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Summary Table

Category	Details
Risk Factors	Pregnancy itself (all trimesters, highest risk postpartum), cesarean delivery, prolonged immobilization/bed rest, prior VTE history, thrombophilia (Factor V Leiden, Prothrombin G20210A mutation, Antiphospholipid syndrome, Protein C/S deficiency), obesity, advanced maternal age, preeclampsia, assisted reproductive technology
Etiology	Hypercoagulable state of pregnancy driven by Virchow's triad: venous stasis from uterine compression of iliac veins, endothelial injury during delivery, and physiologic increase in procoagulant factors
Patient Presentation	Unilateral lower extremity swelling, pain, and warmth; left leg affected in ~80% of cases due to anatomic compression of the left iliac vein by the right iliac artery (May-Thurner physiology)
Classic Physical Exam	Unilateral leg edema with >2 cm circumference difference, calf tenderness, erythema, palpable cord, positive Homans sign (low sensitivity, not relied upon clinically)
Key Diagnostic Results	Compression ultrasonography (CUS) is the best initial and primary diagnostic test; D-dimer is physiologically elevated in pregnancy and therefore unreliable for exclusion
Management	Low-molecular-weight heparin (LMWH) is the anticoagulant of choice throughout pregnancy; warfarin and DOACs are contraindicated in pregnancy
Keywords	"Pregnant woman with unilateral left leg swelling," "postpartum leg pain," "hypercoagulable state of pregnancy," "cannot use warfarin in pregnancy"

1. Pathophysiology

Pregnancy is a prothrombotic state by design. The body prepares for the hemostatic challenge of placental separation at delivery by shifting the coagulation balance toward clot formation. All three components of Virchow's triad are activated simultaneously, which is why pregnancy increases VTE risk roughly 5-fold compared to age-matched non-pregnant women.

Hypercoagulability is the dominant driver. Pregnancy causes a progressive rise in procoagulant factors including fibrinogen, Factor VII, Factor VIII, Factor X, and von Willebrand factor. At the same time, the natural anticoagulant system is suppressed: Protein S levels fall significantly, and there is acquired resistance to activated Protein C. Fibrinolytic activity is also reduced due to increased levels of plasminogen activator inhibitor-1 (PAI-1) and the placenta-derived PAI-2. The net result is a system primed for thrombus formation.

Venous stasis worsens as pregnancy progresses. The enlarging uterus compresses the inferior vena cava and iliac veins, reducing venous return from the lower extremities. Progesterone-mediated venous smooth muscle relaxation further contributes to venodilation and sluggish flow. This compression is more pronounced on the left side, because the right common iliac artery crosses over and compresses the left common iliac vein against the lumbar vertebral body. This anatomic relationship explains why approximately 80-90% of pregnancy-related DVTs occur in the left leg, a pattern distinct from DVT in non-pregnant patients where laterality is more evenly distributed.

Endothelial injury becomes most relevant during delivery, particularly with cesarean section or instrumental vaginal delivery. Surgical trauma to pelvic vessels triggers local activation of the coagulation cascade. This is why the postpartum period, particularly the first 6 weeks, carries the highest per-day risk of VTE across the entire pregnancy timeline.

The combination of these three factors explains why DVT in pregnancy tends to be iliofemoral rather than distal (calf-only), which carries a higher risk of pulmonary embolism and post-thrombotic syndrome compared to the more distally located DVTs seen in the general population.

2. Classification and Clinical Manifestation

Classification	Location	Clinical Features	Clinical Significance
Distal (calf) DVT	Below the popliteal vein (posterior tibial, peroneal, soleal, gastrocnemius veins)	Calf pain, mild swelling, tenderness on palpation	Lower PE risk; may be monitored with serial ultrasound if isolated
Proximal DVT	Popliteal vein and above (femoral, common femoral, external iliac veins)	Significant unilateral thigh and leg swelling, pain, warmth, erythema	High PE risk; requires immediate anticoagulation
Iliofemoral DVT	Iliac and common femoral veins	Entire leg swelling, severe pain, may present with phlegmasia alba dolens (painful white leg) or phlegmasia cerulea dolens (painful blue leg with arterial compromise)	Most common pattern in pregnancy; highest risk of PE and post-thrombotic syndrome
Cerebral venous sinus thrombosis	Dural venous sinuses	Severe headache, seizures, focal neurological deficits, papilledema	Rare but important pregnancy-associated thrombosis; diagnosed with MR venography
Ovarian vein thrombosis	Ovarian vein (right > left)	Postpartum fever, flank/abdominal pain, palpable tender mass	Typically occurs postpartum; associated with endometritis

Key teaching point: Unlike the general population where DVT is most commonly distal, pregnancy-related DVT has a strong predilection for proximal and iliofemoral locations. This distinction matters because proximal clots carry a higher embolic potential and demand immediate treatment without a "watchful waiting" option.

