A case of warfarin-associated venous limb gangrene: implications of anticoagulation in a palliative care setting.

A 52-year-old male veteran with a history of alcoholism, cocaine abuse, and psychiatric illness presented to a Veterans Affairs Medical Center (VAMC) emergency department with a 1-month history of progressive left lower extremity swelling and pain. Two months previously he had been diagnosed with a left lower extremity deep vein thrombosis (DVT). Since then, he had been treated with warfarin and his international normalized ratio (INR) was consistently therapeutic to supratherapeutic. Doppler ultrasound revealed progression of preexisting thrombosis, now involving the common femoral, superficial femoral and popliteal veins. His INR was 8.8. He was admitted for pain management and a work-up for coagulopathy and warfarin failure. A hematology consultation suggested a high index of suspicion for heparin-induced thrombocytopenia as the patient’s platelet count declined from 426 k=mm to 143 k=mm while on concomitant enoxaparin, so this was subsequently withheld. During a hypercoagulable work-up the hematologist noted an enlarged left inguinal lymph node and recommended a workup for occult malignancy. The patient’s hypercoagulability work-up included antithrombin III, proteins C and S, homocysteine, anticardiolipin antibodies, prothrombin 20210, and factor V Leiden. All were initially negative and heparin-induced antibody testing was negative as well. Subsequently, his factor VII and protein C levels were low on repeat testing. The patient underwent contrast-enhanced computed tomography (CT) scans that demonstrated multiple small hypoattenuating hepatic and splenic nodular densities felt to be consistent with malignancy. Liver biopsy confirmed the presence of a moderately differentiated adenocarcinoma of unknown origin. The patient continued to have progressive left lower extremity pain and swelling and the new onset of a violaceous, bullous exanthem on the dorsal lateral left foot. Hematology was concerned about warfarin necrosis versus venous limb gangrene (VLG) and, in light of the patient’s negative heparininduced antibody testing, the patient was restarted on enoxaparin. The patient’s pain remained poorly controlled. Palliative care was consulted. Given his recent development of acute renal failure (ARF) and rising liver function tests, he was started on a fentanyl patch for breakthrough pain. Over the next several days the patient’s ARF worsened and he had progressive hyperagitated delirium and his leg became gangrenous. This precipitated a family meeting to discuss the patient’s options with his health care proxy. Given the patient’s overall poor condition, his health care proxy chose to institute a do-not-resuscitate order (DNR), with the goal of care being comfort. He was admitted to the palliative care unit where he died later that evening. In light of the patient’s precipitous decline and uncertainties in regards to his cause of death, the patient’s health care proxy consented to an autopsy. The autopsy revealed aortic valve, tricuspid valve and myocardial vegetations consistent with marantic endocarditis in the setting of a patent foramen ovale. There was evidence of remote as well as recent myocardial infarction with severe coronary artery disease. The patient had thromboemboli to his kidneys and spleen, as well as a left lower lobe segmental pulmonary embolus. There was evidence of multiple acute emboli in the subcortical white matter. He had a fatty nodular liver with multiple metastases from an advanced stage gastric adenocarcinoma of the signet ring type.