Hereditary sideroblastic anemia with associated platelet abnormalities.
A 62 year old male (R.H.) presented with a mild anemia (Hb 11-12 gm%) and a history of multiple hemorrhagic episodes. The marrow had 40-50% sideroblasts. Marrow chromosomes were normal. His wife was hematologically normal, while one daughter, age 30 years, had a sideroblastic anemia (Hb 11-12 gm%) with 40-50% sideroblasts in the marrow. Her anemia was first noted at age 15 years. Administration of vitamin B6 did not correct the anemia in either the father or daughter. Platelet abnormalities inherited jointly with this disorder are described for the first time. Both R.H. and his daughter had prolonged bleeding times, with normal PTT, PT times, fVIII:C, fVIII:Ag levels, and vWF multimers, which may rule out a von Willebrand's disease. They have normal platelet numbers but abnormally low platelet adhesiveness and greatly depressed ADP, collagen, and epinephrine responsiveness. Response to ristocetin was in the low normal range, and aggregation with thrombin was normal. While desmopressin completely normalized R.H.'s bleeding time, none of these platelet parameters were improved. No differences in the SDS PAGE protein patterns of RH platelets could be detected in comparison to normal samples. His platelets took up and released serotonin (5HT) normally, and electron micrographs defined no morphological abnormalities. However, no ATP was released from platelets activated with collagen, and when followed by thrombin about fourfold greater ATP was released by control platelets as compared to RH platelets. The dense granule fraction derived from RH platelets contained about 20% the level of ATP, 40% the level of ADP, and 50% the level of 5HT detected in a normal sample. The results indicate that the bleeding disorder is related to a non-classical heritable storage pool defect. The connection between the inherited sideroblastic anemia and platelet defects is obscure.
Soslau
G
G
Department of Neoplastic Diseases, Hahnemann University, Philadelphia, PA 19102.
Brodsky
I
I
D000255:Adenosine Triphosphate / Q000097:blood; D000328:Adult; D000756:Anemia, Sideroblastic / Q000097:blood / Q000188:drug therapy / Q000235:genetics*; D001760:Bleeding Time; D001792:Blood Platelets / Q000502:physiology*; D003894:Deamino Arginine Vasopressin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D010973:Platelet Adhesiveness / Q000235:genetics; D010974:Platelet Aggregation / Q000187:drug effects; D010976:Platelet Count; D011736:Pyridoxine / Q000627:therapeutic use; D012701:Serotonin / Q000097:blood
D008565:Membrane Proteins; D012701:Serotonin; D000255:Adenosine Triphosphate; D003894:Deamino Arginine Vasopressin; D011736:Pyridoxine