3. Diagnostic Workup

Test	Role	Key Points
Compression Ultrasonography (CUS)	Best Initial Test	First-line imaging for suspected DVT in pregnancy; high sensitivity and high specificity for proximal DVT; no radiation exposure
D-dimer	Not reliable in pregnancy	Physiologically elevated throughout pregnancy; a normal D-dimer does NOT exclude DVT in pregnant patients; should not be used to "rule out" VTE
Serial CUS	Follow-up if initial CUS negative but clinical suspicion persists	Repeat in 3-7 days to detect propagating distal clots
MR venography (MRV)	Adjunct for iliac vein DVT	Used when CUS is negative but clinical suspicion for isolated iliac vein thrombosis remains high; no radiation; avoids gadolinium if possible
CT venography	Rarely indicated	Reserved for situations where ultrasound and MRV are inconclusive; involves ionizing radiation
Conventional venography	Historical gold standard	Invasive, involves contrast and radiation; almost never performed in pregnancy

Diagnostic reasoning in pregnancy differs from the general population in one critical way: D-dimer is not useful. In non-pregnant patients, a negative D-dimer combined with a low Wells score effectively excludes DVT. In pregnancy, D-dimer levels rise progressively through each trimester and are almost universally elevated by the third trimester. Using D-dimer to exclude DVT in a pregnant patient is a classic exam trap.

Compression ultrasonography is the diagnostic cornerstone. The principle is straightforward: a normal vein collapses completely under probe pressure, while a vein containing thrombus does not compress. CUS has sensitivity above 95% for proximal DVT but lower sensitivity (approximately 50-70%) for isolated calf vein and iliac vein thrombi.

When clinical suspicion is high but the initial CUS is negative, the next step depends on location of concern. If the suspicion is for calf DVT, serial CUS should be repeated in 3-7 days to detect clot propagation. If the suspicion is for isolated iliac vein thrombosis (suggested by entire-leg swelling, buttock/back pain, or left-sided symptoms with a normal femoral/popliteal ultrasound), MR venography without gadolinium is the preferred next step because standard CUS has limited visualization of the iliac veins due to the gravid uterus.

The Wells score, while validated in the general population, has not been validated in pregnant patients and should not be applied in this population. Pregnancy itself mimics many of the clinical features that score points on the Wells criteria (leg swelling, immobilization), making the score unreliable.

4. Management and Treatment

Phase	Treatment	Details
Acute anticoagulation (pregnancy)	Enoxaparin (LMWH)	1 mg/kg subcutaneously every 12 hours (weight-based, using pre-pregnancy or early pregnancy weight); continue throughout pregnancy
Alternative if LMWH unavailable or contraindicated	Unfractionated heparin (UFH)	IV bolus 80 units/kg, then continuous infusion 18 units/kg/hr, titrated to aPTT 1.5-2.5x control; transition to SC dosing for long-term use
Peripartum management	Switch LMWH to UFH at 36-37 weeks	UFH has a shorter half-life and is fully reversible with protamine, allowing safer neuraxial anesthesia and management of delivery bleeding
Delivery timing	Discontinue UFH	Stop IV UFH 4-6 hours before planned delivery or neuraxial anesthesia; stop LMWH at least 24 hours before
Postpartum anticoagulation	Warfarin or LMWH	Resume anticoagulation within 6-12 hours after vaginal delivery (24 hours after cesarean); warfarin is safe during breastfeeding; target INR 2.0-3.0
Total duration	Minimum 3 months, extended through at least 6 weeks postpartum	Whichever endpoint comes later; the postpartum period carries the highest daily VTE risk
Contraindicated medications	Warfarin, DOACs (rivaroxaban, apixaban, edoxaban, dabigatran)	Warfarin is teratogenic (nasal hypoplasia, stippled epiphyses, CNS abnormalities); DOACs cross the placenta and lack safety data in pregnancy

LMWH is the drug of choice for treating DVT in pregnancy. Enoxaparin at 1 mg/kg subcutaneously every 12 hours is the standard regimen. Twice-daily dosing is preferred over once-daily in pregnancy because the increased renal clearance and expanded volume of distribution during pregnancy lead to lower trough levels with once-daily dosing. Anti-Xa levels can be monitored to ensure therapeutic range (target peak anti-Xa: 0.6-1.0 IU/mL, drawn 4 hours post-injection), though routine monitoring is debated and generally reserved for extremes of body weight or renal impairment.

Unfractionated heparin (UFH) is an acceptable alternative, particularly in patients with severe renal insufficiency (where LMWH accumulates) or when a procedure or delivery is imminent and rapid reversibility is needed. Neither UFH nor LMWH crosses the placenta, making both safe for the fetus.

