Biomedical subjects
Publications and source records attributed to G Pfliegler.
Authors survey the most significant haemostatic complications (thrombocytopenia, DIC, vasculitis, thrombotic microangiopathy) as well as their immune and non-immune pathogenesis in infectious diseases. A short summary of therapeutic facilities and the infectious hazards of blood component therapy is also given.
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The protein C activity assay of Francis and Patch (Thromb Res 1983; 32: 605-613) is based on the prolongation of the activated partial thromboplastin time in the presence of activated protein C isolated from the test samples. The assay was modified and standardized by Rapaport et al. (Am J Clin Pathol 1987; 87: 491-497), but could still only be used in patients on heparin therapy after chromatographic removal of the heparin. In this study we attempted to eliminate the heparin separation step without losing the advantages of the modified (Rapaport) method. Heparin was added to the isolated protein C to obtain a rapid and complete antithrombin effect after the thrombin activation step and polybrene was subsequently used to neutralize the excess heparin. Using this modified assay protein C activity ranged from 67 to 133% in the normal population, and from 9 to 25% in coumarin-treated patients. Precision of the modified method was acceptable in both normal and pathological PC ranges: within- and between-batch variations were 5.6 and 3.6%, and 8 and 14%, respectively. The assay correlated well (r = 0.84) with the ELISA technique in both healthy donors and non-coumarin-treated patients.
Thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome have quite uniform or identical histopathological features and share very similar clinical characteristics, so thrombotic microangiopathy may be used as a common descriptive term of the two syndromes. During the past one and a half year five patients with thrombotic microangiopathy, receiving plasma therapy were observed by the authors. Owing to the early, correct diagnosis and plasma administration four patients had been recovered from the disease. The evaluation of clinical signs and symptoms, altogether with some simple laboratory data (megakaryocytic thrombocytopenia, nonimmune acquired haemolytic anaemia, renal insufficiency, neurologic alterations, etc.) remained essential in the recognition and treatment of thrombotic microangiopathy. After giving a short review of the literature the authors deal with the results of some more specific examinations (prostanoids, beta-thromboglobulin, the quantitative and qualitative analysis of Willebrand factor, etc.) which may give further data to the complex aetiopathogenesis of thrombotic microangiopathy.
A 47 year old woman is reported who had life-threatening bleeding due to the spontaneous development of factor VIII:C inhibitor. Cyclosporin combined with prednisone resulted in a full recovery and complete elimination of antibody even when other therapeutic facilities failed to be effective.
A 34-year-old woman with congenital factor XIII (FXIII) deficiency and multiple connective tissue tumours is reported. The subunit a of FXIII was totally absent in her plasma, platelets and histiocytes of breast fibroadenomas and considerably reduced in the monocytes (below 5%). The plasmatic level of subunit b was also reduced (25%). She had a bleeding tendency and habitual abortions. Fresh frozen plasma therapy permitted a successful pregnancy.
A direct demonstration and partial characterization of the insulin receptor on human platelets was obtained by immunoprecipitation with a monoclonal antibody against the human insulin receptor. Two subunits were detected, one with a MW of 95 KD, which dose-dependently was phosphorylated upon challenge of the platelets with insulin and another with a MW of 69 KD that does not become phosphorylated. Retention on wheat germ agglutinin indicates that at least part of the receptor protein is glycosylated. In a search for cellular effects provoked by insulin on platelets, no changes could be detected in cAMP formation or degradation, inositol phosphate formation or phosphorylation of proteins other than the receptor itself.
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Using intact human platelets, we studied the effect of sodium fluoride (NaF) on platelet aggregation and release reaction and correlated the functional changes to intracellular events specific for either agonist-induced or antagonist-induced platelet responses. At lower concentrations, with a peak activity between 30 and 40 mmol/L, NaF induced aggregation and release of adenosine 5'-triphosphate (ATP) that was associated with increased formation of inositol phosphates, a rise in cytosolic free Ca2+, and phosphorylation of 20-kd and 40-kd proteins. At NaF concentrations greater than 40 mmol/L, aggregation and ATP release decreased dose-dependently in parallel with a decrease in Ca2+ mobilization, whereas neither inositol phosphate formation nor 40-kd protein phosphorylation was reduced. At these concentrations, NaF caused a dose-dependent transient rise in platelet cyclic adenosine 3',5'-monophosphate (cAMP) levels that was sufficient to account for the observed reduction in Ca2+ mobilization, aggregation, and ATP release. Stimulated cAMP levels started declining rapidly within 30 seconds of addition of NaF, however. Similarly, prostacyclin (PGI2)-induced cAMP accumulation was temporarily enhanced but subsequently suppressed by NaF, suggesting either stimulation of a cAMP phosphodiesterase or delayed inhibition of adenylate cyclase. Evidence for the latter was provided by the finding that NaF pretreatment of platelets resulted in partial inhibition of PGI2-stimulated cAMP formation in the presence of the cAMP phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (MIX). We conclude that NaF exerts a dual (stimulatory and inhibitory) effect on adenylate cyclase in intact platelets that is accompanied by simultaneous activation of a phosphoinositide-specific phospholipase C; in addition, a cAMP phosphodiesterase may be activated.
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Platelet functions were studied in 64 patients with various myeloproliferative diseases. The characteristic alterations were prolonged bleeding time, decreased platelet aggregation (but normal results induced by ristomycin), elevated level of BTG, high production of MDA, increased level of TXB2 with almost normal level of 6-keto-PGF1. However, considering the bleeding time and the amount of BTG in relation to the whole blood platelet count, no differences could be detected.
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The platelet membrane insulin receptors of healthy and non-insulin dependent (type 2) diabetic patients were studied. Receptor number and affinity proved to be decreased in type 2 diabetes mellitus. The changes in platelet insulin receptor characteristics are in good correlation with the alterations reported in other tissues or cells. The possible role of these phenomena in the pathogenesis of disturbed platelet function in diabetics needs further investigation.