Normal Neutrophil Counts Research Articles

Retrospective evaluation of the incidence and outcome of neutropenia in dogs with acute hemorrhagic diarrhea syndrome (2017-2022): 54 cases.

To report the occurrence of neutropenia in dogs with suspected acute hemorrhagic diarrhea syndrome (AHDS) and to assess its association with survival. Secondary objectives were to assess whether neutropenia was associated with length of hospitalization, fulfillment of systemic inflammatory response syndrome (SIRS) criteria, and whether SIRS status was associated with survival. Finally, the association of antimicrobial use with neutropenia, SIRS status, and survival was evaluated. Single-center, retrospective study from the medical records of dogs diagnosed with AHDS between 2017 and 2022. Private referral hospital. Fifty-four dogs with suspected AHDS referred to the Emergency and Critical Care specialist service. None. Of 54 dogs, 28 (52%) presented with or developed neutropenia during their treatment course. Overall, 9 (17%) dogs were nonsurvivors. A total of 8 of 28 (29%) dogs with neutropenia were nonsurvivors, while only 1 of 26 (4%) dogs with a normal neutrophil count was a nonsurvivor (P=0.025). Upon hospital admission, neutropenic dogs were significantly more likely to fulfill SIRS criteria than nonneutropenic dogs (P=0.0096). There was no difference in mortality between SIRS-positive (fulfilling ≥2 SIRS criteria) and SIRS-negative (fulfilling <2 SIRS criteria) dogs (P=0.14). There was no difference in the median length of hospitalization between neutropenic and nonneutropenic dogs (P=0.49). The incidence of neutropenia is high in this population of dogs presenting with AHDS. In this retrospective study, neutropenia was significantly associated with an increased risk of nonsurvival and an increased likelihood of fulfilling SIRS criteria; however, a fulfillment of SIRS criteria could not be used to predict survival. Neutropenia in dogs with AHDS was not associated with an increased length of hospitalization.

Recurrent late-onset neutropenia following treatment with different B cell-depleting strategies in multiple sclerosis.

As B cell-depleting therapies in multiple sclerosis (MS) have gained significant importance in the last several years, their long-term safety profile is of considerable clinical interest. Late-onset neutropenia (LON) is a rare, but potentially severe, adverse event that was first described in patients with rheumatic disorders under therapy with rituximab. Ofatumumab was approved in 2021 for the treatment of relapsing-remitting multiple sclerosis (RRMS). Neutropenia occurred in 0.2% of patients in clinical phase 3 trials, and to date, no cases of LON have been reported under ofatumumab treatment. Here, we report a case of repetitive symptomatic LON under ocrelizumab as well as ofatumumab treatment. Additionally, we review the literature on rare occurrences of LON in patients with MS, neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) undergoing B cell-depleting therapies, including rituximab, ocrelizumab, ofatumumab, inebilizumab, and ublituximab. In our case, the patient presented with repetitive symptomatic LON under ocrelizumab as well as ofatumumab treatment leading to febrile infections, subsequent use of antibiotics, and application of granulocyte-colony-stimulating factor. After repetitive episodes of LON under both B cell-depleting strategies, cladribine was subsequently initiated. A nine-month follow-up showed a normal neutrophil count and no evidence of disease activity. This case highlights the significance of symptomatic late-onset blood count changes under both ocrelizumab and ofatumumab and emphasizes the importance of continuous monitoring of the differential blood count under B cell-depleting treatment. This study was supported by the Deutsche Forschungsgemeinschaft (DFG; SFB CRC-TR-128 to F.Z., V.F., and S.B..; SFB 1080 and SFB CRC-1292 to F.Z..; and SFB/TRR 355 to S.B.) and the Hermann and Lilly Schilling Foundation (to S.B.).

