scholarly journals 4148 Thrombocytopenia and whole blood transfusion in children with severe falciparum malaria

2020 ◽  
Vol 4 (s1) ◽  
pp. 40-40
Author(s):  
Matthew M. Ippolito ◽  
Jean-Bertin Kabuya ◽  
Manuela Hauser ◽  
Benjamin Kussin-Shoptaw ◽  
Austin Peer ◽  
...  
Keyword(s):  
Blood Transfusion ◽  
Falciparum Malaria ◽  
Whole Blood ◽  
Hemoglobin Concentration ◽  
Rank Test ◽  
Clinical Role ◽  
Platelet Recovery ◽  
Severe Malarial Anemia ◽  
Severe Falciparum Malaria ◽  
Malarial Anemia

OBJECTIVES/GOALS: Severe malarial anemia due to Plasmodium falciparum is often accompanied by thrombocytopenia. Treatment includes transfusion of whole blood, which contains erythrocytes, platelets, and other blood components. The objective of the study was to assess the effect of whole blood transfusion on survival in children with severe falciparum malaria and to examine the potential interaction of thrombocytopenia with malaria mortality and transfusion response. METHODS/STUDY POPULATION: We analyzed a retrospective cohort of 842 hospitalized children in Zambia with severe malarial anemia (703 transfused, 139 not transfused due to stock-out or other reason). Severe malarial anemia was defined as a positive rapid diagnostic test or blood smear in combination with an admission hemoglobin concentration ≤5 g/dL. RESULTS/ANTICIPATED RESULTS: Mortality was 13% (94/703) in the transfused group and 24% (34/139) in the non-transfused group. Kaplan-Meier survival estimates stratified by transfusion status and thrombocytopenia (150,000/μL threshold) showed increased mortality in children with thrombocytopenia who did not undergo transfusion, with no differences in mortality among the other transfused and non-transfused groups (log-rank test P = 0.0001). Effect modification analysis by Cox proportional hazards regression adjusted for age, sex, hemoglobin concentration, blood group type, and eosinophilia showed a significant interaction between platelet count and transfusion status (P = 0.028). Children with thrombocytopenia who were transfused and died had little or no post-transfusion increase in platelets, in contrast to those who survived. Freshness of transfused whole blood, construed from expiration dates, correlated with greater platelet recovery and improved survival. DISCUSSION/SIGNIFICANCE OF IMPACT: The role of platelets in malaria pathophysiology is complex and incompletely understood; prior studies describe preferential binding of platelets to parasitized erythrocytes and direct parasitocidal activity, whereas others detailed deleterious effects in malaria involving the central nervous system vasculature. These findings point to a potential clinical role for platelet-directed transfusion strategies to improve survival in children with severe falciparum malaria, which should be further assessed in randomized interventional studies.

scholarly journals 963. Whole Blood Transcriptome Analysis Reveals Differences in Erythropoiesis and Neurologically Relevant Pathways Between Cerebral Malaria and Severe Malarial Anemia

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S35-S35
Author(s):  
Srinivas Nallandhighal ◽  
Gregory Park ◽  
Yen-Yi Ho ◽  
Robert Opoka ◽  
Chandy John ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cerebral Malaria ◽  
Severe Malaria ◽  
Whole Blood ◽  
Heme Oxygenase 1 ◽  
Specific Gene ◽  
Severe Malarial Anemia ◽  
Specific Gene Expression ◽  
Blood Transcriptome ◽  
Malarial Anemia

