The incidence and risk factors of recurrent venous thromboembolism during pregnancy

Introduction

Recurrent venous thromboembolism (VTE) during pregnancy is a challenging topic with relatively few publications. The aim of this study was to identify the incidence and the risk factors of recurrent antepartum VTE in women with a history of at least one previous VTE episode.

Materials and Methods

This observational cohort study involved 270 pregnant women (369 pregnancies) with at least one previous episode of VTE. The risk factors of recurrent antepartum VTE were identified by using group A (women without recurrent venous thromboembolism VTE) as a control group for group B (women with recurrent VTE despite LMWH (low molecular weight heparin) prophylaxis) and C (women with VTE recurrence in early pregnancy before the planned initiation of LMWH prophylaxis).

Results and Conclusions

The incidence of recurrent VTE was 7.6% (n = 28).Twelve recurrent VTEs in ten women (3.3%) developed during early pregnancy before initiation of LMWH and sixteen recurrent VTEs (4.3%) developed in 15 women despite LMWH prophylaxis.In women with recurrent antepartum VTE, the incidence of a history of two or more previous VTEs (group A vs. B: 5.7% vs. 40.0%, p < 0.001; group A vs. C: 5.7% vs. 30.0%, p = 0.022), previous VTE in connection with antiphospholipid antibody syndrome (group A vs. B: 2.6% vs. 20.0%, p = 0.012) and a history of VTE related to hormonal risk factors (group A vs. B: 60.4% vs. 93.3%, p = 0.011) was significantly higher compared to those with successful LMWH-prophylaxis. The percentage of the women with long-term anticoagulation was also significantly higher among the women with recurrent antepartum VTE (group A vs. B: 7.6% vs. 46.7%, p < 0.001) compared to those with successful LMWH-prophylaxis. The risk of antepartum recurrent VTE is considerable in women with a history of two or more previous VTEs, antiphospholipid antibody syndrome or long-term anticoagulation. The antepartum prophylaxis with prophylactic dose of LMWH or even with intermediate dose of LMWH might not be sufficient in this high-risk population.     

Sex-specific risk factors for recurrent venous thromboembolism

Background

Men have higher risk of recurrent venous thromboembolism (VTE) than women but this sex difference remains unexplained. In addition, whether men and women share same risk factors for recurrent VTE is unclear.

Methods

In a prospective cohort study, 583 patients (234 men and 349 women) aged 18 to 90, with a first idiopathic VTE, were followed for an average of 28 months. We assessed the association between baseline characteristics and VTE recurrence by gender.

Results

Recurrent VTE occurred in 38 women and 36 men (incidence = 4.6% and 7.5% per year respectively; HR = 1.6; 95% CI, 1.0-2.6). This relation between sex and recurrent VTE was more pronounced in patients younger than 50 years and in the presence of factor V Leiden (FVL) mutation. Multivariate analyses showed that obesity (HR, 2.8 (95% CI, 1.3-6.0)) and aging (HR, 1.3 (95% CI, 1.1-1.4) per 10 years increase) were related to an increased risk of recurrent VTE in women while FVL mutation (HR, 3.5 (95% CI, 1.5-8.1)) was a risk factor of recurrent VTE among men.

Conclusion

Men and women do not share the same risk factors for recurrent VTE. Consequently, gender has to be taken into account to improve the risk stratification and prevention of VTE recurrence.     

Socioeconomic and occupational risk factors for venous thromboembolism in Sweden: a nationwide epidemiological study

Our aims were to investigate possible associations between hospitalisation for venous thromboembolism (VTE) and socioeconomic and occupational factors. A nationwide database was constructed by linking Swedish census data to the Hospital Discharge Register (1990-2007). Hospital diagnoses of VTE were based on the International Classification of Diseases. Standardised incidence ratios were calculated for different socioeconomic and occupational groups. A total of 43063 individuals aged > 20 years were hospitalised for VTE. Individuals with > 12 years of education were at lower risk for VTE. Blue-collar workers, farmers, and non-employed individuals had higher risks for VTE, and white collar workers and professionals lower risks. In males and/or females, risks for VTE were increased for assistant nurses; farmers; miners and quarry workers; mechanics, iron and metalware workers; wood workers; food manufacture workers; packers; loaders and warehouse workers; public safety and protection workers; cooks and stewards; home helpers; building caretakers; and cleaners. Decreased risks were observed for technical, chemical, physical, and biological workers; physicians; dentists; nurses; other health and medical workers; teachers, religious, juridical, and other social science-related workers; artistic workers; clerical workers; sale agents; and fishermen, whalers and sealers. High educational level and several occupations requiring high levels of education were protective against VTE, while the risks for VTE were increased for farmers, blue-collar workers and non-employed individuals. The mechanisms are unknown but it might involve persistent psychosocial stress related to low socioeconomic and occupational status.     

