Erythrocytosis: Diagnosis and investigation.

An absolute erythrocytosis is present when the red cell mass is greater than 125% of the predicted. This is suspected when the hemoglobin or hematocrit is above the normal range. An erythrocytosis can be classified as primary or secondary and congenital or acquired. The commonest primary acquired disorder is polycythemia vera. The diagnostic criteria for PV have evolved over time and this is the main diagnosis managed in hematology clinics. There are a variety of rare congenital causes both primary and secondary. In particular in young patients and/or those with a family history a congenital cause is suspected. There remains a larger cohort with acquired erythrocytosis mainly with non-hematological pathology. In order to explore for a cause of erythrocytosis, measurement of the erythropoietin level is a first step. A low erythropoietin level indicates a primary cause and a normal or elevated level indicates a secondary etiology. Further investigation is then dictated by initial findings and includes mutational testing with PCR and NGS for those in whom a congenital cause is suspected. Following this possibly bone marrow biopsy, scans, and further investigation as indicated by history and initial findings. Investigation is directed toward the identification of those with a hematological disorder which would be best managed following guidelines in hematology clinics and referral elsewhere in those for whom there are non-hematological reasons for the elevated hemoglobin.

A retrospective study on the efficacy of Roxadustat in peritoneal dialysis patients with erythropoietin hyporesponsiveness.

BACKGROUND/AIMS: Roxadustat, an oral medication for treating renal anemia, is a hypoxia-inducible factor prolyl hydroxylase inhibitor used for regulating iron metabolism and promoting erythropoiesis. To investigate the efficacy and safety of roxadustat in patients undergoing peritoneal dialysis (PD) with erythropoietin hyporesponsiveness. METHODS: Single-center, retrospective study, 81 PD patients (with erythropoietin hyporesponsiveness) were divided into the roxadustat group (n = 61) and erythropoiesis-stimulating agents (ESAs) group (n = 20). Hemoglobin (Hb), total cholesterol, intact parathyroid hormone (iPTH), brain natriuretic peptide (BNP), related indicators of cardiac function and high-sensitivity C-reactive protein (hs-CRP) were collected. Additionally, adverse events were also recorded. The follow-up period was 16 weeks. RESULTS: The two groups exhibited similar baseline demographic and clinical characteristics. At baseline, the roxadustat group had a mean Hb level of 89.8 ± 18.9 g/L, while the ESAs group had a mean Hb level of 95.2 ± 16.0 g/L. By week 16, the Hb levels had increased to 118 ± 19.8 g/L (p < 0.05) in the roxadustat group and 101 ± 19.3 g/L (p > 0.05) in the ESAs group. The efficacy of roxadustat in improving anemia was not influenced by baseline levels of hs-CRP and iPTH. Cholesterol was decreased in the roxadustat group without statin use. An increase in left ventricular ejection fraction and stabilization of BNP were observed in the roxadustat group. CONCLUSION: For PD patients with erythropoietin hyporesponsiveness, roxadustat can significantly improve renal anemia. The efficacy of roxadustat in improving renal anemia was not affected by baseline levels of hs-CRP0 and iPTH.

Erythropoietin alleviates lung ischemia-reperfusion injury by activating the FGF23/FGFR4/ERK signaling pathway.

