Effect of Anti-Platelet Antibodies on the in Vitro Uptake of 5-Hydroxytryptamine by Blood Platelets

206

A B S T R A C T Formation of lipid peroxides rises sharply when platelets undergo the release reaction. In this study the in vitro effect of vitamin E on platelet aggregation was investigated. a-Tocopherol, an antioxidant of known inhibitory action on lipid peroxidation, was added to platelet suspensions in concentrations up to 1.5 mM. A dose-dependent reduction in platelet aggregation was observed, with complete inhibition of the secondary wave of aggregation at > 0.9 mM atocopherol. The inhibitory effect of a-tocopherol on the platelet release reaction was further documented by the decrease in aggregation-induced release of [14C]5-hydroxytryptamine from prelabeled platelets and by the reduction of N-acetylglucosaminidase activity released into the medium. The sharp rise in lipid peroxides normally associated with platelet aggregation was markedly reduced by a-tocopherol and also by acetylsalicylic acid, a known inhibitor of the platelet release reaction.In vivo studies examined the effect of oral vitamin E administration (1,200-2,400 IU daily) on plasma and platelet levels of a-tocopherol. Up to 1,800 IU daily, increasing dosages of vitamin E resulted in increasing concentrations of a-tocopherol in plasma and platelets, but intake of vitamin E in excess of this dosage failed to show any further increase in plasma or platelet levels.

Section: Methodsmentioning

confidence: 99%

Vitamin E. An inhibitor of the platelet release reaction.

Steiner¹,

Anastasi²

1976

206

“…In 1963, Bridges, Baldini, Fichera, and Dameshek evaluated the inhibition of [14C]serotonin uptake by human platelets as a means of detecting platelet isoantibodies (18). All sera from four multitransfused patients showed suppression of serotonin uptake into unmatched donor platelets but not into their own platelets.…”

Section: Introductionmentioning

confidence: 99%

Detection of platelet isoantibodies by (3H)serotonin platelet release and its clinical application to the problem of platelet matching.

Gockerman¹,

Bowman²,

Conrad³

1975

A B S T R A C T The detection of platelet isoantibodies by the release of ['H]serotonin from platelets has been evaluated. The conditions for optimal release of ['H]serotonin with platelet isoantibodies using a microtechnique have been defined. A group of cardiac surgery patients were followed pre-and post-transfusions, with 48% developing a positive serotonin release assay. Of these patients, 16% also had a platelet complement-fixing and/or lymphocytotoxic isoantibody. There was variation in the degree of correlation between ['H]serotonin release and lymphocytotoxicity using individual National Institutes of Health typing serum. The matching obtained between family members by both techniques showed a close correlation when each technique was evaluated separately using the same NIH typing serum. The detection of isoantibodies in patients with hematological malignancies correlated with the unresponsiveness to unmatched platelet transfusions in 15 out of 17 cases. The use of the patient's isoantibody to matched platelets of family members by ['H]serotonin release correlated well with the clinical response to transfusion with these platelets. The data suggest that (a) platelet isoantibodies can be

“…Unfortunately, these tests, while simple to perform, are relatively insensitive. More sensitive testscomplement fixation (4,7,13), antiglobulin consumption (4, 7), platelet factor 3 activation (10,14), and inhibition of serotonin uptake or release of serotonin and 51Cr from platelets (15,16)-are highly specialized, and are not readily available in most clinical laboratories.…”

Section: Introductionmentioning

confidence: 99%

“…Further, the widespread use of platelet transfusions has emphasized the importance of isoimmune antiplatelet antibodies in determining the survival of infused platelets (1). Not surprisingly, a variety of techniques have been utilized to detect drug-induced and isoimmune antiplate-let antibodies (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). These include direct visual assays such as observation of platelet lysis (2)(3)(4)(5), platelet agglutination, (6)(7)(8)(9)(10), and inhibition of clot retraction (3,11,12).…”

Section: Introductionmentioning

confidence: 99%

The Assessment of Drug-Dependent and Isoimmune Antiplatelet Antibodies by the Use of Platelet Aggregometry

Deykin¹,

Hellerstein²

1972

A B S T R A C T The technique of platelet aggregometry provides a simple, quantitative, and specific method for the detection of drug-dependent and isoimmune antiplatelet antibodies. In the presence of antiquinidine antibody, quinidine causes lysis of normal platelets in platelet-rich plasma. The resulting changes in optical density are readily detected in the aggregometer. The initial rate of lysis is a function of the antibody titer, but is relatively independent of the platelet count. In vitro, quinidine produces platelet swelling and inhibits aggregation of platelets by adenosine diphosphate, epinephrine, and collagen. Isoimmune antibodies cause aggregation of platelets in platelet-rich plasma. In studies of a single family the rate of aggregation is proportional to the number of HL-A antigens present on the normal platelets against which the antibody is directed. The simple technique of platelet aggregometry may be a useful adjunct in the selection of compatible donors for platelet transfusion. Serumn derived from patients with idiopathic thromboytopenic purpura did not cause platelet aggregation.