Acute Hemolysis Research Articles

What is your diagnosis: Acute hemolysis in a Limousin bull.

What is your diagnosis: Acute hemolysis in a Limousin bull.

Serologic investigation and management of an antibody screen negative para-Bombay phenotype during pregnancy

Abstract Introduction/Objective Individuals with the Bombay and para-Bombay red blood cell (RBC) phenotypes express anti- H antibodies associated with acute hemolytic transfusion reactions. The rarity of compatible donor units creates unique logistical challenges. However, para-Bombay individuals have been shown to tolerate transfusion of non- Bombay RBCs without acute hemolysis. Therefore, accurate serologic identification and judicious management of blood products are crucial when planning to transfuse patients with anti-H. This is especially true during pregnancy, as early onset of labor and fetal distress can occur without warning. Methods/Case Report A 24-year-old gravida 2 para 1 (G2P1) at approximately 38 weeks gestation with the fetus in breech position was transferred to our hospital after anti-H antibodies were detected. Although our in-house antibody screen was negative on automated solid-phase red cell adherence (SPRCA) testing, manual tube testing revealed the presence of anti-H antibodies, and forward typing with Ulex europaeus lectin confirmed the absence of H-antigen. Further, Lewis B phenotyping and saliva neutralization demonstrated the presence of H-antigen in secretions, consistent with the O-para-Bombay phenotype. Finally, differential adsorption ruled out other clinically significant allo- antibodies. An external cephalic version (ECV) was initially planned since vaginal delivery carries lower bleeding risk than cesarean section (CS). Three frozen Bombay RBC units were obtained, with one possibly compromised before arrival. Four pre-warmed, cross-match compatible units of O-positive RBCs (non-Bombay) were also prepared. Acknowledging the unpredictability of ECV, the challenge of timing thawed frozen units, and the possibilities of massive hemorrhage versus wasting rare donor blood, our transfusion service ultimately recommended an elective CS with only one Bombay unit deglycerolized. The patient underwent an uneventful procedure without transfusion. Results (if a Case Study enter NA) NA Conclusion Overall, this case highlights key diagnostic and management considerations for patients with Bombay and para-Bombay phenotypes. First, automated SPRCA testing may provide false negative results for anti-H antibodies. Second, backup transfusion strategies for para-Bombay patients may include non-Bombay RBCs. Finally, the procurement, preparation, and use of rare donor blood products requires multidisciplinary clinical decision-making to optimize patient outcomes, especially for high-risk labor when unexpected acute bleeding events can occur.

Bacillary hemoglobinuria in beef cattle infected with Fascioloides magna in Missouri.

Bacillary hemoglobinuria (BH) is an infectious disease, mostly affecting cattle, caused by Clostridium haemolyticum (C. novyi type D), with acute hepatic necrosis and intravascular hemolysis. Cattle are typically predisposed to BH by liver injury caused by Fasciola hepatica, although cases have been reported in cattle without evidence of this parasite. Here we describe a cluster of 14 BH cases from 7 counties in north-central to central Missouri submitted to a veterinary diagnostic laboratory between December 2020 and April 2023. Postmortem examination in all cases revealed hemoglobinuria and acute hepatic necrosis with large numbers of gram-positive bacilli with terminal-to-subterminal spores. Flukes, fluke ova, and/or fluke pigment consistent with Fascioloides magna were identified in 12 of 14 cases. Sequences of the nuclear ribosomal internal transcribed spacer 1 (ITS1) from one fluke had 100% identity to F. magna. C. novyi was detected by fluorescent antibody testing of liver impression smears (11 of 12 cases) and by immunohistochemistry of liver sections (7 of 7 cases). PCR on formalin-fixed, paraffin-embedded tissues amplified the C. haemolyticum beta toxin gene in each of the 7 cases tested. To our knowledge, a confirmed cluster of BH associated with F. magna has not been reported previously in cattle.

