What is the differential diagnosis for a unilaterally enlarged, hard, and painful lower leg contusion in a patient on anticoagulation therapy (warfarin) for a medical condition (atrial fibrillation)?

Differential Diagnosis for Unilaterally Enlarged, Hard, and Painful Lower Leg in a Patient on Warfarin for Atrial Fibrillation

This clinical presentation demands immediate consideration of compartment syndrome, deep vein thrombosis, or warfarin-induced complications including hematoma or purple toes syndrome with progression to limb ischemia—all of which are limb-threatening emergencies requiring urgent diagnostic imaging and potential surgical intervention.

Life-Threatening Diagnoses Requiring Immediate Action

Acute Compartment Syndrome from Intramuscular Hematoma

• Spontaneous compartment syndrome can occur in anticoagulated patients without trauma, presenting with a tense, swollen, painful limb that is hard to palpation 1
• The elevated compartment pressures cause vascular compromise leading to ischemia and possible necrosis, making this a surgical emergency 1
• Clinical findings include: severe pain disproportionate to examination, pain with passive stretch of muscles, tense compartment on palpation, paresthesias, and potentially loss of distal pulses in advanced cases 1, 2
• Diagnosis is primarily clinical—do not delay treatment waiting for compartment pressure measurements if clinical suspicion is high 1
• Venous duplex ultrasound can help identify underlying hematoma but should not delay surgical consultation 1
• Immediate fasciotomy is required if compartment syndrome is confirmed to prevent permanent neuromuscular damage and limb loss 1, 3

Deep Vein Thrombosis (DVT)

• Paradoxically, patients on warfarin can still develop DVT, particularly if INR is subtherapeutic or in the setting of warfarin-induced hypercoagulability during initiation 4
• Presents with unilateral leg swelling, pain, warmth, and a palpable cord (thrombosed vein) 4
• The leg may be firm but typically not as rock-hard as compartment syndrome 4
• Venous duplex ultrasound is the first-line diagnostic test for proximal lower extremity DVT 4
• If ultrasound is negative but clinical suspicion remains high, consider CT venography or MR venography, particularly for iliac vein or IVC thrombosis 4
• Phlegmasia cerulea dolens (massive DVT with venous outflow obstruction) presents with severe pain, cyanosis, and edema—this is a limb-threatening emergency requiring catheter-directed thrombolysis or thrombectomy 4

Warfarin-Induced Limb Ischemia and Necrosis

• Warfarin can cause venous limb ischemia, necrosis, and gangrene, particularly in patients with underlying prothrombotic conditions or when transitioning from heparin 5
• This typically occurs within 3-10 days of warfarin initiation but can occur later 5
• Purple toes syndrome presents with dark, purplish or mottled discoloration of the toes and plantar surfaces that blanches with pressure, accompanied by pain and tenderness 5
• Some cases progress to gangrene requiring debridement or amputation—warfarin should be discontinued immediately if this is suspected 5
• The mechanism involves local thrombosis from rapid depletion of protein C before depletion of factors II, IX, and X 4, 5

Other Important Differential Diagnoses

Large Intramuscular or Subfascial Hematoma (Without Compartment Syndrome)

• Spontaneous bleeding into muscle compartments is a known complication of warfarin therapy 5
• Presents with localized swelling, pain, firmness, and possibly ecchymosis 5
• Check INR immediately—supratherapeutic INR significantly increases bleeding risk 4, 6, 7
• Ultrasound or CT imaging can confirm hematoma and assess size 1
• If INR is elevated and bleeding is significant, reverse anticoagulation with IV vitamin K and prothrombin complex concentrate (PCC) 4, 8, 6

Cellulitis or Soft Tissue Infection

• Presents with erythema, warmth, swelling, and tenderness 4
• Typically has associated fever, elevated white blood cell count, and systemic signs of infection 4
• The leg is usually warm rather than cool, and skin changes (erythema, streaking) are prominent 4
• Less likely to present with the rock-hard consistency described in this case 4

Ruptured Baker's Cyst

• Can mimic DVT with unilateral calf swelling and pain 4
• Ultrasound will show fluid collection in the popliteal fossa with rupture into the calf 4
• The leg is typically not as hard as in compartment syndrome 4

Critical Immediate Workup

Laboratory Studies

• INR and complete coagulation panel (PT, aPTT) to assess degree of anticoagulation 4, 6, 7
• Complete blood count to assess for anemia from bleeding and platelet count 4
• Creatinine and renal function (affects warfarin metabolism and bleeding risk) 4
• Creatine kinase if rhabdomyolysis from compartment syndrome is suspected 1

Imaging Studies

• Venous duplex ultrasound as first-line imaging to evaluate for DVT and identify hematoma 4, 1
• CT with contrast if ultrasound is non-diagnostic or if retroperitoneal extension of hematoma is suspected 4, 3
• Plain radiographs to exclude fracture if any trauma history 1

Physical Examination Findings to Document

• Compartment palpation (tense vs. soft) 1, 2
• Distal pulses (radial, dorsalis pedis, posterior tibial) 1, 2
• Capillary refill 1
• Sensory examination of the affected limb 1, 2
• Pain with passive stretch of muscles in the affected compartment 1, 2
• Skin color and temperature compared to contralateral limb 5
• Presence of ecchymosis or petechiae 5

Management Priorities

If Compartment Syndrome is Suspected

• Immediate surgical consultation for fasciotomy—do not delay for imaging if clinical diagnosis is clear 1, 3
• Reverse anticoagulation with IV vitamin K (10 mg slow infusion) and 4-factor prothrombin complex concentrate 4, 8
• Avoid fresh frozen plasma as sole reversal agent due to volume requirements and delayed effect 4

If DVT is Confirmed

• Continue anticoagulation if no contraindication exists 4
• Consider catheter-directed thrombolysis for phlegmasia cerulea dolens or limb-threatening DVT 4
• Graduated compression stockings may be used for symptom management but do not prevent post-thrombotic syndrome 4

If Warfarin-Induced Necrosis is Suspected

• Discontinue warfarin immediately 5
• Consider transitioning to heparin for continued anticoagulation if still indicated 5
• Vascular surgery consultation for potential debridement if necrosis progresses 5

Common Pitfalls to Avoid

• Do not assume adequate anticoagulation protects against DVT—subtherapeutic INR or warfarin resistance can still allow thrombosis 4
• Do not delay fasciotomy waiting for compartment pressure measurements if clinical presentation is consistent with compartment syndrome 1
• Do not use high-dose vitamin K routinely (>10 mg) as it may create warfarin resistance lasting up to a week 8, 7
• Do not restart warfarin if limb ischemia or necrosis is suspected without first ensuring adequate heparinization and protein C levels 4, 5
• Do not rely solely on ultrasound for iliac vein or IVC thrombosis—CT or MR venography may be needed 4
• Do not use fresh frozen plasma alone for urgent reversal—PCC is superior for rapid INR correction 4, 8