This subanalysis of the FADOI-NoTEVole study provides detailed insight into Italian physicians’ practice regarding the use of pharmacological thromboprophylaxis in IMU inpatients. No specific guidelines were indicated in the study’s protocol regarding the prescription of prophylaxis; the choice was completely left to the physician.

Pharmacological thromboprophylaxis was prescribed in about half of the 3017 patients admitted to 38 Italian IMUs without prior anticoagulation. According to the PPS, almost 50% of patients were considered at high risk of VTE and, according to the IBS, less than 8% were considered at high risk for bleeding. Although not specifically requested by the FADOI-NoTEVole study protocol, the adoption of pharmacological thromboprophylaxis during hospitalization was only partially influenced by the VTE and bleeding RAMs recommended by current guidelines [5, 6]. Indeed, only 66.8% of the patients classified as high risk for VTE, according to the PPS, received thromboprophylaxis. Additionally, the assessment of bleeding risk using the IBS did not appear to impact physicians’ decisions. Interestingly, several other features composing PPS, IBS, and other RAMs [7, 8] were associated with a different use of pharmacological prophylaxis. These included the presence of a CVC, a previous VTE event, the diagnosis of ischemic stroke, perceived reduced mobility, and a platelet count not lower than 70.000/mm3 at the time of admission. On the other hand, as expected, a recent former major bleeding event led to a lower prescription of pharmacological thromboprophylaxis. Many studies have evaluated the role of potential risk factors for VTE and bleeding in patients hospitalized in non-surgical settings. Based on the findings of the IMPROVE VTE score and Padua Prediction score studies, reduced mobility and previous VTE were among the factors most strongly associated with the development of VTE [7, 8]. Venous thromboembolism, including DVT and pulmonary embolism (PE), is a frequent complication in bedridden patients with acute ischemic stroke [13]. Therefore, preventing venous thromboembolic complications of stroke could help reduce the burden of stroke-related disabilities. Randomized-controlled trials and a meta-analysis have clearly demonstrated that the use of antithrombotic prophylaxis with low molecular weight heparin in these patients is associated with a reduced risk of DVT and PE [14]. However, pharmacologic thromboprophylaxis does not affect mortality and is associated with a small but not negligible increased risk of bleeding, leaving some uncertainty regarding its use in this setting [15]. Central venous catheters are increasingly used in clinical practice and have a non-negligible incidence of catheter-related VTE, which is often asymptomatic. Recent studies have failed to find a significant reduction in symptomatic VTE with the use of antithrombotic prophylaxis [16, 17]. Furthermore, the IMPROVE registry indicates that the presence of a central venous catheter results in a significantly increased risk of bleeding [9].

In previous studies, the use of pharmacological thromboprophylaxis in hospitalized non-surgical patients was highly heterogeneous. In the Endorse study, a multinational cross-sectional study designed to assess the prevalence of VTE risk in the acute hospital care setting, the use of pharmacological thromboprophylaxis was generally low, although the risk of VTE was not negligible [18]. Conversely, in a large prospective Italian cohort study, pharmacological thromboprophylaxis was implemented in more than 80% of patients admitted to an IMU with a PPS equal to or above 4 [19].

Several randomized controlled trials and meta-analyses have clearly shown the efficacy of pharmacological thromboprophylaxis compared to placebo in reducing the risk of VTE in non-surgical patients admitted to the hospital [4, 20, 21]. However, this is associated with an increased risk of bleeding and, in general, it has no effect on reducing all-cause mortality, questioning the real importance of this treatment in medical settings. Thus, tools to assess individual risk of VTE and bleeding may be useful in this setting.

In the last few years, many RAMs evaluating these risks have been developed and validated. However, poor evidence is available assessing their real impact in improving the clinical outcomes of these patients [10]. In a small single-center, prospective, quasi-randomized study, the adoption of the Padua Prediction Score was associated with a 50% reduction in the incidence of VTE (i.e., symptomatic and asymptomatic, mainly distal VTE) compared with clinical judgment, with no differences in terms of bleeding and death from all-cause [22]. In a large RCT, employing a strategy including an electronic alert about the thrombotic risk (assessed through a risk score) versus no alert, greatly reduced the occurrence of symptomatic VTE with no increase in the bleeding rate in hospitalized patients [23].

Our study has some limitations. First, the retrospective design is per definition at risk of bias. Data are acquired from clinical records with the risk of suboptimal reporting. This may lead to possible bias in the post-hoc assessment of the RAMs, but the distribution of the thrombotic and bleeding risk appeared to be in line with the previous literature. Second, no information was available about the use of mechanical prophylaxis (i.e., intermittent pneumatic compression and elastic stockings) and early mobilization. Third, the FADOI-NoTEVole study included only patients discharged alive and excluded patients with a life expectancy of less than three months who were transferred to the nursing home, or the palliative care service: this resulted in a lack of data regarding mortality rates. Also, while the sample size is reasonable for analyzing potential predictors for prescribing thromboprophylaxis, it may still be small for some variables, leaving a margin of uncertainty. Lastly, since this is a retrospective observational study, we do not know whether a positive D-dimer value may have sometimes guided the physician’s choice, as previous studies correlated D-dimer with venous thrombosis [24]. Unfortunately, this data was not collected, and thus, it was not used in the study analyses.

In conclusion, our analysis showed some factors that may influence physicians’ prescription of pharmacological thromboprophylaxis, underscoring the daily challenges in assessing the appropriateness of pharmacological thromboprophylaxis in IMU’s patients. Single risk factors for VTE and bleeding appear to modify clinicians’ behavior. Of note, PPS seems to be only a partial driver of the use of pharmacological prophylaxis, and IBS does not appear to modify clinicians’ approach at all.