Refractory Idiopathic Thrombocytopenic Purpura Research Articles

Chimeric Anti CD-20 Monoclonal Antibody-Rituximab in Refractory Childhood Idiopathic Thrombocytopenic Purpura: An Indian Experience.

The treatment of chronic idiopathic thrombocytopenic purpura (ITP) continues to be a challange. A significant proportion of patients continue to be symptomatic despite all available means of therapy. Recently Rituximab, a chimeric anti CD-20 monoclonal antibody has been shown to be an effective mode of therapy in such patients with an overall response rate of appx 50 %.We studied the efficacy and side effects of this therapeutic modality in 10 children (6 girls) with chronic ITP. The patients belonged to pediatric age group (median age: 9 years, range 4–18 years) with 4 children less than 10 years of age. All the patients were screened for systemic illnesses and different secondary causes leading to thrombocytopenia. They all had been treated with standard therapies using conventional and high dose steroids, ciclosporin cyclophosphamide, vincristine, periodic use of high dose IVIG and splenectomy in 6 patients, but had continued to be symptomatic with recurrent mucocutaneous bleeds and markedly low platelet counts (< 20x 109/L). All patients received intravenous Rituximab at a dose of 375 mg/M2 as weekly dose for 4 consecutive weeks. The infusion related side effects were a few (n= 3) and minor. They included urticarial rash (1) and fever(2) that responded to antipyretics. None of these were severe enough to interrupt the treatment. A complete response was defined as a platelet count > 100 x 109/L, partial response (PR) as count > 50x109/L and a minor response as a count < 50x109/L but without the need of continued treatment. Patients showing no significant rise in platelet count were marked as showing no response. Of the 10 evaluable children, 9 (90%) showed overall response; 4 (40%) showed complete response and 4 (40 %) showed partial response. Two (20%) patients showed minor responses. Patients have been under follow up for last 3 years. The patients with CR and PR have been in remission for longer periods (as much as 150 weeks ).The side effects due to the therapy have been few and very mild. Besides infusional reactions in 3 patients (Transient fever in 2 and mild rash in 1) there were no significant toxicities. No correlation could be found between clinical/laboratory parameters with the responsiveness or the duration of response except that patients showing a higher degree of response continued to be in remission for a longer period as compared to the ones with lesser degree of response. The high percentage of response in our patients as compared to the ones in other studies could be due to the fact that our patients belonged to a younger age group. Probably children show a better response.In conclusion, Rituximab offers a safe and convenient modality of treatment in symptomatic children with refractory ITP. Its use is certainly cost effective even in a developing country in view of the good degree of a sustained response in these refractory patients wherein all modalities of treatment have failed.

Recurrent Cerebral Infarctions and Multi-Vessel Thrombosis in a Male Patient with Refractory Idiopathic Thrombocytopenic Purpura: a Case Report

Recurrent Cerebral Infarctions and Multi-Vessel Thrombosis in a Male Patient with Refractory Idiopathic Thrombocytopenic Purpura: a Case Report

Treatment of ITP

Helicobacter eradication therapy is the first-line therapy for patients with Helicobacter positive idiopathic thrombocytopenic purpura (ITP) in Japan. Indications for treatement in patients with Helicobacter negative, or post-Helicobacter eradicated ITP are platelet counts less than 20×106/l or severe bleeding. The first-line treatment for these patients is corticosteroids. Thrombopoietin receptor agonists (TPO-RAs), rituximab, and splenectomy are second-line treatments for patients with corticosteroid refractory ITP. The choice of a second-line treatment should be determined in consideration of the advantages and disadvantages of each treatment. TPO-RAs are effective in over 80% of patients; however, long-term administration is usually needed. Rituximab treatment ends in four weeks, but its durable response rate is relatively low. The durable response rate of splenectomy is relatively high; however, it causes long-term complications. Effective treatments for patients with ITP who are refractory to second-line treatments have not been established. Some novel drugs are under clinical trials, and a treatment strategy for these patients is expected to be established.