Background: The purpose of the present study was to investigate the effect of erythropoietin (EPO) on lung ischemia-reperfusion injury (LIRI). Methods: Sprague Dawley rats and BEAS-2B cells were employed to construct an ischemia-reperfusion (I/R)-induced model in vivo and in vitro, respectively. Afterward, I/R rats and tert-butyl hydroperoxide (TBHP)-induced cells were treated with different concentrations of EPO. Furthermore, 40 patients with LIRI and healthy controls were enrolled in the study. Results: It was observed that lung tissue damage, cell apoptosis and the expression of BAX and caspase-3 were higher in the LIRI model in vivo and in vitro than in the control group, nevertheless, the Bcl-2, FGF23 and FGFR4 expression level was lower than in the control group. EPO administration significantly reduced lung tissue damage and cell apoptosis while also up-regulating the expression of FGF23 and FGFR4. Rescue experiments indicated that EPO exerted a protective role associated with the FGF23/FGFR4/p-ERK1/2 signal pathway. Notably, the expression of serum EPO, FGF23, FGFR4 and Bcl-2 was decreased in patients with LIRI, while the expression of caspase-3 and BAX was higher. Conclusion: EPO could effectively improve LIRI, which might be related to the activation of the FGF23/FGFR4/p-ERK1/2 signaling pathway.

Mechanisms and Cardiorenal Complications of Chronic Anemia in People with HIV.

Chronic anemia is more prevalent in people living with HIV (PLWH) compared to the general population. The mechanisms that drive chronic anemia in HIV are multifaceted and include functional impairment of hematopoietic stem cells, dysregulation of erythropoietin production, and persistent immune activation. Chronic inflammation from HIV infection adversely affects erythropoiesis, erythrocyte lifespan, and erythropoietin response, leading to a heightened risk of co-infections such as tuberculosis, persistent severe anemia, and increased mortality. Additionally, chronic anemia exacerbates the progression of HIV-associated nephrotoxicity and contributes to cardiovascular risk through immune activation and inflammation. This review highlights the cardinal role of chronic inflammation as a link connecting persistent anemia and cardiovascular complications in PLWH, emphasizing the need for a universal understanding of these interconnected pathways for targeted interventions.

Erythropoietin-derived peptide ARA290 mediates brain tissue protection through the ß-common receptor in mice with cerebral ischemic stroke.

AIM: To explore the neuroprotective effects of ARA290 and the role of ß-common receptor (ßCR) in a mouse model of middle cerebral artery occlusion (MCAO). METHODS: This study included male C57BL/6J mice that underwent MCAO and reperfusion. The neuroprotective effect of ARA290 on MCAO-induced brain injury was investigated using neurological function tests (Longa and modified neurological severity score). Cerebral infarction was examined by 2, 3, 5-triphenyl tetrazolium chloride staining, neuronal apoptosis was assessed by immunofluorescence staining, blood parameters were measured using a flow cytometry-based automated hematology analyzer, liquid chromatography with tandem mass spectrometry was used to identify the serum metabolomics signature, inflammatory cytokines and liver index were detected by commercially available kits, and the protein levels of the erythropoietin (EPO) receptor and ßCR were measured by western blot. RESULTS: ARA290 exerted a qualitatively similar neuroprotective effect after MCAO as EPO. ARA290 significantly reduced neuronal apoptosis and the level of inflammatory cytokines in the brain tissue. However, ARA290's neuroprotective effect was significantly suppressed following the injection of siRNA against ßCR. CONCLUSION: ARA290 provided a neuroprotective effect via ßCR in cerebral ischemic mice without causing erythropoiesis. This study provides novel insights into the role of ARA290 in ischemic stroke intervention.

Effect of Minimization of Early Blood Sampling Losses Among Extremely Premature Neonates: A Randomized Clinical Trial.

