Giuseppina Rodorigo

Comparison of the rates of joint arthroplasty in patients with severe factor VIII and IX deficiency: an index of different clinical severity of the 2 coagulation disorders.

Data from the Italian Hemophilia Centres were collected to perform a retrospective survey of joint arthroplasty in patients with severe hemophilia. Twenty-nine of 49 hemophilia centers reported that 328 of the 347 operations were carried out in 253 patients with severe hemophilia A (HA) and 19 in 15 patients with severe hemophilia B (HB). When results were normalized to the whole Italian hemophilia population (1770 severe HA and 319 severe HB), patients with HA had a 3-fold higher risk of undergoing joint arthroplasty (odds ratio [OR], 3.38; 95% confidence interval [CI], 1.97-5.77; P < .001). These results were confirmed after adjustment for age, HIV, hepatitis C virus (HCV), and inhibitor in a Cox regression model (HR, 2.65; 95% CI, 1.62-4.33; P < .001). The survival analysis of time to joint arthroplasty in the subset of patients with severe HA was not affected by the severity of factor VIII (FVIII) gene mutations. A systematic review of literature articles reporting joint arthroplasties in HA and HB showed that the proportion of HA patients who had undergone arthroplasties was higher than that of HB patients, in agreement with the findings in our Italian cohort. These data suggest that the 2 inherited coagulation disorders have a different severity of clinical phenotype.

The Wells rule and D-dimer for the diagnosis of isolated distal deep vein thrombosis

Summary.  Background:  Pretest clinical probability with the Wells rule and D‐dimer have been widely investigated for the diagnosis of symptomatic proximal deep vein thrombosis (DVT) of the lower limbs, but they have not been formally tested for symptomatic isolated distal DVT diagnosis.

Prevalence of Infection with the Hepatitis C Virus among Italian Hemophiliacs before and after the Introduction of Virally Inactivated Clotting Factor Concentrates: A Retrospective Evaluation

In July 1985, all coagulation factor concentrates were withdrawn from the market in Italy and replaced with virally inactivated concentrates. A retrospective survey comparing the prevalence of the antibody to the hepatitis C virus (anti‐HCV) in hemophiliacs multitransfused with nonvirally inactivated concentrates until 1985 with that in previously untreated hemophiliacs transfused exclusively with virally inactivated concentrates since 1985 has been conducted in 9 Italian hemophilia centers. The centers, which follow about one‐fourth of all the Italian hemophiliacs, provided information about 708 patients infused for the first time before 1985 (group A) and 80 patients infused for the first time between 1985 and 1991 (group B). The prevalence of anti‐HCV was 83% (591/708) in group A and 6% (5/80) in group B. For the 5 anti‐HCV‐seropositive patients from group B, dry heating, hydrophobic interaction chromatography plus dry heating (2 patients), hot vapor and pasteurization were the virucidal methods used for the concentrates implicated in HCV transmission. In the case associated with pasteurization, there is the possibility of intrafamilial transmission of HCV. It appears from this retrospective analysis that there has been a substantial reduction in the risk of HCV transmission since the adoption of virucidal methods. However, these methods do not eliminate completely the risk, which might be further reduced by the recent adoption of anti‐HCV screening for plasma donations used to manufacture concentrates.

Protease activities, as well as plasminogen activators, contribute to the "lytic" state during orthotopic liver transplantation.

High levels of tissue plasminogen activator (t-PA) have been reported to be the main component of the high fibrinolytic activity measured in patients during orthotopic liver transplantation. However, a previous study of our group suggested that specific t-PA may not completely account for the massive fibrinolytic activities recorded. In the present study we investigated the fibrinolytic patterns in 10 consecutive liver cirrhosis patients undergoing OLT. Euglobulin fibrinolytic activity, measured either on physiologic (fibrin plates) or amidolytic substrates, increased as expected during anhepatic and reperfusion phases, but largely exceeded the specific activity of t-PA, as proved by quenching procedures using anti-t-PA antibodies. The presence of plasmin- and trypsin-like amidolytic activities was detected in native plasmas at the end of anhepatic and reperfusion phases, together with decreased levels of protease inhibitors, especially α1 Antitrypsin. In conclusion, the hyperfibrinolytic pattern recorded in the central OLT phases is not only attributable to an increased t-PA concentration, and is better described as a complex “lytic” state also including the presence of free proteases (plasmin- and trypsin-like), with limited participation of u-PA. Although t-PA increase is probably the main mechanism of stimulation of the fibrinolytic system during OLT, actual and not just potential proteolytic activities can be found in this condition independent of the occurrence of major hemorrhagic complications.

