Lucia Sarolo

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.

High rate of inter-observer agreement between professional-rated scores of the Villalta scale for the assessment of the post-thrombotic syndrome.

The post thrombotic syndrome (PTS) develops in up to 50% of patients with proximal deep vein thrombosis (DVT) of the lower extremities due to venous hypertension [1–3]. It usually appears within two years since the DVT and in approximately 3–10% of cases is reported as moderate or severe with an important impact in daily-life activities [4]. The Villalta scale is recognized by the International Society on Thrombosis and Haemostasis as the gold standard for the assessment of PTS [5]. This scale is based on the evaluation of seven signs and five symptoms with a severity grade scale for each one (0–3) with the exception of leg ulcers that have a dichotomous value (yes/no). PTS is confirmed when the overall score is N4 and is classified according to the value obtained as mild (5–9), moderate (10–14) and severe (≥15 or presence of leg ulcers) [6]. While the correct assessment of PTS has a great value for the identification of those patients who require proper follow-up and therapeutic management, available studies have reported so far only a moderate agreement between patient-rated and professional-rated assessment of the scale, and few data are available on the inter-observer variability between professionals [7–8]. We sought to evaluate the inter-observer agreement of the Villalta scale between professionals assessing PTS. A cross-sectional study was conducted in two Third-level Centres for Thrombotic Disorders in Italy (Padua and Treviso) between January 2014 and April 2016. Consecutive outpatients referring for their regular follow-up visit after a first-ever episode of acute proximal DVT between three months and two years since the eventwere considered for enrolment. Patientswith a proximal bilateral thrombosis were excluded, aswere thosewith a history of previous DVT (within the previous three years) in the same leg. Two trained clinicians assessed the presence and severity of PTS independently from each other with the use of the Villalta scale. Results obtained were compared, and inter-observer agreement was calculated using the Kappa Cohen test. Out of 150 eligible subjects, 36were excluded due to a previous DVT and 7 for bilateral thrombosis. Of the remaining patients, 11 did not give their informed consent. Table 1 shows the main demographic and clinical characteristics of the 96 patients who were recruited. The inter-observer agreement for the presence of PTS was high (Kappa 0.84, 95% CI 0.69–0.95). Indeed, the two assessors agreed on the presence of PTS in 31 subjects (32.3%) and on its absence in 58 (60.4%), whereas their interpretation was discordant in only 7 (7.3%). Details of PTS assessment are shown in Table 2,which reports K scores for each sign and symptom. Mean PTS score values obtained by the two operators were comparable (3.79 ± 3.5 versus 3.97 ± 3.83; p = 0.74). The inter-observer

Trans-popliteal reflux in limbs with and without deep-vein thrombosis of the same subject: Cross-sectional study

Whether popliteal vein incompetence (PVI) occurring after an episode of deep-vein thrombosis (DVT) of the lower extremities accounts for the development of the post-thrombotic syndrome (PTS) is controversial, as there is data in favor and against this association [1–5]. In addition, PVI is not infrequently found also in patients who do not have a history of DVT, especially in thepresence of chronic venous insufficiency [6,7]. In order to test the plausibility of the association between PVI and the subsequent development of PTS, we assessed the prevalence of PVI in a consecutive series of patients with previous proximal DVT, and compared itwith that detectable in the unaffected contralateral leg of the same subjects. The study was approved by the local Ethical Board. All recruited patients gave their written consent for participation in this investigation. Out of 64 consecutive outpatients referred to the Vascular Medicine Unit of the University Hospital of Padua between January 2015 and January 2016 for their regular follow-up examination after an episode

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.

Challenges in the diagnosis of sub-segmental pulmonary embolism in symptomatic patients: a case report

Newly diagnosis of sub-segmental pulmonary embolism (SSPE) is nowadays increasing due to the growing number of radiological examinations performed with multidetectorrow computer tomography (MDCT) scanners [1]. The reliability of the CT diagnosis of SSPE is still an unresolved issue, as studies comparing the findings of the most recent MDCT scanners with those of pulmonary angiography are lacking. Here, we present the case of a woman that was admitted to our department for a thoracic pain, who had the diagnosis of SSPE by means of an angio-CT scan that was subsequently confuted by clinical and scintigraphic findings.

