Thromboembolism in pregnancy

Venous thromboembolism in pregnancy is a clinical emergency that has been associated with significant risk for maternal and fetal morbidity and mortality. The adaptation of the maternal hemostatic system to pregnancy predisposes women to an increased risk of thromboembolism. A timely diagnosis of deep venous thrombosis is crucial because up to 24% of patients with untreated deep venous thrombosis develop a pulmonary embolism. Recent clinical guidelines identify compression venous ultrasound as the best way to diagnose deep venous thrombosis in pregnancy and CT pulmonary angiography as the best way to diagnose pulmonary embolism in pregnancy. Therapy involves supportive care and anticoagulation with unfractionated or low molecular weight heparin, depending on the clinical scenario.     

The acute management of venous thromboembolism in pregnancy.

Pulmonary thromboembolism is the leading cause of maternal death in the UK. Optimal management of deep venous thrombosis and pulmonary thromboembolism requires an appreciation of risk factors, particularly thrombophilia, and signs or symptoms suggestive of venous thromboembolism, along with objective diagnosis and treatment with anticoagulants. Low molecular weight heparins are now replacing unfractionated heparin for the treatment of deep venous thrombosis and pulmonary thromboembolism in pregnancy because of the lower risk of side effects, ease of administration and reduced need for monitoring.     

Venous thromboembolism in pregnancy

Venous thromboembolism remains a common cause of direct maternal deaths in high-income settings such as the United Kingdom. Pregnancy alone increases the risk of deep vein thrombosis and pulmonary embolus at least five-fold, and many women develop or have additional risk factors for venous thrombosis during pregnancy and the puerperium, the latter representing the period of highest risk. Early and repeated risk stratification and adequate thromboprophylaxis, usually with low molecular weight heparin, is the key to preventing venous thromboembolism (VTE). Women with a past history of VTE, and those affected by thrombophilia, require multidisciplinary care involving an obstetric haematologist. Women suspected of having acute thromboembolism should be commenced on empirical treatment promptly prior to diagnostic confirmation. Pulmonary embolism should be considered as a differential diagnosis in maternal collapse.     

Venous thromboembolism in pregnancy

Venous thromboembolism (VTE) includes deep vein thrombosis (DVT) and pulmonary embolism (PE). In pregnancy, deep vein thrombosis accounts for 75–80% of venous thromboembolism, the remainder are pulmonary embolisms. One half of these VTEs occur during pregnancy and the other half in the postpartum period. Venous thromboembolism is one of the leading causes of maternal mortality worldwide and is also the cause of significant maternal morbidity. This article discusses the risk factors for VTE in pregnancy, the management of the pregnant woman at risk both antenatally and postpartum and the acute management of VTE when it occurs during pregnancy.     

Venous thromboembolism in pregnant Chinese women

OBJECTIVE: To evaluate the incidence, disease pattern, and risk factors for thromboembolism in pregnant Chinese women. METHODS: We conducted a study from January 1998 to December 2000. Women with thromboembolic diseases were identified and their case records retrieved and reviewed. Demographic characteristics were compared between women with and without thromboembolism. RESULTS: Thirty-two women were diagnosed as having thromboembolic disease during the study period. The total number of deliveries over the study period was 16,993, giving an incidence of 1.88 per 1000 deliveries. There were two cases of pulmonary embolism and one resulted in a maternal death. The others had deep vein thrombosis of which over 80% were limited to calf veins only. The ultrasound examinations requested for suspected deep venous thrombosis before and after the event of maternal death were 1.62 and 10.7 per 1000 deliveries (P <.001); and the corresponding cases of deep venous thrombosis diagnosed were 0.29 and 2.94 per 1000 deliveries, respectively (P <.001). The majority (75%) of cases were diagnosed in the postpartum period, mainly after cesarean delivery. Women with venous thromboembolism were older, had higher body mass index, and a higher incidence of preeclampsia. CONCLUSION: Thromboembolic disease is not uncommon among pregnant Chinese women. The incidence was similar to that of the white population, although the sites of vascular occlusion were different. The long-standing belief that thromboembolism is rare among Chinese is at least partly because of underdiagnosis.     

