Higher Reticulocyte Counts Research Articles

Effects of potential confounding variables on accuracy of a commercially available veterinary point-of-care hematocrit meter in the evaluation of blood samples from dogs and cats.

To assess the agreement in measurements of Hct values and hemoglobin (Hgb) concentrations in blood samples from dogs and cats between a commercially available veterinary point-of-care (POC) Hct meter and a laboratory-based (LAB) analyzer and to determine the effects of various conditions (ie, lipemia, hyperbilirubinemia, hemolysis, autoagglutination, and reticulocytosis) on the accuracy of the POC meter. Blood samples from 86 dogs and 18 cats. Blood samples were run in duplicate on the POC meter, which reported Hgb concentration, measured via optical reflectance, and a calculated Hct value. The POC meter results were compared with results from a LAB analyzer. Blood samples with grossly visible lipemia, icterus, hemolysis, and autoagglutination were noted. Mean ± SD values for LAB Hct were 33.9 ± 15.73% (range, 3.9% to 75.8%), and for LAB Hgb were 11.2 ± 5.4 g/dL (range, 1 to 24.6 g/dL). Mean bias between POC Hct and LAB Hct values was -1.8% with 95% limits of agreement (LOAs) of -11.1% to 7.5% and between POC Hgb and LAB Hgb concentrations was -0.5 g/dL with 95% LOAs of -3.8 to 2.8 g/dL. There was no influence of lipemia (14 samples), icterus (23), autoagglutination (14), hemolysis (12), or high reticulocyte count (15) on the accuracy of the POC meter. The POC meter was unable to read 13 blood samples; 9 had a LAB Hct ≤ 12%, and 4 had a LAB Hct concentration between 13% and 17%. Overall, measurements from the POC meter had good agreement with those from the LAB analyzer. However, LOAs were fairly wide, indicating that there may be clinically important differences between measurements from the POC meter and LAB analyzer.

A young girl with chronic isolated cervical lymphadenopathy found to have lupus lymphadenopathy, progressing to develop lupus nephritis: a case report

BackgroundSystemic lupus erythematosus is a rare autoimmune disorder, with the prevalence in Asia ranging from 30 to 50/100,000. The diagnosis of systemic lupus erythematosus is made according to the 2019 European League Against Rheumatism/American College of Rheumatology classification criteria, and it does not contain lymphadenopathy as diagnostic criteria. However, lupus lymphadenopathy has an estimated prevalence of 5–7% at the onset of disease, and 12–15% at any stage of the disease.Case presentationA 19-year-old Sinhalese girl had neck nodules since the age of 5 years, which increased in size and became tender since 1 year. She had alopecia and joint stiffness for 6 months. She presented with a 5-day history of worsening joint pain, fever, and painful, enlarging cervical nodules. She had tender cervical lymphadenopathy, and a vasculitic rash on both lower limbs. She had pancytopenia, an erythrocyte sedimentation rate of 92, positive antinuclear antibody titer, and high anti-double-stranded deoxyribonucleic acid (DNA), with low C3 and C4 complements. She had a high reticulocyte count of 5%, with direct and indirect antiglobulin tests being positive, indicating autoimmune hemolytic anemia. Lymph node biopsy showed moderate reactive follicular hyperplasia, with scattered plasma cells and immunoblasts, with varying degree of coagulative necrosis, suggestive of lupus lymphadenopathy. On immunohistochemistry of the lymph node biopsy, Bcl2 was negative, excluding lymphoma. Contrast-enhanced computed tomography of abdomen and chest was normal with no hepatosplenomegaly or lymphadenopathy. Skin biopsy showed leukocytoclastic vasculitis. Later, with development of generalized edema, she was found to have impaired renal function, and renal biopsy showed lupus nephritis. She was started on hydroxychloroquine, prednisolone, and mycophenolate mofetil, and her symptoms improved and lymphadenopathy regressed.ConclusionIn the case of cervical lymphadenopathy in a patient with systemic lupus erythematosus, the possibilities of lupus lymphadenopathy, Kikuchi–Fujimoto disease, and lymphoma should all be considered, after excluding secondary infection due to immunosuppression. Histology confirms the differentiation of these pathologies. It is important to differentiate the cause for lymphadenopathy in systemic lupus erythematosus as the outcome and treatment varies. Lupus lymphadenopathy is usually generalized, but isolated cervical lymphadenopathy could also rarely be the first presentation of systemic lupus erythematosus. Lupus lymphadenopathy can be the only presenting feature, and needs a high index in suspecting systemic lupus erythematosus, though it is not included in the diagnostic criteria.

