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Antibodies and splenectomy - 10-10-14 8 years 1 month ago #44343

  • Sandi
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Abstract

Many immune thrombocytopenia (ITP) patients, particularly patients with anti-glycoprotein (GP) Ib-IX autoantibodies, do not respond to the conventional treatments such as splenectomy. However, the underlying mechanism remains unclear. Here we found that anti-GPIbα N-terminus antibody AN51, but not other anti-GPIbα antibodies (AK2, HIP1, VM16d, or WM23), induced GPIbα clustering that led to integrin αbβ3-dependent platelet aggregation. After intravenous injection, AN51 dose-dependently induced thrombocytopenia in guinea pigs, and the platelets were mainly removed by macrophages in the liver. N-acetyl-D-glucosamine, previously shown to inhibit integrin αMβ2 mediated phagocytosis of refrigerated platelets, dose-dependently inhibited AN51-induced platelet clearance. Furthermore, AN51 but not VM16d, induced rapid platelet clearance in the liver of cynomolgus macaques. Five of 22 chronic ITP patients had anti-GPIbα autoantibodies, and the autoantibodies from four of the five patients competed with AN51 for binding to platelets. These data indicate that GPIbα clustering induced by anti-GPIbα N-terminus antibody causes integrin αbβ3-dependent platelet aggregation, phagocytosis, and rapid platelet clearance in the liver. Our findings reveal a novel Fc-independent mechanism underlying the pathogenesis of ITP, and suggest new therapeutic strategies for ITP patients with anti-GPIbα autoantibodies.


www.ncbi.nlm.nih.gov/pubmed/25231551

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New articles posted here - update 10-10-14 8 years 1 month ago #44363

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This is a difficult read for me, but if I am reading this right, it is important new information, that a previously unknown mechanism is causing treatment-resistant ITP in some patients, including patients who undergo unsuccessful splenectomies.

[...] antibody AN51 [...] induced [...] clustering that led to [...] platelet aggregation. [...] and the platelets were mainly removed by macrophages in the liver.

I wonder whether this sources of ITP is unresponsive to treatments other than splenectomy, such as Rituxan.
I wonder whether there is a readily available test for AN51.
I wonder if this reaction may also be responsible for some ITPers being vulnerable to blood clots.

There is a possible treatment that reverses the effects AN51.

N-acetyl-D-glucosamine, previously shown to inhibit integrin αMβ2 mediated phagocytosis of refrigerated platelets, dose-dependently inhibited AN51-induced platelet clearance.

This chemical has been shown to be effective in suppressing autoimmune attacks in multiple sclerosis:

www.sciencedaily.com/releases/2011/09/110930123057.htm
Glucosamine-like supplement suppresses multiple sclerosis attacks, study suggests
Date: September 30, 2011
Source: University of California - Irvine
Summary: A glucosamine-like dietary supplement suppresses the damaging autoimmune response seen in multiple sclerosis, according to a new study.


The study comes on the heels of others showing the potential of GlcNAc in humans. One reported that eight of 12 children with treatment-resistant autoimmune inflammatory bowel disease improved significantly after two years of GlcNAc therapy. No serious adverse side effects were noted.
"Together, these findings identify metabolic therapy using dietary supplements such as GlcNAc as a possible treatment for autoimmune diseases," said Demetriou, associate director of UCI's Multiple Sclerosis Research Center. "Excitement about this strategy stems from the novel mechanism for affecting T-cell function and autoimmunity -- the targeting of a molecular defect promoting disease -- and its availability and simplicity."
He cautioned that more human studies are required to assess the full potential of the approach. GlcNAc supplements are available over the counter and differ from commercially popular glucosamine. People who purchase GlcNAc should consult with their doctors before use.


Here is one of the studies linked:
www.jbc.org/content/286/46/40133
N-Acetylglucosamine Inhibits T-helper 1 (Th1)/T-helper 17 (Th17) Cell Responses and Treats Experimental Autoimmune Encephalomyelitis

Background: Multiple sclerosis (MS) has been linked to genetic and environmental dysregulation of Golgi N-glycosylation.

Results: Oral treatment of mice with the sugar N-acetylglucosamine (GlcNAc) enhances N-glycosylation, suppressing inflammatory T cell responses and an MS-like disease when initiated after disease onset.

Conclusion: Disease progression is suppressed by GlcNAc.

