Dataset Information

Up-regulation of platelet activation in hemophilia A.

ABSTRACT:

Background

Platelets are an underappreciated factor in the classification of the bleeding tendency of patients with hemophilia. In this cross-sectional study, we investigated platelet activation status and responsiveness in relation to residual factor VIII activity and, within the group with severe hemophilia (<1% residual factor VIII activity), to annual factor VIII consumption.

Design and methods

Twenty-one patients with mild-moderate hemophilia A, 13 with severe hemophilia A and 21 healthy controls were studied. The basal level of platelet activation and platelet responsiveness to activation and inhibition were determined by the measurement of platelet P-selectin expression and soluble platelet activation markers.

Results

Patients with severe hemophilia A had a higher percentage of activated platelets at baseline (15.9%) when compared to patients with mild-moderate hemophilia A (8.2%, P=0.014) and controls (6.4%, P<0.001). Both patients with mild-moderate hemophilia A and those with severe hemophilia A had higher levels of the soluble platelet activation markers platelet factor 4 (1.4 and 1.8 pg/10(6) platelets), CXCL7 (65.8 and 48.2 pg/10(6) platelets) and RANTES (12.8 and 9.5 pg/10(6) platelets), compared to controls (platelet factor 4: 0.3 pg/10(6) platelets, P<0.001 and <0.001; CXCL7 20.0 pg/10(6) platelets, P<0.001 and <0.001; RANTES 4.5 pg/10(6) platelets, P<0.001 and =0.003, respectively). In support of these observations, we found clinical evidence that higher platelet P-selectin expression correlates with lower factor VIII consumption in patients with severe hemophilia (Spearman's r -0.65, P=0.043).

Conclusions

This study indicates that platelets from patients with severe hemophilia A are in a pre-activated state and that this pre-activated state is associated with factor VIII consumption.

SUBMITTER: van Bladel ER

PROVIDER: S-EPMC3105651 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Publications

Up-regulation of platelet activation in hemophilia A.

van Bladel Esther R ER Roest Mark M de Groot Philip G PG Schutgens Roger E G RE

Haematologica 20110321 6

<h4>Background</h4>Platelets are an underappreciated factor in the classification of the bleeding tendency of patients with hemophilia. In this cross-sectional study, we investigated platelet activation status and responsiveness in relation to residual factor VIII activity and, within the group with severe hemophilia (<1% residual factor VIII activity), to annual factor VIII consumption.<h4>Design and methods</h4>Twenty-one patients with mild-moderate hemophilia A, 13 with severe hemophilia A an ...[more]

PMID: 21422116

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Project description:BackgroundPrevious studies have shown that flow cytometry is a reliable test to quantify platelet function in stored platelet concentrates (PC). It is thought that flow cytometry is laborious and hence expensive. We have optimized the flow cytometry-based quantification of agonist induced platelet activation (PACT) to a labor, time and more cost-efficient test. Currently the quality of PCs is only monitored by visual inspection, because available assays are unreliable or too laborious for use in a clinical transfusion laboratory. Therefore, the PACT was applied to monitor PC activation during storage.Study design and methodsThe optimized PACT was used to monitor 5 PCs during 10 days of storage. In brief, optimized PACT uses a ready-to-use reaction mix, which is stable at -20°C. When needed, a test strip is thawed and platelet activation is initiated by mixing PC with PACT. PACT was based on the following agonists: adenosine diphosphate (ADP), collagen-related peptide (CRP) and thrombin receptor-activating peptide (TRAP-6). Platelet activation was measured as P-selectin expression. Light transmission aggregometry (LTA) was performed as a reference.ResultsBoth PACT and LTA showed platelet function decline during 10-day storage after stimulation with ADP and collagen/CRP; furthermore, PACT showed decreasing TRAP-induced activation. Major differences between the two tests are that PACT is able to measure the status of platelets in the absence of agonists, and it can differentiate between the number of activated platelets and the amount of activation, whereas LTA only measures aggregation in response to an agonist. Also, PACT is more time-efficient compared to LTA and allows high-throughput analysis.ConclusionPACT is an optimized platelet function test that can be used to monitor the activation of PCs. PACT has the same accuracy as LTA with regard to monitoring PCs, but it is superior to both LTA and conventional flow cytometry based tests with regard to labor-, time- and cost efficiency.

Dataset Information

Up-regulation of platelet activation in hemophilia A.

Background

Design and methods

Results

Conclusions

Publications

Up-regulation of platelet activation in hemophilia A.

Similar Datasets

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