Low molecular weight heparin for the treatment of venous thromboembolism in pregnancy: a case series

Objectives To assess the use of low molecular weight heparin for the treatment of venous thromboembolism in pregnancy.
Design A prospective observational study.
Setting The maternity units in two university teaching hospitals and one district general teaching hospital.
Population Thirty-six consecutive women presenting with objectively diagnosed venous thromboembolism during pregnancy and the immediate puerperium.
Methods Treatment with the low molecular weight heparin enoxaparin, approximately 1 mg/kg sc, twice daily, based on early pregnancy weight.
Main outcome measures Peak anti-Xa activity (three hours post-injection), alterations in treatment, side effects and the use of regional anaesthesia.
Results In 33 women, the initial dose of enoxaparin provided satisfactory peak anti-Xa activity (median 0.8 u/mL, range 0.44–1.0 u/mL) and was continued. Three women required dose reduction since peak anti-Xa activities were above the therapeutic range (1.2, 1.2 and 1.1 u/mL). No woman developed thrombocytopaenia, haemorrhagic complication or further thromboembolic episode. Two women developed allergic skin reactions on enoxaparin and were changed to tinzaparin. Fifteen women had regional anaesthesia for delivery, with a reduced dose of enoxaparin (40 mg once daily), all without complication.
Conclusions Enoxaparin is a safe and effective treatment for venous thromboembolism during pregnancy and confers a major advantage over unfractionated heparin through its simplified regimen of administration.     

Comparison of enoxaparin, a low-molecular-weight heparin, and unfractionated heparin, with or without dihydroergotamine, in abdominal hysterectomy.

The effects of administration of low-molecular-weight heparin (enoxaparin 20 mg) once a day, of unfractionated heparin (5000 IU twice a day, and of unfractionated heparin (2500 IU) plus dihydroergotamine (0.5 mg) twice a day were assessed in 100 patients undergoing abdominal hysterectomy. The test medications were given subcutaneously 2 hours before operation and for 3 days thereafter. There were no thromboembolic complications. Intraoperative blood loss, wound haematomas and blood loss via drains during four days after operation were similar in the three groups. None of the 37 patients receiving enoxaparin experienced major postoperative bleeding. Six out of 31 patients receiving unfractionated heparin without dihydroergotamine and two out of 32 patients receiving dihydroergotamine in addition experienced major bleeding necessitating re-operation and/or blood transfusion, (P < 0.05). Enoxaparin caused less major bleeding than unfractionated heparin with or without dihydroergotamine in patients undergoing hysterectomy.     

Management of thromboembolism in pregnancy

The incidence of venous thromboembolism is increased during pregnancy and the postpartum period. This risk is high for women with documented hereditary or acquired risk factors who have experienced a prior thrombotic event. These individuals require a minimum of prophylactic dose anticoagulation with unfractionated or low molecular weight heparin during pregnancy, with anticoagulation continuing for 4 to 6 weeks postpartum. Women receiving therapeutic dose anticoagulation with warfarin before pregnancy for a hereditary or acquired condition should be transitioned to therapeutic doses of unfractionated heparin or low molecular weight heparin before or within 6 weeks of becoming pregnant, and can then resume warfarin postpartum. Women experiencing a thromboembolic event during pregnancy should receive therapeutic treatment with unfractionated heparin or low molecular weight heparin during pregnancy, with anticoagulation continuing for 4 to 6 weeks postpartum, and for a total of at least 6 months.     

Prophylactic and therapeutic enoxaparin during pregnancy: indications, outcomes and monitoring

