Severe Hemolysis Research Articles

Histopatología de juveniles cultivados de Totoaba macdonaldi asociados con aislamientos bacterianos identificados molecularmente como Vibrio spp. durante un evento de aumento de temperatura

Totoaba macdonaldi is an endangered species of croaker endemic to the Gulf of California, Mexico. This species has been cultured for the repopulation of wild stocks and commercialization at the Wildlife Management and Conservation Unit for the culture of T. macdonaldi at the Universidad Autónoma de Baja California, Mexico. A mortality episode was observed in 50 day-old juveniles, that coincided with an increase of temperature from 16 to 25.5˚C that affected the aquaculture facility. Histopathological and bacteriological analysis of survivor fishes were conducted to investigate the possible causes of mortality. Gill damage including severe congestion in gill filaments, necrosis, and epithelial dissociation of lamellae were observed. Moreover, epidermal, hypodermic necrosis, as well as diffuse bacterial colonization of the dermis was detected. Severe congestion and hemolysis were detected in the heart’s atrium and hepatic portal vessels. From the skin lesions, eight colonies of bacteria were isolated, these corresponded to four species of genus Vibrio, tentatively identified by partial sequence of the 16S rRNA gene as Vibrio harveyi, V. rotiferianus, V. brasilensis and V. shilonii. From them, V. harveyi corresponded to 4 of the 8 isolates and was found in all moribund fishes. Characteristics of the tissue alterations related with these opportunistic Vibrio spp. suggest an acute mortality event favoured by a temperature increase. This is the first record of the histopathology of T. macdonaldi juveniles that suffered an unusual mortality event under an increase of temperature in cultured conditions associated with Vibrio spp.

Silicon membranes for extracorporeal life support: a comparison of design and fabrication methodologies.

Extracorporeal life support is an advanced therapy that circulates blood through an extracorporeal oxygenator, performing gas exchange outside the body. However, its use is limited by severe complications, including bleeding, clotting, and hemolysis. Semiconductor silicon-based membranes have emerged as an alternative to traditional hollow-fiber semipermeable membranes. These membranes offer excellent gas exchange efficiency and the potential to increase hemocompatibility by improving flow dynamics. In this work, we evaluate two next-generation silicon membrane designs, which are intended to be mechanically robust and efficient in gas exchange, while simultaneously reducing fabrication complexity. The "window" design features 10 µm pores on one side and large windows on the back side. The "cavern" design also uses 10 µm pores but contains a network of interconnected buried caverns to distribute the sweep gas from smaller inlet holes. Both designs were shown to be technically viable and able to be reproducibly fabricated. In addition, they both were mechanically robust and withstood 30 psi of transmembrane pressure without breakage or bubbling. At low sweep gas pressures, gas transfer efficiency was similar, with the partial pressure of oxygen in water increasing by 10.7 ± 2.3 mmHg (mean ± standard deviation) and 13.6 ± 1.9 mmHg for the window and cavern membranes, respectively. Gas transfer efficiency was also similar at higher pressures. At 10 psi, oxygen tension increased by 16.8 ± 5.7 mmHg (window) and 18.9 ± 1.3 mmHg (cavern). We conclude that silicon membranes featuring a 10 µm pore size can simplify the fabrication process and improve mechanical robustness while maintaining excellent efficiency.