Preparation of composite calcium phosphate cement scaffold loaded with Hedysarum polysaccharides and its efficacy in repairing bone defects

It’s imperative to create a more ideal biological scaffold for bone defect repair. Calcium phosphate bone cements (CPC) could be used as a scaffold. Some ingredients and osteogenic factors could be added to improve its poor mechanical properties and biological activity. As a macromolecule extracted from traditional Chinese medicine, Hedysarum polysaccharides (HPS) would significantly promote the osteogenic activity of bone biomaterials. Zirconium oxide and starch were added to the solid phase and citric acid was added to the liquid phase to optimize CPC. HPS was loaded onto the scaffold as an osteogenic factor, and the prepared CPS + HPS was characterized. Further, the cytocompatibility of CPS + HPS was assessed according to activity, differentiation, and calcification in neonatal rat calvarial osteoblasts, and the biosafety of CPS + HPS was evaluated according to acute toxicity, pyrogen, sensitization, and hemolysis. The success of CPS + HPS in repairing bone defects was evaluated by using a rabbit femur implantation experiment. After optimization, CPS-20-CA-5 containing 10% starch and 5% citric acid displayed the highest mechanical strength of 28.96 ± 0.03 MPa. HPS-50 was demonstrated to exert the best osteogenic effect. The combination of CPS + HPS achieved HPS-loaded CPC. Material characterization, cytocompatibility, biosafety, and femoral implantation experiments indicated that CPS + HPS possessed better pressure resistance and improved osteogenic ability in bone defect repair.CPS + HPS demonstrated effective pressure resistance and superior osteogenic ability, which may be of great significance for bone defects and bone tissue engineering to promote bone regeneration and repair.Graphical The composite CPS loaded with HPS-50 is an excellent scaffold with fine load-bearing ability and sustained release of osteogenic factors to repair bone defects.

Serum microRNAs as new biomarkers for detecting subclinical hemolysis in the nonacute phase of G6PD deficiency

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common enzymopathies worldwide. Patients with G6PD deficiency are usually asymptomatic throughout their life but can develop acute hemolysis after exposure to free radicals or certain medications. Several studies have shown that serum miRNAs can be used as prognostic biomarkers in various types of hemolytic anemias. However, the impact of G6PD deficiency on circulating miRNA profiles is largely unknown. The present study aimed to assess the use of serum miRNAs as biomarkers for detecting hemolysis in the nonacute phase of G6PD deficiency. Patients with severe or moderate G6PD Viangchan (871G > A) deficiency and normal G6PD patients were enrolled in the present study. The biochemical hemolysis indices were normal in the three groups, while the levels of serum miR-451a, miR-16, and miR-155 were significantly increased in patients with severe G6PD deficiency. In addition, 3D analysis of a set of three miRNAs (miR-451a, miR-16, and miR-155) was able to differentiate G6PD-deficient individuals from healthy individuals, suggesting that these three miRNAs may serve as potential biomarkers for patients in the nonhemolytic phase of G6PD deficiency. In conclusion, miRNAs can be utilized as additional biomarkers to detect hemolysis in the nonacute phase of G6PD deficiency.

Anemia and Iron Profile in Hemodialysis and Nonhemodialysis Patients with Chronic Kidney Disease

Abstract BACKGROUND: Chronic kidney disease (CKD) is a global health concern, with anemia being a significant complication. Anemia in CKD patients is multifactorial and often leads to poorer outcomes. Assessing the iron profile, including serum ferritin, iron, and transferrin saturation, is crucial for identifying absolute or functional iron deficiency anemia (IDA). An objective evaluation of the iron profile is essential for effective and comprehensive management of anemia. MATERIALS AND METHODS: The study involved 100 adult patients with CKD and anemia, who were divided into two groups based on age and sex. The patients were divided into two groups: one received regular hemodialysis (HD) 2–3 times per week, whereas the other received no dialysis or dialysis infrequently. Exclusion criteria included infections, inflammation, renal injury, neoplasms, acute hemolysis, and thalassemia. RESULTS: Anemia is a common complication in patients with CKD, both those on HD and non-HD. Among the types of anemia observed, 50% of HD patients and 72% of non-HD CKD patients have normochromic anemia. In addition, 46% of HD patients and 24% of non-HD patients have IDA. Specifically, 24% of HD patients have absolute IDA and 22% have functional IDA, compared to 12% of both absolute and functional IDA in non-HD CKD patients, with a significant statistical difference between the two groups. Furthermore, serum iron and transferrin saturation levels show significant differences between HD and non-HD CKD patients. CONCLUSION: Anemia, especially IDA in CKD patients undergoing HD, requires accurate diagnosis through transferrin saturation and serum iron levels, and customized treatment based on dialysis status and anemia type is crucial.

