Fechtner syndrome: physiologic analysis of macrothrombocytopenia

Fechtner syndrome is a rare autosomal dominant disorder consisting of macro thrombocytopenia and leukocyte inclusions, associated with Alport's syndrom e (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 ther apy. 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 10(9)/l; platelets, 64 x 10(9)/l (mean plate let volume, 13.3 fl; normal platelet volume, 7.6-10.8 fl). Peripheral blood smear revealed thrombocytopenia and leukocytes with inclusions. Electron m icroscopy of the buffy coat confirmed Fechtner inclusions within the patien t's leukocytes. Whole mount and thin section electron microscopy revealed a population of large, although not giant, platelets. Despite thrombocytopen ia, platelet aggregation was normal. Flow cytometry of dilute platelets rev ealed normal glycoprotein alpha(II beta)beta(3) activation and alpha-granul e p-selectin secretory response to 10 nmol/l human alpha-thrombin. Dense gr anule adenosine triphosphate secretory response to thrombin was likewise no rmal. This case illustrates that 'giant' platelets are not universally pres ent in Fechtner syndrome cases, although the platelets are enlarged. Finall y, renal pathology other than Alport's nephropathy may be associated with t his syndrome. Blood Coagul Fibrinolysis 11:243-247 (C) 2000 Lippincott Will iams & Wilkins.