Increased activation of blood coagulation in pregnant women with the Factor V Leiden mutation.

BACKGROUND: The risk of venous thromboembolism is enhanced in pregnant carriers of the Factor V Leiden mutation. The primary aim of the study was to compare prothrombin fragments 1+2, soluble fibrin and D-dimer levels in pregnant Factor V Leiden mutation carriers with those in non-carriers. Secondary aims were to evaluate whether these biomarkers could predict placenta-mediated complications or venous thromboembolism, and to study blood coagulation after caesarean section with thromboprophylaxis and after vaginal delivery without thromboprophylaxis. MATERIAL/METHODS: Prothrombin fragments 1+2, soluble fibrin and D-dimer levels were studied longitudinally in 476 carriers with singleton pregnancies from gestational weeks 23-25 until 8-10 weeks postpartum. RESULTS: Prothrombin fragments 1+2 and D-dimer levels gradually increased during pregnancy. D-dimer levels were higher in carriers, both during pregnancy and puerperium, compared to non-carriers. D-dimer levels above 0.5mg/l were found in about 30% and 20% of the heterozygous carriers at 4-5 and 8-10 weeks postpartum, respectively. Soluble fibrin levels were mainly unchanged during pregnancy, with no difference between carriers and non-carriers. Biomarker levels were similar in carriers with uncomplicated and complicated pregnancies. CONCLUSION: Higher D-dimer levels indicate increased blood coagulation and fibrinolysis activity in carriers. The high proportion of carriers with D-dimer levels exceeding 0.5mg/l postpartum must be considered when assessing the probability of venous thromboembolism. Large overlaps in biomarker levels in normal and complicated pregnancies suggest that these biomarkers cannot be used as predictors. Thromboprophylaxis following caesarean section may prevent increased activation of blood coagulation.

Factor V Leiden mutation and pregnancy-related complications.

OBJECTIVE: The objective of the study was to determine the prevalence of the factor V Leiden (FVL) mutation and its association with obstetric complications, blood loss during delivery, and venous thromboembolism (VTE). STUDY DESIGN: This was a prospective, observational, case-cohort study of 491 FVL carriers and 1055 controls derived from 6003 screened women. Data were analyzed with a Student t test and cross-tabulation. RESULTS: FVL carriership prevalence was 8.3%. Gestational age at delivery, birthweight deviation, gestational hypertension, and preeclampsia incidences did not differ between groups. The incidences of placental abruption, neonatal asphyxia, eclampsia, intrauterine fetal death, intrapartum death, and unexplained late miscarriage were low. The incidence of major blood loss at delivery was lower in carriers. There were 3 VTEs among carriers and none among controls. CONCLUSION: FVL carriership did not influence pregnancy-induced hypertension, birthweight, or prematurity but raised the risk of venous thromboembolism and lowered the risk of major blood loss.

APC resistance during the normal menstrual cycle.

Increased serum levels of endogenous as well as exogenous estrogen are regarded to be responsible for acquired activated protein C (APC) resistance. It was the objective of this study to evaluate whether the physiological increase in serum estradiol concentration during the normal menstrual cycle affects the individual's sensitivity to APC. Seventy-two women with normal menstrual cycles were included in the study. Blood samples for analysis of estradiol (E2), progesterone (P4) and APC resistance were drawn at two time points of the menstrual cycle (day 3-5 and day 22-25). Two methods of measuring APC resistance were used: the activated partial thromboplastin time (aPTT)-based assay and the endogenous thrombin potential (ETP)-based APC resistance test. Independent of the method used, no changes in APC resistance were found, even though the E2 concentration increased significantly between the two menstrual phases. No correlations between E2 levels and APC resistance, P4 levels and APC resistance or changes in E2 concentrations and changes in APC resistance were detected. Ten women were carriers of the factor V(Leiden) mutation. Their baseline APC resistance was increased, but their response to elevated E2 during the menstrual cycle did not differ from that of non-carriers. In conclusion, our observations suggest that physiological differences in serum levels of estradiol and progesterone between the early follicular and the luteal phase in a normal menstrual cycle do not have any significant impact on the individual's sensitivity to APC.

Erythropoietin and intravenous iron therapy in postpartum anaemia.

BACKGROUND: We assessed whether recombinant human erythropoietin (rhEPO) enhances a rise in haemoglobin concentration in postpartum anaemia compared to intravenous iron alone. DESIGN: Some 60 patients with haemoglobin values

Rapid activation of haemostasis after hormonal emergency contraception.

Hormonal emergency contraception (EC) is a well established contraceptive method, recommended to all women, although the effects on haemostais are not fully evaluated. The aim of this study was to evaluate whether exposure to EC has effects on well established cardiovascular risk factors, and also to examine whether differences exist between two EC treatments. In a prospective randomized cross over design 11 women used two different EC methods, one with estrogen and levonorgestrel (EE-EC) and one with levonorgestrel only (LNG-EC). Plasma concentrations of haemostatic factors (APC resistance, antithrombin, fibrinogen, prothrombin fragment 1 + 2, free protein S, factorVII and PAI-1), sex-hormone-binding globulin (SHBG), the apolipoprotein (apo)B/apoA1 ratio and C-reactive protein (CRP) were followed frequently during the following 48 hours. A rapid haemostatic activation was induced with both treatments, although more pronounced with EE-EC. Already two hours after EC, the plasma concentrations of haemostatic parameters and SHBG were significantly different from baseline concentrations. An ETP-based APC-resistance method showed increased APC resistance with EE-EC and decreased APC resistance with LNG-EC. The ApoB/ApoA1 ratio was affected in a favourable direction with EE-EC.CRP increased slightly regardless of treatment. Even a very short exposure to exogenous sex hormones causes prompt effects on hepatic protein synthesis and the coagulation system. This must be taken into consideration whenever exogenous steroid hormones are administered, especially to individuals with a genetic predisposition to thrombosis or transiently disturbed haemostasis.

Different effects of oral contraceptives containing levonorgestrel or desogestrel on plasma lipoproteins and coagulation factor VII.

OBJECTIVE: The objective of the study was to compare the effects of two different combined oral contraceptives on levels of plasma lipoproteins and coagulation factor VII. STUDY DESIGN: A prospective randomized crossover study was undertaken. Thirty-five women were treated with combined oral contraceptives containing the same amount of ethinyl estradiol and either levonorgestrel or desogestrel. Levels of plasma lipoproteins and factor VII were determined before and after 2 months of treatment with each preparation. RESULTS: Levels of high-density lipoprotein cholesterol were increased significantly with treatment with ethinyl estradiol/desogestrel when compared with baseline and treatment with ethinyl estradiol/levonorgestrel. A significant rise in plasma triglyceride levels was obtained with both preparations, although the increase was more pronounced with ethinyl estradiol/desogestrel. Plasma concentrations of factor VII mass concentration and activated factor VII were increased significantly only with ethinyl estradiol/desogestrel. CONCLUSION: The rise in concentrations of high-density lipoprotein cholesterol may be advantageous, whereas the combined elevations of plasma triglyceride and factor VII levels obtained with ethinyl estradiol/desogestrel may reflect a hypercoagulable state.