Prevention of venous thromboembolism in hospitalized acutely ill medical patients: focus on the clinical utility of (low-dose) fondaparinux

Marcello Di Nisio,^1,2 Ettore Porreca<sup>3

1</sup>Department of Medical, Oral and Biotechnological Sciences, University G D'Annunzio of Chieti-Pescara, Chieti, Italy; ²Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands; ³Department of Medicine and Aging, Centre for Aging Sciences, Internal Medicine Unit, University G D'Annunzio Foundation, Chieti, Italy

Abstract: Venous thromboembolism (VTE) is a frequent complication among acutely ill medical patients hospitalized for congestive heart failure, acute respiratory insufficiency, rheumatologic disorders, and acute infectious and/or inflammatory diseases. Based on robust data from randomized controlled studies and meta-analyses showing a reduced incidence of VTE by 40% to about 60% with pharmacologic thromboprophylaxis, prevention of VTE with low molecular weight heparin (LMWH), unfractionated heparin (UFH), or fondaparinux is currently recommended in all at-risk hospitalized acutely ill medical patients. In patients who are bleeding or are at high risk for major bleeding, mechanical prophylaxis with graduated compression stockings or intermittent pneumatic compression may be suggested. Thromboprophylaxis is generally continued for 6 to 14 days or for the duration of hospitalization. Selected cases could benefit from extended thromboprophylaxis beyond this period, although the risk of major bleeding remains a concern, and additional studies are needed to identify patients who may benefit from prolonged prophylaxis. For hospitalized acutely ill medical patients with renal insufficiency, a low dose (1.5 mg once daily) of fondaparinux or prophylactic LMWH subcutaneously appears to have a safe profile, although proper evaluation in randomized studies is lacking. The evidence on the use of prophylaxis for VTE in this latter group of patients, as well as in those at higher risk of bleeding complications, such as patients with thrombocytopenia, remains scarce. For critically ill patients hospitalized in intensive care units with no contraindications, LMWH or UFH are recommended, with frequent and careful assessment of the risk of bleeding. In this review, we discuss the evidence for use of thromboprophylaxis for VTE in acutely ill hospitalized medical patients, with a focus on (low-dose) fondaparinux.

Keywords: venous thromboembolism, medical patient, hospitalization, fondaparinux, heparin