5150 When Few Options Exist: Graves’ Disease Treated with Potassium Iodide and Levothyroxine Block-and-Replace Therapy

Abstract Disclosure: O. Magvanjav: None. S.K. Majumdar: None. Background: In the US, methimazole and propylthiouracil are effective first-line agents for the treatment of Graves’ disease. However, side effects including liver dysfunction may limit their use. In such instances, alternative non-conventional agents such as potassium iodide (KI) may be considered. Here, we present a case of a patient with Graves’ disease successfully treated with KI, drawing on the example of similar treatment experiences in Japan. Clinical case: Our patient is a 29-year-old woman who presented with a 3-week history of palpitations accompanied by fatigue, heat intolerance, itchiness, insomnia, and unintentional weight loss. Exam was notable for tachycardia (135 bmp), elevated blood pressure (BP) (150/81 mmHg), normal temperature, slight thyromegaly, brisk reflexes, mild anxiousness, and tremulousness. She was found to have a TSH of 0.007 mIU/ml (normal: 0.270-4.200 mIU/ml), elevated free T4 of 5.19 ng/dl (normal: 0.80-1.70 ng/dL), total T3 of 330 ng/dl (normal: 72.0-153.0 ng/dl), total T4 of 12.1 ug/dl (normal: 4.5-11.7 ug/dl), and positive antibodies (TSI 443%; TRAB 5.42 IU/L). A thyroid ultrasound showed diffuse hyperemia and a 1.4 cm right lobe TR3 nodule. She had a normal baseline neutrophil count with mild eosinophilia; a baseline hepatic function panel was not obtained. She was started on methimazole 20 mg daily and metoprolol XL 50 mg daily for symptom control. One week into treatment, a hepatic function panel showed elevated liver enzyme levels: AST 70 U/L (normal: 10-35 U/L) and ALT 223 U/L (normal: 10-35 U/L); previous values from 2 years prior were normal. Repeat levels a few days later showed increasing liver enzyme levels (AST 83 U/L; ALT 268 U/L) despite decreasing thyroid hormone levels. Methimazole was stopped, and she was then seen by a gastroenterologist, who concurred with the possibility of an adverse drug reaction to methimazole. She declined definitive therapy with surgery or radioactive iodine therapy and wanted to pursue alternative and less invasive options. Drawing on a previous successful experience from Japan, we initiated her on KI (50 mg twice daily), which resulted in normalization of her thyroid hormones within two weeks of initiation. She subsequently developed hypothyroidism 2 months later, at which point we initiated block-and-replace therapy with the addition of 50 mcg of levothyroxine. Her liver enzymes normalized with normalization of thyroid hormones. Conclusions: We present a patient with symptomatic Graves’ disease who was successfully treated with KI in the setting of limited treatment options, specifically an adverse reaction to methimazole (transaminitis), and who declined both surgery and radioactive iodine. This case demonstrates that KI may be useful in Graves’ disease as either a bridge to more definitive therapy when thioamides are not tolerated, or perhaps as a treatment option for those most likely to go into remission. Presentation: 6/1/2024

Novel neutrophil biology insights underlying atypical chemokine receptor-1/Duffy antigen receptor of chemokines-associated neutropenia.

Atypical chemokine receptor-1 (ACKR1)/Duffy antigen receptor of chemokines (DARC)-associated neutropenia (ADAN; OMIM 611862), previously named benign ethnic neutropenia, and present in two-thirds of individuals identifying as Black in the USA, is associated with mild to moderate decreases in peripheral neutrophil counts that nevertheless do not lead to increased infections. Consequently, recent initiatives have sought to establish normal neutrophil count reference ranges for ADAN, considering it a normal variant rather than a clinical disorder requiring medical intervention. A limited number of studies elucidating the mechanism of neutropenia in ADAN has suggested that neutrophils may redistribute from peripheral blood to the tissues including the spleen: this might explain why ADAN is not associated with increased risks of infection since the total number of neutrophils in the body remains normal. In this review, we critically examine the research underlying the molecular basis of ADAN. Insights into the biology of neutrophils and their trafficking may inform the clinical interpretation of neutropenia in ADAN. The bulk of research suggests that ADAN does not lead to a diminished host defense as do other forms of neutropenia. However, ADAN may lead to increased proinflammatory signaling, with possible implications for senescence of the immune system and predisposition to autoimmunity and cancer.

Association between immune system parameter and clinical characteristics among patients with solid cancer

BACKGROUND Lymphopenia has been reported to be a major predictor of chemotherapy-related toxicity. This study aimed to investigate the correlation between neutrophils, lymphocytes, CD4, and CD8 in solid cancer patients and cancer clinical characteristics. METHODS This was a cross-sectional study of patients who will undergo chemotherapy at the Hematology and Medical Oncology Clinic, Cipto Mangunkusumo Hospital, from June to September 2023. Clinical characteristics, CD4 and CD8 levels, and neutrophil and lymphocyte counts were assessed at the first visit. A comparative test was carried out on the patients’ average CD4, CD8, neutrophil, and lymphocyte counts. RESULTS Types of cancer were associated with CD4 levels. Patients with head and neck cancer had lower CD4 levels (411.3 [119.3–1,427.5] cells/mm³) compared with colorectal (514.7 [129.2–861.3] cells/mm³), breast and gynecological (567.5 [180.1–939 cells/mm³), and other cancers (681.4 [175.1–2,056.9] cells/mm³), with p = 0.009. Patients aged ≥40 years had higher CD8 levels than those aged &lt;40 years (376.4 [142.8–1,293.1] cells/mm³ versus 565.3 [185.9–1,944] cells/mm³, p = 0.01). Additionally, lymphocyte count was associated with cancer type, with the lowest number in head and neck cancer (1,380 [280–2,660] μl, p = 0.044). CONCLUSIONS CD4 levels and lymphocyte counts were associated with the cancer type, whereas CD8 levels were influenced by age.

