Effect of Artemisia annua (Asteraceae) Extracts on Hemolysis in Individuals with G6PD-Deficiency

Individuals with Glucose-6-phosphate dehydrogenase (G6PD) deficiency are susceptible to hemolytic anemia when exposed to pro-oxidant substances. This study investigates the hemolytic impact of Artemisia annua (A. annua) extracts in G6PD-deficient subjects through a mixed experimental approach. In the in vitro phase, red blood cells from G6PD-deficient individuals and rats induced with Dehydroepiandrosterone (DHEA) were exposed to various concentrations of A. annua infusion, with distilled water and physiological saline as positive and negative controls respectively. The in vivo study involved G6PD-deficient Wistar rats divided into three groups receiving A. annua infusion, quinine (positive control), and distilled water (negative control) via gavage. Blood samples were collected for biochemical and hematological analyses. Notably, at a 40% concentration of A. annua infusion, there was a significant increase in the hemolysis rate of G6PD-deficient red blood cells compared to controls (p A. annua exhibited elevated aspartate aminotransferase (129.25 ± 4.55 U/L vs. 80.09 ± 4.03 U/L;p A. annua infusion tested positive for saponins. These findings underscore the risk of hemolysis in G6PD-deficient individuals upon ingesting A. annua.

Hemolysis attributed to high dose vitamin C:Two case reports

BACKGROUND High-dose vitamin C treatment(HVCT)can reduce the adverse effect of chemotherapy and enhance the effect of antitumor therapy,which has been considered one of the safest alternative treatments.However,the severity of its adverse effects may have been underestimated.The most serious adverse effect is hemolysis,which may result in acute kidney injury or death.Although glucose-6-phosphate dehydrogenase(G6PD)deficiency is considered to be the main cause,the probability and pathological mechanism are not completely understood,leading to a lack of effective and standardized treatment methods.CASE SUMMARY Two patients with colorectal cancer developed hemolytic anemia after using 1 g/kg HVCT.In contrast to previous cases,the lowest hemoglobin level in the two cases was<50 g/L,which was lower than previously reported.This may be because Case 1 had chronic hepatitis B for many years,which caused abnormal liver reserve function,and Case 2 had grade II bone marrow suppression.Both patients improved and were discharged after blood replacement therapy.Our cases had the most severe degree of hemolysis but the best prognosis,suggesting that our treatment may be helpful for rescue of drug-induced hemolysis.This is the first review of the literature on hemolysis caused by HVCT,and we found that all patients with G6PD deficiency developed hemolysis after HVCT.CONCLUSION G6PD deficiency should be considered as a contraindication to HVCT,and it is not recommended for patients with bone marrow suppression,moderate-tosevere anemia,hematopoietic abnormalities,or abnormal liver and kidney function.Early blood purification and steroid therapy may avoid acute kidney injury or death caused by HVCT-related hemolytic anemia.

Gas-forming liver abscess associated with rapid hemolysis in a diabetic patient

We experienced a case of liver abscess due to Clostridium perfringens(CP) complicated with massive hemolysis and rapid death in an adequately controlled type2 diabetic patient. The patient died 6 h after his first visit to the hospital. CP was later detected in a blood culture. We searched for case reports of CP septicemia and found 124 cases. Fifty patients survived, and 74died. Of the 30 patients with liver abscess, only 3 cases survived following treatment with emergency surgica drainage. For the early detection of CP infection, detection of Gram-positive rods in the blood or drainage fluid is important. Spherocytes and ghost cells indicate intravascular hemolysis. The prognosis is very poor once massive hemolysis occurs. The major causative organisms of gas-forming liver abscess in diabetic patients are Klebsiella pneumoniae(K. pneumoniae) and Escherichia coli(E. coli). Although CP is relatively rare,the survival rate is very poor compared with those of K. pneumoniae and E. coli. Therefore, for every case that presents with a gas-forming liver abscess, the possibility of CP should be considered, and immediate aspiration of the abscess and Gram staining are important.

