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Therapeutic plasma exchange (PE) is the accepted therapy for thrombotic thrombocytopenic purpura (TTP). Because not all patients achieve remission, other treatment modalities have been used in addition to PE, but no randomized clinical trial evaluated their efficacy. The aim of this multicentric study was to compare the effectiveness of standard- versus high-dose methylprednisolone as an adjunctive treatment to PE in the acute phase of TTP. Sixty patients with idiopathic TTP were randomized to receive methylprednisolone 1 mg/kg/die intravenous or 10 mg/kg/die for 3 days, thereafter, 2.5 mg/kg/die in addition to PE. Both dosages of steroids were well tolerated. At the end of induction therapy (day 23), the percentage of patients failing to achieve complete remission was significantly higher in the standard dose (16 of 30) than in the high-dose group (seven of 30). Also, the number of cases without a good response at day 9 and the number of deaths were higher in the standard-dose arm, but the differences did not reach the statistical significance. Results of present study indicate that the association of PE with high-dose instead of standard-dose steroids reduces the percentage of TTP patients that fail to achieve complete remission.

Eltrombopag (Promacta ® ; Revolade ® ) is an orally active thrombopoietin receptor agonist recently approved in the USA and the EU for use in paediatric patients aged ≥1 year with chronic immune thrombocytopenia (ITP) who have had an insufficient response or are refractory to other ITP treatments (e.g. corticosteroids, immunoglobulins or splenectomy). The efficacy of 7 or 13 weeks’ therapy with oral eltrombopag (up to 75 mg/day) was compared with that of placebo in patients aged 1–17 years with previously treated chronic ITP in randomized, double-blind, multicentre phase II and III trials (PETIT and PETIT-2). In these trials, the platelet response rate (primary endpoint of PETIT) and the sustained platelet response rate (primary endpoint of PETIT-2) were significantly higher with eltrombopag than with placebo. A clinical benefit was shown by a reduction in the need for rescue therapy with eltrombopag versus placebo in both trials and a reduction of clinically significant bleeding in PETIT. During longer-term therapy (open-label treatment period for ≥24 weeks), eltrombopag maintained platelet counts above 50 × 10 9 /L in the majority of patients and approximately one-half of patients were able to reduce or discontinue concurrent ITP drugs. Eltrombopag was generally well tolerated. Current evidence suggests that eltrombopag is a valuable addition to the limited treatment options available for the management of chronic ITP in paediatric patients with an inadequate response to first-line therapies.

Background T-cell dysregulation and T-cell-related cytokine abnormalities are involved in the pathogenesis of immune thrombocytopenia (ITP). One of our previous studies showed that elevated IL-22 correlated to Th1 and Th22 cells plays an important role in the immunopathogenesis of ITP. In this study, we aimed to investigate the effects of high-dose dexamethasone (HD-DXM) on IL-22 production and on the IL-22-producing T-cell subsets in ITP patients. Methods IL-22 plasma levels and the percentages of Th1, Th17, and Th22 cells were determined by enzyme-linked immunosorbent assay and flow cytometry in 25 ITP patients receiving DXM 40 mg/day for 4 consecutive days. Results Plasma IL-22 concentrations and the percentages of Th1 and Th22 cells were significantly increased in pre-therapy patients relative to controls ( P  < 0.05), but the percentage of Th17 cells was not. HD-DXM administration reduced IL-22 production and corrected the imbalance between Th1 and Th22 subsets. IL-22 levels were positively correlated with Th1 and Th22 cells in ITP patients before and after HD-DXM treatment. Conclusion These results suggest that HD-DXM may regulate the production of IL-22 in ITP, possibly by correcting Th1 and Th22 polarization.

Bruton’s tyrosine kinase (BTK) is a target for treatment of hematologic malignancies and autoimmune diseases. TAK‐020 is a highly selective covalent BTK inhibitor that inhibits both B cell receptor and fragment crystallizable receptor signaling. We assessed the safety/tolerability and pharmacokinetics/pharmacodynamics (PDs) of TAK‐020 in healthy subjects. Each cohort of the single‐rising dose (n = 72; 9 cohorts) and the multiple‐rising dose (n = 48; 6 cohorts) portions of the study comprised six TAK‐020‐treated and two placebo‐treated, subjects aged 18–55 years (inclusive). The PD effects were assessed by measuring BTK occupancy and the inhibition of fragment crystallizable epsilon receptor 1 (FcεRI)‐mediated activation of basophils. Overall, treatment‐emergent adverse events (TEAEs) were similar to placebo; there were no serious TEAEs or no TEAEs leading to discontinuation. TAK‐020 was rapidly absorbed (median time to maximum plasma concentration (Tmax) 45–60 minutes) with a half‐life of ~ 3–9 hours at doses ≥ 2.5 mg. TAK‐020 exposure was generally dose proportional for single doses ≤ 70 mg and after multiple doses of ≤ 60 mg once daily. Target occupancy was dose dependent, with doses ≥ 2.5 mg yielding maximum and sustained occupancy > 70% for > 96 hours. Single doses ≥ 4.4 mg reduced FcεRI‐mediated activation of basophils by > 80% and comparable inhibition was observed with daily dosing ≥3.75 mg for 9 days. Inhibition persisted for 24–72 hours postdose and the duration generally increased with dose. TAK‐020 was generally well‐tolerated in healthy subjects after single and multiple doses and demonstrated target engagement and pathway modulation. The PD effects outlasted drug exposures, as expected for covalent inhibition of BTK.

