The meaning of non-criteria clinical manifestations in a real-life primary antiphospholipid syndrome cohort.

OBJECTIVES: We aimed to evaluate the prevalence of non-criteria clinical features in patients with primary antiphospholipid syndrome (APS), and to assess their relationship to thrombosis and damage. METHODS: We retrospectively included 177 primary APS patients, and/or patients who only achieved the serological Sydney criteria but had thrombocytopenia and/or haemolytic anaemia. We registered demographics, serology, treatment, thrombotic/obstetric manifestations and non-criteria clinical manifestations (cutaneous, haematologic, renal, heart valve disease, and neurological). We scored the DIAPS and a modified SLICC index. We used logistic regression and reported OR with 95% CI. RESULTS: 78% were women with a median follow-up of 6.7 years. Thrombosis was found in 74% of patients, 29.3% had obstetric features, and 64% had non-criteria clinical manifestations. The frequency of the non-criteria clinical manifestation was: haematologic 40.1%, cutaneous 20.9%, neurologic 18%, cardiac 5% and renal 4.5%. Non-criteria features were associated with LA (OR 2.3, 95% 1.03-5.1) and prednisone use (OR 8.2, 95% CI 1.7-39.3). A DIAPS score ≥1 was associated with thrombosis (OR 53.1, 95% CI 17.8-15.2), prednisone use (OR 0.27, CI 95% 0.09-0.83) and neurological involvement (OR 6.4, 95% CI 1.05-39.8); whereas a modified SLICC ≥ 1 with thrombosis (OR 10.2; IC 95% 4.43-26.1), neurological involvement (OR 6.4, 95%CI 1.05-39.8), obstetric features (OR 0.32 CI 95% 0.12-0,81) and cutaneous features (OR 5.3, CI 95% 1.4-19), especially livedo reticularis (OR 5.45; IC 95% 1.49-19.8). CONCLUSIONS: Non-criteria clinical manifestations are common and associated with LA. Among them, neurologic involvement and the presence of livedo were associated with damage accrual.

Association of Hydroxychloroquine use and Hemolytic Anemia in Patients With Low Levels of Glucose-6-Phosphate Dehydrogenase.

BACKGROUND: Glucose-6-phosphate dehydrogenase deficiency (G6PD) is linked to hemolytic anemia with certain medications and is the most common enzyme deficiency worldwide. Although the American College of Rheumatology does not recommend routine testing for G6PD prior to initiation of hydroxychloroquine (HCQ), the package insert for HCQ does recommend careful use in patients with G6PD deficiency. METHODS: We identified eligible subjects seen at our tertiary care, urban medical center between 1997 and 2018. Case records were analyzed for G6PD deficiency, HCQ use, length of exposure to HCQ, demographic characteristics, and laboratory evidence of hemolysis. RESULTS: We found 5264 patients who were prescribed HCQ, of which 49.5% (2605 patients) were screened for G6PD deficiency. Of the screened patients, 36 were found to be G6PD-deficient. Of the G6PD-deficient patients, 18 were exposed to HCQ. No evidence of hemolysis was found in these exposed patients. CONCLUSIONS: Despite more than 500 months of cumulative exposure time to HCQ, there were no cases of hemolysis. These findings are in line with recently published data and suggest that this interaction is not associated with clinically significant hemolysis in our population of mainly African American and Hispanic patients. Limitations to our study are potential bias due to case review design and lack of prior assessment of episodes of hemolysis before HCQ exposure. A high proportion of our patients were Hispanic, suggesting no increase of adverse events in this subgroup. A larger longitudinal trial would be needed to definitively answer the question of the safety of HCQ in G6PD-deficient patients.

Characteristics and outcome of breast cancer-related microangiopathic haemolytic anaemia: a multicentre study.

