Risk Of Hemolysis Research Articles

Risk of hemolysis in Plasmodium vivax malaria patients receiving standard primaquine treatment in a population with high prevalence of G6PD deficiency.

Primaquine is essential for the radical cure of Plasmodium vivax malaria, but it poses a potential danger of severe hemolysis in G6PD-deficient (G6PDd) patients. This study aimed to determine whether primaquine is safe in a population with high G6PD prevalence but lacking G6PD diagnosis capacity. In Myanmar, 152 vivax patients were gender- and age-matched at 1:3 for G6PDd versus G6PD-normal (G6PDn). Their risk of acute hemolysis was followed for 28days after treatment with the standard chloroquine and 14-day primaquine (0.25mg/kg/day) regimen. Patients anemic and non-anemic at enrollment showed a rising and declining trend in the mean hemoglobin level, respectively. In males, the G6PDd group showed substantially larger magnitudes of hemoglobin reduction and lower hemoglobin nadir levels than the G6PDn group, but this trend was not evident in females. Almost 1/3 of the patients experienced clinically concerning declines in hemoglobin, with five requiring blood transfusion. The standard 14-day primaquine regimen carries a significant risk of acute hemolytic anemia (AHA) in vivax patients without G6PD testing in a population with a high prevalence of G6PD deficiency and anemia. G6PD testing would avoid most of the clinically significant Hb reductions and AHA in male patients.

Functionalized Erythrocyte Membrane-Coated Nanoparticles for the Treatment of Klebsiella pneumoniae-Induced Sepsis.

Sepsis is a systemic inflammatory response syndrome caused by infection, with high incidence and mortality. Therefore, it is necessary to carry out an effective anti-infection treatment. In this work, we designed and synthesized red blood cell (RBC) membrane-coated PLGA nanoparticles named γ3-RBCNPs, which target the highly expressed intercellular adhesion molecule-1 (ICAM-1) at the site of infection through the γ3 peptide on its surface and kill the Klebsiella pneumoniae through ciprofloxacin encapsulated in its core. In addition, the homogenous RBC membrane coated on the surface of the nanoparticles helps them avoid immune surveillance and prolong the circulation time of the drug in the body. We found that the γ3-RBCNPs target human umbilical vein endothelial cells (HUVECs) activated by TNF-α in vitro and the infected lung of mice in the sepsis model very well. In vitro evaluation suggested that γ3-RBCNPs have a low risk of acute hemolysis and are less likely to be engulfed by macrophages. In vivo evaluation showed that γ3-RBCNPs has a long half-life and good bio-safety. More importantly, we confirmed that γ3-RBCNPs have the good antibacterial and anti-infection ability in vivo and in vitro. Our research provides a new strategy for the nano-drug treatment of Klebsiella pneumoniae-induced sepsis.

Managing Fatigue in Patients with Paroxysmal Nocturnal Hemoglobinuria: A Patient-Focused Perspective.

The most frequently reported symptom in patients with paroxysmal nocturnal hemoglobinuria (PNH), a disease characterized by complement mediated hemolysis and chronic anemia, is “fatigue”. The latter seems the best word to communicate patient’ perception of personal health status and disease impact on daily living, namely quality of life (QoL). Objectivating QoL and grading patient’s fatigue is one of the most difficult medical tasks given the highly heterogeneous communication skills of patients and caregivers and the multitude of meanings that might be attributed to this term. Along with anemia, QoL in PNH is also affected by the emotional burden of a chronic life-long disease with heterogeneous treatment requirement, risk of hemolytic exacerbations (breakthrough hemolysis) and of thrombosis. In the last decade, structured surveys and scores have been adapted from cancer settings to evaluate fatigue and QoL in patients with PNH, and to assess the benefit of complement inhibitors in this setting. Eculizumab was the first drug utilized and was shown to improve QoL scores in the registrative trials. However, the intravenous fortnightly administration, the presence of residual anemia, and the risk of extravascular hemolysis are some of the unmet needs impacting QoL under eculizumab. Several novel drugs have been designed to improve patients’ convenience and alleviate anemia and fatigue. In this review, we focus on available studies that evaluated fatigue and QoL in PNH patients, and the effect of old and new therapeutic strategies.

