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Genotype and Phenotype Correlation in Hereditary Thrombotic Thrombocytopenic Purpura (Upshaw-Schulman Syndrome)

Thrombotic Thrombocytopenic Purpura; Congenital Thrombotic Thrombocytopenic Purpura; Familial Thrombotic Thrombocytopenic Purpura; Thrombotic Thrombocytopenic Purpura, Congenital; Upshaw-Schulman Syndrome



Anticoagulant Therapy in Chronic Idiopathic Thrombocytopenic Purpura.  

National Technical Information Service (NTIS)

The response of a patient with chronic severe idiopathic thrombocytopenic purpura (ITP), refractory to all forms of therapy, to the controlled use of anticoagulation is described. A significant elevation of the platelet count and clinical improvement acco...

R. J. Cohen L. H. Dennis M. E. Conrad



Acute idiopathic thrombocytopenic purpura in childhood: a case report.  


Acute thrombocytopenic purpura is the most common of thrombocytopenias of the childhood. Clinical features include petechial lesions on oral mucosa, gingival bleeding and occasionally hemorrhage. A case of acute thrombocytopenic purpura is presented. PMID:12885010

Hegde, R J; Parimala, K; Shivaprakash



Bilateral retinal detachments in thrombotic thrombocytopenic purpura  

Microsoft Academic Search

Bilateral serous retinal detachments are rare complications of thrombotic thrombocytopenic purpura (TTP). We report the case of a 28-year-old woman with chronic relapsing TTP with bilateral serous retinal detachments, which resolved after prompt aggressive medical therapy. Unlike serveral previous reports, the retinal detachments in our patient were unrelated to systemic hypertension.

Richard E. Wyszynski; K. Ellen Frank; Hans E. Grossniklaus



Thrombotic Thrombocytopenic Purpura Associated with Ticlopidine  

Microsoft Academic Search

Thrombotic thrombocytopenic purpura is a syndrome characterized by hemolytic anemia, thrombocytopenia, neurological symptoms, fever and renal dysfunction. Although the syndrome is usually associated with various infections, vasculitis and pregnancy, rarely can it be associated with certain neoplasms and drugs such as ticlopidine. A 63-year-old woman, who had undergone coronary angioplasty and had been started on ticlopidine, was admitted to our

Orhan Türken; Ahmet Öztürk; Bülent Orhan; Gökhan Kandemir




Microsoft Academic Search

Amegakaryocytic thrombocytopenia, a rare variation of bone marrow aplasia, has been described in association with viral infection, vaccination, alcoholism and drug-toxicity. In the present study, we presented 20 cases of amegakaryocytic thrombocytopenic purpura in a cohort of Iranian patients presented to hematology clinics of two university hospitals with mucocutaneous bleeding. Complete blood counts, reticulocyte counts and repeated bone marrow aspiration\\/biopsy

B. Shafayan; A. Khodabandeh; M. Keyhani; M. Bakhshi


Defibrotide in Recurrent Thrombotic Thrombocytopenic Purpura  

Microsoft Academic Search

Thrombotic thrombocytopenic purpura (TTP) is a common illness characterized by platelet thrombi within the microvascularization. In its natural course, this disease has had a mortality rate of 90%. Plasma infusion or exchange achieved a survival rate of 70% to 90%. However, 10% to 30% of patients surviving the initial TTP episode relapse at regular intervals. The treatment of recurrent forms

Enrico Maria Pogliani; Paolo Perseghin; Matteo Parma; Pietro Pioltelli; Gianmarco Corneo



Mycoplasma-pneumoniae-Induced Thrombotic Thrombocytopenic Purpura  

Microsoft Academic Search

Thrombotic thrombocytopenic purpura (TTP) is a fatal disease characterized by widespread platelet aggregation, hemolytic anemia and fever with renal and neurological involvement. Different factors have been associated with the development of TTP, e.g. infections, pregnancy, chemotherapy, drug therapy and bone marrow transplantation. Recent data imply that all these different causes may induce the disease by decreasing the activity of the

E. Bar Meir; H. Amital; Y. Levy; A. Kneller; Y. Bar-Dayan; Y. Shoenfeld



Idiopathic Thrombocytopenic Purpura and Mononeuropathy multiplex  

Microsoft Academic Search

Peripheral neuropathy is an uncommon complication of idiopathic thrombocytopenic purpura (ITP). We report a 61-year-old man with ITP who developed acute-onset mononeuropathy multiplex. An electrophysiologic study revealed active axonal degenerative alteration, and a sural nerve biopsy showed axonal degeneration. Intraneural hemorrhage was suggested to be the most likely cause.

Toshiharu Ijichi; Manabu Muranishi; Kazuo Shimura; Toru Inaba; Naohisa Fujita; Nobuyuki Oka; Masanori Nakagawa



Laparoscopic splenectomy for idiopathic thrombocytopenic purpura (ITP)  

Microsoft Academic Search

  Background: Although the short-term benefits of laparoscopic splenectomy (LS) have been well documented, long-term follow-up\\u000a data of patients who have undergone LS for ITP are scarce. We report our long-term follow-up data in patients who underwent\\u000a LS for idiopathic thrombocytopenic purpura (ITP). Methods: Data were obtained from a prospectively collected computer database\\u000a of 52 patients who underwent LS between October

D. E. Pace; P. M. Chiasson; C. M. Schlachta; J. Mamazza; E. C. Poulin



Childhood chronic immune thrombocytopenic purpura (ITP)  

Microsoft Academic Search

Chronic immune thrombocytopenic purpura (ITP) develops in approximately 20% of children with acute ITP. Treatment requires differentiating the truly idiopathic state from thrombocytopenias associated with other disorders. Treatment is recommended in cases where platelet counts drop below 20×109\\/L. Therapeutic options include corticosteroids, intravenous immunoglobulin TG(IVIg), and anti-D, as well as splenectomy. The benefits and disadvantages of each modality are reviewed,

V. Blanchette



Immune Thrombocytopenic Purpura Associated with Pulmonary Tuberculosis  

PubMed Central

Thrombocytopenic purpura as a manifestation of pulmonary tuberculosis is very rare. We report a case of 25-year-old female who presented with thrombocytopenia-induced purpuric spots and an abnormal chest X-ray. There was no hepatosplenomegaly while the bone marrow examination revealed normal maturation of myeloid and erythroid series with increased megakaryocytes. Acid fast bacilli were seen in the sputum microscopy. A diagnosis of sputum smear positive pulmonary tuberculosis along with immune thrombocytopenia was made. High dose intravenous immunoglobulin therapy along with antituberculous drugs corrected the thrombocytopenia and also cured pulmonary tuberculosis. This case report illustrates the causal association between immune thrombocytopenia and tuberculosis.

Bairagya, Tapan Das; Das, Sibes Kumar; Jana, Pulak Kumar; Bhattacharya, Somnath



[Partial splenic embolization for idiopathic thrombocytopenic purpura].  


Twelve patients with idiopathic thrombocytopenic purpura (ITP) who were resistant to conventional steroid therapy under went partial splenic embolization (PSE). PSE was effective for 7 out of 10 eligible cases. The reduction ratio of PAIgG was significantly higher in effective cases. The PAIgG level before treatment and platelet counts one week after PSE were higher in effective cases than those of non-effective cases. The effects of PSE did not depent on age, sex, the duration of disease, platelet count, embolization rate or the effect of intravenous immunoglobulin therapy. No serious side effects were observed. PSE can be an alternative therapy to splenectomy for ITP. PMID:9884548

Hayashi, T; Sugawara, N; Takahashi, T; Adachi, Y; Makiguchi, Y; Takahashi, H; Adachi, M; Hinoda, Y; Yamashiro, K; Mukaiya, M; Katsuramaki, T; Hirata, K; Imai, K



Erythromelalgia in a patient with thrombotic thrombocytopenic purpura.  


Erythromelalgia is characterized by paroxysmal burning pain and redness of the distal extremities; primary and secondary forms exist. Secondary erythromelalgia is most commonly associated with essential thrombocythemia and polycythemia vera, and the pathogenic mechanism is thought to be platelet aggregation. Thrombotic thrombocytopenic purpura is characterized by thrombocytopenia, microangiopathic anemia, renal failure, and fluctuating neurologic signs and symptoms. The pathogenic mechanism suggested for thrombotic thrombocytopenic purpura is diffuse platelet aggregation. We describe a female patient in whom thrombotic thrombocytopenic purpura was associated with erythromelalgia. This has not been previously reported. PMID:1613144

Yosipovitch, G; Krause, I; Blickstein, D



Immune thrombocytopenic purpura as a complication of Bartonella henselae infection.  


Immune thrombocytopenic purpura is an infrequent yet well-recognized complication of viral infections, such as mumps, rubella, varicella, cytomegalovirus, parvovirus and infectious monunucleosis by Epstein-Barr virus. Some recent studies have described a possible association between Henoch-Schonlein purpura, a non-thrombocytopenic purpura, and seropositivity for Bartonella henselae, but in the literature only sporadic case reports have described a severe immune thrombocytopenic purpura as a complication of Bartonella henselae infection. We report a case of an immunocompetent child with clinical and serological evidence of Bartonella henselae infection presenting with purpura and cervical lymphoadenopathy and treated with intravenous immunoglobulin. The patient obtained a rapid and persistent increase in platelet count and a complete regression of purpura. PMID:18622151

Palumbo, Emilio; Sodini, Federica; Boscarelli, Giuseppe; Nasca, Giuseppina; Branchi, Maurizio; Pellegrini, Guido



Animal models for thrombotic thrombocytopenic purpura.  


Thrombotic thrombocytopenic purpura (TTP) is a puzzling disorder in many ways. The disease is difficult to diagnose as analogous symptoms are also found in other microangiopathic disorders. Although ADAMTS13 deficiency is generally required to develop TTP, only some patients with severe ADAMTS13 deficiency do spontaneously develop this disease. It is therefore assumed that environmental and/or genetic factors are needed to cause acute TTP. Nevertheless, acute TTP-like symptoms have also been observed in patients with moderate or normal levels of ADAMTS13. The development of animal models for TTP has allowed a closer look at the specific need for ADAMTS13 deficiency and the necessity for additional triggers in the pathophysiology of TTP. Mouse models for congenital TTP and a baboon model for acquired TTP have been generated. These animal models have also proven to be extremely valuable in developing new treatment strategies for TTP. In the current review, we discuss current animal models for TTP, what we have learned from them and how they were used to test new treatment strategies. PMID:23809106

Vanhoorelbeke, K; De Meyer, S F



Immune thrombocytopenic purpura (ITP) plasma and purified ITP monoclonal autoantibodies inhibit megakaryocytopoiesis in vitro  

Microsoft Academic Search

To determine if megakaryocytes are targeted by immune thrombocytopenic purpura (ITP) autoantibodies, as are platelets, we have studied the effects of ITP plasma on in vitro megakaryocytopoiesis. Umbilical cord blood mononuclear cells were incubated in the presence of thrombopoietin and 10% plasma from either ITP patients (n = 53) or healthy donors. The yield of megakaryocytic cells, as determined by

Mei Chang; Peggy A. Nakagawa; Shirley A. Williams; Michael R. Schwartz; Karen L. Imfeld; Jeffrey S. Buzby; Diane J. Nugent


Complete Recovery of Ischemic Cardiomyopathy from Thrombotic Thrombocytopenic Purpura  

PubMed Central

A 50 year old male HIV patient on antiretroviral therapy was admitted for chest pain. Upon admission, the patient was found to have elevated cardiac enzymes, acute thrombocytopenia, hemolytic anemia, acute pancreatitis and acute renal failure. The patient was diagnosed with thrombotic thrombocytopenic purpura/haemolytic uremic syndrome and emergency plasma exchange therapy was initiated along with aspirin, beta-blockers, steroids, and antiretroviral therapy. Patient responded well and demonstrated complete resolution of ischemic cardiomyopathy with left ventricular ejection fraction improving from 35% to 55% by the time of discharge. Essentially, prompt diagnosis and treatment can reverse cardiac damage induced by thrombotic thrombocytopenic purpura.

Gaddam, Sainath; Pablani, Lata; Chainani, Vinod; Kavuda, Ravi Raj; Nagrani, Tarun; Rjaili, Georges Abou; Dhar, Meekoo; Lafferty, James C



Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura  

Microsoft Academic Search

Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. The term thrombotic microangiopathy (TMA) defines a lesion of vessel wall thickening (mainly arterioles or capillaries), intraluminal platelet thrombosis, and partial or complete obstruction of the vessel lumina. Depending on whether renal or brain lesions prevail, two pathologically indistinguishable but somehow clinically different entities have been described: the hemolytic uremic syndrome

Piero Ruggenenti; Marina Noris; Giuseppe Remuzzi



Laparoscopic versus open splenectomy for immune thrombocytopenic purpura  

Microsoft Academic Search

Background. We sought to determine whether laparoscopic techniques can reduce the operative morbidity of surgery in patients undergoing splenectomy for immune thrombocytopenic purpura (ITP).Methods. All patients (60) undergoing splenectomy for ITP at the Royal Adelaide Hospital from January 1985 to November 1995 were reviewed. Results of patients undergoing open operation were obtained by means of retrospective case note review, whereas

David I Watson; Brendon J Coventry; Terence Chin; P. Grantley Gill; Peter Malycha



Idiopathic thrombocytopenic purpura diagnosed during the second decade of life  

Microsoft Academic Search

Objective: To retrospectively review our institutional experience of adolescents with idiopathic thrombocytopenic purpura (ITP). Study design: Medical record review of all patients diagnosed with ITP between the ages of 10 and 18 years seen at our center from January 1976 to March 2000. Results: Data were collected from 126 patients. Of the evaluable 110 cases, 63 (57%) satisfied the criteria

Eric J. Lowe; George R. Buchanan



Plasmapheresis for Thrombotic Thrombocytopenic Purpura following Bone Marrow Transplantation  

Microsoft Academic Search

Recognition of thrombotic thrombocytopenic purpura (TTP)\\/hemolytic uremic syndrome (HUS) following bone marrow transplantation (BMT) has increased in recent years. The use of plasma exchange has greatly improved the outlook of de novo TTP. Fewer data are available on its use in post-BMT TTP but small uncontrolled series showed poor results with low response rates. We present here a case of

O. Kolker; S. Sviri; D. M. Linton; A. Nagler; M. Y. Shapira



Morbidity and mortality in adults with idiopathic thrombocytopenic purpura  

Microsoft Academic Search

To study outcomes of adults with idiopathic thrombocytopenic purpura (ITP), we per- formed a follow-up study in a cohort of 152 consecutive patients who were treated ac- cording to a well-defined algorithm. Long- term outcomes were determined relative to the response 2 years after diagnosis, be- cause most (93%) patients who ultimately attained platelet counts above 30.0 3 109\\/L (30

Johanna E. A. Portielje; Rudi G. J. Westendorp; Hanneke C. Kluin-Nelemans; Anneke Brand



Parvovirus B19 infection and idiopathic thrombocytopenic purpura  

Microsoft Academic Search

The potential association of human parvovirus B19 infection with idiopathic thrombocytopenic purpura (ITP) was studied. All\\u000a 60 adult patients presenting with ITP at the University Hospital Rotterdam – Dijkzigt during a 12-year period (41 with acute\\u000a ITP, 19 with chronic ITP) were included. Patient files were retrospectively analyzed. Stored serum samples were tested for\\u000a parvovirus B19-specific IgG and IgM antibodies,

A.-M. W. van Elsacker-Niele; H. T. Weiland; A. C. M. Kroes; M. C. Kappers-Klunne



Chronic autoimmune thrombocytopenic purpura. A 3-year study.  


Idiopathic (autoimmune) thrombocytopenic purpura (ATP) is accepted to be a disorder resulting from accelerated platelet destruction attributed to an autoimmune process. The patient whose case is presented in this article was first seen by a dentist. The oral findings have been documented as the case was followed for 3 years through acute exacerbations, pregnancy, and delivery of an infant with thrombocytopenia. The patient was managed with intermittent steroid therapy and splenectomy. PMID:6576288

Fotos, P G; Graham, W L; Bowers, D C; Perfetto, S P



Molecular basis of ADAMTS13 dysfunction in thrombotic thrombocytopenic purpura  

Microsoft Academic Search

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathic disorder characterized by thrombocytopenia, hemolytic\\u000a anemia, neurological and renal manifestations, and fever. It is associated with dysfunctional von Willebrand factor (VWF)\\u000a proteolysis and the occurrence of VWF- and platelet-rich thrombi in the microcirculation of multiple organs, including the\\u000a kidneys. Von Willebrand factor is a large glycoprotein that circulates in plasma as a

Minola Manea; Diana Karpman



Overview of 321 patients with idiopathic thrombocytopenic purpura  

Microsoft Academic Search

In this retrospective study, we evaluated the clinical features and the effects of various treatment modalities on the clinical course in patients diagnosed with idiopathic thrombocytopenic purpura (ITP) at our center between 1984-2000. We retrospectively examined the medical records of 321 (229 females, 92 males) ITP patients. One hundred and seventy-one (53.3%) patients were lost to follow-up. When evaluating the

G. Pamuk; Ö. Pamuk; Z. Ba?lar; ?. ÖngÖren; T. Soysal; B. Ferhano?lu; Y. Aydin; B. ÜlkÜ; G. Aktu?lu; N. Akman



Thrombotic thrombocytopenic purpura in the first trimester of pregnancy  

PubMed Central

Thrombotic thrombocytopenic purpura (TTP) occurs more commonly in women and so can be associated with pregnancy. The time during pregnancy with greatest risk for development of TTP is near term and during the post partum period. TTP occurring in early trimester is uncommon and is also associated with great maternal and fetal mortality. We report a successful outcome of pregnancy in a woman with TTP in early first trimester who was treated with therapeutic plasma exchange.

Sikka, Pooja; Chopra, Seema; Aggarwal, Neelam; Suri, Vanita; Chandrasekaran, Abi



Thrombotic thrombocytopenic purpura in the first trimester of pregnancy.  


Thrombotic thrombocytopenic purpura (TTP) occurs more commonly in women and so can be associated with pregnancy. The time during pregnancy with greatest risk for development of TTP is near term and during the post partum period. TTP occurring in early trimester is uncommon and is also associated with great maternal and fetal mortality. We report a successful outcome of pregnancy in a woman with TTP in early first trimester who was treated with therapeutic plasma exchange. PMID:23559773

Sikka, Pooja; Chopra, Seema; Aggarwal, Neelam; Suri, Vanita; Chandrasekaran, Abi



Chronic Refractory Idiopathic Thrombocytopenic Purpura (ITP) and Anti-CD20 Monoclonal Antibody: A Case Report  

Microsoft Academic Search

Idiopathic thrombocytopenic purpura (ITP) is an immune-mediated disorder characterized by accelerated and premature destruction of platelets by reticuloendothelial system. CD20, a trans-membrane B-cell-specific antigen, is a potential target for treatment of certain malignant and nonmalignant plasma cell disorders including refractory ITP. Rituximab is a genetically engineered human anti-CD20 monoclonal antibody, which is approved for the treatment of low-grade non-Hodgkin’s lymphoma.

S. Z. Latifzadeh; V. Entezari



Outcome of Idiopathic Thrombocytopenic Purpura in Pregnancy in King Chulalongkorn Memorial Hospital  

Microsoft Academic Search

Objective: To study the maternal and fetal outcome of idiopathic thrombocytopenic purpura (ITP) in preg- nancy. Material and Method: The medical records of women who were diagnosed to be idiopathic thrombocytopenic purpura during and before pregnancy from January 1995 to December 2004 were reviewed. Results: There were 33 pregnancies from 29 ITP women as four women had two pregnancies each

Sukrutai Nisaratanaporn


Warm-Antibody Autoimmune Hemolytic Anemia Developing after Thrombotic Thrombocytopenic Purpura  

Microsoft Academic Search

Thrombotic thrombocytopenic purpura (TTP) and warm-antibody autoimmune hemolytic anemia (AIHA) are uncommon diseases. Although TTP has been increasingly described in association with autoimmune antibodies, there are very few reports of the association with autoimmune hematological conditions, including idiopathic thrombocytopenic purpura and AIHA. Here we describe a patient with classic manifestations of TTP, who was successfully treated with plasma exchange. A

Daniel Morgensztern; Mohamed A. Kharfan-Dabaja; Han-Mou Tsai; Eric C.-Y. Lian



Rituximab-induced nonspecific interstitial pneumonia like reaction in a patient with idiopathic thrombocytopenic purpura  

Microsoft Academic Search

Rituximab, a chimeric anti-CD20 IgG1 monoclonal antibody, is an effective treatment for haematological autoimmune diseases such as idiopathic thrombocytopenic purpura (ITP). A 72-year-old man was diagnosed with idiopathic thrombocytopenic purpura (ITP). After receiving 4 cycles of rituximab in one month complete response was achieved. However, three weeks after the last infusion he presented to the haematology department with fever, productive

Charalambos Protopapadakis; Katerina M. Antoniou; Argiro Voloudaki; Katerina Samara; Athanasia Proklou; Giorgos Margaritopoulos; Nikolaos M. Siafakas



Low rate of long-lasting remissions after successful treatment of immune thrombocytopenic purpura with rituximab  

Microsoft Academic Search

Idiopathic thrombocytopenic purpura (ITP), also known as immune thrombocytopenic purpura, is thought to be caused primarily\\u000a by the production of autoantibodies directed against platelet surface glycoproteins. Treatment of an acute ITP episode can\\u000a be difficult, and relapses are common. Recent studies have shown that the anti-CD20 antibody rituximab is effective in the\\u000a treatment of relapsed and refractory patients. We report

Christof Schweizer; Frederic J. Reu; Anthony D. Ho; Manfred Hensel



Thrombotic thrombocytopenic purpura with C'3 vascular deposits: report of a case.  


A case of thrombotic thrombocytopenic purpura in a young woman in which platelet microthrombi were distributed in small vessels throughout the body is reported. IgM and complement (C'3) were demonstrated in capillary and small arteriole walls by immunofluorescent microscopy. These findings support the findings of a previous case report, and are further evidence for a possible primary immune etiology for thrombotic thrombocytopenic purpura. PMID:556662

Weisenburger, D D; O'Conner, M L; Hart, M N



Two novel ADAMTS13 gene mutations in thrombotic thrombocytopenic purpura\\/hemolytic-uremic syndrome (TTP\\/HUS)  

Microsoft Academic Search

Two novel ADAMTS13 gene mutations in thrombotic thrombocytopenic purpura\\/hemolytic-uremic syndrome (TTP\\/HUS).BackgroundThrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS) are now considered to be variants of one single syndrome called thrombotic thrombocytopenic purpura\\/hemolytic-uremic syndrome (TTP\\/HUS). Key features are thrombocytopenia, hemolytic anemia, and subsequently impaired function of different organs, especially the kidneys and the central nervous system (CNS). One possible reason is




Thrombotic thrombocytopenic purpura: three peripartum cases and diagnostic challenges.  


Thrombotic thrombocytopenic purpura (TTP) is a medical emergency characterized by occlusive microangiopathy due to intravascular platelet aggregation. This event results in damage to the red blood cells (RBCs) known as microangiopathic hemolytic anemia (MAHA). Schistocytes are circulating fragments of damaged RBCs that have different morphological features including keratocytes, helmet cells, and spherocytes. It is critical to report even a small number of these abnormal RBCs in the peripheral blood and to be alert for the possible diagnosis of TTP, especially in unexplained anemia and thrombocytopenia. The application of pentad criteria in the diagnosis has been reviewed, and the challenges still remained on the hematologic evidence of this disorder. In the 3 cases discussed here, the red cell morphological diagnosis gave an impact on TTP diagnosis, but overdiagnosis might be encountered in obstetrical patients due to nonspecific diagnostic criteria. PMID:24093001

Ab Rahman, Wan Suriana Wan; Abdullah, Wan Zaidah; Mustaffa, Rapiaah; Ahmed, Suhair Abbas; Hassan, Mohd Nazri; Husin, Azlan



Thrombotic Thrombocytopenic Purpura: Three Peripartum Cases and Diagnostic Challenges  

PubMed Central

Thrombotic thrombocytopenic purpura (TTP) is a medical emergency characterized by occlusive microangiopathy due to intravascular platelet aggregation. This event results in damage to the red blood cells (RBCs) known as microangiopathic hemolytic anemia (MAHA). Schistocytes are circulating fragments of damaged RBCs that have different morphological features including keratocytes, helmet cells, and spherocytes. It is critical to report even a small number of these abnormal RBCs in the peripheral blood and to be alert for the possible diagnosis of TTP, especially in unexplained anemia and thrombocytopenia. The application of pentad criteria in the diagnosis has been reviewed, and the challenges still remained on the hematologic evidence of this disorder. In the 3 cases discussed here, the red cell morphological diagnosis gave an impact on TTP diagnosis, but overdiagnosis might be encountered in obstetrical patients due to nonspecific diagnostic criteria.

Ab Rahman, Wan Suriana Wan; Abdullah, Wan Zaidah; Mustaffa, Rapiaah; Ahmed, Suhair Abbas; Hassan, Mohd Nazri; Husin, Azlan



Treatment of immune thrombocytopenic purpura: focus on eltrombopag  

PubMed Central

Immune thrombocytopenic purpura (ITP) is a relatively common autoimmune disorder in which antibodies are produced to circulating platelets. Symptoms can be mild, but for most patients the risk of severe bleeding is unacceptable and treatment is required. Glucocorticoids followed by splenectomy had been the mainstays of therapy. High dose intravenous immunoglobulin and anti-RhD therapy are available for patients with severe illness, but produce only temporary benefit. Rituximab may provide more durable responses, danazol may be underutilized, and immunosuppressants and cytotoxic agents are less often required. Recently the pathophysiology of ITP has been more clearly elucidated, particularly the importance of decreased production of platelets in most patients and the very blunted rise that occurs in serum thrombopoietin (TPO). The isolation of TPO and better understanding of its role in thrombopoiesis has led to the development of new highly effective treatments. TPO analogs had some successes in treating highly refractory ITP patients but were taken out of development due to TPO-antibody induction. Two second-generation TPO-mimetics, romiplostim and the orally available eltrombopag, have recently been licensed in some territories for the treatment of ITP. Approval of eltrombopag was based on results from Phase II and III placebo-controlled clinical trials and a long-term extension study. About 80% of patients achieve significant increases in platelet count (11% of placebo patients), with reduced bleeding and reduced use of concomitant medications; responses are often durable with no tachyphylaxis. The side effects of eltrombopag are generally mild and not worse than placebo, although there are concerns about hepatic dysfunction, and the potentials for thromboses, marrow reticulin fibrosis, rebound thrombocytopenia and cataracts. This is an important new option for highly refractory patients, and its niche in earlier treatment (and for other thrombocytopenic disorders) is yet to be defined.

Rice, Lawrence



Platelet-associated CD154 in immune thrombocytopenic purpura.  


CD40-ligand (CD154) is expressed on activated CD4+ T lymphocytes and is essential for the T cell-dependent activation of B lymphocytes. CD154 is also expressed at the activated platelet surface. In this study, we show that platelet-associated CD154 is increased in immune thrombocytopenic purpura (ITP), a disease characterized by an autoimmune response against proteins of the platelet membrane. CD154 and its messenger RNA were also present in increased amounts in the megakaryocytes of patients with ITP. We found that platelet-associated CD154 is competent to induce the CD40-dependent proliferation of B lymphocytes, and we observed an in vitro CD154-dependent production of antibodies to the GPIIb/IIIa complex (integrin alphaIIbbeta3) when platelets and peripheral blood B lymphocytes from ITP patients with circulating anti-GPIIb/IIIa antibody were cultured together. Therefore, platelet-associated CD154 expression is increased in ITP and is able to drive the activation of autoreactive B lymphocytes in this disease. PMID:15191945

Solanilla, Anne; Pasquet, Jean-Max; Viallard, Jean-François; Contin, Cécile; Grosset, Christophe; Déchanet-Merville, Julie; Dupouy, Maryse; Landry, Marc; Belloc, Francis; Nurden, Paquita; Blanco, Patrick; Moreau, Jean-François; Pellegrin, Jean-Luc; Nurden, Alan T; Ripoche, Jean



Platelet antibody in idiopathic thrombocytopenic purpura and other thrombocytopenias  

SciTech Connect

Platelet-associated immunoglobulin was measured by the use of fluorescent anti-1gG antibody. The method is simple, rapid, and sensitive and provides a precise quantitive assay of bound (direct) and free (indirect) 1gG with platelet specificity. We have evaluated this test in 30 normal volunteers and in 50 patients with immune and nonimmune, treated and untreated thrombocytopenias. All patients with immune thrombocytopenias (acute and chronic idiopathic thrombocytopenic purpura and systemic lupus erythematosus) having platelet counts < 100,000/ had elevated levels of platelet-bound 1gG and 86% had also positive results in the indirect assay. All patients with nonimmunological thrombocytopenias showed normal results in the direct and indirect assay of platelet-associated immunoglobulin. In patients studied repeatedly during the course of their illness, an inverse relation was found between platelet count and level of platelet-bound 1gG. Patients with systemic lupus erythematosus presented clear exceptions to this rule. Investigations of the absorbability of platelet autoantibodies and alloantibodies showed that this assay can readily differentiate between these two antibody species and can also identify specificities of alloantibodies.

Sugiura, K.; Steiner, M.; Baldini, M.G.



Platelet antibody in prolonged remission of childhood idiopathic thrombocytopenic purpura  

SciTech Connect

Evaluations were performed in 20 patients with childhood idiopathic thrombocytopenic purpura (ITP) who remained in remission longer than 12 months. The mean duration of follow-up from diagnosis was 39 months (range 17 to 87 months). Eleven patients (four girls) in group 1 had an acute course of ITP, defined as platelet count greater than 150 X 10(9)/L within 6 months of diagnosis. Nine patients (five girls) in group 2 had a chronic course, defined as platelet count less than 150 X 10(9)/L for greater than or equal to 1 year or requiring splenectomy in an attempt to control hemorrhagic symptoms. Platelet count and serum (indirect) platelet-associated IgG (PAIgG) levels were normal in all 20 patients at follow-up. Both direct and indirect PAIgG levels were measured using a SVI-monoclonal anti-IgG antiglobulin assay. All had normal direct PAIgG levels, except for one patient in group 1 who had a borderline elevated value of 1209 molecules per platelet. These data suggest that the prevalence of elevated platelet antibodies is low during sustained remission without medication in patients with a history of childhood ITP. These data may be relevant for pregnant women with a history of childhood ITP, with regard to the risk of delivering an infant with thrombocytopenia secondary to transplacental passage of maternal platelet antibody.

Ware, R.; Kinney, T.R.; Rosse, W.



Thrombotic thrombocytopenic purpura and cardiac papillary fibroelastoma: a 'unique coexistence'.  


Thrombotic thrombocytopenic purpura (TTP), a complex thrombotic microangiopathy, remains an evolving enigma. A 49-year-old African-American woman presented with acute left hemiplegia, an ischemic cerebrovascular accident involving the right middle cerebral artery. Sequential appearance of thrombocytopenia and evidence of microangiopathic haemolysis led to the diagnosis of acquired idiopathic autoimmune TTP. This was managed with plasma exchange (PEX) and steroids. Early haematologic relapse within a month was managed with the addition of rituximab attaining sustained remission. The patient presented 3 years later with acute confusion and expressive aphasia due to multiple infarcts involving the left parieto-occipital cortex. Transoesophageal echocardiography demonstrated a pedunculated 6?mm mitral valvular mass consistent with a papillary fibroelastoma. Anticoagulation was instituted and the patient was continued on therapeutic oral warfarin. A haematologic relapse of TTP eventually emerged and was managed with PEX, steroids and rituximab. This vignette demonstrates several dilemmas in the clinical presentation, diagnosis and management of TTP in current day practice. Rituximab has adjuvant benefits to PEX and is being investigated as potential first-line therapy. Monitoring ADAMTS13 activity and inhibitor titre, as in our case, prove to have prognostic significance. Cardiac fibroelastomas are rare benign cardiac tumours usually arising from valvular endocardium with thromboembolic potential. One of the proposed mechanisms of origin of these masses is organizing thrombi in the setting of endocardial injury and inflammation questioning a possible link to thrombotic microangiopathy. To the best of our knowledge, this is the first report of this unique coexistence. PMID:24077148

Ramakrishnan Geethakumari, Praveen; Rubin, Alexander; Varadi, Gabor



Virus-associated immune thrombocytopenic purpura in childhood.  


Idiopathic thrombocytopenic purpura (ITP) in children is usually a self-limiting disorder. It may follow a viral infection or immunization and is caused by an inappropriate response of the immune system. Many viruses, such as human immunodeficiency virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella, rubeola, mumps, and parvovirus, have been implicated in childhood ITP. This study is a retrospective chart review of pediatric patients diagnosed with virus-associated ITP at the Hacettepe University, Ihsan Dogramaci Children's Hospital from 1997 to end of 2000. In viral serological studies, the EBV, CMV, and rubella antibodies were investigated for all patients at diagnosis (ELlSA). The proportion of children whose ITP was associated with documented acute viral infection was 13.3% in this group. In the present study, clinical manifestations and laboratory data of virus-associated or not associated groups are similar except age. Median age of the virus-associated group is younger than that of the other, but it is not statistically significant. PMID:12186367

Yenicesu, Idil; Yetgin, Sevgi; Ozyürek, Emel; Aslan, Deniz



A review of immune thrombocytopenic purpura: focus on the novel thrombopoietin agonists  

PubMed Central

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder that is characterized by antibody-mediated platelet destruction and decreased platelet production. ITP and its treatments have been recognized to cause diminished quality of life in those afflicted with this illness on levels comparable to other chronic diseases. The disease can be self-limiting, but in adults it often is a chronic process requiring medical intervention to maintain appropriate platelet counts and to reduce bleeding events. Many patients go on to develop disease that is refractory to current interventions. Historically, the aim of treatment has been focused on reducing the amount of antibody-mediated destruction but newer therapies have centered on the decreased platelet production. Two new medications that target production of platelets have recently been USA, Food and Drug Administration (FDA) approved for the treatment of chronic relapsing ITP. Here, we provide an overview of ITP and a comprehensive review of the newest therapies aimed at the stimulation of platelet production.

Khan, Meaghan; Mikhael, Joseph



Platelet-associated complement C3 in immune thrombocytopenic purpura  

SciTech Connect

Platelet-associated C3 (PA-C3) was measured with a quantitative immunofluorescence assay. With this assay, PA-C3 levels were determined for 78 normal volunteers, 30 patients with immune thrombocytopenic purpura (ITP), and 20 patients with nonimmune thrombocytopenias. Platelet-associatd IgG (PA-lgG) levels were also measured with our standard quantitative immunofluorescence assay. All patients with nonimmune thrombocytopenias and ITP in remission had normal PA-C3 levels. Twenty-four patients with active ITP wre classified into 3 groups: 9 (38%) with increased PA-IgG and normal PA-C3 levels, 10 (42%) with elevated PA-C3 and PA-IgG levels, and 5 (20%) with increased PA-C3 values only. A direct correlation was found between PA-C3 and PA-IgG levels. PA-IgG levels were higher in the group of patients with elevated PA-C3 levels than in those with normal values. Platelet survival studies showed reduced survival times of 1.5-2.5 days for the 5 patients with elevated PA-C3 levels only. Elevated PA-C3 levels returned to normal in 7 ITP patients whose platelet counts increased in response to corticosteriod therapy or to splenectomy. Therefore, PA-C3 and PA-IgG assays can be used to identify patients with ITP, to follow their response to therapy, and to classify them into immunologic subgroups similar to red cell classifiation by Coombs' testing in immune hemolytic anemia.

Myers, T.J.; Kim, B.K.; Steiner, M.; Baldini, M.G.



How I treat patients with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome  

Microsoft Academic Search

Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are, in adults, clinically and patho- logically indistinguishable except for the severity of renal failure. They are best described as a single disorder, TTP-HUS, because the diagnostic evaluation and initial management are the same. Treat- ment with plasma exchange, available for more than 20 years, has dramatically al- tered the course

James N. George


Idiopathic thrombocytopenic purpura in pregnancy: a single institutional experience with maternal and neonatal outcomes  

Microsoft Academic Search

We observed 13 pregnant women of 70 females with idiopathic thrombocytopenic purpura (ITP) from January 1992 through September 2002. Thirteen mothers with ITP gave birth to twelve babies and two fetuses died. One of the pregnancies produced twins. Seven of the cases were diagnosed with ITP before pregnancy and six during pregnancy. One of the thirteen pregnancies was complicated by

R. Ali; F. Özkalemkas; T. Özçelik; V. Özkocaman; Ü. Ozan; Y. Kimya; N. Köksal; E. Bülbül-Baskan; O. Develioglu; M. Tüfekçi; A. Tunali



A case of thrombotic thrombocytopenic purpura in an adult treated with vincristine  

Microsoft Academic Search

The case of a woman with thrombotic thrombocytopenic purpura refractory to prolonged treatment with plasma exchange and steroid\\u000a treatment is described. The addition of vincristine yielded a complete response, which has been maintained for 9?months up\\u000a to the time of this report.

A. Schulz; G. Sitzler; C. Scheid; H. J. Deutsch; J. Chemnitz; R. Abelius; M. Rieping; V. Diehl; D. Söhngen



High Doses of Dexamethasone in Adult Patients with Idiopathic Thrombocytopenic Purpura  

Microsoft Academic Search

BackgroundHigh-dose dexamethasone (DXM) has been used in treatment of patients with idiopathic thrombocytopenic purpura (ITP) who are refractory to other treatments such as prednisone and splenectomy; nevertheless, different studies show variable success rates, this postulated as possibly being due to racial differences. The objective of this study was to determine DXM effectiveness at high doses in Mexican mestizo adult patients

Guillermo R Gutiérrez-Esp??ndola; Manuel R Morales-Polanco; Susana Guerrero-Rivera; Juan O Talavera; Elizabeth Sánchez-Valle; Enrique Gómez-Morales; Javier Pizzuto-Chávez



Low Neonatal Risk of Thrombocytopenia in Pregnancy Associated with Immune Thrombocytopenic Purpura  

Microsoft Academic Search

Objective: To estimate the risk of neonatal thrombocytopenia in infants born to mothers with immune thrombocytopenic purpura (ITP). Methods: During the years 1993–1997, there were 6,082 deliveries. There were 32 infants born to 31 mothers with ITP. Cordocentesis was performed between 34 and 41 weeks of gestation in 16 mothers with ITP. The cord blood platelet count was checked in

Tae-Bok Song; Ji-Young Lee; Yoon-Ha Kim; Young-Youn Choi



Perinatal management of women with immune thrombocytopenic purpura: Survey of United States perinatologists  

Microsoft Academic Search

Objective: The aim of the study was to determine how perinatologists in the United States manage the care of women with immune thrombocytopenic purpura with respect to mode of delivery. Study Design: US members of the Society of Perinatal Obstetricians were surveyed with a 4-question questionnaire. Two mailings were sent. Questions 1 and 2 asked for a response regarding the

David Peleg; Stephen K. Hunter



CNR2 functional variant (Q63R) influences childhood immune thrombocytopenic purpura  

PubMed Central

Immune thrombocytopenic purpura is an acquired autoimmune disorder that is the most common cause of thrombocytopenia in children. The endocannabinoid system is involved in immune regulation. We evaluated a common missense variant (CAA/CGG; Q63R) of the gene encoding the cannabinoid receptor type 2 (GeneID 1269) in 190 children with immune thrombocytopenic purpura and 600 healthy controls. The allelic frequencies and genotype distribution of the polymorphism in the patients were significant compared to control samples (P=0.006 and P=0.0001, respectively). Interestingly, when acute and chronic immune thrombocytopenic purpura patients were analyzed separately with respect to controls, a significant overrepresentation of the RR genotype and of the R allele was observed only for the chronic form (P=0.00021 and P=0.011, respectively). The relative odds ratio suggested the risk of developing chronic form was more than double in immune thrombocytopenic purpura children homozygous for the variant (odds ratio=2.349, 95% CI: 1.544–3.573; P<0.001).

Rossi, Francesca; Mancusi, Silvia; Bellini, Giulia; Roberti, Domenico; Punzo, Francesca; Vetrella, Simona; Matarese, Sofia Maria Rosaria; Nobili, Bruno; Maione, Sabatino; Perrotta, Silverio



High doses of gamma globulin and methylprednisolone therapy for idiopathic thrombocytopenic purpura in children  

Microsoft Academic Search

In four children with chronic idiopathic thrombocytopenic purpura (ITP), high doses of gamma globulin or methylprednisolone were effective in increasing platelet counts transiently, yet there was no quantitative relationship between the platelet responses to these two therapies. This finding suggests a qualitative difference in the mechanisms of increasing platelets by the two drugs. High doses of gamma globulin and methylprednisolone

T. Hara; S. Miyazaki; N. Yoshida; N. Goya



[Effects of PGE1 (alprostadil alpha-cyclodestrin) in a case of probable paraneoplastic thrombocytopenic purpura].  


The authors report the case of a severely vasculopathic patient with pulmonary mediastinal tumour who presented, probably on a paraneoplastic basis, the onset of severe thrombocytopenic purpura persisting for several months. The syndrome was not classifiable in any of the forms known to the authors and was completely resolved by treatment with PGE1 (alprostadil-alpha-cyclodextrine (Prostavasin, Schwarz Pharma). PMID:9053822

Pettine, G; Fiumano, M; Muffatti, A; Avolio, A; Menozzi, G; Libera, E; Mollo, C M; Ezechieli, S



Platelet recovery after eradication of Helicobacter pylori in patients with idiopathic thrombocytopenic purpura  

Microsoft Academic Search

The association between Helicobacter pylori (H. pylori) infection and idiopathic thrombocytopenic purpura (ITP) has been reported by several groups. We investigated the prevalence of H. pylori infection and the effectiveness of its eradication in Japanese patients with ITP. H. pylori infection was found in 21 of 30 patients (70.0%) by 13C urea breath test and presence of serum antibodies to

M. Hino; T. Yamane; T. Takubo; K. Ohta; S. Kitagawa; K. Higuchi; T. Arakawa



Sequential occurrence of thrombotic thrombocytopenic purpura, essential thrombocythemia, and idiopathic thrombocytopenic purpura in a 42-year-old African-American woman: a case report and review of the literature  

PubMed Central

Introduction Thrombotic thrombocytopenic purpura and idiopathic thrombocytopenic purpura are two well recognized syndromes that are characterized by low platelet counts. In contrast, essential thrombocythemia is a myeloproliferative disease characterized by abnormally high platelet numbers. The coexistence of thrombotic thrombocytopenic purpura and idiopathic thrombocytopenic purpura in a single patient has been reported in the literature on a few occasions. However, having essential thrombocythemia complicating the picture has never been reported before. Case presentation We present a case where thrombotic thrombocytopenic purpura, essential thrombocythemia, and idiopathic thrombocytopenic purpura were diagnosed in a 42-year-old African-American woman in the space of a few years; we are reporting this case with the aim of drawing attention to this undocumented occurrence, which remains under investigation. Conclusions As the three conditions have different natural histories and require different treatment modalities, it is important to recognize that these diseases may be seen sequentially. This case emphasizes the importance of reviewing peripheral blood smears for evaluation of thrombocytopenia and bone marrow aspirations for diagnosis of thrombocythemia in order to reach an accurate diagnosis and tailor therapy accordingly. Moreover, this case demonstrates the variability and complexity of platelet disorders. This occurrence of three different types of platelet disorders in one patient remains a pure observation on our part; regardless, this does raise the possibility of a common underlying, as yet undiscovered, pathophysiology that could explain the phenomenon.



The Demonstration of Antibody Binding to Platelet-Associated Antigens in Patients With Immune Thrombocytopenic Purpura  

Microsoft Academic Search

Platelet destruction in chronic immune thrombocytopenic purpura (ITP) is due either to antibody against platelet- associated antigen(s) that attaches by the antigen-specific Fab portion of the molecule or to platelet-bound immune complexes that bind nonspecifically to a platelet Fc receptor. Since pepsin digestion destroys the Fc fragment, the effect of this agent on platelet binding should allow differentiation between these

Patricia Tani; Donna Mason



Idiopathic Thrombocytopenic Purpura: A 10Year Natural History Study at the Childrens Hospital of Alabama  

Microsoft Academic Search

Childhood idiopathic thrombocytopenic purpura (ITP) is a common disorder. However, single-institution, long-term, natural history data are limited. The objective of this paper is to review presenting features, response to therapy, and natural history of ITP treated at a single pediatric academic medical center. A retrospective chart review was made for all children (ages birth-18 years) diagnosed with ITP (ICD 287.3)

Raymond G. Watts



Treatment of autoimmune thrombocytopenic purpura with rhesus antibodies (antiRh 0 (D))  

Microsoft Academic Search

There is evidence that blockade of the reticuloendothelial system (RES) by sequestration of autologous red blood cells (RBC) leads to an elevation of platelet counts in immune thrombocytopenia. To substantiate this hypothesis, 10 Rh0(D)-positive adult patients (9 female, 1 male) with chronic autoimmune thrombocytopenic purpura (ITP) (1 to 21 years duration) were treated with low doses of intravenous IgG-anti-Rh0(D) (200

A. Salama; V. Kiefel; R. Amberg; C. Mueller-Eckhardt



Fatal thrombotic thrombocytopenic purpura as a rare complication following allogeneic stem cell transplantation  

Microsoft Academic Search

Thrombotic thrombocytopenic purpura (TTP) is a rare disease which, together with hemolytic uremic syndrome, is subsumed under\\u000a thrombotic microangiopathy. After stem cell transplantation (SCT), this syndrome represents a possibly fatal complication\\u000a with a higher incidence in allogeneic SCT than in autologous SCT. Although plasmapheresis offers an encouraging treatment\\u000a modality in classic TTP, this seems less effective in bone marrow transplant-associated

J. Chemnitz; M. Fuchs; W. Blau; P. Hartmann; C. Wickenhauser; C. Scheid; A. Schulz; V. Diehl; D. Söhngen



Long-term follow-up of idiopathic thrombotic thrombocytopenic purpura treated with rituximab  

Microsoft Academic Search

Rituximab may be used to treat patients with thrombotic thrombocytopenic purpura (TTP) refractory to plasma exchange or recurrent\\u000a disease. While initial response rates are reported to be high, long-term follow-up data of patients treated with rituximab\\u000a are not available to date, however important to estimate the safety and benefit of this treatment. Twelve patients with non-familial\\u000a idiopathic TTP refractory to

Jens Marcus Chemnitz; Jens Uener; Michael Hallek; Christof Scheid



Life-threatening spontaneous hemothorax in a patient with thrombotic thrombocytopenic purpura  

Microsoft Academic Search

Spontaneous hemothorax in the left pleural space occurred suddenly in a patient with thrombotic thrombocytopenic purpura (TTP).\\u000a In spite of massive blood transfusion, the hemorrhage could not be stopped. The patient suffered shock due to tension hemothorax\\u000a and hypovolemia, resulting in cardiac arrest. After successful cardiopulmonary resuscitation, surgical hemostasis was performed.\\u000a The main cause of the bleeding was rupture of

Takeshi Kubota; Seiji Koizumi; Akimasa Miyata; Waichirou Hamada



Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura  

Microsoft Academic Search

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening systemic illness of abrupt onset and unknown cause. Proteolysis of the blood-clotting protein von Willebrand factor (VWF) observed in normal plasma is decreased in TTP patients. However, the identity of the responsible protease and its role in the pathophysiology of TTP remain unknown. We performed genome-wide linkage analysis in four pedigrees of humans

Gallia G. Levy; William C. Nichols; Eric C. Lian; Tatiana Foroud; Jeanette N. McClintick; Beth M. McGee; Angela Y. Yang; David R. Siemieniak; Kenneth R. Stark; Ralph Gruppo; Ravindra Sarode; Susan B. Shurin; Visalam Chandrasekaran; Sally P. Stabler; Hernan Sabio; Eric E. Bouhassira; Jefferson D. Upshaw; David Ginsburg; Han-Mou Tsai



Health-related quality of life outcomes for patients with immune thrombocytopenic purpura  

Microsoft Academic Search

Immune thrombocytopenic purpura (ITP) is a rare disease with infrequent serious bleeding making clinical trials difficult.\\u000a One solution to this problem is to use alternative outcome measures such as health-related quality of life (HRQL). This review\\u000a describes the various HRQL tools available to researchers including measures that are generic (applicable to many different\\u000a disease types) and disease-specific measures developed explicitly

Robert J. Klaassen; Nancy L. Young



Effect of Helicobacter pylori Eradication on Platelet Recovery in Patients With Chronic Idiopathic Thrombocytopenic Purpura  

Microsoft Academic Search

Background: A relationship between Helicobacter py- lori infection and idiopathic thrombocytopenic purpura (ITP) has previously been reported. We determined the prevalence ofHpylori infection in Japanese patients with chronic ITP and the effect of its eradication on platelet count. Methods: The study population comprised 53 Japa- nese adults with chronic ITP and a platelet count of less than 100103\\/µL. A 13C-urea

Ryugo Sato; Kazunari Murakami; Koichiro Watanabe; Tadayoshi Okimoto; Hajime Miyajima; Masao Ogata; Eiichi Ohtsuka; Masaaki Kodama; Yoshio Saburi; Toshio Fujioka; Masaru Nasu



Correlations among age, cytokines, lymphocyte subtypes, and platelet counts in autoimmune thrombocytopenic purpura.  


While autoimmune thrombocytopenic purpura is mediated by autoantibodies, accumulating evidence suggests that T helper cells and the cytokines they produce also play a key role. We determined correlations among age, serum cytokine concentrations, circulating lymphocyte, and platelet counts in adult (n=19) and children (n=29) with autoimmune thrombocytopenic purpura. Correlations between age and cytokine levels were also assessed in healthy controls (n=50). Significant positive correlations between age and serum levels of interferon-gamma, age and CD4+ lymphocytes, age and natural killer cell count were observed in these patients. Absolute lymphocyte and CD8+ cell count was significantly inversely correlated with age. In adult patients, a significant inverse correlation between platelet and absolute lymphocyte count was observed. In pediatric patients, an inverse correlation of platelet count with serum concentration of interleukin-3 was recorded. In 50 healthy volunteers there were significant positive correlations between age and interleukin-3, -4, -6, and interferon-gamma, and significantly negative correlations with interleukin-2, tumor necrosis factor-alpha, and interferon-alpha. Additional evaluations are necessary to identify the impact of age-related changes in immune function on the clinical course of autoimmune thrombocytopenic purpura. PMID:16933252

Culi?, Srdana; Labar, Boris; Marusi?, Ana; Salamuni?, Ilza



[Variety of thrombotic thrombocytopenic purpura clinical course in Polish family members with ADAMTS 13 gene mutation].  


