Deep vein thrombosis, ecythyma gangrenosum and heparin-induced thrombocytopenia occurring in a man with a heterozygous Factor V Leiden mutation

Abstract

Skin necrosis and limb gangrene are occasional thrombotic manifestations of anticoagulation therapy. We report a man heterozygous for the Factor V Leiden (FVL) mutation, and with a history of recurrent deep venous thrombosis, who initially presented with a necrotic skin lesion of the right flank while on warfarin therapy with a therapeutic international normalized ratio. Warfarin was discontinued and he received intravenous heparin. Thereafter he developed thrombocytopenia and pedal erythema and was diagnosed with heparin-induced thrombocytopenia (HIT). Heparin was replaced with argatroban. He ultimately underwent bilateral below-knee amputations for the thrombotic complications of the HIT. The initial necrotic lesion healed with antibiotics and wound care. Pathologic examination of multiple biopsy specimens revealed two separate lesions. One was necrotic tissue infiltrated with methicillin resistant Staphylococcus aureus having features of ecthyma gangrenosum. The second showed thrombotic changes consistent with HIT. The case illustrates the differential diagnosis of skin necrosis and limb gangrene in patients on warfarin and heparin, and also the clinical complexities that can occur in a FVL heterozygote.

Keywords: Factor V Leiden; deep vein thrombosis.; ecthyma gangrenosum; heparin induced thrombocytopenia.

Figure 1

The figure depicts the initial right flank lesion after wound VAC placement.

Figure 2

Lower extremity gangrene secondary to both arterial and venous thrombosis.

Figure 3

Gross view of left abdominal wall and groin area lesion.

Figure 4

Epidermal necrosis with sub epidermal bullous formation and extravasated red blood cells (H&E stain, 100× magnification)

Figure 5

Dermal venous thrombus with acute inflammatory cell infiltration and endothelial cell damage (H&E stain, 400× magnification).

Figure 6

MRSA specific antibody stain demonstrating bacteria in a blood vessel.

Figure 7

MRSA antibody stain demonstrating bacteria in soft tissue.

Figure 8

CD61 immunostain from the original lesion shows venous platelet microthrombus (Immunohistochemical (IHC) stain for CD61, 400× magnification).

Figure 9

Thrombus in anterior tibial artery (Trichrome stain, 100× magnification).

Figure 10

CD61 immunostain of the lower extremity lesion shows platelet microthrombus (IHC stain for CD61, 250× magnification).

Figure 11

CD61stain shows platelet thrombus (IHC stain for CD6, 100× magnification).