Survival patterns among venous thromboembolism patients with hematologic malignancies in Alberta, Canada from 2003 to 2015

Alam, Arafat Ul; Karkhaneh, Mohammad; Sun, Hao; Wu, Cynthia

doi:10.1016/j.thromres.2020.12.021

Cited by 7 publications

(11 citation statements)

References 54 publications

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“…In addition, as thrombosis has emerged as one of the main contributors to the increased morbidity and mortality of subjects diagnosed with MPNs, identifying new biomarkers with the potential to predict or at least alarm for the risk of thrombotic events would be of paramount importance. For example, median survival decreases with nearly 30 months and the risk of death increases (adjusted HR = 1.60, 95% CI = 1.01–2.51 for MPNs patients diagnosed with pulmonary embolism) in MPNs subjects who experience VTE versus those who did not [ 57 ]. Moreover, in patients whose complete blood count displays leukocytosis, the relative risk of thrombosis is elevated in ET subjects and in ET and PV subjects with a positive history for arterial thrombosis [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

Liquid Biopsy and Potential Liquid Biopsy-Based Biomarkers in Philadelphia-Negative Classical Myeloproliferative Neoplasms: A Systematic Review

Găman

Cozma

Dobrică

et al. 2021

Life

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Myeloproliferative neoplasms (MPNs) are rare, clonal disorders of the hematopoietic stem cell in which an uncontrolled proliferation of terminally differentiated myeloid cells is noted. Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are included in the category of Philadelphia-negative, so-called classical MPNs. The potential applications of liquid biopsy and liquid biopsy-based biomarkers have not been explored in MPNs until now. Thus, a systematic search was computed in PubMed/MEDLINE, Web of Science and The Cochrane Library and, in total, 198 potentially relevant papers were detected. Following the removal of duplicates (n = 85), 113 records were screened. After the exclusion of irrelevant manuscripts based on the screening of their titles and abstracts (n = 81), we examined the full texts of 33 manuscripts. Finally, after we applied the exclusion and inclusion criteria, 27 original articles were included in this review. Overall, the data analyzed in this review point out that liquid biopsy and liquid biopsy-based biomarkers (cell-free DNA, extracellular vesicles, microparticles, circulating endothelial cells) could be used in MPNs for diagnostic and prognostic purposes. Future research is needed to clarify whether this technique can be employed to differentiate between MPN subtypes and secondary causes of erythrocytosis, thrombocytosis and myelofibrosis, as well as to predict the development of thrombosis.

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Section: Discussionmentioning

confidence: 99%

Liquid Biopsy and Potential Liquid Biopsy-Based Biomarkers in Philadelphia-Negative Classical Myeloproliferative Neoplasms: A Systematic Review

Găman

Cozma

Dobrică

et al. 2021

Life

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“…1,2 Cancer-associated venous thromboembolism poses a burden on healthcare systems, disrupts cancer treatment, and contributes to emotional distress and physical discomfort. 3,4 Patients with venous thromboembolism also carry a substantial risk of recurrence. 5 Primary prophylaxis with low-molecular-weight heparin reduces the risk of venous thromboembolism, but the associated bleeding risk and burden of daily injections have hampered its implementation into routine clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Validation of the Khorana score for predicting venous thromboembolism in 40 218 patients with cancer initiating chemotherapy

et al. 2022

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The Khorana score is recommended for guiding primary venous thromboembolism prophylaxis in cancer patients, but its clinical utility overall and across cancer types remains debatable. Also, some previous validation studies have ignored competing risk of death, hereby potentially overestimating venous thromboembolism risk. We identified ambulatory cancer patients initiating chemotherapy without other indications for anticoagulation using Danish health registries and estimated six-month cumulative incidence of venous thromboembolism stratified by Khorana levels. Analyses were conducted with and without considering death as competing risk using the Kaplan-Meier method versus the cumulative incidence function. Analyses were performed overall and stratified by cancer types. Of 40,218 patients, 35.4% were categorized by Khorana as low risk (score 0), 53.6% as intermediate risk (score 1-2) and 10.9% as high risk (score ≥3). Considering competing risk of death, the corresponding six-month risks of venous thromboembolism were 1.5% (95% CI 1.3-1-7), 2.8% (95% CI 2.6-3.1), and 4.1% (95% CI 3.5-4.7), respectively. Among patients recommended anticoagulation by guidelines (Khorana score ≥2), six-month risk was 3.6% (95% CI 3.3-3.9). Kaplan-Meier analysis overestimated incidence up to 23% compared with competing risk analyses. Using the guideline-recommended threshold of ≥2, the Khorana score did not risk stratify patients with hepatobiliary or pancreatic cancer, lung cancer, and gynecologic cancer. In conclusion, the Khorana score was able to stratify ambulatory cancer patients according to risk of venous thromboembolism, but not for all cancer types. Absolute risks varied by methodology but were lower than in key randomized trials. Thus, although certain limitations with outcome identification using administrative registries apply, the absolute benefit of implementing routine primary thromboprophylaxis in an unselected cancer population may be smaller than seen in randomized trials.

