Anticoagulation In Pregnancy Research Articles

Venous thromboembolism in pregnancy and postpartum: an illustrated review

The topic of this review is venous thromboembolism (VTE) during pregnancy and postpartum. The following topics will be addressed: epidemiology and pathophysiology of VTE in pregnancy and postpartum, diagnostic considerations for VTE in pregnancy, indications for prophylactic and therapeutic anticoagulation in pregnancy and postpartum, choice of anticoagulation in pregnancy and breastfeeding, anticoagulation management during labor and delivery, and anticoagulation considerations for assisted reproductive technology.

Hematologic characteristics and coagulopathy in pregnancy with COVID-19 succeeding the first wave: a multicenter retrospective cross-sectional study

BackgroundEarly reports have demonstrated an association of COVID-19 infection during pregnancy and postpartum period with coagulopathy and bleeding complications and indicated that pregnant people with COVID-19 are more likely to experience coagulopathy and venous thromboembolism. A recent report concerning such complications during the first wave of the pandemic was reassuring; however, no publications have evaluated these issues in the context of increased illness severity with the emergence of SARS-CoV-2 variants of concern. ObjectivesWe performed a retrospective, multinational cohort study in Canada, Romania, and the United Kingdom, aiming to provide a comprehensive analysis of the hematologic test characteristics of pregnancies affected by COVID-19 after the first wave of the pandemic. ResultsThree-hundred-seventy patients were evaluated. Markers of inflammation and endothelial dysfunction were significantly elevated, in keeping with observations in the nonpregnant population. Reassuringly, despite more severe disease noted in succeeding waves of the pandemic, there was no significant evidence of COVID-19-associated coagulopathy, and overall, no association was demonstrated between isolated coagulation abnormalities and bleeding risk. Notably, fibrinogen below 2g/L was again linked with the risk of postpartum hemorrhage. Finally, venous thromboembolism risk was low but noted more frequently in those with severe illness despite thromboprophylaxis. ConclusionOur findings add valuable insights into the nature of hematologic test characteristics, bleeding, and thrombotic complications for those affected with COVID-19 in pregnancy, reassuring readers of the low incidence of bleeding and thrombotic complications but inviting further debate as to the degree of thromboprophylaxis that may benefit the subgroup with severe disease.

Report of the ISTH registry on pregnancy and COVID-19-associated coagulopathy (COV-PREG-COAG).

Concerns about COVID-19-associated coagulopathy (CAC) in pregnant individuals were raised in early pandemic. An ISTH-sponsored COVID-19 coagulopathy in pregnancy (COV-PREG-COAG) international registry was developed to describe incidence of coagulopathy, VTE, and anticoagulation in this group. All pregnant patients with COVID-19 from participating centers were entered, providing 430 pregnancies for the first pandemic wave. Isolated abnormal coagulation parameters were seen in 20%; more often with moderate/severe disease than asymptomatic/mild disease (49% vs 15%; p < 0.0001). No one met the ISTH criteria for disseminated intravascular coagulopathy (DIC), though 5/21 (24%) met the pregnancy DIC score. There was no difference in antepartum hemorrhage (APH) with asymptomatic/mild disease versus moderate/severe disease (3.4% vs 7.7%; p = 0.135). More individuals with moderate/severe disease experienced postpartum hemorrhage (PPH) (22.4% vs 9.3%; p = 0.006). There were no arterial thrombotic events. Only one COVID-associated venous thromboembolism (VTE) was reported. Low rates of coagulopathy, bleeding, and thrombosis were observed among pregnant people in the first pandemic wave.

Clinical study of disseminated intravascular coagulation in pregnancy at tertiary care centre - risk factors, complications, management and outcome

Clinical study of disseminated intravascular coagulation in pregnancy at tertiary care centre - risk factors, complications, management and outcome