BACKGROUND: Cancer-related microangiopathic haemolytic anaemia (MAHA) is a rare but life-threatening paraneoplastic syndrome. Only single cases or small series have been reported to date. We set up a retrospective multicentre study focusing on breast cancer-related MAHA. METHODS: Main inclusion criteria were known diagnosis of breast cancer, presence of schistocytes and either low haptoglobin or cytopenia and absence of any causes of MAHA other than breast cancer, including gemcitabine- or bevacizumab-based treatment. Patient characteristics, treatments and outcome were retrieved from digital medical records. RESULTS: Individual data from 54 patients with breast cancer-related MAHA were obtained from 7 centres. Twenty-three (44%) patients had a breast tumour with lobular features, and most primary tumours were low grade (grade I/II, N = 39, 75%). ER+/HER2-, HER2+ and triple-negative phenotypes accounted for N = 33 (69%), N = 7 (15%) and N = 8 (17%) cases, respectively. All patients had stage IV cancer at the time of MAHA diagnosis. Median overall survival (OS) was 28 days (range 0-1035; Q1:10, Q3:186). Independent prognostic factors for early death (≤ 28 days) were PS > 2 (OR = 7.0 [1.6; 31.8]), elevated bilirubin (OR = 6.9 [1.1; 42.6]), haemoglobin < 8.0 g/dL (OR = 3.7 [0.9; 16.7]) and prothrombin time < 50% (OR = 9.1 [1.2; 50.0]). A score to predict early death displayed a sensitivity of 86% (95% CI [0.67; 0.96]), a specificity of 73% (95% CI [0.52; 0.88]) and an area under the curve of 0.90 (95% CI [0.83; 0.97]). CONCLUSIONS: Breast cancer-related MAHA appears to be a new feature of invasive lobular breast carcinoma. Prognostic factors and scores may guide clinical decision-making in this serious but not always fatal condition.

Rates of delayed hemolytic transfusion reactions observed in a trauma center.

BACKGROUND: Delayed hemolytic transfusion reactions (DHTRs) are reported to be rare occurrences but may be more frequently observed in the trauma setting where patients are heavily transfused, followed over long inpatient admissions, and have frequent subsequent blood counts as they undergo multiple surgical interventions. STUDY DESIGN AND METHODS: We examined the rates of DHTRs on a per transfusion and per patient basis in an academic county hospital with a level 1 trauma center serving a four-state region and over a 3-year period. DHTRs were entered sequentially into a registry as they were observed, and a retrospective review of all new alloantibodies detected was performed to identify any additional DHTRs. The number of units of red blood cells (RBCs), the number of unique patients, types of alloantibodies, and number of transfusions were extracted from blood bank records. RESULTS: Twenty-nine DHTRs were observed from January 1, 2017, through December 31, 2019, from newly observed alloantibodies after a median of 12 red blood cells (RBCs) transfusions per patient. These reactions occurred in response to 24,633 unique transfusions in 6905 unique patients, so the observed rates were about 1:849 RBC transfusions and 1:238 transfused patients. Evidence of delayed hemolysis was seen in five additional patients who were transfused during emergency resuscitation and later found to have had known RBC antibodies. DISCUSSION: We report a higher rate of DHTRs than previously described to demonstrate that DHTRs are not rare in trauma centers.

Factors associated with neuropsychiatric involvement in Latin American patients with systemic lupus erythematosus.

INTRODUCTION: Factors related to presentation of neuropsychiatric (NP) SLE manifestations, early in the course of the disease, and during follow up have not been clearly established. PURPOSE: To identify disease and non-disease related factors associated with NP manifestations in early SLE. METHODS: We included 1193 patients from the GLADEL inception cohort free of NP involvement at cohort entry. We evaluated the association of demographic, clinical and laboratory data with NP involvement during follow-up. STATISTICAL METHODS: Independent factors associated with NP involvement were identified using a multivariable Cox regression model. RESULTS: Factors independently associated with NP manifestations were: mestizo ethnicity (HR 1.701, 95% CI 1.282-2.258, p = 0.0002), myalgias/myositis (HR 1.832, 95% CI 1.335-2.515, p = 0.0002), pneumonitis (HR 2.476, 95% CI 1.085-5.648, p = 0.0312), shrinking lung (HR 2.428, 95% CI 1.074-5.493, p = 0.0331) and hemolytic anemia (HR 1.629, 95% CI 1.130-2.347, p = 0.0089). Longer disease duration at cohort entry (13 to 24 months) was associated with a lower risk of developing NP manifestations (HR 0.642, 95% CI 0.441-0.934, p = 0.0206). CONCLUSIONS: Patients with myalgias/myositis, pneumonitis, shrinking lung and hemolytic anemia are at higher risk of NP involvement, whereas longer disease duration at cohort entry is associated with a lower risk of developing NP involvement.

