Higher Nucleated Red Blood Cell Research Articles

EVALUATION OF BLOOD CELL COUNT USING THE SYSMEX XN-1000 AUTOMATIC HEMATOLOGY ANALYZER TO OPTIMIZE COLLECTION OF PERIPHERAL BLOOD PROGENITOR CELLS BY LEUKAPHERESIS

Autologous stem cell transplantation (ASCT) is a treatment modality for several diseases. Prediction of successful mobilization may be useful to optimize hematopoietic stem cell (HSC) collection. The objective was to identify characteristics that can influence the effectiveness of mobilization and create a model to predict the success of mobilization in candidates for ASCT. This was a retrospective study, and data from patient candidates for ASCT between 09/2015 and 12/2021 were analyzed. Participants were assisted in five hospitals and laboratory procedures were performed at the Cell Processing Center (CPC) of Cetebio/Fundação Hemominas, Brazil. The medical records of the participants were reviewed to obtain the following information: gender, age, weight, diagnosis, mobilization, mobilization cycle, number of previous chemotherapy regimens and previous radiotherapy. The laboratory data analyzed were CD34+ cell enumeration and pre-collection peripheral blood (PB) blood count. Enumeration of CD34+ cell was performed using the ISHAGE protocol. The blood count was performed using an automated counter (SYSMEX XN-1000 AS-01). The studied outcome, good mobilization, was defined as a viable CD34+ cell count ≥ 20/uL in the PB. Model derivation was performed using logistic regression. The level of classification accuracy of model was tested in a subset of participants. The study population included 807 patients, 413 (51%) of whom were male. The median age was 54 (1-74) years. Multiple myeloma was the most common diagnosis (58,2%), followed by lymphoma. Of the 807 participants, 74 failed in previous mobilization attempts, totaling 881 cycles of mobilizations and collection attempts. Of the 623 participants, 353 were good mobilizers. Increasing patient weight, lower mean corpuscular volume (MCV), higher nucleated red blood cells (nRBC), peripheral blood mononuclear cells (PBMC), and immature granulocyte count were significantly associated with good mobilization. In addition, participants diagnosed with multiple myeloma were two times more likely to be good mobilizers than patients with lymphoma (OR=1.92; 95%CI: 1.21 – 3.05; P=0.006). The model was applied to the validation set to identify patients who underwent apheresis (CD34+ cells count ≥ 10 μL), resulting in a sensibility of 69%, a specificity of 95%, positive predictive value of 98%, a negative predictive value of 50%. The results of our study are extremely relevant to institutions that do not have a flow cytometer and rely on other institutions to define HSC collection by apheresis. Cetebio serves nine transplant centers. The centers that perform the collection of HSC are located between 40 to 568 km away from Cetebio (place of quantification of CD34+ cells). Predicting the outcome of mobilization may allow the adoption of complementary measures, such as the use of plerixafor. Furthermore, it would better optimize the collection of CPH by apheresis. Thus, it would be possible to avoid additional collection days, reducing costs and risks related to administration of additional doses of G-CSF, catheter maintenance and prolonged hospital stay. Success in mobilization was greater in participants who underwent the first mobilization cycle and who had a diagnosis of multiple myeloma. Furthermore, higher weight and levels of nRBC, immature granulocytes, and PBMC, as well as lower levels of MCV, were associated with successful mobilization.

Significance of cord blood nucleated red blood cell count in pregnancies complicated by preeclampsia as a marker for intra uterine growth restriction