Significance: GlcNAc may provide the first MS therapy that directly targets an underlying mechanism causal of disease.
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Exercise and platelets - update 10-29-14 8 years 1 month ago #44770

  • Sandi
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Sept. 25, 2014--Platelets are an expensive biomedical commodity. These microscopic cells that come to the rescue when our blood vessels need to be repaired cannot be frozen and are stable for only three to five days at room temperature.

Although platelets are life-saving for accident victims, individuals undergoing chemotherapy, and people with diseases associated with a low platelet count, donated natural platelets are often in short supply, and their use comes with the risk of disease transmission between donors and recipients.

www.udel.edu/udaily/2015/sep/platelet-formation-092514.html
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IVIG and vaccines - update 11-3-14 8 years 1 month ago #44831

  • Sandi
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Apparently, there is a recommended time period between IVIG and vaccines. They are listed here.


www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/A/mmr_ig.pdf

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N-Plate and splenectomy - update - 11-17-14 8 years 3 weeks ago #45034

  • Sandi
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Severe Romiplostim-Induced Rebound Thrombocytopenia After Splenectomy for Refractory ITP.
Choe MJ1, Packer CD2.

Abstract
OBJECTIVE:

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).
CASE SUMMARY:

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 × 109/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 × 109/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 × 109/L. After resuming romiplostim at 8 µg/kg, his platelets continued to recover.
DISCUSSION:

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.
CONCLUSION:

Physicians using romiplostim as a bridge to splenectomy should be cautious about withholding a scheduled dose around the time of surgery.

© The Author(s) 2014.

www.ncbi.nlm.nih.gov/pubmed/25325908

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Severe ITP due to Anti-viral meds - 11-19-14 8 years 2 weeks ago #45072

  • Sandi
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Abstract

A 44-year-old man whose platelet count had been at the lower limit of the normal range for years visited the urgent care department of our hospital for treatment of a high fever and severe fatigue. The influenza A virus was detected, and the patient therefore received the intravenous antiviral agent, peramivir. One week later, he developed systemic petechial rashes. A peripheral blood examination showed a markedly decreased platelet count (3.0×10(9) cells/L), and the bone marrow findings were compatible with a diagnosis of immune thrombocytopenia (ITP). Furthermore, a drug-induced lymphocyte-stimulating test was positive for peramivir. The thrombocytopenia slowly responded to treatment with oral prednisolone. This case suggests that neuraminidase inhibitors, including peramivir, can elicit or worsen ITP.

www.ncbi.nlm.nih.gov/pubmed/25318805

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Rituxan - 11-26-14 8 years 1 week ago #45221

  • Sandi
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Abstract

We conducted a prospective multicenter registry of 248 adult patients with immune thrombocytopenia (ITP) treated with rituximab to assess safety. We also assessed response and predictive factors of sustained response. In total, 173 patients received 4 infusions of 375 mg/m(2) and 72 received 2 fixed 1-g infusions 2 weeks apart. The choice of the rituximab regimen was based on the physician's preference and not patient characteristics. Overall, 38 patients showed minor intolerance to rituximab infusions; infusions had to be stopped for only 3 patients. Seven showed infection (n = 11 cases), with an incidence of 2.3 infections/100 patient-years. Three patients died of infection 12 to 14 months after rituximab infusions, but the role of rituximab was questionable. In total, 152 patients (61%) showed an overall initial response (platelet count ≥30 × 10(9)/L and ≥2 baseline value). At a median follow-up of 24 months, 96 patients (39%) showed a lasting response. On multivariate analysis, the probability of sustained response at 1 year was significantly associated with ITP duration <1 year (P = .02) and previous transient complete response to corticosteroids (P = .05). The pattern of response was similar with the 2 rituximab regimens. With its benefit/risk ratio, rituximab used off-label may remain a valid option for treating persistent or chronic ITP in adults. This trial was registered at www.clinicaltrials.gov as #NC1101295.