Incidence, risk factors and clinical features of venous thromboembolism in newly diagnosed lymphoma patients: Results from a prospective cohort study with Asian population

Introduction

Venous thromboembolism (VTE) may be associated with treatment failure rate and quality of life deterioration in lymphoma patients. However, the majority of data regarding VTE has come from retrospective studies done in Western countries.

Materials and methods

We analyzed VTE, including pulmonary embolism and deep vein thrombosis, from Asian patients enrolled a prospective cohort study. All patients were newly diagnosed Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL).

Results

A total of 686 patients were analyzed, and the median follow-up duration was 21.8 months. There were 54 cases of VTE including deep vein thrombosis alone (33/54, 61.1%) and pulmonary embolism (21/54, 38.9%). The median time to VTE was 1.97 months, and the one-year actuarial incidence was 7.9%. The global incidence of VTE was higher in patients with NHL (51/641, 8.0%) than HL (3/45, 6.7%). All cases of VTE occurred in patients receiving chemotherapy whereas no VTE in patients without chemotherapy. VTE was also independently associated with age older than 60 years and primary central nervous system (CNS) lymphoma. No VTE-related deaths were reported among all cases of VTE. Thus, overall survival was not different between patients with and without VTE. The subgroup analysis of patients with diffuse large B-cell lymphoma showed 8.9% of one-year actuarial incidence, but the occurrence of VTE did not influence its overall survival, either.

Conclusions

The incidence of VTE in our study population was comparable to that of Western countries, and VTE was associated with chemotherapy, brain involvement and old age.     

Risk factors in venous thromboembolism

Venous thromboembolism is a serious disorder because of its potential complications, such as pulmonary embolism and the post-thrombotic syndrome. Inherited determinants of venous thromboembolism are only in part known, but in the past decades considerable progress has been made in the understanding of risk factors for the disease and their clinical impact. In particular, the development of molecular biology techniques and the increasing interest in their application, allowed an identification of two causes of inherited thrombophilia, i.e., factor V Leiden and the prothrombin G20210A mutation. Their recent discovery provided a new approach for improving the knowledge of inherited thrombophilia. In contrast to deficiencies of the naturally occurring anticoagulant proteins antithrombin, protein C and protein S, these two mutations cannot be considered true genetic defects, since they are nucleotide substitutions resulting in a more efficient coagulation process. Since they are rather common in the general populations of Caucasian descent and are associated with a moderate increased risk of venous thromboembolism, the effect of the interaction between inherited and environmental risk factors for venous thromboembolism has become an even greater field of interest. Prevention of first events and recurrences of venous thromboembolism can be optimized only through a knowledge of the main risk factors, their effect, and their interaction with environmental factors.     

Symptomatic venous thromboembolism in acute leukemia. Incidence, risk factors, and impact on prognosis

The association between malignant disorders and occurrence of venous thromboembolism is well established. Patients with cancer and venous thromboembolism have adverse prognosis. No systematic study on the incidence and prognostic impact of venous thromboembolism in acute leukemia has been performed as yet. We retrospectively evaluated the incidence of symptomatic venous thromboembolism before chemotherapy in 719 patients (371 males and 348 females, median age of 57.4 years), diagnosed with acute leukemia [534 with acute myelogenous leukemia, 185 with acute lymphoblastic leukemia]. Furthermore, the relationship of venous thromboembolism to clinical and laboratory parameters and its impact on prognosis was assessed. Fifteen patients (2.09%) had venous thromboembolism (objectively confirmed in 13 patients) in close temporal relationship to the onset of acute leukemia. The incidence of venous thromboembolism was the same in acute myelogenous and lymphoblastic leukemia. In five patients, pulmonary embolism was documented. Venous thromboembolism occurred in all subtypes of acute leukemia, but was most common in promyelocytic leukemia. All but one patient were treated with anticoagulants. No patient died from treatment-related bleedings or venous thromboembolism. Overall, survival, disease-free survival, and remission duration did not differ between the patient groups with and without venous thromboembolism. In contrast to solid tumors, venous thromboembolism before or at diagnosis of acute leukemia is not associated with poor prognosis.     