A comparative study between the disease characteristics in adult-onset and childhood-onset systemic lupus erythematosus in Egyptian patients attending a large university hospital.

INTRODUCTION: Disease features and laboratory abnormalities differ among adult-onset and childhood-onset systemic lupus erythematosus (aSLE and cSLE). Socioeconomic status both independent of, and in combination with, ethnicity influences the disease phenotype and outcome. OBJECTIVE: To compare the various disease features among patients with cSLE and aSLE in a limited monetary income Egyptian cohort attending a large free-of-charge university hospital. Patients and methods: Retrospective analysis of the medical records of 714 SLE patients attending Cairo University Hospitals from January 2000 to December 2019. Of them 602 (400 with aSLE and 202 with cSLE) were enrolled in the study. RESULTS: The mean age of disease onset was 28.27 ± 10.55 among aSLE patients compared to 12.88 ± 4.26 years among cSLE patients. Disease duration was 12.03 ± 5.05 and 4.14 ± 3.18 years in aSLE and cSLE, respectively. Female to male ratio was 15:1 among patients with aSLE, as compared to 2.67:1 among cSLE (<0.001). Arthritis (69%), oral ulcers (48.5%), neuropsychiatric (18.3%) and thrombotic manifestations of antiphospholipid syndrome (12%) were significantly more frequent in aSLE. On the other hand, renal (67.8%), serositis (49.6%), fever (49%), lymphopenia (40.6%), hemolytic anemia (38.6%), and discoid lupus (13.4%) were significantly more frequent in cSLE. Weight loss, malar rash, photosensitivity, thrombocytopenia, leucopenia and lymphadenopathy were not significantly different between the two groups. Hypocomplementemia, proteinuria, urinary sediments, hematuria were significantly more frequent in cSLE. For those patients with renal involvement, who underwent renal biopsy (58.3% in aSLE and 63.5% in cSLE), there was no significant difference with regard to the different histopathological classes. Anti-Smith, anti-cardiolipin antibodies and rheumatoid factor were significantly more frequent among aSLE patients, while anti-La antibodies were more frequent among cSLE patients. CONCLUSION: Arthritis was the most common clinical manifestation over time in aSLE compared to renal involvement in cSLE. Renal disease tends to be more active in cSLE. The differences in disease manifestations between this cohort and other studies can be attributed to the ethnic and socioeconomic disparities.

Anti-A/B isoagglutinin reduction in an intravenous immunoglobulin product and risk of hemolytic anemia: a hospital-based cohort study.

BACKGROUND: Intravenous immunoglobulins (IVIG) are derived from large human plasma pools. IVIG-associated hemolytic anemia (HA) is a known class effect, likely attributed to dose-dependent passive transfer of anti-A/B isoagglutinins. Two isoagglutinin reduction steps were implemented in the manufacturing process of Privigen (human 10% liquid IVIG): exclusion of high-anti-A-titer donors in 2013, replaced by specific immunoaffinity chromatography in 2015. We aim to estimate the clinical effectiveness of both measures. STUDY DESIGN AND METHODS: Using the US hospital-based Premier Healthcare Database, three Privigen cohorts were generated based on calendar periods indicative of manufacturing changes: Period 1 (baseline) January 2008 to December 2012, Period 2 (high-anti-A-titer donor exclusion) October 2013 to December 2015, and Period 3 (immunoaffinity chromatography) October 2016 to April 2019. HA within a 10-day at-risk period after Privigen administrations was identified from review of patient record summaries. Incidence rate ratios (IRRs) were estimated from Poisson regression (Period 1 reference) adjusting for hospital setting, sex, age, Privigen indication, dose, and first use. RESULTS: Crude incidence rates of HA were 1.49 per 10,000 person-days in Period 1 (38 HA, 9439 patients), 1.01 in Period 2 (20 HA, 7710 patients), and 0.14 in Period 3 (3 HA, 7759 patients). Adjusted IRR for HA in Period 2 was 0.71 (95% confidence interval [CI], 0.41-1.23), and in Period 3 was 0.10 (0.03-0.33) compared with Period 1. The IRR for HA in Period 3 compared with Period 2 was 0.14 (95% CI, 0.04-0.47). CONCLUSION: Implementation of immunoaffinity chromatography in Privigen manufacturing resulted in a significant 90% reduction of HA risk. HA has become a rare event in association with Privigen use.

