Risk factors predictive of occult cancer detection in patients with unprovoked venous thromboembolism

Ihaddadene, Ryma; Corsi, Daniel J.; Lazo‐Langner, Alejandro; Shivakumar, S; Zarychanski, Ryan; Tagalakis, Vicky; Solymoss, Susan; Routhier, Nathalie; Douketis, James D.; Gal, Grégoire Le; Carrier, Marc

doi:10.1182/blood-2015-11-682963

Cited by 56 publications

(38 citation statements)

References 12 publications

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“…40 Moreover, the associations between sP-selectin and both K s and CLT support growing evidence for the impact of platelet-derived proteins on clot properties reported previously. 41 We confirmed that older age 42 and higher platelet count 7 can predict cancer diagnosis following unprovoked VTE. We did not find male sex to be a risk factor, as opposed to the studies by Jara-Palomares et al 7 and Rieu et al, 43 although evidence for this issue is inconsistent.…”

Section: Discussionsupporting

confidence: 61%

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Prothrombotic fibrin clot properties associated with increased endogenous thrombin potential and soluble P‐selectin predict occult cancer after unprovoked venous thromboembolism

Mrozińska

Cieślik

Broniatowska

et al. 2019

Journal of Thrombosis and Haemostasis

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Background Compact fibrin clots relatively resistant to lysis are observed in patients at increased risk of venous thromboembolism (VTE) including malignancy. The citrullinated histone H3 (H3Cit) predicts VTE in cancer patients. Objectives We performed a cohort study to investigate whether abnormal clot properties predict cancer diagnosis following unprovoked VTE. Methods In 369 consecutive patients aged <70 years without malignancy detected during routine screening, we determined plasma clot permeability (Ks) and clot lysis time (CLT), along with several prothrombotic markers and H3Cit after 2 to 8 months since VTE. Results During follow‐up (median, 37; interquartile range, 33‐39 months), malignancy was diagnosed in 22 patients (6%), who were older. This group had denser fibrin networks (−13% Ks), impaired fibrinolysis (+25.5% CLT), increased endogenous thrombin potential (ETP,+7%), soluble P‐selectin (+40.3%), and H3Cit (+169.2%) measured off anticoagulation after median 4 months since VTE. The Ks and CLT correlated with H3Cit (r = −.58 and r = .31, P < .05, respectively). The Kaplan–Meier survival analysis showed that reduced Ks (the first quartile, ≤6.2 × 10−9 cm2), prolonged CLT (the top quartile, >106 min), and higher ETP (the top quartile, >1657 nM × min) were predictors of cancer diagnosed during follow‐up. The multivariable Cox proportional hazards model showed that patients with the prothrombotic clot phenotype (low Ks and long CLT) had the highest risk of cancer diagnosis [hazard ratio(HR), 23.4; 95% confidence interval (CI), 6.67‐82.15]. Conclusions Prothrombotic clot properties following unprovoked VTE might help identify patients at risk of a diagnosis of cancer within the first 3 years of follow‐up.

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Section: Discussionsupporting

confidence: 61%

“…We did not find male sex to be a risk factor, as opposed to the studies by Jara-Palomares et al 7 and Rieu et al, 43 although evidence for this issue is inconsistent. 3,7,42 The associations between cancer and both diabetes and hypercholesterolemia likely result from older age of VTE patients diagnosed with malignancy (medians, 59 vs.…”

Section: Discussionmentioning

confidence: 99%

Prothrombotic fibrin clot properties associated with increased endogenous thrombin potential and soluble P‐selectin predict occult cancer after unprovoked venous thromboembolism

Mrozińska

Cieślik

Broniatowska

et al. 2019

Journal of Thrombosis and Haemostasis

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“…This has not previously been shown. Ihaddadene et al [17] found no association between sex and occult malignancy, Sørenssen et al [10] found no particular gender difference and Trujillo-Santos et al [15] found an odds ratio of 1.3 for male sex but did not reach significance. The explanation for the increased risk of a cancer diagnosis associated with male sex found here is not fully understood.…”