OBJECTIVE: To evaluate the effect of blood sampling stewardship on transfusion requirements among infants born extremely preterm. STUDY DESIGN: In this single-center, randomized controlled trial (RCT), infants born at <28 weeks of gestation and birth weight of <1000 g were randomized at 24 hours of age to two different blood sampling approaches: restricted sampling (RS) vs conventional sampling (CS). The stewardship intervention in the RS group included targeted reduction in blood sampling volume and frequency and point of care testing methods in the first 6 weeks after birth. Both groups received early recombinant erythropoietin from day three of age. Primary outcome was the rate of early red blood cell (RBC) transfusions in the first six postnatal weeks. RESULTS: A total of 102 infants (mean gestational age: 26 weeks; birth weight: 756 g) were enrolled. Fidelity to the sampling protocol was achieved in 95% of the infants. Sampling losses in the first 6 weeks were significantly lower in the RS group (16.8 ml/kg vs 23.6 ml/kg, P < .001). The RS group had a significantly lower rate of early postnatal RBC transfusions (41% vs 73%, RR: 0.56 [0.39-0.81], P = .001). The hazard of needing a transfusion during neonatal intensive care unit (NICU) stay was reduced by 55% by RS. Mortality and neonatal morbidities were similar between the two groups. CONCLUSION: Minimization of blood sampling losses by approximately one-third in the first 6 weeks after birth leads to substantial reduction in the early red blood cell transfusion rate in infants born extremely preterm and weighing <1000 g at birth. TRIAL REGISTRATION: http://www.ctri.nic.in (CTRI/2020/01/022  964).

An updated systematic review of neuroprotective agents in the treatment of spinal cord injury.

This systematic review aims to summarize the findings from all clinical randomized trials assessing the efficacy of potential neuroprotective agents in influencing the outcomes of acute spinal cord injuries (SCI). Following the PRISMA guidelines, we conducted comprehensive searches in four electronic databases (PubMed, Scopus, Cochrane Library, and Web of Science) up to September 5th, 2023. Our analysis included a total of 30 studies. We examined the effects of 15 substances/drugs: methylprednisolone, tirilazad mesylate, erythropoietin, nimodipine, naloxone, Sygen, Rho protein antagonist, granulocyte colony-stimulating factor, autologous macrophages, autologous bone marrow cells, vitamin D, progesterone, riluzole, minocycline, and blood alcohol concentration. Notable improvements in neurological outcomes were observed with progesterone plus vitamin D and granulocyte colony-stimulating factor. In contrast, results for methylprednisolone, erythropoietin, Sygen, Rho Protein, and Riluzole were inconclusive, primarily due to insufficient sample size or outdated evidence. No significant differences were found in the remaining evaluated drugs. Progesterone plus vitamin D, granulocyte colony-stimulating factor, methylprednisolone, Sygen, Rho Protein, and Riluzole may enhance neurological outcomes in acute SCI cases. It is worth noting that different endpoints or additional subgroup analyses may potentially alter the conclusions of individual trials. Therefore, certain SCI grades may benefit more from these treatments than others, while the overall results may remain inconclusive.

Theranova versus FX80: The impact on anemia management in hemodialysis.

BACKGROUND: Middle uremic toxins (MUTs) can cause anemia and erythropoietin hyporesponsiveness. Theranova dialyzers may improve anemia management by removing MUTs. Hence, the impact of Theranova dialyzers on erythropoietin responsiveness was studied. METHODS: This exploratory single-center prospective observational study, encompassing 50 patients undergoing dialysis with either the Theranova-400 or FX80 membrane for 6 months, involved monthly tracking of hemoglobin levels, weight-adjusted erythropoiesis-stimulating agent (w-ESA) dosing, and erythropoietin resistance index (ERI), with ESA treatment decisions guided by a proprietary algorithm. RESULTS: The groups were similar in terms of demographics and baseline laboratory test results. The median hemoglobin levels, w-ESA and ERI, were found to be similar between FX80 and Theranova-400 groups at both baseline (11.06 vs 10.57, p = 0.808; 92.3 vs 105.2, p = 0.838; 8.1 vs 10.48, p = 0.876) and the end of the study (11.43 vs 11.03, p = 0.076; 48.7 vs 71.5; 4.48 vs 6.41, p = 0.310), respectively. There was a trend toward lower w-ESA and ERI at the end of the study compared to baseline in both groups, but the difference was non-significant. CONCLUSIONS: Based on this study of 50 patients undergoing high-flux dialysis with near-target hemoglobin levels, switching to Theranova 400 dialyzers compared to FX80 dialyzers did not show statistically significant differences in maintaining hemoglobin levels, reducing ESA dose, or lowering ERI. The non-randomized design and small sample size limit the study's power to detect true differences. Larger, randomized trials are needed to confirm findings and definitively assess Theranova 400's benefits.

