Interference of bovine hemoglobin-based oxygen carrier-201 (Hemopure) on four hematology analyzers

Introduction: Hemoglobin-based oxygen carriers, for example HBOC-201 (Hemopure), are aimed to bridge acute anemia when blood transfusion is not available or refused by the patient. However, since HBOC-201 appears free in plasma, it interferes with laboratory tests. This study presents an overview of HBOC-201 interference on four commonly used hematology analyzers and suggests treatment monitoring possibilities. Methods: Blood samples were spiked with therapeutic doses of HBOC-201 and nine hematology parameters were measured with the Sysmex XN-20, Siemens Advia 2120i, Abbott Alinity Hq and Abbot Cell Dyn Sapphire hematology analyzers. The results were compared to control samples and the bias was determined. Results: Most parameters, including all cell counts, hematocrit and MCV, showed a non-significant bias compared to control. However, the standard, total hemoglobin (Hb) measurement as well as MCH and MCHC showed poor agreement with control, as HBOC-201 was included in this measurement. Yet, the flow cytometry-based Hb method quantified intracellular Hb in spiked samples, excluding HBOC-201. Conclusion: Of all included hematology parameters, only total Hb and the associated MCH and MCHC suffered from interference. In contrast, the flow cytometry-based Hb measurement provided an accurate measure of intracellular Hb. The difference between total Hb and cellular Hb represents the HBOC-201 concentration and can be used to monitor HBOC-201 treatment.</p

Knowledge gaps in health-related quality of life research performed in children with bleeding disorders – A scoping review

Introduction: Bleeding disorders (BDs) may influence health-related quality of life (HRQoL) in children and caregivers. Measuring HRQoL gives insight into domains requiring support and provides an opportunity to evaluate the effects of novel therapies. Aim: To gain insight in the current body of literature on HRQoL in children with BDs in order to identify knowledge gaps for research and further development of this field. Methods: Scoping review. Results: We included 53 articles, describing studies mainly performed in Europe and North–America (60.4%) and mostly within the last ten years. Only 32% studies included children &lt;4 years. Almost all studies (47/53, 88.7%) were performed in boys with haemophilia, pooling haemophilia A and B (n = 21) and different disease severities (n = 20). Thirteen different generic and five disease-specific HRQoL-questionnaires were applied; all questionnaires were validated for haemophilia specifically. Six (11,3%) combined generic and disease-specific questionnaires. Self-reports were most frequently applied (40/53, 75.5%), sometimes combined with proxy and/or parent-reports (17/53, 32.1%). Eleven studies used a reference group (20.8%). Statistical analyses mostly consisted of mean and SD (77.4%).Conclusion: HRQoL-research is mainly performed in school-aged boys with haemophilia, treated in developed countries. Pitfalls encountered are the pooling of various BDs, subtypes and severities, as well as the application of multiple generic questionnaires prohibiting comparison of results. More attention is needed for broader study populations including other BDs, young children, feminine such as young children, feminine bleeding issues and platelet disorders, as well as the use of HRQoL as an effect-measurement tool for medical interventions, and more thorough statistical analysis.</p

Knowledge gaps in health-related quality of life research performed in children with bleeding disorders – A scoping review

Introduction: Bleeding disorders (BDs) may influence health-related quality of life (HRQoL) in children and caregivers. Measuring HRQoL gives insight into domains requiring support and provides an opportunity to evaluate the effects of novel therapies. Aim: To gain insight in the current body of literature on HRQoL in children with BDs in order to identify knowledge gaps for research and further development of this field. Methods: Scoping review. Results: We included 53 articles, describing studies mainly performed in Europe and North–America (60.4%) and mostly within the last ten years. Only 32% studies included children &lt;4 years. Almost all studies (47/53, 88.7%) were performed in boys with haemophilia, pooling haemophilia A and B (n = 21) and different disease severities (n = 20). Thirteen different generic and five disease-specific HRQoL-questionnaires were applied; all questionnaires were validated for haemophilia specifically. Six (11,3%) combined generic and disease-specific questionnaires. Self-reports were most frequently applied (40/53, 75.5%), sometimes combined with proxy and/or parent-reports (17/53, 32.1%). Eleven studies used a reference group (20.8%). Statistical analyses mostly consisted of mean and SD (77.4%).Conclusion: HRQoL-research is mainly performed in school-aged boys with haemophilia, treated in developed countries. Pitfalls encountered are the pooling of various BDs, subtypes and severities, as well as the application of multiple generic questionnaires prohibiting comparison of results. More attention is needed for broader study populations including other BDs, young children, feminine such as young children, feminine bleeding issues and platelet disorders, as well as the use of HRQoL as an effect-measurement tool for medical interventions, and more thorough statistical analysis.</p

