Reduced Hb Levels Research Articles

Haematinic and Hepatoprotective Properties of Telfairia occidentalis Fruit Mesocarp on Phenylhydrazine-Induced Anaemia in Experimental Rats.

The level and potential of iron contained in fluted pumpkin (Telfairia occidentalis) has been exploited as a blood tonic; however, the potentials of some other parts of the plant are unknown. The effect of T. occidentalis fruit mesocarp (aqueous extract) on phenylhydrazine (PHZ)-induced anaemia in experimental rats was investigated in a bid to determine its curative properties and potential in reversing haemolytic anaemia and protection of liver health. The LD50 of the fruit extract was determined using Lorke's method for the determination of acute toxicity. The study involved oral administration of varying doses of the extract to different groups of rats which were monitored for 24 hours. The test sample did not show any signs of toxicity at doses of 5000 mg/kg b.wt, which is the highest possible recommended dose for toxicity testing. For the evaluation of the effects of the fruit extract on haematological indices and biochemical enzyme markers in anaemic rats, 30 matured albino Wistar rats were used. The rats were divided into five groups of six rats each. Group 1 consisted of normal rats (control group), Group 2 consisted of anaemic untreated rats, and Group 3 consisted of anaemic rats treated with the standard drug Astymin, while Groups 4 and 5 were made up of anaemic rats given the extract at doses of 600 mg/kg b.wt and 1000 mg/kg b.wt, respectively. The fruit extract failed to show any significant effect in improving the haemoglobin (Hb), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphate (ALP) levels in anaemic rats but rather may have contributed to a reduction in Hb levels and an unhealthy increase in serum enzyme levels. This is indicative of the apparent inability of the aqueous extract of the T. occidentalis fruit mesocarp to reverse PHZ-induced haemolytic anaemia and may suggest a possible detrimental effect of high doses of the extract over a prolonged period.

Extra-cranial hemorrhagic complications in patients with COVID-19 infection: the experience of a secondary care COVID-19 institution

BACKGROUND: COVID-19 patients are considered to be at high risk for thromboembolic events, and are subjected to large doses of anticoagulants. However, the associated risk of major bleeding remains underestimated. The aim of this study was to investigate extracranial major bleeding complications in a cohort of critically ill patients with COVID-19 pneumonia, diagnosed with computed tomography (CT) or magnetic resonance (MR), and to examine their relationship with laboratory data and pro-thrombothic status.METHODS: In this retrospective observational study, patients admitted to a single secondary care center from November 1, 2020 and January 31, 2022, who tested positive for COVID-19 and developed significant anemia (reduction in Hb levels >2 g/dL) over the course of hospitalization were included. Clinical-laboratory parameters and imaging were reviewed.RESULTS: Out of 279 patients, hemorrhagic complications were detected in 18 patients (10 males, 8 females, mean age 78.6 years, range 63-89 years), with CT evidence of atraumatic bleedings in the thoraco-abdominal wall (N.=8, bilaterally in one case), in the thoracic cavity (N.=2), in the iliopsoas compartment (N.=5), and in the intestinal lumen (N.=1). Intra-articular (N.=1) and intraspinal (N.=1) hematomas were also found. 14/18 patients underwent angiographic embolization. Three patients simultaneously showed pulmonary embolism.CONCLUSIONS: Spontaneous major extracranial bleeding, at the thoraco-abdominal level and in other atypical sites, represents a rare but serious complication of COVID-19 infection and must always be considered in case of anemia during the course of the disease and relative hospitalization.

Relationship Between SGLT2 Inhibitors and Hemoglobin Levels: A Retrospective Observational Study.

Diabetes mellitus is a risk for subsequent nephrogenic anemia due to accelerated decline in renal function, and the global diabetic population continues to grow exponentially. In clinical studies, sodium-glucose co-transporter 2 (SGLT2) inhibitors, one of the drugs used to treat diabetes, have recently attracted attention as anemia suppressors, but there is still lack of evidence on this matter. The present study aimed to investigate the effects of SGLT2 inhibitor administration on anemia suppression using hemoglobin (Hb) levels as an indicator. We conducted a longitudinal study to evaluate and compare the changes in Hb levels in diabetes patients treated with SGLT2 inhibitors (n=48) and those treated with DPP-4 inhibitors (n=48). Study participants were stratified into sub-cohorts based on sex, and the Hb level trajectory in the participants was observed for 90 days. We evaluated the use of SGLT2 inhibitors as a prophylactic factor for the decline in Hb levels and compared it to that of DPP-4 inhibitors [odds ratio (OR)=3.40, 95% confidence interval (CI)=1.93-6.00]. Administration of SGLT2 inhibitors and DPP-4 inhibitors resulted in decline of 14.4±0.34 and 12.4±0.31 g/dl (p<0.001), respectively, in male Hb levels from baseline to 90 days. Notably, the prophylactic effect of SGLT2 inhibitors on the reduction in Hb levels was independent of renal function and sex. SGLT2 inhibitors prevent the reduction in Hb levels and exhibit anti-anemic effects.

