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Sample records for thrombocytopenic purpura targeting

  1. Thrombotic Thrombocytopenic Purpura

    MedlinePlus

    ... the NHLBI on Twitter. What Is Thrombotic Thrombocytopenic Purpura? Thrombotic thrombocytopenic purpura (TTP) is a rare blood ... kee-ay). Petechiae may look like a rash. Purpura and Petechiae The photograph shows purpura (bruises) and ...

  2. Thrombotic thrombocytopenic purpura

    MedlinePlus

    ... medlineplus.gov/ency/article/000552.htm Thrombotic thrombocytopenic purpura To use the sharing features on this page, please enable JavaScript. Thrombotic thrombocytopenic purpura (TTP) is a blood disorder that causes blood ...

  3. What Causes Thrombotic Thrombocytopenic Purpura?

    MedlinePlus

    ... the NHLBI on Twitter. What Causes Thrombotic Thrombocytopenic Purpura? A lack of activity in the ADAMTS13 enzyme ( ... This leads to hemolytic anemia . Inherited Thrombotic Thrombocytopenic Purpura In inherited TTP, the ADAMTS13 gene is faulty. ...

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

    ClinicalTrials.gov

    2016-09-01

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

  5. Genetics Home Reference: thrombotic thrombocytopenic purpura

    MedlinePlus

    ... Home Health Conditions thrombotic thrombocytopenic purpura thrombotic thrombocytopenic purpura Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Thrombotic thrombocytopenic purpura is a rare disorder that causes blood clots ( ...

  6. Thrombotic thrombocytopenic purpura preceding systemic lupus erythematosus.

    PubMed Central

    Simeon-Aznar, C P; Cuenca-Luque, R; Fonollosa-Pla, V; Bosch-Gil, J A

    1992-01-01

    The case of a patient admitted with thrombotic thrombocytopenic purpura nine years after developing systemic lupus erythematosus (SLE) is reported. Thrombotic thrombocytopenic purpura associated with SLE has been described on other occasions, but in most patients the diagnosis of SLE precedes that of thrombotic thrombocytopenic purpura. The unusual sequence and the chronological separation of the two diseases is emphasised. PMID:1575591

  7. Multiple domains of ADAMTS13 are targeted by autoantibodies against ADAMTS13 in patients with acquired idiopathic thrombotic thrombocytopenic purpura

    PubMed Central

    Zheng, X. Long; Wu, Haifeng M.; Shang, Dezhi; Falls, Erica; Skipwith, Christopher G.; Cataland, Spero R.; Bennett, Charles L.; Kwaan, Hau C.

    2010-01-01

    Background Type G immunoglobulins against ADAMTS13 are the primary cause of acquired (idiopathic) thrombotic thrombocytopenic purpura. However, the domains of ADAMTS13 which the type G anti-ADAMT13 immunoglobulins target have not been investigated in a large cohort of patients with thrombotic thrombocytopenic purpura. Design and Methods Sixty-seven patients with acquired idiopathic thrombotic thrombocytopenic purpura were prospectively collected from three major U.S. centers. An enzyme-linked immunosorbent assay determined plasma concentrations of anti-ADAMTS13 type G immunoglobulins, whereas immunoprecipitation plus western blotting determined the binding domains of these type G immunoglobulins. Results Plasma anti-ADAMTS13 type G immunoglobulins from 67 patients all bound full-length ADAMTS13 and a variant truncated after the eighth TSP1 repeat (delCUB). Approximately 97% (65/67) of patients harbored type G immunoglobulins targeted against a variant truncated after the spacer domain (MDTCS). However, only 12% of patients’ samples reacted with a variant lacking the Cys-rich and spacer domains (MDT). In addition, approximately 37%, 31%, and 46% of patients’ type G immunoglobulins interacted with the ADAMTS13 fragment containing TSP1 2-8 repeats (T2-8), CUB domains, and TSP1 5-8 repeats plus CUB domains (T5-8CUB), respectively. The presence of type G immunoglobulins targeted against the T2-8 and/or CUB domains was inversely correlated with the patients’ platelet counts on admission. Conclusions This multicenter study further demonstrated that the multiple domains of ADAMTS13, particularly the Cys-rich and spacer domains, are frequently targeted by anti-ADAMTS13 type G immunoglobulins in patients with acquired (idiopathic) thrombotic thrombocytopenic purpura. Our data shed more light on the pathogenesis of acquired thrombotic thrombocytopenic purpura and provide further rationales for adjunctive immunotherapy. PMID:20378566

  8. Hodgkin's disease presenting as idiopathic thrombocytopenic purpura.

    PubMed Central

    Murphy, W. G.; Allan, N. C.; Perry, D. J.; Stockdill, G.

    1984-01-01

    A case of Hodgkin's disease presenting as idiopathic thrombocytopenic purpura in a 23-year-old male is reported. This is a rare presentation of Hodgkin's disease having been previously described in only two cases. PMID:6541338

  9. [Helicobacter pylori infection and idiopathic thrombocytopenic purpura].

    PubMed

    Franchini, Massimo; Veneri, Dino

    2005-03-01

    There are increasing data on the association between Helicobacter pylori infection and idiopathic thrombocytopenic purpura and the significant increase in platelet count after bacterial eradication. The aim of this review was to consider the studies so far published on Helicobacter pylori infection and idiopathic thrombocytopenic purpura in order to evaluate a possible correlation between these two conditions. A review of the literature showed that 306 out of the 524 patients investigated (54.8%) were positive for Helicobacter pylori infection and that the bacterium was eradicated in 83% of cases. Eradication therapy was accompanied by a complete or partial platelet response in approximately half the cases. Overall, these data show that Helicobacter pylori eradication in patients with idiopathic thrombocytopenic purpura is effective in increasing platelet count. However, since the studies so far published are few, sometimes controversial and involve small series of patients, further studies on larger numbers of patients with longer followup are needed to confirm these preliminary findings.

  10. Treatment of thrombotic thrombocytopenic purpura.

    PubMed

    Fontana, S; Kremer Hovinga, J A; Lämmle, B; Mansouri Taleghani, B

    2006-05-01

    Thrombotic thrombocytopenic purpura (TTP), characterized by thrombocytopenia and microangiopathic haemolytic anaemia, was almost universally fatal until the introduction of plasma exchange (PE) therapy in the 1970s. Based on clinical studies, daily PE has become the first-choice therapy since 1991. Recent findings may explain its effectiveness, which may include, in particular, the removal of anti-ADAMTS13 autoantibodies and unusually large von Willebrand factor multimers and/or supply of ADAMTS13 in acquired idiopathic or congenital TTP. Based on currently available data, the favoured PE regimen is daily PE [involving replacement of 1-1.5 times the patient's plasma volume with fresh-frozen plasma (FFP)] until remission. Adverse events of treatment are mainly related to central venous catheters. The potential reduction of plasma related side-effects, such as transfusion-related acute lung injury (TRALI) or febrile transfusion reactions by use of solvent-detergent treated (S/D) plasma instead of FFP is not established by controlled clinical studies. Uncontrolled clinical observations and the hypothesis of an autoimmune process in a significant part of the patients with acquired idiopathic TTP suggest a beneficial effect of adjunctive therapy with corticosteroids. Other immunosuppressive treatments are not tested in controlled trials and should be reserved for refractory or relapsing disease. There is no convincing evidence for the use of antiplatelet agents. Supportive treatment with transfusion of red blood cells or platelets has to be evaluated on a clinical basis, but the transfusion trigger for platelets should be very restrictive. Further controlled, prospective studies should consider the different pathophysiological features of thrombotic microangiopathies, address the prognostic significance of ADAMTS13 and explore alternative exchange fluids to FFP, the role of immunosuppressive therapies and of new plasma saving approaches as recombinant ADAMTS13 and

  11. [Pregnancy and labor in idiopathic thrombocytopenic purpura].

    PubMed

    Tampakoudis, P; Billi, H; Tantanassis, T; Kalachanis, I; Garipidou, B; Sinakos, Z; Mantalenakis, S

    1995-10-01

    Clinical data from eight pregnant women with idiopathic thrombocytopenic purpura (ITP) were retrospectively analyses. The mean age of the women was 28.2 years. Five women underwent splenectomy during childhood. The lowest maternal platelet count observed ranged from 8000 to 88000/mm3. Genital bleeding occurred in only one case. Treatment was based on administration of corticosteroids with or without human-pooled immunoglobulins. Caesarian section was performed in all cases. Six newborns were healthy and had a successful subsequent course. Two infants died, one in utero because of abruptio placentae and the other one 1 month post partum because of a cerebral haematoma. After a mean follow-up of eighteen months, thrombocytopenia is still present in two women, despite the continuous treatment. In conclusion, ITP rather rarely coincides with pregnancy. Treatment is usually successful for the mother but the risk for the fetus remains considerably high.

  12. Thrombotic thrombocytopenic purpura in southeastern New England.

    PubMed

    Crowley, J P; Zaroulis, C G; O'Shea, P A; Clark, D D

    1983-05-01

    Eight patients with thrombotic thrombocytopenic purpura (TTP) originating within a 25-mile radius had their conditions diagnosed in a three-year period at a community teaching hospital in southeastern New England. In the preceding ten years, only one case of TTP had occurred in the same hospital. A niece-uncle relationship was present in two patients, and lymphocyte typing showed that they both shared an HLA haplotype. In the remaining patients, no social, familial, or environmental connection was established. Three patients died, all of whom were female. Six patients received exchange plasmapheresis with excellent responses in five. Autopsies in the three fatal cases showed widespread organ involvement with TTP but did not disclose evidence of any common underlying disease. This unusual occurrence should alert physicians to the possibility of localized outbreaks of TTP and the necessity of considering this diagnosis in all patients with unexplained thrombocytopenia. PMID:6383244

  13. SYSTEMIC INFECTIONS MIMICKING THROMBOTIC THROMBOCYTOPENIC PURPURA

    PubMed Central

    Booth, Kristina K.; Terrell, Deirdra R.; Vesely, Sara K.; George, James N.

    2012-01-01

    The absence of specific diagnostic criteria, the urgency to begin plasma exchange treatment, and the risk for complications from plasma exchange make the initial evaluation of patients with suspected thrombotic thrombocytopenic purpura (TTP) difficult. Systemic infections may mimic the presenting clinical features of TTP. In the Oklahoma TTP-HUS (hemolytic-uremic syndrome) Registry, 1989–2010, 415 consecutive patients have been clinically diagnosed with their first episode of TTP; in 31 (7%) the presenting clinical features were subsequently attributed to a systemic infection. All 31 patients had diagnostic criteria for TTP; 16 (52%) had the complete “pentad” of microangiopathic hemolytic anemia, thrombocytopenia, neurologic abnormalities, renal failure and fever. Four (16%) of 25 patients who had ADAMTS13 measurements had <10% activity; three patients had a demonstrable ADAMTS13 inhibitor. Compared to 62 patients with severe ADAMTS13 deficiency (<10%) who had no recognized alternative disorders, patients with systemic infections had more frequent fever, coma, renal failure, and the complete “pentad” of clinical features. Seventeen different infectious etiologies were documented. A systematic literature review identified 67 additional patients with a diagnosis of TTP or HUS and also a systemic infection. Among all 98 patients, infections with 41 different bacteria, viruses, and fungi were documented, suggesting that many different systemic infections may mimic the presenting clinical features of TTP. Initial plasma exchange treatment is appropriate in critically ill patients with diagnostic features of TTP, even if a systemic infection is suspected. Continuing evaluation to document a systemic infection is essential to determine the appropriateness of continued plasma exchange. PMID:21850657

  14. Thrombocytopenic Purpura Associated with Dietary Supplements Containing Citrus Flavonoids.

    PubMed

    Ghali, Alaa; Bourneau-Martin, Delphine; Dopter, Aymeric; Lainé-Cessac, Pascale; Belizna, Cristina; Urbanski, Geoffrey; Lavigne, Christian

    2015-01-01

    We report a case of thrombocytopenic purpura associated with the intake of two dietary supplements containing mainly citrus flavonoids. This is the first case to be notified to the French Agency for Food, Environmental and Occupational Health Safety (ANSES). It addresses the importance of an accurate medication history interview for each patient. PMID:26242500

  15. Coexisting Situs Inversus Totalis and Immune Thrombocytopenic Purpura

    PubMed Central

    Gundogdu, Kemal; Altintoprak, Fatih; Uzunoğlu, Mustafa Yener; Dikicier, Enis; Zengin, İsmail; Yağmurkaya, Orhan

    2016-01-01

    Situs inversus totalis is a rare congenital abnormality with mirror symmetry of mediastinal and abdominal organs. Immune thrombocytopenic purpura is an autoimmune disease with destruction of thrombocytes. This paper is presentation of surgical approach to a case with coexistence of these two conditions. PMID:26981307

  16. Thrombocytopenic Purpura Associated with Dietary Supplements Containing Citrus Flavonoids.

    PubMed

    Ghali, Alaa; Bourneau-Martin, Delphine; Dopter, Aymeric; Lainé-Cessac, Pascale; Belizna, Cristina; Urbanski, Geoffrey; Lavigne, Christian

    2015-01-01

    We report a case of thrombocytopenic purpura associated with the intake of two dietary supplements containing mainly citrus flavonoids. This is the first case to be notified to the French Agency for Food, Environmental and Occupational Health Safety (ANSES). It addresses the importance of an accurate medication history interview for each patient.

  17. Intravenous Rh immune globulin for treating immune thrombocytopenic purpura.

    PubMed

    Sandler, S G

    2001-11-01

    Intravenous Rh [corrected] immune globulin was licensed by the U. S. Food and Drug administration in 1995 for the treatment of acute and chronic immune thrombocytopenic purpura in children and chronic immune thrombocytopenic purpura in adults. In 1996, the American Society of Hematology published a practice guideline for immune thrombocytopenic purpura, but treatment recommendations of necessity were formulated using only results of early clinical trials with intravenous Rh immune globulin. To date, there are no published results of large-scale clinical trials comparing conventional doses of intravenous immune globulin with the most promising dose range for intravenous Rh immune globulin (50-75 microg/kg). However, clinical experience is accumulating to indicate that intravenous Rh immune globulin is as effective, probably safer, and easier to administer than intravenous immune globulin. Acute intravascular hemolysis after infusions of intravenous Rh immune globulin for immune thrombocytopenic purpura has been reported with an estimated incidence of 1 in 1,115 patients. The risk factors for this adverse event have not been defined.

  18. Thrombotic thrombocytopenic purpura: MR demonstration of reversible brain abnormalities

    SciTech Connect

    D'Aprile, P.; Carella, A.; Pagliarulo, R. ); Farchi, G. )

    1994-01-01

    We report a case of thrombotic thrombocytopenic purpura evaluated by MR, Multiple hyperintense foci on the TS-weighted images, observed principally in the brain stem and in the region of the basal nuclei, and neurologic signs disappeared after 15 days of therapy. 6 refs., 2 figs.

  19. [Laparoscopic splenectomy in immune thrombocytopenic purpura in pregnant women].

    PubMed

    Danishyan, K I; Soboleva, O A; Galstyan, G M; Zvereva, A V; Sorkina, O M

    2016-01-01

    The paper describes 4 cases of laparoscopic splenectomy in pregnant women with immune thrombocytopenic purpura. No complications of surgery were noted in all the patients. The postoperative period was marked by sustained clinical and hematological remission that made it possible to discontinue prednisolone therapy and to ensure an uncomplicated course of pregnancy and labor. PMID:27459624

  20. Immune thrombocytopenic purpura-related hemotympanum presenting with hearing loss.

    PubMed

    Fisgin, Tunc; Atmaca, Sinan; Duru, Feride; Ozyurek, Emel; Cetin, Recep; Albayrak, Davut

    2009-06-01

    A 5-year-old boy was admitted to our center with a major complaint of bilateral hearing loss for 2 days. He was diagnosed with acute immune thrombocytopenic purpura 3 months before the admission and treated with high-dose methylprednisolone 2 months ago. Physical examination revealed wet purpura in the oral mucosa, serous nasal discharge, multiple petechiae and ecchymosis of the lower lip. Otomicroscopic ear examination revealed the presence of bilateral hemotympanum. The patient denied head trauma, ear pain, fever, hypertension and medications, including salicylates. The patient received high-dose intravenous methylprednisolone because of low platelet count and wet purpura for 7 days and oral prophylactic amoxicillin-clavulanate for 14 days. The onset of the response to corticosteroids was rapid, and significant hematologic improvement was observed within a few days. The 2-week follow-up examination revealed intact tympanic membranes with normal color and mobility, and the patient restored normal hearing. In this patient, hemotympanum developed rapidly, and no predisposing cause other than immune thrombocytopenic purpura was found. However, presence of a serous nasal discharge may be a sign of viral upper respiratory tract infection. Therefore, it can be speculated that sneezing or coughing might have caused bilateral hemotympanum by increasing the middle ear pressure abruptly. We would like to emphasize that bleeding may occur in unusual sites and, unlike in healthy people, may cause bizarre symptoms in patients with bleeding diathesis. Hemotympanum can be considered among the indications to start treatment in patients with acute immune thrombocytopenic purpura. PMID:19530341

  1. Thrombotic thrombocytopenic purpura in the first trimester of pregnancy

    PubMed Central

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

    2013-01-01

    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

  2. Thrombotic thrombocytopenic purpura: The role of ADAMTS13.

    PubMed

    Rogers, Heesun J; Allen, Charles; Lichtin, Alan E

    2016-08-01

    Thrombotic thrombocytopenic purpura (TTP) is an uncommon, life-threatening disease requiring prompt diagnosis and initiation of therapeutic plasma exchange to improve patient survival. However, diagnosis is often difficult because of atypical presentations and signs and symptoms that resemble other conditions. Measurements of ADAMTS13 activity, ADAMTS13 inhibitor, and ADAMTS13 autoantibody are useful for diagnosing TTP, guiding therapy, and predicting relapse. PMID:27505881

  3. Immune Thrombocytopenic Purpura During Pregnancy: Laparoscopic Treatment

    PubMed Central

    Anglin, Beth V.; Rutherford, Cynthia; Ramus, Ronald; Lieser, Mark

    2001-01-01

    Background and Objectives: Laparoscopic surgical techniques in pregnancy have been accepted and pose minimal risks to the patient and fetus. We present the first reported case of a pregnant woman with immune thrombocytopenia purpura who underwent laparoscopic splenectomy during the second trimester. Methods and Results: The anesthesia, hematology, and obstetrics services closely followed the patient's preoperative and intraoperative courses. After receiving immunization, stress dose steroids, and prophylactic antibiotics, she underwent a successful laparoscopic splenectomy. After a short hospital stay, the patient was discharged home. Conclusion: Immune thrombocytopenia purpura can be an indication for splenectomy. As demonstrated in appendectomy, cholecystectomy, and our case presentation, laparoscopic splenectomy can be safely performed during pregnancy. PMID:11303997

  4. Immune Thrombocytopenic Purpura Presenting as Unprovoked Gingival Hemorrhage: a Case Report

    PubMed Central

    Bal, Mehmet V; Koyuncuoglu, Cenker Z; Saygun, Işıl

    2014-01-01

    Immune thrombocytopenic purpura is an autoimmune disease characterized by auto-antibody induced platelet destruction and reduced platelet production, leading to low blood platelet count. In this case report, the clinical diagnose of a patient with immune thrombocytopenic purpura and spontaneous gingival hemorrhage by a dentist is presented. The patient did not have any systemic disease that would cause any spontaneous hemorrhage. The patient was referred to a hematologist urgently and her thrombocyte number was found to be 2000/μL. Other test results were in normal range and immune thrombocytopenic purpura diagnose was verified. Then hematological treatment was performed and patient’s health improved without further problems. Hematologic diseases like immune thrombocytopenic purpura, in some cases may appear firstly in the oral cavity and dentists must be conscious of unexplained gingival hemorrhage. In addition, the dental treatment of immune thrombocytopenic purpura patients must be planned with a hematologist. PMID:25317211

  5. Thrombotic thrombocytopenic purpura in a case of brucellosis.

    PubMed

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

    2011-06-01

    Thrombotic thrombocytopenic purpura (TTP) is characterized by disseminated thrombotic occlusions located in the microcirculation and a syndrome of microangiopathic hemolytic anemia, thrombocytopenia, fever, and renal and neurologic abnormalities. Thrombotic thrombocytopenic purpura is encountered in a variety of clinical situations such as viral, bacterial, and mycobacterial infections, autoimmune disorders, drug reactions, connective tissue disease, and solid tumors. In this report, we present TTP in a case of brucellosis because of rare presentation. A 7-year-old girl was admitted with the complaints of headache, fever, hematuria, malaise, jaundice, epistaxis, and purpura. Her physical examination revealed conjunctival pallor, scleral icterus, petechial-purpuric skin lesions on both legs, and confusion. Laboratory tests showed hematocrit 14%; hemoglobin 4.8 g/dL; platelet count 6000/mm(3), and reticulocytosis 6%. Peripheral blood smear revealed fragmented red blood cells and a complete absence of platelets. The clinical and laboratory findings were consistent with TTP. Serum antibrucella titration agglutination test was found to be 1/1280 positive.

  6. Thrombotic Thrombocytopenic Purpura-Haemolytic Uremic Syndrome and pregnancy

    PubMed Central

    Mwita, Julius Chacha; Vento, Sandro; Benti, Tadele

    2014-01-01

    Thrombotic Thrombocytopenic Purpura-Haemolytic Uremic Syndrome (TTP-HUS) is a rare pregnancy and postpartum complication that may simulate the more common obstetric complications, preeclampsia and the syndrome of haemolysis, elevated liver functions tests, low platelets (HELLP). We describe a 26 years old patient who presented with peri-partum TTP-HUSand was initially treated as a case of HELLP syndrome without any improvement. A brief review of the current TTP-HUS treatment options in pregnancy is also presented. PMID:25309655

  7. Helicobacter pylori-associated idiopathic thrombocytopenic purpura: a narrative review.

    PubMed

    Franchini, Massimo; Vescovi, Pier Paolo; Garofano, Massimo; Veneri, Dino

    2012-07-01

    The Gram-negative bacterium Helicobacter pylori has a well-demonstrated role in several gastroduodenal diseases, including peptic ulcer disease, chronic active gastritis, mucosa-associated lymphoid tissue lymphoma, and gastric adenocarcinoma. In addition, more recently, several studies have focused on the possible causal role of H. pylori in various extragastric disorders, such as cardiovascular, respiratory, neurological, skin, and autoimmune conditions. The current status of the research on the pathogenesis, clinical and therapeutic aspects of H. pylori-associated idiopathic thrombocytopenic purpura in adults and children will be addressed in this narrative review.

  8. Accessory spleen compromising response to splenectomy for idiopathic thrombocytopenic purpura

    SciTech Connect

    Ambriz, P.; Munoz, R.; Quintanar, E.; Sigler, L.; Aviles, A.; Pizzuto, J.

    1985-06-01

    Accessory spleens were sought in 28 patients who had undergone splenectomy for chronic idiopathic thrombocytopenic purpura (ITP), using a variety of techniques. Abdominal scintigraphy with autologous erythrocytes labeled with Tc-99m and opsonized with anit-D IgG (radioimmune method) proved to be most useful, clearly demonstrating one or more accessory spleens in 12 cases (43%). Computed tomography (CT) was also helpful. Four out of five patients demonstrated an increased platelet count following surgery, the effectiveness of which was illustrated by the radioimmune scan. Patients who have had splenectomy for chronic ITP should be scanned using radioimmune techniques and CT to determine whether an accessory spleen is present.

  9. Two Mechanistic Pathways for Thienopyridine-Associated Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Bennett, Charles L.; Kim, Benjamin; Zakarija, Anaadriana; Bandarenko, Nicholas; Pandey, Dilip K.; Buffie, Charlie G.; McKoy, June M.; Tevar, Amul D.; Cursio, John F.; Yarnold, Paul R.; Kwaan, Hau C.; De Masi, Davide; Sarode, Ravindra; Raife, Thomas J.; Kiss, Joseph E.; Raisch, Dennis W.; Davidson, Charles; Sadler, J. Evan; Ortel, Thomas L.; Zheng, X. Long; Kato, Seiji; Matsumoto, Masanori; Uemura, Masahito; Fujimura, Yoshihiro

    2011-01-01

    Objectives We sought to describe clinical and laboratory findings for a large cohort of patients with thienopyridine-associated thrombotic thrombocytopenic purpura (TTP). Background The thienopyridine derivatives, ticlopidine and clopidogrel, are the 2 most common drugs associated with TTP in databases maintained by the U.S. Food and Drug Administration (FDA). Methods Clinical reports of TTP associated with clopidogrel and ticlopidine were identified from medical records, published case reports, and FDA case reports (n = 128). Duration of thienopyridine exposure, clinical and laboratory findings, and survival were recorded. ADAMTS13 activity (n = 39) and inhibitor (n = 30) were measured for a subset of individuals. Results Compared with clopidogrel-associated TTP cases (n = 35), ticlopidine-associated TTP cases (n = 93) were more likely to have received more than 2 weeks of drug (90% vs. 26%), to be severely thrombocytopenic (84% vs. 60%), and to have normal renal function (72% vs. 45%) (p < 0.01 for each). Compared with TTP patients with ADAMTS13 activity >15% (n = 13), TTP patients with severely deficient ADAMTS13 activity (n = 26) were more likely to have received ticlopidine (92.3% vs. 46.2%, p < 0.003). Among patients who developed TTP >2 weeks after thienopyridine, therapeutic plasma exchange (TPE) increased likelihood of survival (84% vs. 38%, p < 0.05). Among patients who developed TTP within 2 weeks of starting thienopyridines, survival was 77% with TPE and 78% without. Conclusions Thrombotic thrombocytopenic purpura is a rare complication of thienopyridine treatment. This drug toxicity appears to occur by 2 different mechanistic pathways, characterized primarily by time of onset before versus after 2 weeks of thienopyridine administration. If TTP occurs after 2 weeks of ticlopidine or clopidogrel therapy, therapeutic plasma exchange must be promptly instituted to enhance likelihood of survival. PMID:17868804

  10. Rapid encephalopathy associated with anti-D immune globulin treatment for idiopathic thrombocytopenic purpura.

    PubMed

    Golla, Sunitha; Horkan, Clare; Dogaru, Grigore; Teske, Thomas E; Christopher, Kenneth

    2008-01-01

    Rho (D) immune globulin intravenous (IV RhIG, WinRho SDF) has been shown to be a safe treatment for idiopathic thrombocytopenic purpura. Common side effects of IV RhIG include mild hemolysis, febrile reaction and headache. Significant hemolysis with renal impairment is infrequently noted. A single case of irreversible encephalopathy following IV RhIG has been reported. We report a second case of encephalopathy following an infusion of IV RhIG for treatment of idiopathic thrombocytopenic purpura.

  11. Harmful and beneficial antibodies in immune thrombocytopenic purpura.

    PubMed Central

    Imbach, P A

    1994-01-01

    Two facts support the definition of idiopathic thrombocytopenic purpura (ITP) as an immune disorder. First, antibodies against platelets, which often appear after a viral infection, provoke the increased elimination of these cells. Viral disease may change the complex immune response of the host at different levels. In chronic ITP, the consequences of the dysregulated immune system are autoantibodies, primarily against platelet glycoprotein IIb/IIIa. Second, pooled immunoglobulins from healthy blood donors may influence the imbalanced immune response in ITP. The initial study dose of 5 x 0.4 g of intact 7S IgG/kg body weight can now be reduced to 2 x 0.4 g/kg body weight in the majority of patients. The possible mechanisms of action of intravenous immune globulin (IVIG) are reviewed and updated in this article. The combination of effects on the humoral and cellular immune responses using IVIG in concert with cytokines may open up new therapeutic possibilities. PMID:8033430

  12. Association of primary biliary cirrhosis with idiopathic thrombocytopenic purpura

    PubMed Central

    Toshikuni, Nobuyuki; Yamato, Ryumei; Kobashi, Haruhiko; Nishino, Ken; Inada, Nobu; Sakanoue, Ritsuko; Suehiro, Mitsuhiko; Fujimura, Yoshinori; Yamada, Gotaro

    2008-01-01

    Although both primary biliary cirrhosis (PBC) and idiopathic thrombocytopenic purpura (ITP) are autoimmune diseases, the association of the 2 diseases is rare. Here, we report a case of ITP that developed during the follow-up of PBC in a 74-year-old man. The patient had been diagnosed with PBC 12 years previously, and had received treatment with ursodeoxycholic acid. The platelet count decreased from approximately 60 × 109/L to 8 × 109/L, and the association of decompensated liver cirrhosis (PBC) with ITP was diagnosed. Steroid and immune gamma globulin therapy were successful in increasing the platelet count. Interestingly, human leukocyte antigen genotyping detected the alleles DQB1*0601 and DRB1*0803, which are related to both PBC and ITP in Japanese patients. This case suggests common immunogenetic factors might be involved in the development of PBC and ITP. PMID:18416479

  13. Thrombotic thrombocytopenic purpura: diagnosis, pathogenesis and modern therapy.

    PubMed

    Eldor, A

    1998-06-01

    Thrombotic thrombocytopenic purpura (TTP) is an uncommon multisystem disorder, sometimes associated with predisposing conditions such as pregnancy, cancer, exposure to certain drugs, bone marrow transplantation and HIV-1 infection. An abnormal interaction between the vascular endothelium and platelets which occurs in certain organs leads to thrombosis, endothelial proliferation, minimal inflammation and micro-angiopathic haemolysis. Recent studies suggest that endothelial cell perturbation and apoptosis caused by an as yet unknown plasma factor(s) may lead to the release of abnormal von Willebrand factor which facilitates the deposition of platelet microthrombi. Exchange transfusions of plasma or plasma-cryosupernatant remain the cornerstone of the treatment of TTP along with corticosteroids, platelet inhibitor drugs, vincristine and splenectomy. In most cases remissions can be attained, and cures are now common-although approximately one-half of the patients will relapse. While relapses are usually milder, they still carry a significant mortality and preventive therapies are not always effective.

  14. ADAMTS13 and von Willebrand Factor in Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Zheng, X. Long

    2015-01-01

    Pathogenesis of thrombotic thrombocytopenic purpura (TTP) was a mystery for over half a century until the discovery of ADAMTS13. ADAMTS13 is primarily synthesized in the liver, and its main function is to cleave von Willebrand factor (VWF) anchored on the endothelial surface, in circulation, and at the sites of vascular injury. Deficiency of plasma ADAMTS13 activity (<10%) resulting from mutations of the ADAMTS13 gene or autoantibodies against ADAMTS13 causes hereditary or acquired (idiopathic) TTP. ADAMTS13 activity is usually normal or modestly reduced (>20%) in other forms of thrombotic microangiopathy secondary to hematopoietic progenitor cell transplantation, infection, and disseminated malignancy or in hemolytic uremic syndrome. Plasma infusion or exchange remains the initial treatment of choice to date, but novel therapeutics such as recombinant ADAMTS13 and gene therapy are under development. Moreover, ADAMTS13 deficiency has been shown to be a risk factor for the development of myocardial infarction, stroke, cerebral malaria, and preeclampsia. PMID:25587650

  15. Helicobacter pylori infection and immune thrombocytopenic purpura: an update.

    PubMed

    Franchini, Massimo; Veneri, Dino

    2004-08-01

    Data are accumulating on the association between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP) and the significant increase in platelet count after bacterial eradication. The aim of this review was to consider the studies so far published on H. pylori infection and ITP in order to evaluate a possible correlation between these two conditions. A review of the literature showed that 278 out of the 482 ITP patients investigated (58%) were positive for H. pylori infection and that the bacterium was eradicated in 88% of cases. Eradication therapy was accompanied by a complete or partial platelet response in approximately half the cases. Overall, these data show that H. pylori eradication in patients with ITP is effective in increasing platelet count. However, because the studies so far published are few, are sometimes controversial and involve small series of patients, further studies on larger numbers of patients with longer follow-up are needed to confirm these preliminary findings.

  16. Thrombotic Thrombocytopenic Purpura: Issues in Diagnosis and Treatment.

    PubMed

    Khatun, H; Morshed, M

    2015-10-01

    Thrombotic thrombocytopenic purpura (TTP) is a hematologic emergency fatal without prompt treatment. Plasma exchange (PEX), the treatment of choice for TTP, is not readily available and has major complications. We report seven cases of TTP, both acquired immune and secondary. Two patients had TTP secondary to malignancy and one secondary to SLE. Male to female ratio was 1:3 and median age at presentation 38 years. Six patients had moderate to very high level of LDH while one primary TTP had only mild elevation. Median haemoglobin and platelet at presentation were 6.3 gm/dL and 38 k/UL respectively. Median LDH value was 4595 u/L. All patients were treated with plasma exchange (PEX) except the two cases secondary to malignancy. One patient died of cardiac arrest during plasma exchange. None of the patients treated with PEX had relapsed over a median follow up of 18 months. PMID:26620016

  17. Treatment of immune thrombocytopenic purpura: focus on eltrombopag

    PubMed Central

    Rice, Lawrence

    2009-01-01

    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

  18. Two cases of thrombocytopenic purpura at onset of Zika virus infection.

    PubMed

    Chraïbi, Samy; Najioullah, Fatiha; Bourdin, Carole; Pegliasco, Jean; Deligny, Christophe; Résière, Dabor; Meniane, Jean-Côme

    2016-10-01

    We report here two cases of thrombocytopenic purpura at onset of Zika virus infection. A 26-year-old woman and a 21-year-old man had thrombocytopenia above 5×10(9) platelets/L. Hemorrhagic symptoms were mucosal and subcutaneous bleeding and gross hematuria and they reported episode of conjunctivitis. In both cases blood and bone marrow analysis suggested thrombocytopenic purpura, blood PCR tests for Dengue (DENV), Chikungunya (CHIKV) and Zika virus (ZIKV) were negative. In both cases urinary PCR for ZIKV was positive, Prednisolone yielded early remission. Only three similar cases have been reported so far. In the Caribbean, DENV is also epidemic and responsible for severe thrombocytopenia. Coinfections can occur. Our report underlines the need to include a ZIKV assay in the diagnostic work-up of thrombocytopenic purpura in epidemic areas.

  19. Two cases of thrombocytopenic purpura at onset of Zika virus infection.

    PubMed

    Chraïbi, Samy; Najioullah, Fatiha; Bourdin, Carole; Pegliasco, Jean; Deligny, Christophe; Résière, Dabor; Meniane, Jean-Côme

    2016-10-01

    We report here two cases of thrombocytopenic purpura at onset of Zika virus infection. A 26-year-old woman and a 21-year-old man had thrombocytopenia above 5×10(9) platelets/L. Hemorrhagic symptoms were mucosal and subcutaneous bleeding and gross hematuria and they reported episode of conjunctivitis. In both cases blood and bone marrow analysis suggested thrombocytopenic purpura, blood PCR tests for Dengue (DENV), Chikungunya (CHIKV) and Zika virus (ZIKV) were negative. In both cases urinary PCR for ZIKV was positive, Prednisolone yielded early remission. Only three similar cases have been reported so far. In the Caribbean, DENV is also epidemic and responsible for severe thrombocytopenia. Coinfections can occur. Our report underlines the need to include a ZIKV assay in the diagnostic work-up of thrombocytopenic purpura in epidemic areas. PMID:27596376

  20. Lupus-associated thrombotic thrombocytopenic purpura-like microangiopathy

    PubMed Central

    Blum, Daniel; Blake, Geoffrey

    2015-01-01

    Recently reported cases of lupus complicated by a thrombotic thrombocytopenic purpura (TTP)-like syndrome suggest a survival benefit to early treatment with plasma exchange. The following is a report of the eighth such case in the last ten years. A 44-year-old lady known for lupus presented with the nephrotic syndrome and a renal biopsy was consistent with class 4G lupus nephritis. She was given high-dose steroids and cytotoxic therapy, but her induction therapy was complicated by the classic pentad of TTP. She was subsequently treated with another course of high-dose steroids, a different cytotoxic agent, and plasma exchange, with clinical resolution shortly thereafter. Similar to seven recently reported cases of microangiopathy in lupus, this lady’s TTP-like syndrome improved dramatically after initiation of plasma exchange, despite not having a severely deficient ADAMTS13. This has implications on both current clinical practice and on the pathogenesis of TTP-like syndromes in lupus. PMID:26558190

  1. Bortezomib in the treatment of refractory thrombotic thrombocytopenic purpura.

    PubMed

    Patriquin, Christopher J; Thomas, Mari R; Dutt, Tina; McGuckin, Siobhan; Blombery, Piers A; Cranfield, Tanya; Westwood, John P; Scully, Marie

    2016-06-01

    Acquired thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening condition caused by autoantibody-mediated inhibition of ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type-1 motif, 13). Therapeutic plasma exchange (TPE) improves survival, but disease may be refractory despite therapy. Management and treatment response of refractory TTP is variable, with rituximab and other immunosuppression often being used. Case reports have suggested a benefit of the proteasome inhibitor, bortezomib, possibly due to elimination of the autoreactive plasma cells producing anti-ADAMTS13 antibodies. We evaluated the effect of bortezomib in a series of primary refractory TTP patients unresponsive to intensive therapy. Bortezomib-treated patients were identified from consecutive cases managed at two UK referral centres. Demographic and clinical data were extracted from hospital records. ADAMTS13 activity was measured using a fluorescence resonance energy transfer VWF73 assay, and anti-ADAMTS13 IgG using enzyme-linked immunosorbent asssay. We identified six bortezomib-treated patients out of 51 consecutive cases of acute, acquired TTP. All patients received TPE, methylprednisolone and rituximab. Five of the six achieved complete remission with bortezomib, and one died of cardiac arrest due to underlying disease. No treatment-related adverse events were observed. Mean follow-up time after hospital discharge was 17 months (range: 3-33). Bortezomib appears effective in the treatment of a subgroup of cases with severe, refractory TTP. Prospective trials are required to further investigate this effect. PMID:27009919

  2. Platelet antibody in prolonged remission of childhood idiopathic thrombocytopenic purpura

    SciTech Connect

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

    1985-11-01

    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.

  3. Depression and cognitive impairment following recovery from thrombotic thrombocytopenic purpura.

    PubMed

    Han, Bowie; Page, Evaren E; Stewart, Lauren M; Deford, Cassandra C; Scott, James G; Schwartz, Lauren H; Perdue, Jedidiah J; Terrell, Deirdra R; Vesely, Sara K; George, James N

    2015-08-01

    After recovery from an acute episode of acquired thrombotic thrombocytopenic purpura (TTP), patients often describe problems with memory, concentration, and endurance. We have previously reported the occurrence of depression and cognitive impairment in these patients. In this study, we describe the frequency, severity, and clinical course of depression and cognitive impairment. Fifty-two (85%) out of 61 eligible Oklahoma Registry patients who had recovered from TTP, documented by ADAMTS13 activity <10%, have had at least one (median, four) evaluation for depression over 11 years using the Beck Depression Inventory-II; 31 (59%) patients screened positive for depression at least once; in 15 (29%), the results suggested severe depression at least once. Nine of these 15 patients had a psychiatric interview, the definitive diagnostic evaluation; the diagnosis of major depressive disorder was established in eight (89%) patients. In 2014, cognitive ability was evaluated in 33 patients by the Montreal Cognitive Assessment and the Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Both tests detected significant cognitive impairment in the patients as a group. Fifteen out of the 33 patients had been evaluated by extensive cognitive tests in 2006. The 2014 RBANS results were significantly worse than the 2006 results for the overall score and two out of the five RBANS domains (immediate and delayed memory). Neither depression nor cognitive impairment was significantly associated with the occurrence of relapses or ADAMTS13 activity <10% during remission. These observations emphasize the importance of screening evaluations for depression and cognitive impairment after recovery from acquired TTP.