Prevalence of glucose 6-phosphate dehydrogenase deficiency in highly malaria-endemic municipalities in the Brazilian Amazon: A region-wide screening study

Difficulties associated with the assessment of glucose-6-phosphate dehydrogenase deficiency (G6PDd), particularly in remote areas, hinders the safe use of 8-aminoquinolines such as primaquine (PQ) and tafenoquine against Plasmodium vivax malaria due to the risk of haemolysis. This cross-sectional study was conducted in 41 malaria-endemic municipalities of six states in the Brazilian Amazon, between 2014 and 2018. Male individuals were screened for G6PDd using the qualitative Fluorescent Spot Test using fingerpick-collected whole blood samples. Point and interval estimates of the G6PDd prevalence were calculated for each state. Deficient samples were genotyped for the most prevalent variants in the Amazon. Frequencies of P. vivax malaria recurrences were estimated for G6PDd and non-G6PDd patients. This is one of the largest surveys ever conducted in Latin America, covering the entire malaria endemic area in the Brazilian Amazon. These results indicate that an important proportion of the population is at risk of hemolysis if exposed to PQ and its congener drug tafenoquine. The adoption of G6PDd screening protocols is essential to ensure the safety of individuals treated with those drugs and should also be considered when implementing malaria elimination strategies. A total of 14,847 individuals were included, of which 5.6% presented G6PDd. The state of Acre had the highest G6PDd prevalence (8.3%), followed by Amapá (5.8%), Pará (5.7%), Rondônia (5.4%), Roraima (4.2%) and Amazonas (4.0%). From 828 genotyped samples, African A+ (6.2%), African A- (39.3%) and wild-type (non-African non-Mediterranean; 54.2%) variants were found. A greater proportion of malaria recurrences was found among G6PD deficient individuals [16.7% vs 4.1%, Risk ratio 3.52 (2.16-5.74) p<0.01]. Brazilian Ministry of Health; Fundação de Amparo à Pesquisa do Estado do Amazonas (FAPEAM).

The effect of the blood sampling method on the risk of mechanical hemolysis of erythrocytes in healthy calves and with endogenous intoxication syndrome

In the conditions of the milk production complex in the Voronezh region, where Holstein cattle are kept, studies were conducted to study the degree of injury to blood cells during its selection by various methods in healthy calves and with endogenous intoxication syndrome. In healthy animals, blood sampling by passive leakage does not affect the membranes of erythrocytes. When using vacuum systems, there are no visual signs (hemolysis) of cell destruction, but changes in their cytoskeleton occur with an increase in the sensitivity of membranes to negative pre-analytical factors. In animals with endogenous intoxication syndrome, there are explicit or hidden destruction of erythrocyte membranes, which are manifested by an increase in the content of extra-erythrocyte hemoglobin, the degree of physiological hemolysis, sensitivity to intra- and extravascular hemolytic factors. As a result, already when selecting blood samples by passive gravity, there is a risk of hemolysis, and when using a vacuum system, it is observed in most samples. Therefore, when examining sick animals, it is necessary to take into account the high probability of laboratory diagnostic error at the pre-analytical stage that occurs due to hemolysis of erythrocytes with hypersensitivity to extravascular cytolytic factors, including mechanical effects during blood sampling.

Cost-effectiveness analysis of G6PD diagnostic test for Plasmodium vivax radical cure in Lao PDR: An economic modelling study.