Abstract Background Plasmodium falciparum malaria can rapidly progress to severe disease that can lead to death if left untreated. Severe malaria cases commonly present as severe malarial anemia (SMA), defined in children as hemoglobin (Hb) <5 g/dL with parasitemia, or as cerebral malaria (CM), which manifests as parasitemia with acute neurological deficits and has an inpatient mortality rate of ~20%. The molecular and cellular processes that lead to CM and SMA are unclear. Methods In a cross-sectional study, we compared genome-wide transcription profiles of whole blood obtained from Ugandan children with acute CM (n = 17) or SMA (n = 17) and community children without P. falciparum infection (n = 12) who were enrolled in a parent cohort study of severe malaria. We determined the relationships between gene expression, hematological indices, and plasma biomarkers, including inflammatory cytokines. Results Both CM and SMA demonstrated enrichment of dendritic cell activation, inflammatory/TLR/chemokines, monocyte, and neutrophil modules but depletion of lymphocyte modules. Neurodegenerative disease and neuroinflammation pathways were enriched in CM. Increased Nrf2 pathway gene expression corresponded with increased plasma heme oxygenase-1 and the heme catabolite bilirubin in a manner specific to children with both SMA and sickle cell disease. Reticulocyte-specific gene expression was markedly decreased in CM relative to SMA despite higher Hb levels and appropriate increases in plasma erythropoietin. Viral sensing/interferon regulatory factor (IRF) 2 module (M111) expression and plasma IP-10 levels both negatively correlated with reticulocyte-specific signatures, but only M111 expression independently predicted decreased reticulocyte-specific gene expression after controlling for leukocyte count, Hb level, parasitemia, and clinical syndrome by multiple regression. Conclusion Differences in the blood transcriptome of CM and SMA relate to neurologically relevant pathways and erythropoiesis. Erythropoietic suppression during severe malaria is more pronounced during CM versus SMA and is positively associated with IRF2 blood signatures. Future studies are needed to validate these findings. Disclosures All authors: No reported disclosures.

scholarly journals Delayed iron improves iron status without altering malaria risk in severe malarial anemia

2020 ◽  
Vol 111 (5) ◽  
pp. 1059-1067 ◽  
Author(s):  
Sarah E Cusick ◽  
Robert O Opoka ◽  
Andrew S Ssemata ◽  
Michael K Georgieff ◽  
Chandy C John
Keyword(s):  
Iron Deficiency ◽  
Severe Malaria ◽  
Malaria Incidence ◽  
Iron Status ◽  
Hemoglobin Concentration ◽  
Malaria Risk ◽  
Antimalarial Treatment ◽  
Severe Malarial Anemia ◽  
Iron Treatment ◽  
Malarial Anemia

ABSTRACT Background WHO guidelines recommend concurrent iron and antimalarial treatment in children with malaria and iron deficiency, but iron may not be well absorbed or utilized during a malaria episode. Objectives We aimed to determine whether starting iron 28 d after antimalarial treatment in children with severe malaria and iron deficiency would improve iron status and lower malaria risk. Methods We conducted a randomized clinical trial on the effect of immediate compared with delayed iron treatment in Ugandan children 18 mo–5 y of age with 2 forms of severe malaria: cerebral malaria (CM; n = 79) or severe malarial anemia (SMA; n = 77). Asymptomatic community children (CC; n = 83) were enrolled as a comparison group. Children with iron deficiency, defined as zinc protoporphyrin (ZPP) ≥ 80 µmol/mol heme, were randomly assigned to receive a 3-mo course of daily oral ferrous sulfate (2 mg · kg–1 · d–1) either concurrently with antimalarial treatment (immediate arm) or 28 d after receiving antimalarial treatment (delayed arm). Children were followed for 12 mo. Results All children with CM or SMA, and 35 (42.2%) CC, were iron-deficient and were randomly assigned to immediate or delayed iron treatment. Immediate compared with delayed iron had no effect in any of the 3 study groups on the primary study outcomes (hemoglobin concentration and prevalence of ZPP ≥ 80 µmol/mol heme at 6 mo, malaria incidence over 12 mo). However, after 12 mo, children with SMA in the delayed compared with the immediate arm had a lower prevalence of iron deficiency defined by ZPP (29.4% compared with 65.6%, P = 0.006), a lower mean concentration of soluble transferrin receptor (6.1 compared with 7.8 mg/L, P = 0.03), and showed a trend toward fewer episodes of severe malaria (incidence rate ratio: 0.39; 95% CI: 0.14, 1.12). Conclusions In children with SMA, delayed iron treatment did not increase hemoglobin concentration, but did improve long-term iron status over 12 mo without affecting malaria incidence. This trial was registered at clinicaltrials.gov as NCT01093989.

scholarly journals The effect of SANGUINATE® (PEGylated carboxyhemoglobin bovine) on cardiopulmonary bypass functionality using a bovine whole blood model of normovolemic hemodilution

Perfusion ◽  
2019 ◽  
Vol 35 (1) ◽  
pp. 19-25
Author(s):  
Bryan T Romito ◽  
Mandy M McBroom ◽  
Dawn Bryant ◽  
Jacob Gamez ◽  
Akeel Merchant ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
High Risk ◽  
Blood Transfusion ◽  
Whole Blood ◽  
Oxygen Carrier ◽  
Hemoglobin Concentration ◽  
Arterial Line ◽  
Pump Speed ◽  
Normovolemic Hemodilution