A New Era in Malaria Diagnosis and Surveillance Using an Automated Analyzer

▪Malaria remains a global health threat with 91 countries still endemic for the disease. Despite a recent substantial decline in morbidity and mortality, the magnitude of disease burden is still enormous as indicated by the World Health Organisation (WHO) report of an estimated 212 million new cases and approximately 429 000 deaths in 2015. Sub-Saharan Africa bears the brunt of the disease with 92% of all deaths. Plasmodium falciparum is the most lethal of the 5 parasite species that infect humans, and causes 99% of all deaths. In patients infected with P. falciparum , parasitemia can dramatically escalate every 48 hours or less and can be rapidly fatal if left untreated. Accurate, timely diagnosis is thus a critical first step in the management of malaria and the WHO recommends that all suspected cases must have diagnostic confirmation either by microscopy or rapid diagnostic testing (RDT), prior to initiation of artemisinin combination therapy. Microscopic assessment of peripheral blood is the current gold standard but is subjective and requires a high level of skill, whereas RDTs indirectly detect parasite antigen and can potentially give false positive/negative results. Other methods include PCR and the detection of monocytes with ingested hemozoin, which is a surrogate marker for malaria parasites.This study describes novel technology in the form of an automated Sysmex XN-30 analyzer, which utilizes a blue laser and flow cytometry to detect and count malaria-infected red blood cells. To evaluate the performance of the XN-30, 189 residual EDTA blood samples from suspected malaria cases referred for routine diagnosis by microscopy and RDT, were analyzed within 24 hours of collection. A total of 127 P. falciparum positive samples and 62 negative samples were processed over a 6-month period. Discrepancies between the analyzer and microscopy/RDT were resolved by PCR using dried blood spots prepared at the time of sample reception. The analyzer showed excellent specificity (98.5%) and sensitivity (98.4%). Measurements were reproducible with a precision of 1.24% and showed no carryover between samples. The percentage parasitemia that was accurately detected ranged from 0.003 to 27%. Positive samples were stored at room temperature and 4°C up to 7 days and daily measurements indicated that the parasite count was stable. To exclude interference by non-malaria factors, separate malaria negative samples (20 per index) with low hemoglobin, high reticulocyte count, thrombocytopenia and hemoglobinopathies (thalassemia, sickle cell anemia) were analyzed, but these had no effect on the malaria gates. Other Plasmodium species were also detected, including P. vivax, P. ovale and P. malariae.The direct detection and quantitation of Plasmodium parasites with the XN-30 holds great promise and has many advantages over microscopy/RDT/PCR. It is automated, easy to use and provides rapid, robust and objective diagnosis of malaria, which will ensure prompt treatment and thus undoubtedly improve the quality of healthcare and alleviate the disease burden in endemic countries. Since the XN-30 provides a CBC with each analysis, it may also serve as a valuable diagnostic aid in detecting unsuspected cases with fever of unknown origin. This scenario is becoming more common as international travel to endemic countries increases and tourists often present with symptoms when returning to their home country, where clinicians may not have a high index of suspicion for malaria, but would request a CBC as part of a diagnostic workup. The decline in parasitemia can be monitored by the XN-30 and if the clinical response to therapy is delayed, this may serve as an early warning sign of drug resistance. This will yield valuable data on the spread of artemisinin resistance, which is alarmingly prevalent in the Greater Mekong sub-region. The analyzer can differentiate gametocytes making it useful for detection of asymptomatic carriers who can be treated to prevent the transmission of parasites to the mosquito vector and thus protect communities. This is a vital step in disrupting the lifecycle of the parasite and is in line with global initiatives to eliminate malaria. It can also process finger prick samples making it suitable for infants and population studies, as well as monitoring efficacy of vaccines or new drugs in clinical trials. The XN-30 is currently for research use only but further development and clinical studies are in progress. DisclosuresPillay:Sysmex Corporation: Research Funding. Coetzer:Sysmex Corporation: Research Funding.

Efficacy of Rabbit Anti-Thymocyte Globulin (ATG) Compared to Horse ATG In Severe Aplastic Anemia

AbstractAbstract 2236Intense immunosuppression therapy (IST) using a combination of ATG and cyclosporine A (CsA) produces responses in 60–70% of patients (pts) with severe aplastic anemia (sAA). Until recently, horse ATG (hATG, ATGAM) has been the primary preparation used upfront for sAA. Relapsed or refractory pts may be treated with rabbit ATG (rATG, Thymoglobulin) a second course of IST. However, only limited efficacy data are available for rATG used as initial therapy in sAA. For both ATG preparations, recognition of the biomarkers and clinical parameters predictive of response has been a major focus of research in AA. A significant minority of patients remains refractory to IST and these patients may benefit from an early application of alternative therapeutic approaches such as bone marrow transplantation.We performed a phase II study of rATG/CsA combination (3.5 mg/kg/day × 5 days followed by CsA, dosing based on blood levels) as first line therapy for sAA. We then compared these pts to historical controls who received hATG (40 mg/kg/day × 4 days/CsA) as an initial therapy. sAA was defined according to well established criteria (cellularity <30%, with at least 2 of the following: absolute neutrophil count (ANC) <0.5 × 109/l, absolute reticulocyte count (ARC) <60 × 109/l, platelet count < 20 × 109/l. Responses (as previously defined by Rosenfeld, 2003) were assessed at 3, 6 and 12 months, as were early death rates and overall survival. Immunologic parameters that could potentially predict responses were also assessed.A total of 22 patients with sAA treated initially with rATG (770 days median f/u) were compared to 67 control pts (1165 days median follow-up) who received hATG as initial IST. There were no significant differences in most hematologic characteristics prior to IST administration: age (55 vs 49, p=.34), platelets (14K vs. 14K, p=.35), median ANC (0.60 vs. 0.60, p=.99), median ALC (1.46 vs. 1.42, p=.81), presence of PNH clone >1% (11 versus 21, p=.45) and presence of HLA-DR15 (9 vs. 21 p=1.00), median absolute reticulocyte count (0.020 vs. 0.028, p=.09). Response was similar for pts treated with rATG compared to hATG at 3, 6 and 12 months: 41% vs. 52% (p=.15), 50% vs. 59% (p=.62) and 54% vs 59% (p=.66), respectively. The number of early deaths also did not differ between the ATG preparations, with 2 (9%) for rATG and 6(9%) for hATG (p=.98). Similarly, no difference in overall survival was observed (log rank test p=0.32). Both groups also showed similar relapse rates (14% vs 16%, p=.81) in the observation interval. We then performed a retrospective analysis of patients who received a second course of different ATG preparations (i.e. rATG after hATG and hATG after rATG). 18/67 (26%) patients initially treated with hATG had second treatment with rATG and 6/22 (27%) patients who initially received rATG were retreated hATG. There was no statistically significant difference of response at 12 months between these groups at 50% vs. 56% (p=.88). As rATG and hATG had similar baseline and response characteristics, we performed a combined analysis of all 89 patients for predictor of response at 6 months. The presence of a PNH clone and a higher reticulocyte count were the only variables found to be independent prognostic factors for response (p=.004 and .009, respectively). Similarly, multivariable models (cox proportion hazards) showed that age (p=.003), ALC (p=.02), and ANC (p=.03) were found to be independent predictors for survival. At 5 years, pts with >2 poor prognostic features (i.e. higher age, lower ANC and ALC) had a 16% survival rate compared to 67% for patients with <2 poor prognostic features (p=.001). We also analyzed cytokine gene polymorphisms, particularly TGF-β codons 10/25 and IFN-γ. Our analysis did not show any significant association between a specific genotype and response or survival. Analysis of TCR V beta repertoire by flow cytometry prior to initiation of IST revealed that patients with an expanded CD4 T cell clone were more likely to respond at 3 months to ATG (12/15, 80%) than those without (19/40, 47%, p=.037) indicating that CD4 TCR V beta skewing may be a marker of immune-mediated disease. Conclusion:Our study demonstrates that rATG shows a comparable efficacy to hATG for upfront treatment as well as salvage of sAA in a relapsed and refractory setting. Disclosures:Kalaycio: Genzyme: Speakers Bureau; Genetech: Speakers Bureau; Cephalon: Speakers Bureau. Maciejewski: Genzyme: Research Funding.

Inflammatory Dendritic Cells Contribute to Regulate the Immune Response in Sickle Cell Disease.