Thrombotic risk during pregnancy: a population study.

OBJECTIVE: To determine the incidence of pregnancy-related venous thromboembolic events and the relationship to selected risk factors such as maternal age, parity, smoking, preeclampsia, or cesarean delivery. METHODS: All Swedish women reported as having pregnancy-related venous thromboembolic events during 1990-1993 (608 of 479,422 deliveries) were compared with all thrombosis-free Swedish pregnant women during 1993 (114,940). RESULTS: The incidence of pregnancy-related venous thromboembolic events was 13 per 10,000 deliveries. Cesarean delivery was associated with a fivefold increased risk of venous thromboembolic events. Advanced age was not a significant risk factor itself, but was associated with an age-related increase in frequency of cesareans. Women with preeclampsia were at a threefold higher risk postpartum, but at no increased risk before delivery. There was a tobacco consumption-dependent increase in the risk of thrombosis among smokers. CONCLUSION: The incidence of pregnancy-related thrombosis was 13 per 10,000 and provided new insights to important risk factors such as age, cesarean delivery, smoking, and preeclampsia.     

Activated protein C resistance in cord blood from healthy and complicated newborns.

OBJECTIVES: Newborns are susceptible to thrombosis secondary to the immature hemostatic system and maternal and fetal complications. The contribution of activated protein C resistance (APCR) to thrombosis tendency has not yet been established. This study was conducted to investigate the effects of maternal and fetal complications on APCR levels. METHODS: APCR levels were determined in cord blood from healthy term infants and compared with those in healthy preterm and complicated neonates as well as that in adult venous blood. RESULTS: The mean value of APCR in cord blood from healthy term infants (166 +/- 40 s) was not significantly different from that in adult venous blood (173 +/- 40 s). No significant differences in the mean cord blood APCR values were observed between healthy term and preterm infants, infants with vaginal and cesarean delivery, infants from preeclamptic and non-eclamptic mothers, and infants with or without perinatal asphyxia. The activity levels of protein C, protein S, and antithrombin III were not significantly different between these groups except for lower levels in preterm babies. CONCLUSIONS: The level of APCR in cord blood is comparable to that in adults and not influenced by maternal and fetal complications. It appears that APCR does not contribute to the thrombotic tendency in newborns.     

Placement of a vena cava filter in term pregnancy: case report and review of the literature

During pregnancy there are hemostatic changes that may result in a hypercoagulable state producing thrombotic consequences. This condition may be aggravated in women who are carriers of congenital thrombophilic factors. These factors may increase obstetric complications such as miscarriages, fetal growth restriction, placental abruption and preeclampsia. Trombophilic factors may also cause venous thromboembolism, which is the leading cause of maternal morbidity and mortality. We report a case of a 22-year-old woman with factor V Leiden mutation, whose pregnancy was complicated with deep venous thrombosis requiring placement of a vena cava filter.     

Prothrombin 20210 G-->A, MTHFR C677T mutations in women with venous thromboembolism associated with pregnancy

Over 50 unselected women with maternal venous thromboembolism were screened for the prothrombin 20210 G→A and MTHFR C677T mutations, in addition to screening for other thrombophilias. The prevalence of thrombophilia in these women was compared with its prevalence in the general population in our area. The prothrombin (OR 4.4; 95% CI 1.2-16) and factor V Leiden (OR 4.5; 95% CI 2.1-14.5) mutations were more common in our patients, compared with the general population, whereas women homozygous for the C677T mutation in the methylene tetrahydrofolate reductase gene (OR 0.45; 95% CI 0.13-1.58) were not. It is recommended that women with a personal or strong family history of venous thromboembolism should be screened for the prothrombin mutation either before or early in pregnancy, in addition to screening for other thrombophilias. Screening for the MTHFR mutation does not appear to identify women at increased risk of maternal venous thrombosis.     

