Worldwide vaccination against SARS-CoV-2 has allowed the detection of hematologic autoimmune complications. Adverse events (AEs) of this nature had been previously observed in association with other vaccines. The underlying mechanisms are not totally understood, although mimicry between viral and self-antigens plays a relevant role. It is important to remark that, although the incidence of these AEs is extremely low, their evolution may lead to life-threatening scenarios if treatment is not readily initiated. Hematologic autoimmune AEs have been associated with both mRNA and adenoviral vector-based SARS-CoV-2 vaccines. The main reported entities are secondary immune thrombocytopenia, immune thrombotic thrombocytopenic purpura, autoimmune hemolytic anemia, Evans syndrome, and a newly described disorder, so-called vaccine-induced immune thrombotic thrombocytopenia (VITT). The hallmark of VITT is the presence of anti-platelet factor 4 autoantibodies able to trigger platelet activation. Patients with VITT present with thrombocytopenia and may develop thrombosis in unusual locations such as cerebral beds. The management of hematologic autoimmune AEs does not differ significantly from that of these disorders in a non-vaccine context, thus addressing autoantibody production and bleeding/thromboembolic risk. This means that clinicians must be aware of their distinctive signs in order to diagnose them and initiate treatment as soon as possible.

Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by anti-ADAMTS13 antibodies. Caplacizumab is approved for adults with an acute episode of iTTP in conjunction with PEX and immunosuppression. The objective of this study is to analyze and compare the safety and efficacy of caplacizumab versus the standard of care and assess the effect of the concomitant use of rituximab. A retrospective study from the Spanish TTP Registry of patients treated with caplacizumab vs those who did not receive it was conducted. A total of 155 iTTP patients (77 caplacizumab, 78 no caplacizumab) were included. Patients initially treated with caplacizumab had fewer exacerbations (4.5% vs 20.5% p<0.05) and less refractoriness (4.5% vs 14.1% p<0.05) than those that were not treated. Time to clinical response was shorter when caplacizumab was used as initial treatment vs caplacizumab used after refractoriness or exacerbation. The multivariate analysis showed that its use in the first 3 days after plasma exchange (PEX) was associated with a lower number of PEX (OR 7.5, CI 2.3-12.7; p<0.05) and days of hospitalization (OR 11.2, CI 5.6-16.9; p<0.001) compared to standard therapy. There was no difference in time to clinical remission in patients treated with caplacizumab compared to the use of rituximab. No severe adverse event was described in the caplacizumab group. In summary, caplacizumab reduced exacerbations and refractoriness compared to standard of care regimens. When administered within the first 3 days after PEX it also provided a faster clinical response, reducing hospitalization time and the need for PEX.

No abstract

Background Extracorporeal photopheresis (ECP) is an efficient and established therapy to treat acute and chronic graft vs host disease (GVHD). Using an “off‐line” method, the first step (mononuclear cell [MNC] collection) is decisive, as long as a high MNC yield and purity in the collected product is desirable. Two “off‐line” devices were compared: the COBE Spectra and the Spectra Optia (Terumo BCT), using both continuous and intermittent protocols. Patients and methods Twelve patients with GvHD (7 acute/5 chronic) were enrolled between June 2014 and May 2015 and were alternatively assigned for each procedure to either the COBE Spectra or the Spectra Optia cell separator. Patients characteristics and procedure/product parameters were analyzed. Results Two hundred procedures (100 per device) were included. The Spectra Optia system showed higher total nucleated cells and MNC collection efficiencies (18.6(10.2‐29.7) vs 7.9(4.1‐14.8)% and 43.6(20.3‐59.5) vs 23.3(11.4‐37.1)%, P < .001) and monocyte and lymphocyte collection efficiencies (55.2(17.7‐83.2) vs 22.8(9‐38.9)% and 38.3(26.7‐53.4) vs 22.2(9‐38.9)%, respectively, P < .001). Absolute platelet loss (PL) and PL per liter of blood processed were significantly lower in the Spectra Optia group (22.9(18.3‐28.1) vs 33.6(26.5‐41.1)%, P < .001 and 3.7(3.1‐4.5) vs 4.3(3.5‐4.2)%, P = .01, respectively). However, granulocyte contamination was higher (4.5(1.3‐36) vs 1.2(0.4‐5.7)%, P < .001) and a higher product haematocrit was obtained with the Spectra Optia (1(0.5‐1.6) vs 0.3(0.2‐0.5)%, P < .001), without an impact on irradiation time. Conclusions In our study, Spectra Optia proved to be safe and effective in collecting MNC with high yield and purity for ECP in GvHD.

Summary 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)].

