Evaluating Clinical Outcomes and Potential Prognostic Factors Among 308 Children and Adolescents with Immune Thrombocytopenia (ITP): An 11-Year Retrospective Cohort Study

Abstract Background: Immune thrombocytopenia (ITP) usually is a mild and self-limited disease; however, 25-30% of children develop chronic ITP. Nordic score is a validated clinical prediction tool, yet its use in children is limited and evidence for other prognostic factors is unclear. Purpose: To evaluate clinical outcomes among pediatric ITP patients, and examine their relationship to patient characteristics, including Nordic score. We hypothesized that Nordic score and patient characteristics will be predictive of ITP resolution or development of chronic ITP. Methods: We conducted a retrospective chart review of all children diagnosed with ITP at our institution between May 2008 to May 2019. Data extraction included patients' age, sex, presenting signs and symptoms, laboratory values, treatment decisions, and clinical outcomes. Nordic score calculated with 6 clinical features from diagnosis: abrupt onset <14 days, age < 10 years, preceding infection <1 month, platelet count < 5x10 9/L, wet purpura, and male sex. High scores (10-14) predict a brief disease course (<3 months), whereas low scores (0-4) predict a more prolonged course. Primary outcomes included complete response (CR) (platelets 100 x10 9/L on 2 occasions >7 days apart), recurrence (platelets < 100 after achieving CR), development of chronic ITP, and resolution (long term normal platelet count). Secondary outcomes included early response (platelets 30 x10 9/L in <1 week), time to CR, duration of CR (months between CR and recurrence), and time to resolution. Data presented as odds ratio (OR) with 95% confidence intervals. OR for Nordic score presented per 5-unit increase correlating with Nordic score categories (low 0-4, moderate 5-9, high 10-14). Results: A total of 308 patients were included (median age 5 years, IQR 2.0-10.8; 54.5% male) (Table 1). About 56% presented with platelets < 10 x10 9/L and 42% had bleeding at diagnosis (bleeding score 3 or higher), only 3% were severe. Median Nordic score was 10 (IQR 6-11). Overall, 64% of patients were treated upfront, majority (98%) receiving intravenous immunoglobulin (IVIG). Treatment at diagnosis was more likely for patients with platelets < 10 x10 9/L (OR 21, 10.4-42.5), bleeding score 3 or higher (OR 2.0, 1-4), and higher Nordic score (OR 6.2, 5.6-6.9) (Table 2). Treatment was predictive only of early response in multivariate analysis, not of CR, recurrence, development of chronic ITP, or disease resolution. Additionally, treatment at diagnosis was not associated with reduction in ITP-related complications, such as major bleeding episodes, need for platelet or red cell transfusions, or iron deficiency anemia. Overall rate of CR was 90% over a median of 1 month (IQR 0.3-4 months), while 13% had recurrence after median 19 months (IQR 8.3-26.0 months) and 32% developed chronic ITP. Overall, 80% of all study patients had resolution of ITP after median 1 month (IQR 0.3-5), with 86% achieving this before 12 months. About 36% of patients with chronic ITP had disease resolution over median 25 months (IQR 16.3-46.5 months). Univariate analysis showed significant variation across subgroups for age, viral symptoms, abrupt onset, Nordic score, hospital admission at diagnosis, platelet count, and treatment. Using multivariate regression analysis adjusted for the above variables, Nordic score was the only independent predictor of all primary outcomes. Higher Nordic score group had increased likelihood of CR (OR 6.2, 5.6-6.8) and disease resolution (OR 6.8, 5.1-8.9). Lower Nordic score group was associated with increased likelihood of recurrence (OR 6.5, 5.3-6.9) and development of chronic ITP (OR 8.6, 6.5-11.4). Additionally, higher Nordic score group was associated with increased time to recurrence and duration of response, decreased time to CR and resolution. Conclusions: In our cohort, low platelet count and bleeding symptoms were drivers of upfront treatment in pediatric ITP. Treatment initiation, associated with Nordic score, was predictive of faster increase in platelet count; however, it had no impact on overall disease trajectory or likelihood of complications. Our analysis demonstrate that Nordic score is an independent predictor of CR, resolution, recurrence, and development chronic ITP. Nordic score is a useful, simple prognostic tool that has the potential to help predict clinical course of pediatric ITP and identifying patients who may benefit from closer monitoring. Figure 1 Figure 1. Disclosures Badawy: Bluebird Bio Inc: Consultancy; Sanofi Genzyme: Consultancy; Vertex Pharmaceuticals Inc: Consultancy.

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Romiplostim safety and efficacy for immune thrombocytopenia in clinical practice: 2-year results of 72 adults in a romiplostim compassionate-use program

Blood ◽

10.1182/blood-2011-03-340166 ◽

2011 ◽

Vol 118 (16) ◽

pp. 4338-4345 ◽

Cited By ~ 70

Author(s):

Mehdi Khellaf ◽

Marc Michel ◽

Philippe Quittet ◽

Jean-François Viallard ◽

Magda Alexis ◽

...

