Low Molecular Weight Heparin In Pregnancy Research Articles

The Risk of Bleeding in Pregnant Women with Acute Venous Thromboembolism Treated with Anticoagulants

Introduction Women are at an increased risk of venous thromboembolism (VTE) during pregnancy and the postpartum period. VTE, which includes pulmonary embolism (PE) and deep vein thrombosis (DVT), complicates 1 to 2 of 1000 pregnancies and is an important cause of maternal morbidity and mortality. The risk of VTE during pregnancy is increased five to ten-fold compared to the non-pregnant woman of comparable age. During pregnancy, subcutaneous weight-adjusted low-molecular-weight-heparin (LMWH) is the standard anticoagulation therapy for acute VTE. Women receive a minimum of 3 months of LMWH with treatment generally extended throughout pregnancy and for at least 6 weeks following delivery given the additional increased VTE risk during the postpartum period. Variable estimates are reported in the literature pertaining to the risk of bleeding in pregnant patients treated with therapeutic anticoagulation. The risk of major bleeding, as defined by the study, ranges between 2.9 and 30.0% according to a recent systematic review of the literature. The ability to make inference is limited by the small number of patients included in the studies and the substantial heterogeneity of bleeding definitions used. The paucity of data doesn't allow healthcare providers to accurately estimate the risk of bleeding in this population and prevents adequate patient counselling. As such, we conducted a population-based cohort study to evaluate the risk of bleeding events among pregnant women with acute VTE treated with LMWH anticoagulants. Methods We conducted a retrospective cohort study using data from electronic healthcare databases from the province of Quebec, Canada, including the Régie de l'assurance maladie du Québec (RAMQ), the Maintenance et Exploitation des Données pour l'Étude de la Clientèle Hospitalière (Med-Echo) and the Institut de la statistique du Québec (ISQ). From an inception cohort of Quebec residents with a diagnosis of incident VTE between January 1, 1998, and December 31, 2015, we created a study cohort of pregnant women diagnosed with VTE during pregnancy who received a prescription for LMWH within 15 days of the incident event. When the gestational age of pregnant women was not available in the database, a previously described algorithm was used to extrapolate the date of conception according to the delivery outcome. Women were followed until an inpatient diagnosis of bleeding within 30 days of delivery or censoring due to discontinuation of LMWH use, cessation of medication coverage eligibility, death, or the end of the study period. Major bleeding was defined as a hospitalization for bleeding within the study period. Results Of the 325,560 patients included in the inception VTE cohort, 259 pregnant patients remained after the exclusion criteria were applied. The mean age of patients was 29 years-old, 80.9% of patients had a DVT and 19.5% had a PE. 72.6% of patients received Dalteparin, while the other patients received Tinzaparin or Enoxaparin. In total, 20 patients (7.7%) experienced bleeding requiring hospitalization during the study period, 5 of which were antepartum bleeding events (1.9%). The incidence rate of major bleeding was 310.5 per 1,000 person-years (95% CI 189.6-479.5). There was no bleeding-related or all-cause related mortality in this cohort. Conclusion This study provides a population-derived estimate of bleeding in pregnant women treated with therapeutic anticoagulation for VTE during pregnancy. This study has some limitations. First, data is not available for women who do not use medical services during pregnancy, those who give birth outside a hospital setting. However, given the free universal healthcare system in the province of Quebec, the effect of this on our result is expected to be minimal. Second, the RAMQ database provides information on individuals adherent to the RAMQ drug plan and welfare recipients, but not on individuals who are covered by private insurance. This may affect the generalizability of our study findings if socioeconomic status is an effect modifier. Our results show that Dalteparin is the most used LMWH in pregnancy. This study provides an estimate of bleeding events that are clinically significant and require hospitalization. Further studies are needed to evaluate the factors associated with increased bleeding in this patient population.

How Can Rotational Thromboelastometry as a Point-of-Care Method Be Useful for the Management of Secondary Thromboprophylaxis in High-Risk Pregnant Patients?

