The risk of recurrent venous thromboembolism in pregnancy and puerperium without antithrombotic prophylaxis

Whether or not pregnant women with a previous episode of venous thromboembolism (VTE) should receive antithrombotic prophylaxis is a matter of debate. In order to estimate the rate of recurrent deep venous thrombosis (DVT) or pulmonary embolism (PE) during pregnancy and puerperium we retrospectively investigated a cohort of 1104 women with previous VTE; after a single DVT or isolated PE, 88 of them became pregnant at least once without receiving antithrombotic prophylaxis. Overall, 155 pregnancies and 120 puerperium periods without prophylaxis were recorded. There were nine recurrences during pregnancy and 10 during puerperium, with a rate of 5.8% [95% confidence interval (CI) 3.0-10.6] and 8.3% (95%CI 4.5-14.6) respectively. In pregnancy, the rate of recurrence was 7.5% (95%CI 4.0-13.7) if the first VTE was unprovoked, related to pregnancy or to oral contraceptive use, whereas no recurrence occurred if the first VTE was related to other transient risk factors. In puerperium, the rate of recurrence was 15.5% (95%CI 7.7-28.7) in women with a pregnancy-related first VTE, with a risk 3.9-times higher than in the remaining women. Inherited thrombophilia was not associated with a statistically significant increase in risk of recurrence in pregnancy or in puerperium, yet the rate of recurrence in puerperium was 14.2% (95%CI 5.7-31.4) in overall carriers of factor V Leiden and 30% (95%CI 10.7-60.3) in carriers with a pregnancy-related first VTE, with a risk 6.8 times higher than in women without thrombophilia and with a non pregnancy-related first VTE.     

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.     

6 versus 30 months anticoagulation for recurrent venous thrombosis in patients with high factor VIII

Patients with first venous thromboembolism (VTE) and high factor VIII (FVIII) are at increased risk of recurrence. It is unknown whether these patients benefit from prolonged secondary thrombophrophylaxis. In a prospective trial patients with first spontaneous VTE and FVIII levels >230 IU/dl were randomized to discontinue vitamin K Antagonist (VKA) after 6 months or to continue VKA for additional 24 months. Patients were excluded if they had a natural inhibitor deficiency, lupus anticoagulant, cancer, were pregnant, required long-term antithrombotic therapy or had acute-phase reaction. Primary study endpoints were symptomatic recurrent VTE or major bleeding within 2 years. Follow-up was continued beyond 2 years. Of 3,219 screened patients 34 met the inclusion criteria. Mean observation time was 37 months. Two of 17 patients allocated to discontinue VKA and two of 17 patients randomized to prolonged anticoagulation had recurrent VTE within 2 years. In the prolonged treatment group, one patient had recurrence during VKA therapy and one patient 4 weeks after voluntary discontinuation of VKA. One major nonfatal bleeding (severe epistaxis) after 10 months of VKA occurred in the prolonged treatment group. Five patients allocated to prolonged anticoagulation had recurrent VTE after discontinuation of VKA. The probability of recurrence at 2 years after discontinuation of VKA was 30% (95% CI 13–46%). Patients with high FVIII are at increased risk of recurrence. Our findings in a small number of patients indicate that prolonged anticoagulation seems to be effective but that the benefit is not maintained after discontinuation of anticoagulation.     

Long-term recurrence risk after a first venous thromboembolism in men and women under 50 years old: A French prospective cohort

