Thromboembolism Risk In Pregnant Oncology Patients
Overview
This systematic review and meta-analysis investigated the incidence of venous thromboembolism (VTE) in pregnant individuals with active malignancy compared to those without malignancy. The study, based on seven cohort studies encompassing 5,928 individuals with both active malignancy and pregnancy, yielded the following key findings:
- Elevated VTE Risk: Pregnancy concurrent with active malignancy significantly heightened the odds of VTE, with an odds ratio (OR) of 6.8 (95% confidence interval [CI] 3.8–12.1).
- Cancer-Specific Associations: Distinct cancer types exhibited varying degrees of association with increased VTE risk:
– Elevated odds were observed for thyroid (OR 2.7), cervix (OR 6.6), or other gynecological cancers (OR 10.6), Hodgkin’s lymphoma (OR 8.7), and acute leukemia (OR 17.1).
– No statistically significant increase in odds was noted for brain cancer, breast cancer, malignant melanoma, or non-Hodgkin’s lymphoma.
- Absolute Risk Disparity: The absolute risk for VTE in individuals with active malignancy during pregnancy was 0.9%, notably higher than the 0.2% risk observed in those without active malignancy.
- Prophylactic Anticoagulation Consideration: The absence of data on prophylactic anticoagulation during pregnancy in this population underscores a critical gap in knowledge. The study suggests that considering prophylactic anticoagulation during pregnancy and postpartum may be prudent for individuals with active malignancy.
- Data Limitations: The study acknowledges the underpowered nature of the data to make firm recommendations specific to cancer types.
In conclusion, this meta-analysis highlights the substantially increased risk of VTE in pregnant individuals with active malignancy, emphasizing the importance of considering prophylactic anticoagulation in this patient population. The nuanced associations with different cancer types underscore the complexity of managing VTE risk in pregnant individuals with malignancy. Further research is warranted to address data limitations and provide more targeted recommendations based on cancer type.
Introduction
This systematic review/meta-analysis addresses the critical issue of venous thromboembolism (VTE) in pregnant individuals with active malignancy, a scenario associated with elevated maternal mortality. While clinical guidelines generally recommend thromboprophylaxis during pregnancy for high-risk patients, specific recommendations for those with active malignancy are often lacking. Approximately 1 in 1000 individuals experience active malignancy during pregnancy and the postpartum period, with increasing incidence.
Current management practices for pregnancy with active malignancy primarily rely on expert opinions rather than robust randomized controlled trial evidence. Both active malignancy and pregnancy independently contribute to the risk of VTE, yet guidelines regarding thrombosis in pregnancy rarely address the unique challenges posed by concurrent malignancy.
A recent cohort study revealed a significantly higher rate of VTE (75.2 per 10,000 pregnancies) in individuals with active malignancy compared to those without malignancy (10.7 per 10,000 pregnancies). This stark contrast has prompted some experts to advocate for thromboprophylaxis in this specific patient population due to the substantial incidence of VTE.
The systematic review/meta-analysis aims to comprehensively evaluate the rate of VTE in pregnant patients with active malignancy in comparison to those without malignancy. Additionally, it seeks to assess the potential role of thromboprophylaxis in mitigating the heightened VTE risk in this unique and high-risk population. This research contributes valuable insights into an underexplored intersection of pregnancy and malignancy, offering the potential for improved clinical guidance and risk management strategies.
Method
This review, conducted in adherence to MOOSE (Meta-analyses of Observational Studies in Epidemiology) guidelines, aimed to investigate the incidence of venous thromboembolism (VTE) in pregnant individuals with active malignancy. The search, spanning from database inception to June 2021, covered EMBASE, Medline/PubMed, Cochrane Database, and clinicaltrial.gov, utilizing keywords related to pregnancy, neoplasm, and thrombosis/thromboprophylaxis. A trained librarian assisted in the comprehensive search, and the review was updated to August 2023 before publication to ensure inclusion criteria were met. The search was limited to English and French language publications involving human participants.
The study selection and eligibility criteria focused on populations with active malignancy during pregnancy. Exclusion criteria comprised pre-existing VTE, sole reporting of myeloproliferative disorder malignancy, and benign tumors indicated by pathology. Primary outcomes included VTE incidence during pregnancy or 6 weeks postpartum in women with active malignancy, while secondary outcomes encompassed the use of thromboprophylaxis during pregnancy with active malignancy and potential complications associated with pregnancy.
The screening process involved two stages, with abstract and full-text reviews conducted by two reviewers. Discrepancies were resolved through discussion or consultation with a third independent reviewer, facilitated by the Covidence data-management system. Data extraction adhered to a pre-determined protocol and used a modified form based on the Cochrane data collection form for non-randomized controlled trials. It involved assessing the type of malignancy, gestational age at malignancy, rates of various thrombotic events, prophylactic anticoagulation use during pregnancy/postpartum, and associated complications.
