Risk Factors, Treatment, and Immune Dysregulation in Autoimmune Cytopenia after Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric Patients.

Autoimmune or alloimmune cytopenia (AIC) is a known rare complication of hematopoietic stem cell transplantation (SCT). AIC after SCT is considered difficult to treat and is associated with high morbidity and mortality. In this retrospective study in pediatric patients we evaluated incidence, outcome, potential risk factors, and current treatment strategies. A nested matched case-control study was performed to search for biomarkers associated with AIC. Of 531 consecutive SCTs at our center between 2000 and 2016, 26 were complicated by the development of AIC (cumulative incidence, 5.0%) after a median of 5 months post-SCT. Autoimmune hemolytic anemia was the most common AIC with 12 patients (46%). We identified nonmalignant disease, alemtuzumab serotherapy pre-SCT, and cytomegalovirus (CMV) reactivation as independently associated risk factors. The cytokine profile of patients at the time of AIC diagnosis appeared to skew toward a more pronounced Th 2 response compared with control subjects at the corresponding time point post-SCT. Corticosteroids and intravenous immunoglobulin as first-line treatment or a wait-and-see approach led to resolution of AIC in 35% of cases. Addition of step-up therapies rituximab (n = 15), bortezomib (n = 7), or sirolimus (n = 3) was associated with AIC resolution in 40%, 57%, and 100% of cases, respectively. In summary, we identified CMV reactivation post-SCT as a new clinical risk factor for the development of AIC in children. The cytokine profile during AIC appears to favor a Th 2 response. Rituximab, bortezomib, and sirolimus are promising step-up treatment modalities.

Fatal unexpected death due to familial hemophagocytic lymphohistiocytosis type 3.

Familial hemophagocytic lymphohistiocytosis is a rare autosomal recessive disorder of immune dysregulation associated with uncontrolled activation of cytotoxic T cells and macrophages. Herein, we report a case of a 14-month-old Chinese boy who presented with fever, abdominal distension and thrombopenia, and died within 3 days of admission to the hospital. Postmortem examination revealed pleuroperitoneal fluid, enlarged mesenteric lymph nodes and hepatosplenomegaly. Histopathological examination showed interstitial pneumonia, hepatonecrosis and hemophagocytosis. Immunohistochemical staining of the spleen, lymph node and liver specimens revealed numerous cytotoxic T cells (CD8+) and histiocytes (CD68+). EBER1-positive cells were observed in lymphocytes of the spleen, lymph node, liver and lungs by in situ hybridization. UNC13D mutation was identified, although the boy had no family history. The following medico-legal autopsy case is being reported for its rarity in the forensic setting. We addresses the need for genetic testing in addition to a thorough clinical history, appropriate laboratory tests, histological examination and immunohistochemical analysis for the rapid and accurate diagnosis of familial hemophagocytic lymphohistiocytosis.

[Hemospray: a novel therapeutic option in the management of acute upper gastrointestinal bleeding]. / Hemospray: Új lehetoség az akut felso gastrointestinalis vérzések ellátásában.

INTRODUCTION: Early endoscopic diagnosis and endoscopic therapy are very important in cases of acute gastrointestinal bleeding. Hemospray is an inorganic powder with hemostatic properties recently proposed for the treatment of acute gastrointestinal bleeding. AIM: The aim of the authors was to report the first Hungarian experience obtained with Hemospray in patients with acute gastrointestinal bleeding. METHOD: During a 14-month period 10 acute upper gastrointestinal bleeder patients were treated endoscopically with Hemospray in 11 settings. In 5 patients previous endoscopic hemostatic methods failed and in the remaining 5 patients Hemospray was administrated as a first-line therapy. RESULTS: Primary hemostasis was achieved in 9 of the 10 patients treated with Hemospray. Two patients died during hospitalization (uncontrolled arterial bleeding in one patient and hepatic encephalopathy in the other one patient). Primary hemostasis and hemodynamic stability were achieved in each of the 4 patients who had thrombopenia. CONCLUSIONS: Hemospray as a rescue therapy may ensure primary hemostasis in severe acute gastrointestinal bleeding even in cases with thrombopenia.

