Symptomatic myelodysplasia with normal blood counts: a diagnostic enigma complicating the management of a patient with severe platelet dysfunction

As a rule, myelodysplastic syndromes (MDS) are accompanied by peripheral cytopenia in one or more cell lineages [1]. Platelet function defects (PFDs) are frequently seen in MDS, but usually only cause mild bleeding symptoms [2,3]. We report for the fi rst time a case of MDS that manifested as a clinically severe and initially unexplained PFD with completely normal blood counts. Th e diagnosis of MDS was made retrospectively, after the patient had gradually progressed toward refractory thrombocytopenia with minimal dysplastic features, and fi nally acute myeloid leukemia (AML). Th is is a case of a 56-year-old man who presented with a 6-year history of recurrent rectal blood loss for which he was admitted to our hospital on several occasions. Multiple colonoscopies and gastroscopies could fi nd no clear cause aside from the presence of internal hemorrhoids, for which he was surgically treated. Th is intervention, however, had very little impact on his symptoms. Th e patient reported a recently developed bleeding trend, presenting as recurrent epistaxis, for which cauterization was needed on two occasions, as well as a tendency to develop cutaneous purpura. Th ere was no family history of a bleeding disorder. In between hemorrhagic episodes, complete blood counts and clotting studies, including von Willebrand factor antigen and activity tests, were unremarkable. Kidney and functional liver tests as well as serum protein electrophoresis revealed no abnormalities. Th ere were no signs of increased fi brinolysis (D-dimers 476 μ g/L). Platelet light transmission aggregometry was disturbed with all tested agonists: the aggregation response to adenosine diphosphate, collagen and ristocetin was 35%, 47% and 60%, respectively; there was a strikingly absent response to arachidonic acid. A possible impact of medication was excluded by repeated analysis under controlled circumstances. Due to the lack of any bleeding diathesis in the patient ’ s history, a genetic defect was unlikely. Any plausible explanation for the fi ndings could not be found at that point, and hence the patient was treated symptomatically with frequent erythrocyte transfusions and tranexamic acid, having very little impact on the bleeding frequency. Six years after the first symptoms appeared, the patient developed an isolated thrombocytopenia: hemoglobin concentration 13.4 g/dL, red cell count 4.6 10 12 /L, mean corpuscular volume 90.7 fL, platelet count 95 10 9 /L, white cell count 11.6 10 9 /L. A blood film showed the presence of giant platelets. Hemorrhagic incidents became more common: over a period of 2 years the patient was hospitalized five times because of massive rectorrhagia for which transfusion of red blood cells was frequently mandatory. Endoscopic and colonoscopic investigations were again unremarkable except for the sporadic detection of small arteriovascular malformations. These lesions were difficult to observe because of persistent bleeding and blood clots in the gastrointestinal tract. Both angiography and Meckel scan were negative. Thrombocytopenia and the appearance of large platelets prompted the diagnosis of idiopathic thrombocytopenic purpura (ITP). A bone marrow aspirate revealed an increased number of megakaryocytes, lacking any other significant abnormalities. This finding supported the diagnosis of ITP. The patient was treated with corticosteroids, inducing a modest but only temporary response of platelet count and bleeding. Tranexamic acid was able to stop the blood loss for a brief period, but the patient quickly relapsed despite increasing the dosage. Ultimately, donor platelets were administered at a regular interval, with a good impact on the symptoms. Th is patient ’ s case was put up for reevaluation when cytogenetic analysis of the bone marrow revealed the presence of trisomy 21 as the sole karyotypic abnormality, present in 15 of 20 analyzed metaphases. Th is very rare acquired chromosomal aberration has sporadically been