Keyword(s):

Platelet Count ◽

Clinical Practice ◽

Immune Thrombocytopenia ◽

Intravenous Immunoglobulins ◽

Interquartile Range ◽

Concomitant Treatment ◽

Platelet Response ◽

Compassionate Use ◽

Chronic Itp ◽

Bleeding Score

Abstract Romiplostim, a thrombopoietic agent with demonstrated efficacy against immune thrombocytopenia (ITP) in prospective controlled studies, was recently licensed for adults with chronic ITP. Only France has allowed romiplostim compassionate use since January 2008. ITP patients could receive romiplostim when they failed to respond to successive corticosteroids, intravenous immunoglobulins, rituximab, and splenectomy, or when splenectomy was not indicated. We included the first 80 patients enrolled in this program with at least 2 years of follow-up. Primary platelet response (platelet count ≥ 50 × 109/L and double baseline) was observed in 74% of all patients. Long-term responses (2 years) were observed in 47 (65%) patients, 37 (79%) had sustained platelet responses with a median platelet count of 106 × 109/L (interquartile range, 75-167 × 109/L), and 10 (21%) were still taking romiplostim, despite a median platelet count of 38 × 109/L (interquartile range, 35-44 × 109/L), but with clinical benefit (lower dose and/or fewer concomitant treatment(s) and/or diminished bleeding signs). A high bleeding score and use of concomitant ITP therapy were baseline factors predicting romiplostim failure. The most frequently reported adverse events were: arthralgias (26%), fatigue (13%), and nausea (7%). Our results confirmed that romiplostim use in clinical practice is effective and safe for severe chronic ITP. This trial was registered at www.clinicaltrials.gov as #NCT01013181.

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Association of Interleukin-18 Gene Polymorphism with Severity of Chronic Immune Thrombocytopenia (ITP).

Blood ◽

10.1182/blood.v116.21.3693.3693 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3693-3693

Author(s):

Takayuki Saitoh ◽

Norihiko Moriyama ◽

Tomonori Takani ◽

Takeki Mitsui ◽

Takumi Hoshino ◽

...

Keyword(s):

Platelet Count ◽

Immune Thrombocytopenia ◽

Initial Diagnosis ◽

Severe Thrombocytopenia ◽

Interleukin 18 ◽

Single Nucleotide ◽

Chronic Itp ◽

Significant Difference ◽

Haplotype Frequencies ◽

And Control

Abstract Abstract 3693 Introduction: Immune thrombocytopenia (ITP) is a chronic acquired organ-specific autoimmune disorder characterized by the production of antibodies against antigens on the membranes of platelets. Several cytokine studies have shown Th1 polarization in ITP patients. Interleukin-18 (IL-18) plays an important role in Th1 and Th2 immune response. Recent studies showed that single-nucleotide promoter polymorphisms influence the transcriptions of IL-18 mRNA. IL-18 polymorphism has been implicated in autoimmunity, including Crohn's disease, rheumatoid arthritis, and asthma. We examined the single nucleotide polymorphisms (SNPs) in the promoter regions of the IL-18 genes in patients with ITP, and analyzed the relationship between IL-18 SNPs and clinical features. Patients and Methods: One hundred patients (male/female; 22/78, median age; 54.5) diagnosed as chronic ITP and 151 healthy controls were included. Chronic ITP was defined as thrombocytopenia (platelet count < 100×109/L) persisting greater than 12 months, normal or increased marrow megakaryocytes, and no secondary immune or non-immune abnormality that could account for the thrombocytopenic state. ITP with severe thrombocytopenia was defined as thrombocytopenia (platelet count < 10×109/L) at presentation of ITP. The response criteria of the ITP International Working Group was used. A complete response (CR) is defined as any platelet count of at least 100×109/L, and a response (R) was defined as any platelet count between 30 and 100×109/L and at least doubling of the baseline count. Allparticipants gave written informed consent about the study. Genomic DNA was isolated from peripheral blood using the DNA Kit (QIAGEN, Hilden, Germany). An allele-specific polymerase chain reaction was used to analyze polymorphism in IL-18 –607A/C and -137G/C. Genotype and allele frequencies were compared between the study groups using Χ2-test. The characteristics and laboratory features of the ITP patients with each IL-10 promoter polymorphism were compared using X2-tests and student t-tests. Probability values <0.05 were considered statistically significant. Results: The platelet count was at an initial diagnosis ranged from 1×109/L to 98 ×109/L, with a median of platelet count of 15×109/L. Thirty-five patients (35%) had severe thrombocytopenia. Steroid treatment was given to 68 patients (68%), while splenectomy was used in 11 patients (11%).The frequencies of the genotypes were as follows: AA (34%), AC (57%), and CC (9%) for -607; GG (77%), GC (21%), and CC (2%) for -137 loci. The frequencies of each haplotype were as follows: C-G/C-G haplotype (9%), A-G/C-G haplotype (47%), A-C/C-G haplotype (10%), A-G/A-G haplotype (21%), A-G/A-C haplotype (11%) and A-C/A-C haplotype (2%). No significant differences in the genotype or haplotype frequencies demonstrated between chronic ITP patients and control group. However, patients with -137CC genotypes showed severe thrombocytopenia at initial diagnosis compared to those with -137GG/GC genotypes (5×109/L vs. 22×109/L, p=0.002). Furthermore, patients with A-C/A-C haplotype showed severe thrombocytopenic state (5×109/L vs. 22×109/L, p=0.002) compared to those without A-C/A-C haplotype. No significant difference of treatment response was observed according to IL-18 polymorphism. Conclusion: No significant differences in the genotype or haplotype frequencies demonstrated between chronic ITP patients and control. However, -137CC genotypes or AA/CC haplotype was associated with severity of chronic ITP. Our data suggest that the group with low IL-18 inducibility (i.e. -137CC genotype, A-C/A-C haplotype) may have more severe thrombocytopenia. Disclosures: No relevant conflicts of interest to declare.