Prophylactic versus restrictive platelet transfusion strategy in patients with haematological malignancies in the ICU setting, a propensity-score analysis.

PURPOSE: Prophylactic platelet transfusions (PT) aim to reduce bleeding. We assessed whether restrictive PT compared to prophylactic strategy could apply in ICU. MATERIAL AND METHODS: We conducted a retrospective monocentric study including patients >18 yo with haematological malignancy admitted to the ICU with thrombocytopenia <20 G/L between 2018 and 2021. Patients were classified in 2 groups according transfusion strategy applied during the first 3 days: prophylactic or restrictive transfusion. RESULTS: 180 patients were included, 87 and 93 in the restrictive and prophylactic groups respectively. After propensity-score analysis, 2 groups of 54 matched patients were analyzed. Restrictive strategy led to a significant reduction in PT with incidence rate for 100-ICU-patients-days of 34.9 and 49.9, incidence rate ratio = 0.699 [0.5-0.9], p = 0.006, representing a 31% decrease. Decreased PT persisted until day 28 with platelet concentrates transfusions-free days at day 28 of 21 [13-25] and 16.5 [10.2-21] in the 2 groups (p = 0.04). Restrictive strategy did not result in higher grade ≥ 2 bleeding. Transfusion efficiency was low with similar number of days with platelet <10 or < 20 G/L regardless of strategy. Platelet transfusion strategy was not associated with 28-day mortality. Platelet nadir <5G/L was associated with day-28 mortality with HR = 1.882 [1.011-3.055], p = 0.046. CONCLUSION: A restrictive PT strategy appears feasible in the ICU.

[Severe thrombopenia with iron deficiency anemia: about a case and literature review]. / Thrombopénie sévère d'origine ferriprive : à propos d'un cas et revue de la littérature.

Iron deficiency is the leading cause of anemia worldwide, affecting approximately 600 million individuals. Once established, it typically manifests as a hypochromic microcytic anemia, the severity of which varies depending on the degree of deficiency. This anemia is frequently associated with thrombocytosis, but the presence of associated thrombocytopenia is much rarer. Here, we report a case of severe iron deficiency with an atypical presentation of bicytopenia, involving both severe anemia and profound thrombocytopenia, which rapidly resolved following iron supplementation. We then discuss the hypotheses that exist to explain the link between iron deficiency and regulation of thrombopoiesis.

Severe cytopenia during adjuvant chemotherapy for early breast cancer in a patient with idiopathic CD4+ lymphocytopenia.

Idiopathic CD4+ lymphocytopenia (ICL) is a rare immunodeficiency disorder characterized by decreased CD4+ T-cell counts in the absence of human immunodeficiency virus (HIV) infection. Similar to HIV infection, ICL is commonly associated with acquired immunodeficiency syndrome-defining cancers, such as Kaposi sarcoma, non-Hodgkin lymphoma and cervical cancer; however, the presentation of breast cancer in a patient with ICL is rare. The current study presented the clinical course of a patient with early breast cancer and ICL. Following surgery, the patient underwent adjuvant chemotherapy comprising doxorubicin plus cyclophosphamide, followed by paclitaxel. The patient's immunodeficiency status required the prophylactic administration of clarithromycin, trimethoprim-sulfamethoxazole and valganciclovir. Throughout the course of chemotherapy, the patient experienced severe complications of febrile neutropenia, anemia, neutropenia and thrombocytopenia, and was eventually forced to discontinue anticancer chemotherapy, as the relative dose intensity (RDI) could not be maintained. Similar hematological complications and reduced RDI, leading to worse outcomes, are also common in patients with HIV infection receiving chemotherapy, suggesting that CD4+ T cell-deficient patients are prone to developing cytopenia during chemotherapy. The present study demonstrates the importance of further data accumulation in patients with ICL with cancer and the development of a methodology for maintaining the RDI.

Severe poisoning with naproxen causing coagulopathy.

