Can rituximab replace splenectomy in immune thrombocytopenic purpura?

Aim  Immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by premature platelet destruction. Standard practice is to initiate treatment with corticosteroids, followed by splenectomy. Most published literature for responses from rituximab is in patients with chronic refractory ITP, who have failed multiple prior treatments, including splenectomy. We therefore decided to analyze our patient population with ITP who had been treated with rituximab, mainly as a second line treatment regimen prior to splenectomy. Methods  We performed a retrospective chart review of patients with a diagnosis of ITP who had been treated with rituximab between January 2001 and December 2006 at our institution. Results  18/29 patients (62%) had a CR, 2/29 (7%) patients had a PR, representing an overall response rate of 69%. The average time to response was 5 weeks and all patients have maintained their response for more than 12 months after treatment with rituximab. Conclusion  Our study shows higher CR, comparable overall response rates, but with a longer duration of response when compared to the published literature.     

Helicobacter pylori eradication: Novel therapy for immune thrombocytopenic purpura? A review of the literature

Eradication of Helicobacter pylori (H. pylori ) from the gastric mucosa has been associated with improvement of several systemic diseases, including immune thrombocytopenic purpura (ITP). Over the last 5 years, several studies have reported improved platelet counts in H. pylori-positive ITP patients following standard triple H. pylori eradication therapy. Review of published studies in which eradication of H. pylori has been performed in the ITP population indicates an overall response rate of 52% in 193 subjects in whom H. pylori was eradicated. Cohorts from Japan and Italy report higher response rates. There is no established mechanism to explain how this organism, which does not invade the gastric mucosa, could be implicated in the pathogenesis of this immune-based platelet disorder. Several theories including molecular mimicry, platelet aggregation, and immunomodulatory effects of macrolides have been proposed to explain the platelet response to anti-H. pylori therapy. Large randomized-controlled studies enrolling patients from various ethnic backgrounds will be necessary to determine the response rate and mechanism of response and to gain a better understanding of the pathogenesis of ITP.     

Should rituximab be used before or after splenectomy in patients with immune thrombocytopenic purpura?

PURPOSE OF REVIEW: The anti-CD20 monoclonal antibody rituximab has been used to treat patients with chronic immune thrombocytopenic purpura. This review discusses whether the optimal timing for this therapy is before splenectomy, or after failure of splenectomy. RECENT FINDINGS: No study has directly compared rituximab to splenectomy in patients with chronic immune thrombocytopenic purpura. Rituximab produces an initial response in approximately 60% of cases, with no significant difference between splenectomized and nonsplenectomized patients. Long-term complete responses are observed in 15-20% of cases. Adverse events related to the drug were usually mild or moderate, with a low incidence of infections. Long-term safety data, however, are still lacking. Deaths have been reported for 2.9% of immune thrombocytopenic purpura cases treated with rituximab, but they could not be attributed to the study drug. SUMMARY: Both the response rate and the response duration appear lower following rituximab than following splenectomy. Although the side effects may be fewer, there is insufficient evidence to support the replacement of splenectomy with rituximab as a second-line treatment of chronic immune thrombocytopenic purpura outside a clinical trial. At the present time, the use of immunotherapy before splenectomy can be recommended only in patients at high risk for splenectomy and in those not willing to undergo surgery.     

Helicobacter pylori infection in patients with autoimmune thrombocytopenic purpura

AIM:To compare the prevalence of Helicobacter pylori(Hpylon)infection in autoimmune thrombocytopenic purpura(AITP)patients with that of nonthrombocytopenic controls,and to evaluate the efficacy of the treatment in H pylori( )and H pylor(-)AITP patients.METHODS:The prevalence of gastric H pylori infection in38 adult AITP patients(29 female and 9 male;median age27 years;range 18-39 years)who consecutively admittedto our clinic was investagated.RESULTS:H pylori infection was found in 26 of 38 AITPpatients(68.5%).H pylori infection was found in 15 of 23control subjects(65.2%).The difference in H pylori infectionbetween the 2 groups was not significant.Thrombocytecount of H pylori-positive AITP patients was significantlylower than that of H pylori-negative AITP patients(P<0.05).Thrombocyte recovery of H pylori-positive group was lessthan that of H pylori-negative group(P<0.05).CONCLUSION:H pylori infection should be considerecd inthe treatment of AITP patients with H pylori infection.     