Determining Efficacy of Tranexamic Acid in Reducing Post Partum Haemorrhage in Elective Cesarean Section Patients Evaluating in Referance to Fall in Haemoglobin

Obstetrical haemorrhage is a potentially fatal clinical manifestation of either vaginal delivery or caesarean section. According to reports, it is responsible for almost fifty percent of all pregnancy - related deaths. The prevalence of caesarean section (CS) has dramatically upped in both low income as well as in developed nations, thereby increasing the likelihood of obstetrical haemorrhage. The rationale of this study is that it is important to evaluate the efficacy and safety of TA on blood loss with LSCS. Methods: Cases were separated into two subgroups: case: (A) and control: (B). In the operating theater, participants were given A and B packages to choose from, the contents of whom were only known to the nurse in charge of drug preparation. All meds were injected by an anesthetist who was not in charge of supervising or assessing the patients. Results: Comparison of both %age reduction in Hb levels (&gt;10%) after treatment shows that in Group A 6(20%) and in Group B 15(50%) had &gt;10% reduction in Hb levels after treatment, p-value=0.015. Conclusion: TA administration reduced dramatically the bleeding throughout CS, the proportion of patients who lost more than 1000 mL of blood, and the requirement for supplemental uterotonic substances. As a result, TA can be employed very safely and successfully in patients receiving caesarean section.

Effects of recombinant erythropoietin on hemoglobin levels and blood transfusion needs in patients with preoperative anemia undergoing cardiac surgery.

Preoperative anemia is an important and relatively common problem in patients undergoing cardiac surgery, and its treatment is crucial in improving postoperative outcomes. The use of recombinant erythropoietin is one of the suggested methods in this field. Therefore, in the present study, we sought to evaluate the effects of recombinant erythropoietin on hemoglobin (Hb) levels and blood transfusion needs in cardiac surgery in patients with preoperative anemia. This randomized nonblind clinical trial was performed on patients with mild-to-moderate anemia (Hb &lt;12 g/dL in men and Hb &lt;11 g/dL in women) undergoing cardiac surgery at a referral heart hospital (Tehran, Iran). The patients were randomly divided into two groups of 33 patients. In the intervention group, recombinant erythropoietin was administered at a dose of 500 IU/kg one to three days before surgery. Intra- and postoperative Hb levels and the need for blood transfusion were recorded during surgery and for 3 days afterward. The use of packed red blood cells in the operating room was similar in the intervention and control groups (P = 0.156), but it was significantly lower in the intensive care unit in the intervention group (P = 0.030). The mean Hb, which was initially identical in the two groups (P &gt; 0.05), showed a significantly lower decrease in the intervention group (P = 0.001). No significant differences were observed concerning other variables. The use of recombinant erythropoietin (500 IU/kg/day) one to three days before cardiac surgery in our anemic patients blunted a reduction in Hb levels and decreased blood transfusion needs.

The Hematopoietic Effect of Ninjinyoeito (TJ-108), a Traditional Japanese Herbal Medicine, in Pregnant Women Preparing for Autologous Blood Storage.

Background and Objectives: There are no reports showing the hematopoietic effect of TJ-108 on pregnant women. The aim of this study was to investigate the effect of TJ-108 on the hemoglobin and hematocrit levels, and white blood cell and platelet counts of pregnant women complicated with placenta previa who were managed with autologous blood storage for cesarean section. Materials and Methods: We studied two groups of patients who were complicated with placenta previa and who underwent cesarean delivery. Group A consisted of women who were treated with oral iron medication (100 mg/day), and Group B consisted of women who were treated with TJ-108 at a dose of 9.0 g per day, in addition to oral iron medication, from the first day of blood storage until the day before cesarean delivery. To evaluate the effect of TJ-108, the patients’ red blood cell (RBC); Hb; hematocrit (Ht); white blood cell (WBC); and platelet count (PLT) levels were measured 7 days after storage and at postoperative days (POD) 1 and 5. Results: The study included 65 individuals, 38 in group A and 27 in group B. At the initial storage, a 0.2 g/dL reduction in Hb levels was observed, as compared to the initial Hb levels, in the TJ-108 treated patients, whereas a 0.6 g/dL reduction in Hb levels was observed in the non-TJ-108 treated group. On the other hand, regarding the second and subsequent storages, no significant difference was found in the decrease in the Hb levels of both groups. Conclusions: This study is the first report showing the effect of TJ-108 on improving anemia in pregnant women, presumably by its boosting effect on myelohematopoiesis. Therefore, the combined administration of both iron and TJ-108 is effective as a strategy for pregnant women at a high risk of PPH due to complications such as placenta previa.