Ribavirin induced hemolysis:A novel mechanism of action against chronic hepatitis C virus infection

Hepatitis C virus(HCV)is not usually cleared by our immune system,leading to the development of chronic hepatitis C infection.Chronic HCV induces the production of various cytokines,predominantly by Kupffer cells(KCs),and creates a pro-inflammatory state in the liver.The chronic dysregulated production of interferon(IFN)and other cytokines by KCs also promotes innate immune tolerance.Ribavirin(RBV)monotherapy has been shown to decrease inflammation in liver of patients with chronic hepatitis C.Sustained virological response(SVR)is significantly higher when IFN is combined with RBV in chronic HCV(c HCV)infection.However,the mechanism of their synergy remains unclear.Previous theories have attempted to explain the anti-HCV effect based on direct action of RBV alone on the virus or on the immune system;however,these theories have serious shortcomings.We propose that hemolysis,which universally occurs with RBV therapy and which is considered a limiting side effect,is precisely the mechanism by which the anti-HCV effect is exerted.Passive hemolysis results in anti-inflammatory/antiviral actions within the liver that disrupt the innate immune tolerance,leading to the synergy ofRBV with IFN-α.Ribavirin-induced hemolysis floods the hepatocytes and KCs with heme,which is metabolized and detoxified by heme oxygenase-1(HMOX1)to carbon monoxide(CO),biliverdin and free iron(which induces ferritin).These metabolites of heme possess anti-inflammatory and antioxidant properties.Thus,HMOX1 plays an extremely important anti-oxidant,anti-inflammatory and cytoprotective role,particularly in KCs and hepatocytes.HMOX1 has been noted to have anti-viral effects in hepatitis C infected cell lines.Additionally,it has been shown to enhance the response to IFN-αby restoring interferon-stimulated genes(ISGs).This mechanism can be clinically corroborated by the following observations that have been found in patients undergoing RBV/IFN combination therapy for c HCV:(1)SVR rates are higher in patients who develop anemia;(2)once anemia(due to hemolysis)occurs,the SVR rate does not depend on the treatment utilized to manage anemia;and(3)ribavirin analogs,such as taribavirin and levovirin,which increase intrahepatic ribavirin levels and which produce lesser hemolysis,are inferior to ribavirin for treating c HCV.This mechanism can also explain the observed RBV synergy with direct antiviral agents.This hypothesis is testable and may lead to newer and safer medications for treating c HCV infection.

Antioxidative Effect of Schiff Bases with o-Hydroxybenzylidene Groupon Free Radical Induced Hemolysis of Human Red Blood Cell

The hemolysis of human red blood cells was initiated by a water soluble free radical initiator, 2,2′ azobis (2 amidinopropane hydrochloride)(AAPH), at 37 ℃ in phosphate buffered saline(pH=7.4). The respective addition of 1 [ N (o hydroxybenzylidene)amino]tetradecane(TDCA), 1,2 di[ N (o hydroxybenzylidene)amino]cyclohexane(DACH), 4 [ N (o hydroxybenzylidene)amino]benzoic acid(PABA), 4 nitro[ N (o hydroxybenzylidene)]aniline(APNA) or N (o hydroxybenzylidene)aniline(APA) can all prolong the inhibition period of hemolysis, indicating that the above Schiff bases play an antioxidative role in free radical induced hemolysis. It can be concluded that Schiff base with an alkyl group or a conjugated system in the molecule protect red blood cells against free radical induced hemolysis efficiently. This information may be useful for antioxidant drug design.

Dendritic macromolecules as nano-scale drug carriers:Phase solubility,in vitro drug release,hemolysis and cytotoxicity study

Potential of nanoscale triazine based dendritic macromolecules G1,G2 and G3 as solubility enhancers of drug was investigated.Effect of pH,concentration and generation of synthesized dendritic macromolecules on solubility of ketoprofen was studied.G3 dendrimer was further exploited as carrier for sustained release.Ketoprofen was encapsulated by inclusion complex method and also characterized by Flourier Transform Infrared spectroscopy.Sustained release study of ketoprofen from ketoprofen loaded dendrimer was carried out and compared with free ketoprofen.Hemolytic potential and Cytotoxicity assay using A-549 lung cancer cell lines revealed that synthesized triazine based dendritic macromolecules having more potential that commercially available PAMAM dendrimer.