Enterobius Vermicularis Unusual Cause of Appendicitis: A Case Report

Abdominal pain is common in children (under 18 years) with a strong female preponderance in those aged over 8 years. Of those presenting with acute abdominal pain requiring inpatient assessment, only 25% have acute appendicitis. Pinworms are the most common helminth infection in the USA and Western Europe, with prevalence rates in some communities of as high as 30-50%. Pinworms generally live in the gastrointestinal tract, and helminth infestations have been noted in over one-quarter of acute appendectomies on histologic examination. Acute appendicitis is one of the most common emergent surgeries. Generally, appendicitis is inflammation of the appendix. The medical procedure for the departure of the reference area is called an appendectomy. Appendectomy can be performed through an open or laparoscopic medical procedure, and it is the most effective way to prevent complications is to remove the inflamed appendix early by open surgery or laparoscopically. This case was a 14 years old female with abdominal pain and acute appendicitis that underwent surgery shows Occiur patch was the cause of her signs and symptoms of acute appendicitis that performed resection of appendix and discharge healthy. The present study presents a classic case of parasitic appendicitis in a teenage girl and discusses the clinical features, treatment and global burden of disease. Atypical presentations may indicate an unusual anatomical placement of the appendix. Preoperative diagnosis using cross-sectional computed tomography imaging and a thorough understanding of these situations frequently result in early diagnosis and expeditious surgical care. EV was seen in 9.8% of pediatric appendectomies in our study. Pruritus anus, normal WBC count, normal neutrophil count, and normal CRP level at presentation could predict EV infection in children who present with right iliac fossa pain. E. vermicularis is responsible for 7% of acute appendicitis. It is responsible for a significantly higher negative appendectomy rate which if predicted may avoid unnecessary appendectomy and associated morbidity. Enterobius vermicularis associated appendicular colic and acute appendicitis are rarely encountered in the United States. The high rate of inflammation on pathology found among our patients with pinworm appendicitis suggests an association with presentation as acute appendicitis. Enterobius vermicularis is known to be associated with appendicitis, however a causal relationship between Enterobius and appendicitis has not been established. The aim of this study was to explore the relationship between appendiceal Enterobius and histologic appendicitis. Enterobius-associated appendicitis cases and compare them with acute appendicitis cases in terms of parameters such as the neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP)-to-lymphocyte ratio (CLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Enterobius vermicularis infections are usually asymptomatic and may only cause anal pruritis, with occasional reported cases of ectopic migration into the appendix or the female genital tract by adult pinworms.

Absence of Neutropenia in Patients With Early Exon Nonsense Mutations in ELANE : Clinical Evidence to Support Gene Therapy Approaches for Severe Congenital Neutropenia.

Severe congenital neutropenia is an inherited bone marrow failure disorder characterized by profoundly low neutrophil counts and promyelocytic maturation arrest in bone marrow. Severe congenital neutropenia is most often caused by heterozygous ELANE mutations. In vitro and mouse xenograft studies using CRISPR/Cas9 have shown that introduction of frameshift/nonsense mutations in mutant ELANE may restore neutrophil counts, providing a model for gene therapy. Here, we present 2 children with inherited nonsense mutations in ELANE analogous to those proposed for gene therapy. Their normal peripheral blood neutrophil counts provide support for this approach through human "experiments of nature."

Analysis of maternal Fc gamma receptor IIIb isoantibodies using immunomagnetic negative selected neutrophils.

The isolation of neutrophils and subsequent detection of anti-human neutrophil antigens (HNA) antibodies are crucial in clinical medicine for the diagnosis of autoimmune neutropenia, neonatal alloimmune neutropenia (NAIN) and transfusion-related acute lung injury (TRALI). This study reports two cases of maternal anti-Fc-gamma-receptor-IIIb (FcγRIIIb) isoimmunization without NAIN symptoms and compares the efficiency of immunomagnetic negative selection (IMNS) with traditional dextran/Ficoll for neutrophil isolation in HNA serological assays. Investigating two cases of maternal anti-FcγRIIIb isoimmunization, neutrophils from three donors were isolated from 8 mL of whole blood using IMNS and dextran/Ficoll. Serological assays included the granulocyte agglutination and immunofluorescence test, monoclonal antibody immobilization of granulocyte antigens and the LABScreen Multi (One Lambda). IMNS and dextran/Ficoll were compared in terms of cell yield, viability, time, cost and purity. Maternal anti-FcγRIIIb isoantibodies with FCGR3B gene deletion were detected in both cases. Newborns and fathers exhibited specific gene combinations: FCGR3B*02/FCGR3B*02 (Case 1) and FCGR3B*02/FCGR3B*03 (Case 2). IMNS outperformed dextran/Ficoll, yielding four times more neutrophils (average neutrophil counts: 18.5 × 103/μL vs. 4.5 × 103/μL), efficiently removing non-neutrophil cells and reducing processing time (30-40 min vs. 70-90 min), although it incurred a higher cost (2.7 times). Two cases of maternal anti-FcγRIIIb isoantibodies, unrelated to NAIN, were identified. Although neutropenia has not been described in these cases, we emphasize the importance of identifying asymptomatic cases with the potential for severe neutropenia. Additionally, IMNS is introduced as a rapid, high-yield, high-purity neutrophil isolation technique, beneficial for serological assays detecting anti-HNA antibodies.