Pattern of Hemolytic Anemia Among Egyptian Pediatric Emergency Department Patients.

OBJECTIVES: The emergency department is considered the backbone of the medical service offered in any hospital. Yet, the data on the frequency of pediatric hematological presentation is scanty. Anemia occurs in 9% to 14% of pediatric emergency department (ED) patients. Glucose-6-phosphate dehydrogenase (G6PD) deficiency affects more than 400 million people worldwide. Unfortunately, we do not have screening program for G6PD deficiency in Egypt. The aim of this study is to assess the burden of hemolytic crisis among Egyptian children visiting ED. METHODS: This is a prospective cross-sectional study among children presenting with acute hemolytic crisis in the ED of New Children Hospital, Cairo University from March to June 2016. Cases underwent full history taking, clinical examination, and laboratory tests based on clinical judgment of the resident. We categorized the presenting hemolytic anemias into 3 groups: G6PD deficiency, acute hemolysis in previously diagnosed patients with chronic hemolytic anemia, and acute undiagnosed hemolytic anemia. RESULTS: Our study included 143 patients, 109 males (76.22%) and 34 females (23.76%), with a mean age 36 months (range, 3-188 months), who presented with hemolytic anemia in the ED. Seventy-six cases (53.1%) were diagnosed as G6PD deficiency, 36 (25.2%) were diagnosed as chronic hemolytic anemia, and 31 (21.7%) were diagnosed as undiagnosed acute hemolytic anemia. CONCLUSIONS: Hemolytic anemia is very common presentation in ED. G6PD deficiency is the most common cause, representing 53.1% of the hemolytic anemia.

Molecular detection of Mycoplasma ovis in an outbreak of hemolytic anemia in sheep from Veracruz, Mexico.

Mycoplasma ovis is a small, pleiotropic bacterium, which parasitizes the external surface of erythrocytes of several species of artiodactyl mammals, especially sheep and goats. We here report an outbreak of ovine mycoplasmosis in a sheep flock of a private ranch (Universidad Veracruzana) in Veracruz, Mexico. For the identification of Mycoplasma and other hemoparasitic bacterial agents, we stained blood smears with the DiffQuick® technique and additionally amplified several fragments of 16S rDNA gene. We detected the presence of morulas in erythrocytes from 30 sick female adult sheep, and found Mycoplasma ovis DNA in all of them. Furthermore, three of these animals also tested positive for Anaplasma ovis. Our findings represent the first record of M. ovis and A. ovis in an outbreak of hemolytic anemia in a sheep flock, leading to severe livestock loss in a ranch of Mexico. This study highlights the importance of establishing an active surveillance of both pathogens in the country.

[Severe and complicated malaria]. / Accès palustre grave.

Severe and complicated malaria. About 15% of the 4500 to 5000 cases of malaria occurring each year in France will prove to be severe malaria. Severe forms of malaria mainly involve P. falciparum. Cerebral malaria is the complication, peculiar to P. falciparum, most often fatal, but other forms of damage can occur -multi-organ failure- making severe malaria a parasitic systemic disease with a high rate of mortality. Mortality is strongly correlated with neurological involvement, circulatory shock, respiratory distress, metabolic acidosis, and hyperlactataemia at the time of diagnosis. In addition to the parasitological diagnosis, the biological assessment aims to highlight the existence of biological criteria of gravity. The treatment of severe malaria will be started urgently as soon as the diagnosis is known. The specific treatment of severe malaria is based now on intravenous artesunate for the child, the adult and the pregnant woman. Multi organ failure should be treated in intensive care unit. Mortality in France is less than 5%. Sequelae are possible. In about 15% of patients, an episode of delayed haemolytic anemia may occur after treatment with artesunate -10 days to 3 weeks after the end of treatment-; it must be detected by weekly research on the occurrence of haemolytic anemia in parallel with parasitological monitoring.