The role of preoperative dutasteride in reducing bleeding during transurethral resection of the prostate: A systematic review and meta-analysis of randomized controlled trials

ObjectiveBleeding is one of the most common complications of transurethral resection of the prostate (TURP). Several previous studies reported that administering dutasteride before surgery could reduce perioperative bleeding. We aimed to evaluate the efficacy of preoperative dutasteride treatment in benign prostatic hyperplasia patients undergoing TURP by performing a meta-analysis of relevant randomized controlled trials (RCTs). MethodsA comprehensive literature search was performed through the electronic databases including Medline, Cochrane Library, Google Scholar, and ClinicalTrial.gov in October 2020. RCTs evaluating the role of dutasteride for TURP were screened using the eligibility criteria and the quality of RCTs was assessed using the Cochrane Risk of Bias Tool. The heterogeneity was assessed using I2 statistic. The measured outcomes were hemoglobin (Hb) levels, perioperative blood loss, blood transfusion, microvessel density (MVD), and operation time. Data were pooled as mean difference (MD) and odds ratio (OR). ResultsA total of 11 RCTs consisting of 627 samples from the treatment group and 615 samples from the placebo group were analyzed. Patients that received dutasteride had less reduction in Hb levels (MD −1.10, 95% confidence interval [CI] −1.39 to −0.81, p<0.00001). Dutasteride also significantly reduced the operation time (MD −1.79, 95% CI −2.97 to −0.61, p=0.003) and transfusion rate after surgery (OR 0.34, 95% CI 0.15 to 0.77, p=0.009) compared to the control group. However, the MVD (MD −3.60, 95% CI −8.04 to 0.84, p=0.11) and perioperative blood loss in dutasteride administration for less than 4 weeks (MD 46.90, 95% CI −144.60 to 238.41, p=0.63) and more than 4 weeks (MD −190.13, 95% CI −378.05 to −2.21, p=0.05) differences were insignificant. ConclusionPreoperative administration of dutasteride is able to reduce bleeding during TURP, as indicated by less reduction in Hb level, lower transfusion rate, and less operation time.

Anemia Predicts Poor Outcomes in Patients with HBV-Related Decompensated Cirrhosis.

Anemia is common in patients with severe chronic liver disease, but its role in HBV-related decompensated cirrhosis (DeCi) is still unclear. We therefore aimed to assess the impact of anemia on prognosis in HBV-DeCi patients. One hundred thirty-three patients diagnosed with HBV-DeCi were retrospectively collected. A total of 113 (85.0%) patients suffered from anemia in our cohort. The low hemoglobin (Hb) level group exhibited a significantly increased 28-day mortality rate compared with the high Hb group. Hb level was a predictor of 28-day mortality in HBV-DeCi patients. Reduced Hb levels were associated with unfavorable prognosis in HBV-DeCi patients, and more attention should be paid to anemia in routine clinical assessments of liver cirrhosis.

Alpha-Thalassemia Carrier due to –α3.7 Deletion: Not So Silent

Background/Objective: Alpha-thalassemia is one of the most prevalent genetic diseases, with the –α^3.7 deletion being the most common mutation. Molecular studies have suggested mechanisms to explain the mild phenotype of “silent carrier” heterozygotes. However, the correlation between the clinical laboratory picture and the –α^3.7 heterozygous state remains unclear, thus we chose to investigate. Methods: We analyzed the medical files of 192 children evaluated for microcytosis at our tertiary center between 2007 and 2017 and diagnosed as heterozygotes for the –α^3.7 deletion. Additional α-thalassemia mutations, iron deficiency anemia, and β-thalassemia were ruled out. Laboratory parameters were compared to age- and sex-matched reference values. Results: The –α^3.7 carriers had significantly lower Hb and mean corpuscular volume (MCV) than the reference population, and significantly higher red blood cell counts across all age groups. The greatest reduction in Hb level appeared among male adolescents, while MCV was consistently 2 SDs lower than normal in most patients older than 2 years. Conclusion: Heterozygosity for the –α^3.7 deletion was associated with clinically significant microcytosis and mild anemia in our pediatric population. In the absence of iron deficiency and β-thalassemia, this finding provides a diagnosis for mild microcytic anemia, making additional investigations of microcytosis unnecessary.