BackgroundData on long-term venous thromboembolism (VTE) recurrence risk according to gender are conflicting.ObjectiveTo evaluate long-term VTE recurrence risk after a first VTE in men and women under 50 years old.MethodsSince May 2000, 875 consecutive patients (315 men, 560 women) with a first symptomatic VTE under 50 years old were enrolled in a French prospective multicentre cohort study and were followed up as long as possible. The primary outcome was symptomatic recurrent VTE during follow-up.ResultsAt baseline, men were older and had more comorbidities than women. First VTE was mainly unprovoked in men (80.6%) and hormone-related in women (84.3%). During a median follow-up of 7.0 years (inter-quartile range, 5.0–11.0), recurrent VTE occurred in 97 men (30.8%) and in 72 women (12.9%) (annual incidence rates of recurrent VTE of 4.8% versus 1.8%-person-years, P<0.001). However, there was no difference according to gender in subgroups of patients with a first unprovoked VTE (5.8% versus 3.8%-person-years, P = 0.09). In women, duration of hormonal treatment before first VTE did not influence recurrence risk. In multivariable analysis, unprovoked VTE and family history of VTE were independently associated with recurrence (hazard ratio of 2.50 (95% confidence interval, 1.61 to 3.85) and 1.52 (1.11 to 2.09) respectively).LimitationsNumber of women with unprovoked VTE was low.ConclusionsIn patients with a first VTE under 50 years old, a first unprovoked episode and a family history of VTE, but not gender, were associated with a high risk of long-term recurrence.     

Thrombophilia and its Treatment in Pregnancy

Pulmonary embolism is the most common cause of maternal death during pregnancy and the puerperium in the industrialized world. The risk of venous thromboembolism (VTE) in pregnancy is 0.05%–1.8%, 6 times greater than in the non-pregnant state. The risk is increased in women over 35 years and those with obesity, previous VTE, operative delivery, or underlying thrombophilia. Women presenting with recurrent miscarriages, preeclampsia, intrauterine growth restriction, abruptio placentae, or stillbirth (all associated with microvascular thrombosis in placental blood vessels) have high incidence (65%) of thrombophilia. About 70% of the women who present with VTE during pregnancy are carriers of hereditary or acquired thrombophilia. Treatment of women with VTE during pregnancy, and especially those with thrombophilia, requires individualized dosing and duration of antithrombotic therapy and the formulation of thromboprophylactic strategies for future pregnancies. Warfarin is contraindicated during the first trimester due to fetotoxicity; unfractionated heparin (UFH) is associated with practical disadvantages and the risk of heparin-induced thrombocytopenia (HIT) and osteoporosis with long-term use. Low molecular weight heparins (LMWHs) are convenient to use, do not cross the placenta, carry a lower risk of HIT and osteoporosis, and are safe and effective. LMWHs are replacing UFH as the anticoagulant of choice during pregnancy and improve pregnancy outcome in women with a history of obstetric complications and confirmed thrombophilia.     

Predictors of recurrence after deep vein thrombosis and pulmonary embolism: a population-based cohort study

BACKGROUND: The appropriate duration of oral anticoagulation after a first episode of venous thromboembolism (VTE) is uncertain and depends upon VTE recurrence rates. OBJECTIVE: To estimate VTE recurrence rates and determine predictors of recurrence. METHODS: Patients in Olmsted County, Minnesota, with a first lifetime deep vein thrombosis or pulmonary embolism diagnosed during the 25-year period from 1966 through 1990 (N = 1,719) were followed forward in time through their complete medical records in the community for first VTE recurrence. RESULTS: Four hundred four patients developed recurrent VTE during 10,198 person-years of follow-up. The overall (probable/definite) cumulative percentages of VTE recurrence at 7, 30, and 180 days and 1 and 10 years were 1.6% (0.2%), 5.2% (1.4%), 10.1% (4.1%), 12.9% (5.6%), and 30.4% (17.6%), respectively. The risk of recurrence was greatest in the first 6 to 12 months after the initial event but never fell to zero. Independent predictors of first overall VTE recurrence included increasing age and body mass index, neurologic disease with paresis, malignant neoplasm, and neurosurgery during the period from 1966 through 1980. Independent predictors of first probable/definite recurrence included diagnostic certainty of the incident event and neurologic disease in patients with hospital-acquired VTE. Recurrence risk was increased by malignant neoplasm but varied with concomitant chemotherapy, patient age and sex, and study year. CONCLUSIONS: Venous thromboembolism recurs frequently, especially within the first 6 to 12 months, and continues to recur for at least 10 years after the initial VTE. Patients with VTE with neurologic disease and paresis or with malignant neoplasm are at increased risk for recurrence, while VTE patients with transient or reversible risk factors are at less risk.     