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The Cytokine Polymorphisms Affect the Severity of Thrombocytopenia at Diagnosis in Chronic Immune Thrombocytopenia.

Blood ◽

10.1182/blood.v120.21.2194.2194 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2194-2194

Author(s):

Takayuki Saitoh ◽

Chiaki Ushie ◽

Atsushi Iwasaki ◽

Norihiko Moriyama ◽

Tomonori Takani ◽

...

Keyword(s):

Polymerase Chain Reaction ◽

Platelet Count ◽

Clinical Features ◽

Immune Thrombocytopenia ◽

Steroid Treatment ◽

Severe Thrombocytopenia ◽

Bleeding Tendency ◽

Chain Reaction ◽

Chronic Itp ◽

Polymerase Chain

Abstract Abstract 2194 Introduction: The severity of immune thrombocytopenia (ITP) depends on the degree of the thrombocytopenia and the extent of bleeding. Some investigators have reported the association between the thrombocytopenia and cytokine dysregulation in ITP. We investigated the association between the severity of thrombocytopenia at diagnosis in ITP patients and several cytokine polymorphisms, including IL-10-1082A/G, -819T/C, -592A/C, IL-17F-7488T/C and IL-18-607A/C, −137G/C. Patients and methods: We examined 102 patients (male/female, 24/78; median age, 42) diagnosed with chronic ITP. The definition, response criteria, including complete response (CR)and response (R), loss of CR,and “corticosteroid-dependence” were assessed according to the criteria of the ITP International Working Group. ITP with severe thrombocytopenia (ST group)was defined as thrombocytopenia (platelet count < 10×109/L) at the initial diagnosis of ITP. Genotyping of IL-10 (rs1800870 − 1082 A/G, rs1800871 − 819 T/C, and rs1800872 − 592 A/C) and IL-17F (rs763780, 7488 T/C) polymorphisms were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the genotyping of the IL-18 polymorphism (rs187238 −137G/C and rs1946518−607 A/C) was determined by the allelic specific polymerase chain reaction technique. To confirm the accuracy of the assay, amplification products of several individuals were sequenced using an ABI Prism Genetic Analyzer. Genotype and allele frequencies were compared between the study groups using χ2-test. The characteristics and laboratory features of ITP patients with each polymorphisms were compared using χ2-tests and student t-tests. Odds ratios (OR) and 95% confidence intervals (CIs) were estimated for each study. All patients were provided written information about the study. This study was approved by the Institutional Research Board of Gunma University Hospital. Results: Clinical features of chronic ITP: The platelet count ranged from 1×109/L to 98×109/L with a mean of platelet count of 32×109/L at the initial diagnosis. Fifty seven patients (49%) had bleeding tendency. Steroid treatment was given to 68 patients (66.7%) and eradication of Helicobacter pylori (H. pylori) was performed in 32 patients (31.4%), while splenectomy was performed in only 11 patients (10.8%). Clinical features of ST group vs. non-ST group in chronic ITP: Of these 102 patients, 17 (16.7%) had severe thrombocytopenia (platelet count < 10×109/L) (ST group). ST group were significantly older (ST group: median 59 years vs. non-ST group: 41 years, p<0.01) and had more severe bleeding tendency (ST group: 100% vs. non-ST group: 54%, p<0.0001). Steroid treatment was frequently given to ST group than to non-ST group (ST group: 100% vs. non-ST group: 59.5%, p<0.001). Though the response to corticosteroids treatment was not significantly different between ST group and non-ST group (CR rate, ST group: 50% vs. non-ST group: 51.0%, p=0.94), corticosteroid-dependent patients in ST group was significantly higher than in non-ST group (76.9% vs. 25.3%, p<0.005). Polymorphism study of ST group vs. non-ST group in chronic ITP: The frequencies of genotypes of cytokines in patients with chronic ITP according to the definition of criteria of ST were as follows: AA (93.3% vs. 97.1%) and AG (6.7% vs. 2.9%, p=0.48) for IL-10–1082; TT (46.7% vs. 33.3%), TC (33.3% vs.55 %) and CC (20% vs. 11.7%) for IL-10–819; AA (46.7% vs. 33.3%), AC (33.3% vs.55 %) and CC (12.2% vs. 11.5%) for IL-10–592; TT (100% vs. 81%) and TC (0% vs. 19%) for IL-17F; GG (82.4% vs. 74.4%), GC (17.6% vs. 23.2%) and CC (0% vs. 2.4%) for IL-18–137; AA (35.3% vs. 34.1%), AC (58.8% vs. 53.7%) and CC (5.9% vs 12.2%) for IL-18–607 loci (ST group vs. non-ST group, respectively). No significant difference was observed between ST group and non-ST group according to IL-10–1082A/G, −819T/C, −592A/C, and IL-18–607A/C, −137G/C polymorphism. However, the numbers of IL-17F 7488TT genotype (higher function type) in ST group were significantly higher than in non-ST group (ST group: 100% vs. non-ST group: 81% p<0.05). Conclusion: These findings suggest that severe thrombocytopenia at diagnosis have an impact of bleeding tendency and corticosteroid-dependency of chronic ITP. Furthermore, IL-17F polymorphism may affect the severity of thrombocytopenia of chronic ITP. Disclosures: No relevant conflicts of interest to declare.

