Phospholipid binding proteins antibodies: diagnostic importance and clinical associations in the antiphospholipid syndrome

Venous or arterial the thrombosis, abortion, and the presence of antiphospholipid antibodies [aPL] define the criteria for the antiphospholipid syndrome [APS]. The heterogeneous group of antibodies against phospholipids and plasma proteins may influence several coagulation pathways and lead to thrombophilia. Deep vein thrombosis and pulmonary embolism are the most common venous events. To establish whether antibodies directed against phospholipid-binding plasma proteins such as beta2-glycoprotein [beta2GPI], prothrombin [PT], and annexin V [Anx V] and antithrombin [anti-Thr] antibodies constitute a risk factor for thromboembolism in patients with primary antiphospholipid syndrome [pAPS] and systemic lupus erythematosus [SLE] and for miscarriage-in women with recurrent pregnancy loss [RPL], and whether their determination together with that aCL would help to increase the diagnostic sensitivity of aPL tests. The prevalence of various antibodies directed toward phospholipids [CL] and phospholipid-binding proteins [beta2GPI, PT, Anx V, and anti-Thr] was determined by immunoenzymatic method in 95 patients samples. Twelve patients with aCL-positive primary anti-phospholipid syndrome [pAPS]; 45 patients with SLE, 12 of whom had thrombotic complications [SLE/APS] and 33 of whom has no thrombosis; and 38 women with unexplained recurrent pregnancy loss comprised our study group. Fifty healthy subjects matched for age and sex were studied as the control group. Anti- beta2GPI, anti-PT, and IgG anti-Anx V anti-Thr antibodies were detected in 9[75%], 6 [50%],3[25%] and 3[25%], respectively, of the 12 aCL-positive pAPS patients; IgG and/or IgM aCL, anti- beta2GPI, anti-PT, IgG anti-Anx V and anti-Thr antibodies were detected in 17 [37%], 15 [33%], 20[44%], 6[13%] and 11[24%], of the 45 SLE patients respectively. The highest risk for thrombosis in SLE patients was associated with the presence of IgG anti-PT antibody [odds ratio [OR] 13.4, P<.001, vs. 7.7 aCL, 2.8 anti- beta2GPI, 0.6 anti-Anx V, and 8.7 anti-Thr]. Anti-Pt has slightly lower specificity than aCL however the occurrence of both antibodies brought the specificity 94%. In patients with recurrent pregnancy loss [RPL] the prevalence of IgG and/or IgM aCL, anti- beta2GPI, anti-PT, IgG anti-Anx V and anti -Thr antibodies was 6% [2], 12% [9], 6% [5], 16% [6], 18% [7], and 5% [2] respectively. Anti Anx V was the antibody significantly associated with miscarriage. The result of this study indicates that: It is useful to measure anti-PT antibodies in addition to the more widely used aCL and anti- beta2GPI antibodies in the prognostic evaluation of SLE patients for the risk of thrombosis. The results also confirm that anti-Anx V antibodies may play an important role in recurrent pregnancy loss. The determination of anti-thrombin antibodies may contribute to better diagnosis of APS

Association of inherited thrombophilia with pre-eclampsia

Preeclampsia and its association with thrombophilia remain controversial, due to inconsistent results in different studies, which include different ethnic groups, selection criteria, and patient numbers. The aim of this was to determine the relationship between thrombophilia and preeclamptic patients. In a prospective case-control study, we compared 50 consecutive women with preeclampsia [group 1] with 50 normal pregnant women [group 2]. All women were tested two months after delivery for mutations of factor V Leiden, methylenetetrahydrofolate reductase [MTHFR], and prothrombin gene mutation as well as for deficiencies of protein C, protein S, and antithrombin III. A throinbophilic mutation was found in 22 [44%] and 16 [32%] women in group 1 and group 2, respectively [P>0.05 OR 1.9, 95% CI 0.7-2.3]. The incidence of Factor V Leiden mutation [heterozygous], prothrombin mutation [homozygous] MTHFR mutation [homozygous] was not statistically significant in group 1 compared with group 2 [P>0.05]. Also, deficiencies of protein S, protein C, and antithrombin III were not statistically significant in group 1 compared with group 2 [P>0.05]. There was no difference in thrombophilic mutations between preeclamptic patients and normal pregnant women. Therefore, we suggest that preeclamptic patients should not be tested for thrombophilia