MATERNAL AND FOETAL OUTCOMES IN PREGNANCY WITH GESTATIONAL THROMBOCYTOPENIA: A PROSPECTIVE OBSERVATIONAL STUDY

Thrombocytopeniaissecond to anaemia as the most common hematological abnormality during pregnancy. Accurate etiological diagnosis is essential for optimal therapeutic management and thus can prevent maternal and fetal morbidity and mortality. Aim &Objective:To study the clinical profile, maternal and perinatal outcomes in thrombocytopenic antenatal patients. Design:This Prospective observational study design was carried out in the department of obstetrics and gynecology at Chalmeda Anand Rao Institute of Medical sciences Karimnagar, over a period of 18 months from October 2020 to April 2022. Materials And Methods:All the pregnant women who attended antenatal OPD at Chalmeda Anand Rao Institute of Medical Sciences were tested for thrombocytopenia. 70 pregnant women with thrombocytopenia, platelet count lessthan 150x 109 /L and 70 pregnant women with normal platelet count were recruited into the study and the maternal & Fetal outcomes of both groups were studied and compared. Results: Gestational thrombocytopenia is the most common etiology (57.1%). Incidence of thrombocytopenia due to severe preeclampsia and Hemolysis, Elevated Liver enzymes, Low Platelet (HELLP) syndrome in the study group was 28.5% and 8.5% of them had medical cause like malarial or dengue fever. Major causes were gestational thrombocytopenia (GT), Idiopathic Thrombocytopenic Purpura (ITP), Preeclampsia, HELLP syndrome, Malaria, and Dengue. Maternal complications due to bleeding tendencies like placental abruption, Postpartumhemorrhage were evident in the study population. Fetal complications were significantly higher in the study group. Early neonatal thrombocytopenia depended on etiology rather than severity of maternal thrombocytopenia. Conclusions:Outcome of pregnancy with moderate to severe thrombocytopenia dependsmainly on the etiology of thrombocytopenia. Adverse outcomes are especially seen with pregnancy complicated by preeclampsia and HELLP syndrome. Fetomaternal outcome is favorable in gestational thrombocytopenia. Thus, accurate etiological diagnosis is essential for optimal therapeutic management.

Effect of neonatal reticulocytosis on glucose 6-phosphate dehydrogenase (G6PD) activity and G6PD deficiency detection: a cross-sectional study

BackgroundScreening for G6PD deficiency in newborns can help prevent severe hemolysis, hyperbilirubinemia, and bilirubin encephalopathy, as recommended by the World Health Organization (WHO). It has been speculated that the presence of a high number of reticulocytes in newborns interferes with the diagnosis of G6PD deficiency since reticulocytes contain higher amounts of G6PD enzyme than mature erythrocytes. Therefore, the purposes of this study were to assess the effect of reticulocytosis in the determination of blood G6PD activity in Thai newborns by using a novel automated UV-based enzymatic assay and to validate the performance of this assay for the detection of G6PD deficiency in newborn samples.MethodsThe levels of reticulocytes and G6PD activity were measured in blood samples collected from 1,015 newborns. G6PD mutations were identified using TaqMan® SNP genotyping assay, PCR–restriction fragment length polymorphism (PCR–RFLP), and direct sequencing. The correlation between the levels of reticulocytes and G6PD activity was examined. The performance of the automated method was compared with that of the fluorescent spot test (FST) and the standard quantitative assay.ResultsThe automated assay detected G6PD deficiency in 6.5% of the total newborn subjects compared to 5.3% and 6.1% by the FST and the standard method, respectively. The minor allele frequencies (MAFs) of G6PD ViangchanG871A, G6PD MahidolG487A, and G6PD UnionC1360T were 0.066, 0.005, and 0.005, respectively. The reticulocyte counts in newborns with G6PD deficiency were significantly higher than those in normal male newborns (p < 0.001). Compared with normal newborns after controlling for thalassemias and hemoglobinopathies, G6PD-deficient patients with the G6PD ViangchanG871A mutation exhibited elevated reticulocyte counts (5.82 ± 1.73%, p < 0.001). In a group of G6PD normal newborns, the percentage of reticulocytes was positively correlated with G6PD activity (r = 0.327, p < 0.001). However, there was no correlation between G6PD activity and the levels of reticulocytes in subjects with G6PD deficiency (r = -0.019, p = 0.881). The level of agreement in the detection of G6PD deficiency was 0.999, while the area under the receiver operating characteristic (AUC) curve demonstrated that the automated method had 98.4% sensitivity, 99.5% specificity, 92.4% positive predictive value (PPV), 99.9% negative predictive value (NPV), and 99.4% accuracy.ConclusionsWe report that reticulocytosis does not have a statistically significant effect on the detection of G6PD deficiency in newborns by both qualitative and quantitative methods.