Neck dissection in a patient treated with refractory idiopathic thrombocytopenic purpura who received a thrombopoietin receptor agonist and γ-globulin preoperatively: a case report

Neck dissection in a patient treated with refractory idiopathic thrombocytopenic purpura who received a thrombopoietin receptor agonist and γ-globulin preoperatively: a case report

İDİYOPATİK TROMBOSİTOPENİK PURPURALI HASTALARDA RETİKÜLOTROMBOSİT SAYISININ TEDAVİ CEVABI İLE İLİŞKİSİ

<span style="color: rgb(102, 102, 102);">Objective: Idiopathic thrombocytopenic purpura (ITP) causes thrombocytopenia via the premature destruction of autoantibody covered thrombocytes. It is diagnosed by exclusion of other diseases which cause thrombocytopenia. Reticulothrombocytes (RT) are young thrombocytes containing messenger ribonucleic acid (mRNA) and ribosomal ribonucleic acid (rRNA). Measurement of RT with flow cytometry is reported to reflect thrombopoetic activity in thrombocytopenic patients. The aim of this study is to measure the percentage and absolute number of RT’s in newly diagnosed and refractory ITP patients and to investigate the association between RT percentage and number with response to treatment. </span> <span style="color: rgb(102, 102, 102);">Material and Method: The study group consisted of 16 former ITP patients who were refractory to various treatments, 15 newly diagnosed patients and 20 healthy controls. Thrombocyte counts and mean thrombocyte volume were measured with blood count. RT counts were measured via flow cytometry. Reticulocyte counts of the refractory patients, new patients and healthy controls were compared to each other. </span> <span style="color: rgb(102, 102, 102);">Results: Thirty five (68.6%) of the 51 patients were female. The patients were between 25 and 75 years old with a mean age of 39.15 years and standard deviation of 13.04 years. The refractory ITP patients and newly diagnosed ITP patients were grouped into Group 1 (n=16) and Group 2 (n=15) respectively. The control group was referred to as Group 3 (n=20). The platelet count of Group 3 was found to be significantly higher than the platelet counts of Groups 1 and 2 (p:0.001) and there was no difference between Groups 1 and 2. The RT percentage was found 21.7% in Group 1, 36.2% in Group 2 and 3.2% in Group 3. The RT percentage of Group 3 was calculated to be significantly lower than the RT percentages of Groups 1 and 2 (p:0.001). There was no difference between Groups 1 and 2. The absolute RT count was insignificant between all groups. </span> <span style="color: rgb(102, 102, 102);">Conclusion: The RT percentage count was not statistically different between refractory and newly diagnosed ITP patients. This finding indicates that RT percentage measurement is not helpful in the evaluation of the response to the treatment. The finding of a high RT percentage count in refractory patients suggests that the medical treatment should be continued.</span>