Genetic parameters for haemoglobin levels in sows and piglets as well as sow reproductive performance and piglet survival

Genetic parameters were estimated for haemoglobin (Hb) levels in sows and piglets as well as sow reproductive performance and piglet survival. Reproductive traits were available between 2005 and 2014 for 7857 litters from 1029 Large White and 858 Landrace sows. In 2012 and 2013, Hb levels, sow BW and sow back fat depth were measured on 348 sows with 529 litters 5 days prior to farrowing. In addition, Hb levels were available for 1127 one-day-old piglets from 383 litters (a maximum of three piglets per litter) of 277 sows with Hb levels. The average Hb levels in sows (sow Hb), their litters (litter Hb, based on average Hb of three piglets) and individual piglets (piglet Hb) were 112 ± 12.6 g/l, 103 ± 15.3 g/l and 105 ± 21.7 g/l, respectively. Heritabilities for Hb levels were 0.09 ± 0.07 for sow Hb, 0.19 ± 0.11 for litter Hb and 0.08 ± 0.05 for piglet Hb. Estimates for the permanent environment effect of sows were 0.09 ± 0.09 for sow Hb, 0.11 ± 0.12 for litter Hb and 0.12 ± 0.03 for piglet Hb. In comparison, heritabilities for both number of stillborn piglets and pre-weaning survival were lower (0.05 ± 0.01 and 0.04 ± 0.01). Sow BW had no significant heritability, while sow back fat depth was lowly heritable (0.10 ± 0.08). Positive genetic correlations were found between sow Hb and litter Hb (0.64 ± 0.47) and between litter Hb and sow back fat depth (0.71 ± 0.53). Higher litter Hb was genetically associated with lower number of stillborn piglets (−0.78 ± 0.35) and higher pre-weaning survival (0.28 ± 0.33). Negative genetic correlations between sow Hb and average piglet birth weight of the litter (−0.60 ± 0.34) and between piglet Hb and birth weight of individual piglets (−0.37 ± 0.32) indicate that selection for heavier piglets may reduce Hb levels in sows and piglets. Similarly, selection for larger litter size will reduce average piglet birth weight (rg: −0.40 ± 0.12) and pre-weaning survival (−0.57 ± 0.13) and may lead to lower litter Hb (−0.48 ± 0.27). This study shows promising first results for the use of Hb levels as a selection criterion in pig breeding programs, and selection for higher Hb levels may improve piglet survival and limit further reduction in Hb levels in sows and piglets due to selection for larger and heavier litters.

Restitution volumes at the end of dialysis sessions: A potential influencing factor on patients' haemoglobin levels?

AimTo evaluate whether haemoglobin (Hb) levels are influenced by the restitution volume (RestVol) at the end of the dialysis session, independently of erythropoiesis‐stimulating agents (ESA) and iron doses.DesignOver 12 months, 4,386 haemodialysis patients from 34 centres were enrolled in this observational descriptive study according to the checklist STrengthening the Reporting of Observational Studies in Epidemiology (STROBE).MethodRestVol, Hb levels, ESA and iron doses of every patient were assessed on a monthly basis. To determine the ideal RestVol, the clinics were classified into three groups according to the restitution volumes at the end of the dialysis sessions.ResultsMean age was 69 ± 14 years, and 58.9% were men. The evaluation of 665,712 treatments revealed that RestVol of 380 ml seems to be the most efficient, since the clinics in this group managed to reduce ESA consumption with a negligible reduction in Hb levels.

Tolerability of Erythrocyte Ribavirin Triphosphate Concentrations Depends on the ITPA Genotype.

Ribavirin (RBV) is an antiviral drug that is part of the current standard therapy for chronic hepatitis C (CHC). It is enzymatically converted to ribavirin triphosphate (RTP) that inhibits the activity of viral RNA polymerase, thereby preventing viral replication. However, one of its adverse effects includes hemolytic anemia that limits its application. The variant of ITPA (inosine triphosphatase), which dephosphorylates inosine triphosphate to inosine monophosphate, is a protective factor for RBV-induced anemia. RTP is an important metabolite required for ribavirin action. This study evaluated the time-dependent association of RTP concentrations in erythrocytes, RBV-induced toxicity, and virological response to RBV treatment for hepatitis C. A total of 28 Japanese patients with CHC were treated with RBV/peg-interferon/simeprevir or RBV/sofosbuvir and were genotyped for ITPA variants (rs1127354 and rs7270101). We measured RTP concentrations in erythrocytes in a total of 76 samples collected at 4, 8, and 12 weeks from the initiation of treatment. The ITPA rs1127354 variant was found in 7 patients. This was associated with significantly higher RTP concentrations in erythrocytes than in the wild-type patients (P < 0.001). Moreover, a significant correlation was observed between RTP concentrations and decline in hemoglobin (Hb) levels from baseline values in ITPA wild type and rs1127354 variant 12 weeks after treatment initiation (P < 0.01; r = -0.618 and -0.967, respectively). Multiple regression analysis revealed that ITPA genotype and erythrocyte RTP concentrations were major factors associated with reduced Hb levels in RBV therapy for CHC. However, we did not find any association between erythrocyte concentrations and virological response. The increased tolerability to RTP concentrations in erythrocytes in the ITPA variant rs1127354 plays a role in preventing RBV-induced severe anemia in this ITPA variant.

Predictive factors of anemia during sofosbuvir and ribavirin therapy for genotype 2 chronic hepatitis C patients.

