Pregnancy-associated Venous Thromboembolism Research Articles

Pelvic Magnetic Resonance Venography Reveals High Rate of Pelvic Vein Thrombosis After Cesarean Section

Venous thromboembolism (VTE) not only remains the major cause of direct maternal mortality in developed countries worldwide, but reportedly causes more than half of direct maternal deaths in the United States. Although cesarean section increases the risk of pregnancy-associated VTE, postpartum thromboprophylaxis is not uniformly recommended. Magnetic resonance venography (MRV) appears to be a highly sensitive and specific means of detecting deep venous thrombosis (DVT) in the upper and lower extremities. The investigators report preliminary findings of an ongoing randomized, controlled trial that uses MRV to identify pelvic DVT after operative delivery. Observations were made during the run-in phase of a trial of thromboprophylaxis in women at moderate to high risk of DVT based on a family history of VTE or a personal history of superficial phlebitis, current major illness or infection, immobility for longer than 4 days, obesity, or age greater than 35 years. Other risk factors included gross varicose veins, preeclampsia, parity of 4 or more, emergency cesarean section, and extended surgery such as cesarean hysterectomy. The women were assigned to receive or not to receive open-label tinzaparin, a low-molecular-weight heparin, by subcutaneous injection. Two radiologists independently and blindly assessed the MRV studies. Participants included 15 women with a mean age of 33 years. None of them had compression leg ultrasound findings of DVT. The MRV findings were interpreted as showing definite thrombosis in 46% of women, all of whom were asymptomatic. Clots were found chiefly in the iliac veins, although one patient had thrombosis in the common femoral artery. All clots were less than 1 cm in size and only one occluded the affected vein. Nearly half of these moderate- or high-risk women were found to have definite pelvic DVT after cesarean delivery-many more than expected. The clinical significance of this finding remains to be determined. It is possible that pelvic vein thrombosis is a normal finding after cesarean delivery and also that DVT may be present in lower-risk women. MRV would seem to be a useful measure of outcome in studies evaluating postpartum measures intended to prevent DVT.

Reply

Sir, We would like to respond to the letter from Shukunami et al. A report by Zotz et al. described that ETP-based normalized APC sensitivity ratio (nAPC-sr) in patients with a past history of venous thromboembolism (VTE) in pregnancy or puerperium was not elevated significantly compared with nAPC-sr in healthy women in the blood samples obtained at least six months after thromboembolic events. However, unfortunately they did not show the changes in nAPC-sr in patients with VTE prior to the onset of VTE. On the contrary, we reported that ETP-based nAPC-sr in women during late pregnancy and puerperium was significantly elevated compared with that in non-pregnant women and women during early pregnancy. An animal experiment suggests that hormonal changes enhance ETP, as the changes in ETP in pregnant women and OC users 1. Also, we demonstrated that nAPC-sr in patients with VTE right after onset during puerperium was elevated significantly compared with that in healthy women during puerperium 2. Furthermore, we detected the marked elevation of nAPC-sr prior to the onset of suprasagittal thrombosis during puerperium without marked changes in other coagulation variables 3. These observations suggest that reduced sensitivity to APC in pregnancy and puerperium is related with the onset of thrombotic events although the changes are partly related to thrombosis and/or inflammation. As Zotz et al. pointed out, the retrospective study design does not allow information to be given about possible temporary pregnancy-associated changes in ETP-based nAPC-sr prior to the thrombotic event. At present, we have not concluded that ETP-based nAPC-sr is not a risk marker for pregnancy-associated VTE as far as the temporary changes are determined in sensitivity to APC prior to thrombosis in the future. Furthermore, they also demonstrated that nAPC-sr in normal healthy OC users was elevated significantly compared with that in controls. If nAPC-sr in normal healthy OC users is elevated compared with that in control, nAPC-sr in normal healthy pregnant women should be elevated because the hormonal changes in OC users are similar to those in pregnant women, as we have shown.