© 2014 by The American Society of Hematology.


www.ncbi.nlm.nih.gov/pubmed/25293768

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Epidemiology of incident ITP - 12-3-14 8 years 6 days ago #45299

  • Sandi
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Abstract

The epidemiology of immune thrombocytopenia (ITP) is not well known. The purpose of this study was to assess ITP incidence at a nationwide level (France) with recent data (mid-2009 to mid-2011; 129 248 543 person-years). The data source is the French health insurance database. We selected cases with diagnosis codes for in-hospital stays and long-term disease attributions, thus restricting our search to ITPs necessitating health care. We studied incidence by age, gender, calendar month, regions, and proportion of secondary ITPs, of ITPs becoming persistent or chronic, and of severe bleeding at disease onset. We identified 3771 incident ITP patients. Incidence was 2.9/100 000 person-years, with peaks among children and in those >60 years of age. ITP was more frequent among males in these subgroups. The incidence was lower in overseas Caribbean French departments, suggesting a lower incidence among Afro-American people. There was a north-south gradient in mainland France and seasonal variations (peak in winter and nadir in summer). Persistence or chronicity occurred in 36% of children compared with 67% of adults. Among adults, 18% of ITPs were secondary. Malignancy was the main cause (10.9%). Myelodysplastic syndromes were not rare (2.3%). Severe gastrointestinal or central nervous system bleeding at ITP onset was rare (<1%).

© 2014 by The American Society of Hematology.

www.ncbi.nlm.nih.gov/pubmed/25305203

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Splenectomy - Update 12-9-14 8 years 8 hours ago #45380

  • Sandi
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Introduction:

Splenectomy was historically regarded as the gold standard for treatment in chronic adult immune thrombocytopenic purpura (ITP). However, the recent emergence of new drugs has deeply modified ITP management and splenectomy is no longer viewed as an unavoidable step in adult chronic ITP in many countries. The estimation of the risk over benefit of this potential curative treatment remains challenging both for patients and physicians. A retrospective Italian study focused on long-term outcome of patients splenectomized for ITP gave reassuring data concerning safety. A recent study from a large cohort of American veterans showed an increased risk of death due to septicemia, pulmonary embolism, coronary artery disease and cancer more than 10 years after splenectomy. We reported here the results of the first single center case-control study evaluating the long-term incidence of splenectomy complications with a minimum follow-up of 10 years.

Methods:

We retrospectively selected in a clinical computer database all primary ITP patients splenectomized more than 10 years ago in our unit. We matched 1 by 1 to non-splenectomized ITP patients based on date and age at ITP diagnosis and sex criteria. Clinical data were then completed from medical charts. All patients were interviewed by phone and a standardized questionnaire was used. Medical records from general practitioner or from Medical care center have been systematically obtained if necessary, especially for deceased patients. Comparison between groups were made using Fisher’s test for qualitative variables, Kaplan-Meier method to estimate incidence and Rank test for comparison of cumulative incidence, with p<0.05 defining significance.

Results:

Seventy splenectomized ITP patients were included (19men/51women) with a median age at ITP diagnosis of 37 years (range: 3-92). Sixty one (87%) initially responded to splenectomy but only 34(48.5%) maintained a sustained response after a median follow-up of 189 months (range:120-528). Matched non-splenectomized ITP patients had a median age at diagnosis of 40 years (range: 3-93) and a median follow-up since ITP diagnosis of 197 months (range: 96-504).Cumulative incidence of thromboembolic events was higher in the splenectomized group (p=0.029) (Figure1). Four (6%) episodes of post-operative portal vein thrombosis were observed, 3 were complicated by portal cavernoma requiring long-term anticoagulation. They tended to present with more thromboembolic events on a long-term (n=7) than non-splenectomized ITP patients (n=3, p=0.113). Two splenectomized (2.8%) and 1 non-splenectomized (1.4%) patients were diagnosed with post-embolic pulmonary arterial hypertension. The incidence of cardiovascular events was significantly higher in splenectomized group (9(13%) versus 2(2.8%), p=0.005) (Figure 2) with 6 transient and/or ischemic strokes in splenectomized patients (none in non-splenectomized).Infectious events were similar in the two groups (splenectomized: 12 (17%) vs 10 (14%)) but infections were more frequent and severe in splenectomized patients. Indeed, 12 splenectomized patients presented 20 infectious events requiring hospitalization, 13 of them were pneumonia (Streptococcus Pneumoniae: n=4, Haemophilus Influenzae: n=1, undocumented: n=9). Five complicated septic-shocks leading to 3 deaths. In non-splenectomized group, 10 patients had 10 infectious events (Pneumonia n=4, Streptococcus Pneumoniae n=1), 7 were hospitalized, none had septic-hock. Incidence of cancer was similar in the 2 groups (splenectomized: 11 (16%), non-splenectomized: 10 (14%).Finally, the mortality rate was not different between two groups (splenectomized: n=14 (20%), non-splenectomized n=9, 13%). Ten (38%) of the 36 non-responders patients deceased, 7 from hemorrhage and/or septic shock. Other splenectomized and non-splenectomized patients died from malignant cancer/hemopathy (n=5), coronary artery disease (n=2),other (n=6).