BackgroundPlasmodium vivax (Pv) infections were 68% of the total malaria burden in Laos in 2019. The parasite causes frequent relapses, which can be prevented by primaquine (PMQ). Testing for glucose-6-phosphate-dehydrogenase (G6PD) deficiency is recommended before giving PMQ to avoid haemolysis. Because of the risk of haemolysis in G6PD intermediate deficiencies among females, Laos uses the PMQ 14-days regimen only in G6PD normal females. Among G6PD point-of-care tests, qualitative tests cannot differentiate between G6PD normal and intermediate females. Quantitative tests are required to differentiate between G6PD normal and intermediate deficiencies. However, the quantitative test lacks the cost-effectiveness evidence necessary for decision-making for large-scale adoption. This study examined the cost-effectiveness of quantitative G6PD test, with either supervised PMQ treatment or unsupervised PMQ treatment, against the usual unsupervised PMQ 8-weeks strategy. Supervised PMQ 8-weeks strategy without G6PD testing was also compared against the unsupervised PMQ 8-weeks strategy since the former had recently been adopted in malaria high burden villages that had village malaria volunteers. A budget impact analysis was conducted to understand the incremental cost and effect needed for a nationwide scale-up of the chosen strategy.MethodsA decision tree model compared the cost-effectiveness of implementing four strategies at one health facility with an average of 14 Pv cases in one year. The strategies were unsupervised PMQ strategy, supervised PMQ strategy, G6PD test with unsupervised PMQ strategy, and G6PD test with supervised PMQ strategy. Disability Adjusted Life Years (DALYs) was the effect measure. Costs were calculated from a payer perspective, and sensitivity analyses were conducted. One Gross Domestic Product (GDP) per capita of Laos was set as the cost-effectiveness threshold. Budget impact analysis was conducted using the health facility wise Pv data in Laos in 2020.FindingsSupervised PMQ strategy was extendedly dominated by G6PD test strategies. When compared against the unsupervised PMQ strategy, both G6PD test strategies were more costly but more effective. Their Incremental Cost-Effectiveness Ratios (ICER) were 96.72US$ for the G6PD test with unsupervised PMQ strategy and 184.86US$ for the G6PD test with supervised PMQ strategy. Both ICERs were lower than one GDP per capita in Laos. Following the sensitivity analysis, low adherence for PMQ 14 days made both G6PD test strategies less cost-effective. The lower the Pv case number reported in a health facility, the higher the ICER was. In the budget impact analysis, the expected budget need was only half a million US$ when the G6PD test rollout was discriminately done depending on the Pv case number reported at the health facilities. Indiscriminate roll out of G6PD test to all health facilities was most expensive with least effect impact.

Simulation of Mechanical Heart Valve Dysfunction and the Non-Newtonian Blood Model Approach

The mechanical heart valve (MHV) is commonly used for the treatment of cardiovascular diseases. Nonphysiological hemodynamic in the MHV may cause hemolysis, platelet activation, and an increased risk of thromboembolism. Thromboembolism may cause severe complications and valve dysfunction. This paper thoroughly reviewed the simulation of physical quantities (velocity distribution, vortex formation, and shear stress) in healthy and dysfunctional MHV and reviewed the non-Newtonian blood flow characteristics in MHV. In the MHV numerical study, the dysfunction will affect the simulation results, increase the pressure gradient and shear stress, and change the blood flow patterns, increasing the risks of hemolysis and platelet activation. The blood flow passes downstream and has obvious recirculation and stagnation region with the increased dysfunction severity. Due to the complex structure of the MHV, the non-Newtonian shear-thinning viscosity blood characteristics become apparent in MHV simulations. The comparative study between Newtonian and non-Newtonian always shows the difference. The shear-thinning blood viscosity model is the basics to build the blood, also the blood exhibiting viscoelastic properties. More details are needed to establish a complete and more realistic simulation.

Risk factors for hemolysis with centrifugal pumps in pediatric extracorporeal membrane oxygenation: Is pump replacement an answer?