The congenital form of thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrom) is a result of genetically conditioned dysfunction of protease ADAMTS 13 enzyme which is responsible for von Wiellebrand factor multimer disintegration. The disease is inherited autosomally and recessively. The decrease of ADAMTS 13 activity results in intravascular clotting process activation with rapid lowering of platelet count, haemolytic anaemia, and occurence of schistocytes. Clinically, the disease is characterized by a range of symptoms such as severe jaundice in neonatal period, embolicthrombotic incidents of nervous system and progressive dysfunction of kidneys and other organs. Delaying diagnosis and hence administering of freshly frozen plasma leads to death. Molecular diagnosis allows for identification of genetical profile of the patient, and showing lowered enzyme activity is a basis for regular prophylactic plasma administration which is the protease donor. In our study we present members of a Polish family identified with ADAMTS 13 mutation. 52 old male with heterozygotic mutation of exon 29 (4143_4144insA) and in exon 19 (c2281G>A; Gly761Ser), experienced a few episodes of ischaemic stroke with ongoing neurological deficiency and developed chronic kidney disease. His 16-year old daughter with double homozygotic mutation in exon 29 (4143_4144insA) after severe episode of TTP at the age of 4 has been receiving plasma every 2 weeks for 12 years, which prevented her from other disorders. Target treatment introduced to clinical practice by means of ADAMTS 13 obtained by genetic recombination technology raises hopes. PMID:23700827

Hyla-Klekot, Lidia; Kucharska, Grazyna; S?onka, Karina



Chronic refractory idiopathic thrombocytopenic purpura (ITP) and anti-CD20 monoclonal antibody: a case report.  


Idiopathic thrombocytopenic purpura (ITP) is an immune-mediated disorder characterized by accelerated and premature destruction of platelets by reticuloendothelial system. CD20, a trans-membrane B-cell-specific antigen, is a potential target for treatment of certain malignant and nonmalignant plasma cell disorders including refractory ITP. Rituximab is a genetically engineered human anti-CD20 monoclonal antibody, which is approved for the treatment of low-grade non-Hodgkin's lymphoma. Recent clinical reports suggest that rituximab may be useful in treating certain patients with chronic refractory ITP. A 59-year-old woman with refractory ITP was placed on rituximab (four weekly doses of 375 mg/m(2)) and her condition and platelet count were observed for 18 months. There was a gradual increase in platelet count and she was symptom free in this period and no side effects of the drug were reported. Anti-CD20 antibodies are likely to be used in the treatment of refractory ITP cases, but further studies about treatment schedule and criteria for patient selection should be done. PMID:17000895

Latifzadeh, S Z; Entezari, V



Splenectomy and spontaneous remission in children with chronic idiopathic thrombocytopenic purpura.  


Two hundred thirty of 696 evaluable children were identified as having chronic idiopathic thrombocytopenic purpura (ITP). Splenectomy was performed in 30 (13%), achieving remission in 22 (73%). Favorable response was associated to higher initial platelet count. Spontaneous remission was achieved by 53/200 non-splenectomized patients (26.5%), up to 10 years from diagnosis. More than half of them recovered between 6th and 12th month from diagnosis. The recovery rate was significantly higher (P=0.03) in children aged<9 years (31.2%) than in older children (14.6%). No reliable factor predictive of response in individual cases is still available. PMID:16933257

Donato, Hugo; Picón, Armando; Rapetti, María Cristina; Rosso, Amadeo; Schvartzman, Gabriel; Drozdowski, Constanza; Di Santo, Juan Jose



Surgical treatment of chronic idiopathic thrombocytopenic purpura: results in 107 cases  

SciTech Connect

Between 1972 and 1985, 107 patients with chronic Idiopathic Thrombocytopenic Purpura underwent splenectomy. Platelet life span and sites of sequestration were studied with labelled platelets and external scanning. Medical treatment was always of scarce and transient effectiveness and had considerable side effects. Splenectomy had minimal complications and mortality and caused no hazard of overwhelming sepsis in adults. The results of splenectomy were very satisfying, especially when platelet sequestration was mainly splenic (remission in about 90% of patients). Surgical treatment is at present the most effective in patients with chronic ITP.

Cola, B.; Tonielli, E.; Sacco, S.; Brulatti, M.; Franchini, A.



A review of anti-D treatment of childhood idiopathic thrombocytopenic purpura.  


Treatment of childhood idiopathic thrombocytopenic purpura is still an area of controversy. We reviewed the literature on anti-D treatment. Most studies used intravenous anti-D. Single doses of 50 microg/kg increased the platelet count to >or=20x10(9)/L in 70% of the children within 3 days. Intravenous anti-D seems safe in classic childhood ITP although hemolysis and occasionally renal failure may be of concern. A few studies reported intramuscularly or subcutaneously administered anti-D. Further studies on the optimal dose and route of administration of anti-D are warranted. PMID:16933265

Kjaersgaard, Mimi; Hasle, Henrik



Platelet Recovery in Patients with Idiopathic Thrombocytopenic Purpura after Eradication of Helicobacter Pylori  

Microsoft Academic Search

The relationship betweenHelicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP) has been investi-gated in several studies. We investigated the prevalence\\u000a ofHpylori infection and the clinical effects of eradication in 22 Japan-ese patients with chronic ITP.H pylori infection was found in 14 (63.6%) of the patients by histologie and culture examina-tions of biopsy samples obtained by gastrointestinal\\u000a endoscopy.Hpylori was eradicated by

S. Hashino; A. Mori; S. Suzuki; K. Izumiyama; K. Kahata; M. Yonezumi; K. Chiba; T. Kondo; S. Ota; N. Toyashima; N. Kato; J. Tanaka; M. Tmamura; M. Asa. ka



Thrombocytopenic purpura associated with brucellosis: report of 2 cases and literature review.  


Mild hematologic abnormalities are common in the course of human brucellosis; however, they generally resolve promptly with treatment of the disease. Occasionally, thrombocytopenia is severe and can be associated with bleeding into the skin (purpura) and from mucosal sites. We describe 2 patients infected with Brucella melitensis who presented with thrombocytopenic purpura, and we review 41 additional cases from the literature. Patients ranged in age from 2 to 77 years, and both sexes were affected equally. In the majority of cases, examination of the bone marrow revealed abundant megakaryocytes. Possible mechanisms involved in thrombocytopenia include hypersplenism, reactive hemophagocytosis, and immune destruction of platelets. Recognition of this complication is essential, since hemorrhage into the central nervous system is associated with a high mortality rate. PMID:11049768

Young, E J; Tarry, A; Genta, R M; Ayden, N; Gotuzzo, E



Aetiology and pathogenesis of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome: the role of von Willebrand factor-cleaving protease  

Microsoft Academic Search

Thrombotic thrombocytopenic purpura (TTP) and haemolytic uraemic syndrome (HUS) are today often regarded as variants of one syndrome denoted as TTP\\/HUS, characterized by thrombocytopenia caused by intravascular platelet clumping, microangiopathic haemolytic anaemia, fever, renal abnormalities and neurological disturbances. Unusually large von Willebrand factor multimers have been observed in plasma from patients with chronic relapsing forms of TTP. Their appearance in

Miha Furlan; Bernhard Lämmle



ADAMTS13 and anti-ADAMTS13 antibodies as markers for recurrence of acquired thrombotic thrombocytopenic purpura during remission  

Microsoft Academic Search

Background From 20 to 50% of patients who survive an acute episode of the acquired form of thrombotic thrombocytopenic purpura relapse but clinical and laborator y markers of recurrence are not well established. Design and Methods In 109 patients enrolled in an international registry we evaluated, in the frame of a retrospec- tive cohort stud y, the predictive role of

Flora Peyvandi; Silvia Lavoretano; Roberta Palla; Hendrik B. Feys; Karen Vanhoorelbeke; Tullia Battaglioli; Carla Valsecchi; Maria Teresa Canciani; Fabrizio Fabris; Samo Zver; Marienn Réti; Danijela Mikovic; Mehran Karimi; Gaetano Giuffrida; Luca Laurenti; Pier Mannuccio Mannucci; Angelo Bianchi; Marrow Transplantation; Vittorio Emanuele Ferrarotto-S



Major hemorrhage in children with idiopathic thrombocytopenic purpura: Immediate response to therapy and long-term outcome  

Microsoft Academic Search

Objectives: We retrospectively characterized children with idiopathic thrombocytopenic purpura (ITP) who had major hemorrhage to determine response to therapy and long-term outcome.Study design: We reviewed the medical records of 332 children with ITP diagnosed at our center during the last 10 years for occurrence of major hemorrhage, defined as (1) intracranial hemorrhage, (2) epistaxis requiring cautery or nasal packing, (3)

Desiree Medeiros; George R. Buchanan



Predisposition to idiopathic thrombocytopenic purpura maps close to the major histocompatibility complex class I chain-related gene A  

Microsoft Academic Search

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune condition with poorly known etiology, characterized by platelet destruction. Genetic association studies of this disease are scarce, discrepant, and restricted to major histocompatibility complex (MHC) polymorphisms. Hence, a case–control study was conducted with an aim to map the MHC to IPT susceptibility using HLA-B and nine microsatellite loci encompassing MHC class I, II,

Maria Helena Thomaz Maia; Raquel de Lima Peixoto; Clayton Pereira Silva de Lima; Milena Magalhães; Leonardo Sena; Perpétua do Socorro Silva Costa; Fabíola Brasil Barbosa; Layanna Freitas de Oliveira; Matilde Romero; Christina Nogueira de Araujo Silva; Eduardo José Melo dos Santos



Association of Inflammatory Cytokine Gene Polymorphisms with Platelet Recovery in Idiopathic Thrombocytopenic Purpura Patients after the Eradication of Helicobacter pylori  

Microsoft Academic Search

Background: Idiopathic thrombocytopenic purpura (ITP) is associated with the cytokine response and dysregulation of the cytokine network. Gene polymorphisms of proinflammatory cytokines are associated with several diseases including ITP. Recently, the successful eradication of Helicobacter pylori has been reported to improve the platelet counts in some patients with ITP. The aim of this study was to elucidate the relationship between

Takayoshi Suzuki; Masashi Matsushima; Katsuya Shirakura; Jun Koike; Aya Masui; Atsushi Takagi; Yukari Shirasugi; Yoshiaki Ogawa; Takayuki Shirai; Tetsuya Mine



Intracranial Hemorrhage in Acute and Chronic Childhood Immune Thrombocytopenic Purpura over a Ten-Year Period: An Egyptian Multicenter Study  

Microsoft Academic Search

Intracranial hemorrhage (ICH) is a rare but major cause of death in immune thrombocytopenic purpura (ITP). The authors reviewed data of 1,840 patient with ITP, from 5 pediatric hematology centers in Egypt from 1997 to 2007, to study the incidence and risk factors of ICH. Ten cases of ICH were identified with a median age at presentation of 7.5 years;

Mohsen Elalfy; Nancy Elbarbary; Normine Khaddah; Magy Abdelwahab; Farida El Rashidy; Hoda Hassab; Youssef Al-Tonbary



Helicobacter pylori eradication reduces platelet count in patients without idiopathic thrombocytopenic purpura.  


Discrepant outcomes of Helicobacter pylori eradication in patients with idiopathic thrombocytopenic purpura have been reported. Here patients with dyspepsia and no other complications underwent gastroendoscopic examination and evaluation for Helicobacter pylori infection. Helicobacter pylori-infected patients with gastritis and gastric ulcer received eradication therapy: lansoprazole (60 mg/day), clarithromycin (400 mg/day), and amoxicillin (1500 mg/day) for 1 week. Lansoprazole 30 mg/day was administrated additional 7 weeks. Peripheral platelets were counted before treatment, 8 weeks after initiation of therapy, and at follow-up periods. Platelet counts in patients with both gastritis and gastric ulcer were evaluated with reference to the presence of Helicobacter pylori infection. Eighty-seven patients with gastritis and 35 of those with gastric ulcer underwent successful eradication therapy. Peripheral platelet counts in patients with gastritis decreased from 235+/-55 to 228+/-58 (10(3)/microL) (p=0.0337), and those with gastric ulcer decreased from 248+/-60 to 232+/-48 (10(3)/microL) (p=0.020) 8 weeks after initiation of therapy. Non-eradicated patients did not show such a tendency. Helicobacter pylori eradication reduced peripheral platelet counts in patients with gastritis and gastric ulcer. Amelioration of thrombocytopenia by eradicating Helicobacter pylori appears to involve mechanisms specific to idiopathic thrombocytopenic purpura. PMID:17365854

Matsukawa, Yoshihiro; Kato, Kimitoshi; Hatta, Yoshihiro; Iwamoto, Maho; Mizuno, Shigeaki; Kurihara, Ryuichi; Arakawa, Yasuyuki; Kurosaka, Hanzo; Hayashi, Izumi; Sawada, Shigemasa



Goodpasture's syndrome associated with thrombotic thrombocytopenic purpura secondary to an ADAMTS-13 deficit.  


A 27-year-old man was hospitalized for acute kidney injury associated with antiglomerular basement membrane antibodies (anti-GBM). He underwent immunosuppression and plasma exchange therapy, without recovery of renal function. Later on, he was again admitted to the hospital with seizures. Evidence of microangiopathic hemolytic anemia, with schistocytes in peripheral blood, was present, as well as a persistent low platelet count and activity of von Willebrand factor from adherence to protease (ADAMTS-13) less than 1 %. The presence of IgG antibodies against ADAMTS-13 was documented, leading to a diagnosis of thrombotic thrombocytopenic purpura (TTP) in the context of Goodpasture's syndrome. The TTP was treated with rituximab and plasmapheresis with a good response. We conclude that early measurement of ADAMTS-13 activity dictated the most appropriate therapy and achieved excellent results in this patient. PMID:23111709

Vega-Cabrera, Cristina; Del Peso, Gloria; Bajo, Auxiliadora; Picazo, M-Luz; Rivas-Becerra, Begoña; Benitez, Ana-Lidia; Ara, Jorge Martínez; Olea, Teresa; Selgas, Rafael



A Case of HIV Infection with Thrombocytopenia: Assosiation of HIV, Thrombotic Thrombocytopenic Purpura and Brucellosis.  


To report a case of HIV infection presenting with thrombotic thrombocytopenic purpura (TTP) and brucellosis that responded well to plasmapheresis and anti-infective therapy. A 64-year-old woman with moderate confusion, fever and pancytopenia was admitted. HIV infection history was taken from her family and she was not receiving antiretroviral therapy last one year. She had generalized purpuric skin lesions. Wright tube agglutination test was found positive with a 1:160 dilution and the patient was diagnosed as brucellosis. Detailed literature search showed brucellosis as a possible cause of TTP. Patient was treated by plasma exchange/fresh frozen plasma and antimicrobials and the response was excellent. Although brucellosis seems to explain the clinical picture of this patient, it is revealed that broad differential diagnosis is needed to reach uncommon diagnosis like TTP particularly in HIV infected patients. PMID:22379293

Kurtaran, Behice; Oto, Ozgur Akin; Candevir, Aslihan; Inal, Ayse Seza; Sirin, Yusuf



Long-term management of chronic immune thrombocytopenic purpura in adults  

PubMed Central

Chronic immune thrombocytopenic purpura (ITP) is generally a more benign disease than previously thought. Currently it is recommended that only those patients with severe and/or symptomatic thrombocytopenia definitely require treatment. Additional factors, such as age, lifestyle, and uremia can also influence the hemorrhagic risk and should be carefully assessed before decision-making on the appropriate management of patients with less severe forms of ITP. The recent introduction of new classes of therapeutic agents such as rituximab and the thrombopoietic growth factors has had a major impact on the management of ITP. Updated treatment guidelines have recently been made available but they are based largely on expert opinion rather than on high-quality clinical trial evidence. This structured review is focused on the management of adults with chronic ITP, including the use of new classes of agents.

Palau, Javier; Jarque, Isidro; Sanz, Miguel A



Subcutaneous anti-D treatment of idiopathic thrombocytopenic purpura in children.  


We investigated the effect of subcutaneous anti-D IgG as platelet enhancing therapy in children with idiopathic thrombocytopenic purpura (ITP). Twenty-three children were treated with subcutaneous anti-D 50 microg/kg. The median platelet count increased from 7 x 10(9) to 31 x 10(9)/L on day 3 (P < 0.01). The median decline in hemoglobin was 1.3 g/dl. Two children experienced minor fever and chills within 24 hr of treatment. Pain at the injection site was common but self-limiting with no effect on activity level. These results suggest subcutaneous anti-D IgG 50 microg/kg as an effective and well-tolerated treatment option in childhood ITP. PMID:19722275

Kjaersgaard, Mimi; Edslev, Pernille Wendtland; Hasle, Henrik



[Successful treatment with rituximab in a patient with refractory thrombotic thrombocytopenic purpura refractory to plasma exchange].  


We report a patient with refractory idiopathic thrombotic thrombocytopenic purpura (TTP) who was successfully treated with rituximab. A 50-year-old woman was referred to our hospital with progressive psychoneurotic symptoms, hemolytic anemia and thrombocytopenia. The diagnosis of TTP was confirmed by the absence of ADAMTS13 activity with the presence of circulating ADAMTS13 inhibitor. High-dose steroid therapy and plasma exchange were performed. Despite 21 sessions of plasma exchange, however, there was no remarkable improvement. We then administered rituximab. Fifteen days after the first infusion of rituximab, she achieved complete remission and ADAMTS13 activity increased up to 14%. The patient has remained in remission for more than 9 months. PMID:20379104

Koshino, Mayuko; Kudou, Daisuke; Okoshi, Yasushi; Obara, Naoshi; Simizu, Seiichi; Mukai, Harumi Y; Suzukawa, Kazumi; Hasegawa, Yuichi; Kojima, Hiroshi; Nagasawa, Toshiro; Chiba, Shigeru



The emerging concept of residual ADAMTS13 activity in ADAMTS13-deficient thrombotic thrombocytopenic purpura.  


Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disease characterized by acute episodes of widespread microvascular thrombosis. The discovery that the plasmatic activity of the von Willebrand factor cleaving protease, ADAMTS13, is severely deficient in patients with TTP partially clarified the pathophysiology of the disease. However, the finding of severe deficiency of ADAMTS13 alone is unable to fully explain the clinical heterogeneity of the disease. The recent development of methods that measure ADAMTS13 activity with great analytical precision offers the opportunity to define the relationships between levels of ADAMTS13 activity below 10% (herein defined as "residual ADAMTS13 activity") and the clinical manifestations of the disease. Recent studies suggest that the amount of residual activity of ADAMTS13 may be a major determinant of the clinical heterogeneity of TTP. Herein, we review the recent findings on residual ADAMTS13 activity and their implications for research and clinical practice in the field. PMID:23415418

Lotta, Luca A; Wu, Haifeng M; Musallam, Khaled M; Peyvandi, Flora



Drug-induced thrombotic thrombocytopenic purpura successfully treated with recombinant human soluble thrombomodulin.  


A 61-year-old woman with recurrent non-small cell lung cancer presented with thrombocytopenia, microangiopathic hemolytic anemia, neurological abnormalities, renal failure and a fever that appeared during chemotherapy with gemcitabine and bevacizumab. She was diagnosed with drug-induced thrombotic thrombocytopenic purpura (TTP). After the discontinuation of chemotherapy, the administration of recombinant human soluble thrombomodulin and fresh-frozen plasma rapidly ameliorated the TTP. Hypertension preceded the onset of TTP and required the administration of quadruple therapy on admission. However, after three months, the hypertension was controllable without anti-hypertensive drugs. Twelve months later, the ninth course of vinorelbine was administered safely, preventing the patient's lung cancer from progressing. PMID:23676600

Nishijima, Yu; Hirata, Haruhiko; Himeno, Aiko; Kida, Hiroshi; Matsumoto, Masanori; Takahashi, Ryo; Otani, Yasushi; Inoue, Kouji; Nagatomo, Izumi; Takeda, Yoshito; Kijima, Takashi; Tachibana, Isao; Fujimura, Yoshihiro; Kumanogoh, Atsushi



Reliable predictors of neonatal immune thrombocytopenia in pregnant women with idiopathic thrombocytopenic purpura.  


Of infants born to women with idiopathic thrombocytopenic purpura (ITP), about 10-15% have transient neonatal immune thrombocytopenic purpura (NITP). Of concern is the lack of a reliable predictor for NITP. We conducted a retrospective study of all pregnancies with ITP at Osaka University Hospital over the past 16 years analyzing a total of 127 pregnancies in 88 women with ITP to assess the predictive value of various clinical factors regarding neonatal platelet count in the current pregnancy. We also reviewed the literature concerning ITP in pregnancy and NITP prediction. Neonatal platelet counts were less than 100 × 10(9)/L in 20 of 130 neonates (15.4%), less than 50 × 10(9)/L in 11 neonates (8.5%), and less than 20 × 10(9)/L in three neonates (2.3%). There was a strong correlation between the first and second sibling regarding the occurrence and the severity of NITP with Spearman correlation coefficient of 0.55 (P = 0.001) at birth and 0.63 (P < 0.0001) at nadir after birth. A maternal platelet count less than 100 × 10(9)/L at delivery showed a statistical trend for an association with the occurrence of NITP (P = 0.043). Moreover, maternal ITP refractory to splenectomy correlated with a higher risk for fetal or neonatal ICH according to the review of the literature. In conclusion, pregnant women who have had a previous offspring with NITP or who have ITP refractory to splenectomy may be at particular risk of delivering an offspring with significant NITP. Management decisions, including mode of delivery, may be altered by the degree of risk for potentially severe NITP. PMID:22031338

Koyama, Shinsuke; Tomimatsu, Takuji; Kanagawa, Takeshi; Kumasawa, Keiichi; Tsutsui, Tateki; Kimura, Tadashi



Acquired thrombotic thrombocytopenic purpura. Development of an autoimmune response.  


The von Willebrand factor (VWF)-cleaving metalloprotease, ADAMTS13 (adisintegrin and metalloprotease with thrombospondin type 1 motifs-13) is the only known target of the dysregulated immune response in acquired TTP. Autoantibodies to ADAMTS13 either neutralize its activity or accelerate its clearance, thereby causing a severe deficiency of ADAMTS13 in plasma. As a consequence, size regulation of VWF is impaired and the persistence of ultra-large VWF (ULVWF) multimers facilitates microvascular platelet aggregation causing microangiopathic haemolytic anaemia and ischaemic organ damage. Autoimmune TTP although a rare disease with an annual incidence of 1.72 cases has a mortality rate of 20% even with adequate therapy. We describe the mechanisms involved in ADAMTS13 autoimmunity with a focus on the role of B- and T-cells in the pathogenesis of this disorder. We discuss the potential translation of recent experimental findings into future therapeutic concepts for the treatment of acquired TTP. PMID:23443151

Schaller, M; Studt, J-D; Voorberg, J; Kremer Hovinga, J A



Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome concomitant with systemic sclerosis, immune thrombocytopenic purpura.  


A 58-year-old Japanese woman presented with chronic fluctuating liver dysfunction with purpura. Raynaud's phenomenon had been diagnosed 4 years previously. At the initial examination, skin biopsy showed limited cutaneous systemic sclerosis (SSc). Laboratory investigations revealed liver dysfunction. Anti-nuclear antibodies, anti-mitochondria M2 antibody, anti-thyroglobulin antibody, and platelet-associated IgG were positive. Primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) were diagnosed serologically, clinically and histologically. Immune thrombocytopenic purpura (ITP) was diagnosed by bone marrow puncture, clinical and laboratory findings, and Helicobacter pylori IgG was positive. She was treated with prednisolone 30 mg/day, ursodeoxycholic acid 600 mg/day, and a 7-day course of lansoprazole plus amoxicillin and clarithromycin. Thrombocytes increased rapidly and transaminase improved at day 7. We report a rare case of PBC-AIH overlap syndrome with concurrent ITP and SSc which suggest the presence of shared genetic susceptibility factors in multiple autoimmune conditions including PBC, AIH, ITP and SSc. PMID:19952485

Toyoda, Megumi; Yokomori, Hiroaki; Kaneko, Fumihiko; Yoshida, Hide; Hoshi, Kenta; Takeuchi, Hajime; Tahara, Kumiko; Takahashi, Akihiko; Kudo, Takeo; Motoori, Tadashi; Ohbu, Makoto; Kondo, Hirobumi; Hibi, Toshifumi



Excessive naked megakaryocyte nuclei in myelodysplastic syndrome mimicking idiopathic thrombocytopenic purpura: a complicated pre- and post-transplantation course.  


A boy 3 years 7 months old with thrombocytopenia and history of intracranial hemorrhage who underwent bone marrow transplantation is presented. He was refractory to steroids, immunoglobulin G, vincristine, azathioprine, cyclosporine A, interleukin-11, chemotherapy, and splenectomy. Idiopathic thrombocytopenic purpura was excluded by light /electron microscopic and flow cytometric findings; the diagnosis of refractory cytopenia, a subgroup of pediatric myelodysplastic syndrome, was made. Naked megakaryocyte nuclei were 55.38 +/- 28.2% vs. 31.67 +/- 23.22% of all megakaryocytes in the patient and the control group of 9 patients with idiopathic thrombocytopenic purpura, respectively (p = .016). The posttransplatation course was complicated by delayed platelet engraftment, bronchiolitis obliterans associated with pneumocystis carinii pneumonia, which resolved completely. PMID:19657988

Olcay, Lale; Tuncer, A Murat; Okur, Hamza; Erdemli, Esra; Uysal, Zumrut; Cetin, Mualla; Duru, Feride; Cetinkaya, Duygu Uckan



Immune thrombocytopenic purpura associated with rheumatoid arthritis – a report of five cases and review of the literature  

Microsoft Academic Search

Immune thrombocytopenic purpura (ITP) associated with rheumatoid arthritis (RA) is relatively rare. We describe five cases\\u000a of RA with ITP. In all five patients, platelet counts were low, platelet-associated IgG levels were elevated, and bone marrow\\u000a aspiration showed megakaryocytosis. Glucocorticoid therapy was effective in three cases, but the other two cases required\\u000a immunosuppressants or intravenous ?-globulin in addition to glucocorticoid.

Naomi Ichikawa; Masayoshi Harigai; Ayako Nakajima; Masako Hara; Naoyuki Kamatani



Efficiency of curative and prophylactic treatment with rituximab in ADAMTS13-deficient thrombotic thrombocytopenic purpura: a study of 11 cases  

Microsoft Academic Search

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease that occurs mainly in young adults. Acquired cases are usually a result of antibodies directed againstADAMTS13 (a disintegrin- like and metalloprotease (reprolysin type) with thrombospondin type 1 motif 13), a protease that cleaves the von Willebrand factor multimers. Prognosis has been im- proved by plasma therapy, but some acute severe forms are

Fadi Fakhouri; Jean-Paul Vernant; Agnes Veyradier; Martine Wolf; Gilles Kaplanski; Raynald Binaut; Manfred Rieger; Friedrich Scheiflinger; Pascale Poullin; Benjamin Deroure; Richard Delarue; Philippe Lesavre; Philippe Vanhille; Olivier Hermine; Giuseppe Remuzzi; Jean-Pierre Grunfeld



Clinicopathological Characteristics and Outcome of Chinese Patients with Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome: A 9Year Retrospective Study  

Microsoft Academic Search

Background: The pathogenesis of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is unclear and the prognosis is poor. Few studies have been published focusing on Chinese patients with TTP-HUS. We performed a retrospective study on the clinical characteristics and outcome of Chinese patients with TTP-HUS. Method: Patients with TTP-HUS, admitted to our hospital from 1998 to 2006, were retrospectively analyzed. Results:

Wen Zhang; Hao Shi; Hong Ren; Ping-Yan Shen; Xiao-Xia Pan; Xiao Li; Yong-Xi Chen; Yao-Wen Xu; Xiao-Nong Chen; Ping Zhu; Nan Chen



Two novel heterozygote missense mutations of the ADAMTS13 gene in a child with recurrent thrombotic thrombocytopenic purpura  

PubMed Central

Background Thrombotic thrombocytopenic purpura is a rare, life-threatening disease characterised by microangiopathic haemolytic anaemia, thrombocytopenia and symptoms related to organ ischaemia, mainly involving the brain and the kidney. It is associated with a deficiency of ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor. The congenital form (Upshaw-Schulman syndrome) is rare and is associated with mutations of the ADAMTS13 gene on chromosome 9q34. The clinical symptoms of congenital thrombotic thrombocytopenic purpura are variable, with some patients developing their first episode during the neonatal period or childhood and others becoming symptomatic in adulthood. Materials and methods We describe a case of thrombotic thrombocytopenic purpura, who presented to our attention with a relapsing form of the disease: the first episode occurred at the age of 13 months. Phenotype and genotype tests were performed in the patient and his family. Results The undetectable level of ADAMTS13 in the patient was caused by two novel heterozygote missense mutations on the ADAMTS13 gene: one mutation is c.788C > T (p.Ser263Phe) on exon 7 and the second is c.3251G > A (p.Cys1084Tyr) on exon 25 of the ADAMTS13 gene. All the relatives who have been investigated were found to carry one of these missense mutations in a heterozygous state. Discussion Although Upshaw-Schulman syndrome is a rare disease, it should be considered in all children with thrombocytopenia and jaundice in the neonatal period. In fact, once a child is confirmed to carry mutations of the ADAMTS13 gene causing early thrombotic thrombocytopenic purpura, prophylactic treatment should be started to avoid recurrence of symptoms. Genotype tests of relatives would also be important for those women in the family who could be carriers of ADAMTS13 mutations, particularly during pregnancy.

Rossio, Raffaella; Ferrari, Barbara; Cairo, Andrea; Mancini, Ilaria; Pisapia, Giovanni; Palazzo, Giulia; Peyvandi, Flora



Platelet destruction in autoimmune thrombocytopenic purpura: kinetics and clearance of indium-111-labeled autologous platelets  

SciTech Connect

Using autologous /sup 111/In-labeled platelets, platelet kinetics and the sites of platelet destruction were assessed in 16 normal subjects (13 with and three without spleens), in 17 studies of patients with primary autoimmune thrombocytopenic purpura (AITP), in six studies of patients with secondary AITP, in ten studies of patients with AITP following splenectomy, and in five thrombocytopenic patients with myelodysplastic syndromes. In normal subjects, the spleen accounted for 24 +/- 4% of platelet destruction and the liver for 15 +/- 2%. Untreated patients with primary AITP had increased splenic destruction (40 +/- 14%, p less than 0.001) but not hepatic destruction (13 +/- 5%). Compared with untreated patients, prednisone treated patients did not have significantly different spleen and liver platelet sequestration. Patients with secondary AITP had similar platelet counts, platelet survivals, and increases in splenic destruction of platelets as did patients with primary AITP. In contrast, patients with myelodysplastic syndromes had a normal pattern of platelet destruction. In AITP patients following splenectomy, the five nonresponders all had a marked increase (greater than 45%) in liver destruction compared to five responders (all less than 40%). Among all patients with primary or secondary AITP, there was an inverse relationship between the percent of platelets destroyed in the liver plus spleen and both the platelet count (r = 0.75, p less than 0.001) and the platelet survival (r = 0.86, p less than 0.001). In a stepwise multiple linear regression analysis, total liver plus spleen platelet destruction, the platelet survival and the platelet turnover were all significant independent predictors of the platelet count. Thus platelet destruction is shifted to the spleen in primary and secondary AITP. Failure of splenectomy is associated with a marked elevation in liver destruction.

Stratton, J.R.; Ballem, P.J.; Gernsheimer, T.; Cerqueira, M.; Slichter, S.J.



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. PMID:15801959

Rock, Gail; Anderson, David; Clark, William; Leblond, Pierre; Palmer, Douglas; Sternbach, Marion; Sutton, David; Wells, George



Can thrombelastography be a new tool to assess bleeding risk in patients with idiopathic thrombocytopenic purpura?  


Thrombelastography (TEG) analyses the status of blood coagulation including abnormalities associated with low platelet count. The aim of this study was to investigate the changes in TEG parameters in idiopathic thrombocytopenic purpura (ITP) patients. Thirty nine patients with ITP (platelet count?

Gunduz, Eren; Akay, Olga Meltem; Bal, Cengiz; Gulbas, Zafer



Long term outcome and sequelae in patients after acute thrombotic thrombocytopenic purpura episodes.  


We report on 21 patients with idiopathic thrombotic thrombocytopenic purpura (TTP) whose courses of disease have been followed from the respective diagnosis until now. They had a documented ADAMTS13 activity below 5%, a high autoantibody titer and detectable ultralarge von Willebrand factor (VWF) multimers during their episodes. The initial diagnosis was based on clinical symptoms and on laboratory parameters: thrombocytopenia, haemolytic anaemia, schistocytes and an increased LDH level. 103 acute clinical episodes of 21 TTP-patients during a time period of 30 years are described. Case histories, comorbidities and sequelae were retrospectively documented. Results, conclusion: Although patients are consistently in a prothrombotic status, clinical acute manifestations only occur after triggering. Most common trigger factors are gastrointestinal infections and pregnancy. The relapse risk per month is 0.026; men have a higher risk for relapses (0.044) than women (0.021). Patients recover physically well, except for renal insufficiency in four cases. Nevertheless, major portion of patients suffers persistently from depression, anxiety disorders and persistent neurocognitive impairments. PMID:23599034

Falter, T; Alber, K J; Scharrer, I



Multiple in silico tools predict phenotypic manifestations in congenital thrombotic thrombocytopenic purpura.  


Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare, recessively inherited genetic disorder with varying clinical presentation that is caused by ADAMTS13 mutations. Several studies have found limited associations between ADAMTS13 mutations and cTTP phenotype. The use of in silico tools that examine multiple mutation characteristics may better predict phenotype. We analysed 118 ADAMTS13 mutations found in 144 cTTP patients reported in the literature and examined associations of several mutation characteristics, including N-terminal proximity, the evolutionary conservation of the affected amino acid position, as well as amino acid charge/phosphorylation and genetic codon usage to disease phenotype. Structure-altering mutations were examined for their impact on ADAMTS13 function based on existing ADAMTS13 crystallographic data (AA 77-685). Our in silico data indicate that: (i) The position of the mutation in the N- or C-terminus, (ii) evolutionary conservation and (iii) codon usage of the affected mutation position are associated with disease parameters, such as age of onset, organ damage and fresh frozen plasma prophylaxis. In conclusion, the usage of multiple in silico tools presents a promising strategy in refining predictions for the diverse presentation of cTTP. Enhancing our utilization of in silico tools to find genotype-phenotype associations will create better-tailored approaches for individual patient treatment. PMID:23346910

Hing, Zachary A; Schiller, Tal; Wu, Andrew; Hamasaki-Katagiri, Nobuko; Struble, Evi Budo; Russek-Cohen, Estelle; Kimchi-Sarfaty, Chava



Use of splenic ultrasound: a new wave for immune thrombocytopenic purpura.  

PubMed Central

AIMS--To examine whether a therapeutic dose of ultrasound waves, when directed through the thoracic wall to the spleen, would significantly affect the platelet count in patients with stable immune thrombocytopenic purpura (ITP). METHODS--Continuous ultrasound at 1 W/cm2 spatial average-time average (SATA) intensity for up to one minute/5 cm2 treatment field was well tolerated in 13 patients with ITP and one with non-Hodgkin's lymphoma. Five healthy controls were also similarly treated. Peak platelet increments occurred four to eight hours after ultrasound treatment in the ITP group (n = 16 treatments). RESULTS--The mean peak platelet increment was 6.25 x 10(9)/l with a 5% confidence interval of the mean (95% CI) of 3.32 to 8.93 x 10(9)/l (p = 0.0004). The mean peak platelet increment of normal controls was 6.6 (n = 5; 95% CI = -2.3 to 15.5; p = 0.21) and for sham treated patients it was 0.66 (n = 11; 95% CI = -1.5 to 2.8; p = 0.60). There was a significant inverse correlation between patient age in the ITP group and peak platelet increment (r = -0.60; p = 0.015). CONCLUSIONS--Splenic ultrasound is a novel approach to the treatment of ITP, and may find a place in its diagnosis or management.

Cervi, P; Murdock, A; Rees, D; Garner, S; Grant, D; Wright, S; Dyson, M



Learning from errors: when a low platelet count in neonate excludes immune thrombocytopenic purpura in mother.  


This paper reviews the most common causes of thrombocytopenia in the newborn. It mentions few classification schemes that clearly characterize the most common causes, diagnosis and treatment approaches for neonatal thrombocytopenia. Particular attention is paid to inborn macrothrombocytopenia without congenital anomalies. They represent a rare group of diseases, often captured randomly or during routine examinations. An attention is paid on congenital macrothrombocytopenia variants with mutations in the MYH9 gene. If they are not associated with other disorders (deafness, presenile cataracts, nephritis or renal failure), they may be mistakenly diagnosed as the acquired immune thrombocytopenic purpura (ITP). This distinguishing is essential to avoid potentially harmful and unnecessary treatment. The listed case report points to a situation where a detection of the root causes of neonatal thrombocytopenia led to a review of misdiagnosed ITP in the mother. A platelet size evaluation by both an appropriate cell counter and blood film examination is useful for differentiating a heterogeneous group of rare inherited macrothrombocytopenias. A healthy twin supported autosomal dominant inheritance. The results of investigations of twins and mother confirmed the congenital/inherited macrothrombocytopenia from the group of MYH9-related diseases (Tab. 5, Fig. 2, Ref. 21). PMID:23514558

Gresikova, M



Favorable Response of Chronic Refractory Immune Thrombocytopenic Purpura to Mesenchymal Stem Cells  

PubMed Central

Seven patients with chronic refractory immune thrombocytopenic purpura (ITP) received adipose tissue-derived mesenchymal stem cells (AMSC) from haplo-identical family donors. The AMSC dose was 2.0×106/kg. No side effects were noted after the AMSC infusions. Overall responses were reached in all patients and sustained response rate was 57.1% (4/7). The serum levels of transforming growth factor ?1 (TGF-?1), interleukin (IL)-4, and IL-10 were significantly elevated, whereas those of interferon-? (IFN-?) and IL-2 were significantly decreased after AMSC administration, compared with those in the patients with active ITP. During follow-up, the cytokine profiles in patients maintaining sustained response remained stable compared with the post-treatment level, but IFN-? and IL-2 levels were significantly increased, and those of TGF-?1, IL-4, and IL-10 were significantly reduced again in relapsed patients. AMSC therapy seems to represent reasonable salvage treatment in severe, chronic refractory ITP by causing a shift in the Th1/Th2 cytokine balance to the same levels as normal controls.

Fang, Baijun; Mai, Ling; Li, Ning



Platelet antibodies of the IgM class in immune thrombocytopenic purpura  

SciTech Connect

The clinical course and response to therapy of patients with immune thrombocytopenic purpura (ITP) are not completely determined by the level of IgG present on the platelet surface. It is possible that antibodies of other immunoglobulin classes also play a role in platelet destruction in some of these patients. Therefore, the authors studied 175 patients with ITP for the presence of IgM anti-platelet antibodies using radiolabeled polyclonal or monoclonal anti-IgM. They observed that 57% of patients with clinical ITP had increased levels of IgM on their platelets, compared with normal controls and patients with thrombocytopenia who did not have ITP. They obtained similar results using either radiolabeled polyclonal or monoclonal anti-IgM, reagents whose integrity was first characterized using erythrocytes coated with defined amounts of IgM antibody. Among patients with increased platelet-IgM there was a significant correlation both with the presence of increased platelet-C3 as well as the amount of platelet-C3. The authors demonstrated the presence of warm-reacting IgM anti-platelet antibodies in the plasma of two of these patients who were further studied. These studies demonstrate the presence of warm-reacting IgM anti-platelet antibodies in some patients with ITP. They suggest that the binding of complement to platelets by IgM antibodies may initiate platelet clearance as well as enhance the effect of IgG antibodies in ITP.

Cines, D.B.; Wilson, S.B.; Tomaski, A.; Schreiber, A.D.



Retrospective review of 25 cases of thrombotic thrombocytopenic purpura in Pakistan.  


Thrombotic thrombocytopenic purpura (TTP) is a disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurological abnormalities, and renal dysfunction. Because of the rarity of TTP, no comprehensive data is available in the Pakistani population. The present study aimed to review the therapeutic interventions, relapses and mortality rate in patients with TTP treated at a tertiary care hospital in Pakistan. This was a retrospective review of patients treated over a period of more than nine years (2001-2010). Medical charts were retrieved using the ICD coding system version 9 and each file was reviewed by the principal author for clinical and laboratory details, along with the therapy utilized and the outcome. Twenty-five patients were diagnosed with TTP, including nine males (36%) and 16 females (64%) with a median age of 30 ± 18.4 years for all patients. Idiopathic TTP was seen in 17 patients (68%) and secondary causes were identified in eight (32%). Patients were treated with plasma exchange once the diagnosis of TTP was established. Only neurological and renal involvement at the time of presentation emerged as important indicators in determining the outcome and response to treatment. Most of our patients tolerated plasmapheresis very well; however, delay in starting plasmapheresis due to late presentation was a major hurdle in our set up. PMID:22248203

Sagheer, Safoorah; Moiz, Bushra; Usman, Mohammad; Khurshid, Mohammad



Atypical hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: Clinically differentiating the thrombotic microangiopathies.  


The increased understanding of the pathophysiology of both atypical hemolytic uremic syndrome (aHUS) and thrombotic thrombocytopenic purpura (TTP) in recent years has led to significant therapeutic advances for both conditions. These advances have placed an increased emphasis on a more rapid differentiation of both disorders which remain clinical diagnoses. In particular, recent data demonstrating the effectiveness of complement inhibition in patients with aHUS have increased the need for a more rapid and accurate differentiation of aHUS and TTP. Previously utilized criteria have used the presence or absence of neurologic or renal injury and the pretreatment ADAMTS13 activity to differentiate aHUS from TTP. The use of presenting clinical symptoms and findings alone to differentiate these conditions is problematic given their overlapping clinical presentations. Similarly, the use of the pretreatment ADAMTS13 activity alone to differentiate aHUS from TTP is also problematic, and could lead to the inappropriate witholding of plasma exchange (PEX) therapy. However, when used collectively, the pretreatment clinical findings (symptoms and laboratory data) and ADAMTS13 activity in the context of the patient's response to PEX therapy can allow for a more effective differentiation of these two disorders in a timely fashion that will allow for the prompt initiation of the most appropriate therapy. PMID:23739653

Cataland, Spero R; Wu, Haifeng M



Prospective phase 1/2 study of rituximab in childhood and adolescent chronic immune thrombocytopenic purpura  

PubMed Central

We assessed safety and efficacy of rituximab in a prospective study of 36 patients, age 2.6 to 18.3 years, with severe chronic immune thrombocytopenic purpura (ITP). The primary outcome of sustained platelets above 50 × 109/L (50 000/mm3) during 4 consecutive weeks, starting in weeks 9 to 12, was achieved by 11 of 36 patients (31%, confidence interval [CI], 16% to 48%). Median response time was 1 week (range, 1 to 7 weeks). Attainment of the primary outcome was not associated with age, prior pharmacologic responses, prior splenectomy, ITP duration, screening platelet count, refractoriness, or IgM reduction. First-dose, infusion-related toxicity was common (47%) despite premedication. Significant drug-related toxicities included third-dose hypotension (n = 1) and serum sickness (n = 2). Peripheral B cells were depleted in all subjects. IgM decreased 3.4% per week, but IgG did not significantly decrease. Rituximab was well tolerated, with manageable infusion-related side effects, but 6% of subjects developed serum sickness. Rituximab is beneficial for some pediatric patients with severe, chronic ITP.

Bennett, Carolyn M.; Rogers, Zora R.; Kinnamon, Daniel D.; Bussel, James B.; Mahoney, Donald H.; Abshire, Thomas C.; Sawaf, Hadi; Moore, Theodore B.; Loh, Mignon L.; Glader, Bertil E.; McCarthy, Maggie C.; Mueller, Brigitta U.; Olson, Thomas A.; Lorenzana, Adonis N.; Mentzer, William C.; Buchanan, George R.; Feldman, Henry A.; Neufeld, Ellis J.



Successful rituximab treatment for acquired amegakaryocytic thrombocytopenic purpura complicated with Coombs-negative autoimmune hemolytic anemia.  


Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare disorder characterized by severe thrombocytopenia associated with total absence or a selective decrease in bone marrow megakaryocytes. A 67-year-old male presented with a 2-month bleeding tendency. He was referred to our hospital because of severe thrombocytopenia. Bone marrow biopsy showed complete absence of megakaryocytes without dysplasia in cells of the myeloid and erythroid lineages. AATP was diagnosed. In addition, mild normocytic normochromic anemia and reticulocytosis were also observed and haptoglobin was below the detectable level. Coombs-negative autoimmune hemolytic anemia (AIHA) was diagnosed based on the high titer of RBC-bound IgG and negative direct and indirect coombs test results. He was first treated with cyclosporine 200 mg per day and subsequently with prednisolone but only slight temporary improvement was achieved. Administration of eight doses of rituximab 375 mg/m(2) per week ameliorated both thrombocytopenia and anemia. AATP should be considered in the differential diagnosis of thrombocytopenia, and immunosuppressive therapy is a potential first-line treatment. This is the first case report of AATP accompanied by AIHA successfully treated with rituximab. PMID:23823096

Hashimoto, Akari; Fujimi, Akihito; Kanisawa, Yuji; Matsuno, Teppei; Okuda, Toshinori; Minami, Shinya; Doi, Tadashi; Ishikawa, Kazuma; Uemura, Naoki; Tomaru, Utano



Diagnostic and therapeutic challenges in the thrombotic thrombocytopenic purpura and hemolytic uremic syndromes.  


Evaluation and management of patients with suspected thrombotic thrombocytopenic purpura (TTP) continue to be a critical challenge for hematologists. The diagnostic criteria are not precise, often causing uncertainty about whether it is appropriate to initiate plasma exchange (PEX), the essential treatment for TTP. Initiation of PEX remains a clinical decision; severe ADAMTS13 (< 10% activity) deficiency alone is neither sufficiently sensitive nor specific for the diagnosis of TTP. However, patients who do have severe acquired ADAMTS13 deficiency define the characteristic clinical features of TTP, the response to treatment, and the long-term outcomes. Patients with severe acquired ADAMTS13 deficiency are predominantly young women and the relative frequency of blacks is increased. Patients may present with only microangiopathic hemolytic anemia and thrombocytopenia, neurologic and renal abnormalities are often not present, fever rarely occurs; the complete "pentad" of these clinical features almost never occurs in current practice. Response to PEX is typically rapid but may not be sustained when PEX is stopped. Use of corticosteroids and rituximab has decreased the number of PEX treatments required to achieve a remission and has resulted in fewer PEX-related major complications. Relapse (in approximately 40% of patients) may be the most apparent risk after recovery, but long-term health outcomes are also very important. Minor cognitive abnormalities are common, the frequency of depression is increased, and the frequency of hypertension is increased. Careful long-term follow-up of TTP patients is essential. PMID:23233641

George, James N; Al-Nouri, Zayd L



Thrombotic thrombocytopenic purpura after prophylactic cefuroxime axetil administered in relation to a liposuction procedure.  


Thrombotic thrombocytopenic purpura (TTP) or Moschcowitz's syndrome is characterized by platelet and von Willebrand factor (vWF) deposition in arterioles and capillaries throughout the body, which results in organ ischemia. The diagnostic pentad characterizing TTP consists of thrombocytopenia, microangiopathic hemolytic anemia (MAHA), fever, neurologic manifestations, and renal insufficiency. In terms of type, TTP can be either idiopathic or secondary. The causes of secondary TTP include pregnancy, infections, pancreatitis, collagen vascular disease, cancer, bone marrow transplantation, and drugs (including cephalosporins). Postoperative TTP has been reported after vascular surgery, renal and liver transplantations, and orthopedic, urologic, and abdominal surgical procedures. Therapeutic plasma exchange (TPE) therapy has reduced the mortality rates, but sometimes patients may have to receive immunosuppressive drugs including vincristine (VCR). This report describes a 42-year-old woman with TTP after prophylactic usage of cefuroxime axetil in relation to a liposuction procedure who was treated successfully with plasma exchange and VCR. The patient fully recovered after 17 TPEs and three doses of VCR. At this writing, her TTP still is in remission after 6 months of follow-up evaluation. To the authors' knowledge, this is the first report in the literature describing a patient with TTP after cefuroxime axetil administered in relation to a surgical procedure who was treated successfully with TPE and VCR. PMID:21853406

Eskazan, Ahmet Emre; Salihoglu, Ayse; Gulturk, Emine; Ongoren, Seniz; Soysal, Teoman



Thrombotic Thrombocytopenic Purpura Associated with Mixed Connective Tissue Disease: A Case Report  

PubMed Central

Thrombotic thrombocytopenic purpura (TTP) is a multisystemic disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia, which may be accompanied by fever, renal, or neurologic abnormalities. Cases are divided into acute idiopathic TTP and secondary TTP. Autoimmune diseases, especially systemic lupus erythematosus, in association with TTP have been described so far in many patients. In contrast, TTP occurring in a patient with mixed connected tissue disease (MCTD) is extremely rare and has only been described in nine patients. We describe the case of a 42-year-old female with MCTD who developed thrombocytopenia, microangiopathic hemolytic anemia, fever, and neurological symptoms. The patient had a good clinical evolution with infusion of high volume of fresh frozen plasma, steroid therapy, and support in an intensive care unit. Although the occurrence of TTP is rare in MCTD patients, it is important to recognize TTP as a cause of thrombocytopenia and hemolytic anemia in any patient with autoimmune diseases. Prompt institution of treatment remains the cornerstone of treatment of TTP even if plasma exchange is not available like what frequently happens in developing countries.