Background: Preeclampsia is a pregnancy-specific syndrome of reduced organ perfusion secondary to vasospasm and endothelial activation which is typically characterized by hypertension, proteinuria, edema and fetal compromise which is a leading cause of intra uterine growth restriction (IUGR). Elevated nucleated red blood cell (NRBC) count is introduced as a potential marker of intra-uterine growth restriction (IUGR) hence determination of NRBC counts is essentially helpful in predicting short term neurodevelopment outcome. Objective of the study Elevated nucleated red blood cell (NRBC) count is introduced as a potential marker of intra-uterine growth restriction (IUGR) in term babies born to preeclamptic mothersMethods: A cross sectional study conducted in a tertiary care hospital to evaluate the significance of cord blood NRBC count in term neonates born with pregnancy complicated by preeclampsia. It included 60 healthy mothers (control group) and 60 mothers with PIH. Collected data was analysed with SPSS software.Results: The nucleated red blood cell in cord blood of newborns in preeclampsia group was significantly higher than in the control group (p value 0.013). IUGR is significantly higher in PIH group (p value 0.008).Conclusions: From the observed data it is concluded that IUGR is an important cause of perinatal morbidity and mortality. The commonest maternal cause for IUGR was pregnancy induced hypertension. The other contributing factors were anemia, lack of awareness (unregistered, unbooked cases) among mothers, poor maternal nutrition and poor weight gain during pregnancy. Infants of preeclamptic women have higher nucleated red blood cell count at birth than control which means that preeclampsia may produce an erythropoietic response in the fetus. The positive correlation between cord nucleated red blood cell counts in preeclamptic patients and control group indicates that may be the hypoperfused placenta plays a role in this correlation.

Pulmonary hypertension in non-transfusion-dependent thalassemia: Correlation with clinical parameters, liver iron concentration, and non-transferrin-bound iron

BackgroundPulmonary hypertension is a major cardiac complication in non-transfusion-dependent thalassemia (NTDT). Several clinical and laboratory parameters, including iron overload, have been shown to have a positive correlation with the incidence of pulmonary hypertension. Non-transferrin-bound iron (NTBI) is a form of free-plasma iron that is a good indicator of iron overload.ObjectivesThe aim of this study was to determine the prevalence of pulmonary hypertension in patients with NTDT and to investigate its correlation with the clinical parameters, liver iron concentration (LIC) and NTBI.MethodsPatients with NTDT were evaluated using echocardiography, and magnetic resonance imaging for cardiac T2* and LIC. Pulmonary hypertension was defined as peak tricuspid regurgitation velocity ≥2.9 m/s measured using trans-thoracic echocardiography. Clinical parameters and the status of iron overload as determined by LIC, serum ferritin, and NTBI level were evaluated for their association with pulmonary hypertension.ResultsOf 76 NTDT patients, mean age 23.7 ± 8.5 years, seven patients (9.2%) had pulmonary hypertension. Previous splenectomy (71.4 vs. 24.6%, P-value 0.019), higher cumulative red blood cell (RBC) transfusions (received ≥10 RBC transfusions 85.7 vs. 33.3%, P-value 0.011), higher nucleated RBCs (353 ± 287 vs. 63 ± 160/100 white blood cells, P-value <0.001), and a high NTBI level (5.7 ± 3.0 vs. 3.3 ± 2.8 µmol/l, P-value 0.034) were associated with pulmonary hypertension. There was no significant correlation between LIC or serum ferritin and pulmonary hypertension.ConclusionPulmonary hypertension in NTDT is common, and is associated with splenectomy and its related factors. NTBI level shows a significant correlation with pulmonary hypertension.

Extramedullary haematopoiesis correlates with genotype and absence of cardiac iron overload in polytransfused adults with thalassaemia.

The mechanisms responsible for the sporadic occurrence of extramedullary haematopoiesis in polytransfused thalassaemic patients have not yet been clarified. In this study we tried to elucidate the influence of genotype and other factors on the presence of extramedullary haematopoiesis. We performed a retrospective database review of our polytransfused thalassaemic patients between January 2006 and December 2011. Demographic, transfusional, genetic, radiological and biochemical data were collected and statistically analysed. Extramedullary haematopoiesis was found in 18 out of 67 patients (27%). All of them were splenectomised, had a higher nucleated red blood cell count and higher levels of the soluble form of transferrin receptor with respect to patients without extramedullary haematopoiesis; furthermore, patients with EMH had a lower transfusional iron intake and a higher pre-transfusion haemoglobin level as compared with those without extramedullary haematopoiesis. Ten out of the 18 patients with extramedullary haematopoiesis were compound heterozygotes for IVS 1-6/codon 39. A high frequency of thrombotic events was also recorded among all patients followed at our centre with this genetic profile. Among our cohort of thalassaemic polytransfused patients, extramedullary haematopoiesis was not such a rare event. Furthermore, we identified a group of patients, most of whom were compound heterozygotes for IVS 1-6/codon 39, with increased soluble transferrin receptor levels and excessive expansion of erythroid marrow probably responsible for the tendency to develop extramedullary haematopoiesis.