Recurrent 'migrainelike' episodes in patients with HIV disease.

Recurrent transient neurological deficits have been described in human immunodeficiency virus (HIV)‐infected subjects, but their frequency, pathogenesis, and outcome are still unsettled.

Non‐HLA Lymphocytotoxic Antibodies in HIV‐Seropositive and HIV‐Seronegative Hemophiliacs

Abstract. We tested serum samples from 11 HIV‐seropositive and 32 HIV‐seronegative Italian patients with hemophilia A or B for the presence of lymphocytotoxic antibodies (LCTAs). No patients had the acquired immune deficiency syndrome and all had received over many years heat‐untreated commercial clotting factors. LCTAs directed mainly to B cells, were significantly present in 5/6 HIV‐seropositive patients with hemophilia A and in 5/5 HIV‐seropositive patients with hemophilia B. The presence of LCTAs in HIV‐seronegative hemophiliacs was significantly correlated with both a decrease of T cells and an increase in serum levels of IgG and IgM.

Measurement of factor XIII (FXIII) activity by an automatic ammonia release assay using iodoacetamide blank-procedure: no more overestimation in the low activity range and better detection of severe FXIII deficiencies.

Abstract Background: Laboratory investigation with specific factor XIII (FXIII) assays plays a crucial role in diagnosis of FXIII deficiency. According to the International Society on Thrombosis and Hemostasis (ISTH), it is necessary a blank sample with iodoacetamide, provided by the kit or locally prepared, when the ammonia release assays are used, to avoid FXIII activity overestimation. Methods: In this study we set up a modification of the Berichrom FXIII chromogenic assay, in which iodoacetamide was added by the BCS analyzer in the reaction mixture of the blank sample, without modifications of the original reagents. We analyzed 100 plasma samples of outpatients with clinical symptoms suggestive of a bleeding diathesis (20 samples had FXIII activity <20%). Results: In all samples blank subtraction significantly reduced FXIII activity, mostly in the low activity range group (from 10.1% to 2.4%, p<0.0001). In this group correction with iodoacetamide also increased the agreement with the immunoassay and allowed FXIII activity measure up to 0%. Conclusions: Despite the low number of samples included in the study, the described automatic procedure seemed to decrease FXIII activity overestimation and, especially for low activity range samples (<20%), to improve the agreement between FXIII activity and concentration. Our data suggested that iodoacetamide correction could allow the detection of severe FXIII deficiencies (activity <5%) otherwise undiagnosed using the original method.

Whole-Arm Ultrasound for Suspected Upper- Extremity Deep Venous Thrombosis in Outpatients