Detection and Analysis of Commonly Used Infection Indicators in Patients with Acute Urticaria

Introduction: In this study, we investigated the correlation and clinical significance of peripheral blood leukocytes, neutrophils, C-reactive protein (CRP), and procalcitonin (PCT) in patients with acute urticaria. Methods: Complete blood count with differential, CRP, and PCT tests were conducted on patients with acute urticaria. A total of 614 patients with acute urticaria were divided into three groups: the first group consisted of patients with elevated leukocyte and neutrophil count, the second group consisted of patients with normal leukocyte and neutrophil count, and the third group consisted of patients with abnormal leukocyte and neutrophil count. A correlation analysis was conducted to investigate the levels of leukocytes, neutrophils, CRP, and PCT in the three groups. Results: The results of Kruskal-Wallis’ nonparametric test revealed statistically significant variations in leukocytes, neutrophils, CRP, and PCT among the three groups (p < 0.001). However, CRP and PCT showed no statistically significant differences between the second and third groups (p < 0.001, p = 0.0041, p = 0.0032). Additional multiple comparisons in Spearman correlation analysis indicated statistically significant differences (p = 0.55). Across all groups, there was a statistically significant difference in the correlation between CRP-PCT and leukocytes-neutrophils (p = 0.53). Conclusion: Leukocytes and neutrophils are sensitive to the impact of medications and stress on the body. Combining CRP and PCT, as well as routine blood test, may be a comprehensive assessment of infection presence and severity in patients, providing guidance for antibiotic treatment.

Correlation between inflammatory markers over time and disease severity in status epilepticus: a preliminary study.

Convulsive status epilepticus (CSE) is a major subtype of status epilepticus that is known to be closely associated with systemic inflammation. Some important inflammatory biomarkers of this disorder include the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune inflammation index (SII), and pan-immune inflammation value (PIV). This study aimed to determine the NLR, PLR, MLR, SII, and PIV levels before and after treatment in adult patients with CSE and investigated the relationship of these parameters with disease severity. This retrospective study analyzed data from 103 adult patients with CSE and 103 healthy controls. The neutrophil, monocyte, platelet, and lymphocyte counts, as well as the NLR, PLR, MLR, SII, and PIV, were compared in adult patients with CSE during acute seizures (within 2 h of admission) and after treatment relief (1-2 weeks of complete seizure control). Furthermore, multivariate linear regression analysis investigated the relationship between NLR, PLR, MLR, SII, and PIV with the Status Epilepticus Severity Score (STESS). The data revealed significant differences (p < 0.05) in neutrophils, monocytes, lymphocytes, NLR, PLR, MLR, SII, and PIV between adult patients with CSE during acute seizures and after treatment relief. The average neutrophil count was high during acute seizures in the patient group and decreased after remission. In contrast, the average lymphocyte count was lower after remission (p < 0.05). Furthermore, significant differences (p < 0.05) were observed in monocytes, lymphocytes, platelets, NLR, PLR, MLR, and PIV levels between adult patients with CSE after remission and the healthy control group. Multivariate linear regression analysis showed no significant correlation between NLR, PLR, MLR, SII, and PIV with STESS. The results of this study indicated that adult patients with CSE experienced a transient systemic inflammatory response during acute seizures, which gradually returned to baseline levels after remission. However, there was a lack of robust clinical evidence correlating the severity of adult CSE and systemic inflammatory response.

The Relationship between Endotypes and Exacerbation Events in COPD Patients

Introduction: Acute exacerbations of COPD are responsible for 60% of health costs, reduce patients' quality of life, and accelerate disease progression. COPD endotypes are expected to provide new insights about clinical phenotypic variability and therapeutic response between individuals through certain biomarker approaches. Objective: Our study aims to identify the relationship between COPD endotypes and exacerbation events. Methods: In this cross-sectional study design, participants with stable COPD (n=40) were recruited from the outpatient clinic at Airlangga University Hospital in March-August 2022. Blood was obtained for endotype's biomarker examination, such as α1-antitrypsin (AAT), IL-17A, neutrophil, and eosinophil count. The relationship between COPD endotypes and exacerbation events was analyzed using a non-parametric statistical test Result: The lower limit normal of AAT levels obtained was 12.85ng/ml; 47.5% of subjects have low AAT levels. The average IL-17A levels and blood neutrophil counts were 0.478 ± 0.426 pg/ml and 5,916.95 ± 3,581.08 cells/µl, respectively. The average blood eosinophil count was 298.35 ± 280.44 cells/µl, 16 of 40 (40%) subjects with blood eosinophil count &gt; 300 cells/µl. No significant association was observed between AAT levels (p = 1.000), IL-17A levels (p = 0.944), and blood eosinophil count (p = 0.739) with exacerbation events-only blood neutrophil count (p = 0.033) found to have a significant association with exacerbation events in COPD. Conclusion: AAT levels, IL-17A levels, and blood eosinophil count were not significantly related to exacerbation events in COPD patients. In comparison, blood neutrophil count was the only one associated considerably with exacerbation events. Further research about COPD endotypes is needed to identify exacerbation susceptibility as a precision treatment strategy.