Incidence of Pregnancy-Associated Venous Thromboembolism

Letters21 March 2006Incidence of Pregnancy-Associated Venous ThromboembolismPaul D. Stein, MD, Fadi Kayali, MD, Allen Silbergleit, MD, Russell D. Hull, MBBS, MSc, Ronald E. Olson, PhD, and Frederick A. Meyers, MDPaul D. Stein, MDFrom St. Joseph Mercy-Oakland Hospital, Pontiac, MI 48341; University of Calgary, Calgary, Alberta T2N 2T9, Canada; Oakland University, Rochester, MI 48309; and George Washington University, Washington, DC 20037.Search for more papers by this author, Fadi Kayali, MDFrom St. Joseph Mercy-Oakland Hospital, Pontiac, MI 48341; University of Calgary, Calgary, Alberta T2N 2T9, Canada; Oakland University, Rochester, MI 48309; and George Washington University, Washington, DC 20037.Search for more papers by this author, Allen Silbergleit, MDFrom St. Joseph Mercy-Oakland Hospital, Pontiac, MI 48341; University of Calgary, Calgary, Alberta T2N 2T9, Canada; Oakland University, Rochester, MI 48309; and George Washington University, Washington, DC 20037.Search for more papers by this author, Russell D. Hull, MBBS, MScFrom St. Joseph Mercy-Oakland Hospital, Pontiac, MI 48341; University of Calgary, Calgary, Alberta T2N 2T9, Canada; Oakland University, Rochester, MI 48309; and George Washington University, Washington, DC 20037.Search for more papers by this author, Ronald E. Olson, PhDFrom St. Joseph Mercy-Oakland Hospital, Pontiac, MI 48341; University of Calgary, Calgary, Alberta T2N 2T9, Canada; Oakland University, Rochester, MI 48309; and George Washington University, Washington, DC 20037.Search for more papers by this author, and Frederick A. Meyers, MDFrom St. Joseph Mercy-Oakland Hospital, Pontiac, MI 48341; University of Calgary, Calgary, Alberta T2N 2T9, Canada; Oakland University, Rochester, MI 48309; and George Washington University, Washington, DC 20037.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-144-6-200603210-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Heit and colleagues (1) stated that there are few data regarding the relative risks for venous thromboembolism during pregnancy. After examining 105 patients with deep venous thrombosis (DVT) or pulmonary embolism (PE) during pregnancy or postpartum, the authors estimated that the incidence of DVT during pregnancy remained essentially unchanged over the 30-year period of study and that the incidence of postpartum DVT declined. The authors speculated that early mobilization and shorter hospitalization after delivery may have contributed to this result. This apparently advantageous observation, based on a limited database, may cause physicians to become complacent.We reported ...

Incidence of Pregnancy-Associated Venous Thromboembolism

Incidence of Pregnancy-Associated Venous Thromboembolism

Incidence of Pregnancy-Associated Venous Thromboembolism

Letters21 March 2006Incidence of Pregnancy-Associated Venous ThromboembolismVijay Rajput, MBBS and Huma Q. Rana, BAVijay Rajput, MBBSFrom the Robert Wood Johnson Medical School, University of Medicine & Dentistry of New Jersey, Camden, NJ 08103.Search for more papers by this author and Huma Q. Rana, BAFrom the Robert Wood Johnson Medical School, University of Medicine & Dentistry of New Jersey, Camden, NJ 08103.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-144-6-200603210-00018 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Heit and colleagues' population-based study (1) identifies age and postpartum period as key issues in incidence of venous thromboembolism during and after pregnancy. In the past few decades, incidence of cesarean section in the United States has been 21% (2). The authors do not identify women undergoing cesarean sections as a separate high-risk group. A previous study (3) identified operative vaginal delivery, emergency cesarean section during labor, high body mass index, previous venous thromboembolism, and family history as major risk factors. In 1 small study, thromboembolism incidence was very low in women with no additional risk factors ...

Incidence of Pregnancy-Associated Venous Thromboembolism

Incidence of Pregnancy-Associated Venous Thromboembolism

Pregnancy-associated venous thromboembolism in combined heterozygous factor V Leiden and prothrombin G20210A mutations

