnant woman G1P0 at 38 weeks’ gestation presents with a painful, swollen left calf that is associated with difficulty on walking; the circumference of the left calf is 2 cm greater than that of the right. She has no shortness of breath or chest pain. She has a prior history of distal right lower extremity DVT while on combined oral contraceptives. Her mother also has a history of DVT while bedbound during a prolonged hospitalization at an older age. CUS is negative, and the patient is discharged home. However, 24 hours later she returns to the hospital with worsening swelling and pain in her left leg. Magnetic resonance venography demonstrates a large left external iliac and common iliac DVT. She is admitted and is started on UFH, and a retrievable IVC filter is placed in anticipation of delivery.
What is the risk for VTE recurrence during pregnancy?
A personal and family history of VTE should be obtained when evaluating pregnant patients. A retrospective study of 109 women with prior history of VTE showed recurrence rates per patient-year of 10.9% during pregnancy and 3.7% in the nonpregnant period; the relative risk of recurrent VTE during pregnancy was 3.5 (95% CI 1.6 to 7.8).63 Two large European retrospective cohort studies of VTE in pregnancy showed that the recurrence rate of VTE in women with a history of thrombosis is around 6% during pregnancy, equally distributed among trimesters. The highest incidence of recurrence was in the postpartum period, ranging from 8.3% to 10%.64 The recurrence risk during pregnancy in women with a history of a single episode of VTE was 2.4% antepartum (95% CI 0.2% to 6.9%).65 These risks may be lower in women without thrombophilia or with a temporary risk factor associated with their previous thromboembolic event.65 Recurrence risk is higher if the previous VTE was estrogen-related, either due to pregnancy or through hormonal contraception (10%), than if the previous VTE was non-estrogen-related (2.7%).64,66
The timing of the case patient’s presentation is consistent with reports of increased risk of VTE during the peripartum period. Her prior history of estrogen-related DVT is concerning for a risk of recurrence, particularly during pregnancy. A retrospective cohort study of 1104 women with previous VTE, 88 of whom became pregnant without receiving thromboprophylaxis, showed that the overall rate of VTE recurrence was 5.8% (95% CI 3.0% to 10.6%) and 8.3% (95% CI 4.5% to 14.6%) during pregnancy and postpartum, respectively. The risk of VTE recurrence was absent if the first VTE was related to a transient risk factor other than pregnancy, postpartum period, or hormonal contraception.67 However, the recurrence rate of VTE in women with prior unprovoked VTE and/or thrombophilia has been reported as 5.9% (95% CI 1.2% to 16.2%).65 The presence of an underlying hypercoagulable state can increase the recurrence risk by 25% to 50%, depending on the disorder.68 A retrospective cohort study of 270 pregnancies in 105 carriers of factor V Leiden, identified because of a symptomatic relative with the factor V Leiden mutation, found a VTE risk (mostly in the postpartum period) of 6.4% for heterozygous women, 16.7% for homozygous women, 20% for double heterozygous women, and 1.2% for noncarriers.69
Should the patient be screened for a thrombophilia disorder?
Half of all index thromboses in patients with thrombophilia occur in association with an additional risk factor. In women of child-bearing age, pregnancy, the postpartum period, and the use of combined hormonal contraception are all risk factors for VTE. A 2010 guideline from the British hematology community recommended testing for thrombophilia in women with prior VTE secondary to a minor provoking factor before or during pregnancy, but not testing women with unprovoked VTE (who would receive prophylaxis regardless) or those with VTE secondary to a major provoking factor (who would not require prophylaxis).70 Indications to screen for aPL antibodies include: women with (1) 3 unexplained recurrent first-trimester pregnancy losses or 1 second or third trimester fetal loss of morphologically normal fetuses; (2) severe preeclampsia; (3) intrauterine growth restriction; or (4) premature labor (< 34 weeks’ gestation).71,72
CASE 2 CONCLUSION
The patient is subsequently screened for inherited thrombophilia disorders and is found to be heterozygous for factor V Leiden.
