Roberto Sartori

Non-catheter associated venous thrombosis in hemophilia A and B. A critical review of all reported cases

All reported cases of non-catheter induced venous thrombosis in patients with hemophilia A or B have been carefully evaluated. A total of 27 cases were reported,12 patients with hemophilia A and 15 patients with hemophilia B. The age of patients varied between 9 and 67 years. There were 10 cases of deep vein thrombosis, 8 patients with pulmonary embolism accompanied or not by deep vein thrombosis, 5 cases of superficial vein thrombosis. In addition, there were 3 cases of thrombosis in unusual sites (1 retinal central vein thrombosis and 2 portal vein thrombosis). Finally, in one case, venous thrombosis was multiple. There was a fatality in a hemophilia B patient with pulmonary embolism.The most frequent risk or triggering factor in hemophilia A was the administration of Feiba or rFVIIa concentrates in patients with inhibitors. Surgery together with Prothrombin Complex concentrates was the most frequent cause in hemophilia B patients. Congenital associated prothrombotic risk factors were present in two patients.No or very few therapeutic procedures were initiated in these patients but for a suspension or reduction of concentrates infusion. In a few instances low molecular weight heparin was given for a few days. The frequent association of venous thrombosis with infusion of concentrates indicates the need for a careful evaluation of patients about to receive such therapy.

Combining Slip and Deceleration Control for Brake-by-wire Control Systems: A Sliding-mode Approach

In road vehicles, wheel locking can be prevented by means of closed-loop Anti-lock Braking Systems (ABSs). Two output measured variables are usually considered for regulation: wheel deceleration and wheel longitudinal slip. The traditional controlled variable used in ABS is the wheel deceleration, since it can be easily measured with a simple wheel encoder; however, it can be dynamically critical if the road-surface rapidly changes. On the other hand, the regulation of the longitudinal slip is more robust from the dynamical point of view, but the slip measurement is critical, since it requires the estimation of the longitudinal vehicle speed. In this work we propose a control strategy whose regulated variable is a combination of wheel deceleration and longitudinal slip. In particular, this work proposes a Sliding Mode approach to the design of an active braking controller whose controlled variable is a convex combination of wheel deceleration and wheel slip.

Development and Validation of an Advanced Motorcycle Riding Simulator

This paper illustrates and discusses the main features of the motorcycle riding simulator designed and built at the University of Padua over recent years. The simulator has been developed for a variety of purposes: to develop and test electronic devices aimed at improving rider safety and vehicle performance (antilock braking systems, traction control systems, etc.), to investigate different design choices and parameter effects on vehicle dynamics, to train riders, and to study their behaviours in different scenarios (normal riding, dangerous situations, etc.). Within the simulator the rider sits on a motorcycle mock-up provided with all the inputs available on a real motorcycle (throttle, clutch, brakes, etc.). These controls are used as inputs for an advanced virtual motorcycle model which computes the real-time vehicle dynamics. With the aim of giving the rider a proper motion cue, a washout filter converts the motion of the virtual motorcycle into the proper motion of a five-degrees-of-freedom motorcycle mock-up. Finally the audiovisual cues are delivered with a 180° panel and 5.1 surround sound system. To validate the simulator, a specific protocol which includes both an objective evaluation and a subjective evaluation was designed and carried out. External devices such as advanced rider assistant systems, on-bike information systems, and human–machine interfaces can be easily integrated into the simulator by means of a standard controller area network.

Advanced motorcycle virtual rider

The target of this work is the development of a motorcycle virtual rider model that plans a trajectory and follows it. The reference speed and trajectory are obtained by applying the optimal manoeuvre method (i.e. a nonlinear optimal control technique) to a basic model of the motorcycle. Then, the vehicle control and guidance are obtained using a PID architecture and the gains vary with speed. Separated loops for speed and lateral motion controls have been implemented, the lateral motion control is complex because of the motorcycle instability, whereas the longitudinal control is simpler. The characteristics of the PID control are illustrated and discussed in detail, some examples are given for a cornering manoeuvre first and then for a run in the Mugello circuit.

