Magnetic Resonance Brain Imaging in Regularly Transfused Beta Thalassemia Major and Intermedia Subjects and Prevalence of Thrombophilia Mutations

Recent reports of magnetic resonance (MRI) brain imaging have emerged detecting covert cerebral infarcts in thalassemia subjects. The thalassemia phenotype, and splenectomy and hypercoagulation are suggested mechanisms.

We conducted a retrospective review of all brain MRIs performed in thalassemia subjects at the Weill Cornell/New York Presbyterian Hospital Thalassemia Center over the past 15 years (yrs). Blood counts, platelet counts and ferritin levels at the time of MRI as well as genotype and phenotype diagnoses, splenectomy status and thrombophilia mutational analysis historically performed were reviewed.

16 thalassemia subjects: 7M:9F, mean age = 29. 9 yrs (range: 11 to 45 yrs) were identified who underwent brain MRI studies from 1998 to 2012. Brain MRIs were performed for evaluation of various symptoms including: headaches (6), dizziness (2), growth hormone efficiency (2), unilateral hearing loss (1), optic neuritis (1), cerebral hypoxia (1), acquired human immunodeficiency syndrome (1), s/p craniopharyngioma excision (1), and paresis (1).

MRI findings included 3 chronic infarcts, 2 cerebral white matter disease images consistent with chronic ischemia, 1 acute infarct, 2 opacified maxillary sinuses, 1 sphenoid sinusitis, 1 acute hemorrhage, 1 recurrent hemorrhage, 1 cerebellopontine angle schwannoma and 4 unremarkable studies.

Clinical diagnosis included: 12 Thalassemia Major (TM) subjects who were on regular red blood cell (RBC) hypertransfusion regimens since infancy to maintain pre-transfusion hemoglobin (Hgb) levels greater than 10 gm/dl and 4 Thalassemia Intermedia (TI) subjects (3M/1F) were periodically transfused until adolescence or early adulthood when they were placed on regular RBC hypertransfusion support owing to complications including extramedullary hematopoiesis causing spinal cord compression, progressive anemia with fatigue and thrombosis. All but 2 subjects were splenectomized; all but 6 subjects had platelet counts greater than 500 (mean platelet count = 567; range 175 to 1101). All were on iron chelation therapy including 2 Deferoxamine (DFO), 1 on DFO and Deferiprone (DFP) and 13 on Deferasirox (DFX). Prothrombotic genetic mutations were identified in 10 subjects including: (2) homozygous PAI-1, (5) heterozygous PAI-1, (2) homozygous MTHFR and (4) heterozygous for MTHFR; those 3 TM subjects with lacunar infarcts were heterozygous PAI-1 or negative for other thrombophilia mutations however 1 TM also had a patent foramen ovale. In addition, the 2 TI subjects with cerebral white matter disease had compound heterozygous MTHFR or PAI-1 in association with homozygous PAI-1 or homozygous MTHFR respectively.

Chronic brain infarcts and cerebral white matter disease consistent with ischemia were detected on MRI in 5/16 adolescent and adult thalassemia subjects (31%): TM = 3/16 (19%) and TI = 2/16 (10%) thalassemia subjects. Headache, pain and dizziness were the predominant symptoms in those subjects with brain MRI findings of chronic infarcts and white matter disease. Thrombocytosis was common in all splenectomized subjects Homozygous and compound heterozygous co-inheritance of thrombophilia mutations PAI-1 and MTHFR were relatively more common in subjects with chronic infarcts and white matter disease. Further brain MRI studies need to be performed to address the prevalence, pathogenesis, risk factors, neurological and cognitive outcomes of brain infarcts in at risk adolescent and adult thalassemia subjects for the prevention and development of therapeutic strategies.

No relevant conflicts of interest to declare.