Sickle cell disease (SCD), one of the most common hemoglobinopathies worldwide, is characterized by a chronic inflammatory component, with systemic release of inflammatory cytokines, due to hemolysis and vaso-occlusive processes. Patients with SCD demonstrate dysfunctional T and B lymphocyte responses, and they are more susceptible to infection. Although dendritic cells (DCs) are the main component responsible for activating and polarizing lymphocytic function, and are able to produce pro-inflammatory cytokines found in the serum of patients with SCD, minimal studies have thus far been devoted to these cells. In the present study, we identified the subpopulations of circulating DCs in patients with SCD, and found that the bloodstream of the patients showed higher numbers and percentages of DCs than that of healthy individuals. Among all the main DCs subsets, inflammatory DCs (CD14+ DCs) were responsible for this rise and correlated with higher reticulocyte count. The patients had more activated monocyte-derived DCs (mo-DCs), which produced MCP-1, IL-6, and IL-8 in culture. We found that a CD14+ mo-DC subset present in culture from some of the patients was the more activated subset and was mainly responsible for cytokine production, and this subset was also responsible for IL-17 production in co-culture with T lymphocytes. Finally, we suggest an involvement of heme oxygenase in the upregulation of CD14 in mo-DCs from the patients, indicating a potential mechanism for inducing inflammatory DC differentiation from circulating monocytes in the patients, which correlated with inflammatory cytokine production, T lymphocyte response skewing, and reticulocyte count.

Doppler-defined pulmonary hypertension in β-thalassemia major in Kurdistan, Iraq.

Cardiopulmonary complications are among the most important complications of thalassemia major. Pulmonary hypertension is among these complications and studies addressing its frequency and associations in the latter disorder are sparse from Iraq. For this purpose a total 100 thalassemia major patients (≥ 8 years old) were enrolled from a main thalassemia center in Kurdistan, Northern Iraq. All patients had a full history and clinical examination. Full blood count, biochemical tests and viral screen including hepatitis B surface antigen and hepatitis C virus antibody, in addition to transthoracic Doppler echocardiography for tricuspid regurgitation jet velocity (TRV). The enrolled patients had a mean (SD) age of 17.6 (5.5) years, and included 52 males and 48 females. Pulmonary hypertension as defined by TRV> 2.8 m/s coupled with both exertional dyspnea and an absence of left sided heart failure, was identified in nine patients (9%). The latter subgroup of patients had significantly higher reticulocyte counts, S. LDH, S. ferritin, and hepatitis C sero-positivity compared to those without this complication by univariate analysis. While by multivariate logistic regression only reticulocytes and hepatitis C sero-positivity remained significant. Furthermore, TRV as a continuous variable was positively correlated with reticulocytes, S. bilirubin and LDH (p<0.001, p = 0.002 and p<0.001 respectively), but not with age or S. ferritin (p = 0.77, and p = 0.93 respectively). In conclusion, pulmonary hypertension is not uncommon in Iraqi patients with thalassemia major, and it appears to be linked to chronic hemolysis rather than iron overload.

Optimizing Hydroxyurea Therapy with Reduced Laboratory Monitoring for Children with Sickle Cell Anemia in Sub-Saharan Africa: The Reach Experience

Introduction: Realizing Effectiveness Across Continents with Hydroxyurea (REACH, NCT01966731) is an open-label study of hydroxyurea for children with sickle cell anemia (SCA) in sub-Saharan Africa (Angola, DR Congo, Kenya, and Uganda). Initial results documented the feasibility, safety, and benefits of hydroxyurea for SCA in sub-Saharan Africa but guidance for optimizing hydroxyurea therapy is needed. We describe 5 years of hydroxyurea dosing and monitoring in the largest prospective cohort of children with SCA receiving hydroxyurea to date. Methods: Children 1-10 years of age with SCA were enrolled. The hydroxyurea dose was fixed at 15-20 mg/kg/day for the first 6 months with monthly complete blood counts (CBCs) to ensure safety. From month 6-24, the dose was escalated (5 mg/kg every 8 weeks) to maximum tolerated dose (MTD), defined as mild myelosuppression with absolute neutrophil count (ANC) &amp;lt;4.0 x 109/L on 2 consecutive CBCs without hematological toxicities. CBCs were performed monthly until MTD or a stable dose was achieved, then subsequently every 3 months. Dose limiting toxicities (DLT) requiring a temporary treatment hold were defined as ANC &amp;lt;1.0 x 109/L, Hb &amp;lt;4.0 g/dL, reticulocyte count &amp;lt;80 x 109/L unless Hb &amp;gt;7.0 g/dL, or platelets &amp;lt;80 x 109/L. Known genetic modifiers of SCA, including G6PD deficiency and α-thalassemia trait, were determined for all participants. Results: A total of 606 children initiated hydroxyurea and currently 555 (92%) remain on treatment, with average treatment duration of 48 ± 12 months and a total of 2,441 patient-years of hydroxyurea treatment. Over 85% achieved MTD with an average hydroxyurea dose of 22.5 ± 5.0 mg/kg/day, ranging from 19.0 mg/kg/day in Angola to 25.4 mg/kg/day in Uganda. With dose increases over time, the most recent average dose is 23.9 ± 5.4 mg/kg/day (site range 22.9-24.6 mg/kg/day). Lab benefits have been sustained; Hb increased from 7.3 g/dL at baseline to 8.4 g/dL at MTD and remains 8.3 g/dL at Month 60. Similarly, the average HbF increased from 11% baseline to 25% at MTD and remains 23% at Month 60. The average ANC decreased from 6.8 x 109/L at baseline to 3.2 x 109/L at MTD and remains 3.5 x 109/L at Month 60. Lab toxicities are infrequent, transient, and mostly incidental. Of 19,730 CBCs obtained during the treatment phase, 421 (2.1%) in 225 participants included a DLT. The most common DLT was thrombocytopenia (33%), with only 4 platelet counts &amp;lt;20 x 109/L and no bleeding. Anemia was the second most common DLT (26%), most commonly associated with a high reticulocyte count and malarial infection, unrelated to hydroxyurea. Severe neutropenia (ANC &amp;lt;0.5 x 109/L) was rare (5 events) with no neutropenic infections. Over 2/3 of DLT events were identified incidentally during a scheduled visit when the study participant was asymptomatic, including all 5 severe neutropenic episodes. Weight-for-age and height-for-age Z-scores were not associated with higher rates of DLT during hydroxyurea treatment. Children with two-gene deletional α-thalassemia trait tolerated significantly lower hydroxyurea doses than the normal genotype (MTD dose 20.0 vs. 24.0 mg/kg/day, p &amp;lt;0.001) and had significantly different treatment responses at Month 60 including lower HbF (19.5 vs 24.3%, p &amp;lt;0.0001) and MCV (72 vs 99 fL, p&amp;lt;0.001) but higher hemoglobin (8.5 vs 8.1 g/dL, p=0.016). DLT frequency was unaffected by α-thalassemia status. Males with G6PD A- deficiency did not demonstrate significant differences in dosing, response, or toxicity. Conclusions: Hydroxyurea is safe, well-tolerated, and effective for children with SCA living in sub-Saharan Africa. Treatment responses are robust and sustained in REACH across all 4 clinical sites and unaffected by baseline Z-score. Hydroxyurea optimization requires periodic dose escalation for weight gain and titration to mild myelosuppression. Deletional α-thalassemia trait significantly influences the hydroxyurea dose and treatment responses, but the lab benefits with optimized dosing are still robust regardless of the α-globin genotype. Lab toxicities from hydroxyurea are uncommon and typically asymptomatic, suggesting that routine CBC monitoring is needed only at 3-month intervals once a stable dose is achieved, more to optimize the dose than to identify incidental toxicities. This approach to optimizing hydroxyurea therapy will allow more widespread utilization in low-resource settings with limited laboratory monitoring. Disclosures Aygun: National Heart, Lung, and Blood Institute: Research Funding; National Institute of Nursing Research: Research Funding; Patient-Centered Outsomes Research Institute: Research Funding; bluebird bio: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Comparative Analysis of Clinical Prediction Scores in Acquired Thrombotic Thrombocytopenic Purpura: The Superiority of Plasmic Score

