A prospective study was undertaken to assess the values of platelet aggregometry, lymphocytotoxicity, and mixed lymphocyte cultures in selecting compatible donors for patients refractory to random platelet transfusions. Donors were selected at random without regard to HLA types. Concurrent with each platelet transfusion, platelet aggregometry and lymphocytotoxicity were performed using patient serum and donor cells. The results were compared with HLA types, MLC, and increments in platelet counts. Forty-one transfusions were given to 21 patients; 27 were from related and 14 from unrelated donors. Platelet aggregometry was used successfully in selecting compatible donors in 37 cases (90%) with three false negative and one false positive results. Lymphocytotoxicity was useful in 73 per cent of cases with eight false negative and three false positive results. The response to platelet transfusions correlated poorly with HLA matches or MLC reactions. These data suggest platelet aggregometry and lymphocytotoxicity are useful cross matching techniques in selection of compatible platelet donors.

Adolescent↗

PubMedDate not supplied

Alterations in human vascular endothelial cell function by oxygen free radicals. Platelet adherence and prostacyclin release.

This study was directed to the ability of oxygen free radicals to cause reversible vascular endothelial cell dysfunction. A well-characterized system for the production of the superoxide anion radical (O2(-).) and hydrogen peroxide (H2O2), employing xanthine and xanthine oxidase, was used to sublethally injure human umbilical vein endothelial (HUVE) cells in vitro. We examined the effects of a 15-minute incubation of HUVE cells with xanthine (50 microM) and xanthine oxidase (2.5-100 munits) on platelet adherence and prostacyclin (PGI2) release. All experiments were conducted in a serum-free N-(2-hydroxyethyl)piperazine-N'-(2-ethanesulfonic acid)-Tyrode buffer (pH 7.4) incubation system. Exposure of HUVE cells to sublethal concentrations of oxygen free radicals caused significant enhancement of platelet adherence (65 +/- 6.3%) to injured endothelium. A 12-fold increase in PGI2 release resulted after a 15-minute treatment with xanthine and xanthine oxidase. The addition of exogenous PGI2 (150 mM) to platelet-endothelial systems did not completely prevent the enhanced platelet adherence, suggesting that a lack of PGI2 was not completely responsible for the adherence of platelets to O2(-).-injured cells. When superoxide dismutase (SOD) and catalase, scavengers of O2(-). and H2O2, were added in combination to treated cells, platelet adherence decreased by 42-77% and PGI2 release approached that of control cultures. No decrease in either platelet adherence or PGI2 release occurred when chemically inactivated forms of SOD and catalase or bovine serum albumin were added to oxidant-treated cultures.

Catalase↗

PubMedDate not supplied

Arachidonic acid availability and prostacyclin production by cultured human endothelial cells.

When human umbilical vein endothelial cultures were grown in the presence of supplemental arachidonic acid, the cell phospholipids became enriched with arachidonic acid. Prostacyclin (PGI2) accumulated in the medium during supplementation with arachidonic acid. The capacity of these enriched cultures to produce PGI2 when subsequently incubated with either arachidonic acid or thrombin was reduced by as much as 90%, but release of arachidonic acid from the cell lipids in response to thrombin stimulation was not inhibited. Refractory cultures completely recovered the capacity to form PGI2 within 18 hours after removal of the medium containing supplemental arachidonic acid. However, recovery was prevented by cycloheximide. When enrichment with arachidonic acid was done in the presence of ibuprofen, a reversible cyclooxygenase inhibitor, PGI2 did not accumulate in the medium during supplementation, and the subsequent capacity of the cultures to produce PGI2 in response to thrombin increased by 70% to 240%. By contrast, the capacity of these supplemented cultures to convert added arachidonic acid to PGI2 did not increase. Therefore, the enhancement in thrombin-stimulated PGI2 production when the cultures are supplemented with arachidonic acid probably is due to the larger amount of arachidonic acid available in the intracellular lipid substrate pools, rather than to an activation of the PGI2 synthetic pathway. These findings suggest that changes in the arachidonic acid content of the endothelial cell lipids may modulate the capacity of the endothelium to produce PGI2 in response to stimulation.

Arachidonic Acid↗

PubMedDate not supplied

Diminished platelet adherence to type V collagen.

Different types of collagen vary in their influence on platelet reactivity. Collagen Types III, IV, and V were obtained from human placental tissue, and Type I collagen was prepared from rat skin. Each collagen type was coated onto a plastic surface. Each collagen-coated surface or appropriate plastic surface control was studied using citrated human 51Cr-labeled platelet-rich plasma in both the presence and absence of 10 microM adenosine 5'-diphosphate (ADP). Both unstimulated and ADP-induced platelet adherence were: 1) reduced by Type V collagen coating in comparison to uncoated wells; and 2) increased by Types III and IV collagen coating in comparison to Type V coated or plastic surfaces. Addition of the fast-acting thrombin inhibitor dansylarginine (DAPA) had no significant effect on unstimulated and ADP-induced platelet adherence to Type III, IV or V collagen-coated surfaces. Type I collagen-coated surfaces, studied only in the presence of DAPA, caused greater platelet adherence than those coated with Types III, IV, or V collagen. We conclude that Type V collagen may be less thrombogenic than Types, I, III, or IV.

Adenosine Diphosphate↗

PubMedDate not supplied

Increased platelet aggregates in patients with transient ischemic attacks.

In order to evaluate the pathogenetic importance of platelet aggregates in cerebrovascular disease, a platelet count ratio method was used to study 66 patients with transient ischemic attacks (TIAs). Thirty normal subjects and 22 patients without thromboembolic disorders were also included as controls. The mean platelet aggregate ratio of the TIA group was 0.75 +/- 0.03 SEM which was significantly lower than that of normal subjects (0.90 +/- 0.02) or patients controls (0.88 +/- 0.01) (P less than 0.01). Seventeen patients with TIA were then treated with aspirin (1,200 mg) and dipyridamole (200 mg) daily. The platelet aggregate ratios were normalized in 13 patients. Of four patients who did not respond to this regimen, one did respond to sulfinpyrazone. When sulfinpyrazone was discontinued, recurrence of symptoms was preceded by an increase in platelet aggregates. These findings suggest that platelet aggregates may play an important role in the pathogenesis of cerebrovascular insufficiency. The determination of platelet aggregates appears useful in selecting patients for antiplatelet therapy.

Adult↗

PubMedDate not supplied

XIV. Cerebral ischemia: the role of thrombosis and of antithrombotic therapy. Study group on antithrombotic therapy.

A revival of interest in antithrombotic agents for the treatment of ischemic cerebrovascular disease has resulted in the widespread use of oral anticoagulants for the prophylaxis and therapy of the ischemic variety of stroke, and has generated enthusiasm for the use of platelet-suppressant agents such as aspirin, dipyridamole, and sulfinpyrazone. In delineating the several clinical types of focal ischemic disease and outlining the causes of cerebral ischemia and infarction, the study group considers the problems of data interpretation in the face of inconsistent terminology. The basic mechanisms of hemostasis and thrombogenesis are concisely detailed. Finally, the study group critically reviews extensive earlier reports of clinical trials of anticoagulants, platelet function suppressants, and thrombolytic agents, and reassesses according to present-day statistical standards the significance of the results. The information contained in this report should familiarize the reader with sufficient data to permit him to utilize antithrombotic agents under a variety of circumstances and to appreciate the contraindications and potential dangers in their use.

Aged↗