Souto Filho, Joao Tadeu Damian; de Barros, Philipe Vianna; da Silva, Aline Maria Yamaguti Rios Paes; Barbosa, Fernanda Alves; Ribas, Gustavo Fernandes



Thrombotic thrombocytopenic purpura at presentation of juvenile systemic lupus erythematosus patients.  


Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening hematological abnormality characterized by thrombocytopenia and microangiopathic hemolytic anemia, with neurological abnormalities and/or renal disease. TTP has been rarely reported in juvenile systemic lupus erythematosus (JSLE) patients and, to our knowledge, its prevalence in a paediatric lupus population has not been studied. Therefore, from January 1983 to December 2010, we reviewed the charts of 5,508 patients followed-up at the Paediatric Rheumatology Unit of our university hospital. We identified 279 (5.1%) JSLE cases that met the American College of Rheumatology classification criteria. Two (0.7%) of them had TTP, both at JSLE onset, and were described herein. Both patients had fever, microangiopathic hemolytic anemia (with schistocytes in blood smears), and thrombocytopenia. The male patient had hemiparesis and proteinuria and the female patient had persistent headache and hematuria. Both were treated with intravenous methylprednisolone and courses of plasma exchange therapy at TTP diagnosis. After treatment, TTP did not recur and their hematocrit, platelet count, and lactic dehydrogenase remained normal. In conclusion, TTP is a rare and severe manifestation at JSLE onset. The case reports reinforce the importance of early diagnosis and early aggressive treatment for patients with TTP, due to its high morbidity. PMID:23588522

Campos, Lucia M A; Spadoni, Maria Silvia; Michelin, Cintia M; Jesus, Adriana A; Carneiro, Jorge D A; da Silva, Clovis Artur Almeida



AAV-mediated expression of an ADAMTS13 variant prevents shigatoxin-induced thrombotic thrombocytopenic purpura.  


Severe deficiency of plasma ADAMTS13 activity causes thrombotic thrombocytopenic purpura (TTP), a life-threatening syndrome for which plasma is the only effective therapy currently available. As much as 5% of TTP cases are hereditary, resulting from mutations of the ADAMTS13 gene. Here, we report the efficacy and safety of recombinant adeno-associated virus serotype 8 (AAV8)-mediated expression of a murine ADAMTS13 variant (MDTCS), truncated after the spacer domain, in a murine model of TTP. Administration of AAV8-hAAT-mdtcs at doses greater than 2.6 × 10(11) vg/kg body weight resulted in sustained expression of plasma ADAMTS13 activity at therapeutic levels. Expression of the truncated ADAMTS13 variant eliminated circulating ultralarge von Willebrand factor multimers, prevented severe thrombocytopenia, and reduced mortality in Adamts13(-/-) disease-prone mice triggered by shigatoxin-2. These data support AAV vector-mediated expression of a comparable truncated ADAMTS13 variant as a novel therapeutic approach for hereditary TTP in humans. PMID:23515928

Jin, Sheng-Yu; Xiao, Juan; Bao, Jialing; Zhou, Shangzhen; Wright, J Fraser; Zheng, X Long



Intravenous immunoglobulin (i.v. IgG) for previously treated acute or for chronic idiopathic thrombocytopenic purpura (ITP) in childhood: a prospective multicenter study  

Microsoft Academic Search

In a prospective multicenter study 42 thrombocytopenic (9 platelets\\/l) children with chronic idiopathic thrombocytopenic purpura (ITP) or with acute ITP, dependent on or refractory to corticosteroids, were given 0.4 g i.v. IgG\\/kg body weight\\/day on 5 consecutive days and thereafter once a week if the platelet count fell to 9\\/l or if the patient bled. After the initial 5 days

B. Imholz; P. Imbach; C. Baumgartner; W. Berchtold; G. Gaedicke; E. Gugler; A. Hirt; W. Hitzig; C. Mueller-Eckhardt; H. P. Wagner



A Case of Non-Hodgkin's Lymphoma in Patient with Coombs' Negative Hemolytic Anemia and Idiopathic Thrombocytopenic Purpura.  


Coombs' negative autoimmune hemolytic anemia (AIHA) is a rare disease which shares similar clinical and hematological features with Coombs' positive AIHA, but its exact frequency remains unknown. There have been few reports of idiopathic thrombocytopenic purpura (ITP) and Coombs' negative AIHA associated with other lymphoproliferative disorders (LPDs). Since there is a well known association between LPDs and autoimmune phenomena, it is important to investigate the possibility of an underlying malignancy. We report a case of ITP and Coombs' negative AIHA associated with diffuse large B-cell lymphoma. PMID:22500164

Park, So Yeon; Kim, Soyon; Kim, Eun Sil; Choi, Soon Uk; Hyun, Hee Jae; Ahn, Ju Young; Lee, Ju Hyoung; Ryu, Seo Hee; Park, Jae Hyun; Lee, Gyeong In; Lee, Hyo Jin



A Case of Non-Hodgkin's Lymphoma in Patient with Coombs' Negative Hemolytic Anemia and Idiopathic Thrombocytopenic Purpura  

PubMed Central

Coombs' negative autoimmune hemolytic anemia (AIHA) is a rare disease which shares similar clinical and hematological features with Coombs' positive AIHA, but its exact frequency remains unknown. There have been few reports of idiopathic thrombocytopenic purpura (ITP) and Coombs' negative AIHA associated with other lymphoproliferative disorders (LPDs). Since there is a well known association between LPDs and autoimmune phenomena, it is important to investigate the possibility of an underlying malignancy. We report a case of ITP and Coombs' negative AIHA associated with diffuse large B-cell lymphoma.

Park, So Yeon; Kim, Eun Sil; Choi, Soon Uk; Hyun, Hee Jae; Ahn, Ju Young; Lee, Ju Hyoung; Ryu, Seo Hee; Park, Jae Hyun; Lee, Gyeong In; Lee, Hyo Jin



Autoimmune hepatitis-primary biliary cirrhosis overlap syndrome concomitant with immune hemolytic anemia and immune thrombocytopenic purpura (Evans syndrome).  


Autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) associated with Evans syndrome; combination of autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP) has rarely been reported. We report the case of a 53-year-old patient who presented with weakness, myalgia, arthralgia, shortness of breath and purpura. Initial laboratory investigations revealed liver dysfunction, anemia and thrombocytopenia. Anti-nuclear (ANA) and antimitochondrial M2 (AMA M2) antibodies were positive. Diagnose of PBC-AIH overlap was made by clinical, serological and histological investigations. AIHA and ITP was identified with clinical-laboratory findings and bone marrow puncture. She was treated with IVIG followed by prednisolone and ursodeoxycholic acid. Hemoglobin-thrombocytes increased rapidly and transaminases improved at day 8. We have reported the first case in the literature with AIH-PBC overlap syndrome concurrent by ITP and AIHA which suggest the presence of shared genetic susceptibility factors in multiple autoimmune conditions including AIH, PBC, ITP and AIHA. PMID:23273499

Korkmaz, Huseyin; Bugdaci, Mehmet Sait; Temel, Tuncer; Dagli, Mehmet; Karabagli, Pinar



Prevalence and clinical significance of antithyroid antibodies in children with immune thrombocytopenic purpura.  


Background and objective: To determine the prevalence and the clinical significance of thyroid autoantibodies and their influence on treatment response in children with idiopathic thrombocytopenic purpura (ITP). Patient and Method: We retrospectively analyzed the antithyroglobulin (anti-TG) and antithyroid peroxidase (anti-TPO) antibodies from the records of 151 ITP patients who were admitted to the Pediatric Hematology Department of Gaziantep University between 2009 and 2012. Results: Anti-TPO and/or anti-TG was found positive in 38 (36.8%) of 103 patients whose thyroid autoantibody levels were measured. The comparison of positivity ratios of autoantibodies between acute and chronic ITP patients showed no significant difference. However, the separate comparison of each group of ITP patients with control group showed significantly high positivity ratios of autoantibodies in ITP patients. The initial mean platelet count of anti-TPO positive patients at diagnosis was significantly less than that of the negative patients (P = .008). One month after treatment, platelet count of anti-TPO positive patients was significantly less than that of the negative patients (P = .01). Moreover, the mean platelet counts of anti-TPO positive patients were significantly less than those of the negative patients after intravenous immunoglobulin treatment (P < .001). Conclusion: We demonstrated that the thyroid-autoimmune-diseases-related autoantibodies are frequently found in childhood ITP. Although no recommendation is found in international guidelines regarding screening for thyroid autoantibodies in patients with ITP, in view of the high incidence of antithyroid antibodies and their potential negative effect on treatment response, screening these patients for such antibodies would be recommended. PMID:23301695

Bay, Ali; Coskun, Enes; Leblebisatan, Goksel; Karaoglu, Ozlem; Keskin, Mehmet; Yavuz, Sibel; Yilmaz, Fatih; Dai, Alper; Coskun, Mehmet Yavuz



Inhibitors of von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura.  


Thrombotic thrombocytopenic purpura (TTP), characterized by platelet thrombi in the arterioles and capillaries, is associated with antibodies that inhibit the activity of von Willebrand factor (vWF)-cleaving protease. Using a modified Bethesda method, we studied the inhibitor titers in patients who participated in the trial conducted by the Canadian Apheresis Group. Among the 41 patients investigated, the inhibitor titers at presentation were 1.4 +/- 1.7 U/mL (range -0.2-6.2 U/mL). Thirty-one patients (76%) had a titer > or = 0.2 U/mL, 8 patients (20%) had a titer > or = 2.0 U/mL but none had a titer > or = 10 U/mL. Among the 33 patients with an inhibitor titer < 2.0 U/mL (low titer group) and the 8 patients with an inhibitor titer > or = 2 U/mL (high titer group), 20 (61%) and 8 (100%) respectively had a platelet count < 25x10(9)/L (P = 0.04). Neurological abnormalities were among the presenting problems in 19 (58%) of the low titer and 6 (75%) of the high titer groups. Among the 23 patients who were randomized to plasma exchange, 5 patients had an inhibitor titer > or = 2 U/mL and none responded at the end of the first treatment cycle, while 8 of the 18 patients (44%) with a titer < 2 U/mL responded. This study shows that inhibitors of vWF-cleaving protease are of low titers in most cases of acquired TTP. A higher inhibitor titer is associated with a more advanced stage of the disease and may delay the response to plasma exchange. PMID:11499801

Tsai, H M; Li, A; Rock, G



Increased circulating Ia-positive T cells in patients with idiopathic thrombocytopenic purpura.  

PubMed Central

Peripheral blood T cells from 40 patients with idiopathic thrombocytopenic purpura (ITP) were analysed for the presence of surface Ia antigens using monoclonal antibodies by indirect immunofluorescence. The percentage of Ia-positive (Ia+) T cells was significantly increased in patients with ITP (6.8 +/- 2.9%, P less than 0.005) as compared with normal controls (2.3 +/- 0.9%). There was an inverse correlation between the percentages of Ia+ T cells and platelet counts (r = 0.58, P less than 0.005) and a positive correlation between the percentage of these cells and platelet-associated IgG (PAIgG) values (r = 0.55, P less than 0.01). The percentage of Ia+ T cells was found to decrease within two weeks during therapy with high dose gamma-globulin or corticosteroid. We have previously reported the presence of T cells bearing both helper/inducer (H/I) and suppressor/cytotoxic (S/C) phenotypes (double labelled cells, DLC) in patients with ITP and an inverse correlation between the percentages of DLC and their platelet counts. In the present study, we showed that a major part of Ia+ T cells had both H/I and S/C phenotypes. We also examined the correlation between Ia+ T cells and autologous mixed lymphocyte reaction (AMLR). A defective AMLR was demonstrated in patients with ITP. Furthermore, an inverse correlation was found between the percentages of Ia+ T cells and the proliferative responses to AMLR (r = -0.49, P less than 0.01). These results suggest that increased circulating Ia+ T cells play a role in the abnormalities of the immunoregulatory system of ITP, especially in the regulation of autoantibody production.

Mizutani, H; Tsubakio, T; Tomiyama, Y; Katagiri, S; Tamaki, T; Kurata, Y; Yonezawa, T; Tarui, S



The incidence of immune thrombocytopenic purpura in children and adults: A critical review of published reports.  


Reports of the incidence of ITP are few and their methodology is variable. Accurate estimates of the incidence of immune thrombocytopenic purpura (ITP) are important to understand the medical and public health impact of the disease. To critically review all published reports on the incidence of ITP in children and adults, all articles identified on the Medline database (searched January 1, 1966-August 7, 2009) that reported data on the incidence of ITP were retrieved. Articles which directly estimated the incidence of ITP were selected for review. Eight articles reported the incidence of acute ITP in children. After review, four were determined to have the strongest estimates, based on the method of patient identification and study design. The lowest incidence estimate in these four studies was 2.2 per 10(5) children/year (95% confidence interval 1.9, 2.4) and the highest incidence estimate was 5.3 per 10(5) children/year (95% confidence interval 4.3, 6.4). Three studies reported the incidence of ITP in adults. The estimate from the article with the strongest methodology reported an incidence estimate of 3.3 per 10(5) adults/year. The current strongest estimate of the incidence of acute ITP in children is between 1.9 and 6.4 per 10(5) children/year; for adults the current strongest estimate of the incidence of ITP is 3.3 per 10(5) adults/year. An important limitation of these studies is that they are primarily from Europe and may not be generalizable to all regions. PMID:20131303

Terrell, Deirdra R; Beebe, Laura A; Vesely, Sara K; Neas, Barbara R; Segal, Jodi B; George, James N



Platelet Count Response to Helicobacter pylori Eradication in Iranian Patients with Idiopathic Thrombocytopenic Purpura  

PubMed Central

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune hematological disorder characterized by auto antibody-mediated platelet destruction. Although the main cause of ITP remains unclear, but its relationship with some infection was demonstrated. In recent years, many studies have demonstrated improvement of platelet counts in ITP patients after treating Helicobacter pylori infection. The aim of this study was to investigate the effects of H. pylori eradication on platelet count response in Iranian ITP patients. A total of 26 patients diagnosed with both ITP and H. pylori infection. ITP were diagnosed whose platelet counts were less than 100×103/?L. These patients were tested for H. pylori infection by Urea Breath Test and serum H. pylori antibody. All patients received triple therapy for 7 or 14 days to eradicate H. pylori infection. These patients followed for six months. Prevalence of H. pylori was 67.3%. H. pylori eradication achieved in 89.5% (26/29). Of the 26 patients, 15 (57.7%) exhibited a complete response (CR) and 11 (42.3%) were unresponsive. We did not find partial responders. There was a significant difference in the baseline platelet count of responders and non-responders patients (p<0.001). All responders had platelet count ?50×103/?L and all non-responders had platelet count <50×103/?L. Results of this study revealed that eradication therapy of H. pylori infection can improve platelet counts in ITP patients especially with mild thrombocytopenia and support routine detection and treatment of H. pylori infection in ITP patients in populations with a high prevalence of this infection.

Payandeh, Mehrdad; Sohrabi, Nasrollah; Zare, Mohammad Erfan; Kansestani, Atefeh Nasir; Hashemian, Amir Hossein





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Thrombotic thrombocytopenic purpura with an autoantibody to ADAMTS13 complicating Sjögren's syndrome: two cases and a literature review.  


An association between thrombotic thrombocytopenic purpura (TTP) and Sjögren's syndrome (SS) is rare. This is the first report of two patients with TTP who had inhibitory autoantibodies to ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type 1 repeats) complicating primary SS. A rapid diagnosis of TTP, which is a potentially lethal condition, made it possible to treat the two cases successfully. Only eight similar cases with TTP complicating SS have been reported in the literature. The possible presentation of primary SS without classic sicca symptoms, but with haematological abnormalities including TTP, should be recognised. Furthermore, it is important to measure ADAMTS13 activity and anti-ADAMTS13 antibodies, because TTP with SS seems to be a concurrent overlapping autoimmune disorder. We suggest that plasma exchanges in combination with corticosteroids should be administered as early as possible, since they appeared to be effective in treating TTP with SS, including in our cases. PMID:22526830

Yamashita, Hiroyuki; Takahashi, Yuko; Kaneko, Hiroshi; Kano, Toshikazu; Mimori, Akio



New advances in the treatment of adult chronic immune thrombocytopenic purpura: role of thrombopoietin receptor-stimulating agents  

PubMed Central

Decades of basic science and clinical research have led to an increased understanding of the pathophysiology of immune thrombocytopenic purpura (ITP), the processes underlying thrombopoiesis, and the treatment of chronic ITP. Now, new agents are available to treat ITP in a nonimmunosuppressive fashion. Lessons learned from the clinical trials of recombinant human thrombopoietin (TPO) have led to the development of a novel class of compounds: nonimmunogenic agonists of the thrombopoietin receptor. Representing the first nonimmunosuppressive agents to treat chronic refractory ITP in decades, medications such as romiplostim and eltrombopag were recently approved by the US Food and Drug Administration. These new agents offer physicians a new tool for treating difficult cases of ITP in their medical armamentarium. Additional TPO mimetics are also being developed that show promise in vitro, and await future development.

Metjian, Ara; Abrams, Charles S



Successful perioperative management of a patient with idiopathic thrombocytopenic purpura undergoing emergent appendectomy: Report of a case?  

PubMed Central

INTRODUCTION Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by a low platelet count and normal bone marrow. Patients with ITP undergoing surgery are thought to have increased risk for postoperative complications because of their thrombocytopenia. PRESENTATION OF CASE we report the case of a 66-year-old woman with ITP who required an emergency operation for acute appendicitis associated with disseminated intravascular coagulation. Preoperative therapy consisted of platelet transfusions only, and intraoperative hemostasis was achieved. Postoperatively, high-dose intravenous immunoglobulin (IVIg) therapy led to an increased, stable, and adequate platelet count and good hemostasis. DISCUSSION The outcome of this case suggests that IVIg therapy is not always required for preoperative management of patients with. CONCLUSION IVIg therapy may be useful for postoperative management after emergency surgery.

Toyomasu, Yoshitaka; Shimabukuro, Rinshun; Moriyama, Hatsuo; Eguchi, Daihiko; Ishikawa, Koichi; Kishihara, Fumiaki; Fukuyama, Yasurou; Matsumata, Takashi; Mochiki, Erito; Kuwano, Hiroyuki



Combination therapy of rituximab and corticosteroids for patients with refractory chronic immune thrombocytopenic purpura: report of two cases  

PubMed Central

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder, for which rituximab has been proven to be an effective treatment. The response rate was reported to be approximately 60% in refractory ITP patients. However, the response time is slower than expected, and the mechanism of action of rituximab in ITP is still unclear. Thus, sometimes, the use of a combination therapy with rituximab according to different patient conditions is necessary. We report two refractory chronic ITP cases. The two patients were administered a low dose of dexamethasone (10 mg, weekly) combined with rituximab and a smaller dose of prednisone (10 mg, daily) as maintenance therapy. Although their peripheral B cells were almost eliminated, no complete reaction was observed. The maintenance therapy with prednisone was helpful in the prevention of bleeding. The patients’ responses to rituximab treatment suggest that multiple immunological mechanisms are involved in ITP pathogenesis and that the use of a combination therapy with rituximab according to the different patient conditions is necessary.

Ling, Yun; Qian, Xinyu



Detection of platelet-binding anti-measles and anti-rubella virus IgG antibodies in infants with vaccine-induced thrombocytopenic purpura.  


A 15-month-old infant presented with thrombocytopenic purpura after sequential administration of measles-rubella combined vaccine, varicella vaccine and mumps vaccine every 4 weeks. Her thrombocytopenia persisted for more than 12 months. Both anti-measles and anti-rubella virus IgG antibodies were detected in the patient's-isolated platelets on day 154 of illness, which were not detected when there was a reduction of the serum IgG antibody titers on days 298 and 373 of illness, respectively.We also detected the isolated platelet-binding anti-measles and anti-rubella virus IgG antibodies in two other pediatric patients. This is the first report demonstrating direct evidence of vaccine-induced thrombocytopenic purpura. PMID:21539881

Okazaki, Naho; Takeguchi, Masahiro; Sonoda, Kohji; Handa, Yohsuke; Kakiuchi, Tatsuo; Miyahara, Hiroaki; Akiyoshi, Kensuke; Korematsu, Seigo; Suenobu, Soichi; Izumi, Tatsuro



Is Eradication Therapy Useful as the First Line of Treatment in Helicobacter pylori Positive Idiopathic Thrombocytopenic Purpura? Analysis of 207 Eradicated Chronic ITP Cases in Japan  

Microsoft Academic Search

A retrospective study was performed to determine the prevalence of Helicobacter pylori (H pylori) infection, the effect of\\u000a H pylori eradication on platelet counts, and the characteristic clinical features of chronic immune or idiopathic thrombocytopenic\\u000a purpura (ITP) with H pylori infection. H pylori infection was found in 300 patients, a group that was significantly older (P P = .01) than

Kingo Fujimura; Masataka Kuwana; Yoshiyuki Kurata; Masahiro Imamura; Hiroshi Harada; Hisashi Sakamaki; Masanao Teramura; Kyuhei Koda; Shosaku Nomura; Sayaka Sugihara; Takeshi Shimomura; Tetsuro-Takahiro Fujimoto; Kazuma Oyashiki; Yasuo Ikeda



Plasma therapy in thrombotic thrombocytopenic purpura: review of the literature and the Bern experience in a subgroup of patients with severe acquired ADAMTS-13 deficiency  

Microsoft Academic Search

Based on clinical studies daily plasma exchange (PE) has become the first-choice therapy for thrombotic thrombocytopenic purpura (TTP) since 1991. Recent findings may explain its effectiveness, which particularly may include supply of ADAMTS-13 and removal of anti-ADAMTS-13 autoantibodies and unusually large von Willebrand factor (VWF) multimers. The most preferable PE regimens as well as replacement fluids are discussed and treatment-related

Stefano Fontana; Johanna A Kremer Hovinga; Jan-Dirk Studt; Lorenzo Alberio; Bernhard Lämmle; Behrouz Mansouri Taleghani



Development and validation of a predictive model for death in acquired severe ADAMTS13 deficiency-associated idiopathic thrombotic thrombocytopenic purpura: the French TMA Reference Center experience  

PubMed Central

Background Acquired thrombotic thrombocytopenic purpura is still associated with a 10–20% death rate. It has still not been possible to clearly identify early prognostic factors of death. This study involved thrombotic thrombocytopenic purpura patients with acquired severe (<10% of normal activity) ADAMTS13 deficiency and aimed to identify prognostic factors associated with 30-day death. Design and Methods The study involved a prospective cohort of patients and was carried out between October 2000 and August 2010. A validation cohort of patients was set up from September 2010 to August 2011. Altogether, 281 (analysis cohort) and 66 (validation cohort) consecutive adult thrombotic thrombocytopenic purpura patients with acquired severe ADAMTS13 deficiency were enrolled. The study evaluated 30-day mortality after treatment initiation according to characteristics at inclusion. Results Non-survivors (11%) were older (P=10?6) and more frequently presented arterial hypertension (P=5.10?4) and ischemic heart disease (P=0.013). Prognosis was increasingly poor with age (P=0.004). On presentation, cerebral manifestations were more frequent in non-survivors (P=0.018) and serum creatinine level was higher (P=0.008). The most significant independent variables determining death were age, severe cerebral involvement and LDH level 10 N or over. A 3-level risk score for early death was defined and confirmed in the validation cohort using these variables, with higher values corresponding to increased risk of early death. Conclusions A risk score for early death was defined in patients with thrombotic thrombocytopenic purpura and validated on an independent cohort. This score should help to stratify early treatment and identify patients with a worse prognosis.

Benhamou, Ygal; Assie, Cyrielle; Boelle, Pierre-Yves; Buffet, Marc; Grillberger, Rana; Malot, Sandrine; Wynckel, Alain; Presne, Claire; Choukroun, Gabriel; Poullin, Pascale; Provot, Francois; Gruson, Didier; Hamidou, Mohamed; Bordessoule, Dominique; Pourrat, Jacques; Mira, Jean-Paul; Le Guern, Veronique; Pouteil-Noble, Claire; Daubin, Cedric; Vanhille, Philippe; Rondeau, Eric; Palcoux, Jean-Bernard; Mousson, Christiane; Vigneau, Cecile; Bonmarchand, Guy; Guidet, Bertrand; Galicier, Lionel; Azoulay, Elie; Rottensteiner, Hanspeter; Veyradier, Agnes; Coppo, Paul



The thrombotic thrombocytopenic purpura and hemolytic uremic syndromes: overview of pathogenesis (Experience of The Oklahoma TTP-HUS Registry, 1989–2007)  

Microsoft Academic Search

The Oklahoma TTP (thrombotic thrombocytopenic purpura)—HUS (hemolytic uremic syndrome) Registry, an inception cohort of 382 consecutive patients with TTP–HUS, provides a complete community perspective of these syndromes. TTP is the diagnostic term used for all adults, with or without neurologic or renal abnormalities; it is typically an acquired disorder; it may rarely result from congenital ADAMTS13 deficiency. HUS is the

James N George



Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura  

Microsoft Academic Search

The role of rituximab, a chimeric monoclo- nal antibody directed against the CD20 antigen, in the treatment of patients with chronic idiopathic thrombocytopenic pur- pura (ITP) has not been determined. The effectiveness and side effects of this therapeutic modality were investigated in a cohort of 25 individuals with chronic ITP. All patients had ITP that had been resistant to between

Roberto Stasi; Adalberto Pagano; Elisa Stipa; Sergio Amadori


Population PK/PD modeling of eltrombopag in healthy volunteers and patients with immune thrombocytopenic purpura and optimization of response-guided dosing.  


The relationship between plasma eltrombopag concentrations and increases in platelet counts (PLTC) was characterized in healthy volunteers (HVs) and patients with immune thrombocytopenic purpura (ITP) using population pharmacokinetic/pharmacodynamic (PK/PD) models. The semiphysiological model included 3 PK, 1 precursor production, 2 maturation, and 1 blood platelet compartments and assumed a linear increase in platelet production rate with eltrombopag concentrations. Thrombopoiesis was assumed to be the same in HVs and patients, whereas platelets degraded more rapidly in patients. A mixture model was used, with nonresponders accounting for 19% of the patients. The following covariates were predictive of higher PLTC in ITP patients based on PK or PD differences in descending order of magnitude: East Asian race, age 65 years or older, baseline PLTC greater than 15 Gi/L, female, and concurrent corticosteroid. Simulations support starting eltrombopag at a dose of 50 mg once daily, except in East Asian patients, for whom 25 mg once daily is warranted. Doses can be titrated at 2-week intervals (or longer) to achieve target PLTC. PMID:21148042

Hayes, Siobhan; Ouellet, Daniele; Zhang, Jianping; Wire, Mary B; Gibiansky, Ekaterina



Synergistic interactions between interferon-? and TRAIL modulate c-FLIP in endothelial cells, mediating their lineage-specific sensitivity to thrombotic thrombocytopenic purpura plasma-associated apoptosis  

PubMed Central

Microvascular endothelial cell (MVEC) injury coupled to progression of platelet microthrombi facilitated by ADAMTS13 deficiency is characteristic of idiopathic and HIV-linked thrombotic thrombocytopenic purpura (TTP). Cytokines capable of inducing MVEC apoptosis in vitro are up-regulated in both TTP and HIV infection. However, the concentrations of these cytokines required to elicit EC apoptosis in vitro are 2- to 3-log–fold greater than present in patient plasmas. We report that clinically relevant levels of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) and interferon (IFN)–? act in synergy to induce apoptosis in dermal MVECs, but have no effect on large-vessel ECs or pulmonary MVECs. This reflects the tissue distribution of TTP lesions in vivo. Sensitivity to TTP plasma or TRAIL plus IFN-? is paralleled by enhanced ubiquitination of the caspase-8 regulator cellular FLICE-like inhibitory protein (c-FLIP), targeting it for proteasome degradation. c-FLIP silencing with anti-FLIP short interfering RNA (siRNA) in pulmonary MVECs rendered them susceptible to TTP plasma– and cytokine-mediated apoptosis, while up-regulation of c-FLIP by gene transfer partially protected dermal MVECs from such injury. TTP plasma–mediated apoptosis appears to involve cytokine-induced acceleration of c-FLIP degradation, sensitizing cells to TRAIL-mediated caspase-8 activation and cell death. Suppression of TRAIL or modulation of immunoproteasome activity may have therapeutic relevance in TTP.

Stefanescu, Radu; Bassett, Dustin; Modarresi, Rozbeh; Santiago, Francisco; Fakruddin, Mohamad



Treatment of plasmapheresis refractory thrombotic thrombocytopenic purpura with double-filtration membrane plasmapheresis.  


Thrombotic thrombocytic purpura (TTP) is a life-threatening disorder. Without plasma exchange treatment (PET) the mortality rate is quite high. Double-filtration plasmapheresis is an alternative opportunity for TTP patients refractory to PET. Here we report our experience in a refractory TTP patient who was successfully treated by means of double-filtration plasmapheresis therapy. PMID:23631953

Karakus, Volkan; Deveci, Burak; Kurto?lu, Erdal



Use of intravenous gamma globulin in children and adolescents with idiopathic thrombocytopenic purpura and other immune thrombocytopenias.  


Approximately 85 to 90 percent of cases of idiopathic thrombocytopenic purpura (ITP) in children are of the acute, self-limited variety that generally occurs after a viral infection. The remaining 10 to 15 percent of children with this disorder have the chronic (autoimmune) type of ITP. For these patients, splenectomy is often the recommended treatment if severe bleeding occurs and platelet counts remain below 40,000/mm3. However, splenectomy has associated risks and the response to this surgery cannot always be predicted. Intravenous gamma globulin (IVIG) has proven useful as an alternative to splenectomy, especially in children who are considered too young for splenectomy or in those in whom there is no response to splenectomy. It should be noted that booster shots are frequently required and the patient's ITP may become refractory. IVIG may also be useful in preparing a child with ITP for splenectomy and in treating children or adolescents with ITP who have central nervous system or other serious hemorrhages. Although IVIG is not always effective in raising the platelet count, it does provide a very useful alternative method of treating this disorder. PMID:3118703

Lusher, J M; Warrier, I



Clinical effect and some pathogenic mechanisms of high dose monomeric IgG therapy in childhood chronic idiopathic thrombocytopenic purpura.  


8 children with chronic idiopathic thrombocytopenic purpura received a high dose therapy with monomeric IgG. Before and after the treatment immunological investigations were carried out. All the children showed a positive clinical response, in 5 children there was an increase of thrombocytes to 111-340 X 10(9)/l. A clinico-haematological effect could be shown in those children with an increased percentage of marrow megakaryocytes with IgG fixed on the membrane before treatment. There was no haematological effect neither in cases with fixed IgG and IgA nor IgM and IgA combined, as well as in the case when there was no fixed IgG on the membrane. A steady clinical effect was provided if the number of bone marrow megakaryocytes with fixed IgG reached the norm. The suppression of the synthesis of antithrombocytic antibodies of the same immunoglobulin class can be regarded as a specific mechanism of high IgG doses. PMID:2428711

Koshel, I V; Torubarova, N A; Omarova, K O; Kurmashov, V I



Ten patient stories illustrating the extraordinarily diverse clinical features of patients with thrombotic thrombocytopenic purpura and severe ADAMTS13 deficiency.  


Patients with thrombotic thrombocytopenic purpura (TTP) and severe ADAMTS13 deficiency are often considered to have typical clinical features. However, our experience is that there is extraordinary diversity of the presenting features and the clinical courses of these patients. This diversity is illustrated by descriptions of 10 patients. The patients illustrate that ADAMTS13 activity may be normal initially but severely deficient in subsequent episodes. Patients with established diagnoses of systemic infection as the cause of their clinical features may have undetectable ADAMTS13 activity. Patients may have a prolonged prodrome of mild symptoms with only microangiopathic hemolytic anemia and thrombocytopenia or they may have the sudden onset of critical illness with multiple organ involvement. Patients may die rapidly or recover rapidly; they may require minimal treatment or extensive and prolonged treatment. Patients may have acute and severe neurologic abnormalities before microangiopathic hemolytic anemia and thrombocytopenia occur. Patients may have concurrent TTP and systemic lupus erythematosus. Patients may have hereditary ADAMTS13 deficiency as the etiology of their TTP rather than acquired autoimmune ADAMTS13 deficiency. These patients' stories illustrate the clinical spectrum of TTP with ADAMTS13 deficiency and emphasize the difficulties of clinical diagnosis. PMID:22927184

George, James N; Chen, Qiaofang; Deford, Cassie C; Al-Nouri, Zayd



A collaborative approach to investigating the risk of thrombocytopenic purpura after measles-mumps-rubella vaccination in England and Denmark.  


The assessment of rare adverse events following vaccination may not be possible within a single country due to an insufficiently large denominator population. In 2008 a European consortium (VAESCO) was funded to perform collaborative vaccine safety studies. To help assess the feasibility of multi-country collaboration England and Denmark, who have established vaccine safety research infrastructures, undertook to work to a common protocol and share results and data to estimate the risk of a known true adverse event, thrombocytopenic purpura (TP) following measles-mumps-rubella (MMR) vaccination. TP is a known rare reaction to MMR and therefore provided an opportunity to assess whether two countries would produce similar results when working collaboratively. Despite some initial problems with ensuring data were comparable, the two countries gave very similar estimates of the relative incidence in the 6 weeks after vaccination and a pooled relative incidence estimate of 2.13 (95% confidence interval 1.55-2.94) and attributable risk of 1 in 50,000 doses. Both countries used hospital admissions for TP and the analysis was performed using the self controlled case series method which is particularly suited to collaborative studies because of its implicit control for individual level confounding. The study therefore shows the potential for vaccine safety collaborations across Europe to detect true associations through use of common protocols and sharing of results or data. PMID:21699947

Andrews, Nick; Stowe, Julia; Miller, Elizabeth; Svanström, Henrik; Johansen, Kari; Bonhoeffer, Jan; Hviid, Anders



Combination therapy of rituximab and corticosteroids for patients with refractory chronic immune thrombocytopenic purpura: report of two cases.  


Immune thrombocytopenic purpura (ITP) is an autoimmune disorder, for which rituximab has been proven to be an effective treatment. The response rate was reported to be approximately 60% in refractory ITP patients. However, the response time is slower than expected, and the mechanism of action of rituximab in ITP is still unclear. Thus, sometimes, the use of a combination therapy with rituximab according to different patient conditions is necessary. We report two refractory chronic ITP cases. The two patients were administered a low dose of dexamethasone (10 mg, weekly) combined with rituximab and a smaller dose of prednisone (10 mg, daily) as maintenance therapy. Although their peripheral B cells were almost eliminated, no complete reaction was observed. The maintenance therapy with prednisone was helpful in the prevention of bleeding. The patients' responses to rituximab treatment suggest that multiple immunological mechanisms are involved in ITP pathogenesis and that the use of a combination therapy with rituximab according to the different patient conditions is necessary. PMID:23788996

Ling, Yun; Qian, Xinyu; Cao, Xiangshan



Ticlopidine- and clopidogrel-associated thrombotic thrombocytopenic purpura (TTP): review of clinical, laboratory, epidemiological, and pharmacovigilance findings (1989-2008).  


Thrombotic thrombocytopenic purpura (TTP) is a fulminant disease characterized by platelet aggregates, thrombocytopenia, renal insufficiency, neurologic changes, and mechanical injury to erythrocytes. Most idiopathic cases of TTP are characterized by a deficiency of ADAMTS13 (a disintegrin and metalloprotease, with thrombospondin-1-like domains) metalloprotease activity. Ironically, use of anti-platelet agents, the thienopyridine derivates clopidogrel and ticlopidine, is associated with drug induced TTP. Data were abstracted from a systematic review of English-language literature for thienopyridine-associated TTP identified in MEDLINE, EMBASE, the public website of the Food and Drug Administration, and abstracts from national scientific conferences from 1991 to April 2008. Ticlopidine and clopidogrel are the two most common drugs associated with TTP in FDA safety databases. Epidemiological studies identify recent initiation of anti-platelet agents as the most common risk factor associated with risks of developing TTP. Laboratory studies indicate that most cases of thienopyridine-associated TTP involve an antibody to ADAMTS13 metalloprotease, present with severe thrombocytopenia, and respond to therapeutic plasma exchange (TPE); a minority of thienopyridine-associated TTP presents with severe renal insufficiency, involves direct endothelial cell damage, and is less responsive to TPE. The evaluation of this potentially fatal drug toxicity can serve as a template for future efforts to comprehensively characterize other severe adverse drug reactions. PMID:19180126

Zakarija, Anaadriana; Kwaan, Hau C; Moake, Joel L; Bandarenko, Nicholas; Pandey, Dilip K; McKoy, June M; Yarnold, Paul R; Raisch, Dennis W; Winters, Jeffrey L; Raife, Thomas J; Cursio, John F; Luu, Thanh Ha; Richey, Elizabeth A; Fisher, Matthew J; Ortel, Thomas L; Tallman, Martin S; Zheng, X Long; Matsumoto, Masanori; Fujimura, Yoshihiro; Bennett, Charles L



Adult chronic idiopathic thrombocytopenic purpura (ITP) is the manifestation of a type-1 polarized immune response  

Microsoft Academic Search

Derangement of cellular immunity is central in the pathophysiology of adult autoimmune\\/idiopathic thrombocytope- nic purpura (ITP). Herein we investi- gated cytokine gene expression in pe- ripheral blood mononuclear cells (PBMCs) of adult chronic ITP patients and attempted to correlate cytokine polarization with the degree of throm- bocytopenia. We used semiquantita- tive reverse-transcriptase-polymerase chain reaction (RT-PCR) to measure the expression of

Fotios P. Panitsas; Maria Theodoropoulou; Alexandra Kouraklis; Marina Karakantza; Georgios L. Theodorou; Nicholas C. Zoumbos; Alice Maniatis; Athanasia Mouzaki


Thrombotic thrombocytopenic purpura secondary to ABO group incompatible blood transfusion in a patient after cardiac surgery  

PubMed Central

The triggers of secondary thrombotic thrombopcytopenic purpura (TTP) include drug toxicity, radiation and high-dose chemotherapy, angioinvasive infections, surgery and acute graft versus host disease. TTP secondary to surgery have been reported in a number of cases. Most of the cases have been occurred after open heart surgery. Extensive endothelial damage is held responsible as the initiating mechanism in postoperative TTP cases. However, there is no report of secondary TTP describing development owing to ABO incompatible blood transfusion. Here, we describe a patient who developed TTP after transfusion of ABO incompatible blood during hospitalization for bypass surgery. We also propose a hypothesis which may account for the possible underlying mechanism.

Solak, Yalcin; Selcuk, Nedim Yilmaz; Gaipov, Abduzhappar; Ucar, Ramazan; Biyik, Zeynep; Acar, Kadir



Thrombotic thrombocytopenic purpura: outcome in 24 patients with renal impairment treated with plasma exchange. Canadian Apheresis Study Group.  


The Canadian Apheresis Study Group recently completed a randomized clinical trial involving 102 patients with thrombotic thrombocytopenic purpura (TTP), in which treatment with plasma infusion and treatment with plasma exchange were compared. Thirty-three other patients were ineligible or refused to be randomly assigned in the trial. Of the 33 patients, 24 were assessed as ineligible because they would be unable to tolerate the fluid input that would occur if they were randomly assigned to receive plasma infusion. All 24 patients had oliguria and elevated creatinine and/or blood urea nitrogen level. These 24 patients were treated with acetylsalicyclic acid, dipyridamole, and plasma exchange according to the standardized protocol defined in the trial. Blood for tests of factors possibly involved in the pathogenesis of TTP was drawn before exchange and at intervals during and after exchange. The mean platelet count before exchange was 35.5 x 10(9) per L. In 12 of the 24 patients, the platelet count reached 150 x 10(9) per L or greater by 7 days after the initiation of plasma exchange. Three patients responded partially, in that their platelet count increased to at least twice that at presentation, but remained below 150 x 10(9) per L. One patient died during the first week. Of the eight other patients who experienced treatment failure at the 7-day assessment point, six subsequently responded, four while continuing to receive plasma exchange and two after plasma exchange had been discontinued. Of the 15 patients who either responded fully or responded partially by the end of the first cycle, all survived.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1412677

Rock, G; Shumak, K; Kelton, J; Blanchette, V S; Buskard, N; Nair, R; Spasoff, R



Infection and eradication of Helicobacter Pylorus affecting etiology and curative effect of idiopathic thrombocytopenic purpura: a META analysis.  


The study was aimed to explore the relationship between infection of Helicobacter Pylorus (H. Pylorus) and etiology of idiopathic thrombocytopenic purpura (ITP) and evaluate whether H. Pylorus eradication can increase platelet count in patients with ITP. The data-bases of cqvip, Wanfang, TsingHua TongFang, CNKI and PubMed were searched, inclusion and exclusion criteria and heterogeneity test were determined. The studies of H. Pylorus infection and ITP were investigated with fixed effect mode Meta-analysis. Relationship between H. Pylorus infection and etiology of ITP, H. Pylorus eradication and curative effect of ITP were comprehensively and quantitatively evaluated. OR > 1 indicated that factor of exposure was the risk factor of disease; OR < 1 suggested that factor of exposure was the protective factor of disease; OR = 1 revealed that there were no correlation between factor of exposure and diseases. 95%CI was the confidence interval of total OR. The results showed that a total of 211 cases and 210 controls from 5 studies was included to evaluate the exposure of H. Pylorus between ITP patients and controls, the pooled OR was 1.73 (95%CI = 1.12 - 2.67); a total of 458 cases and 305 controls from 13 studies was included to evaluate the relationship between H. Pylorus eradication and curative effect of ITP, the pooled OR was 6.53 (95%CI = 4.44 - 9.61). It is concluded that H. Pylorus infection plays a role in the etiology of ITP. Eradication of H. Pylorus increases platelet count in patients with ITP. H. Pylorus eradication can be used as the first line measure to treat H. Pylorus-positive ITP. PMID:22040983

Yu, Teng; Wu, Dong; Zhao, Xiao-Ying



The Child With Immune Thrombocytopenic Purpura: Is Pharmacotherapy or Watchful Waiting the Best Initial Management? A Panel Discussion From the 2002 Meeting of the American Society of Pediatric Hematology\\/Oncology  

Microsoft Academic Search

The initial management of immune thrombocytopenic purpura is a topic of debate among pediatric hematologists. The de- cision whether to start a patient on pharmacotherapy or to employ an approach of watchful waiting and patient education is problematic for this group of physicians. A wide variety of research studies and re- view articles have been published on either side of

Paula Bolton-Maggs; Michael D. Tarantino; George R. Buchanan; James B. Bussel; James N. George


Role of ADAMTS13 in the management of thrombotic microangiopathies including thrombotic thrombocytopenic purpura (TTP).  


The clinical presentation of thrombotic thrombocytopenia purpura (TTP) and other thrombotic microangiopathies (TMAs) can often be similar. The role of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) in diagnosing TTP is accepted by most researchers but continues to be debated in a few studies. We report the experience of our single-centre academic institution, where ADAMTS13 is used to diagnose TTP and guide plasma exchange (PLEX). Patients presenting to our institution with thrombotic microangiopathy (60 patients) between January 2006 and December 2012 were divided into two groups based on ADAMTS13 activity and clinical history. Patients with ADAMTS13 activity <10% were included in the TTP (n = 30) cohort while patients with activity >11% were classified as 'other microangiopathies' (TMA, n = 30). PLEX was only initiated in patients with a high likelihood of TTP and discontinued when the baseline ADAMTS13 activity was >11%. Patients with severe ADAMTS13 deficiency (TTP group) showed significant presenting differences: lower platelet counts, less renal dysfunction, higher presence of neurological abnormalities, and greater haemolysis markers as compared to non-deficient patients (TMA group). Most importantly, patients without severe ADAMTS13 deficiency were safely managed without increased mortality despite receiving no PLEX or discontinuing PLEX after a short course (upon availability of ADAMTS13 results). In conclusion, ADAMTS13 can be used to diagnose TTP and guide appropriate PLEX therapy. PMID:24111495

Shah, Neil; Rutherford, Cynthia; Matevosyan, Karen; Shen, Yu-Min; Sarode, Ravi



Successful treatment of sepsis-induced disseminated intravascular coagulation in a patient with idiopathic thrombocytopenic purpura using recombinant human soluble thrombomodulin.  


Disseminated intravascular coagulation (DIC) may complicate a variety of disorders that contribute to mortality, particularly those related to bleeding. It is therefore very difficult to manage DIC in patients with known bleeding disorders. We treated a 62-year-old woman with idiopathic thrombocytopenic purpura (ITP) complicated with sepsis-induced DIC. She had been diagnosed with ITP 8 months prior to admission. Laboratory tests showed an elevation of d-dimer and endotoxin, while pyelonephritis was shown by abdominal computed tomography. Escherichia coli was detected by blood culture. Based on these findings, the patient was diagnosed with sepsis-induced DIC due to urinary tract infection. Thrombocytopenia was refractory despite the use of antibiotics and platelet transfusion, but it was promptly improved in response to recombinant human soluble thrombomodulin (rTM). We suggest that rTM provides a new therapeutic strategy for DIC patients with high hemorrhagic risk. PMID:21240494

Koga, Tomohiro; Inoue, Daisuke; Okada, Akitomo; Aramaki, Toshiyuki; Yamasaki, Satoshi; Nakashima, Munetoshi; Kawakami, Atsushi; Eguchi, Katsumi



Von Willebrand factor-cleaving protease (ADAMTS13) in thrombocytopenic disorders: a severely deficient activity is specific for thrombotic thrombocytopenic purpura  

Microsoft Academic Search

A severe deficiency in von Willebrand factor-cleaving protease (ADAMTS13) ac- tivity (< 5% that in normal plasma) has been observed in most patients with a diagnosis of thrombotic thrombocytope- nic purpura (TTP) but not in those with a diagnosis of hemolytic uremic syndrome. However, ADAMTS13 deficiency has been claimed not to be specific for TTP, since it was observed in

Valentina Bianchi; Rodolfo Robles; Lorenzo Alberio; Miha Furlan; Bernhard Lammle



Expression patterns of Th1 and Th2 cytokine genes in childhood idiopathic thrombocytopenic purpura (ITP) at presentation and their modulation by intravenous immunoglobulin G (IVIg) treatment: their role in prognosis  

Microsoft Academic Search

Childhood idiopathic thrombocytopenic purpura (ITP) resolves usually after the first episode, although it may recur, and in 10% to 20% of patients develops into a chronic disorder. Evidence of the immuno- regulatory role of Th1\\/Th2 responses in autoimmune diseases prompted us to perform a prospective study of Th1\\/Th2 gene expression profiles and transform- ing growth factor (TGF-) plasma levels in

Athanasia Mouzaki; Maria Theodoropoulou; Ioannis Gianakopoulos; Vassiliki Vlaha; Maria-Christina Kyrtsonis; Alice Maniatis



Autoimmune Thrombocytopenic Purpura (\\  

Microsoft Academic Search

cytic leukemia is usually due to involvement of the bone marrow by the primary disease.?4 As such, it represents a serious complicaticn of the terminal phase of leukemia in which the bone marrow is crowded with proliferating or invading lymphocytes, and megakaryocytes are lacking. Involvement oi the spleen with resultant hypersplenism has also been cited as a possible mecha- nism




Idiopathic Thrombocytopenic Purpura (ITP)  


... include fever, headache, nausea and vomiting, low blood pressure, hair loss, and dizziness. H. pylori treatment. Some people with ITP are also infected with Helicobacter pylori, the same bacteria that cause most peptic ulcers. Eliminating the bacteria has helped increase platelet count ...


Ultrastructural study shows morphologic features of apoptosis and para-apoptosis in megakaryocytes from patients with idiopathic thrombocytopenic purpura  

Microsoft Academic Search

To investigate whether altered megakaryo- cyte morphology contributes to reduced platelet production in idiopathic thrombo- cytopenic purpura (ITP), ultrastructural analysis of megakaryocytes was per- formed in 11 ITP patients. Ultrastructural abnormalities compatible with (para-)apo- ptosis were present in 78% 14% of ITP megakaryocytes, which could be reversed by in vivo treatment with prednisone and intravenous immunoglobulin. Immunohis- tochemistry of bone

Ewout J. Houwerzijl; Nel R. Blom; Johannes J. L. van der Want; Mariet T. Esselink; Jan J. Koornstra; Jan W. Smit; Henk Louwes; Edo Vellenga; Joost Th; M. de Wolf


Ticlopidine-, clopidogrel-, and prasugrel-associated thrombotic thrombocytopenic purpura: a 20-year review from the Southern Network on Adverse Reactions (SONAR).  


Thienopyridine-derivatives (ticlopidine, clopidogrel, and prasugrel) are the primary antiplatelet agents. Thrombotic thrombocytopenic purpura (TTP) is a rare drug-associated syndrome, with the thienopyridines being the most common drugs implicated in this syndrome. We reviewed 20 years of information on clinical, epidemiologic, and laboratory findings for thienopyridine-associated TTP. Four, 11, and 11 cases of thienopyridine-associated TTP were reported in the first year of marketing of ticlopidine (1989), clopidogrel (1998), and prasugrel (2010), respectively. As of 2011, the FDA received reports of 97 ticlopidine-, 197 clopidogrel-, and 14 prasugrel-associated TTP cases. Severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was present in 80% and antibodies to 100% of these TTP patients on ticlopidine, 0% of the patients with clopidogrel-associated TTP (p < 0.05), and an unknown percentage of patients with prasugrel-associated TTP. TTP is associated with use of each of the three thienopyridines, although the mechanistic pathways may differ. PMID:23111862

Jacob, Sony; Dunn, Brianne L; Qureshi, Zaina P; Bandarenko, Nicholas; Kwaan, Hau C; Pandey, Dilip K; McKoy, June M; Barnato, Sara E; Winters, Jeffrey L; Cursio, John F; Weiss, Ivy; Raife, Thomas J; Carey, Patricia M; Sarode, Ravindra; Kiss, Joseph E; Danielson, Constance; Ortel, Thomas L; Clark, William F; Rock, Gail; Matsumoto, Masanori; Fujimura, Yoshihiro; Zheng, X Long; Chen, Hao; Chen, Fei; Armstrong, John M; Raisch, Dennis W; Bennett, Charles L



Low-dose autologous in vitro opsonized erythrocytes. Radioimmune method and autologous opsonized erythrocytes for refractory autoimmune thrombocytopenic purpura in adults  

SciTech Connect

Adult patients with chronic autoimmune thrombocytopenic purpura (ATP), which proved refractory to various treatments, received a single dose of autologous in vitro opsonized erythrocytes with 100 micrograms of anti-D IgG. In 1983, 30 of these patients were treated with autologous erythrocytes that had been opsonized and labeled with 25 mCi (740 MBq) of technetium Tc 99m; this treatment was designated as the radioimmune method. Favorable responses were noted in 36% of patients so treated. In 1985, another group of 16 patients with refractory ATP received therapy with autologous opsonized erythrocytes (AOPE) and 55% of these patients showed favorable responses. Five (17%) of the patients treated using the radioimmune method attained a complete, long-term (greater than 35 months) remission of their ATP, and five (31%) of the patients treated using AOPE remained in complete remission over 270 days after cessation of therapy. Major complications were not seen. We concluded that the interaction of macrophages with low-dose AOPE is a successful therapeutic approach in ATP refractory to standard treatment.

