Treatment Of Immune Thrombocytopenic Purpura Research Articles

The Association Between Human Leukocyte Antigens and ITP, TTP, and HIT.

Autoimmune thrombocytopenia in immune thrombocytopenic purpura (ITP), thrombotic thrombocytopenic purpura (TTP), and heparin-induced thrombocytopenia (HIT) is associated with immunologic degradation of platelets and reduced platelet counts in patients, leading to bleeding risk in patients. Considering the role of human leukocyte antigens (HLA) in the development of immune response, in this review, we examine the relationship between HLA and pathogenesis of the above-mentioned diseases. Relevant English-language literature was searched and retrieved from Google Scholar search engine and PubMed database (1979 to 2018). The following keywords were used: "Immune Thrombocytopenic purpura," "Thrombotic Thrombocytopenic Purpura," Human Leukocyte Antigen," and "Heparin-induced thrombocytopenia." In autoimmune thrombocytopenia, HLA molecule presents self-antigens or foreign antigens similar to self-antigens, provoking an immune response against platelets that results in the degradation of platelets in peripheral blood and possible bleeding in the patient. For example, HLA-DRB1 *11 presents the self-antigen and induces an immune response against ADAMTS13, which is associated with thrombocytopenia in TTP patients. HLA alleles can be used as prognostic biomarkers for immunologic disorders of platelet such as ITP, TTP, and HIT. Different DRB1 alleles enable the assessment of resistance to common ITP treatments as well as disease prognosis. Due to the genetic association between HLA-DR1 and HLA-DQ1 alleles and the role of HLA-DRB1 *11 in TTP, the HLA-DQB1 *02: 02 allele may also play a role in TTP pathogenesis.

Efficacy and safety of thrombopoietin receptor agonists in children with chronic immune thrombocytopenic purpura: meta-analysis

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder presenting with low platelet count <100 × 109/L. The condition affects both adults and children. Thrombopoietin receptor agonists (TPO-RAs) are second-line of therapy that includes Romiplostim and Eltrombopag, which stimulate the production of normally functioning platelets. Although the biological effect of these drugs is well established, there has not been a meta-analysis in children. To estimate the efficacy and safety of Romiplostim and Eltrombopag, we performed a systematic review and meta-analysis in children with chronic ITP. Systematic literature search was conducted in the following database: PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL). Review Manager 5.3 for Windows was used to analyze the data. Five randomized controlled trials with total of 261 pediatric patients from 1–17 years of age were included. The efficacy and safety analysis showed TPO-RA groups were superior over placebo, and there was no difference in adverse event occurrence between TPO-RA (Romiplostim and Eltrombopag) and placebo groups. The efficacy and safety of Eltrombopag did not differ significantly from those of Romiplostim. Both drugs were effective in treatment of children with chronic ITP. Our findings extend the currently available data on ITP treatment and is helpful for pediatric health providers and for the design of future clinical trials.

Case report: a case of rare coexistence of immune thrombocytopenic purpura in a child with acute lymphoblastic leukaemia

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder resulting in the peripheral destruction of platelets. It affects 4–6 children per 100,000 annually.1 Co-existing ITP and acute lymphoblastic leukaemia (ALL) is rarely reported in the medical literature. This case report describes an unusual case of refractory ITP in a 7-year-old female during treatment for ALL, who presented with persistent thrombocytopenia with an associated bleeding phenotype. A trial of withholding chemotherapy failed to improve the platelet count and a bone marrow biopsy was performed for further evaluation. Bone marrow biopsy did not demonstrate evidence of relapsed ALL, however did demonstrate an increase in megakaryocytes consistent with ITP. Multiple lines of treatment were trialled unsuccessfully including multiple courses of high dose steroids, immunoglobulin and eltrombopag with supportive care including platelets and tranexamic acid for bleeding episodes. Romiplostim was initiated with an improvement in platelet count within a week and resolution of bleeding complications. This case demonstrates that whilst rare, the diagnosis of ITP should be considered in patients with refractory thrombocytopenia despite ongoing active immunosuppressive treatment for ALL. Furthermore, romiplostim has been effective in the treatment of ITP in this case study and could be considered in similar cases.