Transfusion support and pre-transfusion testing in autoimmune haemolytic anaemia.

Autoimmune haemolytic anaemia (AIHA) is characterized by an increased destruction of red blood cells due to immune dysfunction and auto-antibody production. Clinical manifestations are mainly related to anaemia, which can become life-threatening in case of acute haemolysis. Aiming at counterbalancing severe anaemia, supportive treatments for these patients frequently include transfusions. Unfortunately, free serum auto-antibodies greatly interfere in pre-transfusion testing, and the identification of compatible red blood cell units for AIHA patients can be challenging or even impossible. Problems faced in pre-transfusion testing often lead to delay or abandonment of transfusions for AIHA patients. In this review, we discuss publications concerning global transfusion management in AIHA, with a focus on pre-transfusion testing, and practical clues to manage the selection of transfusion units for these patients. Depending on the degree of transfusion emergency, we propose an algorithm for the selection and laboratory testing of units to be transfused to AIHA patients.

Medications and Acute Hemolysis in G6PD-Deficient Patients - A Real-World Study.

Many drug labels contain precautions of use in G6PD-deficient patients due to hemolytic concerns, but much of this is based on scarce clinical, epidemiological, or structural data. In this real-world study, we aimed to examine if the administration of presumably risky medications for G6PD-deficient patients was followed by hemolysis. The study is based on data from Clalit Health Services database that provides inclusive health care for more than half of the Israeli population (~ 4.7 million). Within the database, we identified all G6PD-deficient patients by G6PD <6 U/g Hb. Within the G6PD-deficient cohort, we identified all hospitalizations with a discharge diagnosis of hemolysis (January 1, 2010 to December 31, 2022), validated the cases, and identified the culprit event. For the rest of the G6PD-deficient patients with no-hemolysis, we recorded filled prescriptions of medications listed as presumably risky. We identified 31,962 G6PD-deficient patients. Within the cohort, there were 71 cases of major hemolysis requiring hospitalization (0.2% of the cohort), of whom 51 (71.8%) had been caused by ingestion of fava beans, six (8.5%) were associated with an infection, and three (4.2%) suggested to be associated with medications (nitrofurantoin, phenazopyridine, and a "pain killer"). Within the 31,875 patients with no major hemolysis, nitrofurantoin has been prescribed safely to 1,366 G6PD-deficient males and females; hundreds/thousands of G6PD-deficient patients had been prescribed safely ciprofloxacin, glibenclamide, ofloxacin, phenazopyridine, sulfamethoxazole/cotrimoxazole, sulfasalazine, hydroxychloroquine, glimepiride, mesalazine, and sulfacetamide. In this real-world study, we are showing that a list of medications, suspected previously as carrying risks for hemolysis in G6PD-deficient patients, have been prescribed safely to G6PD-deficient patients, providing reassurance to patients, prescribers, and regulators.

Acute hemolytic transfusion reaction caused by anti-M antibodies: a case report and literature review.

We report a rare case of acute hemolytic reactions caused by immunoglobulin (Ig)M anti-M antibody and present a literature review. A 61-year-old male patient who underwent blood transfusion developed fever, chills, soy sauce-colored urine, and changes in laboratory test results, including persistently decreased hemoglobin levels, neutrophilia, elevated lactate dehydrogenase level, acute kidney injury, mild acute liver injury, and activation of the coagulation system, indicating acute hemolytic transfusion reaction (AHTR). Antibody screening and major crossmatching results indicated weak positive at 37°C for both posttransfusion and pretransfusion sample. Subsequent serological examinations indicated the presence of IgM anti-M antibodies in plasma but the direct antiglobulin and elution tests were negative. Antibody hemolytic activity assay confirmed AHTR caused by anti-M. The transfused red blood cells were MM and the patient is NN. These signs and symptoms disappeared rapidly and required no additional interventions before discharge. The accurate diagnosis of anti-M antibody-mediated acute hemolysis is essential for guiding treatment decisions.