OBJECTIVES: To evaluate the efficacy and safety of prophylactic and therapeutic enoxaparin in pregnancy. STUDY DESIGN: Three-year prospective audit. SETTING: Tertiary level obstetric hospital. POPULATION: Fifty-two women who received subcutaneous enoxaparin, either a prophylactic dose (40 mg daily) in 26 pregnancies or therapeutic dose (1 mg/kg twice daily) in 32 pregnancies. MATERIALS AND METHODS: Pregnant women treated with enoxaparin were prospectively entered into a register. Data were retrieved by case note review. MAIN OUTCOME MEASURES: Pregnancy outcomes, treatment complications and anti-Xa levels. RESULTS: In the prophylactic group there were no fetal losses, thromboembolic events or complications related to enoxaparin. In the therapeutic group there were four first trimester miscarriages, a termination and 27 live births. Therapeutic enoxaparin prevented further thromboembolism without complications. One woman was treated with intermediate dose enoxaparin when she presented at 5 weeks' gestation on warfarin and 7 weeks after a venous thromboembolism. She developed a recurrent pulmonary embolus 3 weeks later and was subsequently treated with therapeutic enoxaparin. In the therapeutic group the enoxaparin dose/kg correlated poorly with anti-Xa levels, and dose adjustments were made. Therapeutic mean (SD) trough and peak anti-Xa levels were 0.33 U/mL (0.14) and 0.86 U/mL (0.24) in the first trimester and 0.48 U/mL (0.19) and 0.84 U/mL (0.23) in the third trimester. CONCLUSIONS: In the present series, prophylactic and therapeutic enoxaparin treatment during pregnancy was effective and safe. Studies are required to determine the optimal duration of treatment with therapeutic enoxaparin following venous thromboembolism in pregnancy and the clinical relevance of anti-Xa monitoring.     

Comparison of enoxaparin and standard heparin in gynaecologic oncologic surgery: a randomised prospective double-blind clinical study.

OBJECTIVE: This study aimed to compare the haemorrhagic complications and efficacy of enoxaparin, a low molecular weight heparin (LMWH), and conventional standard heparin (SH) in gynaecological oncologic surgery. MATERIALS METHODS: A double blind, randomised trial was performed on 102 consecutive women undergoing gynaecologic cancer surgery with pelvic and paraaortic lymphadenectomy. The women were separated into those who were given 2,500 IU enoxaparin once daily and SH in a dose of 5,000 IU three times daily. The groups were analysed for intraoperative blood loss, drainage, transfusion requirements, perioperative haemoglobin decrease, wound haematoma, and clinical deep venous thrombosis. RESULTS: The two groups were well matched for age, weight, and other factors, which could predispose to the development of deep venous thrombosis (DVT) and haemorrhage. No patient developed clinical significant DVT, wound haematoma or intra-abdominal bleeding. There was no significant difference in bleeding complications between the two regimens. The antiFXa level in the plasma was correlated strongly with patient weight. CONCLUSIONS: A dose of 2,500 IU enoxaparin/day does not cause more bleeding complications than SH 5,000 IU three times daily when used to prevent thrombosis. However, the dose of enoxaparin must be adjusted to the patient's weight.     

Enoxaparin treatment in women with mechanical heart valves during pregnancy

OBJECTIVE: This prospective audit reports pregnancy outcomes, anticoagulation complications, and anti-Xa levels in women with mechanical heart valves who were treated with therapeutic enoxaparin plus aspirin during pregnancy. STUDY DESIGN: Between 1997 and 1999, 11 women with mechanical heart valves were treated with enoxaparin, 1 mg/kg twice daily, and aspirin, 100 to 150 mg daily during 14 pregnancies. Predose and 4-hour postdose anti-Xa levels were monitored monthly. RESULTS: There were 9 live births, 3 miscarriages, and 2 terminations. In 48 months of enoxaparin treatment, one woman who had a documented valve thrombosis when she presented at 8 weeks' gestation also had a valve thrombosis at 20 weeks' gestation. There were no enoxaparin-related hemorrhagic complications. Mean (SD) anti-Xa levels were 0.46 (0.12) U/mL predose and 0.89 (0.22) U/mL 4 hours postdose. CONCLUSION: Successful pregnancy outcome may be achieved with therapeutic subcutaneous enoxaparin, but its efficacy at preventing valve thrombosis remains uncertain. Further data are required before use of enoxaparin during pregnancy in women with mechanical heart valves can be recommended.     

Cost-effectiveness of deep venous thrombosis prophylaxis in gynecologic oncology surgery