Background: Cardiac surgery using cardiopulmonary bypass carries a high risk of bleeding and need for blood transfusion. Blood administration is associated with increased rates of morbidity and mortality. Perioperatively, strategies are often employed to reduce blood transfusions in high-risk patients or in situations where blood transfusion is contraindicated. Normovolemic hemodilution is a blood conservation technique used during cardiac surgery that involves replacement of blood with fluids. SANGUINATE® (PEGylated carboxyhemoglobin bovine) is a novel hemoglobin-based oxygen carrier that can deliver oxygen effectively to tissues in the presence of severe hypoxia. The use of a hemoglobin-based oxygen carrier during hemodilution may augment tissue oxygen delivery and reduce blood transfusion. Methods: Six standardized cardiopulmonary bypass runs simulating normovolemic hemodilution using varying proportions of bovine whole blood and SANGUINATE were performed. Pump speed, flow rate, line pressures, hemoglobin concentration, oxygenation, and degree of anticoagulation were assessed at regular intervals. Membrane oxygenators and arterial line filters were inspected for evidence of clotting following each run. Results: Increases in the pressure drop across the membrane oxygenator were detected during runs 5 and 6. Median activated clotting time values were able to be maintained at goal during the runs, and SANGUINATE did not appear to be thrombogenic. Hemoglobin concentration decreased following the addition of SANGUINATE. Oxygenation was maintained during all runs that included SANGUINATE. Conclusion: SANGUINATE does not impact the performance of the cardiopulmonary bypass circuit in a bovine whole blood model. The results support further evaluation of SANGUINATE in the setting of normovolemic hemodilution and cardiopulmonary bypass.

scholarly journals A Novel Functional Variant in the Stem Cell Growth Factor Promoter Protects against Severe Malarial Anemia

2009 ◽  
Vol 78 (1) ◽  
pp. 453-460 ◽  
Author(s):  
Collins Ouma ◽  
Christopher C. Keller ◽  
Gregory C. Davenport ◽  
Tom Were ◽  
Stephen Konah ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factor ◽  
Cell Growth ◽  
Falciparum Malaria ◽  
Western Kenya ◽  
Production Index ◽  
Severe Malarial Anemia ◽  
Stem Cell Growth Factor ◽  
Reticulocyte Production ◽  
Malarial Anemia

ABSTRACT Plasmodium falciparum malaria is a leading global cause of infectious disease burden. In areas in which P. falciparum transmission is holoendemic, such as western Kenya, severe malarial anemia (SMA) results in high rates of pediatric morbidity and mortality. Although the pathophysiological basis of SMA is multifactorial, we recently discovered that suppression of unexplored hematopoietic growth factors that promote erythroid and myeloid colony development, such as stem cell growth factor (SCGF) (C-type lectin domain family member 11A [CLEC11A]), was associated with enhanced development of SMA and reduced erythropoietic responses. To extend these investigations, the relationships between a novel SCGF promoter variant (−539C/T, rs7246355), SMA (hemoglobin [Hb] < 6.0 g/dl), and reduced erythropoietic responses (reticulocyte production index [RPI], <2.0) were investigated with Kenyan children (n = 486) with falciparum malaria from western Kenya. Circulating SCGF was positively correlated with hemoglobin levels (r = 0.251; P = 0.022) and the reticulocyte production index (RPI) (r = 0.268; P = 0.025). Children with SMA also had lower SCGF levels than those in the non-SMA group (P = 0.005). Multivariate logistic regression analyses controlling for covariates demonstrated that individuals with the homologous T allele were protected against SMA (odds ratio, 0.57; 95% confidence interval [95% CI] 0.34 to 0.94; P = 0.027) relative to CC (wild-type) carriers. Carriers of the TT genotype also had higher SCGF levels in circulation (P = 0.018) and in peripheral blood mononuclear cell culture supernatants (P = 0.041), as well as an elevated RPI (P = 0.005) relative to individuals with the CC genotype. The results presented here demonstrate that homozygous T at −539 in the SCGF promoter is associated with elevated SCGF production, enhanced erythropoiesis, and protection against the development of SMA in children with falciparum malaria.

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