Activated prothrombin complex concentrate to treat bleeding events in acquired hemophilia A: BAHAS study.

OBJECTIVE: Activated prothrombin complex concentrate (aPCC) is a bypassing agent indicated to treat bleeds in patients with acquired hemophilia A (AHA). Nevertheless, its efficacy and safety in the real-world setting have not often been addressed. METHODS: We report the experience of Spanish reference centers for coagulation disorders and from acquired hemophilia Spanish Registry (AHASR) from August 2012 to February 2021. Follow-up period of 30 days after aPCC withdrawal. RESULTS: Thirty patients with a median age of 70 years old, suffering from 51 bleeds treated with aPCC were finally evaluated. As first-line treatment, aPCC stopped bleeding in 13 of 14 (92.9%) cases. aPCC as the second line after recombinant factor VIIa failure, stopped bleeding in all cases. In 17 patients, aPCC was used far from initial bleed control as prophylaxis of rebleeding with 94% effectiveness. No thromboembolic episodes were communicated. One patient developed hypofibrinogenemia, which did not prevent aPCC from halting bleeding. No other serious adverse events possibly or probably associated with aPCC were reported. CONCLUSIONS: This data support aPCC as hemostatic treatment in AHA with high effectiveness and excellent safety profile in acute bleeds and as extended use to prevent rebleedings, even in aging people with high cardiovascular risk.

Incidence, characteristics and clinical profile of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in patients with pre-existing primary immune thrombocytopenia (ITP) in Spain.

Infections are one of the well-known precipitating factors for relapses in patients with immune thrombocytopenia (ITP). Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can sometimes lead to or be associated with thrombocytopenia due to an increase in peripheral platelet destruction from inflammatory hyperactivation. Currently, we do not know if SARS-CoV-2 infection modifies the natural evolution of chronic or persistent ITP or if previous immunosuppression of patients with ITP influences the incidence and severity of coronavirus disease 2019 (COVID-19) in this group. The present study was an observational, multicentre, national series of 32 adult patients with pre-existing ITP and subsequent SARS-CoV-2 infection, collected by the Spanish ITP Group [Grupo Español de Trombocitopenia Inmune (GEPTI)].

A decade of changes in management of immune thrombocytopenia, with special focus on elderly patients.

BACKGROUND: Ten years after their availability, thrombopoietin receptor agonists (TPO-RA) have heralded a paradigm shift in the treatment of immune thrombocytopenia (ITP). This study was aimed to analyze the implementation of current recommendations in the standard practice of adult ITP patients, and how age may influence those changes. METHODS: We included 121 adult patients (> 65 years, n = 54; younger individuals, n = 67) who initiated treatment with TPO-RA between January 2012 and December 2014. RESULTS: Patients older than 65 years treated with TPO-RA presented at diagnosis with significantly higher platelet counts, less bleeding, and a more prothrombotic profile than younger ones. The high efficacy rates of TPO-RA, preferentially used during the last decade in non-chronic phases, precluded from further therapies in the majority of ITP patients. Their administration was associated with a sharp decline in the last decade in the use of splenectomy and intravenous immunoglobulin, especially in younger ITP individuals. CONCLUSION: These results confirm (1) that there is a preferential use of TPO-RAs in elderly ITP patients with fewer bleeding complications but more unfavorable prothrombotic conditions than in younger individuals, and (2) that early use of these agents has been established as an effective therapeutic alternative to other second line therapies.

General concepts on hemophilia A and on women carrying the disease.

Hemophilia A affects one in every 5000 live male births. As the disorder follows a hereditary X-linked recessive pattern, women who inherit the mutation become carriers of the disease. The exact prevalence of carriers of hemophilia A or B is unknown. A search of the literature identified only one study that provides an approximation. According to its authors, for every 100 male with hemophilia there are 277 potential carriers. We will review through this supplement carrier condition from reproductive to care giver and individual point of view.

Deciphering predictive factors for choice of thrombopoietin receptor agonist, treatment free responses, and thrombotic events in immune thrombocytopenia.