OBJECTIVE: To estimate the cost-effectiveness of preventive strategies for deep vein thrombosis (DVT) in patients undergoing surgery for gynecologic cancer. METHODS: A model was constructed to estimate the costs and outcomes associated with the use of external pneumatic compression, unfractionated heparin, and low molecular weight heparin in women with cervical, endometrial, and ovarian cancer. We estimated cost per DVT prevented, per fatal pulmonary embolus (PE) prevented, and per life-year saved. Probability estimates for various outcomes and efficacies were obtained from the literature, using data specific for gynecologic patients when available. RESULTS: Cost-effectiveness estimates ranged from $27 per life-year saved for a 55-year-old endometrial cancer patient to $5132 per life-year saved for a 65-year-old with ovarian cancer. Although low molecular weight heparin and unfractionated heparin were cost-effective compared with no prophylaxis, each was less effective than external pneumatic compression in the base case. The results of the analysis were sensitive to assumptions about the relative risk of DVT, the life expectancy of the patient, the costs of future treatment, and the relative effectiveness of the different strategies: If unfractionated heparin or low molecular weight heparin is at least 2-3% more effective than external pneumatic compression, then the incremental cost per life-year of either would be less than $50,000 compared with external pneumatic compression. CONCLUSION: Prophylaxis of DVT is cost-effective in terms of life-years gained even for patients with relatively short life expectancies, such as ovarian cancer patients. External pneumatic compression appears to be the most cost-effective strategy under our baseline assumptions, but further studies in gynecologic cancer are needed to validate our conclusions.     

Effects of unfractionated and low molecular weight heparin on antiphospholipid antibody binding in vitro

OBJECTIVE: To compare the efficacy of unfractionated heparin and low molecular weight heparin in the in vitro binding of antiphospholipid antibodies obtained from the sera of patients with recurrent pregnancy loss. METHODS: Women with immunoglobulin (Ig) G antibodies to the phospholipids cardiolipin and phosphatidylserine were selected based on a positive test by a standard enzyme-linked immunosorbent assay (ELISA). The sera were reassayed for antiphospholipid antibodies in a modified ELISA using increasing doses of unfractionated heparin or low molecular weight heparin (0, 16, 32, 64, 128, and 256 IU). Sera were fractionated by unfractionated and low molecular weight heparin affinity chromatography to compare the binding avidity and antiphospholipid antibody activity. RESULTS: All sera demonstrated a dose-dependent inhibition in measured antiphospholipid antibody activity with the addition of unfractionated or low molecular weight heparin. Levels of IgG cardiolipin and IgG phosphatidylserine were significantly inhibited in the presence of 32 IU of low molecular weight heparin (P <.001 and P <.05, respectively) and in the presence of 64 IU of unfractionated heparin (P <.001 and P <.05, respectively). Antiphospholipid antibody binding activity in serum as measured in the ELISA was maximally reduced 76-89% with 256 IU of either heparin derivative. Affinity chromatography with unfractionated or low molecular weight heparin columns absorbed 72% and 66% of IgG cardiolipin activity, respectively, and 46% and 54% of IgG phosphatidylserine activity, respectively. CONCLUSION: These data suggest that low molecular weight heparin and unfractionated heparin reduce the in vitro binding of antiphospholipid antibodies on a per unit basis. Both heparins demonstrate binding activity similar to that of antiphospholipid antibodies in vitro.     

Antithrombotic therapy during pregnancy.

Antithrombotic therapy is required during pregnancy for the prevention and treatment of venous and arterial thromboembolism and for the prevention of pregnancy loss in women at risk. The choice of anticoagulant for venous thromboembolism during pregnancy is limited to unfractionated heparin or low molecular weight heparin because the use of warfarin is relatively contraindicated. Much of the information surrounding the pharmacokinetics and dosing of unfractionated heparin and low molecular weight heparin obtained from non-pregnant patients has been applied to pregnant women. Whether this is appropriate in the presence of significant physiological changes in pregnancy is unclear. Specific to pregnancy and unfractionated heparin use, activated partial prothrombin time may be unreliable. In addition, the appropriate dosing of low molecular weight heparin is uncertain. Because venous thromboembolism can cause significant maternal morbidity and mortality, these important issues surrounding appropriate drug dosing of anticoagulants should be addressed.     

Anti-factor Xa plasma levels in pregnant women receiving low molecular weight heparin thromboprophylaxis