Molecular basis of JAK2 activation in erythropoietin receptor and pathogenic JAK2 signaling.

Janus kinase 2 (JAK2) mediates type I/II cytokine receptor signaling, but JAK2 is also activated by somatic mutations that cause hematological malignancies by mechanisms that are still incompletely understood. Quantitative superresolution microscopy (qSMLM) showed that erythropoietin receptor (EpoR) exists as monomers and dimerizes upon Epo stimulation or through the predominant JAK2 pseudokinase domain mutations (V617F, K539L, and R683S). Crystallographic analysis complemented by kinase activity analysis and atomic-level simulations revealed distinct pseudokinase dimer interfaces and activation mechanisms for the mutants: JAK V617F activity is driven by dimerization, K539L involves both increased receptor dimerization and kinase activity, and R683S prevents autoinhibition and increases catalytic activity and drives JAK2 equilibrium toward activation state through a wild-type dimer interface. Artificial intelligence-guided modeling and simulations revealed that the pseudokinase mutations cause differences in the pathogenic full-length JAK2 dimers, particularly in the FERM-SH2 domains. A detailed molecular understanding of mutation-driven JAK2 hyperactivation may enable novel therapeutic approaches to selectively target pathogenic JAK2 signaling.

PCR-Based Equine Gene Doping Test for the Australian Horseracing Industry.

The term 'gene doping' is used to describe the use of any unauthorized gene therapy techniques. We developed a test for five likely candidate genes for equine gene doping: EPO, FST, GH1, IGF1, and ILRN1. The test is based on real-time polymerase chain reaction (PCR) and includes separate screening and confirmation assays that detect different unique targets in each transgene. For doping material, we used nonviral (plasmid) and viral (recombinant adeno-associated virus) vectors carrying complementary DNA for the targeted genes; the vectors were accurately quantified by digital PCR. To reduce non-specific amplification from genomic DNA observed in some assays, a restriction digest step was introduced in the PCR protocol prior to cycling to cut the amplifiable targets within the endogenous genes. We made the screening stage of the test simpler and faster by multiplexing PCR assays for four transgenes (EPO, FST, IGF1, and ILRN1), while the GH1 assay is performed in simplex. Both stages of the test reliably detect at least 20 copies of each transgene in a background of genomic DNA equivalent to what is extracted from two milliliters of equine blood. The test protocol was documented and tested with equine blood samples provided by an official doping control authority. The developed tests will form the basis for screening official horseracing samples in Australia.

Inhibition the ubiquitination of ENaC and Na,K-ATPase with erythropoietin promotes alveolar fluid clearance in sepsis-induced acute respiratory distress syndrome.

Sepsis-induced acute respiratory distress syndrome (ARDS) causes significant fatalities worldwide and lacks pharmacological intervention. Alveolar fluid clearance (AFC) plays a pivotal role in the remission of ARDS and is markedly impaired in the pathogenesis of ARDS. Here, we demonstrated that erythropoietin could effectively ameliorate lung injury manifestations and lethality, restore lung function and promote AFC in a rat model of lipopolysaccharide (LPS)-induced ARDS. Moreover, it was proven that EPO-induced restoration of AFC occurs through triggering the total protein expression of ENaC and Na,K-ATPase channels, enhancing their protein abundance in the membrane, and suppressing their ubiquitination for degeneration. Mechanistically, the data indicated the possible involvement of EPOR/JAK2/STAT3/SGK1/Nedd4-2 signaling in this process, and the pharmacological inhibition of the pathway markedly eliminated the stimulating effects of EPO on ENaC and Na,K-ATPase, and subsequently reversed the augmentation of AFC by EPO. Consistently, in vitro studies of alveolar epithelial cells paralleled with that EPO upregulated the expression of ENaC and Na,K-ATPase, and patch-clamp studies further demonstrated that EPO substantially strengthened sodium ion currents. Collectively, EPO could effectively promote AFC by improving ENaC and Na,K-ATPase protein expression and abundance in the membrane, dependent on inhibition of ENaC and Na,K-ATPase ubiquitination, and resulting in diminishing LPS-associated lung injuries.