Clarifying Indications and Dosing of Anticoagulants in Pregnancy

Clarifying Indications and Dosing of Anticoagulants in Pregnancy

Acute Myelogenous Leukemia in Pregnancy in a 32yr Old Woman

Background: Generally a disease of the elderly, Acute Myelogenous Leukemia (AML) very rarely occurs in pregnancy with an estimated incidence of 1 in 75,000 - 100, 000 pregnancies1, 2. There is hardly any data on the difference in its incidence between pregnant women and non-pregnant women in the reproductive age. However, management options are more in the non-pregnant, asthey are in the elderly. Because there is yet no globally agreed standard way of managing this clinical dilemma in pregnancy, various institutions have proposed different management protocols depending on the AML type, degree of symptomatology, gestational age at diagnosis and the patient’s wishes. The objective of this publication is to present our experience with this condition at the Korle Bu Teaching Hospital, to bring attention to the possibility of the condition in our environment as part of differential diagnoses of anaemia or coagulopathy in pregnancy. Case: We report the case of a 32yr old G3P1+1A, at 32weeks 2days gestation diagnosed with and managed for Acute Myeloid Leukemia at the Korle Bu Teaching Hospital, and review of the available literature on this condition in pregnancy.Conclusion: Acute Myelogenous Leukemia is a very rare condition in pregnancy that lacks universally accepted treatment protocols. Management can pose a challenge to clinicians, patients and their relatives. Early accurate diagnosis is difficult in resource-constrainedsettings, and management options are limited when trying to save both fetus and mother. Early accurate diagnosis and prompt referral for appropriate interventions are key in improving outcomes, even in the face of other obstetric complications.

Experience with direct oral anticoagulants in pregnancy – a systematic review

The experience and use of the new direct oral anti coagulants (DOACs) in pregnancy is limited, but as they offer many practical advantages compared to low molecular weight heparin (LMWH), the pursue of their safety is challenging. Systematic review of studies in which DOACs were used during pregnancy and the puerperal period (PROSPERO registry-CRD42021237688). Searches were performed on MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library databases, until July 2021 and secondary sources using the MeSH terms 'pregnancy', 'pregnancy complications', 'venous thrombosis', 'congenital abnormalities', 'Factor Xa Inhibitors,' and names of specific DOACs. Search was limited to human studies, with English or French as languages of report. Literature search yielded 1,989 results which, after duplicate exclusion, resulted in 672 publications. Studies were then screened using the specified eligibility criteria described and studies that did not meet the criteria were excluded, resulting in 21 full text studies to an in-depth analysis and data extraction. Overall, 339 cases of DOACs usage during pregnancy were reported until now. The data demonstrated 56% live births but a miscarriage rate of 22.2% and an elective termination of pregnancy in 21.8%; fetal abnormalities related to DOACs occurred in 3.6%. Our meta-analysis displayed a higher rate of fetal loss and fetal abnormalities with DOACs use compared to LMWH, notwithstanding similar bleeding complications. The current information available for the 339 cases herein reported does not allow a conclusion that DOACs can be safely used in pregnancy.

Management of anticoagulation in pregnant women with venous thromboembolism: An international survey of clinical practice

IntroductionVenous thromboembolism (VTE) is an important cause of maternal morbidity and mortality. During pregnancy, VTE is treated with low-molecular-weight-heparin (LMWH). Studies assessing the optimal duration and peripartum management of therapeutic anticoagulation are lacking. This survey aimed to assess clinician practices for the management of anticoagulation in pregnant women with acute VTE. MethodsAn electronic survey consisting of clinical scenarios addressing anticoagulation management for VTE in pregnancy was created. The target sample was clinicians likely to be involved in the management of pregnant women with acute VTE. The survey completion rate and proportion of individuals selecting a response were determined. Results96 respondents completed the survey including general internists (56.3%), hematologists (21.9%), and obstetricians (6.3%). In the management of a VTE in first or second trimester, most respondents preferred therapeutic LMWH until 6 weeks postpartum. In the first and second trimester, 48.0% and 37.5% of respondents, respectively, opted to reduce the dose of anticoagulation after 3 or 6 months. 29.2% of physicians opted for bridging with intravenous heparin around delivery when treating a VTE in the third trimester. 73.0% perceived an increased risk of clinically relevant non-major bleeding associated with the use of therapeutic anticoagulation in the peripartum and postpartum periods. ConclusionsThe survey highlights a wide variability of practice in the management of therapeutic anticoagulation in pregnancy. Larger scale studies with relevant clinical outcomes including thrombosis and bleeding risks are needed to inform clinical practice.