Thromboprophylaxis with low-molecular-weight heparin (LMWH) for patients with a history of venous thromboembolism (VTE) is suggested. Rotational thromboelastometry (ROTEM®) represents an innovative point-of-care method enabling the complex and quick evaluation of hemostasis. However, there are only episodic cases of its use for hemostasis assessment and guidance of LMWH in pregnancy. Therefore, we provide the results of unique prospective and longitudinal monitoring of hemostasis in high-risk pregnant women, which we used for the individualized optimalization of secondary thromboprophylaxis. According to the shortening of clot formation time (CFT) in EXTEM (p = 0.0007 from the 26th gestational week vs. controls) and INTEM (p = 0.002 from the 35th gestational week), increase in alpha angle (AA) in EXTEM, INTEM, and HEPTEM, and the persistence of increase in maximum clot firmness (MCF) in EXTEM, INTEM, and HEPTEM (p < 0.001 from the 26th and 35th gestational week vs. controls for EXTEM and INTEM, p = 0.0012 from the 26th gestational week in HEPTEM), LMWH dose was modified. Even after the postpartum period, AA in EXTEM was steeper than in controls (p = 0.0007), indicating that hemostasis is not fully normalized after 6–8 weeks following delivery. Therefore, ROTEM may be a useful tool for the individual evaluation of the termination of anticoagulant thromboprophylaxis.

The Safety of Low-Molecular-Weight Heparin During and After Pregnancy.

In industrialized countries, venous thromboembolism remains a leading cause of mortality in pregnant women. Low-molecular-weight heparin (LMWH) is the most commonly recommended anticoagulant in pregnancy, having been proven effective and safe in multiple prospective clinical trials. The aim of this article is to outline existing recommendations for proper use of LMWH in pregnancy and data on risks of LMWH. Wereviewed guidelines froma number of professional societies.We also examined the current literature behind the various risks associated with LMWH use. Our review outlines the current data that guide the use of LMWH in pregnancy. With prophylactic dosing, LMWH comes with a 0.5% risk of antepartum bleeding and a 1% risk of postpartum hemorrhage that is not different from clinical trial controls. With treatment dosing, there is a 1.5% risk of antepartum bleeding and a 2% risk of postpartum hemorrhage. Overall, current evidence behind these risks is limited, and this review suggests areas of further study moving forward.

Venous Thromboembolism in Pregnancy

Objective. To evaluate the safety of individually dosed low molecular weight heparin (LMWH) for prophylaxis and treatment of thromboembolic complications in pregnancy. Design. Cohort study with a chronologic register-based control group. Setting. Department of Obstetrics and Gynecology, Hillerod Hospital, Denmark. Population. All 166 women treated with LMWH in pregnancy between 1 January 2001 and 31 December 2005. Methods. Women treated with LMWH in pregnancy were identified and individual case records reviewed retrospectively. General data on the LMWH-treated women were compared to the 18,020 untreated pregnancies within the same period and with 306 matched controls as regards to postpartum hemorrhage (PPH). Main outcome measures. Side effects of treatment, thromboembolic manifestations, postpartum bleeding and obstetric outcome. Results. There were no thromboembolic events during therapy, few side effects of treatment and no osteoporotic fractures or episodes of heparin-induced thrombocytopenia. The 166 pregnancies resulted in 159 live infants. There was a significantly higher risk of preterm delivery (13% vs. 6%) and intrauterine growth restriction (4.4% vs. 3.5%). Delivery by cesarean section was more common in these high-risk LMWH-treated pregnancies (33.1%) than in untreated pregnancies (19.2%). In the LMWH-group, the occurrence of PPH was 7.2% compared with 8.8% in the matched untreated control group (p = 0.675). None of the events in the LMWH group were serious and all 166 women were in good health at discharge. Conclusions. Individually dosed LMWH is well tolerated and safe for prophylaxis and treatment of thromboembolic complications during pregnancy, delivery and the postpartum period.

