Study of platelet kinetics in immune thrombocytopenia to predict splenectomy response.

Despite the efficacy of splenectomy for chronic immune thrombocytopenia (ITP), its considerable failure rate and its possible related complications prove the need for further research into potential predictors of response. The platelet sequestration site determined by 111 In-labelled autologous platelet scintigraphy has been proposed to predict splenectomy outcome, but without standardisation in clinical practice. Here, we conducted a single-centre study by analysing a cohort of splenectomised patients with ITP in whom 111 In-scintigraphy was performed at La Paz University Hospital in Madrid to evaluate the predictive value of the platelet kinetic studies. We also studied other factors that could impact the splenectomy outcome, such as patient and platelet characteristics. A total of 51 patients were splenectomised, and 82.3% responded. The splenic sequestration pattern predicted a higher rate of complete response up to 12 months after splenectomy (p = 0.005), with 90% sensitivity and 77% specificity. Neither age, comorbidities, therapy lines nor previous response to them showed any association with response. Results from the platelet characteristics analysis revealed a significant loss of sialic acid in platelets from the non-responding patients compared with those who maintained a response (p = 0.0017). Our findings highlight the value of splenic sequestration as an independent predictor of splenectomy response.

Acquired Haemophilia A: A 15-Year Single-Centre Experience of Demography, Clinical Features and Outcome.

Acquired haemophilia A (AHA) is a rare severe bleeding disorder resulting from the production of autoantibodies directed against coagulation factor VIII. At presentation, bleeding events can be severe, and an early diagnosis and treatment are of major importance. The current study aims to analyse the treated patients who have been diagnosed with AHA for a better understanding of our population and treatment outcome. We conducted a retrospective study with 26 patients who had been diagnosed with AHA and who were treated in our hospital between January 2006 and January 2021. The patients ranged in age from 30 to 85 years old: 46.10% were men, 46.10% had no known underlying condition, 27% had an underlying malignancy, 7.60% presented with other diseases: psoriatic arthritis and Paget's disease, and 19.30% presented with AHA during puerperium. All of the patients had bleeding events and were treated with bypass agents for this as well as with immunosuppressive therapy to eradicate the inhibitor. A total of 53.80% of the patients had major bleeding. Sixty-nine percent of the patients achieved complete remission, but 26.90% died during the follow-up, although bleeding was not the cause of death in any of these cases. Our observations underline the importance of clinical suspicion and early referral to centres with experience and laboratory facilities for managing AHA.

Arthropathy in people with mild haemophilia: Exploring risk factors.

BACKGROUND: It is important to investigate which factors are associated with the development of arthropathy in people with mild haemophilia (PWMH), in order to prevent it and to limit its effect on function and quality of life. PURPOSE: To examine the risk factors associated with arthropathy and to predict its presence and degree of involvement in our PWMH population. METHODS: This was an observational, cross-sectional cohort study of 85 PWMH under follow-up in our centre. Patient variables (age, body mass index, haemophilia type, genetic mutations, baseline factor levels, age at diagnosis, history of inhibitor, level of physical activity and years of practice, history of haemarthrosis and muscle haematoma) were analysed and related to the presence or absence of arthropathy and the degree of arthropathy (measured with HJHS and HEAD-US). Multivariable models were performed. RESULTS: Some 36.5% of PWMH had arthropathy. The variables that showed an independent association with the presence of arthropathy were patient age (median 42 years) and clotting factor levels (median 10.5 IU/dL). The risk of developing arthropathy increased by 7.9% for each additional year of age and decreased by 7.7% for each 1 IU/dL increase in clotting factor. When arthropathy developed, its degree of involvement might have been influenced by the type of physical activity performed. CONCLUSIONS: Patient age and factor levels appear to be the most determinant risk factors associated with the development of arthropathy in mild haemophilia. Monitoring joint health is desirable in this patient population. In patients with arthropathy, physical activities with a low risk of bleeding are the most recommended.

Platelet and immune characteristics of immune thrombocytopaenia patients non-responsive to therapy reveal severe immune dysregulation.

Multifactorial mechanisms leading to diminished platelet counts in immune thrombocytopaenia (ITP) might condition the ability of patients with ITP to respond to treatments. Examining their platelet and immune features, we aimed to detect singular characteristics of patients with ITP who do not respond to any treatment. We studied patients with chronic primary ITP who had been without treatment, or untreated (UT-ITP), for at least six months; included were responders to agonists of thrombopoietin receptors (TPO-RA), patients who showed no response to first- and second-line treatments (NR-ITP), and healthy controls. Platelets from NR-ITP patients exposed a reduced amount of sialic acid residues. Increased loss of platelet surface sialic acid residues was associated with increased platelet apoptosis. NR-ITP patients had an increased fraction of naive lymphocyte (L) B cells and a reduced LTreg (Lymphocyte T-regulator) subset. They also presented an anomalous monocyte and NK (Natural Killer) cells distribution. TPO-RA-treated patients seemed to recover an immune homeostasis similar to healthy controls. In conclusion, our results indicate a severe deregulation of the immune system of NR-ITP. The inverse correlation between loss of sialic acid and LTreg count suggests a potential relationship between glycan composition on the platelet surface and immune response, positing terminal sugar moieties of the glycan chains as aetiopathogenic agents in ITP.