Interference of bovine hemoglobin-based oxygen carrier-201 (Hemopure) on four hematology analyzers

Introduction: Hemoglobin-based oxygen carriers, for example HBOC-201 (Hemopure), are aimed to bridge acute anemia when blood transfusion is not available or refused by the patient. However, since HBOC-201 appears free in plasma, it interferes with laboratory tests. This study presents an overview of HBOC-201 interference on four commonly used hematology analyzers and suggests treatment monitoring possibilities. Methods: Blood samples were spiked with therapeutic doses of HBOC-201 and nine hematology parameters were measured with the Sysmex XN-20, Siemens Advia 2120i, Abbott Alinity Hq and Abbot Cell Dyn Sapphire hematology analyzers. The results were compared to control samples and the bias was determined. Results: Most parameters, including all cell counts, hematocrit and MCV, showed a non-significant bias compared to control. However, the standard, total hemoglobin (Hb) measurement as well as MCH and MCHC showed poor agreement with control, as HBOC-201 was included in this measurement. Yet, the flow cytometry-based Hb method quantified intracellular Hb in spiked samples, excluding HBOC-201. Conclusion: Of all included hematology parameters, only total Hb and the associated MCH and MCHC suffered from interference. In contrast, the flow cytometry-based Hb measurement provided an accurate measure of intracellular Hb. The difference between total Hb and cellular Hb represents the HBOC-201 concentration and can be used to monitor HBOC-201 treatment

Should HLA and HPA-matched platelet transfusions for patients with Glanzmann Thrombasthenia or Bernard-Soulier syndrome be standardized care? A Dutch survey and recommendations

Background: Glanzmann thrombasthenia (GT) and Bernard-Soulier syndrome (BSS) patients require frequent platelet transfusions and hence have an increased risk for alloimmunization against donor Human Leukocyte Antigens (HLA) when no HLA-matching is performed. Knowing that Human Platelet Antigens (HPA) are located on the platelet glycoproteins that can be absent in these patients, preventive HPA-matching may also be considered. Uniform recommendations on this topic lack in transfusion guidelines making standard practice unclear, therefore, we aimed to provide a framework for matched platelet transfusions. Study Design and Methods: We conducted a targeted literature search and a national survey of Dutch (pediatric) hematologists from July to September 2021. Results: We found 20 articles describing platelet transfusion policies in 483 GT-patients and 29 BSS-patients, both adults and children. Twenty surveys were returned for full analysis. All responders treated patients with platelet disorders, including GT (n = 36 reported) and BSS (n = 29 reported). Of respondents, 75% estimated the risk of antibody formation as “likely” for HLA and 65% for HPA. Formation of HLA antibodies was reported in 5 GT and in 5 BSS-patients, including one child. Fifteen respondents gave preventive HLA-matched platelets in elective setting (75%). Three respondents additionally matched for HPA in GT-patients (15%). Main argument for matched platelet transfusions was preventing alloimmunization to safeguard the effectivity of ‘random’ donor-platelets in acute settings. Conclusion: Elective HLA-matching for GT and BSS-patients is already conducted by most Dutch (pediatric) hematologists. HPA-matching is mainly applied when HPA-antibodies are formed. Based on the current literature and the survey, recommendations are proposed.</p

Should HLA and HPA-matched platelet transfusions for patients with Glanzmann Thrombasthenia or Bernard-Soulier syndrome be standardized care? A Dutch survey and recommendations