Overwhelming Intravascular Hemolysis and Acute Renal Failure in Babesiosis Requiring Erythrocytapheresis

Babesia is an obligate intra-erythrocytic parasite transmitted by a tick called Ixodes scapularis . They invade erythrocytes and can present in various hematologic manifestations that can range from mild anemia to severe pancytopenia, splenic rupture, disseminated intravascular coagulation(DIC) or even hemophagocytic lymphohistocytosis1. They are typically self limiting in immunocompetent hosts, however management in splenectomized patients is complex and requires multidisciplinary care. We present the case of a 60 year old homeless male with a history of splenectomy secondary to a motor vehicle accident 6 years ago who presented to us with severe sepsis. On arrival his systolic blood pressure was in low 90s, tachycardic, tachypneic and saturating 93% on room air. Initial labs were significant for hyponatremia (125), hyperkalemia (5.6), acute renal failure (creatinine 2.18, baseline 0.8-1 and GFR 32, baseline 96-98), hyperuricemia(12.5), hyperphosphatemia(5) with congruent hypocalcemia(7.3).On blood counts hemoglobin(hb) was noted at 9.2 with baseline of 15 with appropriate reticulocytosis, leukocytosis(17.4) with monocytosis(26, normal is less than 11). Other labs include lactate dehydrogenase(LDH) which was elevated five times the normal limit(852) and serum haptoglobin was less than 8 (normal:11-44). He was appropriately fluid resuscitated and started on vancomycin and cefepime by emergency department. Overnight, a critical lab result was received, peripheral smear(pic 1) was showing intraerythrocytic parasites. By next morning, hematology confirmed the presence of Maltese cross on peripheral smear and parasite burden was determined at 20%. We subsequently transitioned the patient to atovaquone 750mg twice daily and IV azithromycin 500 mg daily. Doxycycline 100mg BID was later added by Infectious diseases(ID)to the regimen to empirically cover Lyme disease as both babesia and borrelia share the same tick vector. By day 2 of hospitalization patient was producing less than 0.5ml/kg/hour of urine output with decrease in GFR to 16 and concomitant rise in creatinine to 3.86, hb dropped to 7.8 with with notable rise in LDH(1080). Hematology opined for an urgent exchange transfusion specifically erythrocytapheresis and IR was consulted for a peripherally inserted central catheter insertion for the same. Post exchange transfusion, patient was noted to have improving kidney functions with decrease in parasite burden on serial peripheral smears. His hb remained stable around 10 and GFR improved to 63, at which point he was deemed stable for discharge. ID stepped down therapy to oral azithromycin 500mg daily and atovaquone 750 mg BID and doxycycline for total duration of two weeks at discharge. The indications of exchange transfusion in severe babesiosis are not well established. Erythrocytapheresis is typically considered in patients with severe hemolysis (hb less than 10), parasitemia greater than 10% or organ failure. However we did not find any prospective randomized studies to support this approach. The data to support erythrocytapheresis versus whole blood or plasma exchange is limited at best in immunocompetent patients2,3,4,5 .Though it should be noted that a prompt reduction in parasitemia markedly improves mortality in immunocompromised patient such as ours especially when used adjunctively to antimicrobial therapy 6.

Neonatal Exchange Transfusion: When Should We Think about Hereditary Thrombotic Thrombocytopenic Purpura (hTTP)?