Pulmonary Hypertension Risk in Patients with Hemoglobin H Disease: Low Incidence and Absence of Correlation with Splenectomy

Pulmonary hypertension (PHT) is a common complication for patients with β thalassemia intermediate (TI), especially splenectomized patients. However, the frequency and risk factors of PHT in patients with hemoglobin H (HbH) disease is unknown. The purpose of this study was to identify the prevalence of PHT risk manifested as tricuspid regurgitant jet velocity (TRV) ≥2.5 m/s in patients with HbH disease and its correlation with splenectomy. One hundred and ninety-eight patients with HbH disease who visited the 303rd Hospital of the People's Liberation Army (Nanning, China) were investigated. Thirteen subjects (6.5%) were diagnosed as having a risk of PHT. Regression analyses showed that the prevalence of PHT risk was correlated only with age (r = 0.195, p = 0.006) and not with splenectomy. The risk of PHT in patients older than 35 years was 5.7 times (range 1.8-18.6) greater than that for patients younger than 35 years. For splenectomized patients compared to those with HbH disease, patients with TI had a higher frequency of PHT risk, higher nucleated red blood cell counts (46.03 ± 41.11 × 10⁹/l vs. 0.18 ± 1.19 × 10⁹/l, p < 0.001) and a higher platelet counts (837.6 ± 178.9 × 10⁹/l vs. 506.7 ± 146.2 × 10⁹/l, p < 0.001). PHT risk is low in patients with HbH disease and does not correlate with splenectomy. Patients older than 35 years should be monitored regularly.

Risk factors for pulmonary hypertension in patients with β thalassemia intermedia

Background Pulmonary hypertension (PHT) is a common yet poorly understood complication of β thalassemia intermedia (TI). Methods We herein evaluated risk factors for PHT in TI, through comparing 64 TI patients with evidence of PHT by symptomatology and echocardiography (Group I) to age- and sex-matched TI patients without PHT (Group II). Retrieved data included demographics, laboratory parameters, clinical characteristics, and received treatments that may influence PHT development; and reflected the period prior to PHT occurrence in Group I. Results The mean age of Group I patients at development of PHT was 37.3 ± 10.6 years; with 44% being males. Among studied parameters, Group I patients were more likely to be splenectomized (4.9-times), transfusion-naive (3.5-times); hydroxyurea-naive (2.6-times), or iron chelation-naive (2.3-times); and have nucleated red blood cell count ≥ 300 × 10 6/l (2.59-times) or a previous history of thromboembolic events (3.69-times). Conclusion TI patients who eventually develop PHT may be identified early on by being splenectomized, having high nucleated red blood cell counts and a previous history of thromboembolism. Prospective clinical trials that evaluate the efficacy, safety, and cost effectiveness of transfusion, iron chelation, and hydroxyurea therapy in preventing PHT in TI are invited.