Prevalence of venous thromboembolism at a teaching hospital in Okinawa, Japan

Limited data suggest that Asian Americans may have a lower risk of venous thromboembolism (VTE) than Caucasians. However, the actual prevalence of VTE among Asians remains controversial, and has not been described in Japan. We studied all 131,060 patients hospitalized at a single medical centre in Japan (January 1987 - December 1999). Patients with VTE were identified through discharge diagnoses. Hospital records were reviewed for information on patient demographics, risk factors, and diagnostic modalities. VTE occurred in 0.11% of admissions (n=141, 95%CI 0.09-0.13%). Mean age (+/-SD) was 64+/-17 years, 70% were women, 91% had deep vein thrombosis, and 29% pulmonary embolism. Among hospitalized patients 50-69 years old, VTE was significantly more common among women than men (0.31% vs. 0.08%; OR 3.88; 95%CI 1.45-6.31). We found a low prevalence of VTE in Japan compared to that reported in the US. Future studies are needed to clarify the reasons for our findings.     

Effect of ethnicity and gender on the incidence of venous thromboembolism in a diverse population in California in 1996

There have been very few studies that have describe the epidemiology of first-time venous thromboembolism (VTE) in a large, ethnically diverse population. The California Discharge Data Set was used to identify a cohort of cases with incidentVTE in 1996. Cases associated with traditional provoking risk factors were identified and the remaining cases were labeled as idiopathicVTE. Direct standardization using census information was performed to compare incidence rates across races, gender, and gender within race. There were 21,002 cases with incident VTE in 1996, a crude incidence of 90 events per 100,000 adults. Thirty percent of all VTE events were pulmonary embolism. The directly standardized incidence per 100,000 California adults was 93+/-1.7 (+/-95% CI) in women, 85+/-1.7 in men, 103+/-2.1 in Caucasians, 138+/-6.5 in African- Americans, 61+/-2.8 in Hispanics and 29 +/- 2.4 in Asian-Pacific Islanders (p<0.001 for all inter-group comparisons). After adjusting for misclassification of race, the incidence of VTE per 100,000 was 104 in Caucasians, 141 in African-Americans, 55 in Hispanics, and 21 in Asian/Pacific-Islanders. The incidence of idiopathic VTE was significantly lower among both Hispanics and Asian/Pacific-Islanders (p<0.001) than Caucasians or African-Americans. African-Americans were more likely, and Hispanics less likely, to be diagnosed with idiopathic pulmonary embolism compared to Caucasians. The 28 day case-fatality rate among cases with idiopathic VTE was 2%, and it was significantly higher among African-Americans (4.1%) compared to Caucasians (1.8%, p<0.001). There are important differences in the incidence of total and idiopathicVTE and in the proportion of events diagnosed as pulmonary embolism among each of the major racial/ethnic groups in California. Further research is needed to explain these observed differences among the different racial/ethnic groups.     

Ovarian vein thrombosis: incidence of recurrent venous thromboembolism and survival

For patients with ovarian vein thrombosis (OVT), neither the rate of recurrence nor the expected survival are well established. Clarification of these natural history data would aid in defining the optimal management. We studied all female patients with OVT seen at the Mayo Clinic between 1990 and 2006. Survival, recurrent venous thrombosis rates, and prothrombotic factors were compared to a randomly selected group of 114 female patients with lower extremity venous thrombosis (DVT). Patients with OVT (n = 35; mean age 44.8 +/- 17.9 years) were significantly more likely to be under hormonal stimulation (48%), have an underlying malignancy (34%), experienced recent pelvic infection (23%) or undergone recent surgery (20%), compared to DVT patients. During a mean follow-up period of 34.6 +/- 44.3 months, three patients suffered three recurrent venous thrombi (event rate: three per 100 patient years of follow-up). This recurrence rate was comparable to patients with lower extremity DVT (2.2 per 100 patient years). Recurrent thrombosis involved the contralateral ovarian vein, left renal vein, and inferior vena cava. The five-year mortality rate for OVT patients was 43% compared to 20% for DVT patients (p = 0.08). All OVT deaths were cancer related. Survival was greater in OVT patients without cancer compared to those with active cancer (p < 0.0001). In conclusion, venous thromboembolism recurrence rates are low and comparable to lower extremity DVT. Therefore general treatment guidelines for lower extremity DVT may be applicable. Poor survival rates in OVT are principally governed by the presence of malignancy.     

Circulating microparticles and risk of venous thromboembolism

Introduction

Circulating microparticles (MPs) may trigger a hypercoagulable state, leading to thrombotic complications. Data on their association with venous thromboembolism (VTE) are few and inconsistent.

Materials and methods

To investigate whether or not high levels of MPs are associated with an increased risk of VTE, we carried out a case-control study on 186 patients with a first, objectively diagnosed, episode of VTE and 418 healthy controls. Plasma levels of circulating MPs were measured by flow cytometry.