Sofosbuvir (SOF) and ribavirin (RBV) combination therapy has improved the sustained virologic response (SVR) rate and shortened the treatment duration for patients with chronic hepatitis C virus (HCV) genotype 2 infection. Ribavirin-induced hemolytic anemia is one of the most troublesome side-effects of SOF/RBV therapy; however, factors associated with this condition have not been fully elucidated. We aimed to identify a safer way to complete treatment with SOF/RBV therapy by examining factors related to RBV-induced hemolytic anemia and identifying patients who did not develop anemia. Two hundred and one patients with genotype 2 chronic hepatitis C treated with SOF/RBV therapy were studied. Significant factors associated with the decline in hemoglobin (Hb) levels from the baseline were analyzed. The SVR rate was 96.5% (194 out of 201 patients) based on intent-to-treat analysis. In multivariate analysis, inosine triphosphatase (ITPA) gene variation (P < 0.0001) and estimated glomerular filtration rate (eGFR) (0.001) were significantly associated with a decrease in Hb levels less than 2g/dL. All patients were divided into four groups by ITPA and eGFR at baseline, and we identified patients with ITPA CA/AA and eGFR >75 as a group that did not develop anemia. The results presented here suggest that patients with ITPA CA/AA and eGFR >75 had no reduction in Hb levels during the treatment with SOF/RBV in HCV genotype 2-infected patients. Adding RBV to direct-acting antiviral therapy might not be problematic in certain patients, at least in terms of the occurrence of anemia.

The Impact of Selenium Deficiency on a Sickle Cell Disease Mouse Model

Sickle cell disease (SCD) is caused by a mutation in the β-globin gene resulting in a disease that affects more than 100,000 Americans and millions worldwide. Though pain is the hallmark of SCD, patients also suffer damage to most organ systems. Sickle cell hemoglobin (HbS) polymerization occurs when deoxygenated, rendering red blood cells rigid and fragile. Production of excessive reactive oxygen species (ROS) and intracellular hypoxia in RBCs further accelerates the pathology associated with SCD. Recently, vaso-occlusive crisis (VOC) and organ damage were established to be strongly associated with oxidative stress in RBCs. This occurs when there is an increase in oxidants that exceeds the cellular anti-oxidant defenses. Excessive ROS can trigger a cascade of oxidative reactions that damage membrane lipids, and essential enzymatic antioxidants such as GPx-1, ultimately leading to hemolysis and multi-organ dysfunction. ROS generation in RBCs of SCD patients is due to factors such as HbS auto-oxidation and potentially aberrant mitochondrial function. We recently determined that red blood cells obtained from SCD mice and SCD patients retain their mitochondria compared to control subjects. Mitochondria retained SCD RBCs are also associated with elevated levels of ROS and hemolysis. Oxidative stress in the RBCs of SCD patients may be elevated by lower levels of antioxidant proteins such as the selenium-dependent enzyme GPX1. GPX1 was first described as an enzyme capable of protecting hemoglobin from ROS and has been reported to be lower in the RBCs in SCD. Selenium levels are lower among African Americans in the Chicago area and elsewhere. In this regard, it is notable that in the United States, African Americans represent the majority of those with SCD. To investigate the relationship between selenium levels and SCD, we have utilized a mouse model of SCD to examine the impact of a reduced intake of selenium on parameters associated with SCD pathology. SCD mice on a selenium-deficient diet (<0.01 mg/kg diet) were compared to mice fed with a selenium-adequate diet (0.1mg/kg). SCD mice in the selenium-deficient group exhibited an increase in mitochondria retaining RBCs (Se deficient: 26%±6.9%, n=3 vs. Se adequate: 5 % ± 3.5%, n=3, p<0.01), reduced Hb levels (Se deficient 5.7± 0.17 g/dl, n=3 vs. Se adequate 7.0± 0.83 g/dl, n=4 p<0.05), and an increased RBC oxygen consumption rate (OCR). These results support the hypothesis that low selenium status likely results in reduced levels of anti-oxidant selenoproteins and enhanced SCD severity. DisclosuresLavelle:Global Blood therapeutics: Research Funding.

