Blue toes and a new pair of shoes—Challenges in diagnosis and treatment of acute myelogenous leukemia

Case A 63-year-old Caucasian female presented to the emergency department complaining of right foot pain for one day associated with blue toe discoloration for 3 weeks. She initially attributed her symptoms to trauma from a new pair of shoes but became concerned with the onset of pain. Her past medical history included hypertension and cervical cancer treated with hysterectomy 25 years ago. Her family history was noncontributory. She had a 40-pack year smoking history but quit 5 years ago. She was in good health prior to this presentation with an ECOG score of 0. Physical examination was remarkable for a weak right dorsalis pedis pulse and cyanosis of all toes on the right foot. Although a new pair of shoes is a potential explanation for developing blue toes, arterial thrombosis must be ruled out. Interestingly, the patient doesn’t seem to have any reported cardiovascular risk factors or a known hypercoagulable state. It is reassuring that she is otherwise healthy and has a good performance status. We need to quickly identify the site of thrombosis and initiate prompt therapy in order to salvage the limb. It is also important to investigate the reason behind thrombus formation. Initial laboratory analysis was as follows: white cell count, 14,400/mL with 85% neutrophils, 7% lymphocytes, 7% monocytes, and 1% basophils; hemoglobin, 13.1 g/dL; mean corpuscular volume, 89 fL; platelets, 86,000/mL; international normalized ratio (INR), 1.5 [normal, 0.8–1.2]; activated partial thromboplastin time (aPTT), 29 sec [normal, 24–35 sec]; blood urea nitrogen (BUN), 18 mg/dL [normal, 8–24 mg/dL]; and creatinine, 2.0 mg/dL [normal, 0.6–1.2 mg/dL]. Peripheral smear showed granulocytosis with left shift but no blasts, 11 schistocytes, and moderate thrombocytopenia (Fig. 1a). The patient was admitted to the surgical service and empirically started on therapeutic-dose heparin drip and intravenous hydration. Arterial lower extremity Doppler showed small vessel occlusive disease without evidence of large vessel thrombosis. Abdominal vascular ultrasound and CT abdomen without contrast were unremarkable. At this time, anticoagulation was stopped. Hematology consult was called for evaluation of thrombocytopenia. Due to the patient’s elevated creatinine, more sensitive imaging with contrast was not immediately performed. Although the culprit clot has not been identified, major arterial thrombosis remains high on the differential. Small vessel occlusive disease is unlikely to fully explain the patient’s presentation. Her leukocytosis with left shift could represent a reactive process in response to acute inflammation. She also has evidence of coagulopathy, moderate thrombocytopenia, renal dysfunction, and presence of mild schistocytosis on peripheral smear. Differential diagnosis is broad and may include infection, vasculitis, autoimmune connective tissue disorder, and malignancy. Disseminated intravascular coagulation (DIC) with thrombocytopenia from platelet consumption and small renal infarcts is also a possibility. Thrombotic thrombocytopenic purpura (TTP) may present similarly and cases of associated arterial occlusion having previously been reported [1]. Finally, the patient may have two distinct processes occurring simultaneously. On day 2 of hospitalization, additional laboratory work-up revealed: white cell count, 16,700/mL; hemoglobin, 11.6 g/dL; platelets, 65,000/mL; INR, 1.9; aPTT, 32 sec; fibrinogen, 125 mg/dL [normal, 205–390 mg/dL]; DDimer, 16,108 ng/mL [normal, <230 ng/mL]; lactate dehydrogenase (LDH), 672 U/L [normal, 81–175 U/L]; total bilirubin, 0.4 mg/dL [normal, 0.4–1.4 mg/dL]; haptoglobin, 321 mg/dL [normal, 32–213 mg/dL]; direct Coombs test, negative; and creatinine, 1.0 mg/dL. Repeat peripheral smear showed granulocytosis with left shift and occasional atypical large mononuclear cells, 21 schistocytes, and worsening thrombocytopenia (Fig. 1b). At this time, the patient’s right foot pain worsened and loss of dorsalis pedis pulse was noted. Right lower extremity MRI was negative for thrombosis but showed an abnormal marrow signal throughout the skeleton. Whole-body CT scan showed near-complete occlusion of the infrarenal abdominal aorta (Fig. 2). The patient was taken for an emergent aortic thrombectomy, with post-procedure improvement in right lower limb perfusion and restoration of pulses. Low-dose heparin drip was initiated due to thrombocytopenia. She was stabilized in the intensive care unit over the next 24 hr. At this point, we can rule out a hemolytic process and her laboratory pattern is suggestive of significant DIC [2], which appears to be worsening. There are occasional atypical large mononuclear cells appearing on the peripheral smear, which can indicate increased bone marrow stress or an evolving hematologic disorder. Contrast-enhanced imaging was performed as renal function improved with hydration, finally identifying the site of major arterial thrombosis. Although DIC can be precipitated by this major