Case Presentation: A 31-year-old female with no significant past medical history presented to the emergency department (ED) for evaluation of bilateral lower extremity pain. The patient reported that about 2 weeks ago, the pain started in the left lower extremity. At that time she was evaluated in ED and duplex ultrasound was negative for DVT. However pain worsened and she developed pain in RLE as well, so she came back to ED for further evaluation. She denied any recent long-distance travel. She reported that she was a teacher and she sat at her desk most of the day at work. The patient denied any history of DVT, PE, smoking or oral contraceptive pill (OCP) use. Lower extremity duplex ultrasound demonstrated acute DVT in the left gastrocnemius vein. Duplex ultrasound also demonstrated a superficial thrombus in the right lateral ankle and a superficial thrombus in the right arm. Complete blood count (CBC) was remarkable for pancytopenia with WBC 1,260/μL, hgb 8.8 mg/dL, and platelets 131,00/μL. She was started on a therapeutic unfractionated heparin infusion. Work up was initiated for Tick borne illness, paroxysmal nocturnal hemoglobinuria, autoimmune vasculitis/SLE, and acute promyelocytic leukemia (APL). Peripheral blood smear revealed 3% blasts and worsening leucopenia. Flow cytometry revealed 5% blasts concerning APL. FISH for t(15:17) was pending and she was started on all-trans-retinoic acid (ATRA) and prednisone. DIC labs were checked periodically. Bone marrow biopsy demonstrated 44% blasts, the study was suggestive of APL. FISH for t (15;17) from the bone marrow specimen was positive and the patient was diagnosed with APL.
Discussion: Acute promyelocytic leukemia (APL) is one of the subtypes of acute myeloid leukemia (AML). A translocation of chromosomes 15 and 17 is seen in APL which creates an alternation in the retinoic acid receptor-alpha (RAR-alpha) gene. APL is characterized by excessive production of promyelocytic blasts, which are responsible for hemorrhagic complications. Thrombotic complications occur less frequently in APL, mainly seen during the course of treatment. Thrombosis as the initial presentation of APL is rarely seen. APL is an aggressive malignancy, and without treatment, the median survival is less than 1 month. Significantly improved outcomes are seen with ATRA/arsenic trioxide (ATO). Patients with APL typically present with weakness and fatigue secondary to pancytopenia. Patients can also present with signs and symptoms of infection or DIC. The promyelocytic cells release tissue factors and pro-coagulant factors that are thought to be the culprit in the thrombotic events in DIC. In APL, thrombosis related complications include acute myocardial infarction, cerebrovascular accidents, and DVT/pulmonary embolism among others. Thrombotic event before the initiation of chemotherapy is very rare. In this case, the patient presented with an acute lower extremity DVT as an initial presentation of APL.
Conclusions: Thrombotic events in APL are rare and poorly understood. Clinicians should be aware of possible underlying hematologic malignancy while dealing with a patient with an unprovoked acute DVT and pancytopenia.