  4. Pulmonary Hyalinizing Granuloma Associated with Idiopathic Thrombocytopenic Purpura

    PubMed Central

    Coleman, Christopher; Nassar, Aziza; McComb, Barbara

    2014-01-01

    Pulmonary hyalinizing granuloma (PHG) is a rare, benign lung disease of unknown etiology. It manifests as discrete, rounded nodules within the lung parenchyma. A 39-year-old woman presented for investigation after pulmonary nodules were found incidentally. Chest computed tomography showed multiple, discrete, non-enhancing pulmonary nodules bilaterally. Positron emission tomography (PET) was negative. Biopsy demonstrated a non-specific lymphoplasmacytic infiltrate. Open resection yielded two nodules consistent with hyalinizing granulomas. The differential for multiple pulmonary nodules is broad. PET scan can help rule out metastatic disease, although some cancers are not hypermetabolic on PET. Furthermore, some non-malignant conditions, including hyalinizing granuloma, can show increased activity on PET. PHG should be included in the differential of multiple pulmonary nodules, especially if nodule stability can be demonstrated and/or needle biopsies are non-diagnostic. Associated immune-mediated conditions, such as idiopathic thrombocytopenic purpura (ITP) in our patient, may also favor HG. In this case report we find an association between PHG and ITP. PMID:24744965

  5. Pulmonary hyalinizing granuloma associated with idiopathic thrombocytopenic purpura.

    PubMed

    Coleman, Christopher; Nassar, Aziza; McComb, Barbara

    2014-01-01

    Pulmonary hyalinizing granuloma (PHG) is a rare, benign lung disease of unknown etiology. It manifests as discrete, rounded nodules within the lung parenchyma. A 39-year-old woman presented for investigation after pulmonary nodules were found incidentally. Chest computed tomography showed multiple, discrete, non-enhancing pulmonary nodules bilaterally. Positron emission tomography (PET) was negative. Biopsy demonstrated a non-specific lymphoplasmacytic infiltrate. Open resection yielded two nodules consistent with hyalinizing granulomas. The differential for multiple pulmonary nodules is broad. PET scan can help rule out metastatic disease, although some cancers are not hypermetabolic on PET. Furthermore, some non-malignant conditions, including hyalinizing granuloma, can show increased activity on PET. PHG should be included in the differential of multiple pulmonary nodules, especially if nodule stability can be demonstrated and/or needle biopsies are non-diagnostic. Associated immune-mediated conditions, such as idiopathic thrombocytopenic purpura (ITP) in our patient, may also favor HG. In this case report we find an association between PHG and ITP. PMID:24744965

  6. Platelet antibody in idiopathic thrombocytopenic purpura and other thrombocytopenias

    SciTech Connect

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

    1980-10-01

    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/..mu..l 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.

  7. Pregnancy and Birth Outcomes among Women with Idiopathic Thrombocytopenic Purpura

    PubMed Central

    Wyszynski, Diego F.; Carman, Wendy J.; Cantor, Alan B.; Graham, John M.; Kunz, Liza H.; Slavotinek, Anne M.; Kirby, Russell S.; Seeger, John

    2016-01-01

    Objective. To examine pregnancy and birth outcomes among women with idiopathic thrombocytopenic purpura (ITP) or chronic ITP (cITP) diagnosed before or during pregnancy. Methods. A linkage of mothers and babies within a large US health insurance database that combines enrollment data, pharmacy claims, and medical claims was carried out to identify pregnancies in women with ITP or cITP. Outcomes included preterm birth, elective and spontaneous loss, and major congenital anomalies. Results. Results suggest that women diagnosed with ITP or cITP prior to their estimated date of conception may be at higher risk for stillbirth, fetal loss, and premature delivery. Among 446 pregnancies in women with ITP, 346 resulted in live births. Women with cITP experienced more adverse outcomes than those with a pregnancy-related diagnosis of ITP. Although 7.8% of all live births had major congenital anomalies, the majority were isolated heart defects. Among deliveries in women with cITP, 15.2% of live births were preterm. Conclusions. The results of this study provide further evidence that cause and duration of maternal ITP are important determinants of the outcomes of pregnancy. PMID:27092275

  8. Platelet microparticles in immune thrombocytopenic purpura in pediatrics.

    PubMed

    Tantawy, Azza A G; Matter, Randa M; Hamed, Ahmed A; Shams El Din El Telbany, Manal A

    2010-05-01

    Immune thrombocytopenic purpura (ITP) is one of the most common hemorrhagic disorders in childhood. Platelet microparticles (PMPs) arise with platelet activation with procoagulant activity. Elevated PMP levels in adult ITP were reported to be thrombogenic in certain settings. However, their clinical significance in pediatric ITP was not studied. The aims of this study were to assess PMP levels in ITP in children and adolescents, and its correlation with clinical status and bleeding score. The study included 40 ITP patients (20 acute aged 9 +/- 2.19 years and 20 chronic aged 10.8 +/- 4.7 years) randomly selected from the Hematology Clinic, Children's Hospital, Ain Shams University, Cairo, Egypt, and 30 sex- and age-matched healthy controls aged 9 +/- 3.28 years. Patients were subjected to detailed history, assessment of bleeding score, complete hemogram, cytological bone marrow examination, and PMP quantification in peripheral blood by flow cytometry. Acute ITP patients had significant increase in PMPs, PMP/platelet count, and PMP percent compared to controls (P = .002, P < .0001, P < .0001, respectively) and compared to chronic ITP patients (P < .0001, P < .0001, P < .0001, respectively). PMPs were significantly decreased in chronic ITP patients compared to controls (P = .001), but PMP/platelet and PMP percent showed highly significant increase in chronic ITP (P < .0001). No correlation was evident between PMP levels and platelet count in either group (P > .05). Neither higher bleeding score nor thrombotic manifestations were observed in the studied ITP patients with high PMP levels. Elevated PMP levels may be protective against severe bleeding events in pediatric ITP. The role of PMP studies in deciding the management plan of childhood and adolescent ITP needs further evaluation.

  9. Late Results After Splenectomy in Adult Idiopathic Thrombocytopenic Purpura

    PubMed Central

    Vecchio, Rosario; La Corte, Francesco; Marchese, Salvatore; Cacciola, Rossella R.; Cacciola, Emma

    2015-01-01

    Background: We performed a retrospective study on patients with idiopathic thrombocytopenic purpura (ITP) to evaluate the response to splenectomy in relation to preoperative platelet count. Materials and Methods: Two groups of patients operated on with laparoscopic or open splenectomy for ITP, with a platelet count ≤30,000/μL (study group: 22 patients) and >30,000/μL (control group: 18 patients), respectively, were compared. The two groups were homogeneous in relation to age, sex, length of preoperative steroid therapy, and time interval between diagnosis and surgery (Student t test with P > .1). The results of surgery were evaluated at one year after splenectomy. Positive response to surgery, according to the American Society of Hematologic Guidelines, was considered in patients with a postoperative platelet count ≥100,000/μL or in patients with a postoperative platelet count ≥30,000/μL and a twofold increase in platelet count from baseline, in the absence of bleeding. The postoperative platelet count increase rate was statistically related to preoperative platelet count in both the study and control groups. Statistical analysis was performed using the Student's t test for independent sample and the Pearson correlation in a 2-tailed test. Results: No relationship between preoperative platelet count and postoperative platelet percent increase was observed in the control group (r = –0.41; P = .089), whereas a significant negative correlation (r = –0.68; P = .0004) was found in the study group. Conclusions: A higher increase of postoperative percent platelet count may be predicted in patients with a low preoperative platelet count. PMID:25848175

  10. Platelet-associated complement C3 in immune thrombocytopenic purpura

    SciTech Connect

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

    1982-05-01

    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.

  11. Successful management of thrombotic thrombocytopenic purpura in a Jehovah's Witness without plasma exchange.

    PubMed

    Chai, Wanxing; Chaudhry, Abrar; Rabinowitz, Arthur P

    2015-02-01

    Thrombotic thrombocytopenic purpura (TTP) is a hematologic emergency characterized by microangiopathic hemolytic anemia and thrombocytopenia. Plasma exchange is the standard treatment. Treating TTP without plasma exchange is a challenge. Due to religious beliefs, Jehovah's Witnesses do not accept transfusions of blood products. We report a case of successful treatment of TTP in a Jehovah's Witness using plasma exchange with albumin replacement. PMID:24782109

  12. Cerebral venous thrombosis after immune thrombocytopenic purpura and anti-D immune globulin therapy.

    PubMed

    Kayyali, Husam R; Abdelmoity, Ahmed T; Morriss, M Craig; Graf, William D

    2008-03-01

    Cerebral venous thrombosis has multiple etiologies and a wide variety of clinical manifestations. This article reports on a young girl who developed cerebral venous thrombosis after intravenous anti-D immune globulin therapy for immune thrombocytopenic purpura. In this case, venous infarction was manifested by an unusual pattern of restricted diffusion limited to the corpus callosum. The cause of cerebral venous thrombosis in this patient may be related to both immune thrombocytopenia and immunoglobulin therapy.

  13. Rapid irreversible encephalopathy associated with anti-D immune globulin treatment for idiopathic thrombocytopenic purpura.

    PubMed

    Christopher, Kenneth; Horkan, Clare; Barb, Ilie T; Arbelaez, Christian; Hodgdon, Travis A; Yodice, Paul C

    2004-11-01

    Intravenous Rho (D) immune globulin (IV RhIG, WinRho SDF) has been shown to be a safe treatment for idiopathic thrombocytopenic purpura (ITP). Common side effects of IV RhIG include mild hemolysis, febrile reaction, and headache. Significant hemolysis with renal impairment following IV RhIG has been reported. We report a case of irreversible encephalopathy 48 hr following an infusion of IV RhIG for treatment of ITP.

  14. Thrombotic thrombocytopenic purpura and focal segmental glomerulosclerosis associated with the use of ecstasy

    PubMed Central

    Kayar, Yusuf; Kayar, Nuket Bayram; Gangarapu, Venkatanarayana

    2015-01-01

    Ecstasy is a drug, which causes serious side effects and sometimes it can be lethal. These effects are due to idiosyncratic reactions as a result of various stimulations in adrenergic receptors. Here we present a case of a 36-year-old male patient who was diagnosed with thrombotic thrombocytopenic purpura associated with the use of ecstasy. Plasmapheresis along with methylprednisolone treatment restores patient condition to normal. PMID:25878432

  15. Pathogenesis, laboratory, and clinical characteristics of Helicobacter pylori-associated immune thrombocytopenic purpura.

    PubMed

    Franchini, Massimo; Plebani, Mario; Montagnana, Martina; Veneri, Dino; Lippi, Giuseppe

    2010-01-01

    Idiopathic thrombocytopenic purpura (ITP) is a common autoimmune disease mediated by autoantibodies against platelet glycoproteins. This hemorrhagic disorder may be primary or secondary to various illnesses, including lymphoproliferative, autoimmune, or infectious diseases. Among the latter causes, there is increasing laboratory and clinical evidence that documents a pathogenic role of Helicobacter pylori infection in ITP. The aim of this review is to analyze the current knowledge on the pathogenic, diagnostic, clinical, and therapeutic characteristics of H. pylori-associated ITP.

  16. Differentiation between severe HELLP syndrome and thrombotic microangiopathy, thrombotic thrombocytopenic purpura and other imitators.

    PubMed

    Pourrat, O; Coudroy, R; Pierre, F

    2015-06-01

    Pre-eclampsia complicated by severe HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome is a multi-organ disease, and can be difficult to differentiate from thrombotic microangiopathy (appearing as thrombotic thrombocytopenic purpura or hemolytic uremic syndrome), acute fatty liver, systemic erythematous lupus, antiphospholipid syndrome and severe sepsis. Many papers have highlighted the risks of misdiagnosis resulting in severe consequences for maternal health, and this can be fatal when thrombotic thrombocytopenic purpura is misdiagnosed as severe HELLP syndrome. The aim of this paper is to propose relevant markers to differentiate pre-eclampsia complicated by severe HELLP syndrome from its imitators, even in the worrying situation of apparently indistinguishable conditions, and thereby assist clinical decision-making regarding whether or not to commence plasma exchange. Relevant identifiers to establish the most accurate diagnosis include the frequency of each disease and anamnestic data. Frank hemolysis, need for dialysis, neurological involvement and absence of disseminated intravascular coagulation are indicative of thrombotic microangiopathy. The definitive marker for thrombotic thrombocytopenic purpura is undetectable ADAMTS 13 activity. PMID:25879992

  17. [Association of idiopathic thrombocytopenic purpura and type 1 diabetes mellitus--a case report].

    PubMed

    Prusek, Katarzyna; Deja, Grażyna; Jarosz-Chobot, Przemysława

    2010-01-01

    The relation between type 1 diabetes mellitus and autoimmune thyroid diseases is well known. In the pathogenesis of both diseases, chronic autoimmunization plays an essential role. Specific autoantibodies are also responsible for the onset of idiopathic thrombocytopenic purpura. In the paper we present a case of an 11-year-old girl with insulin dependent diabetes in whom the idiopathic thrombocytopenic purpura without bleeding diathesis has been newly diagnosed. The patient had positive titres of thyroid autoantibodies, whilst she did not suffer from thyroid dysfunction. Due to inefficiency of intravenous gammaglobulins the patient was treated with a steroid therapy, which elevated the platelet counts to safe levels. However, the episodes of hyperglycemia have appeared as a side effect. The insulin therapy was modified and the girl was released in a good condition. In this case report, consideration should be given to the wide range of autoimmune diseases that can accompany type one diabetes mellitus--not only can we observe immune diabetic markers, but also thyroid autoantibodies and anti-platelet antibodies. Particular therapeutic dilemmas resulting in a difficult decision on steroid therapy while treating a diabetic patient with idiopathic thrombocytopenic purpura are also presented. PMID:21092704

  18. Presumptive thrombotic thrombocytopenic purpura following a hump-nosed viper (Hypnale hypnale) bite: a case report

    PubMed Central

    2014-01-01

    Hump-nosed viper bites are frequent in southern India and Sri Lanka. However, the published literature on this snakebite is limited and its venom composition is not well characterized. In this case, we report a patient with thrombotic thrombocytopenic purpura-like syndrome following envenoming which, to the best of our knowledge, has not been reported in the literature before. A 55-year-old woman from southern Sri Lanka presented to the local hospital 12 hours after a hump-nosed viper (Hypnale hypnale) bite. Five days later, she developed a syndrome that was characteristic of thrombotic thrombocytopenic purpura with fever, thrombocytopenia, microangiopathic hemolysis, renal impairment and neurological dysfunction in the form of confusion and coma. Her clinical syndrome and relevant laboratory parameters improved after she was treated with therapeutic plasma exchange. We compared our observations on this patient with the current literature and concluded that thrombotic thrombocytopenic purpura is a theoretically plausible yet unreported manifestation of hump-nosed viper bite up to this moment. This study also provides an important message for clinicians to look out for this complication in hump-nosed viper bites since timely treatment can be lifesaving. PMID:24987409

  19. Thrombotic thrombocytopenic purpura presenting as acute coronary syndrome.

    PubMed

    Mouabbi, Jason Aboudi; Zein, Rami; Kafri, Zyad; Al-Katib, Ayad; Hadid, Tarik

    2016-08-01

    In patients presenting with thrombotic thrombocytopenia purpura and non-ST elevation myocardial infarction, prompt initiation of plasma exchange takes precedence over other invasive diagnostic procedures for coronary artery disease. Such procedures should be delayed until clinical condition and laboratory parameters have been stabilized. PMID:27525072

  20. Dameshek W, Miller EB. The megakaryocytes in idiopathic thrombocytopenic purpura, a form of hypersplenism. 1946.

    PubMed

    2016-01-01

    This paper, by one of the legends of hematology, William Dameshek, and his colleague Edward Miller, is from the inaugural issue of Blood. By studying bone marrow specimens from controls, patients with acute or chronic immune thrombocytopenia, or patients with other thrombocytopenic disorders, the authors concluded that, in idiopathic thrombocytopenic purpura (ITP), production of platelets from megakaryocytes is defective, even while marrow megakaryocytes are greatly increased in number. This defect resolved after splenectomy. The authors appropriately credit E. Frank with having proposed defective platelet production from megakaryocytes in ITP in 1915. The idea that platelet production was defective in ITP was superseded or ignored for decades, but it has now been validated by the therapeutic effectiveness of the thrombopoietin mimetics in ITP.

  1. Immune Thrombocytopenic Purpura and Gastritis by H. pylori Associated With Type 1 Diabetes Mellitus.

    PubMed

    Culquichicón-Sánchez, Carlos; Correa, Ricardo; Flores-Guevara, Igor; Espinoza Morales, Frank; Mejia, Christian R

    2016-01-01

    We present the 15th case reported worldwide and 3rd case reported in Latin America of immune thrombocytopenic purpura associated with Type 1 diabetes mellitus in Scopus, MEDLINE, and SciELO. An 11-year-old male patient of mixed ethnicity with immune thrombocytopenic purpura, Type 1 diabetes mellitus, and gastritis due to H. pylori presented to the emergency room with petechiae, ecchymosis, and gingival and conjunctival bleeding that had been worsening for the past three months. The patient had a body mass index of 18.85 kg/m(2) (P75). A biochemical analysis showed 1×10(9) platelets/L, increased prothrombin time, increased partial thromboplastin time, and an HbA1C of 7.84% on admission. He was prescribed a single dose of intravenous methylprednisolone 750 mg in 100 mL of NaCl and daily oral 50 mg prednisolone, with intravenous 250 mg tranexamic acid every eight hours. The patient's glycemic control was continued with the administration of insulin glargine (30 units every 24 hours) and prandial insulin glulisine (five to eight units per meal). Before admission, the patient was on a prescribed treatment of sitagliptin 50 mg and metformin 850 mg, but this was suspended in the emergency room. For the eradication of H. pylori he was prescribed amoxicillin 500 mg every eight hours, oral clarithromycin 335 mg every 12 hours, and IV omeprazole 40 mg. After 15 days, he showed disease resolution and he was discharged to his home with orders to follow-up with pediatrics, hematology, and endocrinology services. The first-line treatment for immune thrombocytopenic purpura patients with active bleeding and a platelet count < 30,000 platelets/μl is the administration of corticosteroids and inmunoglobulin. PMID:27026836

  2. [Protocol for the study and treatment of immune thrombocytopenic purpura (ITP). ITP-2010].

    PubMed

    Monteagudo, E; Fernández-Delgado, R; Sastre, A; Toll, T; Llort, A; Molina, J; Astigarraga, I; Dasí, M A; Cervera, A

    2011-06-01

    Primary immune thrombocytopenia (ITP), formerly known as immune thrombocytopenic purpura, is a disease in which clinical and therapeutic management has always been controversial. The ITP working group of the Spanish Society of Paediatric Haematology and Oncology has updated its guidelines for diagnosis and treatment of ITP in children based on current guidelines, literature review, clinical trials and member consensus. The primary objective was to lessen clinical variability in diagnostic and therapeutic procedures in order to obtain best clinical results with minimal adverse events and good quality of life.

  3. Advances in the pathogenesis, diagnosis and treatment of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome.

    PubMed

    Franchini, Massimo; Zaffanello, Marco; Veneri, Dino

    2006-01-01

    The thrombotic microangiopathies are microvascular occlusive disorders characterized by hemolytic anemia caused by fragmentation of erythrocytes and thrombocytopenia due to increased platelet aggregation and thrombus formation, eventually leading to disturbed microcirculation with reduced organ perfusion. Depending on whether brain or renal lesions prevail, two different entities have been described: thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). However, not rarely the clinical distinctions between these two conditions remain questionable. Recent studies have contributed greatly to our current understanding of the molecular mechanisms leading to TTP and HUS. In this review, we briefly focus on the most important advances in the pathophysiology, diagnosis and treatment of these two thrombotic microangiopathies.

  4. Pulmonary hyalinizing granuloma. Bilateral pulmonary nodules associated with chronic idiopathic thrombocytopenic purpura.

    PubMed

    Satti, Mohamed B; Batouk, Abdelnasir A; Abdelaziz, Muntasir M; Ahmad, Mohamed F; Abdelaal, Mohamed A

    2005-09-01

    We report a case of a 30-year-old female who had been treated periodically with steroids for idiopathic thrombocytopenic purpura ITP over the last 10 years. Recently, during the course of investigation, she was found to have incidental asymptomatic multiple pulmonary nodules on chest CT. Following a needle biopsy to exclude malignancy, 2 nodules were excised and were histologically confirmed as pulmonary hyalinizing granuloma PHG. The remaining 2 nodules regressed on increasing her dose of steroids. The case is discussed with emphasis on the histological and radiological differential diagnosis, in addition to including ITP among the spectrum of immunologic conditions associated with PHG. PMID:16155671

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

    SciTech Connect

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

    1986-07-01

    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.

  6. Clopidogrel-Associated Thrombotic Thrombocytopenic Purpura following Endovascular Treatment of Spontaneous Carotid Artery Dissection

    PubMed Central

    Rubano, Jerry A.; Chen, Kwan; Sullivan, Brianne; Vosswinkel, James A.; Jawa, Randeep S.

    2015-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening multisystem disease secondary to platelet aggregation. We present a patient who developed profound thrombocytopenia and anemia 8 days following initiation of therapy with clopidogrel after stent placement for carotid artery dissection. She did not have a disintegrin and metalloproteinase with thrombospondin domain 13 (ADAMTS 13) deficiency. Management included steroids and therapeutic plasma exchange. Clopidogrel has rarely been associated with TTP. Unlike other causes of acquired TTP, the diagnosis of early clopidogrel-associated TTP is largely clinical given the infrequent reduction in ADAMTS 13 activity. PMID:26623244

  7. Role of myeloid human cytomegalovirus infection in children's idiopathic thrombocytopenic purpura.

    PubMed

    Ding, Yan; Zhao, Lei; Mei, Hong; Zhang, Shu-Ling; Huang, Zhi-Hua

    2007-01-01

    This project explores the specificity of myeloid human cytomegalovirus (HCMV) infection in pathogenesis of idiopathic thrombocytopenic purpura (ITP). Eighty-one subjects with ITP were observed. HCMV early antigen and related myeloid cells in bone marrow, and platelet, HCMV IgM, and IgG in blood were tested. The results presented potent evidence that myeloid HCMV infection is a specific factor in children's ITP: patients of ITP with myeloid HCMV infection had a tendency for exacerbation, refractoriness, and chronic advance. However, HCMV did not affect the quantity of megakaryocyte, which showed the complicated relationships between HCMV and ITP.

  8. Changes in Follicular Helper T Cells in Idiopathic Thrombocytopenic Purpura Patients

    PubMed Central

    Xie, Jue; Cui, Dawei; Liu, Yan; Jin, Jie; Tong, Hongyan; Wang, Lei; Ruan, Guoxiang; Lu, Yun; Yuan, Huiming

    2015-01-01

    Background: Idiopathic thrombocytopenic purpura (ITP) is a primary autoimmune disease with a decreased platelet count caused by platelet destruction mediated mainly by platelet antibodies. T follicular helper (TFH) cells have demonstrated important roles in autoimmune diseases. The aim of this study is to explore the might role of TFH cells in the patients of ITP. Methods: Twenty-three ITP patients and 12 healthy controls (HC) were enrolled in this study. The frequency of circulating TFH cells in both the patients and HC was analyzed by flow cytometry. Serum interleukin (IL)-21 and IL-6 levels were measured using ELISA, and platelet antibodies were tested using a solid phase technique. Additionally, IL-21, IL-6, Bcl-6 and c-Maf mRNA expressions in peripheral blood mononuclear cells (PBMCs) were detected using real-time PCR. Results: The percentages of circulating CXCR5+ CD4+TFH cells with ICOShigh or PD-1high expression were significantly higher in the ITP patients than in the HC. Moreover, the frequencies of circulating CXCR5+ CD4+TFH cells with inducible costimulator (ICOS)high or programmed death-1 (PD-1)high expression were notably higher in ITP with platelet-antibody-positive ( ITP (+) ) patients than in ITP with platelet-antibody-negative ( ITP (-) ) patients and HC, as were the serum IL-21 and IL-6 levels (significant). Moreover, a positive correlation was found between the CXCR5+CD4+TFH cells with ICOShigh or PD-1high expression and the serum IL-21 levels of ITP (+) patients. Additionally, the mRNA expression levels of IL-21, IL-6, Bcl-6 and c-Maf were significantly increased in ITP patients, especially in ITP (+) patients. Conclusions: This study demonstrated TFH cells and effector molecules might play an important role in the pathogenesis of ITP, which are possible therapeutic targets in ITP patients. PMID:25561904

  9. Antiphospholipid antibodies (APLA) in immune thrombocytopenic purpura (ITP) and antiphospholipid syndrome (APS).

    PubMed

    Bidot, Carlos J; Jy, Wenche; Horstman, Lawrence L; Ahn, Eugene R; Yaniz, Miriam; Ahn, Yeon S

    2006-06-01

    Antiphospholipid antibodies (APLA) are associated with anti-phospholipid syndrome (APS), a thrombotic disorder, but they are also frequently detected in immune thrombocytopenic purpura (ITP), a bleeding disorder. To investigate possible differences of APLA between these two disorders, we assayed IgG and IgM APLA by ELISA in 21 patients with ITP and 33 with APS. The APLA reacting against two protein target antigens, beta(2)-glycoprotein 1 (beta2GP1) and FVII/VIIa, and four phospholipids [cardiolipin (CL), phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylethanolamine (PE)] as well as lupus anticoagulant (LA) were analyzed. We made the following observations: (i) IgG and IgM antibodies to beta2GP1 and IgM antibodies to FVII/VIIa were more common in APS than ITP, P < 0.05, while IgG antibodies against the phospholipids (aCL, aPC, aPS, aPE) were more common in ITP than APS, P < 0.05; (ii) multiple APLA > or =3 antigens) were more frequent in APS than ITP, P < 0.05; (iii) LA was frequently associated with APS but was absent in ITP; (iv) APLA is quite common in ITP: two-thirds were positive for at least one APLA. In summary, APLA are prevalent in ITP but their profile differs from APS. In APS, antibodies were predominantly against beta2GP1 and 80% had positive LA, while in ITP the APLA reacted most often with the phospholipids without LA. The difference in APLA may result in opposite clinical manifestations in two disorders.

  10. [Wilson's disease associated with olfactory paranoid syndrome and idiopathic thrombocytopenic purpura].

    PubMed

    Sagawa, Morihiko; Takao, Masaki; Nogawa, Shigeru; Mizuno, Masafumi; Murata, Mitsuru; Amano, Takahiro; Koto, Atsuo

    2003-10-01

    In this study we report an individual of Wilson's disease associated with olfactory paranoid syndrome and idiopathic thrombocytopenic purpura. The initial symptom of this female patient was olfactory paranoia at age 17. Although that psychiatric symptom was well controlled under pharmacological treatment for two years, she developed olfactory paranoia as well as sialorrhea, dysarthria and finger tremor at age 20. A year later rigidity was also present in the extremities. At age 23, idiopathic thrombocytopenic purpura was found based on hematological examinations. Because her extrapyramidal symptoms were progressive, she was referred to our department to evaluate her neurologic condition. She was diagnosed as having Wilson's disease based on (1) the presence of Kayser-Fleischer rings, (2) extrapyramidal signs, and (3) a decreased level of serum copper and ceruloplasmin. T2 and FLAIR images of brain MRI showed hyperintense lesions in the putamen, thalamus and pontine tegmentum. Diffusion-weighted images also showed hyperintense lesions in the thalamus and pontine tegmentum. The biopsy specimen of the liver revealed chronic hepatitis with copper accumulation. Since D-penicillamine treatment was initiated, she has shown no olfactory paranoia and exacerbation of ITP. Her gait disturbance has also improved. Olfactory paranoia and ITP are rare clinical complications of Wilson's disease. Further analysis may warrant consideration of the pathophysiological mechanism of the psychiatric, hematological and neuroradiological condition seen in Wilson's disease.

  11. Flow cytometric analysis of anti-platelet antibodies in idiopathic thrombocytopenic purpura.

    PubMed

    Latorraca, A; Lanza, F; Moretti, S; Ferrari, L; Reverberi, R; Galluccio, L; Castoldi, G

    1994-01-01

    Anti-platelet antibody measurement may be important in defining the pathogenesis of thrombocytopenic states. In this paper we compared three anti-human immunoglobulin reagents by using them to detect anti-platelet antibodies on the platelet surface and in the serum of 14 patients with chronic idiopathic thrombocytopenic purpura (ITP) and 22 thrombocytopenic disorders. Samples were analyzed by both flow cytometry and a fluorescence microscope. In ITP patients, the direct test was positive in 50% of the cases, while the indirect technique proved to be positive in a slightly higher number of those tested (56%). Furthermore, the number of positive cases was similar for the three reagents used in this study, although the mean percentage of positive platelets was higher for the kappa/lambda monoclonal reagent. These data further support the sensitivity and reproducibility of flow cytometry analysis, which was capable of detecting antiplatelet antibodies in all patients with transfused Cooley's disease (regarded as positive control), as well as in a significant number of patients with ITP or related diseases. On the basis of the data presented here, definitive proof regarding the presence of anti-platelet antibodies in patients with thrombocytopenia still has to be found, and further studies are needed in order to ascertain the autoimmune nature of these disorders. PMID:7926978

  12. Thrombotic Thrombocytopenic Purpura associated with Clopidogrel: a case report and review of the literature

    PubMed Central

    Azarm, Taleb; Sohrabi, Ayatollah; Mohajer, Hamid; Azarm, Arezou

    2011-01-01

    Thrombotic Thrombocytopenic Purpura (TTP) is a life threatening, multisystem disease characterized by thrombocytopenia, microangiopathic hemolytic anemia, neurological changes, renal failure, and fever. These signs and symptoms are thought to be caused by microthrombi, composed of agglutinated platelets and fibrin, which deposit in the arterioles and capillaries without mediation by an inflammatory process. TTP can occur in the first two weeks of initiation of Clopidogrel therapy. Early signs of TTP may be a skin reaction, which may precede the onset of TTP or it may be other type of purpura or neurological changes. We report the clinical and laboratory findings in a 67 years old female patient in whom TTP developed soon after treatment with 40 mg/day oral Clopidogrel after 8 days. She developed thrombocytopenia (platelets count 12000 /mm3). Her clinical signs and symptoms were fever (39.6C), bleeding from the nose and gum, large skin bruises (purpura and ecchymoses), neurological changes including hallucinations, bizarre behavior, altered mental status (fluctuating), headache, and renal dysfunction. Physicians should be aware of the possibility early onset of this syndrome when initiate Clopidogrel treatment. PMID:22091257

  13. Rotavirus-associated immune thrombocytopenic purpura in children: A retrospective study

    PubMed Central

    Ai, Qi; Yin, Jing; Chen, Sen; Qiao, Lijin; Luo, Na

    2016-01-01

    Certain studies have previously indicated that an association may exist between rotavirus infection and primary immune thrombocytopenic purpura (ITP). The present retrospective study aimed to investigate whether rotavirus may cause ITP in children. Firstly, the incidence of ITP in children with or without rotavirus diarrhea was compared. A 14.58% incident rate was observed in children with rotavirus diarrhea compared with a 7.22% incident rate in children without rotavirus diarrhea. Subsequently, the clinical features of ITP children with or without rotavirus infection were compared. The results indicated that ITP children with rotavirus infection were significantly younger, showed significantly decreased mean platelet volume (MPV) levels and presented a significantly higher frequency of bleeding score of 3 against ITP children without rotavirus infection. In conclusion, these findings suggest that rotavirus serves a causative role in ITP.

  14. The role of splenectomy in multimodality treatment of thrombotic thrombocytopenic purpura.

    PubMed Central

    Schneider, P A; Rayner, A A; Linker, C A; Schuman, M A; Liu, E T; Hohn, D C

    1985-01-01

    Current treatment modalities for thrombotic thrombocytopenic purpura (TTP) include plasmapheresis (PP), splenectomy, steroids, dextran, other antiplatelet agents, and vinca alkaloids. Prior to the development of PP and use of multimodality treatment for TTP, mortality rates exceeded 50%. This report reviews 11 patients treated for TTP, demonstrates the successful use of splenectomy as salvage therapy, and defines our indications for splenectomy in the treatment of this disorder. Ten of 11 patients were initially treated with PP; three responded completely and one died of fulminant disease. Six patients had a transient partial response to plasmapheresis and were subsequently treated with splenectomy, steroids, and dextran-70. Initial plasmapheresis resulted in improvement in laboratory values and clinical status in those patients requiring splenectomy. Durable remission (6-48 months) was achieved in 91% of patients with minimal morbidity. PMID:2412500

  15. Nocardia transvalensis Disseminated Infection in an Immunocompromised Patient with Idiopathic Thrombocytopenic Purpura

    PubMed Central

    García-Méndez, Jorge; Carrillo-Casas, Erika M.; Rangel-Cordero, Andrea; Leyva-Leyva, Margarita; Xicohtencatl-Cortes, Juan; Arenas, Roberto; Hernández-Castro, Rigoberto

    2016-01-01

    Nocardia transvalensis complex includes a wide range of microorganisms with specific antimicrobial resistance patterns. N. transvalensis is an unusual Nocardia species. However, it must be differentiated due to its natural resistance to aminoglycosides while other Nocardia species are susceptible. The present report describes a Nocardia species involved in an uncommon clinical case of a patient with idiopathic thrombocytopenic purpura and pulmonary nocardiosis. Microbiological and molecular techniques based on the sequencing of the 16S rRNA gene allowed diagnosis of Nocardia transvalensis sensu stricto. The successful treatment was based on trimethoprim-sulfamethoxazole and other drugs. We conclude that molecular identification of Nocardia species is a valuable technique to guide good treatment and prognosis and recommend its use for daily bases diagnosis. PMID:27313917

  16. Neglect-induced pseudo-thrombotic thrombocytopenic purpura due to vitamin B12 deficiency.

    PubMed

    Asano, Takeshi; Narazaki, Hidehiko; Kaizu, Kiyohiko; Matsukawa, Shouhei; Takema-Tochikubo, Yuki; Fujii, Shuichi; Saitoh, Nobuyuki; Mashiko, Kunihiko; Fujino, Osamu

    2015-10-01

    Although thrombotic thrombocytopenic purpura (TTP) is rare, early diagnosis and treatment are important for decreasing the mortality rate. Acquired vitamin B12 deficiency is frequently overlooked because of its rarity in developed countries, particularly in children and adolescents. The hematological changes in vitamin B12 deficiency present as megaloblastic anemia, increased lactate dehydrogenase, vasoconstriction, increased platelet aggregation, and abnormal activation of the coagulation followed by microangiopathy as well as neutropenia and thrombocytopenia. We report herein the case of a 15-year-old girl who had been neglected, which might have caused pseudo-TTP through malnutrition, particularly vitamin B12 deficiency. When we encounter cases of TTP in children, clinicians must be aware of the possibility of malnutrition, particularly with vitamin B12 deficiency, even in developed countries, and investigate the cause of malnutrition including neglect. PMID:26387768

  17. Clopidogrel-induced refractory thrombotic thrombocytopenic purpura successfully treated with rituximab.

    PubMed

    Khodor, Sara; Castro, Miguel; McNamara, Colin; Chaulagain, Chakra P

    2016-06-01

    Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder characterized by microvascular aggregation of platelets and fibrin strands causing thrombocytopenia, microangiopathic hemolytic anemia, and organ dysfunction. TTP can develop as a result of a deficiency in ADAMTS13 enzyme activity due to either a genetic defect or, more commonly, the development of anti-ADAMTS13 autoantibodies. TTP can also be associated with pregnancy, organ transplant, lupus, infections, and drugs. Here, we present a case of TTP that developed shortly after the start of clopidogrel treatment for acute ischemic stroke and acute myocardial infarction, and describe the clinical presentation, refractory course of the disease, and successful induction of remission through the use of rituximab in a setting of pre-existing autoimmune diseases. PMID:26684918

  18. The cost of treating immune thrombocytopenic purpura using intravenous Rh immune globulin versus intravenous immune globulin.

    PubMed

    Sandler, S G; Novak, S C; Roland, B

    2000-03-01

    Multiple factors, including efficacy, toxicity and cost, may influence the decision to treat immune thrombocytopenic purpura (ITP) with intravenous immune globulin (IVIG) or intravenous Rho (D) immune globulin (IV RhIG). We conducted a survey of 50 hospitals in 31 states to determine the costs for treating ITP using conventional doses for IVIG or IV RhIG, based on package insert recommendations. The average cost for a dose of IVIG ($2,771) was 71.7% ($1,157) more than that for a dose of IV RhIG ($1,614). In the absence of clearly defined differences in clinical outcomes when treating ITP with IVIG or IV RhIG, the difference in cost may be an important factor in selecting the treatment.

  19. Apheresis and the thrombotic thrombocytopenic purpura syndrome: current advances in diagnosis, pathophysiology, and management.

    PubMed

    Brailey, L L; Brecher, M E; Bandarenko, N

    1999-02-01

    Endeavors to optimize the management of thrombotic thrombocytopenic purpura (TTP) syndrome and improve mortality and relapse rates are hindered by its poorly understood pathophysiology. Variability in the application of therapeutic plasma exchange (TPE), including replacement fluid strategies, desirable endpoints in the platelet count, serum lactate dehydrogenase concentration, and the use of a TPE taper, limit comparisons among published studies. The diversity of adjunctive therapies such as antiplatelet agents, steroids, and splenectomy further clouds comparisons. Recent progress in the diagnosis, pathophysiology, and management of TTP syndrome are summarized. The possible role of occult infection and newly emerging associations such as ticlopidine therapy are discussed. Advances in possible pathogenic mechanisms, the rationale for different replacement fluids including the recently licensed solvent-detergent treated plasma, and progress in the apheresis management of TTP syndrome are presented.

  20. Nocardia transvalensis Disseminated Infection in an Immunocompromised Patient with Idiopathic Thrombocytopenic Purpura.

    PubMed

    García-Méndez, Jorge; Carrillo-Casas, Erika M; Rangel-Cordero, Andrea; Leyva-Leyva, Margarita; Xicohtencatl-Cortes, Juan; Arenas, Roberto; Hernández-Castro, Rigoberto

    2016-01-01

    Nocardia transvalensis complex includes a wide range of microorganisms with specific antimicrobial resistance patterns. N. transvalensis is an unusual Nocardia species. However, it must be differentiated due to its natural resistance to aminoglycosides while other Nocardia species are susceptible. The present report describes a Nocardia species involved in an uncommon clinical case of a patient with idiopathic thrombocytopenic purpura and pulmonary nocardiosis. Microbiological and molecular techniques based on the sequencing of the 16S rRNA gene allowed diagnosis of Nocardia transvalensis sensu stricto. The successful treatment was based on trimethoprim-sulfamethoxazole and other drugs. We conclude that molecular identification of Nocardia species is a valuable technique to guide good treatment and prognosis and recommend its use for daily bases diagnosis.

  1. Nocardia transvalensis Disseminated Infection in an Immunocompromised Patient with Idiopathic Thrombocytopenic Purpura.