Venous thromboembolism in pregnancy: prophylaxis and treatment with low molecular weight heparin

To evaluate the safety of individually dosed low molecular weight heparin (LMWH) for prophylaxis and treatment of thromboembolic complications in pregnancy. Cohort study with a chronologic register-based control group. Department of Obstetrics and Gynecology, Hillerød Hospital, Denmark. All 166 women treated with LMWH in pregnancy between 1 January 2001 and 31 December 2005. Women treated with LMWH in pregnancy were identified and individual case records reviewed retrospectively. General data on the LMWH-treated women were compared to the 18,020 untreated pregnancies within the same period and with 306 matched controls as regards to postpartum hemorrhage (PPH). Side effects of treatment, thromboembolic manifestations, postpartum bleeding and obstetric outcome. There were no thromboembolic events during therapy, few side effects of treatment and no osteoporotic fractures or episodes of heparin-induced thrombocytopenia. The 166 pregnancies resulted in 159 live infants. There was a significantly higher risk of preterm delivery (13% vs. 6%) and intrauterine growth restriction (4.4% vs. 3.5%). Delivery by cesarean section was more common in these high-risk LMWH-treated pregnancies (33.1%) than in untreated pregnancies (19.2%). In the LMWH-group, the occurrence of PPH was 7.2% compared with 8.8% in the matched untreated control group (p = 0.675). None of the events in the LMWH group were serious and all 166 women were in good health at discharge. Individually dosed LMWH is well tolerated and safe for prophylaxis and treatment of thromboembolic complications during pregnancy, delivery and the postpartum period.

Pregnancy, thrombophlebitis and thromboembolism: what every obstetrician should know

Thrombophlebitis is caused by superficial venous thrombosis and vascular inflammatory changes affecting the lower limbs. The condition is often encountered in pregnancy and symptomatic treatment including compression and analgesia are commonly employed. The obstetrician may become involved in the management of thrombophlebitis; however the potential for embolic complications, and need for adequate assessment remain widely unrecognised. This case report highlights pitfalls in the management of thrombophlebitis, in particular the dangers of clinical assessment without the use of Doppler ultrasound and the potential for deep venous extension and embolic complications. The case also documents the use of low molecular-weight heparin in pregnancy to prevent such complications and promote thrombus resolution; a review of the available treatment options, including surgery, is included. Whilst thromboembolism remains a leading cause of maternal death, the potential dangers of symptomatic thrombophlebitis should not be overlooked.

Anticoagulants in Pregnancy

Venous thromboembolic (VTE) complications are a leading cause of maternal mortality in the developed world. To reduce the incidence of VTE in pregnancy, and improve outcomes, a wider understanding of the risk factors involved and a better identification of women at risk of thrombosis coupled with effective thromboprophylaxis and treatment of VTE are required. As coumarin is unsuitable for use in pregnancy because of problems with embryopathy and risk of fetal bleeding, anticoagulation therapy in pregnancy centres on the use of low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH). There is now extensive experience of the safety and efficacy of LMWH in pregnancy. LMWH's, such as enoxaparin and dalteparin, have clinical and practical advantages compared with UFH in terms of improved safety (significantly lower incidence of osteoporosis and heparin induced thrombocytopenia), and patient convenience with once daily dosing for the majority of women. Such therapy is not restricted only to prevention and treatment of VTE but is now being assessed in additional clinical situations such as the prevention of pregnancy complications.

Prevention of thromboembolism with low-molecular weight heparin in pregnancy

Two patients were anticoagulated during pregnancy with the low molecular weight heparin Kabi 2165 because of side effects on conventional heparin. One patient had to be treated because of deep vein thrombosis in the first pregnancy and the other patient because of a Björk Shiley mitral valve prosthesis. The first patient had developed cutaneous allergic reactions to different conventional heparins and the second patient suffered from extensive local haematomas because of subcutaneous injection of heparin. The doses of the low molecular heparin were 1 X 5000 (patient 1) and 1 X 10,000 (patient 2) anti factor Xa units. The treatment period was 27 and 20 weeks, respectively. No thromboembolism or bleeding occurred. The low molecular weight heparin could not be detected in the umbilical vein or in the breast milk.