Deep Venous Thrombosis

Swollen
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Diagnosis and reasoning

Acute lower limb swelling in pregnancy is due to deep venous thrombosis (DVT) until proven otherwise. Note that DVTs may give rise to a low grade fever, or feeling of feverishness. While the history of diabetes makes cellulitis a possibility, this should be considered after excluding a DVT. Note also that feverishness in a patient with cellulitis indicates systemic invasion - thus, one would typically expect to find tender inguinal lymphadenopathy. Acute arterial thrombosis is also possible (as pregnancy is a procoagulant state). However, this is excluded by the normal pulses in the affected limb. While trauma and a ruptured Baker's cyst are also notable causes for acute lower limb swelling, these need not be considered in the absence of a suggestive history. A lower limb Doppler scan should be arranged as soon as possible - and in this patient is suggestive of obstruction of the left popliteal and femoral veins by a thrombus, confirming the diagnosis. Note that while a negative D-Dimer will virtually rule out a DVT, a positive result in no way confirms the diagnosis, as D-Dimers may be elevated in normal pregnancies (especially near term). Given the absence of a history suggestive of a Baker's cyst, an X-Ray of the knee joint is not indicated. Anticoagulation with unfractionated heparin, low molecular weight heparins (LMWH) such as enoxaparin, or fondaparinux sodium should be commenced upon clinical suspicion. Note that warfarin is not recommended in pregnancy, due to the adverse effects on both the mother and the fetus. Systemic IV thrombolysis is no longer indicated in patients with DVT, as there is a significant risk of bleeding complications. In addition, urgent delivery is not indicated in this patient.


Discussion

Deep venous thrombosis (DVT) is an important manifestation of venous thromboembolism (VTE). Owing to the physiological adaptations in pregnancy, the risk for VTE is significantly higher than that of the general population. The increased risk of VTE in the pregnant population can be explained by thinking of Virchow's triad (vascular stasis, endothelial dysfunction and hypercoagulability). Venous stasis begins in the first trimester and peaks at 36 weeks of gestation. In addition, the enlarging uterus compresses the pelvic veins, predisposing to thrombosis. Finally, pregnancy is a procoagulant state, with the maternal hemostatic system returning to normal only 6 weeks after delivery. Due to these factors, pregnant women are at a 4 to 5 fold higher risk for VTE prior to delivery, with the risk rising to 20 fold during the postpartum period (approximately one-third of all pregnancy related DVTs occur during the puerperium). The overall prevalence of VTE in pregnancy is about 2 per 1000 deliveries and it is responsible for 1.1 deaths per 100,000 deliveries. The most important risk factor for DVT in pregnancy is a history of a previous thromboembolic event (with between 15% to 25% of VTE in pregnancy being recurrences). Other important risk factors include diseases such as systemic lupus erythematosus (SLE), acquired and hereditary thrombophilias and sickle cell disease (all of which induce hypercoagulable states), and also smoking, obesity, heart disease, diabetes and hypertension. Several pregnancy related complications may also increase the risk of VTE. These include multiple gestations, antepartum hemorrhages, hyperemesis, cesarean delivery, and postpartum infections. When DVT complicates pregnancy, it is often more proximal and massive, and more likely to involve the left lower extremity. Approximately 72% of DVTs in pregnant women occur in the iliofemoral vein, in contrast to only 9% in non pregnant women. The classical symptoms of DVT are pain and limb edema (leading to swelling). In addition, some patients may present with a concurrent pulmonary embolism (PE). Doppler ultrasonography is the diagnostic investigation of choice in pregnancy. If the results are negative or equivocal and iliac vein thrombosis is suspected magnetic resonance imaging (MRI) of the pelvis is recommended. Anticoagulants should be started upon clinical suspicion. Low molecular weight heparins (LMWH) are generally preferred over unfractionated heparin (UFH), as there is a smaller risk of bleeding, minimal need for monitoring, and lower risk of heparin induced thrombocytopenia (HIT) and osteoporosis. One advantage of UFH is that its anticoagulant effect can be rapidly reversed with protamine, allowing the effects to wear off in a few minutes. Thus, it may be of value in situations such as delivery or surgery where rapid cessation of anticoagulation is necessary. Current guidelines recommend that anticoagulation should be continued at a therapeutic dose for at least 3 to 6 months from diagnosis, including a minimum of 6 weeks postpartum (certain units may continue anticoagulation for 3 to 6 months postpartum). Note that long term anticoagulation may be advisable in women with thrombophilias or a history of recurrent VTEs. Monitoring of APTT or platelet counts is not required while the patient is on LMWH. Monitoring of anti-factor Xa levels is generally indicated if the patient is obese or if the renal functions are abnormal. Heparin administration should be stopped once the patient is in labor; in an elective delivery heparin should be discontinued 24 hours prior to delivery. Women receiving LMWH may be switched to UFH in the last month of pregnancy, especially if at a high risk for recurrent VTE (for example, patients with mechanical heart valves). Regional analgesic or anesthetic procedures should not be performed until 24 hours after the last therapeutic dose of LMWH (or 12 hours after the prophylactic dose). Warfarin can be used for postpartum anticoagulation but should not be started until the third day postpartum. Graduated compression stockings should be worn on the affected leg for 1 to 2 years to prevent post thrombotic syndrome. Inferior vena cava (IVC) filter insertion may be considered in patients with recurrent PEs, or in whom there are contraindications to anticoagulation (such as heparin induced thrombocytopenia - HIT, or hemorrhagic stroke). Estrogen containing contraceptives are contraindicated in these patients as they increase the risk of future VTEs. However progesterone only contraceptives are generally safe. Note also that neither UFH, LMWH nor warfarin is contraindicated in breastfeeding.


Take home messages

  1. Women are at a significantly higher risk of VTE during pregnancy and the puerperium.
  2. Acute lower limb swelling in pregnancy is due to DVT until proven otherwise.
  3. Doppler ultrasonography is the diagnostic investigation of choice for suspected DVT in pregnancy.
  4. Neither UFH, LMWH nor warfarin is contraindicated in breastfeeding.

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  1. AFP: venous thromboembolism during pregnancy (2008)
  2. Arteriosclerosis, thrombosis and vascular biology: venous thromboembolism in pregnancy (2009)
  3. Green-top guideline No. 37b:The Acute Management of Thrombosis and Embolism During pregnancy and puerperium
  4. Hematology (ASH education program book): evidence base for the management of venous thromboembolism in pregnancy (2010)
  5. Hematology (ASH education program book): pregnancy associated thrombosis (2009)
  6. NEJM: venous thromboembolic disease and pregnancy (2008)
  7. The lancet: maternal and fetal issues (1999)