Altered Fc glycosylation of anti-HLA alloantibodies in hemato-oncological patients receiving platelet transfusions

Background: The formation of alloantibodies directed against class I human leukocyte antigens (HLA) continues to be a clinically challenging complication after platelet transfusions, which can lead to platelet refractoriness (PR) and occurs in approximately 5%–15% of patients with chronic platelet support. Interestingly, anti-HLA IgG levels in alloimmunized patients do not seem to predict PR, suggesting functional or qualitative differences among anti-HLA IgG. The binding of these alloantibodies to donor platelets can result in rapid clearance after transfusion, presumably via FcγR-mediated phagocytosis and/or complement activation, which both are affected by the IgG-Fc glycosylation. Objectives: To characterize the Fc glycosylation profile of anti-HLA class I antibodies formed after platelet transfusion and to investigate its effect on clinical outcome. Patients/Methods: We screened and captured anti-HLA class I antibodies (anti-HLA A2, anti-HLA A24, and anti-HLA B7) developed after platelet transfusions in hemato-oncology patients, who were included in the PREPAReS Trial. Using liquid chromatography-mass spectrometry, we analyzed the glycosylation profiles of total and anti-HLA IgG1 developed over time. Subsequently, the glycosylation data was linked to the patients' clinical information and posttransfusion increments. Results: The glycosylation profile of anti-HLA antibodies was highly variable between patients. In general, Fc galactosylation and sialylation levels were elevated compared to total plasma IgG, which correlated negatively with the platelet count increment. Furthermore, high levels of afucosylation were observed for two patients. Conclusions: These differences in composition of anti-HLA Fc-glycosylation profiles could potentially explain the variation in clinical severity between patients

The quality of platelet concentrates related to corrected count increment: linking in vitro to in vivo

BACKGROUND: Storage of platelet concentrates (PCs) results in reduced recovery and survival of transfused platelets (PLTs). Upon storage PLTs develop storage lesion that can be monitored by several laboratory tests. However, correlation of these descriptive tests with corrected count increments (CCIs), a marker frequently used to establish the effectiveness of PLT transfusions, is limited or unknown. This study investigated to what extent a functional test or a combined in vitro rating score improves the correlation of laboratory tests with 1-hour CCI. STUDY DESIGN AND METHODS: PCs were analyzed using six different laboratory tests (n = 119) before transfusion in a prophylactic setting to 74 hematooncologic patients. Linear regression and Spearman correlation were used to determine associations between descriptive (either separately or combined in an in vitro rating score) or functional test results and 1-hour CCIs obtained after transfusion. RESULTS: CD62P expression (r = −0.45), annexin V binding (r = −0.36), the updated in vitro rating score (r = 0.50), and PLT responsiveness after thrombin receptor activator for peptide-6 (TRAP) (r = 0.43-0.57) or adenosine diphosphate stimulation (r = 0.11-0.51) significantly correlated to 1-hour CCIs obtained after transfusion, whereas lactate concentration, ThromboLUX score, and thromboelastography measurements did not. The strongest correlations were observed for in vitro rating score and PLT responsiveness after TRAP stimulation and these tests could explain 24 and 33% of the observed variation in 1-hour CCI, respectively. CONCLUSION: Combining descriptive markers in one in vitro rating score improved correlation to 1-hour CCI compared to the tests separately. Of all tests investigated, mean PLT responsiveness after TRAP stimulation showed the strongest clinical correlation and was best able to predict the 1-hour CCI

Reported transfusion-related acute lung injury associated with solvent/detergent plasma – A case series