Non-steroidal anti-inflammatory drugs (NSAIDs) are well known for their most frequent side effects (digestive, renal and metabolic disorders) but are lesser known for other effects, such as coagulation disturbances. In this issue, we report the case of a 58-year-old woman who ingested 26 g of naproxen in a suicidal attempt and developed cardiovascular shock, hypocoagulability and thrombopenia. Her outcome was positive (extubation 3 days after admission [D3], correction of haemostatic disruptions on D5 and of thrombopenia on D6). Naproxen plasma concentration was at a toxic concentration of 1320 mg/L at 6 hours after drug ingestion. Only few cases of hypocoagulopathy are reported with the NSAIDs, and this is the first case that can be attributed to naproxen. A possible explanation of this phenomenon following naproxen ingestion is an inhibition of thromboxane A2, usually attributed to NSAIDs, combined with an inhibition of activation of downstream the cascade.

Sarcopenia Is Associated With Hematologic Toxicity During Chemoradiotherapy in Patients With Anal Carcinoma.

PURPOSE: Sarcopenia, defined as a loss of muscle mass and quality, has been associated with impaired oncological outcome and treatment toxicities in several malignancies. However, its role in anal squamous cell carcinoma (ASCC) remains less well explored. METHODS/MATERIALS: Planning CT scans were used to measure cross-sectional skeletal muscle area (SMA) to calculate the skeletal muscle index (SMI). The association of sarcopenia with clinical and treatment-related parameters, and toxicity was assessed in 114 patients with ASCC that underwent standard 5-Fluorouracil/Mitomycin C chemoradiotherapy (CRT). The prognostic impact of sarcopenia on local relapse-free survival (LRFS), disease-free survival (DFS), and overall survival was examined using a Cox regression analysis. RESULTS: 29 (25.4%) patients had sarcopenia. Patients with sarcopenia had lower baseline hemoglobin levels (p = 0.002), worse Karnofsky Performance Status (p = 0.001) lower BMI (p < 0.001), and a significantly lower body surface area (p = 0.03), and lower incidence of involved lymph nodes (p = 0.03). Regarding acute toxicity, sarcopenia was associated with a significantly higher incidence of ≥grade 3leukopenia (OR: 3.5; 95% CI: 1.6-7.5, p = 0.007) and ≥grade 3 thrombopenia (OR: 5.1; 95% CI: 1.3-21, p = 0.018) after CRT. Despite higher hematologic toxicity in sarcopenic patients, total treatment time was similar between patients with and without sarcopenia (median 44 vs 45 days, p = 0.95). There was no significant prognostic impact of sarcopenia on either LRFS, DFS, or OS. CONCLUSION: This is the largest study to assess the impact of sarcopenia on toxicity and oncological outcome in patients with ASCC. Increased clinician awareness of higher hematological toxicity risk is needed for sarcopenic patients with ASCC undergoing CRT to facilitate closer monitoring of side effects and earlier introduction of supportive measures. Further prospective studies are needed to elucidate the prognostic role and impact of sarcopenia on CRT-related toxicity in ASCC.

Early Detection and Assessment of Covid-19.

Background: Since the Covid-19 global pandemic emerged, developing countries have been facing multiple challenges over its diagnosis. We aimed to establish a relationship between the signs and symptoms of COVID-19 for early detection and assessment to reduce the transmission rate of SARS-Cov-2. Methods: We collected published data on the clinical features of Covid-19 retrospectively and categorized them into physical and blood biomarkers. Common features were assigned scores by the Borg scoring method with slight modifications and were incorporated into a newly-developed Hashmi-Asif Covid-19 assessment Chart. Correlations between signs and symptoms with the development of Covid-19 was assessed by Pearson correlation and Spearman Correlation coefficient (rho). Linear regression analysis was employed to assess the highest correlating features. The frequency of signs and symptoms in developing Covid-19 was assessed through Chi-square test two tailed with Cramer's V strength. Changes in signs and symptoms were incorporated into a chart that consisted of four tiers representing disease stages. Results: Data from 10,172 Covid-19 laboratory confirmed cases showed a correlation with Fever in 43.9% (P = 0.000) cases, cough 54.08% and dry mucus 25.68% equally significant (P = 0.000), Hyperemic pharyngeal mucus membrane 17.92% (P = 0.005), leukopenia 28.11% (P = 0.000), lymphopenia 64.35% (P = 0.000), thrombopenia 35.49% (P = 0.000), elevated Alanine aminotransferase 50.02% (P = 0.000), and Aspartate aminotransferase 34.49% (P = 0.000). The chart exhibited a maximum scoring of 39. Normal tier scoring was ≤ 12/39, mild state scoring was 13-22/39, and star values scoring was ≥7/15; this latter category on the chart means Covid-19 is progressing and quarantine should be adopted. Moderate stage scored 23-33 and severe scored 34-39 in the chart. Conclusion: The Hashmi-Asif Covid-19 Chart is significant in assessing subclinical and clinical stages of Covid-19 to reduce the transmission rate.