Background: Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare and life-threatening hematologic disorder. The decision to start plasma exchange is challenging in clinical practice, due to aTTP rarity, and the extensive differential diagnosis with other thrombotic microangiopathies (TMA). Although the ADAMTS13 activity measurement is essential to aTTP diagnosis, a rapid quantification is unavailable in most centers, being necessary to develop clinical prediction models to evaluate severe enzymatic deficiency. The first model developed was Bentley score, followed by French score and more recently PLASMIC score. Studies comparing these 3 methods are scarce. The criteria of published scoring models are summarized in Table1 Aim: To compare and evaluate the discriminative power of the Bentley, French and PLASMIC scores in predicting severe ADAMTS13 deficiency (≤10%) in our group of patients (pts). Methods: We performed a retrospective analysis of pts with ADAMTS13 activity tested between 2008 and 2019, in a single center. Pts were divided in two groups: ADAMTS13 activity ≤10% (ADAMTS13≤10%) and &amp;gt;10% (ADAMTS13&amp;gt;10%) and then stratified according to the 3 scores. We evaluate sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) to predict low ADAMTS13 activity. Diagnostic accuracy was tested using the area under the ROC curve. A P-value of &amp;lt;0.05 was considered statistically significant. Results: ADAMTS13 activity was evaluated in 119 pts with suspected aTTP. There was a female predominance (60.5%; n=72) and the mean age was 54±20 years. Thirty-one pts had ADAMTS13≤10% and 27 (87.1%) of them had been diagnosed with aTTP, two were inherited thrombotic thrombocytopenic purpura and the other two were sepsis associated TMA. Comparing the groups ADAMTS13≤10% and ADAMTS13&amp;gt;10%, pts in the first were younger (46±18 vs 57±21 years; p=0.008), had lower platelet count (23.04±27.1 vs 47.79±37.6x109/L; p&amp;lt;0.001), and lower creatinine value (1.25±0.8 vs 2.92±4.2 mg/dL; p&amp;lt;0.017). ADAMTS13≤10% group had a higher reticulocyte count (5.99±5.0 vs 3.46±3.4%; p=0.005) and higher indirect bilirubin levels (2.59±2.1 vs 1.59±2.2 mg/dL; p=0.013). There were no statistical differences in hemoglobin, MCV, INR, D-Dimers and antinuclear antibodies (ANA's) positivity among the two groups. PLASMIC score was calculated in all pts. Due to missing data, Bentley score was only applied in 44.5% (n=53) and French score in 54.6% (n= 65) pts. Using a high-risk PLASMIC score as the predictor, the sensitivity was 80.6%, specificity 78.4%, PPV 56.8% and NPV 92.0%. The C-statistics for high PLASMIC score cut-offs (&amp;gt;5 points) was 0.80 (95% confidence interval [CI] 0.70-0.89) (fig.1). Applying high-risk Bentley score vs low-to-intermediate-risk score, the sensitivity was 44.4%, specificity 94.3%, PPV 80.0% and NPV 76.7%. The C-statistics was 0.69 (95% CI 0.53-0.86) using the high Bentley score cut-offs (fig.2). The French score had higher sensitivity (83.3%), but lower specificity (36.2%), with 33.3% of PPV and 85.0% of NPV. Using the high French score cut-offs, the C-statistics was 0.60 (95% CI 0.45-0.75) (fig.3). There were not statistically significant differences between PLASMIC and Bentley scores in the ability to predict low ADAMTS13 activity, and both performed better than French score (p&amp;lt;0.001; p=0.02, respectively). Conclusion: In our cohort, the PLASMIC score showed to be the most balanced and efficient clinical prediction score, with high sensitivity and specificity. Bentley score was also a good predictor of ADAMTS13 activity, but had lower sensitivity and less applicability; French score was comparatively inferior. Pts with low PLASMIC score are highly unlikely to have ADAMTS13 deficiency. PLASMIC score is easy to calculate and readily usable in most emergency settings while the French and Bentley scores require additional laboratory data, which is not always accessible. These results support the previously published data, showing PLASMIC score as a helpful complementary tool in clinical practice recognizing high-risk pts when ADAMTS13 activity measurement is not available. Disclosures No relevant conflicts of interest to declare.