Variation in neutrophil levels and artemisinin-based combination therapy efficacy in West-Africa.

Polymorphonuclear neutrophils (PMN) are involved in pathogen clearance by phagocytosis. However, the role of PMNs in the efficacy of artemisinin-based combination therapy (ACT) is poorly understood. In a prospective longitudinal in vivo study, neutrophil rates were compared with malaria carriage after treatment with different ACTs: Artemether - lumefantrine (AL), Artesunate - amodiaquine (ASAQ), Dihydroartemisinin - piperaquine (DP) or Pyronaridine artesunate (PA). The study cases were classified as having neutropenia, normal neutrophil levels or neutrophilia depending on the level of neutrophils in the blood. This study included 3148 patients and was analyzed using R. On day 7, only four patients in the neutropenia group and treated with AL had a malaria positive blood smear based on microscopy. On day 28, the rate of recurrent parasitemia in the AL arm was significantly higher in neutropenia patients (50.9%) than in patients with normal rates of neutrophils (43.1%) or in those with neutrophilia (6.0%) (p < 0.001). In ASAQ arm, the rate of recurrent Plasmodium falciparum parasitemia was 58.8% in the neutropenia group versus 29.4% in patients with normal rates of neutrophils and 11.8% in patients with neutrophilia (p < 0.001). No patient treated with DP with normal neutrophil counts or neutrophilia was carrying malaria parasites on day 28. Among the 15 patients with parasitemia on day 28 in the PA arm, 11 (73.33%) had neutropenia while 4 (26.67%) had a normal neutrophil count (p < 0.001). Patients with neutropenia had higher rates of recurrent P. falciparum parasitemia after ACT.

Overall survival of patients with BRAF-mutant metastatic colorectal cancer treated with encorafenib-cetuximab in a real-world nationwide study in the Netherlands.

3589 Background: Approximately 10-15% of patients with metastatic colorectal cancer (mCRC) have BRAFV600E mutated tumors. Encorafenib plus cetuximab (EC) combination treatment was approved following the results of the randomized phase III BEACON trial and is currently recommended for all pretreated patients with BRAFV600E-mutant mCRC. Selection of patients in randomized controlled trials is based on restrictive eligibility criteria and often not representative of the patient population in daily clinical practice. Complementary real-world effectiveness studies can improve knowledge on the generalizability of trial results, and support decision making in clinical practice. Methods: This population-based study included all mCRC patients in the Netherlands treated with EC since approval in October 2020 until June 2022. Individual patient data and original pathology reports were collected. Primary endpoint was overall survival (OS), defined as time from EC initiation until death by any cause, analyzed by Kaplan-Meier curves. WebPlotDigitizer was used to reconstruct the Kaplan-Meier survival curve of the BEACON trial. Uni- and multivariable analyses were performed. Subgroup analyses were conducted for patients who would have been eligible for the BEACON trial based on key eligibility criteria: BRAFV600E mutation, 1-2 prior regimens, world health organization performance status (WHO PS) of 0-1, normal neutrophil count, absence of brain metastases, no prior RAS/RAF/MEK treatment, and no concurrent malignancies. Results: 155 patients were included with a median follow-up time of 11.1 months. Patient characteristics differed from BEACON in mean age (64 versus 60 years), primary tumor sidedness (69% versus 50% right-sided) and WHO PS (23% versus 51% WHO 0). Median OS of the total real-world cohort was 6.6 months (95% CI: 6.0-8.3) and differed significantly from BEACON (9.3 months; 95% CI: 8.0-11.3; p = 0.003). 35% of real-world patients treated with EC would not have been eligible for the BEACON trial, showing an inferior median OS of 6.0 months (95% CI: 4.6-9.2) compared to 7.0 months (95% CI: 6.4-9.8) in trial eligible real-world patients. WHO PS was independently associated with poor survival in multivariable analysis. Patients with WHO PS≥2 had a median OS of 3.9 months (95% CI: 2.4-NA) with a hazard rate of 2.5 (95% CI: 1.1-5.5; p = 0.003). Conclusions: This largest to date - unselected - population-based cohort of mCRC patients treated with EC showed an efficacy-effectiveness gap for OS. These outcomes should be considered in clinical practice for treatment decision making. Omitting EC for subgroups demonstrating very short OS, such as patients with WHO PS ≥2, needs to be considered. Further research is warranted to adapt treatment guidelines towards a more personalized approach for patients with BRAFV600E-mutated mCRC.