Eltrombopag Plus Pulsed Dexamethasone As First Line Therapy for Subjects with Immune Thrombocytopenic Purpura (ITP)

▪Background: Eltrombopag is an oral thrombopoietin receptor agonist that has been licensed for use as second line therapy in ITP patients. For most subjects, platelet counts usually return to baseline within 2 weeks of eltrombopag discontinuation, however, up to 15% of subjects may maintain a prolonged response after discontinuation (BJH Volume 165(6) 2014 865-869). Therefore, we conducted a pilot study to evaluate whether a 12-week course of eltrombopag plus pulsed dexamethasone as first line therapy can increase the proportion of patients with prolonged response.Methods: This multicenter, single arm, open-label pilot study was performed on subjects with newly diagnosed ITP. Eligible subjects had confirmed ITP and platelet counts <30×109/L or platelet counts < 50×109/L and significant bleeding symptoms (WHO bleeding scale 2 or above). Patients must have no prior ITP treatment except platelet transfusions. All patients provided written informed consent before enrolment. This study was conducted in accordance with the Declaration of Helsinki.Eligibility criteria included isolated thrombocytopenia with exclusions of secondary immune or drug-induced thrombocytopenia, cancer and pregnancy related thrombocytopenia and virus induced thrombocytopenia. Bone marrow examination is not mandatory but must be consistent with peripheral platelet consumptions with no features of dysplasia, extensive fibrosis, aplasia, marrow infiltration if performed.Treatment consisted of eltrombopag 25-75mg daily according to platelet response for 12 weeks plus pulsed dexamethasone, 40mg daily for 4 consecutive days every 4 weeks for 1-3 courses. The primary endpoint was prolonged response defined as platelet counts > 50×109/L for more than 6 months without any ITP therapy after completion of 12-week therapy.The reported prolonged response rate of dexamethasone alone is around 25%, a sample size of 60 subjects will be required to detect a doubling of the prolonged response rate at a significant level of 0.05 with power of 0.9. Differences between prolonged responder and relapsed subject groups were analyzed by the Student's t-test. P values <0.05 were considered significant.Results:46 subjects were enrolled from February 2015 to July 2018. The median age was 40 years, range 18 to 81; 29 were female and 17 were male. Median platelet counts at baseline were 18×109/L, range 1 to 44×109/L. One subject withdrew consent before starting treatment. One was withdrawn because of protocol violations. Three subjects did not have significant increase in platelet counts during the entire 12 weeks treatment despite a maximum of eltrombopag 75mg daily and 3 courses of pulsed dexamethasone. One of them subsequently turned out to be amegakaryocytic thrombocytopenia. These 5 subjects were still included in the final analysis.Twenty-nine subjects had good initial response to treatment and completed at least 6 months follow-up (Fig 1), 19 of them had achieved the primary end point of platelet counts count> 50×109/L for more than 6 months after discontinuation of eltrombopag. The median platelet counts at 6 months were 150×109/L (range 53 to 371×109/L), Average eltrombopag dose was 36.8mg daily and average pulsed dexamethasone was 2.2 courses. Eleven subjects maintained prolonged response for 12 months or more.Four subjects are still receiving treatment and 8 subjects are still on the 6 months off-therapy observation period (median follow up is 12 weeks, range 4 to 21 weeks).Ten subjects relapsed after discontinuation of eltrombopag(Table 1). The median time to relapse was 47.8 days, range 15 to 148 days. Average daily eltrombopag was 45mg and average pulsed dexamethasone was 2.5 courses.So far, the prolonged response rate of 56 % (19/34) among 34 evaluable subjects is very encouraging. According to statistical analysis, seven more prolonged responders among the remaining 26 subjects (14 yet enrolled and 12 pending final evaluation) would suggest that 12-week of eltrombopag plus pulsed dexamethasone as first line therapy may significantly improve prolonged response rate in ITP patients. All subjects tolerated the treatment well and no Grade 3 or above adverse effects were reported.Conclusions: Eltrombopag plus pulsed dexamethasone is an effective and safe treatment for ITP as a first line therapy that can provide sustained prolonged response in adults. This therapy could be a new treatment option for ITP subjects. DisclosuresCheng:Novartis: Research Funding; BMS: Honoraria, Speakers Bureau; Astrazeneca: Honoraria, Speakers Bureau.

Psychiatric Disorders and Quality of Life in Egyptian Patients with Chronic Immune Thrombocytopenic Purpura: A Single Center Study.