Background: Antibody-mediated transfusion-related acute lung injury (TRALI) is caused by donor HLA or HNA antibodies in plasma-containing products. In the Netherlands 55,000 units of solvent/detergent plasma (SDP), a pooled plasma product, are transfused yearly. It's produced by combining plasma from hundreds of donors, diluting harmful antibodies. Due to a lack of reported cases following implementation, some have labeled SDP as “TRALI safe”. Study design and methods: Pulmonary transfusion reactions involving SDP reported to the Dutch national hemovigilance network in 2016–2019 were reviewed. Reporting hospitals were contacted for additional information, cases with TRALI and imputability definite, probable, or possible were included and informed consent was sought. Results: A total of three TRALI and nine TACO cases were reported involving SDP. The imputability of one TRALI case was revised from possible to unlikely and excluded; in one case no informed consent was obtained. We present a case description of TRALI following SDP transfusion in a 69-year-old male, 3 days following endovascular aortic aneurysm repair. The patient received one unit of SDP to correct a heparin-induced coagulopathy, prior to removal of a spinal catheter post-operatively. Within five hours he developed hypoxemic respiratory failure requiring intubation, hypotension, bilateral chest infiltrates, and leucopenia. The patient made a full recovery. Conclusion: This case of TRALI, following transfusion of a single unit of SDP to a patient without ARDS risk factors, demonstrates that TRALI can occur with this product. Clinicians should remain vigilant and continue to report suspected cases, to help further understanding of SDP-associated TRALI

The identification of cases of major hemorrhage during hospitalization in patients with acute leukemia using routinely recorded healthcare data

INTRODUCTION: Electronic health care data offers the opportunity to study rare events, although detecting these events in large datasets remains difficult. We aimed to develop a model to identify leukemia patients with major hemorrhages within routinely recorded health records. METHODS: The model was developed using routinely recorded health records of a cohort of leukemia patients admitted to an academic hospital in the Netherlands between June 2011 and December 2015. Major hemorrhage was assessed by chart review. The model comprised CT-brain, hemoglobin drop, and transfusion need within 24 hours for which the best discriminating cut off values were taken. External validation was performed within a cohort of two other academic hospitals. RESULTS: The derivation cohort consisted of 255 patients, 10,638 hospitalization days, of which chart review was performed for 353 days. The incidence of major hemorrhage was 0.22 per 100 days in hospital. The model consisted of CT-brain (yes/no), hemoglobin drop of ≥0.8 g/dl and transfusion of ≥6 units. The C-statistic was 0.988 (CI 0.981-0.995). In the external validation cohort of 436 patients (19,188 days), the incidence of major hemorrhage was 0.46 per 100 hospitalization days and the C-statistic was 0.975 (CI 0.970-0.980). Presence of at least one indicator had a sensitivity of 100% (CI 95.8-100) and a specificity of 90.7% (CI 90.2-91.1). The number of days to screen to find one case decreased from 217.4 to 23.6. INTERPRETATION: A model based on information on CT-brain, hemoglobin drop and need of transfusions can accurately identify cases of major hemorrhage within routinely recorded health records

The identification of cases of major hemorrhage during hospitalization in patients with acute leukemia using routinely recorded healthcare data

INTRODUCTION: Electronic health care data offers the opportunity to study rare events, although detecting these events in large datasets remains difficult. We aimed to develop a model to identify leukemia patients with major hemorrhages within routinely recorded health records. METHODS: The model was developed using routinely recorded health records of a cohort of leukemia patients admitted to an academic hospital in the Netherlands between June 2011 and December 2015. Major hemorrhage was assessed by chart review. The model comprised CT-brain, hemoglobin drop, and transfusion need within 24 hours for which the best discriminating cut off values were taken. External validation was performed within a cohort of two other academic hospitals. RESULTS: The derivation cohort consisted of 255 patients, 10,638 hospitalization days, of which chart review was performed for 353 days. The incidence of major hemorrhage was 0.22 per 100 days in hospital. The model consisted of CT-brain (yes/no), hemoglobin drop of ≥0.8 g/dl and transfusion of ≥6 units. The C-statistic was 0.988 (CI 0.981-0.995). In the external validation cohort of 436 patients (19,188 days), the incidence of major hemorrhage was 0.46 per 100 hospitalization days and the C-statistic was 0.975 (CI 0.970-0.980). Presence of at least one indicator had a sensitivity of 100% (CI 95.8-100) and a specificity of 90.7% (CI 90.2-91.1). The number of days to screen to find one case decreased from 217.4 to 23.6. INTERPRETATION: A model based on information on CT-brain, hemoglobin drop and need of transfusions can accurately identify cases of major hemorrhage within routinely recorded health records

A predictive model for estimating the number of erythrocytapheresis or phlebotomy treatments for patients with naïve hereditary hemochromatosis