    PubMed

    García-Méndez, Jorge; Carrillo-Casas, Erika M; Rangel-Cordero, Andrea; Leyva-Leyva, Margarita; Xicohtencatl-Cortes, Juan; Arenas, Roberto; Hernández-Castro, Rigoberto

    2016-01-01

    Nocardia transvalensis complex includes a wide range of microorganisms with specific antimicrobial resistance patterns. N. transvalensis is an unusual Nocardia species. However, it must be differentiated due to its natural resistance to aminoglycosides while other Nocardia species are susceptible. The present report describes a Nocardia species involved in an uncommon clinical case of a patient with idiopathic thrombocytopenic purpura and pulmonary nocardiosis. Microbiological and molecular techniques based on the sequencing of the 16S rRNA gene allowed diagnosis of Nocardia transvalensis sensu stricto. The successful treatment was based on trimethoprim-sulfamethoxazole and other drugs. We conclude that molecular identification of Nocardia species is a valuable technique to guide good treatment and prognosis and recommend its use for daily bases diagnosis. PMID:27313917

  2. Cytokine-induced killer cell therapy-associated idiopathic thrombocytopenic purpura: rare but noteworthy.

    PubMed

    Fu, Xiaomin; Zhang, Yong; Gao, Quanli; Lin, Jizhen; Zhang, Qinxian; Xu, Benling; Song, Yongping

    2016-09-01

    Idiopathic thrombocytopenic purpura (ITP) is characterized by a diminished platelet count, an autoimmune condition with antibodies against platelets and an increased tendency to bleed. The association between ITP and solid tumors is uncommon. Cytokine-induced killer (CIK) cell therapy is a well tolerated and promising cancer treatment with minimal toxicity. For the first time, CIK cell therapy was reported to be followed by ITP. The mechanism through which CIK induces ITP remains unclear. Imbalanced ratio of Th cells, decreased numbers or impaired function of Treg cells and excessive secretion of cytokines inducing abnormal activation of B cells may be among the possible reasons. Therefore, a better understanding of this rare condition will require further investigation of these cases. PMID:27485074

  3. Peliosis hepatis presenting with massive hepatomegaly in a patient with idiopathic thrombocytopenic purpura.

    PubMed

    Kim, Sun Bean; Kim, Do Kyung; Byun, Sun Jeong; Park, Ji Hye; Choi, Jin Young; Park, Young Nyun; Kim, Do Young

    2015-12-01

    Peliosis hepatis is a rare condition that can cause hepatic hemorrhage, rupture, and ultimately liver failure. Several authors have reported that peliosis hepatis develops in association with chronic wasting disease or prolonged use of anabolic steroids or oral contraceptives. In this report we describe a case in which discontinuation of steroid therapy improved the condition of a patient with peliosis hepatis. Our patient was a 64-year-old woman with a history of long-term steroid treatment for idiopathic thrombocytopenic purpura . Her symptoms included abdominal pain and weight loss; the only finding of a physical examination was hepatomegaly. We performed computed tomography (CT) and magnetic resonance imaging (MRI) of the liver and a liver biopsy. Based on these findings plus clinical observations, she was diagnosed with peliosis hepatis and her steroid treatment was terminated. The patient recovered completely 3 months after steroid discontinuation, and remained stable over the following 6 months. PMID:26770928

  4. Management of immune thrombocytopenic purpura in children: potential role of novel agents.

    PubMed

    Bredlau, Amy Lee; Semple, John W; Segel, George B

    2011-08-01

    The treatment of immune thrombocytopenic purpura (ITP) in children is controversial, requiring individualized assessment of the patient and consideration of treatment options. If the platelet count is >10 000/μL and the patient is asymptomatic, a 'watch and wait' strategy is appropriate since most children with ITP will recover completely without pharmacotherapy. If therapy is indicated because of bleeding or a platelet count <10 000/μL, then treatment with glucocorticoids, intravenous immunoglobulin (IVIg), or anti-D are possible initial choices. Glucocorticoid treatment is the least expensive and is our usual first choice of therapy. Its use assumes that the blood counts and blood film have been evaluated to ensure the absence of evidence of alternative diagnoses, such as thrombotic thrombocytopenic purpura or incipient acute leukemia. IVIg is expensive and often causes severe headache, nausea and vomiting, and requires hospitalization at our institution. Anti-D therapy is also expensive and can only be used in patients who are Rhesus D positive. These therapies, even if only transiently effective, can be repeated if necessary. Children usually recover from newly diagnosed ITP, with or without multiple courses of medical therapy. If the disease becomes 'persistent' with severe thrombocytopenia and/or bleeding, and is no longer responsive to the three first-line therapies, the next approach includes the use of thrombopoietin receptor agonists or rituximab. When the disease persists for more than 1 year, it is considered chronic, and, if symptomatic, it may become necessary to consider third-line therapies, including splenectomy, alternative immunosuppressive agents, or combination or investigative chemoimmunotherapy. This review considers the indications, mechanism of action, and effectiveness of the traditional and novel treatment options for patients with ITP.

  5. Hemorrhagic Stroke in an Adolescent Female with HIV-Associated Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Rakhmanina, Natella; Wong, Edward CC; Davis, Jeremiah C; Ray, Patricio E

    2014-01-01

    HIV-1 infection can trigger acute episodes of Idiopathic Thrombocytoponic Purpura (ITP), and Thrombotic Thrombocytopenic Purpura (TTP), particularly in populations with advanced disease and poor adherence to antiretroviral therapy (ART). These diseases should be distinguished because they respond to different treatments. Previous studies done in adults with HIV-TTP have recommended the prompt initiation or re-initiation of ART in parallel with plasma exchange therapy to improve the clinical outcome of these patients. Here, we describe a case of HIV-TTP resulting in an acute hemorrhagic stroke in a 16 year old female with perinatally acquired HIV infection and non-adherence to ART, who presented with severe thrombocytopenia, microangiopathic hemolytic anemia, and a past medical history of HIV-ITP. Both differential diagnosis and treatments for HIV-ITP and HIV-TTP were considered simultaneously. A decrease in plasma ADAMTS13 activity (<5%) without detectable inhibitory antibodies confirmed the diagnosis of HIV-TTP. Re-initiation of ART and plasma exchange resulted in a marked decrease in the HIV-RNA viral load, recovery of the platelet count, and complete recovery was achieved with sustained virologic suppression. PMID:25429351

  6. Importance of immature platelet fraction as predictor of immune thrombocytopenic purpura

    PubMed Central

    Naz, Arshi; Mukry, Samina Naz; Shaikh, Mahwish Rauf; Bukhari, Ali Raza; Shamsi, Tahir Sultan

    2016-01-01

    Background and Objective: Immune thrombocytopenic purpura (ITP) is a clinical syndrome in which a decreased number of circulating platelets (thrombocytopenia) manifests as a bleeding tendency, easy bruising (purpura) or extravasation of blood from capillaries into skin and mucous membranes (petechiae). The diagnosis of ITP can be made clinically on the basis of symptoms, we need to see if ITP can be confirmed in patients by quantification of residual RNA containing immature platelets (megakaryocytic mass) or immature platelets fraction (IPF) using automated hematology analyzers (Sysmex XE-2100). Methods: In order to check the efficacy of IPF% parameter of Sysmex XE-2100 a total of 231 patients of thrombocytopenia were included in this study. Complete blood count (CBC) was estimated. The data was statistically analyzed by SPSS version 17. Results: About 62 patients were diagnosed as ITP and 169 patients were diagnosed as non ITP on the basis of clinical history. The mean IPF % value of ITP patients was 16.39% and the IPF % value of Non ITP patients was ~7.69% respectively. There was no significant difference in IPF% values with respect to time between sampling and acquisition of complete blood count. The diagnostic sensitivity of IPF% as biomarker for ITP and non-ITP was 85.71% (95%CI: 84.04% to 85.96%) and 41.76% (95% CI: 39.87% to 43.65%). Conclusion: The mean IPF % value by Sysmex XE-2100 can be used to predict ITP. PMID:27375692

  7. Anti-Ku antibody-positive scleroderma-dermatomyositis overlap syndrome developing Graves' disease and immune thrombocytopenic purpura.

    PubMed

    Kamei, Nozomu; Yamane, Kiminori; Yamashita, Yasuyo; Nakanishi, Shuhei; Watanabe, Hiroshi; Fujikawa, Rumi; Hiyama, Keiko; Ishioka, Shinichi; Mendoza, Ciro; Kohno, Nobuoki

    2002-12-01

    Graves' disease (GD) has been reported to be frequently complicated with other autoimmune diseases. However, it is rarely complicated with scleroderma-polymyositis overlap syndrome. Recently, we encountered a 35-year-old woman who developed GD and immune thrombocytopenic purpura during follow-up observation of scleroderma-dermatomyositis overlap syndrome. Platelet counts recovered after high-dose gamma-globulin therapy and bolus methylprednisolone therapy. The present case is the first report of a combination of scleroderma, dermatomyositis, GD, and immune thrombocytopenic purpura. The patient was anti-Ku antibody-positive and had relatively low natural killer T cell counts, both of which might contribute to the complication of multiple autoimmune diseases.

  8. Vitamin B12 Deficiency and Hemoglobin H Disease Early Misdiagnosed as Thrombotic Thrombocytopenic Purpura: A Series of Unfortunate Events

    PubMed Central

    Andreadis, Panagiotis; Theodoridou, Stamatia; Pasakiotou, Marily; Arapoglou, Stergios; Gigi, Eleni; Vetsiou, Evaggelia; Vlachaki, Efthymia

    2015-01-01

    We herein would like to report an interesting case of a patient who presented with anemia and thrombocytopenia combined with high serum Lactic Dehydrogenase where Thrombotic Thrombocytopenic Purpura was originally considered. As indicated a central venous catheter was inserted in his subclavian vein which led to mediastinal hematoma and finally intubation and Intensive Care Unit (ICU) hospitalization. After further examination patient was finally diagnosed with B12 deficiency in a setting of H hemoglobinopathy. There have been previous reports where pernicious anemia was originally diagnosed and treated as Thrombotic Thrombocytopenic Purpura but there has been none to our knowledge that was implicated with hemothorax and ICU hospitalization or correlated with thalassemia and we discuss the significance of accurate diagnosis in order to avoid adverse reactions and therapy implications. PMID:26609455

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

    SciTech Connect

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

    1989-05-01

    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.

  10. Immune thrombocytopenic purpura (ITP) associated with vaccinations: a review of reported cases.

    PubMed

    Perricone, Carlo; Ceccarelli, Fulvia; Nesher, Gideon; Borella, Elisabetta; Odeh, Qasim; Conti, Fabrizio; Shoenfeld, Yehuda; Valesini, Guido

    2014-12-01

    Immune thrombocytopenic purpura (ITP) is an autoimmune condition characterized by low platelet count with mucocutaneous and other bleedings. Clinical manifestations may range from spontaneous formation of purpura and petechiae, especially on the extremities, to epistaxis, bleeding at the gums or menorrhagia, any of which occur usually if the platelet count is below 20,000 per μl. A very low count may result in the spontaneous formation of hematomas in the mouth or on other mucous membranes. Fatal complications, including subarachnoid or intracerebral, lower gastrointestinal or other internal bleeding can arise due to an extremely low count. Vaccines may induce ITP by several mechanisms. Vaccine-associated autoimmunity may stem not only from the antigen-mediated responses but also from other constituents of the vaccine, such as yeast proteins, adjuvants, and preservatives diluents. The most likely is through virally induced molecular mimicry. The binding of pathogenic autoantibodies to platelet and megakaryocytes may cause thrombocytopenia by different mechanisms, such as opsonization, direct activation of complement, or apoptotic pathways. The autoantibodies hypothesis is not sufficient to explain all ITP cases: In the anti-platelet antibody-negative cases, a complementary mechanism based on T cell immune-mediated mechanism has been suggested. In particular, T cell subsets seem dysregulated with an increased production of pro-inflammatory cytokines, as IFN-γ and TNF, and chemokines, as CXCL10. Vaccines are one of the most striking discoveries in human history that changed dramatically life expectancy. Nonetheless, the occurrence of adverse events and autoimmune phenomena has been described following vaccination, and ITP may represent one of this.

  11. Does Helicobacter pylori play a role in the pathogenesis of childhood chronic idiopathic thrombocytopenic purpura?

    PubMed Central

    Maghbool, Maryam; Maghbool, Masood; Shahriari, Mehdi; Karimi, Mehran

    2009-01-01

    Idiopathic thrombocytopenic purpura (ITP) is an acute self-limited bleeding disorder that can progress to chronic form in 10–15% of the cases. Helicobacter pylori (H. pylori) infection is a possible cause of chronic ITP. We studied 30 children with resistant chronic ITP for H. pylori infection based on the detection of H. pylori fecal antigen. This retrospective study was based on data obtained from medical records of 30 children aged between five and 17 years (median age at ITP diagnosis was ten years). A specially-designed data sheet was used to record information on age, sex, duration of disease, family history of bleeding disorders, previous treatments and median platelet count. In patients with H. pylori infection, antimicrobial treatment consisted of amoxicillin, metronidazol and omeprazol. Response was assessed every month for one year and defined as complete (platelet count >150×109/L) or partial (platelet count between 50 and 150×109/L). We detected H. pylori infection in 5 patients. In 4 of them increased platelet count was seen during one year of follow-up and in one patient the platelet count was acceptable during six months. Although the pathological mechanism of H. pylori-induced thrombocytopenia was unclear in our patient sample, the assessment of H. pylori infection and use of eradication therapy should be attempted in chronic and resistant ITP patients. PMID:21589818

  12. [Clinical significance of Helicobacter pylori in children with idiopathic thrombocytopenic purpura].

    PubMed

    Tang, Ying; Wang, Shu-Chun; Wang, Lu-Juan; Liu, Yong; Wang, Hai-Ying; Wang, Zhan-Ju

    2013-04-01

    This study was aimed to investigate the clinic significance of helicobacter pylori (HP) in children with idiopathic thrombocytopenic purpura (ITP). The infection of HP in 92 ITP children was determined by (13) C-Urea Breath Test, the same test was also performed on 66 healthy children. The 68 children infected with HP were randomly divided into 2 groups: single drug group treated only with corticosteroid and; combined drug group treated with corticosteroid and anti-helicobacter pylori treatment. The results showed that 68 patients infected with HP were found in 92 ITP children (74.7%), 26 patients infected with HP were observed in 66 healthy children (39.4%), which was lower than that in ITP children (74.7%, P < 0.05). After anti-helicobacter pylori therapy, the total effective rate and cure rate of ITP patients increased respectively from 73.5% to 94.1%, and the total recurrence rate (17.0%) was much lower than single drug group (47.1%, P < 0.05). Otherwise, after therapy the platelet count in both two groups increased continuously, and at the same time point, the platelet count in anti-helicobacter pylori group was higher than that in the single drug group (P < 0.05). It is concluded that the ITP children have a higher infection rate of HP, which may be involved in the pathogenesis of ITP. Anti-helicobacter pylori therapy would help to improve the therapeutic efficacy and reduce the recurrence of ITP children.

  13. Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura

    PubMed Central

    Yu, Jin; Heck, Susanne; Patel, Vivek; Levan, Jared; Yu, Yu; Bussel, James B.

    2008-01-01

    Immune thrombocytopenic purpura (ITP) is characterized by the presence of antiplatelet autoantibodies as a result of loss of tolerance. CD4+CD25+ regulatory T cells (Tregs) are important for maintenance of peripheral tolerance. Decreased levels of peripheral Tregs in patients with ITP have been reported. To test whether inefficient production or reduced immunosuppressive activity of Tregs contributes to loss of tolerance in patients with chronic ITP, we investigated the frequency and function of their circulating CD4+CD25hi Tregs. We found a com-parable frequency of circulating CD4+CD25hiFoxp3+ Tregs in patients and controls (n = 16, P > .05). However, sorted CD4+CD25hi cells from patients with chronic ITP (n = 13) had a 2-fold reduction of in vitro immunosuppressive activity compared with controls (n = 10, P < .05). The impaired suppression was specific to Tregs as shown by cross-mixing experiments with T cells from controls. These data suggest that functional defects in Tregs contribute to breakdown of self-tolerance in patients with chronic ITP. PMID:18420827

  14. Refractory Immune Thrombocytopenic Purpura and Cytomegalovirus Infection: A Call for a Change in the Current Guidelines.

    PubMed

    Shimanovsky, Alexei; Patel, Devbala; Wasser, Jeffrey

    2016-01-01

    Immune thrombocytopenic purpura (ITP) is characterized by a decreased platelet count caused by excess destruction of platelets and inadequate platelet production. In many cases, the etiology is not known, but the viral illness is thought to play a role in the development of some cases of ITP. The current (2011) American Society of Hematology ITP guidelines recommend initial diagnostic studies to include testing for HIV and Hepatitis C. The guidelines suggest that initial treatment consist of observation, therapy with corticosteroids, IVIG or anti D. Most cases respond to the standard therapy such that the steroids may be tapered and the platelet counts remain at a hemostatically safe level. Some patients with ITP are dependent on long-term steroid maintenance, and the thrombocytopenia persists with the tapering of the steroids. Recent case reports demonstrate that ITP related to cytomegalovirus (CMV) can persist in spite of standard therapy and that antiviral therapy may be indicated. Herein we report a case of a 26-year-old female with persistent ITP that resolved after the delivery of a CMV-infected infant and placenta. Furthermore, we review the current literature on CMV-associated ITP and propose that the current ITP guidelines be amended to include assessment for CMV, even in the absence of signs and symptoms, as part of the work-up for severe and refractory ITP, especially prior to undergoing an invasive procedure such as splenectomy.

  15. Refractory Immune Thrombocytopenic Purpura and Cytomegalovirus Infection: A Call for a Change in the Current Guidelines

    PubMed Central

    Shimanovsky, Alexei; Patel, Devbala; Wasser, Jeffrey

    2016-01-01

    Immune thrombocytopenic purpura (ITP) is characterized by a decreased platelet count caused by excess destruction of platelets and inadequate platelet production. In many cases, the etiology is not known, but the viral illness is thought to play a role in the development of some cases of ITP. The current (2011) American Society of Hematology ITP guidelines recommend initial diagnostic studies to include testing for HIV and Hepatitis C. The guidelines suggest that initial treatment consist of observation, therapy with corticosteroids, IVIG or anti D. Most cases respond to the standard therapy such that the steroids may be tapered and the platelet counts remain at a hemostatically safe level. Some patients with ITP are dependent on long-term steroid maintenance, and the thrombocytopenia persists with the tapering of the steroids. Recent case reports demonstrate that ITP related to cytomegalovirus (CMV) can persist in spite of standard therapy and that antiviral therapy may be indicated. Herein we report a case of a 26-year-old female with persistent ITP that resolved after the delivery of a CMV-infected infant and placenta. Furthermore, we review the current literature on CMV-associated ITP and propose that the current ITP guidelines be amended to include assessment for CMV, even in the absence of signs and symptoms, as part of the work-up for severe and refractory ITP, especially prior to undergoing an invasive procedure such as splenectomy. PMID:26740871

  16. A complement-dependent model of thrombotic thrombocytopenic purpura induced by antibodies reactive with endothelial cells.

    PubMed

    Ren, Guohui; Hack, Bradley K; Minto, Andrew W; Cunningham, Patrick N; Alexander, Jessy J; Haas, Mark; Quigg, Richard J

    2002-04-01

    Thrombotic thrombocytopenic purpura (TTP) is an immunologically mediated disease characterized by thrombocytopenia, hemolytic anemia, and pathologic changes in various organs, including the kidney, which are secondary to widespread thromboses. Central to TTP is platelet activation, which may occur from a variety of mechanisms, including endothelial cell activation or injury. In this study, injection of K6/1, a monoclonal antibody with widespread reactivity toward endothelia, led to dose-dependent thrombocytopenia in rats. This was magnified if animals were preimmunized with mouse IgG, thereby resulting in an accelerated autologous phase of injury. In this setting, significant anemia also resulted. Rats injected with K6/1 developed renal injury, consisting of tubular damage and glomerular thrombi. Thrombocytopenia and renal morphological abnormalities were eliminated if animals were complement depleted with cobra venom factor prior to K6/1 injection and worsened when the activity of the ubiquitous complement regulator Crry was inhibited with function-neutralizing antibodies. Therefore, we have developed a complement-dependent model of TTP in rats by injecting monoclonal antibodies reactive with endothelial cells. Antibody-directed complement activation leads to stimulation of platelets, through direct interactions with complement fragments and/or indirectly through endothelial cell activation or injury, with the subsequent development of TTP.

  17. When the picture is fragmented: Vitamin B12 deficiency masquerading as thrombotic thrombocytopenic purpura

    PubMed Central

    Panchabhai, Tanmay S.; Patil, Pradnya D.; Riley, Elizabeth C.; Mitchell, Charlene K.

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) has high mortality and necessitates prompt recognition of microangiopathic hemolytic anemia (MAHA) and initiation of plasmapheresis. We present a challenging diagnostic workup and management of a 42-year-old man who presented with anemia, thrombocytopenia, and schistocytes on peripheral smear, all pointing to MAHA. Plasmapheresis and steroid therapy were promptly initiated, but hemolysis continued. Further workup showed megaloblastic anemia, severe Vitamin B12 deficiency, high iron saturation, and absent reticulocytosis, none of which could be explained by TTP. Severe Vitamin B12 deficiency can lead to hemolytic anemia from the destruction of red cells in the marrow that have failed the process of maturation. However, this should not cause thrombotic microangiopathy. Previous reports of B12 deficiency presenting with MAHA and a TTP-like manifestation have identified acute hyperhomocysteinemia as a missing link between B12 deficiency and MAHA, so this possibility was further explored. Our patient similarly had significantly elevated serum homocysteine levels, confirming this suspicion of Vitamin B12 deficiency. Vitamin B12 replacement led to normalization of the elevated levels of homocysteine, the disappearance of schistocytes on the peripheral smear, and resolution of the microangiopathic hemolysis, thereby confirming the diagnosis. It is pertinent that intensivists not only know the importance of early recognition and treatment of TTP but are also familiar with rare conditions that can present in a similar fashion. PMID:27308258

  18. When the picture is fragmented: Vitamin B12 deficiency masquerading as thrombotic thrombocytopenic purpura.

    PubMed

    Panchabhai, Tanmay S; Patil, Pradnya D; Riley, Elizabeth C; Mitchell, Charlene K

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) has high mortality and necessitates prompt recognition of microangiopathic hemolytic anemia (MAHA) and initiation of plasmapheresis. We present a challenging diagnostic workup and management of a 42-year-old man who presented with anemia, thrombocytopenia, and schistocytes on peripheral smear, all pointing to MAHA. Plasmapheresis and steroid therapy were promptly initiated, but hemolysis continued. Further workup showed megaloblastic anemia, severe Vitamin B12 deficiency, high iron saturation, and absent reticulocytosis, none of which could be explained by TTP. Severe Vitamin B12 deficiency can lead to hemolytic anemia from the destruction of red cells in the marrow that have failed the process of maturation. However, this should not cause thrombotic microangiopathy. Previous reports of B12 deficiency presenting with MAHA and a TTP-like manifestation have identified acute hyperhomocysteinemia as a missing link between B12 deficiency and MAHA, so this possibility was further explored. Our patient similarly had significantly elevated serum homocysteine levels, confirming this suspicion of Vitamin B12 deficiency. Vitamin B12 replacement led to normalization of the elevated levels of homocysteine, the disappearance of schistocytes on the peripheral smear, and resolution of the microangiopathic hemolysis, thereby confirming the diagnosis. It is pertinent that intensivists not only know the importance of early recognition and treatment of TTP but are also familiar with rare conditions that can present in a similar fashion. PMID:27308258

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

    PubMed

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

    2012-04-01

    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.

  20. Renal failure after anti-D globulin treatment of idiopathic thrombocytopenic purpura.

    PubMed

    Kees-Folts, Deborah; Abt, Arthur B; Domen, Ronald E; Freiberg, Andrew S

    2002-02-01

    Idiopathic thrombocytopenic purpura (ITP) is a disorder of rapid destruction of antibody-coated platelets. Anti-D immune globulin has been used for treatment of ITP in the United States since 1995. Initial studies identified no significant side effects of treatment. However, a recent report highlighted occasional episodes of intravascular hemolysis after anti-D immune globulin. We describe two children with ITP who developed acute renal failure (ARF) after treatment with anti-D immune globulin and also analyze ten additional cases of ARF reported to the manufacturer, Cangene Corporation, through postmarketing surveillance. All episodes of ARF were associated with intravascular hemolysis. Four patients required dialysis. Patient age ranged from 1 to 82 years, but those requiring dialysis were all under age 15 years. Several patients with ARF had preexisting creatinine elevation. Three of the patients with ARF had serologic evidence of acute Epstein-Barr virus (EBV) infection. Renal biopsy in one patient showed acute tubular necrosis, with findings consistent with pigment nephropathy. Anti-D immune globulin, used to treat ITP, may be associated with intravascular hemolysis and resultant ARF. Renal function should be monitored in patients with evidence of intravascular hemolysis. Children and adolescents may have increased risk of ARF requiring dialysis.

  1. Vaccine administration and the development of immune thrombocytopenic purpura in children.

    PubMed

    Cecinati, Valerio; Principi, Nicola; Brescia, Letizia; Giordano, Paola; Esposito, Susanna

    2013-05-01

    The most important reasons cited by the opponents of vaccines are concerns about vaccine safety. Unlike issues such as autism for which no indisputable documentation of direct relationship with vaccine use is available, immune thrombocytopenic purpura (ITP) is an adverse event that can really follow vaccine administration, and may limit vaccine use because little is known about which vaccines it may follow, its real incidence and severity, the risk of chronic disease, or the possibility of recurrences after new doses of the same vaccine. The main aim of this review is to clarify the real importance of thrombocytopenia as an adverse event and discuss how it may interfere with recommended vaccination schedules. The available data clearly indicate that ITP is very rare and the only vaccine for which there is a demonstrated cause-effect relationship is the measles, mumps and rubella (MMR) vaccine that can occur in 1 to 3 children every 100,000 vaccine doses. However, also in this case, the incidence of ITP is significantly lower than that observed during the natural diseases that the vaccine prevents. Consequently, ITP cannot be considered a problem limiting vaccine use except in the case of children suffering from chronic ITP who have to receive MMR vaccine. In these subjects, the risk-benefit ratio of the vaccine should be weighed against the risk of measles in the community. PMID:23324619

  2. Acquired Idiopathic ADAMTS13 Activity Deficient Thrombotic Thrombocytopenic Purpura in a Population from Japan

    PubMed Central

    Matsumoto, Masanori; Bennett, Charles L.; Isonishi, Ayami; Qureshi, Zaina; Hori, Yuji; Hayakawa, Masaki; Yoshida, Yoko; Yagi, Hideo; Fujimura, Yoshihiro

    2012-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a type of thrombotic microangiopathy (TMA). Studies report that the majority of TTP patients present with a deficiency of ADAMTS13 activity. In a database of TMA patients in Japan identified between 1998 and 2008, 186 patients with first onset of acquired idiopathic (ai) ADAMTS13-deficient TTP (ADAMTS13 activity <5%) were diagnosed. The median age of onset of TTP in this group of patients was 54 years, 54.8% were female, 75.8% had renal involvement, 79.0% had neurologic symptoms, and 97.8% had detectable inhibitors to ADAMTS13 activity. Younger patients were less likely to present with renal or neurologic dysfunction (p<0.01), while older patients were more likely to die during the TTP hospitalization (p<0.05). Findings from this cohort in Japan differ from those reported previously from the United States, Europe, and Korea with respect to age at onset (two decades younger in the other cohort) and gender composition (60% to 100% female in the other cohort). We conclude that in one of the largest cohorts of ai-TTP with severe deficiency of ADAMTS13 activity reported to date, demographic characteristics differ in Japanese patients relative to those reported from a large Caucasian registry from Western societies. Additional studies exploring these findings are needed. PMID:22427934

  3. Residual plasmatic activity of ADAMTS13 is correlated with phenotype severity in congenital thrombotic thrombocytopenic purpura.

    PubMed

    Lotta, Luca A; Wu, Haifeng M; Mackie, Ian J; Noris, Marina; Veyradier, Agnes; Scully, Marie A; Remuzzi, Giuseppe; Coppo, Paul; Liesner, Ri; Donadelli, Roberta; Loirat, Chantal; Gibbs, Richard A; Horne, April; Yang, Shangbin; Garagiola, Isabella; Musallam, Khaled M; Peyvandi, Flora

    2012-07-12

    The quantification of residual plasmatic ADAMTS13 activity in congenital thrombotic thrombocytopenic purpura (TTP) patients is constrained by limitations in sensitivity and reproducibility of commonly used assays at low levels of ADAMTS13 activity, blunting efforts to establish genotype-phenotype correlations. In the present study, the residual plasmatic activity of ADAMTS13 was measured centrally by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (limit of detection = 0.5%) in 29 congenital TTP patients. The results were used to study correlations among ADAMTS13 genotype, residual plasmatic activity, and clinical phenotype severity. An ADAMTS13 activity above 0.5% was measured in 26 (90%) patients and lower levels of activity were associated with earlier age at first TTP episode requiring plasma infusion, more frequent recurrences, and prescription of fresh-frozen plasma prophylaxis. Receiver operating characteristic curve analysis showed that activity levels of less than 2.74% and 1.61% were discriminative of age at first TTP episode requiring plasma infusion < 18 years, annual rate of TTP episodes > 1, and use of prophylaxis. Mutations affecting the highly conserved N-terminal domains of the protein were associated with lower residual ADAMTS13 activity and a more severe phenotype in an allelic-dose dependent manner. The results of the present study show that residual ADAMTS13 activity is associated with the severity of clinical phenotype in congenital TTP and provide insights into genotype-phenotype correlations.

  4. [Acquired thrombotic thrombocytopenic purpura after vascular prosthesis implantation for impending rupture of an abdominal aortic aneurysm].

    PubMed

    Naito, Chiaki; Ogawa, Yoshiyuki; Yanagisawa, Kunio; Ishizaki, Takuma; Mihara, Masahiro; Handa, Hiroshi; Isonishi, Ayami; Hayakawa, Masaki; Matsumoto, Masanori; Nojima, Yoshihisa

    2016-03-01

    Acquired thrombotic thrombocytopenic purpura (TTP) is caused by autoantibodies against ADAMTS13. TTP patients run a rapidly fatal course unless immediate plasma exchange (PEX) is initiated upon diagnosis. Herein, we report a 72-year-old man with TTP, which developed after he underwent artificial blood vessel replacement surgery for an abdominal aneurysm with impending rupture. In the perioperative period, the patient received several platelet transfusions for severe thrombocytopenia (minimum platelet count: 0.6×10(4)/μl). Thereafter, he was admitted to our department for rapidly progressing coma with multiple cerebral infarctions, and was transferred to the ICU. Based on the tentative diagnosis of TTP, we immediately began PEX and steroid pulse therapy. The diagnosis was confirmed thereafter by markedly reduced ADAMTS13 activity (<0.5%) and his being positive for the ADAMTS13 inhibitor. We performed PEX for five consecutive days and administered high-dose prednisolone (PSL). On the second hospital day (HD), his platelet count rose along with improvement of his consciousness level. The ADAMTS13 inhibitor was not detected on the 10th HD. TTP did not relapse and his general condition improved despite tapering of PSL. In this case, by closely monitoring ADAMTS13-related parameters and minimizing the number of plasma exchanges, the patient was able to achieve a remission without the use of boosting inhibitors. PMID:27076251

  5. [Sudden death associated with myocardial damage caused by microthrombi in a patient with thrombotic thrombocytopenic purpura].

    PubMed

    Yamamoto, Kiyoko; Hattori, Yukinori; Shimada, Koki; Araki, Yoko; Adachi, Tatsuya; Tsushita, Keitaro

    2015-11-01

    We describe a 35-year-old woman with Down's syndrome who was admitted to a clinic with anorexia and vomiting. Since laboratory findings showed anemia (Hb 7.4 g/dl) and thrombocytopenia (0.5 × 10⁴/μl), she was transferred to our hospital for treatment. Further laboratory examinations revealed schistocytes, LDH elevation, and a negative Coombs' test. Thrombotic thrombocytopenic purpura (TTP) was suspected. Plasma exchange (PEX) and prednisolone administration were thus immediately initiated. Prior to these treatments, ADAMTS13 activity was less than 5% and inhibitors were detected at a level of 0.8 Bethesda U/ml. Although her platelet count had risen to 13.0 × 10⁴/μl by day 6 (post 4 sessions of PEX), it had decreased to 1.8 × 10⁴/μl on day 7. Despite ongoing PEX, thrombocytopenia persisted. On day 21, she suddenly died. Autopsy findings revealed no evidence of myocardial necrosis or coronary artery thrombosis. Extensive microthrombi were, however, detected in precapillary arterioles, capillaries, and post-capillary venules of the heart. Therefore, this patient's sudden death was clinically suspected to have been caused by cardiomyopathy, which had produced cardiogenic shock. PMID:26666721

  6. The role of N-acetylcysteine in the treatment of thrombotic thrombocytopenic purpura.

    PubMed

    Rottenstreich, Amihai; Hochberg-Klein, Sarit; Rund, Deborah; Kalish, Yosef

    2016-05-01

    Thrombotic thrombocytopenic purpura (TTP) is an acute, thrombotic microangiopathy with a high mortality rate if left untreated. Plasma exchange (PEX) is the current standard of care. However, a significant number of patients are refractory to this treatment. N-acetylcysteine (NAC) was recently suggested as a potential therapeutic adjunct for patients with TTP. This study reports a series of three patients with TTP successfully treated with NAC in addition to standard therapy. Detailed chart reviews on these patients were conducted. We discuss clinical features, laboratory findings and management of three patients who presented with microangiopathic hemolytic anemia and thrombocytopenia. Anti-ADAMTS13 antibodies and low levels of ADAMTS13 were detected and confirmed the diagnosis of acquired TTP. Based upon their severe presentation or lack of response to initial treatment with PEX, corticosteroids and other immunosuppressive agents, NAC was added. Under this combined treatment, all three patients hada significant clinical improvement of symptoms with concurrent normalization of platelet count and ADAMTS13 activity level. This report highlights the potential therapeutic utility of NAC in the treatment of TTP. Randomized controlled studies will be required to better characterize the risk-to-benefit ratio of NAC in the treatment of TTP. PMID:26245827

  7. Methorexate therapy in a patient with rheumatoid arthritis complicated by idiopathic thrombocytopenic purpura

    PubMed Central

    Komoğlu, Sabiha; Silte, Duygu; Sertbaş, Meltem; Sertbaş, Yaşar; Özdemir, Ali

    2015-01-01

    The association of rheumatoid arthritis (RA) and immune thrombocytopenic purpura (ITP) has been reported rarely. Methotrexate, which is used for RA treatment, causes thrombocytopenia. Therefore, in medical practice, physicians avoid using methotrexate for RA in patients who have both RA and ITP. Here, we report an RA case that also had ITP, which did not decrease in platelet count after methotrexate therapy. A 50-year-old woman was diagnosed with diabetes mellitus in 1990, RA in 1995, and ITP in 2000. She had received hydroxychloroquine for more than 5 years. She was treated with prednisolone 16 mg/daily between 2006 and 2007, but she discontinued this therapy because of weight gain. Laboratory findings were not remarkable, except for thrombocytopenia. We started methotrexate therapy 10 mg per week for treatment of RA, and hydroxychloroquine therapy was stopped due to nonresponse. The methotrexate dose was increased up to 15 mg/week. Her complete blood cell count was monitored frequently. We did not observe any decrease in platelet count, while active arthritis symptoms of the patient were relieved. This case shows that methotrexate may be used in patients diagnosed with RA that is associated with ITP under strict monitoring.

  8. Successful rituximab treatment in an elderly patient with recurrent thrombotic thrombocytopenic purpura.

    PubMed

    Matsubara, Etsuko; Yamanouchi, Jun; Hato, Takaaki; Takeuchi, Kazuto; Niiya, Toshiyuki; Yasukawa, Masaki

    2016-07-01

    An 81-year-old man presenting with fever, neurological symptoms, thrombocytopenia, and hemolytic anemia was diagnosed with acquired idiopathic thrombotic thrombocytopenic purpura (TTP). His disintegrin-like and metalloproteinase with thrombospondin type 1 motifs 13 (ADAMTS13) activity was <1% and the ADAMTS13 inhibitor titer was 3.2 BU/ml. He received plasma exchange and steroid administration until remission was achieved. Seven months later, he suffered from paralysis of the right hand, hemolytic anemia, and thrombocytopenia. We confirmed TTP recurrence based on ADAMTS13 activity <1% and an ADAMTS13 inhibitor titer of 19.4 BU/ml. Four infusions of rituximab were administered in addition to plasma exchange and steroid pulse therapy. Platelet count recovery was observed within 5 days. No severe side effects related to rituximab occurred. Although rituximab has not been approved for TTP in Japan, we report the efficacy and safety of rituximab in an elderly patient with recurrent TTP. We suggest that rituximab therapy should be started as soon as possible for recurrent TTP in patients with high titers of ADAMTS13 inhibitor. PMID:27498731

  9. Refractory thrombotic thrombocytopenic purpura associated with primary Sjogren syndrome treated with rituximab: a case report.

    PubMed

    Toumeh, Anis; Josh, Navpreet; Narwal, Rawan; Assaly, Ragheb

    2014-01-01

    Thrombotic thrombocytopenic purpura (TTP) is an uncommon, serious disease that involves multiple organs and is rapidly fatal if left untreated. TTP is associated with multisystem symptoms, such as thrombocytopenia, microangiopathic hemolytic anemia, renal impairment, central nervous system involvement, and fever. TTP is idiopathic in about 37% of the cases and can be associated with autoimmune diseases in 13% of the cases. Autoimmune disease-associated TTP can be refractory to plasma exchange and requires immunosuppressive therapy. We report a case of a previously healthy 55-year-old African American female who presented with shortness of breath, hemolytic anemia, renal impairment, and thrombocytopenia. The diagnosis of TTP was made, and plasmapheresis was initiated. However, recurrence happened 48 hours after plasmapheresis was stopped. Autoimmune workup for refractory TTP revealed positive antinuclear antibodies, Anti-SSA, and Anti-SSB. Lip biopsy revealed findings consistent with Sjogren syndrome. Treatment with Rituximab was started, and significant clinical and laboratory response was achieved. The patient remained asymptomatic thereafter. A high clinical suspicion of autoimmune diseases is important as TTP tends to be refractory to plasma exchange in these cases, and immunosuppressive therapy is a key. PMID:23011161

  10. Thrombotic Thrombocytopenic Purpura in Black People: Impact of Ethnicity on Survival and Genetic Risk Factors

    PubMed Central

    Martino, Suella; Jamme, Mathieu; Deligny, Christophe; Busson, Marc; Loiseau, Pascale; Azoulay, Elie; Galicier, Lionel; Pène, Frédéric; Provôt, François; Dossier, Antoine; Saheb, Samir; Veyradier, Agnès; Coppo, Paul

    2016-01-01

    Black people are at increased risk of thrombotic thrombocytopenic purpura (TTP). Whether clinical presentation of TTP in Black patients has specific features is unknown. We assessed here differences in TTP presentation and outcome between Black and White patients. Clinical presentation was comparable between both ethnic groups. However, prognosis differed with a lower death rate in Black patients than in White patients (2.7% versus 11.6%, respectively, P = .04). Ethnicity, increasing age and neurologic involvement were retained as risk factors for death in a multivariable model (P < .05 all). Sixty-day overall survival estimated by the Kaplan-Meier curves and compared with the Log-Rank test confirmed that Black patients had a better survival than White patients (P = .03). Salvage therapies were similarly performed between both groups, suggesting that disease severity was comparable. The comparison of HLA-DRB1*11, -DRB1*04 and -DQB1*03 allele frequencies between Black patients and healthy Black individuals revealed no significant difference. However, the protective allele against TTP, HLA-DRB1*04, was dramatically decreased in Black individuals in comparison with White individuals. Black people with TTP may have a better survival than White patients despite a comparable disease severity. A low natural frequency of HLA-DRB1*04 in Black ethnicity may account for the greater risk of TTP in this population. PMID:27383202

  11. Splenic dynamics of indium-111 labeled platelets in idiopathic thrombocytopenic purpura

    SciTech Connect

    Syrjaelae, M.T.Sa.; Savolainen, S.; Nieminen, U.; Gripenberg, J.; Liewendahl, K.; Ikkala, E. )

    1989-09-01

    Splenic dynamics of {sup 111}In-labeled platelets and platelet-associated IgG in 33 patients with idiopathic thrombocytopenic purpura (ITP) were studied. Two half-lives were calculated for the biexponential splenic time-activity curve after i.v. injection of {sup 111}In-labeled platelets. There was no difference in the mean half-life of the rapid component of the splenic curve (ST1) when patients with negative or slightly positive platelet suspension immunofluorescence test (PSIFT) were compared to those with strongly positive PSIFT (3.0 {plus minus} 0.7 min vs. 3.6 {plus minus} 0.4, p greater than 0.05). Mean half-life of the slow component of the splenic curve (ST2) was found to be longer in patients with a strongly positive than a negative or weakly positive PSIFT (26 {plus minus} 5 min vs. 13.2 {plus minus} 1.0 min, p less than 0.01). It seems that determination of the two components of the splenic time-activity curve provides a useful method for studying platelet kinetics in ITP.

  12. Platelet antibodies of the IgM class in immune thrombocytopenic purpura

    SciTech Connect

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

    1985-04-01

    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.

  13. [Long-term follow-up of chronic idiopathic thrombocytopenic purpura in children].

