Assessment of Risk of Thromboprophylaxis Failure in Hospitalized Patients with Cancer (Artic Study)
Authors: Louzada Martha L , Kovacs Michael J. , Al-Ani FAtimah , Lazo-Langner Alejandro , Siqueira Lenicio 
Published: October 2019

Background: Venous thromboembolism (VTE) remains the major cause of morbidity and mortality in hospitalized patients. Three randomized placebo controlled trials have demonstrated the superiority low molecular weight heparin (LMWH) and 1 heparinoid in the prevention of VTE in hospitalized medical patients with a 50% absolute risk reduction in VTE compared to placebo, but an overall failure rate of 5%. Current guidelines suggest that hospitalized cancer patients receive venous thromboprophylaxis with LMWH, if their hospital stay is longer than 3 days. In this study we sought to evaluate the incidence of VTE in hospitalized patients with cancer receiving VTE prophylaxis with subcutaneous 5000 units of dalteparin daily during the admission period.

Methods: This is a single centre retrospective cohort study (London, Canada). We collected data from adult patients with active cancer admitted for acute medical reasons who received VTE prophylaxis with LMWH during their hospital stay. We considered failure of prophylaxis if objective diagnosis of pulmonary embolism or deep venous thrombosis occurred: a) during hospitalization; b) within 1 month or 3 months of most recent discharge from hospital.

We included patients 18 years old or older; with any type of active cancer (except basal cell and squamous cell carcinoma of the skin) admitted for at least 3 days for treatment of an acute medical reason directly associated to their cancer or not. We did not include patients admitted at the intensive care unit.

We need 713 patients to demonstrate a 5 to 7.5% failure rate in VTE prophylaxis (MCID 2.5%) in hospitalized patients with cancer with a 0.025 one-sided alpha and 80% power.

Results: Between January 2011 and December 2013 our hospital registered 4262 admissions of patients with active malignancy for treatment of an acute medical illness. 875 patients (total 1132 admissions) fulfilled our eligibility criteria. 434 were males (49.5%), mean age 64.3 (SD= 13.5). There were 180 (20%) hematological and 695 (80%) solid malignancies. The most frequent tumor sites were genitourinary (n=170), lung (n=158), colorectal (n=128) and others (n= 239). 559 (70%) patients with solid tumors had stage III or IV. Reason for admission was failure to thrive (n=232); fever/ infection (n= 202); need for cancer treatment (n= 154); pain control (n=126); respiratory distress (n=108) or CNS symptoms (n=53). Mean hospitalization days were 14.7 (±12). 491 (56%) patients had a single admission.

VTE occurred in 70 of 875 patients (8.0%). The incidence of VTE was most frequent during the hospitalization period [34 of 70 patients (48.0%)] compared to 1 month [14 (20.0%)] or 3 months [22 (31.5%)] following the most recent hospitalization. Univariate analysis suggested that being male (OR= 1.69; 95%CI: 1.03 – 2.78; p=0.039); age 65 or older (OR=1.39; 95%CI: 0.4 -1.8; p=0.052); admission due to respiratory distress (OR=2.61; 95%CI: 0.9 – 6.8; p=0.052) or failure to thrive (OR=2.52; 95%CI: 1.1 – 5.9; p=0.036) were significantly associated with VTE risk. Having pancreas or colorectal cancer approached significance (Table).

Total bleeding rate was 18 of 875 (2%) with 5 major bleeding events. 175 (20%) patients died during the study period: 125 (75%) due to malignancy progression.

Conclusion: Hospitalized patients with active cancer are at high risk for VTE prophylaxis failure (8%). It appears that reason of admission, age and male sex are significant risk factors of VTE prophylaxis failure. Having colorectal or pancreatic cancer may also pose a risk for VTE. New VTE prophylactic strategies for this population should be investigated in future prospective studies.

Table. Univariate analysis to assess potential risk factors for LMWH prophylaxis failure in hospitalized patients with cancer Risk Factors Odds Ratio (95% CI) p-value Male 0.95 (0.6 -1.5) 0.808 Age ≥65 1.39 (0.4 -1.8) 0.052 Stage I - II Stage III - IV 1.03 (0.4 -2.5)1.27 (0.7 -2.4) 0.9090.478 Primary tumor site* Lung Colorectal Breast Pancreas Others 1.79 (0.8 - 7.4)2.67(0.9 - 4.7)1.63 (0.9 -10.7)3.11 (0.6 - 3.8)1.33 (0.9 - 5.6) 0.1690.0600.3630.0730.452 Reason for admission^ Fever CNS symptoms Respiratory distress Pain Failure to thrive 1.32 (0.5 - 3.4)1.703 (0.5 - 6.0)2.61 (0.9 - 6.8)1.79 (0.7 - 4.8)2.52 (1.1 - 5.9) 0.5720.4110.0520.2480.036 Number of admissions ** <4 ≥ 4 1.21 (0.7 - 2.0)1.46 (0.4 -5.0) 0.4620.553 Reference: *hematological; ^anticancer treatment ** single admission

Disclosures

No relevant conflicts of interest to declare.