Ambriz, R.; Munoz, R.; Pizzuto, J.; Quintanar, E.; Morales, M.; Aviles, A.



Micromegakaryocytes in a patient with partial deletion of the long arm of chromosome 11 [del(11)(q24.2qter)] and chronic thrombocytopenic purpura  

SciTech Connect

Thrombocytopenia or pancytopenia is frequently reported in patients with partial 11q deletion but there are no reports on bone marrow morphology of these patients. We report on a patient with partial deletion of the long arm of chromosome 11 [del(11)(q24.2qter)] and its classical clinical manifestations including chronic thrombocytopenic purpura in whom micromegakaryocytes were found in the bone marrow aspirate. This is the first report of the presence of micromegakaryocytes in the bone marrow of a patient with 11q deletion. Accurate examination of the bone marrow of other patients with the 11q deletion may clarify whether the observation of micromegakaryocytes is common in these patients. Micromegakaryocytes may indicate a defect of development. Two genes for two DNA binding proteins that are likely to be involved in hematopoiesis map in the 11q region: Ets-1, that maps to 11q24, close to D11S912, and the nuclear-factor-related-kB gene that maps to 11q24-q25. It is possible that these genes, when present in only one copy, result in thrombocytopenia or pancytopenia as observed in this patient. 23 refs., 2 figs., 1 tab.

Gangarossa, S.; Mattina, T.; Romano, V.; Milana, G.; Mollica, F.; Schiliro, G. [Universita di Catania (Italy)



Platelet turnover and kinetics in immune thrombocytopenic purpura: results with autologous 111In-labeled platelets and homologous 51Cr-labeled platelets differ  

SciTech Connect

Mean platelet survival and turnover were simultaneously determined with autologous 111In-labeled platelets (111In-AP) and homologous 51Cr-labeled platelets (51Cr-HP) in ten patients with chronic immune thrombocytopenic purpura (ITP). In vivo redistribution of the 111In-AP was quantitated with a scintillation camera and computer-assisted image analysis. The patients were divided into two groups: those with splenic platelet sequestration (spleen-liver 111In activity ratio greater than 1.4), and those with diffuse sequestration in the reticuloendothelial system. The latter patients had more severe ITP reflected by pronounced thrombocytopenia, decreased platelet turnover, and prominent early hepatic platelet sequestration. Mean platelet life span estimated with 51Cr-HP was consistently shorter than that of 111In-AP. Platelet turnover determined with 51Cr-HP was thus over-estimated. The difference in results with the two isotope labels was apparently due to greater in vivo elution of 51Cr. Although the limitations of the techniques should be taken into account, these findings indicate that platelet turnover is not always normal or increased in ITP, but is low in severe disease. We suggest that this may be ascribed to damage to megakaryocytes by antiplatelet antibody. The physical characteristics in 111In clearly make this radionuclide superior to 51Cr for the study of platelet kinetics in ITP.

Heyns A du, P.; Badenhorst, P.N.; Loetter, M.G.P.; Pieters, H.; Wessels, P.; Kotze, H.F.



Ticlopidine-, Clopidogrel-, and Prasugrel-Associated Thrombotic Thrombocytopenic Purpura: A 20-Year Review from the Southern Network on Adverse Reactions (SONAR)  

PubMed Central

Thienopyridine-derivatives (ticlopidine, clopidogrel, and prasugrel) are the primary antiplatelet agents. Thrombotic thrombocytopenic purpura (TTP) is a rare drug-associated syndrome, with the thienopyridines being the most common drugs implicated in this syndrome. We reviewed 20 years of information on clinical, epidemiologic, and laboratory findings for thienopyridine-associated TTP. Four, 11, and 11 cases of thienopyridine-associated TTP were reported in the first year of marketing of ticlopidine (1989), clopidogrel (1998), and prasugrel (2010), respectively. As of 2011, the FDA received reports of 97 ticlopidine-, 197 clopidogrel-, and 14 prasugrel-associated TTP cases. Severe deficiency of ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was present in 80% and antibodies to 100% of these TTP patients on ticlopidine, 0% of the patients with clopidogrel-associated TTP (p < 0.05), and an unknown percentage of patients with prasugrel-associated TTP. TTP is associated with use of each of the three thienopyridines, although the mechanistic pathways may differ.

Jacob, Sony; Dunn, Brianne L.; Qureshi, Zaina P.; Bandarenko, Nicholas; Kwaan, Hau C.; Pandey, Dilip K.; McKoy, June M.; Barnato, Sara E.; Winters, Jeffrey L.; Cursio, John F.; Weiss, Ivy; Raife, Thomas J.; Carey, Patricia M.; Sarode, Ravindra; Kiss, Joseph E.; Danielson, Constance; Ortel, Thomas L.; Clark, William F.; Rock, Gail; Matsumoto, Masanori; Fujimura, Yoshihiro; Zheng, X. Long; Chen, Hao; Chen, Fei; Armstrong, John M.; Raisch, Dennis W.; Bennett, Charles L.



Efficacy and Safety Profile of Solvent/Detergent Plasma in the Treatment of Acute Thrombotic Thrombocytopenic Purpura: A Single-Center Experience  

PubMed Central

Summary Background Thrombotic thrombocytopenic purpura (TTP) is a rare clinical disorder which was associated with poor prognosis for a long time. The outcome has been improved by the consistent introduction of thera-peutic plasma exchange (TPE) as standard treatment of TTP. Patients and Methods We describe our experience in the use of solvent/detergent-treated plasma (SDP) for TPE in TTP. We retrospectively analyzed acute TTP epi-sodes in 8 patients (mean age = 27 years, range 18–44 years) treated with TPE using SDP with regard to tolerability and efficacy. Results All 8 patients were positive for anti-ADAMTS-13 antibody. Seven out of 8 had a se-vere ADAMTS-13 deficiency. All patients responded rapidly to SDP TPE with an increase in platelet count to above 150 × 109/l. Hemolytic anemia disappeared over the treatment period. Approximately 2,000 l SDP were used for more than 500 treatments. Treatment with SDP was well tolerated; none of the patients experienced an adverse drug reaction after exposure to SDP. No major complications occurred even after multiple TPE. Conclusion Our investigations suggest that TPE using SDP as replacement fluid is an effective treatment for TTP. The data described also indicate that SDP might offer the benefit of reducing adverse drug reactions.

Edel, Elvira; Al-Ali, Haifa Kathrin; Seeger, Susanne; Kauschat, Dorte; Matthes, Gert



ADAMTS13 unbound to larger von Willebrand factor multimers in cryosupernatant: implications for selection of plasma preparations for thrombotic thrombocytopenic purpura treatment.  


BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is characterized by deficient ADAMTS13 activity. Treatment involves plasma exchange (PE). Both fresh-frozen plasma (FFP) and cryosupernatant (CSP) are used, but it remains to be determined which is more effective. STUDY DESIGN AND METHODS: To analyze the interaction between von Willebrand factor (VWF) and ADAMTS13, we used large-pore isoelectric focusing (IEF) analysis followed by detection with anti-ADAMTS13 monoclonal antibody. FFP, CSP, cryoprecipitate (CP), and purified ADAMTS13 were analyzed for their effects on high shear stress-induced platelet aggregation (H-SIPA). RESULTS: IEF analysis of normal plasma revealed three groups of ADAMTS13 bands with pI of 4.9 to 5.6, 5.8 to 6.7, and 7.0 or 7.5. Two band groups (pI 4.9-5.6 and 5.8-6.7) were found in plasma of a patient with Type 3 von Willebrand disease, in which VWF is absent, whereas no bands were found in plasma of a patient with congenital ADAMTS13 deficiency. Mixing these plasmas generated the bands at pI 7.0 or 7.5, representing the VWF-ADAMTS13 complex; these bands were absent in CSP. FFP and purified ADAMTS13 down regulated H-SIPA in a dose-dependent manner. However, CP did not inhibit H-SIPA in the initial phase, and the degree of inhibition at the endpoint was almost indistinguishable from those of the other two plasma products. CONCLUSION: Both plasma products (FFP and CSP) are effective for PE in TTP patients. However, CSP may be more favorable, because it has lower levels of VWF and almost normal ADAMTS13 activity, but lower levels of ADAMTS13 in complex with larger VWF multimers. PMID:23560518

Hori, Yuji; Hayakawa, Masaki; Isonishi, Ayami; Soejima, Kenji; Matsumoto, Masanori; Fujimura, Yoshihiro



High prevalence of infectious events in thrombotic thrombocytopenic purpura and genetic relationship with toll-like receptor 9 polymorphisms: experience of the French Thrombotic Microangiopathies Reference Center.  


BACKGROUND: Infectious events have been reported as major environmental triggers of thrombotic thrombocytopenic purpura (TTP). We detail here the potential association between infections and TTP. STUDY DESIGN AND METHODS: We recruited randomly and prospectively a cohort of 280 consecutive TTP patients during a 9-year period. Features of infection were systematically recorded. RESULTS: Features consistent with an infectious event were observed in 114 patients (41%) at time of TTP diagnosis. Infectious agents were documented in 34 cases and were mainly Gram-negative bacilli. At time of diagnosis infected patients more frequently had fever (p?

Morgand, Marjolaine; Buffet, Marc; Busson, Marc; Loiseau, Pascale; Malot, Sandrine; Amokrane, Kahina; Fortier, Catherine; London, Jonathan; Bonmarchand, Guy; Wynckel, Alain; Provôt, François; Poullin, Pascale; Vanhille, Philippe; Presne, Claire; Bordessoule, Dominique; Girault, Stéphane; Delmas, Yahsou; Hamidou, Mohamed; Mousson, Christiane; Vigneau, Cécile; Lautrette, Alexandre; Pourrat, Jacques; Galicier, Lionel; Azoulay, Elie; Pène, Frédéric; Mira, Jean-Paul; Rondeau, Eric; Ojeda-Uribe, Mario; Charron, Dominique; Maury, Eric; Guidet, Bertrand; Veyradier, Agnès; Tamouza, Ryad; Coppo, Paul



Management of chronic immune thrombocytopenic purpura: targeting insufficient megakaryopoiesis as a novel therapeutic principle  

PubMed Central

Traditionally, anti-platelet autoantibodies accelerating platelet clearance from the peripheral circulation have been recognized as the primary pathopysiological mechanism in chronic immune thrombocytopenia (ITP). Recently, increasing evidence supports the co-existence of insufficient megakaryopoiesis. Inadequate low thrombopoietin (TPO) levels are associated with insufficient proliferation and differentiation of megakaryocytes, decreased proplatelet formation, and subsequent platelet release. Recently two novel activators of TPO receptors have been made available: romiplostim and eltrombopag. In several phase III studies, both agents demonstrated increase of platelet counts in about 80% of chronic ITP patients within 2 to 3 weeks. These agents substantially broaden the therapeutic options for patients with chronic ITP although long-term results are still pending. This review will provide an update on the current conception of underlying mechanisms in ITP and novel, pathophysiologically based treatment options.

Rank, Andreas; Weigert, Oliver; Ostermann, Helmut



Immune Thrombocytopenic Purpura of Childhood  

Microsoft Academic Search

Immune mediated thrombocytopenia (ITP) is a com- mon manifestation of autoimmune disease in children. Although patients often present with bruises, pete- chiae, and some mucosal bleeding, the incidence of life-threatening hemorrhage is rare (0.2-0.9%) but can be fatal when presenting in vital organs. A wide range of therapeutic regimens are currently in use, including observation alone, as the majority of

Diane J. Nugent


The diagnostic dilemma of thrombotic thrombocytopenic purpura\\/hemolytic uremic syndrome in the obstetric triage and emergency department: lessons from 4 tertiary hospitals  

Microsoft Academic Search

OBJECTIVE: We report a series of occurrences of thrombotic thrombo- cytopenic purpura (TTP)\\/hemolytic uremic syndrome (HUS) in preg- nancy that emphasizes early diagnosis. STUDY DESIGN: Fourteen pregnancies with TTP (n 12) or HUS (n 2) were studied. Analysis focused on clinical and laboratory find- ings on examination, initial diagnosis, and treatment. RESULTS: There were 14 pregnancies in 12 patients; 2

Caroline L. Stella; John Dacus; Edwin Guzman; Pushpinder Dhillon; Kristin Coppage; Helen How; Baha Sibai



Idiopathic thrombocytopenic purpura: Pathophysiology and management  

Microsoft Academic Search

Our understanding of the pathophysiology of ITP owes to pioneering work of W J Harrington in 1951, delineating the immunologic\\u000a nature of platelet destruction. In ITP, antibody-coated platelets are destroyed by macrophages of RES. However, other mechanisms\\u000a are also implicated: C-mediated platelet lysis and newly described C-independent peroxide injury. Both induce platelet fragmentation\\u000a and lysis, generating procoagulant platelet microparticles (PMP).

Yeon S. Ahn; Lawrence L Horstman



Psychogenic purpura  

PubMed Central

Psychogenic purpura, also known as Gardner-Diamond syndrome, is a rare, distinctive, localized cutaneous reaction pattern mostly affecting psychologically disturbed adult women. Repeated crops of tender, ill-defined ecchymotic lesions on the extremities and external bleeding from other sites characterize the condition. We report here a case of psychogenic purpura because of the rarity of the condition and to emphasize the importance of consideration of this entity during evaluation of a patient with recurrent ecchymoses. Early diagnosis of this condition will not only minimize the cost of the medical evaluation but will also benefit the patient.

Sarkar, Sharmila; Ghosh, Sudip Kumar; Bandyopadhyay, Debabrata; Nath, Saswati



Cryofibrinogenemic purpura.  


A 50-year-old male patient had three episodes of acrally located purpura within 12 years without any other symptoms. The first two episodes which lasted several months coincided with the intake of beta-blockers; the third episode developed after a respiratory infection. A cryofibrinogenemia was found without any evidence of an underlying primary disease, especially not of a neoplasm. The clinical, histological, immunohistological, and electron microscopical findings, as well as the results obtained by intravital fluorescence videomicroscopy are presented. PMID:3310920

Brüngger, A; Brülisauer, M; Mitsuhashi, Y; Schneider, B V; Bollinger, A; Schnyder, U W



Bilateral nephrectomy for the treatment of refractory lupus nephritis with features overlapping with thrombotic microangiopathy resembling thrombotic thrombocytopenia purpura.  


We report a patient with a diagnosis of systemic lupus erythematosus who concurrently developed a syndrome of thrombotic microangiopathy that resembled thrombotic thrombocytopenic purpura. The patient underwent plasma exchange and immunosuppressive therapy for months before clinical improvement was finally achieved through bilateral nephrectomy. Ultimately, our patient died of disseminated aspergillosis from prolonged immunosuppression. We believe that recognition of bilateral nephrectomy as a potential treatment earlier in her course would have spared her this unfortunate demise. We hope that this review of current literature will help the reader to consider bilateral nephrectomy in patients with refractory systemic lupus erythematosus with clinical overlap of thrombotic microangiopathy resembling thrombotic thrombocytopenic purpura. PMID:22647858

Mai, Tuan Van; Tse, Kevin; Gehr, Marc Kenneth; George, James; Baranski, Joel; Xavier, Marin



Henoch-Schonlein purpura  


Henoch-Schonlein purpura is a disease that involves purple spots on the skin, joint pain, gastrointestinal problems, ... Abdominal pain Joint pain Purple spots on the skin ( purpura ), ... legs, and elbows Bloody stools Hives or angioedema Nausea Diarrhea ...


Safety and Efficacy Study of Romiplostim to Treat ITP in Pediatric Subjects

Idiopathic Thrombocytopenic Purpura; Thrombocytopenia; Thrombocytopenia in Pediatric Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP); Thrombocytopenia in Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP); Thrombocytopenic Purpura



Platelet-associated CD154 in immune thrombocytopenic purpura  

Microsoft Academic Search

and its messenger RNA were also present in increased amounts in the megakaryo- cytes of patients with ITP. We found that platelet-associated CD154 is competent to induce the CD40-dependent prolifera- tion of B lymphocytes, and we observed an in vitro CD154-dependent production of antibodies to the GPIIb\\/IIIa complex (integrin IIb3) when platelets and pe- ripheral blood B lymphocytes from ITP

Anne Solanilla; Jean-Max Pasquet; Jean-Francois Viallard; Cecile Contin; Christophe Grosset; Julie Dechanet-Merville; Maryse Dupouy; Marc Landry; Francis Belloc; Paquita Nurden; Patrick Blanco; Jean-Francois Moreau; Jean-Luc Pellegrin; Alan T. Nurden; Jean Ripoche



Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura  

Microsoft Academic Search

Von Willebrand factor (vWF), a glycoprotein critical for supporting platelet adhesion and aggregation at sites of vessel injury, exists in the plasma as a series of multimers. Recent studies have shown that a metalloprotease cleaves endothelial vWF to a series of multimers. A deficiency of the protease activity due to autoimmune IgG inhibitors or genetic mutations is associated with thrombotic

Han-Mou Tsai



Erythropoietin in thrombotic thrombocytopenic purpura and acute renal failure  

Microsoft Academic Search

In this study, erythropoietin serum levels were serially determined in eight patients with acute renal failure to get a lead on the etiology of anemia in acute renal failure and to address the relationship between erythropoietin synthesis and renal excretory performance. Erythropoietin serum levels rapidly decreased after onset of acute renal failure to values of 12.8 ± 10.3 mU\\/ml compared

S. Heidenreich; K.-H. Rahn; W. Zidek



Thrombosis warning in children suffering from henoch-schonlein purpura.  


Henoch-Schonlein Purpura (HSP) is one of the most common types of vasculitis in children. The characteristic clinical manifestations include non-thrombocytopenic purpura, arthritis or arthralgia, abdominal pain, gastrointestinal hemorrhage and renal abnormalities. Thrombosis has been reported as, a rare complication of HSP. We present the case of a 14-year-old boy who was diagnosed with HSP and suspected superior mesenteric vein thrombosis. We reviewed the relevant literature and found eight similar reported cases. HSP is associated with thrombosis and HSP itself and some risk factors may result in thrombosis. We suggest that physicians should monitor patients with HSP who are at a higher risk of developing thrombosis more closely. PMID:24082216

Li, Luan; Zhang, Jingwen; Zhang, Yunying; Ji, Hong



Thrombosis Warning in Children Suffering from Henoch-Schonlein Purpura  

PubMed Central

Henoch-Schonlein Purpura (HSP) is one of the most common types of vasculitis in children. The characteristic clinical manifestations include non-thrombocytopenic purpura, arthritis or arthralgia, abdominal pain, gastrointestinal hemorrhage and renal abnormalities. Thrombosis has been reported as, a rare complication of HSP. We present the case of a 14-year-old boy who was diagnosed with HSP and suspected superior mesenteric vein thrombosis. We reviewed the relevant literature and found eight similar reported cases. HSP is associated with thrombosis and HSP itself and some risk factors may result in thrombosis. We suggest that physicians should monitor patients with HSP who are at a higher risk of developing thrombosis more closely.

Li, Luan; Zhang, Jingwen; Zhang, Yunying; Ji, Hong



Henoch-Schonlein Purpura  


... microscopic hallmark of HSP is the deposition of IgA (an antibody found in blood, saliva, tears, etc.) ... skin biopsy and the consequent failure to detect IgA. Treatment and Course of Henoch-Schönlein Purpura NSAIDs ...


Anti-Human Immunodeficiency Virus Type 1 Antibody Complexes on Platelets of Seropositive Thrombocytopenic Homosexuals and Narcotic Addicts  

Microsoft Academic Search

Patients with human immunodeficiency virus type 1 (HIV-1) infection develop an immunologic thrombocytopenic purpura associated with markedly elevated platelet IgG, IgM, and C3C4 as well as serum immune complexes determined by the polyethylene glycol (PEG) method. Analysis of their serum PEG-precipitable immune complexes as well as platelet acid eluates revealed the presence of anti-HIV-1 antibody existing as a complex that

S. Karpatkin; M. Nardi; E. T. Lennette; B. Byrne; B. Poiesz



Progressive pigmentary purpura.  


A 58-year-old man presented for evaluation and treatment of non-tender, non-pruritic, annular patches on the right temple and frontal aspect of the scalp that reddened with exercise. A biopsy specimen showed a purpuric dermatitis with features of lymphocytic vasculitis; a diagnosis of exercise-induced progressive pigmentary purpura was made. Whereas progressive pigmentary purpura is purported to be caused by exercise, other similar appearing entities are associated with exercise, namely exercise-induced vasculitis (EIV). EIV may be considered as an acute microcirculatory deficiency and thermoregulation decompensation that occurs after episodes of exhaustive major muscular activity or after unusual or excessive exercise. The combination of age greater than 50 years, heat, and prolonged exercise are the most potent contributing factors. This is the first report of exercise-induced progressive pigmentary purpura. PMID:22031640

Brauer, Jeremy A; Mundi, Jyoti; Chu, Julie; Patel, Rishi; Meehan, Shane; Greenspan, Alan H; Stein, Jennifer



Novel developments in thrombotic microangiopathies: is there a common link between hemolytic uremic syndrome and thrombotic thrombocytic purpura?  

Microsoft Academic Search

Thrombotic microangiopathies (TMA) represent a spectrum of related disorders associated with newly formed thrombi that block\\u000a perfusion and thus affect the function of either renal or neurological organs and tissue. Recent years have seen a dramatic\\u000a development in the field of TMA and for the two major forms hemolytic uremic syndrome (HUS) and thrombocytopenic purpura (TTP),\\u000a new genetic causes and

Peter F. Zipfel; Gunter Wolf; Ulrike John; Karim Kentouche; Christine Skerka


Hypergammaglobulinemic purpura of Waldenström.  


We report a case of a 33-year-old-woman with a one-year history of bilateral lower extremity vasculitis and laboratory evidence of hypergammaglobulinemia with otherwise unremarkable routine laboratory and rheumatologic studies. Her clinical picture, together with histopathologic evidence of leukocytoclastic vasculitis, favor a diagnosis of hypergammaglobulinemic purpura of Waldenström. PMID:23286792

Lewin, Jesse M; Hunt, Raegan; Fischer, Max; Kamino, Hidelo; Franks, Andrew G



Systemic lupus erythematosus and thrombotic thrombocytopenia purpura: A refractory case without lupus activity.  


The association between systemic lupus erythematosus (SLE) and thrombotic thrombocytopenic purpura (TTP) has been infrequently reported. Usually, patients with TTP have more SLE activity and frequent renal involvement. Here we present a case of TTP associated to low-activity SLE. The absence of renal and major organ involvement increased the difficulty in making the initial diagnosis. ADAMTS13 activity in plasma in this patient was very low, as seen in other similar cases. The evolution of the patient was poor, needing plasma exchanges and immunosuppressive therapy, including the use of rituximab. PMID:23473755

Garcia Boyero, Raimundo; Mas Esteve, Eva; Mas Esteve, Maria; Millá Perseguer, M Magdalena; Marco Buades, Josefa; Beltran Fabregat, Juan; Cañigral Ferrando, Guillermo; Belmonte Serrano, Miguel Angel



The B-cell compartment as the selective target for the treatment of immune thrombocytopenias  

Microsoft Academic Search

utoimmune thrombocytopenias represent a diverse group of diseases associated with the production of antibodies reacting against platelet antigens. They may develop as isolated thrombocytopenias, of unknown etiopathogenesis, and in that case they are called idio- pathic thrombocytopenic purpura (ITP). In other cases, autoimmune thrombocytopenias develop during a lym- phoproliferative disorder, more frequently chronic lym- phocytic leukemia (CLL), or a systemic



Thrombotic Microangiopathy with Targeted Cancer Agents  

PubMed Central

Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are clinically similar disorders characterized by microvascular thrombosis, hemolysis, thrombocytopenia, and end organ damage. Although they may present with overlapping symptoms, multiple etiologies have been proposed for these thrombotic microangiopathies (TMAs). Chemotherapy-induced TMA has been described with the use of mitomycin, gemcitabine, and others and has a poor prognosis. Recently, reports of TMA associated with targeted cancer agents have surfaced in the literature. We discuss the clinical presentation, outcome, and etiology of TMA reported with the use of immunotoxins, monoclonal antibodies, and tyrosine kinase inhibitors. A search of PubMed and meeting abstracts was conducted for cases of TMA with the use of targeted cancer agents. The defining symptoms, laboratory values, time to onset, and patient outcomes were compiled. Consistent definitions of TMA and grading of severity in these cases are lacking. However, presentation of TMA in these cases revealed the importance of monitoring for renal toxicity, hemolysis, and thrombocytopenia. Patient outcomes appear to differ from those seen in cases of chemotherapy-induced TMA and may reflect a different underlying etiology. Little is known about the pathogenesis of TMA with targeted cancer agents. In contrast to chemotherapy-induced TMA, partial to full reversibility may be a common outcome. However, further research is warranted into optimal management of patients diagnosed with TMA following treatment with targeted agents.

Blake-Haskins, John A.; Lechleider, Robert J.; Kreitman, Robert J.



Anagrelide, a selective thrombocytopenic agent.  


The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of anagrelide are reviewed. Anagrelide is a selective thrombocytopenic agent with FDA-approved labeling for the treatment of essential thrombocythemia. Clinical trials have shown that the drug may have a role in the treatment of other chronic myeloproliferative disorders, including polycythemia vera, chronic myeloid leukemia, and agnogenic myeloid metaplasia. The mechanism by which anagrelide reduces platelet count is not yet clear. The current hypothesis is that anagrelide affects the late (postmitotic) phases of megakaryocyte development. Anagrelide has a large volume of distribution and is extensively metabolized; less than 1% is recovered unchanged in the urine. Plasma half-life after a 0.5-mg dose is 1.3 hours. Anagrelide's efficacy and safety have been evaluated in open-label, noncomparative trials, in which the response rate was 60-93%. Adverse effects include headache, diarrhea, edema, palpitations, and abdominal pain. Patients with renal or hepatic dysfunction need to be closely monitored for signs of toxicity. The recommended starting dosage is 0.5 mg four times a day or 1 mg twice a day, with dosage adjustment to the lowest effective amount required to reduce and maintain platelet count below 600 x 10(9)/L. The wholesale acquisition price for 0.5-mg capsules is $350 per 100. Whether anagrelide will replace hydroxyurea as first-line therapy in some or all patients remains to be determined. Anagrelide is effective in the treatment of essential thrombocythemia and may have a role in the treatment of other myeloproliferative disorders. PMID:9784784

Oertel, M D



Possible mechanisms of intravenous immunoglobulin treatment in childhood idiopathic thrombocytopenic purpura (ITP)  

Microsoft Academic Search

Childhood ITP is an acquired condition which often represents a sequela of infection. It is characterized by marked thrombocytopenia despite an increased platelet production in the bone marrow, resulting from a drastically shortened lifespan of platelets. In most patients an increased amount of platelet-associated IgG is observed. Whereas the disease normally regresses regardless of therapeutic intervention, it lasts for more

Paul Imbach; Thomas W. Jungi



Intravenous immunoglobulin and Anti-D in Idiopathic Thrombocytopenic Purpura (ITP): Mechanisms of Action  

Microsoft Academic Search

& Infusion of large amounts of intrave- nous immunoglobulin (IVIG) or anti-D can reverse the low platelet count in patients with ITP within hours of the initiation of treatment. In some cases, the effects of IVIG appear to far outlast several half-lives of the product. Several mechanisms have been proposed to explain these rapid and long term effects and these

Alan H. Lazarus; John Freedman; John W. Semple



Accessory spleens: Clinical significance with particular reference to the recurrence of idiopathic thrombocytopenic purpura  

Microsoft Academic Search

One of the important stages during splenectomy is the search for accessory spleens. The average frequency of accessory spleens is an estimated 11%. In our own material in 611 patients who had splenectomy in hematological disorders, accessory spleens were found in 110 patients (18%). The surgical anatomy, embryology, and clinical significance of the accessory spleens, with particular reference to the

Witold J. Rudowski



Atypical thrombotic thrombocytopenic purpura in a middle-aged woman who presented with a recurrent stroke.  


An atypical clinical presentation makes TTP diagnosis difficult, which prevents prompt management of TTP. This case highlights the importance of early recognition of TTP in patients with atypical presentations who may not have the expected clinical or laboratory findings. The level of suspicion should be especially high in young and middle-aged patients with strokes or acute coronary syndrome who do not have other risk factors for cardiovascular events. This is particularly so for those patients who have a previous episode of TTP or patients with subtle laboratory abnormalities, which may suggest the potential existence of a thrombotic microangiopathic process. PMID:22641399

Idowu, Modupe; Reddy, Preethi



Eltrombopag - a novel approach for the treatment of chronic immune thrombocytopenic purpura: review and safety considerations  

PubMed Central

Eltrombopag is one of a number of novel agents recently developed for use in the treatment of patients with immune thrombocytopenia (ITP). Rather than preventing destruction of platelets, these agents increase the production of platelets, presumably overwhelming the immune system resulting in normal platelet counts in individuals refractory to or dependent on other therapies. These treatments are well tolerated and in randomized controlled trials show an improvement in platelet counts and a reduction in bleeding in refractory patients. This article summarizes the development of this new class of drug and evaluates the safety and efficacy of eltrombopag in patients with ITP.

Cook, Lucy; Cooper, Nichola



Thrombotic thrombocytopenic purpura associated with everolimus use in a renal transplant patient  

Microsoft Academic Search

Thrombotic microangiopathy (TMA) in renal transplantation (RTX) generally develops during treatment with calcineurin inhibitors.\\u000a We present a RTX case that developed TMA under everolimus treatment. A 40-year-old woman received a kidney allograft from\\u000a her 77-year-old mother. She initially received tacrolimus, mycophenolate mofetil and steroids. She was discharged with a creatinine\\u000a level of 2.2 mg\\/dl after treatment for a cellular rejection attack

Vural Taner Y?lmaz; Hüseyin Koçak; Ali B. Avc?; Ozan Salim; Fevzi F. Ersoy; Gültekin Süleymanlar



Thrombotic thrombocytopenic purpura associated with everolimus use in a renal transplant patient.  


Thrombotic microangiopathy (TMA) in renal transplantation (RTX) generally develops during treatment with calcineurin inhibitors. We present a RTX case that developed TMA under everolimus treatment. A 40-year-old woman received a kidney allograft from her 77-year-old mother. She initially received tacrolimus, mycophenolate mofetil and steroids. She was discharged with a creatinine level of 2.2 mg/dl after treatment for a cellular rejection attack within the first two weeks after transplantation. Later on, tacrolimus was replaced with everolimus. One year later, she presented with fever and increased creatinine level (4 mg/dl), anemia and thrombocytopenia. Her peripheral blood smear revealed signs of microangiopathic hemolysis. Bone marrow examination revealed an increased number of megakaryocytes. We diagnosed the case as TMA and initiated plasma exchange, I.V. pulse steroid treatment and stopped everolimus. This approach improved laboratory and clinic abnormalities. The development of TMA after treatment with everolimus and the exclusion of other possible causes suggested TMA associated with proliferating signal inhibitors (PSIs) in our case. PMID:20495869

Y?lmaz, Vural Taner; Koçak, Hüseyin; Avc?, Ali B; Salim, Ozan; Ersoy, Fevzi F; Süleymanlar, Gültekin



Prognostic factors for positive immune thrombocytopenic purpura outcome after laparoscopic splenectomy  

Microsoft Academic Search

Laparoscopic splenectomy is considered as a second step treatment for ITP patients. The purpose of this study was to determine\\u000a efficiency of laparoscopic splenectomy for ITP patients and to identify the independent prognostic factors that may predict\\u000a the positive outcome. Two hundred and thirty nine patient medical records were analyzed retrospectively. The special questionnaire,\\u000a which included present platelet count, the

Mindaugas Kiudelis; Antanas Mickevicius; Ruta Dambrauskiene; Rolandas Gerbutavicius; Rasa Grini?t?; Dalia Adukauskiene



Thrombotic Thrombocytopenic Purpura: A Thrombotic Disorder Caused by ADAMTS13 Deficiency  

PubMed Central

Synopsis A serious disorder with characteristic microvascular thrombosis involving the brain and other organs, TTP typically presents with thrombocytopenia, hemolysis with schistocytes on blood smears and mental changes or seizures and may rapidly progresses to a fatal end if the patients are not immediately treated with plasma. Recent advances have shown that TTP is caused by deficiency of a circulating, von Willebrand factor cleaving metalloprotease, ADAMTS13. This new knowledge will provide clues to improve the diagnosis and management of this intriguing disease.

Tsai, Han-Mou



Thrombotisch-thrombozytopenische Purpura (Moschcowitz-Syndrom)  

Microsoft Academic Search

Zusammenfassung Hintergrund: Die 1924 erstmals durch Moschcowitz beschriebene thrombotisch-thrombozytopenische Purpura (TTP) stellt ein heterogenes klinisches Syndrom dar, das durch Thrombozytopenie, Coombs-negative hämolytische Anämie, neurologische Ausfälle, Nierenfunktionsstörung und Fieber charakterisiert ist. Die Ätiologie der Erkrankung ist nicht vollständig geklärt. Allerdings ist die Entstehung einer TTP nach verschiedenen viralen und bakteriellen Infektionen, im Rahmen von Autoimmunerkrankungen sowie medikamenteninduziert beschrieben worden. Pathogenese: Pathogenetisch

Jens Chemnitz; Armin Schulz; Volker Diehl; Dietmar Söhngen



[Treatment of thrombotic thrombopenic purpura. Results of a multicenter randomized clinical study].  


A controlled multicentre trial was conducted in France over a period of five years in 40 patients with thrombotic thrombocytopenic purpura (TTP) to try to determine the best treatment of this disease. Patients presenting eligibility criteria were centrally randomized into two therapeutic groups: Group A) daily plasma exchanges with a solution of fresh frozen plasma (15 ml/kg) in albumin (45 ml/kg) versus Group B) daily transfusions of fresh frozen plasma (15 ml/kg), both systematically associated with intravenous antiplatelet therapy. When the treatment was started early after the first symptoms of TTP, there was no significant difference among plasma exchange and plasma transfusion. But the later the treatment was started, the lesser was the initial therapeutic response and the poorer the prognosis. Furthermore, the excessive use of plasma transfusions in initially unresponsive patients could be dangerous, resulting in some cases in irreversible development of the disease. The overall survival rate in groupe A was 85 percent with 80 percent complete remissions and 15 percent deaths, as opposed to a 57 percent survival rate with 52 percent complete remission and 43 percent deaths in groupe B. Thus plasma exchanges with fresh frozen plasma if started early and performed daily in sufficient amounts, appear to be undoubtedly safer than plasma transfusions. PMID:1836595

Henon, P



Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial  

Microsoft Academic Search

Methods In two parallel trials, 63 splenectomised and 62 non-splenectomised patients with ITP and a mean of three platelet counts 30×10?\\/L or less were randomly assigned 2:1 to subcutaneous injections of romiplostim (n=42 in splenectomised study and n=41 in non-splenectomised study) or placebo (n=21 in both studies) every week for 24 weeks. Doses of study drug were adjusted to maintain

David J Kuter; James B Bussel; Roger M Lyons; Vinod Pullarkat; Terry B Gernsheimer; Francis M Senecal; Louis M Aledort; James N George; Craig M Kessler; Miguel A Sanz; Howard A Liebman; Frank T Slovick; J Th M de Wolf; Emmanuelle Bourgeois; Troy H Guthrie; Adrian Newland; Jeffrey S Wasser; Solomon I Hamburg; Carlos Grande; François Lefrère; Alan Eli Lichtin; Michael D Tarantino; Howard R Terebelo; Jean-François Viallard; Francis J Cuevas; Ronald S Go; David H Henry; Robert L Redner; Lawrence Rice; Martin R Schipperus; D Matthew Guo; Janet L Nichol



Quantitative kinetics of In-111 autologous (In-AP) and homologous (Cr-HP) platelets in immune thrombocytopenic purpura (ITP)  

SciTech Connect

Contrary to the accepted view, the authors have found that platelet turnover is not always increased in ITP if the mean platelet survival time (PS) is measured with In-AP. The authors investigated the possible cause of the discrepancy by comparing kinetics of In-AP with those of Cr-HP in 10 patients with ITP. PS was estimated with the multiple hit model. The equilibrium and final in vivo distribution of In-AP was quantitated with the geometrical mean method. The patients could be divided into either those with splenic or diffuse RES platelet destruction. The authors conclude that in ITP platelet survival of In-AP is significantly (P < .05) longer than that of Cr-HP. Platelet turnover measured with In-AP is only normal in patients with mainly splenic platelet sequestration. Results with Cr-HP give a false impression of PS. It seems that in ITP those patients with severe disease also have a platelet production defect.

Lotter, M.G.; Heyns, A.D.P.; Badenhorst, P.N.; Minnaar, P.C.



Age as the major predictive factor of long-term response to splenectomy in immune thrombocytopenic purpura.  


Sixty-one consecutive patients undergoing splenectomy for chronic immune thrombocytopenia were retrospectively evaluated. Platelet response was considered as complete (CR) when platelet count rose to > 100 x 109/l, partial (PR) when 30-100 x 109/l or absent (NR) if otherwise. Follow-up (mean time 7.6 years) was possible in 54 patients. Forty-eight patients (88%) had an immediate response to splenectomy (39 CR, 9 PR) whereas six (12%) were NR. Thirty-six responders (67%) had sustained remission (31 CR; 5 PR) without further treatment; thrombocytopenia recurred in 12 patients (33%). The probability curve of continued remission showed a constant relapse-rate during the first 36 months; a further step of relapse was observed beginning 70 months after surgery. The only positive predictive factor for the long-term response to splenectomy was age < 40 (P < 0.005). Neither duration of thrombocytopenia nor previous response to medical treatment (steroids and/or intravenous immunoglobulins) were related to splenectomy response. PMID:11260065

Fabris, F; Tassan, T; Ramon, R; Carraro, G; Randi, M L; Luzzatto, G; Moschino, P; Girolami, A



A collaborative approach to investigating the risk of thrombocytopenic purpura after measles–mumps–rubella vaccination in England and Denmark  

Microsoft Academic Search

The assessment of rare adverse events following vaccination may not be possible within a single country due to an insufficiently large denominator population. In 2008 a European consortium (VAESCO) was funded to perform collaborative vaccine safety studies. To help assess the feasibility of multi-country collaboration England and Denmark, who have established vaccine safety research infrastructures, undertook to work to a

Nick Andrews; Julia Stowe; Elizabeth Miller; Henrik Svanström; Kari Johansen; Jan Bonhoeffer; Anders Hviid


Mechanisms of thrombocytopenia in chronic autoimmune thrombocytopenic purpura. Evidence of both impaired platelet production and increased platelet clearance.  

PubMed Central

Mechanisms of thrombocytopenia were studied in 38 patients with mild to moderately severe chronic autoimmune thrombocytopenia (AITP). 51Cr and 111In-labeled autologous platelet turnover studies and in vitro analysis of committed megakaryocyte progenitors (CFU-Meg) were used as independent measures of platelet production. Autologous 111In-labeled platelet localization studies were performed to assess platelet clearance. Although there was no increase in the frequency of marrow CFU-Meg, a specific increase in the CFU-Meg [3H]TdR suicide rate was seen which was inversely correlated with the platelet count (P less than 0.001). Platelet turnover studies showed significant numbers of patients had inappropriate thrombopoietic responses to their reduced platelet counts. Platelet-associated antibody levels correlated inversely with platelet turnover suggesting that antiplatelet antibody impairs platelet production. The circulating platelet count was best predicted by an index relating platelet production (i.e., turnover) to the spleen-liver platelet clearance that correlated directly with platelet survival (P less than 0.001). In summary, both depressed platelet production and increased platelet clearance by the liver and spleen contribute to the thrombocytopenia of AITP.

Ballem, P J; Segal, G M; Stratton, J R; Gernsheimer, T; Adamson, J W; Slichter, S J



Henoch-Schönlein purpura nephritis associated with polycythemia vera.  


We present a 53-year-old man with rapidly progressive glomerulonephritis and Henoch-Schönlein purpura which developed during the course of treatment for polycythemia vera. An initial renal biopsy specimen showed mesangial proliferative glomerulonephritis. The patient was admitted to the hospital with cutaneous purpura and progressive renal failure after having received 700 mg of ranimustine over a 29 month period as therapy for the polycythemia vera. A second renal biopsy specimen revealed crescentic glomerulonephritis with deposition of immunofluorescent IgA. These data suggest that Henoch-Schönlein purpura nephritis may occur in response to ranimustine therapy. PMID:8180441

Kanauchi, M; Dohi, K; Shiiki, H; Fujii, Y; Ishikawa, H



Thrombotisch-thrombozytopenische Purpura (Moschcowitz-Syndrom), verursacht durch Ticlopidin  

Microsoft Academic Search

Zusammenfassung\\u000a ? Hintergrund  In wenigen Fallbeschreibungen wurde bisher die Einnahme von Ticlopidin mit der thrombotisch-thrombozytopenischen Purpura in\\u000a Verbindung gebracht, wobei diese Assoziation kontrovers diskutiert wird.\\u000a \\u000a \\u000a \\u000a ? Falldarstellung  Bei einer 57jährigen Patientin, die mit fluktuierenden neurologischen Ausfallserscheinungen und generalisierter Purpura zur\\u000a Aufnahme kam, konnte die Diagnose einer thrombotisch-thrombozytopenischen Purpura (TTP; Morbus Moschcowitz) gestellt werden.\\u000a Bei Aufnahme lagen eine ausgeprägte Anämie und Thrombozytopenie vor.

Jens Markus Chemnitz; Armin Schulz; Aida Salameh; Christof Scheid; Ralf Müller; Andreas Draube; Volker Diehl; Dietmar Söhngen



Retiform purpura: a new stigmata of illicit drug use?  


We report a 50-year-old woman who presented with a six-month history of recurrent retiform purpura of uncertain etiology. Laboratory findings included neutropenia, positive anticardiolipin IgM antibody, and a weakly positive p-ANCA. Histopathology revealed a leukocytoclastic vasculitis with intravascular thrombi. Urine toxicology screen was positive for cocaine. These findings are similar to recent reports of agranulocytosis and purpura induced by levamisole-tainted cocaine. A review of the clinical and histopathological findings associated with levamisole-induced purpura will be discussed. PMID:21382290

Geller, Lauren; Whang, Talley B; Mercer, Stephen E; Phelps, Robert



Bleeding into the skin  


... under the tissue in larger flat areas (called purpura ), or in a very large bruised area (called ... in the newborn) Aging skin (ecchymosis) Idiopathic thrombocytopenic purpura (petechiae and purpura) Henoch-Schonlein purpura (purpura) Leukemia ( ...


Idiopathic thrombocytopaenic purpura in patients during remission of Hodgkin's disease.  


Four patients with Hodgkin's disease developed thrombocytopaenic purpura during remission phase. The interval at which it occurred following chemotherapy ranged from a period of 4 months to 4 years. Detailed investigations failed to reveal recurrence of Hodgkin's disease. All patients responded well to steroid therapy. In the median duration of one year follow-up Hodgkin's disease remained under control. Thus, the occurrence of thombocytopaenic purpura in patients treated for Hodgkin's lymphoma need not imply recurrence or active Hodgkin's disease. PMID:2808278

Tahiliani, R R; Banavali, S D; Parikh, P M; Charak, B S; Nair, C N; Saikia, T K; Gopal, R; Advani, S H



Purpura associated with hypergammaglobulinemia, renal tubular acidosis and osteomalacia.  

PubMed Central

Two patients with hyperglobulinemia associated with purpura were studied. One had features of Sjögren's syndrome, while the other appeared to have a primary condition -- "chronic benign purpura". Both patients also had renal tubular acidosis, osteomalacia and renal calculi, with disturbed calcium metabolism and acid-base balance. Autoantibodies were detected in the serum of both patients, and mononuclear cell infiltrates were noted in skin and kidney biopsies from both. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4

Marquez-Julio, A.; Rapoport, A.; Wilansky, D. L.; Rabinovich, S.; Chamberlain, D.




PubMed Central

The purpura accompanying the two foregoing cases of sarcoimatosis would seem to find its explanation in the coexistence of several factors, the main feature being an involvement of the vascular system by the sarcomatous elements. There existed in Case I a direct lesion of the vessel wall whereby the sarcoma cells invaded directly the various coats, and were found mainly between the intima and the adventitia, dissecting their way, as it were, along these tracts in the vessel walls. There was further an extensive involvement of the perivascular lymphatics, from which point, indeed, it would seem that the sarcoma cells had invaded the walls of the vessels themselves. In Case II, moreover, not only was there a definite invasion of the lymph spaces near the vessels, but, furthermore, there was undoubted evidence of the existence of emboli of sarcoma cells in the lumina of the blood vessels; and in the immediate vicinity of such conditions hæmorrhages were invariably found. While some vessels, and indeed a great many, were quite free from such emboli, in others the lumina were completely occluded by spindle cells, so as to preclude the possibility that these were merely a collection of desquamated endothelial cells, such as is frequently found as the result of post-mortem changes. That such an embolic condition can exist is by no means an unreasonable supposition, and, while it is generally recognised that multiple sarcomata are usually made up of small round cells, in this case we have an undoubted example of sarcomatosis of the spindle-celled variety. There are numerous instances of this " embolic purpura," as it may be called, especially in French and German literature, the condition being associated with rheumatism, valvular lesions of the heart, and other diseases which induce directly or indirectly the formation of emboli. Krauss, Gimard, Leloir, and others have insisted with considerable emphasis on the embolic origin of many purpuric conditions, and in some instances they have verified their observations by histological examination. Leloir assumes that, in addition to the presence of the ordinary emboli and the changes in the vessel walls with desquamative endarteritis, the blood itself may be much altered chemically, and that in the cachectic conditions clots may be thrown down from the circulating blood and be carried onward to form capillary emboli, with resulting hæmorrhagic infarctions. Krogerer, some ten years ago, in examining the skin removed from patients with symptomatic purpura, found definite thromboses in the smaller veins, and even in the arteries. According to his view, the alterations in the vessel walls gave rise to slowed circulation and tendency to thrombosis, bringing about a liability to hæmorrhages. His plates bear out his theories regarding the thrombi, many of which show considerable organization. But a careful examination of the purpuric areas shows further that a mere invasion of the vascular system by sarcoma cells can not explain all the various blood effusions present. On examining the skin, for instance, in those areas where large irregular hæmorrhages had occurred, there was but little evidence of vascular invasion, while the emboli, on the other hand, seemed to exist mainly in the localized smaller and more circumscribed patches. One must therefore conclude that in such instances a combination of factors will alone afford a rational explanation of the purpura, and that in the general condition of the patient we shall find another cause for the enormous effusions of blood. In both of our cases there were high fever, cachexia, and a rapid progressive asthenia, all being the results of a sarcomatosis, and implying also grave alterations in the composition of the blood. From this we may infer an altered condition of the vessel walls, and hence probably a combination of circumstances sufficient to explain the incidence of hæmorrhage. The raised cutaneous nodules in our second case, some of which were hæmorrhagic, can not be regarded as pure sarcomatous metastases

Martin, C. F.; Hamilton, W. F.



[Localized purpura revealing vascular prosthetic graft infection].  


Prosthetic graft infection after vascular reconstruction is a rare but serious complication. We report a case of infection occurring late after implantation of an iliofemoral prosthetic vascular graft. The Staphylococcus aureus infection was revealed by vascular purpura localized on the right leg 7 years after implantation of a vascular prosthesis. This case illustrates an uncommonly late clinical manifestation presenting as an acute infection 7 years after the primary operation. In this situation, the presentation differs from early infection, which generally occurs within the first four postoperative months. Diagnosis and treatment remain a difficult challenge because prosthetic graft infection is a potentially life-threatening complication. Morbidity and mortality rates are high. Here we detail specific aspects of the clinical and radiological presentation. PMID:23746928

Boureau, A S; Lescalie, F; Cassagnau, E; Clairand, R; Connault, J



Protein-losing enteropathy associated with Henoch-Sch?nlein purpura  

PubMed Central

The gastrointestinal manifestations of Henoch-Schönlein purpura include abdominal pain, gastrointestinal bleeding, intussusception, and perforation. Protein-losing enteropathy is rarely associated with Henoch-Schönlein purpura. Two pediatric patients with Henoch-Schönlein purpura who developed protein-losing enteropathy are reported. Tc-99m human serum albumin scintigraphy is useful in the detection of protein-losing enteropathy.

Nakamura, Ayako; Fuchigami, Tatsuo; Inamo, Yasuji



Meningococcal interaction to microvasculature triggers the tissular lesions of purpura fulminans.  


