Clinical Chemistry
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Clinical Chemistry 50: 677-678, 2004; 10.1373/clinchem.2003.029314
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(Clinical Chemistry. 2004;50:677-678.)
© 2004 American Association for Clinical Chemistry, Inc.


Letters to the Editor

Factor V Leiden in Blood Donors in Baghdad (Iraq)

Nasir A. Al-Allawi1,a, Jaladet M.S. Jubrael2 and Ferial A. Hilmi1

1 Department of Pathology, College of Medicine, and 2 Department of Molecular Biology, College of Science, University of Baghdad, Baghdad, Iraq

aAuthor for correspondence: Department of Pathology, College of Medicine, University of Baghdad, Bab-Almuaddem, Baghdad, Iraq. E-mail nallawi{at}yahoo.com; secondary e-mail nasirallawi{at}hotmail.com.


To the Editor:

Human coagulation factor V is a 330-kDa single-chain glycoprotein that plays an important role in the coagulation pathway. After its activation by thrombin and factor Xa, activated factor V (Va) forms an essential part of the prothrombinase complex, which catalyzes the conversion of prothrombin to thrombin in the presence of calcium and a phospholipid membrane (1). Activated protein C (APC) inactivates factor Va and requires factor V as a cofactor in the APC-mediated inactivation of factor VIII (1)(2). Resistance to APC action leads to increased risk of thrombosis and is mostly attributable to a single point mutation in the factor V gene (factor V Leiden) with a G-to-A substitution at nucleotide 1691 (3).

Several studies have demonstrated the high prevalence of factor V Leiden in some Middle Eastern countries, with suggestions that the eastern Mediterranean basin maybe the site where this mutation arose ~21 000–34 000 years ago (4)(5). Despite the fact that Iraq lies within this region, no such prevalence studies have been reported on the incidence of factor V Leiden in that country. We report here the results of the first such study.

Between September 21, 2002, and February 22, 2003, we evaluated a total of 100 blood donors attending the national blood bank, the only blood-banking facility serving the population of Baghdad City and the surrounding regions in central Iraq. Samples were collected, through venipunctures separate from those used for donation, from 10 donors randomly selected by use of random numbers (between 1 and 40, generated for each day) from among the first 40 attending the bank on 10 alternate Saturdays throughout the study. During the first nine collection sessions, one randomly selected donor declined participation, and one sample was hemolyzed; therefore, on the last session, 12 random samples were taken. The study was approved by the Council of the College of Medicine-University of Baghdad, and informed consent was obtained from all donors evaluated.

All included patients were males, consistent with the donation pattern in Iraq, with ages ranging from 18 to 52 years (median, 30.5 years). A second-generation APC resistance test was performed on all included patients with a STACLOT® APC-R reagent set (Diagnostica Stago) with modifications; 100 µL of prediluted test plasma (1:10 in factor V-deficient plasma) was incubated for exactly 3 min at 37 °C with 100 µL of Crotalus viridius helleri venom, after which 100 µL of APC/calcium chloride was added, and the clotting time was recorded. The clotting times ranged from 39 to 111 s, with a mean (SD) of 70.4 (13.5) s. The cutoff point for "resistant" cases was 48 s as determined by logarithmic transformation of clotting times, after exclusion of outliers (>3 SD above or below the mean) and calculation of the mean - 1.96 SD. All included donors had their DNA extracted, amplified, hybridized to wild- and mutant-type DNA probes, and detected by enzyme immunoassay according to the instructions of the manufacturer (ViennaLab).

Four cases (4%) were below the calculated cutoff point of the second-generation APC test and were thus considered resistant. Three cases (3%) were found to be heterozygous for factor V Leiden by DNA studies (all of whom were APC resistant with clotting times of 43, 45, and 48 s). The remaining case, resistant by second-generation APC resistance tests (clotting time, 39 s) was a noncarrier of factor V Leiden, This may indicate that an alternative mutation involving the factor V gene maybe responsible for APC resistance in this particular case (6).

The prevalence rate of 3% in Iraqi blood donors, although it is much lower than the prevalence rates of 14.2%, 13.6%, and 12.25% reported in Lebanon, Syria, and Jordan, respectively (4)(7), and to a lesser extent than the rates in Turkey (7.4%) (8) and Iran (5.5%)(9), is comparable to the prevalence of 2.5% reported in Saudi Arabia (10). The latter may be related to a common origin and closer links between the population of Iraq (including Baghdad) and that of the Arabian Peninsula throughout history.


References

  1. Nicolaes GAF, Dahlback B. Factor V and thrombotic disease. Description of a Janus-faced protein. Arterioscler Thromb 2002;22:530-538.[Abstract/Free Full Text]
  2. Varadi K, Rosing J, Tans G, Pabinger I, Keil B, Schwarz HP. Factor V enhances the cofactor function of protein S in the APC mediated inactivation of factor VIII: influence of factor V R506Q mutation. Thromb Haemost 1996;76:208-214.[Web of Science][Medline] [Order article via Infotrieve]
  3. Bertina RM, Koeleman BPC, Koster T, Rosendaal FR, Dirven RJ, de Ronde H, et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994;369:64-67.[CrossRef][Medline] [Order article via Infotrieve]
  4. Irani-Hakime N, Tamim H, Elias G, Finan RR, Daccache JL, Almawi WY. High prevalence of factor V mutation (Leiden) in the eastern Mediterranean. Clin Chem 2000;46:134-136.[Free Full Text]
  5. Zivelin A, Griffin JH, Xu X, Pabinger I, Samama M, Conrad J, et al. A single genetic origin for a common Caucasian risk factor for venous thrombosis. Blood 1997;89:397-402.[Abstract/Free Full Text]
  6. Bernarde F, Faioni EM, Castoldi E, Lunghi B, Castaman G, Sacchi E, et al. A factor V genetic components differing from factor V R506Q contributes to the activated protein C resistance phenotype. Blood 1997;90:1552-1557.[Abstract/Free Full Text]
  7. Awidi A, Shannak M, Bseiso A, Kailani MA, Omar N, Anshasi B, et al. High prevalence of factor V Leiden in healthy Jordanian Arabs. Thromb Haemost 1999;81:582-584.[Web of Science][Medline] [Order article via Infotrieve]
  8. Ozbek U, Tangun Y. Frequency of factor V Leiden (Arg506Gln) in Turkey. Br J Haematol 1997;97:504-505.[Medline] [Order article via Infotrieve]
  9. Zeinali S, Duca F, Zarbakhsh B, Tagliabue L, Mannucci PM. Thrombophilic mutations in Iran [Letter]. Thromb Haemost 2000;83:351-352.[Web of Science][Medline] [Order article via Infotrieve]
  10. Dzimiri N, Meyer B. World distribution of factor V Leiden [Letter]. Lancet 1996;347:481-482.[Web of Science][Medline] [Order article via Infotrieve]




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Right arrow Hemostasis and Thrombosis


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