Efficacy of human interleukin-11 analogs for treating dengue fever-associated thrombocytopenia: a prospective cohort.

AIM: Dengue fever (DF), carried by Aedes mosquitoes, affects millions worldwide. Platelet-inducing human IL-11 analogues may be effective in treating DF-associated thrombocytopenia. METHODOLOGY: A prospective study was done at Dr. Ziauddin Hospital, a tertiary care hospital in Karachi, Pakistan, from September 2023 to April 30, 2024. RESULTS: This study recruited 300 DF patients characterized by thrombocytopenia (platelet count < 30,000), including 159 in the treatment and 141 in the control group. The median age of patients was 34 ± 11.05 years, with 187 males (62.3%) and 113 females (37.7%). The treatment group had a higher proportion of fever (80%, p < 0.0001) and headache (96%, p = 0.012) compared to the control group; however, no significant changes were observed in other clinical parameters between the two groups. Following treatment for 5 days, platelet counts of the treatment group increased significantly in response to IL-11 treatment compared to the control group at all time intervals (day 0, day 1, day 2, day 3, day 4, and day 5). Following treatment, males consistently exhibited higher platelet counts than females (all p < 0.05). In addition, patients admitted on day 3 of their course of illness showed a significantly slow response to the treatment compared to those admitted on day 5. Although young individuals exhibited a significant increase in platelet count, the age showed no significant intergroup differences. CONCLUSIONS: IL-11 analogs have promising potential for treating DF-associated thrombocytopenia. Additional investigation is necessary to refine administration protocols and examine the wider therapeutic ramifications of IL-11 in managing DF.

[Chinese expert consensus on the diagnosis and treatment of Evans syndrome (2024)].

Evans syndrome (ES) is a rare autoimmune disorder characterized by the presence of at least two autoimmune cytopenias (AIC), including immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and autoimmune neutropenia (AIN). Secondary ES accounts for 21%-50% of cases. ES is characterized by recurrent relapses, serious complications such as thrombosis and infection, and high mortality. The management of ES is highly heterogeneous, necessitating treatment for AIC, the primary disease, as well as associated complications. However, there remains a lack of prospective evidence, randomized clinical trials for ES. To standardize the diagnosis and management of ES in China effectively, this consensus was developed by the Red Blood Cell Diseases (Anemia) Group under the Chinese Society of Hematology within the Chinese Medical Association. It aims to provide valuable guidance for diagnosing and managing ES in clinical practice based on international consensus and comprehensive review of both domestic and international literature.

Disseminated Tuberculosis: Rare Presentation.

India contributes to 26% of the global tuberculosis (TB) burden, with very high mortality and morbidity. The exact incidence of disseminated TB cannot be established among the general population but accounts for <2% of cases among immunocompromised hosts and constitutes 20% of all extrapulmonary TB cases. Disseminated TB has a very high mortality rate of around 25-30%. Miliary TB, a disseminated form, is another entity of TB that poses a health burden due to its difficulty in diagnosis. This entity usually presents with subclinical symptoms and poses a diagnostic challenge in the absence of specific diagnostic tests. We present a case of a young female with epistaxis and thrombocytopenia who was diagnosed with disseminated TB [miliary, bone cyst, bone marrow (BM) involvement].

Postoperative bleeding after dentoalveolar surgery in patients with thrombocytopenia-are prophylactic platelet transfusions necessary?