Hemolysis during pediatric extracorporeal membrane oxygenation (ECMO) is associated with increased risk for renal failure and mortality. We aim to describe risk factors for hemolysis in pediatric ECMO supported by centrifugal pumps. We conducted an analysis of retrospective data collected at an academic children's hospital from January 2017 to December 2019. Plasma-free hemoglobin (PFH) levels were measured daily, and hemolysis was defined as PFH>50mg/dL. Of 46 ECMO runs over 528 ECMO days, hemolysis occurred in 23 (58%) patients over a total of 40 (8%) ECMO days. In multivariable logistic regression models, VA-ECMO (aOR=4.69, 95% CI: 1.01-21.83) and higher hemoglobin (aOR = 1.38, 95% CI: 1.06-1.81) were independently associated with hemolysis. There were also non-significant trends toward increased risk for hemolysis with higher rotational pump speed (aOR=2.39, 95% CI: 0.75-7.65), higher packed red blood cell transfusions (aOR=1.15, 95% CI: 0.99-1.34), and higher cryoprecipitate transfusions (aOR=2.01, 95% CI: 0.83-4.86). Isolated pump exchanges that were performed in 12 patients with hemolysis led to significant decreases in PFH levels within 24h (89 vs 11mg/dL, p<0.01). Hemolysis is common in pediatric ECMO using centrifugal pumps. Avoidance of high pump speeds and conservative administration of blood products may help to mitigate the risk for hemolysis. Furthermore, pump exchange may be an effective first-line treatment for hemolysis.

Pulmonary Artery Pulsatility Index and Hemolysis during Impella-Incorporated Mechanical Circulatory Support.

Background: Impella is a percutaneous transcatheter left ventricular assist device. Device-related hemolysis is a serious complication that is sometimes encountered depending on the device position, device speed, and support duration. However, the impact of hemodynamics on the occurrence of hemolysis remains unknown. In this study, we aimed to clarify the relationships between hemodynamics, especially right ventricular function, and the occurrence of hemolysis during Impella-incorporated mechanical circulatory support. Methods: Consecutive patients who received Impella (2.5, CP, and 5.0) support at our institute between March 2018 and July 2021 were retrospectively included. The relationships between the pulmonary artery pulsatility index (PAPi) immediately after Impella insertion and the occurrence of hemolysis were investigated. Results: Forty-two patients (median 71 years old, 60% men) were included. Hemolysis occurred in 20 patients (48%). A cutoff of PAPi to predict hemolysis was calculated as 1.3, with 80.0% sensitivity and 72.7% specificity. Lower PAPi (<1.3) significantly correlated with the occurrence of hemolysis with an odds ratio of 11.65 (95% confidence interval 1.58–85.98, p = 0.017), adjusted for other potential confounders. Survival discharge was significantly lower in patients with lower PAPi (<1.3) (50% vs. 86%, p = 0.019). Conclusions: The results of this study suggest that patients with right ventricular impairment indicated by lower PAPi following the initiation of Impella-incorporated mechanical circulatory support have a higher risk of hemolysis.

Experimental Hemodynamics Within the Penn State Fontan Circulatory Assist Device.

For children born with a single functional ventricle, the Fontan operation bypasses the right ventricle by forming a four-way total cavopulmonary connection and adapts the existing ventricle for the systemic circulation. However, upon reaching adulthood, many Fontan patients exhibit low cardiac output and elevated venous pressure, eventually requiring a heart transplantation. Despite efforts in developing a new device or using an existing device for failing Fontan support, there is still no Food and Drug Administration-approved device for subpulmonary support. Penn State University is developing a hydrodynamically levitated Fontan circulatory assist device (FCAD) for bridge-to-transplant or destination therapy. The hemodynamics within the FCAD, at both steady and patient averaged pulsatile conditions for three physiological pump operating conditions, were quantified using particle image velocimetry (PIV) to determine the velocity magnitudes and Reynolds normal and shear stresses within the device. Data were acquired at three planes (0 mm and ±25% of the radius) for the inferior and superior vena cavae inlets and the pulmonary artery outlet. The inlets had a blunt velocity profile that became skewed toward the collecting volute as fluid approached the rotor. At the outlet, regardless of the flow condition, a high-velocity jet exited the volute and moved downstream in a helical pattern. Turbulent stresses observed at the volute exit were influenced by the rotor's rotation. Regardless of inlet conditions, the pump demonstrated advantageous behavior for clinical use with a predictable flow field and a low risk of platelet adhesion and hemolysis based on calculated wall shear rates and turbulent stresses, respectively.