Neisseria meningitidis is a strict human pathogen that closely interacts with human endothelial cells via type IV pili in vitro. To decipher whether this interaction plays a role in vivo, we set up an experimental model of fulminant meningococcemia in human skin grafted SCID mice using the wild-type strain 2C4.3. Human skin and mouse tissues were sampled 24 hours after bacterial challenge for histopathology, immunohistochemistry and ultrastructural analysis. In all infected mice, N. meningitidis targeted the human vasculature, leading to bacterial and blood thrombi, infectious vasculitis and vascular leakage. Mouse vessels, including brain vessels, remained unaffected by the infectious and thrombotic process, and a nonpiliated ? pilE derivative of 2C4.3 failed to target human graft vessels and to induce vascular damages. These data demonstrate that N. meningitidis targets human endothelial cells in vivo and that this interaction triggers the vascular damages that characterize purpura fulminans. PMID:23840047

Join-Lambert, Olivier; Lecuyer, Hervé; Miller, Florence; Lelievre, Lucie; Jamet, Anne; Furio, Laetitia; Schmitt, Alain; Pelissier, Philippe; Fraitag, Sylvie; Coureuil, Mathieu; Nassif, Xavier



Meningococcal purpura fulminans in children: I. Initial orthopedic management  

Microsoft Academic Search

Background  Purpura fulminans is a rare and extremely severe infection, mostly due to Neisseria meningitidis frequently causing early orthopedic lesions. Few studies have reported on the initial surgical management of acute purpura\\u000a fulminans. The aim of this study is to look at the predictive factors in orthopedic outcome in light of the initial surgical\\u000a management in children surviving initial resuscitation.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Nineteen

E. Nectoux; A. Mezel; S. Raux; D. Fron; M. Maillet; B. Herbaux



Meningococcal purpura fulminans in children. II: Late orthopedic sequelae management  

Microsoft Academic Search

Background  Purpura fulminans is a rare and extremely severe infection, mostly due to Neisseria meningitidis. Nineteen patients were followed up immediately after the initial multivisceral failure in order to diagnose late-onset orthopedic\\u000a sequelae. We report our experience with these 19 patients, in light of our medical follow-up protocol and surgical management.\\u000a \\u000a \\u000a \\u000a \\u000a Materials and methods  Nineteen patients were referred for acute purpura fulminans

E. Nectoux; A. Mezel; S. Raux; D. Fron; C. Klein; B. Herbaux



MMR vaccine and idiopathic thrombocytopaenic purpura  

PubMed Central

Aims To estimate the relationship between idiopathic thrombocytopaenic purpura (ITP) and the measles, mumps and rubella (MMR) vaccination in children; calculating the relative risk estimate for ITP with in 6 weeks after MMR vaccination and the attributable risk of ITP within 6 weeks after MMR vaccination. Methods Using the General Practice Research Database we identified children with a first-time diagnosis of ITP from a base population of children aged less than 6 years between January 1988 and December 1999. After describing the characteristics of all the children identified with ITP, we focused on cases aged 13–24 months to perform a population-based, case–control analysis to estimate the relative risk of developing ITP within 6 weeks after MMR vaccination. We also calculated the risk of ITP attributable to the MMR vaccination. Results Sixty-three children with a first time diagnosis of ITP were identified; 23 cases were between 13 and 24 months old. The relative risk estimate for ITP within 6 weeks after MMR vaccination, compared to the combined group of unvaccinated children and children vaccinated with MMR more than 26 weeks previously was 6.3 (95% CI 1.3–30.1). The attributable risk of developing ITP within 6 weeks after MMR vaccination was estimated to be 1 in 25 000 vaccinations (95% confidence interval 21 300, 89 400). Conclusion This study confirms the increased risk of ITP within 6 weeks after MMR vaccination. However, the attributable risk of ITP within 6 weeks after MMR vaccination is low.

Black, Corri; Kaye, James A; Jick, Hershel



Treatment of purpura fulminans in meningococcemia with protein C concentrate  

Microsoft Academic Search

Objective: To evaluate the clinical and laboratory effects of protein C concentrate as an adjunct to conventional therapy in the treatment of meningococcemia with purpura fulminans. Design: Case series (pilot study). Setting: Intensive care unit in a tertiary care pediatric hospital. Patients: Four children (aged 3 months to 15 years) requiring intensive treatment for meningococcemia with shock, disseminated intravascular coagulation,

Georges E. Rivard; Michèle David; Catherine Farrell; Hans Peter Schwarz



Henoch-Schönlein purpura and meningococcal B vaccination.  


The risk of Henoch-Schönlein purpura (HSP) following vaccination with a group B meningococcal vaccine was assessed through active hospital safety monitoring. There was no increase in the relative incidence of HSP within 30 days after vaccination nor recurrence in HSP cases who received one or more further vaccine doses (re-challenge). PMID:18650242

Sexton, K; McNicholas, A; Galloway, Y; Radke, S; Kieft, C; Stehr-Green, P; Reid, S; Neutze, J; Drake, R



Simultaneous presentation of Henoch Schonlein purpura in monozygotic twins.  


Henoch Schonlein purpura is a relatively common and well recognized paediatric condition. We report a case of 2 monozygotic twins that presented with typical Henoch Schonlein symptoms, starting simultaneously. Both children had positive throat cultures for Streptococcus pyogenes and skin biopsies typical for HS disease. Their genotype was determined and compared with studies suggesting predisposition according to HLA typing. PMID:16126577

Spyridis, Nikolaos; Salapata, Marianella; Fessatou, Smaragdi; Kontaxaki, Chrisi; Spyridis, Panayiotis



Increased efficacy of breast cancer chemotherapy in thrombocytopenic mice.  


Platelets contribute to homeostasis of the tumor vasculature by helping prevent hemorrhage. Thus, we hypothesized that inducing thrombocytopenia would increase tumor vascular leakiness and facilitate the effective delivery of chemotherapeutic agents to tumors. In a mammary carcinoma murine model, platelet depletion induced bleeding specifically at the tumor site, favoring the accumulation of fluorescently labeled microspheres only in the tumor. Moreover, induction of thrombocytopenia in tumor-bearing mice before injection of paclitaxel increased its intratumoral accumulation and reduced growth of both slow- and fast-growing tumors, compared with mice with normal platelet counts that were treated only with paclitaxel. Histologic analysis confirmed the expectation of an increase in tumor apoptosis and a reduction in tumor proliferation in thrombocytopenic mice receiving chemotherapy. No increased toxicity was seen in other organs or blood cells. Taken together, our results indicate that low platelet count selectively induces leakiness of tumor vessels and favors the delivery of chemotherapy to tumor sites, enhancing its tumoricidal effects. PMID:21212409

Demers, Mélanie; Ho-Tin-Noé, Benoit; Schatzberg, Daphne; Yang, Janie J; Wagner, Denisa D



Meningococcal purpura fulminans in children: I. Initial orthopedic management  

PubMed Central

Background Purpura fulminans is a rare and extremely severe infection, mostly due to Neisseria meningitidis frequently causing early orthopedic lesions. Few studies have reported on the initial surgical management of acute purpura fulminans. The aim of this study is to look at the predictive factors in orthopedic outcome in light of the initial surgical management in children surviving initial resuscitation. Methods Nineteen patients referred to our institution between 1987 and 2005 were taken care of at the very beginning of the purpura fulminans. All cases were retrospectively reviewed so as to collect information on the total skin necrosis, vascular insufficiency, gangrene, and total duration of vasopressive treatment. Results All patients had multiorgan failure; only one never developed any skin necrosis or ischemia. Eighteen patients lost tissue, leading to 22 skin grafts, including two total skin grafts. There was only one graft failure. Thirteen patients were concerned by an amputation, representing, in total, 54 fingers, 36 toes, two transmetatarsal, and ten transtibial below-knee amputations, with a mean delay of 4 weeks after onset of the disease. Necrosis seems to affect mainly the lower limbs, but there is no predictive factor that impacted on the orthopedic outcome. We did not perform any fasciotomy or compartment pressure measurement to avoid non-perfusion worsening; nonetheless, our outcome in this series is comparable to existing series in the literature. V.A.C.® therapy could be promising regarding the management of skin necrosis in this particular context. While suffering from general multiorgan failure, great care should be observed not to miss any additional osseous or articular infection, as some patients also develop local osteitis and osteomyelitis that are often not diagnosed. Conclusions We do not advocate very early surgery during the acute phase of purpura fulminans, as it does not change the orthopedic outcome in these children. By performing amputations and skin coverage some time after the acute phase, we obtained similar results to those found in the literature.

Mezel, A.; Raux, S.; Fron, D.; Maillet, M.; Herbaux, B.



Cryofibrinogenemia in Henoch-Schönlein purpura: report of a case.  


A patient with Henoch-Schönlein purpura (HSP) had exacerbations of disease that correlated closely with the presence of cryofibrinogenemia. Cryofibrinogen was absent consistently during asymptomatic intervals. To our knowledge, such a pattern has not been described previously in typical HSP. We suggest that all patients with HSP be screened for cryofibrinogenemia during the active phase of disease to determine the incidence of this abnormality. PMID:443956

Cwazka, W F; Sprenger, J D; Naguwa, S N; Birnberg, F A



Gangrenous appendicitis in a child with Henoch-Schonlein purpura.  


Abdominal pain is common feature of Henoch-Schonlein purpura, which may mimic appendicitis, leading to unnecessary laparotomy. Accordingly, the diagnosis must be confirmed by ultrasonography or computed tomography scan before laparotomy is performed. The authors report a case of simultaneous occurrence of Henoch-Schonlein Purpura and gangrenous appendicitis in an 18 year-old boy. The patient was admitted with abdominal pain, cramps, and mild dehydration. He also complained of small reddish purple on his lower limbs, bilateral knee pain, low-grade fever, as well as bloody stools. The symptoms subsided completely. Eight days later, he returned with nonbloody, nonbilious emesis, abdominal cramps, and right lower quadrant abdominal tenderness. Abdominal ultrasound evaluation was performed to rule out an intussusception but demonstrated appendiceal dilatation with a possible appendicolith without any evidence of intussusception. A laparotomy was undertaken, and appendectomy was performed for gangrenous appendicitis. Simultaneous occurrence of Henoch-Schonlein purpura and acute appendicitis is rarely observed. Clinical features of the patients may mislead the clinicians, resulting in delayed diagnosis or misdiagnosis. The use of ultrasonography and computed tomography scan would confirm the diagnosis before surgery. PMID:18970918

Jangjoo, Ali; Amouzeshi, Ahmad; Jalali, Ali Najib



Improved survival of children with sepsis and purpura: effects of age, gender, and era  

Microsoft Academic Search

BACKGROUND: To gain insight into factors that might affect results of future case-control studies, we performed an analysis of children with sepsis and purpura admitted to the paediatric intensive care unit (PICU) of Erasmus MC-Sophia Children's Hospital (Rotterdam, The Netherlands). METHODS: Between 1988 and 2006, all 287 children consecutively admitted with sepsis and purpura were included in various sepsis studies.

Martine Maat; Corinne MP Buysse; Marieke Emonts; Lodewijk Spanjaard; Koen FM Joosten; Ronald de Groot; Jan A Hazelzet



Two cases of infectious purpura fulminans and septic shock caused by Capnocytophaga canimorsus transmitted from dogs.  


We report 2 cases of Capnocytophaga canimorsus-induced septicaemia complicated by purpura fulminans in previously healthy individuals, both of whom had been exposed to dog saliva prior to disease. They both presented with purpuric skin lesions, as well as the tetrad of abdominal symptoms, haemolytic anaemia, metabolic acidosis, and renal failure, which may be common in C. canimorsus-associated purpura fulminans. The patients survived after treatment with broad-spectrum antibiotics and supportive intensive care. C. canimorsus should be considered as a possible cause of infectious purpura fulminans in the unresolved critically ill patient with a history of dog exposure. PMID:22497463

Christiansen, Claus Behrend; Berg, Ronan M G; Plovsing, Ronni R; Møller, Kirsten



Interim evaluation of two cooperative studies assessing the effects of intravenous immunoglobulin (i.v. IgG) on childhood idiopathic thrombocytopenic purpura (ITP)  

Microsoft Academic Search

Since in a pilot study i.v. IgG was shown to induce a rapid rise of thrombocytes in children with ITP two prospective multicenter ITP studies were started: one comparing i.v. IgG with oral corticosteroids in previously untreated acute ITP, the other investigating the response to i.v. IgG in pretreated acute or chronic ITP in childhood. In this report preliminary results

P. Imbach; G. Gaedicke; P. Joller



Autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura in pediatric solid organ transplant recipients, report of five cases and review of the literature.  


Cytopenias are common among pediatric SOT; however, autoimmune cytopenias are infrequently reported. We report five cases of autoimmune cytopenias in pediatric LT patients: two with isolated IgG-mediated AIHA, two with ITP, and one with Evans syndrome (ITP and AIHA). All patients were maintained on tacrolimus as immunosuppression. Viral illness commonly preceded the autoimmune cytopenias. All patients responded well to medical therapy (steroids, intravenous immunoglobulin, and rituximab) and lowering tacrolimus serum level. Prognosis appears to be worse when more than one cell line (e.g., Evans syndrome) is affected, and/or there is no preceding viral illness. A critical literature review of autoimmune cytopenias in children following SOT is conducted. Autoimmune cytopenias are a rarely reported complication of pediatric SOT, but clinicians taking care of pediatric transplant recipients need to be aware of this complication. PMID:22112003

Miloh, Tamir; Arnon, Ronen; Roman, Elizabeth; Hurlet, Anne; Kerkar, Nanda; Wistinghausen, Birte



Post-Renal Transplant Thrombotic Thrombocytopenic Purpura (TTP): Attributable to Immunosuppression or Graft Rejection: Report of Three Cases and Literature Review.  

National Technical Information Service (NTIS)

The immunomodulatory drug FK-506 (Tacrolimus) is a calcineurin inhibitor that, as such, indirectly inhibits the transcription of a gene encoding interleukin 2, a cytokine that is vital to the immune response process. Since its introduction in 1987, sporad...

J. P. Pelletier O. Fadare Y. Wu



Megakaryocyte size and concentration in the bone marrow of thrombocytopenic and nonthrombocytopenic neonates.  


Thrombocytopenia is frequent among sick neonates, but little is known about its underlying mechanisms. It is known, however, that neonatal megakaryocytes are smaller and of lower ploidy than their adult counterparts and that smaller megakaryocytes produce fewer platelets than larger, more polyploid, megakaryocytes. We hypothesized that neonatal megakaryocytes would not increase their size in response to thrombocytopenia, thus limiting the ability of neonates to mount a response. To test this, we obtained marrow specimens from thrombocytopenic and nonthrombocytopenic neonates and adults. Megakaryocytes were immunohistochemically stained, quantified using an eyepiece reticle, and measured using an image analysis system with incorporated electronic micrometer. We found that, after adjusting for differences in cellularity, neonates and adults had similar megakaryocyte concentrations. When samples from the same sources were compared (tibial clot and vertebral body sections in neonates, iliac crest biopsies in adults), there were also no differences in megakaryocyte concentration between thrombocytopenic and nonthrombocytopenic subjects. The megakaryocyte diameter, however, was greater in adults than in neonates (19.4 +/- 3.0 versus 15.3 +/- 1.7 microm, p<0.0001). Thrombocytopenic adults also had a higher proportion of large megakaryocytes than nonthrombocytopenic adults (p<0.001). This was not observed among thrombocytopenic neonates, suggesting a developmental limitation in their ability to increase megakaryocyte size. PMID:17515875

Sola-Visner, Martha C; Christensen, Robert D; Hutson, Alan D; Rimsza, Lisa M



Renal involvement in Henoch-Schönlein purpura: A multivariate analysis of prognostic factors  

Microsoft Academic Search

Renal involvement in Henoch-Schönlein purpura: A multivariate analysis of prognostic factors. This study is the first report in which the relationship between the progression of renal involvement in Henoch-Schönlein purpura (HSP) and various factors was evaluated using a multivariate analysis. Sixty-five (33.5%) of 194 patients with HSP developed renal involvement from three days to 17 months after the onset of

Yoshitsugu Kaku; Kaoru Nohara; Sunao Honda



Schönlein-Henoch purpura during pregnancy with successful outcome for mother and newborn  

Microsoft Academic Search

ABSTRAC: BACKGROUND: Schönlein-Henoch purpura is a systemic vasculitis that affects vessels of a small caliber and rarely reported in the literature. CASE PRESENTATION: We report on a 35-year-old woman who developed palpable purpura with necrotizing cutaneous lesions on the lower limbs at 27 weeks of gestation. She also complained of epigastric pain and arthralgias. Histologic examination of a skin biopsy

Robert Feldmann; Walter Rieger; Paul G Sator; Friedrich Gschnait; Friedrich Breier



The pathogenesis and treatment of pediatric Henoch–Schönlein purpura nephritis  

Microsoft Academic Search

Henoch–Schönlein purpura (HSP) is a systemic disorder characterized by leukocytoclastic vasculitis involving the capillaries\\u000a and the deposition of IgA immune complexes. Renal involvement is the principal cause of morbidity and mortality in children\\u000a with HSP. Thus, it is important to clarify the onset mechanism of Henoch–Schönlein purpura nephritis (HSPN) and to identify\\u000a the most appropriate treatment. We herein review the

Yukihiko Kawasaki


Varicella-Associated Purpura Fulminans: Chicken Pox Is Not Always Benign  

Microsoft Academic Search

Objective: To report a 6-year-old boy with post-chicken pox purpura fulminans (PF). Clinical Presentation and Intervention: A 6-year-old boy presented with purpura of the legs that rapidly progressed to other parts of the limbs and the buttocks. The patient had had chicken pox 10 days prior to presentation. He was afebrile and the chicken pox lesions were dry. He received

A. Abdulmalik; W. Al-Ateeqi; M. Al-Khawari; S. Al-Osaimi



Assessment of the Interplay between Blood and Skin Vascular Abnormalities in Adult Purpura Fulminans.  


Rationale: Purpura fulminans in adults is a rare but devastating disease. Its pathophysiology is not well known. Objectives: To understand the pathophysiology of skin lesions in purpura fulminans, the interplay between circulating blood and vascular alterations was assessed. Methods: Prospective multicenter study in four intensive care units. Patients with severe sepsis without skin lesions were recruited as control subjects. Measurements and Main Results: Twenty patients with severe sepsis and purpura fulminans were recruited for blood sampling, and skin biopsy was performed in deceased patients. High severity of disease and mortality rates (80%) was observed. Skin biopsies in purpura fulminans lesions revealed thrombosis and extensive vascular damage: vascular congestion and dilation, endothelial necrosis, alteration of markers of endothelial integrity (CD31) and of the protein C pathway receptors (endothelial protein C receptor, thrombomodulin). Elevated plasminogen activating inhibitor-1 mRNA was also observed. Comparison with control patients showed that these lesions were specific to purpura fulminans. By contrast, no difference was observed for blood hemostasis parameters, including soluble thrombomodulin, activated protein C, and disseminated intravascular coagulation markers. Bacterial presence at the vascular wall was observed specifically in areas of vascular damage in eight of nine patients tested (including patients with Streptococcus pneumoniae, Neisseria meningitidis, Escherichia coli, and Pseudomonas aeruginosa infection). Conclusions: Thrombi and extensive vascular damage with multifaceted prothrombotic local imbalance are characteristics of purpura fulminans. A "vascular wall infection" hypothesis, responsible for endothelial damage and subsequent skin lesions, can be put forward. PMID:23924269

Lerolle, Nicolas; Carlotti, Agnes; Melican, Keira; Aubey, Flore; Pierrot, Marc; Diehl, Jean-Luc; Caille, Vincent; Hékimian, Guillaume; Gandrille, Sophie; Mandet, Chantal; Bruneval, Patrick; Dumenil, Guillaume; Borgel, Delphine



Management of pregnancy-associated thrombotic thrombocytopenia purpura.  


Thrombotic thrombocytopenia purpura (TTP) is an infrequent but serious disease. Pregnancy is a known risk factor for presentation or relapse of TTP. Difficulties in differentiating TTP from preeclampsia/HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome, and current treatment recommendations are discussed in this case report. A woman with previously treated and stable TTP had a relapse at 36 weeks' gestation. Careful surveillance led to an early diagnosis. Severe disease in the peripartum period was treated successfully with cryosupernatant plasma-based plasmapheresis and platelet transfusion, with good maternal and neonatal outcomes. Cryosupernatant plasma is a viable alternative to fresh frozen plasma for plasmapheresis for TTP and may offer some therapeutic and logistical advantages. Platelet transfusion can be undertaken safely if needed to prevent or treat significant hemorrhage. PMID:23943710

Fyfe-Brown, Ashley; Clarke, Gwen; Nerenberg, Kara; Chandra, Sujata; Jain, Venu



[Possible aggravation of a Henoch Schoenlein purpura by isotretinoin].  


We report on a 16 year old patient with a hemorrhagic bullous form of a Henoch-Schönlein purpura. The cause for the event could not be determined, but the patient recovered without complications. Since he had begun a therapy with isotretinoin due to an acne inversa 3 weeks before, a possible association between the event and the treatment could not be excluded, and the case was reported to Swissmedic. In the comment, we discuss the pharmacology of isotretinoin, drug-induced vasculitis, and its pathomechanisms. As a general reminder, the criteria for the causality assessment of adverse drug reactions as well as the reporting system of adverse drug reactions in Switzerland are discussed. PMID:22715073

Derungs, A; Eberhardt, K; Heiniger, U; Rudin, C; Brauchli Pernus, Y B



Complications of Evans' syndrome in an infant with hereditary spherocytosis: a case report  

Microsoft Academic Search

Hereditary spherocytosis (HS) is a genetic disorder of the red blood cell membrane clinically characterized by anemia, jaundice and splenomegaly. Evans' syndrome is a clinical syndrome characterized by autoimmune hemolytic anemia (AIHA) accompanied by immune thrombocytopenic purpura (ITP). It results from a malfunction of the immune system that produces multiple autoantibodies targeting at least red blood cells and platelets. HS

Hideki Yoshida; Hiroyuki Ishida; Takao Yoshihara; Takashi Oyamada; Masataka Kuwana; Toshihiko Imamura; Akira Morimoto



Is there a crossroad between infections, genetics, and Henoch-Schönlein purpura?  


Henoch-Schönlein purpura is the most common systemic vasculitis in childhood, characterized by the presence of immunoglobulin A deposits in the small vessels of skin, gastrointestinal tube, joints and kidneys. Although there have been great efforts made in elucidating its pathogenic mechanisms, Henoch-Schönlein purpura etiology remains unknown: the basic scene comes across an abnormal inflammatory process deriving from immune reactions to various antigenic stimuli, which might be bacterial, viral, or parasitic agents, in a genetically prone individual. Then, a peculiar immune complex deposition in the vascular walls and overproduction of different proinflammatory molecules elicit different clinical signs, which might be differentiated according to either a specific trigger or a specific genetic make-up. The aim of this review is to make a critical appraisal of the last 15years' medical literature concerning the relationship between infections, genetics, and Henoch-Schönlein purpura in pediatrics. PMID:23684700

Rigante, Donato; Castellazzi, Luca; Bosco, Annalisa; Esposito, Susanna



A Structured Approach to the Management of Purpura Fulminans  

PubMed Central

A 5-year-old boy with purpura fulminans (PF) was successfully managed with a protocol in which fresh frozen plasma (FFP) was administered, followed by a trial of certain therapeutic agents. This approach was based upon combined experience both with the reference patient and with a subject with a chronic form of PF. FFP controlled the acute disseminated intravascular coagulation in both instances and permitted venous antithrombotic drugs to be evaluated in safety. The PF syndrome in the index case was found to be heparin responsive, while the atypical case was coumarin responsive (heparin resistant). Initial administration of FFP was recommended rather than heparin in order to minimize the risk of hemorrhage while maintaining the likelihood of a swift response. When FFP is effective, a sequential trial should be undertaken with agents from the following categories: (1) venous antithrombotic, (2) antiplatelet, (3) antifibrinolytic, and (4) antiproteolytic. This process permits therapies to be thoroughly tested and used as investigative probes into the mechanisms of a particular case of PF. Should FFP prove ineffective, the list can serve as a guide for the investigation of various fastacting agents in the acute phases of disseminated intravascular coagulation. PF treatments are ranked in accordance with the number of positive outcomes in the literature. ImagesFigure 1Figure 2

Branson, Herman E.; Katz, Jacob



Familial cases of Henoch-Schönlein purpura in Taiwanese Aborigines.  


Henoch-Schönlein purpura (HSP) is a disorder whose cause and pathogenesis is unknown; some familial cases of this disease have been reported. The clinical heterogeneity in HSP may be conferred by a number of genetic loci, including the major histocompatibility complex. The racial and genetic factors responsible for the occurrence of the familial cases of HSP in Taiwan are unclear. The purpose of this study was to examine the racial and genetic factors in familial HSP cases in Taiwan. We retrospectively collected the HSP cases in our hospital during 2006 through 2010 and observed that familial HSP cases were only in Taroko Aborigines. Six cases of HSP in 3 Taroko families were found, and their human leukocyte antigens (HLA) were studied in the tissue typing laboratory of our hospital, to determine the possible association with familial HSP cases in Taiwanese Aborigines. Our results suggest an increased frequency of familial HSP cases with HLA-A24 in Taiwanese Taroko Aborigines. We concluded that racial and genetic predisposition was the possible cause for the familial occurrence of and renal involvement in HSP in Taiwanese Aborigines. PMID:23084726

Chen, Yu-Hung; Lin, Teng-Yi; Chen, Chia-Jung; Chen, Li-Kuang; Jan, Rong-Hwa



A case of anaphylactoid purpura nephritis accompanied by pulmonary hemorrhage and review of the literature.  


Cases of Henoch-Schönlein purpura and purpura nephritis accompanied by pulmonary hemorrhage are rare. Mild cases are easily ignored due to a lack of evident bleeding, and severe cases may be fatal. We have only treated one patient with Henoch-Schönlein nephritis (HSPN), a female child. The clinical manifestations were not evident, however, the imaging manifestations were clear. Finally, the patient was definitively diagnosed with HSPN accompanied by pulmonary hemorrhage. Following treatment with antiinflammatory and steroidal agents, tripterygium glycosides and traditional Chinese medicine, the patient recovered. In the present study, we report the diagnosis and treatment of this disease, with a review of the literature. PMID:23737885

Ren, Xianqing; Zhang, Wenjuan; Dang, Weili; Zhai, Wensheng; Guo, Qingyin; Ding, Yin; Yang, Xiaoqing



Stroke and skin rash: A rare case of Henoch-Schonlein purpura.  


Henoch-Schonlein purpura (HSP) is a small vessel vasculitis that is rare in adults. Here, we present a case of a woman who presented with palpable purpura, abdominal pain, arthritis and ischemic stroke. The patient met the diagnostic criteria of HSP. However, cerebrovascular disease is reported as an uncommon, yet fatal, complication of HSP. The patient responded to aggressive immunosuppression with pulses of corticosteroids and cyclophosphamide. In the absence of an established protocol of treatment of such neurologic emergency in HSP patients, this report demonstrates a successful outcome. PMID:23349600

Ghosh, Kaushik; Chatterjee, Atri; Sau, Jyoti Tanmay; Dey, Sandip



Henoch-Schönlein purpura without systemic involvement beginning with acute scrotum and mimicking torsion of testis.  


Henoch-Schönlein purpura (HSP) is the most common systemic vasculitis in children. Typical presentations of HSP are palpable purpura of the small vessels in the hips and lower limbs, abdominal pain, arthritis, and hematuria. Scrotal involvement manifested by the presence of scrotal pain and swelling during the course of the disease is rarely seen. HSP without systemic involvement with acute scrotum mimicking testicular torsion is even rare in the medical literature. In most cases, patients with this disease achieve complete recovery. Herein, we report an interesting HSP case with skin symptoms but without systemic involvement and then progression to acute scrotum resembling torsion of testis. PMID:23695408

Verim, Levent; Cebeci, Filiz; Erdem, M Remzi; Somay, Adnan



My patient is thrombocytopenic! Is (s)he? Why? And what shall I do? A practical approach to thrombocytopenia.  


Solving the riddle of a thrombocytopenic patient is a difficult and fascinating task. The spectrum of possible aetiologies is wide, ranging from an in vitro artefact to severe treatment-resistant thrombocytopenic bleeding conditions, or even life-threatening prothrombotic states. Moreover, thrombocytopenia by itself does not protect from thrombosis and sometimes a patient with a low platelet count requires concomitant antithrombotic treatment as well. In order to identify and treat the cause and the effects of the thrombocytopenia, you have to put together several pieces of information, solving a unique jig-jaw puzzle. The present work is not a textbook article about thrombocytopenia, rather a collection of differential diagnostic thoughts, treatment concepts, and some basic knowledge, that you can retrieve when facing your next thrombocytopenic patient. Enjoy reading it, but most importantly enjoy taking care of patients with a low platelet count. I bet the present work will assist you in this challenging and rewarding clinical task. PMID:23666381

Alberio, L



Postinfectious purpura fulminans caused by an autoantibody directed against protein S  

Microsoft Academic Search

Objective. To determine the mechanism responsible for idiopathic purpura fulminans, we investigated the procoagulant and anticoagulant pathways in five consecutive patients, four after varicella, and the fifth after a nonspecific infection. Methods. Procoagulant and anticoagulant factors, including protein C, protein S, and antithrombin III, were measured by quantitative or functional assays. Anti–protein S autoantibodies were identified by dot blotting and

Michael Levin; Brian S. Eley; Jacques Louis; Hannah Cohen; Lisa Young; Robert S. Heyderman



Purpura fulminans in a Child as a Complication of Chickenpox Infection  

Microsoft Academic Search

Purpura fulminans is a thrombotic disease that can occur during infections, disseminated intravascular coagulation or in the context of an acquired or congenital protein C or S deficiency. Here we report the case of a 4-year-old child who developed, 5 days after a chickenpox infection, large painful ecchymotic, necrotizing and retiform plaques on the lower extremities. Laboratory analyses revealed very

Alexandre Campanelli; Gürkan Kaya; Ayse Hulya Ozsahin; Giorgio La Scala; Cédric Jacquier; Mélanie Stauffer; Françoise Boehlen; Philippe de Moerloose; Jean-Hilaire Saurat



Cryofibrinogenemia, monoclonal gammopathy, and purpura. Report of a case and review of the literature.  


A patient with purpura, acral blisters, and ulcerations was evaluated and found to have cryofibrinogenemia and an IgG K light chain monoclonal gammopathy. No other systemic illness was found. The overall incidence of significant cryofibrinogenemia include neoplastic, thrombotic, infectious, and miscellaneous disorders. The patient described was not easily classified. This case is probably best considered primary or idiopathic cryofibrinogenemia. PMID:426532

Martin, S



Idiopathic purpura fulminans and varicella gangrenosa of both hands, toes and integument in a child  

Microsoft Academic Search

Chicken pox is a common childhood illness and, though a vaccine is readily available, it is not routinely included in the vaccination schedule of most countries owing to its mild clinical nature. However, varicella gangrenosa is a rare complication of this disease, infrequently reported in the literature. We report the case of a child who developed purpura fulminans in the

G. Alexander; H. M. Basheer; M. K. Ebrahim; I. Ghoneim



Incidence of renal complications in Schönlein—Henoch purpura syndrome in dependence of an early administration of steriods  

Microsoft Academic Search

Between 1976 and 1986, the authors treated 33 children with Schönlein-Henoch purpura (S-H purpura), with physiological urinary\\u000a finding on admission. Twentythree of them received prednisone already at the beginning of hospitalization, 10 were not given\\u000a any prednisone at all. In patients with prednisone, nephropathy occurred only once (4.3%), in those without prednisone it\\u000a occurred 5 times (50%), the incidence being

J. Buchanec; V. Galanda; ?. Beláková; M. Minárik; M. Zibolen



Platelet Activation Test in Unprocessed Blood (Pac-t-UB) to Monitor Platelet Concentrates and Whole Blood of Thrombocytopenic Patients  

PubMed Central

Summary Background Platelet concentrate transfusion is the standard treatment for hemato-oncology patients to compensate for thrombocytopenia. We have developed a novel platelet activation test in anticoagulated unprocessed blood (pac-t-UB) to determine platelet function in platelet concentrates and in blood of thrombocytopenic patients. Methods We have measured platelet activity in a platelet concentrate and in anticoagulated unprocessed blood of a post-transfusion thrombocytopenic patient. Results Our data show time-dependent platelet activation by GPVI agonist (collagen related peptide; CRP), PAR-1 agonist (SFLLRN), P2Y12 agonist (ADP), and thromboxane receptor agonist (U46619) in a platelet concentrate. Furthermore, pac-t-UB showed time-dependent platelet activation in unprocessed blood of a post-transfusion patient with thrombocytopenia. Testing platelet function by different agonists in relation to storage show that 3-day-old platelet concentrates are still reactive to the studied agonists. This reactivity rapidly drops for each agonists during longer storage. Discussion Pac-t-UB is a novel tool to estimate platelet function by different agonists in platelet concentrates and in unprocessed blood of thrombocytopenic patients. In the near future, we will validate whether pac-t-UB is an adequate test to monitor the quality of platelet concentrates and whether pac-t-UB predicts the bleeding risk of transfused thrombocytopenic patients.

Roest, Mark; van Holten, Thijs C.; Fleurke, Ger-Jan; Remijn, Jasper A.



Posterior reversible encephalopathy syndrome in a child with Henoch-Schonlein purpura.  


Henoch-Schönlein purpura (HSP) is a small vessel vasculitis that affects the gastrointestinal and central nervous systems and the kidneys. The disease primarily affects children, but may occur in elderly children with allergic purpura and also in adults. Central nervous system involvement may be the first sign; however, it is rarely encountered. Posterior reversible encephalopathy syndrome (PRES) is a clinical syndrome of encephalopathy, headache, visual disturbance and seizures. Its radiological signs can be observed in grey and white matter at the posterior region of the cerebral hemispheres. HSP should be considered in children with PRES in the presence of rash, joint and gastrointestinal symptoms. We reported a 5-year-old patient who developed acute renal failure and PRES by reason of HSP. PMID:23946524

Sivrioglu, Ali Kemal; Incedayi, Mehmet; Mutlu, Hakan; Meral, Cihan



Methylprednisolone pulse therapy in the treatment of severe forms of Schönlein-Henoch purpura nephritis  

Microsoft Academic Search

.  ?Between 1980 and 1994, 38 children with severe forms of Schönlein-Henoch purpura glomerulonephritis were entered into a prospective\\u000a study to evaluate methylprednisolone pulse therapy on the outcome of nephropathy in terms of clinical symptoms and histopathological\\u000a changes. The patients were considered at risk of developing chronic renal failure when they presented with a nephrotic syndrome\\u000a and\\/or had 50% or more

Patrick Niaudet; Renée Habib



Goodpasture syndrome during the course of a Schönlein-Henoch purpura  

Microsoft Academic Search

Two months after surgical resection of a bronchogenic carcinoma, a 69-year-old patient presented with Schönlein-Henoch purpura with kidney involvement followed by pulmonary hemorrhage. The presence of an IgA linear pattern on the kidney biopsy specimen and circulating anti-glomerular basement membrane (GBM) IgA antibodies led to the diagnosis of Goodpasture syndrome, which implies the possibility that the well-known pulmonary involvement during

Luis Carreras; Rafael Poveda; Jordi Bas; Mariona Mestre; Inés Rama; Marta Carrera



Henoch Schönlein Purpura Presenting as Duodenal Ulcer and Gastric Outlet Obstruction.  


Henoch-Schönlein purpura (HSP) is an acute small vessel leucocytoclastic vasculitis. It is the commonest vasculitis in children, with an incidence of about 10 cases per 100, 000 a year. Gastrointestinal manifestations are commonly encountered, however hematemesis and gastric outlet obstruction are rarely reported. The authors present the case of a 5-y-old boy having hematemesis, gastric outlet obstruction and multiple duodenal ulcers. He improved with steroids and conservative management. PMID:23564516

Rathore, Mukesh; Shrivastava, Rimjhim; Goyal, Ravinder; Radotra, B D; Thapa, B R




Microsoft Academic Search

I N RECENT summary articles by Nickerson and Sunderland,' Rosenthal,2 Tocantins,3 Wiseman, Doan and Wilson,4 Limarzi and Schleicher,5 and Dame- shek and Miller,6 the extensive literature dealing with idiopathic hemorrhagic purpura is reviewed, and the known facts relating to the megakaryocytes and to the bone marrow are presented. The majority of observations have been made on autopsy material, and there



Integra Artificial Skin as a useful adjunct in the treatment of purpura fulminans.  


Purpura fulminans is a devastating disorder characterized by rapidly progressing hemorrhagic necrosis of the skin, vascular collapse, and disseminated intravascular coagulation. It is most often seen in children, and it is usually preceded by meningococcemia or another infection. Most often, the disorder results in severe skin loss, but it can also result in the need for extremity amputations. In extreme cases, wound coverage after excision may be problematic because of the limited existence of donor sites and the need for amputation revisions. The case of a 21/2-year-old male requiring amputations of all four extremities due to severe purpura fulminans is presented to illustrate the use of Integra Artificial Skin (Integra Lifesciences Corp., Plainsboro, NJ) to obtain immediate wound closure. Integra Artificial Skin is a bilayered skin substitute that engrafts to a viable wound bed. In the case presented here, where the viability of the underlying tissue of the amputated stumps was questionable, the artificial skin acted as an indicator of that viability. It engrafted well onto the upper extremity stumps, which were of excellent viability, but it needed to be replaced on the lower extremity stumps, which required further debridement and amputation revisions. The use of artificial skin spared the patient the immediate use of his limited and valuable autograft sites. In conclusion, Integra Artificial Skin can be a useful adjunct in the treatment of severe purpura fulminans that includes skin and extremity necrosis. PMID:9710731

Besner, G E; Klamar, J E


Occurrence of thrombosis in congenital thrombocytopenic disorders: a critical annotation of the literature.  


Patients with a low platelet count are prone to bleeding. The occurrence of a thrombotic event in congenital thrombocytopenic patients is rare and puzzling. At least nine patients with Glanzmann thrombasthenia have been reported to have had a thrombotic event, eight venous and one arterial (intracardiac, in the left ventricle). On the contrary, three patients with Bernard-Soulier syndrome have been shown to have had arterial thrombosis (myocardial infarction) but no venous thrombosis. Finally, seven patients with the familiar macrothrombocytopenia due to alterations of the MYH9 gene have been reported to have had thrombosis (five myocardial infractions, one ischemic stroke, one deep vein thrombosis and one portal vein thrombosis). The significance of these findings is discussed with particular emphasis on the discrepancy between venous and arterial thrombosis seen in patients with Glanzmann thrombasthenia and Bernard-Soulier syndrome. PMID:23037321

Girolami, Antonio; Sambado, Luisa; Bonamigo, Emanuela; Vettore, Silvia; Lombardi, Anna M



Acute ITP due to insect bite: report of 2 cases.  


Immune thrombocytopenic purpura (ITP) of childhood is a common hematologic disorder. Immune thrombocytopenic purpura is characterized by increased destruction of antibody-coated platelets in the reticuloendothelial system. In the majority of children with acute ITP, thrombocytopenia occurs within 1 to 3 weeks after an infectious disease. Immune thrombocytopenic purpura may also occur after rubella, rubeola, chickenpox, or live virus vaccination. Here we report 2 cases with acute ITP that were developed after honeybee and insect bite. PMID:20460348

Akbayram, Sinan; Akgun, Cihangir; Dogan, Murat; Caksen, Hüseyin; Oner, Ahmet Faik



Henoch-Schönlein purpura: clinicopathologic correlation of cutaneous vascular IgA deposits and the relationship to leukocytoclastic vasculitis.  


Significant cutaneous vascular IgA deposits are common in Henoch-Schönlein purpura but not in other vasculitides. The specificity for IgA vascular deposits for Henoch-Schönlein purpura is not well defined. To examine the specificity of IgA vascular deposits for this disease, we compared clinicopathologic features of 92 cases with IgA vascular deposits and a direct immunofluorescence impression of vasculitis with 90 similar cases without IgA deposits. Henoch-Schönlein purpura was diagnosed in 24% of cases with vascular IgA deposits on direct immunofluorescence examination. IgA deposits were frequent in erythema nodosum and venous stasis-related problems and in cryoglobulinemia, coagulopathic vasculopathies, and livedoid vasculitis. Of our cases, 78% exhibited vascular fluorescence with multiple conjugates. No histologic or immunofluorescence pattern alone was specific. The diagnostic specificity for Henoch-Schönlein purpura is improved if gastrointestinal involvement, upper respiratory infection, or age < 20 years is present. We propose diagnostic criteria for Henoch-Schönlein purpura incorporating clinical findings yielding sensitivity and specificity > 90%. PMID:7604640

Helander, S D; De Castro, F R; Gibson, L E



Immune Globulin Intravenous (IGIV) Indications  

Center for Biologics Evaluation and Research (CBER)

... Immune Globulins. -. Immune Globulin Intravenous (IGIV) Indications. ... B-cell Chronic Lymphocytic Leukemia; Immune Thrombocytopenic Purpura; ... More results from


Cervarix Long-term Safety Surveillance

Myositis; Guillain-Barre Syndrome; Autoimmune Thyroiditis; Multiple Sclerosis; Cutaneous Lupus; Lupus Erythematosus; Inflammatory Arthritis; Type 1 Diabetes; Central Demyelination; Dermatomyositis; Idiopathic Thrombocytopenic Purpura; Graves Disease





... Nonallergic rhinitis Trauma to the nose Less common causes of nosebleeds include: Alcohol use Hemophilia Hereditary hemorrhagic telangiectasia Idiopathic thrombocytopenic purpura (ITP) Leukemia ...


Bleeding disorders  


... XII deficiency Hemophilia A Hemophilia B Idiopathic thrombocytopenic purpura (ITP) Von Willebrand's disease (types I, II, and ... disorders: the bleeding history and differential diagnosis of purpura. In: Hoffman R, Benz EJ Jr., Shattil SJ, ...


A case of Henoch-Schönlein purpura in the elderly: not just a 'second childhood'.  


Henoch-Schönlein Purpura (HSP) is a small vessel-vasculitis that usually affects children and adolescents; its onset in adults is uncommon.We describe a case of HSP complicated with nephritis and extensive deep vein thrombosis in an 81-year-old Caucasian woman, successfully treated with oral corticosteroids. Even at the extremes of age, HSP should be considered in the differential diagnosis of leukocytoclastic vasculitis, with a particular attention to renal involvement, because of its potential morbidity and mortality in the elderly; in addition, ruling out an occult thrombotic event in course of HSP is mandatory, especially in the presence of additional thrombotic risk factors. PMID:22732439

Soriano, Alessandra; Galati, Giovanni; Vespasiani-Gentilucci, Umberto; Gallo, Paolo; de Vincentis, Antonio; Picardi, Antonio; Afeltra, Antonella



Conservative Treatment for Small Intestinal Intussusception Associated with Henoch-Schönlein's Purpura  

Microsoft Academic Search

.  \\u000a \\u000a Purpose: Emergency laparotomy is generally considered the appropriate course of action for small bowel intussusception associated\\u000a with Henoch-Sch?nlein's purpura (HSP). In this paper, we define a conservative approach after witnessing spontaneous reduction\\u000a of ileoileal invagination at laparotomy in a patient with HSP who had been on steroid therapy for renal involvement.\\u000a \\u000a \\u000a \\u000a \\u000a Methods: HSP was diagnosed by the appearance of

Kaan Sönmez; Zafer Turkyilmaz; Billur Demirogullari; Ramazan Karabulut; Yusuf Z. Aral; Öznur Konu?; A. Can Ba?aklar; Nuri Kale



Protein C and S deficiency in severe infectious purpura of children: A collaborative study of 40 cases  

Microsoft Academic Search

We studied, in 40 children (mean age: 52 months) with severe infectious purpura, the relationships between protein C (PC) and protein S (PS) levels, and shock, disseminated intravascular coagulation (DIC) and outcome. We determined, on admission, PC antigen (ELISA) and activity (chromogenic test), and total PS (ELISA). Results were expressed as % of normal adult values. Statistical analysis was performed

F. Leclerc; J. Hazelzet; B. Jude; W. Hofhuis; V. Hue; A. Martinot; E. Van der Voort



Treatment of progressive pigmented purpura with oral bioflavonoids and ascorbic acid: An open pilot study in 3 patients  

Microsoft Academic Search

Background: Bioflavonoids and ascorbic acid have been shown to increase capillary resistance and to mediate potent antioxidative radical scavenging activities. Objective: We evaluated the clinical effect of oral bioflavonoids and ascorbic acid in patients with chronic progressive pigmented purpura (PPP). Methods: In an open pilot study, oral rutoside (50 mg twice a day) and ascorbic acid (500 mg twice a

U. Reinhold; S. Seiter; S. Ugurel; W. Tilgen



[Varicella-associated purpura fulminans and deep vein thrombosis: a pediatric case report].  


Purpura fulminans (PF) and deep vein thrombosis are rare complications secondary to chicken pox disease. The presence of antibodies reflects an ongoing immunological process and requires specialized management. The present study reports a 4-year-old boy with no medical history who presented with purpura on the legs 10 days after chicken pox eruption. Laboratory tests showed a disseminated intravascular coagulation associated with low plasma protein C and S activities, and the presence of anti-protein S antibodies. A replacement therapy with protein C infusions and fresh frozen plasma was prescribed. The patient also underwent regular sessions of hyperbaric oxygen followed by the surgery. Fourteen days after the beginning of the purpuric lesions, he presented deep vein thrombosis (DVT) of the lower limbs and was treated with unfractionated heparin. This case report illustrates the pathophysiology of DVT occurring in a patient with chicken pox disease (i.e., acquired protein C and S deficiencies and anti-protein S autoantibodies) and emphasizes the utility of thrombophilia testing in order to better adapt treatment. PMID:21616651

Baur, A; Pouyau, R; Meunier, S; Nougier, C; Teyssedre, S; Javouhey, E; Floret, D; Gillet, Y



[The case of Henoch-Schönlein Purpura associated with Blastocystis hominis].  


Blastocystis hominis (B. hominis) is a parasite that often causes gastrointestinal symptoms in patients with immune deficiency and has a controversial pathogenicity in healthy people, although some symptoms are reported outside of the gastrointestinal system in healthy persons. Henoch-Schönlein Purpura (HSP) vasculitis is an acute autoimmune disease characterised by IgA storage of small vessels that is believed to include infectious factors in its aetiology. A 30-month follow-up with a boy diagnosed with HSP being treated with steroid therapy showed that he had recurrent symptoms within two days, and B. hominis was detected in the faecal analysis. His symptoms including rash, abdominal pain, and arthritis improved after treatment with steroid and co-trimaksazol. This paper is the first to present a case of HSP associated with B. hominis. PMID:23955912

Tutanç, Murat; Silfeler, Ibrahim; Ozgür, Tümay; Motor, Vicdan Köksald?; Kurto?lu, Ahmet Ibrahim



Purpura fulminans during meningococcal sepsis treated with Drotrecogin alpha. A clinical case.  


A male patient, 29 years old, was admitted to our unit with purpura fulminans, coagulation deficiency, renal failure and subsequent septic shock accompanied by respiratory insufficiency in the absence of meningeal signs. The serum levels of endogenous protein C, ATIII and calcium were well below the norm. The bacteriological examination revealed the presence of gram-negative diplococci. The onset of adult respiratory distress syndrome (ARDS) revealed aa early complication of the meningococcal sepsis. Forty-eight hours after being admitted, the recombinant protein C infusion was started at a dose of 24 microg/kg/h for the duration of 96 h. The skin lesions regressed, starting from the ecchymosis and the edema of the face, trunk and auricular pavilions. A week after the onset of the symptomatology the chest X-ray appeared clear, the renal function had normalised, and the signs of shock had disappeared. PMID:16570037

Belloni, G; Ramello, P; Salcuni, M R; Scavone, L; Girotto, M; Di Bassiano, F



Purpura and fillers: a review of pre-procedural, intra-procedural, and post-procedural considerations.  


Injectable aesthetic fillers are associated with the common and expected side effect of purpura or bruising. There are pre-procedural, intra-procedural and post-procedural considerations that can potentially minimize bruising. Traditional and newer techniques are discussed in this review and the benefits and risks of each technique will be provided.

J Drugs Dermatol. 2013;12(10):1138-1142. PMID:24085049

Schlesinger, Todd E; Cohen, Joel L; Ellison, Sarah



Henoch-Schönlein purpura following influenza vaccinations during the pandemic of influenza A (H1N1)  

Microsoft Academic Search

Although the etiology of Henoch-Schönlein purpura (HSP) remains unclear, influenza vaccinations have been implicated as possible\\u000a triggers for HSP. We describe four patients with HSP following influenza vaccinations which developed during the pandemic\\u000a of influenza A (H1N1) 2009 and review the literature concerning HSP associated with this vaccine. HSP in patients developed\\u000a in October and November, 2009. Four patients exhibited

Toru Watanabe



Prise en charge d'un purpura fulminans varicelleux : à propos d'un cas pédiatrique  

Microsoft Academic Search

The authors report a case of a 4 years old girl who had presented a chicken-pox purpura fulminans. Lesions appeared 5 days after chicken-pox start and were quickly evoluted in cutaneous and sub-cutaneous necrosis on external side of thighs and behind side of right calf. A medical management was done with fresh plasma, blood, antithrombine 3, and fibrin. Specifics treatments were done:

S. Domergue; M. Rodiere; M. Bigorre; E. Guye; G. Captier



Improvement of amyloid-related symptoms after autologous stem cell transplantation in a patient with hepatomegaly, macroglossia and purpura  

Microsoft Academic Search

AL amyloidosis was diagnosed in a 56-year-old woman with spontaneous purpura, macroglossia and hepatomegaly, a serum IgGk monoclonal gammopathy and a 25% plasma cell bone marrow infiltration. She was started on high-dose treatment consisting of four monthly cycles of VID chemotherapy, then underwent a stem cell collection after priming with cyclophosphamide + G-CSF. Myeloablative therapy was with melphalan and busulfan.

F Patriarca; A Geromin; R Fanin; D Damiani; A Sperotto; M Baccarani



A Case of Elderly-Onset Crescentic Henoch-Sch?nlein Purpura Nephritis with Hypocomplementemia and Positive MPO-ANCA  

PubMed Central

Henoch-Schönlein purpura (HSP) is common in childhood and often self-limiting. There have been limited studies on elderly-onset HSP nephritis (HSPN). A 76-yr-old man was transferred to our hospital with a 1-month history of oliguria, abdominal pain, edema and palpable purpura in the legs. Three months ago, he was admitted to another hospital with jaundice, and consequently diagnosed with early common bile duct cancer. The patient underwent a Whipple's operation. Antibiotics were administrated because of leakage in the suture from the surgery. However, he showed progressive renal failure with edema and purpura in the legs. Laboratory investigations showed serum creatinine 6.4 mg/dL, 24-hr urine protein 8,141 mg/day, myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA) 1:40 and C3 below 64.89 mg/dL. Renal biopsy showed crescentic glomerulonephritis, as well as mesangial and extracapillary Ig A deposition. We started steroid therapy and hemodialysis, but he progressed to end-stage renal failure and he has been under maintenance hemodialysis. We describe elderly onset HSPN with MPO-ANCA can be crescentic glomerulonephritis rapidly progressed to end stage renal failure.