Physician experiences in management of COVID‐19‐associated coagulopathy in pregnancy: Communication from the ISTH SSC Subcommittee on Women's Health Issues in Thrombosis and Haemostasis

BackgroundCoronavirus disease 2019 (COVID‐19) occurs following infection with the potentially fatal, severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) virus. Infection can be complicated by coagulopathy, at times featuring thrombocytopenia and thrombosis alongside other coagulation abnormalities, also termed COVID‐19‐associated coagulopathy (CAC). Data concerning CAC in pregnancy are limited. Better understanding of physician experiences is essential to identify current practice patterns and knowledge gaps. ObjectivesTo determine physician experiences and practice patterns regarding CAC in pregnancy. MethodsSelf‐administered survey using the RedCap online platform; supported by the ISTH Subcommittee on Women's Health Issues in Thrombosis and Hemostasis. ResultsSeventy‐five respondents fully or partially completed the survey. Of 1546 reported cases, disease severity was specified in 1298. Sixty‐four percent of COVID‐19 infections were mild, whereas 4% were severe. Of all cases, 1% developed CAC, with 65% classified as severe. The most frequent abnormalities included thrombocytopenia, elevated C‐reactive protein, D‐dimer, and lymphopenia. Low molecular weight heparin was the anticoagulant of choice in CAC and was provided by 77% of respondents, with 60% using standard prophylactic dosing. Thrombosis occurred in seven anticoagulated patients who were receiving standard prophylactic (four) or weight‐based (three) dosing. Disease severity and additional thrombosis risk factors dictated anticoagulation duration. ConclusionIn the select population reported by our survey, CAC appears to be uncommon in pregnancy. Anticoagulation practices vary and may not reflect current guidelines. Venous thromboembolism was observed in some CAC patients despite prophylactic anticoagulation (including standard and weight‐adjusted dosing). Urgent research is required to determine appropriate anticoagulant dosing and duration in pregnant women with COVID‐19 infection.

Risk stratification for pregnancy-associated venous thromboembolism: Potential role for global coagulation assays.

Risk assessment for venous thromboembolism in pregnancy and the puerperium is currently limited to stratifying clinical surrogate risk factors without high-quality evidence. While the absolute risk of pregnancy-associated venous thromboembolism is low for the vast majority of women, associated morbidity and mortality remains significant. As guidelines for thromboprophylaxis vary widely, some women may be under- or over-anticoagulated, contributing to poor outcomes. New global coagulation assays provide a holistic view of coagulation and may have the potential to detect hypercoagulability in pregnancy, unlike clinically available coagulation assays. However, there are major technical challenges to overcome before global coagulation assays can be realistically proposed as an adjunct to risk assessment for pregnancy-associated venous thromboembolism. This review summarises the literature and controversies in the prediction and prevention of pregnancy-associated venous thromboembolism and outlines the new tools in haematology that may assist in our future understanding of hypercoagulability in pregnancy.

Hypercoagulability in pregnant trauma patients

Circulating hormones affect coagulopathy in pregnancy and after trauma. The hemostatic profile of pregnant women after injury has not been characterized. We hypothesized that injured pregnant females would present with...