Accès palustre grave. Environ 15 % des 4 500 à 5 000 cas de paludisme survenant chaque année en France vont s'avérer être des accès palustres graves. Les formes graves de paludisme impliquent majoritairement P. falciparum. Le neuropaludisme est la complication propre à P. falciparum, le plus souvent mortelle, de l'accès palustre grave, mais d'autres atteintes existent -atteinte multiorganique-, faisant du paludisme grave une atteinte parasitaire systémique à haut risque de mortalité. La mortalité est étroitement corrélée à la présence d'une atteinte neurologique, d'un état de choc, d'une détresse respiratoire, d'une acidose métabolique et d'une hyperlactatémie, au moment du diagnostic de l'infection. Outre le diagnostic parasitologique, le bilan biologique complémentaire vise à mettre en évidence l'existence de critères biologiques de gravité. Le traitement de l'accès grave est débuté en urgence dès le diagnostic connu. Le traitement spécifique de l'accès grave repose maintenant sur l'artésunate intraveineux chez l'enfant, l'adulte, la femme enceinte. Les défaillances d'organes relèvent d'une prise en charge en service de réanimation. La mortalité en France est inférieure à 5 %. De séquelles sont possibles. Chez environ 15 % des patients, un épisode d'anémie hémolytique retardé -10 jours à 3 semaines après la fin du traitement- peut survenir après un traitement par artésunate ; elle doit être dépistée par la recherche hebdomadaire de la survenue d'une anémie hémolytique en parallèle du suivi parasitologique.

Autoimmune Cytopenias and Associated Conditions in CVID: a Report From the USIDNET Registry.

PURPOSE: Autoimmune cytopenia is frequently a presenting manifestation of common variable immune deficiency (CVID). Studies characterizing the CVID phenotype associated with autoimmune cytopenias have mostly been limited to large referral centers. Here, we report prevalence of autoimmune cytopenias in CVID from the USIDNET Registry and compare the demographics and clinical features of patients with and without this complication. METHODS: Investigators obtained demographic, laboratory, and clinical data on CVID patients within the USIDNET Registry. Patients were considered to have autoimmune cytopenia if they had a diagnosis of hemolytic anemia, immune thrombocytopenia (ITP), or autoimmune neutropenia. Baseline characteristics and associated complications of those with autoimmune cytopenia (+AC) and those without (-AC) were compared. RESULTS: Of 990 CVID patients included in the analysis, 10.2% (N = 101) had a diagnosis consistent with autoimmune cytopenia: ITP was diagnosed in 7.4% (N = 73), hemolytic anemia in 4.5% (N = 45), and autoimmune neutropenia in 1% (N = 10). Age at diagnosis, gender, and baseline Ig values did not differ between the +AC and -AC groups. The +AC group was significantly more likely to have one or more other CVID-associated non-infectious complications (OR = 2.9; 95%-CI: 1.9-4.6, P < 0.001), including lymphoproliferation, granulomatous disease, lymphomas, hepatic disease, interstitial lung diseases, enteropathy, and organ-specific autoimmunity. CONCLUSIONS: Autoimmune cytopenias are a common manifestation in CVID and are likely to be associated with other non-infectious CVID-related conditions. In light of prior studies showing increased morbidity and mortality in CVID patients with such complications, a diagnosis of autoimmune cytopenia may have prognostic significance in CVID.

Active haematological manifestations of systemic lupus erythematosus lupus are associated with a high rate of in-hospital mortality.