Introduction Neonatal exchange transfusion (NExT) is a procedure to treat severe neonatal hyperbilirubinemia persisting despite phototherapy, to remove red cell allo-antibodies associated with excessive neonatal hemolysis and to correct severe anemia. During the past decades, the number of NExT preformed have steadily decreased, particularly since the introduction of rhesus prophylaxis in rhesus negative women. Hereditary thrombotic thrombocytopenic purpura (hTTP) because of severe congenital ADAMTS13 deficiency is a rare, autosomal recessively inherited disorder with an estimated prevalence of one case per million. Although excessive neonatal hemolysis (often in conjunction with thrombocytopenia) seems to be prevalent in hTTP, patients are seldom diagnosed with hTTP in the neonatal period, possibly because hTTP is not recognized as a differential diagnosis of severe neonatal hyperbilirubinemia and NExT. In this study, we investigated the prevalence of severe neonatal hyperbilirubinemia necessitating NExT among confirmed hTTP patients enrolled in the International Hereditary TTP Registry (www.ttpregistry.net; ClinicalTrials.gov Identifier: NCT01257269), at participating sites and in the literature in the past 20 years. Methods The International Hereditary TTP Registry is a cohort study for patients with confirmed hTTP and their family members, established in 2006. The hTTP Registry collects clinical and treatment information, as well as laboratory parameters retrospectively up to enrollment (including performance of NExT), and then prospectively during annual follow-up visits. Participating study sites and/or national coordinating centers were asked to provide information on the number of and indication for all NExT performed between January 2001 and July 2022. Finally, we performed a literature search to identify reports on NExT / neonatal exchange blood transfusion over the same 20-year period. Results At present, the International Hereditary TTP Registry has enrolled 178 confirmed hTTP patients. Forty-two (24%) of them had required NExT because of severe hyperbilirubinemia in the neonatal period, which led to early diagnosis of hTTP in 7/42 (16%) cases. In the remaining 33 patients treated with NExT, hTTP diagnosis was established in infancy/early childhood (between 3 months - ≤6 years of age) in 20 patients, and in 15 instances after 6 years of age. Of the 136 hTTP patients not requiring NExT, 35 (26%) had a disease onset in the neonatal period although only four of them (11%) were diagnosed at this time, while the majority (20/35 patients, 57%) received their hTTP diagnosis following further acute episodes in late adolescence or adulthood. Twelve of the 20 sites or national coordination centers participating in the International Hereditary TTP Registry answered our survey and reported 70 neonates treated with NExT over a period of 20 years. Indication for NExT were severe hyperbilirubinemia and or severe anemia due to AB0 or Rhesus incompatibility. In none of the cases hTTP was suspected or diagnosed, as immune-hematological findings indicated severe allo-antibody mediated hemolysis. We retrieved from PubMed 887 publications mentioning NExT or neonatal exchange blood transfusion, of which we excluded 229 papers, that did not describe patients treated with exchange transfusions. In the remaining 658 publications, patients were treated with exchange transfusions because of severe hyperbilirubinemia due to AB0-, Rhesus- or minor blood group incompatibilities, glucose-6-phosphate deficiency, sickle cell disease and severe infections. Only three publications mentioned the indication TTP. Conclusions Despite increased awareness and tools to diagnose hTTP, prompt recognition and diagnosis remain a critical impediment and result in delayed diagnosis and treatment. Early and persistent severe hyperbilirubinemia (often in conjunction with thrombocytopenia) necessitating NExT prevalent in newborns later in life diagnosed with hTTP. Differential diagnosis of severe neonatal hyperbilirubinemia should include hTTP and we suggest to determine ADAMTS13 activity together with molecular analysis of the ADAMTS13 gene in case of an ADAMTS13 activity <10% in any newborn requiring NExT for severe hyperbilirubinemia.

Catastrophic antiphospholipid syndrome after pregnancy complicated by hemolysis, elevated liver enzymes and low platelets syndrome.

Antiphospholipid syndrome (APLS) is rarely complicated by catastrophic antiphospholipid syndrome (CAPS). Peripartum CAPS is rarer still and can masquerade as other obstetric disorders. A high degree of suspicion is critical for early diagnosis and specific management given the significant morbidity and mortality associated with this disorder. We report a case of a 27-year-old at 22 week's gestation with a history of APLS found to have severe hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, resulting in termination of pregnancy. Further workup revealed the diagnosis of CAPS followed by prompt treatment with triple therapy leading to clinical improvement. CAPS should be considered within the differential in an obstetric patient with a history of APLS who has evidence of multiorgan involvement with macro- or microvascular thrombosis. Although this may mimic alternative disorders, prompt diagnosis is imperative for appropriate therapy and reduction in maternal morbidity and mortality.

G6PD testing and radical cure for Plasmodium vivax in Cambodia: A mixed methods implementation study.