MYH9-related disease: it does exist, may be more frequent than you think and requires specific therapy.

In this issue of ckj, Tabibzadeh et al. report one of the largest series of patients with MYH9 mutations and kidney disease. The cardinal manifestation of MYH9-related disease is thrombocytopenia with giant platelets. The population frequency of pathogenic MYH9 mutations may be at least 1 in 20 000. The literature abounds in misdiagnosed cases treated for idiopathic thrombocytopenic purpura with immune suppressants and even splenectomy. Additional manifestations include neurosensorial deafness and proteinuric and hematuric progressive kidney disease (at some point, it was called Alport syndrome with macrothrombocytopenia), leucocyte inclusions, cataracts and liver enzyme abnormalities, resulting in different names for different manifestation combinations (MATINS, May-Hegglin anomaly, Fechtner, Epstein and Sebastian syndromes, and deafness AD 17). The penetrance and severity of kidney disease are very variable, which may obscure the autosomal dominant inheritance. A correct diagnosis will both preclude unnecessary and potentially dangerous therapeutic interventions and allow genetic counselling and adequate treatment. Morphological erythrocyte, granulocyte and platelet abnormalities may allow the future development of high-throughput screening techniques adapted to clinical peripheral blood flow cytometers.

Hematological complications in children subjected to extracorporeal membrane oxygenation. / Complicaciones hematológicas en niños tratados con oxigenación por membrana extracorpórea.

OBJECTIVES: To analyze the hematological complications and need for transfusions in children receiving extracorporeal life support (ECLS). DESIGN: A retrospective study was carried out. SETTING: A pediatric intensive care unit. PATIENTS: Children under 18 years of age subjected to ECLS between September 2006 and November 2015. INTERVENTIONS: None. VARIABLES OF INTEREST: Patient and ECLS characteristics, anticoagulation, hematological and coagulation parameters, transfusions and clinical course. RESULTS: A total of 100 patients (94 with heart disease) with a median age of 11 months were studied. Seventy-six patients presented bleeding. The most frequent bleeding point was the mediastinum and 39 patients required revision surgery. In the first 3days, 97% of the patients required blood transfusion (34.4ml/kg per day), 94% platelets (21.1ml/kg per day) and 90% plasma (26.6ml/kg per day). Patients who were in the postoperative period, those who were bleeding at the start of ECLS, those requiring revision surgery, those who could not suspend extracorporeal circulation, and those subjected to transthoracic cannulation required a greater volume of transfusions than the rest of the patients. Thromboembolism occurred in 14 patients and hemolysis in 33 patients. Mortality among the children who were bleeding at the start of ECLS (57.6%) was significantly higher than in the rest of the patients (37.5%) (P=.048). CONCLUSIONS: Children subjected to ECLS present high blood product needs. The main factors related to transfusions were the postoperative period, bleeding at the start of ECLS, revision surgery, transthoracic cannulation, and the impossibility of suspending extracorporeal circulation. Children with bleeding suffered greater mortality than the rest of the patients.

Pharmacokinetic and toxicodynamic evaluation of oxaliplatin-induced neuropathy and hematological toxicity in rats.

