Megadose Methylprednisolone for Immune Thrombocytopenia in an Infant Positive for SARS-CoV-2: A Case Report.

BACKGROUND Immune thrombocytopenia (ITP) is rare in infants under 1 year old. Bleeding often occurs when the platelet count is <20 000/uL. The disease can progress because of accompanying COVID-19 disease. CASE REPORT A 9-month-old boy, weighing 8.5 kg, came to the hospital with petechiae on the forehead, cheeks, mouth, and extremities. The patient had rhinorrhea for 3 days previously and was febrile, pale, weak, and could not drink. He had the measles-rubella vaccination 19 days prior. Physical examination showed no abnormalities of the eyes, ears, nose, throat, and mouth. Heart and lungs were within normal limits, with no organomegaly, lymphadenopathy, or congenital anomaly of the abdomen. Laboratory examination showed hemoglobin, 12.7 g/dL; leukocytes, 7420/uL; platelet count, 16 000/uL; and hematocrit, 37.9%. Erythrocyte sedimentation rate was 14 mm at 1 h and 21 mm at 2 h. Peripheral blood smear showed normal RBC morphology, normal leukocytes, and few platelets. IgG was reactive and IgM was nonreactive on rapid antibody test. RT-PCR was positive for SARS-COV-2. Chest-X-ray showed pneumonia. The diagnosis was newly diagnosed ITP with COVID-19. Patient was treated with 30 mg/kg body weight/day of IV methylprednisolone for 3 days (250 mg); then 20 mg/kg body weight/day (175 mg) orally for 4 days in 3 divided doses. Azithromycin 100 mg/day, zinc 20 mg/day, and vitamin C 50 mg/day orally were also given. CONCLUSIONS COVID-19 screening is highly recommended during this pandemic to identify it as a potential cause of childhood ITP. Megadose methylprednisolone had an excellent response in alleviating ITP with confirmed COVID-19 in an infant.

All-trans retinoic acid plus high-dose dexamethasone as first-line treatment for patients with newly diagnosed immune thrombocytopenia: a multicentre, open-label, randomised, controlled, phase 2 trial.

BACKGROUND: High-dose dexamethasone is the standard initial treatment for patients with immune thrombocytopenia, but many patients still relapse and require further treatments. All-trans retinoic acid has been shown to exert immunomodulatory effects and promote thrombopoiesis, and so we aimed to assess the activity and safety of all-trans retinoic acid plus high-dose dexamethasone as a first-line treatment for newly diagnosed patients with immune thrombocytopenia. METHODS: This multicentre, open-label, randomised, controlled, phase 2 trial was done at six different tertiary medical centres in China. Eligible participants were adults (aged >18 years) with treatment-naive, newly diagnosed, primary immune thrombocytopenia who had either a platelet count of less than 30 × 109 platelets per L or a platelet count of less than 50 × 109 platelets per L and clinically significant bleeding. We randomly assigned (1:1) participants to receive either all-trans retinoic acid (10 mg orally twice daily for 12 weeks) plus high-dose dexamethasone (40 mg/day intravenously for 4 consecutive days) or high-dose dexamethasone alone using a central, web-based randomisation system. If patients did not respond by day 14, the 4-day course of dexamethasone was repeated. The primary endpoint was 6-month sustained response, defined as the maintenance of a platelet count of at least 30 × 109 platelets per L and at least 2-times higher than the baseline count and the absence of bleeding, with no need for rescue medication at this time. The primary endpoint was analysed by intention-to-treat and safety was assessed in all participants who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov, NCT04217148, and is now completed. FINDINGS: Between Jan 1, 2020, and June 30, 2020, 132 patients were randomly assigned to either all-trans retinoic acid plus high-dose dexamethasone (n=66) or high-dose dexamethasone alone (n=66). Three patients did not receive their allocated treatment, leaving 129 in the safety analysis set. At 6 months, a significantly higher proportion of participants in the all-trans retinoic acid plus high-dose dexamethasone group (45 [68%] of 66) than in the high-dose dexamethasone monotherapy group (27 [41%] of 66) had a sustained response (OR 3·095, 95% CI 1·516-6·318; p=0·0017). The most common adverse events were dry skin (31 [48%] of 64 patients), headaches (12 [19%]), and insomnia (12 [19%]) in the combination group, and insomnia (ten [15%] of 65 patients) and anxiety or mood disorders (eight [12%]) in the monotherapy group. Both treatments were well tolerated and no grade 4 or worse adverse events occurred. There were no treatment-related deaths. INTERPRETATION: The combination of all-trans retinoic acid and high-dose dexamethasone was safe and active in newly diagnosed patients with primary immune thrombocytopenia, providing a sustained response. This regimen represents a potential first-line treatment in this setting, but further studies are needed to validate its efficacy and safety. FUNDING: The Beijing Municipal Science and Technology Commission, the National Natural Science Foundation of China, the Beijing Natural Science Foundation, the National Key Research and Development Program of China, and the Foundation for Innovative Research Groups of the National Natural Science Foundation of China.