Hemolysis of PM_(10) on RBCs in vitro:An indoor air study in a coal-burning lung cancer epidemic area

Epidemiological studies have suggested that inhalation exposure to indoor ambient air from coal-burning environments is causally associated with respiratory health risks.In order to explore the toxicological mechanisms behind the adverse health effects,the hemolytic activity of PM_(10)(particulate matter with an aerodynamic diameter of 10 um or less)samples collected from homes burning coal in the recognized China"cancer village"Xuanwei were evaluated and matched against their trace elemental contents.The results demonstrated that the hemolytic activity of indoor PM_(10) in coal-burning environments ranged from 4.28%to 5.24%,with a clear positive dose-response relationship.Although low dose samples exhibited a reduced hemolytic activity,PM_(10) could have a toxic effect upon people in a coal-burning indoor environment for extended time periods.The concentrations of analyzed trace elements in PM_(10) samples ranged from 6966 to 12,958 ppm.Among the analyzed elements,Zn,Ti,Ni,Cu,Pb,Ba,Mn,Cr and V were found at higher concentrations and accounted for over 95%of the total elements.The concentrations of total analyzed elements in the PM_(10) samples revealed a significant positive correlation with PM_(10) hemolytic activity.Of the analyzed elements,Zn,Pb and Cs positively correlated with hemolysis,while Li,U and V negatively correlated with the hemolysis of human red blood cells(RBCs).Therefore,the heavy metal elements could be one of the main factors responsible for the hemolytic capacity of indoor PM_(10) in coal-burning environments.

Comprehensive review of hemolysis in ventricular assist devices

Ventricular assist devices(VADs)have played an important role in altering the natural history of end-stage heart failure.Low-grade hemolysis has been traditionally described in patients with VADs,indicating effective device functionality.However,clinically significant hemolysis could be crucial in terms of prognosis,calling for prompt therapeutic actions.The absence of solid and widely approved diagnostic criteria for clinically significant hemolysis,render the utilization of hemolysis laboratory markers challenging.Hemolysis incidence varies(5%-18%)depending on definition and among different VAD generations,being slightly higher in continuous-flow devices than in pulsatile devices.Increased shear stress of red blood cells and underlying device thrombosis appear to be the main pathogenetic pathways.No certain algorithm is available for the management of hemolysis in patients with VADs,while close clinical and laboratory monitoring remains the cornerstone of management.Imaging examinations such as echocardiography ramp test or computed tomography scan could play a role in revealing the underlying cause.Treatment should be strictly personalized,including either pharmacological(antithrombotic treatment)or surgical interventions.

New indicators in evaluation of hemolysis,elevated liver enzymes,and low platelet syndrome:A case-control study

BACKGROUND Indices such as the neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),mean platelet volume(MPV),platelet distribution width(PDW),and red cell distribution width(RDW)are considered new markers of the systemic inflammatory response(SIR),and have been widely implemented for the diagnosis of patients with inflammatory diseases.These new indicators have also been widely investigated in preeclampsia(PE)but less analyzed in hemolysis,elevated liver enzymes,and low platelet(HELLP)syndrome.AIM To compare SIR markers among HELLP patients,PE only patients,and healthy gravidae.METHODS This retrospective case-control study enrolled 630 cases,including 210 patients with HELLP syndrome(HELLP group),210 patients with only PE(PE group)and 210 healthy gravidae(control group).The three groups were matched by age,parity,status of assisted reproduction,and multiple pregnancies.Birthweight,gestational age at complete blood count collection,gestational age at delivery,mode of delivery,etc.were recorded.The main indices as NLR,PLR,MPV,PDW,and RDW among the groups were compared,as well as some secondary outcomes including neutrophil,platelets,and hemoglobin.RESULTS The NLR(6.4 vs 4.3 vs 3.5),MPV(11.9 vs 11.2 vs 10.7),PDW(16.4 vs 13.3 vs 14.2),leukocyte(12.4×10^(9)/L vs 9.7×10^(9)/L vs 8.7×10^(9)/L)and neutrophil count(9.9×10^(9)/L vs 7.3×10^(9)/L vs 6.1×10^(9)/L)were highest in the HELLP group,lower in the PE group,and lowest in the control group.Both the overall comparisons between the three groups(all bP<0.01)and pairwise comparisons between every two groups elicited statistically significant differences(all dP<0.01,except control vs PE:cP<0.05 in PDW).The average lymphocyte counts were 1.4(1.1,2.0)×10^(9)/L in the HELLP group,1.6(1.3,2.0)×10^(9)/L in the PE group and 1.7(1.4,2.0)×10^(9)/L in the control group.The overall comparison of lymphocyte count within the three groups had statistically significant differences(P=0.000).The pairwise comparisons between every two groups demonstrated that the HELLP group had a lower lymphocyte count than both the PE(P=0.019)and control groups(P=0.000),but the difference between the PE and control groups was not statistically significant(P=0.432).The overall comparisons on platelet counts and the PLR among these three groups also showed statistically significant differences(both P=0.000),from low to high being those in the HELLP group(43.4×10^(9)/L,64.0),control group(180.5×10^(9)/L,103.6)and PE group(181.5×10^(9)/L,112.8).Pairwise comparisons of neither index displayed statistically significant differences between the PE and control groups(both P>0.05),while the differences in the two indices between the HELLP group and the two other groups were still statistically significant(all P=0.000).RDW values were highest in the HELLP group(14.5%[13.6,15.3]),lower in the control group(14.1%[13.5,14.8])and lowest in the PE group(13.9%[13.4,14.9]).The difference between the PE and control group did not show statistical significance(P=1.000),while RDW values in the HELLP group were higher than those in the other two groups(cP<0.05 vs control,dP<0.01 vs PE).CONCLUSION SIR markers such as NLR,RDW,MPV,and PDW were increased and PLR was decreased in HELLP.These SIR markers may become new indicators in the evaluation of HELLP syndrome.