PURPOSE: Oxaliplatin (L-OHP) is a third-generation, platinum-based chemotherapeutic agent and is widely used in gastroenterological cancer regimens. It is important to complete chemotherapy cycles to improve treatment efficacy for cancer patients. However, undesirable side effects, including acute and chronic neuropathies, and myelosuppression, lead to the discontinuation of chemotherapy in some treatment regimens. To predict and prevent the onset of side effects, and to establish appropriate dose adjustment, pharmacokinetic and toxicodynamic studies were performed to investigate the effects of L-OHP in rats. METHODS: Rats were administered intravenous L-OHP, once a week for 4 weeks, at doses of 3, 5, or 8 mg/kg. Pharmacokinetic profiles were observed on Day 1 and Day 22. Acute and chronic neuropathies were evaluated over 4 weeks; cold allodynia was evaluated using an acetone test and mechanical allodynia using the von Frey test. Hematological parameters were also investigated during the same period. RESULTS: The mean AUC0-∞ values for L-OHP were 0.4 ± 0.2, 2.4 ± 0.4, and 3.5 ± 0.9 ng h/mL, increasing dose-dependently on Day 1. The accumulation of L-OHP on Day 22 was observed after repeated administration of L-OHP, as shown by mean AUC0-∞ values of 0.6 ± 0.2, 4.0 ± 1.0, and 14.1 ± 9.8 ng·h/mL, for the three doses. Cold allodynia was observed from Day 3 in the 5 and 8 mg/kg groups, and the extent of this response was dose-dependent. Mechanical allodynia was also observed from Day 10 in the 5 and 8 mg/kg groups. Moreover, the platelet count was the most sensitive among the hematological parameters. CONCLUSION: These results provide useful experimental data for clinical cancer patients undergoing chemotherapy, to establish a pharmacokinetic and toxicodynamic model of L-OHP for adequate dose adjustment.

Thrombopénie sévère chez un nouveau né de mère splénectomisé pour purpura thrombopénique idiopathique: Severe thrombopenia in an infant born to mother splenectomized for idiopathic thrombopenic purpura.

Neonatal thrombopenia is the most common hemostatic abnormality in newborns. It is defined as a platelet count below 150.000/mm3. 40% of newborns to mothers with a history of autoimmune thrombopenia are at risk of developing neonatal thrombopenia while 10-15% of them are at risk of developing severe thrombopenia. We here report the case of a 20 days old newborn to mother splenectomized for idiopathic thrombopenic purpura in order to highlight the relationship between the severity of maternal disease and the severity of the neonatal thrombopenia and thereby to avoid the risk of intracranial hemorrhage resulting in death or neurological sequelae.

[Hemolytic-uremic syndrome (HUS) in children at the University Hospital Center in Dakar: about four cases]. / Syndrome hémolytique et urémique de l'enfant au Centre Hospitalier Universitaire (CHU) de Dakar: à propos de quatre observations.

Hemolytic-uremic syndrome (HUS) is a common cause of organic acute renal failure (ARF) in children. It is a progressive complication of acute gastroenteritis (AGE), especially caused by Escherichia coli in children. This study aimed to describe the clinical, therapeutic and evolutionary aspects of this affection in four children. We collected four cases of HUS. The average age was 10,5 months (5-15mois), exclusively boys. Clinical examination revealed a hemolytic anemia (pallor and jaundice), oligoanuria and edematous syndrome (2 cases), arterial hypertension (1 patient), AGE associated with severe dehydration and hypovolemic shock (2 patients), consciousness disorders. ARF was found in all patients as well as thrombocytopenia and schizocytes smear. Direct Coombs test was negative. Hyperkalemia was found in 3 patients, of whom 1 with hyperkalemia level of more than 9.2 mmol/L, hyponatremia at 129 mmol/l (1 patient) and hypernatremia at 153 mmol/l (1 patient). HUS was secondary to pneumococcal pneumonia (1 patient) while AGE was secondary to E. coli (1 patient). The treatment was mainly symptomatic and included fluid restriction, transfusion of red cell concentrates, diuretics, peritoneal dialysis and hemodialysis. The evolution was marked by the onset of chronic renal failure (1 patient) after 6 months of follow-up and by recovery (1 case). Three patients died. HUS is the most common cause of organic acute renal failure in newborns. Diagnosis is essentially biological, treatment is mostly symptomatic.