Early descriptions of COVID-19 associated coagulopathy identified it as a disseminated intravascular coagulation (DIC). However, recent studies have highlighted the potential role of endothelial cell injury in its pathogenesis, and other possible underlying mechanisms are being explored. This study aimed to analyse the coagulation parameters of critically and noncritically ill patients with COVID-19 bilateral pneumonia, determine if coagulation factors consumption occurs and explore other potential mechanisms of COVID-19 coagulopathy. Critically and noncritically ill patients with a diagnosis of COVID-19 bilateral pneumonia were recruited. For each patient, we performed basic coagulation tests, quantification of coagulation factors and physiological inhibitor proteins, an evaluation of the fibrinolytic system and determination of von Willebrand Factor (vWF) and ADAMTS13. Laboratory data were compared with clinical data and outcomes. The study involved 62 patients (31 ICU, 31 non-ICU). The coagulation parameters assessment demonstrated normal median prothrombin time (PT), international normalized ratio (INR) and activated partial thromboplastin time (APTT) in our cohort and all coagulation factors were within normal range. PAI-1 median levels were elevated (median 52.6 ng/ml; IQR 37.2–85.7), as well as vWF activity (median 216%; IQR 196–439) and antigen (median 174%; IQR 153.5–174.1). A mild reduction of ADAMTS13 was observed in critically ill patients and nonsurvivors. We demonstrated an inverse correlation between ADAMTS13 levels and inflammatory markers, D-dimer and SOFA score in our cohort. Elevated vWF and PAI-1 levels, and a mild reduction of ADAMTS13 in the most severe patients, suggest that COVID-19 coagulopathy is an endotheliopathy that has shared features with thrombotic microangiopathy.

Background Immune‐mediated thrombotic thrombocytopenic purpura (iTTP) is a rare disease characterized by the presence of anti‐ADAMTS13 autoantibodies. Achieving accurate information on incidence and customary disease management is important to provide appropriate diagnostic and therapeutic resources. The aim of this study was to determine the incidence and outcomes of iTTP in Spain. Study design and methods A cross‐sectional survey was carried out among Spanish hospitals, focused on iTTP patients ≥16 years old attended between 2015 and 2017, and those at follow‐up before that interval. Incidence, prevalence, mortality, refractoriness, exacerbations, treatment complications, relapses, and sequelae were estimated. Results Forty‐two hospitals covering roughly 20 million inhabitants answered the survey and reported 203 episodes (138 newly‐diagnosed and 65 relapses), of which 193 (95.1%) were treated. Incidence was 2.67 (95% CI 1.90‐3.45) patients per million inhabitants per year and prevalence 21.44 (95% CI% 19.10‐23.73) patients per million inhabitants. At diagnosis, ADAMTS13 activity and anti‐ADAMTS13 autoantibody were measured in 97% and 84.3% of reported episodes, respectively. Fifteen patients (7.4%) died as a direct consequence of iTTP, 6 of them before receiving any iTTP‐specific treatment. Thirty‐one (16.1%) of the 193 treated episodes were refractory to plasma exchange and corticosteroids, and 51 (26.4%) suffered at least one exacerbation. Conclusion iTTP incidence and prevalence were somewhat higher than those documented in neighboring countries. Together with data on treatments and outcomes, this information will allow us to better estimate what is needed to improve diagnosis and prognosis of iTTP patients in Spain.

Introduction Thrombotic thrombocytopenic purpura (TTP) is a rare life‐threatening thrombotic microangiopathy (TMA) characterized by the severe deficiency of ADAMTS13 activity (<10%). Rapid ADAMTS13 testing is crucial for early diagnosis and optimal management of TTP patients and other TMAs. The objective of this study was to retrospectively evaluate the performance of the recently commercialized HemosIL Acustar® ADAMTS13 activity chemiluminescent immunoassay (Instrumentation Laboratory, Bedford, Massachusetts, United States) in a multicentric study between Spain and Portugal. Methods A comparison method was performed to compare HemosIL Acustar® with an in‐house FRETS‐VWF73 assay and two commercial ELISA assays: the TECHNOZYM® ADAMTS13 Activity (Technoclone GmbH, Vienna, Austria) and the DG‐EIA ADAMTS‐13 Activity (Diagnostic Grifols, SA, Barcelona, Spain). A set of 241 frozen plasma samples with known ADAMST13 levels was used. Agreement between methods was assessed with focus on two cut‐off ADAMTS13 activity values: <10% (the clinical accepted cut‐off value to confirm TTP diagnosis) and <5%. Results HemosIL AcuStar® showed high agreement with the other methods in correctly classify patients with ADAMTS13 values below 10% (Kappa = 0.89) and even below 5% (Kappa = 0.94) with no false negatives and few false positives (5.40%; 95% CI: 2.20 to 8.60%). However, it also tended to underestimate ADAMTS13 levels, especially for the high assay range values (>40%) (absolute mean bias of 8.40% (95% CI: 6.53 to 10.42%)) when compared to other assays. Conclusions HemosIL AcuStar® is highly sensitive to detect ADAMTS13 values below 10% and 5%. A large prospective validation study is needed to corroborate its utility in clinical practice.