Fechtner syndrome: physiologic analysis of macrothrombocytopenia

Fechtner syndrome is a rare autosomal dominant disorder consisting of macrothrombocytopenia and leukocyte inclusions, associated with Alport's syndrome (hereditary nephropathy, sensorineural hearing loss, and ocular anomalies). We describe a 71-year-old Caucasian male with a history of hearing loss and asymptomatic macrothrombocytopenia incidentally noted in 1985. Several challenges to hemostasis were uneventful, including total hip arthroplasty. He subsequently developed progressive renal failure, with 'nil lesions' by light and electron microscopy, which was responsive to corticosteroid therapy. Eight family members are affected variably by either thrombocytopenia or renal failure. Laboratory testing gave the following results: hemoglobin, 10.2 g/dl; leukocytes, 5.0 x 109/l; platelets, 64 x 109/l (mean platelet volume, 13.3 fl; normal platelet volume, 7.6-10.8 fl). Peripheral blood smear revealed thrombocytopenia and leukocytes with inclusions. Electron microscopy of the buffy coat confirmed Fechtner inclusions within the patient's leukocytes. Whole mount and thin section electron microscopy revealed a population of large, although not giant, platelets. Despite thrombocytopenia, platelet aggregation was normal. Flow cytometry of dilute platelets revealed normal glycoprotein alphaII beta beta3 activation and alpha-granule p-selectin secretory response to 10 nmol/l human alpha-thrombin. Dense granule adenosine triphosphate secretory response to thrombin was likewise normal. This case illustrates that 'giant' platelets are not universally present in Fechtner syndrome cases, although the platelets are enlarged. Finally, renal pathology other than Alport's nephropathy may be associated with this syndrome.