The impact of chronic immune thrombocytopenic purpura (ITP) on the psychological health and quality of life is evident among children and adolescents. We aimed to describe psychological disorders and assess quality of life in children with chronic ITP and compared their results with their healthy peers. A cross-sectional comparative study was carried out in a tertiary care university-affiliated hospital during a period from November, 2015 till April, 2018. We enrolled 119 children with chronic ITP and compared with 220 healthy peers. Relevant demographic and clinical data were collected and statistically analyzed. Quality of life for both patients and control groups was measured using pediatric quality of life inventory version 4 (Arabic one). Also psychiatric evaluation of both groups was done using Arabic version of Mini-International Neuropsychiatric Interview for Children (Mini-KID). Majority of patients (90.7%) exhibited mucocutaneous bleeding. Most of patients (61.3%) did not need any definitive treatment for chronic ITP while 38.6% received second line therapy. About one-third of the patients needed rescue medications to control active bleeding. The scores of all sub-scales of Peds QL 4.0 were significantly decreased among patients group when compared to their healthy peers (P < 0.001). General anxiety disorder and oppositional defiant disorders were the commonest psychiatric disorders among children with chronic ITP. Quality of life in children with chronic ITP is markedly impaired with occurrence of a variable spectrum of psychiatric disorders among the studied patients.

Subcutaneous Anti-D versus intravenous methylprednisolone for the treatment of immune thrombocytopenic purpura

Background: Established treatment option for immune thrombocytopenic purpura (ITP) are intravenous immunoglobulin (IVIg), anti-D immunoglobulin’ and high dose intravenous methyl prednisolone (HIVMP). The present study was undertaken to compare the efficacy of subcutaneous bolus anti-D over HIVMP in the treatment of ITP.Methods: A randomized clinical trial was conducted on a total 20 children with ITP, presented with extensive bleeding manifestation and platelet count &lt;20 × 109/L;10 children received single dose subcutaneous anti-D (75 microgram/kg) and 10 children received HIVMP (30 mg/kg/dose) for 3 consecutive days. Patients were monitored for response to treatment and adverse events, platelet count and hemoglobin label were done in all patients at 24-hour, 48-hour, 72 hour, 1st week, 2nd week, 1st month, 2nd month and 3rd month after treatment to observe the change. Response rate define as a platelet count over 20 × 109/L within 72 hours of treatment. All the data were analyzed with the help of SPSS software version 16.0.Results: By 24 hours of treatment 40% patient of anti-D and 10% patients of HIVMP group had platelet count &gt;20 x109/L, by 72 hours 90% patients of both group achieved complete response (P =1.750). In HIVMP group the rate of remission gradually decreasing but in anti-D group it was persistently remain high. In anti-D group hemoglobin concentration decreased in 80% cases (P=0.023) but rate of decrease was not significant. New hemorrhage or significant extension of hemorrhage did not observe in any group.Conclusions: A single dose of subcutaneous anti-D raised platelet count in children with ITP more rapidly and effectively than HIVMP (30 mg/kg/dose) with an acceptable safety profile.

Therapeutic Doses of Eltrombopag do not Inhibit Hepatic BCRP in Healthy Volunteers: Intravenous Ceftriaxone as a Model.