Medium-Dose Formoterol Attenuated Abdominal Aortic Aneurysm Induced by EPO via ß2AR/cAMP/SIRT1 Pathway.

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease but effective drugs for treatment of AAA are still lacking. Recently, erythropoietin (EPO) is reported to induce AAA formation in apolipoprotein-E knock out (ApoE-/-) mice but an effective antagonist is unknown. In this study, formoterol, a ß2 adrenergic receptor (ß2AR) agonist, is found to be a promising agent for inhibiting AAA. To test this hypothesis, ApoE-/- mice are treated with vehicle, EPO, and EPO plus low-, medium-, and high-dose formoterol, respectively. The incidence of AAA is 0, 55%, 35%,10%, and 55% in these 5 groups, respectively. Mechanistically, senescence of vascular smooth muscle cell (VSMC) is increased by EPO while decreased by medium-dose formoterol both in vivo and in vitro, manifested by the altered expression of senescence biomarkers including phosphorylation of H2AXserine139, senescence-associated ß-galactosidase activity, and P21 protein level. In addition, expression of sirtuin 1 (SIRT1) in aorta is decreased in EPO-induced AAA but remarkably elevated by medium-dose formoterol. Knockdown of ß2AR and blockage of cyclic adenosine monophosphate (cAMP) attenuate the inhibitory role of formoterol in EPO-induced VSMC senescence. In summary, medium-dose formoterol attenuates EPO-induced AAA via ß2AR/cAMP/SIRT1 pathways, which provides a promising medication for the treatment of AAA.

Targeting EphA2: a promising strategy to overcome chemoresistance and drug resistance in cancer.

Erythropoietin-producing hepatocellular A2 (EphA2) is a vital member of the Eph tyrosine kinase receptor family and has been associated with developmental processes. However, it is often overexpressed in tumors and correlates with cancer progression and worse prognosis due to the activation of its noncanonical signaling pathway. Throughout cancer treatment, the emergence of drug-resistant tumor cells is relatively common. Since the early 2000s, researchers have focused on understanding the role of EphA2 in promoting drug resistance in different types of cancer, as well as finding efficient and secure EphA2 inhibitors. In this review, the current knowledge regarding induced resistance by EphA2 in cancer treatment is summarized, and the types of cancer that lead to the most cancer-related deaths are highlighted. Some EphA2 inhibitors were also investigated. Regardless of whether the cancer treatment has reached a drug-resistance stage in EphA2-overexpressing tumors, once EphA2 is involved in cancer progression and aggressiveness, targeting EphA2 is a promising therapeutic strategy, especially in combination with other target-drugs for synergistic effect. For that reason, monoclonal antibodies against EphA2 and inhibitors of this receptor should be investigated for efficacy and drug toxicity.

The Use of Anemia Control Model Is Associated with Improved Hemoglobin Target Achievement, Lower Rates of Inappropriate Erythropoietin Stimulating Agents, and Severe Anemia among Dialysis Patients.