Very few data exist on when a particular thrombopoietin-receptor agonist (TPO-RA) is favored in clinical practice for the treatment of patients with immune thrombocytopenia (ITP), about novel risk factors for vascular events (VE) with these drugs, nor about predictive factors for therapy free responses (TFR). We conducted an observational, retrospective, long-term follow-up multicenter study from November 2016 to January 2018 of 121 adult ITP patients initiating TPO-RA between January 2012 to December 2014. Data reflected that a platelet count ≤25 × 109/l at the time when the TPO-RA was initiated was associated with a 2.8 higher probability of receiving romiplostim vs. eltrombopag (P = 0.010). VE on TPO-RA was related to previous neoplasia in patients over 65 years (50% vs. 2.2%, P < 0.001), and to previous splenectomy in younger patients (100% vs. 33%, P = 0.001). Receiving romiplostim as first TPO-RA with no subsequent TPO-RA switching was associated with a 50% likelihood of TFR after 2.9 years of therapy (3.3 years in chronic ITP patients). These real-world data help deciphering some areas of uncertainty, and offer insight into some of the most relevant challenges of ITP which may help clinicians make appropriate treatment decisions in the management of adult ITP patients with TPO-RA.

Involvement of antifactor VIII autoantibodies specificity in the outcome of inhibitor eradication therapies in acquired hemophilia a patients.

: We hypothesized that inhibitor specificity may predict the outcome of antifactor VIII autoantibodies eradication treatment in acquired hemophilia A. Our objective was to analyze the association between factor VIII domains recognized by inhibitors and outcome of the immunosuppressive therapies (ISTs) in a prospective, observational study. 16 patients were recruited. Inhibitor specificities were assessed at diagnosis and throughout the study. Their association with IST outcome was addressed. First-line IST succeeded in 56% of patients. Inhibitors reacted mainly with light chain domains (69%) and/or the A2 domain (44%). 31% inhibitors recognized more than one domain. Significantly, the number of patients whose inhibitors recognized the light chain was significantly higher in the group of those who did not reach complete remission after first line IST when compared with those who did [6/7 (85.7%) vs. 4/9 (44.4%), P < 0.05]. Therefore, inhibitor specificity could predict the success of IST in acquired hemophilia A.

Treatment characteristics, efficacy and safety of thrombopoietin analogues in routine management of primary immune thrombocytopenia.

: Thrombopoietin receptor agonist (TPO-RAs) have demonstrated good efficacy and tolerance in clinical trials in refractory chronic primary immune thrombocytopenia (ITP) or chronic ITP with contraindication for splenectomy. No head-to-head study is available, and differences in trials design do not allow comparisons. Information on the use of TPO-RAs in nonchronic ITP is scant. We described our experience with TPO-RAs in ITP (chronic, persistent and newly diagnosed ITP) in routine clinical practice. Retrospective series of 100 adult ITP patients was analysed; 41 treated with eltrombopag, 37 with romiplostim and 22 with both. Response-related and safety variables were evaluated. With a median follow-up of 86.5 weeks (interquartile range, 34.3-128 weeks), no differences were found in response rate, time to response, stability of response or response duration based on the type of TPO-RA used. Of all, 25% of patients with newly diagnosed or persistent ITP and 7.2% with chronic responded and maintained their response when TPO-RAs were stopped. Regarding safety, two developed bone marrow fibrosis grade 3, with loss of response to both drugs. Incidence of vascular events was 7%. Both TPO-RAs may be useful in all types of ITP, not only chronic but also persistent and newly diagnosed. Similar results were noted in efficacy and safety variables for both drugs.

Adult severe haemophilia A patients under long-term prophylaxis with factor VIII in routine clinical practice.

There is no clear consensus on the best practice for long-term prophylaxis in adults with severe haemophilia A. This is a single-centre prospective case series study. We describe here the demographic data, type and reason of prophylaxis in adult patients (>18 years old) with severe (<1%) haemophilia A, treated in our centre from 2006 to 2013. Prophylaxis was tailored according to pharmacokinetic studies and posterior factor VIII (FVIII) trough level adjustment. We analysed FVIII consumption, bleeding rate, adherence and adverse events in this group of patients. In adult patients who initiated long-term prophylaxis during this period, we compared FVIII consumption and bleeding rate with the previous on-demand period. We analysed data from 18 patients. Median annual FVIII consumption was 2374.2 IU/kg/year. Among the patients receiving tertiary prophylaxis, initiated from 2006 onwards, the annual FVIII consumption was 2557.8 vs. 1696.8 IU/kg per year during the on-demand period (P = 0.312). In this group of patients, there was a decrease in annual bleeding events of 88.3% during prophylaxis compared with the on-demand therapy (P < 0.0001). A high adherence to prophylaxis was observed (84%). No cases of anaphylaxis or symptomatic thromboembolic events were recorded. In adult severe haemophilia A patients, the type of and reason to indicate long-term prophylaxis are diverse nowadays. FVIII consumption varies depending on the justification of prophylaxis. The observations reported provide further support for the efficacy of long-term prophylaxis in adult haemophilia A patients.