Ceftriaxone elimination occurs through breast cancer resistance transporter (BCRP) and multidrug resistance-associated protein 2 (MRP-2) which are expressed on the canalicular membrane of hepatocytes. Eltrombopag, a thrombopoetin receptor agonist used in the treatment of immune thrombocytopenic purpura, is reported in in vitro studies as an inhibitor of intestinal BCRP but not an inhibitor of hepatic BCRP. Thus, the present study evaluates the effect of therapeutic doses of eltrombopag on the clinical pharmacokinetics of intravenous ceftriaxone. Healthy adult (n=12) were treated with oral doses of eltrombopag (0, 25 or 50 mg) 28 and 4 h prior to intravenous ceftriaxone administration (1g). Serial blood samples were collected up to 48 h after ceftriaxone administration and plasma samples were analysed by LC-MS/MS using 50 μL aliquots (total concentration) and 100 μL (unbound concentration). A method to analyze total and unbound ceftriaxone in plasma using LC-MS/MS was developed and validated with linearity from 1 to 200 μg/mL. Both methods are sensitive, precise and accurate with coefficients of variation less than 15% in the study of inter- and intra-assay precision and accuracy. Ceftriaxone pharmacokinetics in healthy adults were described using a bicompartmental model, with a mean clearance of 0.96 L/h (CI95% 0.71-1.20) and AUC0-∞of 1106 mg.h/mL (CI95% 811-1400) for volunteers that received only ceftriaxone; clearance of 0.95 L/h (CI95% 0.77-1.13) and AUC0-∞ of 1083 mg.h/mL (CI95% 876-1290) for volunteers that received ceftriaxone plus 25 mg of eltrombopag and clearance of 0.96 L/h (CI95% 0.74-1.19) and AUC0-∞ of 1072 mg.h/mL (CI95% 872-1273) for volunteers that received ceftriaxone plus 50 mg of eltrombopag. The results do not support the existence of a clinical pharmacokinetic drug interaction involving hepatic BCRP in human subjects receiving intravenous ceftriaxone and oral eltrombopag.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Integrated Network Pharmacology and Metabolomics Analysis of the Therapeutic Effects of Zi Dian Fang on Immune Thrombocytopenic Purpura.

Current hormone-based treatments for immune thrombocytopenic purpura (ITP) are associated with potentially serious adverse reactions. Zi Dian Fang (ZDF) is a multi-target Traditional Chinese Medicine (TCM) used to treat both the symptoms and root causes of ITP, with fewer side effects than hormone-based treatments. This study analysis of the therapeutic effects of ZDF on ITP from three aspects: platelet proliferation, immunoregulation, and inflammation. After detection of 52 chemical constituents of ZDF by UPLC-Q-TOF/MS, The main targets and pathways affected by ZDF were screened by network pharmacology and verified by Western blot and ELISA. Meanwhile, metabolomics analysis were applied to a mouse model of ITP to identify and screen endogenous terminal metabolites differentially regulated by ZDF. Integrated network pharmacology and metabolomics analysis of the therapeutic effects of ZDF on ITP may be as follows: ZDF counteracts ITP symptoms mainly by inhibiting Ras/MAPKs (Ras/Mitogen-activated protein kinases) pathway, and the expression of upstream protein (Ras) and downstream protein (p-ERK, p-JNK, p-p38) were inhibited, which affects the content of effect index associated with proliferation (Thrombopoietin, TPO; Granulocyte-macrophage colony stimulating factor, GM-CSF), inflammation (Tumor necrosis factor-α, TNF-α; Interleukin-6, IL-6), immune (Interleukin-2, IL-2; Interferon-gamma, IFN-γ; Interleukin-4, IL-4), so that the body’s arginine, Δ12-prostaglandin j2 (Δ12-PGJ2), 9-cis-Retinoic Acid, sphingosine-1-phosphate (S1P), oleic acid amide and other 12 endogenous metabolites significantly changes. Considering the established safety profile, the present study suggests ZDF may be a useful alternative to hormone-based therapies for the treatment of ITP.

Rituximab - A novel therapy for severe ITP in pregnancy: A case report.

Rituximab is a novel second-line agent for the treatment of immune thrombocytopenic purpura. Minimal data exist on the use of rituximab in pregnancy. This case illustrates the successful treatment of severe immune thrombocytopenic purpura diagnosed in pregnancy, refractory to all other medical management. A 32-year-old nulliparous woman was diagnosed with severe immune thrombocytopenic purpura at the time of booking for antenatal care (platelet level of 13 × 109/L). Standard treatment failed to adequately increase her platelet count. Therapy with rituximab was instituted, and her platelet count rose to normal levels, without side effects, and remained at a normal level throughout the pregnancy. There were no maternal or neonatal ill-effects of rituximab therapy. Rituximab is potentially a safe treatment option for the management of immune thrombocytopenic purpura in pregnancy with good maternal and neonatal outcome when conventional treatments have been unsuccessful. Research is limited to case reports, and therefore limited information currently exists to guide clinicians.

Efficacy of treatment immune thrombocytopenic purpura in pregnancy with corticosteroids and intravenous immunoglobulin: a prospective follow-up of suggested practice.