2081 Idiopathic Thrombocytopenic Purpura: An Uncommon Extra-intestinal Manifestation of Crohn's Disease

INTRODUCTION: Idiopathic thrombocytopenic purpura (ITP) is characterized by the presence of autoantibodies against platelet surface antigens with immune-mediated platelet destruction. While the association of ITP and inflammatory bowel disease (IBD) has been described in few case reports, management of ITP as an extra-intestinal manifestation of Crohn’s disease (CD) is less studied. CASE DESCRIPTION/METHODS: A 27-year-old man with history of CD and ITP presented with 3 days of bloody diarrhea and non-bloody, nonbilious vomiting. Physical exam notable for mild periumbilical tenderness, no hepatosplenomegaly present. Admission labs showed platelets of 18, ESR of 49, CRP of 8.04. He was started on IV methylprednisone and given platelet transfusions with only a brief response in platelet count. He was then treated with 2 doses of intravenous immunoglobulin (IVIg). His platelet count had only a transient response to combined steroids and IVIg, so rituximab was given on hospital day 10. He continued to have hematochezia and underwent endoscopy, revealing body and fundus gastropathy as well as moderate-severe proctosigmoiditis. Given a history of thrombocytopenia with adalimumab and infliximab, he received ustekinumab for his CD flare on day 14. He was taken to the operating room for colectomy and splenectomy on day 25 for ongoing CD flare and thrombocytopenia requiring daily transfusions. After surgery, platelets increased without transfusions. Discharge platelet count was 571. Colon pathology showed changes consistent with chronic IBD, severe disease activity. His CD has been controlled on maintenance ustekinumab and 6-mercaptopurine in the 5 months following discharge. Platelets remain stable at 170 without additional medical management. DISCUSSION: There are roughly a dozen cases published on the management of dually diagnosed CD/ITP patients. Previous reports postulate that the mechanism of ITP in CD is through the presence of circulating immune complexes in the serum and antigenic mimicry due to increased mucosal permeability in active colitis, which may explain why CD surgery can also result in remission of ITP. Indeed, our literature review identified 1 case where ITP was refractory to steroids and splenectomy, but responded after bowel resection and another case where medically refractory ITP responded to bowel resection alone. These cases, as well as the one we have presented, suggest that colectomy should be considered in the treatment of medically refractory ITP among patients with concomitant CD.

2 Cases of Refractory Idiopathic Thrombocytopenic Purpura in Pregnancy

2 Cases of Refractory Idiopathic Thrombocytopenic Purpura in Pregnancy

Therapeutic effects of rituximab combined with cyclophosphamide on refractory idiopathic thrombocytopenic purpura.

Therapeutic effects of rituximab combined with cyclophosphamide on refractory idiopathic thrombocytopenic purpura (ITP) were investigated. We retrospectively analyzed 249 patients with refractory ITP who were admitted to Qingdao Hiser Medical Group between March 2013 and March 2017. Curative effects of patients treated with rituximab, cyclophosphamide, and combination therapy were observed and the changes of platelet count, PA IgG, and lymphocyte CD20 before and after treatment, as well as the incidence of adverse reactions after treatment, were compared. There was no significant difference in the expression of lymphocyte CD20, PA IgG and platelet count among the three groups of refractory ITP patients before treatment (P>0.05). After treatment, the expression levels of CD20 and PA IgG in lymphocytes were significantly downregulated, and platelet counts significantly increased in the three groups (P<0.05). After treatment, CD20 and PA IgG levels in combined therapy group were significantly lower, and platelet count was significantly higher, than those in the rituximab and cyclophosphamide groups (P<0.05). Also, after rituximab treatment, the expression levels of CD20 and PA IgG in lymphocytes were significantly lower than those in cyclophosphamide group (P<0.05), and platelet count was higher than that in cyclophosphamide group (P<0.05). After treatment, the total effective rate in combined therapy group was higher than that in the rituximab and cyclophosphamide group (P<0.05). Total effective rate of rituximab group was significantly higher than that of cyclophosphamide group (P<0.05). The incidence of adverse reactions in combined therapy group was 14.29% (12/84), which was significantly lower than that in cyclophosphamide group (40.70%, 35/86, P<0.05) and rituximab group (29.11%, 23/79, P<0.05). The application of rituximab combined with cyclophosphamide in the treatment of refractory ITP can improve patients clinical symptoms. The efficacy of this technique is promising with no serious adverse reactions. This technique should be popularized in clinical practice.

Platelet count on preoperative day 1 predicts the long-term responses to laparoscopic splenectomy for Chinese patients with medically refractory idiopathic thrombocytopenic purpura