Distribution of maternal red cell antibodies and the risk of severe alloimmune haemolytic disease of the foetus in a Chinese population: a cohort study on prenatal management

BackgroundHaemolytic disease of the foetus and newborn (HDFN) is the most common aetiology of haemolytic anaemia and hyperbilirubinaemia in foetuses and neonates. Studies on the distribution of antibodies that cause haemolytic disease of the foetus (HDF) in China are limited, and the effects of multiple antibodies on the severity of HDF need further evaluation.MethodsAn observational cohort study from January 2005 to December 2019 was conducted in two hospitals affiliated with Sun Yat-sen University. Maternal red cell alloimmunization was identified by the Guangzhou Blood Centre. In total, 268 pregnant woman-foetus pairs were divided into four groups according to the type of maternal alloantibodies: anti-D, anti-D combined with other antibodies, other single-antibody and other multiple antibodies. The obstetric history, antibody characteristics, incidence of severe HDF and foetal outcomes were collected and compared. Logistic regression analysis of the risk factors for HDF and survival analysis of the severe HDF-free interval were conducted.ResultsAnti-D was the most common cause of HDF, followed by anti-M. No anti-K- or isolated anti-c-associated HDF was found. The incidence of severe HDF was higher in the group with anti-D combined with other antibodies than in the group with anti-D alone (P = 0.025), but no significant difference was found in haemoglobin level and reticulocyte count in the anaemic foetuses between these two groups. Foetuses in the other single-antibody group had a lower reticulocyte count (P = 0.007), more IUTs (P = 0.007) and an earlier onset of severe HDF (P = 0.012). The maximum antibody titre was significantly lower in the other single-antibody group than in the anti-D group (P < 0.001). A high maternal antibody titre (P < 0.001), multiple affected pregnancies (P < 0.001) and other single-antibody (P = 0.042) were independent risk factors for HDF. A higher reticulocyte count (P = 0.041) was an independent risk factor for severe HDF in anaemia foetuses affected by Rh(D) alloimmunization.ConclusionsThe distribution of HDF-associated antibodies in China is different from that in Western countries. Other single non-Rh(D) antibodies could increase the risk of HDF, and anti-D combined with other antibodies would not influence the severity of foetal anaemia compared with anti-D alone.

A novel PIEZO1 mutation in a patient with dehydrated hereditary stomatocytosis: a case report and a brief review of literature

BackgroundDehydrated hereditary stomatocytosis (DHS) or hereditary xerocytosis is a rare, autosomal dominant hemolytic anemia characterized by macrocytosis, presence of stomatocytes and dehydration of red blood cells (RBCs). The dehydration is caused by a defect in cellular cation content. The most frequent expression of the pathology is hemolytic well-compensated anemia with high reticulocyte count, a tendency to macrocytosis, increased mean corpuscular hemoglobin concentration (MCHC) and mild jaundice. We here describe a new mutation of PIEZO1 gene, the most frequent mutated gene in DHS, in a family affected by hereditary hemolytic anemia.Case presentationWe describe the case of a 12-years-old girl with well-compensated chronic hemolysis, increased MCHC and a father who had the same hematological characteristics. After excluding secondary causes of chronic hemolysis and enzymatic defects of the RBCs, microscopic observation of the peripheral blood smear, tests of RBC lysis, ektacytometry, SDS-PAGE and in last instance genetic analysis has been performed. This complex diagnostic workup identified a new variant in the PIEZO1 gene, never described in literature, causative of DHS. This pathogenetic variant was also detected in the father.ConclusionsThis case report highlights the importance of a correct and exhaustive diagnostic-workup in patients with clinical suspicious for hemolytic anemia in order to make a differential diagnosis. This is relevant for the management of these patients because splenectomy is contraindicated in DHS due to high thrombotic risk.

Гематологічні характеристики та показники еритрокінетики у малих ховрахів у динаміці пробудження від зимової сплячки

During hibernation, the small mammals pass through multiple cold (torpor) and warm (arousal) phases, as well as adaptive changes in red blood cells are vital for an adequate oxygen supply to tissues. Here, we have analyzed the structural and functional indices of red blood cells in little ground squirrels during arousal from hibernation. In a torpid state, a count of red blood cells, HGB and MCH levels in blood were established as not significantly changed, but MCV and HCT decreased, while MCHC and RDW increased as compared to the control. In hibernating animals, the reticulocyte count in blood decreased and the period of erythrocyte elimination in bloodstream was shortened, but the ability to produce the red blood cells remained at the control level. During arousal, the body temperature of 25-30°C was critical for rearrangement of structural and functional parameters of red blood cells. This was evidenced by RDW increase and the tendency to rise in HCT, MCV; high reticulocyte count in blood and extended time of their maturation; increased half-life of red blood cells. When the body temperature was fully normalized, the production of red blood cells was significantly increased due to the reduced reticulocyte maturation time. Probl Cryobiol Cryomed 2020; 30(2): 132–147

Prevalence and Predictors of Elevated Pulmonary Artery Pressure in Nigerian Children with Sickle Cell Anaemia

Background: Sickle Cell Anaemia (SCA) is the most common inherited disorder in Nigeria. Pulmonary Hypertension (PH) is a known complication of SCA that commences from childhood and progresses as they grow older.&#x0D; Aim: To determine the prevalence and predictors of elevated pulmonary artery pressure (PAP) in children with SCA.&#x0D; Study Design: This is an analytical cross-sectional study.&#x0D; Methods: Three hundred subjects with SCA in steady state and 300 HbAA controls, aged 6 months – 15 years, were enrolled into the study. Children with SCA were recruited by simple random sampling, from the Paediatric Sickle Cell Clinic, Usmanu Danfodiyo University Teaching Hospital, Sokoto. All the children had clinical evaluation, echocardiography, full blood count and reticulocyte count. Pulmonary artery systolic pressure (PASP) and mean pulmonary artery pressure (MPAP) were determined by measurement of tricuspid regurgitant velocity (TRV) and mean gradient (MG) respectively. &#x0D; Results: Seventy-two children with SCA (24.0%) had elevated PAP (defined as TRV ≥ 2.5 m /s) while only 9 (3.0%) had pulmonary hypertension (defined as MPAP ≥ 25 mmHg). Older age (O.R = 1.03, p &lt; 0.001), high systolic blood pressure (O.R = 1.2, p = 0.01), and high reticulocyte count (O.R = 1.33, p = 0.04) were weakly associated with increased likelihood of elevated PAP. Normal pulse oxygen saturation (SPO2 ≥ 95%, O.R = 0.4, p = 0.002) and normal heart sounds on auscultation (O.R = 0.2, p = 0.04) were associated with a reduced likelihood of elevated PAP. Presence of left parasternal heave (O.R = 8.4, p = 0.001) significantly predicted elevated PAP in children with SCA.&#x0D; Conclusion: PH occurs as a complication in children with SCA and certain clinical and laboratory parameters do predict this complication in children.