Iliopsoas bursitis and femoral vein thrombosis complicating total hip arthroplasty in an elderly patient

Predominantly, cystic or solid extra-articular pelvic masses have been increasingly recognized as a complication of hip arthroplasty and have been described in association with both metal-on-polyethylene and metal-on-metal implants. Although predominantly associated with implant wear, pelvic masses developing after hip arthroplasty may result from direct iliopsoas muscle irritation with malpositioned or prominent hip implants [1]. These late and uncommon complications cause a number of clinical symptoms, including limb swelling and erythema, pain, limp or restricted movement, palpable groin lump, femoral nerve irritation or palsy. Here, we report a case of a hemorrhagic cystic mass causing deep vein thrombosis (DVT) in the femoral vein 9 years after the patient had undergone a ceramic-on-ceramic cementless total hip arthroplasty. Case presentation

Autonomic dysfunction and flow-mediated dilation in polycystic ovary syndrome (PCOS): A case-control study. Dysautonomia in polycistic ovary syndrome

Aim: a case-control study was conducted on women with polycystic ovary syndrome (PCOS) with a view to identifying endothelial and autonomic nervous system dysfunctions capable of explaining the higher cardiovascular risk associated with PCOS. Material and methods: 35 women (mean age 26.51 ±3; BMI 24.25 ±1.65) with documented PCOS and 35 controls matched for age, BMI and cardiovascular risk factors were studied during a solar year. Endothelial dysfunction was assessed using flow-mediated dilation (FMD) and early atherosclerosis from the intima media thickness (IMT) of the carotid district measured using eco-color Doppler. Autonomic dysfunction was assessed with the classic tests (tilt, lying-to-standing, deep breath, Valsalva, Stroop). Results: by comparison with controls, patients with PCOS had an altered response in some of the autonomic tests, i.e. lying-to-standing (mean values 3.25 ±4 mmHg vs -3.4 ±2.04, p<0.01); deep breath (RR max/RR min 1.03 ±0.04 vs 1.35 ± 0.05, p<0.01) and Valsalva (RRmax/RRmin 1.10 ± 0.05 vs 1.35 ± 0.05, p<0.01), but no relevant differences in the tilt, hand grip and Stroop tests. A diminished FMD (0.56 ± 0.8mm vs 0.74 ± 0.06mm, p<0.01) and a greater IMT (0.72 ± 0.03 vs 0.67 ± 0.03mm, p=0.031) were found in cases than in controls. Conclusions: PCOS coincides with an endothelial dysfunction and a greater IMT, and autonomic assessment reveals sympathetic hyperactivity. These two findings may explain the link between PCOS and cardiovascular disease. Further studies are needed to shed light on this apparent link and demonstrate whether it is real and quantifiable.

Carotid Atherosclerosis and Flow Mediated Dilatation in the Brachial Artery in Patients with Antiphospholipid Syndrome: A Case-control Study

Correlation between Primary Antiphospholipid Syndrome (PAPS) and cardiovascular events is well-known. For this reason it is important to evidence early atherosclerosis to prevent future events. Aim: to better evaluate Flow Mediated Dilation (FMD) in a group of subjects affected by PAPS paired with a control group, homogeneous for age, sex and without cardiovascular risk factors. Subjects and methods: 31 subjects affected by PAPS and 31 healthy controls underwent EchoDoppler of brachial artery and evaluation of FMD. Results: PAPS cases perhaps revealed a reduced FMD respect controls. The correlation between age, sex, duration and severity of disease, arterious or venous thrombosis and severity of thrombocythaemia did not influence FMD. Coagulation parameters and presence of s2 IgM and s2 IgG antibodies correlated with FMD alterations. Conclusions: FMD is reduced in patients with PAPS and it correlates with coagulation parameters and presence of antibodies that can explain the rise of arterious imbalance. FMD evaluation is necessary in PAPS subjects to prevent fatal cardiovascular events. KeywordsPrimary Antiphospholipid Syndrome; Ultrasound; Flow Mediated Dilation (FMD); Intima-Media Thickness (IMT)