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Among patients with thrombotic thrombocytopenic purpura, the addition of caplacizumab, an anti–von Willebrand factor humanized, bivalent variable-domain-only immunoglobulin fragment, to daily plasma exchange resulted in faster platelet recovery, fewer TTP-related deaths, and fewer recurrences and thromboembolic events.

Congenital thrombotic thrombocytopenic purpura results from hereditary deficiency of ADAMTS13. Prophylactic administration of recombinant ADAMTS13 achieved normal blood levels with limited toxicity and no neutralizing antibodies.

Thrombotic thrombocytopenic purpura is often caused by an autoantibody to ADAMTS13, resulting in ultralarge von Willebrand factor, which induces platelet aggregation. Caplacizumab blocks platelet aggregation and speeds recovery when combined with plasma exchange. Acquired thrombotic thrombocytopenic purpura (TTP) is a potentially life-threatening thrombotic microangiopathy resulting from systemic microvascular thrombosis and leading to profound thrombocytopenia, hemolytic anemia, and organ failure of varying severity. 1 Acquired TTP is caused by a severe deficiency of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) due to the presence of inhibitory autoantibodies. 2 Decreased ADAMTS13 activity leads to an accumulation of ultralarge von Willebrand factor multimers, which bind to platelets and induce aggregation. 3 These microthrombi cause tissue ischemia and organ dysfunction (commonly involving the brain, heart, and kidneys), resulting in early death 4 , 5 or in . . .

Eltrombopag is an oral thrombopoietin receptor agonist for the treatment of thrombocytopenia. We aimed to compare the response to once daily eltrombopag versus placebo in patients with chronic immune thrombocytopenia during a 6-month period. We undertook a phase 3, double-blind, placebo-controlled study in adults with previously treated immune thrombocytopenia of more than 6 months' duration who had baseline platelet counts lower than 30 000 per μL. Patients were randomly allocated (in a 2:1 ratio) treatment with local standard of care plus 50 mg eltrombopag or matching placebo once daily for 6 months. Randomisation was done centrally with a computer-generated randomisation schedule and was stratified by baseline platelet count (≤15 000 per μL), use of treatment for immune thrombocytopenia, and splenectomy status. Patients, investigators, and those assessing data were masked to allocation. Dose modifications were made on the basis of platelet response. Patients were assessed for response to treatment (defined as a platelet count of 50 000–400 000 per μL) weekly during the first 6 weeks and at least once every 4 weeks thereafter; the primary endpoint was the odds of response to eltrombopag versus placebo. Analysis was by intention to treat. This study is registered at ClinicalTrials.gov, number NCT00370331. Between Nov 22, 2006, and July 31, 2007, 197 patients were randomly allocated to treatment groups and were included in the intention-to-treat analysis (135 eltrombopag, 62 placebo). 106 (79%) patients in the eltrombopag group responded to treatment at least once during the study, compared with 17 (28%) patients in the placebo group. The odds of responding were greater in patients in the eltrombopag group compared with those in the placebo group throughout the 6-month treatment period (odds ratio 8·2, 99% CI 3·59–18·73; p<0·0001). 37 (59%) patients receiving eltrombopag reduced concomitant treatment versus ten (32%) patients receiving placebo (p=0·016). 24 (18%) patients receiving eltrombopag needed rescue treatment compared with 25 (40%) patients receiving placebo (p=0·001). Three (2%) patients receiving eltrombopag had thromboembolic events compared with none in patients on placebo. Nine (7%) eltrombopag-treated patients and two (3%) in the placebo group had mild increases in alanine aminotransferase concentration, and five (4%) eltrombopag-treated patients ( vs none allocated to placebo) had increases in total bilirubin. Four (7%) patients taking placebo had serious bleeding events, compared with one (<1%) patient treated with eltrombopag. Eltrombopag is effective for management of chronic immune thrombocytopenia, and could be particularly beneficial for patients who have not responded to splenectomy or previous treatment. These benefits should be balanced with the potential risks associated with eltrombopag treatment. GlaxoSmithKline.