OBJECTIVE: To report the incidence of prophylactic, subprophylactic, and supraprophylactic anti-factor Xa activity in pregnant patients receiving low molecular weight heparin for venous thromboembolism prophylaxis, and to evaluate whether maternal weight, body mass index, age, gestational age, or the low molecular weight heparin dose correlated with anti-factor Xa levels. METHODS: We reviewed 321 anti-factor Xa levels in 77 patients from one Maternal-Fetal Medicine faculty practice. All patients were administered low molecular weight heparin that subsequently was adjusted based upon serial assessment of peak plasma (at 4 hours postinjection) anti-factor Xa levels at less than 36 weeks gestation. Targeted prophylactic range of peak plasma anti-factor Xa level was 0.2-0.4 units/mL. RESULTS: Only 59% of anti-Xa concentrations were in the prophylactic range, whereas 26% were subprophylactic, and 15% were supraprophylactic. Anti-Xa values were not significantly more likely to be prophylactic in early compared with late pregnancy, obese compared with nonobese patients, or in patients receiving a weight-based minimal dose compared with patients receiving less than a weight-based minimal dose. Anti-factor Xa levels did not correlate with maternal age, weight, body mass index, or gestational age, but there was a positive correlation with the percent of the minimal weight-based dose. CONCLUSION: Even with enhanced low molecular weight heparin dosing, 26% of patients have subprophylactic anti-factor Xa levels. Serial anti-factor Xa assessment for dose adjustment should be considered for all pregnant women receiving low molecular weight heparin.     

A longitudinal study of maternal dose response to low molecular weight heparin in pregnancy

OBJECTIVE: To assess the maternal response to low molecular weight heparin during pregnancy, by estimation of plasma anti-Xa activity, at three specified gestation points and in the nonpregnant state. METHODS: A longitudinal, prospective, observational study was set in a tertiary referral recurrent miscarriage clinic. Twenty-four women, attending consecutively, were invited to participate and gave informed consent. Each woman had a history of recurring pregnancy loss and positive preconception screening for antiphospholipid syndrome. After confirmation of a viable pregnancy all subjects began taking 5000 IU of dalteparin once daily subcutaneously. Serial measurement of plasma anti-Xa activity after administration of dalteparin was performed at three standard gestation points (12, 24, and 36 weeks) and in the nonpregnant state (6 weeks postpartum). RESULTS: Peak anti-Xa levels occurred at 4 hours postbolus in pregnancy, as compared with 2 hours in the nonpregnant state. The mean anti-Xa levels at 12, 24, and 36 weeks' gestation were significantly reduced, at 2 hours postinjection, as compared with the nonpregnant state (P <.001, P <.01, P <.001, respectively). The lowest dose-response curve was at 36 weeks' gestation. A repeated-measures analysis of variance found a significant difference (P <.05) between the 36-week group and the postterm group but not between any of the other groups. CONCLUSION: During pregnancy, differences in the pharmacokinetics of low molecular weight heparin were observed, with an overall reduction in anti-Xa activity. On the basis of this study it is questionable to extrapolate dosing and lack of dose monitoring, in pregnant women, using data derived from a nonpregnant population.     

A prospective trial that demonstrates that dalteparin requirements increase in pregnancy to maintain therapeutic levels of anticoagulation

OBJECTIVE: The purpose of this study was to determine whether standard therapeutic doses of dalteparin maintain peak therapeutic levels of anticoagulation during pregnancy. STUDY DESIGN: This was a prospective trial in which 13 pregnancies that required therapeutic anticoagulation were treated with dalteparin 100 U/kg every 12 hours; peak and trough (predose) low molecular weight heparin (anti-Xa activity) levels were monitored every 2 weeks. Dosage adjustments were made to maintain peak anti-Xa activity between 0.5 and 1.0 IU/ml. Bone density and bone turnover markers were measured. RESULTS: A total of 250 peak and trough low-molecular-weight heparin (LMWH) levels were obtained. Eighty-five percent of pregnancies (11/13) required an upward dosage adjustment. Trough levels were in the therapeutic range only 9% of the time, despite the maintenance of therapeutic peak levels. Bone resorption markers and density were unchanged in singleton pregnancies. CONCLUSION: Dalteparin dosing, based on weight alone, every 12 hours is inadequate to maintain most pregnant women in the therapeutic range throughout pregnancy as measured by anti-Xa activity. Trough levels are rarely in the therapeutic range, despite maintenance of therapeutic peak levels. These notable changes in low molecular weight heparin peak may explain reported failures in pregnancy.     

Enoxaparin versus unfractionated heparin in the management of recurrent abortion secondary to antiphospholipid syndrome

Objective

To determine whether low molecular weight heparin (LMWH) plus low-dose aspirin (LDA) is comparable in efficacy and safety to unfractionated heparin (UFH) plus LDA in the management of pregnant women with a history of recurrent spontaneous abortion secondary to antiphospholipid syndrome (APS).

Methods

In a randomized prospective study, 60 women with a history of 3 or more consecutive spontaneous abortions and positive antiphospholipid antibodies were assigned in equal numbers to receive either UFH (5000 units, twice daily) plus LDA, or LMWH (enoxaparin 40 mg, once daily) plus LDA as soon as pregnancy was diagnosed.

