The relationship between cancer and thrombosis is a well-established and intricate interplay within the realm of medical science. It is widely recognized that individuals with cancer face an increased risk of developing thrombosis. This connection works both ways, influencing the onset and progression of both conditions .
Thrombosis and cancer
On the one hand, active cancer stands as a potent catalyst for venous thromboembolism (VTE), a condition encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE). Research has consistently demonstrated that cancer patients are more susceptible to VTE, with a substantial proportion of initial VTE occurrences being directly related to an underlying malignancy . Studies have indicated that approximately 20-30% of all first-time VTE cases are intricately linked to cancer . This heightened risk has led to a growing recognition of the need for vigilance and preventive measures in this subset of patients.
Occult cancer and thrombosis
On the other hand, the relationship extends further, with thrombosis sometimes unmasking an otherwise concealed cancer. In some instances, VTE episodes, particularly when unprovoked, can serve as a warning sign, heralding the presence of an occult malignancy that might not have been detected otherwise. This dual-directional association between cancer and thrombosis adds complexity to the medical landscape, warranting careful consideration in patient care .
Some studies show that 2.4% of VTE patients are diagnosed with cancer within 6 months, and 5–10% within 1 year [5, 6]. The complexity of cancer-associated VTE’s development involves factors, such as tumor-induced platelet aggregation, direct coagulation pathway activation, reduced fibrinolysis, and cancer cells promoting inflammation .
Currently, there’s no standardized approach for screening occult cancer in unprovoked VTE patients, leaving clinicians and patients uncertain . Deciding the extent of cancer screening in non-provoked VTE cases is challenging. Identifying a subgroup of VTE patients at higher risk of hidden cancer is crucial for targeted screening. Some suggested factors linked to increased cancer risk in VTE patients include age, smoking, prior provoked VTE, gender, chronic lung disease, anemia, and elevated platelet counts .
PE and occult cancer
Regarding PE, understanding its association with hidden cancer and determining the appropriate level of cancer screening remains less conclusive.
A recent study aimed to predict cancer in patients hospitalized with acute PE. The primary hypothesis was that D-dimer levels could predict cancer .
The retrospective study, conducted at Centro Hospitalar Universitário São João (CHUSJ), examined a cohort of patients hospitalized between 2006 and 2013 with acute PE. It involved 562 patients, of which 219 (39.0 %) were men, with a median age of 72 years .
Eligibility criteria for the study involved patients referring to pulmonary embolism and infarction. Each patient was included in the study only once, and if they were readmitted due to another acute PE, they were not considered for the study .
Pulmonary embolism was categorized as unprovoked if no significant risk factors were present, such as active cancer, immobilization, major trauma/surgery, established thrombophilia (either congenital or acquired), or hormonal therapy (including estrogen contraceptives or hormone replacement) .
The patients were divided into three groups based on their cancer status:
- Those with a known concurrent cancer,
- Those who were diagnosed with cancer during their acute PE hospitalization or within the subsequent two years,
- Those without any documented cancer during the follow-up period .
All patients were tracked for up to two years from the time of acute PE diagnosis. Relevant hospital records were consulted to identify occurrences of cancer after the acute PE diagnosis, whether in the hospital or after discharge .
Among the patients, 126 (22.4%) had confirmed active cancer. Out of the remaining 436 patients, 47 (10.8%) were diagnosed with cancer after the initial acute PE diagnosis within a span of up to 2 years. Among these new cancer diagnoses, 11 (23.4%) were lung cancers, 8 (17.0%) were pancreatic, 7 (14.9%) were gastric, 4 (8.5%) were colorectal, and 8 (17.0%) were distributed across various other types. Notably, 39 cases were diagnosed while patients were still hospitalized due to acute PE, while eight cases were diagnosed within the following 2 years .
D-dimer: a prognostic factor for occult cancer in the presence of PE
Among various analyzed factors, the D-dimer level emerged as a robust and independent predictor of future cancer development.
For every 5 ng/mL increase in D-dimer, the odds ratio (OR) for discovering an as-yet undetected cancer was 1.07 (95% CI: 1.01–1.14). Specifically, for patients with D-dimer levels exceeding 15.0 μg/mL, the OR for future cancer diagnosis was 2.01 (1.05–4.18) .
Based on the prevalence of future cancer diagnoses (10.8%) within two years of acute PE diagnosis, along with the sensitivity and specificity of the D-dimer cutoff at 15 μg/mL (34.0% and 78.1%, respectively), the negative predictive value for detecting future cancer in acute PE patients with D-dimer levels ≤15 μg/mL was determined to be 90.7% .
Even when considering only patients with unprovoked PE for analysis (260 + 47 diagnosed with cancer during acute PE hospitalization or within 2 years), the outcomes remained similar. For those with D-dimer levels exceeding 15 μg/mL, the adjusted risk of future cancer diagnosis in the following 2 years was 2.32 (1.12–4.81) .
Notably, anemia also emerged as an independent predictor of future cancer in patients with unprovoked acute PE, with an odds ratio of 2.13 (1.08–4.16) when compared to patients without anemia .
These results underscore the value of D-dimer levels as a diagnostic tool for ruling out thrombotic events and potentially identifying patients at higher risk of concurrent or future cancer. The findings suggest that higher D-dimer levels could prompt more comprehensive cancer screening in acute PE patients.
Despite the study’s limitations, such as its retrospective nature and single-center focus, it points to the need for larger prospective investigations that could enhance risk models for predicting future cancer in patients with acute PE.
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