Rebound hyperbilirubinemia in a sample of newborns with jaundice

Background and objectives: Neonatal jaundice represents a prevalent public health problem in Erbil city. Rebound jaundice after termination of phototherapy is common and related to many factors, so the aim of the study is to estimate the prevalence of rebound jaundice among neonates after termination of phototherapy and identifying any associated factors. Method:A cross sectional study was conducted in Neonatal Care Unit of Raparin Teaching Hospital in Erbil during the period from 1st of September, 2018 to 28th of February, 2019 on sample of 100 neonates with jaun- dice. The selected neonates were followed for up to 72 hours after discharge from hospital. Total serum bilirubin levels of neonates were measured at admission, on discharge and within 72 hours of phototherapy termination. Results:The rebound jaundice was present in 20% of neonates after stopping the phototherapy. Those were significantly related to certain socioeconomic and clinical data like (male gender, prematurity, low birth weight, Glucose-6-phosphate de- hydrogenase deficiency, higher total serum bilirubin at admission, lower total serum bilirubin at discharge, low hemo- globin, high reticulocyte counts and shorter phototherapy duration). Conclusions:The prevalence of rebound jaundice after termination of phototherapy was high. So follow up is mandatory within 72 hours of phototherapy termination.

Phenotypic Corrections of Ex Vivo Erythrocytes Derived from Chronic Hemolytic Anemia Patients Due to Krϋppel-like Factor 1 (KLF-1) Mutations By AG-348: A Novel Synthetic Pyruvate Kinase Activator

Introduction: Pyruvate kinase-red blood cell (PK-R) enzyme is an isoform of PK-liver (PK-L) expressed by tissue-specific promoter on the PKLR gene. The PK-R functions in the glycolytic pathway to generate pyruvate &amp; adenosine triphosphate (ATP), the energy carrier molecule supporting 120-day red blood cells (RBCs) survival. Patients with PKLR mutations have PK deficiency (PKD) &amp; defective RBCs leading to different degree of chronic hemolysis from non-transfusion to transfusion dependent. A novel synthetic AG-348 compound, an allosteric activator of PK, enhances PK-R activity in patients with PKD (Kung et al., 2017). Previously, our group described a novel form of severe hemolytic anemia due to mutations of the Krϋppel-like factor 1 (KLF1 disease) (Viprakasit et al., 2014). Besides deregulated globin gene switching with persistent embryonic globin expression, all KLF1 patients had low PK-R activity leading to hemolytic anemia &amp; transfusion dependency. Decreased KLF1 expression in trans lead to phenotypes mimic that of PKD since the PKLR genes are regulated by the KLF1. At present, there is no specific treatment for KLF1 disease besides supportive care &amp; RBCs transfusion. Objective: To determine ex vivo effects of AG-348 on PK-R activity, ATP production &amp; potential adverse effects on RBC physiology (hemolysis, inducing reactive oxygen species (ROS) and apoptosis) in RBCs from KLF1 patients. Methods: EDTA-whole blood samples were collected from two non-regularly transfused KLF-1 patients. The genotypes of the PKLR and KLF1 genes were confirmed by Sanger sequencing. RBCs were isolated by cellulose column and prepared into a suspension; 1 x 108 RBCs/mL and subsequently incubated with various concentrations of AG-348 (Agios Co. Ltd.); 0.002 - 10 μM at 37⁰C overnight. The AG-348-treated RBCs were then harvested and determined for PK-R activity by coupled enzyme assay with lactate dehydrogenase and ATP production. Furthermore, we evaluated possible adverse consequences of this compound by evaluating hemolysis, intracellular ROS and apoptosis and numeration by flow cytometry. Results: Two adolescent patients: patient A &amp; B had chronic anemia with baseline hemoglobin (Hb) ≤ 8 g/dL with high reticulocyte count (10 %) and high level of Hb F. The genotypes of KLF1 gene were identified in both subjects as compound heterozygotes of one null and one missense mutation (Table 1). Both patients had low PK-R activity but no PKLR gene mutation identified. Using an ex vivo assay, the PK-R activities of patients' RBCs significantly increased after incubation with AG-348 in a dose-dependent manner for 100% to 150% compared to baseline and 0.1% DMSO as control. Moreover, the ATP production, a direct product from RBC glycolytic pathway driven by PK catalysis also significantly increased in AG-348 incubated RBCs in a similar manner (Figure 1A and 1B). Nevertheless, there were no changes in normal RBC controls for both PK activity and ATP generation. Also, AG-348 did not adversely induce hemolysis in the KLF1-mutated RBCs as determined by Hb released (µg/mL) in the culture medium compared with 0.1% DMSO (Figure 1C). Similarly, intracellular ROS detected by mean fluorescent intensity (MFI) &amp; apoptotic signals did not increase in normal and KLF1-mutated RBCs (data not shown). Conclusion: Our ex vivo study using RBCs derived from KLF-1 patients is the first investigation to suggest a potential clinical role of the AG-348 as a therapeutic intervention in this hereditary condition. Our results were consistent with the previous study that AG-348 enhanced PK-R activity &amp; ATP production in RBCs from patients with classical PKD due to PKLR mutations (Kung et al., 2017) and currently this compound is under investigation in patients with non-transfusion dependent &amp; transfusion dependent PKD (NCT03548220 and NCT03559699, respectively). For the safety profile, the AG-348 does not induce ROS and apoptosis in our ex vivo setting. Interestingly, our data showed that AG-348 might be effective for RBCs with lower PK activity and potentially improves RBCs survival, no matter the causes of PKD. Our study warrants further investigation to determine whether this PK correction could be translated into a clinical benefit in our KLF-1 patients. Finally, our finding suggests that the activity of AG-348 might include those with higher RBCs turnover &amp; exhaust PK activity such as other hemolytic anemias especially thalassemia &amp; hemoglobinopathy. Disclosures No relevant conflicts of interest to declare.