Yu, Jung-Hee; Lee, Jae Eun; Kim, Hyang; Kim, Kyungeun; Jang, Ki-Seok; Park, Moon Hyang



Comparison of platelet counts by sysmex XE 2100 and LH-750 with the international flow reference method in thrombocytopenic patients.  


Background: There are several methods for counting platelets, of which the international flow reference method (IRM) is considered to be the gold standard. We compared the platelet count given by this method to the count given by automated analyzers using other methods, such as optical fluorescence and impedance. Aims: The aim of this study is to compare the platelet counts obtained by Sysmex XE 2100 by Impedance (Sysmex-I), optical florescence (Sysmex-O) and reported (Sysmex-R) based on the switching algorithm and LH-750 by Impedance (LH-750) with the IRM in thrombocytopenic blood samples. To calculate the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of various technologies at the clinically relevant transfusion thresholds of 10 × 10 9 /l and 20 × 10 9 /l. Materials and Methods: A total of 118 blood samples with platelet count of <50 × 10 9 /l were selected for the study. Platelet counts of all samples were analyzed by all methods using the Sysmex analyzer, LH-750 and IRM in parallel within 6 h of collection. Statistical Analysis Used: Pearson correlation, bland Altman analysis, sensitivity and specificity, PPV and NPV. Results and Conclusions: Sysmex-R had the least Bias and 95% limits of agreement (95%LA) range and thus correlated best with IRM values. LH-750 had a higher Bias compared to Sysmex-O and Sysmex-R, but a strikingly similar 95% LA ensures similar results in all three methods. In fact, in the oncology subset, it had the narrowest 95% LA, which made it the best performer in this subgroup. Of the three Sysmex results, Sysmex-I had the highest bias, widest 95% LA and highest potential risk of over transfusion. Hence, Sysmex-R and LH-750 were found to be reliable tools for estimation of platelet count in thrombocytopenic patients. PMID:24056646

Dadu, Tina; Sehgal, Kunal; Shaikh, Anjum; Khodaiji, Shanaz


Self-organizing phenomena induced by LLLT in Henoch-Schoenlein purpura  

NASA Astrophysics Data System (ADS)

Henoch-Schoenlein purpura is characterized by vasculitis of small vessels, particularly those of the skin, gastrointestinal tract, and kidney. Patients have characteristic purpuric skin rash plus all or some of the following: migratory polyarthralgias or polyarthritis, colicky abdominal pain, nephritis. Because until now there is no satisfactory treatment, we applied low level laser therapy (LLLT) in order to compare it with the classical therapy. Twenty-three children (2-15 years of age) have been treated at debut of the disease. They were randomly divided: group A (11 children) received LLLT; group B (12 children) was administrated classical therapy. Two GaAlAs diode lasers (670 nm and 830 nm) were used. The density of energy (4-8 J/cm2), irradiating frequency (2.4 Hz) was applied one session daily, using scanning technique under a special treatment protocol on cutaneous purpuric areas (20 sessions). The best results were obtained in laser group. Despite the complex medication, some patients from group B fell back into the former state after apparent improvement, and two children developed nephritis. The results could be explained by self-organization. LLLT is acting as a trigger factor causing certain systemic effects through circulating blood and a response of the entire immune system, by way of synergetic mechanisms.

Ailioaie, Laura; Ailioaie, C.



Endothelin 1 levels in relation to clinical presentation and outcome of Henoch Schonlein purpura  

PubMed Central

Background Henoch Schonlein purpura (HSP) is a common vasculitis of small vessels whereas endothelin-1 (ET-1) is usually reported elevated in vasculities and systematic inflammation. The aim of the present study was to investigate whether ET-1 levels are correlated with the clinical presentation and the outcome of HSP. Methods The study sample consisted of thirty consecutive patients with HSP. An equal number of healthy patients of similar age and the same gender were served as controls. The patients' age range was 2–12.6 years with a mean ± SD = 6.3 ± 3 years. All patients had a physical examination with a renal, and an overall clinical score. Blood and urinary biochemistry, immunology investigation, a skin biopsy and ET-1 measurements in blood and urine samples were made at presentation, 1 month later and 1 year after the appearance of HSP. The controls underwent the same investigation with the exception of skin biopsy. Results ET-1 levels in plasma and urine did not differ between patients and controls at three distinct time points. Furthermore the ET-1 were not correlated with the clinical score and renal involvement was independent from the ET-1 measurements. However, the urinary ET-1 levels were a significant predictor of the duration of the acute phase of HSP (HR = 0.98, p = 0.032, CI0.96–0.99). The ET-1 levels did not correlate with the duration of renal involvement. Conclusion Urinary ET-1 levels are a useful marker for the duration of the acute phase of HSP but not for the length of renal involvement.

Fessatou, S; Nicolaidou, P; Gourgiotis, D; Georgouli, H; Douros, K; Moustaki, M; Fretzayas, A



Performance of automated platelet quantification using different analysers in comparison with an immunological reference method in thrombocytopenic patients  

PubMed Central

Background Rapidly available and accurate platelet counts play an important role in the evaluation of haemorrhagic status and in assessing the need for platelet transfusions. We, therefore, evaluated platelet counting performance of haematology analysers using optical, impedance and immunological methods in thrombocytopenic patients. Materials and Methods We considered 99 patients with a platelet (plt) count under 50x109 plt/L. We compared the platelet counts obtained using ADVIA 2120 (optical method), Cell-Dyn Sapphire (optical, impedance and immunological methods with CD61) and a reference, double staining (CD41+CD61) immunological method. Results The platelet counts of all the considered methods showed good correlation with those of the reference method, despite an overestimation in platelet quantification. The degree of inaccuracy was greater for platelet counts under 20 x109 plt/L. Conclusions Clinicians who use platelet thresholds below 20 x109 plt/L for making clinical decisions must be aware of the limitations in precision and accuracy of cell counters at this level of platelet count. Inaccurate counts of low platelet numbers could create problems if attempts are made to reduce the threshold below 20x109 plt/L.

Trabuio, Ernesto; Valverde, Sara; Antico, Francesco; Manoni, Fabio; Gessoni, Gianluca



Vitamin k deficiency bleeding presenting as nodular purpura in infancy: a rare and life-threatening entity.  


Vitamin K deficiency bleeding (VKDB) disorder is an uncommon entity, which occurs due to inadequate activity of vitamin K-dependant coagulation factors. An 8-months-old exclusively breast-fed male infant presented with multiple, purpuric and nodular non-collapsible swellings on trunk of 4 days duration. Investigations revealed raised activated partial thromboplastin time and prothrombintime. Fibrinogen level and platelet counts were normal. Late VKDB usually presents as intra-cranial or mucosal hemorrhages.([1]) Though skin and mucosal bleeding may occur in 1/3(rd) of infants with VKDB, 'nodular purpura' is not the common presenting feature. Earlier recognition of VKDB and immediate investigation/treatment helps prevent the potentially fatal outcome of the disease. Very little is mentioned about this entity in dermatology literature. PMID:24082204

Gahalaut, Pratik; Chauhan, Sandhya



Improvement of amyloid-related symptoms after autologous stem cell transplantation in a patient with hepatomegaly, macroglossia and purpura.  


AL amyloidosis was diagnosed in a 56-year-old woman with spontaneous purpura, macroglossia and hepatomegaly, a serum IgGk monoclonal gammopathy and a 25% plasma cell bone marrow infiltration. She was started on high-dose treatment consisting of four monthly cycles of VID chemotherapy, then underwent a stem cell collection after priming with cyclophosphamide + G-CSF. Myeloablative therapy was with melphalan and busulfan. Hematologic recovery was fast and uncomplicated. At follow-up 22 months from ASCT, the patient shows a complete remission of the clonal plasma cell disorder, normalization of liver size and alkaline phosphatase level and a significant improvement in the signs of vascular and soft tissue amyloid infiltration. PMID:10467336

Patriarca, F; Geromin, A; Fanin, R; Damiani, D; Sperotto, A; Baccarani, M



Expression of acid-sensing ion channels of gastric mucosa from patients with Henoch-Schönlein purpura.  


Acid-sensing ion channels (ASICs) are members of the voltage-insensitive, amiloride-sensitive degenerin/epithelial Na channel family of cation channels and have been shown to mediate pain associated with tissue acidosis after inflammation or injury; however, the expression and role of ASICs in gastrointestinal tract of Henoch-Schönlein purpura (HSP) patients were still uncertain. The present study was designed to examine the expression and localization of ASICs in gastric mucosa from patients with HSP using immunochemical techniques. The results showed that there was a significant increase in the mean relative optical density of ASIC2 and ASIC3 but not ASIC1a in the lining epithelium and glandular tubes of gastric mucosa from HSP patients with HSP. This finding suggested that ASICs may be related to the pathogenesis of gastrointestinal manifestations in patients with HSP. PMID:22157923

Yuan, Li-ping; Bo, Yan; Ming, Gui; Zhou, Qi-lian



A novel mutation c.1048A>T at codon 350(Lys>Stop) in PROC gene causing neonatal purpura fulminans.  


Purpura fulminans in the neonatal period due to severe congenital protein C deficiency (protein?C activity <1?IU/dl) is a rare autosomal recessive disorder. If untreated, it is fatal. Early identification of such patients may be lifesaving. Acquired deficiency of protein C caused by increased consumption as overt disseminated intravascular coagulation (DIC) and severe infection creates a diagnostic dilemma. Mutation analysis plays a critical role in confirming the diagnosis of the disease and offering prenatal diagnosis. In this report, we describe a newborn who presented with purpura fulminans and DIC, molecular analysis showed a novel c.1048A>T transversion in a homozygous state at codon 350 (Lys>Stop) of protein C (PROC) gene. Prenatal diagnosis in subsequent pregnancy was done which revealed the affected fetus had the same mutation in homozygous form. PMID:24158118

Jain, Rakhi; T, Leenath; Chandran, Jolly; Jayandharan, Giridhara R; Palle, Arpana; Moses, Prabhakar D



Drotrecogin alfa (activated) in patients with severe sepsis presenting with purpura fulminans, meningitis, or meningococcal disease: a retrospective analysis of patients enrolled in recent clinical studies  

Microsoft Academic Search

INTRODUCTION: We report data from adult and pediatric patients with severe sepsis from studies evaluating drotrecogin alfa (activated) (DrotAA) and presenting with purpura fulminans (PF), meningitis (MEN), or meningococcal disease (MD) (PF\\/MEN\\/MD). Such conditions may be associated with an increased bleeding risk but occur in a relatively small proportion of patients presenting with severe sepsis; pooling data across clinical trials

Jean-Louis Vincent; Simon Nadel; Demetrios J Kutsogiannis; RT Noel Gibney; S Betty Yan; Virginia L Wyss; Joan E Bailey; Carol L Mitchell; Samiha Sarwat; Stephen M Shinall; Jonathan M Janes



Are there specific haemostatic abnormalities in children surviving septic shock with purpura and having skin necrosis or limb ischaemia that need skin grafts or limb amputations?  

Microsoft Academic Search

More than 10% of children surviving septic shock with purpura have skin necrosis or limb ischaemia (SNLI.). Among 44 children\\u000a consecutively admitted to our pediatric intensive care unit, 35 (80%) survived, 6 of them (17%) developed SNLI (defined as\\u000a the need of a surgical procedure). Two timed haemostasis measurements included the determination of coagulation factors, protein\\u000a C (PC), protein S

R. Cremer; F. Leclerc; B. Jude; A. Sadik; S. Leteurtre; C. Fourier; A. Martinot; J. F. Diependaele



Microcirculatory Disturbances and Human Myocardial Infarction.  

National Technical Information Service (NTIS)

Thirty-nine cases of thrombotic thrombocytopenic purpura (Moschcowitz's disease) were examined, and the severe, obstructive involvement of the intramyocardial arterial branches was compared to the myocardial condition. In only 4 cases (10.2 per cent) was ...

G. Baroldi W. C. Manion



Haematology and neurology  

Microsoft Academic Search

This review aims to update the reader on advances in the understanding of haematological conditions that may arise in neurological practice. Thrombophilia, antiphospholipid antibody syndrome, thrombotic thrombocytopenic purpura, sickle cell and clonal disorders associated with neuropathy are discussed.

Steven Austin; Hannah Cohen; Nick Losseff



Medical Journal. Volume 92, Number 1, 1970.  

National Technical Information Service (NTIS)

Contents: The immunology of tumors; The appearance of antigamma globulin in acute glomerulonephritis and some other diseases in childhood; Generalized lupus erythematosus - A diagnostic problem; Megakaryocytic thrombocytopenic purpura (A report on 56 case...



Rhophylac® Rh0(D) Immune Globulin Intravenous (Human) ...  

Center for Biologics Evaluation and Research (CBER)

Text Version... A multicenter study of the treatment of childhood chronic idiopathic thrombocytopenic purpura with anti-D. J Pediatr. 1992;120:522-5277. ... More results from




... such as idiopathic thrombocytopenic purpura (ITP), polycythemia vera, thalassemia and sickle cell anemia, may require splenectomy. But ... lymphoma (Hodgkin's disease) Polycythemia vera Sickle cell anemia Thalassemia General anesthesia Related Guides References Splenomegaly. The Merck ...



Center for Biologics Evaluation and Research (CBER)

Text Version... disease K – Idiopathic Thrombocytopenic Purpura (ITP) PD-12-40 Risk factors associated with Creutzfeldt-Jakob Disease - brain surgery PD-12-41 ... More results from


Meningococcal septicaemia and purpura fulminans in children - surgical management and outcome: a 22 year review of 68 patients Rode H, FCS (SA) FRCS(Ed) • Millar AJW, FRCS (Eng) (Ed) FRACSArgent A, FCPAEDS (SA) MMed (Paed) • Hudson D, FCS (SA) FRCS (Eng) • Davies J, FC PATH (SA)  

Microsoft Academic Search

Meningococcal septicaemia complicated by purpura fulminans remains a devastating illness with rapid onset, debilitating morbidity and high mortality. The clinical course of management of 68 children (average age 3.4 years) with purpura fulminans seen over a 22 year period is described. All patients received maximum systemic support. Standard surgical techniques were utilised for skin grafting and amputations. Overall mortality was

Rode H; Argent A; Hudson D; Davies J


Adhesion of Neisseria meningitidis to Dermal Vessels Leads to Local Vascular Damage and Purpura in a Humanized Mouse Model  

PubMed Central

Septic shock caused by Neisseria meningitidis is typically rapidly evolving and often fatal despite antibiotic therapy. Further understanding of the mechanisms underlying the disease is necessary to reduce fatality rates. Postmortem samples from the characteristic purpuric rashes of the infection show bacterial aggregates in close association with microvessel endothelium but the species specificity of N. meningitidis has previously hindered the development of an in vivo model to study the role of adhesion on disease progression. Here we introduced human dermal microvessels into SCID/Beige mice by xenografting human skin. Bacteria injected intravenously exclusively associated with the human vessel endothelium in the skin graft. Infection was accompanied by a potent inflammatory response with the secretion of human inflammatory cytokines and recruitment of inflammatory cells. Importantly, infection also led to local vascular damage with hemostasis, thrombosis, vascular leakage and finally purpura in the grafted skin, replicating the clinical presentation for the first time in an animal model. The adhesive properties of the type IV pili of N. meningitidis were found to be the main mediator of association with the dermal microvessels in vivo. Bacterial mutants with altered type IV pili function also did not trigger inflammation or lead to vascular damage. This work demonstrates that local type IV pili mediated adhesion of N. meningitidis to the vascular wall, as opposed to circulating bacteria, determines vascular dysfunction in meningococcemia.

Melican, Keira; Michea Veloso, Paula; Martin, Tiffany; Bruneval, Patrick; Dumenil, Guillaume



Limb fitting for quadruple amputees: Report of two cases of symmetrical peripheral gangrene caused by pneumococcal purpura fulminans.  


Background:We report our experiences of prosthetic fitting in quadruple amputees. Two patients underwent quadruple amputation after suffering from disseminated intravascular coagulation in conjunction with pneumococcemia with purpura fulminans.Case description and methods:The first patient, a 52-year-old man, underwent bilateral transradial, left transtibial, and right transfemoral amputation, and the second patient, a 62-year-old man, underwent bilateral transradial and bilateral transfemoral amputation, both for symmetrical peripheral gangrene subsequent to septic shock.Findings and outcomes:The amputations were accompanied by skin damage due to ischemic tissue changes both on the stumps and on the nose and/or lips. The combination of the intensive prosthetic rehabilitation program and supportive medical care led to completely independent functioning, including driving a car, with the use of four prosthetic limbs and a wheelchair in both cases.Conclusion:Early initiation of a multidisciplinary approach can properly address impairments and minimize future disability.Clinical relevanceWe have reported our experience of limb fitting in two patients who had undergone quadruple amputation after suffering peripheral gangrene. Appropriate limb fitting that provides support in daily activities can address impairments and minimize disability. PMID:23558402

Yoshimoto, Kenji; Okuma, Yusuke; Nakamura, Takashi; Mita, Tomoki; Mitsumoto, Atsuko; Yamasaki, Nobuya; Tobimatsu, Yoshiko; Akai, Masami



Efficacy of HPA-1a (PlA1)-negative platelets in a patient with post-transfusion purpura.  


Post-transfusion purpura (PTP) is a rare form of alloimmune thrombocytopenia that is self-limited but which carries a 10-15% mortality related to fatal hemorrhage. Immunomodulatory therapies such as plasmapheresis and intravenous immunoglobulin G (IVIg) can shorten the duration of thrombocytopenia. However, in a bleeding patient with PTP, more urgent therapy may be required. Textbooks of hematology [1-3] as well as reports in the literature [4,5] suggest that patients do not respond to platelet transfusions. We report a case of PTP in a patient homozygous for HPA-1b who suffered an intracranial hemorrhage. The patient was treated with IVIg and plasmapheresis. Because of her life-threatening bleeding, we also transfused the patient with HPA-1a-negative platelets. These transfusions consistently resulted in transient improvements in her platelet counts and may have limited the degree of intracranial bleeding. Our experience suggests that transfusion of platelets that lack the offending epitope in patients with PTP may be efficacious. PMID:15224362

Loren, Alison Wakoff; Abrams, Charles S



Circulating adhesion molecules ICAM-1, E-selectin, and von Willebrand factor in Henoch-Sch?nlein purpura.  

PubMed Central

Adhesion molecules play an important part in leucocyte transendothelial migration and thus may provide a useful marker of surface expression at inflammatory sites. In 20 patients with Henoch-Schönlein purpura serum intercellular adhesion molecule 1 (ICAM-1), E-selectin, and plasma von Willebrand factor (vWF) were determined by ELISA during the active and inactive phase of the disease. Twelve healthy children were studied as a control group. Serum ICAM-1 concentrations increased during the active phase of the disease and differed significantly compared with the inactive phase (p < 0.05). However ICAM-1 in the active phase did not differ significantly compared with controls (p = 0.08). Serum E-selectin concentrations did not differ in the active and inactive phase of the disease. By contrast, vWF increased in the active phase of the disease and differed significantly compared with inactive disease and control groups (p < 0.01). Considering the adhesion molecules and vWF, only vWF correlated well with the C reactive protein measurement in the active phase, which is considered a good marker of disease activity. These data suggest that plasma vWF is a good marker of vascular inflammation and endothelial damage. Circulating ICAM-1 might be an additional parameter in some of the patients.

Soylemezoglu, O; Sultan, N; Gursel, T; Buyan, N; Hasanoglu, E



Sputter target  


The disclosure relates to an improved sputter target for use in the deposition of hard coatings. An exemplary target is given wherein titanium diboride is brazed to a tantalum backing plate using a gold-palladium-nickel braze alloy.

Gates, Willard G. (Kansas City, MO); Hale, Gerald J. (Overland Park, KS)



Autologous Peripheral Blood Stem Cell Transplantation in Patients With Life Threatening Autoimmune Diseases

Purpura, Schoenlein-Henoch; Graft Versus Host Disease; Anemia, Hemolytic, Autoimmune; Rheumatoid Arthritis; Churg-Strauss Syndrome; Hypersensitivity Vasculitis; Wegener's Granulomatosis; Systemic Lupus Erythematosus; Giant Cell Arteritis; Pure Red Cell Aplasia; Juvenile Rheumatoid Arthritis; Polyarteritis Nodosa; Autoimmune Thrombocytopenic Purpura; Takayasu Arteritis



Similar disturbances in B cell activity and regulatory T cell function in Henoch-Schonlein purpura and systemic lupus erythematosus  

SciTech Connect

The immunoglobulin synthesizing activities of peripheral mononuclear cells (MNC) from five patients with Henoch-Schonlein purpura (HSP) and eight patients with active systemic lupus erythematosus (SLE) were compared. Cumulative amounts of IgM, IgG, and IgA synthesized and secreted by unstimulated and PWM-stimulated patient cells over a 12-day period were determied in a solid-phase radioimmunoassay. In unstimulated control cultures mean rates of IgM, IgG, and IgA synthesis were less than 250 ng/ml. The synthetic activities of patient MNC were markedly increased. In HSP cultures IgA was the major immunoglobulin class produced (2810 x/divide 1.33 ng/ml) followed by IgG (1754 x/divide 1.32 ng/ml) and IgM (404 x/divide 1.16 ng/ml). In SLE cultures IgA and IgG syntheses were equally elevated (4427 x/divide 1.20 and 4438 x/divide 1.49 ng/ml, respectively) whereas IgM synthesis averaged 967 x/divide 1.66 ng/ml. PWM stimulation of pateient MNC caused a sharp decline in the synthesis of all three immunoglobulin classes. After T cell depletion B cell-enriched fractions from HSP and SLE patients maintained high levels of IgA and IgG synthesis that were inhibited by PWM and by normal allogeneic but not autologous T cells. In PWM-stimulted co-cultures, patient T cells nonspecifically suppressed the synthetic activities of autologous and control B cells. in contrast patient B cells achieved normal levels of immunoglobulin synthesis when cultured with control T cells plus PWM. In longitudinal studies patient B and T cell disturbances persisted despite clinical improvement.

Beale, M.G. (St. Louis Children's Hospital, MO); Nash, G.S.; Bertovich, M.J.; MacDermott, R.P.



Studies on the HLA Class-II Antigens of a Patient Presenting a Double Alloimmunization Following Posttransfusion Purpura.  


In the Caucasian population, platelet incompatibility within the HPA-1 (Pl(A1/A2)) and HPA-5 (Br(a/b)) alloantigen systems are the two most likely causes of post-transfusion purpura (PTP) and neonatal alloimmune thrombocytopenia. However, the way in which HLA (class-II) antigens participate in alloantibody formation is unclear. The patient (M-J.G.) is a middle aged woman with two children who developed a severe PTP (< 2000 platelets/µ1) 8 days after receiving red cell concentrates during coronary bypass surgery. During treatment with intravenous gamma-globulin and corticosteroids, her platelet count peaked, fell again, and returned to normal over a period of several months. Western blotting and/or the monoclonal antibody specific-immobilization of platelet antigens (MAIPA) assay performed with serum prepared at the height of her initial thrombocytopenia revealed antibodies to both the Pl(A1) and the Br(a) alloantigens. This rare combination prompted us to study the expression of specific HLA class II antigens in the patient. HLA-DR and DQ typing was performed from genomic DNA by the recently developed polymerase chain reaction-restriction fragment length polymorphism procedure (PCR-RFLP). The patient was found to express the DRB1*1302/1303 and DRB3*0101/0301 alleles (serological specificities: HLA-DR6 and DR52a/c respectively). She also expressed the DQA1*0102/0501, DQB1*0601 and DQB1*0301 alleles. Thus, this case provides further evidence linking an immune response to Pl(A1) and Br(a) antigens with HLA-DR52a/c and DR6. PMID:21043601

Jallu, V; Merel, P; Morel-Kopp, M C; Comeau, F; Pigeonnier, V; Vezon, G; Kaplan, C; Hourdillé, P; Nurden, A T



Palpable purpura complicated by streptococcal toxic shock syndrome resulting in limb necrosis and amputation: a case of levamisole and cocaine coingestion.  


Palpable purpura resulting from cocaine and levamisole coingestion has been reported with increasing frequency over the last several years as distribution of this drug combination becomes more universal. Toxicity from ingestion of this dangerous combination is difficult to diagnose due to the multitude of possible clinical presentations, variety of possible adulterants, and elusive nature of levamisole given its short half-life and limited availability of detection methods. Levamisole is a chemotherapeutic and immunomodulatory agent currently marketed as a veterinary anthelmintic. We describe the case of a 48-year-old woman admitted to our intensive care unit with a diagnosis of streptococcal toxic shock syndrome (STSS), confirmed from fluid taken from an elbow lesion that grew Streptococcus pyogenes. She was noted to have bullae of the elbow and diffuse purpura with necrotic centers covering a large portion of her body (trunk, legs, arms, back, toes, fingers, and tip of nose). On further evaluation, she was found to have ingested levamisole-tainted cocaine. The patient's complications related to either cocaine and levamisole coingestion or STSS included thrombocytopenia, acute renal failure, and limb necrosis. Thrombocytopenia gradually improved upon treatment with prednisone, and acute renal failure improved with intravenous fluid resuscitation; however, she subsequently required several appendage amputations due to severe gangrene. Clinicians must have high suspicion for ingestion of this drug combination and request prompt testing of urine samples for levamisole if a patient who admits to illicit drug use presents with purpuric or necrotic skin lesions. PMID:22392427

Freyer, Craig W; Peters, Michael



Sputter target  

Microsoft Academic Search

The disclosure relates to an improved sputter target for use in the deposition of hard coatings. An exemplary target is given wherein titanium diboride is brazed to a tantalum backing plate using a gold-palladium-nickel braze alloy. 8 claims.

W. G. Gates; G. J. Hale



Sputter target  

Microsoft Academic Search

The disclosure relates to an improved sputter target for use in the deposition of hard coatings. An exemplary target is given wherein titanium diboride is brazed to a tantalum backing plate using a gold-palladium-nickel braze alloy. 1 fig.

W. G. Gates; G. J. Hale



Sputter target  

SciTech Connect

The disclosure relates to an improved sputter target for use in the deposition of hard coatings. An exemplary target is given wherein titanium diboride is brazed to a tantalum backing plate using a gold-palladium-nickel braze alloy. 1 fig.

Gates, W.G.; Hale, G.J.



Sputter target  

SciTech Connect

The disclosure relates to an improved sputter target for use in the deposition of hard coatings. An exemplary target is given wherein titanium diboride is brazed to a tantalum backing plate using a gold-palladium-nickel braze alloy. 8 claims.

Gates, W.G.; Hale, G.J.



Antigen and substrate withdrawal in the management of autoimmune thrombotic disorders.  


Prevailing approaches to manage autoimmune thrombotic disorders, such as heparin-induced thrombocytopenia, antiphospholipid syndrome and thrombotic thrombocytopenic purpura, include immunosuppression and systemic anticoagulation, though neither provides optimal outcome for many patients. A different approach is suggested by the concurrence of autoantibodies and their antigenic targets in the absence of clinical disease, such as platelet factor 4 in heparin-induced thrombocytopenia and ?(2)-glycoprotein-I (?(2)GPI) in antiphospholipid syndrome. The presence of autoantibodies in the absence of disease suggests that conformational changes or other alterations in endogenous protein autoantigens are required for recognition by pathogenic autoantibodies. In thrombotic thrombocytopenic purpura, the clinical impact of ADAMTS13 deficiency caused by autoantibodies likely depends on the balance between residual antigen, that is, enzyme activity, and demand imposed by local genesis of ultralarge multimers of von Willebrand factor. A corollary of these concepts is that disrupting platelet factor 4 and ?(2)GPI conformation (or ultralarge multimer of von Willebrand factor oligomerization or function) might provide a disease-targeted approach to prevent thrombosis without systemic anticoagulation or immunosuppression. Validation of this approach requires a deeper understanding of how seemingly normal host proteins become antigenic or undergo changes that increase antibody avidity, and how they can be altered to retain adaptive functions while shedding epitopes prone to elicit harmful autoimmunity. PMID:22966172

Cines, Douglas B; McCrae, Keith R; Zheng, X Long; Sachais, Bruce S; Luning Prak, Eline T; Siegel, Don L



Targeted Metabolomics  

PubMed Central

The metabolome is the terminal downstream product of the genome and consists of the total complement of all the low molecular weight molecules (metabolites) in a cell, tissue or organism. Metabolomics aims to measure a wide breadth of small molecules in the context of physiological stimuli or in disease states. Metabolomics methodologies fall into two distinct groups; untargeted metabolomics, an intended comprehensive analysis of all the measurable analytes in a sample including chemical unknowns, and targeted metabolomics, the measurement of defined groups of chemically characterized and biochemically annotated metabolites. The methodologies considered in this unit focus on the processes of conducting targeted metabolomics experiments, and the advantages of this general approach are highlighted herein. This unit outlines the procedures for extracting nitrogenous metabolites, including the amino acids, lipids, and intermediary metabolites, including the TCA cycle oxoacids, from blood plasma. Specifically, protocols for the analysis of these metabolites using liquid chromatography-mass spectrometry-based targeted metabolomics experiments is discussed.

Roberts, Lee D.; Souza, Amanda L.; Gerszten, Robert E.; Clish, Clary B.



Successful use of recombinant factor VIIa in a child with Schoenlein-Henoch purpura presenting with compartment syndrome and severe factor XIII deficiency.  


In this article, we present a 7-year-old boy with Schoenlein-Henoch purpura (HSP) presented with compartment syndrome and factor XIII deficiency and treated with recombinant factor VIIa and fasciotomy. Treatment decisions for patients with HSP presenting with compartment syndrome should be made on a case-by-case basis. Factor XIII deficiency should be in mind in these patients. The use of recombinant factor VIIa might be effective and well tolerated for treating hemorrhage in patients with HSP and compartment syndrome. Surgical treatment should be preferred in patients with compartment syndrome. However, in patients who have a coagulation defect, the first priority is to correct the clotting deficiency. The use of recombinant factor VIIa is a treatment option for children who develop compartment syndrome due to a coagulation defect. PMID:23103728

Alioglu, Bulent; Ozsoy, M Hakan; Tapci, Esra; Karamercan, Sirma; Agras, Pinar I; Dallar, Yildiz



Lack of association between macrophage migration inhibitory factor gene promoter (-173 G/C) polymorphism and childhood Henoch-Schönlein purpura in Turkish patients.  


Henoch-Schönlein purpura (HSP) is a small-vessel vasculitis of autoimmune hypersensitivity with rash, arthritis, abdominal pain and renal involvements. Macrophage migration inhibitory factor (MIF) is a immunoregulatory proinflammatory cytokine, and a major mediator at the inflammatory sites. The pathogenesis of HSP has not been fully elucidated. Here we aimed to assess the influence of macrophage migration inhibitory factor gene (-173 G/C) polymorphism in the susceptibility and clinical expression of patients with Henoch-Schönlein purpura (HSP). HSP patients (n:139) and ethnically matched healthy controls (n:100) were genotyped by PCR-RFLP. Genotype analysis of both polymorphisms did not reveal a significant deviation from Hardy-Weinberg equilibrium in any group (p > 0.05). No significant difference was obtained in genotype distribution (p > 0.05) and allele frequencies (p > 0.05) between patients and controls. A statistically significant genotype-phenotype correlation was not obtained when HSP patients were stratified by the presence of certain systemic complications and the macrophage migration inhibitory factor gene (-173 G/C) polymorphism (p > 0.05). A significant risk was not observed in the subjects both with the GC+CC genotype (p = 0.06, OR: 0.5538, 95% CI: 0.2985-1.0274) and C allele (odds ratio: C vs. G: 1.799, 95% CI: 1.002-3.23, p = 0.05). Our findings suggest that MIF gene -173 G/C polymorphism is not associated with HSP in the present Turkish population. PMID:23523092

Nalbantoglu, Sinem; Tabel, Y?lmaz; Mir, Sevgi; Berdeli, Afig



Targeting Women  

Microsoft Academic Search

Over the past three decades, numerous studies have examined the portrayal of women in advertisements. This issue is of vital interest to marketers who are developing Segmentation strategies with women as targets. The study described here provides an updated assessment of this portrayal. The study utilized a content analysis of magazine advertisements to determine if a sample of females were

Robin T. Peterson



Target assembly  


A target for a proton beam which is capable of generating neutrons for absorption in a breeding blanket includes a plurality of solid pins formed of a neutron emissive target material disposed parallel to the path of the beam and which are arranged axially in a plurality of layers so that pins in each layer are offset with respect to pins in all other layers, enough layers being used so that each proton in the beam will strike at least one pin with means being provided to cool the pins. For a 300 mA, 1 GeV beam (300 MW), stainless steel pins, 12 inches long and 0.23 inches in diameter are arranged in triangular array in six layers with one sixth of the pins in each layer, the number of pins being such that the entire cross sectional area of the beam is covered by the pins with minimum overlap of pins.

Lewis, Richard A. (Falls Church, VA)



On Target  

NSDL National Science Digital Library

In this design challenge activity, learners modify a cup so it can carry a marble down a zip line and also drop it onto a target. Learners are encouraged to brainstorm answers to design questions, build a prototype using simple materials, and test, evaluate, and redesign their structure. The activity guide includes troubleshooting tips. The related Leader's Notes guide contains information on how to connect this to NASA and aerospace engineering.




Unilateral lower leg purpura.  


We present a case of an extensive, purpuric eruption on the lower leg with peculiar clinical findings in 55-year-old woman with rheumatoid arthritis. The purpuric lesions were present unilaterally on the left lower leg, where prominent varices and telangiectasia were noted. Histological examination revealed a perivascular infiltration of lymphocytic cells and eosinophils and extravasation of erythrocytes in the upper and middle dermis. There was no evidence of vasculitis. The eruption responded well to treatment with hemostatic agents and elastic stockings. Based on the clinical and histological findings, we concluded that the main pathophysiology of the purpuric eruption is an extravasation of erythrocytes related to increased venous pressure secondary to venous stasis. PMID:23374958

Ogawa, Satoshi; Oka, Masahiro; Kunisada, Makoto; Nishigori, Chikako



PlayStation purpura.  


A 16-year-old boy presented with a number of asymptomatic pigmented macules on the volar aspect of his index fingers. Dermoscopy of each macule revealed a parallel ridge pattern of homogenous reddish-brown pigment. We propose that these lesions were induced by repetitive trauma from a Sony PlayStation 3 (Sony Corporation, Tokyo, Japan) vibration feedback controller. The lesions completely resolved following abstinence from gaming over a number of weeks. Although the parallel ridge pattern is typically the hallmark for early acral lentiginous melanoma, it may be observed in a limited number of benign entities, including subcorneal haematoma. PMID:20695869

Robertson, Susan J; Leonard, Jane; Chamberlain, Alex J



Henoch-Schönlein Purpura  


... treatments called dialysis or a kidney transplant. 1 McCarthy JH, Tizard EJ. Clinical practice: diagnosis and management ... Pan, M.D.; William Primack, M.D.; and Michael Somers, M.D. You may also find additional ...


Analysis of Pathogen-Host Cell Interactions in Purpura Fulminans: Expression of Capsule, Type IV Pili, and PorA by Neisseria meningitidis In Vivo  

PubMed Central

The pattern of meningococcal surface structure expression in different microenvironments following bloodstream invasion in vivo is not known. We used immunohistochemistry to determine the expression of capsule, type IV pili, and PorA by meningococci residing in the skin lesions of children with purpura fulminans. All the skin biopsy samples showed evidence of thrombosis and, frequently, a perivascular inflammatory cell infiltrate consisting of neutrophils (elastase positive) and monocytes/macrophages (CD68 positive). Modified Gram staining revealed 20 to over 100 gram-negative diplococci in each 4-?m-thick section, usually grouped into microcolonies. Immunoperoxidase staining demonstrated that the invading meningococci expressed PorA, capsule, and type IV pilin. Expression of these antigens was not restricted to any particular environment and was found in association with meningococci located in leukocytes, small blood vessels, and the dermal interstitium. Confocal laser scanning microscopy demonstrated coexpression of pilin and capsule by numerous microcolonies. However, there was some discordance in capsule and pilin expression within the microcolonies, suggesting phase variation. The strategy employed in this study will be helpful in investigating invasive bacterial diseases where antigenic and phase variation has a significant impact on virulence and on vaccine design.

Harrison, O. B.; Robertson, B. D.; Faust, S. N.; Jepson, M. A.; Goldin, R. D.; Levin, M.; Heyderman, R. S.



Aberrant glycosylation of IgA1 is inherited in both pediatric IgA nephropathy and Henoch-Schönlein purpura nephritis.  


Serum galactose-deficient immunoglobulin A1 (Gd-IgA1) is an inherited risk factor for adult IgA nephropathy (IgAN). In this paper, we determined the heritability of serum Gd-IgA1 levels in children with IgAN and Henoch-Schönlein purpura nephritis (HSPN), two disorders with clinical phenotypes sharing common pathogenic mechanisms. Serum Gd-IgA1 concentrations were quantified using a Helix aspersa-lectin-based enzyme-linked immunosorbent assay. As a group, 34 children with either disorder (20 with HSPN and 14 with IgAN) had significantly higher Gd-IgA1 levels compared with 51 age- and ethnicity-matched pediatric controls. Serum levels of Gd-IgA1 were also elevated in a large fraction of 54 first-degree relatives of pediatric IgAN and HSPN patients compared with 141 unrelated healthy adult controls. A unilineal transmission of the trait was found in 17, bilineal transmission in 1, and sporadic occurrence in 5 of 23 families when both parents and the patient were analyzed. There was a significant age-, gender-, and household-adjusted heritability of serum galactose-deficient IgA1 estimated at 76% in pediatric IgAN and at 64% in HSPN patients. Thus, serum galactose-deficient IgA1 levels are highly inherited in pediatric patients with IgAN and HSPN, providing support for another shared pathogenic link between these disorders. PMID:21326171

Kiryluk, Krzysztof; Moldoveanu, Zina; Sanders, John T; Eison, T Matthew; Suzuki, Hitoshi; Julian, Bruce A; Novak, Jan; Gharavi, Ali G; Wyatt, Robert J



Serum levels of galactose-deficient IgA in children with IgA nephropathy and Henoch-Schönlein purpura.  


IgA nephropathy and Henoch-Schönlein purpura nephritis (HSPN) are related diseases characterized by deposits of IgA1-containing immune complexes in the renal mesangium. Adult patients with IgA nephropathy have aberrantly glycosylated IgA1 (galactose-deficient O-linked glycans) in the circulation and renal deposits. However, IgA1 glycosylation has not been studied in pediatric patients with IgA nephropathy. Using our quantitative lectin enzyme-linked immunosorbent assay (ELISA) test, we measured serum levels of galactose-deficient IgA1 of children with IgA nephropathy and HSPN and controls. Children with IgA nephropathy and HSPN had serum levels higher than those of healthy children or renal-disease controls with C1q nephropathy. Furthermore, lectin ELISA identified patients with HSPN whose clinical course mimicked that of IgA nephropathy. In summary, pediatric patients with IgA nephropathy and HSPN have an aberrancy in the glycosylation in IgA1 O-linked glycans that is similar to that in adults with IgA nephropathy. PMID:17943324

Lau, Keith K; Wyatt, Robert J; Moldoveanu, Zina; Tomana, Milan; Julian, Bruce A; Hogg, Ronald J; Lee, Jeannette Y; Huang, Wen-Qiang; Mestecky, Jiri; Novak, Jan



A study on the association between C1GALT1 polymorphisms and the risk of Henoch-Schönlein purpura in a Chinese population.  


Henoch-Schönlein purpura (HSP) is the most common systemic vasculitis of childhood. The molecular etiology of HSP is not well understood. The purpose of this study is to investigate the association between polymorphisms in C1GALT1 gene and the risk of HSP in a Chinese population. A total of unrelated 542 northern Chinese were enrolled in this study. PCR-RFLP method was used to genotype the five tagging SNPs in the C1GALT1 gene. Chi-squared test and logistic regression analysis were used for the comparison of genotype distribution between cases and controls. The five tagging SNPs were all in Hardy-Weinberg equilibrium in controls. SNP7 was significantly associated with HSP risk, P = 0.005. The DI genotype, compared with the DD genotype, was associated with a significantly higher risk of developing HSP (OR 1.72; 95 % CI 1.11-2.67). The II genotype, compared with the DD genotype, was associated with a significantly higher risk of developing HSP (OR 3.39; 95 % CI 1.16-9.30). Other SNPs were not associated with HSP risk. Variations in the C1GALT1 gene were found to be associated with HSP risk. Further studies are warranted to validate our findings and to investigate into its underlining mechanism. PMID:23624553

An, Jindan; Lü, Qiang; Zhao, Hongtao; Cao, Yong; Yan, Bin; Ma, Zhihong



Endothelial cells and thrombotic microangiopathy.  


Thrombotic microangiopathy represents the clinical picture of thrombocytopenia and hemolytic anemia in the setting of small blood vessel thrombosis, accompanied by varying degrees of organ dysfunction. Well known to both nephrologists and hematologists alike, among the most common and best-studied thrombotic microangiopathy are hemolytic-uremic syndrome and thrombotic thrombocytopenic purpura. Despite sharing a strong clinical and historical relationship, these disorders represent distinct clinical and pathophysiological entities. This article reviews recent progress into the pathogenesis of thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome, focusing on events taking place at the endothelial surface. PMID:22617770

Motto, David



Tuberculose pulmonaire r?v?l?e par un purpura thrombop?nique chez l'enfant-? propos d'un cas clinique observ? au service de p?diatrie des Cliniques Universitaires de Lubumbashi  

PubMed Central

Nous rapportons le cas d'un enfant de 7 ans, de sexe masculin ayant présenté un purpura thrombopénique avec épistaxis, hématémèse, otorragies et pétéchies généralisées. Durant la même hospitalisation, nous avons mis en évidence une tuberculose pulmonaire documentée par la présence de bacilles acido-alcoolo résistants à l'examen des crachats. Nous avons observé une majoration du taux de plaquettes en une semaine de corticothérapie intraveineuse à haute dose, avant l'instauration d'une poly chimiothérapie antituberculeuse. Nous rappelons également la controverse que suscite la prise en charge de cette association rarement rapportée.

Lubala, Toni Kasole; Mutombo, Augustin Mulangu; Munkana, Arthur Ndundula; Manika, Michel Muteya



[Thrombotic microangiopathies].  


Thrombotic microangiopathies (TMA) encompass various diseases characterized by a microangiopathic hemolytic anemia, platelet clumping, and organ failure of variable severity. Thrombotic thrombocytopenic purpura (TTP) is a particularly severe form of TMA characterized by systemic organ failure which results from a severe defect in ADAMTS13, a plasma enzyme specifically involved in the cleavage of highly hemostatic unusually large (UL) von Willebrand factor (VWF) multimers into smaller and less adhesive VWF forms. Failure to degrade these UL-VWF multimers leads to excessive platelet aggregates and capillary occlusion. Hemolytic uremic syndrome (HUS) is characterized prominently by a renal failure. In most cases, HUS is caused by entero-hemorrhagic Escherichia coli strains which secrete a shiga-like toxin (STX). STX-negative HUS, termed atypical HUS, was associated with a dysfunction in complement pathway. The major improvement in our understanding of TMA pathophysiology allows now a more accurate molecular classification of TMA syndromes, which opens fascinating perspectives of targeted therapies. PMID:23513771

Moulinier, Constance; Veyradier, Agnès; Rondeau, Eric; Coppo, Paul



Magnetically attached sputter targets  


An improved method and assembly for attaching sputtering targets to cathode assemblies of sputtering systems which includes a magnetically permeable material is described. The magnetically permeable material is imbedded in a target base that is brazed, welded, or soldered to the sputter target, or is mechanically retained in the target material. Target attachment to the cathode is achieved by virtue of the permanent magnets and/or the pole pieces in the cathode assembly that create magnetic flux lines adjacent to the backing plate, which strongly attract the magnetically permeable material in the target assembly. 11 figures.

Makowiecki, D.M.; McKernan, M.A.



Magnetically attached sputter targets  


An improved method and assembly for attaching sputtering targets to cathode assemblies of sputtering systems which includes a magnetically permeable material. The magnetically permeable material is imbedded in a target base that is brazed, welded, or soldered to the sputter target, or is mechanically retained in the target material. Target attachment to the cathode is achieved by virtue of the permanent magnets and/or the pole pieces in the cathode assembly that create magnetic flux lines adjacent to the backing plate, which strongly attract the magnetically permeable material in the target assembly.

Makowiecki, Daniel M. (Livermore, CA); McKernan, Mark A. (Livermore, CA)



Human target acquisition performance  

NASA Astrophysics Data System (ADS)

The battlefield has shifted from armored vehicles to armed insurgents. Target acquisition (identification, recognition, and detection) range performance involving humans as targets is vital for modern warfare. The acquisition and neutralization of armed insurgents while at the same time minimizing fratricide and civilian casualties is a mounting concern. U.S. Army RDECOM CERDEC NVESD has conducted many experiments involving human targets for infrared and reflective band sensors. The target sets include human activities, hand-held objects, uniforms & armament, and other tactically relevant targets. This paper will define a set of standard task difficulty values for identification and recognition associated with human target acquisition performance.

Teaney, Brian P.; Du Bosq, Todd W.; Reynolds, Joseph P.; Thompson, Roger; Aghera, Sameer; Moyer, Steven K.; Flug, Eric; Espinola, Richard; Hixson, Jonathan



Doppler target signal generator  

NASA Astrophysics Data System (ADS)

The Threat Radar Simulator (TRS), utilized in DREO's ECM facility, is equipped with a Moving Target Indicator (MTI) processor used to detect the skin echo of moving targets. The MTI unit makes use of a Doppler shift, associated with the moving target, to discriminate between the target and unwanted clutter. To facilitate the MTI's requirement for Doppler shifts in the return pulses, a Doppler Target Signal Generator (DTSG) has been developed at DREO. The DTSG is an X-band programmable frequency synthesizer with three independent outputs. Two of the outputs are used in the generation of target returns and the third output provides a Doppler shift to the clutter return signal.

Doucet, Keith R.; Nielson, John



Endothelial microparticles correlate with high-risk angiographic lesions in acute coronary syndromes  

Microsoft Academic Search

Background: Endothelial Microparticles (EMP) are small fragments of endothelial cell membrane shed during apoptosis or activation. Our group has previously reported elevations of EMP in patients with coronary artery disease (CAD), thrombotic thrombocytopenic purpura (TTP), pre-eclampsia, multiple sclerosis (MS), and severe hypertension (HTN). In the present study, we evaluate the possible relationship between EMP levels and the angiographic severity and

Leon Bernal-Mizrachi; Wenche Jy; Christian Fierro; Rick Macdonough; Hermes A. Velazques; Joshua Purow; Joaquin J. Jimenez; Lawrence L. Horstman; Alexandre Ferreira; Eduardo de Marchena; Yeon S. Ahn



Bilateral Decompressive Craniectomy for Refractory Intracranial Hypertension in a Child with Severe ITP-Related Intracerebral Haemorrhage  

Microsoft Academic Search

We report a 13-month-old infant who developed acutely elevated intracranial pressure (ICP) as a result of a spontaneous intracerebral haemorrhage (ICH), secondary to idiopathic thrombocytopenic purpura (ITP). Her ICP remained severely elevated despite aggressive medical measures, with persistent obtundation, right hemiparesis and a dilated left pupil. Bilateral decompressive craniectomies (DCs) were performed, which resulted in a rapid decline in ICP.

Adrianna Ranger; Artur Szymczak; Douglas Fraser; Marina Salvadori; Lawrence Jardine



Autoimmune forms of thrombotic micorangiopathy and membranoproliferative glomerulonephritis: Indications for a disease spectrum and common pathogenic principles  

Microsoft Academic Search

There is increasing evidence that Thrombotic Thrombocytopenic Purpura (TTP), atypical Hemolytic Uremic Syndrome (aHUS) and Membranoproliferative Glomerulonephritis (MPGN), especially subtype II (also termed Dense Deposit Disease) represent a spectrum of related disorders. Thrombi are common for all three disorders, develop in different microvascular beds and appear relevant for organ dysfunction. TTP not only develops primarily at neurological sites, but also

Christine Skerka; Christoph Licht; Michael Mengel; Barbara Uzonyi; Stefanie Strobel; Peter F. Zipfel; Mihály Józsi



Mechanism of action of IVIG and anti-D in ITP  

Microsoft Academic Search

Infusion of large amounts of intravenous immunoglobulin (IVIG) or polyclonal anti-D can reverse thrombocytopenia in patients with idiopathic thrombocytopenic purpura within hours of the administration of these products. It has been suggested that the effects of IVIG appear to far outlast several half-lives of the product. Several mechanisms have been proposed to explain both the acute and long term effects

Alan H. Lazarus; Andrew R. Crow



Long-term follow-up study of children with chronic ITP  

Microsoft Academic Search

A total of 126 children with chronic idiopathic thrombocytopenic purpura, including 35 splenectomized cases, were investigated in a long-term follow-up study, with regard to residual hematologic and immunologic abnormalities, complications and physical growth. Such hemorrhagic symptoms as petechiae, ecchymosis and epistaxis were still observed in about 22% – 28% of the patients with a period of morbidity ranging from 3

Jun-ichi Akatsuka; Koji Fujisawa; Naoko Ishidoya; Nobuyuki Taguchi; Ichiro Tsukimoto; Giichi Tsujino; Takeshi Nagao; Tatsutoshi Nakahata; Sumio Miyazaki; Takeo Takeda; Taro Akabane



Presence of ADAMTS13 Activity in a Patient with Metastatic Cancer and Thrombotic Microangiopathy  

Microsoft Academic Search

Patients with metastatic cancers occasionally present with microangiopathic hemolysis and thrombocytopenia. A patient with metastatic adenocarcinoma of the colon and microangiopathic hemolysis was treated with plasma exchange for a presumptive diagnosis of thrombotic thrombocytopenic purpura (TTP). However, her condition continued to deteriorate and a determination of ADAMTS13 activity revealed that she did not have TTP. Despite similarity in clinical manifestation,

Robin B. Forman; Seth A. Benkel; Yelena Novik; Han-Mou Tsai



Brain Abscess Due to Listeria Monocytogenes: First Case Report in Thailand  

Microsoft Academic Search

Brain abscess with bacteremia caused by Listeria monocytogenes in a young woman with immune thrombocytopenic purpura was reported. The clinical features included fever, headache, and left-side weakness. Computed tomography and magnetic resonance imaging of the brain showed a large single abscess at the right frontoparietal area. L. monocytogenes was isolated from a blood culture. The patient promptly received a surgical

Somporn Srifeungfung


Severe Ehrlichia chaffeensis Infection in a Lung Transplant Recipient: A Review of Ehrlichiosis in the Immunocompromised Patient  

Microsoft Academic Search

We describe a case of human ehrlichiosis in a lung transplant recipient and review published reports on ehrlichiosis in immu- nocompromised patients. Despite early therapy with doxycy- cline, our patient had unusually severe illness with features of thrombotic thrombocytopenic purpura. Of 23 reported cases of ehrlichiosis in immunocompromised patients, organ failure occurred in all patients and 6 (25%) died.