    PubMed

    Amendola, G; Danise, P; D'Arco, A

    2000-01-01

    Idiopathic thrombocytopenic purpura (ITP) is a common acquired bleeding disorder in infancy and childhood. Most children rapidly improve, exhibiting a rise in platelet count to hemostatically normal levels within weeks to several months. Traditionally, chronic ITP is defined as persistence of thrombocytopenia (platelet count < 150 x 10(9)/L) for greater than 6 months. The Authors retrospectively evaluated 16 patients with chronic ITP, identified during a 12-year period of time in their Department of Pediatrics. The most important clinical and hematological parameters of patients were analyzed, including age at diagnosis, type and response to the initial treatment, number of multiple treatments, and duration of follow-up. At the last evaluation (december 1999) one patient was lost to the follow-up; one died of overwhelming postsplenectomy sepsis; four still require intermittent or chronic infusions of intravenous gamma-globulin; seven are in stable partial remission (PLT > 50 x 10(9)/L < 150 x 10(9)/L) and do not require any treatment; three are in complete remission (PLT > 150 x 10(9)/L). Finally, the Authors discuss of the natural history and management of this rare disease. Presently there are insufficient trial data to support evidence-based treatment guidelines in childhood chronic ITP and therefore it is reasonable to encourage future multicentre collaboration.

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

    PubMed

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

    2005-04-01

    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.

  15. Platelet Kinetics in Idiopathic Thrombocytopenic Purpura Patients Treated with Thrombopoietin Receptor Agonists

    PubMed Central

    Meyer, Oliver; Herzig, Eric; Salama, Abdulgabar

    2012-01-01

    Aim Thrombopoietin receptor agonists (Tpo RA) increase platelet counts in the majority of chronic autoimmune thrombocytopenia (idiopathic thrombocytopenic purpura; ITP) patients. It is unknown whether this treatment may also improve platelet survival (PS) in these patients. Methods In order to determine platelet survival (PS), autologous platelets were labeled with 111In oxine and retransfused in six patients under treatment with Tpo RA (romiplostim n = 3; eltrombopag n = 3). Results Stable platelet counts of greater than 100 × 103/μl were observed in all 6 patients. Platelet survival was decreased in all cases (mean 2.10 days; range 0.13–3.73 days). No correlation was found between platelet count and PS. Similarly, there was no significant relationship between platelet turnover and platelet count. However, a high platelet turnover, exceeding 25 or three times the norm was observed in 2 patients who presented the lowest PS (0.13 or 0.83 days). Two patients had a moderately shortened PS (1.91 or 2.42 days), and, correspondingly, a moderately increased platelet turnover rate (63,072 or 72,872 platelets/μl/day). Conclusion These results indicate that Tpo RA may not only overcompensate platelet destruction in ITP, but may interfere with other mechanisms, which, in some cases, results in a reduced platelet destruction rate. PMID:22896760

  16. Balancing Therapy with Thrombopoietin Receptor Agonists and Splenectomy in Refractory Immune Thrombocytopenic Purpura: A Case of Postsplenectomy Thrombocytosis Requiring Plateletpheresis

    PubMed Central

    Zimmerman, Jacquelyn; Norsworthy, Kelly J.

    2016-01-01

    Immune thrombocytopenic purpura (ITP) causes thrombocytopenia through the autoimmune destruction of platelets. Corticosteroids remain the first line of therapy, and traditionally splenectomy has been the second. While the availability of thrombopoietin receptor agonists (TPO-RAs) has expanded treatment options, there is little data for the ideal management of these agents in preparation for splenectomy. Thrombocytosis has been reported after splenectomy in patients treated with TPO-RA preoperatively, with one prior case requiring plateletpheresis for symptomatic thrombocytosis. We present a case report and review of the literature pertaining to this complication and provide recommendations for preventing postsplenectomy thrombocytosis in ITP patients on TPO-RAs. PMID:27812394

  17. Two cases of Vici syndrome associated with Idiopathic Thrombocytopenic Purpura (ITP) with a review of the literature.

    PubMed

    Huenerberg, Katherine; Hudspeth, Michelle; Bergmann, Shayla; Pai, Shashidhar; Singh, Balvir; Duong, Angie

    2016-05-01

    Vici syndrome is a rare congenital disorder first described in 1988. To date, 31 cases have been reported in the literature. The characteristic features of this syndrome include: agenesis of the corpus callosum, albinism, cardiomyopathy, variable immunodeficiency, cataracts, and myopathy. We report two Hispanic sisters with genetically confirmed Vici syndrome who both developed Idiopathic Thrombocytopenic Purpura. To our knowledge, this is an immunologic process that has been previously undescribed within the phenotype of Vici syndrome and should be added to the spectrum of variable immune dysregulation that can be found in these patients. PMID:26854214

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

    PubMed

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

    2013-04-01

    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.

  19. Single nucleotide polymorphisms of the inflammatory cytokine genes in adults with chronic immune thrombocytopenic purpura.

    PubMed

    Satoh, Takashi; Pandey, Janardan P; Okazaki, Yuka; Yasuoka, Hidekata; Kawakami, Yutaka; Ikeda, Yasuo; Kuwana, Masataka

    2004-03-01

    Single nucleotide polymorphisms (SNPs) of inflammatory cytokine genes were examined in 84 adult Japanese patients with chronic immune thrombocytopenic purpura (ITP) and 56 race-matched healthy controls. The SNPs examined were within the genes encoding tumour necrosis factor (TNF)-alpha (-238 G/A and -308 G/A), TNF-beta (+252 G/A), and interleukin (IL)-1beta (-511 C/T and +3953 T/C). Of these SNPs, the frequency of the TNF-beta (+252) G/G phenotype was significantly higher in ITP patients than in healthy controls (21% vs. 7%, P = 0.04, odds ratio = 3.6, 95% confidence interval 1.1-11.1), while no significant association was detected for the other SNPs. The distribution of the TNF-beta (+252) phenotype was not associated with human leucocyte antigen class II alleles or the therapeutic response in ITP patients. The frequency of circulating anti-glycoprotein IIb/IIIa antibody-producing B cells was significantly higher in ITP patients with the TNF-beta (+252) G/G phenotype than in those with the G/A or A/A phenotype (11.9 +/- 4.9 vs. 6.8 +/- 4.9 and 3.7 +/- 2.8 per 10(5) peripheral blood mononuclear cells; P = 0.02 and P < 0.001, respectively). These findings suggest that the SNP located at TNF-beta (+252) contributes to susceptibility to chronic ITP by controlling the autoreactive B-cell responses to platelet membrane glycoproteins.

  20. Helicobacter pylori Eradication in Patients with Immune Thrombocytopenic Purpura: A Review and the Role of Biogeography

    PubMed Central

    Frydman, Galit H.; Davis, Nick; Beck, Paul L.; Fox, James G.

    2015-01-01

    Idiopathic thrombocytopenic purpura (ITP) is typically a diagnosis of exclusion, assigned by clinicians after ruling out other identifiable etiologies. Since a report by Gasbarrini et al. in 1998, an accumulating body of evidence has proposed a pathophysiological link between ITP and chronic Helicobacter pylori (H. pylori) infection. Clinical reports have described a spontaneous resolution of ITP symptoms in about 50% of chronic ITP patients following empirical treatment of H. pylori infection, but response appears to be geography dependent. Studies have also documented that ITP patients in East Asian countries are more likely to express positive antibody titers against H. pylori-specific cytotoxic-associated gene A (CagA), a virulence factor that is associated with an increased risk for gastric diseases including carcinoma. While a definitive mechanism by which H. pylori may induce thrombocytopenia remains elusive, proposed pathways include molecular mimicry of CagA by host autoantibodies against platelet surface glycoproteins, as well as perturbations in the phagocytic activity of monocytes. Traditional treatments of ITP have been largely empirical, involving the use of immunosuppressive agents and immunoglobulin therapy. However, based on the findings of clinical reports emerging over the past 20 years, health organizations around the world increasingly suggest the detection and eradication of H. pylori as a treatment for ITP. Elucidating the exact molecular mechanisms of platelet activation in H. pylori-positive ITP patients, while considering biogeographical differences in response rates, could offer insight into how best to use clinical H. pylori eradication to treat ITP, but will require well-designed studies to confirm the suggested causative relationship between bacterial infection and an autoimmune disease state. PMID:25728540

  1. Helicobacter pylori Eradication in Patients with Immune Thrombocytopenic Purpura: A Review and the Role of Biogeography.

    PubMed

    Frydman, Galit H; Davis, Nick; Beck, Paul L; Fox, James G

    2015-08-01

    Idiopathic thrombocytopenic purpura (ITP) is typically a diagnosis of exclusion, assigned by clinicians after ruling out other identifiable etiologies. Since a report by Gasbarrini et al. in 1998, an accumulating body of evidence has proposed a pathophysiological link between ITP and chronic Helicobacter pylori (H. pylori) infection. Clinical reports have described a spontaneous resolution of ITP symptoms in about 50% of chronic ITP patients following empirical treatment of H. pylori infection, but response appears to be geography dependent. Studies have also documented that ITP patients in East Asian countries are more likely to express positive antibody titers against H. pylori-specific cytotoxic-associated gene A (CagA), a virulence factor that is associated with an increased risk for gastric diseases including carcinoma. While a definitive mechanism by which H. pylori may induce thrombocytopenia remains elusive, proposed pathways include molecular mimicry of CagA by host autoantibodies against platelet surface glycoproteins, as well as perturbations in the phagocytic activity of monocytes. Traditional treatments of ITP have been largely empirical, involving the use of immunosuppressive agents and immunoglobulin therapy. However, based on the findings of clinical reports emerging over the past 20 years, health organizations around the world increasingly suggest the detection and eradication of H. pylori as a treatment for ITP. Elucidating the exact molecular mechanisms of platelet activation in H. pylori-positive ITP patients, while considering biogeographical differences in response rates, could offer insight into how best to use clinical H. pylori eradication to treat ITP, but will require well-designed studies to confirm the suggested causative relationship between bacterial infection and an autoimmune disease state. PMID:25728540

  2. CD16 and CD32 Gene Polymorphisms May Contribute to Risk of Idiopathic Thrombocytopenic Purpura.

    PubMed

    Xu, Jiannan; Zhao, Liyun; Zhang, Yan; Guo, Qingxu; Chen, Hui

    2016-01-01

    BACKGROUND Epidemiological studies have evaluated the associations of CD16 158F>V and CD32 131H>R gene polymorphisms with the risk of idiopathic thrombocytopenic purpura (ITP). MATERIAL AND METHODS Published studies on CD16 158F>V and CD32 131H>R polymorphisms with susceptibility to ITP were systematically reviewed until April 1, 2014. The Cochrane Library Database, Medline, CINAHL, EMBASE, Web of Science, and Chinese Biomedical Database (CBM) were used to search for relevant studies and then a meta-analysis was conducted by using Stata 12.0 software in order to produce consistent statistical results. RESULTS In total, 10 clinical case-control studies with 741 ITP patients and 1092 healthy controls were enrolled for quantitative data analysis. Results of this meta-analysis suggest that CD16 158F>V polymorphism had strong correlations with the susceptibility to ITP under 5 genetic models (all P<0.05). However, no similar associations were found between CD32 131H>R polymorphism and the susceptibility to ITP (all P>0.05). Subgroup analysis by ethnicity revealed that CD16 158F>V polymorphism was associated with the increased risk of ITP among both Caucasian and non-Caucasian populations. Nevertheless, no statistically significant correlations between CD32 131H>R polymorphism and the risk of ITP were observed among Caucasians and non-Caucasians (all P>0.05). CONCLUSIONS Our findings indicate that CD16 158F>V polymorphism may contribute to the increased risk of ITP, whereas CD32 131H>R polymorphism may not be an important risk factor for ITP. PMID:27315784

  3. Helicobacter pylori Eradication in Patients with Immune Thrombocytopenic Purpura: A Review and the Role of Biogeography.

    PubMed

    Frydman, Galit H; Davis, Nick; Beck, Paul L; Fox, James G

    2015-08-01

    Idiopathic thrombocytopenic purpura (ITP) is typically a diagnosis of exclusion, assigned by clinicians after ruling out other identifiable etiologies. Since a report by Gasbarrini et al. in 1998, an accumulating body of evidence has proposed a pathophysiological link between ITP and chronic Helicobacter pylori (H. pylori) infection. Clinical reports have described a spontaneous resolution of ITP symptoms in about 50% of chronic ITP patients following empirical treatment of H. pylori infection, but response appears to be geography dependent. Studies have also documented that ITP patients in East Asian countries are more likely to express positive antibody titers against H. pylori-specific cytotoxic-associated gene A (CagA), a virulence factor that is associated with an increased risk for gastric diseases including carcinoma. While a definitive mechanism by which H. pylori may induce thrombocytopenia remains elusive, proposed pathways include molecular mimicry of CagA by host autoantibodies against platelet surface glycoproteins, as well as perturbations in the phagocytic activity of monocytes. Traditional treatments of ITP have been largely empirical, involving the use of immunosuppressive agents and immunoglobulin therapy. However, based on the findings of clinical reports emerging over the past 20 years, health organizations around the world increasingly suggest the detection and eradication of H. pylori as a treatment for ITP. Elucidating the exact molecular mechanisms of platelet activation in H. pylori-positive ITP patients, while considering biogeographical differences in response rates, could offer insight into how best to use clinical H. pylori eradication to treat ITP, but will require well-designed studies to confirm the suggested causative relationship between bacterial infection and an autoimmune disease state.

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

    PubMed

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

    2001-01-01

    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.

  5. Plasma microRNA profiling of pediatric patients with immune thrombocytopenic purpura.

    PubMed

    Bay, Ali; Coskun, Enes; Oztuzcu, Serdar; Ergun, Sercan; Yilmaz, Fatih; Aktekin, Elif

    2014-06-01

    Immune thrombocytopenic purpura (ITP) is a commonly acquired autoimmune bleeding disorder in children. MicroRNAs (miRNAs) are small RNAs which are found in cells and circulation, and play a role in protein synthesis and regulation. In this study, we aimed to determine a biomarker for childhood ITP comparing the plasma miRNA levels of children having ITP with healthy children. A total of 86 patients with ITP and 56 healthy children followed up by the Department of Pediatric Hematology and Oncology in University of Gaziantep since July 2011 were enrolled in the study. The 86 patients with ITP were evaluated in two groups as 43 acute ITP (aITP) and 43 chronic ITP (cITP) patients. Plasma expression levels of 379 miRNAs were investigated by RT-PCR (quantitative RT-PCR) technique and they were compared between aITP, cITP, and control groups. For all miRNAs, the average of raw quantification cycle values of three groups separately in the analysis chip was accepted as the reference gene value, and normalization was done according to this value. Statistically significant differences were detected in seven miRNAs (miR-302c-3p, miR-483-5p, miR-410, miR-544a, miR-302a-3p, miR-223-3p, and miR-597) investigated between the groups with respect to the expression levels. The expression rates were found to be over 95% in miR-302c-3p and miR-483-5p, over 75% in miR-410, and over 40% in miR-544, miR-302a-3p, and miR-223-3p in all three groups. The detection of significant differences between plasma miRNA levels of aITP and cITP patients and healthy children may provide useful information in the prediction of the course of disease, determination of disease etiopathogenesis, and the development of new therapeutic modalities.

  6. Purpura

    MedlinePlus

    Blood spots; Skin hemorrhages ... and 10 mm (millimeters) in diameter. When purpura spots are less than 4 mm in diameter, they are called petechiae . Purpura spots larger than 1 cm (centimeter) are called ecchymoses. ...

  7. Eltrombopag for the treatment of chronic immune or idiopathic thrombocytopenic purpura: a NICE single technology appraisal.

    PubMed

    Boyers, Dwayne; Jia, Xueli; Jenkinson, David; Mowatt, Graham

    2012-06-01

    The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of eltrombopag (GlaxoSmithKline) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of patients with chronic immune or idiopathic thrombocytopenic purpura (ITP), as part of the their Single Technology Appraisal (STA) process. The Aberdeen Technology Assessment Review (TAR) Group, commissioned to act as the evidence review group (ERG), critically reviewed and supplemented the submitted evidence. This paper describes the company submission, the ERG review and NICE's subsequent decisions. The ERG critically appraised the clinical and cost-effectiveness evidence submitted by the manufacturer, independently searched for relevant literature, conducted a critical appraisal of the submitted economic models and explored the impact of altering some of the key model assumptions as well as combining relevant sensitivity analyses. Three trials were used to inform the safety and efficacy aspects of this submission; however, one high-quality randomized controlled trial (RAISE study) was the principal source of evidence and was used to inform the economic model. Eltrombopag had greater odds of achieving the primary outcome of a platelet count between 50 × 10^⁹/L and 400 × 10^⁹/L during the 6-month treatment period than placebo (odds ratio [OR] 8.2, 99% CI 3.6, 18.7). In the eltrombopag group, 50/83 (60%) of non-splenectomized patients and 18/49 (37%) of splenectomized patients achieved this outcome. The median duration of response was 10.9 weeks for eltrombopag (splenectomized 6 and non-splenectomized 13.4) compared with 0 for placebo. Eltrombopag patients required less rescue medication and had lower odds of bleeding events for both the splenectomized and the non-splenectomized patients. For a watch-and-rescue strategy of care, the comparator was placebo and the ERG found that substantial reductions in the cost of eltrombopag are needed

  8. Refractory thrombotic thrombocytopenic purpura associated with oral contraceptives and factor V Leiden: a case report

    PubMed Central

    Tsirakis, George; Mantadakis, Elpis; Xylouri, Irini; Foudoulakis, Andreas; Vardaki, Eleftheria; Katsipi, Irene; Daphnis, Eugene; Samonis, George

    2009-01-01

    Introduction Thrombotic microangiopathies constitute a heterogeneous group of diseases characterised by microangiopathic haemolytic anaemia and thrombocytopaenia associated with platelet aggregation in the microcirculation responsible for ischaemic manifestations. Classically, thrombotic microangiopathies are described as encompassing two main syndromes: thrombotic thrombocytopaenic purpura and the haemolytic-uraemic syndrome Many cases of idiopathic thrombotic thrombocytopaenic purpura have, to date, been associated with severe ADAMTS13 metalloprotease deficiency while haemolytic uraemic syndrome usually occurs in the context of normal protease activity. Oestrogens and factor V Leiden have rarely been implicated in the pathogenesis of thrombotic microangiopathy. Case presentation We describe the case of a 17-year-old female with refractory thrombotic thrombocytopaenic purpura. The patient was receiving a new generation of oral contraceptives for dysmenorrhoea and had factor V Leiden. After undergoing prolonged and intense plasma exchange therapy for 40 days and high dose oral corticosteroids therapy for 90 days, our patient recovered fully. Conclusion Patients with refractory thrombotic thrombocytopaenic purpura should likely be evaluated for congenital thrombophilic disorders and for ingestion of drugs that have been associated with this rare form of thrombotic microangiopathy. Identification of these and as yet other unknown genetic and/or acquired risk factors may lead to more judicious treatment approaches. PMID:19829833

  9. Anti-platelet antibodies associated with the Canale–Smith syndrome bind to the same platelet glycoprotein complexes as those of idiopathic thrombocytopenic purpura patients

    PubMed Central

    GRODZICKY, T; BUSSEL, J B; ELKON, K B

    2002-01-01

    The Canale–Smith syndrome (CSS) is an inherited disease characterized by massive lymphadenopathy, hepatosplenomegaly and systemic autoimmunity to erythrocytes and platelets. Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease in which approximately 60–80% of patients have anti-platelet antibodies directed against specific platelet glycoprotein complexes (GPCs) located on their membrane: GP IIb/IIIa, GPIb/IX, and GPIa/IIa. Almost all (95–100%) of the antibody-positive patients have antibodies directed against GPIIb/IIIa alone, or in combination with other glycoprotein targets. Our objective was to determine the specificities of the anti-platelet antibodies in CSS patients. The detection of anti-platelet antibodies was performed using a commercially available ELISA, the Pak-AUTO (GTI, Brookfield, WI), in which highly purified GPIIb/IIIa, GPIb/IX, and GPIa/IIa are immobilized on microtitre plates, incubated with serum or plasma, and subsequently developed with an antihuman polyclonal immunoglobulin. Of 14 CSS patients tested, 11 (79%) had anti-platelet antibodies in their serum directed toward at least one of the three major GPC, nine (82%) of which were against GPIIb/IIIa alone or in combination. Antibodies detected in the sera of ITP patients had similar specificities. No such antibodies were detected in samples from 25 consecutive normal controls. These results demonstrate that a genetically defined defect in lymphocyte apoptosis results in a humoral autoimmune response with anti-platelet specificities very similar to the common idiopathic form of autoimmune thrombocytopenia. PMID:11876752

  10. The effect of platelet autoantibodies on the course of the disease and clinical response of patients with idiopathic thrombocytopenic purpura.

    PubMed

    Sikorska, A; Konopka, L; Maślanka, K

    2008-02-01

    In this study, we evaluated the response to treatment of 409 idiopathic thrombocytopenic purpura (ITP) patients who were tested for the presence of platelet-associated autoantibodies by direct-platelet immunofluorescence test (PIFT) and for the presence of plasma antibodies directed against the GPIIb/IIIa, GPIb and GPIa/IIa by monoclonal antibody immobilization of platelet antigens (MAIPA). In patients with platelet autoantibodies in comparison with patients without antibodies more frequently were observed the chronic form of disease (83.5%vs. 68.5%) and severe symptoms of haemorrhage diathesis (17.3%vs. 6.9%). Evaluation of the treatment response (to corticosteroids, immunosuppressive drugs and splenectomy) referred to patients with complete response, e.g. complete remission defined as platelet count of >100 x 10(9)/l for at least 2 years. The percentage of complete response in the whole population of ITP patients, both with and without autoantibodies regardless of the method of treatment, was similar (about 54%). However, the presence of platelet autoantibodies had effect on patients treated with corticosteroids: complete response approximately 71% (36/51) of patients with autoantibodies and in 60% (72/120) of patients without antibodies, as well as in patients treated with immunosuppressive drugs (cyclophosphamide, azathioprine, vincristin and vinblastin); complete response approximately 51% (11/21) of patients with autoantibodies and in 34.8% (6/17) of patients without autoantibodies. The presence of autoantibodies had no effect on the response of splenectomy patients. PMID:18190469

  11. Human/BALB radiation chimera engrafted with splenocytes from patients with idiopathic thrombocytopenic purpura produce human platelet antibodies.

    PubMed Central

    Dekel, B; Marcus, H; Shenkman, B; Shimoni, A; Shechter, Y; Canaan, A; Berrebi, A; Varon, D; Reisner, Y

    1998-01-01

    We have previously shown that lethally irradiated normal strains of mice, radioprotected with severe combined immunodeficient (SCID) bone marrow, can be engrafted with human peripheral blood mononuclear cells (PBMC). The human/mouse radiation chimera can mount marked humoral and cellular responses to recall antigens, as well as primary responses. In the present study, we adoptively transferred splenocytes from patients with chronic immune thrombocytopenic purpura (ITP) into lethally irradiated BALB/c mice, radioprotected with SCID bone marrow. High titres of total human immunoglobulin appeared as early as 2 weeks post-transplant and declined after 6 weeks, while human anti-human platelet antibodies were detected 2-8 weeks after the transfer of splenocytes. The immunoglobulin G (IgG) fraction contained antibodies against glycoprotein (GP) IIb/IIIa (CD41) or GPIb/IX (CD42). The human platelet antibodies showed a low level of cross-reactivity with mouse platelets, and thrombocytopenia in the animals was not observed. Splenocytes from individual ITP patients differed in their capacity to produce either human platelet antibodies or total human immunoglobulin. Furthermore, antibodies produced in the murine system were not always identical to the original antibodies present in the serum of the patients. The study of the serological aspects of autoantibodies against human platelets in an animal model might be useful for the investigation of potential therapeutics in ITP. PMID:9767425

  12. Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome associated with high-dose interleukin-2 for the treatment of metastatic melanoma.

    PubMed

    Alexandrescu, Doru T; Maddukuri, Prasad; Wiernik, Peter H; Dutcher, Janice P

    2005-01-01

    Various drugs have been associated with the development of thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Among the biologic agents, alpha-interferon therapy, used for treatment of hepatitis B and chronic myelogenous leukemia, has been associated with TTP in a few recent reports. The authors report the first case of TTP/HUS occurring in a metastatic melanoma patient receiving treatment with high-dose interleukin-2 (IL-2). A 57-year-old patient with malignant melanoma presented with seizures 3 days after completing the first week of high-dose IL-2, and the characteristic hematologic picture revealed TTP/HUS. This occurrence is unlikely to be explained by the association with malignant melanoma, which was not presenting with widespread visceral disease at the time of the occurrence, or by the use of other medications. Similar cytokine release profiles are encountered in TTP, HUS caused by Shiga toxin-1, HUS caused by E. coli O157, after IL-2 or IL-2-containing biochemotherapy, as well as in TTP caused by interferon-alpha. This cytokine profile could reflect a common cause, or just the presence of similar pathways involved. PMID:15725958

  13. Intracranial hemorrhage in acute and chronic childhood immune thrombocytopenic purpura over a ten-year period: an Egyptian multicenter study.

    PubMed

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

    2010-01-01

    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; 4 patients had acute ITP, 2 persistent and 4 chronic. The platelet count was <10 x 10(9)/l in 7 cases, and only 1 patient had a history of head trauma. Seven children were on treatment prior to or at the time of occurrence of ICH and all were treated by pharmacotherapy. Two children died shortly afterwards due to late referral to a specialized center. Our results suggest that treatment does not prevent ICH and that it can occur at any time during the course of the disease. Delayed referral can be considered a risk factor for unfavorable outcome of ICH, highlighting the importance of teaching sessions for patients and their parents to minimize subsequent morbidity and mortality of ICH in children with ITP. PMID:19955713

  14. Tumor necrosis factor-α -308G/A gene polymorphism in Egyptian children with immune thrombocytopenic purpura.

    PubMed

    El Sissy, Maha H; El Sissy, A H; Elanwary, Sherif

    2014-07-01

    Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by increased platelet destruction. Although the cause of ITP remains unclear, it is accepted that both environmental and genetic factors play an important role in the development of the disease. Children with ITP have a T-helper 1-type cytokine pattern with elevated levels of tumor necrosis factor-alpha (TNF-α) as in most autoimmune diseases. Researchers have shown that polymorphism in the TNF-α gene at position -308 affects gene transcriptions with increased TNF-α production. The current case-control study aimed at detecting the frequency of TNF-α -308G/A gene polymorphism as genetic markers in Egyptian children with ITP, and to clear out their possible role in choosing the treatment protocols of therapy, using PCR restriction fragment length polymorphism assay. Ninety-two ITP patients and 100 age and sex-matched healthy controls were recruited in the study. The results obtained revealed that the frequency of TNF-α -308A/A homotype in ITP patients was significantly higher than that of the controls, and conferred almost six-fold increased risk of ITP acquisition. The polymorphic A allele frequency was significantly higher in ITP patients than in the controls, conferring almost two-fold increased ITP risk. In conclusion, our study suggests the possibility that TNF-α -308 gene polymorphism may contribute to the susceptibility of childhood ITP in Egyptian children.

  15. A systematic review of randomized controlled trials for plasma exchange in the treatment of thrombotic thrombocytopenic purpura.

    PubMed

    Brunskill, S J; Tusold, A; Benjamin, S; Stanworth, S J; Murphy, M F

    2007-02-01

    The mainstay of treatment for thrombotic thrombocytopenic purpura (TTP) is plasma exchange (PE). A systematic review was undertaken to summarize the randomized controlled trial (RCT) evidence, to date, on PE as treatment for TTP. Seven randomized RCTs were identified till May 2005. A statistical reduction in mortality was found in patients receiving PE compared with patients receiving plasma infusion (relative risk 0.31, 95% confidence interval 0.12-0.79). No statistical difference in mortality was found in trials comparing different replacement fluids for PE. There were few differences in the response to treatment and the resolution of the presenting signs of TTP in any trial. Lack of data prevented a full assessment of the incidence of adverse events. None of the studies included measured patients' quality of life. Further research is required to determine the benefits and side effects associated with different replacement fluids for PE. It is recommended that there should be consistency in the diagnostic criteria, measurement of clinical outcomes and length of follow up. Continued support of existing TTP patient registries and establishment of new registries would facilitate this. PMID:17266701

  16. Acute renal failure after intravenous anti-D immune globulin in an adult with immune thrombocytopenic purpura.

    PubMed

    Chun, Nancy S; Savani, Bipin; Seder, Richard H; Taplin, Mary Ellen

    2003-12-01

    Intravenous anti-D immune globulin (anti-D IGIV) is indicated for the treatment of immune thrombocytopenic purpura (ITP) in nonsplenectomized patients who are Rh(D)-positive. Recent reports have described episodes of intravascular hemolysis (IVH) and acute renal failure (ARF) after anti-D IGIV. We report the first adult patient with ITP who required and received dialysis after IVH and ARF complicating treatment with anti-D IGIV. Whether the transfusion of 2 units of Rh(D)-positive red cells, indicated for the resulting anemia, exacerbated the IVH and renal failure is unclear. Three weeks after the administration of anti-D IGIV (13 days after two hemodialysis treatments), the patient's renal function had returned to normal. This case highlights the infrequent but potentially serious side effects of anti-D IGIV and the need to monitor a patient's renal function closely if there is evidence of IVH after infusion of anti-D IGIV. If red cell transfusion is indicated, we recommend the use of Rh(D)-negative red cell products.

  17. Thrombotic thrombocytopenic purpura-like syndromes following bone marrow transplantation: an analysis of associated conditions and clinical outcomes.

    PubMed

    Roy, V; Rizvi, M A; Vesely, S K; George, J N

    2001-03-01

    The diagnosis and treatment of thrombotic thrombocytopenic purpura (TTP) in patients following BMT are often uncertain and unsuccessful. To better understand the evaluation and management of these patients, we describe 17 patients treated with plasma exchange for a presumptive diagnosis of TTP following BMT during a 10 year period, 1989-1998. Because of the uncertainty of the diagnosis, these patients are described as having a 'TTP-like syndrome'. All 17 patients had received an allogeneic BMT. Comparison with the other 245 patients who had an allogeneic BMT during the same period demonstrated that patients with a TTP-like syndrome more frequently had unrelated and/or HLA-mismatched donors, and had also experienced more serious complications: grade III-IV acute GVHD and systemic bacterial, fungal, and viral infections. Three months after the diagnosis of the TTP-like syndrome, only four of 17 patients (24%) were alive; currently only one patient survives. These data emphasize: (1) the diagnosis of TTP following BMT is uncertain because of the presence of multiple BMT-associated complications. (2) The outcome of patients with TTP-like syndromes following BMT is poor. (3) Urgent intervention with plasma exchange when TTP is suspected following BMT may not always be appropriate. Alternative explanations for the signs and symptoms should be considered and treated aggressively. PMID:11319595

  18. Novel hypomorphic mutation in IKBKG impairs NEMO-ubiquitylation causing ectodermal dysplasia, immunodeficiency, incontinentia pigmenti, and immune thrombocytopenic purpura.

    PubMed

    Ramírez-Alejo, Noé; Alcántara-Montiel, Julio C; Yamazaki-Nakashimada, Marco; Duran-McKinster, Carola; Valenzuela-León, Paola; Rivas-Larrauri, Francisco; Cedillo-Barrón, Leticia; Hernández-Rivas, Rosaura; Santos-Argumedo, Leopoldo

    2015-10-01

    NF-κB essential modulator (NEMO) is a component of the IKK complex, which participates in the activation of the NF-κB pathway. Hypomorphic mutations in the IKBKG gene result in different forms of anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) in males without affecting carrier females. Here, we describe a hypomorphic and missense mutation, designated c.916G>A (p.D306N), which affects our patient, his mother, and his sister. This mutation did not affect NEMO expression; however, an immunoprecipitation assay revealed reduced ubiquitylation upon CD40-stimulation in the patient's cells. Functional studies have demonstrated reduced phosphorylation and degradation of IκBα, affecting NF-κB recruitment into the nucleus. The patient presented with clinical features of ectodermal dysplasia, immunodeficiency, and immune thrombocytopenic purpura, the latter of which has not been previously reported in a patient with NEMO deficiency. His mother and sister displayed incontinentia pigmenti indicating that, in addition to amorphic mutations, hypomorphic mutations in NEMO can affect females. PMID:26117626

  19. Occurrence of both hemolytic anemia and thrombocytopenic purpura (Evans' syndrome) in systemic lupus erythematosus. Relationship to antiphospholipid antibodies.

    PubMed

    Delezé, M; Oria, C V; Alarcón-Segovia, D

    1988-04-01

    Ten of 12 patients with systemic lupus erythematosus (SLE) who had hemolytic anemia and thrombocytopenic purpura (Evans' syndrome) during their course had evidence of antiphospholipid antibodies either because they had a false positive VDRL test (8 patients), a prolonged partial thromboplastin time (5 patients), a lupus anticoagulant (3/4 patients), and/or anticardiolipin antibodies as determined by an ELISA method (7 patients). Antibodies to cardiolipin were found in very high levels (up to 38 standard deviations above the mean of normal controls) and were of both IgG and IgM isotypes. The 2 patients with SLE and Evans' syndrome who did not have evidence of antiphospholipid antibodies were studied at the onset of SLE which occurred with Evans' syndrome. Although cardiolipin is not a constituent of the cell wall of either platelets or erythrocytes, other phospholipids that cross react antigenically with cardiolipin are and can be exposed through cell damage. This could be a mechanism whereby hemolytic anemia and thrombocytopenia could occur in the same patient with SLE. Whether absorption of the antiphospholipid antibody during the acute episode of hemocytopenia could occur, and thus prevent its detection at such time, remains undetermined.

  20. Complement activation on platelets correlates with a decrease in circulating immature platelets in patients with immune thrombocytopenic purpura.

    PubMed

    Peerschke, Ellinor I B; Andemariam, Biree; Yin, Wei; Bussel, James B

    2010-02-01

    The role of the complement system in immune thrombocytopenic purpura (ITP) is not well defined. We examined plasma from 79 patients with ITP, 50 healthy volunteers, and 25 patients with non-immune mediated thrombocytopenia, to investigate their complement activation/fixation capacity (CAC) on immobilized heterologous platelets. Enhanced CAC was found in 46 plasma samples (59%) from patients with ITP, but no samples from patients with non-immune mediated thrombocytopenia. Plasma from healthy volunteers was used for comparison. In patients with ITP, an enhanced plasma CAC was associated with a decreased circulating absolute immature platelet fraction (A-IPF) (<15 x 10(9)/l) (P = 0.027) and thrombocytopenia (platelet count < 100 x 10(9)/l) (P = 0.024). The positive predictive value of an enhanced CAC for a low A-IPF was 93%, with a specificity of 77%. The specificity and positive predictive values increased to 100% when plasma CAC was defined strictly by enhanced C1q and/or C4d deposition on test platelets. Although no statistically significant correlation emerged between CAC and response to different pharmacological therapies, an enhanced response to splenectomy was noted (P < 0.063). Thus, complement fixation may contribute to the thrombocytopenia of ITP by enhancing clearance of opsonized platelets from the circulation, and/or directly damaging platelets and megakaryocytes. PMID:19925495

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

    PubMed Central

    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.

    2012-01-01

    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

  2. Late side effects of high-dose steroid therapy on skeletal system in children with idiopathic thrombocytopenic purpura.

    PubMed

    Yildirim, Zühal Keskin; Büyükavci, Mustafa; Eren, Suat; Orbak, Zerrin; Sahin, Ali; Karakelleoğlu, Cahit

    2008-10-01

    Corticosteroids have been widely used in the treatment of idiopathic thrombocytopenic purpura (ITP). We evaluated the late side effects of high-dose methylprednisolone (HDMP) therapy on bone metabolism in children with ITP. Twenty-eight children with acute ITP treated with HDMP (30 mg/kg/d for 3 d then 20 mg/kg/d for 4 d) and 28 controls were enrolled in the study. Bone mineral density (BMD), urinary calcium creatinine ratio, urinary levels of deoxypyridinoline, serum levels of calcium, phosphate, parathyroid hormone, total alkaline phosphatase, and bone-specific alkaline phosphatase were measured in both groups. Magnetic resonance imaging of the femoral head was performed only in study group. The mean levels of serum phosphate, parathyroid hormone, urinary deoxypyridinoline, and calcium creatinine ratio were significantly increased in the study group. There was no significant difference between the 2 groups in terms of serum calcium, total alkaline phosphatase, bone-specific alkaline phosphatase, and BMD values. There was a statistically significant negative correlation between cumulative steroid dose and BMD values in study group (r = -0.379). Osteonecrosis was observed in 3 of 25 patients by magnetic resonance imaging. In conclusion, HDMP therapy, especially in high cumulative doses, increases the bone resorption and may cause osteonecrosis in children with ITP.

  3. Comparison of single port and three port laparoscopic splenectomy in patients with immune thrombocytopenic purpura: Clinical comparative study

    PubMed Central

    Barbaros, Umut; Aksakal, Nihat; Tukenmez, Mustafa; Agcaoglu, Orhan; Bostan, Mustafa Sami; Kilic, Berkay; Kalayci, Murat; Dinccag, Ahmet; Seven, Ridvan; Mercan, Selcuk

    2015-01-01

    AIM: Single-port laparoscopic surgery (SILS) has become increasingly popular during the last decades. This prospective study was undertaken to evaluate the feasibility of single-port laparoscopic splenectomy compared with conventional multiport laparoscopic splenectomy. MATERIALS AND METHODS: Between February 2, 2009 and August 29, 2011, a total of 40 patients with the diagnosis of immune thrombocytopenic purpura were included to study. Patients were alienated into two groups according to the procedure type including SILS and conventional multiport splenectomy. RESULTS: There were 19 patients in group 1, and 21 in group 2. Operative time was significantly shorter in group 1 versus group 2 (112.4 ± 13.56 vs 71.2 ±18.1 minutes, respectively, P < 0.05). One patient in group 1 had converted to laparatomy due to preoperative bleeding. Postoperative pain analyses (VAS Score) revealed superiority of SILS in the early post-operative days (P < 0.05). CONCLUSIONS: SILS splenectomy is a safe and effective alternative to standard laparoscopic splenectomy. PMID:26195874

  4. Rituximab in a child with autoimmune thrombotic thrombocytopenic purpura refractory to plasma exchange.

    PubMed

    Narayanan, Parameswaran; Jayaraman, Aparna; Rustagi, Rashi S; Mahadevan, S; Parameswaran, Sreejith

    2012-07-01

    A nine-year-old girl presented with headache, purpura and mild left hemiparesis. Laboratory evaluation revealed thrombotic microangiopathy with ADAMTS13 deficiency, with auto-antibodies to ADAMTS13. She was treated with plasma exchange and steroids, following which she improved transiently, relapsing within 2 months. The relapse was refractory to conventional therapy and rituximab was tried. She had good response to rituximab and has been in remission for the past 12 months. Rituximab may be a promising option for children with acquired TTP refractory to plasma exchange and steroids.

  5. Use of Recombinant Factor VIIa in a Pediatric Patient With Initial Presentation of Refractory Acute Immune Thrombocytopenic Purpura and Severe Bleeding

    PubMed Central

    Gurion, Reut; Siu, Anita; Weiss, Aaron R.; Masterson, Margaret

    2012-01-01

    Severe bleeding in acute immune thrombocytopenic purpura (ITP) is rare but can cause significant complications to the patient. Here we report the case of a pediatric patient with acute ITP and hematuria refractory to anti-D immune globulin, high dose intravenous immunoglobulin G, and high dose steroids. Her hematuria was successfully treated with recombinant factor VIIa (rFVIIa). While further investigation on the use of rFVIIa in ITP is warranted, this case report contributes to the pediatric literature for its use during the course of an initial presentation of ITP with hemorrhagic complications. PMID:23258971

  6. Thrombotic thrombocytopenic purpura in a postoperative patient taking cephalexin responding to plasmapheresis: A case report and review of cephalosporin-induced TTP.

    PubMed

    Patel, Ritu; Amber, Kyle T

    2016-10-01

    The clinical presentation of thrombotic thrombocytopenic purpura (TTP) is often atypical delaying diagnosis and treatment. A number of drugs have been implicated in the development of TTP, including cyclosporine, tacrolimus, clopidogrel, and quinine. To our knowledge, only three cases of cephalosporin-induced TTP have been described, with two of these cases occurring with these use of cephalexin. We herein describe a case of TTP occurring in a postoperative patient taking cephalexin, requiring plasmapheresis. Following plasmapheresis, the patient's mental status and platelet count significantly improved. J. Clin. Apheresis 31:473-475, 2016. © 2015 Wiley Periodicals, Inc. PMID:26274019

  7. Comparison of anti-D immunoglobulin, methylprednisolone, or intravenous immunoglobulin therapy in newly diagnosed pediatric immune thrombocytopenic purpura.