Management of venous thromboembolism in pregnancy

Pulmonary thromboembolism (PTE) is the major cause of maternal death in the UK, with recent trends showing an increase in the numbers of deaths. Underlying PTE is the problem of deep venous thrombosis (DVT). An appreciation of risk factors, particularly, thrombophilia, and signs or symptoms suggestive of thromboembolism, coupled with objective diagnosis and treatment should reduce mortality and morbidity. There are particular considerations with regard to the management of thrombosis in pregnancy, especially the use of anticoagulants. Low-molecular-weight heparins are now replacing unfractionated heparin for the treatment of DVT and PTE in pregnancy.     

Upper body venous thrombosis associated with ovarian stimulation: case report and review of the literature

Thromboembolic events are a serious complication of assisted conception treatment. Thrombosis may be either arterial or venous but the latter is far more common. This phenomenon is more frequent in the lower limb, but several cases of upper extremity thrombosis have been described in the literature. Although the aetiology of these thromboembolic disorders is not fully understood, the mechanism is thought to be due to a hypercoagulable state associated with haemostasis and thrombophilia. Predisposing factors seem to be hyperoestrogenism, ovarian hyperstimulation syndrome, a hereditary hypercoagulable state and multifoetal pregnancy. We report a case of superior sagittal sinus thrombosis that developed in a patient following successful assisted conception in the absence of evident risk factors. In the current literature, the site of thrombosis, possible predisposing factors, oestrogen levels, number of foetuses, maternal and foetal outcomes, and management of thrombosis were analysed.     

Activated protein C resistance in cord blood from healthy and complicated newborns

Objectives. Newborns are susceptible to thrombosis secondary to the immature hemostatic system and maternal and fetal complications. The contribution of activated protein C resistance (APCR) to thrombosis tendency has not yet been established. This study was conducted to investigate the effects of maternal and fetal complications on APCR levels.

Methods. APCR levels were determined in cord blood from healthy term infants and compared with those in healthy preterm and complicated neonates as well as that in adult venous blood.

Results. The mean value of APCR in cord blood from healthy term infants (166 ± 40 s) was not significantly different from that in adult venous blood (173 ± 40 s). No significant differences in the mean cord blood APCR values were observed between healthy term and preterm infants, infants with vaginal and cesarean delivery, infants from preeclamptic and non-eclamptic mothers, and infants with or without perinatal asphyxia. The activity levels of protein C, protein S, and antithrombin III were not significantly different between these groups except for lower levels in preterm babies.

Conclusions. The level of APCR in cord blood is comparable to that in adults and not influenced by maternal and fetal complications. It appears that APCR does not contribute to the thrombotic tendency in newborns.     

The natural history of postoperative venous thromboemboli in gynecologic oncology: a prospective study of 382 patients

Three hundred eighty-two patients who underwent major operations for gynecologic malignancy were studied prospectively to determine the natural history of postoperative venous thromboemboli. Iodine 125-labeled fibrinogen leg counting, to diagnose deep venous thrombosis, was performed daily. Sixty-three patients (17%) developed postoperative venous thromboembolic complications. Deep venous thrombosis initially arose in the calf veins in 52 patients. Twenty-seven percent of these thrombi lysed spontaneously. Four percent of thrombi in the calf veins progressed to deep venous thrombosis in the femoral vein, and 4% resulted in pulmonary emboli. Nine other patients developed proximal deep venous thrombosis without prior thrombosis in the calf veins. One patient with proximal deep venous thrombosis also had a pulmonary embolus. Two patients with no evidence of deep venous thrombosis on prospective 125I-labeled fibrinogen leg counting developed pulmonary emboli, including one fatal pulmonary embolus that was found at autopsy to have arisen from the internal iliac veins. Fifty percent of all venous thromboemboli were detected within 48 hours of operation, although two patients developed significant deep venous thrombosis and pulmonary emboli after discharge from the hospital. These results add important information to our understanding of this disease process, and raise issues related to appropriate treatment and prophylaxis of venous thromboembolism in patients after gynecologic operations.     