Validation of Hemolytic Anemia Codes in the French Hospital Database

Introduction: Hemolytic anemia is a group of rare diseases. National databases are useful data sources to assess the epidemiology and the management of such diseases. The French national health database covers the entire French population (66 million inhabitants). It links sociodemographic data, out-hospital data including dispensing data and hospital data. As a consequence, this database is very useful for population-based studies on rare diseases. For instance, it has been used for epidemiological and pharmacoepidemiological studies on immune thrombocytopenia. Diseases are identified using the national hospital database (named PMSI) that contains discharge diagnoses for all hospital stays in all private and public hospitals in France. This study was aimed at assessing the positive predictive value (PPV) of hemolytic anemia diagnoses in the French hospital database. Methods: In the PMSI database, every hospital stay contains one primary diagnosis, and possibly one related and several associated diagnoses. They are coded using the International Classification of Diseases, 10th revision (ICD-10) by the physician in charge of the patient or trained nurses from the medical chart. We selected all hospital stays at Toulouse University Hospital, South of France (2860 beds) with a diagnosis of hemolytic anemia (D55.0-D59.9 ICD-10 codes) between January 2017 and December 2017. Medical charts and biological data were reviewed. Hemolytic anemia was defined by anemia with high reticulocyte count (&amp;gt;150 x 109/L), plus at least two of the three following signs of hemolysis: low serum haptoglobin level, hyperbilirubinemia and elevated serum lactate dehydrogenase level. PPVs and their 95% confidence intervals (CI) were calculated by categories of hemolytic anemia: autoimmune hemolytic anemia (AIHA; D59.1 ICD-10 code), enzyme deficiency (D55.0-D55.9 ICD-10 codes), hereditary spherocytosis (D58.0 ICD-10 code) and hemoglobinopathy (D56.0-D57.9 and D58.2 ICD-10 codes). AIHA was defined by positive direct antiglobulin test (DAT); enzyme deficiency was defined by low enzyme dosage and negative DAT; hereditary spherocytosis was defined by negative DAT and either positive flow cytometry osmotic fragility test either positive eosin-5'-maleimide binding test; hemoglobinopathy was defined by compatible blood count and positive hemoglobin electrophoresis. Results: During the study period, 54 patients had at least one hospital stay with a discharge diagnosis of AIHA, 12 with enzyme deficiency, 10 with hereditary spherocytosis, 92 with thalassemia and 285 with sickle cell disease. We further excluded 13 patients due to missing data, precluding disease classification. AIHA was confirmed in 49/53 patients; the PPV was 92.5% (95% CI: 85.3%-99.6%). Enzyme deficiency was confirmed in 8/12 patients (including G6PD deficiency: 7/9) and hereditary spherocytosis in 10/10 patients. Thalassemia was confirmed in 72/83 patients; the PPV was 86.7% (95% CI: 79.5%-94.0%); however, the code of thalassemia type was not adequately coded in most cases (PPV&amp;lt;30%). Sickle cell disease was confirmed in 279/284 patients; the PPV was 98.2% (95% CI: 96.7%-99.8%). Conclusions: Overall, this study confirms high PPV values for hemolytic anemia discharge diagnoses recorded in the French hospital database, allowing epidemiological studies using this source of data. Disclosures Moulis: CSL Behring: Research Funding; Amgen pharma: Research Funding, Speakers Bureau; Novartis pharma: Research Funding, Speakers Bureau.

Assessment of the Plasmic Score Utility for Classification of Pediatric Thrombotic Microangiopathies

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a rare form of microangiopathic hemolytic anemia characterized by congenital or acquired deficiency of the enzyme ADAMTS13. Both inherited TTP (Upshaw-Schulman Syndrome) and acquired TTP can present in childhood. As TTP is particularly uncommon in pediatric patients, there are frequent delays in diagnosis that can prolong time to life-saving treatment with therapeutic plasma exchange (TPE). The PLASMIC score is a validated clinical prediction tool used to stratify adult patients with thrombotic microangiopathies (TMAs) based upon their risk of having severe ADAMTS13 deficiency. The purpose of this study is to characterize a cohort of pediatric patients presenting with TMAs and to determine whether the PLASMIC score can accurately identify those children at risk for severe ADAMTS13 deficiency. Methods: We created a registry of all consecutive pediatric cases of suspected TTP at 3 academic medical centers in Boston, MA from January 2004 through November 2018. Suspected cases were defined as any patient with TMA who received ADAMTS13 activity testing during this period. Patients were included in the cohort if they were ≤18 years-old, thrombocytopenic (platelet count less than lower limit of normal for age), and had schistocytes on peripheral blood smear. Exclusion criteria included individuals tested as outpatients and potential interferents with ADAMTS13 testing (hemolyzed specimen, total bilirubin &gt;15 mg/dL, sample sent less than 24 hours after exposure to plasma). For each patient, the ADAMTS13 test result as well as additional laboratory, demographic, and clinical parameters were recorded. The PLASMIC score was calculated for each patient. Results: Of the 125 unique pediatric patients who underwent ADAMTS13 testing during the study period, 59 presented with a thrombotic microangiopathy and met the inclusion criteria. Nine of the 59 patients (15.3%) had severe ADAMTS13 deficiency with ADAMTS13 activity of ≤10%. Eight of these 9 patients had detectable autoantibody inhibitor titers, consistent with acquired/immune TTP. One patient with severe ADAMTS13 deficiency had a history of renal transplant and was the only patient with ADAMTS13 levels ≤10% who had no detectable inhibitor. Compared to patients with ADAMTS13 levels &gt;10%, patients with severe ADAMTS13 deficiency were older, predominantly female, and more frequently presented with neurological symptoms (see table). At the time of ADAMTS13 testing, patients with severe ADAMTS13 deficiency also had a lower platelet count, a higher LDH, a higher reticulocyte count, and higher levels of total and indirect bilirubin. There were non-significant trends toward improved one-year and overall survival in patients with ADAMTS13 levels ≤10%. Forty-eight patients in the cohort had all necessary data for calculation of the PLASMIC score. As the youngest patient with severe ADAMTS13 deficiency in this cohort was 3 years-old, we restricted our analysis to patients 2 years and older (N=41). All pediatric patients with ADAMTS13% ≤10% in our cohort had a PLASMIC score of 6 or 7. Nine out of 16 patients with a PLASMIC score of &gt;5 had severe ADAMTS13 deficiency. The C statistic for the resultant ROC curve was 0.92 (95% CI 0.796 to 0.983). Conclusion: The small number of pediatric patients with TTP identified over the 14-year period of our study cohort emphasizes the rarity of this disease in children and the potential utility for a clinical prediction tool to aid in diagnosis and to help determine on whom ADAMTS13 testing should be performed. The PLASMIC score can accurately identify pediatric patients at high risk for severe ADAMTS13 deficiency, facilitating rapid diagnosis and initiation of appropriate therapy. Figure Disclosures No relevant conflicts of interest to declare.

Identification of Clinical and Laboratory Parameters Associated with the Development of Acute Chest Syndrome during Vaso-Occlusive Episodes in Children with Sickle Cell Disease: A Preliminary Step before Assessing Specific and Early Treatment Strategies.

