Clinical depression has been proposed to be an independent risk factor for cardiovascular disease. While it is suggested that selective serotonin reuptake inhibitors (SSRIs) reduce the risk of acute cardiovascular problems of depressed patients, the effect of SSRIs on platelets, the only blood cells committed to serotonin (5-HT) transport, remains largely unknown. The goal of this pilot study was to measure the 5-HT levels in platelets of untreated and SSRI-treated depressed patients and normal subjects and to determine whether the interaction of SSRIs with platelets can explain their possible cardiovascular benefit in patients with depression. Platelet 5-HT was determined by an immunocytochemical assay and high-pressure liquid chromatography with electrochemical detection (HPLC-ECD). In normal control subjects without cardiovascular disease, 78 +/- 8% of platelets were 5-HT-positive (n = 14). Depression caused a significant reduction in platelet 5-HT to 46 +/- 21% in untreated patients (n = 13) and 22 +/- 13% in SSRI-treated patients (n = 14). As a class, all selective serotonin reuptake inhibitors significantly reduced the 5-HT concentration in patient platelets. An inverse relationship of 5-HT level and dose of medication might be suggested. These results correlated well with 5-HT data from HPLC (r = 0.8509, p < 0.001). SSRIs did not affect platelet aggregation and dense granule release in response to thrombin, but significantly reduced ADP-induced platelet aggregation and dense granule release in both patient and normal control samples. The active inhibition of platelet aggregation by SSRIs might explain their cardiovascular benefit.
BACKGROUND:A reduced response to aspirin and clopidogrel predicts ischemic events, but reliable tests are needed to identify low responders. We compared 3 platelet-function tests during long-term dual treatment with aspirin and clopidogrel.
In this pilot study, the ThromboLUX score strongly correlated with transfusion outcome (PLT recovery and survival) independent of clinical and product issues.
Bleeding problems are symptomatic of platelet delta-storage pool diseases (SPDs) such as Hermansky-Pudlak syndrome. Although at present no cure is available for delta-SPD, early diagnosis is of great importance for prophylactic and supportive treatment. This study tested the usefulness of a flow cytometric assay for platelet serotonin in children. The assay was used to diagnose delta-SPD in a 10-year-old girl. Platelet serotonin levels were significantly lower in the patient than in all healthy control subjects (10 children and 10 adults). The serotonin results were supported by traditional tests, which are transmission electron microscopy of whole mounts and adenosine triphosphate release by lumi-aggregometry. The flow cytometric serotonin assay is a major improvement to current pediatric diagnostics. The advantages of this test are small sample volume of fresh or fixed/frozen platelets, availability of objective results within 2 hours of obtaining the blood sample, and automated analysis by flow cytometry.
Familial bleeding problems are frequently difficult to diagnose because currently used clinical tests cannot identify intracellular molecular defects of platelets. Using platelet proteomics, a comprehensive analytical tool, we diagnosed a family with severe bleeding problems of unknown origin with Quebec Platelet Disorder. Prior to proteomic analysis, we determined platelet counts, presence of glycoprotein (GP) Ib and GPIIb/IIIa, platelet aggregation, dense granule content and release, plasma levels of fibrinogen, Factor XIII and fibrin degradation products in four family members. Abnormalities were detected in platelet aggregation studies, which revealed variably reduced responses to ADP, collagen and epinephrine with concomitantly decreased ATP/serotonin secretion. In addition, D-dimer levels were significantly elevated 72 hours after in vitro thrombin stimulation of platelet-rich plasma. Together with the autosomal dominant inheritance and the delayed onset of bleeding in two of the four patients these results did not support any known platelet disorder. Therefore, the proteome of platelet lysates separated by one-dimensional SDS-PAGE was analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Platelet proteomics showed reduced amounts of alpha-granule proteins multimerin, fibrinogen and thrombospondin-1 in patient compared to control samples suggestive of Quebec Platelet Disorder. The diagnosis of Quebec Platelet Disorder was confirmed by urokinase-specific Western blots. Urokinase causes the degradation of alpha-granule proteins in this disorder. Diagnosis of rare bleeding disorders has important implications for prophylactic and acute treatment of bleeding patients. This is the first report using proteomics to identify a familial platelet defect.
Thrombocytopenic patients with acute leukemia may show high post-transfusion count increments that significantly exceed the number of transfused platelets. This study demonstrates that the automated hematology analyzer Sysmex XE-2100 reports erroneously high optical platelet counts when the blood sample contains particles in the size range of platelets or smaller. Thrombocytopenic or low-normal whole blood samples were spiked with 1 mum latex beads (n = 14) to mimic contaminants under controlled conditions. Optical and impedance measurements of spiked and control samples with the Sysmex XE-2100 were compared with the Advia 120 and the manual counts. The added beads unexpectedly increased the automated optical platelet counts in the Sysmex XE-2100 and, to a lesser extent, the Advia 120 (Wilcoxon signed ranks test, P < 0.05), while the beads were not included in the impedance or the manual microscopic platelet counts. Differential interference contrast microscopy was used to investigate samples from platelet concentrates for transfusion. Platelet concentrates (32/128) were identified as possible sources for particles that were microscopically distinct from platelets but would be included in the automated optical count. Transfusion of platelet concentrates containing contaminating particles can lead to unexpectedly high post-transfusion platelet counts and misdiagnosis of thrombocytopenic patients.
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