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Is a decrease of microparticles related to improvement of hemostasis after FVIII injection in hemophilia A patients
F Mobarrez1, D Mikovic, A Antovic
1Division of Cardiovascular Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden. fariborz.mobarrez@ki.se
Background:
Microparticles (MPs) are small membrane vesicles (0.1-1 μm) released from various cells after activation and/or apoptosis. There are limited data about their role in hemophilia A.
Patients And Methods:
Blood samples were taken before and 30 min after FVIII injection in 18 patients with severe hemophilia A treated on demand. Flow-cytometric determination of total MPs (TMPs) using lactadherin, platelet MPs (PMPs) (CD42a), endothelial MPs (EMPs) (CD144) and leukocyte MPs (LMPs) (CD45) was performed. The results were compared with data on endogenous thrombin potential (ETP), overall hemostatic potential (OHP), fibrin gel permeability and thrombin-activatable fibrinolysis inhibitor (TAFI).
Results And Conclusions:
TMPs and PMPs decreased after treatment (to 1015 ± 221 [SEM] and 602 ± 134 × 10(6) L(-1) ) in comparison with values before treatment (2373 ± 618 and 1316 ± 331; P < 0.01). EMPs also decreased after treatment (78 ± 12 vs. 107 ± 13; P < 0.05) while LMPs were not influenced. Both TMP and PMP counts were inversely correlated, moderately but statistically significantly, with data on OHP, ETP, fibrin network permeability and TAFI/TAFIi (P < 0.05 for all). EMP counts were correlated only with ETP (P < 0.05), while LMP counts did not show any correlation. TMP and PMP counts were also inversely correlated with FVIII levels (P < 0.05). TMP, PMP and EMP counts decreased after on-demand treatment with FVIII concentrate in hemophilia A patients. The decrease in circulating MPs, which were inversely correlated with hemostatic activation, may imply that MPs are incorporated in the hemostatic plug formed after FVIII substitution at the site of injury.
Insights
Microparticle levels in hemophilia A patients significantly decreased after FVIII treatment, suggesting their role in clot formation. This finding offers new insights into hemophilia A pathophysiology and treatment.
Area of Science:
- Hematology
- Hemostasis and Thrombosis
- Cell Biology
Background:
- Microparticles (MPs) are cell-derived vesicles implicated in various physiological and pathological processes.
- Limited data exist regarding the specific role of MPs in hemophilia A, a genetic bleeding disorder.
Purpose of the Study:
- To investigate the levels and behavior of different MP populations in severe hemophilia A patients undergoing on-demand treatment with Factor VIII (FVIII).
- To explore the correlation between MP levels and markers of hemostatic activation.
Main Methods:
- Flow cytometry was used to quantify total MPs (TMPs), platelet MPs (PMPs), endothelial MPs (EMPs), and leukocyte MPs (LMPs) before and after FVIII injection in 18 severe hemophilia A patients.
- MP levels were compared with endogenous thrombin potential (ETP), overall hemostatic potential (OHP), fibrin gel permeability, and TAFI levels.
Main Results:
- Circulating TMPs and PMPs significantly decreased post-FVIII treatment, as did EMPs, while LMPs remained unchanged.
- TMP and PMP levels showed significant inverse correlations with OHP, ETP, fibrin network permeability, TAFI, and FVIII levels.
- EMP levels correlated with ETP, but LMP levels did not correlate with any hemostatic markers.
Conclusions:
- On-demand FVIII treatment in hemophilia A patients leads to a reduction in circulating TMPs, PMPs, and EMPs.
- The inverse correlation between MP counts and hemostatic activation markers suggests MPs may be incorporated into the hemostatic plug at the site of injury following FVIII substitution.
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