A Qualitative Platelet Defect in Severe Vitamin B12 Deficiency Response, Hyperresponse, and Thrombosis After

Three patients with vitamin B12 deficiency had profound qualitative platelet abnormalities: lack of secondary aggregation (release reaction) with ADP stimulation, total lack of aggregation in response to standard amounts of epinephrine or collagen, and, in two patients, bleeding times of more than 20 minutes. Vitamin B12 therapy corrected all these defects. Serial studies, after vitamin B12 administration, showed increased platelet aggregation response in two of the patients, when compared with 60 healthy controls. All three developed increased platelet factor 3 availability. One patient developed evidence of arterial and venous thrombi at this time, with no thrombocytosis. A retrospective chart review suggests that thrombotic episodes during recovery from vitamin B12 deficiency are not rare. The platelet apparently is one of the cells of the body that are susceptible to metabolic abnormality in severe vitamin B12 deficiency. Platelet function may be extremely important in the pathogenesis of both hemorrhage and thrombosis. IN 1943 MINOT AND STRAUSS (1) commented on the response of erythrocytes, leukocytes, and platelets to parenteral liver extract in pernicious anemia. They observed that "venous thromboses occasionally occur coincident with the response of the three formed bone marrow elements. " Smith, Smith, and Fletcher (2) subsequently studied the therapeutic response to vitamin B i 2 in a group of nine patients with thrombo-cytopenia caused by pernicious anemia. Interestingly