Hemolysis effect and calcium-phosphate precipitation of heat-organic-film treated magnesium

A heat-organic-films process was employed to induce calcium-phosphate apatites formation on magnesium, consequently the corrosion resistance and hemolysis properties of magnesium were improved for biomedical applications. Firstly, magnesium samples were heat-treated at 773 K for 10 h; secondly, stearic acid films were coated on the surface of the heat-treated magnesium. Then the surface modified magnesium was soaked in simulated body fluid (SBF) to test its corrosion resistance. The results show that the heat treatment process allows magnesium to form a dense oxide layer with a thickness of around 20 μm, thereby the surface modified magnesium has higher corrosion resistance. After 24 h in SBF island apatite was deposited on magnesium. The unevenly precipitates were characterized by XRD and FTIR as the mixture of hydroxyapatite(HA) and octacalcium phosphate(OCP). The preliminary hemolysis experiment indicates that untreated magnesium has hemolytic effect (about 60%); whereas the heat-organic film treated samples has no hemolytic effect. The mechanism of fast nucleation and growth of calcium-phosphate apatites on surface modified magnesium in SBF was also discussed.

Left ventricular assist device hemolysis leading to dysphagia

A 41-year-old man with a continuous- flow left ventricular assist device presented for evaluation of dysphagia and dark urine. He was found to have a significantly elevated L-lactate dehydrogenaseand an elevated plasma free hemoglobin consistent with intravascular hemolysis.After the hemolysis ceased,both the black urine and dysphagia resolved spontaneously.Transient esophageal dysfunction,as a manifestation of gastrointestinal dysmotility,is known to occur in the setting of hemolysis.Paroxysmal nocturnal hemoglobinuria is another recognized cause of massive hemolysis with gastrointestinal dysmotility occurring in25%-35%of patients during a paroxysm.Intravascular hemolysis increases plasma free hemoglobin,which scavenges nitric oxide(NO),an important second messenger for smooth muscle cell relaxation.The decrease in NO can lead to esophageal spasm and resultant dysphagia.In our patient the resolution of hemolysis resulted in resolution of dysphagia.

Studies on Hemolysis of Hemolysin Produced by Synechocystis sp. PCC 6803

Hemolysin produced by various bacteria,may destroy erythrocyte membranes via a pore-forming mechanism,a deter-gent action,or a lipase activity.Previous to this experiment,the mode of action used by cyanobacterial hemolysin had not been re-ported.To characterize the action mode of hemolysin produced by the wild-type strain of Synechocystis sp.PCC6803,hemolysis of erythrocytes originating from human,mouse,sheep,rabbit and goldfish was studied.The erythrocytes of mouse,sheep and rabbit were sensitive,while those of human and fish were resistant,to this hemolysin.Using rabbit erythrocytes,it was shown that hemoly-sis occurred in two steps:a binding step within the first 10 min of treatment and a lytic step after 30 min.Both binding and lysis were highly temperature-dependent.Effects of erythrocyte density on hemolysis suggest that the hemolysin might target erythrocytes via a multiple-hit mechanism.In the osmotic protection experiment,all tested osmotic protectants,with molecular diameters ranging from 0.9 ?5.66 nm,failed to effectively inhibit hemolysis.Scanning electron micrographs showed that the hemolysin caused protuberances or echinocytes in rabbit erythrocytes,and then disrupted and ruptured the erythrocytes.Characteristics of hemolysis showed distinct differences from other pore-forming mechanisms,suggesting that this hemolysin might act through a detergent-like or lipase mecha-nism,rather than a pore-forming mechanism.