Anticoagulation in pregnancy

Anticoagulation in pregnancy

Антикоагулянтное ведение беременных с коронавирусной инфекцией

Введение. Частота распространения новой коронавирусной инфекции COVID-19 (НКИ COVID-19) среди беременных сравнима с общепопуляционными показателями, что требует особого внимания в связи с повышенным риском материнской смертности в результате осложнений инфекционного процесса. Учитывая наличие гиперкоагуляционного статуса во время физиологически протекающей беременности, инфицирование вирусом COVID-19 может способствовать еще большему усилению прокоагулянтных свой ств крови. Патогенетически обоснованным является применение антикоагулянтной терапии во время беременности при условии верифицированной коронавирусной инфекции с целью снижения риска развития тромботических осложнений. Материалы и методы. Представлены 2 клинических случая успешного применения антикоагулянтов (низкомолекулярного гепарина) у беременных с подтвержденным инфицированием COVID-19. Результаты. Ретроспективный анализ лабораторных и клинических данных продемонстрировал эффективность парнапарина натрия в качестве средства профилактики тромботических осложнений у беременных с НКИ COVID-19. Заключение. Применение антикоагулянтной терапии у беременных с НКИ COVID-19 позволяет снизить риск развития тромботических эпизодов и улучшить репродуктивные исходы беременности. Background. The COVID-19 frequency among pregnant women is comparable to general population but it requires specific approach due to increased risk of maternal mortality as a result of infectious complications. The hypercoagulation is during physiological pregnancy, and COVID-19 can enhance further a procoagulant conditions. In such cases the anticoagulant therapy is aimed to reduce the thrombotic risk. Patients / Methods. The article presents 2 clinical cases of successful use of anticoagulants (low molecular weight heparin) in pregnant women with confirmed COVID-19. Results. A retrospective analysis of laboratory and clinical data has demonstrated the effi cacy of parnaparin sodium as a means of preventing thrombotic complications in pregnant women with COVID-19. Conclusions. Anticoagulant therapy in pregnant women with COVID-19 allows to reduce the thrombotic risk and improve the reproductive outcomes of pregnancy.

Anticoagulation in Pregnancy and Post-partum: New Options

Anticoagulation in Pregnancy and Post-partum: New Options

North American Physician Practice Patterns in the Management of Anticoagulation in Pregnancy.

Background: During pregnancy and in the postpartum period women are at increased risk of venous thromboembolism (VTE) owing to hypercoagulability and mechanical issues, as well as nonpregnancy conditions including inherited and acquired thrombophilia. Although guidelines exist for the use of thromboprophylaxis in this setting, there are differences in the specifics of the recommendations among expert societies. We assessed the current practice patterns of North American providers in the prevention of pregnancy-associated VTE in women with thrombophilia. Methods: A survey was created and distributed with case studies and questions addressing VTE prevention during the antepartum and postpartum periods. Results: Surveys were completed by 28% of adult providers queried, with broad geographic representation. There was consistent use of a prophylactic dose of low-molecular weight heparin (LMWH) ante- and postpartum for individuals with low-risk thrombophilia and past estrogen-provoked VTE but a lack of a consensus of anticoagulant (AC) use and dose in individuals with higher risk thrombophilia. There was variability in the dose selection and monitoring of AC when using induction versus spontaneous labor, with 47% of providers switching from LMWH to unfractionated heparin for those not having a scheduled delivery, and there were differences in the duration of postpartum prophylaxis based upon delivery mode. Conclusion: In this survey of North American experienced specialists' responses to a variety of commonly encountered scenarios of thrombophilia and pregnancy and the management of AC were not always consistent with published guidelines.

COVID‐19 coagulopathy in pregnancy: Critical review, preliminary recommendations, and ISTH registry—Communication from the ISTH SSC for Women’s Health

BackgroundNovel coronavirus (SARS‐CoV‐2), which causes COVID‐19, has thus far affected more than 15 million individuals, resulting in more than 600 000 deaths worldwide, and the number continues to rise. In a large systematic review and meta‐analysis of the literature including 2567 pregnant women, 7% required intensive care admission, with a maternal mortality ~1% and perinatal mortality below 1%. There has been a rapid increase in publications on COVID‐19–associated coagulopathy, including disseminated intravascular coagulopathy and venous thromboembolism, in the non‐pregnant population, but very few reports of COVID‐19 coagulopathy during pregnancy; leaving us with no guidance for care of this specific population. MethodsThis is a collaborative effort conducted by a group of experts that was reviewed, critiqued, and approved by the International Society on Thrombosis and Haemostasis Subcommittee for Women's Health Issues in Thrombosis and Hemostasis. A structured literature search was conducted, and the quality of current and emerging evidence was evaluated. Based on the published studies in the non‐pregnant and pregnant population with a moderate to high risk of bias as assessed by Newcastle‐Ottawa scale and acknowledging the absence of data from randomized clinical trials for management of pregnant women infected with SARS‐CoV‐2, a consensus in support of a guidance document for COVID‐19 coagulopathy in pregnancy was identified. Results and ConclusionsSpecific hemostatic issues during pregnancy were highlighted, and preliminary recommendations to assist in the care of COVID‐19–affected pregnant women with coagulopathy or thrombotic complications were developed. An international registry to gather data to support the management of COVID‐19 and associated coagulopathy in pregnancy was established.