INTRODUCTION: The Anemia Control Model (ACM) is a certified medical device suggesting the optimal ESA and iron dosage for patients on hemodialysis. We sought to assess the effectiveness and safety of ACM in a large cohort of hemodialysis patients. METHODS: This is a retrospective study of dialysis patients treated in NephroCare centers between June 1, 2013 and December 31, 2019. We compared patients treated according to ACM suggestions and patients treated in clinics where ACM was not activated. We stratified patients belonging to the reference group by historical target achievement rates in their referral centers (tier 1: <70%; tier 2: 70-80%; tier 3: >80%). Groups were matched by propensity score. RESULTS: After matching, we obtained four groups with 85,512 patient-months each. ACM had 18% higher target achievement rate, 63% smaller inappropriate ESA administration rate, and 59% smaller severe anemia risk compared to Tier 1 centers (all p < 0.01). The corresponding risk ratios for ACM compared to Tier 2 centers were 1.08 (95% CI: 1.08-1.09), 0.49 (95% CI: 0.47-0.51), and 0.64 (95% CI: 0.61-0.68); for ACM compared to Tier 3 centers, 1.01 (95% CI: 1.01-1.02), 0.66 (95% CI: 0.63-0.69), and 0.94 (95% CI: 0.88-1.00), respectively. ACM was associated with statistically significant reductions in ESA dose administration. CONCLUSION: ACM was associated with increased hemoglobin target achievement rate, decreased inappropriate ESA usage and a decreased incidence of severe anemia among patients treated according to ACM suggestion.

Hookworm infection as a model for deepen knowledge of iron metabolism and erythropoiesis in anemia.

Over the years, there has been progress in understanding the molecular aspects of iron metabolism and erythropoiesis. However, despite research conducted both in laboratories and living organisms, there are still unanswered questions due to the complex nature of these fields. In this study we investigated the effects of hookworm infection on iron metabolism and how the hosts response to anemia is affected using hamsters infected with Ancylostoma ceylanicum as a model. Our data revealed interesting relationships between infection-induced anemia, erythropoiesis, iron metabolism, and immune modulation, such that the elevated production of erythropoietin (EPO) in renal tissue indicated intensified erythropoiesis in response to anemia. Additionally, the increased expression of the erythroferrone (ERFE) gene in the spleen suggested its involvement in iron regulation and erythropoiesis. Gene expression patterns of genes related to iron metabolism varied in different tissues, indicating tissue-specific adaptations to hypoxia. The modulation of pro-inflammatory and anti-inflammatory cytokines highlighted the delicate balance between immune response and erythropoiesis. Data derived from the investigation of changes induced in iron metabolism and stress erythropoiesis following anemia aid in our understanding of mechanisms related to blood spoliation and anemia, which could potentially be extrapolated or compared to other types or causes of anemia. These findings also contribute to our understanding of the pathophysiology of erythropoiesis in the context of blood loss.

Successful treatment pure red cell aplasia after ABO major mismatched allogeneic hematopoietic stem cell transplantation with avatrombopag and low dose rituximab.

BACKGROUND: Pure red cell aplasia (PRCA) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) with ABO major incompatibility is characterized by transfusion dependent anemia. No standard treatment existed for PRCA following allo-HSCT yet. STUDY DESIGN AND METHODS: We conducted a retrospective study, and reported our experience with the use of avatrombopag and lower dose rituximab to treat five patients with PRCA subsequent to major ABO-incompatible allo-HSCT. RESULTS: Five cases of PRCA were identified from 72 patients who underwent allo-HSCT with major or bidirectional ABO mismatch. Cumulative incidence at Day +60 was 6.9% (5/72) at our center. All donor and recipient blood groups were A+  and O+ , respectively. In the first three cases we reported, patients received erythropoietin, plasma exchange, and donor lymphocyte infusion, but none of them had any effect. After 4 weeks of treatment with low dose rituximab (100 mg/week) combined with avatrombopag (40 mg/day), favorable outcomes were obtained. According to the aforementioned experience, Cases 4 and 5 were administered low-dose rituximab and avatrombopag in 3 months after transplantation, and erythroid response was observed on 3 weeks after treatment. Our patients tolerated low-dose rituximab and avatrombopag well and experienced rapid efficacy, with a median duration of 3 weeks. Furthermore, no severe infection or thrombocytosis necessitated a dose adjustment. CONCLUSION: Low-dose rituximab and avatrombopag may be an effective treatment for patients with PRCA after major ABO-incompatible allo-HSCT. The patients should be treated at least 90 days post transplantation if conventional erythropoietin therapy fails.