Heme-induced loss of renovascular endothelial protein C receptor promotes chronic kidney disease in sickle mice

AbstractChronic kidney disease (CKD) is a major contributor to morbidity and mortality in sickle cell disease (SCD). Anemia, induced by chronic persistent hemolysis, is associated with the progressive deterioration of renal health, resulting in CKD. Moreover, patients with SCD experience acute kidney injury (AKI), a risk factor for CKD, often during vaso-occlusive crisis associated with acute intravascular hemolysis. However, the mechanisms of hemolysis-driven pathogenesis of the AKI-to-CKD transition in SCD remain elusive. Here, we investigated the role of increased renovascular rarefaction and the resulting substantial loss of the vascular endothelial protein C receptor (EPCR) in the progressive deterioration of renal function in transgenic SCD mice. Multiple hemolytic events raised circulating levels of soluble EPCR (sEPCR), indicating loss of EPCR from the cell surface. Using bone marrow transplantation and super-resolution ultrasound imaging, we demonstrated that SCD mice overexpressing EPCR were protective against heme-induced CKD development. In a cohort of patients with SCD, plasma sEPCR was significantly higher in individuals with CKD than in those without CKD. This study concludes that multiple hemolytic events may trigger CKD in SCD through the gradual loss of renovascular EPCR. Thus, the restoration of EPCR may be a therapeutic target, and plasma sEPCR can be developed as a prognostic marker for sickle CKD.

A case report of acute oxidative haemolysis following medicinal plant ingestion in a patient with G6PD deficiency

A case report of acute oxidative haemolysis following medicinal plant ingestion in a patient with G6PD deficiency

Hydroxychloroquine inhibits hemolysis-induced arterial thrombosis ex vivo and improves lung perfusion in hemin-treated mice

BackgroundFree labile hemin acts as a damage-associated molecular pattern during acute and chronic hemolysis and muscle injury, supporting platelet activation and thrombosis. ObjectivesTo investigate the anti-thrombotic potential of hydroxychloroquine on hemolysis-induced platelet activation and arterial thrombosis. MethodsThe effect of hydroxychloroquine on hemin-induced platelet activation and hemolysis-induced platelet recruitment and aggregation was measured in washed platelets and hemolyzed blood, respectively. Its effect on ferric-chloride (FeCl3)-induced arterial thrombosis and lung perfusion following hemin injection was assessed in wild-type mice. ResultsErythrocyte lysis and endothelial cell activation cooperatively supported platelet aggregation and thrombosis at arterial shear stress. This thrombotic effect was reversed by hydroxychloroquine. In a purified system, hydroxychloroquine inhibited platelet build-up on immobilized von Willebrand factor in hemolyzed blood without altering initial platelet recruitment. Hydroxychloroquine inhibited hemin-induced platelet activation and phosphatidylserine exposure independently of reactive oxygen species generation. In the presence of hemin, hydroxychloroquine did not alter glycoprotein VI shedding but reduced C-type-lectin-like-2 expression on platelets. In vivo, hydroxychloroquine reversed pulmonary perfusion decline induced by exogenous administration of hemin. In arterial thrombosis models, hydroxychloroquine inhibited ferric-chloride–induced thrombosis in the carotid artery and reduced von Willebrand factor accumulation in the thrombi. ConclusionHydroxychloroquine inhibited hemolysis-induced arterial thrombosis ex vivo and improved pulmonary perfusion in hemin-treated mice, supporting a potential benefit of its use as an adjuvant therapy in hemolytic diseases to limit arterial thrombosis and to improve organ perfusion.