Item does not contain fulltextBACKGROUND AND AIMS: Standard treatment for naïve hereditary hemochromatosis patients consists of phlebotomy or a personalized erythrocytapheresis. Erythrocytapheresis is more efficient, but infrequently used because of perceived costs and specialized equipment being needed. The main aim of our study was to develop a model that predicts the number of initial treatment procedures for both treatment methods. This information may help the clinician to select the optimal treatment modality for the individual patient. METHODS: We analyzed retrospective data of 125 newly diagnosed patients (C282Y homozygous), treated either with phlebotomy (n = 54) or erythrocytapheresis (n = 71) until serum ferritin (SF) reached levels ≤100 μg/L. To estimate the required number of treatment procedures multiple linear regression analysis was used for each treatment method separately. RESULTS: The linear regression model with the best predictive quality (R(2)  = 0.74 and 0.73 for erythrocytapheresis and phlebotomy respectively) included initial SF, initial hemoglobin (Hb) level, age, and BMI, where initial SF was independently related to the total number of treatment procedures for both treatment methods. The prediction error expressed in RMSPE and RMSDR was lower for erythrocytapheresis than for phlebotomy (3.8 and 4.1 vs 7.0 and 8.0 respectively), CONCLUSIONS: Although the prediction error of the developed model was relatively large, the model may help the clinician to choose the most optimal treatment method for an individual patient. Generally erythrocytapheresis halves the number of treatment procedures for all patients, where the largest reduction (between 55% and 64%) is reached in patients with an initial Hb level ≥ 9 mmol/L (14.5 g/dL). ClinicalTrials.gov number NCT00202436

The association between haemorrhage and markers of endothelial insufficiency and inflammation in patients with hypoproliferative thrombocytopenia:a cohort study

In daily haematological practice, predicting bleeding in thrombocytopenic patients is difficult, and clinicians adhere to transfusion triggers to guide patients through the aplastic phase of chemotherapy. Platelet count is not the only determinant of bleeding and additional mechanisms for impending haemostasis are likely. Beside clot formation, platelets are essential for the maintenance of integrity of vascular beds. We therefore prospectively investigated associations between biomarkers for endothelial damage (urine albumin excretion) and inflammation (C-reactive protein) and bleeding (WHO grading) in 88 patients with 116 on-protocol episodes. We found an increase in grade 2 bleeding with a higher urine albumin/creatinine ratio one day after the measurement [odds ratio (OR) 1 center dot 24 for every doubling of the ratio, 95% CI 1 center dot 05-1 center dot 46, P-value 0 center dot 01] and a 29% increase in the odds of grade 2 bleeding for every doubling of serum C-reactive protein (CRP) (95% CI 1 center dot 04-1 center dot 60, P-value 0 center dot 02) after correction for morning platelet count. The 24 h post-transfusion corrected count increment (CCI24) showed a significant association with these biomarkers: increasing urine albumin/creatinine ratio and CRP were associated with lower CCI24. We report two inexpensive and easy-to-apply biomarkers that could be useful in designing a prediction model for bleeding risk in thrombocytopenic patients

Zoonotic Infection With Pigeon Paramyxovirus Type 1 Linked to Fatal Pneumonia

The characteristics and risk factors of pigeon paramyxovirus type 1 (PPMV-1) infection in humans are poorly known. We performed virological, pathological, and epidemiological analyses of a Dutch case, and compared the results with those of a US case. Both infections occurred in transplant patients under immunosuppressive therapy and caused fatal respiratory failure. Both virus isolates clustered with PPMV-1, which has pigeons and doves as reservoir. Experimentally inoculated pigeons became infected and transmitted the virus to naive pigeons. Both patients were likely infected by contact with infected pigeons or doves. Given the large populations of feral pigeons with PPMV-1 infection in cities, increasing urbanization, and a higher proportion of immunocompromised individuals, the risk of severe human PPMV-1 infections may increase. We recommend testing for avian paramyxovirus type 1, including PPMV-1, in respiratory disease cases where common respiratory pathogens cannot be identified

Storage time of platelet concentrates and risk of a positive blood culture:a nationwide cohort study

Clinical epidemiolog