Venetoclax plus hypomethylating agents versus intensive chemotherapy for hematological relapse of myeloid malignancies after allo-HSCT.

Since allogeneic stem cell transplantation (allo-HSCT) is considered one of the curative treatments for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), hematological relapse following allo-HSCT remained a crucial concern for patients' survival. We retrospectively compared patients who received venetoclax plus hypomethylating agents (VEN+HMA, n=23) or intensive chemotherapy (IC, n=42) for hematological relapse of myeloid malignancies after allo-HSCT. HMA selection included decitabine (n=2) and azacitidine (n=21), and combined donor lymphocyte infusion was administered to 21 and 42 patients in VEN+HMA and IC groups, respectively. Median age of all patients was 39 (16-64) years old. Overall response rates, including complete response (CR), CR with incomplete recovery of normal neutrophil or platelet counts (CRi) and partial response (PR), were not significantly different between VEN+HMA and IC groups (60.1% versus 64.3%, P=0.785). CR/CRi rate was 52.2% in VEN+HMA and 59.5% in IC group (P=0.567). The rate of relapse after response was 66.7% in VEN+HMA group and 40.7% in IC group (P=0.176). Median overall survival was 209.0 (95%CI 130.9-287.1) days for VEN+HMA group versus 211.0 (95%CI 28.7-393.3) days for IC group (P=0.491). The incidence of lung infection (17.4% versus 50.0%, P=0.010), thrombocytopenia (73.9% versus 95.2%, P=0.035) and acute graft-versus-host disease (aGvHD) (50.0% versus 13.0%, P=0.003) was significantly higher in IC group. In conclusion, VEN+HMA is not inferior to IC regimen in terms of improving response and survival, and is associated with a lower incidence of adverse events and aGvHD. However, further research is required to enhance long-term survival.

The full blood count in screening asymptomatic infants for early-onset sepsis: A cross-sectional study.

The full blood count (FBC) is commonly measured as part of a partial septic work-up in asymptomatic infants at increased risk of early-onset neonatal sepsis (EOS). To determine the impact of FBC parameters on infants' subsequent management a retrospective cross-sectional study was performed. Infants, born at ≥34 weeks gestation, asymptomatic at birth, undergoing a partial septic work-up and receiving prophylactic antibiotics due to increased risk of EOS in a single centre over a 2-year period, were included. The primary outcome measure was frequency of FBC result impacting on duration of antibiotic therapy. Secondary outcome measures included frequency of FBC parameters outside of the reference range and incidental diagnoses. In total, 16 726 live-born infants were delivered during the study period. A total of 802 (4.8%) were included. Thirteen infants (1.6%) received a prolonged course of antibiotics due to suspicion for EOS. Two of these infants had elevated white cell counts. All had normal neutrophil counts. In no case did the FBC result influence the decision to prolong the antibiotic course. In a cohort of 802 infants, asymptomatic at birth and at increased risk of EOS, the FBC result did not impact on the decision to prolong the course of antibiotics for suspicion of EOS.

Acute urachal cystitis in two children

Persistent Urachal cysts (UC) are rare congenital pathologies caused by failure of obliteration of urachal remnant. This can lead to potential morbidities including infection and fistula formation. Presentation of such pathology varies resulting in significant delay in diagnosis. This article reports mysterious presentations of UC in children investigated for non-specific abdominal pain. Two cases presented with worsening central abdominal pain associated with occasional vomiting for the previous 4–6 months. Physical examination of the girl revealed tenderness over peri-umbilical area with no palpable masses. She had normal white cell (WCC), neutrophil count and C-Reactive Protein (CRP). Her Ultrasound scan noted a cylindrical hypoechoic structure in keeping with a urachal cyst. However, the boy experienced lower abdominal tenderness with on masses felt and an elevated WCC and neutrophil count but normal CRP. USS reported a rounded, fibrosed lesion with a fibrosed tract, in keeping with non-complicated urachal remnant. Laparoscopic findings for first case, noted UC with a visible midline patent tract connecting to urinary bladder; such connection confirmed using injected saline. During the second case, the cystic structure, was connected to the umbilical stump. In both cases, both the UC and tract were dissected off and completely resected. Both had an uneventful post-operative recovery, with no further episodes of abdominal pain during follow-up appointments. Persistent UC could be easily mis-diagnosed with other commoner surgical abdominal pains. High suspicion, careful examination, and relevant radiological investigations, lead to earlier diagnosis and proper surgical management.