Validation of an algorithm identifying incident primary immune thrombocytopenia in the French national health insurance database.

OBJECTIVES: To evaluate the accuracy of an algorithm identifying newly diagnosed immune thrombocytopenia (ITP) patients in the French national health insurance database (SNIIRAM). METHODS: The source of data was the SNIIRAM of Midi-Pyrenees region (southwest of France, three million inhabitants). Data of patients with at least one ITP code (D69.3 code of the International Classification of Disease, version 10) were extracted between January 1, 2012, and December 31, 2014. We used an algorithm that identifies newly diagnosed primary ITPs. Medical charts of incident ITPs were reviewed. Positive predictive values (PPVs) of identification of true, incident, and primary ITP cases were estimated. RESULTS: Of the 168 patients selected, 161 were true ITP cases yielding a PPV of 95.8% (95% confidence interval-95% CI: 92.8-98.8). Among them, 128 were truly incident according to symptom onset date and 134 according to the diagnosis date yielding PPVs of 79.5% (95% CI: 73.2-85.7) and 83.2% (95% CI: 77.4-89.0), respectively. Median time between estimated diagnosis date by the algorithm and true diagnosis date was 0 days (interquartile range: 0 to 15). CONCLUSIONS: This study showed a very good PPV of this algorithm identifying incident primary ITP patients in the SNIIRAM.

Controversies in the treatment of immune thrombocytopenia.

PURPOSE OF REVIEW: We address three current controversies in management of immune thrombocytopenia (ITP): Should asymptomatic children with newly diagnosed ITP and severe thrombocytopenia be treated? Does intensification of up-front therapy in adults with newly diagnosed ITP impact long-term outcomes? Is splenectomy still the second-line treatment of choice in adults with chronic ITP? RECENT FINDINGS: Severe bleeding is rare in children with ITP. There is little evidence that the platelet count predicts or that treatment prevents severe bleeding in this population. Intensified treatment with high-dose dexamethasone and rituximab in adults with newly diagnosed ITP is associated with improved platelet responses at 6 and 12 months but greater toxicity compared with standard therapy. Rituximab and thrombopoietin receptor agonists have emerged as suitable alternatives to splenectomy for second-line management of adults with chronic ITP. SUMMARY: We generally observe children with newly diagnosed ITP and mild or no bleeding symptoms, irrespective of platelet count. We do not routinely use intensified up-front therapy in adults with newly diagnosed ITP. We discuss the advantages and disadvantages of splenectomy, rituximab, and thrombopoietin receptor agonists with our patients and make a joint decision that takes into consideration age, comorbidities, lifestyle, values, preferences, and financial considerations.

Profiling of miRNA expression in immune thrombocytopenia patients before and after Qishunbaolier (QSBLE) treatment.

Immune thrombocytopenia (ITP), also known as idiopathic thrombocytopenic purpura, is an autoimmune disease characterized by low platelet count and increased bleeding tendency. Currently, glucocorticoid and splenectomy are the main therapies for ITP but with obvious side effects including tendency of relapse and risk of internal bleeding. In this study, we report the Mongolian medicine Qishunbaolier (QSBLE) can significantly and efficiently increase platelet count with a low recurrent rate and unnoticeable side effect. We profiled the microRNA (miRNA) expression in the blood sample of ITP patients and identified 44 miRNAs that are differentially expressed in ITP patients before and after QSBLE treatment. Out of these 44 miRNAs, 25 are expressed in control subjects and are downregulated in ITP patients, whereas the treatment with QSBLE restores their expressions to the level of control subjects. This result suggests that abnormal expression of these 25 miRNAs might be connected to the pathogenesis of ITP. Interestingly, 14 of those 44 miNRAs are predicted to target at least once on 31 known IPT associated genes, indicating the possible mechanism of QSBLE on ITP therapy.

