The incidence of thrombotic complications chronologically related to L‐asparaginase administration is retrospectively analyzed in 238 adult ALL patients treated according to the GIMEMA protocol ALL 0288. The patients (126 males and 112 females, aged 12–68 years, median 29) received E. coli L‐asparaginase (L‐ase) in the induction phase at a dosage of 6000 U/m2/day × 7 d starting on d 15, as well as vincristine, prednisone, daunorubicin and cyclophosphamide, the last‐named by random 1:1. Ten patients (4.2%) developed thrombotic complications 5–15 d (median lid) after the start of L‐ase treatment. The thrombotic events, which were lethal in 5 patients, involved the cerebral sinus (5 cases), the cerebral arteria (2 cases), the portal vein (1 case), the pulmonary district (1 case), and a deep vein in the lower extremity (1 case). The occurrence of these complications was not related to the general thrombotic risk factors, nor to the main clinical and laboratory data registered at diagnosis and immediately before the start of L‐asparaginase treatment. The present study documents for the first time in a sufficiently large series of adult ALL patients that the incidence and the severity of thrombotic events related to L‐ase administration are relevant and need further consideration.

In 30 subjects on stabilized oral anticoagulant treatment, factor VII activity (VII:C) and factor VII antigen (VIl·Ag) were evaluated. The average VII:C and VIl·Ag levels were 8.7 and 30.7, respectively. All plasma samples were treated with 1 M barium chloride: all the activity and a corresponding average amount of antigen were adsorbed by the salt. The cold-promoted activation of factor VII was found in 5/30 subjects. Corresponding amounts of VII:C and VII: Ag were also removed from the plasma of these subjects after cold activation following the addition of barium chloride. It clearly results from these studies that a portion of VIl·Ag cannot be adsorbed by barium chloride because of a reduction (or a lack) of the γ-carboxyglutamic groups. This portion of VIl·Ag can therefore be identified as Pivka VII.

Abnormal fibrinolysis and thrombotic complications have been often observed in patients who had undergone surgery for meningioma. Fourteen patients, affected by meningioma, were studied before surgery, during surgery and 24 h after surgery in order to evaluate the modifications of the fibrinolysis system and the coagulation physiological inhibitors. Before surgery, no patient showed hyperfibrinolysis and/or modifications of coagulation physiological inhibitors. During surgery, an activation of fibrinolysis with pathological levels of tissue plasminogen activator activity (x = 6.33 U/dl, SD = 7.9, p = 0.02) and increased levels of fibrin degradation products (x = 0.21, SD = 0.18, p = 0.002) was noted. Modifications of the fibrinolysis parameters occurred only in 9/14 patients (64%). These patients presented a more vascularized tumour, revealed before surgery by computerized tomography scan and cerebral arteriography and directly confirmed during the resection. Twenty-four hours after surgery no patient presented fibrinolysis activation. There was no evidence of disseminated intravascular coagulation in our patients. None of them presented pathological decrease of the physiological coagulation inhibitors or thrombotic complications. In conclusion, during surgery, fibrinolysis parameters show important modifications in patients with vascularized meningioma suggesting an ongoing tumour-host interaction. These variations must be taken in account, in order to plan timely a correct therapeutic approach.

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Background. Rituximab, a chimeric anti-CD20 monoclonal antibody effective in B-cell depletion, may be useful in autoimmune disorders by interfering with the production of auto-antibodies. Aims. To investigate the efficacy of Rituximab in patients with resistant ITP. Patients and Methods. Fourteen adult ITP patients (3 males, 11 females; median age 44.5 years [21.1–67.6]) were treated with Rituximab (375 mg/m2/weekly for four doses). The median time between diagnosis and start of Rituximab was 2 years (0.2–33.1 months). All patients had already received at least two lines of therapy (median 3; 2–6): prednisone, pulsed high-dose dexamethasone, azathioprine, immunoglobulins, interferon or splenectomy. At the start of Rituximab, the median platelet count was 10 x 109/L (3–20 x 109/L). Response definitions: complete response (CR), platelet count ≥150 x 109/L; partial response (PR), >50 <150 x 109/L; minimal response (MR), >20 ≤50 x 109/L; no response (NR) ≤20 x 109/L. After completing therapy, patients were evaluated for platelet count after 1 and 3 months, and thereafter every 3 months until relapse or start of a different treatment. Peripheral blood B lymphocytes were evaluated by flow-cytometry as CD19+ cells before treatment, 1 and 3 months after stopping therapy, and then every 3 months up to recovery. Results. One month after Rituximab therapy, 7 responses (2 CR, 4 PR, 1 MR; 50%) and 7 NR (50%) were observed. Two relapses occurred 5 and 18 months after response. The median follow-up of all treated patients is 6 months (1.8–34.6), while the median follow-up of all responsive patients is 6.1 months (2–18.7). Before starting therapy, 11/14 cases were evaluable for flow-cytometry studies. The median baseline value of peripheral blood CD19+ B cells was 137 x 106/L (58–476). One month after completing therapy, 7/9 evaluable cases showed absence of CD19+ cells and 2/9 showed a count of 9 and 4.4 x 106/L CD19+ cells, respectively. At the last available control (median follow-up of 6.8 months; 1.9–32.5), 11/14 evaluable patients had still not recovered the baseline CD19+ cell count (median value: 5.5 x 106/L; 0–287). The following side effects were observed: 1 case of papulosquamous dermatitis, 2 cases of fever. Conclusions. Seven out of 14 (50%) ITP patients had an early response to Rituximab (2 CR, 4 PR, 1 MR), that persisted in 5 cases. No late responses were observed. The response was independent of the post-therapy CD19+ cell numbers. No serious infections were observed during the clinical follow-up. No patient had to stop therapy because of severe side effects.