BackgroundLaparoscopic splenectomy (LS) is regarded as a second-line treatment for medically refractory idiopathic thrombocytopenic purpura (ITP), but the predictive factors for the long-term postoperative responses to ITP are still a matter of debate. We aimed to investigate the factors that can predict the long-term response after LS for Chinese patients with medically refractory ITP.MethodsFrom January 2011 to September 2016, 78 Chinese patients with ITP who underwent LS were retrospectively analyzed. Twelve parameters were analyzed by univariate and multivariate methods.ResultsUnivariate analysis revealed that platelet count on preoperative day (PRD) 1 (P < 0.001) and operative time (P = 0.011) were significantly associated with long-term response of ITP after LS. Multivariate analysis revealed that platelet count on PRD 1 was a predictive factor of long-term response (P < 0.001). Furthermore, a long-term, stable response of platelet count on PRD 1 of > 30.0 × 109/L was easier to achieve than a platelet count on PRD 1 ≤ 30.0 × 109/L after LS for ITP.ConclusionsLS is a valuable and effective option in the treatment of medically refractory ITP. Platelet count on PRD 1 is an independent predicting factor for long-term response after LS for Chinese patients with ITP.

A491 - “Two birds, one stone”: ITP managed at the time of bariatric surgery

Background: There is a growing prevalence of obesity, with a subsequent increase in bariatric surgeries. As a result, the patient population undergoing surgery has become widely varied with multiple additional medical and surgical problems. Some of those additional problems, on occasions, require surgical management. This can sometimes become tricky and pose a challenge in the decision to proceed safely with an elective bariatric procedure. One such consideration is ITP (idiopathic thrombocytopenic purpura), which, if refractory to medical management requires surgical treatment. Low platelets are known to increase the risk of bleeding complications. Besides chronic anemia, thrombocytopenia has been described as a potential hematological alteration after bariatric surgery and this can understandably create a decision dilemma. Here we present a novel case of a 33 year old lady with medically refractory ITP who underwent surgical management for her ITP along with bariatric surgery, and rather than being a contra-indication for the weight loss procedure, her thrombocytopenia was managed effectively and safely at the same time.

Management of a Patient with Refractory Idiopathic Thrombocytopenic Purpura

Management of a Patient with Refractory Idiopathic Thrombocytopenic Purpura

Fatal Coxsackie meningoencephalitis in a patient with B-cell lymphopenia and hypogammaglobulinemia following rituximab therapy

Fatal Coxsackie meningoencephalitis in a patient with B-cell lymphopenia and hypogammaglobulinemia following rituximab therapy

Successful Eculizumab Therapy in Thrombotic Thrombocytopenic Purpura (TTP) Refractory to Plasma Exchange, Steroids and Rituximab