Total ankle replacement for end-stage arthropathy in patients with haemophilia

Dear Editor, In Haemophilia November 2006 van der Heide [1] and colleagues reported on the feasibility of a total ankle prosthesis (TAP) in two patients with coagulation disorders. Even though it is a recognized fact that the ankle is one of the most affected joints, in haemophiliacs prostheses are uncommon, at least in this group of patients, being considered to be an innovative surgical approach. It is well known that from an early age the ankle joint is frequently affected by bleeding in haemophiliacs and standard haemarthrosis treatment, including replacement therapy administered as primary prophylaxis or on-demand, is not always able to prevent joint damage. Physical therapy, footwear modification or orthoses may be useful but when chronic haemophilic synovitis occurs and recurrent haemarthroses become unresponsive to substitution therapy, synoviorthesis is to be considered using intra-articular injections of radioactive material or chemical substances [2]. These procedures, although effective in reducing the frequency of bleeding, are not able to alter the natural history of a degenerative arthropathy. When advanced ankle arthropathy develops arthrodesis is considered the standard treatment for pain relief [3] but total ankle replacement may also be considered for persistent pain and/or motion improvement [4]. As only limited reports have been published on this subject to date it is hoped that the following description of surgical intervention performed on two of our patients affected by severe haemophilia A (HA) will be helpful. Patient 1 was a 30-year-old male with severe HA and chronic HCV infection. The World Federation of Haemophilia joint score developed by Pettersson and Gilbert was used as the assessment instrument, according to this scale the total ankle score was 8 at the time of orthopaedic evaluation. Surgery was indicated because of limited motion and severe pain but in the year 2000 the patient, being worried about the possibility of further movement loss, refused ankle fusion. In the past he had been identified as being low responder anti-factor VIII (FVIII) inhibitor (max. titre 2 BU), before the surgery in question, however, the inhibitor was not detected. At the beginning of the operation, performed under general anaesthesia, replacement therapy was started with a bolus infusion of 100 IU kg of high-purity plasma-derived FVIII concentrates (Emoclot D.I., Kedrion, Italy) to obtain 100% plasma level. The prosthesis was implanted according to the instructions given by manufacturer, all the components were inserted without cement. Substitution treatment was continued by bolus injections every 12 h and the total amount of FVIII concentrates was 50 000 IU (684 IU Kg). PTT (partial thromboplastin time) and plasma FVIII levels were measured daily and concentrate dosage was adjusted in order to obtain >70% plasma activity. After the surgery the ankle was placed in a splint for 30 days. The postoperative period was uneventful, morphine was given to control the pain, no drainage was applied, there were no haemorrhages and the substitution treatment lasted a total of 10 days. This patient has had a 7-year followup, during which time he has had painless ankle movement and improved walking ability. There have not been any radiographic signs of prosthetic loosening or infection. A STAR prothesis cementless was used; Figs 1 and 2 show postoperative radiographs of this patient. Patient 2 was a 43-year-old male with severe HA, co-infected with HCV and HIV. HIV infection was kept under control by using highly Correspondence: Paolo Radossi, Transfusion Service, Haemophilia and Regional Blood Diseases Centre, Italy. Tel.: +39 0423 732336; fax: +39 0423 732337; e-mail: radossi.p@alice.it

Numerical investigation of engine-to-slip dynamics for motorcycle traction control applications

This work discusses the motorcycle engine-to-slip dynamics which are strictly related to the traction control design. A street motorcycle is analysed by means of an advanced mathematical model which also includes the tyre flexibility and the transmission compliance. The effects of the following parameters on engine-to-slip dynamics are investigated: vehicle speed, engaged gear ratio, sprocket absorber flexibility and road properties. Guidelines for increasing the maximum achievable closed-loop bandwidth are given.

Measurement of serum monoclonal components: comparison between densitometry and capillary zone electrophoresis.

Abstract Quantitative measurement of serum monoclonal protein (M-protein) is one of the most important tools for monitoring disease activity in monoclonal gammopathies. The aims of this study were to evaluate serum M-protein quantification by capillary zone electrophoresis (CZE) and to compare results with those obtained by densitometric scanning of high-resolution agarose gel electrophoresis (HRE-AGE). The evaluation was carried out on 82 samples from patients with various monoclonal gammopathies. All the suspected M-proteins were confirmed and characterised by immunofixation on agarose gel (IFE). CZE was performed on a Paragon CZE™ 2000 system (Beckman Coulter). Passing-Bablok regression was: y (CZE)=1.27×(HRE-AGE)–5.21g/L. The correlation coefficient was 0.92. Bland-Altman analysis demonstrated a mean difference of −1.83g/L (95% CI −0.76 to −2.90) with clear evidence of a concentration-related bias. Densitometry gave higher values at low M-spikes (<20g/L), whereas CZE gave higher values at large M-spikes (>20g/L). The concentration-related bias was found to be independent of the immunoglobulin isotype. In conclusion, to compare previous results obtained by M-protein densitometric scanning with those obtained by direct measurement of CZE peaks, the calculation of a univocal transforming factor appears to be unreliable.

