Management of inherited thrombophilia in pregnancy

Abstract

The endogenous anticoagulants, activated protein C (APC) and its vitamin K-dependent cofactor protein S, are reduced in pregnancy. 4-6 Fibrinolysis is reduced in pregnancy largely due to placenta-derived PAI-2; however, this normalises rapidly post-delivery. 7 As pregnancy advances, tissue factor-dependent thrombin generation increases, along with Factors VII, VIII, IX, fibrinogen, prothrombin fragment 1+2 and

Oxidative status of maternal blood in pregnancies burdened by inherited thrombophilias

“…Inherited thrombophilias were detected by evaluating the presence of specific mutations/ deficiencies: protein S deficiency, prothrombin i.e. coagulation factor II (F2) gene mutation, Factor V Leiden mutation, plasminogen activator inhibitor-1 (PAI-1) gene polymorphism, and methylenetetrahydrofolate reductase (MTHFR) gene mutation [35,36]. All patients were diagnosed before the index pregnancy.…”

Thrombophilia in Pregnancy

“…Hypercoagulability, venous stasis and vessel damageknown as Virchow's triad-represent the mechanisms leading to the occurrence of VTE. The hypercoagulable state in pregnancy, representing an adaptive transient mechanism in preparation for hemostasis during birth, results from a progressive increase in the levels of Factors VII, VIII, X and fibrinogen throughout pregnancy, with a peak at delivery, and a decrease in protein S, antithrombin and fibrinolysis [8]. An acquired activated protein C resistance may be found in 40% of pregnant women.…”

“…D-dimer levels, with a threshold of 1.0 mg/L up to week 30 of pregnancy and, respective, 2.0 mg/L just prior to delivery, peaks on the first day postpartum and then decrease, indicating that the coagulation and fibrinolytic systems begin to return to the baseline [9]. However, a procoagulant state lasts for 6-8 weeks after giving birth or longer, up to 12 weeks postpartum [8,9]. Venous stasis is due to several mechanisms such as: the vasodilatation induced by pregnancy-related hormones, decreased venous tone, increased venous pressure, reduced venous flow velocity and compression of the left iliac vein [10,11].…”

“…However, a recent systematic review and metaanalysis has shown that protein C and protein S deficiencies represent high risk thrombophilias in pregnancy whereas the compound heterozygosity for FV Leiden and prothrombin G20210A mutation present a lower absolute risk of VTE [12]. Other inherited thrombophilias, methylenetetrahydrofolate reductase polymorphisms C677T and A1298C, leading to hyperhomocysteinemia, are not associated with VTE in pregnancy, partly explained by the routinely administration of folic acid supplements which reduce homocysteinemia [1,8]. FV Leiden and protrombin G20210A mutation represent the most common inherited thrombophilias (with the highest prevalence in South Europe) whereas protein S, protein C and antithrombin deficiencies are rare in general population [1,14].…”

“…Research is required to identify possible biomarkers (e.g. ANXA5 M2 haplotype) for the stratification of the risk and a better-targeted antithrombotic therapy [8,20]. Further investigations may take also into consideration the bio-psychosocial model, to detect better the symptoms of anxiety, depression and stress in pregnant women with thrombophilia, which may overlap, creating difficulties in screening and intervention.…”