IntroductionWe present a case of TTP refractory to usual therapies treated successfully with eculizumab.Case presentationA 64 year-old African American female with history of diabetes and hypertension presented with left sided weakness and seizure-like activity preceded by 2 days of headaches and 2 weeks of easy bruising. On admission her vital signs and physical exam were unremarkable. Her basic metabolic panel, ANA panel, hepatitis panel, HIV, and anti-phospholipid panel was negative. Her hemoglobin was 9.0 g/dL, platelets were 13K/uL, LDH was 954IU/L, haptoglobin <30 mg/dL, eGFR was 50, and blood smear showed 4-5 schistocytes/high power field. ADAMTS13 activity was <5% and there was an inhibitor level of 1.1BU. C3 level was 75.3 (normal range 90-180mg/dL), C4 was <10 mg/dL (normal range 15-45 mg/dL). On day 1, she was started on oral prednisone (1mg/kg/day) and daily plasma exchange (TPE). changes. After 6 days of TPE without signs of improvement, the first dose of rituximab 375 mg/msq/dose was given on day 7. During the second week of hospitalization, patient also developed delirium and mental status changes. Vincristine 2 mg was given on day 13 for refractory TTP. Due to clinical worsening of microangiopathy and mental status, a decision was made to administer eculizumab 900 mg on day 17. Within a few hours of eculizumab administration, her platelets improved from 8k/uL to 21k/uL and to 47k/uL 12 hours later. After the second dose of eculizumab on day 24, platelets improved to 117k/uL and continued to rise. Eculizumab 900 mg was given weekly for 4 weeks, at which time ADAMTS13 activity was 75% and ADAMTS13 inhibitor was undetectable. Eculizumab 1200 mg was then given every two weeks, for a total of 3 more doses, during which the CBC, LDH, and haptoglobin remained in the normal range. Eculizumab was stopped, and after four months of close follow up, platelets, LDH, renal function and mental status were still normal range. C3 level was 203 (normal range 90-180 mg/dl), C4 was 35 mg/dl (normal range 15-45 mg/dl), ADAMTS 13 activity assay is >100% and there is no inhibitor.DiscussionTTP and aHUS are both thrombotic microangiopathies (TMA). TTP is caused by acquired or inherited deficiency of the ADAMTS 13 protein or due the formation of an inhibitor to the ADAMTS13 protein. aHUS results, in most cases, from a genetic mutation in complement factor H in the alternative pathway of the complement cascade. Recent studies have described the importance of the complement system in all forms of TMA (Update on the role of the complement system in the pathogenesis of thrombotic microangiopathies. Prilozi. 2014;35(1):115-22). While plasma exchange is the cornerstone of TTP treatment, complement inhibition with drugs such as eculizumab is the treatment of choice for aHUS. The use of complement inhibiting drugs has not yet been studied in TTP.We report an unusual case of TTP, with confirmed ADAMTS 13 inhibitor and low activity, which did not respond to conventional treatment for TTP. Theorizing that this patient either had concurrent aHUS or had TTP with a dysregulated alternate complement pathway, we used eculizumab, to which the patient had a remarkable and persistent response.There are other reports in literature of patients with aHUS having reduced levels of ADAMTS13 protein; however, these patients did not have an inhibitor as was seen in our patient (Partial ADAMTS13 deficiency in atypical hemolytic uremic syndrome. Blood. 2013 Aug 22;122(8):1487-93). There is one other case in the literature where TTP was treated successfully with eculizumab. In that case, discontinuation of eculizumab was associated with a relapse of TTP and so had to be continued (Eculizumab in the treatment of refractory idiopathic thrombocytopenic purpura. Br J Haematology. 2012 June;157 (6):772-4). To our knowledge, we report the first case of a confirmed diagnosis of TTP treated successfully with eculizumab with remission continuing 3 months after discontinuation of the drug.The use of eculizumab and the role of the complement pathway in TTP deserves further study. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Longitudinally extensive transverse myelitis: a rare association with common variable immunodeficiency

Transverse myelitis requires careful investigation, as although many causes respond acutely to immunomodulation, the longer term management depends upon its precise cause. We describe a patient presenting acutely with a...

Severe romiplostim-induced rebound thrombocytopenia after splenectomy for refractory ITP.

To report a case of severe rebound thrombocytopenia after temporary discontinuation of romiplostim during splenectomy in the context of refractory immune (idiopathic) thrombocytopenic purpura (ITP). A 65-year-old man with a history of severe refractory ITP failing multiple treatments was considered for romiplostim therapy. He was initiated on 1 µg/kg and titrated upward to 4 µg/kg to elevate and stabilize his platelet levels prior to splenectomy. On day 74 of his clinical course, his platelets increased to 434 × 10(9)/L, and his scheduled dose of romiplostim was withheld on day 75 for fear of romiplostim-induced postsplenectomy rebound thrombocytosis. On day 78, his platelets dropped precipitously to 9 × 10(9)/L, and he experienced multiple episodes of epistaxis. He was reinitiated at 5 µg/kg and soon recovered. He later missed a scheduled dose of romiplostim, and his platelets fell to 23 × 10(9)/L. After resuming romiplostim at 8 µg/kg, his platelets continued to recover. Romiplostim, a thrombopoietin mimetic is directly regulated by megakaryocytes and existing circulating platelets via a negative feedback mechanism. This explains the theoretical risk of rapid clearance of romiplostim caused by an increased platelet pool. Clinically, alternative causes of his severe postoperative thrombocytopenia were considered and deemed unlikely. The rebound effect was observed after romiplostim was withdrawn on 2 occasions, and platelet counts improved after restarting romiplostim. The Naranjo Adverse Drug Reaction Probability Score of 7 suggests a probable adverse drug reaction. Physicians using romiplostim as a bridge to splenectomy should be cautious about withholding a scheduled dose around the time of surgery.