Perihepatic adhesions: An unusual complication of hemolysis, elevated liver enzymes and low platelet syndrome

We present a case of symptomatic perihepatic adhesions,which developed after a pregnancy complicated by hemolysis,elevated liver enzymes and low platelet(HELLP)syndrome,in which a subcapsular liver hematoma occurred.Our patient presented with complaints of persistent,severe right-sided upper abdominal pain.The complaints developed gradually,one year after a pregnancy that had been complicated by HELLP syndrome with a subcapsular liver hematoma.The hematoma had resolved spontaneously.An upperabdominal magnetic resonance imaging revealed a density between liver and diaphragm at the site of the former subcapsular hematoma,suspect of perihepatic adhesions.The presence of perihepatic adhesions was confirmed during a laparoscopy and treated by adhesiolysis in the same session.The adhesions may have developed in response to the degradation process of the subcapsular liver hematoma during conservative treatment.This case of perihepatic adhesions may therefor be the first presentation of a long term sequel of subcapsular liver hematoma in HELLP syndrome.

Correlation between microbubble-induced acoustic cavitation and hemolysis in vitro

Microbubbles promise to enhance the efficiency of ultrasound-mediated drug delivery and gene therapy by taking advantage of artificial cavitation nuclei. The purpose of this study is to examine the ultrasound-induced hemolysis in the application of drug delivery in the presence of microbubbles. To achieve this goal, human red blood cells mixed with microbubbles were exposed to 1-MHz pulsed ultrasound. The hemolysis level was measured by a flow cytometry, and the cavitation dose was detected by a passive cavitation detecting system. The results demonstrate that larger cavitation dose would be generated with the increase of acoustic pressure, which might give rise to the enhancement of hemolysis. Besides the experimental observations, the acoustic pressure dependence of the radial oscillation of microbubble was theoretically estimated. The comparison between the experimental and calculation results indicates that the hemolysis should be highly correlated to the acoustic cavitation.

Resolution of hemolysis from pump thrombus during left ventricular assist device exchange

A 50-year-old male who underwent a Heart Mate Ⅱ left ventricular assist device placement for ischemic cardiomyopathy presented with discolored urine and hemolysis 3 mo after the operation. His hemolysis was thought to be due to thrombosis within the pump. Imaging studies were not able to visualize a left ventricular thrombus. Medical management with anticoagulation failed and he underwent surgery for a pump exchange. Intraoperatively, a firm thrombus was found within the pump of the Heart Mate Ⅱ, and the color of the urine changed dramatically from cola-colored to yellow which enabled us to confirm the diagnosis.

Effect of cationic microemulsion on hemolysis and immune cell uptake

Squalene-based oil-in-water nanoemulsions, constituents in influenza vaccines, have been approved in Europe as human licensed adjuvants (1)With similar constituents but easier manufacturing procedure and greater physical stability [2],microemulsion was of interest. To improve cellular uptake,positive surface charge of nanosystems has been reported(3)In the present study, cationic microemulsions were prepared, characterized and evaluated in immune cell.

Severe and delayed immune-mediated hemolysis post-liver transplantation

To the Editor:Hemolysis,which is caused by a variety of immune and non-immune mechanisms,is a well-recognized complication of solid organ transplantation.;Hemolysis post-liver transplantation can be induced by drug,infection,autoimmune disorders,blood-group incompatible

Erythrocyte Fragment Count Predicts Hemolysis in Roller Pumps

Objective: Hemolysis in blood pumps has been measured by various in vitro test methods, in which normalized index of hemolysis (NIH) was established. As NIH is complicated and difficult to calculate, erythrocyte fragment count is proposed in the present study to predict hemolysis in roller pumps.Methods: Five paired in vitro tests were conducted using the POLYSTAN pediatric pump(group A) and COBE pump(group B).Ten whole blood samples (400 m1) were circled in the roller pump for 16 h. Erythrocyte fragments count and plasma-free hemoglobin (FHb) were measured before pumping and every two hours through circulation after four-hour-pumping. The morphological changes of erythrocyte were observed by scanning electron microscope.Results: The two groups’EFC and FHb levels were increased linearly during a long duration of pumping and linear regression of erythrocyte fragments count and plasma-free hemoglobin were correlated.Conclusion: Erythrocyte fragments count could be used as an index in evaluating the in vitro hemolytic properties of blood pumps.