Correcting Non-Transfusion Dependent β-Thalassemia by Utilizing a Combined Therapy that Modulates EPO Activity by Limiting Erythroid Cellular Iron Intake

Β-thalassemia intermedia is a disorder characterized by ineffective erythropoiesis (IE), anemia, splenomegaly and systemic iron overload. Administration of agents that increase erythropoiesis (such as erythropoietin-Epo) can potentially improve anemia by enhancing the production of red blood cells (RBC). However, this improvement will likely result in exacerbation of splenomegaly and worsening of iron overload due to further suppression of hepcidin, the hormone that controls dietary iron absorption. However, we postulated that, following Epo administration, some level of iron restriction will limit the splenomegaly and iron overload without preventing the improvement of anemia.To increase circulating Epo levels and increase erythropoiesis, we infused animals with primary dermal fibroblasts transduced with a helper dependent adenoviral vector carrying the Epo gene (TARGTEpo). Pharmacokinetic studies indicated that 1e6 cells were sufficient to significantly increase Epo synthesis (up to 47.6%in Hbbth3/+ and 90% in WT). This led to an increase in hemoglobin levels in both mouse models (average of 3-4 g/dL) through the end of the treatment (6 weeks). In Hbbth3/+ mice, Hb levels rose to 10.7±1.0 g/dL in the first week and remained elevated through the end of the 6-weeks of treatment (compared to 7.7±0.7 g/dL in controls). As expected, stimulation of erythropoiesis led to worsening of splenomegaly and suppression of hepcidin.To test our hypothesis, we then combined TARGTEpo with low iron diet or antisense oligonucleotides targeting Tmprss6 mRNA (Tmprss6-ASO; the last treatment only for Hbbth3/+ animals). It has already been shown that inhibition of Tmprss6 increases hepcidin expression leading to decreased iron absorption and limited erythroid iron intake, improving anemia, IE, splenomegaly and iron overload in Hbbth3/+ mice (Guo et al, JCI, 2013).In WT animals, after three weeks, the combination of TARGTEpo with low iron diet significantly reduced Hb levels (-40%), RBC number (-38%) and reticulocytes (-80%), when compared to animals overexpressing Epo and receiving a normal iron diet. In contrast, Hbbth3/+ animals on an iron-deficient diet or treated with Tmprss6-ASO in the presence of TARGTEpo showed decreased hemichrome formation and improved anemia through the end of treatment. In particular, Hb levels increased (on average 4 g/dL), reaching levels of 11-12g/dl, corresponding to +36% more than baseline levels in Hbbth3/+ (7.7g/dL) and +25% more compared to Hbbth3/+ mice treated with Tmprss6-ASO alone (9.0g/dL). Animals receiving TARGTEpo with Tmprss6-ASO showed a significant reduction in splenomegaly when compared to baseline levels (-35%) and to animals treated only with TARGTEpo (-52.4%). Preliminary data indicate that organ iron concentration improved or normalized compared to control Hbbth3/+ mice when iron restriction was applied.We then inquired how these two treatments combined improved erythropoiesis. We quantified the number of nucleated erythroid cells positive for the phosphorylated form of pAkt and pJak2, proteins activated by Epo but whose activity is potentially limited by iron restriction. For pAkt+ cells in the spleen, the number of proerythroblasts were increased in Hbbth3/+ treated with TARGTEpo (+35% compared to control Hbbth3/+ mice), while they were reduced in Hbbth3/+ treated with Tmprss6-ASO or TARGTEpo+Tmprss6-ASO (-72% and -43% respectively, compared to control Hbbth3/+ mice). Other erythroid populations showed a comparable profile for both pAkt+ and pJak2+ nucleated erythroid cells. The total number of progenitor erythroid cells (i.e. BFUe) also followed a similar trend. Cell cycle analysis of splenic erythroid progenitor cells showed a decrease in the percentage of nucleated erythroid cells in mice treated with Tmprss6-ASO or TARGTEpo+Tmprss6-ASO compared to control or TARGTEpo-treated Hbbth3/+ mice. Given that the number of RBC in circulation was highest in mice treated with TARGTEpo+Tmprss6-ASO, this data suggests that co-administration of these two drugs maximize the ability of each erythroid cell to develop into a functional RBC.In conclusion, we propose that in β-thalassemia, combination of erythropoietic stimulating agents with iron restriction could maximize correction of anemia while improving splenomegaly and iron overload. DisclosuresCasu:Aevi Genomic Medicine, Inc: Research Funding; Ionis Pharmaceuticals, Inc.: Research Funding. Aghajan:Ionis Pharmaceuticals, Inc: Employment. Neil:Aevi Genomic Medicine, Inc: Employment, Other: Officer and share holder. Guo:Ionis Pharmaceuticals, Inc: Employment. Rivella:Ionis Pharmaceuticals, Inc: Consultancy; MeiraGTx: Other: SAB; Disc Medicine: Consultancy; Protagonist: Consultancy.