: The current study is performed to assess a routine for treatment of immune thrombocytopenic purpura in pregnancy. A prospective programme for monitoring and treatment with intravenous immunoglobulin or cortisone in pregnancies with immune thrombocytopenic purpura was suggested to all delivery units in Sweden. Treatment should be avoided if platelet counts were more than 20 × 10/l during pregnancy with no bleeding complications and with a target of 100 × 10/l at delivery. Descriptive statistics and logistic regression analysis were used. Seventy-five pregnancies were followed; treatment was given in 29 (39%) of the pregnancies; in 13 intravenous immunoglobulin, in six cortisone, in nine a combination of both immunoglobulin and cortisone and in one platelets was given. The mean platelet increase before delivery after immunoglobulin was 46 × 10/l approximately 3 days later. At delivery, 34 (45%) of all pregnancies reached target platelet level more than 100 × 10/l, whereas five (7%) had platelets less than 50 × 10/l. Mode of delivery and blood loss were similar to a reference group. Of the neonates, 23% had platelets less than 50 × 10/l with a nadir reached on day 2-4; 9% required treatment. Women with platelets less than 20 × 10/l in pregnancy or with prior neonatal thrombocytopenia were at a, respectively, five-fold and eight-fold increased risk of neonatal thrombocytopenia. A routine to avoid treatment when platelets are at least 20 × 10/l during pregnancy and to aim for 100 × 10/l at delivery seem safe. Severe maternal thrombocytopenia and prior neonatal thrombocytopenia were predictors of neonatal thrombocytopenia.

Dapsone Induced Agranulocytosis And Hemolytic Anemia During The Treatment Of Immune Thrombocytopenic Purpura

Dapsone Induced Agranulocytosis And Hemolytic Anemia During The Treatment Of Immune Thrombocytopenic Purpura

Effect of thrombopoietin receptor agonists on leukocyte and haematopoietic stem and progenitor cells in the peripheral blood of patients with immune thrombocytopenic purpura.

The thrombopoietin receptor agonists (TPO-RAs), romiplostim and eltrombopag, stimulate megakaryopoiesis and thereby increase platelet counts. Both drugs are increasingly used in the treatment of immune thrombocytopenic purpura (ITP). To assess the effect of TPO-RAs on trilineage haematopoiesis, colony-forming cell (CFC) assays were performed on peripheral blood mononuclear cells of 8 healthy donors and 52 ITP patients. Additionally, we revaluated the regular and complete blood counts (CBCs) performed during romiplostim therapy in 45 patients and the CBCs performed in 9 patients during eltrombopag therapy. The clonogenic capacity of PBMCs was significantly increased in patients treated with TPO-RAs compared with healthy donors and untreated patients [BFU-E, 69±47; CFU-GM, 61±48; CFU-GEMM, 16±11; CFU-total, 145±94; P values <0.05)]. Relative leukocytosis was observed in routine blood counts in 12 of 45 (26%) patients treated with romiplostim. The regular CBCs, performed time dependent within the first 5days, revealed a maximum increase of leukocytes on days 2 and 3 following romiplostim administration. There were no significant changes in red blood cell parameters. None of the affected patients did recognise any significant symptom, which may be related to leukocytosis. Similarly, we observed a statistically significant increase of leukocyte count in a small cohort of ITP patients (n=9) in whom CBCs were controlled following treatment initiation (P=0.044). Our results indicate that TPO-RAs may also mobilize haematopoietic stem and progenitor cells (HSPCs) in peripheral blood and the occurrence of such relative leukocytosis may signalize an early symptom of myelofibrosis due to treatment with TPO-RAs.

Treatment of immune thrombocytopenic purpura associated with cytomegalovirus infection in a child with pre-B cell acute lymphoblastic leukaemia after central nervous system relapse

A 13-year-old male patient with a history of pre-B cell acute lymphoblastic leukaemia (ALL) with isolated central nervous system relapse on maintenance chemotherapy presented with severe thrombocytopenia refractory to platelet...

