Prothrombin and Factor V Mutations in Women with a History of Thrombosis during Pregnancy and the Puerperium

Gerhardt, Andrea; Scharf, Rüdiger E.; Beckmann, Matthias W.; Struve, Sabine; Bender, Hans; Pillny, M.; Sandmann, W.; Zotz, Rainer B.

doi:10.1056/nejm200002103420602

Cited by 467 publications

(278 citation statements)

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“…Other groups have also emphasised the importance of a hereditary AT defi ciency as a high risk thrombophilic disorder, especially during pregnancy [20,21]. In contrast, the presence of a homozygous methylene tetrahydrofolate reductase (MTHFR) C677T mutation did not contribute to the risk of VTE in pregnant women [19,22]. Although not well studied, women with known antiphospholipid syndrome (APS) and previous VTE seem to be at high risk for recurrent VTE during pregnancy.…”

Section: Risk Factorsmentioning

confidence: 99%

Diagnosis of pregnancy-associated venous thromboembolism - position paper of the Working Group in Women’s Health of the Society of Thrombosis and Haemostasis (GTH)

Linnemann¹,

Scholz

Rott

et al. 2016

Vasa

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EpidemiologyVTE is a leading cause of maternal morbidity in the developed world and, in the case of PE, of mortality as well [1]. While the relative risk of VTE is greatly increased during pregnancy compared with that in non-pregnant women, the absolute risk remains low: estimates of the incidence of pregnancy-associated VTE have varied from 1:500 to 1:1500 pregnancies [2 -7]. The risk of VTE is approximately 5-fold greater in pregnant women than in non-pregnant women.Approximately 80 % of pregnancy-associated VTEs are isolated DVTs, and approximately 20 % are PEs or both DVTs and PEs [5]. Although a systematic review reported weighted event rates for DVT of 21.9 %, 33.7 % and 47.6 % for the fi rst, second and third trimesters, respectively [6], a recent study suggested that the risk might in fact increase exponentially over the duration of the pregnancy [7], with 12.4 % of VTEs diagnosed in the fi rst trimester, 15.3 % in the second trimester and 72.3 % in the third trimester. This detailed risk assessment for each gestational week demonstrated a 21-fold increased risk for the last two weeks before delivery [7]. Summary: Pregnancy and the postpartum period are associated with an increased risk of venous thromboembolism (VTE). Over the past decade, new diagnostic algorithms have been established, combining clinical probability, laboratory testing and imaging studies for the diagnosis of deep vein thrombosis (DVT) and pulmonary embolism (PE) in the non-pregnant population. However, there is no such generally accepted algorithm for the diagnosis of pregnancy-associated VTE. Studies establishing clinical prediction rules have excluded pregnant women, and prediction scores currently in use have not been prospectively validated in pregnancy or during the postpartum period. D-dimers physiologically increase throughout pregnancy and peak at delivery, so a negative D-dimer test result, based on the reference values of non-pregnant subjects, becomes unlikely in the second and third trimesters. Imaging studies therefore play a major role in confi rming suspected DVT or PE in pregnant women. Major concerns have been raised against radiologic imaging because of foetal radiation exposure, and doubts about the diagnostic value of ultrasound techniques in attempting to exclude isolated iliac vein thrombosis grow stronger as pregnancy progresses. As members of the Working Group in Women's Health of the Society of Thrombosis and Haemostasis (GTH), we summarise evidence from the available literature and aim to establish a more uniform strategy for diagnosing pregnancy-associated VTE. Review Diagnosis of pregnancy-associated

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Section: Risk Factorsmentioning

confidence: 99%

Diagnosis of pregnancy-associated venous thromboembolism - position paper of the Working Group in Women’s Health of the Society of Thrombosis and Haemostasis (GTH)

Linnemann¹,

Scholz

Rott

et al. 2016

Vasa

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Section: Hypoxemic Hypoxia (Uteroplacental Insufficiency)mentioning

confidence: 99%

“…Hypoxemic growth-restricted fetuses also demonstrate a whole range of abnormalities that persist in adult life [4][5][6][7][8][9][10] . Cross-sectional studies in pregnancies with growth-restricted fetuses have shown that increased impedance to flow in the uterine and umbilical arteries is associated with fetal hypoxemia and acidemia 11,12 , resulting in:(1) Failure of the normal development of maternal placental arteries into low-resistance vessels and therefore reduced oxygen and nutrient supply to the intervillous space 13 ; (2) Reduction in the number of placental terminal capillaries and small muscular arteries in the tertiary stem villi and therefore impaired maternal-fetal transfer 14 .Doppler ultrasound has enabled the non-invasive confirmation of the so-called 'brain-sparing' effect in human fetuses 15 . …”