PURPOSE: Benefits of prophylactic platelet (PLT) transfusion before dentoalveolar surgery are unclear. This study investigated the effect of prophylactic PLT transfusions on the incidence of postoperative bleeding (POB) in patients with thrombocytopenia and a PLT count ≤ 75*109/L. METHODS: The cohort in this retrospective study comprised 83 patients with thrombocytopenia ≤ 75*109/L who had undergone dentoalveolar surgery. Exclusion criteria were other coagulation deficiencies or medications that would affect hemostasis. In all, 144 teeth had been removed. POB events were extracted and compared between the group that had received prophylactic PLT transfusion before dentoalveolar surgery and the group that had not. RESULTS: POB events were observed in 5 of 83 patients (6.0%) who had a median PLT count of 35*109/L before any transfusion. The group with no postoperative bleeding (NPOB) had a median PLT count of 34*109/L. Two (4.2%) of the 48 patients who had received prophylactic PLT transfusions before dentoalveolar surgery developed POB. Three (8.6%) of the 35 patients who had not received a transfusion experienced POB. The difference between these two groups was not significant (p = 0.646). When two or more teeth were removed in the same session, a significantly higher incidence of POB was observed (p = 0.042). CONCLUSIONS: Our data indicate that prophylactic PLT transfusions in thrombocytopenic patients with PLT counts ≤ 75*109/L do not reduce the incidence of POB after dentoalveolar surgery. However, caution is warranted when extracting multiple teeth in the same surgical session since we found this to be significantly associated with an increased risk of POB.

Thrombocytopenia in dengue infection: mechanisms and a potential application.

Thrombocytopenia is a common symptom and one of the warning signs of dengue virus (DENV) infection. Platelet depletion is critical as it may lead to other severe dengue symptoms. Understanding the molecular events of this condition during dengue infection is challenging because of the multifaceted factors involved in DENV infection and the dynamics of the disease progression. Platelet levels depend on the balance between platelet production and platelet consumption or clearance. Megakaryopoiesis and thrombopoiesis, two interdependent processes in platelet production, are hampered during dengue infection. Conversely, platelet elimination via platelet activation, apoptosis and clearance processes are elevated. Together, these anomalies contribute to thrombocytopenia in dengue patients. Targeting the molecular events of dengue-mediated thrombocytopenia shows great potential but still requires further investigation. Nonetheless, the application of new knowledge in this field, such as immature platelet fraction analysis, may facilitate physicians in monitoring the progression of the disease.

Clinical analysis of bleeding and thrombotic events in haematological-oncology patients with severe thrombocytopenia and a high risk of thrombosis.

BACKGROUND: Haematological patients with severe thrombocytopenia and high thrombotic risk face challenges related to balancing bleeding and thrombosis risks. This study investigated factors associated with bleeding and thrombosis in high-risk haematological oncology patients with severe thrombocytopenia not receiving anticoagulant therapy and characterized their clinical features when both events occurred. METHODS: A total of 446 haematological oncology patients with Caprini scores ≥ 5 were included from July 2022 to June 2023 at Mianyang City Central Hospital. Those not receiving prophylactic anticoagulants due to an admission platelet count < 50 × 109/L were studied. Patients were categorized into bleeding/nonbleeding and thrombotic/nonthrombotic groups on the basis of hospital course. Relevant clinical data were collected, and univariate/multivariate logistic regression was used to analyse the influencing factors. The platelet count at admission was assessed via ROC curves for thrombosis prediction. RESULTS: In the bleeding group, higher proportions of patients with leukaemia, myeloid tumours, lung infections, and a central venous catheter (CVC) with two lumens were observed, along with shorter catheter durations, lower initial and minimum platelet counts during hospitalization, and prolonged plasminogen times (all P < 0.05). The thrombotic group had a greater thrombosis history, initial platelet count, use of two venous catheter lumens, parenteral nutrition, sedation, and autologous haematopoietic stem cell transplantation (Auto-HSCT), with a lower leukaemia proportion (P < 0.05). Logistic regression identified lymphoma type and minimum platelet count as bleeding protective factors and the Charlson Comorbidity Index (CCI) score as an independent risk factor. Thrombosis history, two venous catheter lumens, and sedation were risk factors for thrombosis. The median platelet count was lower at bleeding and thrombosis than at admission (P = 0.007). The platelet count at admission had predictive value for thrombosis, especially severe thrombocytopenia, with an AUC of 0.735 (95% CI 0.613-0.858, P = 0.003) and a cut-off value of 42.5 × 109/L. CONCLUSIONS: For haematological neoplasm patients with a high risk of venous thromboembolism (VTE), severe thrombocytopenia and high CCI scores, risk prevention and control of bleeding take precedence over thrombosis prophylaxis. Prophylactic anticoagulation is still recommended for patients with lymphoma assessed at high risk for VTE and with platelet counts of at least 42.5 × 109/L.