A risk score for the management of pregnant women with increased risk of venous thromboembolism: a multicentre prospective study

Patients with thrombophilia and/or a history of venous thromboembolism (VTE) exhibit a high risk of thrombosis during pregnancy. The present multicentre study prospectively assessed a prophylaxis strategy, based on a risk score, in pregnancies with increased risk of VTE. Among 286 patients included in the study, 183 had a personal history of VTE (63·98%) and 191 patients (66·8%) had a thrombophilia marker. Eighty nine (46·6%) thrombophilic women had a personal history of VTE. Patients were assigned to one of three prophylaxis strategies according to the risk scoring system. In postpartum, all patients received low molecular weight heparin (LMWH) prophylaxis for at least 6 weeks. In antepartum, LMWH prophylaxis was prescribed to 61·8% of patients with high risk of VTE. Among them, 37·7% were treated in the third trimester only and 24·1% were treated throughout pregnancy. In this cohort, one antepartum-related VTE (0·35%) and two postpartum-related VTE (0·7%) occurred. No case of pulmonary embolism was observed during the study period. The rate of serious bleeding was 0·35%. There was no evidence of heparin-induced thrombocytopenia or osteoporosis. The use of a risk score may provide a rational decision process to implement safe and effective antepartum thromboprophylaxis in pregnant women at high risk of VTE.     

Factor V Leiden mutation and the risk of venous thromboembolism in pregnant women.

BACKGROUND AND OBJECTIVES: In this retrospective, single center, cohort study we assessed the risk of pregnancy-related venous thromboembolism (VTE) in women belonging to a large number of families identified because of a symptomatic proband with single identified factor V Leiden mutation. DESIGN AND METHODS: Female family members who had experienced at least one full-term pregnancy were enrolled in the study. Two hundred and seventy pregnancies occurred in 105 carriers and 215 pregnancies in 81 non-carriers of factor V Leiden mutation. RESULTS: The frequency of VTE was 6.4% for heterozygous, 16.7% for homozygous, 20% for double heterozygous carriers of thrombophilic defects, and 1.2% for non-carriers. The majority of VTE events related to pregnancy occurred in the post-partum period. The relative risks of developing pregnancy-related VTE in women who were carriers of heterozygous and homozygous (or combined heterozygous) factor V Leiden mutation as compared to non-carriers were 5.3 (95% CI, 0.6 to 43.9) and 15.4 (95% CI, 1.4 to 164), respectively. INTERPRETATION AND CONCLUSIONS: Factor V Leiden mutation is a risk factor for pregnancy-related VTE, especially in its homozygous form and in combination with other thrombophilic abnormalities. Screening of families with this mutation might be useful for women of fertile age, as they may take advantage from thromboprophylaxis during pregnancy and the post-partum period.     

Taller women are at greater risk of recurrent venous thromboembolism: the Iowa Women's Health Study

Venous thromboembolism (VTE) recurs frequently. Greater height is associated with increased risk of incident VTE, but it is unclear whether height is related to risk of VTE recurrence. Recurrent VTE is associated with substantial morbidity and mortality, thus identifying individuals at greatest risk of experiencing a recurrent event, who may benefit from extended anticoagulant therapy, is vitally important. Using data from the Iowa Women,s Health Study, we explored whether greater height was associated with increased risk of VTE recurrence.Among 1,691 women who experienced an initial VTE event, 286(16.9%) experienced a recurrent event. Risk of recurrence was 76%(95% CI: 16% -186%) higher among women >66 inches [168 cm] tall relative to those ≤62 inches [158 cm] tall, after adjustment for age and waist circumference. Future research should evaluate whether body height improves clinical prediction of VTE recurrence risk.     