Risk Factors for Pulmonary Hypertension In Patients with Thalassemia Intermedia

AbstractAbstract 2069 Introduction:Mechanisms leading to pulmonary hypertension (PHT) in patients with thalassemia intermedia (TI) are still controversial. Moreover, clinical and laboratory characteristics of patients who eventually develop PHT have not been identified. Our aim was to identify factors that characterize TI patients who develop PHT. Methods:Data was retrospectively retrieved from the Thalassemia Intermedia Registry, a database of 584 TI patients currently registered at six comprehensive care centers in Lebanon, Italy, Iran, Egypt, United Arab Emirates, and Oman. Institutional review boards at each center approved the study protocol. Two Groups of patients were identified: Group I, TI patients with documented PHT (n=64; mean age 37.3 ± 10.6; 44% males); and Group II, age- and sex-matched TI patients without PHT (n=64; mean age 37.9 ± 11.4; 44% males). Collected data included demographics, laboratory parameters, disease-complications, and received treatments that may influence PHT development and reflected the period prior to PHT occurrence. Results:There were no statistically significant differences in mean platelet counts, total or fetal hemoglobin levels between the two Groups. However, mean serum ferritin level was higher in Group I compared to Group II (1233.2 ± 499.2 vs. 654.7 ± 234.5 ng/ml; P=0.01). Moreover, mean nucleated red blood cell (NRBC) count was higher in Group I compared to Group II (354.2 ± 199.2 vs. 214.7 ± 94.5 ×10⋀6/l; P=0.03). A higher proportion of patients were splenectomized (84.4% vs. 46.9%; P<0.001) or had a previous history of thromboembolic events (40.6% vs. 7.8%; P<0.001) in Group I compared to Group II. Conversely, a higher proportion of patients received transfusion (78.1% vs. 56.2%; P<0.001), iron chelation (62.5% vs. 37.5%; P<0.001), or hydroxycarbamide (34.4% vs. 17.2%; P<0.001) therapy in Group II compared to Group I. There were no statistically significant differences in the proportion of patients with heart failure, prothrombotic mutations, or receiving antiplatelet or anticoagulant therapy between the two Groups. Multivariate logistic regression analysis revealed that patients in Group I are more likely to be splenectomized (OR:4.9, 95%CI:1.9-8.5); transfusion-naive (OR:3.5, 95%CI:2.1-6.25); on no hydroxycarbamide (OR:2.6, 95%CI:1.1-5.25) or iron chelation therapy (OR:2.3, 95%CI:1.2-4.25); and have NRBC count >300 ×10⋀6/l (OR:2.59, 95%CI:1.69-6.05) or a previous history of thromboembolism (OR:3.69, 95%CI:2.38-7.05). Conclusion:Splenectomy, previous history of thromboembolism, and a high NRBC count characterize TI patients who develop PHT. Transfusion, iron chelation, and hydroxycarbamide therapy deserve evaluation for a protective role against PHT in TI. Disclosures:No relevant conflicts of interest to declare.

Splenectomy and thrombosis: the case of thalassemia intermedia.

Hypercoagulability in splenectomized patients with thalassemia intermedia (TI) has been extensively evaluated. However, clinical and laboratory characteristics of patients who eventually develop overt thromboembolic events (TEE) are poorly studied. Three Groups of TI patients (n=73 each) were retrospectively identified from a registry involving six centers across the Middle East and Italy: Group I, all splenectomized patients with a documented TEE; Group II, age- and sex-matched splenectomized patients without TEE; and Group III, age- and sex-matched non-splenectomized patients without TEE. Retrieved data included demographics, laboratory parameters, clinical complications, and received treatments that may influence TEE development, and reflected the period prior to TEE occurrence in Group I. The mean age of Group I patients at development of TEE was 33.1±11.7years, with a male to female ratio of 33:40. TEE were predominantly venous (95%) while four patients (5%) had documented stroke. Among studied parameters, Group I patients were more likely to have a nucleated red blood cell (NRBC) count ≥300×10(6) L(-1) , a platelet count ≥500×10(9) L(-1) and evidence of pulmonary hypertension (PHT), or be transfusion naïve. The median time to thrombosis following splenectomy was 8years. Patients with an NRBC count ≥300×10(6) L(-1) , a platelet count ≥500×10(9) L(-1) , or who were transfusion naive also had a shorter time to thrombosis following splenectomy. Splenectomized TI patients who will develop TEE may be identified early on by high NRBC and platelet counts, evidence of PHT, and transfusion naivety.

Early Markers of Brain Damage in Premature Low-Birth-Weight Neonates Who Suffered from Perinatal Asphyxia and/or Infection

We studied 57 low-birth-weight premature neonates, of whom 29 suffered from perinatal asphyxia and/or infection, while the remaining 28 did not and served as controls. We measured peripheral nucleated red blood cell (NRBC) absolute numbers as well as interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α cytokine serum levels at 24 h postnatally and on days 3 and 7 following birth. Fourteen of the asphyxiated/infected neonates and 12 controls had neurologic assessments at the corrected postnatal age of 18 months. We found NRBC absolute numbers and serum IL-1β and IL-6 cytokine levels at 24 h postnatally to be significantly higher in neonates with perinatal asphyxia/infection than in the controls (p = 0.022, p = 0.036 and p = 0.037, respectively). TNF-α levels did not differ. Neurologic examination at the corrected postnatal age of 18 months showed 8 out of the 14 children who had been asphyxiated/infected as neonates to have abnormal findings, while 12 children who were used as controls during their neonatal period were normal. Abnormal neurologic findings correlated with high NRBC counts and IL-1β and IL-6 levels at 24 h postnatally. In conclusion, increased NRBC counts and proinflammatory cytokine levels in asphyxiated/infected neonates represent early markers for subsequent neurologic impairment.