Does the site of platelet sequestration predict the response to splenectomy in adult patients with immune thrombocytopenic purpura?

Splenectomy is the only potentially curative treatment for chronic immune thrombocytopenic purpura (ITP) in adults. However, one-third of the patients relapse without predictive factors identified. We evaluate the predictive value of the site of platelet sequestration on the response to splenectomy in patients with ITP. Eighty-two consecutive patients with ITP treated by splenectomy between 1992 and 2013 were retrospectively reviewed. Platelet sequestration site was studied by ¹¹¹Indium-oxinate-labeled platelets in 93% of patients. Response to splenectomy was defined at last follow-up as: complete response (CR) for platelet count (PC) ≥100?×?10⁹/L, response (R) for PC≥30?×?10⁹/L and <100?×?10⁹/L with absence of bleeding, no response (NR) for PC<30?×?10³/L or significant bleeding. Laparoscopic splenectomy was performed in 81 patients (conversion rate of 16%), and open approach in one patient. Median follow-up was 57 months (range, 1–235). Platelet sequestration study was performed in 93% of patients: 50 patients (61%) exhibited splenic sequestration, 9 (11%) hepatic sequestration and 14 patients (17%) mixed sequestration. CR was obtained in 72% of patients, R in 25% and NR in 4% (two with splenic sequestration, one with hepatic sequestration). Preoperative PC, age at diagnosis, hepatic sequestration and male gender were significant for predicting CR in univariate analysis, but only age (HR?=?1.025 by one-year increase, 95% CI [1.004–1.047], p?=?0.020) and pre-operative PC (HR?=?0.112 for?>?100 versus <=100, 95% CI [0.025–0.493], p?=?0.004) were significant predictors of recurrence-free survival in multivariate analysis. Response to splenectomy was independent of the site of platelet sequestration in patients with ITP. Pre-operative platelet sequestration study in these patients cannot be recommended.     

Can drugs cause autoimmune thrombocytopenic purpura?

A wide range of medications can cause life-threatening immune thrombocytopenia (ITP), hemolytic anemia, or neutropenia in sensitive individuals. The antibodies associated with these conditions usually require soluble drug to be present in order to react with the cell membrane glycoproteins for which they are specific. However, some patients make drug-independent antibodies (autoantibodies) as well. Occasionally, only autoantibodies are produced following exposure to a drug. Although drugs and other small molecules can become conjugated to proteins in vivo, which may induce an immune response, only fragmentary information is available to explain how exogenous substances sometimes perturb the immune system in such a way that antibodies capable of causing immune cytopenia are produced. Platelets are affected by drug-induced antibodies more often than any other blood element. For many drug-induced thrombocytopenias, the targeted membrane glycoproteins are readily accessible for laboratory investigation and methods for detecting the responsible antibodies are well developed. Techniques for studying cellular aspects of the immune response induced by drugs through in vitro manipulation of T and B lymphocytes are also advancing rapidly. Studies of drug-induced ITP may provide clues to the general mechanisms whereby drugs and other xenobiotics induce immune diseases. Clinicians should consider the possibility of an exogenous trigger in patients who present with apparent autoimmune thrombocytopenia.     

