A 24-year-old man was admitted to our institution with refractory thromboembolic disease. His medical history began at 7 months of age when he was found to have a haemoglobin value of 10.0 g/dl during closure of a ventricular septal defect. A peripheral smear showed ‘target cells and siderocytes’. No investigation was performed until age 14 when a bone marrow biopsy was performed. Results showed a normocellular marrow with increased iron stores, ring sideroblasts and erythroid hypoplasia (). Treatment with vitamin B6 200 mg by mouth daily was initiated but the patient was not compliant with treatment. He was lost to follow-up until the age of 20 when he underwent open splenectomy for splenic rupture in the setting of infectious mononucleosis. Pathology of the spleen described findings consistent with viral infection.
Insufficient protoporphyrin production decreases use of iron delivered to the erythroblasts. Iron accumulates in the mitochondria leading to the development of characteristic ring sideroblasts (arrows).
The family history was remarkable for his mother dying suddenly at age 47 due to unknown causes; an autopsy was not performed. She had had multiple miscarriages while she was alive. A brother with a history of diabetes and hypertension died at age 39 secondary to a possible drug overdose. He has a paternal aunt diagnosed as having colon cancer at age 57 and a paternal uncle who died at age 50 with lung and throat cancer. There was no family history of anaemia, thrombosis or iron overload.
Approximately 4 months after the splenectomy, the patient developed pain and swelling of the left lower extremity. Duplex ultrasonography revealed acute deep vein thrombosis (DVT). He experienced two further episodes of lower extremity DVT while on warfarin; the prothrombin (PT) and international normalised ratio (INR) (PT/INR) status is not known during these events. Thereafter a Greenfield filter was inserted and warfarin was continued.
Approximately 3 years later, the patient presented with left upper extremity pain. A duplex ultrasound showed evidence of acute DVT in the left basilic vein in the setting of a subtherapeutic PT/INR. At the time of admission, peripheral smear showed target cells with microcytes, nucleated red blood cells, basophilic stippling and Pappenheimer bodies with possible spherocytes. Heparin bridging was administered until the PT/INR was therapeutic on warfarin. While awaiting a therapeutic PT/INR, the patient developed left knee pain. The duplex ultrasound showed findings consistent with a left popliteal vein DVT. He was transferred to our institution for evaluation of thrombophilia.
He was seen in the outpatient's clinic after discharge and was again given pyridoxine 200 mg by mouth daily. He tolerated this well but had no improvement in his anaemia. He was followed by our haematology clinic who sought to keep his PT/INR between a goal of 2.5 and 3.5. At 6 months post discharge from the hospital, he returned to the Emergency Department with superficial vein thrombosis in the setting of a supratherapeutic INR. This was determined to be a failure while on warfarin and twice daily weight-based enoxaparin was given instead.
Approximately 1 year later, the enoxaparin was held for 2 days at the discretion of his dentist and he developed bilateral pulmonary emboli. He was discharged on twice-daily weight-based enoxaparin. A factor Xa level was drawn after discharge and returned 0.26 IU/ml. Enoxaparin was subsequently increased from 90 to 110 mg twice daily at the direction of our haematologists.