A case of a geriatric patient with thrombocytopenia after partial recovery from COVID-19.

The global emergence of -COVID-19 has prompted rapid therapeutic and vaccine advancements; however, clinical evidence remains limited. With around a 50% fatality rate for COVID-19 patients with acute respiratory distress syndrome (ARDS), early intervention is crucial. This report details a severe case of post-COVID-19 thrombocytopenia in a 79-year-old man and emphasizes its critical nature. Despite negative initial COVID-19 test results, subsequent positive results led to treatment initiation, and severe thrombocytopenia persisted resulting in bleeding complications and death. Recognized as a hematological manifestation of COVID-19, thrombocytopenia in this geriatric patient highlights the need for extended post-COVID-19 monitoring and management. This underscores the importance of vigilance and timely intervention, especially in vulnerable populations, and emphasizes the need for further research to understand the intricate relationship between COVID-19 and thrombocytopenia.

Clinical features and prognostic model for viral encephalitis after allogeneic haematopoietic stem cell transplantation.

The objective of this study was to identify independent prognostic factors of viral encephalitis (VE) after allogeneic haematopoietic stem cell transplantation (allo-HSCT) and establish a prognostic model to identify post-transplant VE patients with a greater likelihood of mortality. Among 5380 patients in our centre from 2014 to 2022, 211 patients who developed VE after allo-HSCT were reviewed in this retrospective study. Prognostic factors were selected, and a prognostic model was constructed using Cox regression analysis. The model was subsequently validated and estimated using the area under the receiver operating characteristic curve (AUC), a calibration plot and decision curve analysis (DCA). Glasgow Coma Scale score <9, lesions >3 lobes on magnetic resonance imaging and severe thrombocytopenia were identified as independent prognostic risk factors for VE patients who underwent allo-HSCT. The prognostic model GTM (GTM is an abbreviation for a model composed of three risk factors: GCS score <9, severe thrombocytopenia [platelet count <20 000 per microliter], and lesions >3 lobes on MRI) was established according to the regression coefficients. The validated internal AUC was 0.862 (95% confidence interval [CI], 0.773-0.950), and the external AUC was 0.815 (95% CI, 0.708-0.922), indicating strong discriminatory ability. Furthermore, we constructed calibration plots that demonstrated good consistency between the predicted outcomes and the observed outcomes. DCA exhibited high accuracy in this system, leading to potential benefits for patients.

Haemorrhagic intracranial complications associated with vaccine-induced thrombocytopenia or central venous thrombosis after COVID-19 vaccination: postulated underlying mechanisms with literature and case review.

Despite the unequivocal medical and social advantages of introducing vaccines against the novel coronavirus SARS-CoV-2, there were also some concerns regarding possible post-vaccination adverse events. Most of these are mild. But in rare cases, severe neurological symptoms including ischaemic stroke, intracranial haemorrhage (ICH), cerebral venous and sinus thrombosis (CVT), and thrombosis with thrombocytopenia (TTS) have been observed. Literature data suggests that thrombosis with thrombocytopenia was the major underlying cause of the ICH; dural venous sinuses/cerebral veins were indicated as the primarily affected sites of thrombosis. Our review confirms the previously documented suspicion that CVT and TTS are most likely to occur following vector-type, rather than mRNA, vaccine administration. The postulated mechanism of TTS is similar to heparin-induced thrombocytopenia (HIT) both clinically and serologically. Although ICH and VITT are very rare side effects of the COVID-19 vaccine, for patients with risk factors for thrombosis (e.g. pregnancy), physicians should carefully consider the benefit/risk ratio of vaccination.

Outcomes and prognostic factors for survival of children with oesophageal atresia.