    PubMed

    Celik, Muhittin; Bulbul, Ali; Aydogan, Gönül; Tugcu, Deniz; Can, Emrah; Uslu, Sinan; Dursun, Mesut

    2013-02-01

    This study aimed to evaluate the efficacy, cost, and effects of anti-D immunoglobulin (anti-D Ig), methylprednisolone, or intravenous immunoglobulin (IVIG) therapy on the development of chronic disease in children who are Rh-positive with diagnosed immune thrombocytopenic purpura (ITP). Children with newly diagnosed ITP and platelet count <20,000/mm(3) were prospectively randomized to treatment with anti-D Ig (50 μg/kg), methylprednisolone (2 mg/kg/day), or IVIG (0.4 g/kg/day, 5 days). Sixty children with a mean age of 6.7 years were divided into three equal groups. No difference was observed between platelet counts before treatment and on day 3 of treatment. However, platelet counts at day 7 were lower in the methylprednisolone group than in the IVIG group (P = 0.03). In the anti-D Ig group, hemoglobin and hematocrit levels were significantly lower at the end of treatment (P < 0.05). Chronic ITP developed in 30% of the anti-D Ig group, 35% of the methylprednisolone group, and 25% of the IVIG group, but no significant difference was noted among the groups. The cost analysis revealed that the mean cost of IVIG was 7.4 times higher than anti-D Ig and 10.9 times higher than methylprednisolone. In the treatment of ITP in childhood, one 50 μg/kg dose of anti-D Ig has similar effects to IVIG and methylprednisolone. Among patients who were treated with anti-D Ig, serious anemia was not observed, and the cost of treatment was less than that of IVIG treatment.

  8. Kinetics and sites of destruction of /sup 111/In-oxine-labeled platelets in idiopathic thrombocytopenic purpura: a quantitative study

    SciTech Connect

    Heyns, A.D.; Loetter, M.G.; Badenhorst, P.N.; de Kock, F.; Pieters, H.; Herbst, C.; van Reenen, O.R.; Kotze, H.; Minnaar, P.C.

    1982-04-01

    Kinetics and quantification of the sites of destruction of /sup 111/In-oxine-labeled autologous platelets were investigated in eight patients with idiopathic thrombocytopenic purpura. The mean platelet count was 17 +/- 9 X 10(9)/liter; platelets were separated by differential centrifugation and labeled with 5.6 +/- 2.5 MBq /sup 111/In. Whole body and organ /sup 111/In-platelet distribution was quantitated with a scintillation camera and a computer-assisted imaging system acquisition matrix. Areas of interest were selected with the computer and organ /sup 111/In-radioactivity expressed as a percentage of whole body activity. Mean platelet survival was 49.5 +/- 29.6 hr and the survival curves were exponential. Equilibrium percentage organ /sup 111/In-radioactivity was (normal values in parentheses): spleen 33.7 +/- 8.8 (31.1 +/- 10.2); liver 16.1 +/- 9.5 (13.1 +/- 1.3); thorax 22.8 +/- 3.7 (28.2 +/- 5.6). Percentage organ /sup 111/In-activity at the time when labeled platelets had disappeared from the circulation was: spleen 44.5 +/- 16.4 (40 +/- 16); liver 16.0 +/- 11.5 (32.4 +/- 7.2); thorax 19.7 +/- 6.0 (17.7 +/- 10.3). Thorax activity corresponds to bone marrow radioactivity. Three patterns of platelet sequestration were evident. Three patients had mainly splenic sequestration, two mainly hepatic sequestration, and three diffuse reticuloendothelial system sequestration with a major component of platelets destroyed in the bone marrow. Splenectomy was performed in two patients. The pattern of /sup 111/In-platelet sequestration was not predictive of response of glucocorticoid therapy or indicative of the necessity for splenectomy. Quantitative /sup 111/In-labeled autologous platelet kinetic studies provide a new tool for the investigation of platelet disorders.U

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

    PubMed

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

    1992-10-01

    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)

  10. The mechanisms of action of intravenous immunoglobulin and polyclonal anti-d immunoglobulin in the amelioration of immune thrombocytopenic purpura: what do we really know?

    PubMed

    Crow, Andrew R; Lazarus, Alan H

    2008-04-01

    Intravenous immunoglobulin (IVIg) has been used for more than 25 years to treat an ever-increasing number of autoimmune diseases including immune thrombocytopenic purpura. Although the exact mechanism of action of IVIg has remained elusive, many theories have been postulated, including mononuclear phagocytic system blockade/inhibition, autoantibody neutralization by anti-idiotype antibodies, pathogenic autoantibody clearance due to competitive inhibition of the neonatal immunoglobulin Fc receptor, cytokine modulation, complement neutralization, and immune complex formation leading to dendritic cell priming. Polyclonal anti-D immunoglobulin is a polyclonal IVIg product enriched for antibodies directed to the RhD antigen on red blood cells and that has also been successfully used to treat immune thrombocytopenia in RhD(+) patients. The primary theory to explain polyclonal anti-D immunoglobulin function has classically been mononuclear phagocytic system blockade, although modulation of Fcgamma receptor expression and/or immunomodulation may also play a role. Work using a murine model of immune thrombocytopenic purpura to further our understanding of the mechanism of action of these 2 therapeutic agents is a focus of this article.

  11. Generation of Anti-Murine ADAMTS13 Antibodies and Their Application in a Mouse Model for Acquired Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Deforche, Louis; Tersteeg, Claudia; Roose, Elien; Vandenbulcke, Aline; Vandeputte, Nele; Pareyn, Inge; De Cock, Elien; Rottensteiner, Hanspeter; Deckmyn, Hans; De Meyer, Simon F.; Vanhoorelbeke, Karen

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy linked to a deficiency in the metalloprotease ADAMTS13. In the current study, a novel mouse model for acquired TTP was generated to facilitate development and validation of new therapies for this disease. Therefore, a large panel (n = 19) of novel anti-mouse ADAMTS13 (mADAMTS13) monoclonal antibodies (mAbs) of mouse origin was generated. Inhibitory anti-mADAMTS13 mAbs were identified using the FRETS-VWF73 assay. Four mAbs strongly inhibited mADAMTS13 activity in vitro (∼68–90% inhibition). Injecting a combination of 2 inhibitory mAbs (13B4 and 14H7, 1.25 mg/kg each) in Adamts13+/+ mice resulted in full inhibition of plasma ADAMTS13 activity (96 ± 4% inhibition, day 1 post injection), leading to the appearance of ultra-large von Willebrand factor (UL-VWF) multimers. Interestingly, the inhibitory anti-mADAMTS13 mAbs 13B4 and 14H7 were ideally suited to induce long-term ADAMTS13 deficiency in Adamts13+/+ mice. A single bolus injection resulted in full ex vivo inhibition for more than 7 days. As expected, the mice with the acquired ADAMTS13 deficiency did not spontaneously develop TTP, despite the accumulation of UL-VWF multimers. In line with the Adamts13-/- mice, TTP-like symptoms could only be induced when an additional trigger (rVWF) was administered. On the other hand, the availability of our panel of anti-mADAMTS13 mAbs allowed us to further develop a sensitive ELISA to detect ADAMTS13 in mouse plasma. In conclusion, a novel acquired TTP mouse model was generated through the development of inhibitory anti-mADAMTS13 mAbs. Consequently, this model provides new opportunities for the development and validation of novel treatments for patients with TTP. In addition, these newly developed inhibitory anti-mADAMTS13 mAbs are of great value to specifically study the role of ADAMTS13 in mouse models of thrombo-inflammatory disease. PMID:27479501

  12. Generation of Anti-Murine ADAMTS13 Antibodies and Their Application in a Mouse Model for Acquired Thrombotic Thrombocytopenic Purpura.

    PubMed

    Deforche, Louis; Tersteeg, Claudia; Roose, Elien; Vandenbulcke, Aline; Vandeputte, Nele; Pareyn, Inge; De Cock, Elien; Rottensteiner, Hanspeter; Deckmyn, Hans; De Meyer, Simon F; Vanhoorelbeke, Karen

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy linked to a deficiency in the metalloprotease ADAMTS13. In the current study, a novel mouse model for acquired TTP was generated to facilitate development and validation of new therapies for this disease. Therefore, a large panel (n = 19) of novel anti-mouse ADAMTS13 (mADAMTS13) monoclonal antibodies (mAbs) of mouse origin was generated. Inhibitory anti-mADAMTS13 mAbs were identified using the FRETS-VWF73 assay. Four mAbs strongly inhibited mADAMTS13 activity in vitro (∼68-90% inhibition). Injecting a combination of 2 inhibitory mAbs (13B4 and 14H7, 1.25 mg/kg each) in Adamts13+/+ mice resulted in full inhibition of plasma ADAMTS13 activity (96 ± 4% inhibition, day 1 post injection), leading to the appearance of ultra-large von Willebrand factor (UL-VWF) multimers. Interestingly, the inhibitory anti-mADAMTS13 mAbs 13B4 and 14H7 were ideally suited to induce long-term ADAMTS13 deficiency in Adamts13+/+ mice. A single bolus injection resulted in full ex vivo inhibition for more than 7 days. As expected, the mice with the acquired ADAMTS13 deficiency did not spontaneously develop TTP, despite the accumulation of UL-VWF multimers. In line with the Adamts13-/- mice, TTP-like symptoms could only be induced when an additional trigger (rVWF) was administered. On the other hand, the availability of our panel of anti-mADAMTS13 mAbs allowed us to further develop a sensitive ELISA to detect ADAMTS13 in mouse plasma. In conclusion, a novel acquired TTP mouse model was generated through the development of inhibitory anti-mADAMTS13 mAbs. Consequently, this model provides new opportunities for the development and validation of novel treatments for patients with TTP. In addition, these newly developed inhibitory anti-mADAMTS13 mAbs are of great value to specifically study the role of ADAMTS13 in mouse models of thrombo-inflammatory disease. PMID:27479501

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

    PubMed

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

    2011-12-01

    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.

  14. High prevalence of sustained remission of idiopathic thrombocytopenic purpura after Helicobacter pylori eradication: a long-term follow-up study.

    PubMed

    Veneri, Dino; Krampera, Mauro; Franchini, Massimo

    2005-03-01

    We studied the effect of Helicobacter pylori (H. pylori) eradication in 43 consecutive H. pylori-infected patients with idiopathic thrombocytopenic purpura. H. pylori was eradicated with antibiotics in 41 of them (95.3%). The difference between the mean platelet count before and after therapy was statistically significant (54.3 x 10(9)/l vs. 119.1 x 10(9)/l; P < 0.001). A sustained remission was observed in 20 patients (48.8%), after a median follow-up of 31.2 months. None of the patients still infected by H. pylori after therapy reached normal platelet values. The long-term follow-up confirms the efficacy of H. pylori eradication in H. pylori-infected ITP patients.

  15. [A Case of Thrombotic Thrombocytopenic Purpura in a Patient Undergoing FOLFOX6 plus Panitumumab Therapy for Unresectable Recurrent Rectal Cancer with a Rapidly Progressive Course].

    PubMed

    Kato, Kuniyuki; Michishita, Yoshihiro; Oyama, Kenichi; Hatano, Yoshiaki; Nozawa, Tatsuru; Ishibashi, Masahisa; Konda, Ryuichiro; Sasaki, Akira

    2016-01-01

    A 71-year-old male patient began FOLFOX6 plus panitumumab treatment for unresectable recurrent rectal cancer. He developed thrombocytopenia after 2 courses of treatment and therefore a platelet transfusion was performed. The day after transfusion, the patient developed jaundice and hematuria. His lactate dehydrogenase levels had increased and a peripheral blood smear review revealed the presence of schistocytes. Anti-ADAMTS13 antibodies were present, and there was a reduction in ADAMTS13 activity. The patient was diagnosed with thrombotic thrombocytopenic purpura and treated with a plasma exchange. The day after the plasma exchange, his clinical condition rapidly worsened and he died. Thrombocytopenia due to chemotherapy often appears as myelosuppression. If conditions such as jaundice, indirect bilirubinemia, or hematuria appear during the course of chemotherapy, this condition must be considered as a differential diagnosis. PMID:26809542

  16. The expression of IFN-gamma, IL-4, Foxp3 and perforin genes are not correlated with DNA methylation status in patients with immune thrombocytopenic purpura.

    PubMed

    Zhao, Haifeng; Du, Weiting; Wang, Donghai; Gu, Dongsheng; Xue, Feng; Ge, Jing; Sui, Tao; Yang, Renchi

    2010-01-01

    We investigated the relationship between the expression of IFN-gamma, IL-4, Foxp3 and perforin gene and the methylation status of their promoters in immune thrombocytopenic purpura (ITP) patients. Gene expression and DNA methylation were determined by quantitative PCR and bisulfite genomic sequencing, respectively. The expression of IFN-gamma was higher, while the expression of IL-4 was notably lower in ITP patients when compared with the controls. Most importantly, the Th1/Th2 (IFN-gamma/IL-4) was remarkably higher in ITP patients, showing that the ITP patients were mainly in the Th1 polarization response. Although the methylation rate of CpGs located at -409 of perforin was higher (p = 0.0376) and that of IFN-gamma were relatively higher (p = 0.0582) in ITP, we did not find the negative correlation between the expression of those genes and the methylation of their promoters. PMID:20100010

  17. Comparison of intravenous immune globulin and high dose anti-D immune globulin as initial therapy for childhood immune thrombocytopenic purpura.

    PubMed

    Kane, Ian; Ragucci, Dominic; Shatat, Ibrahim F; Bussel, James; Kalpatthi, Ram

    2010-04-01

    This report documents our experience with intravenous immune globulin (IVIG) (1 g/kg, iv) and high-dose, anti-D immune globulin (anti-D) (75 microg/kg) as initial treatment for childhood immune thrombocytopenic purpura (ITP). The medical records of children diagnosed with ITP at a single institution between January 2003 and May 2008 were retrospectively reviewed. Participants received either IVIG or high-dose anti-D immune globulin as their initial treatment for ITP. For the 53 patients included for analysis, there was no statistical difference in efficacy between each group; however, patients who received anti-D experienced a higher rate of adverse drug reactions (ADRs), particularly chills and rigours, and 2 of 24 patients in the anti-D group developed severe anaemia requiring medical intervention. Patients who presented with mucosal bleeding had higher rates of treatment failure (32%) compared to those who presented with dry purpura (6%), regardless of treatment. Both IVIG and high-dose anti-D are effective first-line therapies for childhood ITP. However, we observed increased ADRs in the high-dose anti-D group in contrast to previously published reports. Further studies are needed to evaluate safety and premedications for high-dose anti-D and to determine the utility of using the presence of mucosal bleeding to predict treatment failure.

  18. Randomized trial comparing intravenous immunoglobulin with methylprednisolone pulse therapy in acute idiopathic thrombocytopenic purpura. Danish I.T.P. Study Group.

    PubMed

    Rosthøj, S; Nielsen, S; Pedersen, F K

    1996-08-01

    Forty-three children with newly diagnosed idiopathic thrombocytopenic purpura (ITP), platelet count (PC) below 20 x 10(9)l-1, and either continued bleeding or failure to show a spontaneous rise in the PC after a 3 day observation period were randomized to treatment with either intravenous immunoglobulin (IVIG) infusions 1 g kg-1 (n = 23) or intravenous methylprednisolone pulse therapy (MPPT) 30 mg kg-1 (n = 20) on two consecutive days. After 72 h, IVIG had induced greater platelet responses (mean PC 188 x 10(9) versus 77 x 10(9)l-1, 2p < 0.001) and raised the PC to a haemostatically safe level above 50 x 10(9)l-1 more frequently (91 versus 50%, one-sided exact p = 0.003). Children responding poorly were then given the alternative treatment in addition. After 6 days, a normal PC of over 150 x 10(9)l-1 had been obtained more frequently in the group given first-line IVIG (70 versus 50%, p = 0.16). The relapse rates during 6 months of follow-up were not significantly different (26 versus 40%, p = 0.26). Cross-over treatment in 11 children with relapse confirmed the superior response to IVIG. The treatment given was restricted to the two initial infusions more often in the IVIG group (70 versus 35%, p = 0.05). These results indicate that IVIG may be preferable to MPPT as the initial treatment for ITP. PMID:8863869

  19. DNA methyltransferase 3B (DNMT3B -579G>T) promotor polymorphism and the susceptibility to pediatric immune thrombocytopenic purpura in Egypt.

    PubMed

    Khorshied, Mervat Mamdooh; El-Ghamrawy, Mona Kamal

    2012-12-10

    Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by increased platelet destruction. Although the etiology of ITP remains unclear, it is accepted that both environmental and genetic factors play an important role in the development of the disease. The present study aimed at exploring a novel molecular determinant that may influence the susceptibility and course of ITP in Egyptian children. To achieve our aim, genotyping of DNMT3B -579G>T promotor polymorphism by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. The current study was conducted on 140 ITP patients and 150 age and gender matched healthy controls. The results obtained revealed that DNMT3B -579 TT homotype was significantly higher in ITP patients and conferred almost three fold increased risk of ITP (OR=3.16, 95%CI=1.73-5.79). There was no statistically significant difference between ITP patients with wild or mutant genotypes as regards their clinical or laboratory data. Furthermore, there was no statistical difference in the distribution of DNMT3B -579G>T genotypes between acute and chronic ITP patients. In conclusion, DNMT3B -579G>T promotor polymorphism represents a novel genetic risk factor for ITP but not a predictor for tendency to chronicity in pediatric ITP in Egypt.

  20. Disseminated intravascular coagulation associated with acute hemoglobinemia or hemoglobinuria following Rh(0)(D) immune globulin intravenous administration for immune thrombocytopenic purpura.

    PubMed

    Gaines, Ann Reed

    2005-09-01

    The Food and Drug Administration (FDA) licensed Rh(o)(D) immune globulin intravenous (anti-D IGIV) on March 24, 1995, for treatment of immune thrombocytopenic purpura (ITP). A previous review described data on 15 patients who experienced acute hemoglobinemia or hemoglobinuria following anti-D IGIV administration for ITP or secondary thrombocytopenia. Eleven of those patients also experienced clinically compromising anemia, transfusion with packed red blood cells, renal insufficiency, dialysis, or death. That review suggested that patients receiving anti-D IGIV be monitored for those and other potential complications of hemoglobinemia, particularly disseminated intravascular coagulation (DIC). Through November 30, 2004, the FDA received 6 reports of DIC associated with "acute hemolysis" (or similar terms), 5 of which involved fatalities. The attending or consulting physicians assessed that acute hemolysis or DIC caused or contributed to each death. This review presents the first case series of DIC associated with acute hemoglobinemia or hemoglobinuria following anti-D IGIV administration for ITP. The purpose of this review is to increase awareness among physicians and other health care professionals that DIC may be a rare but potentially severe complication of anti-D IGIV treatment. Increased awareness of DIC as a diagnostic possibility may enable prompt recognition and medical intervention in affected patients.

  1. Efficacy, safety, and dose response of intravenous anti-D immune globulin (WinRho SDF) for the treatment of idiopathic thrombocytopenic purpura in children.

    PubMed

    Freiberg, A; Mauger, D

    1998-01-01

    We analyzed data from 20 children treated for acute or chronic idiopathic (immune) thrombocytopenic purpura (ITP) at a single institution to determine the relationship between dose of intravenous anti-D immune globulin (WinRho SDF; Nabi, Boca Raton, FL), increase in platelet count, and decrease in hemoglobin in the therapy of ITP. Higher doses of anti-D were clearly associated with a greater therapeutic response in the platelet count, with no increase in hemolysis for both acute and chronic ITP. A significant correlation was found between dose and peak increase in platelet count measured in the 14 days following administration. This effect was present for both acute ITP (17 infusions, P = .0001) and chronic ITP (30 infusions, P = .038). Although hemolysis was seen in nearly all infusions, with a median hemoglobin fall of 1.9 g/dL (range, 0 to 4.2), the decrease in hemoglobin was greater than 2.5 for only three infusions, and the largest fall in hemoglobin (4.2) was in a child with an underlying hemolytic anemia. Furthermore, for both acute and chronic ITP there was no relationship between the decrease in hemoglobin and the dose given (P = .22), nor between the increase in platelet count and fall in hemoglobin (P = .27). This analysis supports the use of higher doses of anti-D for the treatment of ITP, and demonstrates the need for a trial of high-dose anti-D (>100 microg/kg) in acute and chronic ITP.

  2. Helicobacter pylori infection and chronic immune thrombocytopenic purpura: long-term results of bacterium eradication and association with bacterium virulence profiles.

    PubMed

    Emilia, Giovanni; Luppi, Mario; Zucchini, Patrizia; Morselli, Monica; Potenza, Leonardo; Forghieri, Fabio; Volzone, Francesco; Jovic, Gordana; Leonardi, Giovanna; Donelli, Amedea; Torelli, Giuseppe

    2007-12-01

    Eradication of Helicobacter pylori may lead to improvement of chronic immune thrombocytopenic purpura (ITP), although its efficacy over time is uncertain. We report the results of H pylori screening and eradication in 75 consecutive adult patients with ITP. We also used molecular methods to investigate lymphocyte clonality and H pylori genotypes in the gastric biopsies from 10 H pylori-positive patients with ITP and 19 H pylori-positive patients without ITP with chronic gastritis. Active H pylori infection was documented in 38 (51%) patients and successfully eradicated in 34 (89%) patients. After a median follow-up of 60 months, a persistent platelet response in 23 (68%) of patients with eradicated infection was observed; 1 relapse occurred. No differences in mucosal B- or T-cell clonalities were observed between patients with ITP and control participants. Of note, the frequency of the H pylori cagA gene (P = .02) and the frequency of concomitant H pylori cagA, vacAs1, and iceA genes (triple-positive strains; P = .015) resulted statistically higher in patients with ITP than in control participants. All asymptomatic H pylori-positive patients with ITP were suffering from chronic gastritis. Our data suggest a sustained platelet recovery in a proportion of patients with ITP by H pylori eradication alone. Overrepresentation of specific H pylori genotypes in ITP suggests a possible role for bacterium-related factors in the disease pathogenesis. PMID:17652264

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

    PubMed

    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

    2012-11-01

    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.

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

    SciTech Connect

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

    1987-01-01

    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.

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

    SciTech Connect

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

    1986-01-01

    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.

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

    SciTech Connect

    Gangarossa, S.; Mattina, T.; Romano, V.; Milana, G.; Mollica, F.; Schiliro, G.

    1996-03-15

    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.

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

    PubMed Central

    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.

    2013-01-01

    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

  8. Thrombotic thrombocytopenic purpura following salvage chemotherapy with paclitaxel, ifosfamide and cisplatin in a patient with a refractory germ cell tumor: A case report and review of the literature

    PubMed Central

    ULAS, ARIFE; SILAY, KAMILE; AKINCI, SEMA; AKINCI, MUHAMMED BULENT; SENDUR, MEHMET ALI; DEDE, DIDEM SENER; POLAT, YUNUS HALIL; YALCIN, BULENT

    2015-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy that is characterized by microvascular thrombosis, thrombocytopenia, hemolysis and end organ damage. An extensive variety of drugs, including certain chemotherapeutic agents, have been associated with TTP. However, paclitaxel, cisplatin and ifosfamide regimen (TIP)-induced TTP has not previously been described. The present study reports the case of a 43-year-old patient with a refractory testicular germ cell tumor who developed acute TTP during TIP chemotherapy. Following the third cycle of TIP chemotherapy, the patient developed fever, anemia, thrombocytopenia and confusion. A diagnosis of TTP was established. Plasmapheresis was initiated as daily treatment in the first week, then continued every other day for 4 weeks. TIP chemotherapy was discontinued. The patient's clinical and neurological symptoms improved markedly after a week. Renal function and hemolysis improved, and the patient was discharged in a stable condition. The patient did not develop any complications and has been in remission for 5 months. The Naranjo adverse drug reaction probability scale indicated a likely association between TTP and the TIP chemotherapy regimen in this patient. This case is also investigated with regard to the associated literature to increase the awareness of TTP following chemotherapy. PMID:26622823

  9. Acute onset hemoglobinemia and/or hemoglobinuria and sequelae following Rh(o)(D) immune globulin intravenous administration in immune thrombocytopenic purpura patients.

    PubMed

    Gaines, A R

    2000-04-15

    Rh(o)(D) immune globulin intravenous (anti-D IGIV) was licensed by the United States Food and Drug Administration (FDA) in March 1995 to treat patients with immune thrombocytopenic purpura (ITP). Anti-D IGIV induces extravascular hemolysis, an expected adverse reaction that is consistent with the presumed mechanism of action. Between licensure and April 1999, the FDA received 15 reports of hemoglobinemia and/or hemoglobinuria following anti-D IGIV administration that met the case definition for this review. The mechanism responsible for hemoglobinemia and/or hemoglobinuria is unexplained. Review of these reports was prompted by the seriousness and the unexpectedness of treatment-associated sequelae experienced by 11 patients. Of these patients, 7 developed sufficient onset or exacerbation of anemia that orders were written for packed red blood cell transfusions, although only 6 patients were transfused. Eight patients experienced the onset or exacerbation of renal insufficiency, and 2 patients underwent dialysis. One patient died due to complications of exacerbated anemia. Six patients experienced 2 to 3 sequelae. Absent validated incidence data, a 1.5% estimated incidence rate from published clinical trial data and a 0.1% estimated reporting rate from FDA and drug utilization data were calculated for reported cases of hemoglobinemia and/or hemoglobinuria. This review presents the first case series of anti-D-IGIV-associated hemoglobinemia and/or hemoglobinuria and provides pretreatment and posttreatment clinical and laboratory findings of the case series patients. The primary purpose of this review is to increase awareness of this potentially serious occurrence among physicians and health care professionals who manage ITP patients treated with anti-D IGIV, thereby enabling prompt recognition and treatment of sequelae. (Blood. 2000;95:2523-2529)

  10. The Relationship between Self-esteem and Quality of Life of Patients with Idiopathic Thrombocytopenic Purpura at Isfahan's Sayed Al-Shohada Hospital, Iran, in 2013

    PubMed Central

    Hemati, Zeinab; Kiani, Davood

    2016-01-01

    Background: Idiopathic thrombocytopenic purpura (ITP) is a chronic disease which is accompanied with hopelessness and loss of the sense of well-being due to its symptoms and treatment. It also affects patients' sense of social and spiritual well-being. This disorder decreases patients' self-esteem and their quality of life by changing their mental image and self-confidence. This study was performed to find the relationship between self-esteem and quality of life of patients with ITP. Subjects and Methods: This was a descriptive-analytical study on 64 patients with ITP who referred to Isfahan's Sayed Al-Shohada Hospital, Iran. In this study, patients with ITP were selected randomly using a random number chart. The data collection tools consisted of the World Health Organization Quality of Life (WHOQOL)-BREF and Coopersmith Self-esteem Inventory (CSEI). Data were analyzed using SPSS and chi-square and Mann-Whitney tests and the Pearson and Spearman’s rank correlation coefficients. Results: In total, 64 patients completed the questionnaires. Results showed that 32% of subjects were over 36 years of age and 59% were women. In addition, 29.7% of ITP patients had low self-esteem and quality of life. Chi-square test showed a significant relationship between self-esteem and quality of life of patients with ITP. Conclusions: The results of the present study showed that considerable attention must be paid to self-esteem, as one of the most important factors influencing the promotion of quality of life. Therefore, it is suggested that patient’s self-esteem be improved by the implementation of educational and psychological programs in order to decrease the consequences of poor quality of life. PMID:27252807

  11. The D173G mutation in ADAMTS-13 causes a severe form of congenital thrombotic thrombocytopenic purpura. A clinical, biochemical and in silico study.

    PubMed

    Lancellotti, Stefano; Peyvandi, Flora; Pagliari, Maria Teresa; Cairo, Andrea; Abdel-Azeim, Safwat; Chermak, Edrisse; Lazzareschi, Ilaria; Mastrangelo, Stefano; Cavallo, Luigi; Oliva, Romina; De Cristofaro, Raimondo

    2016-01-01

    Congenital thrombotic thrombocytopenic purpura (TTP) is a rare form of thrombotic microangiopathy, inherited with autosomal recessive mode as a dysfunction or severe deficiency of ADAMTS-13 (A Disintegrin And Metalloprotease with ThromboSpondin 1 repeats Nr. 13), caused by mutations in the ADAMTS-13 gene. About 100 mutations of the ADAMTS-13 gene were identified so far, although only a few characterised by in vitro expression studies. A new Asp to Gly homozygous mutation at position 173 of ADAMTS-13 sequence was identified in a family of Romanian origin, with some members affected by clinical signs of TTP. In two male sons, this mutation caused a severe (< 3%) deficiency of ADAMTS-13 activity and antigen level, associated with periodic thrombocytopenia, haemolytic anaemia and mild mental confusion. Both parents, who are cousins, showed the same mutation in heterozygous form. Expression studies of the mutant ADAMTS-13, performed in HEK293 cells, showed a severe decrease of the enzyme's activity and secretion, although the protease was detected inside the cells. Molecular dynamics found that in the D173G mutant the interface area between the metalloprotease domain and the disintegrin-like domain significantly decreases during the simulations, while the proline-rich 20 residues linker region (LR, 285-304) between them undergoes extensive conformational changes. Inter-domain contacts are also significantly less conserved in the mutant compared to the wild-type. Both a decrease of the inter-domain contacts along with a substantial conformational rearrangement of LR interfere with the proper maturation and folding of the mutant ADAMTS-13, thus impairing its secretion.

  12. Novel Recombinant Glycosylphosphatidylinositol (GPI)-Anchored ADAMTS13 and Variants for Assessment of Anti-ADAMTS13 Autoantibodies in Patients with Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Li, Dengju; Xiao, Juan; Paessler, Michele; Zheng, X. Long

    2011-01-01

    Summary Immunoglobulin Gs (IgGs) against ADAMTS13 are major causes of acquired (idiopathic) thrombotic thrombocytopenic purpura (TTP). We report here a novel cell-based assay using glycosylphosphatidylinositol (GPI)-anchored ADAMTS13 or variants expressed on cell membrane for assessment of autoantibodies in patients with TTP. We showed that IgGs from all 26 patients with acquired TTP bound to cells expressing a GPI anchored full-length ADAMTS13 (gFL) and a variant truncated after the spacer domain (gS). Also, IgGs from 25/26 (96.7%) of these TTP patients bound to cells expressing a GPI-anchored C-terminal fragment, TSP1 2-8 plus CUB (gT2C). In contrast, none of the 20 healthy blood donors showed detectable binding of their IgGs to the cells expressing gFL, gS, and gT2C. A moderate, but statistically significant correlation was observed between plasma concentrations of anti-ADAMTS13 IgG and positive cells expressing gFL (r=0.65), gS (r=0.67), and gT2C (r=0.42). These results suggest that the microtiter-plate assay and the cell-based assay may detect differential antigenic epitopes. Moreover, antigens clustered on cell membrane may enhance antibody binding affinity, thereby increasing analytical sensitivity. Finally, our assay was able to determine kinetic changes of plasma levels of anti-ADAMTS13 IgGs in TTP patients during plasma therapy. Together, our findings suggest that the novel cell-based assay may be applicable for rapid identification and mapping of anti-ADAMTS13 autoantibodies in patients with acquired TTP. PMID:21901237

  13. Inhibitory autoantibodies against ADAMTS-13 in patients with thrombotic thrombocytopenic purpura bind ADAMTS-13 protease and may accelerate its clearance in vivo

    PubMed Central

    SHELAT, S. G.; SMITH, P.; AI, J.; ZHENG, X. L.

    2008-01-01

    Summary Background Many patients with acquired thrombotic thrombocytopenic purpura (TTP) harbor autoantibodies that may bind and/or inhibit ADAMTS-13 proteolytic activity and accelerate its clearance in vivo. Methods To test this hypothesis, we determined ADAMTS-13 activity and antigen levels in parallel plasma samples from patients clinically diagnosed with TTP. Collagen binding, GST-VWF73 and FRETS-VWF73 assays were used to determine ADAMTS-13 activity and to detect inhibitory autoantibodies. Enzyme-linked immunosorbent assay (ELISA) and immunoprecipitation plus Western blotting (IP/WB) were used to detect total anti-ADAMTS-13 IgG (inhibitory and non-inhibitory). Results Among 40 patients with TTP (21 idiopathic and 19 non-idiopathic), inhibitory autoantibodies were detected (by FRETS-VWF73) in 52% of idiopathic and 0% of non-idiopathic TTP patients. In contrast, non-inhibitory IgG autoantibodies were detected in 29% of idiopathic and 50% of non-idiopathic TTP patients. The concentration of inhibitory IgG autoantibody in idiopathic TTP patients was significantly higher than that of non-inhibitory IgG in either idiopathic or non-idiopathic TTP patients. Idiopathic TTP patients demonstrated significantly reduced ADAMTS-13 activity compared with non-idiopathic patients, but only slightly lower ADAMTS-13 antigen levels. Interestingly, patients with inhibitory autoantibodies exhibited significantly lower ADAMTS-13 antigen levels than those with only non-inhibitory IgG autoantibodies or no autoantibody. Serial plasma exchanges increased levels of ADAMTS-13 activity and antigen concurrently in patients with inhibitory autoantibodies. Conclusion The identification of severe ADAMTS-13 deficiency and autoantibodies or inhibitors appears to be assay-dependent; the inhibitory IgG autoantibodies, in addition to binding and inhibiting ADAMTS-13 proteolytic activity, may accelerate ADAMTS-13 clearance in vivo. PMID:16879212

  14. The European Medicines Agency review of eltrombopag (Revolade) for the treatment of adult chronic immune (idiopathic) thrombocytopenic purpura: summary of the scientific assessment of the Committee for Medicinal Products for Human Use.

    PubMed

    Nieto, Maria; Calvo, Gonzalo; Hudson, Ian; Feldschreiber, Peter; Brown, David; Lee, Ching Cheng; Lay, Geoffrey; Valeri, Anna; Abadie, Eric; Thomas, Angela; Pignatti, Francesco

    2011-09-01

    On 11(th) March 2010, the European Commission issued a marketing authorization valid throughout the European Union for Revolade for the treatment of adult chronic immune (idiopathic) thrombocytopenic purpura. Revolade is an orphan medicinal product indicated for splenectomized patients with immune (idiopathic) thrombocytopenic purpura who are refractory to other treatments (e.g. corticosteroids, immunoglobulins) and as second-line treatment for non-splenectomized patients where surgery is contraindicated. The active substance of Revolade is eltrombopag (ATC code B02BX05). Eltrombopag increases platelet production through activation of the thrombopoietin receptor. The recommended oral dose is 50 mg once daily to achieve and maintain a platelet count of the 50×10(9)/L or more necessary to reduce or prevent the risk of bleeding. The benefit of Revolade is a durable response in maintaining platelet levels. The most common side effects include headache, nausea, hepatobiliary toxicity, diarrhea, fatigue, paresthesia, constipation, rash, pruritus, cataract, arthralgia and myalgia. The decision to grant the marketing authorization was based on the favorable recommendation of the Committee for Medicinal Products for Human Use of the European Medicines Agency. The objective of this paper is to describe the data submitted to the European Medicines Agency and to summarize the scientific review of the application. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the European Medicines Agency website (www.ema.europa.eu). PMID:21712542

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

    PubMed Central

    Rank, Andreas; Weigert, Oliver; Ostermann, Helmut

    2010-01-01

    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. PMID:20531970

  16. Analysis of B- and T-cell clonality and HLA class II alleles in patients with idiopathic thrombocytopenic purpura: correlation with Helicobacter pylori infection and response to eradication treatment.

    PubMed

    Veneri, Dino; De Matteis, Giovanna; Solero, Pietro; Federici, Francesca; Zanuso, Carla; Guizzardi, Elisabetta; Arena, Silvia; Gaio, Monica; Pontiero, Patrizia; Ricetti, Maria M; Franchini, Massimo

    2005-08-01

    Many authors have recently found a positive correlation between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP), the most common autoimmune hematological disorder. In order to clarify the pathogenic mechanism of H. pylori-associated ITP, we have investigated 52 consecutive ITP adult patients for Helicobacter pylori infection, B- and T-cell clonality and HLA class II alleles. Thirty-four ITP patients (65.4%) were infected by H. pylori and bacterium eradication was accompanied by a long-term platelet response in 17 (53.1%) of them. A B-cell clonality was found in three patients (5.8%, two patients H. pylori-negative and one patient H. pylori-positive). The ITP patients with H. pylori infection showed a HLA-DRB1*11, *14 and -DQB1*03 frequencies significantly higher and a -DRB1*03 frequency significantly lower than in H. pylori-negative patients. Moreover, an HLA-DQB1*03 pattern was associated with a higher probability of platelet response to eradication treatment. If our study documents the efficacy of eradication treatment in H. pylori-infected ITP patients, it may also help to identify different subgroups of ITP patients with probably different pathogeneses of thrombocytopenia and, finally, different responses to eradication treatment.

  17. A phase-II sequential case-series study of all patients presenting to four plasma exchange centres with presumed relapsed/refractory thrombotic thrombocytopenic purpura treated with rituximab.

    PubMed

    Clark, William F; Rock, Gail; Barth, David; Arnold, Donald M; Webert, Kathyrn E; Yenson, Paul R; Kelton, John G; Li, Lihua; Foley, Steven R

    2015-07-01

    The primary objective of this phase II study was to evaluate the efficacy of rituximab in the management of adult patients with physician-diagnosed presumed thrombotic thrombocytopenic purpura (TTP); relapsed or refractory. We conducted a multicentre study in four Canadian hospital-based apheresis units. Forty patients with presumed TTP (20 refractory and 20 relapsing) were sequentially enrolled and all received rituximab in a standardized manner. A complete response was documented in 14 of 19 refractory patients by week 8 and 15/16 were alive and in remission at 52 weeks (one patient was lost to follow-up, one was a non-responder, and three died). Among relapsing patients, 16/18 had a complete response at week 8 and 18/18 at week 52 (one patient lost to follow-up and one withdrew). At 1 year, all relapsing and 85% of refractory patients survived. Of 38/40 patients who had ADMATS13 testing at study entry, 13/19 refractory and 10/19 relapsing patients had ADAMTS13 < 10% (typical TTP); whereas 6/19 refractory and 9/19 relapsing cases had ADAMTS13 > 10% (other thrombotic microangiopathy; TMA). Refractory-typical TTP in contrast to refractory-other TMA and all relapsing patients treated with plasma exchange and rituximab, were less likely to be responsive and more likely to die or relapse. PMID:25855259

  18. Investigation of whether the acute hemolysis associated with Rho(D) immune globulin intravenous (human) administration for treatment of immune thrombocytopenic purpura is consistent with the acute hemolytic transfusion reaction model

    PubMed Central

    Gaines, Ann Reed; Lee-Stroka, Hallie; Byrne, Karen; Scott, Dorothy E.; Uhl, Lynne; Lazarus, Ellen; Stroncek, David F.