Safety of Outpatient Kidney Biopsies

Background: Kidney biopsy is frequently performed in our centre as an outpatient procedure. The aim of this study was to evaluate the safety of biopsy in the outpatient setting. Methods: We analysed kidney biopsies performed from March 2013 to February 2017. Seven hundred twenty-five biopsies performed in the outpatient setting were identified: There were 592 transplant and 133 native biopsies including 3 solitary kidney biopsies. All were performed under ultrasound guidance using a 16G or 18G needle, with freehand technique. In all patients with estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m² desmopressin was administered. Patients were observed for 6h before discharge, with a complete blood count and urine test after 4 h. Major complications were haemorrhage requiring therapeutic intervention or transfusion. Minor complications were significant reduction in haemoglobin (Hb) levels (>10%), without need for transfusion or intervention and macrohaematuria. Results: There were 506 (69.8%) male patients. Average age was 50.3 ± 12.7 years. Indications for native kidney biopsy included nephrotic syndrome (39.8%), nephritic syndrome (42.9%), follow-up biopsy (15.8%), and other (1.5%). There were no major complications. A decline in Hb was observed in 72% of patients. Average Hb decline was 4.2 ± 6.3 g/L. In 10.1% patients there was >10% reduction in Hb level, with no evident bleeding, including by ultrasonography. In 2.5% of patients, macrohaematuria was present. In a multivariate analysis, male gender, lower eGFR, higher pre-biopsy Hb and native kidney biopsy were predictive for Hb decline. No therapeutic interventions were required. Conclusion: We found that kidney biopsy performed in an outpatient setting in select patients is only rarely associated with adverse events and is a safe procedure.

Ex Vivo Gene Therapy Approach By Targt Technology for the Treatment of β-Thalassemia Intermedia

β-Thalassemia intermedia or non-transfusion dependent thalassemia (NTDT) is a genetic blood disorder characterized by ineffective erythropoiesis (IE), anemia, splenomegaly and systemic iron overload mediated by down-regulation of hepcidin. Using Hbbth3/+animals affected by NTDT, we have shown that iron restriction improves anemia and reduces splenomegaly by reducing the formation of hemichromes and improving the lifespan of red blood cells (RBC; Gardenghi et al, JCI, 2010; Guo et al, JCI, 2013; Casu et all Blood 2016). These findings emphasize the strong correlation between erythropoiesis, RBC synthesis and iron metabolism. In theory, agents that can stimulate erythropoiesis (such as erythropoietin or EPO) could improve anemia by increasing the production of RBC and, under conditions of reduced iron absorption, correct the iron overload by consuming the excess of iron stored in organs. Here we used a new ex vivo technology called TARGT (Transduced Autologous Restorative Gene Therapy) for prolonged production and secretion of therapeutic agents. Primary dermal fibroblasts transduced with helper dependent adenovirus expressing mouse Epo were embedded in Matrigel and implanted in the dorsal area of 2-3 months old Hbbth3/+and wild-type (WT) C57BL/6 mice. Three groups were generated for each genotype using different amounts of genetically modified fibroblasts (10e5, 5x10e5 and 1x10e6 transduced cells), while one group received no transduced fibroblasts as control. Complete blood count and serum harvest for Epo levels measurement were performed one week after implantation and then every ten days until the end of the experiment, at six weeks. In WT mice, already one week after fibroblasts implantation, hemoglobin (Hb) levels raised 2/3 g/dL, showing erythrocytosis. At the end of the treatment animals showed significantly increased Hb levels (18.5±1.7 g/dL, 19.4±0.5 g/dL and 19.8±0.8 g/dL in the groups implanted with 10e5, 5x10e5 and 1x10e6 fibroblasts, respectively, compared to 13.5±0.8 g/dL in controls). RBC numbers and HTC follow the same trend, showing increases in the range of 27% to 39%.In Hbbth3/+mice Hb levels rose about 3 g/dl already one week after fibroblasts implantation and remained elevated until the end experiment (8.7±0.3 g/dL, 10.7±1.0 g/dL and 10.6±1.8 g/dL in the groups implanted with 10e5, 5x10e5 and 1x10e6 fibroblasts, respectively, compared to 7.7±0.7 g/dL in controls). RBC numbers and HTC follow the same trend, showing increases in the range of 7% to 27%. At the end of the treatment, serum Epo levels were markedly increased at all doses both in Hbbth3/+and WT animals (more than 50% and up to 90%) when compared with their respective controls.However, as expected, stimulation of erythropoiesis led to worsening of splenomegaly and suppression of hepcidin, likely preventing the beneficial effect of erythroid-mediated consumption of stored iron in Hbbth3/+animals. Here we postulated that, in presence of agents that increase erythropoiesis such as Epo, some level of iron restriction is required to improve the anemia, prevent exacerbation of the splenomegaly and, concurrently, decreased iron overload. As a proof of principle of the ability of this technology to improve anemia and decrease iron overload, TARGTEPO was combined with low iron diet or iron chelation. We expect that decreased iron intake will improve the quality of the RBC, while the larger number of RBC produced should utilize more stored iron, reversing the iron overload in Hbbth3/+animals. Preliminary results at three weeks from the beginning of the experiment indicated that in WT implanted-animals the combination of TARGTEPO with low iron diet significantly reduced Hb levels (-40%), HTC (-42%), RBC number (-38%) and reticulocytes (-80%) when compared to animals overexpressing Epo and receiving normal iron diet or iron chelation. This indicates that in WT animals, after 3 weeks, the stored iron is insufficient to support the increased erythropoiesis. In contrast, in Hbbth3/+animals this drop in Hb was not seen, suggesting that this effect is delayed due to the highest level of stored iron. Complete characterization of these models and their parameters is in progress. These preliminary results suggest that the TARGTplatformcould be utilized, in combination with drugs that limit iron intake, to improve anemia and decrease iron overload in NTDT. Additional experiments are in progress to test this hypothesis. DisclosuresCasu:Ionis Pharmaceuticals: Research Funding; Medgenics LLC: Research Funding; Merganser Biotech: Research Funding. Neil:Medgenics: Employment. Miari:Medgenics: Employment. Shapir:Medgenics: Employment.

