Circulating microparticles are elevated in carriers of factor V Leiden.
BACKGROUND
Microparticles (MP) are small membrane bound cellular particles that play an important role in thrombosis. This study was carried out to evaluate if increased numbers or procoagulant potential of circulating MP contribute to the heterogeneity in occurrence of thrombosis in heterozygotes carrying Factor V Leiden (FVL) mutation.


METHODS
Levels of circulating platelet (CD41a), endothelial (CD62e) as well as leukocyte (CD45) derived MP from 45 FVL heterozygous individuals were enumerated by flow cytometry and compared with normal controls. Functional studies included enzyme linked immunoassay based prothrombinase activity (ELISA) and modified dilute Russell Viper venom test (DRVVT).


RESULTS
Circulating MP were significantly higher in the FVL cohort compared to the controls (median=2100 vs. 1508 MP/microl, respectively p=0.0021).All subsets of MP (platelet, endothelial and leukocyte) were significantly elevated in the FVL group, the most striking disparity seen in the number of CD45 positive leukocyte MP. Despite the differences in the number of MP between the controls and FVL cohorts, there was no significant difference in the prothrombinase activity recorded by the ELISA (2.0 vs 2.4 PS equivalents; p=0.7374) or clotting time assessed by the DRVVT (47 vs 46 sec, p=0.8118). When the FVL cohort was considered alone there was no significant difference in MP parameters between FVL subjects with or without a history of thrombosis.


CONCLUSIONS
This is the first study on circulating MP levels in subjects who are heterozygote for factor V Leiden. We report that circulating platelet and leukocyte MP are elevated in carriers of this mutation and may be important contributors to risk of thrombosis.
Enjeti
Anoop K
AK
Hunter Haematology Research Group, Calvary Mater Newcastle, Edith Street, Waratah, NSW 2298, Australia. Anoop.Enjeti@mater.health.nsw.gov.au
Lincz
Lisa F
LF
Scorgie
Fiona E
FE
Seldon
Michael
M
D020016:Activated Protein C Resistance / Q000097:blood* / Q000235:genetics; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000235:genetics; D001792:Blood Platelets / Q000378:metabolism*; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D019040:E-Selectin / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005165:Factor V / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D017493:Leukocyte Common Antigens / Q000097:blood; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009517:New South Wales; D010641:Phenotype; D040201:Platelet Membrane Glycoprotein IIb / Q000097:blood; D011517:Prothrombin Time; D013927:Thrombosis / Q000097:blood* / Q000235:genetics; D015854:Up-Regulation
D015415:Biomarkers; D019040:E-Selectin; D040201:Platelet Membrane Glycoprotein IIb; C095381:factor V Leiden; D005165:Factor V; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human