Impact of sex and traditional cardiovascular risk factors on the risk of recurrent venous thromboembolism: results from the German MAISTHRO Registry

As arterial and venous thrombosis share common risk factors, a link between arterial and venous thrombosis has been suggested recently. Therefore, we aimed to investigate the impact of established cardiovascular risk factors on the risk of recurrent venous thromboembolism (VTE). With a cross-sectional study design, we analyzed the data of 1006 patients (582 F, 424 M) consecutively treated in our outpatient department for VTE (i.e. lower extremity deep vein thrombosis and/or pulmonary embolism) and registered in the MAISTHRO (MAin-ISar-THROmbosis) database. Of the total cohort, 324 (32.2%) patients suffered a recurrent VTE. Compared with the patients with a single thromboembolic event, patients with recurrent VTE were more frequently male (39.4 vs. 27.0%, P < 0.001). In univariate analysis, the relative risk of recurrent VTE was 1.9 [95% confidence interval (CI) 1.53-2.39] for male sex and 1.6 (1.25-1.95) for age over 50 years (PAOD). After adjustments for age, sex, thrombophilia and other common VTE risk factors, male sex [hazard ratio (HR) = 1.7 (1.38-21.9)] and arterial hypertension [HR = 1.4 (1.05-1.78)] were independent risk factors of recurrent VTE. The higher risk in men than in women persisted even after the exclusion of women with transient hormonal risk factors [HR = 1.57 (1.19-2.07)]. In contrast, no association between the presence of diabetes, obesity, hypercholesterolemia or smoking and the risk of VTE recurrence was observed. Male sex and arterial hypertension are independently associated with an increased risk of recurrent VTE after termination of anticoagulant therapy for the first VTE event.     

Risk of first venous thromboembolism in and around pregnancy: a population-based cohort study

Knowledge of the absolute and relative risk of venous thromboembolism (VTE) in and around pregnancy would be crucial in identifying when to commence and cease thromboprophylaxis in women who would benefit from such intervention. We addressed this hypothesis using a large prospective primary care database from the United Kingdom, containing details on 972 683 women aged 15–44 years between 1987 and 2004. Risks of a first VTE during antepartum, postpartum and outside of pregnancy were compared using Poisson regression. The rate of VTE during the third trimester antepartum was six times higher than time outside pregnancy [Incidence Rate Ratio (IRR) = 6·1; 95% confidence interval, 4·7–7·9]. In contrast, both the first (IRR = 1·6) and second (IRR = 2·1) trimesters conferred little increase in risk. The first 6 weeks postpartum was associated with a 22‐fold increase in risk, with the peak occurring in the first 3 weeks. Increased age was found to be associated with VTE during postpartum and outside of pregnancy, but not during antepartum. Our findings of a notably raised risk of VTE persisting for 3 weeks postpartum and of a raised antepartum risk constrained to the third trimester have implications for modifying the current recommendations for VTE prophylaxis in pregnancy and the puerperium.     

Treatment of DVT: how long is enough and how do you predict recurrence

Abstract Currently available anticoagulants are effective in reducing the recurrence rate of venous thromboembolism (VTE). However, anticoagulant treatment is associated with an increased risk for bleeding complications. Thus, anticoagulation has to be discontinued when benefit of treatment no longer clearly outweigh its risks. The duration of anticoagulant treatment is currently framed based on the estimated individual risk for recurrent VTE. The incidence of recurrent VTE can be estimated through a two-step decision algorithm. Firstly, the features of the patient (gender), of the initial event (proximal or distal deep vein thrombosis or pulmonary embolism), and the associated conditions (cancer, surgery, etc) provide essential information on the risk for recurrence after anticoagulant treatment discontinuation. Secondly, at time of anticoagulant treatment discontinuation, d-dimer levels and residual thrombosis have been indicated as predictors of recurrent VTE. Current evidence suggests that the risk of recurrence after stopping therapy is largely determined by whether the acute episode of VTE has been effectively treated and by the patient’s intrinsic risk of having a new episode of VTE. All patients with acute VTE should receive oral anticoagulant treatment for three months. At the end of this treatment period, physicians should decide for withdrawal or indefinite anticoagulation. Based on intrinsic patient’s risk for recurrent VTE and for bleeding complications and on patient preference, selected patients could be allocated to indefinite treatment with VKA with scheduled periodic re-assessment of the benefit from extending anticoagulation. Alternative strategies for secondary prevention of VTE to be used after conventional anticoagulation are currently under evaluation. Cancer patients should receive low molecular-weight heparin over warfarin in the long-term treatment of VTE. These patients should be considered for extended anticoagulation at least until resolution of underlying disease. Abbreviated abstract The risk for recurrent venous thromboembolism can be estimated through a two-step algorithm. Firstly, the features of the patient (gender), of the initial event (proximal or distal deep vein thrombosis or pulmonary embolism), and the associated conditions (cancer, surgery, etc) are essential to estimate the risk for recurrence after anticoagulant treatment discontinuation. Secondly, a correlation has been shown between d-dimer levels and residual thrombosis at time of anticoagulant treatment discontinuation and the risk of recurrence. Currently available anticoagulants are effective in reducing the incidence of recurrent venous thromboembolism, but they are associated with an increased risk for bleeding complications. All patients with acute venous thromboembolism should receive oral anticoagulant treatment for three months. At the end of this treatment period physicians should decide for definitive withdrawal or indefinite anticoagulation with scheduled periodic re-assessment of the benefit from extending anticoagulation.     