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“…It is unclear whether VTE directly increases risk of disease progression and death or is simply a marker of uncontrolled systemic inflammation and immune dysregulation. In the cancer literature, VTE has been identified as an independent predictor of death in both solid and hematological malignancies, even after adjusting for cancer stage and site 19,20 . It is important to note that while we identified an association between VTE and poor overall survival, it is unlikely that this is causal in nature, due to the lack of replicable results in other populations, lack of biological explanations, and presence of unadjusted confounders (markers of uncontrolled inflammation and multiorgan failure, markers of poor response to therapy).…”

Section: Discussionmentioning

confidence: 59%

“…In the cancer literature, VTE has been identified as an independent predictor of death in both solid and hematological malignancies, even after adjusting for cancer stage and site. 19,20 It is important to note that while we identified an association between VTE and poor overall survival, it is unlikely that this is causal in nature, due to the lack of replicable results in other populations, lack of biological explanations, and presence of unadjusted confounders (markers of uncontrolled inflammation and multiorgan failure, markers of poor response to therapy). Within our analysis, VTE emerged as a significant predictor of adverse OS, but not 90-day mortality on multivariable analysis, further challenging the biological significance of VTE as an independent risk factor for death.…”

Section: Discussionmentioning

confidence: 78%

“…There were no significant differences in the distribution of age, sex, etiology of HLH, or pharmacologic thromboprophylaxis in patients with and without bleeding (Table 2). Bleeders were more likely than non-bleeders to have a delayed time to diagnosis (median 11 [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] vs.…”

Section: Incidence and Risk Factors Of Bleedingmentioning

confidence: 99%

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Incidence of bleeding and thromboembolism and impact on overall survival in adult patients with hemophagocytic lymphohistiocytosis: A 20‐year provincial retrospective cohort study

Croden

Bilston

Taparia

et al. 2022

Journal of Thrombosis and Haemostasis

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Background Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome characterized by uncontrolled immune activation and high risk of death. There is scarce data on the incidence of bleeding and thromboembolism in HLH. Objectives To determine the cumulative incidence of bleeding and thromboembolism and impact on survival in adults with HLH. Patients/Methods We conducted a multicenter retrospective cohort study of adults with HLH in Alberta, Canada (1999–2019). The cumulative incidence of bleeding and thromboembolism were calculated, accounting for competing risks. Cox proportional hazards models were used to assess the impact of bleeding and thromboembolism on overall survival (OS). Results We identified 97 adults with HLH (median age 46 years). Venous thromboembolism (VTE) occurred in 11 (11%) patients at a median of 9 days from admission. ISTH major bleeding and clinically relevant non‐major bleeding occurred in 39 (40%) patients, at a median of 16 days after admission. Nadir platelet count (adjusted odds ratio [aOR] 1.8 per log decrease, 95% confidence interval [CI] 1.2–2.8) and mechanical ventilation (aOR 4.9, 95% CI 1.8–14.8) were independent predictors of bleeding on multivariable analysis. Adjusting for competing risks, the 90‐day cumulative incidences of bleeding and thromboembolism were 39% and 13%, respectively. The median OS was 18.8 months. VTE, but not bleeding, was significantly associated with adverse OS (adjusted hazard ratio 2.5, 95% CI 1.1–5.7). Conclusions In adults with HLH, VTE appears more common than previously described and is a predictor of mortality, although this may be due to unadjusted confounding. VTE prevention and treatment are challenging due to high bleeding rates.

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Survival patterns among venous thromboembolism patients with hematologic malignancies in Alberta, Canada from 2003 to 2015

Cited by 7 publications

References 54 publications

Liquid Biopsy and Potential Liquid Biopsy-Based Biomarkers in Philadelphia-Negative Classical Myeloproliferative Neoplasms: A Systematic Review

Liquid Biopsy and Potential Liquid Biopsy-Based Biomarkers in Philadelphia-Negative Classical Myeloproliferative Neoplasms: A Systematic Review

Validation of the Khorana score for predicting venous thromboembolism in 40 218 patients with cancer initiating chemotherapy

Incidence of bleeding and thromboembolism and impact on overall survival in adult patients with hemophagocytic lymphohistiocytosis: A 20‐year provincial retrospective cohort study

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