The aim of this study was to estimate the impact of the haematological manifestations of systemic lupus erythematosus (SLE) on mortality in hospitalized patients. For that purpose a case-control study of hospitalized patients in a medical referral centre from January 2009 to December 2014 was performed. For analysis, patients hospitalized for any haematological activity of SLE ( n = 103) were compared with patients hospitalized for other manifestations of SLE activity or complications of treatment ( n = 206). Taking as a variable outcome hospital death, an analysis of potential associated factors was performed. The most common haematological manifestation was thrombocytopenia (63.1%), followed by haemolytic anaemia (30%) and neutropenia (25.2%). In the group of haematological manifestations, 17 (16.5%) deaths were observed compared to 10 (4.8%) deaths in the control group ( P < 0.001). The causes of death were similar in both groups. In the analysis of the variables, it was found that only haematological manifestations were associated with intra-hospital death (odds ratio 3.87, 95% confidence interval 1.8-88, P < 0.001). Our study suggests that apparently any manifestation of haematological activity of SLE is associated with poor prognosis and contributes to increased hospital mortality.

Cancer risk in East Asian patients associated with acquired haemolytic anaemia: a nationwide population-based cohort study.

BACKGROUND: This study investigated whether patients with acquired haemolytic anaemia (AHA) would have elevated cancer risk including that for non-haematological solid tumours. We further examined whether the cancer risk would be different between patients with autoimmune type AHA (AIHA) and patients of non-AIHA. METHODS: Using nationwide population-based insurance claims data of Taiwan we identified a cohort of patients with AHA with no pre-existing cancer, (n = 3902) and a comparison cohort (n = 39020) without AHA, frequency-matched by gender, age, urbanization of residency and diagnosis date. Incidence and Cox method estimated adjusted hazard ratios (aHR) of cancers controlling covariates by the end of 2010 were calculated. Risks between patients with AIHA and non-AIHA were compared. Sensitivity analysis was carried out to measure the risk of cancer between patients with and without AHA by follow-up years. RESULTS: Patients with AHA had a 90% greater incidence of cancer than controls, with an aHR of 1.78 (95% confidence interval (CI), 1.50-2.12)]. The overall aHRs of cancer for patients with AIHA and non-AIHA were 2.01 (95% CI, 1.56-2.59) and 1.87 (95% CI, 1.53-2.29), respectively, compared with the comparison cohort. The aHRs for lymphatic-haematopoietic malignancy were 19.5 and 9.59 in the AIHA and non-AIHA cohorts, respectively. No hazard of colorectal, lung, liver or breast cancer was significant. CONCLUSIONS: There is a near 2-fold elevated risk for subsequent cancer in patients with AHA, particularly for lymphatic-haematopoietic malignancy, which is much greater for patients with AIHA than non-AIHA. These findings can help clinicians decide patient-centred personalized long-term management.

Adverse event monitoring of the human papillomavirus vaccines in Scotland.

BACKGROUND: Human papillomavirus (HPV) vaccines are currently utilised globally in national immunisation programmes. While evidence from clinical trials and epidemiological studies suggest that the HPV vaccines are both effective and safe, concerns about the safety of the vaccine and scientifically unproven associations with severe adverse events following immunisation have led to dramatic decreases in vaccine uptake in Japan and acceptance issues in other countries. AIM: In Scotland, we utilised hospital admissions data to assess the impact of the HPV immunisation programme on the incidence of 60 diagnoses between 2004 and 2014 in both girls and boys; with boys acting as a comparator group. METHODS: Tabular and graphical outputs of the number of admissions, the incidence and the incidence ratio of 59 diagnoses were created to assess trends before and after the introduction of the HPV vaccine. Data linkage was utilised to investigate further the increase in Bell palsy diagnoses. RESULTS: Fifty-four diagnoses showed no change in incidence following the introduction of the national immunisation programme, and while small increases in incidence were observed for Bell palsy, coeliac disease, ovarian dysfunction, juvenile onset of type 1 diabetes, demyelinating disease and juvenile rheumatoid arthritis, none was statistically significant. CONCLUSIONS: Consistent with previous evidence, we present disaggregate data that reiterate the safety of both HPV vaccines.

Incidence and patterns of hemolytic anemia in acute dapsone overdose.