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Association Of Platelet Function Markers, Independent Of Platelet Count, With Bleeding Score In Patients With Immune Thrombocytopenia

Blood ◽

10.1182/blood.v122.21.3534.3534 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3534-3534

Author(s):

Andrew L. Frelinger ◽

Anja J Gerrits ◽

Michelle A. Berny-Lang ◽

Travis Brown ◽

Sabrina L. Carmichael ◽

...

Keyword(s):

Platelet Count ◽

Platelet Activation ◽

Platelet Function ◽

Research Funding ◽

Immune Thrombocytopenia ◽

Univariate Analysis ◽

Blood Draw ◽

Platelet Surface ◽

Platelet Counts ◽

Bleeding Score

Abstract Background Immune thrombocytopenia (ITP) patients with similarly low platelet counts differ in their tendency to bleed. Aim To determine if differences in platelet function in ITP patients with similarly low platelet counts partly account for the variation in bleeding tendency. Methods The relationship between bleeding scores and platelet function markers was investigated in a single center cross-sectional study of pediatric patients with ITP. Following informed consent, blood was collected from ITP patients and bleeding was graded using the Buchanan and Adix Score (J Pediatr 2002) at routine clinic visits or while admitted to the hospital. Bleeding scores were obtained by one of three hematologists blinded to platelet function results, and investigators performing platelet function tests were blinded to clinical results. Platelet function was assessed by whole blood flow cytometric measurement of unstimulated, ADP- or TRAP-stimulated platelet surface activated GPIIb-IIIa (as measured by PAC1 binding), P-selectin, and GPIb and by unstimulated, convulxin-, or ADP plus TRAP-stimulated platelet surface phosphatidylserine expression (as determined by annexin V binding). Platelet count, immature platelet fraction (IPF) and mean platelet volume (MPV) were determined by a Sysmex XE-2100, and platelet forward angle light scatter (FSC) was measured by flow cytometry. Results Platelet function and bleeding scores were evaluated in 34 consecutive consenting pediatric ITP patients (16 female, 18 male, age 9.7 ± 5.7 years [mean ± SD]). ITP was newly diagnosed (< 3 months) in 10 patients, persistent (3 -- 12 months) in 7 patients, and chronic (>12 months) in 17 patients. Platelet count at the time of the blood draw was 47 ± 55 x 109/L. The median bleeding score on day of blood draw was 1 (range 0 to 4). By univariate analysis, higher IPF, and lower platelet count were significantly associated with a higher bleeding score (odds ratio [OR] >1, p<0.05) but MPV was not. Multiple measures of platelet function were associated with bleeding scores by univariate analysis: higher levels of platelet FSC (a measure affected by multiple variables including size) surface GPIb on unstimulated, ADP- or TRAP-stimulated platelets, surface P-selectin on unstimulated platelets, and platelet FSC were associated with increased odds for higher bleeding scores (ORs each >1, p<0.05), while higher ADP- and TRAP-stimulated platelet surface activated GPIIb-IIIa and P-selectin were associated with reduced odds of higher bleeding scores (ORs each <1, p<0.05). After adjustment for platelet count, higher levels of platelet surface P-selectin on unstimulated platelets, GPIb on TRAP-stimulated platelets, and FSC remained significantly associated with increased odds for higher bleeding scores (Figure), but IPF did not. Similarly, after adjustment for platelet count, higher TRAP-stimulated percentage of P-selectin and activated GPIIb-IIIa positive platelets remained significantly associated with reduced odds of higher bleeding scores (Figure). These findings were independent of recent ITP-related treatment. Conclusions In this study of pediatric ITP patients, we identified selected platelet function markers which, independent of platelet count, are associated with increased (platelet FSC, platelet surface P-selectin on unstimulated platelets, and GPIb on TRAP-stimulated platelets) or decreased (TRAP-stimulated percent P-selectin and GPIIb-IIIa positive platelets) odds of high bleeding scores. Possible hypotheses to explain these associations are as follows: 1) Increased P-selectin on unstimulated platelets demonstrates in vivo platelet activation, possibly as a consequence of the recent bleeding. 2) Because platelet activation results in a reduction in platelet surface GPIb and increases in platelet surface activated GPIIb-IIIa and P-selectin, the ORs associated with all of these markers could be explained by reduced ability of platelets in patients with higher bleeding scores to respond to agonists. 3) While platelet FSC is partly related to size, the finding that MPV and IPF, adjusted for platelet count, were not associated with bleeding score suggests that factors other than size account for the association of platelet FSC with higher bleeding scores. Further study is required to validate these findings and determine if differences in platelet function are associated with future risk for bleeding. Disclosures: Off Label Use: Eltrombopag was given to WAS/XLT patients for treatment of thrombocytopenia. Neufeld:Shire: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Apopharma: Consultancy. Michelson:Sysmex: Honoraria.

