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Protein C (PC) is a vitamin K-dependent proenzyme with anticoagulant activity, and patients with congenital PC deficiency are at high risk for thrombotic episodes. In patients with PC deficiency, starting treatment with oral anticoagulant drugs is associated with a transient hypercoagulable state and clinically overt thromboembolic complications before reaching a full anticoagulant effect. This report describes a successful supplementation with PC concentrate in two adult patients with moderately severe PC deficiency during the initiation of oral anticoagulation and a course of therapeutic dose of low-molecular-weight heparin for acute venous thromboembolism. Plasma PC levels above 50% were observed in both patients and maintained during the entire supplementation treatment period with PC concentrate until a stable therapeutic anticoagulation level has been reached. These results have been obtained within a short time, thus allowing a safe administration of a loading dose of warfarin. No adverse reactions to the PC concentrate, i.e. skin necrosis and other thromboembolic complications, bleedings or allergic reactions, were observed. We conclude that PC concentrate seems to be effective for the prevention of thromboembolic complications and safe in patients with congenital PC deficiency while initiating oral anticoagulants.

Background: Intracranial haemorrhage (ICH) is a serious and potentially fatal complication of oral anticoagulant therapy (OAT). Prothrombin complex concentrates (PCCs) produce a rapid and effective reversal of OAT effects, but little evidence exists on their efficacy and safety in the management of ICH in patients on OAT. Aim:To evaluate the efficacy and safety of PCCs for the rapid reversal of OAT in patients with ICH. Methods: Patients suffering from acute ICH while receiving OAT were eligible for this prospective cohort study if their international normalized ratio (INR) was ≥2.0. Stratified 35–50 IU kg–1 PCC doses were infused based on initial INR. Results: A total of 92 patients (50 males; mean age 74 years, range 34–92 years) were included. The median INR at presentation was 3.3 (range 2–9). At 30 min after PCC administration the median INR was 1.4 (range 0.9–3.1), declining to ≤1.5 in 75% of patients. The benefit of PCC was maintained for a long time, since in 98% of all post-infusion time points through 96 h the median INR remained ≤1.5 (median 1.19; range 0.9–2.3). During hospitalization neither thrombotic complications nor significant adverse events were observed and 11 patients died (11.9%). None of the deaths was judged to be related to PCC administration. Conclusions: PCC administration is an effective, rapid and safe treatment for the urgent reversal of OAT in patients with ICH. Broader use of PCC in this clinical setting appears to be appropriate.

Venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism, is a major cause of morbidity and mortality in patients undergoing major orthopedic surgery, and routine thromboprophylaxis has been the standard of care over the last 20 years. Currently available options for the prevention of VTE in major orthopedic surgery include low-molecular-weight heparins, vitamin K antagonists and, more recently, the synthetic pentasaccharide fondaparinux. Although effective, these drugs have several limitations, and new oral antithrombotics offering predictable, effective and safe anticoagulation are strongly needed. This overview focuses on the most advanced oral direct inhibitors of factor Xa, rivaroxaban, apixaban, LY517717, YM150 and betrixaban. Specifically, the results of phase II and III studies and the designs of ongoing clinical trials in patients undergoing elective hip and knee replacement are reviewed.

Background: Venous thromboembolism (VTE) is a common life-threatening complication of major trauma. Although clinical guidelines clearly suggest routine VTE prevention with low-molecular-weight heparin (LMWH) in this specific group of patients, there is still a lack of strong recommendations regarding the timing and the modality of heparin administration and the role of mechanical prophylaxis. We tested the hypothesis that there is significant practice variation in thromboprophylaxis management of patients with major trauma among intensive care unit (ICU) specialists. Methods: Two hundred Italian ICU specialists, representing 200 ICU throughout the country, were contacted by telephone and were asked (1) whether they routinely prescribe pharmacological antithrombotic prophylaxis in patients with major trauma, whether prophylaxis is prescribed to all patients or to selected patients, and the type of prophylaxis and the timing of administration and (2) whether they recommend physical prevention, whether this is prescribed to all patients or to selected patients, and the type of physical prophylaxis. Results: In patients with major trauma, 85% of the interviewed ICU specialists answered that they prescribe pharmacological prophylaxis for VTE. 37.6% of them prescribe prophylaxis only to selected patients based on the level of risk, 87.7% prescribe low-molecular-weight heparin, and 42.4% start prophylaxis immediately after hospitalization. Only 61% of the interviewed specialists prescribe physical prophylaxis; 82.8% of them use elastic stockings, 9.8% intermittent pneumatic compression, and 7.4% other mechanical devices. Physical prophylaxis is prescribed to all patients by 41%, and by 59% only in case of contraindication to pharmacological prevention. Inferior vena cava (IVC) filter insertion is considered by 47% when anticoagulation is contraindicated; 91.4% of them recommend the IVC filter only if deep vein thrombosis (DVT) has been diagnosed. Conclusions: Even when there are clinical guidelines, prescription of VTE prevention in patients with major trauma is underused and timing and modality of prophylaxis are rather heterogeneous. When anticoagulation is contraindicated, IVC filters are commonly recommended only in the presence of DVT.

Several epidemiological studies have shown a high prevalence of venous thromboembolism (VTE) complications in patients with acute heart failure; in addition, the level of risk associated with this disease is notable, ranging from 15 to 30%. Three large clinical trials have clearly demonstrated the efficacy and safety of pharmacological prophylaxis in internal medicine patients hospitalized for an acute medical disease; on the contrary, until now there are no studies which have evaluated antithrombotic prophylaxis in a selected population of patients with heart failure only. Moreover, discrepancies existing among recommendations reported in different guidelines may produce uncertainties in the management of VTE prevention in patients with heart failure and may contribute to an underuse of thromboprophylaxis in the daily clinical practice. The aim of this review is to analyze the existing evidence about VTE risk in patients with heart failure as well as the efficacy and safety of antithrombotic prevention, and to underline which are the most important unmet clinical issues for the optimal management of thromboprophylaxis in this particular clinical setting.