BACKGROUND: Hemolytic anemia is one of the complications related to the chronic consumption of dapsone. However, in acute dapsone overdose, there have been few case reports regarding hemolytic anemia. Herein, we reported the prevalence and patterns of hemolytic anemia in acute dapsone overdose, and compared clinical features including mortality in the non-hemolytic anemia and the hemolytic anemia groups. METHODS: We conducted a retrospective review of 43 consecutive acute dapsone overdose cases that were diagnosed and treated at the emergency department of the Wonju Severance Christian Hospital between January 2006 and January 2014. RESULTS: There were 13 male patients (30.2%) and the ages of all patients ranged from 18 to 93 years with a median of 67 years. The ingested dose varied from a minimum of two 100-mg tablet to a maximum of twenty five 100-mg tablets. All patients had methemoglobinemia irrespective of the presence of hemolytic anemia. Among 43 patients, 30 patients (69.8%) were shown to have hemolytic anemia and hemolytic anemia developed the day after admission and persisted for more than 6 days after admission. Even though mortality rate was not significantly higher in the hemolytic anemia group, the hemolytic anemia group had significantly longer total admission and intensive care unit admission stays than the non-hemolytic group. CONCLUSIONS: A significant proportion of the patients with acute dapsone overdose is associated with occurrence of hemolytic anemia. Hemolytic anemia may be developed the day after admission and persisted for more than 6 days after admission. Therefore, monitoring of serum hemoglobin level is necessary.

Frequency of neutropenia among Turkish and Syrian pediatric thalassemia patients under deferiprone monotherapy.

Weekly monitoring of absolute neutrophil count (ANC) under deferiprone therapy in thalassemia patients is recommended to avoid agranulocytosis adverse event. Actually, this recommendation may not be applicable in clinical setting. Our study aimed to establish incidence of neutropenia under deferiprone (DFP) monotherapy when it was monitored bimonthly due to socioeconomic conditions effecting local and refugee thalassemic patients including Syrian origin (SYR; n = 26) and Turkish origin (TR; n = 26) groups. Patients on DFP were followed up for 12 months. Fifteen neutropenic episodes were seen in 5 patients. All 5 patients (4 from SYR group and 1 from TR group) had splenomegaly and hypersplenism, and neutropenia ceased in 4 patients after splenectomy despite continuation of deferiprone. In the TR group, the frequency of patients who have neutropenia (absolute neutrophil count [ANC] <1500/mm(3)) was 3.8% (n = 1) in the 1st month, no patients in TR group had neutropenia until 10th month when again there was 1 patient with mild neutropenia. In SYR group, the frequency of patients who have neutropenia was 3.8% (n = 1), 7.7% (n = 2), and 11.5% (n = 3) in the 1st, 2nd, and 3rd months, respectively, and was found to be 3.8% (n = 1) between 6 and 12 months. Whether or not DFP therapy should be interrupted in case of mild neutropenia and the frequency of monitoring ANC in real-life conditions should be documented with further studies. Other causes of neutropenia in DFP-treated patients should also be kept in mind.

Delayed-onset hemolytic anemia in patients with travel-associated severe malaria treated with artesunate, France, 2011-2013.

Artesunate is the most effective treatment for severe malaria. However, delayed-onset hemolytic anemia has been observed in ≈20% of travelers who receive artesunate, ≈60% of whom require transfusion. This finding could discourage physicians from using artesunate. We prospectively evaluated a cohort of 123 patients in France who had severe imported malaria that was treated with artesunate; our evaluation focused on outcome, adverse events, and postartesunate delayed-onset hemolysis (PADH). Of the 123 patients, 6 (5%) died. Overall, 97 adverse events occurred. Among the 78 patients who received follow-up for >8 days after treatment initiation, 76 (97%) had anemia, and 21 (27%) of the 78 cases were recorded as PADH. The median drop in hemoglobin levels was 1.3 g/dL; 15% of patients with PADH had hemoglobin levels of <7 g/dL, and 1 required transfusion. Despite the high incidence of PADH, the resulting anemia remained mild in 85% of cases. This reassuring result confirms the safety and therapeutic benefit of artesunate.

[Diagnosis and treatment of hemolytic anemia].