IntroductionCambodia aims to eliminate malaria by 2025, however tackling Plasmodium vivax (P.v) presents multiple challenges. The prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency has prevented the deployment of 8-aminoquinolones for “radical cure”, due to the risk of severe haemolysis. Patients with P. vivax have therefore continued to experience recurrent relapses leading to cumulative health and socioeconomic burden. The recent advent of point of care testing for G6PD deficiency has made radical cure a possibility, however at the time of the study lack of operational experience and guidance meant that they had not been introduced. This study therefore aimed to design, implement and evaluate a new care pathway for the radical cure of P.vivax.MethodsThis implementation study took place in Pursat province, Western Cambodia. The interventions were co-developed with key stakeholders at the national, district, and local level, through a continuous process of consultations as well as formal meetings. Mixed methods were used to evaluate the feasibility of the intervention including its uptake (G6PD testing rate and the initiation of primaquine treatment according to G6PD status); adherence (self-reported); and acceptability, using quantitative analysis of primary and secondary data as well as focus group discussions and key informant interviews.ResultsThe co-development process resulted in the design of a new care pathway with supporting interventions, and a phased approach to their implementation. Patients diagnosed with P.v infection by Village Malaria Workers (VMWs) were referred to local health centres for point-of-care G6PD testing and initiation of radical cure treatment with 14-day or 8-week primaquine regimens depending on G6PD status. VMWs carried out follow-up in the community on days 3, 7 and 14. Supporting interventions included training, community sensitisation, and the development of a smartphone and tablet application to aid referral, follow-up and surveillance. The testing rate was low initially but increased rapidly over time, reflecting the deliberately cautious phased approach to implementation. In total 626 adults received G6PD testing, for a total of 675 episodes. Of these 555 occurred in patients with normal G6PD activity and nearly all (549/555, 98.8%) were initiated on PQ14. Of the 120 with deficient/intermediate G6PD activity 61 (50.8%) were initiated on PQ8W. Self-reported adherence was high (100% and 95.1% respectively). No severe adverse events were reported. The pathway was found to be highly acceptable by both staff and patients. The supporting interventions and gradual introduction were critical to success. Challenges included travel to remote areas and mobility of P.v patients.ConclusionThe new care pathway with supporting interventions was highly feasible with high levels of uptake, adherence and acceptability in this setting where high prevalence of G6PD deficiency is high and there is a well-established network of VMWs. Scaling up of the P.v radical cure programme is currently underway in Cambodia and a decline in reduction in the burden of malaria is being seen, bringing Cambodia a step closer to elimination.

Inexpensive, Accurate, and Stable Method to Quantitate Blood Alanine Aminotransferase (ALT) Levels.

Alanine aminotransferase (ALT) levels are frequently determined in serum and plasma samples and are a primary measure to quantitate hepatocellular injury in rodents, humans, and other organisms. An accurate, reliable, and scalable assay is hence of central importance. Here, we describe a methodology that fulfills those requirements, and demonstrates an excellent performance similar to a commercial ALT kit, with a long stable performance over several subsequent runs. Further, anticoagulation of blood samples with ethylenediaminetetraacetic acid (EDTA) or heparin results in similar ALT concentrations with this assay, whereas no anticoagulation significantly increases ALT levels. Mild hemolysis does not significantly increase ALT levels; however, moderate to severe hemolysis does lead to higher ALT levels. The assay provides stable results over a wide range of associated triglyceride concentrations that can be expected in serum and plasma samples from rodents and humans with dyslipidemia. It also performs well in diluted samples with a reduction of ALT levels corresponding to the factor used to dilute the samples. The described ALT reagent is also very affordable, costing less than 1/80 of comparable commercial kits. Based on the characteristics above, this methodology is suitable for a broad spectrum of applications in mice and possibly humans, where ALT concentrations need to be determined.

Management of fulminant myocarditis: peripheral venoarterial extracorporeal membranous oxygenation and associated complications

Abstract Background Fulminant Myocarditis (FM) leads to cardiogenic shock with multi-organic dysfunction, being peripheral venoarterial extracorporeal membranous oxygenation (VA-ECMO) a rescue technique. Despite growing experience, it is still related with several complications. We aim to appraise the management of patients with FM and the adverse events associated to VA-ECMO. Methods We conducted a retrospective study in a ECMO centre in Portugal, which included 15 patients diagnosed with FM and managed on VA-ECMO from 2008 to 2018. Hemorrhage or infection on cardiac device site, cardiac tamponade, limb ischemia, ischemic stroke, cerebral hemorrhage, severe hemolysis and accidental decannulation were considered major complications. Results For sample characteristics and resumed complications, see Table. Inotropic and mechanical ventilation support were transversal to all, with only one patient extubated before decannulation. Six patients received renal replacement therapy, whom half recovered renal function and the remaining died. VA-ECMO operated on average for 8,5 days (range, 1 to 20 days). 3 patients had concomitant Impella heart pump and one of them had a third assistance device with Intra-Aortic Ballon pump. Major complications were observed in 9 patients (60%), being ischemic stroke the most common. Limb ischemia, observed in 5 patients, related with longer duration of VA-ECMO support (limb ischemia vs non-limb ischemia; 12,8±4,9 vs. 6,8±6,5 days). Two patients presented hemorrhage on cardiac assistance device site, and 1 patient had a cardiac tamponade, all with fatal outcome. Infection on cardiac site, cerebral hemorrhage, severe hemolysis and accidental decannulation were not observed. Conclusion The most common complications were ischemic stroke and limb ischemia, both not apparently related with mortality. Differently, hemorrhage on cardiac site and cardiac tamponade were less frequent but presented ominous outcome. Overall, adverse events can be serious and hinder recovery and discharge. Funding Acknowledgement Type of funding sources: None.