Coagulation activation during extracorporeal membrane oxygenation (ECMO)

IntroductionExtracorporeal membrane oxygenation (ECMO) can be life-saving, but suffers from thrombus formation in the circuit with associated risks of oxygenator occlusion, hemolysis and arterial embolism. The formation of thrombin is the key step to thrombus formation and two factors are needed for sustained thrombin generation, a coagulation activator to initiate the process and a procoagulant phospholipid surface for the coagulation system to assemble on. Materials and methodsThe purpose of this study was to use thrombin generation potential (TGP) and other assays to determine the specific coagulation activators and sources of procoagulant phospholipid that are present in ECMO patient plasma. Samples were collected from 60 patients on ECMO (age 1d-19y) followed evaluation of native and stimulated TGP, measurement of factor II levels and determination of procoagulant extracellular vesicle levels by flow cytometry. ResultsDuring ECMO, native (unstimulated) TGP was increased, followed by a decrease back towards normal after ECMO ended. The main activator of TGP in ECMO plasma was increased FXIa (100% of samples tested), while increased tissue factor activity was present in 7%. Procoagulant phospholipids were present in plasma from ECMO patients in the form of circulating platelet and red cell extracellular vesicles, which were increased 2 to 7-fold compared to normal. Procoagulant extracellular vesicle levels correlated with increased plasma native TGP activity. ConclusionsECMO activates coagulation in plasma primarily through activation of the contact system and formation of activated factor XIa and generation of circulating procoagulant extracellular vesicles through platelet and red cell activation.

Pulmonary artery pulsatility index and hemolysis during Impella support

Abstract Funding Acknowledgements Type of funding sources: None. Background Impella-related hemolysis is a well-known complication, which we sometimes experience in the clinical practice depending on various hemodynamic status including right ventricular impairment. Methods We enrolled consecutive patients with cardiogenic shock who received Impella support between March 2018 and December 2020. The association between pulmonary artery pulsatility index (PAPi) immediately after Impella insertion and the occurrence of hemolysis was investigated. Hemolytic event was defined as detection of hemoglobinuria and elevated lactate dehydrogenase level over 2.5 folds of upper normal range. Results Among 38 patients (median 71 y; men 61%; LVEF 29%) included in this study, hemolysis occurred in 18 patients (47%). Incidence of hemolysis was significantly higher in the low PAPi group (&amp;lt; 1.3) compared with the normal PAPi group (≥ 1.3) (67% vs. 33%, p = 0.0176; Figure 1). The low PAPi (&amp;lt;1.3) was significantly associated with the occurrence of hemolysis with a hazard ratio of 5.71 (95% confidence interval 1.09–29.91, p = 0.0313) adjusted for other clinically significant variables. Conclusions In patients with right ventricular impairment with lower PAPi, it might be encouraged to be aware of the risk of hemolysis, maintaining volume status and considering inotropes administration. Abstract Figure.

Successful use of veno-venous extracorporeal membrane oxygenation for acute chest syndrome in a child with sickle cell disease and SARS-CoV-2.

Children with sickle cell disease (SCD) are at increased risk for severe illness due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We describe the successful native lung recovery of a child with SCD referred for lung transplant (LTx) evaluation who was on prolonged veno-venous extracorporeal membrane oxygenation (VV-ECMO). He initially presented with acute chest syndrome complicated by SARS-CoV-2 infection that ultimately required dual-lumen, single bicaval VV-ECMO cannulation for respiratory support. Despite the increased risk of hemolysis and thrombosis from SCD and SARS-CoV-2 infection, he was successfully supported on VV-ECMO for 71 days without complications leading to native lung recovery with meticulous management of his SCD therapy. This report provides new insight on our approach to VV-ECMO support in a child with SCD and SARS-CoV-2 infection. With a successful outcome, the patient has returned home but still on mechanical ventilation with LTx still an option if he is not eventually liberated from invasive respiratory support.