INTRODUCTION: Oesophageal atresia (EA) is a life-threatening congenital oesophageal deformity that causes considerable newborn morbidity and death. Many prognostic variables have been linked to the survival of infants with EA, although the results of the studies are still conflicting. Furthermore, studies on EA effects in developing countries still need to be included. Here, we aimed to determine the survival of children with EA and link it to prognostic variables in a particular developing country. MATERIALS AND METHODS: A cross-sectional observational retrospective study was conducted using medical records of paediatric patients with EA at our institution from January 2014 to December 2020. RESULTS: A total of 53 children with EA were included in the study. Log-rank analysis showed that definitive surgery and thrombocytopenia were significantly associated with the survival of children with EA, with a p-value of 0.007 and 0.002, respectively, whereas, sex, EA type, pneumonia and sepsis were not (p = 0.898, 0.919, 0.255, and 0.499, respectively). Multivariate analysis revealed that thrombocytopenia and definitive surgery were strongly associated with the survival of children with EA with a pvalue of 0.014 (hazard ratio (HR) = 2.67 [95% confidence interval (CI) = 1.22-5.85]) and 0.022 (HR =0.39 [95% CI = 0.17- 0.87]), respectively. CONCLUSION: Our study shows that thrombocytopenia might increase mortality, while definitive surgery might be beneficial for the survival of paediatric patients with EA. It implies that definitive surgery should be performed as early as necessary to prevent further morbidity and mortality. Our study comprehensively provides the survival of children with EA and links it to prognostic variables in a particular developing country. It serves as a potential research project that can be applied to the clinical setting to help clinicians manage EA better.

Hantavirus Cardiopulmonary syndrome: Another Reason to Avoid Mice.

Hantavirus cardiopulmonary syndrome is a severe illness transmitted by rodent excretions. We describe a case of a 24-year-old man who presented to the emergency department with cough, shortness of breath, chills, myalgias, nausea, and diarrhea. Physical examination and laboratory analysis revealed signs of respiratory distress and thrombocytopenia. The trajectory of his illness led to acute respiratory distress syndrome (ARDS) and hemodynamic instability. Serum testing was positive for hantavirus IgM and IgG antibodies. The patient was managed with supportive care and improved. This case highlights the importance of considering hantavirus when managing patients who develop thrombocytopenia, ARDS, and hemodynamic instability in the appropriate clinical setting.

Eighty-six cases of clinical characteristics and outcomes of systemic lupus erythematosus-associated macrophage activation syndrome: A meta-analysis study.

OBJECTIVE: To improve our understanding of systemic lupus erythematosus (SLE)-macrophage activation syndrome (MAS). METHODS: A systematic review was performed, to retrieve all those papers on patients with SLE-MAS, in individual or aggregated form. The data in each of these medical records were extracted and analyzed to identify the characteristics of SLE-MAS. RESULTS: A total of 86 SLE-MAS patients were included (25 males and 61 females. The mean (±standard error of the mean) age was 31.21 ± 1.694 years. MAS occurred as the initial presentation of SLE in 47 people (54.65%) and during the course of SLE in 39 (45.35%). A coinfection was reported in 23 (26.74%) patients. The mean Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score was 16.54 ± 0.9462. Overall, 10 patients (11.63%) died. The SLEDAI-2K score was higher in patients with MAS as an initial manifestation of SLE than in those where MAS occurred during the course of SLE. The proportion of patients receiving steroid pulse therapy was lower in patients with coinfections. The deceased group demonstrated lower platelet and ferritin levels. Multiple regression analysis revealed that age and thrombocytopenia were independent factors associated with poor prognosis. In receiver operating characteristic analysis, a platelet count cutoff value of ≤47 × 109/L was a predictor of poor outcome. CONCLUSIONS: SLE-MAS patients demonstrated high lupus activity, and lupus activity was especially higher in patients with MAS as an initial manifestation. Lupus activity was the predominant trigger of lupus MAS. Thrombocytopenia was an independent factor for poor prognosis.

