Platelet Secretion Defects In Patients With Minimal Brain Dysfunction

Twelve MBD patients (P) with mucocutaneous bleeding diathesis (ages: 10-58 years, 11 females) had normal bleeding time, platelet count, activated PTT, PT and F-VIII activity. The mean threshold concentrations of ADP, epinephrine, collagen and ristocetin to elicit secondary aggregation or >20% secretion of preabsorbed ¹⁴C-serotonin in the patients’ platelet rich plasma (citrate) were normal. The aggregation response of gel-filtered platelets to 8uM divalent cationophore A23187 was markedly reduced (P=20.9 ± 6.6%, normal (N) = 61.4 ± 5.7%; p<0.001). The platelet contents of ATP, ADP, low-affinity platelet factor-4 (LA-PF₄), β-N-acetyl- glucosaminidase (β-N), β-glucuronidase (β-G), and α- mannosidase (α-M), were normal. However, secretion of ATP + ADP (P=31.1 ± 5.3%, N=51.5 ± 6.4%, p<0.05), β-N (P=6.1 ± 2.5%, N=29.8 ± 5.2%, p<0.001) and β-G (P=1.8 ± 1.1%, N=10.5 ± 2.6%, p<0.01) in response to centrifugation of unfixed A23187-treated platelets from patients was markedly impaired, while of LA-PF₄ and α-M was normal. Secretion with 0.1 u/ml thrombin was impaired for ATP + ADP, β-N and α-M; secretion of LA-PF₄ and β-G was normal. Liberation of pre-incorporated ¹⁴C-arachidonate from phospholipids by thrombin (0.05-5u/ml) and production of thromboxane B₂ during blood clotting were normal. Thus, platelets from these MBD patients have normal stores of secretable constituents and normal arachidonate pathway, but markedly impaired mechanism for dense granule and acid hydrolase secretion and impaired aggregation response to A23187, suggesting that impairment is in pathway common to aggregation and secretion. Similarity of secretion in platelets and other tissues, raises the question whether a defect in neuronal secretion is part of pathophysiology of MBD.