Sex,thrombosis and inherited thrombophilia

The incidence of venous thromboembolism (VTE) is two-fold higher in women than in men during reproductive age, which is likely explained by the use of hormonal contraceptives and by pregnancy in this phase of life. After adjustment for these factors, men have a two-fold higher risk of developing a first VTE compared with women, which is in line with earlier observations that men have a two-fold higher risk of recurrent VTE. These findings indicate that the intrinsic risk of VTE is higher in men than in women. Hormonal contraceptives increase the risk of VTE and the risk varies per type, dose, and administration route. In women with a high baseline risk of VTE, avoidance of some hormonal contraceptives should be considered, as well as thrombosis prophylaxis during pregnancy. Presence of hereditary thrombophilia increases the risk of a first VTE episode. This review focuses on the differences in risk of VTE between men and women, hormonal risk factors for women, and how these interact with common types of hereditary thrombophilia.     

Pregnancy outcome in patients with antiphospholipid syndrome after cerebral ischaemic events: an observational study

Among the most prominent features associated with antiphospholipid syndrome (APS) are cerebral ischaemic events (CVE). Pregnancy with APS increases the risk of thrombosis, including CVE. This study was undertaken to assess the risk of obstetric complications and recurrence of CVE during pregnancy in women with APS and previous CVE. We prospectively observed 23 pregnancies in 20 women (median age 31 years) with primary (n?=?8) or secondary APS (n?=?12). Eight patients had transient ischaemic attacks (TIA) and 12 had stroke before pregnancy. All patients received aspirin 100?mg daily in combination with low molecular weight heparin (LMWH) during their pregnancies. The live birth rate was 91.3% (n?=?21). Obstetrical complications consisted mainly of preeclampsia (n?=?8, 34.8%) and preterm delivery (n?=?9, 42.9%). The risk for preeclampsia increased in patients who were positive for multiple antiphospholipid antibodies (aPL) (odds ratio (OR) 3.06 (95% confidence interval (CI) 1.01-9.32)) per positive aPL test (i.e anticardiolipin antibody, anti-?2-glycoprotein I antibody, lupus anticoagulant) (p 0.049). Three patients experienced recurrent CVE in the context of pregnancy (one during pregnancy, two in the postpartum period). We found an increased, but not significant, risk of a new episode of cerebral ischaemia in patients with pregnancies complicated by preeclampsia (two out of the eight preeclampsia (p 0.15). Despite treatment, there is a significant risk for pregnancy complications in APS patients with previous CVE. Especially in the context of preeclampsia, anticoagulation should be given rigorously to prevent recurrence of CVE.     