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confidence: 99%

3 Invited speakers abstracts

2017

Journal of Perinatal Medicine

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Eclampsia remains one of the five major causes of maternal mortality in developing countries. Advances in diagnosis and management have led to a significant reduction in maternal mortality and morbidity from this disease in developed countries. In developing countries the incidence of maternal death attributed to eclampsia remains high and, in Ethiopia, maternal mortality from this complication has instead risen over the last decade. The purpose of this study was to review the incidence of eclampsia at the largest feto-maternal center in the country over one year in an attempt to determine what quality improvement measures are needed and could realistically be implemented within the system to decrease this complication.There were a total of 104 eclamptic patients during the study period. The hospital incidence of eclampsia was 82/10,000 deliveries excluding those arriving to the hospital in the postpartum period (28 cases). There were 8 maternal deaths making the case fatality rate 1 in 13 cases. The median convulsion to arrival time, referral to arrival time and magnesium sulphate administration time were found to be 3, 2 and 3 hours respectively. The probability of multiple seizures (≥ 3 episodes) was increased significantly with the prolongation of these time variables. Occurrence of multiple seizures was intern significantly associated with adverse maternal outcomes (ICU admission, morbidities and mortalities).As expected, there was a high incidence of eclampsia and eclampsia related maternal death in the hospital. We recommend a thorough assessment of the referral system, upgrading and capacity building of more health facilities, organizing trainings and drills in health facilities; and availing magnesium sulphate in all health centers among others.J. Perinat. Med. 45 (2017) • Copyright © by Walter de Gruyter • Berlin • Boston. DOI 10.1515DOI 10. /jpm-2017DOI 10. -2007 48 Unauthenticated Download Date | 5/12/18 10:39 AM DEEP TONGUE LACERATION; A RARE COMPLICATION OF INTRAPARTUM ECLAMPSIA Huawa AbdullahiBackground: Eclampsia remains a common cause of maternal morbidities and mortalities with higher incidence in developing than developed counties. This is attributed to poor utilization of maternal health care facilities. A good understanding of eclampsia is important in the communities of Northern Nigeria because of the socio-cultural and religious barrier which prevent the women from attending clinics coupled with scarcity of antenatal facilities and inadequate manpower. This is a case of a 23years old unbooked primigravida who is unsure of her date but said to be nine month Amenorrhoec. She presented with complain of convulsions several times at home and bite her tongue in the process. She bled torrentially from the site. They went to three Hospitals before coming to Aminu Kano Teaching Hospital. She was resuscitated, stabilized and delivered via Caesarean Section. The tongue was also repaired by Maxillo fascial surgeons. Conclusion:Preventing pre eclampsia is the main tool of preventing Eclampsia. This is...

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“…thrombophilia is substantially increased. The risk of VTE in pregnant women may be further amplified by the type of underlying genetic predisposition, like, homozygosity for a mutation, the presence of multiple mutations (multigenic defects) or thrombophilic anomalies [16][17][18][19].Thrombophilia and adverse pregnancy outcome Preeclampsia, abruptio placenta, intrauterine growth restriction (IUGR) and intrauterine fetal death (IUFD) greatly contribute to maternal and fetal morbidity and mortality. Their causes are unknown, but all of them may be associated with abnormal placental vasculature and disturbances of hemostasis leading to inadequate maternal-fetal circulation [11][12][13][14][15]20,21].…”

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confidence: 99%

Thrombophilia and pregnancy

Brenner¹

2005

Eur J Clin Investigation

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Pregnancy is hypercoagulable state. The field of thrombophilia; the tendency to thrombosis, has been developed rapidly and has been linked to many aspects of pregnancy. It is recently that severe pregnancy complications such as severe preeclampsia intrauterine growth retardation abruptio placentae and stillbirth has been shown to be associated with thrombophilia. Recurrent miscarriage and has also been associated with thrombophilia. Finally, thromboembolism in pregnancy as in the non-pregnant state is linked to thrombophilia. In this review all aspects of thrombophilia in pregnancy are discussed, and also all prophylactic and therapeutic implications.Thrombophilias are inherited or acquired conditions which predispose an individual to thromboembolism. Deficiencies of protein S C and antithrombin are rare and each of them is found in about 3% of patients with thrombosis. Recently, three important inherited thrombophilias were discovered which are responsible of the majority of thromboembolic events in patients with otherwise no apparent risk for thrombosis. Resistance to activated protein C caused by an adenine 506 guanine (A506G) mutation in factor V (factor V Leiden) has been linked with an increased risk for venous thromboembolism [1][2][3]. Heterozygosity for the factor V (FV) Leiden mutation is found in about 5% of the population and the mutation is responsible of 20-30% of venous thromboembolism events. A recently described guanine 20210 adenine mutation in prothrombin is associated with higher plasma prothrombin concentrations and increased risk for venous thromboembolism [4] and cerebral-vein thrombosis [5]. Homozygosity for the cytosine 677 thymine (C677T) mutation in methylenetetrahydrofolate reductase (MTHFR) results in decreased synthesis of 5-methyltetrahydrofolate, the primary methyl donor in the conversion of homocysteine to methionine and the resulting increase in plasma homocysteine concentrations is a risk factor for thrombosis [6,7]. The mutation is responsible for reduced MTHFR activity and is the most frequent cause of mild hyperhomocysteinemia and can be found in 5-15% of the population.Homocysteine is an independent risk factor for atherosclerosis, stroke, peripheral vascular disease and cardiovascular diseases [8,9]. Homocysteine concentrations are affected by nutrition. A deficiency in folate, B-6, and/or B-I2 causes elevation of homocysteine. Homocysteine concentrations are also affected by genetics such as cystathionine beta-synthase deficiency (10) and C677T MTHFR gene mutation [7]. Hyperhomocysteinemia promotes vascular damage by several mechanisms. Many of the endothelial vascular changes associated with hyperhomocysteinemia can be found in preeclampsia [11][12][13][14][15]. thrombophilia is substantially increased. The risk of VTE in pregnant women may be further amplified by the type of underlying genetic predisposition, like, homozygosity for a mutation, the presence of multiple mutations (multigenic defects) or thrombophilic anomalies [16][17][18][19].Thrombophilia and ad...

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Prothrombin and Factor V Mutations in Women with a History of Thrombosis during Pregnancy and the Puerperium

Cited by 467 publications

References 21 publications

Diagnosis of pregnancy-associated venous thromboembolism - position paper of the Working Group in Women’s Health of the Society of Thrombosis and Haemostasis (GTH)

Diagnosis of pregnancy-associated venous thromboembolism - position paper of the Working Group in Women’s Health of the Society of Thrombosis and Haemostasis (GTH)

3 Invited speakers abstracts

Thrombophilia and pregnancy

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