The effect of a standard whole blood donation on oxygen uptake and exercise capacity: a systematic review and meta-analysis.

Blood is a life-saving product for many people worldwide. Voluntary blood donation serves the demand for blood but there are concerns among potential donors about the impact of blood loss on exercise performance. This systematic review aimed to collect the best available evidence of the effect of a standard whole blood donation on aerobic exercise performance. Studies from six databases dealing with a standard whole blood donation (400-500 mL) followed by (sub)maximal exercise were retained. The outcomes included exercise-related blood variables (hemoglobin [Hb] concentration, hematocrit, and red blood cell count) and endurance exercise variables ((sub)maximal oxygen uptake, peak work rate, and time to exhaustion). Overall effects at different time points postdonation were investigated by performing meta-analyses and calculating mean differences (and 95% confidence intervals). The GRADE methodology (Grades of Recommendation, Assessment, Development, and Evaluation) was used to assess the quality of evidence. We identified 6237 references and finally included 18 before-after studies of low quality. Twenty-four to 48 hours after a blood donation, 1) Hb concentration was reduced (7% decrease) until 14 days after the blood donation (4% decrease), 2) maximal oxygen uptake (VO2max ) was lower (7% decrease), and 3) a reduction in maximal exercise capacity (10% decrease) was present. The best available evidence indicates that a standard whole blood donation (400-500 mL) leads to small but potentially physiologically important reductions in Hb levels, VO2max , and maximal exercise capacity in the first 2 days after the blood donation.

Effect of Closed Suction Drain on Blood Loss and Transfusion Rates in Simultaneous Bilateral Total Knee Arthroplasty: A Prospective Randomized Study.

PurposeSimultaneous bilateral total knee arthroplasty (TKA) is associated with excessive blood loss and morbidity arising from postoperative reduction in hemoglobin (Hb). The purpose of this prospective randomized study was to determine if drains have any effect on blood loss, postoperative reduction in Hb levels and transfusion rates compared to no drainage in simultaneous bilateral TKAs.Materials and MethodsTwo hundred and thirty patients who underwent simultaneous bilateral TKA by a single surgeon were randomly allotted to drain or no-drain group (n=115 in each group). Postoperative Hb level, blood loss volume and transfusion rate were compared between the two groups.ResultsThe mean postoperative Hb level (p=0.38), blood loss volume (p=0.33) and transfusion rate (p=0.52) in the drain group were not significantly different compared to the no-drain group. No statistical difference was found in terms of complications, readmissions and mortality rates between the two groups.ConclusionsNo significant difference was observed in the two groups with respect to blood loss and blood transfusion. Non-drainage does not offer an advantage over drainage with respect to conserving blood in simultaneous bilateral TKA.

Association between hematologic parameters and functional impairment among geriatric inpatients: Data of a prospective cross-sectional multicenter study (“GeriPrävalenz2013”)

ObjectivesObjective of this study was to analyse the association between impairment of Barthel Index items and hematologic parameters in geriatric inpatients. MethodsPatient recruitment of the “GeriPrävalenz2013” study has been described before. Inclusion criteria: in-patient aged>=70years; exclusion criteria: actual cancer disease or cancer associated treatment. Anemia was defined according to WHO criteria. Physical impairment was assessed by Barthel Index (BI). Association between all 10 items of the BI and hematologic parameters was statistically evaluated. ResultsAnemia prevalence was 55.1% (319/579) with BI impairment in 96.2% patients. T-test revealed significant lower BI in anemic patients (47.9 vs 54.3; p=0.004). Binary logistic regression revealed that growing age, reduced MCV, reduced iron levels and reduced Hb levels were associated with increased impairment of several items of the Barthel-Index. Interestingly, increased levels of albumin and folic acid (FA) were associated with increased impairment of BI items. ConclusionAnemia and lower levels of anemia related parameters showed a negative impact on ADL and physical performance based on BI items. An impaired total BI should result in an analysis of BI subitems, particularly if anemia related laboratory parameters are deviant. Reasons for the negative impact of elevated FA and albumin levels on BI remain speculative.