Antonino Cannavò

Measurement and prevalence of circulating ADAMTS13-specific immune complexes in autoimmune thrombotic thrombocytopenic purpura

The formation of ADAMTS13‐specific circulating immune complexes (CICs) may be a pathophysiologic mechanism in autoimmune thrombotic thrombocytopenic purpura (TTP), but has not been systematically investigated.

Timing and severity of inhibitor development in recombinant versus plasma-derived factor VIII concentrates: a SIPPET analysis

Essentials Recombinant factor VIII (rFVIII) was contrasted with plasma‐derived FVIII (pdFVIII). In previously untreated patients with hemophilia A, rFVIII led to more inhibitors than pdFVIII. Inhibitors with rFVIII developed earlier, and the peak rate was higher than with pdFVIII. Inhibitors with rFVIII were more severe (higher titre) than with pdFVIII.

Nonneutralizing antibodies against factor VIII and risk of inhibitor development in severe hemophilia A

The development of anti-factor VIII (FVIII) neutralizing antibodies (inhibitors) is the major complication in hemophilia A. Nonneutralizing antibodies (NNAs) have been detected in hemophilia patients and also in unaffected individuals. The aim of this study was to assess the prevalence of NNAs and to evaluate whether their presence is associated with the development of inhibitors in a cohort of previously untreated or minimally treated patients with hemophilia A; plasma samples of 237 patients with severe hemophilia A enrolled in the SIPPET trial were collected before any exposure to FVIII concentrates and analyzed for the presence of anti-FVIII NNAs. Patients were observed for the development of neutralizing antibodies. NNAs were found in 18 (7.6%) of 237 patients at screening, and there was a clear age gradient. Of those with NNAs, 7 patients subsequently developed an inhibitor for a cumulative incidence of 45.4% (95% confidence interval [CI], 19.5% to 71.3%); among the 219 patients without NNAs, 64 (29%) developed an inhibitor (cumulative incidence, 34.0%; 95% CI, 27.1%-40.9%). In Cox regression analyses, patients with NNAs at screening had an 83% higher incidence of inhibitor development than patients without NNAs (hazard ratio [HR], 1.83; 95% CI, 0.84-3.99). For high-titer inhibitors, the incidence rate had an almost threefold increase (HR, 2.74; 95% CI, 1.23-6.12). These associations did not materially change after adjustment. The presence of anti-FVIII NNAs in patients with severe hemophilia A who were not previously exposed to FVIII concentrates is associated with an increased incidence of inhibitors.

Successful management with intravenous immunoglobulins in alemtuzumab-induced acute inflammatory demyelinating neuropathy: clinical report of three patients

Several neurological complications have been associated with the use of monoclonal antibodies (mAbs), and demyelinating disorders have been estimated to affect the 0.02–0.20% of treated patients. Alemtuzumab is a humanized chimeric mAbthat targets the CD52 antigen, it is currently approved for relapsed/refractory and high-risk untreated chronic lymphocytic leukemia (CLL). The major complication of alemtuzumab therapy is the increased risk of opportunistic infections secondary to the profound immunosuppression. Autoimmune diseases as Graves disease, immune thrombocytopenic purpura and Good pasture syndrome, have been reported to be associated to the treatment. In the present report, we present three CLL patients developing acute inflammatory demyelinating neuropathy during treatment with alemtuzumab. Despite the severity of the complication, all the patients showed an univocal good clinical response after treatment with intravenous immunoglobulin (IVIG). As alemtuzumab represents, nowadays, a key therapeutic option for CLL, clinicians should be aware of this rare and disabling toxicity.

The ISTH Bleeding Assessment Tool and the risk of future bleeding

Essentials ISTH Bleeding Assessment Tool (ISTH‐BAT) is used to assist the diagnosis of bleeding disorders. We examined whether the ISTH‐BAT is capable of predicting the risk of future bleeding. 136 subjects were administered the ISTH‐BAT and followed for up to four years. The ISTH‐BAT score failed to predict the risk of future bleeding.