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DIOPATHIC thrombocytopenic purpura (ITP, also I known as primary immune thrombocytopenic purpura) is a hematologic disorder for which appropriate diagnostic and treatment strategies are uncertain. In 1994, the American Society of Hematology (ASH) established a panel to produce explicitly developed practice guidelines for the diagnosis and management of ITP. "Explicitly developed," evidencebased practice guidelines, which are being issued increasingly by medical specialty societies, combine a critical appraisal of scientific evidence with practice recommendations that state clearly to what extent the guidelines are based either on published scientific evidence or opinion (eg, clinical experience).I4 More details about the clinical practice guideline movement are provided elsewhere.'.' This report begins with a brief summary of the panel's recommendations, followed by a more detailed analysis of its methodology, the findings of the comprehensive literature review, and a full presentation of the recommendations. The report concludes with recommendations for future research. As explained later, the recommendations are based on the panel's opinion, derived from a systematic scoring methodology. (Only recommendations receiving scores of 1 .O to 3.0 or 7.0 to 9.0, as defined later in the text, are cited in this summary.)

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.

Methods have been developed to isolate human platelet membrane fragments from plasma and serum. Rabbit antibody produced against the human platelet membrane glycoprotein complex, IIb/IIIa, was utilized in an immunoelectrophoretic assay to evaluate the amount of this antigen in various microparticle preparations. The serum concentration of platelet microparticles was more than tenfold greater than that observed for plasma (65 micrograms/ml versus 4.4 micrograms/ml, respectively). Ultrastructural evaluation of either plasma or serum- derived microparticles disclosed a variety of membrane fragments and membrane-bound vesicles with occasional fragments of red blood cells, white blood cells, and platelets. In contrast, microparticle preparations derived from isolated washed platelets after thrombin stimulation contained a heterogeneous array of membrane fragments, vesicles, and granules but no identifiable red cell, white cell, or platelet fragments. Thus, these studies demonstrate that normal human plasma and serum contain platelet membrane fragments that are produced during cell activation. If a similar loss of platelet membranes occurs in vivo following reversible platelet activation, it is possible that the resulting membrane modifications may be of importance in both the structural and functional changes that develop during platelet senescence.

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