Venous thromboembolism as a cause of severe maternal morbidity and mortality in the United States

In the U.S., deaths due to pulmonary embolism (PE) account for 9.2% of all pregnancy-related deaths or approximately 1.5 deaths per 100,000 live births. Maternal deaths and maternal morbidity due to PE are more common among women who deliver by cesarean section. In the past decade, the clinical community has increasingly adopted venous thromboembolism (VTE) guidelines and thromboprophylaxis recommendations for pregnant women. Although deep vein thrombosis rates have decreased during this time-period, PE rates have remained relatively unchanged in pregnancy hospitalizations and as a cause of maternal mortality. Changes in the health profile of women who become pregnant, particularly due to maternal age and co-morbidities, needs more attention to better understand the impact of VTE risk during pregnancy and the postpartum period.     

Coagulation and anticoagulation systems in newborns--correlation with their mothers at delivery. Lower levels of anticoagulants and fibrinolytic activity in the newborn

The neonatal period is probably the only time when a higher incidence of spontaneous thromboembolic complications may occur in the otherwise normal healthy individual, and this may be related to the activation of the coagulation system at the time of parturition. This study was performed to look at the newborn coagulation and anticoagulation systems and compare these with the changes in the maternal circulation in normal cases. Paired umbilical cord venous and maternal venous blood samples were obtained and plasma levels of protein C, protein S, antithrombin III, fibrinopeptide A, fibrinogen, plasminogen, and fibrinolytic inhibitory activity were measured. The maternal plasma level was significantly higher in all cases except for fibrinopeptide A which was similar, and for fibrinolytic inhibitory activity which was lower (p less than 0.05). A significant correlation exists between maternal and newborn protein C levels (p less than 0.02) and fibrinolytic inhibitory activity (p less than 0.05). The findings indicate that parturition leads to a similar degree of activation of the newborn coagulation system as shown by the fibrinopeptide A level. As their anticoagulants and fibrinolytic activity levels are lower and the fibrinolytic inhibitory activity is higher, the newborns are thus predisposed to thrombosis even in the absence of complications such as sepsis.     

Assessment of the effectiveness of using low molecular weight heparin in the prophylaxis of venous thrombo-embolic diseases in obstetrics

OBJECTIVES: Assessment of the effectiveness of using low molecular weight heparin in the prophylaxis of venous thrombo-embolic diseases in pregnant women, parturients and puerperants. MATERIAL AND METHODS: 14,106 female patients were retrospectively analysed in the period between 1990-1999. The patients were divided into 4 groups: I--142 pregnant patients with crural varices, II--10 pregnant patients who had suffered from deep venous thrombosis, III--5 patients with implanted artificial cardiac valves, IV--13,949 patients without any risk factors. In the patients in groups I-III low molecular weight heparin was used prophylactically. RESULTS: In the studied groups no cases of pulmonary embolism were observed. Superficial venous thrombosis occurred in 10 women (3 in group I and 7 in group IV). Deep venous thrombosis occurred in 5 patients (2 in group I and 3 in group IV). In patients who received low molecular weight heparin over a long period of time, no excessive bleeding during delivery was observed. Other complications in the form of osteoporosis and thrombocytopenia were also not observed. CONCLUSIONS: 1. Administering of low molecular weight heparin during pregnancy, labour and puerperium has no influence on the increase of maternal et fetal complications. 2. Administering of low molecular weight heparin in pregnant women, in labour and in puerperium with increase risk of thrombo-embolic disease allows to avoid pulmonary arteries embolism. 3. Pregnant women and women in puerperium with increased risk of venous thrombo-embolic disease should be under control of experienced obstetrician in cooperation with vascular surgeon and hematologist.     