S3046 Hepatitis B Causing Severe Hemolysis and Multi-Organ Failure in Patients With Undiagnosed G6PD

Introduction: Hepatitis B is a viral infection that attacks the liver and can cause both acute and chronic disease. WHO estimates 1.5 million new infections annually. Most people remain asymptomatic; however, some people have acute illness that lasts several weeks, which can at times be complicated with acute liver failure. Glucose-6-phosphate dehydrogenase (G6PD) X-linked deficiency is the most common human enzymopathy. Case Description/Methods: A 73-year-old male presented with loss of appetite, and dark colored urine. On examination, vitals were within normal range. Scleral icterus was present, along with hepatomegaly. Patient was alert and oriented. Patient's lab work was concerning for AST was 3017 unit/L, ALT 2712 Unit/L, BUN 74 mg/dL, Cr 3.6 mg/dL, total bilirubin 72.4 mg/dL, direct bilirubin 41.8 mg/dL, indirect bilirubin 30.6 mg/dL, hemoglobin 12.9 g/dL, white count 17,000 per microliter and platelet count of 173,000 per microliter (mcL). Patient’s hepatitis panel was positive for Hepatitis B Core Antibody Total, Hepatitis B Core Antibody IgM, Hepatitis B Surface Antibody, log 10 HBV IU/mL 2914. Hematological work up was done which was concerning for LDH 4,875, ferritin > 7500, reticulocyte, Peripheral smear did not show schistocytes. Erythrocyte G6PD level was performed which was low Patient was started on hemodialysis due to electrolyte derangement and oliguria. The patient was given intravenous fluids and was started on Entecavir for acute complicated Hepatitis B infection, Renal Biopsy was done which was suggestive of acute tubular injury. Patient liver function, labs as well as renal function continued to improve and no longer required dialysis. Discussion: Hemolytic anemia has been associated with viral hepatitis, but the degree is usually mild to moderate. With cases of severe intravascular hemolysis, a diagnosis in addition to hepatitis should be sought out. Our case is unique since this is the first reported case of severe hemolysis and renal failure precipitated by acute HBV in an undiagnosed G6PD deficient patient and treatment with Entecavir causing marked improvement. With early recognition and establishing diagnosis of complicated hepatitis B leading to severe hemolysis as well as renal failure, prompt treatment with anti-viral as well as supportive treatment for G6PD deficiency can help with early recovery of patients and prevent life threatening organ failure.

BABESIA MICROTI INFECTION WITH LOW-GRADE PARASITEMIA CAUSING ARDS IN AN IMMUNOCOMPETENT PATIENT

BABESIA MICROTI INFECTION WITH LOW-GRADE PARASITEMIA CAUSING ARDS IN AN IMMUNOCOMPETENT PATIENT

Multiple Organ Dysfunction Syndrome Secondary to Multiple Wasp Stings: A Case Report

Wasp sting is common in resource-limited countries like Viet Nam. Symptoms can range from mild (itching, urticaria, and angioedema) to severe (multiorgan dysfunction), which increases mortality. Rhabdomyolysis and acute respiratory distress syndrome are rare complications but yield a high risk of death, thus requiring emergent interventions. We present a case of a 32-year-old man suffering from multiple wasp stings. The patient manifested several swollen, erythematous, and tender stings, and then developed a high fever, dyspnea, and reddish urine. He was diagnosed with multiple organ dysfunction syndrome, including severe hemolysis, acute kidney injury, liver injury, and acute respiratory distress syndrome.