Conclusion:

Based on this case control single center study, we observed that long-term splenectomized patients have not only an increase risk of life-threatening infections, but also an increased risk of thromboembolic, and cardiovascular events. A long-term follow-up is therefore recommended in this patient population regardless the status of ITP in order to better prevent and manage such complications.

ash.confex.com/ash/2014/webprogram/Paper68906.html

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Post-operative counts - splenectomy - 12-10-14 7 years 11 months ago #45398

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Background: Immune thrombocytopenia (ITP) in adults is generally a chronic disorder that may lead to severe thrombocytopenia and bleeding. Though several medical modalities such as thrombopoietin receptor agonists have become available for the management of ITP withinin the last decade, splenectomy remains a valuable option for management of refractory ITP, with approximately 2/3 of treated patients remaining in complete remission 10 years afterwards. However, there are no consistent and reliable predictors of splenectomy response for an individual patient with ITP. Since patients with ITP who fail to respond to splenectomy can develop significant bleeding in the postoperative period it is important to identify those individuals early after their surgical procedure so that aggressive medical intervention may be employed. Despite this concern, there is little information available on the value of postoperative platelet counts obtained soon after splenectomy in predicting the ultimate outcome of surgery.

Objectives: The goal of this study was to define the value of platelet counts determined soon after splenectomy on the ultimate success of splenectomy in inducing remission of ITP.

Methods: We reviewed the medical records of 66 patients who underwent splenectomy for ITP at the Cleveland Clinic from 2000-2013. A complete response was defined as a stable platelet count >100 x109/L two months after splenectomy without medical therapy. Stepwise logistic regression with backward selection was used to identify significant predictors of complete response.

Results: The 66 patients had a median age of 41(IQR 21-56) with a male:female ratio of 1:2. The median platelet count at the time of diagnosis was 12 x 109/L and 43% of the patients had severe ITP (defined per IWG guidelines as bleeding that mandates treatment). Ninety percent of patients were steroid dependent, and 39%, 15% and 5% had been treated with rituximab, eltrombopag or romiplostim respectively. The median time to splenectomy from diagnosis of ITP was 22 months (IQR 6-44 months). At a median follow up of 35 months after splenectomy, 39 patients (59%) achieved a complete response. The median platelet count prior to and 24 hours after splenectomy in responders and non-responders is shown in Table 1.

Logistic regression analyses identified a post-op day 1 platelet count greater than the median platelet count of 112 x 109/L (OR- 3.72, CI- 1.14-12.16, p<0.03) and post-operative day 3 platelet count greater than median platelet count of 175x 109/L (OR- 4.87, CI- 1.37-17.2, p<0.01) as a significant predictor of splenectomy response. The probability of response based on the post-operative day 1 platelet count is depicted in Figure 1. The difference between the pre-splenectomy and post-operative day 1 platelet count was also a significant predictor of response (OR 1.01 (1.0001-1.02), p=0.04), (figure 2). The log of the time from the diagnosis of ITP to splenectomy (OR- 0.61, CI 0.40-0.94, p<0.02) was also a weak, but significant predictor. Increased numbers of prior treatments for ITP prior to splenectomy correlated with a decreased response, although this relationship was not statistically significant.

Conclusion: The platelet count on postoperative day 1 is a significant predictor of long term response to splenectomy, with almost 4-fold increased probability of achieving remission if this value is >112 x 109/L .This is among the first studies to examine the prognostic value of the platelet count obtained this early after splenectomy, and suggests that in patients with severe ITP and a persistently low postoperative platelet count on day 1, medical therapy should be considered to prevent bleeding. Our data also suggests that responses to splenectomy may be less frequent in patients with a longer interval between ITP diagnosis and splenectomy.

ash.confex.com/ash/2014/webprogram/Paper74358.html

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PRituxan and HBV - Update 12-15-14 7 years 11 months ago #45457

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BACKGROUND: It is estimated that >1.4 million people in the US are living with chronic HBV, many of whom are unaware of their infection. Chronic infection is responsible for the majority of HBV-related morbidity and mortality ranging from hepatitis to fulminant hepatic failure. The monoclonal anti-CD20 antibody, rituximab, is used to treat a variety of malignant and non-malignant conditions. Its use is associated with reactivation of HBV (HBV-R), including in historically low risk populations (i.e., HBV core antibody (HBcAb) positivity) and HBV-R may occur >8-10 months after completion of therapy. Professional societies such as the CDC and Infectious Diseases Society of America (IDSA) recommend screening all persons receiving cytotoxic or immunosuppressive therapy for HBV infection, although not all guidelines surrounding this topic are consistent. The primary aim of this study was to determine the rate of rituximab-related HBV screening and HBV-R over a recent time period across multiple medical specialties and disease conditions.