Modern management of leukemoid reactions

ABSTRACT. Leukemoid reaction (LR) is a transient hematological syndrome of reactive nature characterized by persistent leukocytosis of more than 50,000 cells/µL. LR can be caused by a variety of factors, including infections, intoxications, malignant neoplasms, severe hemorrhages, or acute hemolysis.&#x0D; The most common form of LR is neutrophilic myeloid reaction, which occurs in 80-90 % of cases. The diagnosis of LR is based on clinical examination and laboratory test results, including complete blood count with differential leukocyte formula, determination of leukocyte alkaline phosphatase level, aspiration and biopsy of bone marrow.&#x0D; Differential diagnosis of LR from other forms of leukemia is a challenging task. For this, it is necessary to conduct a thorough examination, including cytogenetic and molecular analysis of peripheral blood and bone marrow granulocytes. Despite certain advances in the differential diagnosis of LR, the mortality rate of patients in the world remains high, which requires the attention of doctors of various profiles.&#x0D; Treatment of LR depends on the underlying cause that caused it. The article proposes a diagnostic and treatment algorithm for LR in the case of its toxico-infectious origin.

Acalypha indica induced acute oxidative haemolysis and methaemoglobinaemia: two case reports

BackgroundHerbal products and traditional remedies are commonly used by individuals worldwide for the management of common ailments, even though most are not without risks. Acalypha indica is a popular medicinal plant consumed in some Asian countries.Case presentationThis case report presents a 40-year-old previously unevaluated Sri Lankan female and her 8-year-old son who presented with severe glucose-6-phosphate dehydrogenase (G6PD) deficiency related acute intravascular oxidative haemolysis and methaemoglobinaemia precipitated by Acalypha indica consumption, successfully managed with supportive care and blood transfusion.ConclusionsThis case highlights the potential hemolytic and methaemoglobinaemic effects of ingesting oxidant herbal products and the importance of considering such exposures in patients presenting with hemolysis and multiorgan involvement, particularly in communities where herbal product intake is popular. Healthcare providers should be aware of the risks associated with traditional remedies and maintain a high index of suspicion to ensure prompt recognition and appropriate management.

Kidney involvement in Wilson's disease: a review of the literature.

Wilson's disease (WD) is a rare inherited disease due to the mutation of the ATP7B gene, resulting in impaired hepatic copper excretion and its pathological accumulation in various organs such as the liver, the nervous system, or the kidneys. Whereas liver failure and neuropsychiatric disorders are the most common features, less is known about the renal complications. We conducted a review of the literature to define the characteristics and pathophysiology of kidney involvement during WD. This review shed light on strong evidence for direct copper toxicity to renal tubular cells. Excessive tubular copper accumulation might present with various degrees of tubular dysfunction, ranging from mild hydroelectrolytic and acid-base disorders to complete Fanconi syndrome. Proximal and distal renal tubular acidosis also favors development of nephrolithiasis, nephrocalcinosis, and bone metabolism abnormalities. Indirect complications might involve renal hypoperfusion as occurs in hepatorenal or cardiorenal syndrome, but also tubular casts' formation during acute hemolysis, rhabdomyolysis, or bile cast nephropathy. Acute kidney failure is not uncommon in severe WD patients, and independently increases mortality. Finally, specific and long-term therapy by D-penicillamin, one of the most efficient drugs in WD, can cause glomerular injuries, such as membranous nephropathy, minimal-change disease, and, rarely, severe glomerulonephritis. Altogether, our study supports the need for interdisciplinary evaluation of WD patients involving nephrologists, with regular monitoring of tubular and glomerular functions, to provide adequate prevention of renal and bone involvement.