High Ferritin Is Not Needed in Hemodialysis Patients: A Retrospective Study of Total Body Iron and Oral Iron Replacement Therapy.

In vivo iron levels can be adjusted through intestinal iron absorption to be maintained at a suitable level; however, optimal iron levels in hemodialysis (HD) patients are unclear. In this study, we investigated total body iron (TBI), calculated as the sum of red blood cell (RBC) iron and iron stores, during courses of low-dose oral iron replacement therapy, and evaluated in vivo iron sufficiency and its indicators in HD patients. We analyzed data on 105 courses of low-dose iron replacement therapy administered to 83 patients on maintenance HD over 7 months. We evaluated changes in TBI, RBC iron, and iron stores from the initiation of treatment to month 7 in two groups of patients, namely, iron-therapy responders and non-responders. TBI showed significant increases until month 4 and plateaued thereafter in iron-therapy responders, and tended to increase and then reached a similar plateau in non-responders (month 7: 1900 ± 447 vs. 1900 ± 408 mg). Steady-state TBI was strongly correlated with body surface area (y = 1628.6x - 791.91, R2 = 0.88, p < 0.001). We observed constant TBI during oral iron replacement therapy suggesting the activation of a "mucosal block". The results suggest that body surface area has utility for estimating the required TBI with regression equations.

Suspected renal interstitial cell tumor causing polycythemia in two dogs.

Here we report a case series of two dogs diagnosed as renal interstitial cell tumor (RICT) accompanied by elevated serum erythropoietin level and marked polycythemia. RICT is a rare tumor in dogs, originating from renal interstitial cells. While several renal tumors such as renal lymphoma, adenocarcinoma, carcinoma, sarcoma, fibrosarcoma and nephroblastoma may cause polycythemia, polycythemia caused by RICT has never been reported in dogs. The tumors in both dogs were solitary and lied within cortex or cortico-medullary junction. Histopathology revealed spindle-shaped cells suggesting mesenchymal origin, with no mitotic figures suggesting that the tumors in both dogs were benign. Following surgical removal of the affected kidney, serum erythropoietin level and polycythemia normalized in both dogs.

Serum erythropoietin in acute ischemic stroke: preliminary findings.

Ischemic stroke is the most common stroke, caused by occlusion of cerebral vessels and leading causes of disability. Erythropoietin (EPO) has non-hematopoietic effects as a neuroprotectant after ischemic event. This study aimed to learn the serum level of EPO in acute ischemic stroke. This cross-sectional study of ischemic stroke patients with onset < 24 h and consecutive sampling was used to collect the data from medical records review, physical examinations, head CT, 24-h EPO, 24-h and seventh-day NIHSS. A total of 47 patients consisting of 59.6% women, with a median age of 53 years old (21-70). The median 24 h EPO level was 808.6 pg/mL (134.2-2988.9). The relationship between 24 h-EPO and 24-h NIHSS were not significant (r = 0.101; p = 0.250), nor to 7th day NIHSS (r = - 0.0174; p = 0.121) and to delta NIHSS (r = 0.186; p = 0.106). The relationship of blood collection time (hour) and EPO was significant (r = - 0.260; p = 0.039). There was a statistically significant difference between serum EPO levels in ischemic stroke patients with lacunar stroke compared to non-lacunar stroke (288.5 vs. 855.4 ng/mL; p = 0.021). There was a relationship between the time of collection of blood and the level of EPO and also there was difference EPO level in lacunar stroke subtype compared with non-lacunar. The relationship between EPO and NIHSS lost significance after analysis. There is a need for a future study comparing each stroke risk factor and the same blood collection time.