METHODS: We completed a single center, retrospective cohort study at an urban, academic medical center reviewing all patients (pts) ≥ 18 years of age who received rituximab 1/1/06 to 7/31/13 who had at least 12 months of follow-up following the final rituximab dose. Eligible pts were queried using an electronic pharmacy database and reviewed by 3 physicians. Detailed data included demographics, indication for rituximab, number of rituximab doses, HBV screening serology, vaccination status, and comorbidities and risk factors for HBV-R.

RESULTS: We identified 407 pts; of these, 10 were excluded due inadequate follow-up, 7 for incomplete records, and 1 was due to age <18 years with 389 pts meeting inclusion criteria. 47% of pts were female and the median age was 63 years (range, 19-94 years). The median number of rituximab doses received was 5 (1-35) and 86% of pts had a hematologic or oncologic diagnosis (most common: DLBCL n=84, CLL n=49, follicular lymphoma n=35, marginal zone lymphoma n=17, mantle cell lymphoma n=15, acute leukemia n=14, myeloma/amyloid n=13, ITP n=12, hemolytic anemia, n=10 and Burkitt’s n=9) and 14% of pts had a non-oncology indication (most common: rheumatoid arthritis n=20, lupus n=5, vasculitits n=4, scleritis n=3, Wegner’s n=3, Sjogren’s n=3, and dermatomyositis n=3) for rituximab therapy. Overall, 32% of pts were screened for HBV <6 months prior to the 1st rituximab dose. Among hematology/oncology pts, 31% had HBV screening prior to rituximab with 24% occurring within 6 months prior to the 1st dose (3% 6-12 months, 3% 12-24 months, and 1% >24 months prior). For non-oncology pts, 40% had HBV screening with 26% occurring within 6 months prior to the 1st dose (6% 6-12 months, 2%, 12-24 months, and 6% >24 months prior). Interestingly, the type of HBV screening tests varied widely with no consistent panel of serologies tested, although the majority of pts who had screening had testing for HBV surface antigen (90.7%). HBcAb was not checked as often (66%), which represents a subset of pts at risk for developing HBV-R. Of pts screened for HBcAb, 15/88 (17%) were found to be positive for HBV (n=14 HBcAb and n=1 pt was positive for HBV surface antigen). 8/15 pts had no known or obvious risk factors for HBV infection. Of the 14 pts testing positive for HBcAb prior to rituximab, only 1 pt received anti-HBV prophylactic therapy. 3 of 14 pts without HBV prophylaxis experienced HBV-R (all HBcAb+ lymphoma pts treated with rituximab/chemotherapy), one of who died due to multiorgan failure.

CONCLUSION: At our academic center, we identified a relatively low rate of HBV screening amongst pts receiving rituximab irrespective of disease specialist or diagnostic condition. In addition, among pts who were screened, testing panels were inconsistent and a significant minority of pts did not have testing for HBcAb. Furthermore, we identified a relatively high rate of occult positivity for HBcAb including in a significant fraction of pts without known risk factors. It is advocated that a National unified guideline be instituted towards rituximab-related HBV screening and institutions implement and adhere to these guidelines. Likewise, a standardized panel of HBV serology is essential, both for initial testing and follow up. This is especially important given the increasing number of FDA approvals of other anti-CD20 and related monoclonal antibodies that carry similar risks of HBV-R.

ash.confex.com/ash/2014/webprogram/Paper76598.html

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Discontinuing eltrombopag Update 1-13-15 7 years 10 months ago #45800

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The discontinuation of eltrombopag appeared safe in patients in complete remission of primary immune thrombocytopenia, according to study results.