Pregnancy and puerperium raise the risk of thromboembolic events, and these risks are increased in women who are carriers of thrombophilia factors. Prothrombin (FII) G20210A and factor V Leiden heterozygous mutations are associated with moderate risk of thrombosis. The association of these thrombophilic conditions is very rare in pregnancy, and the real risk of thrombosis is unknown. We describe a case of a pregnant woman who was found to be carrier of heterozygous factor V Leiden and prothrombin (FII) G20210A mutations. Five years before pregnancy she had had an episode of extensive deep venous thrombosis in the ileofemoral region, while using hormonal contraceptives. Anticardiolipin antibody (ACA), lupus anticoagulant and deficiencies of protein C, protein S and antithrombin III were evaluated by means of enzyme-linked immunosorbent assay (ELISA), dilute Russell Viper Venom time (dRVVT), coagulometric and chromogenic methods. Deoxyribonucleic acid (DNA) was amplified using the polymerase chain reaction (PCR) to study the factor V Leiden and G20210A mutations in the prothrombin gene and C677T mutation in the methylene tetrahydrofolate reductase (MTHFR) gene. In the sixth week of her first pregnancy, she developed another episode of deep venous thrombosis in the femoropopliteal veins of the right leg. She was treated with low-molecular weight heparin (nadroparin) until parturition (0.3 ml or 2,850 UI/day). The pregnancy evolved without any significant obstetric morbidity. The patient delivered a healthy baby by cesarean section. During the puerperium, she used prophylactic doses of nadroparin for (0.3 ml or 2,850 UI/day) six weeks and had no complications. We suggest that women who have an association of thrombophilia factors and a prior episode of venous thromboembolism must have antepartum anticoagulation management using unfractioned or low-molecular weight heparin and postpartum management using low-molecular weight heparin or oral anticoagulants. Anticoagulation is recommended during pregnancy because the real magnitude of the risk of major and life-threatening thromboembolic events in these women is unknown.

Evaluating the Risk for Pregnancy-Associated Venous Thromboembolism: A 30-Year Study

Evaluating the Risk for Pregnancy-Associated Venous Thromboembolism: A 30-Year Study

Risk of pregnancy‐associated recurrent venous thromboembolism in women with a history of venous thrombosis

Limited data exist on the risk of pregnancy-associated venous thromboembolism (VTE) in women with a history of VTE. To evaluate the risk of recurrent pregnancy-associated thrombosis in women with previous VTE in a large retrospective cohort study. One hundred and fifty-nine women with at least one pregnancy (293 pregnancies in total) after a VTE were included into the study. The patients underwent a standardized interview on their history of thrombosis and pregnancy-associated complications. Eight recurrent events occurred during 197 pregnancies without thrombosis prophylaxis. The probability of VTE during pregnancy without thrombosis prophylaxis was 6.2% (95% confidence interval 1.6-10.9%). The risk was constant over the whole period of pregnancy. Of the eight women with VTE during pregnancy four had heterozygous FV:R506Q, two in combination with hyperhomocysteinemia. No VTE occurred during 87 pregnancies with thrombosis prophylaxis. In the postpartum period 15 VTEs occurred, two of 83 (2.4%) after pregnancy termination, one of 53 (1.9%) after miscarriage, three of 10 (30%) after stillbirth and nine of 138 (6.5%) after live birth. Without thrombosis prophylaxis the risk for recurrent symptomatic VTE is substantial during the whole period of pregnancy in women with previous VTE. The majority of events occurred after delivery, reflecting the very high risk during the postpartum period. Prospective and comparative trials to ascertain efficacy and safety of prophylactic heparin are urgently needed.

Venous thromboembolism during pregnancy is not associated with persistent elevated activated protein C (APC) sensitivity ratio based on the endogenous thrombin potential

Women who are using oral contraceptives can acquire APC resistance, measured by the effect of APC on the endogenous thrombin potential (ETP). The objective of our study was to examine whether persistentAPC resistance determined with an ETP-based normalized APC sensitivity ratio (nAPCsr) is a risk marker for venous thromboembolism in women with pregnancy-associated thromboembolism. We determined the activities of antithrombin, protein C, protein S, and performed a genetic analysis of factor V Leiden G1691A, prothrombin mutation G20210A, and methylenetetrahydrofolate reductase mutation (MTHFR C677T) in 65 women with venous thromboembolism during pregnancy or the puerperium and in 114 normal women. A significantly (p<0.05) higher nAPCsr was present in normal women using hormones, in younger women (<or=45 yrs), and in women with carrier status of factorV Leiden. In normal women without factor V Leiden a significant (p<0.05) negative correlation of nAPCsr with age (r=-0.39), antithrombin activity (r=-0.38), protein S activity (r=-0.26), and a significant positive correlation with hormone intake (r=0.36) was present. nAPCsr is influenced by several coagulation parameters, which are modified by the use of oral contraceptives. Consequently, a multivariate analysis of our data did not show a significant association of nAPCsr to venous thromboembolism, neither as a continuous variable (odds ratio 0.8, 95% CI 0.6-1.1, p=0.10) nor using a cutoff value (nAPCsr cut-off 3.1: odds ratio 1.2, 95% CI 0.3-5.3, p=0.77). Our study demonstrates that nAPCsr is not a risk marker for pregnancy-associated venous thromboembolism.