DNA damage repair in megakaryopoiesis: molecular and clinical aspects.

INTRODUCTION: Endogenous DNA damage is a significant factor in the damage of hematopoietic cells. Megakaryopoiesis is one of the pathways of hematopoiesis that ends with the production of platelets and plays the most crucial role in hemostasis. Despite the presence of efficient DNA repair mechanisms, some endogenous lesions can lead to mutagenic alterations, disruption of pathways of hematopoiesis including megakaryopoiesis and potentially result in human diseases. AREAS COVERED: The complex regulation of DNA repair mechanisms plays a central role in maintaining genomic integrity during megakaryopoiesis and influences platelet production efficiency and quality. Moreover, anomalies in DNA repair processes are involved in several diseases associated with megakaryopoiesis, including myeloproliferative disorders and thrombocytopenia. EXPERT OPINION: In the era of personalized medicine, diagnosing diseases related to megakaryopoiesis can only be made with a complete assessment of their molecular aspects to provide physicians with critical molecular data for patient management and to identify the subset of patients who could benefit from targeted therapy.

Lowering platelet-count threshold for transfusion in preterm neonates decreases the number of transfusions without increasing severe hemorrhage events.

Thrombocytopenia is common in preterm neonates and can be associated with hemorrhage. Most platelet transfusions are prophylactic. Previously, higher platelet-count thresholds were recommended for neonates, but this recommendation has been questioned in recent studies. In the PlaNeT2 trial, mortality and serious bleeding were more frequent in neonates with the highest platelet-count threshold than in others. Following this trial, we changed our platelet transfusion practice by lowering the platelet-count threshold for prophylactic transfusion from 50,000 to 25,000/mm3. We conducted a before-after retrospective cohort study to quantify the frequency of platelet transfusions and assess the new protocol by analyzing death and serious hemorrhage events. This retrospective monocentric study included neonates born before 37 weeks of gestation with platelet count < 150,000/mm3 during the 2 years preceding the new platelet transfusion protocol (high prophylactic transfusion threshold, 50,000/mm3) and during the 2 years after the new platelet transfusion protocol (low prophylactic transfusion threshold, 25,000/mm3). The primary outcome was the proportion of neonates receiving at least one platelet transfusion in both groups. We also compared the proportion of deaths and severe hemorrhage events. A total of 707 neonates with thrombocytopenia were identified. In the high-threshold group, 99/360 (27.5%) received at least one platelet transfusion as compared with 56/347 (16.1%) in the low-threshold group (p < 0.001). The groups did not differ in proportion of deaths or severe hemorrhage events. CONCLUSIONS: A reduced platelet-count threshold for transfusion allowed for a significant reduction in the number of platelet transfusions without increasing severe hemorrhage events. WHAT IS KNOWN: • A recent randomized trial suggested that restrictive platelet-count thresholds for platelet transfusion could be beneficial for preterm neonates. WHAT IS NEW: • On lowering the platelet-count threshold for transfusion from 50,000 to 25,000/mm3, the number of transfusions significantly decreased without increasing severe hemorrhage events in a neonatal intensive care unit.

Comparison of laser and traditional lancing devices for capillary blood sampling in patients with diabetes mellitus and high bleeding risk.