Factor V Leiden mutation in pregnancy

Normal maternal adaptation to pregnancy significantly increases the risk for thrombus formation. Inherited thrombophilias further increase risk for deep venous thrombosis and adverse outcome in pregnancy. Factor V Leiden mutation is the most common inherited thrombophilia, occurring in approximately 5% of the White and 1% of the Black populations. Nurses should be knowledgeable about screening for and diagnosis of factor V Leiden mutation, risk reduction counseling, recommended care of the affected patient, and implications of anticoagulant therapy during the perinatal period.     

Diagnosis and therapy of leg and pelvic deep vein thrombosis in pregnancy

OBJECTIVE: To establish differences in the management of acute thrombosis in the deep venous system associated with pregnancy in patients undergoing thrombectomy and in patients receiving heparin therapy. MATERIALS AND METHODS: From 1984 to 1995 the course of pregnancy was assessed retrospectively in 26 patients with acute deep vein thrombosis. Thirteen patients underwent thrombectomy with establishment of an arteriovenous fistula and 13 patients received conservative treatment with heparin therapy. In addition to the assessment of clinical symptoms, signs of thrombosis, diagnoses established with imaging techniques and of laboratory parameters, early complications and obstetric data obtained in surgically and conservatively treated patients were compared. RESULTS: The incidence of deep vein thrombosis in the 26 patients (median age 28 years) was 0.21%. In 53.8% of the cases the occurrence of thrombosis was observed in the second trimester (median: 27.5 weeks of gestation). The presence of risk factors was demonstrated in 58% of cases. The most frequently reported symptoms were swelling of the affected leg (88.5%) and pain (61.5%). A marked predilection for the left leg was recorded in 88% of cases. In contrast to phlebography, twice the number of sonographic studies were performed. The comparison of both therapeutic regimes showed a three-fold increase in the rate of early complications in patients after thrombectomy. The rate of recurrent thrombosis in these patients was 58.3% compared to a recurrence rate of 15.4% in patients undergoing heparin therapy. CONCLUSIONS: Recurrent thrombosis and pulmonary embolism represent the most frequent complications associated with thrombosis in the deep venous system during pregnancy. Although currently there is a lack of conclusive data on the development of postthrombotic syndrome, heparin therapy appears to be associated with fewer maternal risks. Interdisciplinary cooperation is urgently needed.     

Evaluation of Doppler test for venous thrombosis in obstetrics and gynecology

The use of the ultrasonic Doppler test to diagnose venous thrombosis was evaluated in an obstetric and gynecological unit. Both asymptomatic postoperative patients and those with suspected venous thrombosis were studied.Detection of ilio-femoral thrombosis was possible, but the incidence in unselected gynecological patients was low. The technique was of greater value in clarifying the diagnosis in suspected venous thrombosis.     

The role of inherited thrombophilia in venous thromboembolism associated with pregnancy.

Venous thromboembolism is an important cause of maternal morbidity and mortality. The puerperium should be regarded as the period of greatest risk. However, fatalities in early pregnancy emphasise the need to assess thrombotic risk at all stages of pregnancy. In many cases those at increased risk are potentially identifiable on clinical grounds alone such as those with a personal or family history of venous thromboembolism, obesity, or surgery. Identification of women with multiple clinical risks for thrombosis during pregnancy remains the key to reducing the incidence of this condition. In women who present with a personal or family history of proven venous thromboembolism, thrombophilia screening should be performed in early pregnancy, since the results may influence subsequent management during pregnancy. The investigation and management of patients considered at increased risk of venous thrombosis during pregnancy requires close liaison between obstetricians and haematologists familiar with this rapidly expanding and complex field of thrombophilia.