Haematological abnormalities in mitochondrial disorders.

INTRODUCTION: This study aimed to assess the kind of haematological abnormalities that are present in patients with mitochondrial disorders (MIDs) and the frequency of their occurrence. METHODS: The blood cell counts of a cohort of patients with syndromic and non-syndromic MIDs were retrospectively reviewed. MIDs were classified as 'definite', 'probable' or 'possible' according to clinical presentation, instrumental findings, immunohistological findings on muscle biopsy, biochemical abnormalities of the respiratory chain and/or the results of genetic studies. Patients who had medical conditions other than MID that account for the haematological abnormalities were excluded. RESULTS: A total of 46 patients ('definite' = 5; 'probable' = 9; 'possible' = 32) had haematological abnormalities attributable to MIDs. The most frequent haematological abnormality in patients with MIDs was anaemia. 27 patients had anaemia as their sole haematological problem. Anaemia was associated with thrombopenia (n = 4), thrombocytosis (n = 2), leucopenia (n = 2), and eosinophilia (n = 1). Anaemia was hypochromic and normocytic in 27 patients, hypochromic and microcytic in six patients, hyperchromic and macrocytic in two patients, and normochromic and microcytic in one patient. Among the 46 patients with a mitochondrial haematological abnormality, 78.3% had anaemia, 13.0% had thrombopenia, 8.7% had leucopenia and 8.7% had eosinophilia, alone or in combination with other haematological abnormalities. CONCLUSION: MID should be considered if a patient's abnormal blood cell counts (particularly those associated with anaemia, thrombopenia, leucopenia or eosinophilia) cannot be explained by established causes. Abnormal blood cell counts may be the sole manifestation of MID or a collateral feature of a multisystem problem.

Peripherally inserted central catheter placement in patients with coagulation disorders: A retrospective analysis.

OBJECTIVE: To assess the safety of peripherally inserted central venous catheter (PICC) placement in patients with altered and uncorrected coagulation parameters or receiving antiplatelet therapy. MATERIALS AND METHODS: Medical charts of all patients with major primary and secondary hemostasis disorders, combined hemostasis disorders or on antiplatelet therapy and who had undergone non-tunneled PICC placement from December 2009 to December 2013, were retrospectively reviewed. A hemostatic disorder was defined as a platelet count (PC)≤50×10(9)/L, an international normalized ratio (INR) ≥ 2, or an activated partial thromboplastin time (aPTT)≥66s, alone or in combination. Underlying hemostasis disorders were not corrected and antiplatelet therapy was not interrupted before PICC placement in any patient. 4, and 5-Fr single and dual lumen PICCs were used. RESULTS: A total of 378 PICCs were placed in 271 patients (180 men and 91 women; mean age=62±13.4years; range, 18-93 years)) with coagulation disorders. Eighty-nine (23%) PICCs were placed in patients who were receiving antiplatelet therapy (aspirin, clopidogrel, rivaroxaban). Thrombocytopenia was noted in 269PICC placements (71%). Among these patients, 23 had disseminated intravascular coagulation. Prolonged INR and aPTT were observed in 42 procedures (11.1%). PICC placement was achieved in all patients, with a mean number of 1.14 attempts. Peripheral venous access was obtained through the basilic and the brachial vein respectively in 295 (79.1%) and 83 (20.9%) of patients. The placements were performed by residents and fellows in 108 (28.5%) and 270 (71.5%) procedures, respectively. No early or late complications were reported after any procedure. No accidental puncture of the brachial artery occurred. CONCLUSION: In patients with severe primary and secondary hemostasis disorders, combined hemostasis disorders or on antiplatelet therapy, PICC placement is a feasible and safe procedure and does not require correction of coagulation parameters or discontinuation of antiplatelet therapy.