Bone mass and biochemical markers of bone turnover in children and adolescents with chronic immune thrombocytopenia: relation to corticosteroid therapy and vitamin D receptor gene polymorphisms.

Optional drug therapy in refractory chronic immune thrombocytopenia (ITP) includes standard oral, pulsed high-dose steroid therapy, intravenous gamma globulin, anti-D, and immunosuppressive therapy or thrombopoietin receptor agonists. This work aimed to study the bone mass in children and adolescents with chronic ITP in relation to biochemical markers of bone turnover, cumulative steroid therapy, and the possible modulating effect of vitamin D receptor (VDR) gene polymorphisms. Thirty-six children and adolescents with chronic ITP were recruited from the Hematology Clinic, Children's Hospital, Ain Shams University and the Hematology Clinic of the National Research Centre in Egypt and compared with 43 healthy age- and sex-matched controls. The total cumulative dose of steroids was calculated. Bone markers (serum osteocalcin (OC) and propeptide I precollagen (PICP) and urinary deoxypyridinoline (DPD) excretion), analysis of VDR gene distribution, and dual energy X-ray absorptiometry at lumbar and hip regions were performed for patients and controls. Compared to controls, chronic ITP patients had higher body mass index (BMI) and lower height for age standard deviation score (SDS). Chronic ITP patients had lower levels of OC and C-terminal propeptide of type I procollagen (PICP) and higher urinary DPD excretion, and bone mineral density (BMD) was significantly lower for both spine and hip z-score (<0.001). BMD was inversely correlated with urinary DPD excretion, age, BMI, and cumulative steroid dose. There was significant negative correlation between cumulative oral steroid dose and BMD (r = -0.4, P = 0.01 and r = -0.45, p = 0.001 for spine and hip z-scores, respectively), but the correlation was non-significant in relation to cumulative pulsed steroid therapy. FokI polymorphism was significantly related to BMD for both spine and hip z-score (p = 0.015 and p = 0.008, respectively), but there was no relation between BMD and Bsm1 polymorphism. FokI gene polymorphism may be one of the contributing factors in bone loss in patients on chronic steroid therapy. High cumulative doses of corticosteroids increased bone resorption in young chronic ITP patients. Longitudinal studies are needed to confirm the effect of different steroid protocols on bone turnover. Protocols of therapy of chronic ITP should restrict corticosteroid use in growing children and favor alternative less harmful therapies.

Supporting diagnostic decisions using hybrid and complementary data mining applications: a pilot study in the pediatric emergency department.

INTRODUCTION: This article demonstrates the capacity of a combination of different data mining (DM) methods to support diagnosis in pediatric emergency patients. By using a novel combination of these DM procedures, a computer-based diagnosis was created. METHODS: A support vector machine (SVM), artificial neural networks (ANNs), fuzzy logics, and a voting algorithm were simultaneously used to allocate a patient to one of 18 diagnoses (e.g., pneumonia, appendicitis). Anonymized data sets of patients who presented in the emergency department (ED) of a pediatric care clinic were chosen. For each patient, 26 identical clinical and laboratory parameters were used (e.g., blood count, C-reactive protein) to finally develop the program. RESULTS: The combination of four DM operations arrived at a correct diagnosis in 98% of the cases, retrospectively. A subgroup analysis showed that the highest diagnostic accuracy was for appendicitis (97% correct diagnoses) and idiopathic thrombocytopenic purpura or erythroblastopenia (100% correct diagnoses). During the prospective testing, 81% of the patients were correctly diagnosed by the system. DISCUSSION: The combination of these DM methods was suitable for proposing a diagnosis using both laboratory and clinical parameters. We conclude that an optimized combination of different but complementary DM methods might serve to assist medical decisions in the ED.

