In this study, we evaluated the clinical factors associated with the development of thromboprophylaxis failure and found that BMI, active cancer, leukocytosis and need for intensive care were significantly associated with this outcome.
Obesity is known to be a prothrombotic state secondary to chronic inflammation (18) and is an independent factor that increases the risk of developing VTD by up to 6.2-fold (19). Our findings in a predominantly medical population are consistent with those reported in the literature. To reduce the risk of TF in obese patients, strategies such as increasing the dose of low molecular weight heparin (LMWH) have been evaluated with inconsistent results. In a retrospective cohort study of 1335 patients, the incidence of VTD was similar in the high-dose and low-dose groups, with a higher incidence of bleeding complications in the high-dose group (20). More recently, a meta-analysis of 6266 patients was published showing that the high-dose group had a lower incidence of VTD (OR: 0.47, 95% CI: 0.27–0.82, p:0.007) and a similar incidence of bleeding events (OR: 0.86, 95% CI: 0.69–1.08) compared with the standard-dose group (21). Another proposed strategy for thromboprophylaxis in obese patients is to monitor anti-Xa levels and titrate the dose according to the results; however, this strategy also showed no benefit over the usual dose (22) and is therefore not currently recommended. At present, the appropriate dose of LMWH to reduce VTD in patients with a BMI > 30 kg/m2 remains controversial and is not currently recommended in international guidelines; however, this recommendation is likely to change in the future as additional evidence becomes available.
Our results are also consistent with the literature on active cancer as a factor associated with FT; it has been described that the malignant tumor expresses procoagulant proteins that, among other mechanisms, directly activate the coagulation cascade or platelets, thus representing a prothrombotic state (23). Oncology patients have a 4.1-fold increased risk of thrombosis, rising to 6.5-fold in the setting of active chemotherapy (6), a risk that may increase during hospitalization. Therefore, the American Hematology Association guidelines for the prevention of thrombotic events consider combined thromboprophylaxis for surgery with high thrombotic risk and low bleeding risk (24). A randomized clinical trial comparing weight-adjusted versus fixed-dose low-molecular-weight heparin in hospitalized patients found no difference in bleeding; however, the cumulative incidence of VTD at day 14 was 5.9% in the weight-adjusted arm (CI90%, 0%-20.5%).(25) The evidence provided by this study is very limited given the small sample size and lack of control for other potential confounders such as obesity, so further studies are needed to make a recommendation in medical patients.
Leukocytosis was also associated with FT in our study. Leukocytosis can be caused by a variety of factors including neoplasia, drugs, hypersensitivity reactions and infection (26), with infection being the most common cause. Sepsis has been shown to be an independent risk factor for VTD (OR 1.74; 95%CI, 1.59–1.90). Risk factors associated with sepsis include age, diabetes, chronic kidney disease, chronic obstructive pulmonary disease, stroke, malignancy and antibiotic use (27), most of which are risk factors for thrombosis. Among septic patients, those requiring mechanical ventilation (28) had a higher risk of thromboprophylaxis failure, suggesting that the greater the severity of the infectious process, the greater the risk of thrombosis.
ICU admission is recognized as a risk factor for failed thromboprophylaxis (29), which is consistent with our study. Risk factors have been identified in ICU patients such as mechanical ventilation (OR 1.56; 95% CI 0.23–10.45, p: 0.64), prolonged immobility (OR 2.14; 95% CI 0.11–40.87, p: 0.61) and femoral venous catheter use (OR 2.24, 95% CI 0.41–12.20, p: 0.35) (30). In septic patients, ARDS has also been associated with an increased risk of thrombosis (31), all of which may be secondary to the prothrombotic state associated with these conditions. Pharmacological thromboprophylaxis in conjunction with mechanical thromboprophylaxis to reduce failed thromboprophylaxis is being studied and results are awaited (32, 33); however, there are currently no studies to suggest additional interventions.
Strengths of this study include the high proportion of medical patients; however, the recommendations and findings of this study cannot be generalized to obstetric patients. Although this is an uncommon pathology, the required sample size was exceeded, which means greater statistical power. The results obtained are mostly in line with what has been demonstrated in the clinical literature.