Patient selection for thromboprophylaxis in medical inpatients.

Acutely ill medical patients may be at increased risk of venous thromboembolism, both during hospitalization and after discharge. International guidelines recommend thromboprophylaxis for high-risk medical patients with low bleeding risk for a maximum of 14 days. There are two approaches to identify the high-risk patient: adhering to the inclusion criteria used in randomized clinical trials or using risk assessment models. With both approaches, about 40% of medical inpatients should result at increased risk of venous thrombosis. However, in the real world, medical inpatients are more fragile than patients enrolled in clinical trials, and thus also require a careful assessment of the individual bleeding risk. The complex balance between risks and benefits of thromboprophylaxis has become particularly relevant in studies assessing extended prophylaxis beyond hospitalization in this setting. In the present review, we will summarize the most recent evidence on this topic.

Novel oral anticoagulants for the prevention of venous thromboembolism in surgical patients.

Pharmacologic prophylaxis with low-dose unfractionated heparin, low molecular weight heparin or fondaparinux has clearly demonstrated to reduce the rate of thromboembolic events in surgical patients. In the last decade, several novel oral anticoagulants have been tested in surgical patients, but only in the setting of major orthopedic surgery. Based on the results of the studies, dabigatran, rivaroxaban and apixaban have been approved by the European Medicines Agency for the prevention of venous thromboembolism after elective hip or knee replacement surgery. The novel anticoagulants represent an appealing alternative to current prophylaxis strategies that are mostly based on subcutaneous injection of low molecular weight heparin and have also been recommended by recently updated guidelines. Their role in other settings, such as hip fracture surgery, or in non-orthopedic surgery, may deserve future evaluation.

Thromboprophylaxis in surgical and medical patients.

Venous thromboembolism (VTE) remains the most common preventable cause of death in hospitalized patients. There is much evidence to show the efficacy of prophylactic strategies to prevent VTE in at-risk hospitalized patients. For example, pharmacological prophylaxis reduces the risk of pulmonary embolism by 75% in general surgical patients and by 57% in medical patients. Thus international guidelines strongly recommend effective preventive strategies for all hospitalized patients defined as moderate to high risk for VTE. Effective pharmacological thromboprophylaxis includes low-dose unfractionated heparin (UFH), low molecular weight heparin (LMWH), fondaparinux, and warfarin. Mechanical prophylaxis with graduated compression stockings and intermittent pneumatic compression is also recommended as an alternative or in combination with pharmacological prophylaxis. Although the volume of evidence supporting the use of thromboprophylaxis is growing, the number of patients receiving adequate prophylaxis is not. Several studies have shown that nearly half of the patients undergoing major surgery or hospitalized for medical illnesses do not receive appropriate antithrombotic prophylaxis. Reducing the discrepancy between evidence-based recommendations and clinical practice seems to be a cost-effective goal. Developing and promoting local protocols and educational activities to encourage prophylaxis in daily clinical practice may be effective. New oral anticoagulant drugs with potentially favorable pharmacokinetic and pharmacodynamic characteristics have been developed. After the positive results of phase 3 clinical trials, some of these drugs have been approved for clinical use in the prevention of VTE in the high-risk setting of major orthopedic surgery. These agents include the direct thrombin inhibitor dabigatran etexilate and the direct factor Xa inhibitors rivaroxaban and apixaban.

Fondaparinux for the treatment of superficial vein thrombosis in the legs: the CALISTO study.

Superficial vein thrombosis (SVT) is quite a common disease that is associated with a non-negligible risk of progression to the deep venous system and, in some cases, of embolization to the lungs. However, SVT has traditionally been regarded as a benign disease and its optimal management has been poorly studied. Recently, fondaparinux, a subcutaneous, selective, indirect Factor Xa inhibitor, has been assessed in the treatment of SVT in the CALISTO study, with encouraging results. Fondaparinux was found to be more effective than placebo in reducing the risk of SVT extension or progression to deep vein thrombosis or pulmonary embolism without a significant increase in the risk of bleeding. Treatment of SVT with a once-daily, 2.5 mg injection of fondaparinux without the need for platelet monitoring appears as a simple, effective, and well-tolerated strategy, and has the potential to change the clinical management of SVT.

Prevalence of renal failure and use of antithrombotic prophylaxis among medical inpatients at increased risk of venous thromboembolic events.

BACKGROUND: Evidence-based guidelines recommend the use of antithrombotic prophylaxis in medical patients at risk of venous thromboembolism (VTE). Low molecular weight heparins (LMWHs) are usually preferred to unfractionated heparin. However, when prophylactic doses of LMWH are administered, patients with renal failure (RF) are exposed to the risk of excessive accumulation, and thus to an increased risk of bleeding. We aimed to assess the prevalence of RF among medical inpatients at increased risk of VTE and the use and dosage of antithrombotic prophylaxis in these patients. METHODS: In a cross sectional study carried out at three different hospitals, information on all medical inpatients was collected. Patients were defined at increased risk of VTE according to the American College of Chest Physicians guidelines. Data on the proportion of patients with renal RF, on the use and dosage of antithrombotic prophylaxis, and on the presence of contraindications to antithrombotic therapy were ascertained. RESULTS: 439 hospital charts were examined; 158 patients (36.0%) were defined at increased risk of VTE and had no contraindications to antithrombotic treatment. Thromboprophylaxis was prescribed to 61.4% of these patients. Eighty (50.7%) of them also had moderate or severe RF. There was no difference in the rate of prescription nor in the doses of antithrombotic prophylaxis between patients with and without RF (p=0.81 and p=0.94, respectively). CONCLUSIONS: RF is frequently present in medical patients at risk of VTE. A considerable proportion of these patients may not receive the optimal type or dose of antithrombotic prophylaxis.