[Thrombocytopenia associated with iron deficiency: a rare differential diagnosis of auto-immune thrombocytopenic purpura]. / Thrombopénie ferriprive : un diagnostic différentiel rare du purpura thrombopénique auto-immun.

INTRODUCTION: Iron deficiency is typically associated with microcytic anemia and thrombocytosis. It is a very uncommon cause of thrombocytopenia. CASE REPORT: A 17-year-old female presented with marked fatigue and dyspnea on exertion. Review of systems was only remarkable for abundant menstruations during the past two years. The hemogram revealed a profound microcytic anemia (4.4 g/dL, mean corpuscular volume [MCV] 49 fL) and a thrombocytopenia (33 G/L). Marked iron deficiency was also present: ferritinemia <3 µg/L. Investigations did not find any cause of iron deficiency anemia other than excessive menstrual loss. Bone marrow examination showed an increase number of megakaryocytes, compatible with an immune thrombocytopenia purpura. Iron supplementation completely normalized the platelet count within 48 hours. CONCLUSION: Iron affects thrombopoiesis. Because the number of megakaryocytes may then increase in the bone marrow, "iron deficiency thrombocytopenia" may be falsely diagnosed as immune thrombocytopenic purpura, leading to inappropriate corticosteroid therapy. Iron supplementation is the appropriate treatment of iron deficiency thrombocytopenia and allowed a rapid correction of the platelet count in all the 24 cases that have been previously reported with sufficient detail to be analyzed in the literature.

Características clínicas del púrpura trombocitopénico inmune: revisión de 52 casos / Clinical characteristics of inmune thrombocytopenic purpura

Introducción: El Púrpura Trombocitopénico Inmune (PTI) suele ser autolimitado pero 10-20 por ciento persisten a los 6 meses, es decir de evolución crónica. Su tratamiento es controvertido y existen pocos datos nacionales. Objetivo: Conocer algunas características clínicas y de laboratorio del PTI, su relación con evolución crónica y el manejo actual. Método: Estudio retrospectivo de los 52 pacientes con PTI evaluados en Hospital Luis Calvo Mackenna, entre marzo 1998 y febrero 2003. Se consignó: sexo, edad, manifestaciones clínicas, conducta terapéutica y recuento plaquetario (RP) al diagnóstico, 15-60 días y 6 meses. Se aplicaron Test de Fisher y Odd Ratio. Resultados: Mediana de edad: 4,4 años (0,7 a 16,1), el RP fue < - 20 000 x mm3 en 37/52. No hubo hemorragia del sistema nervioso central. Se manejó con observación clínica 34/52, corticoides 17/52 e inmunoglobulinas endovenosas con corticoides 1/52. Completaron control (6 meses) 48/52 pacientes. Presentaron curso crónico 11/48, asociado a RP 15 días < - 20 000 x mm3 (p = 0,01) OR = 9 (IC95 por ciento: 1,26-80,16) y RP a los 60 días < - 50 000 x mm3 (p = 0,0000003) OR= 124 (IC95 por ciento: 7,77 - 4951,52). Conclusiones: La mayoría de los pacientes requirieron sólo observación clínica. Presentaron evolución crónica 23 por ciento siendo factores de riesgo RP a los 15 días £ 20 000 x mm3 y RP a los 60 días £ 50 000 x mm3.

Using decision analysis techniques to deal with "unanswerable" questions in idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenic purpura (ITP) is a common disorder with rare adverse outcomes. This makes it a particularly difficult area in which to undertake conventional studies. An alternative method for solving clinical questions is decision analysis, which is in essence a computer-assisted synthesis of the literature. Using the example of a newly diagnosed ITP patient, the author attempts to answer the question of whether a bone marrow aspirate (BMA) is required prior to starting steroids. Using decision analysis methodology, the author determines that BMA is not essential prior to starting steroids. More importantly, three variables critical to the decision-making process are determined: the risk of death from the BMA procedure, the altered chance of survival for a patient with acute lymphoblastic leukemia (ALL) inappropriately given steroids, and how sensitive the complete blood count is at determining the risk of ALL. This scenario demonstrates the value of decision analysis and lays the groundwork for future endeavors.