Heavy hemolysis after organophosphate poisoning by chlorpyrifos ethyl

Organophosphates (OPs) inactivate the acetylcholinesterase enzyme, thus increasing the cholinergic effect. In a clinical setting, patients with OP poisoning may experience nausea and vomiting, diarrhea, and abdominal pain, or in severe cases respiratory failure, seizures, and death. Rarely, acute hemolysis has also been observed. The existing literature contains few descriptions of several delayed diseases associated with OP poisoning. This article presents the case of a patient who experienced severe hemolysis approximately one week after OP exposure. Only a small number of similar cases have been previously examined.

The design of cell-selective tryptophan and arginine-rich antimicrobial peptides by introducing hydrophilic uncharged residues

Antimicrobial peptides (AMPs) are considered to be powerful weapons in the fight against traditional antibiotic resistance due to their unique membrane-disruptive mechanism. The combination of traditional and classical hydrophobic tryptophan (W) residues and hydrophilic charged arginine (R) residues is considered as the first choice for the minimalist design of AMPs due to its potent performance in antibacterial activity. However, some W- and R-rich AMPs that are not rationally designed and contain excessive repeats of W and R residues may cause severe cytotoxicity and hemolysis. To address this issue, we designed the (WRX)n (where X = hydrophilic uncharged amino residues; n = number of repeat units) series engineered peptides with high cell selectivity by introducing hydrophilic uncharged threonine (T), serine (S), glutamine (Q) or asparagine (N) residues into the minimalist design of W- and R-rich AMPs. The results showed that the introduction of these hydrophilic uncharged amino residues, especially T residues, significantly improved the cell selectivity of the W- and R-rich engineered peptides. Among (WRX)n series engineered peptides, T6 presents a mixture structure of β-turn and α-helix. It has broad spectrum and potent antibacterial activity (no activity against probiotics), good biocompatibility, high selectivity index, strong tolerance (physiological salts, serum acid, alkali, and heat conditions), rapid and efficient time-kill kinetics, and no tendency of resistance. Studies on antibacterial mechanism show that T6 exert antibacterial activity mainly by disrupting bacterial cell membrane and inducing the accumulation of reactive oxygen species in bacterial cells. Furthermore, T6 exhibited potent antibacterial and antiinflammatory capabilities in vivo in a mouse peritonitis-sepsis model infected with Escherichia coli. In conclusion, our study confirms an effective strategy for the minimalist design of highly cell selective W- and R-rich AMPs by introducing hydrophilic uncharged T residues, which may trigger widespread attention to hydrophilic uncharged amino acid residues, including T residues, and provide new insights into the design of peptide-based antibacterial biomaterials. Statement of significanceWe have introduced hydrophilic uncharged T, S, Q or N residues into the minimalist design of W- and R-rich engineered peptides and found that the introduction of these hydrophilic uncharged amino residues, especially the T residues, can significantly improve the cell selectivity of W- and R-rich engineered peptides. The target compound T6 showed potent antibacterial activity, high cell selectivity, strong tolerance, good in vivo efficacy and killed bacteria through multiple mechanisms mainly membrane-disruptive. These findings may spark widespread interest in hydrophilic uncharged amino acid residues, and provide new insights into the design of peptide-based antimicrobial biomaterials.

71-Year-Old Man With a New Heart Murmur

71-Year-Old Man With a New Heart Murmur

Abstract P346: Cardiac Arrest During Delivery Hospitalization And Severe Hypertensive Disorders Of Pregnancy, United States, 2017-2019

