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Concept: Idiopathic thrombocytopenic purpura


In some patients with refractory thrombotic thrombocytopenic purpura (TTP), efforts to reduce the causative antibody to ADAMTS13 by depleting B cells with rituximab are often effective. In a patient in whom such therapy failed, bortezomib was effective.

Concepts: Protein, Patient, Idiopathic thrombocytopenic purpura, Thrombotic thrombocytopenic purpura


Background. The treatment of choice in steroid-resistant immune thrombocytopenia is still controversial, due to the recent advent of new drugs (anti-CD20 antibodies and thrombopoietin mimetics) which have encouraged a generalized tendency to delay splenectomy. Consequently, the importance to define the efficacy and safety of splenectomy in the long-term is substantial. Patients and Methods. We retrospectively analyzed the data of 233 patients affected by immune thrombocytopenia, who underwent splenectomy between 1959 and 2001, in 6 European hematological Institutions and have now a minimum follow-up of 10 years from surgery. Results. Of the 233 patients, 180 (77%) achieved a complete response and 26 (11%) a response. Sixty-eight out of 206 (33%) responsive patients relapsed, mostly (75%) within 4 years from first response. In 92 patients (39.5%), further treatment was required after splenectomy, which was effective in 76 cases (83%). In 138 patients (59%) response was maintained, free of any treatment, at last contact. No significant association between baseline characteristics and likelihood of stable response was found. Overall, 73 (31%) and 58 (25%) patients experienced at least one infectious or hemorrhagic complication, which were fatal in 2 and 3 patients, respectively. A stable response to splenectomy was associated with a lower rate of infections (p=0.004) and hemorrhages (p<0.0001). Thrombosis developed in 18 patients (8%), fatal in 4. Conclusions. Splenectomy achieved a long-term stable responses in around 60% of cases. Complications mainly affected non-responding patients and were fatal in a minority of the cases.

Concepts: Immune system, Antibody, Blood, Retrospective, Platelet, Leukemia, Bleeding, Idiopathic thrombocytopenic purpura


Immune thrombocytopenia (ITP) is a hematological disorder with an isolated decrease in number of circulating platelets. Bee venom therapy (BVT) is a form of alternative medicine. It is still being practiced in the Middle East and other parts of Asia. In BVT, acupuncture points are used to inject diluted bee venom into the body. The pharmacological basis behind BVT is not fully understood. However, it has been used to treat various medical conditions such as arthritis and low back pain. On the other hand there have been a number of reported complications of BVT use such as ITP. We present a case report on ITP after BVT.

Concepts: Medicine, Low back pain, Platelet, Middle East, Acupuncture, Alternative medicine, Asia, Idiopathic thrombocytopenic purpura


Background Acquired thrombotic thrombocytopenic purpura (TTP) is caused by aggregation of platelets on ultralarge von Willebrand factor multimers. This microvascular thrombosis causes multiorgan ischemia with potentially life-threatening complications. Daily plasma exchange and immunosuppressive therapies induce remission, but mortality and morbidity due to microthrombosis remain high. Methods Caplacizumab, an anti-von Willebrand factor humanized single-variable-domain immunoglobulin (Nanobody), inhibits the interaction between ultralarge von Willebrand factor multimers and platelets. In this phase 2, controlled study, we randomly assigned patients with acquired TTP to subcutaneous caplacizumab (10 mg daily) or placebo during plasma exchange and for 30 days afterward. The primary end point was the time to a response, defined as confirmed normalization of the platelet count. Major secondary end points included exacerbations and relapses. Results Seventy-five patients underwent randomization (36 were assigned to receive caplacizumab, and 39 to receive placebo). The time to a response was significantly reduced with caplacizumab as compared with placebo (39% reduction in median time, P=0.005). Three patients in the caplacizumab group had an exacerbation, as compared with 11 patients in the placebo group. Eight patients in the caplacizumab group had a relapse in the first month after stopping the study drug, of whom 7 had ADAMTS13 activity that remained below 10%, suggesting unresolved autoimmune activity. Bleeding-related adverse events, most of which were mild to moderate in severity, were more common with caplacizumab than with placebo (54% of patients vs. 38%). The frequencies of other adverse events were similar in the two groups. Two patients in the placebo group died, as compared with none in the caplacizumab group. Conclusions Caplacizumab induced a faster resolution of the acute TTP episode than did placebo. The platelet-protective effect of caplacizumab was maintained during the treatment period. Caplacizumab was associated with an increased tendency toward bleeding, as compared with placebo. (Funded by Ablynx; number, NCT01151423 .).

Concepts: Clinical trial, Coagulation, Platelet, Von Willebrand factor, Von Willebrand disease, Thrombocytopenia, Idiopathic thrombocytopenic purpura, Thrombotic thrombocytopenic purpura


Thrombotic thrombocytopenic purpura (TTP), a rare thrombotic microangiopathy, is defined by a mechanical hemolytic anemia, severe thrombocytopenia, and visceral ischemia due to systemic platelet-rich microthrombi. Specifically in TTP microthrombi, von Willebrand factor, not fibrinogen, is the protein that binds to platelets.(1) Von Willebrand factor is a multimeric glycoprotein that is crucial for physiologic platelet adhesion and aggregation at high shear rates of blood flow, and the largest von Willebrand factor multimers are the most adhesive. The hemostatic power of von Willebrand factor is regulated by a specific cleaving metalloprotease named ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 repeats, . . .