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Prognostic evaluation of immune thrombocytopenia outcomes in Egyptian children: a retrospective single-center experience

Pediatric Hematology/Oncology and Immunopathology ◽

10.24287/1726-1708-2021-20-3-26-30 ◽

2021 ◽

Vol 20 (3) ◽

pp. 26-30

Author(s):

Aliaa Mohammed Diab ◽

AlRawhaa Ahmed Abouamer ◽

Ghada Saad Abdel Motaleb ◽

Khaled Abdelaziem Eid ◽

Heba Ismaiel Abdelnaiem

Keyword(s):

Platelet Count ◽

Immune Thrombocytopenia ◽

Laboratory Data ◽

Lactate Dehydrogenase Level ◽

Female Gender ◽

University Hospitals ◽

Female Ratio ◽

Chronic Itp ◽

Egyptian Children ◽

Significant Difference

Immune thrombocytopenia (ITP) is the most common cause of thrombocytopenia in children. This retrospective study was designed to analyze presenting features of ITP cases in Benha, evaluate outcomes in children and determine prognostic factors. This research was accepted by Research Ethics Committee (REC) of Faculty of Medicine, Benha University (chairman: Prof. Nermeen Adly Mahmoud). Ethics comittee refrence number MS 40-3/2019. Records of 308 children with ITP in Benha University Hospitals and Benha Children Hospital haematology clinics between May 2014 and January 2021 were retrospectively analyzed. Socio-demographic, clinical, and laboratory data of the studied children such as age, gender, the type of residence, the date of diagnosis, complaints at presentation, preceding vaccination or infection, the type of bleeding, initial platelet count, LDH (lactate dehydrogenase) level, initial treatment, and outcomes were recorded. A total of 308 children diagnosed with ITP were included, clinical courses were determined as newly diagnosed and chronic in 71.4% and 28.6%, respectively. The median age of patients at diagnosis was 5 ± 3.4 years. The male/female ratio was 1.14. The median age at diagnosis was significantly higher in chronic ITP patients (p < 0.001); patients ≥ 10 years were more likely to develop chronic ITP than younger ones (p = 0.029). Regarding residency, seasonality, type of bleeding and history of preceding infection or vaccination, the difference was not statistically significant. Initial platelet counts > 20 × 109 were significantly more prevalent in chronic ITP (p < 0.001). LDH level at presentation was significantly higher in chronic cases (p = 0.046). Initial lines of treatment were the following: steroids, IVIG, and IVIG with steroids (in 88%, 5.2%, and 2.9% of the cases, respectively). A total of 3.9% of the children did not receive any treatment. There was no significant difference in the outcomes between the initial lines of treatment (p = 0.105). In our study, age > 10 years, female gender, higher platelet count and high LDH level at presentation were found to increase the probability of chronic ITP.

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Epidemiology and Management of Immune Thrombocytopenia in Adult Patients in Algeria: A Non-Interventional, Longitudinal, Nationwide Estimation Study

Blood ◽

10.1182/blood-2020-139569 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 3-4

Author(s):

Mohamed-Amine Bekadja ◽

Mohamed Bradai ◽

Hocine Ait Ali ◽

Selma Hamdi ◽

Nadia Boudjerra ◽

...

Keyword(s):