Incidence of Typical Neutrophil Count with Fy(a-b-) Status Among Hematology Referrals for Neutropenia at an Urban Safety-Net Hospital

Typical neutrophil count with Fy(a-b-) status, known variously as Duffy null phenotype or Benign Ethnic Neutropenia, causes asymptomatic neutropenia without clinical sequelae.[i][ii] Fy(a-b-) phenotype is correlated to homozygosity of a single nucleotide polymorphism in the promoter region of atypical chemokine receptor 1 (ACKR1; formerly known as DARC), a decoy chemokine receptor, and may protect against malaria infection.[iii][iv] This genotype is enriched in malaria-endemic regions.[v] 25% to 50% of people of African ancestry in the United States are thought to have Fy(a-b-) status and are often erroneously identified as having pathologically low neutrophil counts. We performed a retrospective chart review of new neutropenia referrals to Hematology Clinic at Boston Medical Center (BMC) to evaluate diagnostic patterns for typical neutrophil count with Fy(a-b-) status. Overall, 103 new referrals for evaluation of neutropenia were made to BMC Hematology Clinic from 1/2020 to 2/2022, of which 78 were included for further analysis. Demographic and laboratory data are summarized in the accompanying Table. Typical neutrophil count with Fy(a-b-) status was identified as the primary etiology for neutropenia in 64.1% (50 of 78 referrals), of which 41 (82%) identified as African American or Black or were born in an African or Caribbean country. Of patients suspected of having Duffy null phenotype, 66% (33 of 50 patients) underwent confirmatory blood bank testing, and 97% (32 of 33) of these patients were found to have Fy(a-b-) status. Average cost of laboratory visit was calculated for each new referral using the Outpatient Price Transparency Tool from BMC Billing Department, which is based on chargemaster prices for the hospital. Patients with typical neutrophil count with Fy(a-b-) status on average had lower, but not negligible, cost of workup ($363.82 vs $689.46; p<.005 by unpaired student's T test assuming unequal variance) and were statistically less likely to have a follow up appointment (p=0.039 by unpaired student's T test assuming unequal variance) compared to those without. Though this phenotype reflects normal variation of white cell count in non-White populations, it is a "...label that illustrates how common phenotypes seen in non-White individuals continue to be considered nonstandard in the medical community." Workup of referrals that have typical neutrophil count with Fy(a-b-) status is not currently recommended, unless they have a change in their baseline white cell count or new, atypical features concerning for a secondary etiology.[vi] In our study, asymptomatic referrals were the majority and represent an unnecessary cost burden on an overtaxed healthcare system. Fy(a,b) antigen testing provides a low-cost alternative to hematology referral for confirmation of Fy(a-b-) status for patients or providers who require reassurance. Expanded use of serological Fy(a,b) antigen testing by primary care providers for patients with ancestry from malaria-endemic regions and chronic, asymptomatic neutropenia could reduce cost of care and referrals to Hematology clinic. [i] Ortiz MV, Meier ER, Hsieh MM. Identification and Clinical Characterization of Children With Benign Ethnic Neutropenia. J Pediatr Hematol Oncol. 2016 Apr;38(3):e140-3. doi: 10.1097/MPH.0000000000000528. PMID: 26925714; PMCID: PMC5102334. [ii] Merz LE, Achebe M. When non-Whiteness becomes a condition. Blood. 2021 Jan 7;137(1):13-15. doi: 10.1182/blood.2020008600. PMID: 33181819. [iii] Reich D et al. Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene. PLoS Genet. 2009 Jan;5(1):e1000360. doi: 10.1371/journal.pgen.1000360. Epub 2009 Jan 30. PMID: 19180233; PMCID: PMC2628742. [iv] Miller LH, Mason SJ, Clyde DF, McGinniss MH. The resistance factor to Plasmodium vivax in blacks. The Duffy-blood-group genotype, FyFy. N Engl J Med. 1976 Aug 5;295(6):302-4. doi: 10.1056/NEJM197608052950602. PMID: 778616. [v] Haddy TB, Rana SR, Castro O. Benign ethnic neutropenia: what is a normal absolute neutrophil count? J Lab Clin Med. 1999 Jan;133(1):15-22. doi: 10.1053/lc.1999.v133.a94931. PMID: 10385477. [vi] Gibson C, Berliner N. How we evaluate and treat neutropenia in adults. Blood (2014) 124 (8): 1251-1258. https://doi.org/10.1182/blood-2014-02-482612 Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Risperidone induced neutropenia in a 75-year-old man

IntroductionWe discuss the case of a 75-year-old man with no psychiatric history, presenting with complex auditory hallucinations, both commentary and imperative, delusions of persecution and prejudice, severe anxiety, modified behaviour, and altered sleep patterns.ObjectivesThe patient was started on oral risperidone, with favourable evolution of symptoms after reaching a daily dose of 3 mg/day. After three weeks of treatment, the laboratory results showed a low number of neutrophils. Interdisciplinary approach and examinations which included both clinical and paraclinical evaluation concluded that another cause of neutropenia was highly unlikely.MethodsThe patient was switched to olanzapine, with gradually increasing doses up to 10 mg/day. A significant improvement of the neutrophils’ level was noticed, with a return to normal parameters after a few days. Nevertheless, the clinical course was unfavourable, with reoccurrence of auditory hallucinations and delusions in two weeks’ time. Decision to rechallenge was made, with careful monitoring of the blood test results, particularly neutrophil levels. Risperidone was started at low doses of 0.5 mg/day and gradually increased up to 2 mg/day.ResultsSeven days after risperidone reinitiation laboratory tests showed normal absolute neutrophil count. However, another week later, neutrophils fell again out of the normal range.ConclusionsThe patient was discharged with haloperidol, with adequate control of symptoms and no adverse reactions.DisclosureNo significant relationships.