Epidemiology of venous thromboembolism

The annual incidence of diagnosed venous thromboembolism (VTE) is 1 to 2 events per 1000 of the general population. VTE is very uncommon before age 20 years and, after 40 years of age, the incidence about doubles with each decade. Over half of episodes of VTE are deep vein thrombosis (DVT), and three quarters are first episodes. The incidence of VTE is similar in men and women and lower in Asians than it is in Caucasians or Africans. Hereditary risk factors include the factor V Leiden mutation; the G20210A prothrombin gene mutation; and deficiencies of protein C, protein S, and antithrombin. Hyperhomocysteinemia and elevated levels of factors I, VIII and XI, which may be hereditary and/or acquired, are also risk factors. Acquired risk factors include malignancy, hospitalization, surgery, venous trauma, immobilization, estrogen therapy, pregnancy, and the antiphospholipid antibodies. Risk factors for a first episode of VTE are generally also risk factors for recurrence, although the associated relative risk for thrombosis may differ for a first and subsequent event.     

The negative predictive value of D-dimer on the risk of recurrent venous thromboembolism in patients with multiple previous events: a prospective cohort study (the PROLONG PLUS study)

The optimal duration of anticoagulation after recurrent venous thromboembolism(VTE) is poorly established [1,2]. Recent studies suggested that D-dimer may identify patients at low risk of recurrence after a first VTE [3,4]. In a pilot, prospective, cohort study we aimed to assess the negative predictive value of D-dimer in patients with recurrent VTE. Patients with negative D-dimer while on treatment stopped anti coagulation and underwent repeated testing after 7, 15, and 30 days; treatment was resumed if D-dimer turned positive and permanently stopped if it remained negative. The study was interrupted after the enrolment of 75 patients. At that time, treating physicians decided treatment resumption in 12.2% of the patients, but the majority of events were distal or superficial vein thromboses. The rate of objectively documented recurrent proximal deep vein thrombosis (DVT) and/or pulmonary embolism (PE) was 2.56% (95% CI 0.13, 15.07%) in the 39 patients with persistently negative D-dimer at 30 days, for an annual incidence of VTE of 5.65 events/100 patient/years. These preliminary findings suggest that negative D-dimer may identify patients with history of previous VTE at low risk of recurrences, but this approach should be tested in larger trials in highly selected patients.     

Secondary prophylaxis of venous thromboembolism

Making decisions about any modality of secondary prophylaxis in patients with venous thromobembolism (VTE) has to balance the risk of bleeding induced by anticoagulants against the benefit of reducing the risk of recurrent disease. It has to be kept in mind that the magnitude of risk is not only defined by the number of events per time period but also by the impact of the event on the fate of the patient. With standard intensity Vitamin K antagonists, the risk of bleeding is more closely related to comorbidities than to other factors, e.g. age. The risk of VTE recurrence differs largely between patient groups. The criterion of presence, or absence of a permanent or transient clinical trigger factor for the actual VTE episode has a greater impact than an abnormal result in thrombophilia testing. The standard period ofsecondary prophylaxis for proximal deep vein thrombosis and for pulmonary embolism is three to six months. The concept of prolonging this period for several months according to the risk of recurrence is seriously challanged by the observation that the prolongation period seems to delay recurrencies rather than truly avoiding them. For this reason, patients who clearly are threatened by recurrent episodes should receive indefinitive secondary prophylaxis. This is the case for cancer patients, patients with the antiphospholipid syndrome, and those who belong to families with severe and symptomatic protein C, protein S, or antithrombin deficiencies. Patients with recurrent VTE, with idiopathic VTE, or with combined thrombophilic conditions may only benefit from indefinitive secondary prophylaxis if the bleeding risk of the anticoagulant regimen under consideration is very low.     