PURPOSE: Despite the importance of self-monitoring blood glucose (SMBG) for management of diabetes mellitus (DM), frequent blood sampling is discouraged by bleeding risk due to dual-antiplatelet agent therapy (DAPT) or thrombocytopenia. METHODS: We compared the bleeding time (BT) of sampling by using a laser-lancing-device (LMT-1000) and a conventional lancet in patients with DM and thrombocytopenia or patients undergoing DAPT. BT was measured using the Duke method, and pain and satisfaction scores were assessed using numeric rating scale (NRS) and visual analog scale (VAS). The consistency in the values of glucose and glycated-hemoglobin (HbA1c) sampled using the LMT-1000 or lancet were compared. RESULTS: The BT of sampling with the LMT-1000 was shorter than that with the lancet in patients with thrombocytopenia (60s vs. 85s, P = 0.024). The NRS was lower and the VAS was higher in laser-applied-sampling than lancet-applied sampling in the DAPT-user group (NRS: 1 vs. 2, P = 0.010; VAS: 7 vs. 6, P = 0.003), whereas the group with thrombocytopenia only showed improvement in the VAS score (8 vs. 7, P = 0.049). Glucose and HbA1c sampled by the LMT-1000 and lancet were significantly correlated in both the DAPT-user and the thrombocytopenia groups. CONCLUSION: The LMT-1000 can promote SMBG by shortening BT in subject with thrombocytopenia and by increasing satisfaction score, as well as by showing reliable glucose and HbA1c value.

[Clinical management of thrombocytopenia in cirrhosis].

Thrombocytopenia is one of the common complications of cirrhotic patients, which can induce an increasing bleeding risk and closely correlate with bleeding following invasive procedures. Consequently, how to respond to thrombocytopenia is crucial for improving the prognosis of patients with cirrhosis. This article reviews the main mechanisms of cirrhosis concurrent with thrombocytopenia, as well as the corresponding clinical management strategies.

[Pay attention to the diagnosis and treatment of "easily neglected" complications in liver cirrhosis].

Managing cirrhosis complications is an important measure for improving patients' clinical outcomes. Therefore, in order to provide a complete disease assessment and comprehensive treatment, improve quality of life, and improve the prognosis for patients with cirrhosis, it is necessary to pay attention to complications such as thrombocytopenia and portal vein thrombosis in addition to common or severe complications such as ascites, esophagogastric variceal bleeding, hepatic encephalopathy, and hepatorenal syndrome. The relevant concept that an effective albumin concentration is more helpful in predicting the cirrhosis outcome is gradually being accepted; however, the detection method still needs further standardization and commercialization.

[An analysis of related factors in thrombocytopenia combined with cirrhosis: a cross-sectional study of 2 517 cases].

Objective: To explore the related factors of thrombocytopenia (TCP) occurrence in patients with cirrhosis. Methods: A cross-sectional study was conducted. Inpatients with an initial diagnosis of cirrhosis at Peking University First Hospital from January 1, 2010 to December 31, 2020 were included. Clinical data such as demographic characteristics, etiology of cirrhosis, complications of cirrhosis, laboratory indicators, Child-Pugh grade, invasive procedures, and mortality during hospitalization were collected. A logistic regression model was used to explore the related factors of TCP occurrence in patients with cirrhosis. Categorical variables were compared by the χ(2) test. The inter-group comparison was performed using continuous variables, a t-test, one-way analysis of variance (ANOVA), or a nonparametric test. Results: There were a total of 2 592 cases of cirrhosis. 75 cases with incomplete clinical data were excluded. 2 517 cases were included for analysis. The median age was 58 (50, 67) years. Males accounted for 64%. 1 435 cases (57.0%) developed TCP, and 434 cases (17.2%) had grade 3-4 TCP. Gender, primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and concomitant esophagogastric varices (EGV) were the major factors associated with TCP. Females were more prone to combine with TCP (OR=1.32, 95%CI: 1.12-1.56, P=0.001). Patients combined with EGV (OR=3.09, 95%CI: 2.63-3.65, P<0.001) were more prone to develop TCP, which was associated with the increased incidence of hypersplenism (P<0.001). Patients with PBC (OR=0.64, 95%CI: 0.50-0.82, P<0.001) and PSC (OR=0.23, 95%CI: 0.06-0.65, P=0.010) were less prone to develop TCP, which was due to the shorter prothrombin time and better coagulation function of PBC patients (P<0.001), and the lower proportion of hypersplenism in combined PSC patients (P=0.004). Patients with TCP and grade 3-4 TCP had a higher rate of hemostatic procedures (P<0.05), but a lower rate of liver biopsy (P<0.05). Patients with grade 3-4 TCP had a higher nosocomial mortality rate compared to those without (P=0.004). Conclusion: TCP is common in patients with cirrhosis. However, TCP occurrence is higher in female patients with EGV and lower in patients combined with PBC and PSC. TCP affects invasive procedures and is associated with adverse outcomes.