The assessment of risk of bias utilized the Newcastle-Ottawa scale, with two authors independently evaluating studies and discrepancies resolved through consensus meetings with a third author. Statistical analyses, performed using RevMan 5.4 software, calculated odds ratios (OR) and 95% confidence intervals (CI) for the primary outcome. The Mantel-Haenszel random effects model was employed for data pooling, and statistical heterogeneity was assessed using Higgins I2 statistics.
This review, registered in PROSPERO (CRD42021245886), did not have a published protocol, and patient consent and institutional review board approval were deemed unnecessary for this study type.
Statistical Analyses
The analysis utilized RevMan 5.4 software to calculate the odds ratio (OR) and corresponding 95% confidence interval (CI) for the primary outcome. Statistical heterogeneity was assessed through the Higgins I2 statistics. The pooling and analysis of data from various studies were conducted using the Mantel-Haenszel random effects model.
It is noted that the review was registered in PROSPERO with the registration number CRD42021245886. However, no published protocol is available for reference. Additionally, patient consent and institutional review board approval were deemed unnecessary for this particular study design.
Result
The initial search identified 3821 studies, of which 141 full texts were assessed, and seven retrospective cohort studies met inclusion criteria. All studies focused on individuals with active malignancy during pregnancy, with a total of 5928 participants. Risk of bias assessment using the Newcastle-Ottawa scale revealed high quality and low risk across all studies.
The odds of venous thromboembolism (VTE) were significantly higher in individuals with active malignancy during pregnancy compared to those without (OR 6.8, 95% CI 3.8–12.1). The absolute risk for VTE in active malignancy was 0.9%, contrasting with 0.2% in pregnancy without malignancy. No publication bias was observed. Sensitivity analysis using exclusive cohorts yielded consistent results, affirming the increased risk of VTE in active malignancy during pregnancy.
Specifically, the odds of deep vein thrombosis and pulmonary embolism were significantly elevated in individuals with malignancy (OR 4.9, 95% CI 2.4–9.8 and OR 7.5, 95% CI 2.1–27.7, respectively). However, data on prophylactic anticoagulation, timing of VTE, or other VTE types were not provided. Further analysis based on malignancy types revealed increased odds for VTE in thyroid, cervix, gynecological (non-cervical), Hodgkin’s lymphoma, and acute leukemia cases during pregnancy.
In summary, this review establishes a substantial association between active malignancy during pregnancy and an elevated risk of VTE, emphasizing the importance of heightened clinical awareness and potential prophylactic measures for this specific population.
Conclusion
The meta-analysis reveals a significant increase in the risk of venous thromboembolism (VTE) during pregnancy with active malignancy. Notably, none of the included cohort studies reported the use of prophylactic anticoagulation during pregnancy in this patient group. Due to the rarity of this population, randomized controlled trials addressing this topic are unlikely.
Pregnancy and active malignancy present conditions where all components of Virchow’s triad for VTE development are present. Pregnancy and cancer physiology contribute to a heightened risk due to venous stasis, hypercoagulable states, and endothelial vessel-wall damage. Current guidelines recognize cancer as a risk factor for VTE in pregnancy, but none recommend thromboprophylaxis if active malignancy is the sole risk factor. However, this meta-analysis suggests a much higher VTE risk in patients with active malignancy during pregnancy than previously reported.
Prophylactic anticoagulation with low-molecular-weight heparins (LMWH) is deemed safe in pregnancy, despite potential downsides such as patient discomfort, medication costs, and a slight increase in the risk of antepartum hemorrhage, skin reactions, and osteoporosis. The meta-analysis indicates that LMWH is preferred by pregnant individuals for thromboprophylaxis, given its overall benefit. Limited data from a prospective trial suggest that prophylaxis may reduce maternal morbidity and mortality in pregnant individuals with malignancy, emphasizing its potential role in mitigating the increased VTE risk in this population.
When assessing VTE risk based on cancer type, not all malignancies exhibit increased odds for VTE. However, data limitations and overlapping years in some trials hinder subgroup analysis and specific recommendations for cancer types. The study acknowledges several limitations, including challenges in data reporting, potential over-reporting of VTE risk, and a lack of information on prophylactic anticoagulation in the included studies. Future research directions include the development of a prospective database to collect comprehensive data on VTE rates and prophylactic anticoagulation use in individuals with active malignancy during pregnancy.
Pregnancy in individuals with an active malignancy significantly elevates the risk of venous thromboembolism (VTE). Considering this heightened risk, the utilization of prophylactic anticoagulation during both pregnancy and the postpartum period warrants consideration within this specific population. This proactive approach aligns with the imperative need to address the distinct challenges posed by the simultaneous presence of pregnancy and active malignancy, emphasizing the importance of tailored medical strategies for optimal maternal health.
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