Association of ABO incompatibility with elevation of nucleated red blood cell counts in term neonates

Objective: Nucleated red blood cells in the circulation in term neonates have been associated with a wide range of pathologic conditions. We sought to examine the relationship between nucleated red blood cells in the circulation of term neonates and maternal-neonatal blood type compatibility. Study Design: We prospectively collected umbilical blood from all live-born neonates delivered at our institution. Venous blood was analyzed for nucleated red blood cells and is reported as the number of nucleated red blood cells per 100 white blood cells. We reviewed maternal and neonatal records for neonates born at ≥37 weeks’ gestation for correlative clinical data. Statistical analysis was performed with the SAS statistical software package (version 6.12; SAS Institute, Inc, Cary, NC). Kruskal-Wallis analysis was used as a nonparametric test. Results: We evaluated 1661 neonates delivered during the study period and found a mean (±SD) of 9.29 ± 18.56 nucleated red blood cells per 100 white blood cells (range, 0-327 nucleated red blood cells per 100 white blood cells). Nucleated red blood cell counts were lower in ABO-compatible maternal-fetal dyads (mean ± SD, 8.29 ± 12.84 nucleated red blood cells per 100 white blood cells; range, 0-216 nucleated red blood cells per 100 white blood cells) than in ABO-incompatible dyads (mean ± SD, 13.16 ± 13.16 nucleated red blood cells per 100 white blood cells; range, 0-327 nucleated red blood cells/100 white blood cells; P =.006). Neonates of mothers with blood groups A and B had significantly lower nucleated red blood cell counts (P <.05). Dyads with maternal type O and neonate type B had significantly higher nucleated red blood cell counts (P <.002). Nonparametric testing determined that type O mother and type B neonate combinations had significantly higher umbilical cord nucleated red blood cell counts (P <.001). Conclusion: Maternal-fetal ABO incompatibility is associated with elevation of nucleated red blood cell count in term neonates. Nucleated red blood cell elevation does not always connote a serious pathologic process, however, because ABO incompatibility usually does not adversely affect neonatal outcome. The clinical significance of an elevated nucleated red blood cell count thus is limited. (Am J Obstet Gynecol 2000;183:1532-6.)

Absent umbilical artery end-diastolic velocity in growth-restricted fetuses: a risk factor for neonatal thrombocytopenia

Objective: To examine the relationship between umbilical artery (UA) end-diastolic flow and neonatal thrombocytopenia. Methods: We prospectively examined 115 anatomically normal single fetuses with UA pulsatility indices more than two standard deviations above the gestational age mean and subsequent birth weights below the tenth percentile. Peripheral neonatal platelet counts in fetuses with positive UA end-diastolic velocity were compared with those of fetuses with absent or reversed UA end-diastolic velocity. Results: Sixty-seven fetuses (58.3%) had positive UA end-diastolic velocity and 48 (41.7%) had absent or reversed UA end-diastolic velocity. Three neonates in the positive-flow group and 22 neonates in the absent- or reversed-flow group had platelet counts of less than 100,000/mm 3 (relative risk 10.2; 95% confidence interval; 3.2, 32.3; P < .001). Absent or reversed end-diastolic velocity had a sensitivity of 88%, specificity of 71%, positive predictive value of 46%, and negative predictive value of 96% for predicting neonatal thrombocytopenia. Neonates with absent or reversed flow also had lower median platelet counts (101,500/mm 3 versus 208,000/mm 3, P < .001), hemoglobin levels (15.1 versus 16.4 g/dL, P < .01), and hematocrits (47.6 versus 51.1%, P < .05), as well as higher nucleated red blood cell counts (191 versus 15 per 100 white blood cells, P < .001). Conclusion: Absent or reversed UA end-diastolic velocity in growth-restricted fetuses is associated with a statistically significant increase in risk of neonatal thrombocytopenia.