Management of acute breakthrough hemolysis with intensive pegcetacoplan dosing in patients with PNH

AbstractParoxysmal nocturnal hemoglobinuria (PNH) is characterized by complement-mediated intravascular hemolysis leading to anemia, fatigue, and potentially life-threatening thrombotic complications. Breakthrough hemolysis (BTH) was first described in patients with PNH treated with terminal complement C5 inhibitors when intravascular hemolysis reoccurred despite treatment. Pegcetacoplan, the first proximal complement C3 inhibitor, offers broad hemolysis control in patients with PNH. While experience of managing BTH on C5 inhibitors is documented, very limited guidance exists for proximal complement inhibitors. This interim analysis assessed the effect of intensive treatment with pegcetacoplan following an acute BTH event in a subset of patients enrolled in the ongoing open-label extension study of pegcetacoplan in PNH. Thirteen patients with acute BTH included in the analysis received either a single IV dose of 1080 mg (n = 4) or 1080 mg subcutaneous (SC) dosing on 3 consecutive days (n = 9). A potential, clinically-relevant complement-amplifying condition, such as infection or vaccination, was reported in approximately half of the patients experiencing an acute BTH. Lactate dehydrogenase (LDH) levels decreased between day 1 and day 2 in 8 of 12 evaluable patients and in all 13 patients at day 7 to 12. Nine of 13 patients (69%) achieved LDH <2× the upper limit of normal by day 14 to 19. All adverse events associated with the acute BTH event were considered resolved by the investigators. Overall, intensive treatment with pegcetacoplan was safe and well tolerated. These novel data support effective management of acute BTH events in patients on pegcetacoplan with intensive IV or SC pegcetacoplan dosing. This trial was registered at www.clinicaltrials.gov as #NCT03531255.

Collage of cases and brief review of the laboratory diagnosis and molecular testing in autoimmune haemolytic anaemia.

Autoimmune haemolytic anaemia (AIHA) is an acquired heterogenous clinical entity with variable presentations like acute haemolysis or mild, chronic haemolysis compounded with acute exacerbation in winters or fatal uncompensated haemolysis. A step-wise approach to the diagnosis and characterisation of AIHA should be undertaken, firstly the diagnosis of haemolysis followed by the establishment of immune nature with the aid of direct agglutination tests (DAT). Simultaneously the other causes of immune haemolysis need to be excluded too. In light of advancements in diagnostics, a wide array of investigations can be used like absolute reticulocyte count, bone marrow responsiveness index to establish the evidence of haemolysis, sensitive gel technology, enhanced DAT assays, e.g., modified DAT with low ionic strength saline solution (LISS) at 4°C, DAT assays utilizing reagents such as anti-IgA and anti-IgM and DAT by flowcytometry, to detect RBC bound autoantibodies (Abs) and monospecific DAT to establish immune causes of haemolysis and characterisation of the autoantibodies. The compensatory role of bone marrow and synchronous pathologies like clonal lymphoproliferation, dyserythropoiesis, fibrosis are important factors in the evolution of the disease and aid in the customisation of treatment modalities. The laboratory work up should aim to diagnose underlying diseases like chronic lymphoproliferative disorders, autoimmune disorders and infectious diseases. Also, tests like autoimmune lymphoproliferative syndromes (ALPS) screening panel and Next-generation sequencing (NGS) panel for RBC membrane disorders, RBC enzymopathies, and congenital dyserythropoietic aneamia have found their place. It is incumbent upon the clinicians to use the all-available diagnostic modalities for the accurate diagnosis, prognostication and customisation of the therapy.

Newborn screening and diagnosis for Glucose-6-phosphate dehydrogenase deficiency at Danang Hospital for Women and Children

Background: G6PD deficiency can result in acute hemolysis anemia during times of increased reactive oxygen species production. This study aimed to investigate the rate of high risk among newborns who were screened for G6PD deficiency, as well as some clinical characteristics of those who had this disease at Da Nang Hospital for Women and Children. Materials and Methods: 10,020 newborns were screened for G6PD deficiency using dried heel blood spots,. Samples of peripheral venous blood is drawn from high-risk infants for diagnostic testing. Results: The proportion of high-risk newborns was 1.12%, with boys having a greater incidence than girls (1.71% versus 0.48%). G6PD activity was higher in premature infants than in term infants. G6PD activity was higher in infants having low birth weight (&lt; 2500 g) than in ones having normal birth weight (≥ 2500 g). Only 45.54% of high-risk newborns were tested for diagonosis. Among them, 92.16% had diagnostic confirmation. G6PD deficiency in class II accounts for 31.91%, whereas class III accounts for 68.09%. Boys accounted for 87.23% and jaundice accounted for 82.98% of infants with G6PD deficiency. Only 6.38% of those had a family history of G6PDD deficiency. Conclusion: Da Nang Hospital for Women and Children’s newborn screening programme identified 1.12% of newborns as high risk for G6PD deficiency. Most neonates with G6PD deficiency were in classes II and III, with males being the main gender, and jaundice being the most common symptom. Key words: G6PD deficiency, newborn screening, hell blood, enzyme activity