The combination of rituximab, bendamustine, and cytarabine for heavily pretreated relapsed/refractory cytogenetically high-risk patients with chronic lymphocytic leukemia.

Treatment of patients with B‐cell chronic lymphocytic leukemia (CLL) relapsed/refractory (R/R) to conventional treatments is particularly challenging. The combination of bendamustine and cytarabine has demonstrated distinct and synergistic mechanisms of action in preclinical studies on cell lines and primary tumor cells of several B‐cell lymphomas, including 17p deleted or TP53 mutated CLL. The efficacy of rituximab (375 mg/m2, Day 1), plus bendamustine (70 mg/m2, days 1–2), and cytarabine (800 mg/m2, Day 1–3; R‐BAC), every 28 days for up to four courses, was evaluated in a pilot trial enrolling 13 patients with very selected high‐risk R/R CLL. All patients (median age 60 years, range 53–74) had symptomatic Binet stage B or C active disease requiring treatment, were characterized by adverse cytogenetics (17p deletion, 11q deletion, or both), unmutated immunoglobulin heavy‐chain variable region, and were heavily pretreated (1–5, median three previous lines). Overall, R‐BAC was well tolerated with limited non‐hematological toxicity. Major toxicities were transient Grade 3/4 neutropenia and thrombocytopenia in 84% and 85% of patients, respectively. Overall response rate (OR) was 84%, including complete and partial response in 38% and 46% of patients, respectively. Patients with 17p deletion had an OR of 78%. After a median follow‐up of 17 months, median progression‐free survival was 16 months while median overall survival (OS) was not reached (1‐year OS: 75 ± 13%). R‐BAC is an active regimen in R/R heavily pretreated high‐risk patients with CLL, representing an option for the treatment of patients that are usually refractory to standard therapy. Am. J. Hematol. 88:289–293, 2013.

Remission in hairy cell leukemia-variant following splenic radiotherapy alone

The therapeutic approach to hairy cell leukemia (HCL) is in some instances still debated. A variant form of HCL (HCL-V) characterized by high white cell count, splenomegaly, hypercellular and aspirable bone marrow has been described; differential diagnosis often arises with some other B-cell disorders which also show circulating hairy or villous lymphocytes. Conventional treatment for HCL is often less effective in HCL-V. In this report we describe a case with features consistent with HCL-variant treated with splenic radiotherapy. We not only obtained an hematological response but also the near total disappearance of bone marrow infiltration, compatible with a clinical complete remission. Clinical and biological implications of this phenomenon are discussed on the basis of this unexpected therapeutic result, obtained with splenic radiotherapy alone.

The JAK2(V617F) tyrosine kinase mutation in blood donors with upper-limit haematocrit levels.

BACKGROUND It is not rare to observe in blood donors a level of haematocrit (Hct) above or close to the highest normal limit. In the case of blood donors the diagnosis and clinical evaluation of this alteration may be complicated by regular blood donations that can mask an underlying disease such as polycythaemia vera. Recently a single acquired mutation in the Janus kinase 2 gene (JAK2) on chromosome 9 was identified and it was found that the incidence of this mutation was high in patients with polycythaemia vera. MATERIAL AND METHODS From the January 1, 2006 to December 31, 2006 all consecutive donors with a Hct above 50% if males (n=84) and 46% if females (n=19) underwent JAK2 mutation analysis. Seventy-nine donors (59 males and 20 females) whose Hct was normal at their last blood donation were randomly selected and used as controls. RESULTS Among the group of blood donors with a high Hct, we identified one donor who was positive for the JAK2 mutation. This man had a Hct of 50.6% at his last donation, while his average Hct in the preceding year was 51.7%. The prevalence of the JAK2 mutation could be estimated to be 1%, 0.6% or 0.02% in the three different populations considered: donors with a Hct level above the upper limit of normal, all tested donors or the entire donor cohort attending our transfusion service, respectively. CONCLUSIONS The present study suggests that apparently healthy subjects with repeatedly high levels of Hct may have the acquired mutation in JAK2. Laboratory screening tests for JAK2 may be offered to blood donors at transfusion services with expertise in molecular genetics.