Pregnancy-associated venous thromboembolism (VTE) in combined heterozygous factor V Leiden (FVL) and prothrombin (FII) 20210 A mutation and in heterozygous FII single gene mutation alone.

The risk of venous thromboembolism (VTE) in the absence of prophylaxis was evaluated in a retrospective study of 47 women (84 pregnancies) with combined thrombophilia [heterozygous factor V Leiden (FVL) plus prothrombin (FII) 20210A mutation (group I)] and in 82 women (193 pregnancies) with the FII alone (group II). VTE was more frequent in group I than in group II [17.8% versus 6.2%, P = 0.003, relative risk (RR) 2.9, 95% confidence interval (CI) 1.4-5.9], ante partum (7.1% and 2.1%) and post partum (11.5% and 4.2%). The risk was higher in index cases than in family members (RR 2.5, 95% CI 1.2-5.2 and RR 2.1, 95% CI 0.2-22.3 respectively) Even women who had no history of VTE before pregnancy had an increased risk (RR 2.2, 95% CI 1.0-4.8). Our results suggest that, during ante partum, prophylaxis is indicated in women with combined thrombophilia and with a VTE before pregnancy. In those without VTE before pregnancy, prophylaxis might be decided for each individual case, taking into consideration all risk factors. In women with the FII mutation alone, the low risk may not justify prophylaxis in the absence of previous VTE. In post partum, prophylaxis is indicated in all cases.

Pregnancy-associated thrombosis.

Venous thromboembolism (VTE) occurs infrequently but is a leading cause of illness and death during pregnancy and the puerperium. In the general population the incidence of pregnancy associated VTE is approximately 1 in 1500 deliveries The risk of VTE is five times higher in a pregnant than in a non-pregnant woman. Postpartum the VTE-risk is even higher. Women with congenital abnormalities or persistent presence of antiphospholipid antibodies have an increased risk of VTE during pregnancy and the puerperium. In individuals with well defined hereditary thrombosis risk factors, such as the factor V:R506Q mutation, the factor II:G20210A variation, antithrombin-deficiency or protein C-deficiency, a relative risk of pregnancy associated VTE between 3.4 and 15.2 has been found. Women with previous VTE have an approximately 3.5 fold increased risk of recurrent VTE during pregnancy compared to non-pregnant periods. Our ability to diagnose pregnancy-associated VTE clinically is generally poor, since dyspnea, tachypnea, swelling and discomfort in the legs are common. Objective diagnosis is essential for treatment decisions. Exposure to radiation of less than 50,000 microGy (5 rad) has not been associated with a significant risk of fetal injury Therefore, besides sonography, routine diagnostic procedures should be performed, if clinically necessary. Heparin does not cross the placenta and is therefore the anticoagulant of choice. In case of acute thrombosis during pregnancy, treatment is performed like in nonpregnant patients. There is ongoing debate, whether or not pregnant women with previous venous thrombosis should routinely receive prophylactic anticoagulation. In patients who have hereditary antithrombin deficiency, antiphospholipid antibodies, a combined abnormality or a history of a severe thrombotic event (pulmonary embolism, extended deep vein thrombosis) should be advised to use prophylactic heparin during pregnancy, starting during the first trimester. Post partum prophylaxis should be given in all women with an increased risk for VTE.

Changes in haemostasis during normal pregnancy: does homocysteine play a role in maintaining homeostasis?

Homocysteine, derived from the demethylation of the amino acid methionine, is either further catabolised by trans-sulfuration to cysteine or remethylated to methionine. Remethylation to methionine requires the cofactors, folate and vitamin B12. Folate is an effective homocysteine-lowering agent and, thus, homocysteine and folate status are inversely related. Hyperhomocysteinaemia is a strong independent risk factor for venous thromboembolism (VTE) and is associated with adverse pregnancy outcomes such as pre-eclampsia, placental abruption, early pregnancy loss and neural-tube defects. Pregnancy is a risk factor for VTE as a result of prothrombotic changes in levels of haemostatic factors. However, despite this hypercoagulable state, the incidence of pregnancy-associated VTE is relatively low. Hyperhomocysteinaemia is associated with abnormalities in markers of coagulation activation, and recent research suggests that folic acid supplementation, as well as lowering homocysteine, lowers markers of coagulation activation and increases levels of coagulation inhibitors. Tissue factor (TF) is the initiator of blood coagulation in vivo, and homocysteine induces TF expression in vitro. During pregnancy, monocyte TF expression is lower than that in the non-pregnant state, and this lowering of TF may act to counterbalance increases in coagulation activation. Furthermore, despite a high folate requirement, several studies have reported that homocysteine is lower in normal pregnancy than in the non-pregnant state. Although the exact mechanism of homocysteine lowering during pregnancy is unclear, one possible outcome of lower homocysteine may be the protection of women from pregnancy complications and VTE, and thus lower homocysteine may contribute to maintaining homeostasis in haemostasis.