Nasia Safdar; Robert B. Love; Dennis G. Maki



A case of acute stent thrombosis during treatment with the thrombopoietin receptor agonist peptide--romiplostim.  


Romiplostim is a thrombopoietin receptor agonist that increases platelet counts and restores platelet function in patients with chronic immune thrombocytopenia (ITP). Increase in platelet count and platelet activation has been associated with increased thromboembolic risk. The present case report describes an interesting case of acute stent thrombosis in a patient with chronic immune thrombocytopenic purpura (ITP) being treated with romiplostim. PMID:21963397

Rayoo, Rinku; Sharma, Naveen; van Gaal, William J



Maternal thrombocytopenia in pregnancy: Time for a reassessment  

Microsoft Academic Search

Antiplatelet autoantibodies in women with autoimmune thrombocytopenic purpura can cause fetal thrombocytopenia and serious bleeding problems. Obstetricians have used fetal scalp sampling, cordocentesis, and cesarean delivery in this disorder to avoid fetal complications such as intracranial hemorrhage. Accumulating evidence indicates that the fetal risk of intracranial hemorrhage is much lower than initially reported. Moreover, these invasive lests and treatments are

Robert M. Silver; D. Ware Branch; James R. Scott



Thrombotic Microangiopathies: From Animal Models to Human Disease and Cure  

Microsoft Academic Search

Thrombotic microangiopathies are a group of microvascular disorders, with reduced organ perfusion and hemolytic anemia. The two most relevant conditions characterized by thrombotic microangiopathic anemia (TMA) are thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). In TTP, systemic microvascular aggregation of platelets causes ischemia in the brain and other organs. In HUS, platelet-fibrin thrombi predominantly occlude the renal circulation.

Jessica Caprioli; Giuseppe Remuzzi; Marina Noris



Increasing platelets without transfusion: is it time to introduce novel thrombopoietic agents in neonatal care?  

Microsoft Academic Search

The Food and Drug Administration recently approved two novel thrombopoiesis-stimulating agents, Romiplostim (AMG-531, Nplate) and Eltrombopag (Promacta), for the treatment of adults with immune thrombocytopenic purpura. For physicians taking care of critically ill neonates, this offers the opportunity of decreasing platelet transfusions and potentially improving the outcomes of neonates with severe and prolonged thrombocytopenia. However, several developmental factors need to

H Sallmon; R K Gutti; F Ferrer-Marin; Z-J Liu; M C Sola-Visner



47,Xxx in an adolescent with premature ovarian failure and autoimmune disease  

Microsoft Academic Search

Background: Premature ovarian failure (POF) is often associated with autoimmune disorders. The 47,XXX karyotype has also been associated with POF and other genitourinary abnormalities. Following is a case of a 17 year old with immune thrombocytopenic purpura (ITP), POF, 47,XXX and a positive antinuclear antibody (ANA).Case Report: A 17 year old Caucasian female was referred to the Adolescent Health Clinic

Cynthia Holland



Severe Ehrlichia chaffeensis Infection in a Lung Transplant Recipient: A Review of Ehrlichiosis in the Immunocompromised Patient  

PubMed Central

We describe a case of human ehrlichiosis in a lung transplant recipient and review published reports on ehrlichiosis in immunocompromised patients. Despite early therapy with doxycycline, our patient had unusually severe illness with features of thrombotic thrombocytopenic purpura. Of 23 reported cases of ehrlichiosis in immunocompromised patients, organ failure occurred in all patients and 6 (25%) died.

Love, Robert B.; Maki, Dennis G.



Inactivation of Escherichia coli O157:H7 by cinnamic aldehyde purified from Cinnamomum cassia shoot  

Microsoft Academic Search

Escherichia coli O157:H7 is a pathogen, which causes the hemorrhagic colitis, hemolytic uremic syndrome and thrombotic thrombocytopenic purpura in humans. Control of the bacterial cells in foods is an important factor to reduce outbreaks of the foodborne diseases. In this study, cinnamic aldehyde possessing antimicrobial activity against the bacterial cells was purified from the extract of cinnamon (Cinnamomum cassia Blume)

H.-O. Kim; S.-W. Park; H.-D. Park




NCI Guidelines for Administrative Supplements in Support of Expanding the Childhood Cancer TARGET Initiative Title: Childhood Cancer TARGET Initiative Expansion – Tissue Collections and Characterization Announcement Number: NOT-OD-09-056 NIH Announces


Laser Thermonuclear Targets.  

National Technical Information Service (NTIS)

The methods of manufacture, processing and monitoring of laser targets developed in the last several years are in principle important for laser thermonuclear fusion. Analysis of target technology shows that we can attain comparatively high accuracy of man...

E. G. Gamalii A. I. Gromov A. I. Isakov L. A. Krupinina Y. S. Leonov



Targeted Financial Sanctions Simulation.  

National Technical Information Service (NTIS)

The objective of the Targeted Financial Sanctions (TFS) Research Project at the Watson Institute for International Studies is to develop practical proposals to help refine the use and increase the effectiveness of multilateral, targeted financial sanction...



Analytical modeling of laser pulse heating of embedded biological targets: An application to cutaneous vascular lesions  

NASA Astrophysics Data System (ADS)

Detailed understanding of the thermal processes in biological targets undergoing laser irradiation continues to be a challenging problem. For example, the contemporary pulsed dye laser (PDL) delivers a complex pulse format which presents specific challenges for theoretical understanding and further development. Numerical methods allow for adequate description of the thermal processes, but are lacking for clarifying the effects of the laser parameters. The purpose of this work is to derive a simplified analytical model that can guide the development of future laser designs. A mathematical model of heating and cooling processes in tissue is developed. Exact analytical solutions of the model are found when applied to specific temporal and spatial profiles of heat sources. Solutions are reduced to simple algebraic expressions. An algorithm is presented for approximating realistic cases of laser heating of skin structures by heat sources of the type found to have exact solutions. The simple algebraic expressions are used to provide insight into realistic laser irradiation cases. The model is compared with experiments on purpura threshold radiant exposure for PDL. These include data from four independent groups over a period of 20 years. Two of the data sets are taken from previously published articles. Two more data sets were collected from two groups of patients that were treated with two PDLs (585 and 595 nm) on normal buttocks skin. Laser pulse durations were varied between 0.5 and 40 ms radiant exposures were varied between 3 and 20 J/cm2. Treatment sites were evaluated 0.5, 1, and 24 hours later to determine purpuric threshold. The analytical model is in excellent agreement with a wide range of experimental data for purpura threshold radiant exposure. The data collected by independent research groups over the last 20 years with PDLs with wavelengths ranged from 577 to 595 nm were described accurately by this model. The simple analytical model provides an accurate description of a wide range of experimental data. The model can be used to guide the development of future laser designs and help refine laser parameters.

Mirkov, Mirko; Sherr, Evan A.; Sierra, Rafael A.; Lloyd, Jenifer R.; Tanghetti, Emil



Target Acquisition with STIS  

Microsoft Academic Search

The STIS on-board target acquisition and acquisition\\/peakup routines have been designed to accurately locate a target in the center of a slit or behind a bar\\/wedge. All acquisitions use the CCD camera to initially obtain a direct image of the target field. The on-board flight software then processes the image to locate the position of the target, and centers the

R. M. Katsanis; R. A. Downes; S. B. Kraemer



Polarized nuclear targets  

SciTech Connect

The static and dynamic methods for producing polarized targets are briefly discussed and compared. Nuclei that have been polarized by these methods are summarized. The equipment necessary for producing a working target is described, as are the capabilities presently available at LAMPF. A short description is presented of a polarized /sup 13/C target proposed for use at the LAMPF HRS spectrometer, as an example of a polarized target for use in nuclear physics research.

Jarmer, J.J.



The Targeting of Advertising  

Microsoft Academic Search

An important question that firms face in advertising is developing effective media strategy. Major improvements in the quality of consumer information and the growth of targeted media vehicles allow firms to precisely target advertising to consumer segments within a market. This paper examines advertising strategy when competing firms can target advertising to different groups of consumers within a market. With

Ganesh Iyer; David Soberman; J. Miguel Villas-Boas



Validating cancer drug targets  

Microsoft Academic Search

A cancer drug target is only truly validated by demonstrating that a given therapeutic agent is clinically effective and acts through the target against which it was designed. Nevertheless, it is desirable to declare an early-stage drug target as `validated' before investing in a full-scale drug discovery programme dedicated to it. Although the outcome of validation studies can guide cancer

John D. Benson; Ying-Nan P. Chen; Susan A. Cornell-Kennon; Marion Dorsch; Sunkyu Kim; Magdalena Leszczyniecka; William R. Sellers; Christoph Lengauer



Doppler Target Signal Generator.  

National Technical Information Service (NTIS)

The Threat Radar Simulator (TRS), utilized in DREO's ECM facility, is equipped with a Moving Target Indicator (MTI) processor used to detect the skin echo of moving targets. The MTI unit makes use of a doppler shift, associated with the moving target, to ...

J. Nielson K. R. Doucet



Nova target experiments  

SciTech Connect

The Nova laser, at the Lawrence Livermore National Laboratory, provides unique opportunities for target experiments. It has unprecedented energy on target and significant flexibility. The paper presented by John Hunt described the capabilities and the status of Nova. This paper discusses plans for future experiments using Nova, and the present status of target experiments. We plan to perform high-quality physics experiments that exploit the unique capabilities of Nova. Because this is our goal, we are fielding an extensive array of well-characterized target diagnostics to measure the emissions from the target. The first section of this paper discusses the basic target diagnostics. We are also taking care to quantify the performance of the laser.

Drake, R.P.



Effective neutron targets  

SciTech Connect

Because of the lack of a free neutron target, deuterium targets have been used extensively in studying the neutron structure. The unique spin structure of the {sup 3}He ground state wave function and the recent developments in laser technologies made polarized {sup 3}He targets widely used in many experiments from neutron electromagnetic form factor studies to nucleon spin structure function measurements at all major electron accelerator facilities. In this talk, the current status of the polarized {sup 3}He targets will be reviewed. The author will focus on neutron electromagnetic form factor studies using polarized {sup 3}He targets. The polarized nucleon spin structure function measurements using polarized {sup 3}He targets will also be discussed.

Gao, H.





The design of targets for use in the investigation of nuclear reactions of hydrogen isotopes by bombardment with accelerated particles is described. The target con struction eomprises a backing disc of a metal selected from the group consisting of molybdenunn and tungsten, a eoating of condensed titaniunn on the dise, and a hydrogen isotope selected from the group consisting of deuterium and tritium absorbed in the coatiag. The proeess for preparing these hydrogen isotope targets is described.

Ashley, R.W.



Integrin Targeted MR Imaging  

PubMed Central

Magnetic resonance imaging (MRI) is a powerful medical diagnostic imaging modality for integrin targeted imaging, which uses the magnetic resonance of tissue water protons to display tissue anatomic structures with high spatial resolution. Contrast agents are often used in MRI to highlight specific regions of the body and make them easier to visualize. There are four main classes of MRI contrast agents based on their different contrast mechanisms, including T1, T2, chemical exchange saturation transfer (CEST) agents, and heteronuclear contrast agents. Integrins are an important family of heterodimeric transmembrane glycoproteins that function as mediators of cell-cell and cell-extracellular matrix interactions. The overexpressed integrins can be used as the molecular targets for designing suitable integrin targeted contrast agents for MR molecular imaging. Integrin targeted contrast agent includes a targeting agent specific to a target integrin, a paramagnetic agent and a linker connecting the targeting agent with the paramagnetic agent. Proper selection of targeting agents is critical for targeted MRI contrast agents to effectively bind to integrins for in vivo imaging. An ideal integrin targeted MR contrast agent should be non-toxic, provide strong contrast enhancement at the target sites and can be completely excreted from the body after MR imaging. An overview of integrin targeted MR contrast agents based on small molecular and macromolecular Gd(III) complexes, lipid nanoparticles and superparamagnetic nanoparticles is provided for MR molecular imaging. By using proper delivery systems for loading sufficient Gd(III) chelates or superparamagnetic nanoparticles, effective molecular imaging of integrins with MRI has been demonstrated in animal models.

Tan, Mingqian; Lu, Zheng-Rong



Helios target positioning system  

Microsoft Academic Search

The Los Alamos Scientific Laboratory Helios laser fusion system focuses eight powerful CO2 laser beams onto a tiny (typical 300-micron-diam) DT-filled target. The focusing is accomplished inside a vacuum chamber that is 3.5 m in diameter by 3.5 m high. The target positioning system places the target to within 5.0 microns of a predetermined point in space. This is accomplished

R. D. Day; C. E. Cummings; J. A. Hanlon; H. E. Tucker; R. W. Teasdale



SETI target selection  

NASA Astrophysics Data System (ADS)

The NASA high resolution microwave survey (HRMS) consists of two elements, a survey of the entire sky and a targeted search of nearby stars which is much more sensitive. Strategies are proposed for target selection for the targeted search with goals of improving the chances of successful detection of signals from technological civilizations that inhabit planets around solar-type stars, and to minimize the chances of missing signals from unexpected sites.

Latham, David W.; Soderblom, David R.



Targeting the tumor microenvironment  

SciTech Connect

Despite some notable successes cancer remains, for the most part, a seemingly intractable problem. There is, however, a growing appreciation that targeting the tumor epithelium in isolation is not sufficient as there is an intricate mutually sustaining synergy between the tumor epithelial cells and their surrounding stroma. As the details of this dialogue emerge, new therapeutic targets have been proposed. The FDA has already approved drugs targeting microenvironmental components such as VEGF and aromatase and many more agents are in the pipeline. In this article, we describe some of the 'druggable' targets and processes within the tumor microenvironment and review the approaches being taken to disrupt these interactions.

Kenny, P.A.; Lee, G.Y.; Bissell, M.J.



Targeted Radionuclide Therapy  

PubMed Central

Targeted radiotherapy is an evolving and promising modality of cancer treatment. The killing of cancer cells is achieved with the use of biological vectors and appropriate radionuclides. Among the many advantages of this approach are its selectiveness in delivering the radiation to the target, relatively less severe and infrequent side effects, and the possibility of assessing the uptake by the tumor prior to the therapy. Several different radiopharmaceuticals are currently being used by various administration routes and targeting mechanisms. This article aims to briefly review the current status of targeted radiotherapy as well as to outline the advantages and disadvantages of radionuclides used for this purpose.

Ersahin, Devrim; Doddamane, Indukala; Cheng, David



Prioritising target markets  

Microsoft Academic Search

Target marketing is a key decision area for all businesses. Market size, growth rates, competitive forces, customer fit and profitability are just a few of the criteria which can be used by businesses assessing the attractiveness of their target markets. Yet despite the wealth of variables available to managers and the development of a range of decision tools to help

Lyndon Simkin; Sally Dibb



LANSCE Target Calculations.  

National Technical Information Service (NTIS)

The LANSCE target operates at a beam current of 30 microamps. We present here the results of the finite-element calculations for the temperatures and stresses in the present target operated at 100 microamps. The calculations were run using the ABAQUS fini...

D. L. Grisham R. D. Brown



Targeting novel sites  

PubMed Central

Restriction-like endonuclease (RLE) bearing non-LTR retrotransposons are site-specific elements that integrate into the genome through target primed reverse transcription (TPRT). RLE-bearing elements have been used as a model system for investigating non-LTR retrotransposon integration. R2 elements target a specific site in the 28S rDNA gene. We previously demonstrated that the two major sub-classes of R2 (R2-A and R2-D) target the R2 insertion site in an opposing manner with regard to the pairing of known DNA binding domains and bound sequences—indicating that the A- and D-clades represent independently derived modes of targeting that site. Elements have been discovered that group phylogenetically with R2 but do not target the canonical R2 site. Here we extend our earlier studies to show that a separate R2-A clade element, which targets a site other than the canonical R2 site, does so by using the N-terminal zinc fingers and Myb motifs. We further extend our targeting studies beyond R2 clade elements by investigating the ability of the N-terminal zinc fingers from the nematode NeSL-1 element to target its integration site. Our data are consistent with the use of an N-terminal DNA binding domain as one of the major targeting determinants used by RLE-bearing non-LTR retrotransposons to secure a protein subunit near the insertion site. This N-terminal DNA binding domain can undergo modifications, allowing the element to target novel sites. The binding orientation of the N-terminal domain relative to the insertion site is quite variable.

Shivram, Haridha; Cawley, Dillon



Drug target central.  


Background: One of the primary pillars of drug discovery is the drug target, its relationship to both the drugs designed against it and the biological processes in which it is involved. Here we review the informatics approaches required to build a complete catalogue of known drug targets. Objective: Using Pfizer's internal target database as a narrative, we review the steps involved in the construction of an integrated, enterprise target-informatics system. We consider how compiling the drug target universe requires integration across several resources such as competitor intelligence and pharmacological activity databases, as well as input from techniques such as text-mining. In particular, we address data standards and the complexities of representing targets in a structured ontology as well as opportunities for future development. Conclusion: Drug target-orientated databases address important areas of drug discovery such as chemogenomics, drug/candidate repurposing and business intelligence. As research in industry and academia drives continued expansion of the druggable genome, it is crucial that such systems be maintained to provide an accurate picture of the landscape. This power of this information stretches beyond drug discovery and into the wider scientific community where small molecule tool compounds can enable the dissection of complex cellular pathways. PMID:23496271

Harland, Lee; Gaulton, Anna



Passive Infrared Resolution Target.  

National Technical Information Service (NTIS)

According to this patent application an infrared measurement system is provided for determining the resolution of infrared sensors wherein perforated aluminum panels are positioned in a conventional target array for determining photographic resolution. Th...

L. O. Vroombout



Passive Infrared Resolution Target.  

National Technical Information Service (NTIS)

This patent describes a passive target array, for measuring the resolution of infrared reconnaissance sets, having a heat retaining background pad. A plurality of perforated aluminum strips are laid on the pad in a conventional photographic resolution tar...

L. O. Vroombout



Targeted cytokine production.  


It has been well established that bispecific antibodies containing anti-T-cell receptor MAbs crosslinked to anti-tumor MAbs induce T cells to lyse tumor cells, as measured in a 51Cr-release assay. Such lysis requires direct attachment between target and cytotoxic cells and most probably involves the exocytosis of cytolytic substances into the cell:cell interface. In addition, targeted T cells mediate a second activity, the secretion into the medium of factors that can block the growth of bound tumor cells and unbound bystander cells. In order to test how targeted effector cells mediate anti-tumor effects in vivo, we are currently developing a totally syngeneic murine system in which murine T cells are targeted against mouse mammary tumors. The system allows us to treat both primary tumors and tumor transplants, using a mammary-tumor-virus antigen as the entity that is specifically recognized on the tumor cells. PMID:1428400

Segal, D M; Qian, J H; Titus, J A; Moreno, M B; George, A J; Jost, C R; Kurucz, I; el-Gamil, M; Wunderlich, J R



High Target Visibility Analysis.  

National Technical Information Service (NTIS)

This paper presents an approach to visibility analysis for a target located high over a terrain made of discrete elevation points. This analysis is a special subset of a general terrain intervisibility analysis problem. It is an efficient algorithm based ...

J. J. Kim



Target Temperature Modeling.  

National Technical Information Service (NTIS)

A computerized mathematical model for the prediction of time-dependent surface temperatures and radiances of planar targets and backgrounds has been formulated. The model accounts for the effects of (1) solar insulation, (2) radiative transfer, (3) natura...

D. Bornemeier R. Bennett R. Horvath



SETI target selection.  

NASA Astrophysics Data System (ADS)

The NASA High Resolution Microwave Survey consists of two complementary elements: a Sky Survey of the entire sky to a moderate level of sensitivity; and a Targeted Search of nearby stars, one at a time, to a much deeper level of sensitivity. The authors propose strategies for target selection with two goals: to improve the chances of successful detection of signals from technical civilizations that inhabit planets around solar-type stars, and to minimize the chances of missing signals from unexpected sites.

Latham, D. W.; Soderblom, D. R.



Drug-target network.  


The global set of relationships between protein targets of all drugs and all disease-gene products in the human protein-protein interaction or 'interactome' network remains uncharacterized. We built a bipartite graph composed of US Food and Drug Administration-approved drugs and proteins linked by drug-target binary associations. The resulting network connects most drugs into a highly interlinked giant component, with strong local clustering of drugs of similar types according to Anatomical Therapeutic Chemical classification. Topological analyses of this network quantitatively showed an overabundance of 'follow-on' drugs, that is, drugs that target already targeted proteins. By including drugs currently under investigation, we identified a trend toward more functionally diverse targets improving polypharmacology. To analyze the relationships between drug targets and disease-gene products, we measured the shortest distance between both sets of proteins in current models of the human interactome network. Significant differences in distance were found between etiological and palliative drugs. A recent trend toward more rational drug design was observed. PMID:17921997

Yildirim, Muhammed A; Goh, Kwang-Il; Cusick, Michael E; Barabási, Albert-László; Vidal, Marc



Plutonium Ceramic Target for MASHA.  

National Technical Information Service (NTIS)

We are currently developing a plutonium ceramic target for the MASHA mass separator. The MASHA separator will use a thick plutonium ceramic target capable of tolerating temperatures up to 2000 degrees C. Promising candidates for the target include oxides ...

P. A. Wilk D. A. Shaughnessy K. J. Moody J. M. Kenneally



Mesothelin targeted cancer immunotherapy  

PubMed Central

Mesothelin is a tumour differentiation antigen that is normally present on the mesothelial cells lining the pleura, peritoneum and pericardium. It is however highly expressed in several human cancers including malignant mesothelioma, pancreatic, ovarian and lung adenocarcinoma. The normal biologic function of mesothelin is unknown but recent studies have shown that it binds to CA-125 and may play a role in the peritoneal spread of ovarian cancer. The limited mesothelin expression in normal tissues and high expression in many cancers makes it an attractive candidate for cancer therapy. Three mesothelin targeted agents are in various stages of clinical evaluation in patients. These include SS1P (CAT-5001) a recombinant immunotoxin targeting mesothelin, MORAb-009 a chimeric anti-mesothelin monoclonal antibody and CRS-207 a live-attenuated Listeria monocytogenes vector encoding human mesothelin. These ongoing clinical trials will help define the utility of mesothelin as a target for cancer therapy.

Hassan, Raffit; Ho, Mitchell



Penetration of concrete targets  

SciTech Connect

We developed penetration equations for ogive-nosed projectiles that penetrated concrete targets after normal impact. Our penetration equations predict axial force on the projectile nose, rigid-body motion, and final penetration depth. For target constitutive models, we conducted triaxial material experiments to confining pressures of 600 MPa and curve-fit these data with a linear pressure-volumetric strain relation and with a linear Mohr-Coulomb, shear strength-pressure relation. To verify our penetration equations, we conducted eleven penetration experiments with 0.90 kg, 26.9-mm-diameter, ogive-nosed projectiles into 1.37-m-diameter concrete targets with unconfined compressive strengths between 32-40 MPa. Predictions from our penetration equation are compared with final penetration depth measurements for striking velocities between 280--800 m/s.

Forrestal, M.J. [Sandia National Labs., Albuquerque, NM (United States); Cargile, J.D. [Corps of Engineers, Vicksburg, MS (United States). Waterways Experiment Station; Tzou, R.D.Y. [New Mexico Univ., Albuquerque, NM (United States). Dept. of Mechanical Engineering



Setting reference targets  

SciTech Connect

Reference Targets are used to represent virtual quantities like the magnetic axis of a magnet or the definition of a coordinate system. To explain the function of reference targets in the sequence of the alignment process, this paper will first briefly discuss the geometry of the trajectory design space and of the surveying space, then continue with an overview of a typical alignment process. This is followed by a discussion on magnet fiducialization. While the magnetic measurement methods to determine the magnetic centerline are only listed (they will be discussed in detail in a subsequent talk), emphasis is given to the optical/mechanical methods and to the task of transferring the centerline position to reference targets.

Ruland, R.E.



Targeting the tumor microenvironment  

PubMed Central

Persistent JAK-STAT3 signaling is implicated in many aspects of tumorigenesis. Apart from its tumor-intrinsic effects, STAT3 also exerts tumor-extrinsic effects, supporting tumor survival and metastasis. These involve the regulation of paracrine cytokine signaling, alterations in metastatic sites rendering these permissive for the growth of cancer cells and subversion of host immune responses to create an immunosuppressive environment. Targeting this signaling pathway is considered a novel promising therapeutic approach, especially in the context of tumor immunity. In this article, we will review to what extent JAK-STAT3-targeted therapies affect the tumor microenvironment and whether the observed effects underlie responsiveness to therapy.

Bournazou, Eirini; Bromberg, Jacqueline



Targeted polypeptide degradation  


This invention pertains to compositions, methods, cells and organisms useful for selectively localizing polypeptides to the proteasome for degradation. Therapeutic methods and pharmaceutical compositions for treating disorders associated with the expression and/or activity of a polypeptide by targeting these polypeptides for degradation, as well as methods for targeting therapeutic polypeptides for degradation and/or activating therapeutic polypeptides by degradation are provided. The invention provides methods for identifying compounds that mediate proteasome localization and/or polypeptide degradation. The invention also provides research tools for the study of protein function.

Church, George M. (Brookline, MA); Janse, Daniel M. (Brookline, MA)



Hypoxia: targeting the tumour.  


Solid tumours contain regions of very low oxygen concentrations that are said to be hypoxic. Hypoxia is a natural phenotype of solid tumours resulting from an imperfect vascular network. There are a number of consequences associated with tumour hypoxia including: resistance to ionising radiation, resistance to chemotherapy and the magnification of mutated p53. In addition tissue hypoxia has been regarded as a key factor for tumour aggressiveness and metastasis by activation of signal transduction pathways and gene regulatory mechanisms. It is clear that hypoxia in solid tumours promotes a strong oncogenic phenotype and is a phenomenon that occurs in all solid tumours. As such this provides a significant target for drug discovery particularly for tumour-targeting agents. A range of chemical classes (N-oxides, quinones, nitro-aromatics) have been explored as bioreductive agents that target tumour hypoxia. The most advanced agent, tirapazamine, is in phase III clinical trials in combination with cis-platin. The aim of this review is to give a brief overview of the current molecules and strategies being explored for targeting tumour hypoxia. PMID:16842231

Boyle, Robert George; Travers, Stuart



Infrared target recognition  

NASA Astrophysics Data System (ADS)

In this thesis, three approaches were used for Automatic Target Recognition (ATR). These approaches were shape, moment and Fourier generated features, Karhunen-Loeve Transform (KLT) generated features and Discrete Cosine Transform (DCT) generated features. The KLT approach was modelled after the face recognition research by Suarez, AFIT, and Turk and Pentland, MIT. A KLT is taken of a reduced covariance matrix, composed all three classes of targets, and the resulting eigenimages are used to reconstruct the original images. The reconstruction coefficients for each original image are found by taking the dot product of the original image with each eigenimage. These reconstruction coefficients were implemented as features into a three layer backprop with momentum network. Using the hold one-cut-out technique of testing data, the net could correctly differentiate the targets 100 percent of the time. Using standard features, the correct classification rate was 99.33 percent. The DCT was also taken of each image, and 16 low frequency Fourier components were kept as features. These recognition rates were compared to FFT results where each set contained the top five feature, as determined by a saliency test. The results proved that the DCT and the FFT were equivalent concerning classification of targets.

Singstock, Brian D.



Target-Rich Environment  

ERIC Educational Resources Information Center

|Target marketing is defining school enrollment goals and then developing a strategic plan to accomplish those goals through the use of specific communication vehicles and community focus. It is critical to reach the right audience, with the right message, at the right time, for the right cost. In this brief article, the author describes several…

Perna, Mark C.



Targeted headache history.  


Armed with information obtained from the targeted headache history, clinicians can almost always make an accurate diagnosis or at least determine sick from well. Through using the information obtained, clinicians can craft a safe and cost-effective treatment plan that has a high likelihood of success. PMID:23419620

Waldman, Steven D



Active Target Simulation  

NASA Astrophysics Data System (ADS)

We have simulated an existing experimental design to determine the resolution improvement upon energy measurements of neutron unbound nuclei. A number of experiments of this type have been performed at the National Superconducting Cyclotron Laboratory (NSCL), located at Michigan State University. An excited nucleus is typically produced with a radioactive beam interacting with a passive Beryllium target. Many different nuclei are produced in experiment, each of which immediately decays into a charged particle and neutron. The charged particles are detected and the neutrons interact in scintillation detectors such as the Modular Neutron Array (MoNA) and Large Multi-Institutional Scintillation Array (LISA). In our simulation, we have constructed an active target that provides additional information such that the point of nuclear interaction within the target may be determined. This information improves the resolution in decay energy measurements of neutron unbound isotopes. This presentation will cover some aspects of the simulation process, as well as showing some of the results that demonstrate the simulated improvement over a passive target.

Smith, Nathan; Draznik, Peter; Frank, Nathan



Targeting of somatic hypermutation  

Microsoft Academic Search

Somatic hypermutation (SHM) introduces mutations in the variable region of immunoglobulin genes at a rate of ?10?3 mutations per base pair per cell division, which is 106-fold higher than the spontaneous mutation rate in somatic cells. To ensure genomic integrity, SHM needs to be targeted specifically to immunoglobulin genes. The rare mistargeting of SHM can result in mutations and translocations

Valerie H. Odegard; David G. Schatz



Personnel Targeting Operations.  

National Technical Information Service (NTIS)

The U.S. military is not currently organized to conduct effective personnel targeting operations outside of the United States. The Department of Defense needs to create an organization that can find, capture or kill designated personnel. With the events o...

C. W. Clark



Targeting the RAS oncogene  

PubMed Central

Introduction The Ras proteins (K-Ras, N-Ras, H-Ras) are GTPases that function as molecular switches for a variety of critical cellular activities and their function is tightly and temporally regulated in normal cells. Oncogenic mutations in the RAS genes, which create constitutively-active Ras proteins, can result in uncontrolled proliferation or survival in tumor cells. Areas covered The paper discusses three therapeutic approaches targeting the Ras pathway in cancer: 1) Ras itself, 2) Ras downstream pathways, and 3) synthetic lethality. The most adopted approach is targeting Ras downstream signaling, and specifically the PI3K-AKT-mTOR and Raf-MEK pathways, as they are frequently major oncogenic drivers in cancers with high Ras signaling. Although direct targeting of Ras has not been successful clinically, newer approaches being investigated in preclinical studies, such as RNA interference-based and synthetic lethal approaches, promise great potential for clinical application. Expert opinion The challenges of current and emerging therapeutics include the lack of “tumor specificity” and their limitation to those cancers which are “dependent” upon aberrant Ras signaling for survival. While the newer approaches have the potential to overcome these limitations, they also highlight the importance of robust preclinical studies and bidirectional translational research for successful clinical development of Ras-related targeted therapies.

Takashima, Asami




EPA Science Inventory

A GIS based targeting methodology which uses multi-media state and federal regulatory data to identify watersheds in Texas, Louisiana, Arkansas, Oklahoma, and New Mexico that are vulnerable to environmental damage and/or have high chemical emissions to the environment. The assess...


ISAC target vacuum system  

Microsoft Academic Search

The Isotope Separator and Accelerator (ISAC) facility at TRIUMF has been in full operation since 1999. The ISAC east and west targets use proton beam from the cyclotron to produce various radioactive isotopes, which are then ionized and extracted. The ions are then passed through the mass separator and selected ions are transferred to the low energy experiments or injected

Dimo Yosifov; Igor Sekachev



Targeted cancer therapy  

PubMed Central

“Shoot the driver” is the paradigm of targeted cancer therapy. However, resistance to targeted inhibitors of signaling pathways is a major problem. In part, the redundancy of signaling networks can bypass targeted inhibitors and thereby reduce their biological effect. In this case, the driver turns out to be one of several potential messengers and is easily replaced. Cocktails of multiple targeted inhibitors are an obvious solution. This is limited, however, by the lack of potent inhibitors and may also produce increased toxicity. Therefore, we explored the direct blockade of a key biological activity downstream from multiple converging oncogenic signals. Specifically, several oncogenic signaling pathways, including AKT, MAPK and PIM kinase signals, converge on the activation of cap-dependent translation. In cancer cells, aberrant activation of cap-dependent translation favors the increased expression of short-lived oncoproteins like c-MYC, MCL1, CYCLIND1 and the PIM kinases. Intriguingly, cancer cells are especially sensitive to even temporary reductions in these proteins. We will discuss our findings concerning translational inhibitor therapy in cancer.

Wendel, Hans-Guido



Costly Targeted Persuasive Advertising  

Microsoft Academic Search

Traditionally, advertising has been thought of as an informative message displayed by firms to a large number of potential consumers in order to educate them about their product's characteristics. Recently, other aspects of advertising have moved to the forefront. Improvements in technology allow for the targeting of specific consumers with messages, and for collecting enough data on individuals so that

Christopher Willmore


Targeting Pituitary Tumors  

Microsoft Academic Search

Background: Pituitary tumors are common and usually grow insidiously over many years. Rarely fatal, treatment still requires multiple cytoreductive surgeries and\\/or radiation therapy with its attendant side effects. As a disease process of regulatory pathways, pituitary tumors offer numerous potential therapeutic targets, and many, such as the membranal dopamine2 and somatostatin receptors, have been successfully exploited for many years. Nuclear

Anthony P. Heaney



Inflation targeting in Brazil  

Microsoft Academic Search

The purpose of this paper is to examine the Inflation Targeting (IT) framework as it is applied in the case of Brazil since its adoption in June 1999. For this purpose we first summarize the macroeconometric model utilized by the Central Bank of Brazil (BCB) in its pursuit of the IT framework. While the focus of this paper is on

Philip Arestis; Luiz Fernando de Paula



Targeting nanoparticles to cancer.  


Nanotechnology applications in medicine, termed as nanomedicine, have introduced a number of nanoparticles of variable chemistry and architecture for cancer imaging and treatment. Nanotechnology involves engineering multifunctional devices with dimensions at the nanoscale, similar dimensions as those of large biological vesicles or molecules in our body. These devices typically have features just tens to hundred nanometers across and they can carry one or two detection signals and/or therapeutic cargo(s). One unique class of nanoparticles is designed to do both, providing this way the theragnostic nanoparticles (therapy and diagnosis). Being inspired by physiologically existing nanomachines, nanoparticles are designed to safely reach their target and specifically release their cargo at the site of the disease, this way increasing the drug's tissue bioavailability. Nanoparticles have the advantage of targeting cancer by simply being accumulated and entrapped in tumours (passive targeting). The phenomenon is called the enhanced permeation and retention effect, caused by leaky angiogenetic vessels and poor lymphatic drainage and has been used to explain why macromolecules and nanoparticles are found at higher ratios in tumours compared to normal tissues. Although accumulation in tumours is observed cell uptake and intracellular drug release have been questioned. Polyethyleneglycol (PEG) is used to protect the nanoparticles from the Reticulo-Endothelial System (RES), however, it prevents cell uptake and the required intracellular drug release. Grafting biorecognition molecules (ligands) onto the nanoparticles refers to active targeting and aims to increase specific cell uptake. Nanoparticles bearing these ligands are recognised by cell surface receptors and this leads to receptor-mediated endocytosis. Several materials are suggested for the design of nanoparticles for cancer. Polymers, linear and dendrimers, are associated with the drug in a covalent or non-covalent way and have been used with or without a targeting ligand. Stealth liposomes are suggested to carry the drug in the aqueous core, and they are usually decorated by recognition molecules, being widely studied and applied. Inorganic nanoparticles such as gold and iron oxide are usually coupled to the drug, PEG and the targeting ligand. It appears that the PEG coating and ligand decoration are common constituents in most types of nanoparticles for cancer. There are several examples of successful cancer diagnostic and therapeutic nanoparticles and many of them have rapidly moved to clinical trials. Nevertheless there is still a room for optimisation in the area of the nanoparticle kinetics such as improving their plasma circulation and tumour bioavailability and understanding the effect of targeting ligands on their efficiency to treat cancer. The need to develop novel and efficient ligands has never been greater, and the use of proper conjugation chemistry is mandatory. PMID:20380880

Wang, M; Thanou, M



ISAC target vacuum system  

SciTech Connect

The Isotope Separator and Accelerator (ISAC) facility at TRIUMF has been in full operation since 1999. The ISAC east and west targets use proton beam from the cyclotron to produce various radioactive isotopes, which are then ionized and extracted. The ions are then passed through the mass separator and selected ions are transferred to the low energy experiments or injected into a radio frequency quadrupole accelerator. The accompanying radioactive contamination from the production of radioactive ions requires a complex vacuum system. The main target vacuum space consists of two semiseparate (primary and secondary) volumes pumped by turbo-molecular pumps. The primary volume uses four pumps while the secondary volume uses two pumps. Two hermetic rotary vane pumps are used as backing pumps. The nominal vacuum in both volumes is about 1.33x10{sup -4} Pa (1.0x10{sup -6} Torr). The pressure is monitored by two cold cathode and two hot filament ion gauges. The cold cathode gauges are used to interlock the system, which is critical during the bake out of the target and beam production. The exhaust gas from the vacuum pumps can be radioactive. Three gas storage tanks (decay tanks) are used for temporary storage of the radioactive exhaust and its controlled release to the atmosphere. Gas-species insensitive membrane gauges are used for monitoring the pressure in the storage tanks. This article describes the details of the ISAC target vacuum system as well as some procedures related to the handling of the exhaust gas with traces of radioactive contamination produced by the targets.

Yosifov, Dimo; Sekachev, Igor [TRIUMF, Canada's National Laboratory for Particle and Nuclear Physics, Vancouver, British Columbia V6T 2A3 (Canada)



Plastids and protein targeting.  


Plastids with two bounding membranes--as exemplified by red algae, green algae, plants, and glaucophytes--derive from primary endosymbiosis; a process involving engulfment and retention of a cyanobacterium by a phagotrophic eukaryote. Plastids with more than two bounding membranes (such as those of euglenoids, dinoflagellates, heterokonts, haptopytes, apicomplexa, cryptomonads, and chlorarachniophytes) probably arose by secondary endosymbiosis, in which a eukaryotic alga (itself the product of primary endosymbiosis) was engulfed and retained by a phagotroph. Secondary endosymbiosis transfers photosynthetic capacity into heterotrophic lineages, has apparently occurred numerous times, and has created several major eukaryotic lineages comprising upwards of 42,600 species. Plastids acquired by secondary endosymbiosis are sometimes referred to as "second-hand." Establishment of secondary endosymbioses has involved transfer of genes from the endosymbiont nucleus to the secondary host nucleus. Limited gene transfer could initially have served to stabilise the endosymbioses, but it is clear that the transfer process has been extensive, leading in many cases to the complete disappearance of the endosymbiont nucleus. One consequence of these gene transfers is that gene products required in the plastid must be targeted into the organelle across multiple membranes: at least three for stromal proteins in euglenoids and dinoflagellates, and across five membranes in the case of thylakoid lumen proteins in plastids with four bounding membranes. Evolution of such targeting mechanisms was obviously a key step in the successful establishment of each different secondary endosymbiosis. Analysis of targeted proteins in the various organisms now suggests that a similar system is used by each group. However, rather than interpreting this similarity as evidence of an homologous origin, I believe that targeting has evolved convergently by combining and recycling existing protein trafficking mechanisms already existing in the endosymbiont and host. Indeed, by analyzing the multiple motifs in targeting sequences of some genes it is possible to infer that they originated in the plastid genome, transferred from there into the primary host nucleus, and subsequently moved into the secondary host nucleus. Thus, each step of the targeting process in "second-hand" plastids recapitulates the gene's previous intracellular transfers. PMID:10461382

McFadden, G I


Targeted adenoviral vectors  

NASA Astrophysics Data System (ADS)

The practical implementation of gene therapy in the clinical setting mandates gene delivery vehicles, or vectors, capable of efficient gene delivery selectively to the target disease cells. The utility of adenoviral vectors for gene therapy is restricted by their dependence on the native adenoviral primary cellular receptor for cell entry. Therefore, a number of strategies have been developed to allow CAR-independent infection of specific cell types, including the use of bispecific conjugates and genetic modifications to the adenoviral capsid proteins, in particular the fibre protein. These targeted adenoviral vectors have demonstrated efficient gene transfer in vitro , correlating with a therapeutic benefit in preclinical animal models. Such vectors are predicted to possess enhanced efficacy in human clinical studies, although anatomical barriers to their use must be circumvented.

Douglas, Joanne T.


Solvent recovery targeting  

SciTech Connect

One of the environmental challenges faced by the pharmaceutical and specialty chemical industries is the widespread use of organic solvents. With a solvent-based chemistry, the solvent necessarily has to be separated from the product. Chemical species in waste-solvent streams typically form multicomponent azeotropic mixtures, and this often complicates separation and, hence, recovery of solvents. A design approach is presented whereby process modifications proposed by the engineer to reduce the formation of waste-solvent streams can be evaluated systematically. This approach, called solvent recovery targeting, exploits a recently developed algorithm for elucidating the separation alternatives achievable when applying batch distillation to homogeneous multicomponent mixtures. The approach places the composition of the waste-solvent mixture correctly in the relevant residue curve map and computes the maximum amount of pure material that can be recovered via batch distillation. Solvent recovery targeting is applied to two case studies derived from real industrial processes.

Ahmad, B.S.; Barton, P.I. [Massachusetts Inst. of Tech., Cambridge, MA (United States)



Foucault on targets.  


This paper seeks to gain an insight into the behavior of a large NHS trust, in its attempt to meet a 90 percent patient access target, in a week long national audit in March 2003. Why did individuals act in dramatically different ways to their norm over this period. The work of Michel Foucault is used to explore these issues. The discourses of power, knowledge, discipline and governmentality are identified as key foucaudian themes that offer an alternative interpretation of how individuals behave in their place of work. The importance of the historical context of discourse within the NHS cannot be underestimated in shaping the behavior of individuals and groups today. Power and knowledge permeate NHS organizations through disciplinary practices and dressage. Governmentality seeks to maintain the status quo through disciplinary processes such as national healthcare targets. The natural response of NHS organizations is therefore, to seek order and conformity rather than disorder and conflict. PMID:15366279

Lynch, John



B cell targeted therapies  

PubMed Central

Although the precise pathogenesis of rheumatoid arthritis (RA) remains unclear, many cell populations, including monocytes, macrophages, endothelial cells, fibroblasts and B cells, participate in the inflammatory process. Ongoing research continues to evaluate the critical roles played by B cells in sustaining the chronic inflammatory process of RA. These findings have contributed to the development of targeted therapies that deplete B cells, such as rituximab, as well as inhibitors of B lymphocyte stimulation, such as belimumab. In a phase I trial, belimumab treatment significantly reduced CD20+ levels in patients with systemic lupus erythematosus. Phase I and phase II trials of rituximab found that rituximab plus methotrexate achieved significantly better American College of Rheumatology 50% responses for patients with RA than those patients receiving monotherapy with methotrexate. These clinical trial data present promising evidence for B cell targeted therapies as future therapeutic options for RA.



Biological and Targeted Therapies  

Microsoft Academic Search

\\u000a Biotherapy and molecular targeted therapies are innovative methods of treatment for cancer and have recently become standard\\u000a modalities for pediatric oncology, both alone and as adjuvants to other modalities such as surgery, radiation, and chemotherapy.\\u000a Bio-therapy uses the body's immune system, either directly or indirectly, to attack malignant cells or to minimize the side\\u000a effects caused by traditional cancer treatments.

Lindsay Gainer


FOS Target Acquisition Test  

NASA Astrophysics Data System (ADS)

FOS onboard target acquisition software capabilities will be verified by this test -- point source binary, point source firmware, point source peak-up, wfpc2 assisted realtime, point source peak-down, taled assisted binary, taled assisted firmware, and nth star binary modes. The primary modes are tested 3 times to determine repeatability. This test is the only test that will verify mode-to-mode acquisition offsets. This test has to be conducted for both the RED and BLUE detectors.

Koratkar, Anuradha



Targeting biodefense markets.  


The "World Vaccine Congress 2009" held in Washington D.C. (April 20-23, 2009) sponsored several sessions focused on the vaccine market targeting biodefense. On day one of the congress, a panel discussion outlined the federal progress in medical countermeasure preparedness that included emerging infections, influenza, and biodefense focuses. The second day, a session focused on the biodefense vaccine market with both government and industry members discussing the opportunities and challenges associated with the budding market. PMID:19855169

Olinger, Gene Garrard



Characterizing Kepler asteroseismic targets  

NASA Astrophysics Data System (ADS)

Stellar structure and evolution can be studied in great detail by asteroseismic methods, provided data of high precision are available. We determine the effective temperature (Teff), surface gravity (log g), metallicity and the projected rotational velocity (v sin i) of 44 Kepler asteroseismic targets using our high-resolution (R > 20 000) spectroscopic observations; these parameters will then be used to compute asteroseismic models of these stars and to interpret the Kepler light curves. We use the method of cross-correlation to measure the radial velocity (RV) of our targets, while atmospheric parameters are derived using the ROTFIT code and spectral synthesis method. We discover three double-lined spectroscopic binaries, HIP 94924, HIP 95115 and HIP 97321 - for the last system, we provide the orbital solution, and we report two suspected single-lined spectroscopic binaries, HIP 94112 and HIP 96062. For all stars from our sample we derive RV, v sin i, Teff, log g and metallicity, and for six stars, we perform a detailed abundance analysis. A spectral classification is done for 33 targets. Finally, we show that the early-type star HIP 94472 is rotating slowly (v sin i= 13 km s-1) and we confirm its classification to the Am spectral type which makes it an interesting and promising target for asteroseismic modelling. The comparison of the results reported in this paper with the information in the Kepler Input Catalogue (KIC) shows an urgent need for verification and refinement of the atmospheric parameters listed in the KIC. That refinement is crucial for making a full use of the data delivered by Kepler and can be achieved only by a detailed ground-based study. The data used in this paper have been obtained at the Catania Astrophysical Observatory (Italy), the F. L. Whipple Observatory, Arizona (USA) and the Oak Ridge Observatory, Massachusetts (USA).

Molenda-?akowicz, J.; Latham, D. W.; Catanzaro, G.; Frasca, A.; Quinn, S. N.



SETI target selection.  


The NASA High Resolution Microwave Survey consists of two complementary elements: a Sky Survey of the entire sky to a moderate level of sensitivity; and a Targeted Search of nearby stars, one at a time, to a much deeper level of sensitivity. In this paper we propose strategies for target selection. We have two goals: to improve the chances of successful detection of signals from technical civilizations that inhabit planets around solar-type stars, and to minimize the chances of missing signals from unexpected sites. For the main Targeted Search survey of approximately 1000 nearby solar-type stars, we argue that the selection criteria should be heavily biased by what we know about the origin and evolution of life here on Earth. We propose that observations of stars with stellar companions orbiting near the habitable zone should be de-emphasized, because such companions would prevent the formation of habitable planets. We also propose that observations of stars younger than about three billion years should be de-emphasized in favor of older stars, because our own technical civilization took longer than three billion years to evolve here on Earth. To provide the information needed for the preparation of specific target lists, we have undertaken an inventory of a large sample of solar-type stars out to a distance of 60 pc, with the goal of characterizing the relevant astrophysical properties of these stars, especially their ages and companionship. To complement the main survey, we propose that a modest sample of the nearest stars should be observed without any selection biases whatsoever. Finally, we argue that efforts to identify stars with planetary systems should be expanded. If found, such systems should receive intensive scrutiny. PMID:11540737

Latham, D W; Soderblom, D R


Monitoring target specific anticoagulants.  


New, target specific, oral anticoagulants have been shown to be safe and effective in prevention and treatment of thromboembolism without laboratory monitoring. However, clinical use of the drugs dabigatran, rivaroxaban, and apixaban requires laboratory measurement of their anticoagulant effect in specific clinical situations. This paper reviews the data available on use of screening and specialized testing to measure the anticoagulant effect and drug levels in patients prescribed these medications. Their effect on other coagulation assays is also reviewed. PMID:23381464

Konkle, Barbara A



Targeted endoscopic imaging.  


Endoscopy has undergone explosive technological growth in recent years, and with the emergence of targeted imaging, its truly transformative power and impact on medicine lies just over the horizon. Today, our ability to see inside the digestive tract with medical endoscopy is headed toward exciting crossroads. The existing paradigm of making diagnostic decisions based on observing structural changes and identifying anatomic landmarks may soon be replaced by visualizing functional properties and imaging molecular expression. In this novel approach, the presence of intracellular and cell surface targets unique to disease are identified and used to predict the likelihood of mucosal transformation and response to therapy. This strategy could result in the development of new methods for early cancer detection, personalized therapy, and chemoprevention. This targeted approach will require further development of molecular probes and endoscopic instruments, and will need support from the US Food and Drug Administration for streamlined regulatory oversight. Overall, this molecular imaging modality promises to significantly broaden the capabilities of the gastroenterologist by providing a new approach to visualize the mucosa of the digestive tract in a manner that has never been seen before. PMID:19423025

Li, Meng; Wang, Thomas D



Targeting Inactive Enzyme Conformation  

PubMed Central

There has been considerable interest in protein tyrosine phosphatase 1B (PTP1B) as a therapeutic target for diabetes, obesity, as well as cancer. Identifying inhibitory compounds with good bioavailability is a major challenge of drug discovery programs targeted toward PTPs. Most current PTP active site-directed pharmacophores are negatively charged pTyr mimetics which cannot readily enter the cell. This lack of cell permeability limits the utility of such compounds in signaling studies and further therapeutic development. We identify aryl diketoacids as novel pTyr surrogates and show that neutral amide-linked aryl diketoacid dimers also exhibit excellent PTP inhibitory activity. Kinetic studies establish that these aryl diketoacid derivatives act as noncompetitive inhibitors of PTP1B. Crystal structures of ligand-bound PTP1B reveal that both the aryl diketoacid and its dimeric derivative bind PTP1B at the active site, albeit with distinct modes of interaction, in the catalytically inactive, WPD loop open conformation. Furthermore, dimeric aryl diketoacids are cell permeable and enhance insulin signaling in hepatoma cells, suggesting that targeting the inactive conformation may provide a unique opportunity for creating active site-directed PTP1B inhibitors with improved pharmacological properties.