PROTEIN S DEFICIENCY IN PREGNANCY: TO TREAT OR NOT TO TREAT. A CASE SERIES.

Introduction: Protein S deficiency is rare occurring in only about 3 out of 10,000 women. Thrombophilias, whether inherited or acquired, have been associated with adverse reproductive outcomes such as recurrent first trimester pregnancy losses, second and third trimester pregnancy losses, pre-eclampsia, fetal growth restriction, placental abruption and venous thrombo-embolism. Treatment of protein S deficiency with anticoagulation in pregnancy is usually individualized depending on patient prior history and presenting symptoms. We report of 2 cases of women with protein S deficiency in pregnancy who had varied management and conduct a literature review on the salient features of this condition in pregnancy. &#x0D; Cases: Two women, who were sisters and had a prenatal diagnosis of protein S deficiency, were managed in their current pregnancies. One was on her fifth pregnancy having had adverse pregnancy outcomes and the other in her first pregnancy. One of the lady was on anti-thrombotic agents prior to the pregnancy which was continued during the pregnancy and the other was not started on anti-coagulation. They both had good pregnancy outcomes in the documented pregnancies. &#x0D; Conclusion: Protein S deficiency in pregnancy is a rare medical condition which most clinicians may not come across in their practice. The patients outlined had a prenatal diagnosis and hence presented no diagnostic dilemma. However, thrombophilias should be suspected in women with recurrent adverse pregnancy outcomes that have not been explained with other causes. The management of these patients largely involve use of anti-thrombotic agents with multi-disciplinary care being of benefit in improving outcomes.

PROTEIN S DEFICIENCY IN PREGNANCY: TO TREAT OR NOT TO TREAT. A CASE SERIES.

Introduction: Protein S deficiency is rare occurring in only about 3 out of 10,000 women. Thrombophilias, whether inherited or acquired, have been associated with adverse reproductive outcomes such as recurrent first trimester pregnancy losses, second and third trimester pregnancy losses, pre-eclampsia, fetal growth restriction, placental abruption and venous thrombo-embolism. Treatment of protein S deficiency with anticoagulation in pregnancy is usually individualized depending on patient prior history and presenting symptoms. We report of 2 cases of women with protein S deficiency in pregnancy who had varied management and conduct a literature review on the salient features of this condition in pregnancy. &#x0D; Cases: Two women, who were sisters and had a prenatal diagnosis of protein S deficiency, were managed in their current pregnancies. One was on her fifth pregnancy having had adverse pregnancy outcomes and the other in her first pregnancy. One of the lady was on anti-thrombotic agents prior to the pregnancy which was continued during the pregnancy and the other was not started on anti-coagulation. They both had good pregnancy outcomes in the documented pregnancies. &#x0D; Conclusion: Protein S deficiency in pregnancy is a rare medical condition which most clinicians may not come across in their practice. The patients outlined had a prenatal diagnosis and hence presented no diagnostic dilemma. However, thrombophilias should be suspected in women with recurrent adverse pregnancy outcomes that have not been explained with other causes. The management of these patients largely involve use of anti-thrombotic agents with multi-disciplinary care being of benefit in improving outcomes.

Comparative analysis of the impact on pregnancy of low-dose aspirin, low-molecular-weight heparine and combined treatment objectified by values of Doppler velocimetry