Anticoagulation during pregnancy.

Venous thromboembolism (VTE) occurs infrequently but is a leading cause of illness and death during pregnancy and the puerperium. In the general population the incidence of pregnancy-associated VTE is approximately 1 in 1500 deliveries. The risk of VTE is five times higher in a pregnant than in a nonpregnant woman. Postpartum the VTE risk is even higher. Women with congenital abnormalities or persistent presence of antiphospholipid antibodies have an increased risk of VTE during pregnancy and the puerperium. Women with previous VTE have an approximately 3.5-fold increased risk of recurrent VTE during pregnancy. Heparin does not cross the placenta and is therefore the anticoagulant of choice. In case of acute thrombosis during pregnancy, treatment is performed in the same manner as for nonpregnant patients. There is an ongoing debate whether pregnant women with previous venous thrombosis should routinely receive prophylactic anticoagulation. Patients who have hereditary antithrombin deficiency, antiphospholipid antibodies, a combined abnormality, or a history of a severe thrombotic event (pulmonary embolism or extended deep vein thrombosis) should be advised to use prophylactic heparin during pregnancy, starting during the first trimester. Postpartum prophylaxis should be given to all women with an increased risk for VTE. A large body of evidence has been presented that hypercoagulability may cause recurrent abortions, stillbirth, and preeclampsia. There is no doubt that the antiphospholipid syndrome is strongly associated with fetal loss. The combination of heparin and aspirin significantly decreases the fetal loss rate during pregnancy and thus this is the treatment of choice in this patient group. Several studies indicate that women with recurrent miscarriage may benefit from heparin administration during pregnancy, however, data from controlled trials have not yet been published. In women with artificial heart valves, maternal and fetal complications are frequent despite anticoagulation, but oral anticoagulants can reduce the risk for maternal complications.

Cumulative incidence of venous thromboembolism during pregnancy and puerperium: a hospital-based study.

Pregnancy is associated with an increased risk of venous thromboembolism. The rate of occurrence of this complication has not been reported from this area previously. The aim of this study was to establish the incidence of venous thromboembolism in pregnancy and puerperium by using objective diagnostic methods. From January 1986 to December 1998, 39,757 deliveries were registered at King Fahad Hospital, Al Baha, and 59 of these were referred to hematology services with a clinical suspicion of venous thromboembolism. The majority (86%) of these underwent objective diagnostic methods such as ascending venogram (AV) and color Doppler imaging (CDI) of the venous system for the diagnosis of deep venous thrombosis (DVT). Pulmonary scintigraphy was performed when available and echocardiography was included towards the end of the study. Fifty-nine patients with suspicion of pregnancy-associated venous thromboembolism (PAVTE) were studied. The diagnosis was confirmed in 50 patients, who received anticoagulation therapy. DVT was diagnosed in 35 (70%) cases and pulmonary embolism in 27 (54%) cases. The cumulative incidence of PAVTE was 1.25 cases per 1,000 deliveries (95% confidence interval = 0.89-1.16). One patient died during the study period (0.025 case per 1,000 deliveries). There was a predominance of venous thromboembolism during the postpartum period (66%), and DVT occurred more frequently in the left leg (77%). The risk of pregnancy-associated venous thromboembolism is low and a resulting death rare. Proximal or whole-limb DVT occurs more frequently and there is a predilection for the left leg. The majority of events occur in the postpartum period. A hypercoagulable state probably exists and needs further evaluation.