Tomás José González-López, MD, PhD, of the department of hematology at the Hospital Universitario de Burgos in Spain, and colleagues evaluated data from 260 adults (mean age, 62 years) with primary immune thrombocytopenia (ITP). The cohort included 165 women and 95 men treated with eltrombopag (Promacta, GlaxoSmithKline) for an average of 24 months after ITP diagnosis.

Researchers reported complete remissions in 201 patients; of these patients, 80 discontinued treatment with eltrombopag.

Thirty-three patients discontinued eltrombopag because they demonstrated persistent response even with a reduction in dose. Twenty-nine patients discontinued treatment because they achieved a platelet count >400/L x 109/L. Other reasons for discontinuation were patient response (n=5), elevated aspartate aminotransferase levels (n=3), diarrhea (n=3) and thrombosis (n=3). Four patients discontinued due to other reasons.

Forty-nine patients were valuable after eltrombopag discontinuation. At a mean follow-up of 9 months post-discontinuation, 26 (mean age, 59 years; 15 female) of these patients achieved a sustained response with no additional ITP therapy. In this subset, the average time since ITP diagnosis was 46.5 months, and four of the 26 had ITP for less than 1 year. These patients received a mean of four previous treatment lines, and 42% were splenectomized.

“No predictive factors of sustained response after eltrombopag withdrawal were identified,” the researchers wrote. “Platelet response following eltrombopag cessation may be sustained in an important percentage of adult primary ITP patients who achieved complete response with eltrombopag. However, reliable markers for predicting which patients will have this response are needed.”

www.healio.com/hematology-oncology/hematology/news/online/%7B15bcd4ec-a427-4fcc-843c-fb638d301006%7D/discontinuation-of-eltrombopag-deemed-safe-after-complete-remission-of-primary-itp

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Hep B vaccine and ITP 1-19-15 7 years 10 months ago #45865

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Abstract

Hepatitis B vaccine has been administered in children and adults routinely to reduce the incidence of the disease. Even though, hepatitis B vaccine is considered as highly safe, some adverse reactions have been reported. A literature search was carried out in PubMed, accessed via the National Library of Medicine PubMed interface, searching used the following keywords: Hepatitis B vaccine and complications from 1980 to 2014. A total of 1147 articles were obtained out of which articles, which discuss the complications occurring orally or occurring elsewhere in the body, which have the potential to manifest orally after hepatitis B vaccination were selected. A total of 82 articles were identified which included 58 case series or case reports, 15 review articles, 4 cross sectional studies, 3 prospective cohort studies, one retrospective cohort study and a case control study. After reviewing the literature, we observed that complications seen after Hepatitis B vaccination are sudden infant death syndrome, multiple sclerosis, chronic fatigue syndrome, idiopathic thrombocytopenic purpura, vasculititis optic neuritis, anaphylaxis, systemic lupus erytymatosus, lichen planus and neuro-muscular disorder. Of these complications, some are manifested orally or have the potential to manifest orally. Although, most of the complications are self-limiting, some are very serious conditions, which require hospitalization with immediate medical attention.

www.ncbi.nlm.nih.gov/pubmed/25506472

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Bleeding 1-21-15 7 years 10 months ago #45893

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Abstract
BACKGROUND:

The burden of severe bleeding in adults and children with immune thrombocytopenia (ITP) has not been established.
OBJECTIVES:

To describe the frequency and severity of bleeding events in patients with ITP, and the methods used to measure bleeding in ITP studies.
PATIENTS/METHODS:

We performed a systematic review of all prospective ITP studies that enrolled 20 or more patients. Two reviewers searched Medline, Embase, CINAHL and the Cochrane registry until May 2014. Overall weighted proportions were estimated using a random effects model. Measurement properties of bleeding assessment tools were evaluated.
RESULTS:

We identified 118 studies that reported bleeding (n=10,908 patients). Weighted proportions for intracerebral hemorrhage (ICH) were 1.4% for adults [95% confidence interval (CI), 0.9-2.1%] and 0.4% for children (95% CI, 0.2-0.7%; p<0.01) most of whom had chronic ITP. Weighted proportion for severe (non-ICH) bleeding was 9.6% for adults (95% CI, 4.1-17.1%) and 20.2% for children (95% CI, 10.0-32.9%; p<0.01) with newly-diagnosed or chronic ITP. Methods of reporting and definitions of severe bleeding were highly variable among primary studies. Two bleeding assessment tools (Buchanan 2002 for children; and Page 2007 for adults) demonstrated adequate inter-rater reliability and validity in independent assessments.
CONCLUSIONS:

ICH was more common in adults and tended to occur during chronic ITP; other severe bleeds were more common in children and occurred at all stages of disease. Reporting of non-ICH bleeding was variable among studies. Further attention to ITP-specific bleeding measurement in clinical trials is needed to improve standardization of this patient-important outcome. This article is protected by copyright. All rights reserved.

www.ncbi.nlm.nih.gov/pubmed/25495497

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H Pylori - 1-22-15 7 years 10 months ago #45914

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Abstract

The practical usefulness of Helicobacter pylori eradication for immune thrombocytopenia (ITP) patients is still controversial. However, some ITP patients respond to H. pylori eradication. We conducted a multi-center, open label, prospective phase II study to define the efficacy and toxicities of H. pylori eradication as the first line treatment for persistent or chronic ITP patients with moderate thrombocytopenia. Patients with persistent or chronic ITP showing moderate thrombocytopenia (30 × 109/L ≤ platelet count ≤ 70 × 109/L) and positive C13-urea breath test (UBT) were selected. Medication consisted of lansoprazole 30 mg, amoxicillin 1000 mg, and clarithromycin 500 mg orally twice daily for a week. Complete response (CR) rate at 4 weeks, 3 months, 6 months, 12 months, and maximal response was 19.2, 50.0, 50.0, 26.9, and 65.4 %, respectively. Overall response rate (ORR) at 4 weeks, 3 months, 6 months, 12 months, and maximal response was 19.2, 57.7, 65.4, 30.8, and 69.2 %, respectively. Median maximal platelet count during the first 3 months was 110 × 109/L (range, 40-274). Median time to CR was 8 weeks (95 % CI = 5.429-10.571). Median time to ORR was 4 weeks (95 % CI = 1.228-6.772). Only per-protocol population was a response predictor for ORR at 3 months (70.0 %, p = 0.054) and maximal ORR (80.0 %, p = 0.051), but not for CR at 3 months (60.0 %, p = 0.160). Therefore, eradication of H. pylori is an effective and durable first line treatment for persistent or chronic ITP with moderate thrombocytopenia with high ORR and rapid onset in this study.

www.ncbi.nlm.nih.gov/pubmed/25501820

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Inherited THrombocytopenias - update 2 -11-15 7 years 9 months ago #46229

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New Treatment 7 years 9 months ago #46515

  • mrsb04
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I have started on the fostamatinib trial

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New articles posted here - update 2-11-15 7 years 9 months ago #46517

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Good Luck, Mrs.B!
Keep us posted,please.

Fostamatanib research:
A Syk inhibitor for sick platelets?
www.bloodjournal.org/content/113/14/3133
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New articles posted here - update 2-11-15 7 years 9 months ago #46529

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Thank you Rob 16. I will do..however there will be nothing to report for the first 4 weeks. If platelets have not reached 50 by then the dose is increases by 50% . Starting platelets were 17. 1 in 3 participants are on the placebo. Fingers crossed I'm not one of them.

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New articles posted here - update 2-20-15 7 years 9 months ago #46542

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I don't know why this wouldn't apply to adults as well. This also does not surprise me, it's something I've just assumed for a long time.


Background:Growing evidence has revealed a link between autoimmune and allergic diseases. However, few studies have assessed the relationship between allergic diseases and primary immune thrombocytopenia (ITP), an autoimmune disease frequently occurring in children. This population-based case-control study investigated the association between common allergic diseases and the subsequent risk of developing ITP during childhood.Methods:This study investigated 1,203 children younger than 18 y of age who were diagnosed with ITP between 1998 and 2008, as well as 4,812 frequency-matched controls. The odds ratios of the association between ITP and preexisting allergic diseases were calculated.Results:Children with every type of allergic disease examined in this study (except asthma) exhibited an increased risk of developing ITP; the lowest adjusted odds ratio (aOR) was 1.39 for allergic conjunctivitis (95% confidence interval (CI) = 1.09-1.79), whereas the greatest aOR was 1.84 for allergic rhinitis (95% CI = 1.49-2.27). The aORs increased with the number of concurrent allergic diseases to 2.89 (95% CI = 1.98-4.22) for children with at least three allergic diseases.Conclusion:Children with atopic diathesis have a greater risk of subsequently developing ITP. The fundamental determinants of this relationship warrant further study.