Results

Patients had higher median plasma levels of total MPs than controls (2184 per μL vs 1769 per μL, p < 0.0001). The risk of VTE increased progressively with increasing MPs, with a linear dose-response effect in the log odds. Individuals with MPs above the 90th percentile of the controls’ distribution (P₉₀ = 3263 per μL) had a 5-fold increased risk of VTE than those with MPs below the 10th percentile of controls (P₁₀ = 913 per μL), independently of sex, age, body mass index, thrombophilia, and plasma factor VIII levels [adjusted odds ratio: 5.30 (95%CI: 2.05-13.7)]. Using the 95th percentile of controls as cut-off (P₉₅ = 4120 per μL), the adjusted odds ratio was 2.20 (1.01-4.79) for individuals with MPs > P₉₅ compared with those having MPs ≤ P₉₅. After exclusion of individuals with antiphospholipid antibodies and hyperhomocysteinemia, the interaction between MPs > P₉₅ and thrombophilia increased the VTE risk from 1.63 (0.60-4.50) to 6.09 (1.03-36.1).

Conclusions

High levels of circulating MPs are a possible independent risk factor for VTE.     

Incidence and risk factors associated with in-hospital venous thromboembolism after aneurysmal subarachnoid hemorrhage

Our purpose was to determine the incidence and risk factors associated with in-hospital venous thromboembolism (VTE) in patients with aneurysmal subarachnoid hemorrhage (aSAH). The Nationwide Inpatient Sample database was queried from 2002 to 2010 for hospital admissions for subarachnoid hemorrhage or intracerebral hemorrhage and either aneurysm clipping or coiling. Exclusion criteria were age <18, arteriovenous malformation/fistula diagnosis or repair, or radiosurgery. Primary outcome was VTE (deep vein thrombosis [DVT] or pulmonary embolus [PE]). Multivariate logistic regression was used to assess association between risk factors and VTE. Secondary outcomes were in-hospital mortality, discharge disposition, length of stay and hospital charges. A total of 15,968 hospital admissions were included. Overall rates of VTE (DVT or PE), DVT, and PE were 4.4%, 3.5%, and 1.2%, respectively. On multivariate analysis, the following factors were associated with increased VTE risk: increasing age, black race, male sex, teaching hospital, congestive heart failure, coagulopathy, neurologic disorders, paralysis, fluid and electrolyte disorders, obesity, and weight loss. Patients that underwent clipping versus coiling had similar VTE rates. VTE was associated with pulmonary/cardiac complication (odds ratio [OR] 2.8), infectious complication (OR 2.8), ventriculostomy (OR 1.8), and vasospasm (OR 1.3). Patients with VTE experienced increased non-routine discharge (OR 3.3), and had nearly double the mean length of stay (p < 0.001) and total inflation-adjusted hospital charges (p < 0.001). To our knowledge, this is the largest study evaluating the incidence and risk factors associated with the development of VTE after aSAH. The presence of one or more of these factors may necessitate more aggressive VTE prophylaxis.     

Importance of hyperhomocysteinemia as a risk factor for venous thromboembolism in a Taiwanese population. A case-control study

OBJECTIVE: To determine the current status of hyperhomocysteinemia, which is a known risk for venous thrombosis (DVT), in Taiwan. Subjects: 101 unselected patients with a minimum of one episode of deep leg DVT, either initial inpatients or current compliant outpatients in a teaching hospital. METHODS: Various thrombophilic risks, gene polymorphism and clinical predisposition were evaluated. RESULTS AND CONCLUSIONS: Patients presented higher fast total plasma homocysteine (hcy) levels than age- and sex-matched controls did (14.1 vs. 9.94 microM). Based on the 95th percentile of control values, hyperhomocysteinemia had a four- to nine-fold risk for DVT, irrespective of clinical predisposition, as well as other thrombophilic risks surveyed. Polymorphism of a metabolizing enzyme, methylenetetrahydrofolate reductase (MTHFR), was not associated with DVT, although homozygous thermolabile mutation tended to have higher plasma hcy levels. Factor V Leiden was absent in analysis of 80 patients. In complete evaluation (hcy, antithrombin (AT), protein S (PS), protein C (PC), lupus anticoagulant (LA), anticardiolipin antibody) of a subset of 83 patients hyperhomocysteinemia was the most prevalent risk (33.7%), with PC or PS deficiencies following (22.9%). Thus, hyperhomocysteinemia is a prominent risk for DVT in Taiwan.