Platelet Count ◽

Immune Thrombocytopenia ◽

Epidemiological Data ◽

Bleeding Risk ◽

Peripheral Circulation ◽

Public Hospitals ◽

Case Report Form ◽

Low Grade ◽

Treatment Regimens ◽

Bleeding Score

Background: Immune thrombocytopenia (ITP), is an acquired immune mediated disease characterized by a platelet count of <50×103/mm3, accelerated destruction of platelets from peripheral circulation, and impaired platelet production. Diagnosis is based on exclusion of other causes of thrombocytopenia. Treatment goal is to ensure sufficient platelet count to prevent bleeding. ITP occurs mainly in women, either at the onset of puberty, or in their 3rd/4th decade, with higher mortality in older patients. To date, no accurate epidemiological data on ITP is available for Algeria. This study assessed the incidence (by age, sex, diagnosis stage, and province), prevalence, characteristics, and treatment regimens received by ITP patients (pts) in Algeria. Methods: This non-interventional, longitudinal, nationwide estimation study investigated the epidemiology and care of ITP pts treated in public hospitals in Algeria from September 2017─August 2018. Data were collected at inclusion visit on a case report form. Data on bleeding score and platelet count were also collected after study termination. Pts ≥16 years (y) of age, either previously (before 1st September 2017) or newly (September 2017─August 2018) diagnosed with ITP, having given written consent, were included. The incidence and prevalence of ITP were estimated with Poisson distribution (95% confidence interval [CI]). Results: Overall 1,746 pts were listed, of whom 587 without consent. Of the 1,164 enrolled pts, 1,159 were included (male: 264 [22.8%]); 5 pts (0.4%) were excluded for major protocol deviations. Among eligible pts, 173 (14.9%) were newly and 986 (85.1%) had been previously diagnosed with ITP. No comorbidities conferring bleeding risk were found in 966 pts (83.3%). At diagnosis, median age was 36y (quartiles: 25y, 50y) and platelet count (103/mm3) was 0-30 in 124 (71.7%), 30-50 in 20 (11.6%), and 50-100 in 28 (16.2%) pts. Khellaf score was ≤8 for 45 (26.0%) and >8 for 8 (4.6%) pts; 120 pts (69.4%) had missing Khellaf score. Bleeding risk (as per WHO bleeding score) was low (grade 0) in 50 (28.9%), grade I in 24 (13.9%), grade II in 34 (19.7%), grade III in 52 (30.1%), and grade IV in 13 (7.5%) pts. 55 (31.8%) pts were asymptomatic, 58 (33.5%) were ecchymotic, and 60 (34.7%) were severely hemorrhagic. Steroids comprised the major treatment for both new (n [%]: 136 [78.6]) and previously (795 [80.7]) diagnosed ITP pts. First line ITP treatments included corticosteroids (937 [80.8]), immunoglobulins (39 [3.4]), antineoplastic agents (15 [1.3]), rituximab (14 [1.2]) and antibacterials (2 [0.2]). Last/ongoing treatments at inclusion comprised corticosteroids (712 [72.2]), rituximab (56 [5.7]), immunoglobulins (30 [3.0]), romiplostim (19 [1.9]), and antibacterials (4 [0.4]). Among previously diagnosed ITP pts, 172 (17.4%) had a splenectomy with a median time from ITP diagnosis of 19 months. Incidence of ITP in pts ≥16y was 0.85 cases (95% CI: 0.75, 0.96) per 100,000 inhabitants. Incidence increased with age from 0.5 (95% CI: 0.43, 0.68) in pts aged 15-35y to 2.4 (95% CI: 1.60, 3.51) in pts ≥75y old. Female pts had a higher incidence of ITP (1.2 [95% CI: 1.02, 1.37]) vs male pts (0.5 [95% CI: 0.43, 0.67]; male:female ratio 0.3). Incidence of ITP varied with diagnosis stage (asymptomatic: 0.4 [95% CI: 0.31, 0.45]; ecchymosis: 0.1 [95% CI: 0.10, 0.19]; severe hemorrhage: 0.1 [95% CI: 0.06, 0.13]), and province (lowest: 0.1 [95% CI: 0.02, 0.92] in a public site in Tebessa; highest: 1.6 [95% CI: 0.93, 2.89] in a public site in Sidi Bel Abbès). Prevalence of ITP was 5.7 (95% CI: 5.39, 5.93) per 100,000 inhabitants. Prevalence increased with age from 3.2 (95% CI: 2.78, 3.67) in pts aged 15-25y to 11.9 (95% CI: 9.68, 13.08) in pts aged 65-75y, then decreased in pts ≥85y old (7.6 [95% CI: 4.79, 12.06]). Female pts had a higher prevalence of ITP (8.8 [95% CI: 8.33, 9.29]) vs male pts (2.6 [95% CI: 2.34, 2.85]). Conclusion: The incidence and prevalence of ITP in Algeria were higher in females and increased with age conforming to global trends, but lower than occidental data thus requiring further investigations. Corticosteroids were the most commonly used agents in different lines of treatment; splenectomy was the second option in cases of corticosteroid failure. Rituximab and romiplostim were the last/ongoing treatment before inclusion for a small number of pts. The study highlighted the need for more data on the use of romiplostim prior to splenectomy for adult ITP pts in Algeria. Disclosures Tiaiba: Amgen Middle East:Current Employment.Saad:Amgen Inc:Current Employment.

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Results of the Russian Registry of Primary Immune Thrombocytopenia in Pediatric Patients

Blood ◽

10.1182/blood.v126.23.4643.4643 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4643-4643

Author(s):

Anastasia Shamardina ◽

Inna Markova ◽

Tatyana Sycheva ◽

Elena Volodicheva ◽

Alexander Rumyantsev ◽

...

Keyword(s):