Section: Discussionmentioning

confidence: 99%

Venous thromboembolism and cancer risk

Sandén

Svensson²,

Själander

2016

J Thromb Thrombolysis

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Cancer increases the risk of venous thromboembolism (VTE) and about 20 % of all VTE are associated with cancer. VTE can also be used as a marker for occult cancer. The objective was to examine the correlation between VTE and cancer regarding predictors for a subsequent cancer diagnosis. Patients treated for VTE between January 1st 2006 and December 31th 2011 were extracted from the Swedish national quality register AuriculA and crossmatched with the Swedish National Patient Register. In total 7854 patients corresponding to 14284 treatments years were examined. Primary VTE was found in 6451 patients, with 3936 first and 2515 recurrent VTE. There were 1403 patients with secondary VTE. After a first or recurrent primary VTE the incidence of cancer diagnose was high being 9.4–10.0 % the first year compared to 2.7–2.5 % during the second year. Cancer in the digestive organs was the most common type of cancer among those with first primary VTE with 19.2 % of diagnoses. In multivariable analysis age was found to increase the risk of cancer diagnosis after both first and recurrent primary VTE HR 1.02 (CI 1.02–1.03) and HR 1.02 (CI 1.01–1.03). For a first primary VTE anemia HR 2.13 (CI 1.48–3.08) and male sex HR 1.38 (CI 1.09–1.76) increased the risk while hypertension HR 0.74 (0.57–0.96), dementia HR 0.30 (CI 0.10–0.95) and history of major bleeding HR 0.52 (CI 0.28–0.97) reduced the risk of a subsequent cancer diagnosis. There is a substantial proportion of patients being diagnosed with cancer the first year after a primary VTE, anaemia and male sex confers an increased risk.

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“…Risk factors predictive of occult cancer in patients with unprovoked VTE have already been identified. These include smoking, previous provoked VTE and older age (≥60 years) . Similarly, clinical prediction models incorporating multiple risk factors represent a promising approach for such risk stratification.…”

Section: The Futurementioning

confidence: 99%

Occult cancer detection in venous thromboembolism: the past, the present, and the future

Khan

Rahman

Carrier

2017

Research and Practice in Thrombosis and Haemostasis

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Essentials Unprovoked venous thromboembolism (VTE) may be the first manifestation of an undiagnosed cancer.The rate of occult cancer detection in patients with unprovoked VTE is approximately 5%.Clinicians should keep a low threshold of suspicion for occult cancer in these patients.Patients should only undergo a limited as well as age‐ and gender‐specific cancer screening. Unprovoked venous thromboembolism (VTE) can be the first manifestation of an undiagnosed cancer. Recently published studies have suggested that approximately 4‐5% of patients with new unprovoked VTE will be diagnosed with cancer within 12 months of follow‐up. Therefore, it is important for clinicians to keep a low threshold of suspicion for occult cancer in this patient population. After an unprovoked VTE diagnosis, patients should undergo a thorough medical history, physical examination, basic laboratory investigations (ie, complete blood count and liver function tests), chest X‐ray, as well as age‐ and gender‐specific cancer screening (breast, cervical, colon, and prostate). More intensive cancer screening including additional investigations (eg, computed tomography of the abdomen/pelvis) does not seem to increase the rate of occult cancer detection, decrease cancer‐related morbidity, or increase survival or cost‐effectiveness.

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Risk factors predictive of occult cancer detection in patients with unprovoked venous thromboembolism

Abstract: Key Points• It remains unclear whether a subgroup of high-risk patients could potentially benefit from a more extensive screening strategy.• Age, prior provoked VTE, and smoking status may be important predictors of occult cancer detection in patients with first unprovoked VTE.

Cited by 56 publications

References 12 publications

Prothrombotic fibrin clot properties associated with increased endogenous thrombin potential and soluble P‐selectin predict occult cancer after unprovoked venous thromboembolism

Prothrombotic fibrin clot properties associated with increased endogenous thrombin potential and soluble P‐selectin predict occult cancer after unprovoked venous thromboembolism

Venous thromboembolism and cancer risk

Occult cancer detection in venous thromboembolism: the past, the present, and the future

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