Inherited thrombophilias: Implications for pregnancy-associated venous thromboembolism and obstetric complications

Inherited thrombophilias: Implications for pregnancy-associated venous thromboembolism and obstetric complications

Incidence, clinical characteristics, and timing of objectively diagnosed venous thromboembolism during pregnancy

Objective: To estimate the incidence, timing, and associated clinical characteristics of objectively diagnosed pregnancy-associated venous thromboembolism. Methods: We retrospectively reviewed venous thromboembolism cases (deep venous thrombosis and pulmonary embolism) that occurred between 1978 and 1996. Study inclusion criteria required the objective diagnosis with either Doppler ultrasound, venography, impedance plethysmography, pulmonary angiography, ventilation-perfusion scanning, or computed tomography or magnetic resonance imaging. Results: Among 268,525 deliveries there were 165 (0.06%) episodes of venous thromboembolism (one per 1627 births). There were 127 cases of deep venous thrombosis and 38 cases of pulmonary embolism. Only 14% (23 of 165 patients) had a history of venous thromboembolism. Most cases of deep venous thrombosis were in the left leg (104 of 127, 81.9%), with nearly three quarters of them (94 of 127, 74.8%) occurring during the antepartum period. Among cases of antepartum deep venous thrombosis, half were detected before 15 weeks’ gestation (47 of 95, 49.5%), and only 28 cases occurred after 20 weeks ( P < .001). Most of the pulmonary embolisms occurred in the postpartum period (23 of 38, 60.5%) and were strongly associated with cesarean delivery (19 of 36,470 compared with four of 232,032, P < .001). Conclusion: The incidence of venous thromboembolism during pregnancy is lower than has been previously described. Most cases occurred in the antepartum period, with the risk of deep venous thrombosis appearing to begin even before the second trimester.

Incidence, clinical characteristics, and timing of objectively diagnosed venous thromboembolism during pregnancy

Objective: To determine the incidence, timing, and associated clinical characteristics of objectively diagnosed pregnancy-associated venous thromboembolism (VTE). Methods: A retrospective review of VTE cases occurring between 1978 and 1996 was performed. Cases of deep venous thrombosis (DVT) and pulmonary embolism (PE) were identified by ICD-9 discharge diagnosis code and review of antepartum and coagulation laboratory databases. Study inclusion criteria required the objective diagnosis of VTE with either Doppler ultrasound, impedance plethysmography, pulmonary angiography, ventilation-perfusion scanning, or CT/MRI. Results: Among 268,525 deliveries there were 165 (0.06%) episodes of VTE (1/1627 births). There were 127 cases of DVT and 38 cases of PE. Only 14% (23/165) had a prior history of DVT or PE. Most DVTs occurred in the left leg (104/127, 81.9%). Nearly three quarters of the DVTs (95/127, 74.8%) occurred in the antepartum period. Among the antepartum DVT cases, half were detected prior to 15 weeks of gestation (47/95, 49.5%), with only 28 cases occurring after 20 weeks ( P < .0001). The majority of the PEs occurred in the postpartum period (23/38, 60.5%). There were only 3 maternal deaths due to PE, all associated with cesarean section. Only 1 patient developed PE while on heparin therapy for DVT while 11 others had complications attributable to heparin use. Conclusion: Most pregnancy-related VTE occurs in the antepartum period. The risk of deep venous thrombosis appears to begin early in pregnancy, even before the second trimester. The highest risk period for pulmonary embolism is after cesarean delivery. Maternal complications of heparin anticoagulation during pregnancy are rare.

Risk Factors for Pregnancy Associated Venous Thromboembolism

In an attempt to reduce the incidence of pregnancy associated venous thromboembolism (PA-VTE), some researchers have advocated screening of all women for the factor V(Leiden) mutation during early pregnancy. We have conducted a large retrospective study (over 72,000 deliveries) to determine if this would be useful. Sixty-two objectively confirmed venous thrombotic events (51 DVT, 11 PE) were recorded at two maternity units in the UK. The incidence of DVT was 0.71 per 1000 deliveries (95% CI 0.5-0.9) with 0.50 occurring in the antenatal period (95% CI 0.34-0.66) and 0.21 in the puerperium (95% CI 0.11-0.31). The incidence of PE was 0.15 per 1000 deliveries (95% CI 0.06-0.24), 0.07 antenatal (95% CI 0.01-0.13) and 0.08 in the puerperium (95% CI 0.02-0.14). Of these 62, 50 attended for follow-up and thrombophilia screening. 28% of all episodes of PA-VTE had no clinical risk factor for thrombosis or an identifiable thrombophilic abnormality. Deficiency of antithrombin was identified in 12% of individuals (95% CI 3-21) and the factor V(Leiden) mutation in 8% (95% CI 0.5-15.5). Based on estimates of the prevalence of the factor V(Leiden) mutation in the population, we estimate that the thrombotic risk for a woman during pregnancy or the puerperium with the defect is approximately 1 in 400-500. This figure would not lend support to the idea of random screening for the mutation in early pregnancy.