Results

Twenty-four women in the LMWH group (80%) and 20 women in the UFH group (66.67%) delivered a viable infant (P = 0.243). There were no significant differences in pregnancy complications or neonatal morbidity between the 2 groups. There were no incidences of excessive bleeding, thrombocytopenia, or osteoporotic fractures in either group.

Conclusion

LMWH plus LDA was successfully used as an alternative to UFH plus LDA in the management of recurrent abortion secondary to APS. The results highlight the need for a larger randomized controlled trial to determine whether LMWH plus LDA should be the treatment of choice for recurrent abortion secondary to APS.Clinicaltrials.govNCT01051778.     

Thromboprophylaxis after vaginal delivery: a district general hospital experience.

The Confidential Enquiries into Maternal Deaths (RCOG 2001) recommends risk assessment and appropriate thromboprophylaxis after vaginal delivery. This study examines the risk group and the need for thromboprophylaxis after vaginal delivery in our local population and the cost implications for the same. It is a retrospective study of women who delivered in the month of November 2003. There were 307 deliveries, of these 251 (81.7%) were vaginal deliveries. Confidential Enquiries into Maternal Deaths (CEMD) risk classification was possible for 243 women. A total of 170 women were low risk, 66 (27.16%) moderate risk and 7 (2.88%) high risk. The costs of thromboprophylaxis for the year in our unit were calculated as pound7,339.71 for unfractionated heparin (UFH) 5,000 IU twice daily and pound7,098.27 for 40 mg enoxaparin once daily. A total of 30% of our District General Hospital population were classified as moderate or high risk for thromboprophylaxis after vaginal delivery. It is less expensive to use enoxaparin compared with unfractionated heparin for thromboprophylaxis.     

Preference and compliance in postoperative thromboembolism prophylaxis among gynecologic oncology patients

OBJECTIVE: To compare low molecular weight heparin and external pneumatic compression in terms of patient preference and compliance to determine if either of these two methods is superior in postoperative thromboembolism prophylaxis of gynecologic oncology patients. METHODS: A total of 211 patients undergoing major surgery for a suspected gynecologic malignancy were randomized to receive thromboembolism prophylaxis with either external pneumatic compression or low molecular weight heparin. Surveys regarding thromboembolism prophylaxis were completed by patients before surgery and approximately 7 days postoperatively. Patient preferences as well as reasons for patient dissatisfaction with prophylactic methods were elicited in the questionnaires. In addition, patient compliance with prophylaxis was recorded twice a day during hospitalization. Patients were not considered to be compliant with prophylaxis if the external pneumatic compression device was not functioning properly or if the administration of low molecular weight heparin was not given in a timely manner. RESULTS: The majority of patients were satisfied with the prophylactic method that they received to the extent that they would prefer the treatment they received to one they had not necessarily experienced. The postoperative preferences of 78% of patients receiving low molecular weight heparin and 74% of those wearing external pneumatic compression corresponded to what the patients actually received as a method of thromboembolism prevention. Patient compliance with prophylaxis was noted to be inadequate in ten of 104 (9.6%) patients receiving external pneumatic compression and seven of 103 (6.8%) patients receiving low molecular weight heparin. CONCLUSION: Pneumatic compression and low molecular weight heparin are similar both in terms of patient preference and compliance among gynecologic oncology patients receiving postoperative thromboembolism prophylaxis.     

The use of unfractionated heparin and low molecular weight heparins in pregnancy

Currently unfractionated heparin (UH) and low molecular weight heparins (LMWH) are the agents of choice for anticoagulation in pregnancy. LMWH have been used safely without monitoring in nonpregnant patients; however, because of documented changes in the pharmacokinetics of these agents in pregnancy, monitoring with anti-Xa levels is necessary in pregnancy to maintain target therapeutic ranges. Patients requiring only prophylaxis during pregnancy with either UH or LMWH might benefit from occasional assessment of anti-Xa levels to confirm that target prophylactic ranges are being achieved. Although LMWH may cause less osteoporosis than UH at therapeutic doses, the incidence of heparin-induced osteoporosis seems to be low when only prophylactic dosing is used and therefore LMWH do not seem to offer this advantage at low doses. Experience with newer agents such as pentasaccharide inhibitors and direct thrombin inhibitors are limited in pregnancy and it remains to be seen what role these agents will play in women who require anticoagulation in pregnancy.     