Platelet Count ◽

Immune Thrombocytopenia ◽

Disease Onset ◽

Specific Treatment ◽

Complete Response ◽

Second Line ◽

Second Line Therapy ◽

Chronic Itp ◽

Line Therapy ◽

Clinically Significant

Abstract Study objectives We aim to evaluate disease characteristics and treatment practices of pediatric pts. with Immune thrombocytopenia (ITP) in Russia. Materials and methods The ITP Registry was a multicenter, prospective, observational cohort study. Inclusion criteria: diagnosis of primary ITP, informed consent of the patient/guardians. Exclusion criteria: secondary or congenital thrombocytopenia. Data from medical records were registered in the e-CRF in average every 3 months. Descriptive statistics were used. Patients were registered since June 2011 till June 2014. Results Ninety-three pediatric pts, 46 male (49.5%) and 47 female (50.5%) with a median age 8.4 yrs (range 0.5-17.8) from 5 centers in various regions of Russia were included. The mean observation period reached 17.1 ± 6.5 mo (range1.4 to 28.6 months). Seventy (75.3%) pts had acute and 24.7% pts had insidious disease onset. The presence of trigger factors for ITP development was found in more than half of the cases (in 61.3% of patients), they are listed in Table 1. Table 1. Triggers N % No triggers 36 38.7% Infection 46 49.5% Vaccination 8 8.6% Other 3 3.2% Total 93 100% Median disease duration at enrollment was 1.07 years (range 0 to 16.7 yrs). ITP duration shorter than 5 years at the enrollment was reported in 89.2% pts, up to 1 year - in 43 (46.2%), 1- 5 years - in 40 (43%), 5-10 years - in 8 (8.6%), >10 years - in 2 (2.2%) pts. Newly diagnosed ITP was reported in 35 (37.6 %) pts, persistent ITP - in 12 (12.9 %), chronic ITP - in 46 (49.5 %) pts.Median platelets count was 12,0 x 109/L (range 0.0 - 72.0 109/L). Ninety-two (98%) pts experienced hemorrhagic manifestations during the course of ITP: skin hemorrhages - in 98.9%, oral bleeding - in 15.1%, epistaxis - in 36.6%, gastrointestinal bleeding - in 1.1%, intracranial bleeding - in 1.1%, hematuria - in 1.1%, and other hemorrhages - in 9.7% of pts. Relationship between hemorrhagic syndrome and platelet count at the enrollment is provided in table 2. Table 2. Relationship between hemorrhagic syndrome and platelet count (at enrollment) Hemorrhage highest grade according to WHO Platelet count (visit 1) Total pts / % < 30,000 30,000 -50,000 >50,000 0 3 5.5% 3 5.5% 49 89.1% 55 100% 1 11 40.7% 5 18.5% 11 40.7% 27 100% 2 5 62.5% 0 0% 3 37.5% 8 100% 3 2 66.7% 1 33.3% 0 0% 3 100% Total 21 22,6% 9 9.7% 63 67.7% 93 100% Severe course of ITP after enrollment was observed in 12 (13%) pts (of whose 6 (6.5%) had clinically significant hemorrhage at the disease onset and 6 (6.5%) had new clinically significant hemorrhages during follow-up period. Refractory ITP at enrollment was reported in 9 (9.7%) pts and was associated with the resistance to the first-, second- and subsequent lines of therapy. At enrollment 42 (45.2%) pts received specific treatment for ITP. Before enrollment, splenectomy was reported in only 1 (1.1%) 14-years old patient who had a complete response. During the study, splenectomy was performed in 6 (6.6%) pts with chronic ITP; the duration of the disease at the time of splenectomy varied from 2 to 10 years, with average duration of 4.69 years (median - 4.5 years). Complete response to splenectomy was observed in 3 (50%) pts, a partial response - in 2 (33.3%), no response - in 1 (16.7%) patient. Loss of response to splenectomy was not reported. During the study, severe ITP was reported in 8 (8.7%) pts, 41 (44.6%) pt had various hemorrhagic manifestations of ITP at least at 1 visit, grade IV hemorrhagic syndrome was not reported. Thirty-eight (41%) pts received 1-st line treatment: glucocorticosteroids (GCS) - 23 (60.5%) pts, IVIG - 5 (13.2%), alfa-interferons -16 pts (42.1%). Twenty-three pts (24.7%) received second-line therapy: GCS - 1 (4.3%), IVIG -1 (4.3%), immunosupression - 1 (4.3%), rituximab - 2 (8.7%), romiplostim - 11 (47.8%), eltrombopag - 14 (60.9%). Conclusion For the first time new information on the features of the disease and patterns of management of pediatric pts with primary ITP in Russia was obtained in a prospective study. Interestingly, the preferred therapy for the 2nd or subsequent lines are TPO receptor agonists used outside the approved indications in research institutions, based on published clinical trial data. Splenectomy rate before and during the study was only 7.5% (7 pts) with chronic ITP; in 1 child (14.3%) splenectomy was ineffective. Low acceptance of splenectomy suggests TPO-mimetics as potential second-line therapy. In total, good disease control is achievable in the majority of pediatric pts with ITP. Disclosures Off Label Use: use of TPO-mimetics in children.

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Clinical and laboratory predictors of chronic immune thrombocytopenia in children: a systematic review and meta-analysis

Blood ◽

10.1182/blood-2014-04-570127 ◽

2014 ◽

Vol 124 (22) ◽

pp. 3295-3307 ◽

Cited By ~ 62

Author(s):

Katja M. J. Heitink-Pollé ◽

Joyce Nijsten ◽

Chantal W. B. Boonacker ◽

Masja de Haas ◽

Marrie C. A. Bruin

Keyword(s):

Risk Factors ◽

Systematic Review ◽

Platelet Count ◽

Immune Thrombocytopenia ◽

Meta Analysis ◽

Chronic Itp ◽

Insidious Onset ◽

Key Points ◽

Immunoglobulin Treatment ◽

Chronic Immune Thrombocytopenia

Key Points Older age, insidious onset, no preceding infection, mild bleeding, and higher platelet count are the strongest risk factors for chronic ITP. Intravenous immunoglobulin treatment seems to protect against development of chronic ITP.

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COVID-19 vaccination associated severe immune thrombocytopenia

Experimental Hematology and Oncology ◽

10.1186/s40164-021-00235-0 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Syed Raza Ali Shah ◽

Sherpa Dolkar ◽

Jacob Mathew ◽

Prakash Vishnu

Keyword(s):

