Association of ADAMTS13 Activity with Gender in Normal Adult Cohort

Background: the metalloprotease ADAMTS13 ( A Disintegrin And Metalloprotease with ThromboSpondin type 1 motif 13) cleaves von Willebrand within nascent platelet rich thrombi and its functional deficiency is associated with acute idiopathic or congenital thrombotic thrombocytopenic purpura (TTP). This disorder occurs more frequently in women especially during late pregnancy and postpartum period. However there is little information, some times controversial, on the protease behavior among healthy individuals in terms of gender and other demographic factors.

Materials and methods: samples from 92 healthy Greek blood donors of childbearing age (17–50) were submitted. Fifty males, 42 females were tested (median age 38/33 respectively). The ADAMTS13 activity was measured by fluorescent technique (FRETS normal range >65%). Von Willebrand Factor Antigen and Activity as well as FVIII Activity were estimated by automated latex enhanced immunoassay. Whole blood count was determined concurrently. ABO phenotyping was performed. Demographic data (body mass index, blood pressure, parity) and social habits (cigarette smoking, alcohol intake ) were recorded. Pregnancy, preaclampsia, personal or family history of miscarriage, bleeding/thromboembolism, hypertension, use of oral contraception pills or any other medication were defined as exclusion criteria. All data were analyzed by Mann Whitney U-test, Kruskal Wallis statistics and Spearman’s correlations. All individuals signed informed consent before sampling.

Aim: we conducted a prospective study in order to measure ADAMTS13 activity in healthy population and identify possible factors that may influence enzyme’s range.

Results: statistical significance was obtained when we examined ADAMTS13 activity in terms of gender (138,42% versus 109,12 %-mean values-for males and females respectively, p<0,001). We found protease’s activity below normal in 5 cases ( 4 females 26% –55%, 1 male 45% ) without any clinical relevance. Overall, there was a strong positive correlation between VWF:Ag and FVIII activity (p<0.001) and between VWF:Ag and VWF:Activity (p<0,001). Although ADAMTS13 activity decreased slightly with VWF:Ag increase there was no statistically significant inverse correlation between them. There was no difference in ADAMTS13 activity for the different blood groups. Negative correlation was revealed between platelets count and enzyme’s activity (p=0.005). In females, nulliparous group reached lower values of ADAMTS13 activity compared to those of parous women though without statistical significance. There were no correlations between ADAMTS13 activity and age, body mass index or cigarette and alcohol use.

Conclusions: the main finding of the present study is that plasma levels of ADAMTS13 activity differed significantly between the two genders. Yet previous studies have shown controversial results. In our knowledge this is the first attempt to measure ADAMTS13 activity in Greeks healthy individuals with age restriction (childbearing adults). In agreement with current literature on ADAMTS13 activity in pregnancy, where there is progressive decrease during gestation, we speculate the feasibility of oestrogen control over protease levels. Our results indicate probable hormonal penetration as mechanism which in part explains the different values we found between men and women. Probably is the lower ADAMTS13 activity, yet within normal, compared to men’s, that leaves women more prone to TTP under predisposing conditions. This together with the preference of autoimmunity for women may offer an explanation on the higher incidence of TTP in females. The inverse correlation between ADAMTS13 activity and platelets count was unexpected and needs to be further investigated.