www.ncbi.nlm.nih.gov/pubmed/25580738

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New articles posted here - update 2-24-15 7 years 9 months ago #46680

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Key Points

ITP is defined as an isolated platelet count of less than 100 × 109/L (100,000/μL) and usually presents without symptoms.
Patients without symptoms who have a platelet count above 30 × 109/L should generally not be treated unless they have an increased risk of bleeding.
Recent studies suggest that viruses and other pathogens play an important role in secondary ITP.
Initially, corticosteroids are usually given as prednisone (1–2 mg/kg/day, then tapered), though recent studies suggest that dexamethasone pulses (40 mg/day for 4 days) may provide more durable responses when used in this setting.
Thrombopoietic agents are important new treatments, although their place in the overall therapy of ITP has not been established.

More at:

www.ccjm.org/index.php?id=107953&cHash=010515&tx_ttnews%5Btt_news%5D=365505

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Rituxan and TPO's - update 3-5-15 7 years 9 months ago #46949

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This study aimed to compare the efficacy and safety of rituximab (RTX) plus recombinant human thrombopoietin (rhTPO) with RTX alone in patients with immune thrombocytopenia (ITP) who had failed to respond to corticosteroids or relapsed. Recruited patients were randomized at a ratio of 2:1 into 2 groups: the combination group (RTX + rhTPO, n = 77) and the monotherapy group (RTX, n = 38). Overall response was achieved in 79.2% of patients in the combination group vs 71.1% in the monotherapy group (P = .36), and the complete response (CR) rate was 45.4% in the combination group compared with 23.7% in the monotherapy group (P = .026). The combination group had significantly shorter time to response (TTR; median and range, 7 and 4-28 days) compared with the monotherapy group (28 and 4-90 days) (P < .01). There was no difference between these 2 groups in terms of the long-term response (P = .12). Our findings demonstrated that the combination of RTX and rhTPO significantly increased the CR rate and shortened TTR compared with RTX monotherapy in the treatment of corticosteroid-resistant or relapsed ITP but failed to show a beneficial effect on the long-lasting response. This study is registered at www.clinicaltrials.gov as #NCT01525836.

Submitted June 16, 2014.
Accepted January 3, 2015.

www.bloodjournal.org/content/125/10/1541.abstract?sso-checked=true

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Splenectomy and thromboembolism - update 3-5-15 7 years 9 months ago #46953

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Splenectomy and thromboembolism - update 3-5-15 7 years 9 months ago #46958

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cannot access it at all

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Splenectomy and thromboembolism - update 3-5-15 7 years 9 months ago #46960

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Splenectomy and thromboembolism - update 3-5-15 7 years 9 months ago #46962

  • mrsb04
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That worked thank you but I can't read the splenectomy one at all

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Splenectomy and thromboembolism - update 3-5-15 7 years 9 months ago #46964

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Which splenectomy one? The last two should work. The others you can only see the abstract and the rest is behind a "pay wall".

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Oxidative stress and ITP - update 3-11-15 7 years 8 months ago #47153

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Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by increased platelet destruction or decreased platelet production. The mechanism of the disease has been extensively studied so that we now have a much improved understanding of the pathophysiology; however, the trigger of the autoimmunity remains unclear. More recently, oxidative stress was identified to be involved in the pathogenesis of ITP and provides a new hypothesis for the initiation of autoimmunity in patients with ITP. In this review, oxidative stress and its impact on autoimmunity, particularly ITP, will be covered.

See more.....

www.sciencedirect.com/science/article/pii/S0037196313000942

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New articles posted here - update 11-5-13 7 years 8 months ago #47342

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Interesting article regarding the low vitamin D and link to auto-immune and EBV. I went to a rheumatologist 2 and a half years ago since I was very achy in my joints and just didn't feel well for a long time. She diagnosed me with severe vitamin D deficiency (which was treated at the time) but no positive ANA factor so auto immune wasn't diagnosed (although I had Type 2 diabetes and newly diagnosed hypothyroidism at the time). Fast forward to last August, now I have a positive ANA factor for auto-immune, have low blood platelets - ITP, and now have Lupus (newly diagnosed). Wonder if all this was there 2 1/2 years ago, or just starting, but no diagnosed? How do they test for EBV, or do they?

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New articles posted here - update 2-11-15 7 years 8 months ago #47343

  • mrsb04
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Platelets up to 39 from 17 in 4 weeks..Trial drug dose increased by 50%

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