Platelet Count ◽

Medical History ◽

Blood Test ◽

Immune Thrombocytopenia ◽

Physical Exam ◽

Past Medical History ◽

Platelet Counts ◽

Chronic Itp ◽

Oral Dexamethasone ◽

History Of

Abstract Background Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has emerged as a deadliest global pandemic after its identification in December 2019 in Wuhan, China resulting in more than three million deaths worldwide. Recently FDA issued emergency authorization for three vaccines for prevention of COVID-19. Here in, we report three cases of severe immune thrombocytopenia (ITP) following COVID-19 vaccination and their clinical course. Case presentations Case #1: 53 year old male with past medical history of Crohn’s disease was admitted for myalgias and diffuse petechial rash 8 days after receiving second dose of Pfizer-BioNTech COVID-19 vaccine. A complete blood test showed a platelet count of 2 × 109/L. Patient did not have a prior history of thrombocytopenia and other causes of thrombocytopenia were ruled out by history and pertinent lab data. He received two doses of intravenous immunoglobulin and oral dexamethasone for 4 days resulting in normalization of platelet counts. Case #2: 67 year male with past medical history of chronic ITP in remission was admitted for melena 2 days after receiving his first dose of Pfizer-BioNTech COVID-19 vaccine. A complete blood test showed a platelet count of 2 × 109/L. Physical exam showed generalized petechiae. There was no history of recent flares of ITP and patient had normal platelet counts following his splenectomy 4 years ago. He received two doses of IVIG and oral dexamethasone for 4 days with gradual improvement in platelet counts. Case #3: 59 year old female with past medical history of chronic ITP secondary to SLE was admitted for bloody diarrhea 2 days after receiving her first dose of Johnson and Johnson COVID-19 vaccine. Physical exam was unremarkable. A complete blood test showed platelet count of 64 × 109/L which dropped to 27 × 109/L during hospital course. She received oral dexamethasone for 4 days with improvement in platelet counts. Conclusion COVID-19 vaccination induced ITP has been recently acknowledged. However, given very few cases and limited data, currently there are no guidelines for management of ITP caused by COVID-19 vaccine as well as vaccination of people with predisposing conditions.

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Increased FVIII and Anti-Phospholipid Antibodies Do Not Modify the Clinical Course of Chronic Immune Thrombocytopenia

Blood ◽

10.1182/blood.v124.21.5013.5013 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5013-5013

Author(s):

Meet Kumar ◽

Maitryee Bhattyacharyya ◽

Shyamali Datta

Keyword(s):

Platelet Count ◽

Lupus Anticoagulant ◽

Immune Thrombocytopenia ◽

Clinical Course ◽

Conflicts Of Interest ◽

Age Groups ◽

Platelet Counts ◽

Bleeding Score ◽

Chronic Immune Thrombocytopenia

Abstract INTRODUCTION: Immune thrombocytopenia is a heterogenous disease with majority patients having a mild bleeding phenotype and one-fourth being asymptomatic. Bleeding episodes are usually seen in patients with platelet counts typically <30,000/cumm. There is no study till date to identify patients with platelet count <30,000/cumm and at high risk for bleeding. Although patients who harbor anti phospholipid antibodies have a higher risk of arterial and venous thrombosis, it is not known whether presence of acquired thrombophilia modifies the clinical course of bleeding in low platelet count ITP patients. We evaluated the role of FVIII and lupus anticoagulant in modifying the clinical course of such patients. MATERIALS AND METHODS: Patients of all age groups with persistent and chronic immune thrombocytopenia were eligible for study enrolment. Patients with acute ITP and secondary ITP were excluded. Eligible patients were evaluated with baseline parameters, ITP bleeding score (ITP-BAT, version 1.0 by IWG on ITP) at baseline and then at every visit and FVIII and lupus anticoagulant at baseline and repeat at six months.Patients were called for monthly scheduled visits if platelet counts were >30,000/cummand more frequently at lower platelet counts. Patients with any evidence of underlying infection or raised c-reactive protein and procalcitonin were deferred evaluation.All patients were treated as per institutional protocol to avoid treatment bias. Patients were followed up for one year. We finally calculated the average bleeding scores of all patients at different platelet counts (for eg. average of skin, mucosal and organ bleeding scores of all patients that had platelet counts <10,000/cumm, 10-30,000/cumm etc) and analysed it with FVIII and anti-phospholipid antibody levels. RESULTS: A total of 45 patients were enrolled with M:F=1:3.2. Median age of patients is 28years (3-72 years). Two patients were excluded (both progressed to SLE) and another two were lost to follow-up. Median duration from ITP diagnosis to study enrolment was 62.4months (8-590 months). Median follow-up of all patients was 14.2 months (13.2-16.4 months). Nine patients had persistent and 32 patients had chronic ITP. ITP-BAT could differentiate intensity of bleeding at different platelet counts by means of bleeding scores (Table 1). Correlation of bleeding scores with prothrombotic markers could not establish a disease course modifying relationship between the two (Table 2). CONCLUSION: Presence of high FVIII and anti phosphoilipid antibodies donot modify the bleeding risks in patients with ITP and low platelet counts. Table 1Platelet count (x109/cumm)Total episodesAverage bleeding scoreP value<1014S2.4 M1.4 O0 0.00210-3015S1.4 M0.9 O030-6018S0.3 M0.1 O0>600S0 M0 O0 Table 2 Platelet count <10,000/cumm Platelet count 10-30,000/cumm N Av BS P= N Av BS P= FVIII>150 5 S2.5M1.1O0 0.02 6 S1.1M0.8O0 0.1 FVIII<150 9 S2M0.7O0 11 S1.4M0.6O0 LA1:LA2>2 1 S2.2M1.5O0 0.03 S1.1M0.8O0 0.2 LA1:LA2<1 12 S2.6M1.2O0 S1.2M0.6O0 Table 3 Platelet count 30-60,000/cumm Av BS P= FVIII>150 4 S0.9M0.1O0 0.2 FVIII<150 11 S0.3M0.1O0 LA1:LA2>2 Nil LA1:LA2<1 9 S1.1M0.4O0 Disclosures No relevant conflicts of interest to declare.

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