Does cryosupernatant plasma improve outcome in thrombotic thrombocytopenic purpura? No answer yet

A randomized prospective trial compared cryosupernatant plasma (CSP) to fresh frozen plasma (FFP) for treatment of thrombotic thrombocytopenic purpura (TTP). A total of 236 patients were required: 28 patients were treated with CSP and 24 with FFP within 30 months. There were no differences in survival at 1 month. By day 9, 17 of 26 patients with CSP and 18 of 24 with FFP had a platelet count >100 x 10(9)/l. At entry, von Willebrand factor (VWF) multimers were normal in all patients (range 1.1-3.95 IU/ml). ADAMTS-13 levels showed large variations ranging from 10% to 100% activity. At entry, no individual had <5% VWF cleaving protease. By day 9 (end of cycle), 89% (FFP) and 67% (CSP) had levels >50% of the controls. At 6 months some patients showed inhibitors to the enzyme in spite of adequate or normal platelet counts. The data from this study do not show an apparent advantage to the use of CSP in TTP. A large number of patients will be required to determine appropriate replacement therapy. We were not able to find a statistically significant relationship between the low level of protease activity at presentation of TTP and response.     

Evidence-Based Minireview: Should caplacizumab be used routinely in unselected patients with immune thrombotic thrombocytopenic purpura?

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Learning Objectives

• Understand the evidence base for the safety and efficacy of caplacizumab in iTTP, including through comparison of observational data
• Assess the bleeding risk associated with caplacizumab use in iTTP
• Analyze the cost-effectiveness of caplacizumab in the treatment of iTTP

     

Does treatment with intermittent infusions of intravenous anti-D allow a proportion of adults with recently diagnosed immune thrombocytopenic purpura to avoid splenectomy?

This study explored whether repeated infusions of intravenous anti-D could allow adults with recently diagnosed immune thrombocytopenic purpura (ITP) who had failed an initial steroid course to postpone and ultimately avoid splenectomy. Twenty-eight Rh(+), nonsplenectomized adults with ITP diagnosed within 1 to 11 months and platelet counts 30 x 10(9)/L (30 000/microL) or below were enrolled. Anti-D was infused whenever the platelet count decreased to 30 x 10(9)/L (30 000/microL) or below. "Response" was defined as a platelet increase of more than 20 x 10(9)/L (20 000/microL) to more than 30 x 10(9)/L (30 000/microL) within 7 days of treatment. Patients were a median 3.5 months from ITP diagnosis at enrollment and had received a median of 2 previous therapies, including prednisone in 26 of 28 cases. They were followed for a median 26 months. A total of 93% responded to their initial infusion of anti-D, and 68% repeatedly responded with counts maintained above 30 x 10(9)/L (30 000/microL) using anti-D alone. Currently, 12 (43%) of 28 patients have been off all treatment for more than 6 months without undergoing splenectomy, 6 maintaining counts above 100 x 10(9)/L (100 000/microL). Seven continue on treatment, 8 underwent splenectomy, and 1 was lost to follow-up at 10 months. One patient discontinued anti-D because of toxicity. Patients with platelet counts at least 14 x 10(9)/L (14 000/microL) at enrollment were more likely to discontinue treatment (P <.05). Anti-D was an effective maintenance treatment for two thirds of Rh(+), nonsplenectomized adults with ITP who had failed an initial steroid course. Intermittent infusions of intravenous anti-D allowed more than 40% of these adults to avoid splenectomy and to achieve stable platelet counts off all therapy, even after many months of treatment. Platelet count at study entry was the primary predictor of outcome.     

Does H. Pylori infection play a role in idiopathic thrombocytopenic purpura and in other autoimmune diseases?

Idiopathic thrombocytopenic purpura (ITP), an autoimmune disease caused by sensitization of platelets by autoantibodies leading to platelet destruction, has been associated with some infectious agents, including Helicobacter pylori. The study by Suzuki et al., published in this issue, provides further evidence of the role of H. pylori infection in the pathogenesis of ITP, as confirmed by the increase in the platelet count in patients with ITP, following H. pylori eradication. Interestingly, H. pylori infection has also been shown to play a role in other diseases in which autoimmune mechanisms may be predominant, such as acne rosacea, idiopathic chronic urticaria, and atherosclerosis. While H. pylori eradication is usually recommended in patients with gastric diseases, there are no specific indications for extraalimentary diseases. In the light of the recent findings, a revision of the current guidelines for the management of H. pylori infection may be needed.