Symptomatic pulmonary embolism and the risk of recurrent venous thromboembolism

BACKGROUND: In patients with a first symptomatic pulmonary embolism (PE), the risk of recurrence is unknown. We therefore investigated the risk of recurrence among patients with spontaneous symptomatic PE and among those with deep vein thrombosis (DVT) without symptoms of PE. METHODS: After discontinuation of secondary thromboprophylaxis for a first venous thromboembolism (VTE), we prospectively observed 436 patients for an average of 30 months. Patients with secondary VTE, natural inhibitor deficiencies, lupus anticoagulant, cancer, long-term antithrombotic therapy, vena cava filters, or pregnancy were excluded. The study outcome was objectively documented recurrent symptomatic VTE. RESULTS: Recurrent VTE was seen among 28 (17.3%) of 162 patients with symptomatic PE and among 26 (9.5%) of 274 patients with DVT without symptoms of PE. Compared with patients with DVT, the relative risk of recurrent VTE among patients with symptomatic PE was 2.2 (95% confidence interval, 1.3-3.7; P =.005). The relative risk was not affected by age, sex, presence of factor V Leiden or prothrombin G20210A, hyperhomocysteinemia, or high factor VIII levels. Compared with patients with DVT without symptoms of PE, patients with symptomatic PE had an adjusted relative risk of PE at recurrence of 4.0 (95% confidence interval, 1.3-12.3; P =.03). CONCLUSION: Patients with a first symptomatic PE not only have a higher risk of recurrent VTE than those with DVT without symptoms of PE, but are also at high risk of symptomatic PE at recurrence.     

Ten years of cerebral venous thrombosis: male gender and myeloproliferative neoplasm is associated with thrombotic recurrence in unprovoked events

Cerebral venous thrombosis (CVT) is a rare venous thrombotic event. We review our local experience in the management of CVT in comparison to other venous thromboembolism (VTE) with specific focus on risk factors for thrombotic recurrence. Retrospective evaluation of consecutive CVT presentations from January 2005 to June 2015, at two major tertiary hospitals in Northeast Melbourne, Australia. This population was compared to a separate audit of 1003 consecutive patients with DVT and PE. Fifty-two patients (30 female, 22 male) with a median age of 40 (18–83) years, presented with 53 episodes of CVT. Twenty-nine episodes (55 %) were associated with an underlying risk factor, with hormonal risk factors in females being most common. The median duration of anticoagulation was 6 months with 11 receiving life-long anticoagulation. Eighty-one percent had residual thrombosis on repeat imaging, which was not associated with recurrence at the same or distant site. Nine (17 %) had CVT-related haemorrhagic transformation with two resultant CVT-related deaths (RR 22.5; p = 0.04). All three VTE recurrences occured in males with unprovoked events (RR 18.2; p = 0.05) who were subsequently diagnosed with myeloproliferative neoplasm (MPN). Compared to the non-cancer VTE population, non-cancer CVT patients were younger, had similar rate of provoked events and VTE recurrence, although with significantly higher rate of MPN diagnosis (RR 9.30 (2.29–37.76); p = 0.002) CVT is a rare thrombotic disorder. All recurrences in this audit occurred in male patients with unprovoked events and subsequent diagnosis of MPN, suggesting further evaluation for MPN may be warranted in patients with unprovoked CVT.     

Recurrence risk of venous thromboembolism and hormone use in women from England: a cohort study using clinical practice research datalink

It is vital to identify people with low recurrence risk of venous thromboembolism (VTE) so as to protect them from dangers of prolonged anticoagulation therapy. Among women who develop VTE following hormone use, the evidence as to whether their risk of recurrence is low if they cease this therapy is conflicting. We investigated whether women whose initial VTE event was hormone‐related have a lower risk of VTE recurrence than women whose initial event had no obvious cause (unprovoked). A cohort study utilising the Clinical Practice Research Datalink linked to Hospital Episode Statistics data from England was conducted. We selected 4170 women aged between 15 and 64 years who were diagnosed with a first VTE event between 1997 and 2011. Cox regression models were used to obtain hazard ratios (HR). Hormone users had 29% lower recurrence risk than non‐users (adjusted HR = 0·71; 95% confidence interval 0·58–0·88), a relationship which existed both in women aged 15–44 years (predominantly oral contraceptive users) and those aged 45–64 years (predominantly hormone replacement therapy users). In conclusion, having a hormone‐associated VTE is associated with a lower recurrence risk than one that is unprovoked after discontinuation of the hormone‐containing preparation. Prolonged anticoagulation may therefore be unjustified in such women.