Introduction. The fact that thrombophilia is a factor involved in the pathogenesis of preeclampsia is a hypothesis supported bidirectionally by numerous contradictory results; however, it is estimated that approximately 40% of patients with preeclampsia have a thrombophilic substrate. Most valid studies do not support an association between inherited thrombophilia and preeclampsia, intrauterine growth restriction or spontaneous abortion, thus implicitly not supporting the prophylactic anticoagulant treatment with low-molecular-weight heparin (LMWH) for the prevention of the aforementioned conditions. Materials and method. We selected pregnant women with developing or spontaneous discontinued pregnancy undergoing anticoagulant or antiplatelet treatment. In the context where clear protocols for the administration of anticoagulants in pregnancy have not yet been established, we aimed to perform a comparative analysis of the clinical and anamnestic aspects on which the indication of treatment with antiplatelet, anticoagulant or the two combined in pregnancy were based and the impact on placental function by comparative analysis of the values of the Doppler measurements for the uterine, umbilical and average cerebral arteries of the patients included in the three study groups. Results. Spontaneous abortions or intrauterine fetal death in the antecedents was the main criterion for recommending antiplatelet, anticoagulant or combined treatment. In the presence of a personal history of thrombotic events, the combined treatment of LMWH and low-dose aspirin was chosen. We did not obtain a significant difference in the frequency of spontaneous pregnancy loss between the three study groups, the proportion of this condition being similar. Conclusions. The combined treatment of LMWH and low-dose aspirin in pregnancy was significantly correlated with the values of the resistance and pulsatility index of the uterine arteries closest to the normal values, with an average pulsatility index lower than 1, in particular for the left uterine artery, compared to the results obtained for the single treatment with low-dose aspirin or LMWH.

Retrospective Analysis of Bleeding in Pregnant Patients on Anticoagulation: A Single Center Experience

Background During pregnancy, women develop a physiologic hypercoagulable state related to hormonal changes and physical factors which can predispose them to the development of venous thromboembolism (VTE). Anticoagulation may be prescribed for underlying conditions that add additional risk of developing a thromboembolism during pregnancy or to minimize the risk of pregnancy loss. Heparin and low molecular weight heparin are believed to be safe to use during pregnancy, however these agents do present potential risks, particularly of bleeding for both the mother and fetus. Examination of the clinical outcomes, specifically bleeding and transfusion requirements at the time of delivery and the immediate postpartum period, in patients taking enoxaparin or heparin during high-risk pregnancies can provide further information on the safety of anticoagulants in pregnancy. Methods We conducted a retrospective case-control analysis of patients admitted to Georgetown University Hospital (GUH) for labor and delivery from the maternal fetal medicine service taking anticoagulation ante- and postpartum (N=13) as compared to matched controls (N=26) from January 2016 through December 2017. Individuals were matched for age (+/- 2 years), delivery date (+/- 1 month), delivery method (Cesarean or Vaginal), and gravidity. Women who underwent supplemental surgical procedures during delivery, with exception of tubal ligation, were excluded. Means independent t-tests were utilized to determine if women taking anticoagulants during pregnancy were more likely than matched controls to have increased estimated blood losses (EBL), blood transfusion requirements, or changes in antepartum hemoglobin (Hgb) or hematocrit Hct) (≤48 hours prior to delivery) verses postpartum (≤48 hours after delivery). Results with p &amp;lt; 0.05 were deemed significant. Results There was no significant difference in EBL between individuals taking anticoagulants during pregnancy as compared to controls (615.37mL vs 594.23 mL, p = 0.064). There was also no significant difference between antepartum Hgb or Hct (11.76 g/dL vs11.92 g/dL, p = 0.358 and34.99% vs 35.70%, p = 0.766, respectively), or postpartum Hgb or Hct (10.13 g/dL vs10.16 g/dL, p = 0.959 and 30.465vs30.57%, p = 0.338, respectively). Furthermore, the difference in Hgb or Hct before delivery to immediately after was not statistically significant (1.63 g/dL vs 1.76 g/dL, p = 0.056 and 4.53% vs5.13% p = 0.236, respectively) between the two groups. Interestingly, the mean number of units of RBCs transfused was significantly higher for patients on Enoxaparin as compared to controls (0.77 units vs 0.00 units respectively, p = 0.003), however only one patient in the Enoxaparin group required transfusions. Conclusion These data suggest that anticoagulation during high-risk pregnancies is not associated with an increased estimated blood loss or significant reduction in postpartum Hgb and Hct. Although an overall mean increase in units of blood transfused was noted for the anticoagulation group this was based on one patient and may not be representative. Although these results are reassuring that there are minimal risks to anticoagulation in a high risk maternal fetal medicine population additional analyses should be completed from a larger patient population. Figure Disclosures Broome: Sanofi Genzyme: Honoraria, Research Funding; Rigel: Research Funding; Cellphire: Research Funding; Alexion: Honoraria, Research Funding; Incyte: Research Funding.