The peripartum period requires careful planning. At approximately 36-37 weeks, LMWH is typically converted to UFH because of its shorter half-life and complete reversibility with protamine sulfate. This conversion is driven by the need to safely administer neuraxial anesthesia (epidural/spinal): LMWH must be discontinued at least 24 hours before needle placement, while UFH requires only 4-6 hours. For patients on therapeutic LMWH who present in spontaneous labor, neuraxial anesthesia is contraindicated if the last dose was within 24 hours due to epidural hematoma risk.

Postpartum, anticoagulation is resumed and the patient has expanded treatment options. Warfarin becomes an option because the teratogenic risk is no longer relevant, and warfarin is safe during breastfeeding (it does not pass into breast milk in clinically significant amounts). The total duration of anticoagulation is a minimum of 3 months and must extend through at least 6 weeks postpartum, whichever is longer. For example, a DVT diagnosed at 36 weeks would be treated for approximately 3 months total (covering the remaining pregnancy plus 6+ weeks postpartum).

DOACs (rivaroxaban, apixaban, dabigatran, edoxaban) are contraindicated throughout pregnancy and breastfeeding. These agents cross the placenta, and there are no adequate safety studies in human pregnancy.

IVC filters are reserved for patients with acute proximal DVT who have an absolute contraindication to anticoagulation (e.g., active hemorrhage). Retrievable filters are preferred, with planned removal once anticoagulation can be safely initiated.

5. Differential Diagnosis and Distractors

Differential Diagnosis	Why It Is Similar	Key Discriminator
Physiologic edema of pregnancy	Bilateral lower extremity swelling is common in late pregnancy	Bilateral and symmetric; no unilateral tenderness, erythema, or cord; no circumference asymmetry >2 cm
Superficial thrombophlebitis	Palpable tender cord along a vein, erythema, pain	Involves superficial veins (visible/palpable); no deep venous involvement on CUS; treated with warm compresses and NSAIDs (or LMWH if near the saphenofemoral junction)
Cellulitis	Unilateral leg erythema, warmth, pain	Erythema has a well-defined advancing border; skin changes are predominant; no venous obstruction on ultrasound; fever and leukocytosis are more prominent
Baker cyst rupture	Acute calf pain and swelling mimicking DVT	History of knee joint pathology; ultrasound shows popliteal cyst with fluid tracking into the calf; no intraluminal thrombus
Iliac vein compression syndrome (May-Thurner)	Left leg swelling and DVT in a young woman	Chronic left leg swelling/venous insufficiency even without acute thrombosis; diagnosed with CT or MR venography showing external iliac vein compression; May-Thurner is a predisposing anatomic variant, not the thrombosis itself
Preeclampsia with edema	Lower extremity swelling, often in the third trimester	Accompanied by hypertension (>140/90), proteinuria, and often facial/hand edema; edema is generalized rather than unilateral
Lymphedema	Unilateral limb swelling	Non-pitting edema; chronic and progressive; no acute onset of pain; ultrasound shows no thrombus

6. Traps and High-Yield Pearls

The most frequently tested concept in DVT in pregnancy is the inapplicability of D-dimer. The exam will present a pregnant patient with leg swelling and then offer D-dimer as a diagnostic option. Students who reflexively apply the standard DVT workup algorithm (Wells score followed by D-dimer) will fall into this trap. In pregnancy, the answer is always go directly to compression ultrasonography without wasting time or clinical reasoning on D-dimer.

The second major trap involves anticoagulant selection. Warfarin is teratogenic and DOACs lack pregnancy safety data, so the only appropriate anticoagulant during pregnancy is heparin (LMWH preferred, UFH acceptable). However, warfarin becomes appropriate postpartum and is safe during lactation. The exam may test this transition point, presenting a postpartum patient and asking whether warfarin can be started while breastfeeding (the answer is yes).

A subtle but testable pearl is the left leg predominance. When a vignette describes a pregnant woman with left leg swelling, this is a strong clue pointing toward DVT rather than physiologic edema, because the anatomic compression of the left iliac vein makes pregnancy-associated DVT overwhelmingly left-sided. Bilateral edema, by contrast, points toward physiologic changes or preeclampsia.

Finally, students must recognize the peripartum heparin bridging concept. Switching from LMWH to UFH near term is done specifically to allow safe neuraxial anesthesia. The exam may present a patient on therapeutic LMWH who arrives in labor and ask about epidural safety. If the last LMWH dose was within 24 hours, the answer is that neuraxial anesthesia is contraindicated due to epidural hematoma risk. This tests the student's understanding of the pharmacokinetic rationale behind the peripartum anticoagulation strategy.

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