Fluctuations in levels of antiphospholipid antibodies and increased coagulation activation markers in normal andheparin-treated antiphospholipid syndrome pregnancies

Abstract

Antiphospholipid antibodies (aPL) are associated with an increased risk of thrombosis and recurrent miscarriage. We assessed levels of coagulation activation markers and aPL during normal pregnancy and in women with the antiphospholipid syndrome (aPS). Fluctuations in aPL levels were observed in all patients with aPS. No particular pattern of antibody positivity, or fluctuation in aPL level, was associated with poor pregnancy outcome. A significant increase was observed in levels of factor Xlla (FXIIa; P < 0.001), factor VIIa (FVIIa, P < 0.001), thrombin antithrombin complexes (TAT; P < 0.001), prothrombin fragment F1.2 (F1.2; P < 0.001) and D-dimer (DD; P < 0.05) during normal pregnancy. Factor VIIa, TAT, F1.2 and DD increased significantly before 20 weeks gestation, while a statistically significant increase in FXIIa levels was first detected between weeks 20 and 30 of gestation. In pregnant women with aPS, increases in FXIIa were similar to those in normal pregnancy, but increased FVIIa levels were not observed until after 30 weeks gestation. Similar to normal pregnancy, increased levels of TAT and F1.2 were detected in aPS pregnancies before 20 weeks gestation, but increased DD were not observed until after week 20. Surprisingly, women with aPS receiving low molecular weight heparin prophylaxis had significantly higher (P = 0.02) levels of TAT (median 8.6; interquartile range (IQR) 6.5-20.8) between weeks 20 and 30 of gestation compared to the normal pregnant population (median 5.9; IQR 4.7-7.9), thus indicating increased thrombin generation in women with aPS in mid-pregnancy.

Haemostasis in normal pregnancy: a balancing act?

“…Factor XIII, fibrinstabilizing factor, increases in the early stages of pregnancy, returning to non-pregnant values in the third trimester [12]. Levels of factor XII, X and IX increase progressively during pregnancy [13][14][15][16]. In contrast, levels of factor XI decrease during pregnancy [13], and it has previously been suggested that this may be a consequence of increased factor XI consumption [17].…”

“…Levels of vWF (von Willebrand factor), which serves as a carrier for factor VIII and plays a role in platelet adhesion, also increase progressively in pregnancy [18,20]. Factor VII also increases gradually during normal pregnancy [14][15][16][17]. Increases in factor V concentration in early pregnancy are followed by a decrease and stabilization [15], whereas factor V coagulation activity (Vc) shows a gradual rise throughout gestation [18].…”

“…Factor XIII Increases in early pregnancy, returns to non-pregnant values by third trimester [12] Factors XII, X, IX, VIII, VII, Vc Increase throughout pregnancy [13][14][15][16][17][18][19] Factor V Increases in early pregnancy, followed by a decrease and stabilization [15] Factor XI Decreases throughout pregnancy [13] vWF, fibrinogen Increase throughout pregnancy [13,15,16,[18][19][20][21][22] Factor II (prothrombin) Increases in early pregnancy, returns to non-pregnant values by third trimester/no change [15,18] Soluble TF No change [28] Monocyte TF Decreases throughout pregnancy, returns to non-pregnant values by 3 days post-partum [29,30] expressed by non-vascular cells and aberrantly expressed on monocytes and endothelial cells in the presence of inducers such as the inflammatory cytokines [23], endotoxin [24], Creactive protein [25] and homocysteine [26], whereas some anti-inflammatory cytokines are known to inhibit monocyte TF expression [27]. Although concentrations of soluble TF remain constant during normal pregnancy [28], monocyte TF activity and expression are lower when compared with non-pregnant subjects [29,30].…”

Expression of Adhesion Molecules on Peripheral Blood Monocytes During Pregnancy

“…По дан-ным некоторых исследователей, Mac-1 моноци-тов периферической крови может связываться с фактором X каскада свертываемости крови [19], в результате моноциты могут индуцировать фор-мирование протромбиназного комплекса. Таким образом, повышение количества CD11b + моно-цитов беременности может быть одной из при-чин повышения прокоагулянтной активности, предрасполагающей к развитию тромбофиличе-ских осложнений [6].…”

Association of recurrent pregnancy loss and anticardiolipin antibodies: prevalence and prognosis of subsequent pregnancy in women with recurrent pregnancy loss

“…7,[9][10][11][12][13][15][16][17] In the prospective studies, the effect of ACA on live birth rate has been reported very differently, The different results in the prospective studies could partly be attributed to poorly standardized ACA tests reflected in a significant interlaboratory variation in the detection of ACA significant fluctuations of the antibody levels over time in the same patient and very different cut off levels. [17][18][19][20][21][22][23][24] For an obstetrician who is treating patients with recurrent pregnancy loss, previous studies do not adequately answer the question: what are the prognostic value of an elevated ACA titre and the development of late pregnancy complications such as preeclampsia, low birth weight and preterm labour? Therefore, present study objective was to compare the prevalence of ACA in patients with recurrent pregnancy loss and normal healthy pregnant women and its association of complication and obstetric outcomes.…”