Nucleated red blood cell count in the differentiation of fetuses with pathologic growth restriction from healthy small-for-gestational-age fetuses

Objective: The purpose of this study was to evaluate the utility of the neonatal nucleated red blood cell count in differentiating the fetus with growth restriction from the small but otherwise healthy fetus. Study Design: Perinatal outcomes were evaluated prospectively for all neonates admitted to the neonatal intensive care unit in 1997. Nonanomalous neonates with normal phenotype and a complete blood cell count performed within the first 6 hours after birth were included in the study. All neonates with birth weights lower than the 10th percentile for gestational age were considered small for gestational age. Neonates were divided into four groups: small-for-gestational-age neonates with elevated nucleated red blood cell counts, appropriately grown neonates with elevated nucleated red blood cell counts, small-for-gestational-age neonates with normal nucleated red blood cell counts, and appropriately grown neonates with normal nucleated red blood cell counts. Analysis of variance, χ 2 tests, and stepwise regression were used for statistical analysis. Results: Two hundred thirty-seven neonates met the inclusion criteria. Forty-three were small for gestational age. Small-for-gestational-age neonates with high nucleated red blood cell counts had significantly lower umbilical artery pH and were more likely to require mechanical ventilation or blood pressure support agents. Subgroup analysis demonstrated that small-for-gestational-age neonates with elevated nucleated red blood cell counts had significantly more adverse outcomes than did small-for-gestational-age neonates with normal nucleated red blood cell counts. Outcomes of small-for-gestational-age neonates with normal nucleated red blood cell counts were essentially identical to those of appropriately grown neonates. Conclusion: An elevated nucleated red blood cell count may distinguish the fetus with growth restriction from the small but healthy fetus. (Am J Obstet Gynecol 2000;182:1107-9.)

Neonatal nucleated red blood cell counts in growth-restricted fetuses: Relationship to arterial and venous Doppler studies

Objective: Elevated nucleated red blood cell count in neonatal blood and Doppler-detected circulatory decompensation in fetuses with intrauterine growth restriction are associated with hypoxemia. We sought to determine the relationship between the nucleated red blood cell count at birth and the circulatory status of fetuses with intrauterine growth restriction. Study Design: Eighty-four fetuses with elevated umbilical artery pulsatility index values >2 SD above the gestational age mean and a subsequent birth weight <10th percentile were examined serially. Umbilical and middle cerebral artery pulsatility index, inferior vena cava and ductus venosus peak velocity index, and flow pattern in the umbilical vein (umbilical vein constant vs pulsatile) were recorded. Fetuses were grouped as follows, on the basis of the last examination before delivery: 1, elevated umbilical artery pulsatility index only; 2, middle cerebral artery pulsatility index >2 SD below the gestational age mean in addition to abnormal umbilical artery pulsatility index; 3, either peak velocity index >2 SD above the gestational age mean in the inferior vena cava and ductus venosus or pulsatile flow in the umbilical vein, or both. Nucleated red blood cells per 100 white blood cells were ascertained in a peripheral blood sample obtained within 1 hour of delivery with daily follow-up samples until the nucleated red blood cell count was <5/100 white blood cells. Results: Groups 2 (median 38.5, range 1-273) and 3 (median 145, range 2-3180) had higher nucleated red blood cell counts than group 1 (median 8.5, range 1-270) ( P < .05 and P < .005, respectively). The persistence of the nucleated red blood cell count elevation was also longer in groups 3 (median 4 days, range 1-19 days) and 2 (median 2.5 days, range 1-7 days) than in group 1 (median 1 day, range 1-8 days). Neonates in group 3 also had lower platelet count, hemoglobin value, hematocrit value, and white blood cell count. The umbilical cord artery bicarbonate level was the strongest independent determinant of the peak nucleated red blood cell count and persistence of nucleated red blood cell elevation ( r 2 = 0.27, P < .001 and r 2 = 0.47, P < .0001). Conclusion: Increasing abnormality of arterial and venous flows in fetuses with intrauterine growth restriction is associated with increasing nucleated red blood cell count at birth. Metabolic acidemia rather than altered P O 2 associated with this circulatory state appears to be the main determinant of the rise in nucleated red blood cells. (Am J Obstet Gynecol 1999;181:190-5.)