    2012-01-01

    BACKGROUND Immune thrombocytopenic purpura and secondary thrombocytopenia patients treated with Rho(D) immune globulin intravenous (human; anti-D IGIV) have experienced acute hemolysis, which is inconsistent with the typical presentation of extravascular hemolysis—the presumed mechanism of action of anti-D IGIV. Although the mechanism of anti-D-IGIV–associated acute hemolysis has not been established, the onset, signs/symptoms, and complications appear consistent with the intravascular hemolysis of acute hemolytic transfusion reactions (AHTRs). In transfusion medicine, the red blood cell (RBC) antigen-antibody incompatibility(-ies) that precipitate AHTRs can be detected in vitro with compatibility testing. Under the premise that anti-D-IGIV–associated acute hemolysis results from RBC antigen-antibody–mediated complement activation, this study evaluated whether the incompatibility(-ies) could be detected in vitro with a hemolysin assay, which would support the AHTR model as the hemolytic mechanism. STUDY DESIGN AND METHODS Seven anti-D IGIV lots were tested to determine the RBC antibody identities in those lots, including four lots that had been implicated in acute hemolytic episodes. Hemolysin assays were performed that tested each of 73 RBC specimens against each lot, including the RBCs of one patient who had experienced acute hemolysis after anti-D IGIV administration. RESULTS Only two anti-D IGIV lots contained RBC antibodies beyond those expected. No hemolysis endpoint was observed in any of the hemolysin assays. CONCLUSION Although the findings did not support the AHTR model, the results are reported to contribute knowledge about the mechanism of anti-D-IGIV–associated acute hemolysis and to prompt continued investigation into cause(s), prediction, and prevention of this potentially serious adverse event. PMID:19220820

  19. Effects of cytotoxin-associated gene A (CagA) positive Helicobacter pylori infection on anti-platelet glycoprotein antibody producing B cells in patients with primary idiopathic thrombocytopenic purpura (ITP)

    PubMed Central

    Cheng, Yuan-Shan; Kuang, Li-Ping; Zhuang, Chun-Lan; Jiang, Jia-Dian; Shi, Man

    2015-01-01

    Objective: To explore the effects of cytotoxin-associated gene A (CagA) positive Helicobacter pylori (H. pylori or HP) infection on circulating B cells producing specific platelet glycoprotein antibodies and the association between therapeutic outcomes in primary idiopathic thrombocytopenic purpura (ITP) patients. Methods: A total of 76 newly diagnosed primary ITP patients were included in the study which was conducted at the first affiliated hospital of Shantou University Medical college, in Shantou city China, between January 2013 and January 2014. These patients were tested for H. pylori infection by 13C urea breath test and for anti-CagA antibody in H. pylori positive cases by enzyme-linked immunosorbent assay (ELISA) method. Anti-GPIb and anti-GPIIb/IIIa antibody-producing B cells were measured using an enzyme-linked immunospot (ELISPOT) assay in all ITP patients and 30 controls. Anti-nuclear antibody (ANA) was also detected in ITP patients. Results: The numbers of anti-GPIIb/IIIa antibody-producing B cells in HP+CagA+ patients were higher than in HP+CagA- or HP- patients. However, anti-GPIb antibody-producing B cells were found higher in HP- patients. Analysis of treatment outcomes showed that a therapeutic response was more likely in patients presenting anti-GPIIb/IIIa B cells, but the poor response was found to be associated with anti-GPIb B cells and ANA presences. Conclusion: CagA antigen of H. pylori may induce anti-GPIIb/IIIa antibodies production by a molecular mimicry mechanism. Anti-GPIIb/IIIa and anti-GPIb antibody producing B Cells detection is useful for predicting treatment effects of primary ITP. PMID:25878627

  20. Correlation of Notch1/Hes1 Genes Expression Levels in Egyptian Paediatric Patients with Newly Diagnosed and Persistent Primary Immune(Idiopathic) Thrombocytopenic Purpura.

    PubMed

    Gawdat, Rania Mohsen; Hammam, Amira Ahmed; Ezzat, Dina Ahmed

    2016-09-01

    Notch signalling is involved in the development of several autoimmune diseases, one of such diseases is ITP. The aim of this study was to investigate and compare the expression levels of Notch1 receptor and its target Hes1 gene in Egyptian paediatric ITP patients. Real-time quantitative reverse transcriptase polymerase chain reaction was used to analyse the expression levels of Notch1 and Hes1 in 42 children with primary ITP (22 newly diagnosed and 20 persistent) cases. Twenty age and sex matched non-ITP controls were included. The expression levels of Notch1 were higher in newly diagnosed and persistent cases than controls with high statistical significant difference (P value < 0.001, P < 0.001) respectively, similarly as regards the expression levels of HES1 (P value < 0.001, P < 0.007) respectively. A significant positive correlation was found between Notch1 and Hes1 expression levels in newly diagnosed cases (r = 0.587, P value = 0.004). There was an association between levels of both genes in most of ITP patients but Hes1 was markedly elevated than Notch1 in few cases. High expression levels of Notch1/Hes1 indicated the important role of Notch signalling in both newly diagnosed and persistent ITP. High expression levels of Hes1 than Notch1 may shed light on its value as a therapeutic target for future research in ITP. PMID:27429531

  1. How Is Thrombotic Thrombocytopenic Purpura Treated?

    MedlinePlus

    ... and surgery. Treatments are done in a hospital. Plasma Therapy Plasma is the liquid part of your blood. It ... nutrients to your body. TTP is treated with plasma therapy. This includes: Fresh frozen plasma for people ...

  2. Psychogenic purpura

    PubMed Central

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

    2013-01-01

    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. PMID:23825859

  3. Progressive Pigmentary Purpura

    MedlinePlus

    ... Category: Share: Yes No, Keep Private Progressive Pigmentary Purpura Share | Progressive pigmentary purpura (we will call it PPP) is a group ... conditions ( Schamberg's disease , Lichenoid dermatitis of Gourgerot-Blum, purpura annularis telangiectodes of Majocchi and Lichen aureus). Schamberg's ...

  4. Henoch-Schonlein Purpura

    MedlinePlus

    ... Types of Vasculitis / Henoch-Schönlein Purpura Henoch-Schönlein Purpura Fast Facts First Description Who gets Henoch-Schönlein ... to serious kidney involvement. Who gets Henoch-Schönlein Purpura (the “typical” patient)? Usually, HSP affects a child ...

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

    ClinicalTrials.gov

    2016-01-13

    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; Immune Thrombocytopenia

  6. [Clinical analysis of 200 cases of idiopathic thrombocytopenic purpura].

    PubMed

    García-Stivalet, Lilia Adela; Muñoz-Flores, Aarón; Montiel-Jarquín, Alvaro José; Barragán-Hervella, Rodolfo Gregorio; Bejarano-Huertas, Ruth; García-Carrasco, Mario; López-Colombo, Aurelio

    2014-01-01

    INTRODUCCIÓN: la púrpura trombocitopénica idiopática se caracteriza por la extravasación de sangre en el tejido subcutáneo, membranas, mucosas o piel, que puede generar manifestaciones clínicas de sangrado como lesiones equimóticas, petequias de aparición brusca, epistaxis, gingivorragia y complicaciones graves como hemorragia intracraneal, debido a destrucción plaquetaria mediada por anticuerpos dirigidos contra la superficie de las plaquetas. El objetivo de este informe es presentar las características clínicas de los pacientes con púrpura trombocitopénica idiopática en un hospital de tercer nivel de atención, con la finalidad de tener estadísticas para estudios analíticos posteriores. MÉTODOS: se realizó un estudio descriptivo de 200 pacientes atendidos en el servicio de hematología con diagnóstico de púrpura trombocitopénica idiopática. Se describen sus manifestaciones clínicas, el diagnóstico y el tratamiento médico y quirúrgico empleados.

  7. Henoch Schonlein purpura associated with bee sting: case report.

    PubMed

    Gálvez-Olortegui, José; Álvarez-Vargas, Mayita; Durand-Vergara, Juan; Díaz-Lozano, Marisol; Gálvez-Olortegui, Tomas; Armas-Ramírez, Indira; Hilario-Vargas, Julio

    2015-10-30

    Henoch Schonlein purpura (HSP) is a common childhood vasculitis, characterized by a non-thrombocytopenic palpable purpura and systemic features. It can be triggered by conditions like infections and insect bites. We present the case of a six-year-old girl with palpable maculopapular lesions on the lower limbs, itching, mild pain, swelling of feet, limitation of limb mobility, and a history of bee sting. Thigh skin biopsy was performed, with a report of leucocytoclastic vasculitis, and was diagnosed as HSP. She was prescribed bed rest, and was given oral hydration. The patient outcome was favorable and was discharged after five days. This is the fifth report of a HSP case associated with a bee sting with an uncomplicated course, which is in contrast to previous case reports.

  8. Henoch Schonlein purpura associated with bee sting: case report.

    PubMed

    Gálvez-Olortegui, José; Álvarez-Vargas, Mayita; Durand-Vergara, Juan; Díaz-Lozano, Marisol; Gálvez-Olortegui, Tomas; Armas-Ramírez, Indira; Hilario-Vargas, Julio

    2015-01-01

    Henoch Schonlein purpura (HSP) is a common childhood vasculitis, characterized by a non-thrombocytopenic palpable purpura and systemic features. It can be triggered by conditions like infections and insect bites. We present the case of a six-year-old girl with palpable maculopapular lesions on the lower limbs, itching, mild pain, swelling of feet, limitation of limb mobility, and a history of bee sting. Thigh skin biopsy was performed, with a report of leucocytoclastic vasculitis, and was diagnosed as HSP. She was prescribed bed rest, and was given oral hydration. The patient outcome was favorable and was discharged after five days. This is the fifth report of a HSP case associated with a bee sting with an uncomplicated course, which is in contrast to previous case reports. PMID:26610057

  9. Targeting reservoirs to control human infections – a one health approach

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Shiga toxin producing Escherichia coli (STEC) cause hemorrhagic colitis and potentially fatal extraintestinal sequelae, such as the hemolytic uremic syndrome and thrombotic thrombocytopenic purpura, in humans. Currently, treatment of human STEC disease is only symptomatic and supportive. Antibioti...

  10. Exercise-induced purpura.

    PubMed

    Leung, A K; Grant, R M; Truscott, R

    1990-09-01

    A 11-year-old boy developed purpura on the back and chest on more than 5 occasions following vigorous exercise. This eruption should be added to the list of differential diagnosis of the dermatosis experienced by athletes.

  11. Thrombocytopenic syndromes in pregnancy.

    PubMed

    Yan, Matthew; Malinowski, Ann K; Shehata, Nadine

    2016-03-01

    The physiological changes in pregnancy result in platelet counts that are lower than in nonpregnant women. Consequently, thrombocytopenia is a common finding occurring in 7-12% of pregnant women. Gestational thrombocytopenia, the most common cause of low platelet counts, tends to be mild in most women and does not affect maternal, fetal or neonatal outcomes. Gestational thrombocytopenia needs to be distinguished from other less common causes of isolated thrombocytopenia, such as immune thrombocytopenia, which affects approximately 3% of thrombocytopenic pregnant women and can lead to neonatal thrombocytopenia. Hypertensive disorders of pregnancy and thrombotic microangiopathies are both associated with thrombocytopenia. They share a considerable number of similar characteristics and are associated with significant maternal and neonatal morbidity and rarely mortality. Accurate identification of the aetiology of thrombocytopenia and appropriate management are integral to optimizing the pregnancy, delivery and neonatal outcomes of this population. Clinical cases are described to illustrate the various aetiologies of thrombocytopenia in pregnancy and their treatment. PMID:27512485

  12. A new approach to detect reticulated platelets stained with thiazole orange in thrombocytopenic patients.

    PubMed

    Fujii, T; Shimomura, T; Fujimoto, T T; Kimura, A; Fujimura, K

    2000-03-15

    Recent studies have shown that reticulated platelets stained with Thiazole Orange (T.O.) are useful markers for thrombopoiesis. The percentage of T.O. positive platelets tends to be inconsistent using the original method, especially when the peripheral blood platelet count is very low. We measured T.O. positive platelet levels in patients with severe thrombocytopenic disorders, using concentrated platelet-rich plasma and carrying out a two-color analysis involving T.O. and an anti-glycoprotein IIb/IIIa monoclonal antibody. This method allowed us to obtain consistent T.O. positive platelet rates in patients with thrombocytopenia whose platelet counts were below 20 approximately 30x10(9)/l. By this method, the T.O. positive rates of platelets from idiopathic thrombocytopenic purpura patients were found to be significantly higher than in the control group. The T.O. positive rates of other thrombocytopenic disorders were similar to those of the control group. These results are consistent with those previously reported. We conclude that our technique of measuring of T.O. positive platelets using platelet-rich plasma is useful for analyzing severe thrombocytopenic disorders.

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

    PubMed

    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

    2013-01-01

    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.

  14. Safety and Efficacy Study of Romiplostim (AMG 531) to Treat ITP in Pediatric Subjects

    ClinicalTrials.gov

    2014-07-18

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

  15. Fatal purpura fulminans and Waterhouse-Friderichsen syndrome from fulminant Streptococcus pneumoniae sepsis in an asplenic young adult.

    PubMed

    Hale, Andrew J; LaSalvia, Mary; Kirby, James E; Kimball, Allison; Baden, Rachel

    2016-01-01

    Asplenic patients are at increased risk for sepsis and fulminant infection. Sepsis in these patients is typically secondary to encapsulated bacteria, with Streptococcus pneumoniae being the most frequent pathogen. Rare complications of severe sepsis include purpura fulminans and bilateral adrenal hemorrhage (Waterhouse-Friderichsen syndrome). We present the case of a 36-year-old woman, healthy except for splenectomy years prior for idiopathic thrombocytopenic purpura treatment, who presented with fever. Upon presentation to our hospital, three hours after symptoms onset, she had purpura fulminans and shock. Despite timely antimicrobials and maximal resuscitative efforts, her disease progressed and she expired 12 hours after symptoms onset. Autopsy revealed bilateral adrenal hemorrhage; acute adrenal crisis likely contributed to her refractory shock. Prior to her presentation, she had not received guideline-based post-splenectomy care. Sepsis in asplenic patients can be fulminant and rapidly fatal. Streptococcus pneumoniae remains the most frequent cause, despite decreasing rates in recent years related to widespread pneumococcal vaccination. Guideline-based vaccinations and "pill-in-pocket" therapy can be life-saving for asplenic patients. Purpura fulminans represents an extreme manifestation of disseminated intravascular coagulation, is more common in asplenic patients, and portends a poor prognosis. Waterhouse-Friderichsen syndrome can be seen concurrently with purpura fulminans and further portends a poor prognosis; pre-mortem diagnosis requires a high index of suspicion. PMID:27583208

  16. Henoch-Schönlein Purpura

    MedlinePlus

    ... PDF, 345 KB)​​​​​ Alternate Language URL Henoch-Schönlein Purpura Page Content On this page: What is Henoch- ... to Remember Clinical Trials What is Henoch-Schönlein purpura (HSP)? Henoch-Schönlein purpura is a disease that ...

  17. [Treatment of chronic refractory idiopathic thrombocytopenia purpura. 10 years experience at the Salvador Zubiran National Institute of Nutrition].

    PubMed

    Pita-Ramírez, L; Hurtado-Monroy, R; Labardini-Méndez, J

    1992-01-01

    A total of 126 patients with chronic idiopathic thrombocytopenic purpura were diagnosed from January 1980 to January 1990 in our institute. In this group of patients, 21 were refractory to prednisone therapy, splenectomy or both, or had had a relapse after a good response with these treatments. They were given other therapies. There was enough information for evaluation in 16 of the 21 patients. The treatment responses were classified according to the post-therapy platelet counts: complete response (CR) = > 150 x 10(9)/L for more than three months; partial response (PR) = 50-150 x 10(9)/L for more than three months; any response (AR) = CR + PR; no response (NR) = < 50 x 10(9)/L. There were 15 women and one male. The median age was 41 years (range 11 to 65). 6-mercaptopurine was given in all patients with CR = 31.2%, PR = 18.8%, AR = 50% and NR = 50%. Seven patients received cyclophosphamide with CR = 28.6%, PR = 14.3%, AR = 42.9% and NR = 57%. Vincristine was given in four patients with only one PR. Interferon alpha 2B was given in four patients with two transitory PR. One patient received colchicine and vitamin C without response. It is concluded that 6-mercaptopurine and cyclophosphamide are useful drugs in refractory thrombocytopenic purpura. PMID:1485028

  18. Idiopathic thromobocytopenic purpura in two mothers of children with DiGeorge sequence: A new component manifestation of deletion 22q11?

    SciTech Connect

    Levy, A.; Philip, N.; Michel, G.

    1997-04-14

    The phenotypic spectrum caused by the microdeletion of chromosome 22q11 region is known to be variable. Nearly all patients with DiGeorge sequence (DGS) and approximately 60% of patients with velocardiofacial syndrome exhibit the deletion. Recent papers have reported various congenital defects in patients with 22q11 deletions. Conversely, some patients have minimal clinical expression. Ten to 25% of parents of patients with DGS exhibit the deletion and are nearly asymptomatic. Two female patients carrying a 22q11 microdeletion and presenting with idiopathic thrombocytopenic purpura are reported. Both had children with typical manifestations of DGS. 12 refs., 4 figs., 1 tab.

  19. How we use WinRho in patients with idiopathic thrombocytopenic purpura.

    PubMed

    Stotler, Brie A; Schwartz, Joseph

    2015-11-01

    Primary immune thrombocytopenia (ITP) is an autoimmune disease that affects children and adults. WinRho SDF is a D immune globulin product that is Food and Drug Administration approved for the treatment of ITP in D+ pediatric and adult patients. WinRho is a plasma-derived biologic product dispensed from blood banks. Transfusion medicine physicians serve as a resource to health care providers regarding blood component and derivative usage and, as such, should be familiar with the use of WinRho for ITP, including the dosage, administration, and contraindications. This report details the transfusion medicine consultation practice and guidelines at a tertiary care academic medical center for the usage of WinRho SDF in patients with ITP. PMID:26094894

  20. Intravenous usage of gammaglobulin: humoral immunodeficiency, immune thrombocytopenic purpura, and newer indications.

    PubMed

    Bussel, J B; Cunningham-Rundles, C

    1985-01-01

    Intravenous gammaglobulin is effective therapy of ITP and other autoantibody-mediated immune cytopenias. All children as well as adults unresponsive to splenectomy or with known immune deficiency are probably the best candidates for treatment with IVGG. Its major advantage, in addition to its efficacy of treatment and possible remission-inducing effect, is that it has the fewest side effects of any treatment of ITP so that it is the best maintenance therapy of patients when effective. Future uses of IVGG remain to be determined. Premature infants with a high mortality from sepsis and with hypogammaglobulinemia due to termination of pregnancy prior to transplacental antibody transfer may benefit from IVGG. A preliminary study suggested such benefit and also showed safety of IVGG treatment in that there was no impaired immune responsiveness of these prematures at 2 years of age (28). Another potential usage of IVGG involves the treatment of the hypogammaglobulinemia associated with certain types of malignancy. Patients with CLL, especially in the advanced stages, are often hypogammaglobulinemic. Multiple myeloma and Waldenstrom's macroglobulinemia are two other B-cell malignancies associated with antibody production defects which might benefit from antibody replacement therapy. Therapeutic IgG levels may be harder to obtain due to hypercatabolism of immunoglobulin. The issue of immune hyporesponsiveness during intensive chemotherapy is also unexplored. Secondary antibody responses do not seem to be impaired, but primary responses, as tested in numerous immunization studies, are decidedly impaired. Certain protocols, especially those treating high-risk acute leukemias and neuroblastoma during induction therapy are intensive with high rates of sepsis, and may warrant trials of prophylactic IVGG. Similarly, some form of humoral prophylaxis is becoming an important part of the handling of the patient undergoing bone marrow transplantation not only to prevent bacterial sepsis but also to prevent cytomegalovirus (CMV) interstitial pneumonitis. A likely additional usage is gammaglobulin replacement for patients undergoing plasmapheresis, especially if performed multiple times. Finally, the broad spectrum of antibacterial and antiviral antibodies present in the preparations (such as anti-CMV, anti-Group B strep, and antiendotoxin) and the ease and safety of delivery allow the preparations to be used in situations where a hyperimmune preparation might be desired and/or where more than one pathogen is possible. In summary, IVGG is a treatment capable of safely conferring significant benefits to selected patients.(ABSTRACT TRUNCATED AT 400 WORDS)

  1. How we use WinRho in patients with idiopathic thrombocytopenic purpura.

    PubMed

    Stotler, Brie A; Schwartz, Joseph

    2015-11-01

    Primary immune thrombocytopenia (ITP) is an autoimmune disease that affects children and adults. WinRho SDF is a D immune globulin product that is Food and Drug Administration approved for the treatment of ITP in D+ pediatric and adult patients. WinRho is a plasma-derived biologic product dispensed from blood banks. Transfusion medicine physicians serve as a resource to health care providers regarding blood component and derivative usage and, as such, should be familiar with the use of WinRho for ITP, including the dosage, administration, and contraindications. This report details the transfusion medicine consultation practice and guidelines at a tertiary care academic medical center for the usage of WinRho SDF in patients with ITP.

  2. Rituximab for the treatment of childhood chronic idiopathic thrombocytopenic purpura and hemophilia with inhibitors.

    PubMed

    Franchini, Massimo; Zaffanello, Marco; Veneri, Dino; Lippi, Giuseppe

    2007-07-01

    Rituximab, a monoclonal chimeric antibody to the CD20 antigen, is an effective treatment for non-Hodgkin lymphomas. Moreover, rituximab has also shown efficacy in various autoimmune disorders. In this review, we will focus on the use of rituximab in childhood disorders of hemostasis associated with inhibitor formation. Although the results presented suggest that rituximab can be useful in the treatment of this subset of pediatric patients, most of the data come from isolated case reports or descriptions of small, uncontrolled series. Therefore, large, prospective, and randomized trials are needed to confirm the positive, preliminary results.

  3. Primary Splenic Angiosarcoma Presenting as Idiopathic Thrombocytopenic Purpura: A Case Report and Review of the Literature

    PubMed Central

    Goldenberg-Sandau, Anna; Roy, Darshan; Sandau, Roy

    2016-01-01

    Angiosarcoma of the spleen is a rare malignancy that arises from vascular endothelial origin. This neoplasm is highly malignant and diagnosis is often delayed due to the vague presentation of clinical symptoms. A case report and concise review of the current diagnostic criteria and surgical treatment are provided to aid in the detection and treatment of this malignancy. We present a case of a 56-year-old female who presented with massive splenomegaly secondary to angiosarcoma of the spleen. The patient suffered from longstanding symptomatic anemia and thrombocytopenia. Diagnosis of a splenic angiosarcoma can be difficult due to the vague presentation and lack of concrete risk factors. Early identification and splenectomy are paramount. However, it is an aggressive malignancy with poor prognosis. We reviewed the literature of the current diagnostic and surgical treatment of primary splenic angiosarcoma. PMID:27651973

  4. Primary Splenic Angiosarcoma Presenting as Idiopathic Thrombocytopenic Purpura: A Case Report and Review of the Literature.

    PubMed

    Frontario, S Christopher N; Goldenberg-Sandau, Anna; Roy, Darshan; Sandau, Roy

    2016-01-01

    Angiosarcoma of the spleen is a rare malignancy that arises from vascular endothelial origin. This neoplasm is highly malignant and diagnosis is often delayed due to the vague presentation of clinical symptoms. A case report and concise review of the current diagnostic criteria and surgical treatment are provided to aid in the detection and treatment of this malignancy. We present a case of a 56-year-old female who presented with massive splenomegaly secondary to angiosarcoma of the spleen. The patient suffered from longstanding symptomatic anemia and thrombocytopenia. Diagnosis of a splenic angiosarcoma can be difficult due to the vague presentation and lack of concrete risk factors. Early identification and splenectomy are paramount. However, it is an aggressive malignancy with poor prognosis. We reviewed the literature of the current diagnostic and surgical treatment of primary splenic angiosarcoma. PMID:27651973

  5. Primary Splenic Angiosarcoma Presenting as Idiopathic Thrombocytopenic Purpura: A Case Report and Review of the Literature

    PubMed Central

    Goldenberg-Sandau, Anna; Roy, Darshan; Sandau, Roy

    2016-01-01

    Angiosarcoma of the spleen is a rare malignancy that arises from vascular endothelial origin. This neoplasm is highly malignant and diagnosis is often delayed due to the vague presentation of clinical symptoms. A case report and concise review of the current diagnostic criteria and surgical treatment are provided to aid in the detection and treatment of this malignancy. We present a case of a 56-year-old female who presented with massive splenomegaly secondary to angiosarcoma of the spleen. The patient suffered from longstanding symptomatic anemia and thrombocytopenia. Diagnosis of a splenic angiosarcoma can be difficult due to the vague presentation and lack of concrete risk factors. Early identification and splenectomy are paramount. However, it is an aggressive malignancy with poor prognosis. We reviewed the literature of the current diagnostic and surgical treatment of primary splenic angiosarcoma.

  6. Henoch-Schönlein purpura

    MedlinePlus

    Ardoin SP, Fels E. Vasculitis syndromes. In: Kliegman RM, Stanton B, St. Geme J, Schor N, Behrman ... Elsevier Saunders; 2011:chap 161. Marcdante KJ, Kliegman RM. Henoch-Schöenlein purpura. In: Marcdante KJ, Kliegman RM, ...

  7. An improbable and unusual case of thrombotic thrombocytopenia purpura.

    PubMed

    Patel, Jaymon; Patel, Preeti; Ahmed, Zohair

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening medical emergency which may be difficult to recognize given the wide spectrum in which it presents. A delay in treatment may be catastrophic as untreated cases of TTP have a mortality rate exceeding 90%. Given the high fatality rate of untreated TTP and its range of presenting symptoms, we present our unusual case of TTP in a post-splenectomy patient with early treatment and positive outcome. This case describes a 54-year-old female who presented with hematuria and gingival bleeding, followed by the development of a bilateral lower extremity petechial rash. Her past medical history was significant for multiple episodes of TTP, the last of which resulted in a splenectomy and a 20-year history of remission thereafter. On exam, she was alert, well appearing, and neurologically intact. Her only significant finding was a bilateral lower extremity petechial rash. Laboratory studies revealed mild anemia and thrombocytopenia, an elevated lactate dehydrogenase, and a decreased haptoglobin. Peripheral smear showed poikilocytosis, helmet cells, and schistocytes. Corticosteroid therapy was promptly initiated, her platelets were monitored closely, and she underwent urgent therapeutic plasma exchange. Due to the risk of significant morbidity and mortality that may result from delayed treatment of TTP as well as the significant variations of presentation, TTP requires a consistently high index of suspicion. Our patient suffered multiple relapses of TTP within a 30-year span, underwent splenectomy in early adulthood, and presented with atypical symptoms during her most recent relapse illustrating how persistent TTP can be as well as how unusually it may present. Providers should be aware of the vast spectrum of presentation and remember that TTP may recur following splenectomy despite prolonged remission. PMID:27609730

  8. An improbable and unusual case of thrombotic thrombocytopenia purpura

    PubMed Central

    Patel, Jaymon; Patel, Preeti; Ahmed, Zohair

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening medical emergency which may be difficult to recognize given the wide spectrum in which it presents. A delay in treatment may be catastrophic as untreated cases of TTP have a mortality rate exceeding 90%. Given the high fatality rate of untreated TTP and its range of presenting symptoms, we present our unusual case of TTP in a post-splenectomy patient with early treatment and positive outcome. This case describes a 54-year-old female who presented with hematuria and gingival bleeding, followed by the development of a bilateral lower extremity petechial rash. Her past medical history was significant for multiple episodes of TTP, the last of which resulted in a splenectomy and a 20-year history of remission thereafter. On exam, she was alert, well appearing, and neurologically intact. Her only significant finding was a bilateral lower extremity petechial rash. Laboratory studies revealed mild anemia and thrombocytopenia, an elevated lactate dehydrogenase, and a decreased haptoglobin. Peripheral smear showed poikilocytosis, helmet cells, and schistocytes. Corticosteroid therapy was promptly initiated, her platelets were monitored closely, and she underwent urgent therapeutic plasma exchange. Due to the risk of significant morbidity and mortality that may result from delayed treatment of TTP as well as the significant variations of presentation, TTP requires a consistently high index of suspicion. Our patient suffered multiple relapses of TTP within a 30-year span, underwent splenectomy in early adulthood, and presented with atypical symptoms during her most recent relapse illustrating how persistent TTP can be as well as how unusually it may present. Providers should be aware of the vast spectrum of presentation and remember that TTP may recur following splenectomy despite prolonged remission. PMID:27609730

  9. Psychogenic Purpura (Gardner-Diamond Syndrome)

    PubMed Central

    Bhattacharya, Gaurav

    2015-01-01

    Psychogenic purpura, also known as Gardner-Diamond syndrome or autoerythrocyte sensitization syndrome, is a rare condition characterized by spontaneous development of painful edematous skin lesions progressing to ecchymosis over the next 24 hours. Severe stress and emotional trauma always precede the skin lesions. The condition is most commonly seen in women, but isolated cases have been reported in adolescents and in males. Psychodermatologic evaluation and dermatology and psychiatry liaison have been successful in the treatment of these patients. This report provides an overview of psychogenic purpura and presents the case of a 15-year-old girl. PMID:26137346

  10. Pruritis and palpable purpura from leeches in the Australian Rainforest

    PubMed Central

    Seiverling, Elizabeth V.; Khalsa, Amrit; Ahrns, Hadjh T.

    2014-01-01

    Leeches are prevalent in the Australian Rainforest. We report two cases of leech bites resulting in pruritis and palpable purpura. The dermatologic sequelae of leech bites, differential diagnosis of pruritic palpable purpura, leech bite treatment, prevention, and complications are reviewed. PMID:26839767

  11. Henoch-Schönlein purpura with preceding abdominal pain.

    PubMed

    Toshihiko, Kakiuchi; Tomonobu, Aoki

    2015-06-01

    Diagnosing HSP can be difficult, especially when abdominal symptoms precede the onset of characteristic palpable purpura (Chen MJ et al. 2005, World Gastroenterol., 11, 2354). Therefore, it is necessary to consider the possibility of HSP in patients with prolonged strong abdominal pain, even in cases without purpura.

  12. Henoch–Schönlein purpura with preceding abdominal pain

    PubMed Central

    Toshihiko, Kakiuchi; Tomonobu, Aoki

    2015-01-01

    Key Clinical Message Diagnosing HSP can be difficult, especially when abdominal symptoms precede the onset of characteristic palpable purpura (Chen MJ et al. 2005, World Gastroenterol., 11, 2354). Therefore, it is necessary to consider the possibility of HSP in patients with prolonged strong abdominal pain, even in cases without purpura. PMID:26185663

  13. Henoch-Schönlein purpura with preceding abdominal pain.

    PubMed

    Toshihiko, Kakiuchi; Tomonobu, Aoki

    2015-06-01

    Diagnosing HSP can be difficult, especially when abdominal symptoms precede the onset of characteristic palpable purpura (Chen MJ et al. 2005, World Gastroenterol., 11, 2354). Therefore, it is necessary to consider the possibility of HSP in patients with prolonged strong abdominal pain, even in cases without purpura. PMID:26185663

  14. Nanocarriers for spleen targeting: anatomo-physiological considerations, formulation strategies and therapeutic potential.

    PubMed

    Jindal, Anil B

    2016-10-01

    There are several clinical advantages of spleen targeting of nanocarriers. For example, enhanced splenic concentration of active agents could provide therapeutic benefits in spleen resident infections and hematological disorders including malaria, hairy cell leukemia, idiopathic thrombocytopenic purpura, and autoimmune hemolytic anemia. Furthermore, spleen delivery of immunosuppressant agents using splenotropic carriers may reduce the chances of allograft rejection in organ transplantation. Enhanced concentration of radiopharmaceuticals in the spleen may improve visualization of the organ, which could provide benefit in the diagnosis of splenic disorders. Unique anatomical features of the spleen including specialized microvasculature environment and slow blood circulation rate enable it an ideal drug delivery site. Because there is a difference in blood flow between spleen and liver, splenic delivery is inversely proportional to the hepatic uptake. It is therefore desirable engineering of nanocarriers, which, upon intravenous administration, can avoid uptake by hepatic Kupffer cells to enhance splenic localization. Stealth and non-spherical nanocarriers have shown enhanced splenic delivery of active agents by avoiding hepatic uptake. The present review details the research in the field of splenotropy. Formulation strategies to design splenotropic drug delivery systems are discussed. The review also highlights the clinical relevance of spleen targeting of nanocarriers and application in diagnostics. PMID:27334277

  15. Nanocarriers for spleen targeting: anatomo-physiological considerations, formulation strategies and therapeutic potential.

    PubMed

    Jindal, Anil B

    2016-10-01

    There are several clinical advantages of spleen targeting of nanocarriers. For example, enhanced splenic concentration of active agents could provide therapeutic benefits in spleen resident infections and hematological disorders including malaria, hairy cell leukemia, idiopathic thrombocytopenic purpura, and autoimmune hemolytic anemia. Furthermore, spleen delivery of immunosuppressant agents using splenotropic carriers may reduce the chances of allograft rejection in organ transplantation. Enhanced concentration of radiopharmaceuticals in the spleen may improve visualization of the organ, which could provide benefit in the diagnosis of splenic disorders. Unique anatomical features of the spleen including specialized microvasculature environment and slow blood circulation rate enable it an ideal drug delivery site. Because there is a difference in blood flow between spleen and liver, splenic delivery is inversely proportional to the hepatic uptake. It is therefore desirable engineering of nanocarriers, which, upon intravenous administration, can avoid uptake by hepatic Kupffer cells to enhance splenic localization. Stealth and non-spherical nanocarriers have shown enhanced splenic delivery of active agents by avoiding hepatic uptake. The present review details the research in the field of splenotropy. Formulation strategies to design splenotropic drug delivery systems are discussed. The review also highlights the clinical relevance of spleen targeting of nanocarriers and application in diagnostics.

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

    SciTech Connect

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

    1984-01-01

    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.

  17. Recurrent adult onset Henoch-Schonlein Purpura: a case report.

    PubMed

    Gaskill, Neil; Guido, Bruce; Mago, Cynthia

    2016-01-01

    Henoch-Schonlein purpura is an immunoglobulin A (IgA)-immune complex mediated leukocytoclastic vasculitis that classically manifests with palpable purpura, abdominal pain, arthritis, and hematuria or proteinuria. The condition is much more predominant in children (90% of cases) and commonly follows an upper respiratory infection. We present a case of recurrent Henoch-Schonlein purpura (HSP) complicated by nephritis in an adult female initially categorized as IgA nephropathy (IgAN). We review the pathophysiologic basis of HSP nephritis as the variant of HSP accompanied by renal involvement and its pathogenetic commonality with IgA nephropathy. PMID:27617937

  18. A role for plasma cell targeting agents in immune tolerance induction in autoimmune disease and antibody responses to therapeutic proteins.

    PubMed

    Rosenberg, A S; Pariser, A R; Diamond, B; Yao, L; Turka, L A; Lacana, E; Kishnani, P S

    2016-04-01

    Antibody responses to life saving therapeutic protein products, such as enzyme replacement therapies (ERT) in the setting of lysosomal storage diseases, have nullified product efficacy and caused clinical deterioration and death despite treatment with immune-suppressive therapies. Moreover, in some autoimmune diseases, pathology is mediated by a robust antibody response to endogenous proteins such as is the case in pulmonary alveolar proteinosis, mediated by antibodies to Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF). In this work, we make the case that in such settings, when the antibody response is high titered, sustained, and refractory to immune suppressive treatments, the antibody response is mediated by long-lived plasma cells which are relatively unperturbed by immune suppressants including rituximab. However, long-lived plasma cells can be targeted by proteasome inhibitors such as bortezomib. Recent reports of successful reversal of antibody responses with bortezomib in the settings of ERT and Thrombotic Thrombocytopenic Purpura (TTP) argue that the safety and efficacy of such plasma cell targeting agents should be evaluated in larger scale clinical trials to delineate the risks and benefits of such therapies in the settings of antibody-mediated adverse effects to therapeutic proteins and autoantibody mediated pathology. PMID:26928739

  19. Spleen Tyrosine Kinase: A Crucial Player and Potential Therapeutic Target in Renal Disease.

    PubMed

    Ma, Terry King-Wing; McAdoo, Stephen P; Tam, Frederick Wai-Keung

    2016-01-01

    Spleen tyrosine kinase (Syk), a 72 kDa cytoplasmic non-receptor protein-tyrosine kinase, plays an important role in signal transduction in a variety of cell types. Ever since its discovery in the early 1990s, there has been accumulating evidence to suggest a pathogenic role of Syk in various allergic disorders, autoimmune diseases and malignancies. Additionally, there is emerging data from both pre-clinical and clinical studies that Syk is implicated in the pathogenesis of proliferative glomerulonephritis (GN), including anti-glomerular basement membrane disease, anti-neutrophil cytoplasmic antibody-associated GN, lupus nephritis and immunoglobulin A nephropathy (IgAN). Moreover, recent animal studies have shed light on the importance of Syk in mediating acute renal allograft rejection, Epstein Barr virus-associated post-transplant lymphoproliferative disease and kidney fibrosis. Fostamatinib, an oral Syk inhibitor, has undergone clinical testing in rheumatoid arthritis, refractory immune thrombocytopenic purpura, leukemia and lymphoma. The recent STOP-IgAN trial showed that the addition of non-selective immunosuppressive therapy to intensive supportive care did not improve clinical outcomes in high-risk IgAN patients. A Syk-targeted approach may be beneficial and is currently being evaluated in a phase II randomized controlled trial. In this review, we will discuss the pathogenic role of Syk and potential use of Syk inhibitor in a variety of renal diseases. PMID:27476075

  20. Bleeding into the skin

    MedlinePlus

    ... 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 ( ...

  1. Genetics Home Reference: immune thrombocytopenia

    MedlinePlus

    ... develop frequent bruising or red or purple spots (purpura) on the skin caused by bleeding just under ... of immune thrombocytopenia: Genetic Testing Registry: Idiopathic thrombocytopenic purpura Johns Hopkins Medicine MedlinePlus Encyclopedia: Idiopathic Thrombocytopenic Purpura ( ...

  2. Endoscopy in neutropenic and/or thrombocytopenic patients

    PubMed Central

    Tong, Michelle C; Tadros, Micheal; Vaziri, Haleh

    2015-01-01

    AIM: To evaluate the safety of endoscopic procedures in neutropenic and/or thrombocytopenic cancer patients. METHODS: We performed a literature search for English language studies in which patients with neutropenia and/or thrombocytopenia underwent endoscopy. Studies were included if endoscopic procedures were used as part of the evaluation of neutropenic and/or thrombocytopenic patients, yielding 13 studies. Two studies in which endoscopy was not a primary evaluation tool were excluded. Eleven relevant studies were identified by two independent reviewers on PubMed, Scopus, and Ovid databases. RESULTS: Most of the studies had high diagnostic yield with relatively low complication rates. Therapeutic endoscopic interventions were performed in more than half the studies, including high-risk procedures, such as sclerotherapy. Platelet transfusion was given if counts were less than 50000/mm3 in four studies and less than 10000/mm3 in one study. Other thrombocytopenic precautions included withholding of biopsy if platelet count was less than 30000/mm3 in one study and less than 20000/mm3 in another study. Two of the ten studies which examined thrombocytopenic patient populations reported bleeding complications related to endoscopy, none of which caused major morbidity or mortality. All febrile neutropenic patients received prophylactic broad-spectrum antibiotics in the studies reviewed. Regarding afebrile neutropenic patients, prophylactic antibiotics were given if absolute neutrophil count was less than 1000/mm3 in one study, if the patient was undergoing colonoscopy and had a high inflammatory condition without clear definition of significance in another study, and if the patient was in an aplastic phase in a third study. Endoscopy was also withheld in one study for severe pancytopenia. CONCLUSION: Endoscopy can be safely performed in patients with thrombocytopenia/neutropenia. Prophylactic platelet transfusion and/or antibiotic administration prior to endoscopy may be

  3. [Henoch-Schonlein purpura involving the penis: a case report].

    PubMed

    Croche Santander, Borja; Campos, Elena; Sánchez, Adela; Marcos, Laura; Díaz, Isabel; Toro, Cristóbal

    2016-08-01

    Schonlein-Henoch purpura accounts for the majority of cases of systemic vasculitis in children. Classical presentation is characterized by palpable purpura, glomerulonephritis, arthralgias and abdominal pain. Although genitourinary manifestations, in form of testicular and scrotal involvement, have been widely described, penile involvement remains an extremely rare complication. We report a case of a 6-year-old boy who presented with purpuric rash on the glans, prepuce and penile shaft, with painful edema in the penile region. He also had a 3-days history of fever, palpable purpuric rash on the buttocks and lower extremities along with right wrist pain. He was admitted with the diagnosis of Schonlein-Henoch purpura with penile involvement. After 2 days on oral steroids therapy (prednisone) a marked improvement was observed. PMID:27399026

  4. Purpura fulminans associated with acute West Nile virus encephalitis.

    PubMed

    Shah, Sheevam; Fite, Laura Paul; Lane, Natalie; Parekh, Palak

    2016-02-01

    Purpura fulminans is a progressive thrombotic disorder that presents with widespread purpura due to deficiency or dysfunction of protein C or protein S. Lesions present as well-demarcated erythematous macules that progress to irregular areas of hemorrhagic necrosis.West Nile virus is a member of the Flaviviridae family transmitted to humans through the bite of various mosquito species. It manifests as West Nile fever in 25% of those infected and less commonly as neuroinvasive disease. An African American man in his fortiespresented with altered mental status and was noted to have evidence of disseminated intravascular coagulation according to his lab data. He then developed dusky skin discoloration and systemic flaccid bullae with desquamation. Biopsy was consistent with purpura fulminans and the patient eventually developed symmetric peripheral gangrene, requiring amputations of all four extremities. Infectious work up revealed positive testing for IgM and IgG antibodies in serum and cerebrospinal fluid leading to the diagnosis of acute West Nile Virus encephalitis. We present this case to describe the rarely reported association of purpura fulminans with West Nile Virus infection.

