Platelets are believed to play a role in the pathogenesis of atherosclerosis and of the vascular obstruction that causes the acute complications of coronary artery disease. Since specific behavioral patterns appear to be related to the development of coronary artery disease and since emotional stress may predispose an individual to acute cardiovascular ischemia, it was hypothesized that platelet activation by catecholamines might be involved in these events. To study emotional stress, plasma samples were obtained from 61 senior medical residents immediately before they were to speak in public. There were significant increases in the plasma concentrations of the platelet-secreted proteins platelet factor 4 and ,B-thromboglobulin and epinephrine and norepinephrine immediately before speaking, which demonstrates that platelet activation and secretion occur in association with this type of emotional stress. Four trials were carried out to study the mechanism for this observed platelet secretion: (1) phenoxybenzamine, (2) propranolol, (3) 650 mg aspirin, and (4) 80 mg aspirin were given several hours before the public speaking engagement. Neither phenoxybenzamine nor propranolol in doses that blocked the hemodynamic effects of a,-and 3,1-adrenergic stimulation modified platelet secretion. Aspirin also did not block platelet secretion, which suggests that platelets were not being stimulated through a cyclooxygenase-dependent pathway. This study provides direct evidence of platelet secretion in vivo in association with emotional stress, and underscores the potential importance of platelet activation and secretion in the acute events that occur in patients with vascular disease.

We conducted a randomized clinical trial in adults with a new diagnosis of ITP and a platelet count <30,000/mL to test the hypothesis that initial intermittent treatment with anti-D may avoid or defer the need for splenectomy when compared to current routine care (glucocorticoid treatment, followed by splenectomy). Splenectomy was to be performed in the anti-D group if patients failed to respond to three consecutive anti-D treatments given within 10 days. The incidences of splenectomy were 14 of 37 (38%) in the routine care group and 14 of 33 (42%) in the anti-D group (absolute risk reduction = 4.6% in favor of the routine care group, 95% CI, -18.4 to 27.6%). However, splenectomy was performed prematurely, not according to the protocol, in 11 of 14 patients in the anti-D group. The median time to splenectomy was 36 days (range, 9-78) in the routine care group and 112 days (range, 19-558) in the anti-D group (P = 0.045 at 100 days after randomization, P = 0.840 at 1 year after randomization, using log-rank analysis). Patients in the anti-D group were treated with prednisone for fewer days (70 days) compared to the routine care group (112 days, P = 0.01). No major bleeding events occurred. In this study, initial treatment of patients with intermittent anti-D initially deferred splenectomy. Whether our aggressive regimen of anti-D could have prevented splenectomy if it had been adhered to in all patients remains uncertain. However, compliance with this anti-D regimen was not feasible for many patients and/or their physicians. Am.

Ten patients scheduled to receive intensive chemotherapy were plateletapheresed and the platelet-rich plasma was frozen with 5 percent dimethyl sulfoxide at -80 to -95 degrees C until needed. Paired comparisons of frozen autologous platelets with fresh single-donor platelets were made in seven patients using corrected platelet increments at 1 and 24 hours, and pre- and posttransfusion bleeding times. In vitro tests of 12 units of platelet-rich plasma before and after freezing included platelet factor 4 (PF4) secretion, malondialdehyde production, and electron microscopic evaluation of morphology. Fresh platelets provided significantly better 1- and 24-hour corrected increments compared with frozen autologous platelets. In only one case of alloimmunization did frozen autologous platelets provide a better increment than fresh platelets. Bleeding times after transfusion showed no consistent improvement regardless of type of transfusion or platelet count. Secretable PF4 remained constant after freezing, but malondialdehyde production fell significantly. Platelets showed considerable structural damage with 33 percent balloon forms counted after thawing, compared to less than 1 percent before freezing. Except in the case of alloimmunization, frozen autologous platelets are inferior to single-donor fresh platelets, and are significantly damaged in the freezing process.

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