PK-driven prophylaxis versus standard prophylaxis: When a tailored treatment may be a real and achievable cost-saving approach in children with severe hemophilia A.

BACKGROUND: Prophylaxis is the gold standard for the treatment of children with severe hemophilia. In the last years a new approach to prophylaxis based on annual bleeding rate (ABR), pharmacokinetics (PK) and lifestyle of each patient has begun to be adopted in hemophilia treatment. AIM: Aim of our observational retrospective study was to evaluate whether in a group of children with severe hemophilia A (HA) a tailored approach may be used to replace standard therapy, reducing costs. METHODS: PK evaluation was carried out in six hemophiliac children followed at our Hemophilia Center, and already receiving recombinant factor VIII (rFVIII) on prophylaxis, using a computing program (MyPKfit®). Bayesian curve was created for each child and tailored prophylaxis was estimated considering a trough level of 1%. RESULTS: The weekly frequency of infusions was reduced in one patient, while it was slightly increased in three children. As to the remaining children, only the dosage was changed. Scheduled follow-up revealed a complete adherence to treatment, a reduction of bleeds using PK-regimen and a general improvement in the quality of life. The comparison between the direct and indirect costs of treatment during standard and PK-driven prophylaxis showed a total saving of € 54,797.40 (-10.67%) in case of tailored prophylaxis. CONCLUSION: A therapeutic approach based on PK and clinical characteristics of each patient may change standard treatment. Based on our results, tailored prophylaxis could be an effective option for children with HA reducing costs.

Recanalization rate in patients with proximal vein thrombosis treated with the direct oral anticoagulants.

BACKGROUND: The recanalization rate in patients with deep venous thrombosis (DVT) of the legs treated with the direct oral anticoagulants (DOAC) is unknown. METHODS: In an Italian cohort, we investigated the rate of residual vein thrombosis (RVT) after three and/or six months in 352 patients with proximal DVT who had been treated with the DOACs as a stand-alone therapy or lead-in parenteral anticoagulants, and compared it to that recorded in a historical cohort of 1094 patients in which vitamin K antagonists (VKAs) had been employed. In both cohorts, RVT was defined as the ultrasound persistence of thrombotic material resulting in a diameter of at least 4mm of incompressibility of the proximal veins. RESULTS: RVT was detected in 143 patients treated with DOACs (41.2%) after three months and in 58 patients (21.1%) after six months; the corresponding figure in patients treated with conventional anticoagulation was 52.3% and 54.5%, respectively. After adjusting for the baseline characteristics, the odds ratio of RVT in patients treated with the DOACs as compared with those treated with conventional anticoagulation was 0.63 (95% CI, 0.48-0.81) after three months, and 0.17 (95% CI; 0.11-0.26) after six months. CONCLUSIONS: In patients with proximal DVT treated with the DOACs, the persistence of ultrasound detectable RVT is likely to occur less frequently than in patients treated with conventional anticoagulation. These results may have implications for the prognosis of patients with DVT.

The impact of deep vein thrombosis on the risk of subsequent cardiovascular events: a 14-year follow-up study.

BACKGROUND: The association between deep vein thrombosis (DVT) and atherosclerosis is still controversial. METHODS: We examined the rate of subsequent symptomatic atherosclerosis in patients with unprovoked as compared to secondary DVT with a retrospectively follow-up of a cohort of patients who 14 years earlier had developed an episode of DVT not preceded by arterial cardiovascular events. We collected information on the development of coronary heart disease, ischemic stroke, peripheral artery disease or sudden otherwise unexplained death. RESULTS: We retrieved information from 138 patients with unprovoked and 123 with secondary DVT. The cumulative incidence of symptomatic atherosclerosis was 17.6% (95% CI, 8.3 to 26.0) in patients with unprovoked DVT, and 5.1% (95% CI: 0.0 to 10.7) in those with secondary DVT. After adjusting for age, sex, smoking, hypertension, diabetes and dyslipidemia, the hazard ratio (HR) for development of symptomatic atherosclerosis among patients with unprovoked DVT as compared to those with secondary DVT was 2.89 (95% CI, 1.06 to 7.88; P=0.038). CONCLUSIONS: The risk of subsequent symptomatic atherosclerosis among patients with unprovoked DVT is approximately three times as high as that of patients with secondary events.

Optimal duration of anticoagulation in patients with unprovoked venous thromboembolism: the impact of novel anticoagulants.

Once anticoagulation is stopped, the risk of recurrent venous thromboembolism (VTE) over years approaches 50% of all patients with a first episode of unprovoked VTE. The persistence of residual vein thrombosis at ultrasound assessment has consistently been shown to increase the risk, as do persistently high values of D-dimer. Although the latest international guidelines suggest indefinite anticoagulation for most patients with the first episode of unprovoked VTE, strategies that incorporate the assessment of residual vein thrombosis and D-dimer have the potential to identify a substantial proportion of subjects in whom anticoagulation can be safely discontinued. For those patients in whom anticoagulation cannot be discontinued, new opportunities are offered by the availability of low-dose anti-Xa compounds, which have been found to possess an extremely favourable benefit/risk profile.

Incidence of arterial embolism in patients on treatment with old and new anticoagulants for venous thromboembolism.

The separate nature of venous and arterial thrombotic disorders has recently been challenged. Patients with venous thromboembolism (VTE) have an increased risk of subsequent symptomatic arterial cardiovascular events, the risk being higher in those with unexplained episodes. Among the implications of this association, there is the potential for old and new antithrombotic drugs to impact on the development of both venous and arterial cardiovascular events. According to the results of recent studies, aspirin in low doses, when administered for the long-term management of patients with unprovoked VTE, reduces by approximately 35% the risk of recurrent VTE while offering a considerable protection against the development of arterial cardiovascular events. By contrast, there is no room to expect a reduction in the risk of subsequent arterial cardiovascular events in patients treated with vitamin K antagonists (VKA) in comparison to patients in whom VKAs are discontinued. According to the results from recent randomized clinical trials, the likelihood of arterial cardiovascular events in patients on the novel direct factor Xa inhibitors is unlikely to differ from that of patients receiving conventional anticoagulation. As dabigatran has been associated with a slight increase in the risk of myocardial infarction over warfarin, its use should be discouraged in patients with coronary heart disease. The long-term use of low-dose apixaban beyond the first months in patients with unprovoked VTE may decrease the long-term risk of arterial, as well as venous, thrombotic events.