Advances in pathogenesis of chronic idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura （ITP）,as a heterogeneous autoimmune disease,is the most common bleeding disorder,of which etiology and pathogenesis are still unclear. Health related quality of life are severely affected,especally in chronic patients . Studys on chronic idiopathic thrombocytopenic purpura pathogenesis ,both in China and abroad,have found that genetic factors may be involved in the occurrence and prognosis of the disease. The paper gives a review from the follow aspects,such as its risk factors,relationship between genetic polymorphisms or expression levels and chronic ITP susceptibility and seriousness,the role of epigenetic,researchs about chronic and refractory ITP,et al. Key words: Chronic idiopathic thrombocytopenic purpura; Gene polymorphism; Gene expression; Epi-genetic

DI-062 Romiplostim and eltrombopag in the treatment of Idiopatic Thrombocytopenic Purpura

BackgroundRomiplostim and eltrombopag have a novel mechanism of action that expands treatment options for idiopathic thrombocytopenic purpura (ITP). Both have proven effective in increasing platelet counts in splenectomised patients.PurposeTo describe...

Transumbilical single-incision endoscopic splenectomy: Report of ten cases

To investigate the feasibility and clinical application of transumbilical single-incision endoscopic splenectomy using conventional laparoscopic instruments. Between 2010 and 2012, transumbilical single-incision endoscopic splenectomy was performed in 10 patients in our department, of whom 4 had refractory idiopathic thrombocytopenic purpura, 4 had enlarged splenic cyst and 2 had splenic hematoma. A 2.5-cm curved incision was made at the lower umbilicus edge, and a 10 mm laparoscope was inserted into the middle of the incision. A 5-mm harmonic scalpel was placed on the right side, and a 5-mm auxiliary instrument on the left side of the laparoscope. Splenic ligaments were incised with a harmonic scalpel, and the splenic pedicle was cut with an Endo-gastrointestinal anastomosis. The spleen was dissected and placed in a large retrieval bag, blended, and then removed. All transumbilical single-incision endoscopic splenectomies were performed successfully with mean operative time of 80 ± 5 min and mean blood loss of 150 ± 20 mL. Conversion to laparotomy or multi-port laparoscopic surgery was not required in all cases. All patients were discharged on postoperative days 4-6. During the postoperative hospitalization period, no painkillers were required. No intra-abdominal complications such as infection, ascites, gastric leakage, pancreatic leakage, or wound infection occurred in any case during the 6-mo follow-up. Transumbilical single-incision endoscopic splenectomy using conventional laparoscopic instruments is technically feasible and safe in selected patients.

Bortezomib induces clinical remission and reduction of ADAMTS13 inhibitory antibodies in relapsed refractory idiopathic thrombotic thrombocytopenic purpura

Bortezomib induces clinical remission and reduction of <scp>ADAMTS</scp>13 inhibitory antibodies in relapsed refractory idiopathic thrombotic thrombocytopenic purpura

Age Old Dapsone in the Treatment of Idiopathic Thrombocytopenic Purpura—A Case Report With Review

Idiopathic thrombocytopenic purpura (ITP) is characterized by premature platelet destruction in the reticuloendothelial system due to the presence of autoantibodies against the platelet membrane proteins. Patients who are resistant to the traditional treatment options that include the administration of steroids, IV immunoglobulin, and antirhesus D immunoglobulin and the performance of a splenectomy are diagnosed to have refractory chronic ITP. Management options in these patients are not well defined. Long-term steroids, rituximab, danazol, azathioprine, and cyclophosphamide have variable efficacy and at the same time carry significant side effects. We present the case of a patient treated effectively with dapsone, a drug that is much safer than other drugs and which can be used before resorting to splenectomy; we also include a review of the literature establishing its role in the management of ITP.