Comparative treatment-related adverse event cost burden in immune thrombocytopenic purpura

Aims: Real-world evidence on the safety profile and costs associated with immune thrombocytopenic purpura (ITP) treatment in adults is lacking. This study quantifies and compares adverse event (AE) crude rates and costs associated with ITP treatments as found in claims data.Materials and methods: A retrospective claims-based analysis was conducted using IMS Pharmetrics Plus database. Included patients were ≥18 years old, with a diagnosis of ITP (2007–2012); an ITP-related claim for anti-D, intravenous immunoglobulin (IVIG), rituximab, romiplostim, or eltrombopag; and 1-year continuous enrollment (3-years for rituximab) during follow-up. AEs and event costs were identified during active treatment, defined from the first claim of each drug to a pre-defined treatment gap or end of study period. Descriptive statistics were reported with Wilcoxon rank-sum significance tests.Results: A total of 2,518 patients were identified (mean age = 50.8 (±16.3 years); 55.8% male). Of all patients, 22.8% experienced any AE. Significantly fewer anti-D patients had any AE (13.8% vs IVIG: 21.1%, rituximab: 29.4%, romiplostim: 28.1%, eltrombopag: 22.4%). Nausea/vomiting and arthralgia/musculoskeletal pain were most common across treatments, and hemolytic events did not differ significantly across treatments. Most costly AEs were urinary tract infection, aseptic meningitis, and fever ($5000+/case); headache, nasal congestion, and hemolytic event were $4,000–5,000/case. Cost per AE did not differ by treatment.Limitations and conclusions: Although lower than trial-based AE rates, claims for ITP treatment-related AEs are common, with higher numbers for rituximab and lower numbers for anti-D. This disparity suggests a possible differential cost burden overall that future analysis should explore.

New mechanisms of the TCM spleen-based treatment of immune thrombocytopenia purpura from the perspective of blood neurotransmitters

ObjectiveTo explore new mechanisms of the traditional Chinese medicine (TCM) spleen-based treatment of immune thrombocytopenic purpura (ITP) from the perspective of blood neurotransmitters. MethodsIn this randomized controlled multi-center clinical study, 271 ITP patients who met the diagnostic criteria of “syndrome of spleen failing to manage blood” were randomized into three groups: group A administered Jianpi Yiqi Shexue (JYS) granules, 1 bag per treatment, bid; group C administered prednisone as a draught at an initial dose of 1.0–1.5 mg/kg/day at 8:00 AM; and group B administered a combination of the interventions in groups A and C. Each treatment cycle lasted 21 days. ResultsAfter treatment, scores of platelet distribution width (PDW) were significantly decreased in groups B and C, and there were significant differences among the three groups (P = .0131). Pairwise comparisons showed that PDW was significantly different between group A and group B (P = .005) and between group A and group C (P = .041) but not between group B and group C. Hemorrhage grading scores were significantly different between day 1 and day 7 in group A and group B (P < .001) but not in group C. The hemorrhage grading scores on day 14 and day 21 were significantly different from that on day 1 in all three groups (P < .001). Serum 5-hydroxytryptaminelevels did not change significantly before and after treatment in the three groups (P > .05). Serum β-endorphin and vasoactive intestinal peptide levels were significantly different between group A and group B (both P < .001). ConclusionsThe JYS prescription may regulate the expression levels of blood neurotransmitters via the brain-gut axis in patients with “spleen deficiency” ITP and thus activate hemostatic mechanisms to promote hemostasis. β-EP and VIP are key neurotransmitters of the JYS-induced functional regulation.

Intravenous infusion umbilical cord-derived mesenchymal stem cell in primary immune thrombocytopenia: A two-year follow-up.

Four patients with chronic refractory immune thrombocytopenic purpura (ITP) received human umbilical cord-derived mesenchymal stem cells (hUC-MSCs). The hUC-MSC dose was 5×107 to 1×108. Complete remission (CR) was achieved in three patients in 12 months and one patient in 24 months. Three patients received the second hUC-MSC transplantation with the same dose. The median time between hUC-MSC transplantation and response was 12.5 days (range, 7–16). There were no severe adverse events during and post hUC-MSC transplantation. During follow-up (median, 17 months; range, 13–24) no other immunosuppressive drugs were used post-first hUC-MSCs transplantation. In conclusion, hUC-MSC transplantation is a reasonable salvage treatment in chronic refractory ITP. Prospective randomized large-scale clinical trials are needed to further elucidate the efficacy of hUC-MSCs transplantation therapy on ITP.