An International Survey of Glucose-6-Phosphate Dehydrogenase Laboratory Reporting Practices.

Glucose-6-phosphate dehydrogenase (G6PD) activity is used in the evaluation of hemolysis risk in patients being assessed for G6PD deficiency. A long-acting 8-aminoquinoline drug (tafenoquine) used in malaria treatment is contraindicated in patients with G6PD deficiency (<70% normal G6PD activity). The current state of G6PD reporting practices to support clinical eligibility assessment is poorly understood. To assess clinical laboratory reporting practices for G6PD testing. In October 2019 and October 2020, voluntary questionnaires were distributed to 327 and 324 laboratories participating in the College of American Pathologists G6PD proficiency testing (PT). Two hundred fifty-seven and 119 laboratories responded to the 2019 and 2020 questionnaires, respectively. Few laboratories have received clinical questions about average normal G6PD activity (US/Canada, 2.0% [3 of 149]; international, 8.4% [9 of 107]), whereas slightly more have determined the average normal G6PD activity for their own assay and patient populations (US/Canada, 6.7% [10 of 149]; international, 19.4% [21 of 108]). Few laboratories report G6PD activity in percent of normal format (US/Canada, 2.7% [4 of 149]; international, 8.3% [9 of 108]). The most common unit of measurement in use for quantitative G6PD reporting is unit per gram of hemoglobin. Reference intervals vary based on assay, reaction temperature, and participant laboratory and demonstrate moderate correlation (r = .46-.51) to G6PD activity measured from a "normal" PT challenge specimen. Nearly half of participants (47.8% [85 of 178]) categorized a quantitatively "intermediate" G6PD PT challenge as "normal" when using qualitative assays. Percent of normal G6PD activity reporting would facilitate patient eligibility assessment for drugs, such as tafenoquine. Quantitative assays are better able to differentiate "intermediate" specimens than qualitative assays.

Does COVID-19 cause pre-eclampsia?

Does COVID-19 cause pre-eclampsia?

Thrombotic risk in autoimmune hemolytic anemia

Autoimmune hemolytic anemia (AIHA) is a type of anemia caused by the destruction of red blood cells due to autoantibodies targeting membrane proteins. AIHA is divided into two types based on the thermal amplitude: warm AIHA (at 37°C) and cold AIHA (at <37°C). Anemia and jaundice are the major symptoms of AIHA, and in cold agglutinin disease the peripheral circulation disturbance deteriorates patients' quality of life. Cumulative evidence has revealed that both types of AIHA increase the risk of thrombosis and intravascular hemolysis appears to be the most critical factor in the pathogenesis. Complement activation plays an important role in the intravascular hemolysis of AIHA, though the coagulation and hemostatic systems and the crosstalk between these systems also contributes significantly to the pathogenesis of thrombosis. Future treatment of AIHA should be targeted at not only alleviating anemia but also reducing thrombotic risk.

Comparative analyses of blood flow through mechanical trileaflet and bileaflet aortic valves

Purpose: The primary aim of the present study was to compare the bileaflet and trileaflet aortic valves’ performance during uniform blood flow model and boundary conditions. The secondary aim of the study was to determine the effect of Newtonian/non-Newtonian fluid flow assumption on blood flow directly behind the trileaflet valve. Methods: The geometrical model of the whole system consist of the left ventricle, fragment of the aorta and mechanical valves. A representation of pulsatile flow was obtained by measuring blood flow velocity (Doppler ultrasound examination). We have assumed turbulent blood flow. We considered two blood models, Newtonian and non-Newtonian (Carreau model). The valves’ performance was assessed using the reduced stress in the valves, the shear stress in the aortic wall, flow velocity field and the effective orifice area. Results: The maximum von Mises stress for the bileaflet valve leaflets was 0.3 MPa and for the trileaflet valve – 0.06 MPa. The maximum flow velocity for the bileaflet valve was 4.52 m/s for 40° and for the trileaflet valve – 5.74 m/s. Higher shear stress was present in the bileaflet (151.5 Pa) than for the trileaflet valve (49.64 Pa). Conclusions: The results indicate that central blood jet for the trileaflet valve contributes to more physiological blood flow and decreases the risk of haemolysis. The central flow minimises the risk of leaflet dislocation. In addition, lower stresses extend the durability of the valve. However, the trileaflet valve geometry has also disadvantages, for instance, small peripheral streams or relatively low effective orifice area.