Neuraxial Anesthesia Following Thrombocyte Transfusion in Women with Severe Thrombocytopenia Prior to a Cesarean Delivery: A Retrospective Study and Literature Review.

BACKGROUND: Cesarean delivery (CD) is one of the most common surgeries performed worldwide, with increasing yearly rates. Although neuraxial techniques remain the preferred anesthesia method for CD, maternal thrombocytopenia remains a prominent contraindication. Formation of spinal\epidural hematomas are extremely rare, however the minimal thrombocyte count required for safe neuraxial anesthesia is still under debate. Although transfusion of thrombocytes for the purpose of neuraxial anesthesia is still not recommended, patients with severe thrombocytopenia (less than 50 × 103/uL) are given thrombocyte transfusion for surgical hemostasis. OBJECTIVES: To evaluate the anesthetic approach to caesarean deliveries in parturients with severe thrombocytopenia who received thrombocyte transfusion aimed for improved surgical hemostasis. METHODS: We conducted a single center, retrospective cohort study. Results: A total of five cases were found, four of which were given spinal anesthesia immediately following thrombocyte transfusion. One patient was denied spinal anesthesia because her thrombocyte count following transfusion failed to reach safe levels. None of our cases had anesthesia-related complications recorded. CONCLUSIONS: We examined the anesthetic management parturients with severe thrombocytopenia who needed cesarean delivery and were transfused with thrombocytes for surgical hemostasis. In such cases, spinal anesthesia may be considered due to the serious risks associated with general anesthesia.

Diagnosis and management of Evans syndrome in adults: first consensus recommendations.

Evans syndrome is a rare disease marked by a severe clinical course, high relapse rate, infectious and thrombotic complications, and sometimes fatal outcome. Management is highly heterogeneous. There are several case reports but few large retrospective studies and no prospective or randomised trials. Here, we report the results of the first consensus-based expert recommendations aimed at harmonising the diagnosis and management of Evans syndrome in adults. After reviewing the literature, we used a fuzzy Delphi consensus method, with two rounds of a 42-item questionnaire that were scored by a panel of 13 international experts from five countries using a 7-point Likert scale. Panellists were selected by the core panel on the basis of their personal experience and previous publications on Evans syndrome and immune cytopenias; they met virtually throughout 2023. The panellists recommended extensive clinical and laboratory diagnostic tests, including bone marrow evaluation and CT scan, and an aggressive front-line therapy with prednisone (with or without intravenous immunoglobulins), with different treatment durations and tapering for immune thrombocytopenia and autoimmune haemolytic anaemias (AIHAs). Rituximab was strongly recommended as first-line treatment in cold-type AIHA and as second-line treatment in warm-type AIHA and patients with immune thrombocytopenia and antiphospholipid antibodies, previous thrombotic events, or associated lymphoproliferative diseases. However, rituximab was discouraged for patients with immunodeficiency or severe infections, with the same applying to splenectomy. Thrombopoietin receptor agonists were recommended for chronic immune thrombocytopenia and in the case of previous grade 4 infection. Fostamatinib was recommended as third-line or further-line treatment and suggested as second-line therapy for patients with previous thrombotic events. Immunosuppressive agents have been moved to third-line or further-line treatment. The panellists recommended the use of recombinant erythropoietin in AIHA in the case of inadequate reticulocyte counts, use of the complement inhibitor sutimlimab for relapsed cold AIHA, and the combination of rituximab plus bendamustine in Evans syndrome secondary to lymphoproliferative disorders. Finally, recommendations were given for supportive therapy, platelet or red blood cell transfusions, and thrombotic and antibiotic prophylaxis. These consensus-based recommendations should facilitate best practice for diagnosis and management of Evans syndrome in clinical practice.