Hemolytic anemia is defined as anemia due to a reduction of the RBC lifespan to less than the normal range of approximately 120 days. Patients with anemia and jaundice are often suspected to have hemolysis. Herein, different causes of hemolysis and the diagnostic algorithm are reviewed. Currently, there is no generic treatment for hemolytic anemia. Appropriate management of a patient with hemolytic anemia requires determination of the underlying cause. Treatments for the different causes of hemolytic anemia are also reviewed.

Interpretation of HbA1c : association with mean cell volume and haemoglobin concentration.

AIM: The utility of HbA1c in diabetes diagnosis is reduced in settings associated with altered haemoglobin glycation. We have studied whether HbA1c varies with mean cell volume and mean cell haemoglobin concentration as measures of haemoglobin metabolism. METHODS: Randomly selected adults from rural Victoria, Australia, were invited for biomedical assessment. After excluding patients with known diabetes and/or serum creatinine ≥ 0.12 mmol/l, 1315 adults were included. Demography, arthropometric measurements, oral glucose tolerance test, analyses of full blood count and HbA1c were undertaken. RESULTS: After adjusting for age, sex, ethnicity, BMI, town and socio-economic status, there were no significant differences in haemoglobin, mean cell volume or mean cell haemoglobin concentration by glycaemic status (defined by oral glucose tolerance test). HbA1c was significantly and independently associated with fasting glucose, town, mean cell haemoglobin concentration, ethnicity, age and BMI among men < 50 years (R² = 33.8%); fasting glucose, 2-h glucose, mean cell haemoglobin concentration and town among men ≥ 50 years (R² = 47.9%); fasting glucose, mean cell volume, mean cell haemoglobin concentration, town, 2-h glucose and age among women < 50 years (R² = 46.3%); fasting glucose, mean cell haemoglobin concentration, mean cell volume and 2-h glucose among women ≥ 50 years (R² = 51.6%). A generalized linear model showed a gradient from an adjusted mean HbA1c of 36 (95% CI 34-38) mmol/mol with a mean cell haemoglobin concentration of ≤ 320 g/l to 30 (95% CI 29-31) mmol/mol with a mean cell haemoglobin concentration of > 370 g/l. The gradient across mean cell volume was negative, but only by 1 mmol/mol (0.1%) HbA1c . CONCLUSION: A mean HbA1c difference of 5 mmol/mol (0.5%) across the mean cell haemoglobin concentration reference range suggests that an accompanying full blood count examination may be required for its use in the diagnosis of diabetes. Further studies are required to confirm this.

Record fragmentation due to transfusion at multiple health care facilities: a risk factor for delayed hemolytic transfusion reactions.

BACKGROUND: Patients transfused at more than one health care facility face safety risks, because their transfusion record is fragmented. Blood group antibodies documented at one facility may be unknown to others. Because many antibodies are evanescent, access to prior antibody records is important for preventing incompatible transfusions and delayed hemolytic reactions. The study goal was to quantify multisite transfusion activity and its impact on antibody record accuracy. STUDY DESIGN AND METHODS: Patients (n = 100) undergoing hospital transfusion testing were surveyed to determine the locations and dates of any prior transfusions. Also, transfusion records were examined to determine whether patients (n = 200) known to be alloimmunized at one hospital had antibody testing done at another nearby hospital and, if so, how often the results were discrepant. RESULTS: Twenty-three percent (23/100) of patients undergoing type-and-screen testing reported receiving transfusions at 24 other facilities. Locations of transfusions that occurred elsewhere were 54.2% (13/24) at eight other in-state hospitals, 12.5% in bordering states, 20.8% in more distant states, and 12.5% during military service. Twenty-one percent (42/200) of patients known to be alloimmunized at one hospital had antibody test results on record at another nearby hospital. Antibody discrepancies were noted in 64.3% (27/42) of cases. The most common discrepancy was the failure of one facility to detect an antibody. CONCLUSION: Multisite transfusions were common. For patients seen at both of two nearby hospitals, antibody records were frequently discrepant. The findings support the need for interfacility sharing of transfusion records, particularly at the regional level.