Whole-Arm Ultrasound for Suspected UpperExtremity Deep Venous Thrombosis in Outpatients To the Editor We read with interest the article by Sartori and colleagues1 regarding the safety of single ultrasonography to rule out upper-extremity deep vein thrombosis (UE-DVT) in outpatients. Some aspects of the current work and differences with our recent diagnostic management study2 require attention and may help to direct future research in the field. In the ARMOUR study,2 ultrasonography was safely withheld in 21% of patients based on a low clinical probability combined with a normal D-dimer level. Avoidance of ultrasonography in one-fifth of suspected cases is expected to reduce costs and overall burden for patients. As for suspected deep vein thrombosis of the lower extremities, the sequential application of a clinical decision rule and D-dimer preceding ultrasonography can thus still be regarded as a valuable tool to reduce the number of imaging tests. Whether the efficiency of the algorithm is consistent across subgroups of high-risk patients deserves further investigation. The prevalence of UE-DVT in the ARMOUR study2 was twice that of the investigation by Sartori and colleagues1 (25% vs 13%) which likely reflects the inclusion of populations with different characteristics and distribution of risk factors. In the ARMOUR study, for example, inclusion was not restricted to outpatients, and significantly higher proportions of patients had cancer (34% vs 17%) or a central venous catheter (35% vs 7%). These apparent differences hamper a proper judgment of the safety and effectiveness of the 2 strategies relative to each other. At the same time, as acknowledged by the authors, the inclusion of patients in a single institution may limit the generalizability of the findings of Sartori and colleagues. Validation of their diagnostic management strategy in a large and multicenter study is therefore needed. Although serial ultrasonography adds to the complexity and burden of the algorithm, this approach appeared crucial in the ARMOUR study2 where repeated ultrasonography detected UE-DVT in 3 of 45 cases with normal findings on first ultrasonography. These cases would have been missed by a single-ultrasonography approach. In this regard, the 5 patients lost to follow-up in the study by Sartori and colleagues1 (as opposed to no loss to follow-up in the ARMOUR study) may be a concern. In a worst-case scenario, there would be 6 vein thromboses during follow-up, for an incidence of 1.9% (95% CI, 0.8%-4.0%). While both the study by Sartori and colleagues1 and our ARMOUR study2 are important steps forward in the field, the best diagnostic strategy to confirm or refute UE-DVT is still to be determined.

The subjective experience of living with haemophilia in the transition from early adolescence to young adulthood: the effect of age and the therapeutic regimen

Abstract The main aim of the research is to study how youths affected by haemophilia, a congenital hemorrhagic chronic disease, make sense of their condition, with particular reference to the transition from early adolescence to early adulthood. We administered face-to-face semi-structured interviews to 20 Italian youths with haemophilia, aged 11–25 years, in on-demand treatment or prophylaxis therapy. A thematic analysis was performed with the help of software for textual data to figure out the main topics and the role of the two selected variables in the emergence of the themes (age and type of therapy). The results highlight how the experience of suffering from haemophilia is organized around five core themes (fragmented body, intimacy, family history, autonomy, dreams), that are more or less typical of some age group or kind of treatment. These results may be useful for designing appropriate and differentiated interventions for psychosocial support.

Diagnostic Accuracy of a New d-Dimer Assay (Sclavo Auto d-Dimer) for Exclusion of Deep Vein Thrombosis in Symptomatic Outpatients

In patients presenting non-high clinical pretest probability (PTP), a negative d-dimer can exclude venous thromboembolism without imaging tests. However, each d-dimer assay should be validated in prospective studies. We evaluated an automated d-dimer immunoassay using the Sclavo Auto d-dimer (Sclavo Diagnostics Int, Sovicille, Italy) provided by Dasit Diagnostica (Cornaredo, Milan, Italy). Three hundred two consecutive outpatients suspected of leg deep vein thrombosis (DVT) with non-high PTP were included. The Sclavo Auto d-dimer assay was evaluated on 2 analyzers (Sysmex CA-7000 and Sysmex CS-2100; Sysmex Corporation, Kobe, Japan, provided by Dasit). The cutoff value (200 ng/mL) was established a priori. Prevalence of DVT was 11.9%. Since no false-negative patients were detected, the sensitivity and negative predictive values (NPVs) were 100% (sensitivity = CA-7000: 100% [95% confidence interval, CI: 93.3-100], CS-2100: 100% [95% CI: 93.3-100]; NPV = CA-7000: 100% [95% CI: 97.9-100], CS-2100: 100% [95% CI: 98.0-100]). Specificity was 65.4% (95% CI: 59.4-71.1) and 69.2% (95% CI: 63.3-74.7) for CA-7000 and CS-2100, respectively. Specificity increased when a higher cutoff value (234 ng/mL) was used for patients aged ≥60 years without compromising the safety. Assay reproducibility was satisfactory at concentrations near the cutoff value (total coefficient of variations <10%). In conclusion, the Sclavo Auto d-dimer assay was accurate when used for DVT diagnostic workup in outpatients with non-high PTP. Based on its high sensitivity and NPV, it can be used as a stand-alone test in outpatients with non-high PTP. Given its high specificity, the number of patients in whom further imaging techniques can be avoided increased, improving the yield of the test.