Liu, Sijiu; Zeng, Li-Fan; Wu, Li; Yu, Xiao; Xue, Ting; Gunawan, Andrea M.; Ya-Qiu, Long; Zhang, Zhong-Yin



Targeted Endoscopic Imaging  

PubMed Central

Summary Endoscopy has undergone explosive technological growth in over recent years, and with the emergence of targeted imaging, its truly transformative power and impact in medicine lies just over the horizon. Today, our ability to see inside the digestive tract with medical endoscopy is headed toward exciting crossroads. The existing paradigm of making diagnostic decisions based on observing structural changes and identifying anatomical landmarks may soon be replaced by visualizing functional properties and imaging molecular expression. In this novel approach, the presence of intracellular and cell surface targets unique to disease are identified and used to predict the likelihood of mucosal transformation and response to therapy. This strategy can result in the development of new methods for early cancer detection, personalized therapy, and chemoprevention. This targeted approach will require further development of molecular probes and endoscopic instruments, and will need support from the FDA for streamlined regulatory oversight. Overall, this molecular imaging modality promises to significantly broaden the capabilities of the gastroenterologist by providing a new approach to visualize the mucosa of the digestive tract in a manner that has never been seen before.

Li, Meng; Wang, Thomas D



Novel diuretic targets.  


As the molecular revolution continues to inform a deeper understanding of disease mechanisms and pathways, there exist unprecedented opportunities for translating discoveries at the bench into novel therapies for improving human health. Despite the availability of several different classes of antihypertensive medications, only about half of the 67 million Americans with hypertension manage their blood pressure appropriately. A broader selection of structurally diverse antihypertensive drugs acting through different mechanisms would provide clinicians with greater flexibility in developing effective treatment regimens for an increasingly diverse and aging patient population. An emerging body of physiological, genetic, and pharmacological evidence has implicated several renal ion-transport proteins, or regulators thereof, as novel, yet clinically unexploited, diuretic targets. These include the renal outer medullary potassium channel, ROMK (Kir1.1), Kir4.1/5.1 potassium channels, ClC-Ka/b chloride channels, UTA/B urea transporters, the chloride/bicarbonate exchanger pendrin, and the STE20/SPS1-related proline/alanine-rich kinase (SPAK). The molecular pharmacology of these putative targets is poorly developed or lacking altogether; however, recent efforts by a few academic and pharmaceutical laboratories have begun to lessen this critical barrier. Here, we review the evidence in support of the aforementioned proteins as novel diuretic targets and highlight examples where progress toward developing small-molecule pharmacology has been made. PMID:23863472

Denton, Jerod S; Pao, Alan C; Maduke, Merritt



The Rosetta Target Asteroids  

NASA Astrophysics Data System (ADS)

The final selection of the two Rosetta target asteroids will be done in a successive phase of the Rosetta project development, when the engineering parameters will be frozen. That allows the planetary science community to discuss in order to help the ESA Rosetta Project in the selection process. This poster presents the today scenario of the Rosetta target asteroids and the related available data base. The Rosetta mission baseline includes the fly--by of the asteroids 3840 Mimistrobell and 140 Siwa or 2703 Rodari. Barucci and Lazzarin (1995, Icarus 118, 216) and Barucci et al. (1996, in preparation), on the basis of the spectra of these objects obtained at ESO 1.5m and CFHT 3.6m telescopes, classify Mimistrobell as a S--type asteroid and Siwa as a C/D type asteroid. The Rodari's spectrum is under reduction. The spectra of several other asteroid possible fly--by candidates, if the launch date is changed (see the list in the Rosetta phase A Report, ESA SCI(93)7), have been also obtained (Barucci et al., 1996, in preparation). Only the lightcurve of 1992 Galvarino, one of the objects of this complementary list, is available (Birlan et al., 1996, PSS 44, 555). The authors together with the Rosetta mission trajectory definition team at ESOC will examine the possibility to add new ``more primitive'' candidate asteroids, starting a search of the objects which will require some more resources to be flown--by. We urge the community to devote some observational time to complete this data base including new candidates. The EARN (European Asteroid Research Node) in Berlin will open a section on the Rosetta target asteroids and all the observers are invited to feed this data base.

Fulchignoni, M.; Barucci, M. A.



Event parameters - fixed target  

SciTech Connect

This subgroup has focussed on detectors for fixed target experiments which have full azimuthal coverage. The general scope of the working group was to consider (1) the configuration of an idealized detector, and (2) various configurations of practical detectors that could be implemented on a relatively short time scale. The second category includes possible upgrades and modifications of existing experimental facilities. Beams of both 15 GeV/A sulphur at the AGS and 200 GeV/A oxygen at the SPS were considered.

Poskanzer, A.; Ritter, H.G.; Ludewigt, B.; Foley, K.; Borenstein, S.; Platner, E.; Love, W.; Keane, D.; Plasil, F.



TARGETing "When" and "Where"  

NSDL National Science Digital Library

In Drosophila, the cyclic adenosine monophosphate (cAMP) pathway has been shown to be crucial for learning and memory, but whether this represents a developmental or a specific effect has not been resolved. Research with a new targeting system that allows both spatial and temporal control of gene expression shows that expression of rutabaga-encoded adenylyl cyclase, a component of the cAMP signaling pathway, in the mushroom bodies of adult flies is necessary and sufficient to rescue the learning defect of rutabaga mutant. This demonstrates an acute role for Rutabaga in learning and memory.

Yalin Wang (Cold Spring Harbor Laboratory; REV); Yi Zhong (Cold Spring Harbor Laboratory; REV)



Targeting the androgen receptor.  


Androgen receptor (AR)-mediated signaling is critical to the growth and survival of prostate cancer. Although medical castration and antiandrogen therapy can decrease AR activity and lower PSA, castration resistance eventually develops. Recent work exploring the molecular structure and evolution of AR in response to hormonal therapies has revealed novel mechanisms of progression of castration-resistant prostate cancer and yielded new targets for drug development. This review focuses on understanding the mechanisms of persistent AR signaling in the castrate environment, and highlights new therapies either currently available or in clinical trials, including androgen synthesis inhibitors and novel direct AR inhibitors. PMID:23084523

Friedlander, Terence W; Ryan, Charles J



YSOs as Photometric Targets  

NASA Astrophysics Data System (ADS)

(Abstract only) Young stellar object research is an active and growing field within astronomy, and YSOs are targets for both optical photometry and multiwavelength studies from ground and space. They vary due to a number of different physical processes; they are also often red objects in dust-rich environments, making their spectra complex. Understanding of their optical variations requires calibrated photometry in standardized filters. In this short talk, we cover the most straightforward ways to perform observations of these objects that yield scientifically useful data.

Henden, A. A.



[Targeted therapies in oncology].  


The development of anticancer targeted therapies is the result of a knowledge transfer from biology research to clinical practice. Indeed these drugs act on proliferation signal pathways involved in oncogenesis. Monoclonal antibodies (antiHER1 or cetuximab, antiHER2 or trastuzimab, antiVEGF or bevacizumab...) or inhibitor proteins (antiHER1 or cetuximab, antityrosine kinase c-Kit or imatinib...) are used in the treatment of several cancers types (breast, colon-rectum, lung, kidney...) alone or in association with chemotherapies since they improve patients' prognosis and survival. However additional clinical studies are still required to optimize their administration. PMID:18303784

Fournel-Federico, Cécile; You, Benoît; Trillet-Lenoir, Véronique



Target Mass Corrections Revisited  

SciTech Connect

We propose a new implementation of target mass corrections to nucleon structure functions which, unlike existing treatments, has the correct kinematic threshold behavior at finite Q{sup 2} in the x {yields} 1 limit. We illustrate the differences between the new approach and existing prescriptions by considering specific examples for the F{sub 2} and F{sub L} structure functions, and discuss the broader implications of our results, which call into question the notion of universal parton distribution at finite Q{sup 2}.

W. Melnitchouk; F. Steffens



Targeting adipose tissue  

PubMed Central

Two different types of adipose tissues can be found in humans enabling them to respond to starvation and cold: white adipose tissue (WAT) is generally known and stores excess energy in the form of triacylglycerol (TG), insulates against cold, and serves as a mechanical cushion. Brown adipose tissue (BAT) helps newborns to cope with cold. BAT has the capacity to uncouple the mitochondrial respiratory chain, thereby generating heat rather than adenosine triphosphate (ATP). The previously widely held view was that BAT disappears rapidly after birth and is no longer present in adult humans. Using positron emission tomography (PET), however, it was recently shown that metabolically active BAT occurs in defined regions and scattered in WAT of the adult and possibly has an influence on whole-body energy homeostasis. In obese individuals adipose tissue is at the center of metabolic syndrome. Targeting of WAT by thiazolidinediones (TZDs), activators of peroxisome proliferator-activated receptor ? (PPAR?) a ‘master’ regulator of fat cell biology, is a current therapy for the treatment of type 2 diabetes. Since its unique capacity to increase energy consumption of the body and to dissipate surplus energy as heat, BAT offers new perspectives as a therapeutic target for the treatment of obesity and associated diseases such as type 2 diabetes and metabolic syndrome. Recent discoveries of new signaling pathways of BAT development give rise to new therapeutic possibilities in order to influence BAT content and activity.



Liquid Hydrogen: Target, Detector  

SciTech Connect

In 1952 D. Glaser demonstrated that a radioactive source's radiation could boil 135 deg. C superheated-diethyl ether in a 3-mm O glass vessel and recorded bubble track growth on high-speed film in a 2-cm3 chamber. This Bubble Chamber (BC) promised improved particle track time and spatial resolution and cycling rate. Hildebrand and Nagle, U of Chicago, reported Liquid Hydrogen minimum ionizing particle boiling in August 1953. John Wood created the 3.7-cm O Liquid Hydrogen BC at LBL in January 1954. By 1959 the Lawrence Berkley Laboratory (LBL) Alvarez group's '72-inch' BC had tracks in liquid hydrogen. Within 10 years bubble chamber volumes increased by a factor of a million and spread to every laboratory with a substantial high-energy physics program. The BC, particle accelerators and special separated particle beams created a new era of High Energy Physics (HEP) experimentation. The BC became the largest most complex cryogenic installation at the world's HEP laboratories for decades. The invention and worldwide development, deployment and characteristics of these cryogenic dynamic target/detectors and related hydrogen targets are described.

Mulholland, G.T. [Applied Cryogenics Technology, Ovilla TX 75154 (United States); Harigel, G.G. [CERN, European Organization for Nuclear Research, 1211 Geneva 23 (Switzerland)



Gelina neutron target optimisation.  


A study is being performed on the properties of the Geel Electron Linear Accelerator (GELINA), a powerful white neutron source, designed for the high-energy resolution time-of-flight measurements. The main aim of this study is to reduce the time spread of neutrons of the given energy without compromising the neutron yield. Both time spread and neutron intensity influence the experimental accuracy of high-resolution neutron cross section measurements, which are particularly important in the resonance region. The quantities of interest have been simulated with coupled electron-photon-neutron steady state and transient MCNP4C3 calculations. Following benchmarking of the code to the properties of the existing target, neutron yield, energy spectra, resolution functions, and neutron and heat spatial distributions have been determined for various alternative geometries and materials. At a fixed accelerator power, actinides deliver the highest neutron yield and a small target provides the best time resolution. The resulting high-power density requires a joint optimisation of the thermal hydraulics and neutronics properties. PMID:16381756

Flaska, M; Plompen, A J M; Mondelaers, W; Lathouwers, D; van der Hagen, T H J J; van Dam, H



Targeting adipose tissue.  


Two different types of adipose tissues can be found in humans enabling them to respond to starvation and cold: white adipose tissue (WAT) is generally known and stores excess energy in the form of triacylglycerol (TG), insulates against cold, and serves as a mechanical cushion. Brown adipose tissue (BAT) helps newborns to cope with cold. BAT has the capacity to uncouple the mitochondrial respiratory chain, thereby generating heat rather than adenosine triphosphate (ATP). The previously widely held view was that BAT disappears rapidly after birth and is no longer present in adult humans. Using positron emission tomography (PET), however, it was recently shown that metabolically active BAT occurs in defined regions and scattered in WAT of the adult and possibly has an influence on whole-body energy homeostasis. In obese individuals adipose tissue is at the center of metabolic syndrome. Targeting of WAT by thiazolidinediones (TZDs), activators of peroxisome proliferator-activated receptor ? (PPAR?) a 'master' regulator of fat cell biology, is a current therapy for the treatment of type 2 diabetes. Since its unique capacity to increase energy consumption of the body and to dissipate surplus energy as heat, BAT offers new perspectives as a therapeutic target for the treatment of obesity and associated diseases such as type 2 diabetes and metabolic syndrome. Recent discoveries of new signaling pathways of BAT development give rise to new therapeutic possibilities in order to influence BAT content and activity. PMID:23102228

Haas, Bodo; Schlinkert, Paul; Mayer, Peter; Eckstein, Niels



Gene targeting in plants  

PubMed Central

Although the generation of transgenic plants is now routine, the integration of foreign genetic information has so far been at random sites in the genome. We now present evidence for directed integration into a predicted location in the host plant genome. Protoplasts of transgenic tobacco (Nicotiana tabaccum) plants carrying copies of a partial, non-functional drug-resistance gene in the nuclear DNA were used as recipients for DNA molecules containing the missing part of the gene. Molecular and genetic data confirm the integration of the foreign DNA through homologous recombination within overlapping parts of the protein coding region, resulting in the formation of an active gene in the host chromosome. This approach is referred to as gene targeting. The gene targeting frequency (the number of drug-resistant clones resulting from gene correction compared to the number of resistant clones from parallel experiments with a similar non-interrupted hybrid gene) was 0.5-4.2×10-4. These experiments demonstrate the possibility of producing transgenic plants with desired modifications to a specific nuclear gene. Images

Paszkowski, Jerzy; Baur, Markus; Bogucki, Augustyn; Potrykus, Ingo



Extrapolating target tracks  

NASA Astrophysics Data System (ADS)

Steady-state performance of a tracking filter is traditionally evaluated immediately after a track update. However, there is commonly a further delay (e.g., processing and communications latency) before the tracks can actually be used. We analyze the accuracy of extrapolated target tracks for four tracking filters: Kalman filter with the Singer maneuver model and worst-case correlation time, with piecewise constant white acceleration, and with continuous white acceleration, and the reduced state filter proposed by Mookerjee and Reifler.1, 2 Performance evaluation of a tracking filter is significantly simplified by appropriate normalization. For the Kalman filter with the Singer maneuver model, the steady-state RMS error immediately after an update depends on only two dimensionless parameters.3 By assuming a worst case value of target acceleration correlation time, we reduce this to a single parameter without significantly changing the filter performance (within a few percent for air tracking).4 With this simplification, we find for all four filters that the RMS errors for the extrapolated state are functions of only two dimensionless parameters. We provide simple analytic approximations in each case.

Van Zandt, James R.



Tankyrases as drug targets.  


Tankyrase 1 and tankyrase 2 are poly(ADP-ribosyl)ases that are distinguishable from other members of the enzyme family by the structural features of the catalytic domain, and the presence of a sterile ?-motif multimerization domain and an ankyrin repeat protein-interaction domain. Tankyrases are implicated in a multitude of cellular functions, including telomere homeostasis, mitotic spindle formation, vesicle transport linked to glucose metabolism, Wnt-?-catenin signaling, and viral replication. In these processes, tankyrases interact with target proteins, catalyze poly(ADP-ribosyl)ation, and regulate protein interactions and stability. The proposed roles of tankyrases in disease-relevant cellular processes have made them attractive drug targets. Recently, several inhibitors have been identified. The selectivity and potency of these small molecules can be rationalized by how they fit within the NAD(+)-binding groove of the catalytic domain. Some molecules bind to the nicotinamide subsite, such as generic diphtheria toxin-like ADP-ribosyltransferase inhibitors, whereas others bind to a distinct adenosine subsite that diverges from other diphtheria toxin-like ADP-ribosyltransferases and confers specificity. A highly potent dual-site inhibitor is also available. Within the last few years, tankyrase inhibitors have proved to be useful chemical probes and potential lead compounds, especially for specific cancers. PMID:23648170

Lehtiö, Lari; Chi, Nai-Wen; Krauss, Stefan



Advances in Targeted Therapies Tutorial

A tutorial for health professionals that gives an overview of targeted therapies, an emerging approach to cancer treatment. Includes examples of the main types of targeted therapies and describes their mechanisms of action.


Revised target information for ICF reactor studies.  

National Technical Information Service (NTIS)

This report discusses the following topics: summary of target gain and driver requirements for short wavelength laser driven indirect drive targets; direct drive laser targets; heavy ion target gain; and target costing and output. 5 figs. (LSP)

R. Bangerter



Oxide fiber targets at ISOLDE  

Microsoft Academic Search

Many elements are rapidly released from oxide matrices. Some oxide powder targets show a fast sintering, thus losing their favorable release characteristics. Loosely packed oxide fiber targets are less critical since they may maintain their open structure even when starting to fuse together at some contact points.The experience with various oxide fiber targets (titania, zirconia, ceria and thoria) used in

U. Köster; U. C. Bergmann; D. Carminati; R. Catherall; J. Cederkäll; B. Crepieux; M. Dietrich; K. Elder; V. N. Fedoseyev; L. Fraile; S. Franchoo; H. Fynbo; U. Georg; T. Giles; A. Joinet; O. C. Jonsson; R. Kirchner; Ch. Lau; J. Lettry; H. J. Maier; V. I. Mishin; M. Oinonen; K. Peräjärvi; H. L. Ravn; T. Rinaldi; M. Santana-Leitner; U. Wahl; L. Weissman



Mobile target ladar ATR system  

Microsoft Academic Search

The Mobile Target Acquisition System (MTAS) is an automatic target recognition (ATR) system developed by the Naval Air Warfare Center Weapons Division, China Lake, CA, under funding by the Office of Naval Research (ONR) to detect and identify mobile target laser detection and ranging (LADAR) range signatures. The primary objective was to achieve high correct system identification rates for range

Jesse L. Hodge; David H. DeKruger; Alden E. Park



Target Costing: Uncharted Research Territory  

Microsoft Academic Search

Target costing is a strategic weapon that is being increasingly adopted by a number of leading firms across the world. What first captured the attention of managers is the competitive advantage that target costing has given to the Japanese auto companies—the longest and most consistent users of target costing. Ironically, as Japan exported the technique to South Korea, a number

Shahid Ansari; Jan Bell; Hiroshi Okano



Electromagnetic targeting of guns  

SciTech Connect

This is the final report of a one-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). Electromagnetic pulse (EMP) signals produced from explosives being fired have been reported in the literature for fifty years. When a gun is fired it produces an EMP muzzle blast signal. The strength and nature of these signals was first analyzed in the early 1970s, while the results were interesting, no follow-up studies were conducted. With modern detection and signal processing technology, we believe that these signals could be used to instantaneously locate guns of virtually all calibers as they fire. The objective of our one-year project was to establish the basic nature of these signals and their utility in the concept of electromagnetic targeting of guns.

Pogue, E.W.; Boat, R.M.; Holden, D.N.; Lopez, J.R. [and others



Laser target speckle eliminator  

NASA Astrophysics Data System (ADS)

An apparatus for eliminating the phenomenon of speckle with regard to laser light reflected from a distant target whose roughness exceeds the wavelength of the laser light. The apparatus includes a half plate wave member, a first polarizing beam splitter member, a totally reflecting right angle prism, and a second polarizing beam splitter member, all of which are in serial optical alignment, that are used in combination to convert a linearly (i.e., vertically) polarized light beam, which is emitted by a laser having a known coherence length, into two coincident, orthogonally polarized, beams that are not coherent with each other, and that have an optical path difference which exceeds the known coherence length of the emitting laser, to eliminate the speckle.

Scully, C. N.



Targeting Histone Demethylases  

PubMed Central

In addition to genetic disorders, epigenetic alterations have been shown to be involved in cancer, through misregulation of histone modifications. Miswriting, misreading, and mis-erasing of histone acetylation as well as methylation marks can be actually associated with oncogenesis and tumor proliferation. Historically, methylation of Arg and Lys residues has been considered a stable, irreversible process due to the slow turnover of methyl groups in chromatin. The discovery in recent years of a large number of histone Lys demethylases (KDMs, belonging to either the amino oxidase or the JmjC family) totally changed this point of view and suggested a new role for dynamic histone methylation in biological processes. Since overexpression, alteration, or mutation of a number of KDMs has been found in many types of cancers, such enzymes could represent diagnostic tools as well as epigenetic targets to modulate for obtaining novel therapeutic weapons against cancer. The first little steps in this direction are described here.

Rotili, Dante; Mai, Antonello



ORION laser target diagnostics.  


The ORION laser facility is one of the UK's premier laser facilities which became operational at AWE in 2010. Its primary mission is one of stockpile stewardship, ORION will extend the UK's experimental plasma physics capability to the high temperature, high density regime relevant to Atomic Weapons Establishment's (AWE) program. The ORION laser combines ten laser beams operating in the ns regime with two sub ps short pulse chirped pulse amplification beams. This gives the UK a unique combined long pulse/short pulse laser capability which is not only available to AWE personnel but also gives access to our international partners and visiting UK academia. The ORION laser facility is equipped with a comprehensive suite of some 45 diagnostics covering optical, particle, and x-ray diagnostics all able to image the laser target interaction point. This paper focuses on a small selection of these diagnostics. PMID:23126904

Bentley, C D; Edwards, R D; Andrew, J E; James, S F; Gardner, M D; Comley, A J; Vaughan, K; Horsfield, C J; Rubery, M S; Rothman, S D; Daykin, S; Masoero, S J; Palmer, J B; Meadowcroft, A L; Williams, B M; Gumbrell, E T; Fyrth, J D; Brown, C R D; Hill, M P; Oades, K; Wright, M J; Hood, B A; Kemshall, P



Carbon Monoxide Targeting Mitochondria  

PubMed Central

Mitochondria present two key roles on cellular functioning: (i) cell metabolism, being the main cellular source of energy and (ii) modulation of cell death, by mitochondrial membrane permeabilization. Carbon monoxide (CO) is an endogenously produced gaseoustransmitter, which presents several biological functions and is involved in maintaining cell homeostasis and cytoprotection. Herein, mitochondrion is approached as the main cellular target of carbon monoxide (CO). In this paper, two main perspectives concerning CO modulation of mitochondrial functioning are evaluated. First, the role of CO on cellular metabolism, in particular oxidative phosphorylation, is discussed, namely, on: cytochrome c oxidase activity, mitochondrial respiration, oxygen consumption, mitochondrial biogenesis, and general cellular energetic status. Second, the mitochondrial pathways involved in cell death inhibition by CO are assessed, in particular the control of mitochondrial membrane permeabilization.

Queiroga, Claudia S. F.; Almeida, Ana S.; Vieira, Helena L. A.



Targeting HER2  

PubMed Central

The potential of the HER2-targeting antibody trastuzumab as a radioimmunoconjugate useful for both imaging and therapy was investigated. Conjugation of trastuzumab with the acyclic bifunctional chelator CHX-A?-DTPA yielded a chelate:protein ratio of 3.4 ± 0.3; the immunoreactivity of the antibody unaffected. Radiolabeling was efficient, routinely yielding a product with high specific activity. Tumor targeting was evaluated in mice bearing subcutaneous (s.c.) xenografts of colorectal, pancreatic, ovarian and prostate carcinomas. High uptake of the radioimmunoconjugate, injected intravenously (i.v.), was observed in each of the models and the highest tumor %ID/g (51.18 ± 13.58) was obtained with the ovarian (SKOV-3) tumor xenograft. Specificity was demonstrated by the absence of uptake of 111In-trastuzumab by melanoma (A375) s.c. xenografts and 111In-HuIgG by s.c. LS-174T xenografts. Minimal uptake of i.v. injected 111In-trastuzumab in normal organs was confirmed in non-tumor-bearing mice. The in vivo behavior of 111In-trastuzumab in mice bearing intraperitoneal (i.p.) LS-174T tumors resulted in a tumor %ID/g of 130.85 ± 273.34 at 24 h. Visualization of tumor, s.c. and i.p. xenografts was achieved by ?-scintigraphy and PET imaging. Blood pool was evident as expected but cleared over time. The blood pharmacokinetics of i.v. and i.p. injected 111In-trastuzumab was determined in mice with and without tumors. The data from these in vitro and in vivo studies supported advancement of radiolabeled trastuzumab into two clinical studies, a Phase 0 imaging study in the Molecular Imaging Program of the National Cancer Institute and a Phase 1 radioimmunotherapy study at the University of Alabama.

Wong, Karen J; Baidoo, Kwamena E; Nayak, Tapan K; Regino, Celeste AS; Garmestani, Kayhan; Brechbiel, Martin W



Mobile target ladar ATR system  

NASA Astrophysics Data System (ADS)

The Mobile Target Acquisition System (MTAS) is an automatic target recognition (ATR) system developed by the Naval Air Warfare Center Weapons Division, China Lake, CA, under funding by the Office of Naval Research (ONR) to detect and identify mobile target laser detection and ranging (LADAR) range signatures. The primary objective was to achieve high correct system identification rates for range signatures of relatively low numbers of pixels on target and, at the same time, maintain a low system identification false alarm rate. MTAS met this objective by stressing conservation and efficient exploitation of target information at all levels of processing. Adaptive noise cleaning conserves target information by filtering pixels only when the pixel and its neighbors satisfied the criteria for range dropouts. The MTAS detector holds false alarms to a low level by convolving synthetic templates with the gradient of the range image and fusing the resulting correlation surface with a blob size filter. Mobile target identification fuses 2-D silhouette shape with 3-D (21/2-D) volumetric shape where the mixture of 2- and 3-D shapes is controlled by a single parameter. The match between the measured LADAR range signature and the synthetic range template efficiently and effectively exploits scarce target information by including all target and template pixels in the Fuzzy Tanimoto Distance similarity measure. This system has successfully detected and identified measured mobile LADAR target signatures with 200 pixels on target and greater with a low confuser identification rate and no system clutter identification false alarms.

Hodge, Jesse L.; DeKruger, David H.; Park, Alden E.



Coronary Artery Bypass Grafting in Idiopathic Thrombocytopenia  

PubMed Central

Patients with idiopathic thrombocytopenic purpura have safely undergone cardiac surgical procedures; however, platelets were transfused in 20 of 24 reported instances, and no point-of-care testing of coagulation status was performed. Herein, we report the case of a patient with idiopathic thrombocytopenic purpura who required urgent coronary artery bypass grafting and intra-aortic balloon pump support. Rotational thromboelastometry was used as a point-of-care test of the patient's coagulation status. No preoperative prophylactic transfusion of allogeneic platelets was necessary, and in fact the patient required no allogeneic blood products during his hospitalization. We believe that point-of-care coagulation tests such as thromboelastometry warrant further evaluation regarding their usefulness in the clinical decision of whether to transfuse platelets and other blood products.

Rossi, Michele; Lewis, Michael; Hutchinson, Nevil



Gallbladder cancer-associated thrombotic microangiopathy.  


Cancer-associated thrombotic microangiopathy (TMA) is a rare but serious condition seen in patients diagnosed with malignancy. Certain tumor characteristics highlight this entity, such as large tumor burden, adenocarcinoma histology with mucinous features and bone marrow infiltration. Although these tumors may originate from any site, the majority are of stomach, breast or prostate origin. The optimal therapy is unknown but there is evidence that immediate initiation of an effective antineoplastic regimen is important. However, it is difficult to differentiate cancer-associated TMA from primary thrombotic thrombocytopenic purpura in a timely manner. We present the first case of cancer-associated TMA in a patient secondary to a locally advanced gallbladder adenocarcinoma that lacked mucinous features and bone marrow involvement. The clinical presentation closely mimicked primary thrombocytopenic purpura and led to the ineffective use of plasma exchange. Nonetheless, the patient eventually received systemic chemotherapy and had a remarkable response by the resolution of her TMA. PMID:24156330

Gonsalves, Wilson I; Gupta, Vinay; Smeltzer, Jacob P; Singh, Preet P; McWilliams, Robert R; Gangat, Naseema



Thrombocytopenia in pregnancy.  


The implications of thrombocytopenia in pregnancy vary with the etiology of the thrombocytopenia. This article focuses on defining what those etiologies are and assessing risk and therapy for each. Most important, the need to diagnose the largest and most benign entity of incidental thrombocytopenia is emphasized so that patients can be reassured and not subjected to further intervention. The angiopathic entities of preeclampsia, HELLP syndrome (hemolytic anemia, elevated liver function tests, and low platelets), disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, and hemolytic-uremic syndrome may also cause severe thrombocytopenia. The controversy surrounding the particular therapeutic dilemma of immune thrombocytopenic purpura is explored, with evaluation of the actual danger to the mother, method of delivery, and treatment for the neonate. The serious nature of alloimmune thrombocytopenia is emphasized, and current modes of risk assessment and therapy are discussed. PMID:7949823

Billett, H H



Using the Nova target chamber for high-yield targets  

SciTech Connect

The existing 2.2-m-radius Nova aluminum target chamber, coated and lined with boron-seeded carbon shields, is proposed for use with 1000-MJ-yield targets in the next laser facility. The laser beam and diagnostic holes in the target chamber are left open and the desired 10/sup -2/ Torr vacuum is maintained both inside and outside the target chamber; a larger target chamber room is the vacuum barrier to the atmosphere. The hole area available is three times that necessary to maintain a maximum fluence below 12 J/cm/sup 2/ on optics placed at a radius of 10 m. Maximum stress in the target chamber wall is 73 MPa, which complies with the intent of the ASME Pressure Vessel Code. However, shock waves passing through the inner carbon shield could cause it to comminute. We propose tests and analyses to ensure that the inner carbon shield survives the environment. 13 refs.

Pitts, J.H.



[Target volume margins for lung cancer: Internal target volume/clinical target volume].  


The aim of this study was to carry out a review of margins that should be used for the delineation of target volumes in lung cancer, with a focus on margins from gross tumour volume (GTV) to clinical target volume (CTV) and internal target volume (ITV) delineation. Our review was based on a PubMed literature search with, as a cornerstone, the 2010 European Organisation for Research and Treatment of Cancer (EORTC) recommandations by De Ruysscher et al. The keywords used for the search were: radiotherapy, lung cancer, clinical target volume, internal target volume. The relevant information was categorized under the following headings: gross tumour volume definition (GTV), CTV-GTV margin (first tumoural CTV then nodal CTV definition), in field versus elective nodal irradiation, metabolic imaging role through the input of the PET scanner for tumour target volume and limitations of PET-CT imaging for nodal target volume definition, postoperative radiotherapy target volume definition, delineation of target volumes after induction chemotherapy; then the internal target volume is specified as well as tumoural mobility for lung cancer and respiratory gating techniques. Finally, a chapter is dedicated to planning target volume definition and another to small cell lung cancer. For each heading, the most relevant and recent clinical trials and publications are mentioned. PMID:23988437

Jouin, A; Pourel, N



Immunotherapy Targets in Pediatric Cancer  

PubMed Central

Immunotherapy for cancer has shown increasing success and there is ample evidence to expect that progress gleaned in immune targeting of adult cancers can be translated to pediatric oncology. This manuscript reviews principles that guide selection of targets for immunotherapy of cancer, emphasizing the similarities and distinctions between oncogene-inhibition targets and immune targets. It follows with a detailed review of molecules expressed by pediatric tumors that are already under study as immune targets or are good candidates for future studies of immune targeting. Distinctions are made between cell surface antigens that can be targeted in an MHC independent manner using antibodies, antibody derivatives, or chimeric antigen receptors versus intracellular antigens which must be targeted with MHC restricted T cell therapies. Among the most advanced immune targets for childhood cancer are CD19 and CD22 on hematologic malignancies, GD2 on solid tumors, and NY-ESO-1 expressed by a majority of synovial sarcomas, but several other molecules reviewed here also have properties which suggest that they too could serve as effective targets for immunotherapy of childhood cancer.

Orentas, Rimas J.; Lee, Daniel W.; Mackall, Crystal



2-Butoxyethanol enhances the adherence of red blood cells  

Microsoft Academic Search

We recently presented a unique, chemically-induced rat model of hemolytic anemia and disseminated thrombosis. In this 2-butoxyethanol (BE)-induced model the organs developing infarction are comparable to those seen in human diseases, characterized by hemolysis and thrombosis (e.g., thalassemia, sickle-cell disease, paroxysmal nocturnal hemoglobinuria, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, and hemolytic uremic syndrome). Red blood cells (RBCs) have special flow

Alexander Koshkaryev; Gregory Barshtein; Abraham Nyska; Nathan Ezov; Tal Levin-Harrus; Shay Shabat; Meir Nyska; Meir Redlich; Felix Tsipis; Saul Yedgar



Multi-dysfunctional pathophysiology in ITP  

Microsoft Academic Search

Idiopathic thrombocytopenic purpura (ITP) is an organ-specific autoimmune disorder characterized by a low platelet count and mucocutaneous bleeding. The decrease of platelets is caused by increased autoantibodies against self-antigens, particularly IgG antibodies against GPIIb\\/IIIa. The production of these autoantibodies by B cells depends on a number of cellular mechanisms that form a network of modulation, with T cells playing a

Bin Zhou; Hui Zhao; Ren Chi Yang; Zhong Chao Han



A pilot study of rhuIL-11 treatment of refractory ITP  

Microsoft Academic Search

The objective of this research was to determine whether rhuIL-11 is an effective treatment in patients with refractory immune thrombocytopenic purpura (ITP). Platelet production is decreased in certain cases of refractory ITP. IL-11 stimulates megakaryocytopoiesis in vitro and was licensed for its clinical effects to ameliorate chemotherapy-induced throm- bocytopenia. A pilot study was initiated, intending to enroll 12 patients with

James B. Bussel; Robin Mukherjee; Anne J. Stone



Comparison of platelet immunity in patients with SLE and with ITP  

Microsoft Academic Search

Idiopathic thrombocytopenic purpura (ITP) is characterized by the development of a specific anti-platelet autoantibody immune response mediating the development of thrombocytopenia. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of a wide variety of autoantibodies. In 15–20% of SLE cases, patients develop thrombocytopenia which appears to be autoimmune in nature (SLE-TP). To better understand the pathogenesis

Alan H Lazarus; Janet Ellis; John W Semple; Meera Mody; Andrew R Crow; John Freedman



ADAMTS13 is expressed in hepatic stellate cells  

Microsoft Academic Search

ADAMTS13 is a circulating zinc metalloprotease that cleaves the hemostatic glycoprotein von Willebrand factor (VWF) in a shear-dependent manner. Deficiency in ADAMTS13, owing to genetic mutations or autoimmune inhibitors, causes thrombotic thrombocytopenic purpura (TPP). Northern blot analysis has shown that ADAMTS13 is expressed primarily in the liver. By using real-time RT-PCR, we confirmed that in mice the liver had the

Wenhua Zhou; Mari Inada; Tai-Ping Lee; Daniel Benten; Sergey Lyubsky; Eric E Bouhassira; Sanjeev Gupta; Han-Mou Tsai



ADAMTS13 autoantibodies in patients with thrombotic microangiopathies and other immunomediated diseases  

Microsoft Academic Search

Autoantibodies neutralizing human ADAMTS13 (a disintegrin-like and metallo- proteinase with thrombospondin type 1 motif),themetalloproteasethatphysiolog- ically cleaves von Willebrand factor, are a major cause of severe deficiency of the protease and of acquired thrombotic thrombocytopenic purpura (TTP). We evaluated prevalence of anti-ADAMTS13 antibodies in 59 patients with thrombotic microangiopathies (TMAs) and in 160 pa- tients with immunologic or thrombocyto- penic diseases

Manfred Rieger; Johanna A. Kremer Hovinga; Andrea Herzog; Gabi Gerstenbauer; Christian Konetschny; Klaus Zimmermann; Inge Scharrer; Flora Peyvandi; Miriam Galbusera; Giuseppe Remuzzi; Martina Bohm; Barbara Plaimauer; Bernhard Lammle; Friedrich Scheiflinger



Cloning, expression, and functional characterization of the von Willebrand factor-cleaving protease (ADAMTS13)  

Microsoft Academic Search

Deficient von Willebrand factor (VWF) deg- radation has been associated with throm- botic thrombocytopenic purpura (TTP). In hereditary TTP, the specific VWF-cleaving protease (VWF-cp) is absent or function- ally defective, whereas in the nonfamilial, acquired form of TTP, an autoantibody inhibiting VWF-cp activity is found tran- siently in most patients. The gene encod- ing for VWF-cp has recently been identi-

Barbara Plaimauer; Klaus Zimmermann; Dirk Volkel; Gerhard Antoine; Randolf Kerschbaumer; Pegah Jenab; Miha Furlan; Helen Gerritsen; Bernhard Lammle; Hans Peter Schwarz; Friedrich Scheiflinger



Evaluation and clinical application of a new method for measuring activity of von Willebrand factor-cleaving metalloprotease (ADAMTS13)  

Microsoft Academic Search

Thrombotic thrombocytopenic purpura (TTP) is associated with acquired or congenital deficiency of a plasma von Willebrand factor-cleaving protease (VWFcp). Based on partial amino acid sequence and genome-wide linkage analysis of pedigrees with congenital TTP, VWFcp was recently identified as a new member of the ADAMTS family and designated ADAMTS13. We developed a new, rapid, and simple method for measuring VWFcp

M. Böhm; T. Vigh; I. Scharrer



Mutations and common polymorphisms in ADAMTS13 gene responsible for von Willebrand factor-cleaving protease activity  

Microsoft Academic Search

von Willebrand factor (VWF) is synthesized primarily in vascular endothelial cells and secreted into the plasma as unusually large VWF multimers. Normally, these multimers are quickly degraded into smaller forms by a plasma metalloproteinase, VWF-cleaving protease (VWF-CP). Decreases in the activity of this enzyme result in congenital and acquired thrombotic thrombocytopenic purpura (TTP). The human VWF-CP has recently been purified.

Koichi Kokame; Masanori Matsumoto; Kenji Soejima; Hideo Yagi; Hiromichi Ishizashi; Masahisa Funato; Hiroshi Tamai; Mutsuko Konno; Kei Kamide; Yuhei Kawano; Toshiyuki Miyata; Yoshihiro Fujimura



Autoantibodies Against the Platelet Glycoprotein lib\\/Illa Complex in Patients With Chronic ITP  

Microsoft Academic Search

Chronic idiopathic thrombocytopenic purpura (ITP) is caused by an antibody reactive with platelet-associated antigens. The present studies provide direct evidence that some patients with chronic ITP have autoantibodies against the platelet glycoprotein (GP) lIb\\/Illa complex. Microtiter wells. coated with a monoclonal antibody (2G12) specific for GPIIb\\/GPIlIa were reacted with GPlIb\\/GPlIla contained in a platelet extract. Control wells containing the same

Virgil L. Woods; Esther H. Oh; Donna Mason; Robert McMillan



Hyposplenism from Mycobacterium avium Complex Infection in a Patient with AIDS and Immune Thrombocytopenia  

Microsoft Academic Search

We describe a patient with HIV-related immune thrombocytopenic purpura with known Mycobacterium avium complex (MAC) infection presenting with intracerebral hemorrhage associated with severe thrombocytopenia who failed splenectomy following unsuccessful trials of corticosteroids and intravenous immunoglobulin. His presplenectomy peripheral blood smear showed Howell-Jolly bodies and microscopic examination of his spleen demonstrated multiple granulomas with numerous acid-fast organisms replacing the normal splenic

Amir M. Khan; Robert D. Harrington; Martin Nadel; Bernard R. Greenberg



Hospital-Acquired Pneumonia and Bacteremia Caused by Legionella pneumophila in an Immunocompromised Patient  

Microsoft Academic Search

\\u000a Abstract\\u000a   The Legionella species is an important cause of communityand hospital-acquired pneumonia. Bacteremic pneumonia caused by L. pneumophila is rarely reported. We describe the first reported case of hospital-acquired pneumonia and bacteremia caused by L. pneumophila from Taiwan in a patient with idiopathic thrombocytopenic purpura who received steroid treatment. The patient was successfully\\u000a treated with ceftazidime and clindamycin initially, followed

C.-C. Lai; C.-K. Tan; C.-H. Chou; H.-L. Hsu; Y.-T. Huang; C.-H. Liao; P.-R. Hsueh



Filter membrane-based automated therapeutic plasma exchange: a report of two cases from Nigeria.  


These case reports demonstrated the diagnostic dilemma encountered in patients with systemic lupus erythematosus and thrombotic thrombocytopenic purpura particularly in settings with limited diagnostic facilities and laboratory support. The similarities in the diagnostic criteria for both conditions make clear distinction as well as management decisions difficult. We present the difficulties encountered with both the diagnosis and the management of these two patients that were managed in our facility. PMID:23420598

Arogundade, Fatiu A; Sanusi, Abubakr A; Akinbodewa, Akinwunmi A; Hassan, Muzamil O; Omotosho, Bolanle O; Balogun, Rasheed A; Akinsola, Adewale



The Presence of Precursors of Benign Pre-B Lymphoblasts (Hematogones) in the Bone Marrow of a Paediatric Patient with Cytomegalovirus Infection  

PubMed Central

Hematogones are normal B-lymphoid precursors that multiply in the bone marrow of small children and of adults with ferropenic anaemia, neuroblastoma or idiopathic thrombocytopenic purpura. They are not normally found in peripheral blood, and the immunophenotype is virtually indistinguishable from that of B lymphoblasts. We discuss the case of a 3-month infant with an active cytomegalovirus infection, with hepatitis and pancytopenia associated with 13% hematogones in the bone marrow.

Moreno-Madrid, F; Uberos, J; Diaz-Molina, M; Ramirez-Arredondo, A; Jimenez-Gamiz, P; Molina-Carballo, A



Neonatal autoimmune thrombocytopenia: role of high-dose intravenous immunoglobulin G therapy  

Microsoft Academic Search

High-dose intravenous immunoglobulin G (IVIgG) therapy results in a rapid reversal of thrombocytopenia in over 80% of children with acute immune thrombocytopenic purpura (ITP). Comparable results were observed in eleven infants with an analogous condition, neonatal autoimmune thrombocytopenia (NATP), who received IVIgG (2 g\\/kg body weight) administered alone (n=6) or in combination with steroids (n=5). The median platelet count pre-IVIgG

Victor Blanchette; Maureen Andrew; Max Perlman; Emily Ling; Ami Ballin



Severe Thrombocytopenia in Aged Rhesus Macaques (Macaca mulatta) Infected with Simian Varicella Virus  

PubMed Central

Simian varicella virus was diagnosed in 2 geriatric rhesus macaques (Macaca mulatta). The macaques presented with typical skin lesions as well as severe thrombocytopenia as a result of infection. Idiopathic thrombocytopenic purpura is a known complication of varicella zoster virus infection in humans; however, this condition has not been reported previously as a complication of SVV infection. This case report discusses the clinical presentation, pathology, and thrombocytopenia of the affected macaques.

Halliday, Lisa C; Fortman, Jeffrey D



Splenic scintigraphy using Tc99m-labeled heat-denatured red blood cells in pediatric patients: concise communication  

Microsoft Academic Search

Ten children underwent splenic imaging with heat-denatured red blood cells labeled with technetium-99m (Tc-99m DRBC). The presenting problems included the heterotaxia syndrome, recurrent idiopathic thrombocytopenic purpura following splenectomy, mass in the left posterior hemithorax, and blunt abdominal trauma. In nine patients, the presence or absence of splenic tissue was established. A splenic hematoma was identified in the tenth patient. All

C. P. Ehrlich; N. Papanicolaou; S. Treves; R. A. Hurwitz; P. Richards



Thrombotic Microangiopathy with Skin Localization Secondary to Cytarabine-Daunorubicin Association: Report of a Case  

PubMed Central

The thrombotic microangiopathy is a syndrome characterized by the combination of mechanical hemolytic anemia, peripheral thrombocytopenia, and organ failure of variable severity. In addition to the idiopathic form, several cases are identified as secondary to pregnancy, infections, disease systems, organ transplants, and cancer. Other forms are secondary to drugs including antimitotics. We report the case of a patient followed for acute myelogenous leukemia. She received induction chemotherapy combining daunorubicin and cytarabine, complicated by thrombotic thrombocytopenic purpura.

Regragui, S.; Amelal, S.; Astati, S.; Zine, M.; Alami Drideb, N.; Al Bouzidi, A.; Messaoudi, N.; Benkirane, M.; Doghmi, K.; Mikdame, M.



Thrombotic microangiopathy with skin localization secondary to cytarabine-daunorubicin association: report of a case.  


The thrombotic microangiopathy is a syndrome characterized by the combination of mechanical hemolytic anemia, peripheral thrombocytopenia, and organ failure of variable severity. In addition to the idiopathic form, several cases are identified as secondary to pregnancy, infections, disease systems, organ transplants, and cancer. Other forms are secondary to drugs including antimitotics. We report the case of a patient followed for acute myelogenous leukemia. She received induction chemotherapy combining daunorubicin and cytarabine, complicated by thrombotic thrombocytopenic purpura. PMID:22953078

Regragui, S; Amelal, S; Astati, S; Zine, M; Alami Drideb, N; Al Bouzidi, A; Messaoudi, N; Benkirane, M; Doghmi, K; Mikdame, M



Target support for inertial confinement fusion  

SciTech Connect

General Atomics (GA) plays an important industrial support role for the US Inertial Confinement Fusion (ICF) program in the area of target technology. This includes three major activities: target fabrication support, target handling systems development, and target chamber design. The work includes target fabrication for existing ICF experiments, target and target system development for future experiments, and target research and target chamber design for experiments on future machines, such as the National Ignition Facility (NIF).

Schultz, K.R.



Contraceptive vaccines targeting sperm.  


Overpopulation is a global problem of significant magnitude, with grave implications for the future. Development of new contraceptives is necessary, as existing forms of birth control are unavailable, impractical and/or too expensive for many individuals due to sociological, financial or educational limitations. Immunocontraception and, in particular, the targeting of antibodies to sperm-specific antigens implicated in sperm-egg binding and fertilisation offers an attractive approach to control fertility. Sperm-specific antibodies may impair fertility by inhibiting sperm motility, by reducing penetration of the cervical mucus by sperm, or by interfering in sperm capacitation or the acrosome reaction; alternatively, antisperm antibodies may invoke the complement cascade, resulting in sperm lysis. The antibodies raised against sperm-specific antigens have proved to be extremely effective at reducing sperm-egg interactions in vitro; fertility trials in subhuman primates will eventually be needed to prove the effectiveness of the sperm antigens in terms of contraceptive efficacy before trials in humans can be justified. In addition, existing and emerging strategies (such as sperm proteomics, the determination of molecular and structural details of sperm proteins, and the modelling of protein-ligand interactions using X-ray and/or NMR structures to name a few) are expected to provide the experimental foundation for the design of small molecule inhibitors with antifertility effects. The technology underpinning vaccine development is constantly being developed and the introduction of DNA/RNA vaccines is certain to impact upon the field of immunocontraception. PMID:15833075

Suri, Anil



Targeting Cancer Metabolism  

PubMed Central

The understanding that oncogenes can have profound effects on cellular metabolism and the discovery of mutations and alterations in several metabolism-related enzymes (IDH1, IDH2, SDH, FH, PKM2) has renewed interest in cancer metabolism and renewed hope of taking therapeutic advantage of cancer metabolism. Otto Warburg observed that aerobic glycolysis was a characteristic of cancer cells. More than 50-years later, we understand that aerobic glycolysis and uptake of glutamine and glycine allow cancer cells to produce energy (ATP) and the nucleotides, amino acids and lipids required for proliferation. Expression of the MYC oncogene drives the increase in cellular biomass facilitating proliferation. PKM2 expression in cancer cells stimulates aerobic glycolysis. Amongst intermediary metabolism enzyme, mutations in succinate dehydrogenase (SDH) occur in gastointestinal stromal tumors and result in a pseudohypoxic metabolic milieu. Fumarate hydratase (FH) mutations lead to a characteristic renal cell carcinoma. Isocitrate dehydrogenase (IDH1/2) mutations have been found in leukemias, gliomas, prostate cancer, colon cancer, thyroid cancer and sarcomas. These recently recognized oncogenic metabolic lesions may be selective targets for new anticancer therapeutics.

Teicher, Beverly A.; Linehan, W. Marston; Helman, Lee J.



Targeting DNA Methylation  

PubMed Central

Two nucleoside inhibitors of DNA methylation, azacitidine and decitabine, are now standard of care for the treatment of the myelodysplastic syndrome, a deadly form of leukemia. These old drugs, developed as cytotoxic agents and nearly abandoned decades ago were resurrected by the renewed interest in DNA methylation. They have now provided proof of principle for epigenetic therapy, the final chapter in the long saga to provide legitimacy to the field of epigenetics in cancer. But challenges remain; we don’t understand precisely how or why the drugs work or stop working after an initial response. Extending these promising findings to solid tumors face substantial hurdles from drug uptake to clinical trial design. We do not know yet how to select patients for this therapy and how to move it from life extension to cure. The epigenetic potential of DNA methylation inhibitors may be limited by other epigenetic mechanisms that are also worth exploring as therapeutic targets. But the idea of stably changing gene expression in-vivo has transformative potential in cancer therapy and beyond.

Issa, Jean-Pierre J.; Kantarjian, Hagop M.