Is the monitoring of anti-Xa activity necessary in pregnant women undergoing thromboprophylaxis?

Thromboprophylaxis is increasingly advocated in pregnancy for certain clinical conditions. Low molecular weight heparins offer potential benefit over unfractionated heparins with increased bioavailability and a longer half-life, thus allowing for once daily administration. This study aims to determine if monitoring of anti-Xa activity is necessary in pregnant women undergoing thromboprophylaxis. Twenty-five pregnancies were prospectively followed where either tinzaparin or enoxparin was employed for thromboprophylaxis. Once the anti-Xa levels were in the thromboprophylactic range (0.03-0.5 U/ml) no patient required a change of dose. Frequent monitoring of Anti-Xa levels, once in the thromboprophylactic range, may not be required.     

低分子肝素治疗重度子痫前期患者效果的研究

目的:探讨重度子痫前期患者应用不同剂量低分子肝素的临床效果及安全性。方法:随机将重度子痫前期62例分为3组:A组(大剂量组),在常规治疗的基础上加用低分子肝素5000U/d;B组(小剂量组),加用低分子肝素2500U/d;C组,常规治疗组。通过临床症状、体征及辅助检查的变化判断各治疗组的治疗效果及对母儿的影响。结果:3组患者纳入研究时临床指标无差异(P>0·05);加用低分子肝素组(A、B两组)的临床疗效评分显著高于常规治疗组(C组)(13·43±2·75,11·95±3·46vs9·43±3·81(P<0·05));A组的平均得分高于B组,但统计学分析无显著差异(P>0·05);3组孕妇的肝肾功能、胎儿宫内状况、分娩方式及产后出血量等均无显著差异(P>0·05)。结论:低分子肝素有助于改善重度子痫前期孕妇的治疗效果;低分子肝素对母儿安全。     

Does combined prednisolone and low molecular weight heparin have a role in unexplained implantation failure?

Purpose

To study the effect of combined oral prednisolone and LMW heparin in ICSI in women with previously unexplained, failed implantation.

Methods

A prospective quasi-randomized, controlled trial was conducted at a university teaching hospital and a private practice setting. A total of 334 cycles (women with previously unexplained, failed one or two ICSI attempts) were assigned randomly to receive standard treatment or combined prednisolone (20 mg/day), starting on the first day of ovarian stimulation and LMW heparin 1 mg/kg/day starting 1 day after oocyte retrieval in addition to standard treatment.

Results

The mean age, number of previously failed IVF attempts, and basal FSH levels were comparable between both groups. The pregnancy and the implantation rates were significantly different between the study and control groups.

Conclusions

A combination of oral prednisolone and low molecular weight heparin may have a significant effect on pregnancy and implantation rates in prior unexplained, failed implantation.     

The effect of thrombophylaxis on pregnancy outcome in patients with recurrent pregnancy loss associated with factor V Leiden mutation

Objective To observe the effect of thrombophylaxis on pregnancy in women with a history of unexplained recurrent pregnancy loss also carrying the factor V Leiden mutation.
Methods Between 1 January and 31 December 1996, activated protein C (APC) resistance and factor V Leiden mutation were prospectively measured in 56 nonpregnant women, with a history of two or more unexplained recurrent pregnancy losses. During the same study period, seven women carrying the factor V Leiden mutation conceived, and were subsequently followed throughout their pregnancy. Subcutaneous low molecular weight heparin (LMWH, enoxaparin, 40 mg/day) and oral low dose aspirin (100 mg/day) were administered throughout the pregnancies, starting at early first trimester. Ultrasound and Doppler umbilical and fetal middle cerebral arterial flow studies were performed in the second and third trimesters, and the course and outcome of the pregnancies were documented.
Results Activated protein C resistance and factor V Leiden were found in 20 (36%) and 12 (21%) women of the study, respectively. Five of the seven pregnancies occuring progressed uneventfully to term with normal fetal growth, normal Doppler flow studies and uneventful neonatal outcome. Two of the seven women had early missed abortions.
Conclusions Thrombophylaxis, beginning in early pregnancy, in women with unexplained recurrent pregnancy loss associated with factor V Leiden mutation, seems to be safe and allow normal fetal development and good neonatal outcome. To prove the efficacy of thrombophylaxis by LMWH and low dose aspirin in this setting prospective controlled studies seem to be justified.