We report a case of early-onset hereditary thrombotic thrombocytopenic purpura in a 16-year-old girl who suffered from thrombocytopenia and was misdiagnosed with immune thrombocytopenia for years until two failed gestations finally revealed the underlying cause. The novel compound heterozygous mutation c.2865G > A:p.Trp955X and c.721delG: p.Gly241fs in the ADAMTS13 gene were identified and are predicted to be associated with this disease. The patient responded to plasma therapy, including plasma infusion and plasma exchange, but renal dysfunction may be longstanding.

Hereditary thrombotic thrombocytopenic purpura is an autosomal recessive disorder caused by the absence of a functional protease (ADAMTS13) that processes von Willebrand factor multimers into smaller fragments. The multimers bind to platelets and initiate abnormal clotting, thrombosis, and hemolysis.

The phenotypes of VITT were defined in 220 patients in the United Kingdom who presented a median of 14 days after the first ChAdOx1 nCoV-19 vaccination. Half had cerebral venous sinus thrombosis, a third of whom also had intracranial hemorrhage. Mortality was 22%. Intravenous immune globulin may reverse VITT.

Immune thrombocytopenia in patients who present with serious bleeding is treated with platelet transfusions, glucocorticoids, and intravenous immune globulin. In patients without serious bleeding, treatment decisions are guided by the platelet count and other factors. Commonly used agents include glucocorticoids, thrombopoietin-receptor agonists, and rituximab.

Eltrombopag is an oral, non-peptide, thrombopoietin-receptor agonist that stimulates thrombopoiesis, leading to increased platelet production. This study assessed the efficacy, safety, and tolerability of once daily eltrombopag 50 mg, and explored the efficacy of a dose increase to 75 mg. In this phase III, randomised, double-blind, placebo-controlled study, adults from 63 sites in 23 countries with chronic idiopathic thrombocytopenic purpura (ITP), platelet counts less than 30 000 per μL of blood, and one or more previous ITP treatment received standard care plus once-daily eltrombopag 50 mg (n=76) or placebo (n=38) for up to 6 weeks. Patients were randomly assigned in a 2:1 ratio of eltrombopag:placebo by a validated randomisation system. After 3 weeks, patients with platelet counts less than 50 000 per μL could increase study drug to 75 mg. The primary endpoint was the proportion of patients achieving platelet counts 50 000 per μL or more at day 43. All participants who received at least one dose of their allocated treatment were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT00102739. 73 patients in the eltrombopag group and 37 in the placebo group were included in the efficacy population and were evaluable for day-43 analyses. 43 (59%) eltrombopag patients and six (16%) placebo patients responded (ie, achieved platelet counts ≥50 000 per μL; odds ratio [OR] 9·61 [95% CI 3·31–27·86]; p<0·0001). Response to eltrombopag compared with placebo was not affected by predefined study stratification variables (baseline platelet counts, concomitant ITP drugs, and splenectomy status) or by the number of previous ITP treatments. Of the 34 patients in the efficacy analysis who increased their dose of eltrombopag, ten (29%) responded. Platelet counts generally returned to baseline values within 2 weeks after the end of treatment. Patients receiving eltrombopag had less bleeding at any time during the study than did those receiving placebo (OR 0·49 [95% CI 0·26–0·89]; p=0·021). The frequency of grade 3–4 adverse events during treatment (eltrombopag, two [3%]; placebo, one [3%]) and adverse events leading to study discontinuation (eltrombopag, three [4%]; placebo, two [5%]), were similar in both groups. Eltrombopag is an effective treatment for managment of thrombocytopenia in chronic ITP. GlaxoSmithKline.

In patients with immune thrombotic thrombocytopenic purpura (iTTP), autoantibodies against the metalloprotease ADAMTS13 lead to catastrophic microvascular thrombosis. However, the potential benefits of recombinant human ADAMTS13 (rADAMTS13) in patients with iTTP remain unknown. Here, we report the clinical use of rADAMTS13, which resulted in the rapid suppression of disease activity and complete recovery in a critically ill patient whose condition had proved to be refractory to all available treatments. We also show that rADAMTS13 causes immune complex formation, which saturates the autoantibody and may promote its clearance. Our data support the role of rADAMTS13 as a novel adjunctive therapy in patients with iTTP. In a 28-year-old woman with postpartum immune thrombotic thrombocytopenic purpura, plasma exchange was unsuccessful. Near death while receiving vasopressors, she was treated with recombinant ADAMTS13, and the disease abated.