Neutrophils Mediate Pulmonary Artery Thrombosis In Situ.

Pulmonary embolism is a life-threatening condition, which can result in respiratory insufficiency and death. Blood clots occluding branches of the pulmonary artery (PA) are traditionally considered to originate from thrombi in deep veins (usually in legs). However, growing evidence suggests that occlusion of the vessels in the lungs can develop without preceding deep vein thrombosis (DVT). In this work, we used an inferior vena cava (IVC) complete ligation model of DVT in Wistar rats to explore the possibility and mechanisms of PA thrombosis under the conditions where all routes of thrombotic mass migration from peripheral veins are blocked. We demonstrate that rats both with normal and reduced neutrophil counts developed thrombi in the IVC, although, neutropenia caused a substantial decrease in thrombus size and a shift from fresh fibrin toward mature fibrin and connective tissue inside the thrombus. Massive fibrin deposition was found in the PA branches in the majority of DVT rats with normal neutrophil counts, but in none of the neutropenic animals. Neutrophil ablation also abolished macroscopic signs of lung damage. Altogether, the results demonstrate that thrombi in the lung vasculature can form in situ by mechanisms that require local neutrophil recruitment taking place in the DVT setting.

Coeliac Disease Presenting as Chronic Neutropenia and Leukopenia in a 14‐Year‐Old

Coeliac disease (CD) is an immune-mediated multisystem disorder due to gluten hypersensitivity. Common findings of CD include chronic diarrhoea, weight loss, short stature, iron and folate deficiency and delayed puberty.1, 2 Leukopenia and neutropenia are rare presenting features of CD.3, 4 We report a 14-year-old girl with neutropenia probably caused by CD resolving on a gluten-free diet (GFD). A previously healthy 14-year-old girl presented to her general practitioner with lethargy. Investigations revealed a normal haemoglobin and platelets, leukopenia (WCC 3.2 × 109/L), neutropenia (1.33 × 109/L) and low ferritin (18 μg/L). She was commenced on iron supplements. Repeat full blood count (FBC) in 4 months showed persistent leukopenia and neutropenia prompting a referral to a paediatric clinic in regional New South Wales. Further evaluation in clinic found no history of a viral infection or medications and no family history of a haematological disorder. Physical examination was unremarkable with no lymphadenopathy or hepatosplenomegaly; and the weight and height were at 25th and 75th percentiles. Subsequent FBCs, 8 and 11 months later demonstrated persistent leukopenia (3.6 and 3.1 × 109/L) and neutropenia (1.2 and 1.2 × 109/L). Blood picture, vitamin B12, folate, EBV and CMV serology, anti-neutrophil antibodies, ferritin and copper levels were normal. A presumptive diagnosis of benign chronic neutropenia was made, and in view of previous low ferritin coeliac serology was performed. Serum tTG IgA (>100 U/mL), anti-deamidated Gliadin IgG (80 U), anti-endomysial IgA (positive) were high. A duodenal biopsy revealed prominent villous atrophy with blunting and multiple intraepithelial lymphocytes (more than 30 lymphocytes per 100 enterocytes) suggestive of Marsh 3b type of CD. She was commenced on a GFD. An FBC 6 months after commencement of GFD revealed normal leukocyte and neutrophil counts and the coeliac antibodies were negligible. The causes of chronic neutropenia in children include congenital, cyclic, viral, medications, autoimmune, B12, folate, copper and zinc deficiency, and benign chronic. Neutropenia and leukopenia are uncommon manifestations in CD with only a few cases reported in literature.3, 4 Neutropenia in CD could be caused by deficiency of B12, folate, zinc and copper due to malabsorption of nutrients or else it could be due to autoimmunity. In our patient, B12, folate and copper levels were normal and zinc levels were not done. CD is an immune-mediated disease. In the absence of a nutritional deficiency, we postulate that an autoimmune reaction targeting clones of neutrophils or its precursors is the most likely cause of isolated leukopenia and neutropenia in our patient.4 Our case highlights that coeliac serology could be an important second-line investigation of children with persistent neutropenia. It also reiterates the famous medical maxim: uncommon presentations of common disease are more common than common presentations of uncommon disease.