Computational Fluid Dynamics Simulations of Mitral Paravalvular Leaks in Human Heart.

In recent years, computational fluid dynamics (CFD) has been extensively used in biomedical research on heart diseases due to its non-invasiveness and relative ease of use in predicting flow patterns inside the cardiovascular system. In this study, a modeling approach involving CFD simulations was employed to study hemodynamics inside the left ventricle (LV) of a human heart affected by a mitral paravalvular leak (PVL). A simplified LV geometry with four PVL variants that varied in shape and size was studied. Predicted blood flow parameters, mainly velocity and shear stress distributions, were used as indicators of how presence of PVLs correlates with risk and severity of hemolysis. The calculations performed in the study showed a high risk of hemolysis in all analyzed cases, with the maximum shear stress values considerably exceeding the safe level of 300 Pa. Results of our study indicated that there was no simple relationship between PVL geometry and the risk of hemolysis. Two factors that potentially played a role in hemolysis severity, namely erythrocyte exposure time and the volume of fluid in which shear stress exceeded a critical value, were not directly proportional to any of the characteristic geometrical parameters (shape, diameters, circumference, area, volume) of the PVL channel. Potential limitations of the proposed simplified approach of flow analysis are discussed, and possible modifications to increase the accuracy and plausibility of the results are presented.

Complement-mediated hemolysis persists year round in patients with cold agglutinin disease.

Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia mediated by immunoglobulin M autoantibodies that bind to the "I" antigen on erythrocytes. IgM binding results in either agglutination at ≤37°C, activation of the classical complement pathway, or both. Patients with CAD can have transient agglutination-mediated circulatory symptoms triggered by exposure to cold conditions. Separately, patients with CAD can experience complement-mediated symptoms such as anemia, hemolysis, and fatigue, but the effect of the season on these complement-mediated manifestations of CAD and clinical outcomes is not well understood. Using data from the Optum® de-identified Electronic Health Record dataset, we compared hemoglobin, markers of hemolysis (bilirubin and lactate dehydrogenase [LDH]), and healthcare resource utilization (HRU) between seasons for 594 patients (62% female; 66% aged ≥65 years) with CAD (defined as having CAD-related terms in their clinical notes on ≥3 separate occasions between December 2008 and May 2016). Laboratory parameters and HRU were compared between seasons using multivariate regression models. Estimated median hemoglobin (9.87 g/dL in summer and 9.86 g/dL in winter; P=0.944) and bilirubin (1.04 mg/dL in summer and 1.09 mg/dL in winter; P=0.257) were similar in winter versus summer. While LDH was statistically significantly higher in winter compared with summer (P < 0.001), the estimated median value was above normal for both seasons (309 U/L in summer and 367 U/L in winter). HRU measures and transfusion and thromboembolism rates were similar across seasons. Patients with CAD had evidence of persistent chronic hemolysis, HRU, and thromboembolism risk year round.

Hemolysis After Medication Exposure in Pediatric Patients With G6PD Deficiency.

Hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficiency varies by mutation status and the oxidative stressor. Although classified by percent of enzymatic deficiency, variability in normal G6PD values clouds assessment of hemolysis risk by level. This was a retrospective, single institution, cohort study assessing risk of postexposure medication-induced hemolysis in G6PD deficient patients. Exposures occurred in 87 of 1415 deficient patients. Only 2 of 87 medication-exposed patients had hemolytic episodes and both had very low enzymatic activity. No hemolytic events occurred with G6PD levels >7 units/g hemoglobin. Correlation of levels with mutation may improve predictive capacity for hemolysis in G6PD deficiency.