Case Reports of Idiopathic Thrombocytopenia Unresponsive to First-Line Therapies Treated With Traditional Herbal Medicines Based on Syndrome Differentiation

The objective of our study is to present two cases showing the effects of traditional Korean herbal medicines based on traditional Korean medicine (TKM) for the treatment of immune thrombocytopenic purpura (ITP). One patient showed no response to treatment with steroids and an immunosuppressive agent. Moreover, liver toxicity and side effects of steroids were evident. However, after he ceased conventional treatment and started to take an herbal medicine, his liver function normalized and the steroid side effects resolved. Ultimately, he achieved complete remission. Another patient with ITP had sustained remission after steroid therapy in childhood, but extensive uterine bleeding and thrombocytopenia recurred when she was 16 years old. She was managed with steroids again for 2 years, but severe side effects occurred, and eventually she ceased taking steroids. She refused a splenectomy, and was then treated with a herbal medicine for 7 months, ultimately leading to sustained remission again. Many patients with resistance to first-line treatments tend to be reluctant to undergo a splenectomy, considered a standard second-line treatment. In conclusion, herbal medicines, based on TKM, may offer alternative treatments for persistent or chronic ITP that is resistant to existing first-line treatments.

Diagnosis of the Combination of Immune Thrombocytopenia and Woodhouse-Sakati Syndrome

Woodhouse-Sakati Syndrome (WSS) is a rare autosomal recessive syndrome characterized by sensorineural hearing loss, ECG ST-T changes, partial alopecia, hypogonadism, diabetes, and moderate mental retardation. A 23-year-old male patient was admitted to our hospital with complaints of purpura and petechial rashes. His platelet count was 3.04 x 109/L and the peripheral blood smear was compatible with this count. No atypical cell was observed. He had mild mental retardation. He had hearing loss since childhood. Physical examination showed widespread petechiae and purpura on bilateral lower extremities. Significant growth retardation was detected and male pattern hair growth was less. In genital examination, bilateral testicles were small; penis length was 1 cm and it was 4 cm when elongated. T negativity was present in precordial derivations of ECG. He was diagnosed Immune thrombocytopenic purpura (ITP) and WSS according to these findings. In addition to ITP treatment with steroids, the combination of testosterone propionate and testosterone phenyl propionatewas also administered to him. Upon we observed that there was an increase in his platelet number, he was discharged from the hospital. WSS is a very rare disease. Different components of the syndrome have been reported in different patients.It is the first time in the literature that ITP is observedtogether with WSS in a male patient.

Glatiramer Acetate-associated Refractory Immune Thrombocytopenic Purpura.

We present a case of glatiramer acetate-associated refractory immune thrombocytopenic purpura (ITP) in a female patient with multiple sclerosis. A search of MEDLINE/PubMed did not find any connection between glatiramer acetate and thrombocytopenia, specifically ITP. The autoimmune reaction was resistant to conservative ITP treatment, and was eventually managed only by splenectomy. To the best of our knowledge, this is the first report of glatiramer acetate-associated ITP. Physicians should be aware of this condition, and consider performing routine blood counts at the beginning of glatiramer acetate treatment.LEARNING POINTSWe present a unique case of glatiramer acetate-associated refractory immune thrombocytopenic purpura (ITP) in a female patient with multiple sclerosis, which was eventually managed only by splenectomy.Although glatiramer acetate is known for its immunomodulatory effect, a literature search did not reveal any reports of an association with ITP.Physicians should be aware of this condition, and consider performing routine blood counts at the beginning of and during glatiramer acetate treatment.

Experience with the drug 5 % human normal immunoglobulin for intravenous administration of Ig Vena N.I.V. in the treatment of immune thrombocytopenic purpura in children

Intravenous immunoglobulin (IVIG) is the first-line therapy for immune thrombocytopenia (ITP) at children. However, IVIGs are not absolutely comparable, as routine practice shows, so the choice of IVIG requires analysis of specific clinical cases and studies. IVIGs application requires to take into account not only effectiveness, but also tolerability. We investigated effectiveness and safety of Ig VENA (Kedrion S.p.A., Italy) administration for treatment of 62 patients with initially diagnosed ITP at the age of 6 months to 15 years. Positive effect of application of the medication reached at 85.5 % of children with this disease. None of the patients experienced serious adverse events during the study period. Short-term adverse events (fever, nausea, headache) were registered at 16.1 % of patients and did not require discontinuation of Ig VENA therapy. Thus, our study demonstrated the high effectiveness and safety of Ig VENA therapy for children with ITP.