  5. [Randomized comparison of intravenous immunoglobulin and methylprednisolone pulse therapy in children with newly diagnosed idiopathic thrombocytic purpura. The Danish ITP Study Group].

    PubMed

    Rosthøj, S; Nielsen, S M; Pedersen, F K

    1998-03-01

    Forty three children with newly diagnosed idiopathic thrombocytopenic purpura (ITP), platelet count (pl.c.) below 20 x 10(9)/l, and either clinically significant bleeding or failure to show a spontaneous platelet rise within three days of admission were randomly allocated to treatment with intravenous infusions of either immunoglobulin (IVIG) 1 g/kg or methylprednisolone (MPPT) 30 mg/kg on two consecutive days. Prompt induction of partial remission with pl.c. > 50 x 10(9)/l after 72 hours was seen in 21/23 given IVIG versus 10/20 given MPPT (exact p = 0.003); mean pl.c.s after 72 hours were 188 versus 77 x 10(9)/l (2p < 0.001). Poor responders were then given the alternative infusions in addition. After six days, complete remission with pl.c. > 150 x 10(9)/l was achieved in 16/23 versus 10/20 (p = 0.16). During six months follow-up, there were no significant differences regarding relapse rates or chronic course. Eleven children with relapse were crossed over to the alternative treatment arm: the estimated treatment effect in pl.c. after 72 hours was 134 x 10(9)/l in favour of IVIG. These results indicate that IVIG infusions may be preferable to high-dose corticosteroids as initial treatment for children with ITP. PMID:9522658

  6. Vasculitic purpura in vinyl chloride disease: a case report

    SciTech Connect

    Magnavita, N.; Bergamaschi, A.; Garcovich, A.; Giuliano, G.

    1986-05-01

    Vinyl chloride (VC), a volatile substance mostly used for polyvinyl chloride (PVC) synthesis, is a systemic toxicant particularly noxious to endothelium. Angiosarcoma of the liver, Raynaud's phenomenon, scleroderma-like lesions, acroosteolysis and neuritis are known to be typical vinyl chloride-associated manifestations (VC disease). A so far unknown feature of the disease is purpura. This was first observed by the authors in a worker of a PVC-producing plant. The skin eruption was characterized by small purpuric maculae with tiny, palpable spots and papulae, mostly concentrated on the lower part of the legs, changing into bullae, pustules and crusts and tending to spontaneous regression after withdrawal from VC exposure. A skin biopsy revealed marked inflammatory reaction with a mostly lymphocytic and histiocytic infiltration around and in the walls of dermal arterioles. The finding of increased circulating immune complexes and anti-smooth muscle autoantibodies strengthens the hypothesis that immunologic changes play a role in the appearance of ''vinylic purpura.''

  7. Special Blood Donation Procedures

    MedlinePlus

    ... type of abnormal antibody formation), and thrombotic thrombocytopenic purpura (a rare clotting disorder). In cytapheresis, excess numbers ... generally does not cure them. However, thrombotic thrombocytopenic purpura can be cured with apheresis. Directed or designated ...

  8. What Causes Thrombocytopenia?

    MedlinePlus

    ... Transfusion Disseminated Intravascular Coagulation Immune Thrombocytopenia Thrombotic Thrombocytopenic Purpura Send a link to NHLBI to someone by ... low platelet count. Two examples are thrombotic thrombocytopenic purpura (TTP) and disseminated intravascular coagulation (DIC). TTP is ...

  9. Platelet associated antibodies

    MedlinePlus

    ... of the following: For unknown reasons (idiopathic thrombocytopenic purpura, or ITP ) Side effect of certain drugs such ... 2012:chap 134. Read More Antibody Idiopathic thrombocytopenic purpura (ITP) Platelet count Serum globulin electrophoresis Thrombocytopenia Update ...

  10. Drug-related Henoch-Schönlein Purpura.

    PubMed

    Escudero, A; Lucas, E; Vidal, J B; Sánchez-Guerrero, I; Martínez, A; Illán, F; Ramos, J

    1996-01-01

    We report the case of a patient with Henoch-Schönlein Purpura related to a treatment with cefuroxime and diclofenac who presented important systemic manifestations including a glomerulonephritis with IgA mesangial deposits. Skin testing with beta lactam antibiotics and diclofenac were negative in immediate and late reaction as well as RAST test to penicillins G and V. No cautious administration of drugs was done because of the illness severity. Although a reaction to diclofenac could not be excluded we thought that the more probably implicated drug was cefuroxime because the patient referred a purpuric rash after the intake of cephradine for a mastitis, ten years ago. PMID:8882757

  11. [Use of anti-D (Rh) IgG or intramuscular polyvalent human immunoglobulin in the treatment of chronic autoimmune thrombocytopenic purpura].

    PubMed

    Vizcaíno, G; Diez-Ewald, M; Arteaga-Vizcaíno, M; Torres, E

    1992-01-01

    The present study compares the effect of the intramuscular injection of low doses of IgG anti-D or human polyvalent immunoglobulin (Ig) on the platelet count of patients with CATP. Forty patients (14 children, 26 adults), 11 who had undergone splenectomy, were divided in the following groups of treatment: 20 patients received a single injection of 300 micrograms of IgG anti-D, 6 patients received the same dose as above plus 0.5 mg/kg daily of prednisone v.o and 14 patients received 640 mg of polyvalent Ig. Each patient was sequentially studied by measuring peripheral blood parameters, reticulocyte index, direct Coombs' test and C3-C4 determinations. Their blood group and Rh factor had been previously determined. The platelet response was evaluated as refractory (no response) and favorable (platelet increment over 50,000/microliters compared with initial platelet count). Patients with a favorable response over a month were considered as a prolonged remission. The results showed a favorable platelet response in 74% of the patients that received a single injection of IgG anti-D alone (one of the patients was Rh negative) or associated to prednisone, and 42.8% of the cases when polyvalent Ig was used. The patients who had not undergone splenectomy obtained better results than the group with splenectomy (62% vs 45%) and children showed a better response than adults (78.5% vs 46.1%). Forty five percent of prolonged remissions (including the Rh negative patient) were obtained with both schemes of IgG anti-D administration and only 28.5% when polyvalent Ig was used. The remissions were significantly longer with IgG anti-D (p < 0.01). The hematological and serological parameters did not show any significant modifications in all the cases and there was no adverse effects with the treatment. In conclusion, the intramuscular injection of immunoglobulins, especially IgG anti-D, produce an increase in the platelet count in some patients with CATP, several of them can obtain prolonged remissions, particularly children and patients that had not received immunoglobulins previously. This treatment is safe, ambulatory, easy to administer, and relatively inexpensive.

  12. Multiple myeloma developing during long-term clinical course of refractory immune thrombocytopenic purpura: a case report and review of literature

    PubMed Central

    Yao, Han; Zhang, Xi; Liu, Jia; Zhu, Lidan; Chen, Guo; Wu, Sha; Gao, Lei

    2015-01-01

    Immune thrombocytopenia (ITP) is an acquired, immune-mediated disease that is characterized by increased destruction of platelets by autoantibodies. Although the onset of the disease and clinical course are highly variable, the disease typically has a benign course. ITP associated with multiple myeloma (MM) has been rarely reported; it is even rarer for MM to develop during a long-term ITP (almost 20 years). Here, we first report on a case with a 20-year long clinical course of refractory ITP followed by newly diagnosed MM. PMID:26823908

  13. Simultaneous Manifestation of Chronic Myelomonocytic Leukemia and Multiple Myeloma during Treatment by Prednisolone and Eltrombopag for Immune-Mediated Thrombocytopenic Purpura

    PubMed Central

    Inoue, Morihiro; Kodama, Kenichiro; Uchida, Tomoyuki; Hua, Jian

    2016-01-01

    An 80-year-old man was admitted to our hospital because of severe thrombocytopenia. He was diagnosed with idiopathic thrombocytopenia, and prednisolone together with eltrombopag was started, leading to significant improvement of platelet counts. Four years later, there was a prominent increase of peripheral blood monocytes, which was accompanied by recurrence of thrombocytopenia. Bone marrow aspirates and serum electrophoresis revealed coexistence of chronic myelomonocytic leukemia (CMML) and multiple myeloma (MM). The patient received lenalidomide plus dexamethasone therapy but died due to exacerbation of the disorder. It was supposed that thrombocytopenia was secondarily caused by CMML and MM developed at a later period. PMID:27597907

  14. Simultaneous Manifestation of Chronic Myelomonocytic Leukemia and Multiple Myeloma during Treatment by Prednisolone and Eltrombopag for Immune-Mediated Thrombocytopenic Purpura.

    PubMed

    Hagihara, Masao; Inoue, Morihiro; Kodama, Kenichiro; Uchida, Tomoyuki; Hua, Jian

    2016-01-01

    An 80-year-old man was admitted to our hospital because of severe thrombocytopenia. He was diagnosed with idiopathic thrombocytopenia, and prednisolone together with eltrombopag was started, leading to significant improvement of platelet counts. Four years later, there was a prominent increase of peripheral blood monocytes, which was accompanied by recurrence of thrombocytopenia. Bone marrow aspirates and serum electrophoresis revealed coexistence of chronic myelomonocytic leukemia (CMML) and multiple myeloma (MM). The patient received lenalidomide plus dexamethasone therapy but died due to exacerbation of the disorder. It was supposed that thrombocytopenia was secondarily caused by CMML and MM developed at a later period. PMID:27597907

  15. Urological Manifestations of Henoch-Schonlein Purpura: A Review

    PubMed Central

    Dalpiaz, Amanda; Schwamb, Richard; Miao, Yimei; Gonka, Jacquelyn; Walzter, Wayne; Khan, Sardar A.

    2015-01-01

    Henoch-Schonlein purpura (HSP) is an immune-mediated systemic vasculitis generally found in children. The standard manifestations of HSP are palpable purpura, arthritis, abdominal pain, and renal complications. Although less common, there are significant urological manifestations associated with HSP. The primary objective of this review is to encourage better understanding and management of HSP by emphasizing the common and rare manifestations of HSP, how they are diagnosed, and the latest treatment options for mild to severe complications. Medline searches of HSP and its urological manifestations were conducted along with searches on current diagnostic and treatment methods. Urological manifestations of HSP involve the kidney, ureter, bladder, prostate, scrotum, testicle, and penis. Diagnosis and management of HSP are not always clear due to differential diagnosis and diversity of symptom presentation. Treatment for HSP is mainly supportive and includes use of nonsteroidal anti-inflammatory drugs for pain relief. In more severe cases, glucocorticoids, methylprednisolone, plasmapheresis, and peritoneal and hemodialysis are reported successful. It is important to note different symptoms of HSP in order to distinguish HSP from other diseases. Early diagnosis may prevent severe complications. Treatment options vary from conservative to invasive depending on the severity of the disease and time frame of diagnosis. PMID:26889120

  16. Henoch-Schonlein purpura nephritis: pathophysiology, treatment, and future strategy.

    PubMed

    Davin, Jean-Claude

    2011-03-01

    Henoch-Schönlein purpura nephritis is a rare kidney disease leading to chronic kidney disease in a non-negligible percentage of patients. Although retrospective studies suggest beneficial effects of some therapies, prospective randomized clinical trials proving treatment efficacy are still lacking. The dilemma of spontaneous recovery even in patients with severe clinical and histologic presentation and of late evolution to chronic kidney disease in patients with mild initial symptoms renders it difficult for clinicians to expose patients to treatment protocols that are not evidence-based. A better understanding of the pathophysiology of progression to chronic kidney disease in Henoch-Schönlein purpura patients could be achieved by designing prospective international multicenter studies looking at determinants of clinical and histopathological evolution as well as possible circulating and urinary markers of progression. Such studies should be supported by a database available on the web and a new histologic classification of kidney lesions. This paper reports clinical, pathologic, and experimental data to be used for this strategy and to assist clinicians and clinical trial designers to reach therapeutic decisions.

  17. /sup 111/In-oxine platelet survivals in thrombocytopenic infants

    SciTech Connect

    Castle, V.; Coates, G.; Kelton, J.G.; Andrew, M.

    1987-09-01

    Thrombocytopenia is a common occurrence (20%) in sick neonates, but the causes have not been well studied. In this report we demonstrate that thrombocytopenia in the neonate is characterized by increased platelet destruction as shown by shortened homologous /sup 111/In-oxine-labeled platelet life spans. Thirty-one prospectively studied thrombocytopenic neonates were investigated by measuring the /sup 111/In-labeled platelet life span, platelet-associated IgG (PAIgG), and coagulation screening tests. In every infant, the thrombocytopenia was shown to have a destructive component since the mean platelet life span was significantly shortened to 65 +/- 6 (mean +/- SEM) hours with a range of one to 128 hours compared with adult values (212 +/- 8; range, 140 to 260; gamma function analysis). The platelet survival was directly related to the lowest platelet count and inversely related to both the highest mean platelet volume and duration of the thrombocytopenia. In 22 infants the percent recovery of the radiolabeled platelets was less than 50%, which suggested that increased sequestration also contributed to the thrombocytopenia. Infants with laboratory evidence of disseminated intravascular coagulation (n = 8) or immune platelet destruction evidenced by elevated levels of PAIgG (n = 13) had even shorter platelet survivals and a more severe thrombocytopenia compared with the ten infants in whom an underlying cause for the thrombocytopenia was not apparent. Full-body scintigraphic images obtained in 11 infants showed an increased uptake in the spleen and liver, with a spleen-to-liver ratio of 3:1. This study indicates that thrombocytopenia in sick neonates is primarily destructive, with a subgroup having evidence of increased platelet sequestration.

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

    PubMed

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

    2007-04-01

    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

  19. Acute Scrotal Swelling in Henoch-Schonlein Purpura: Case Report and Review of the Literature

    PubMed Central

    Modi, Sunny; Mohan, Muhunthan; Jennings, Andrew

    2016-01-01

    Henoch-Schönlein purpura (HSP) is a systemic vasculitis characterized classically by purpura, arthritis and abdominal pain. Epididymitis/orchitis is rarely seen as a complication of HSP. Testicular or scrotal involvement has been reported in children with Henoch-Schonlein purpura and must be distinguished from testicular torsion. We report a case of a 5 year old boy diagnosed with Henoch-Schönlein purpura with acute scrotal swelling. He was managed successfully with conservative approach. The history, clinical examination findings and scrotal ultrasound evaluation should suffice to make the correct diagnosis and avoid surgery. Steroid treatment and/or antibiotics appeared to be effective for this condition. PMID:27169017

  20. Purpura fulminans associated with Streptococcus pneumoniae septicemia in an asplenic pediatric patient.

    PubMed

    Konda, S; Zell, D; Milikowski, C; Alonso-Llamazares, J

    2013-09-01

    Purpura fulminans is a rapidly progressive syndrome of small-vessel thrombosis and hemorrhagic necrosis of the skin accompanied by disseminated intravascular coagulation. We describe a case of Streptococcus pneumoniae septicemia in an asplenic 5-year-old boy on oral tacrolimus, with a past medical history of multivisceral organ transplantation and subsequent development of purpura fulminans on his chest and distal extremities. The acute infectious form of purpura fulminans is usually caused by gram-negative bacteria. Cases secondary to gram-positive encapsulated bacteria usually occur when individuals are immuno-suppressed or have anatomic or functional asplenia. Our patient had both, which likely increased his susceptibility, and he responded well to antimicrobial therapy in addition to prophylactic coverage in the setting of his immunosuppression. We review the literature for similar cases due to S. pneumoniae in the pediatric population and discuss the etiology and treatment of purpura fulminans. PMID:23985086

  1. Purpura fulminans associated with Streptococcus pneumoniae septicemia in an asplenic pediatric patient.

    PubMed

    Konda, S; Zell, D; Milikowski, C; Alonso-Llamazares, J

    2013-09-01

    Purpura fulminans is a rapidly progressive syndrome of small-vessel thrombosis and hemorrhagic necrosis of the skin accompanied by disseminated intravascular coagulation. We describe a case of Streptococcus pneumoniae septicemia in an asplenic 5-year-old boy on oral tacrolimus, with a past medical history of multivisceral organ transplantation and subsequent development of purpura fulminans on his chest and distal extremities. The acute infectious form of purpura fulminans is usually caused by gram-negative bacteria. Cases secondary to gram-positive encapsulated bacteria usually occur when individuals are immuno-suppressed or have anatomic or functional asplenia. Our patient had both, which likely increased his susceptibility, and he responded well to antimicrobial therapy in addition to prophylactic coverage in the setting of his immunosuppression. We review the literature for similar cases due to S. pneumoniae in the pediatric population and discuss the etiology and treatment of purpura fulminans.

  2. Henoch-Schönlein Purpura Associated with Gangrenous Appendicitis: A Case Report

    PubMed Central

    SEMEENA, NK; ADLEKHA, Shashikant

    2014-01-01

    Henoch-Schönlein Purpura (HSP) is a leucocytoclastic vasculitis of unclear aetiology characterised by symmetrical, non-traumatic, nonthrombocytopenic purpura mostly involving the lower limbs and buttocks, as well as arthritis, gastrointestinal manifestations, and occasional nephritis. A 35 years old male presented with purpuric rash on the lower extremities, abdominal pain, fever, arthralgia, and melaena. A diagnosis of HSP with appendicitis was made, which is an exceedingly rare phenomenon. PMID:24876811

  3. Henoch-Schönlein purpura with c-ANCA antibody in an adult*

    PubMed Central

    Torraca, Pedro de Freitas Silva; de Castro, Bruna Corrêa; Hans Filho, Günter

    2016-01-01

    The Henoch-Schönlein purpura is the vasculitis associated with deposits of immunoglobulin A in small vessels. Its association with cytoplasmic antineutrophil cytoplasmic antibodies is possible, but rare. This vasculitis is uncommon in adults and the main clinic manifestations are purpuric lesions in lower limbs with gastrointestinal symptoms and renal involvement. The present work describes a rare case of Henoch-Schönlein purpura in an adult with cytoplasmic antineutrophil cytoplasmic antibodies.

  4. Purpura fulminans secondary to rickettsial infections: A case series

    PubMed Central

    Katoch, Saloni; Kallappa, Ravindra; Shamanur, Murugesh B.; Gandhi, Sneha

    2016-01-01

    Purpura fulminans (PF) is a descriptive term used to describe a heterogeneous group of disorders characterized by rapidly progressive purpuric lesions that may develop into extensive areas of skin necrosis, and peripheral gangrene. This rare disorder is associated with laboratory evidence of consumptive coagulopathy and is often fatal. PF is usually associated with many infections, most notably with meningococcal, staphylococcal, and streptococcal infections. However, there are very few reports of this entity with spotted fever and scrub typhus from India. Rickettsial infections are an underdiagnosed group of diseases presenting as acute febrile illness, with high mortality in untreated cases. Of the available tests, Weil–Felix is a handy and economical tool for early diagnosis of this fatal disease especially in resource poor settings. We present four infants with PF secondary to rickettsial fever diagnosed by the Weil–Felix test. PMID:26955583

  5. Relapses in patients with Henoch–Schönlein purpura

    PubMed Central

    Calvo-Río, Vanesa; Hernández, José Luis; Ortiz-Sanjuán, Francisco; Loricera, Javier; Palmou-Fontana, Natalia; González-Vela, Maria C.; González-Lamuño, Domingo; González-López, Marcos A.; Armesto, Susana; Blanco, Ricardo; González-Gay, Miguel A.

    2016-01-01

    Abstract To further investigate into the relapses of Henoch–Schönlein purpura (HSP), we analyzed the frequency, clinical features, and predictors of relapses in series of 417 unselected patients from a single center. After a median follow-up of 12 (interquartile range [IQR]: 2–38) years, almost one-third of the 417 patients (n = 133; 32%; 85 men/48 women) had experienced at least 1 relapse. At the time of disease diagnosis, patients who later experienced relapses had less commonly infections than those who never suffered flares (30.8% vs 41.9%; P = 0.03). In contrast, patients who experienced relapses had a longer duration of the first episode of palpable purpura than those without relapses (palpable purpura lasting >7 days; 80.0% vs 68.1%; P = 0.04). Abdominal pain (72.3% vs 62.3%; P = 0.03) and joint manifestations (27.8% vs 15.5%; P = 0.005) were also more common in patients who later developed relapses. In contrast, patients who never suffered relapses had a slightly higher frequency of fever at the time of disease diagnosis (9.3% vs 3.8%; P = 0.06). At the time of disease diagnosis, corticosteroids were more frequently given to patients who later had relapses of the disease (44% vs 32% in nonrelapsing patients; P = 0.03). Relapses generally occurred soon after the first episode of vasculitis. The median time from the diagnosis of HSP to the first relapse was 1 (IQR: 1–2) month. The median number of relapses was 1 (IQR 1–3). The main clinical features at the time of the relapse were cutaneous (88.7%), gastrointestinal (27.1%), renal (24.8%), and joint (16.5%) manifestations. After a mean ± standard deviation follow-up of 18.9 ± 9.8 years, complete recovery was observed in 110 (82.7%) of the 133 patients who had relapses. Renal sequelae (persistent renal involvement) was found in 11 (8.3%) of the patients with relapses. The best predictive factors for relapse were joint and gastrointestinal manifestations at HSP diagnosis (odds ratio [OR]: 2

  6. Mathematical model of platelet turnover in thrombocytopenic and nonthrombocytopenic preterm neonates.

    PubMed

    Kulshrestha, Mudit; Sola-Visner, Martha; Widness, John A; Veng-Pedersen, Peter; Mager, Donald E

    2015-01-01

    Neonatal thrombocytopenia affects 22-35% of all neonates admitted to neonatal intensive care units. The purpose of this study was to develop a mathematical model for characterizing platelet (PLT) kinetics in thrombocytopenic preterm neonates. Immature PLT fraction (IPF) and PLT counts were measured for up to 35 days after birth in 27 very low birth weight preterm neonates. PLT transfusions were administered to 8 of the 27 (24%) subjects. The final model included a series of four transit compartments to mimic the production and survival of IPF and PLT. Model parameters were estimated using nonlinear mixed effects modeling with the maximum likelihood expectation maximization algorithm. The model adequately captured the diverse phenotypes expressed by individual subject profiles. Typical population survival values for IPF and PLT life spans in nonthrombocytopenic patients were estimated at 0.912 and 10.7 days, respectively. These values were significantly shorter in thrombocytopenic subjects, 0.429 and 2.56 days, respectively. The model was also used to evaluate the influence of growth and laboratory phlebotomy loss on the time course of IPF and PLT counts. Whereas incorporating body weight was essential to correct for expanding blood volume due to growth, phlebotomy loss, a possible covariate, did not significantly influence PLT kinetics. This study provides a platform for identifying potential covariates that influence the interindividual variability in model parameters regulating IPF and PLT kinetics and for evaluating future pharmacological therapies for treating thrombocytopenic neonates. PMID:25362135

  7. A case of neutrophilic dermatosis who develop palpable purpura during the use of montelukast

    PubMed Central

    Çetin, Gözde Yıldırım; Sayarlıoğlu, Hayriye; Erhan, Çiğdem; Kahraman, Hasan; Cıralık, Harun; Sayarlıoğlu, Mehmet

    2014-01-01

    In this case report, we present a female patient with neutrophilic dermatosis (ND) occurring as palpable purpura after using montelukast. Neutrophilic dermatoses (NDs) are characterized by skin lesions in which mature neutrophils are predominantly located in the epidermis and dermis in the absence of any infective pathology. Classification of the NDs is based upon the recognition of clinical and pathologic features, as well as the identification of associated diseases, like Sweet’s syndrome, pyoderma gangrenosum, generalized pustular psoriasis, and Behçet’s disease. Cutaneous findings in NDs are variable and can include vesiculopustules, plaques, nodules, or ulcerations. Drug-induced NDs are not uncommon, but ND with palpable purpura is uncommon. The current patient appeared with a rare presentation as palpable purpura without vasculitis regarding ND. It is important that this is the first case report. PMID:27708908

  8. [Henoch-Schönlein Purpura with lung abscess].

    PubMed

    Nakazawa, Junji; Watanabe, Atsushi; Nakajima, Tomohiro; Mishina, Taijiro; Miyajima, Masahiro; Higami, Tetsuya

    2013-09-01

    A 72-year-old man had underwent left lower lobectomy for squamous cell carcinoma in our hospital in 2008. Postoperative stage was I A (T1N0M0). In 2010, follow-up chest computed tomography (CT) images showed similar cavitary nodules in segments 2 and 8 of the right lung with positive uptake on fluorodeoxyglucose-positron emission tomography (FDG-PET) images. Physical examination, blood tests, and levels of serum tumor markers showed no abnormality. Transbronchial lung biopsy revealed the absence of malignant cells. Segment 8 of the right lower lobe with the nodule was partially resected, and pathological examination demonstrated lung abscess. He was discharged but was hospitalized in another hospital for purpuric rash, fever, and arthralgia. Microscopic albuminuria was noted, and renal biopsy revealed nephritis with immunoglobulin A( IgA)deposition. He was made a diagnosis of Henoch-Schönlein purpura. Oral steroid therapy( prednisolone 60 mg/d) was initiated, resulting in the improvement of symptoms and disapearance of the cavitary nodule in the right lung segment 2. PMID:24008637

  9. Severe myalgia of the lower extremities as the first clinical feature of meningococcal purpura fulminans.

    PubMed

    de Souza, Alexandre Leite; Sztajnbok, Jaques; Salgado, Maristela Marques; Romano, Carla C; Alkmin, Maria das Graças Adelino; Duarte, Alberto J S; Seguro, Antonio Carlos

    2007-10-01

    In patients with meningococcal infection, devastating presentations, such as purpura fulminans, which can progress to extensive tissue necrosis of the limbs and digits, have a significant social impact. The case presented herein illustrates such a phenomenon in a patient who developed bilateral necrosis of the lower extremities as a result of infection with Neisseria meningitis. We emphasize that severe myalgia was the first clinical manifestation of meningococcal purpura fulminans in our case. However, myalgia has typically been overlooked and undervalued as an early clinical feature of meningococcal sepsis. Early recognition and prompt initial antibiotic therapy continue to be the cornerstones of the successful management of this dramatic disease, reducing morbidity and mortality.

  10. Gastrointestinal manifestations of Henoch-Schonlein purpura: A report of two cases.

    PubMed

    Prathiba Rajalakshmi, Parameswaran; Srinivasan, Kalyanasundaram

    2015-03-28

    Henoch-Schonlein purpura (HSP) is a small vessel vasculitis mediated by type III hypersensitivity with deposition of IgA immune complex in the walls of vessels. It is a multi-system disorder characterized by palpable purpura, arthritis, glomerulonephritis and gastrointestinal manifestations and commonly occurs in children and young adults. The patients with gastrointestinal involvement usually present with colicky abdominal pain, vomiting and melena. The imaging findings include multifocal bowel thickening with mucosal hyperenhancement, presence of skip areas, mesenteric vascular engorgement, with involvement of unusual sites like stomach, duodenum and rectum. These imaging findings in a child or young adult with appropriate clinical findings could suggest HSP. PMID:25825636

  11. Gastrointestinal manifestations of Henoch-Schonlein purpura: A report of two cases

    PubMed Central

    Prathiba Rajalakshmi, Parameswaran; Srinivasan, Kalyanasundaram

    2015-01-01

    Henoch-Schonlein purpura (HSP) is a small vessel vasculitis mediated by type III hypersensitivity with deposition of IgA immune complex in the walls of vessels. It is a multi-system disorder characterized by palpable purpura, arthritis, glomerulonephritis and gastrointestinal manifestations and commonly occurs in children and young adults. The patients with gastrointestinal involvement usually present with colicky abdominal pain, vomiting and melena. The imaging findings include multifocal bowel thickening with mucosal hyperenhancement, presence of skip areas, mesenteric vascular engorgement, with involvement of unusual sites like stomach, duodenum and rectum. These imaging findings in a child or young adult with appropriate clinical findings could suggest HSP. PMID:25825636

  12. Maternal anti-HLA class I antibodies are associated with reduced birth weight in thrombocytopenic neonates.

    PubMed

    Dahl, J; Husebekk, A; Acharya, G; Flo, K; Stuge, T B; Skogen, B; Straume, B; Tiller, H

    2016-02-01

    In this comparative cross-sectional study, possible associations between maternal anti-HLA class I antibodies and birth weight in neonatal thrombocytopenia are explored. Although commonly detected in pregnancies and generally regarded as harmless, it has been suggested that such antibodies might be associated with fetal and neonatal alloimmune thrombocytopenia (FNAIT). As a link between FNAIT due to human platelet antigen 1a-specific antibodies and reduced birth weight in boys has previously been demonstrated, we wanted to explore whether maternal anti-HLA class I antibodies might also affect birth weight. To examine this, suspected cases of FNAIT referred to the Norwegian National Unit for Platelet Immunology during the period 1998-2009 were identified. Pregnancies where the only finding was maternal anti-HLA class I antibodies were included. An unselected group of pregnant women participating in a prospective study investigating maternal-fetal hemodynamics at the University Hospital North Norway during the years 2006-2010 served as controls. Twenty-nine percent of controls had anti-HLA class I antibodies. The thrombocytopenic neonates had a significantly lower adjusted birth weight (linear regression, P=0.036) and significantly higher odds of being small for gestational age (OR=6.72, P<0.001) compared with controls. Increasing anti-HLA class I antibody levels in the mother were significantly associated with lower birth weight and placental weight among thrombocytopenic neonates, but not among controls. These results indicate that maternal anti-HLA class I antibodies in thrombocytopenic neonates are associated with reduced fetal growth. Further studies are needed to test if placental function is affected.

  13. Group A Escherichia coli-Related Purpura Fulminans: an Unusual Manifestation Due to an Unusual Strain?

    PubMed Central

    Amara, Marlène; Bonacorsi, Stéphane; Bedel, Jérôme; Mira, Jean-Paul; Laurent, Virginie; Socha, Koryna; Bruneel, Fabrice; Pangon, Béatrice; Bédos, Jean-Pierre

    2014-01-01

    We describe an exceptional case of life-threatening group A Escherichia coli-induced purpura fulminans. Genotyping of common polymorphisms in genes involved in innate immunity or coagulation did not reveal known susceptibility to such a manifestation. Genetic analysis of the strain revealed an unusual conserved virulence plasmidic region, pointing out its potential virulence. PMID:25232165

  14. Thromboelastometric Monitoring of the Hemostatic Effect of Platelet Concentrates Transfusion in Thrombocytopenic Children Undergoing Chemotherapy

    PubMed Central

    Solomon, Cristina; Cadamuro, Janne; Jones, Neil

    2015-01-01

    Prophylactic platelet concentrates transfusion represents a therapeutic choice in patients with chemotherapy-induced thrombocytopenia. This prospective, non-interventional study evaluated the effects of platelet concentrates transfusion on thromboelastometric parameters of platelet function in 36 transfusion occasions for 11 thrombocytopenic children undergoing chemotherapy. Pre- and posttransfusion (1-2 hours) blood samples were analyzed using standard coagulation tests and thromboelastometry (ROTEM) measurements (EXTEM and FIBTEM tests). Platelet component of the clot was calculated based on the EXTEM and FIBTEM maximum clot elasticity (MCE) results. After transfusion, mean platelet count increased from 16.5 × 109/L to 43.0 × 109/L (P < .001) and platelet component increased from 34.1 to 73.0 (P < .001). Statistically significant increases for posttransfusion EXTEM parameters A10, A20, and maximum clot firmness (MCF) were observed compared to pretransfusion values (P < .001). The EXTEM α-angle values increased posttransfusion (P < .05). The FIBTEM measurements were comparable pre- and posttransfusion. The study showed that platelet concentrates transfusion in thrombocytopenic children undergoing chemotherapy improves platelet-related coagulation pattern. PMID:25525046

  15. Antigenic Complementarity in the Origins of Autoimmunity: A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura

    PubMed Central

    Root-Bernstein, Robert; Couturier, Jacob

    2006-01-01

    We describe a novel, testable theory of autoimmunity, outline novel predictions made by the theory, and illustrate its application to unravelling the possible causes of idiopathic thrombocytopenia purpura (ITP). Pairs of stereochemically complementary antigens induce complementary immune responses (antibody or T-cell) that create loss of regulation and civil war within the immune system itself. Antibodies attack antibodies creating circulating immune complexes; T-cells attack T-cells creating perivascular cuffing. This immunological civil war abrogates the self-nonself distinction. If at least one of the complementary antigens mimics a self antigen, then this unregulated immune response will target host tissues as well. Data demonstrating that complementary antigens are found in some animal models of autoimmunity and may be present in various human diseases, especially ITP, are reviewed. Specific mechanisms for preventing autoimmunity or suppressing existing autoimmunity are derived from the theory, and critical tests proposed. Finally, we argue that Koch's postulates are inadequate for establishing disease causation for multiple-antigen diseases and discuss the possibility that current research has failed to elucidate the causes of human autoimmune diseases because we are using the wrong criteria. PMID:16603444

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

    PubMed Central

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

    2013-01-01

    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

  17. Association of endothelial nitric oxide synthase gene polymorphism with the risk of Henoch-Schönlein purpura/Henoch-Schönlein purpura nephritis.

    PubMed

    Zhong, Weiqiang; Zhou, Tian-Biao; Jiang, Zongpei

    2015-04-01

    Association between endothelial nitric oxide synthase (eNOS) gene polymorphism and Henoch-Schönlein purpura (HSP)/Henoch-Schönlein purpura nephritis (HSPN) risk is still controversial. A meta-analysis was performed to evaluate the association between eNOS gene polymorphism and HSP/HSPN susceptibility. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic database. Three articles were identified for the analysis of association between eNOS gene polymorphism and HSPN/HSP risk. eNOS G894T gene polymorphism was not associated with HSPN susceptibility and the risk of patients with HSP developing into HSPN. Interestingly, eNOS G894T T allele and GG genotype were associated with HSP susceptibility, but not the TT genotype. eNOS T786C TT genotype was associated with HSPN susceptibility, but not C allele and CC genotype. Furthermore, eNOS T786C gene polymorphism was not associated with HSP risk and the risk of patients with HSP developing into HSPN. In conclusion, eNOS T786C TT genotype was associated with and eNOS G894T T allele and GG genotype were associated with HSP susceptibility. However, more studies should be performed in the future. PMID:25585947

  18. Sirolimus for Autoimmune Disease of Blood Cells

    ClinicalTrials.gov

    2016-04-22

    Autoimmune Pancytopenia; Autoimmune Lymphoproliferative Syndrome (ALPS); Evans Syndrome; Idiopathic Thrombocytopenic Purpura; Anemia, Hemolytic, Autoimmune; Autoimmune Neutropenia; Lupus Erythematosus, Systemic; Inflammatory Bowel Disease; Rheumatoid Arthritis

  19. Bruising and Bleeding

    MedlinePlus

    ... or purple dots (petechiae), red or purple patches (purpura), bruises (ecchymoses), or small blood vessels that are ... syndrome HIV infection Immune thrombocytopenia Leukemia Thrombotic thrombocytopenic purpura Increased number of platelets (which often causes excessive ...

  20. Platelet Count

    MedlinePlus

    ... rash Small purplish spots on the skin called purpura, caused by bleeding under the skin Testing may ... Idiopathic thrombocytopenia (ITP), also known as immune thrombocytopenic purpura, is the result of antibody production against platelets. ...

  1. How Is Immune Thrombocytopenia Treated?

    MedlinePlus

    ... Blood Transfusion Bone Marrow Tests Thrombocytopenia Thrombotic Thrombocytopenic Purpura Send a link to NHLBI to someone by ... who have bleeding symptoms, other than merely bruising (purpura), usually are treated. Children who have mild ITP ...

  2. Anaphylactoid Purpura Manifested after Acute Gastroenteritis with Severe Dehydration in an 8-Year-Old Male Child: A Case Report.

    PubMed

    Thakkar, Umang G; Vanikar, Aruna V; Trivedi, Hargovind L

    2015-12-01

    Anaphylactoid purpura, also known as Henoch-Schönleinpurpura (HSP), is an IgA-mediated vasculitis that tends to be a benign disease of childhood. Up to 50% of cases are preceded by an upper tract respiratory infection caused by group-A beta-hemolytic streptococcus and present with the common tetrad of abdominal pain, arthritis, purpuric rash, and renal involvement. The majority of patients recover completely. Here we document a rare case of anaphylactoid purpura which manifested with skin lesions in the form of palpable purpura following about of acute gastroenteritis with severe dehydration; it was treated with a short regimen of steroid therapy, which resulted in the complete remission of the disease. We conclude that prompt diagnosis and multidisciplinary intervention will lead to appropriate management-consisting of the installation of early short-course steroid therapy and thus, prevent further complications and the recurrence of the disease. PMID:26602584

  3. Effects of increased von Willebrand factor levels on primary hemostasis in thrombocytopenic patients with liver cirrhosis.

    PubMed

    Wannhoff, Andreas; Müller, Oliver J; Friedrich, Kilian; Rupp, Christian; Klöters-Plachky, Petra; Leopold, Yvonne; Brune, Maik; Senner, Mirja; Weiss, Karl-Heinz; Stremmel, Wolfgang; Schemmer, Peter; Katus, Hugo A; Gotthardt, Daniel N

    2014-01-01

    In patients with liver cirrhosis procoagulant and anticoagulant changes occur simultaneously. During primary hemostasis, platelets adhere to subendothelial structures, via von Willebrand factor (vWF). We aimed to investigate the influence of vWF on primary hemostasis in patients with liver cirrhosis. Therefore we assessed in-vitro bleeding time as marker of primary hemostasis in cirrhotic patients, measuring the Platelet Function Analyzer (PFA-100) closure times with collagen and epinephrine (Col-Epi, upper limit of normal ≤ 165 s) or collagen and ADP (Col-ADP, upper limit of normal ≤ 118 s). If Col-Epi and Col-ADP were prolonged, the PFA-100 was considered to be pathological. Effects of vWF on primary hemostasis in thrombocytopenic patients were analyzed and plasma vWF levels were modified by adding recombinant vWF or anti-vWF antibody. Of the 72 included cirrhotic patients, 32 (44.4%) showed a pathological result for the PFA-100. They had mean closure times (± SD) of 180 ± 62 s with Col-Epi and 160 ± 70 s with Col-ADP. Multivariate analysis revealed that hematocrit (P = 0.027) and vWF-antigen levels (P = 0.010) are the predictors of a pathological PFA-100 test in cirrhotic patients. In 21.4% of cirrhotic patients with platelet count ≥ 150/nL and hematocrit ≥ 27.0%, pathological PFA-100 results were found. In thrombocytopenic (< 150/nL) patients with cirrhosis, normal PFA-100 results were associated with higher vWF-antigen levels (462.3 ± 235.9% vs. 338.7 ± 151.6%, P = 0.021). These results were confirmed by multivariate analysis in these patients as well as by adding recombinant vWF or polyclonal anti-vWF antibody that significantly shortened or prolonged closure times, respectively. In conclusion, primary hemostasis is impaired in cirrhotic patients. The effect of reduced platelet count in cirrhotic patients can at least be partly compensated by increased vWF levels. Recombinant vWF could be an alternative to platelet transfusions in the future.