Artemisinin-naphthoquine plus lower-dose primaquine to treat and prevent recurrence of Plasmodium vivax malaria: an open-label randomized and non-inferiority trial.

Plasmodium vivax malaria, with the widest geographic distribution, can cause severe disease and death. Primaquine is the main licensed antimalarial drug that can kill hypnozoites. The dose-dependent acute haemolysis in individuals with glucose-6-phospate dehydrogenase (G6PD) deficiency is the main safety concern when using primaquine. The recommended treatment regimen for P. vivax malaria is chloroquine plus primaquine for 14days (CQPQ14) in Myanmar. The study aimed to evaluate the therapeutic efficacy, safety and adherence for the regimen of artemisinin-naphthoquine plus primaquine for 3days (ANPQ3) in patients with P. vivax infections compared to those with CQPQ14. The patients in the ANPQ3 group were given fixed-dose artemisinin-naphthoquine (a total 24.5mg/kg bodyweight) plus a lower total primaquine dose (0.9mg/kg bodyweight) for 3days. The patients in the CQPQ14 group were given a total chloroquine dose of 30mg/kg body weight for 3days plus a total primaquine dose of 4.2mg/kg bodyweight for 14days. All patients were followed up for 365days. A total of 288 patients completed follow-up, 172 in the ANPQ3 group and 116 in the CQPQ14 group. The first recurrence patients were detected by day 58 in both groups. By day 182, 16 recurrences had been recorded: 12 (7.0%) patients in the ANPQ3 group and 4 (3.4%) in the CQPQ14 group. The difference in recurrence-free patients was 3.5 (-8.6 to 1.5) percentage points between ANPQ3 and CQPQ14 group (P = 0.2946). By day 365, the percentage of recurrence-free patients was not significant between the two groups (P = 0.2257). Mean fever and parasite clearance time of ANPQ3 group were shorter than those in CQPQ14 group (P ≤ 0.001). No severe adverse effect was observed in ANPQ3 group, but five (3.9%) patients had acute haemolysis in CQPQ14 group (P = 0.013). Medication percentage of ANPQ3 group was significantly higher than that of CQPQ14 group (P < 0.0001). Both ANPQ3 and CQPQ14 promised clinical cure efficacy, and the radical cure efficacy was similar between the ANPQ3 and CQPQ14 group. ANPQ3 clears fever and parasites faster than CQPQ14. ANPQ3 is safer and shows better patient adherence to the regimen for treatment of P. vivax malaria along the China-Myanmar border. ChiCTR-INR-17012523. Registered 31 August 2017, https://www.chictr.org.cn/showproj.html?proj=21352.

Hb Mizuho Case Report; Early Genomic Testing Facilitates a Life Changing Diagnosis

Unstable variant hemoglobinopathies are an uncommon cause of hemolysis in the pediatric patient and may cause a delay in diagnosis if there is not a high index of suspicion. Hemoglobin (Hb) Mizuho is a rare unstable hemoglobinopathy caused by a pathogenic variant of the HBB gene with a severe phenotype. Here we report on the first known case of Hb Mizuho in Australia, presenting with features of acute and chronic hemolysis. The morphological features on blood film review, in conjunction with biochemical findings and other clinical features, did not immediately suggest an alternative diagnosis and a Next Generation Sequencing gene analysis approach was taken to investigate genes associated with red blood cell disorders and atypical uremic syndrome. The HBB Mizuho variant was detected and established the diagnosis. This report highlights the challenge of diagnosing Hb Mizuho on conventional testing and the need for early genomic testing to clarify a diagnosis.