Background: Cardiac arrest is a rare and sometimes fatal maternal complication. Severe hypertensive disorders of pregnancy (HDP) including preeclampsia with severe features, eclampsia, and Hemolysis, Elevated Liver enzymes, and Low Platelets (HELLP) syndrome are risk factors for maternal cardiac events. Surveillance on cardiac arrest and severe HDP during delivery is critical to informing evidence-based strategies to reduce pregnancy-related death. Methods: Using pooled data from the National Inpatient Sample from 2017-2019, we identified delivery hospitalizations among women aged 12-55 years. Delivery hospitalizations, cardiac arrest, and maternal medical conditions were identified using ICD-10-CM codes. Survival to hospital discharge was based on patient discharge disposition. Prevalence of cardiac arrest, severe HDP, and survival following cardiac arrest were calculated. We estimated the prevalence of severe HDP among delivery hospitalizations with cardiac arrest, cardiac arrest frequency among delivery hospitalizations with severe HDP, and survival to hospital discharge with co-occurring cardiac arrest and severe HDP. All estimates were weighted to account for complex sampling. Results: During 2017-2019, an estimated 10,921,784 delivery hospitalizations among which 1,465 cardiac arrests were identified. Overall cardiac arrest prevalence was 13.4 per 100,000 delivery hospitalizations (95% CI, 11.9-14.9). Of these, 1,005 (68.6% [95% CI, 63.2-74.0]) survived to hospital discharge. Overall prevalence of severe HDP was 2.7% (95% CI, 2.6-2.7) compared with 15.4% (95% CI 11.2-19.5) of delivery hospitalizations with cardiac arrest. Frequency of cardiac arrest per 100,000 delivery hospitalizations with severe HDP was 76.9 (95% CI, 54.6-99.2). Survival to hospital discharge with co-occurring cardiac arrest and severe HDP was 77.8% (95% CI, 65.6-89.9). Conclusion: Delivery hospitalizations affected by cardiac arrest are rare, and over two thirds survived to hospital discharge. Cardiac arrest disproportionately affected delivery hospitalizations among patients who had severe HDP.

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.

Incidence and risk factors for intravenous immunoglobulin-related hemolysis: A systematic review of clinical trial and real-world populations.

BackgroundSevere hemolysis rarely occurs in patients receiving intravenous immunoglobulin (IVIG) therapy. A systematic review was performed to assess the incidence of IVIG‐related hemolysis and the impact of patient and product risk factors.Study Design and MethodsA systematic literature search for terms related to “IVIG products”, “hemolysis,” and “adverse events” was conducted in Embase for articles published between January 1, 2015, and May 31, 2021. Studies with no clinical datasets, no IVIG treatment, or where IVIG was used to treat hemolytic conditions were excluded. Of the 430 articles retrieved, 383 were excluded based on titles/abstracts and 14 were excluded after in‐depth review.ResultsIn total, 33 articles were analyzed and separated into observational studies (n = 16), clinical trials (n = 8), and case reports (n = 9). The incidence proportion for IVIG‐related hemolysis ranged from 0% to 19% in observational studies and 0%–21% in clinical trials. A higher incidence of IVIG‐related hemolysis was consistently reported in patients with blood groups A and AB. Hemolysis occurred more frequently in patients treated with IVIG for some conditions such as Kawasaki disease; however, this may be confounded by the high dose of IVIG therapy. IVIG‐related hemolysis incidence was lower in studies using IVIG products citing manufacturing processes to reduce isoagglutinin levels than products that did not.ConclusionThis analysis identified patient and product risk factors including blood group, IVIG dose, and IVIG manufacturing processes associated with elevated IVIG‐related hemolysis incidence.

Macromolecules in polysorbate 80 for injection: an important cause of anaphylactoid reactions

Polysorbate 80 for injection (TW80) is a common excipient used for injection whose macromolecular impurities, including those that cause anaphylactoid reactions, are frequently ignored. The main aim of this study was to prove that the macromolecular impurities in the excipient are an important cause of anaphylactoid reactions. Component A (containing macromolecules > 100 kDa), Component B (containing macromolecules from 10 to 100 kDa), and Component C (containing substances < 10 kDa) were prepaired from the original TW80 using ultrafilters. The original TW80 contained numerous substances with molecular weights > 10kD. The original TW80 and Components A and B caused strong anaphylactoid reactions in both guinea pigs and rabbits by intravenous administration. Moreover, the original TW80 and Components A and B even caused strong passive cutaneous anaphylactoid (PCA) reactions and pulmonary capillary permeability. The PCA reaction and increased permeability were partly prevented by cromolyn sodium. Additionally, the original TW80 and Components A and B caused vasodilation and severe hemolysis in vitro. The anaphylactoid reactions were associated with histamine release but not with mast cell degranulation. Nevertheless, Component C almost caused no anaphylactoid reactions or hemolysis and was weaker in the few reactions that ocurred. Taken together, these results suggest that macromolecular substances are one of the main risk factors responsible for anaphylactoid reactions and hemolysis caused by TW80.