This prospective observational study sought to ascertain clinical and laboratory parameters associated with the development of acute chest syndrome (ACS) during vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD). It was performed at the pediatric department of the university Intercommunal Créteil hospital. All children with SCD (all sickle genotypes) consecutively admitted from November 2013 to December 2016 for painful VOEs and no evidence of ACS were included. Clinical and laboratory parameters collected at admission and within 48 h after admission were compared for children in whom ACS developed or not. Variables that were statistically significant on univariate analysis or considered to be clinically relevant were included in a multivariable model to ascertain the risk factors associated with the development of ACS during a VOE. The variables retained in the multivariate model were used to construct a predictive score for ACS. For each included child and during the study period, only data from the first VOE and/or the first ACS were analyzed. Among 191 hospitalizations for painful VOEs, for 176 children with SCD, ACS developed in 35 during hospitalization. Mean hospital stay was longer for children with ACS versus VOEs alone (7.6 (±2.3) vs. 3.3 (±1.8) days, p < 0.0001), and all children with ACS versus 28/156 (17.9%) with VOEs alone received red blood cell transfusion (p < 0.0001). The multivariate model retained pain score (≥9/10), pain localization (abdominal or spinal pain or involving more than two limbs), and high reticulocyte (≥260 × 109/L) and neutrophil (>10 × 109/L) counts, at admission, as independently associated with ACS development. The area under the receiver operating characteristic curve for the ACS predictive score was 0.82 (95% CI: 0.74–0.89), and the negative predictive value was 97.7%. The evolution profiles during the first 48 h differed between children with ACS and VOEs alone, with a more rapid decline of pain score and leucocytosis in children with VOEs. Clinical and laboratory measurements at admission may be simple parameters to identify children with increased risk of ACS development during VOEs and to facilitate early diagnosis of this respiratory complication. Also, the persistent elevation of leukocyte count on day 2 may be considered a sign of evolving ACS.

Echocardiographic Screening of Cardiovascular Status in Pediatric Sickle Cell Disease.

Although elevated right ventricular pressure and left ventricular diastolic dysfunction measured by echocardiogram are independent predictors of death in adults with sickle cell disease (SCD), the utility of routine echocardiographic screening in the pediatric population is controversial. We performed a 3-year retrospective review of children ≥ 10years of age with SCD who underwent an outpatient transthoracic echocardiogram as part of a screening program. Of 172 patients referred for screening, 105 (61%) had a measurable tricuspid regurgitation jet velocity (TRV): median 2.4m/s (IQR 2.3-2.5). Elevated right ventricular (RV) pressure (TRV ≥ 2.5m/s, 25mmHg), documented in 30% (32/105), was significantly associated with chronic transfusion therapy and elevated lactate dehydrogenase. Left ventricle (LV) dilation, documented in 25% (44/172), was significantly associated with lower hemoglobin, and higher reticulocyte count, lactate dehydrogenase level, and bilirubin level. There was no association between elevated right ventricular pressure or left ventricle dilation and indices of biventricular systolic or diastolic function. The one death in the cohort during the study period had normal echocardiographic findings. In conclusion, mild RV pressure elevation and LV dilation in children with SCD is associated with abnormal laboratory markers of disease severity, but not with ventricular dysfunction over the 3-year study period.

The Complexity of Genotype-Phenotype Correlations in Hereditary Spherocytosis: A Cohort of 95 Patients: Genotype-Phenotype Correlation in Hereditary Spherocytosis.

Hereditary spherocytosis (HS) is a phenotypically and genetically heterogeneous disease. With the increased use of Next Generation Sequencing (NGS) techniques in the diagnosis of red blood cell disorders, the list of unique pathogenic mutations underlying HS is growing rapidly. In this study, we aimed to explore genotype-phenotype correlation in 95 HS patients genotyped by targeted NGS as part of routine diagnostics (UMC Utrecht, Utrecht, The Netherlands). In 85/95 (89%) of patients a pathogenic mutation was identified, including 56 novel mutations. SPTA1 mutations were most frequently encountered (36%, 31/85 patients), primarily in patients with autosomal recessive forms of HS. Three SPTA1 (α-spectrin) mutations showed autosomal dominant inheritance. ANK1 (ankyrin1) mutations accounted for 27% (23/85 patients) and SPTB (β-spectrin) mutations for 20% (17/85 patients). Moderate or severe HS was more frequent in patients with SPTB or ANK1 mutations, reflected by lower hemoglobin concentrations and higher reticulocyte counts. Interestingly, mutations affecting spectrin association domains of ANK1, SPTA1 and SPTB resulted in more severe phenotypes. Additionally, we observed a clear association between phenotype and aspects of red cell deformability as determined by the Laser assisted Optical Rotational Cell Analyzer (LoRRca MaxSis). Both maximal deformability and area under the curve were negatively associated with disease severity (respectively r = -0.46, p < 0.01, and r = -0.39, p = 0.01). Genotype-phenotype prediction in HS facilitates insight in consequences of pathogenic mutations for the assembly and dynamic interactions of the red cell cytoskeleton. In addition, we show that measurements of red blood cell deformability are clearly correlated with HS severity.

Association between human T cell leukemia virus 1 (HTLV-1) infection and advanced periodontitis in relation to hematopoietic activity among elderly participants: a cross-sectional study

BackgroundWe reported that human T cell leukemia virus 1 (HTLV-1) infection is positively associated with atherosclerosis. Recent evidence has revealed a close association of periodontitis with atherosclerosis, endothelial dysfunction, and disruption of the microcirculation. However, the association between HTLV-1 and advanced periodontitis has not been investigated to date. Since hematopoietic activity is closely linked to endothelial maintenance activity and is known to decline with age, we hypothesized that the state of hematopoietic activity influenced the association between HTLV-1 and advanced periodontitis in elderly participants.MethodsA cross-sectional study was performed including 822 elderly participants aged 60–99 years who participated in a dental health check-up. Advanced periodontitis was defined as a periodontal pocket ≥ 6.0 mm. Participants were classified as having low or high hematopoietic activity according to the median values of reticulocytes.ResultsHTLV-1 infection was positively related to advanced periodontitis among participants with lower hematopoietic activity (lower reticulocyte count), but not among participants with higher hematopoietic activity (higher reticulocyte count). The adjusted odds ratio (95% confidence interval) considering potential confounding factors was 1.92 (1.05–3.49) for participants with a lower reticulocyte count and 0.69 (0.35–1.36) for participants with a higher reticulocyte count.ConclusionsAmong elderly participants, the association between HTLV-1 infection and advanced periodontitis is influenced by hematopoietic activity. Since hematopoietic activity is associated with endothelial maintenance, these findings provide an efficient tool for clarifying the underlying mechanism of the progression of periodontitis among elderly participants.