To assess safety and efficacy of a 10% intravenous immunoglobulin in patients with primary immune thrombocytopenic purpura (ITP). ITP patients in two multicenter studies (Trials A/B) were treated with 2 g/kg Flebogamma 10% DIF (over 2-5 days) and were followed up to 1-3 months. 18 patients in Trial A and 58 in Trial B were enrolled (12 children in Trial B). The response rate (platelet count ≥50 × 10 /l) was 72.2% (Trial A) and 76.1/100% (adults/children; Trial B). Most patients improved bleedings (83.3% Trial A; 88.9% Trial B). Potential treatment-related adverse events were reported by 38.9% (Trial A) and 30.4/83.3% (adults/children; Trial B) of patients. All serious adverse events (five patients) resolved without sequelae. Flebogamma 10% DIF was effective and safe in patients with primary ITP.

We conducted this randomized trial to investigate the efficacy and safety of rapamycin treatment in adults with chronic immune thrombocytopenia (ITP). Eighty-eight patients were separated into the control (cyclosporine A plus prednisone) and experimental (rapamycin plus prednisone) groups. The CD4+CD25+CD127low regulatory T (Treg) cells level, Foxp3 mRNA expression, and the relevant cytokines levels were measured before and after treatment. The overall response (OR) was similar in both groups (experimental group versus control group: 58% versus 62%, P=0.70). However, sustained response (SR) was more pronounced in the experimental group than in the control group (68% versus 39%, P<0.05). Both groups showed similar incidence of adverse events (7% versus 11%, P=0.51). As expected, the low pretreatment baseline level of Treg cells was seen in all patients (P<0.001); however, the experimental group experienced a significant rise in Treg cell level, and there was a strong correlation between the levels of Treg cells and TGF-beta after the treatment. In addition, the upregulation maintained a stable level during the follow-up phase. Thus, rapamycin plus low dose prednisone could provide a new promising option for therapy of ITP.

Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is associated with antibodies that target platelet factor 4 (PF4) and are heparin-independent. VITT antibodies are implicated in acute, transient prothrombotic disorders that are triggered by adenoviral vector vaccines against coronavirus disease 2019 or by adenovirus infection. We describe chronic prothrombotic disorders featuring anticoagulant-refractory thromboses and intermittent thrombocytopenia that were associated with VITT-like antibodies in five patients (four patients with newly reported cases and the index patient). The patients had low levels of M proteins (median level, 0.14 g per deciliter); in each patient, we found that the M protein was the VITT-like antibody. The antibody clonotype profiles and binding epitopes on PF4 were different from those observed with the acute disorders occurring after vaccination or viral infection, features that reflect distinct immunopathogenesis. Treatment strategies besides anticoagulation alone are needed for the chronic disorders, referred to as VITT-like monoclonal gammopathy of thrombotic significance. (Funded by the Canadian Institutes of Health Research and others.) Patients with a prothrombotic clinical course often associated with thrombocytopenia may have a monoclonal paraprotein, even at low levels, that activates platelets by binding to platelet factor 4.

A woman with refractory thrombocytopenia complicating systemic lupus erythematosus had a response to CD19 CAR T cells with an increase in platelet counts and minimal symptoms of cytokine release syndrome.

Hepatitis C virus (HCV) infection has been associated with the production of autoantibodies and the development of several autoimmune disorders. Immune thrombocytopenic purpura (ITP) is an immune-mediated syndrome of unknown etiology characterized by the presence of autoantibodies against platelet membrane proteins. Retrospective chart review. Seven patients with chronic HCV infection (five with cirrhosis and two with chronic active hepatitis) developed thrombocytopenia, out of proportion to their liver disease, and were diagnosed with ITP based on the presence of anti-platelet antibodies and their response to treatment. The number of patients with ITP which occurred in a population of 3440 HCV patients seen over this time interval is much greater than would be expected by chance (p < 0.00001). Six patients required treatment and four required hospitalization. Four of the six responded to corticosteroids alone. Both of the patients who failed to respond to corticosteroids responded to cyclophosphamide. No mortality occurred from complications of thrombocytopenia. ITP occurs more commonly in patients with chronic HCV infection than would be expected by chance. This should be considered in patients with liver disease and unexplained thrombocytopenia, as well as in patients with newly diagnosed ITP. Evaluation of antiplatelet antibodies, using an antigen-specific assay, was useful in supporting this diagnosis. Therapy with either corticosteroids or cyclophosphamide was successful in the six patients who required treatment.

VITT is caused by a somatic hypermutation of an anti–adenovirus pVII antibody that generates more avid binding of platelet factor 4 than of adenovirus pVII, its original target, which results in platelet activation.