Concepts: Red blood cell, Coagulation, Platelet, Hematology, Von Willebrand factor, Thrombocytopenia, Idiopathic thrombocytopenic purpura, Thrombotic thrombocytopenic purpura


BACKGROUND: Evans' syndrome is an uncommon condition defined by the combination (either simultaneously or sequentially) of immune thrombocytopenia purpura and autoimmune hemolytic anemia with a positive direct antiglobulin test in the absence of known underlying etiology. OBJECTIVES: We present a case of Evans' syndrome following influenza vaccination. CASE REPORT: A 50-year-old man with no prior medical history developed Evans' syndrome 4 days after receiving influenza immunization. The patient improved following treatment with oral prednisone and intravenous immunoglobulin. CONCLUSION: Influenza vaccine is one of the most commonly used vaccines worldwide, with millions of people being vaccinated annually. Despite its wide use, only sparse information has been published concerning any hematological effects of this vaccine. The rarity of such effects supports the safety of using this vaccine.

Concepts: Immune system, Vaccine, Vaccination, Immunology, Hematology, Blood disorders, Idiopathic thrombocytopenic purpura, Influenza vaccine


Along with their immunogenic role, dendritic cells (DCs) are also critical in maintaining tolerance to self-antigens by inducing regulatory T cells (Tregs) via the expression of the immunomodulatory enzyme indoleamine 2,3-dioxygenase 1 (IDO1). In turn, Tregs modulate the maturation and/or function of DCs. In immune thrombocytopenia (ITP), the interaction between DCs and Tregs has never been investigated although decreased number/function of Tregs as well as altered DCs have been described. Here, we ask whether, in ITP: (1) IDO1 expression/activity is decreased in mature DCs; (2) IDO1-mediated Treg generation is impaired; and (3) DC maturation is abnormally modulated by Tregs. We found that in ITP, DCs show reduced capability of upregulating the expression/activity of IDO1. This finding results in the reduced ability of mature DCs of converting T cells into Tregs. In turn, Tregs are characterized by decreased interleukin-10 production and show lower ability of inhibiting DC maturation. In conclusion, these data point out the role of IDO1 in the impaired regulatory T cell development of ITP patients and suggest that the cross-talk between Tregs and DCs is hampered and plays a pathogenetic role.

Concepts: Enzyme, T cell, T cells, Thrombocytopenia, Autoimmunity, Idiopathic thrombocytopenic purpura, Human cells, Regulatory T cell


A recognized paradigm for the therapeutic action of intravenous immunoglobulin (IVIG) in immune thrombocytopenia (ITP) involves up-regulation of the inhibitory Fcγ receptor (FcγRIIB) in splenic macrophages. However, published data have indicated that opposing results are obtained when using FcγRIIB-deficient mice on different strain backgrounds. Herein we show BALB/c FcγRIIB(-/-) and wild-type, with or without spleens, all recover ITP with similar dynamics after IVIG (1 g/kg) treatment; however, this was not the case for C57BL/6 (B6) FcγRIIB(-/-). In investigating this conundrum, we found that wild-type B6 mice are much less sensitive than BALB/c to IVIG-mediated amelioration of ITP, requiring approximately 2- to 2.5-fold more IVIG than BALB/c. When using 2.5 g/kg IVIG in FcγRIIB(-/-) B6 mice, amelioration of ITP was as in wild-type in all animals. Our findings led us to the conclusion that different strains of mice respond differently to IVIG and that FcγRIIB plays no role in the mechanism of effect of IVIG in experimental ITP.

Concepts: Immune system, White blood cell, Antibody, Platelet, Spleen, Intravenous immunoglobulin, X-linked agammaglobulinemia, Idiopathic thrombocytopenic purpura


Therapeutic plasma exchange is established treatment for patients with thrombotic thrombocytopenic purpura (TTP) and for refractory cases immunosuppressive therapy can also be considered. We present a refractory case of TTP which was managed with therapeutic plasma exchange and rituximab.

Concepts: Idiopathic thrombocytopenic purpura, Thrombotic thrombocytopenic purpura, Plasmapheresis


Patients presenting with microangiopathic hemolysis and thrombocytopenia are often given the diagnosis of thrombotic thrombocytopenic purpura and treated with plasma exchange until the acute episode is over. Recent findings have shown that acquired thrombotic thrombocytopenic purpura is a chronic autoimmune disease with inhibitory antibodies of a disintegrin and metalloprotease with thrombospondin repeat, member 13 and are at risk of relapses that may be preventable. Furthermore, many of the patients given the diagnosis of thrombotic thrombocytopenic purpura really have atypical hemolytic uremic syndrome due to defective complement regulation that can be more effectively treated to prevent death and end-stage renal failure with eculizumab, a humanized monoclonal antibody of complement C5. These advances indicate that an accurate differential diagnosis of microangiopathic hemolysis is essential for optimal patient management.

Concepts: Immune system, Renal failure, Medical terms, Monoclonal antibodies, Thrombocytopenia, Idiopathic thrombocytopenic purpura, Hemolytic-uremic syndrome, Thrombotic thrombocytopenic purpura