Background: Glanzmann thrombasthenia (GT) and Bernard-Soulier syndrome (BSS) patients require frequent platelet transfusions and hence have an increased risk for alloimmunization against donor Human Leukocyte Antigens (HLA) when no HLA-matching is performed. Knowing that Human Platelet Antigens (HPA) are located on the platelet glycoproteins that can be absent in these patients, preventive HPA-matching may also be considered. Uniform recommendations on this topic lack in transfusion guidelines making standard practice unclear, therefore, we aimed to provide a framework for matched platelet transfusions. Study Design and Methods: We conducted a targeted literature search and a national survey of Dutch (pediatric) hematologists from July to September 2021. Results: We found 20 articles describing platelet transfusion policies in 483 GT-patients and 29 BSS-patients, both adults and children. Twenty surveys were returned for full analysis. All responders treated patients with platelet disorders, including GT (n = 36 reported) and BSS (n = 29 reported). Of respondents, 75% estimated the risk of antibody formation as “likely” for HLA and 65% for HPA. Formation of HLA antibodies was reported in 5 GT and in 5 BSS-patients, including one child. Fifteen respondents gave preventive HLA-matched platelets in elective setting (75%). Three respondents additionally matched for HPA in GT-patients (15%). Main argument for matched platelet transfusions was preventing alloimmunization to safeguard the effectivity of ‘random’ donor-platelets in acute settings. Conclusion: Elective HLA-matching for GT and BSS-patients is already conducted by most Dutch (pediatric) hematologists. HPA-matching is mainly applied when HPA-antibodies are formed. Based on the current literature and the survey, recommendations are proposed.</p

Pediatric Fibrinogen PART I-Pitfalls in Fibrinogen Evaluation and Use of Fibrinogen Replacement Products in Children

Fibrinogen is a key coagulation protein, playing a critical role in hemostasis. It is the first factor to decrease to critical levels during bleeding. Hypofibrinogenemia is an important risk factor for bleeding in clinical settings, including pediatric surgery. Yet, the optimal measurement of fibrinogen levels is subject to debate, as is the critical threshold for intervention. Fibrinogen replacement may be provided by cryoprecipitate and fibrinogen concentrate. Whilst both products contain fibrinogen, they are not equivalent, each has its own advantages and disadvantages, especially for pediatric use. Unfortunately, medical literature to support fibrinogen replacement in children is limited. In this article we review the current diagnostic tools to measure fibrinogen, with respect to their use in the pediatric critical care setting. Secondly, we evaluate the different fibrinogen replacement therapies, focusing on cryoprecipitate and fibrinogen concentrate and examine their individual product characteristics, associated risks and benefits, different dosing strategies and specific pitfalls for use in children. We summarize by highlighting current knowledge gaps and areas for future research

Acute haemolytic transfusion reaction after transfusion of fresh frozen plasma in a neonate—Preventable by using solvent/detergent-treated pooled plasma?

Background: Plasma is a commonly used blood product and is available in the form of fresh frozen plasma (FFP) or pooled solvent/detergent-treated plasma. In the Netherlands, solvent/detergent-treated plasma has become the standard product in the adult population since several years, but for neonatal use, FFP remains the product of preference. Description: A preterm neonate developed lung bleeding at day 8 postpartum, for which intubation and mechanical ventilation was required and transfusions with packed red blood cells and plasma, in the form of FFP, were given. Five hours after transfusion, a red discoloration of the urine occurred. An acute haemolytic transfusion was suspected, confirmed by laboratory investigations (fast decrease in haemoglobin, increased free haemoglobin, decreased haptoglobin, increased lactate dehydrogenase and a positive direct antiglobulin test [IgG 2+]). Additional research showed that the FFP product contained nonspecific auto-antibodies that reacted with the transfused erythrocytes, most test erythrocytes and the donor's own erythrocytes. Conclusion: A neonate experienced an acute haemolytic reaction, most probably caused by administrating a FFP product containing auto-antibodies. If transfused with solvent/detergent-treated plasma, such antibodies would have been diluted or captured. This case adds a new argument to the discussion on expanding the use of solvent/detergent-treated plasma to the paediatric population