  4. Purpura Fulminans Associated with Hemiparesis Following Measles Infection in a Nigerian Girl: A Case Report

    PubMed Central

    Ibrahim, Aliyu

    2013-01-01

    Purpura fulminans is a life-threatening hematologic emergency characterized by extensive skin necrosis with hemorrhagic infarction, hypotension and gangrene which may arise from severe sepsis; mostly gram negative sepsis though also associated with some gram positive organisms, similarly viral infections like varicella and measles have been implicated; it may also arise from congenital deficiency of the anticoagulants protein C, S, and antithrombin III; and it may also be idiopathic. Its clinical manifestation may be quite extensive resulting in multiorgan failure. Treatment will require aggressive management with use of fresh frozen plasma, heparin, antibiotics, and surgical debridement of necrotic tissue. PMID:26664850

  5. Koebner's Phenomenon in Childhood Henoch-Schönlein Purpura: A Report of Two Cases.

    PubMed

    Sharma, Shreya; Chandrasekaran, Venkatesh; Krishnamurthy, Sriram; Mekala, Suresh; Mahadevan, Subramanian

    2016-07-01

    Koebner's phenomenon occurs rarely in connection with Henoch-Schönlein purpura (HSP). We report two children with HSP who developed Koebner's phenomenon on the second day after the onset of rash. The first was an 11-year-old girl with rheumatic heart disease who presented with abdominal pain for 1 month and subsequently developed rash and nephritis. The second patient was a 7-year-old girl who presented with rash and polyarthritis. To the best of our knowledge, Koebner's phenomenon in childhood HSP has not been reported. PMID:27282588

  6. Adult Onset Henoch-Schonlein Purpura and Intussusception: A Rare Presentation

    PubMed Central

    Nahas, Joseph

    2016-01-01

    We present an unusual case of a young 26-year-old male who was diagnosed with Henoch-Schonlein Purpura (HSP). Initial presentation was primarily mild gastrointestinal symptoms, which progressed to a life threatening intussusception and subsequently resolved with prompt glucocorticoid use rather than typical surgical intervention. Of importance, the patient's initial gastrointestinal symptoms without associated skin manifestations made the diagnosis difficult. In conclusion, it is important to recognize uncommon presentations of HSP as it may lead to life threatening complications and surgical intervention may be avoided with prompt treatment.

  7. [Successful treatment of allergic purpura nephritis associated with thrombotic microangiopathy using plasma exchange: a case report].

    PubMed

    Kuwabara, Takashige; Ohnishi, Takahiro; Kakuta, Yutaka; Nomura, Shinsuke; Joh, Kensuke

    2004-01-01

    A 73-year-old man, who had an allergy to shellfish, was admitted to our hospital because of proteinuria, hematuria, purpura and extremity edema after eating oysters. Laboratory data on admission were proteinuria 2.0 g/day, hematuria 3+, serum creatinine (Cr) 1.2 mg/dl, total protein 6.3 g/dl, and albumin 3.1 g/dl. He presented a high fever with neutrophilia and rapid deterioration of renal function after admission. Based on the skin biopsy, we made a diagnosis of leukocytoclastic vasculitis with IgA deposition. Oral prednisolone (40 mg/day) following drip intravenous methylprednisolone (500 mg/day, 3 days) was administered. However, renal function and urinary findings showed no sign of improvement. In the first renal biopsy, although there were no crescentic formations, most of the glomeruli showed thrombotic microangiopathy and endocapillary proliferation with IgA deposition and electron dense deposits. Therefore, a plasma exchange was performed resulting in an improvement of the renal function. The serum Cr. level was reduced from 2.7 to 0.8 mg/dl and proteinuria from 3.7 to 0.1 g/day. In the second biopsy, the electron dense deposits with an IgA deposition had disappeared. These findings suggested that plasma exchange was effective in leading remission in a case of allergic purpura nephritis associated with thrombotic microangiopathy.

  8. Immunoglobulin A multiple myeloma presenting with Henoch-Schönlein purpura associated with reduced sialylation of IgA1.

    PubMed

    Van Der Helm-Van Mil, Annette H M; Smith, Alice C; Pouria, Shideh; Tarelli, Edward; Brunskill, Nigel J; Eikenboom, Heroen C J

    2003-09-01

    Henoch-Schönlein purpura is characterized by immunoglobulin A1 (IgA1) depositions in blood vessels of the skin or in glomeruli, resulting from altered hinge region O-glycosylation. Henoch-Schönlein purpura is seldom reported as a complication of IgA1 myeloma, even when the circulating IgA concentration is very high. We report two patients with IgA1 myeloma presenting with Henoch-Schönlein purpura. The O-glycosylation of these patients' IgA1 was studied. Both patients showed increased binding to peanut agglutinin lectin, suggesting a low degree of sialylation of the hinge region of IgA1 that was confirmed by mass spectrometry. IgA multiple myeloma, secreting IgA1 molecules with decreased sialylation, presenting with a Henoch-Schönlein purpura-like syndrome was diagnosed.

  9. Immunoglobulin A multiple myeloma presenting with Henoch-Schönlein purpura associated with reduced sialylation of IgA1.

    PubMed

    Van Der Helm-Van Mil, Annette H M; Smith, Alice C; Pouria, Shideh; Tarelli, Edward; Brunskill, Nigel J; Eikenboom, Heroen C J

    2003-09-01

    Henoch-Schönlein purpura is characterized by immunoglobulin A1 (IgA1) depositions in blood vessels of the skin or in glomeruli, resulting from altered hinge region O-glycosylation. Henoch-Schönlein purpura is seldom reported as a complication of IgA1 myeloma, even when the circulating IgA concentration is very high. We report two patients with IgA1 myeloma presenting with Henoch-Schönlein purpura. The O-glycosylation of these patients' IgA1 was studied. Both patients showed increased binding to peanut agglutinin lectin, suggesting a low degree of sialylation of the hinge region of IgA1 that was confirmed by mass spectrometry. IgA multiple myeloma, secreting IgA1 molecules with decreased sialylation, presenting with a Henoch-Schönlein purpura-like syndrome was diagnosed. PMID:12956761

  10. Henoch Schonlein Purpura as a Cause of Renal Failure in an Adult

    PubMed Central

    Vimalachandran, Pradeepa; Kunadharaju, Rajesh; Mehta, Vishisht; Colanta, Agnes

    2016-01-01

    Henoch Schonlein purpura (HSP) is an immune mediated disease associated Immunoglobulin A (IgA) deposition within the affected organs. While the disease is commonly seen in the pediatric age group, it is rarely seen in adults. We report the case of a 93-year-old Caucasian lady who presented with nonthrombocytopenic purpuric rash and acute kidney injury after an episode of bronchitis. Rapid and progressive deterioration of renal function prompted a kidney biopsy, which showed findings consistent with IgA nephropathy confirming the diagnosis of HSP. The patient was treated with high dose intravenous methylprednisolone followed by oral prednisone; however, her kidney disease progressed to end stage renal disease requiring hemodialysis. HSP is usually a self-limiting disease in children. However, adults are at an increased risk of severe renal involvement including end stage renal disease. Purpuric skin rash with renal involvement should raise suspicion for HSP. This is the oldest known patient with HSP. PMID:27672395

  11. Association of acquired thrombotic thrombocytopaenic purpura in a patient with pernicious anaemia.

    PubMed

    Podder, Sidhertha; Cervates, Jose; Dey, Bimalangshu R

    2015-01-01

    Pernicious anaemia is an autoimmune disease caused by intrinsic factor antibody; it leads to vitamin B12 deficiency and is marked by ineffective erythropoiesis. Haematological features reveal macrocytosis, hyperchromasia and hypersegmented neutrophils. Schistocytes are typically seen in microangiopathy, such as in thrombotic thrombocytopaenic purpura (TTP)/haemolytic uraemic syndrome or disseminated intravascular haemolysis (DIC). We report a case of a patient with severe anaemia who presented to the emergency room. Peripheral smear revealed macrocytosis, hypersegmented neutrophils and marked schistocytosis. The patient also had high reticulocyte count with high serum lactate dehydrogenase, elevated D-dimer, low fibrinogen and low haptoglobin. Vitamin B12 level came back low and the presence of intrinsic factor antibody confirmed pernicious anaemia. ADAMTS13 level was noted to be mildly reduced, which raised the suspicion of the association of acquired TTP with pernicious anaemia. Acquired TTP is another autoimmune disorder and its association with pernicious anaemia needs further evaluation. PMID:26464409

  12. Henoch Schonlein Purpura as a Cause of Renal Failure in an Adult

    PubMed Central

    Vimalachandran, Pradeepa; Kunadharaju, Rajesh; Mehta, Vishisht; Colanta, Agnes

    2016-01-01

    Henoch Schonlein purpura (HSP) is an immune mediated disease associated Immunoglobulin A (IgA) deposition within the affected organs. While the disease is commonly seen in the pediatric age group, it is rarely seen in adults. We report the case of a 93-year-old Caucasian lady who presented with nonthrombocytopenic purpuric rash and acute kidney injury after an episode of bronchitis. Rapid and progressive deterioration of renal function prompted a kidney biopsy, which showed findings consistent with IgA nephropathy confirming the diagnosis of HSP. The patient was treated with high dose intravenous methylprednisolone followed by oral prednisone; however, her kidney disease progressed to end stage renal disease requiring hemodialysis. HSP is usually a self-limiting disease in children. However, adults are at an increased risk of severe renal involvement including end stage renal disease. Purpuric skin rash with renal involvement should raise suspicion for HSP. This is the oldest known patient with HSP.

  13. Pneumococcal Sepsis Complicated by Splenic Abscesses and Purpura Fulminans in a 15-Month-Old Child

    PubMed Central

    Pangonis, Scott; Patamasucon, Pisespong; Fitzpatrick, Ellen

    2016-01-01

    Streptococcus pneumoniae is an invasive organism that causes a wide range of common diseases, including sinusitis, acute otitis media, and pneumonia. Splenic abscesses and purpura fulminans (PF) are rare complications of pneumococcal disease. Splenic abscesses caused by S pneumoniae have only been reported in the adult literature. PF has been described in the pediatric population as a rare complication in patients with invasive pneumococcal disease (IPD) with and without underlying immunological disorders such as asplenia. Here, we report a patient with IPD complicated by splenic abscesses and PF. Our patient initially presented with bacteremia, septic shock, and disseminated intravascular coagulation. She subsequently developed PF and splenic abscesses. She survived her illness after receiving a total of 8 weeks of antibiotic therapy. This case highlights 2 rare complications of IPD and demonstrates the need to keep pneumococcal disease in the differential diagnosis even in children whose vaccination status is up to date. PMID:27006958

  14. Henoch Schonlein Purpura as a Cause of Renal Failure in an Adult.

    PubMed

    Kukrety, Shweta; Vimalachandran, Pradeepa; Kunadharaju, Rajesh; Mehta, Vishisht; Colanta, Agnes; Abu Hazeem, Mahmoud

    2016-01-01

    Henoch Schonlein purpura (HSP) is an immune mediated disease associated Immunoglobulin A (IgA) deposition within the affected organs. While the disease is commonly seen in the pediatric age group, it is rarely seen in adults. We report the case of a 93-year-old Caucasian lady who presented with nonthrombocytopenic purpuric rash and acute kidney injury after an episode of bronchitis. Rapid and progressive deterioration of renal function prompted a kidney biopsy, which showed findings consistent with IgA nephropathy confirming the diagnosis of HSP. The patient was treated with high dose intravenous methylprednisolone followed by oral prednisone; however, her kidney disease progressed to end stage renal disease requiring hemodialysis. HSP is usually a self-limiting disease in children. However, adults are at an increased risk of severe renal involvement including end stage renal disease. Purpuric skin rash with renal involvement should raise suspicion for HSP. This is the oldest known patient with HSP. PMID:27672395

  15. Plantar Purpura as the Initial Presentation of Viridians Streptococcal Shock Syndrome Secondary to Streptococcus gordonii Bacteremia

    PubMed Central

    Liao, Chen-Yi; Su, Kuan-Jen; Lin, Cheng-Hui; Huang, Shu-Fang; Chin, Hsien-Kuo; Chang, Chin-Wen; Kuo, Wu-Hsien; Ben, Ren-Jy; Yeh, Yen-Cheng

    2016-01-01

    Viridians streptococcal shock syndrome is a subtype of toxic shock syndrome. Frequently, the diagnosis is missed initially because the clinical features are nonspecific. However, it is a rapidly progressive disease, manifested by hypotension, rash, palmar desquamation, and acute respiratory distress syndrome within a short period. The disease course is generally fulminant and rarely presents initially as a purpura over the plantar region. We present a case of a 54-year-old female hospital worker diagnosed with viridians streptococcal shock syndrome caused by Streptococcus gordonii. Despite aggressive antibiotic treatment, fluid hydration, and use of inotropes and extracorporeal membrane oxygenation, the patient succumbed to the disease. Early diagnosis of the potentially fatal disease followed by a prompt antibiotic regimen and appropriate use of steroids are cornerstones in the management of this disease to reduce the risk of high morbidity and mortality. PMID:27366188

  16. [Henoch-Schönlein purpura in a cocaine consumer man with HIV infection and ANCA-p positivity].

    PubMed

    De Paoli, María C; Moretti, Dino; Scolari Pasinato, Carlos M; Buncuga, Martín G

    2016-01-01

    The Henoch-Schönlein purpura (HSP) is a small vessel vasculitis with IgA immune complex deposition. The presentation in adults is rare and severe. Reported cases of HSP in patients infected with HIV are scarce. Neutrophil cytoplasmic antibodies (ANCA) are commonly found in other systemic vasculitis, but rarely in HSP and even more unusual the perinuclear pattern. Beside small vessel vasculitis, positivity of ANCA can be detected in a number of different pathological conditions in association with infectious processes, including HIV, or cocaine use, and especially the pattern of ANCA-p, associated with drugs, inflammatory bowel or autoimmune diseases. We report the case of a 35 years old man with toxic habits (cocaine, marijuana) who consulted for abdominal pain, hematochezia and purpura on lower extremities, and later fever, joint pain and progression of purpura associated with nephritic syndrome and ANCA-p (+). During hospitalization HIV infection was detected. Renal biopsy showed IgA nephropathy with favorable response to corticosteroid and antiproteinuric treatment. The communication of the case is due to the rarity of the presentation and therapeutic diagnostic challenge. It remains to elucidate the role of ANCA in the pathogenesis and management of adult PSH. PMID:27576285

  17. Polyangitis overlap syndrome: a fatal case combined with adult Henoch-Schönlein purpura and polyarteritis nodosa.

    PubMed

    Watanabe, Kazuo; Abe, Hiroyuki; Mishima, Tomoko; Ogura, Go; Suzuki, Toshimitsu

    2003-08-01

    Henoch-Schönlein purpura (HSP) is a rather common disease characterized by systemic hypersensitivity vasculitis in the skin and other visceral organs. It has a favorable prognosis unless it is complicated by severe glomerular disease. We report a distinctive fatal case of systemic vasculitis combined with HSP and polyarteritis nodosa (PN) in a 56-year-old man who died of progressive renal failure one month after the onset of the disease. He complained of arthralgia, purpura of both lower extremities, nasal bleeding and tarry stool, and acute renal failure was noted at the time of admission to hospital. A skin biopsy from the purpura lesion exhibited leucocytoclastic vasculitis with IgA deposition, and HSP was considered. However, renal failure progressed rapidly and subsequently was complicated by acute myocardial infarction. Postmortem examination revealed PN type necrotizing vasculitis in the kidneys, heart and mesentery resulting in acute multiple infarctions of these organs. We think the current case was a polyangitis overlap syndrome. It is important to suspect the polyangitis overlap syndrome positively when progressive acute renal failure is seen in a patient with HSP and to begin appropriate therapy immediately.

  18. Flow cytometric analysis of thiazole orange uptake by platelets: a diagnostic aid in the evaluation of thrombocytopenic disorders.

    PubMed

    Kienast, J; Schmitz, G

    1990-01-01

    Thiazole orange (TO), a fluorescent dye originally synthesized for reticulocyte analysis, is characterized by a large fluorescence enhancement and high quantum yield on binding to nucleic acids, particularly RNA. In addition, the dye readily permeates live cell membranes. We applied TO staining, followed by fluorescence-activated flow cytometric analysis, to platelets in whole blood samples from hematologically normal subjects and patients with various quantitative platelet disorders. The percentage of TO-positive platelets in 50 control subjects was 8.6 +/- 2.8% (mean +/- SD) ranging from 2.8% to 15.8%. In 21 thrombocytopenic patients whose bone marrow contained normal to increased numbers of megakaryocytes, the percentage of fluorescently labeled platelets was significantly elevated (P less than .0001) to 26.9 +/- 10.9% (range, 13.3% to 57.1%). In contrast, the proportion of positively stained platelets in 23 patients with thrombocytopenia due to impaired platelet production (various conditions with reduced marrow megakaryocytes) did not significantly differ from the controls, whereas the absolute counts of TO-positive platelets were significantly lowered (P less than .0001). Differences in the distributions of the percentage values as well as of the absolute counts for TO-positive platelets between the two patient groups were again highly significant (P less than .0001). Both the sensitivity and the specificity of this method in distinguishing between these categories of thrombocytopenia were greater than or equal to 95%. We conclude that flow cytometric analysis of platelets after staining with TO is a sensitive and specific test that rapidly provides information on the thrombopoietic activity in thrombocytopenic disorders. Our data further suggest that increased amounts of residual RNA characterize platelets released under conditions of "stress thrombopoiesis."

  19. Lifetime cost of meningococcal disease in France: Scenarios of severe meningitis and septicemia with purpura fulminans.

    PubMed

    Bénard, Stève; Wright, Claire; Voisine, Jimmy; Olivier, Catherine W; Gaudelus, Joël

    2016-01-01

    Invasive meningococcal disease (IMD) is life-threatening and can result in severe sequelae. In France, no data have been published on the costs of severe IMD cases. Two realistic scenarios were developed with national experts (clinicians and social workers): a 6-year-old child with purpura fulminans with amputation of both legs below the knee (case A) and a 3-year-old with meningitis and severe neurological sequelae (case B). Additional scenarios included other typical sequelae of IMD such as chronic kidney disease (CKD), profound deafness and epilepsy. Data on healthcare, disability, educational and other resource use were obtained from experts and families of patients with similar sequelae. Unit costs (2013) were mainly obtained from the literature and the National Health Insurance (NHI). Time horizon was based on life expectancies of patients (77 and 55 years, respectively). A 4% discount rate decreasing to 2% after 30 years was applied. Costs are presented from the perspective of the NHI, publicly funded organizations and patients' families or their private health insurances. purpura fulminans with amputations is associated with a lifelong discounted cost of €768,875. Adding CKD doubles the amount (€1,480,545). Meningitis with severe neuro-cognitive sequelae results in a lifelong discounted cost of €1,924,475. Adding profound deafness and epilepsy slightly increases the total cost (€2,267,251). The first year is the most expensive in both scenarios (€166,890 and €160,647 respectively). The main cost drivers for each scenario are prostheses and child/adult stays in healthcare facilities, respectively. Overall, patients' families or his private insurance had to pay around 13% of total cost (101,833€ and 258,817€, respectively). This study fills a gap in the body of knowledge on IMD sequelae care and lifetime costs in France. The potentially high economic burden of IMD, in addition to its physical, psychological and social burden, reinforces the

  20. A Lower Proportion of Regulatory B Cells in Patients with Henoch–Schoenlein Purpura Nephritis

    PubMed Central

    Qu, Zhihui; Zhao, Songchen; Zhang, Li; Li, Man; Sun, Xiguang; Jiang, Yanfang

    2016-01-01

    Background Henoch—Schoenlein purpura is the one of most common types of systemic vasculitis that involves impaired renal function and Henoch-Schoenlein purpura nephritis (HSPN). The diagnosis of this condition is largely based on immunohistologic detection of immunoglobulin A1-containing immune complex in the glomerular deposits of mesangium. Despite clinical advances, the etiopathogenesis of HSPN is still largely unknown. Methods In this study, we enrolled 25 newly diagnosed HSPN patients and 14 healthy controls. Then, fractions of B cell subtypes were determined in venous blood using flow cytometry. The serum interleukin (IL)-10 concentration was determined by enzyme-linked immunosorbent assay. Results Compared to those in healthy controls, the numbers of CD38+CD19+, CD86+CD19+, CD38+CD86+CD19+, and CD95+CD19+ B cells per microliter of blood were significantly higher in HSPN patients. In contrast, the numbers of CD5+CD19+, IL-10+CD19+, CD5+CD1d+CD19+, and IL-10+CD5+CD1d+CD19+ B cells per microliter of blood and the serum IL-10 concentration were significantly lower in HSPN patients. Following treatment, the numbers of CD38+CD19+ and CD86+CD19+ B cells per microliter of blood were significantly reduced in HSPN patients. However, the numbers of CD5+CD1d+CD19+, CD5+CD1d+IL-10+CD19+, and IL-10+CD19+ B cells per microliter of blood and the serum IL-10 concentration were significantly increased in HSPN patients following treatment. The estimated glomerular filtration rate (eGFR) was negatively correlated with the number of CD38+CD19+ B cells but positively correlated with the numbers of IL-10+CD19+, CD1d+CD5+CD19+, and IL-10+CD1d+CD5+CD19+B cells per microliter of blood and the serum IL-10 concentration. The 24-h urinary protein concentration was positively correlated with the number of CD38+CD19+B cells but negatively correlated with the numbers of IL-10+CD19+, CD1d+CD5+CD19+, and IL-10+CD1d+CD5+CD19+B cells per microliter of blood and the serum IL-10 concentration

  1. Corticosteroids May Improve Clinical Outcomes During Hospitalization for Henoch-Schönlein Purpura

    PubMed Central

    Weiss, Pamela F.; Klink, Andrew J.; Localio, Russell; Hall, Matt; Hexem, Kari; Burnham, Jon M.; Keren, Ron; Feudtner, Chris

    2012-01-01

    OBJECTIVE To characterize the effect of corticosteroid exposure on clinical outcomes in children hospitalized with new-onset Henoch-Schönlein purpura (HSP). PATIENTS AND METHODS We conducted a retrospective cohort study of children discharged with an International Classification of Diseases, Clinical Modification code of HSP between 2000 and 2007 by using inpatient administrative data from 36 tertiary care children’s hospitals. We used stratified Cox proportional hazards regression models to estimate the relative effect of time-varying corticosteroid exposure on the risks of clinical outcomes that occur during hospitalization for acute HSP. RESULTS During the 8-year study period, there were 1895 hospitalizations for new-onset HSP. After multivariable regression modeling adjustment, early corticosteroid exposure significantly reduced the hazard ratios for abdominal surgery (0.39 [95% confidence interval (CI): 0.17– 0.91]), endoscopy (0.27 [95% CI: 0.13– 0.55]), and abdominal imaging (0.50 [95% CI: 0.29 – 0.88]) during hospitalization. CONCLUSIONS In the hospital setting, early corticosteroid exposure was associated with benefits for several clinically relevant HSP outcomes, specifically those related to the gastrointestinal manifestations of the disease. PMID:20855386

  2. Variation in inpatient therapy and diagnostic evaluation of children with Henoch Schönlein purpura

    PubMed Central

    Weiss, Pamela F.; Klink, Andrew J.; Hexem, Kari; Burnham, Jon M.; Leonard, Mary B.; Keren, Ron; Localio, Russell; Feudtner, Chris

    2009-01-01

    Objective To describe variation regarding inpatient therapy and evaluation of children with Henoch Schönlein purpura (HSP) admitted to children’s hospitals across the United States. Study design We conducted a retrospective cohort study of children discharged with a diagnosis of HSP between 2000 and 2007 using inpatient administrative data from 36 children’s hospitals. We examined variation among hospitals in the use of medications, diagnostic tests, and intensive care services using multivariate mixed effects logistic regression models. Results During the initial HSP hospitalization (N=1,988), corticosteroids were the most common medication (56% of cases), followed by opioids (36%), NSAIDs (35%), and anti-hypertensives (11%). After adjustment for patient characteristics, hospitals varied significantly in their use of corticosteroids, opioids, and NSAIDs; the use of diagnostic abdominal imaging, endoscopy, laboratory testing, and renal biopsy; and the utilization of intensive care services. By contrast, hospitals did not differ significantly regarding administration of anti-hypertensives or performance of skin biopsy. Conclusions The significant variation identified may contribute to varying HSP clinical outcomes between hospitals, warrants further investigation, and represents a potentially important opportunity to improve quality of care. PMID:19643437

  3. Current views of the relationship between Helicobacter pylori and Henoch-Schonlein purpura in children

    PubMed Central

    Xiong, Li-Jing; Mao, Meng

    2016-01-01

    Helicobacter pylori (H. pylori) is one of the factors involved in the pathogenesis of various gastrointestinal diseases and may play a potential role in certain extra-intestinal diseases. H. pylori infection are mainly acquired during childhood, and it has been reported that in endemic areas of China the infection rates are extraordinarily higher in HSP children, particular those with abdominal manifestations. Furthermore, eradication therapy may ameliorate Henoch-Schonlein purpura (HSP) manifestations and decrease the recurrence of HSP. Therefore, results suggested that detection of H. pylori infection by appropriate method ought to be applied in HSP children. Current evidences indicate that local injury of gastric mucosa and immunological events induced by H. pylori infection are involved in the development of HSP. Increased serum IgA, cryoglobulins, C3 levels, autoimmunity, proinflammatory substances and molecular mimicry inducing immune complex and cross-reactive antibodies caused by H. pylori infection might play their roles in the course of HSP. However, there are no investigations confirming the causality between H. pylori infection and HSP, and the pathogenesis mechanism is still unclear. More bench and clinical studies need to be executed to elaborate the complex association between H. pylori and HSP. PMID:26862506

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

    NASA Astrophysics Data System (ADS)

    Ailioaie, Laura; Ailioaie, C.

    2001-06-01

    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.

  5. IgA myeloma presenting as Henoch-Schönlein purpura with nephritis.

    PubMed

    Zickerman, A M; Allen, A C; Talwar, V; Olczak, S A; Brownlee, A; Holland, M; Furness, P N; Brunskill, N J; Feehally, J

    2000-09-01

    IgA nephropathy (IgAN) and Henoch-Schönlein purpura (HSP) are both characterized by IgA-mediated tissue injury, including mesangial proliferative glomerulonephritis. Abnormalities of IgA1 glycosylation are described in IgA nephropathy and HSP nephritis. IgA-antineutrophil cytoplasmic antibodies (ANCA) have been inconsistently described in the serum of patients with HSP. In IgA myeloma, the paraprotein-mediated renal lesion is typically cast nephropathy; IgAN or HSP have only rarely been reported in myeloma even when an IgA paraprotein is circulating in large concentrations. We report the case of a 50-year-old man with IgA myeloma who presented with HSP including nephritis and rapidly progressive renal failure. His IgA1 had altered O-glycosylation in the pattern seen in IgAN and also contained an IgA-ANCA. This case adds further weight to the evidence that IgA1 O-glycosylation abnormalities predispose to mesangial IgA deposition and also that IgA-ANCA may have a pathogenic role in the development of HSP. PMID:10977812

  6. Posterior Reversible Encephalopathy Syndrome in Henoch-Schonlein Purpura and Hemolytic Uremic Syndrome

    PubMed Central

    Fidan, Kibriya; Kandur, Yasar; Ucar, Murat; Gucuyener, Kivilcim; Soylemezoglu, Oguz

    2016-01-01

    Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological syndrome, composed of symptoms such as headache, seizures, visual disturbances, lethargy, confusion, stupor, focal neurologic findings and radiological findings of bilateral gray and white matter abnormalities suggestive of edema in the posterior regions of the cerebral hemispheres. PRES is associated with significant morbidity and mortality if it is not expeditiously recognized. Magnetic resonance image (MRI) represents the most sensitive imaging technique for recognizing PRES. PRES has been seen in various clinical settings including renal disorders such as acute glomerulonephritis, lupus nephritis, nephrotic syndrome, and drug usage such as calcineurin inhibitors. We aimed to present two study cases for such clinical setting. In this report, we present two patients with PRES in whom the primary diagnosis was hemolytic uremic syndrome (HUS) and Henoch-Schonlein purpura (HSP). Both of them were treated with anticonvulsant and proper antihypertensive drugs. A repeated MRI scan of the head, an ophthalmologic assessment, and a follow-up electroencephalogram produced normal results with no sequelae. Early recognition of PRES as a complication during different diseases and therapies in childhood may facilitate the appropriate treatment, so that intensive treatment should be performed as soon as possible to avoid neurological sequelae. PMID:27298664

  7. [A case of disseminated nontuberculous mycobacteriosis during purpura associated with hypergammaglobulinemia and hepatitis type C].

    PubMed

    Ueno, Shiro; Miyauchi, Shunichi; Umekita, Kunihiko; Kusumoto, Norio; Takajo, Ichiro; Kuroki, Masayuki; Kai, Yasufumi; Nagatomo, Yasuhiro; Okayama, Akihiko

    2008-11-01

    A 74-year-old woman with hepatitis due to hepatitis C virus followed up using oral predonisolone (3 mg/day) for two years because of hypergammaglobulinemia-associated purpura reported fever and lumbago in February 2005. Upon admission in June, she was found in chest-computed tomography to have atelectasia in the right middle lung lobe and a nodule with a cavity in the right lower lobe. She tested positive for tuberculous glycolipid antibody. Gallium scintigraphy showed an abnormal accumulation in the lower lumbar vertebra. Magnetic resonance imaging showed abnormal enhancement at L4, L5, and their intervertebral disc. Mycobacterium intracellulare (M. intracellulare) was detected in blood culture, bronchoalveolar lavage, and a biopsy specimen from the intervertebral disc, yielding a diagnosis of disseminated nontuberculous mycobacteriosis (NTM) due to M. intracellulare. She was treated with clarithromycin (CAM), ethambutol (EB), and rifampicin (RFP), but EB and RFP were discontinued due to of the fever they induced. She was then treated with a combination of CAM, levofloxacin, and streptomycin and followed up as an out patient. Based on case reports of disseminated NTM infection in Japan, the prognosis is poor and a protocol must be established for its treatment. PMID:19086421

  8. The first case of Henoch-Schonlein purpura associated with rosuvastatin: colonic involvement coexisting with small intestine.

    PubMed

    Gonen, Korcan Aysun; Erfan, Gamze; Oznur, Meltem; Erdogan, Cuneyt

    2014-01-01

    Henoch-Schönlein purpura (HSP) is a systemic vasculitis affecting small vessels. It is the most common systemic vasculitis in children, and is rare in adults. Serious gastrointestinal complications are more common in childhood. Infections and drugs are the most prominent factors in the aetiology. Wall thickening in segments of the small intestine is commonly seen in imaging studies in gastrointestinal system (GIS) involvement. Simultaneous involvement of small intestine and colon is rare. An HSP case involving small intestine and colon in an adult patient due to the use of rosuvastatin, an antihyperlipidaemic agent, is presented, and is first of its kind reported in the literature.

  9. Henoch-Schönlein purpura complicated by acalculous cholecystitis and intussusception, and following recurrence with appendicitis.

    PubMed

    Özkaya, Ahmet Kağan; Güler, Ekrem; Çetinkaya, Ahmet; Karakaya, Ali Erdal; Göksügür, Yalçın; Katı, Ömer; Güler, Ahmet Gökhan; Davutoğlu, Mehmet

    2016-05-01

    Henoch-Schönlein purpura (HSP) is the most common childhood systemic vasculitis. Gastro-intestinal involvement occurs in two-thirds of patients. The characteristic skin lesions generally precede abdominal symptoms or present concurrently. A 7-year-old boy presented with intussusception and acalculous cholecystitis and had a cholecystectomy. Two weeks later he was re-admitted with features typical of HSP which responded to corticosteroids. Eleven months later he presented with abdominal pain and recurrence of HSP and, at laparotomy, there was acute appendicitis. This is the first case of a child presenting with HSP complicated by acalculous cholecystitis. PMID:27077617

  10. Henoch-Schönlein purpura associated with a neuroblastoma: Report of one case and a review of the literature

    PubMed Central

    Dong, Qiaoli; Cao, Shanshan; Zhang, Hongwen; Geng, Hui

    2012-01-01

    Summary Malignancies such as solid tumors and hematologic malignancies can often induce or be associated with Henoch-Schönlein purpura (HSP) in older males but not in children. Described here is the case of a 5-year-old boy who clinically presented with HSP. An imaging study of the abdomen revealed a right retroperitoneal neoplasm that histopathology postoperatively confirmed to be a neuroblastoma. Malignancies are sometimes associated with HSP mostly in older males, though children are affected, albeit rarely. Thus, all patients with HSP must be carefully examined to identify or exclude an underlying disease. PMID:25343092

  11. Predictors of hospital length of stay in pediatric Henoch-Schönlein purpura.

    PubMed

    Cohen, Neta; Mimouni, Francis B; Friedel, Nadav; Amarilyo, Gil

    2015-09-01

    Henoch-Schönlein purpura (HSP) is a common, benign vasculitis in childhood which occasionally follows a protracted course and prolonged length of hospital stay. We aimed to determine clinical and laboratory characteristics that allow prediction of prolonged length of hospital stay (4 or more days) in HSP patients. We have retrospectively reviewed all HSP cases that were admitted to the Dana Duek Children's hospital between 2000 and 2013. Univariable analysis was performed to study the variables that were statistically related to length of hospital stay. These variables along with other clinically relevant variables were analyzed using stepwise backward multiple regression analysis. Variables that remained significant in the final analysis were correlated with length of stay, were each given specific weight (according to their contribution to the final R(2)) and were used to assemble an HSP presentation severity score. Out of 107 charts that were screened, 89 children were retrieved for analysis. In univariate analysis, variables that were associated with prolonged (>4 days) length of stay were: abdominal pain as initial sole presentation, C-reactive protein (CRP) 45 mg/dL (1 or 0 point) and patient's age > 6 years (0.5 or 0 points). A score of ≥3 in patients diagnosed with HSP predicted a prolonged length of stay with a positive predictive value of 93 %. The HSP presentation severity score index that we describe here may serve as a practical tool to assess severity of HSP which may eventually reflected as prolonged length of hospital stay. This score should be validated in the future in an ongoing prospective study. PMID:25804958

  12. Cocaine/levamisole-induced systemic vasculitis with retiform purpura and pauci-immune glomerulonephritis

    PubMed Central

    Veronese, F.V.; Dode, R.S.O.; Friderichs, M.; Thomé, G.G.; da Silva, D.R.; Schaefer, P.G.; Sebben, V.C.; Nicolella, A.R.; Barros, E.J.G.

    2016-01-01

    Levamisole has been increasingly used as an adulterant of cocaine in recent years, emerging as a public health challenge worldwide. Levamisole-associated toxicity manifests clinically as a systemic vasculitis, consisting of cutaneous, hematological, and renal lesions, among others. Purpura retiform, cutaneous necrosis, intravascular thrombosis, neutropenia, and less commonly crescentic nephritis have been described in association with anti-neutrophil cytoplasmic antibodies (ANCAs) and other autoantibodies. Here we report the case of a 49-year-old male who was a chronic cocaine user, and who presented spontaneous weight loss, arthralgia, and 3 weeks before admission purpuric skin lesions in the earlobes and in the anterior thighs. His laboratory tests on admission showed serum creatinine of 4.56 mg/dL, white blood count 3,800/μL, hemoglobin 7.3 g/dL, urinalysis with 51 white blood cells/μL and 960 red blood cells/μL, and urine protein-to-creatinine ratio 1.20. Serum ANCA testing was positive (>1:320), as well as serum anti-myeloperoxidase and anti-proteinase 3 antibodies. Urine toxicology screen was positive for cocaine and levamisole, with 62.8% of cocaine, 32.2% of levamisole, and 5% of an unidentified substance. Skin and renal biopsies were diagnostic for leukocytoclastic vasculitis and pauci-immune crescentic glomerulonephritis, respectively. The patient showed a good clinical response to cocaine abstinence, and use of corticosteroids and intravenous cyclophosphamide. Last serum creatinine was 1.97 mg/dL, white blood cell count 7,420/μL, and hemoglobin level 10.8 g/dL. In levamisole-induced systemic vasculitis, the early institution of cocaine abstinence, concomitant with the use of immunosuppressive drugs in severe cases, may prevent permanent end organ damage and associate with better clinical outcomes. PMID:27119429

  13. Interleukin 12 levels during the initial phase of septic shock with purpura in children: relation to severity of disease.

    PubMed

    Hazelzet, J A; Kornelisse, R F; van der Pouw Kraan, T C; Joosten, K F; van der Voort, E; van Mierlo, G; Suur, M H; Hop, W C; de Groot, R; Hack, C E

    1997-09-01

    Plasma levels of interleukin 12 (IL-12), a cytokine consisting of two different polypeptide subunits (p40 and p35), were measured together with interferon gamma (IFN-gamma) and other cytokines in 46 children with septic shock and purpura. The median (range) plasma IL-12 p40 level on admission was 457 (244-2677) pg/ml in non-survivors vs 189 (< 40-521) pg/ml in survivors (P = < 0.001). IL-12 p70 levels were elevated in only nine patients. IL-12 p40 plasma levels were positively correlated with tumour necrosis factor alpha (TNF-alpha), IL-6, IL-8, IL-10 and PRISM-score, whereas they were negatively correlated with C-reactive protein (CRP), whole blood cell (WBC) and serum glucose levels. Twelve (29%) of the patients had detectable levels of IFN-gamma. Thus, circulating levels of IL-12 p40 and to a lesser extent those of IL-12 p70, are elevated in children with septic shock and purpura, and correlate with severity of disease and outcome.

  14. Henoch-Schönlein purpura from vasculitis to intestinal perforation: A case report and literature review

    PubMed Central

    Lerkvaleekul, Butsabong; Treepongkaruna, Suporn; Saisawat, Pawaree; Thanachatchairattana, Pornsri; Angkathunyakul, Napat; Ruangwattanapaisarn, Nichanan; Vilaiyuk, Soamarat

    2016-01-01

    Henoch-Schönlein purpura (HSP) is generally a self-limited vasculitis disease and has a good prognosis. We report a 4-year-old Thai boy who presented with palpable purpura, abdominal colicky pain, seizure, and eventually developed intestinal ischemia and perforation despite adequate treatment, including corticosteroid and intravenous immunoglobulin therapy. Imaging modalities, including ultrasonography and contrast-enhanced computed tomography, could not detect intestinal ischemia prior to perforation. In this patient, we also postulated that vasculitis-induced mucosal ischemia was a cause of the ulcer, leading to intestinal perforation, and high-dose corticosteroid could have been a contributing factor since the histopathology revealed depletion of lymphoid follicles. Intestinal perforation in HSP is rare, but life-threatening. Close monitoring and thorough clinical evaluation are essential to detect bowel ischemia before perforation, particularly in HSP patients who have hematochezia, persistent localized abdominal tenderness and guarding. In highly suspicious cases, exploratory laparotomy may be needed for the definite diagnosis and prevention of further complications. PMID:27468201

  15. Henoch-Schönlein purpura from vasculitis to intestinal perforation: A case report and literature review.

    PubMed

    Lerkvaleekul, Butsabong; Treepongkaruna, Suporn; Saisawat, Pawaree; Thanachatchairattana, Pornsri; Angkathunyakul, Napat; Ruangwattanapaisarn, Nichanan; Vilaiyuk, Soamarat

    2016-07-14

    Henoch-Schönlein purpura (HSP) is generally a self-limited vasculitis disease and has a good prognosis. We report a 4-year-old Thai boy who presented with palpable purpura, abdominal colicky pain, seizure, and eventually developed intestinal ischemia and perforation despite adequate treatment, including corticosteroid and intravenous immunoglobulin therapy. Imaging modalities, including ultrasonography and contrast-enhanced computed tomography, could not detect intestinal ischemia prior to perforation. In this patient, we also postulated that vasculitis-induced mucosal ischemia was a cause of the ulcer, leading to intestinal perforation, and high-dose corticosteroid could have been a contributing factor since the histopathology revealed depletion of lymphoid follicles. Intestinal perforation in HSP is rare, but life-threatening. Close monitoring and thorough clinical evaluation are essential to detect bowel ischemia before perforation, particularly in HSP patients who have hematochezia, persistent localized abdominal tenderness and guarding. In highly suspicious cases, exploratory laparotomy may be needed for the definite diagnosis and prevention of further complications. PMID:27468201

  16. Clinical features and outcomes of diffuse endocapillary proliferation Henoch-Schönlein purpura nephritis in children

    PubMed Central

    Fu, Haidong; Mao, Jianhua; Xu, Yanping; Gu, Weizhong; Zhu, Xiujuan; Liu, Aimin

    2016-01-01

    OBJECTIVE: To investigate the outcomes of childhood diffuse endocapillary proliferation Henoch-Schönlein purpura nephritis (DEP-HSPN) in response to early diagnosis and prompt treatment. METHODS: Eleven cases of DEP-HSPN in children were investigated in comparison to HSPN without diffuse endocapillary proliferation (non-DEP-HSPN). RESULTS: DEP-HSPN had a higher prevalence of nephrotic syndrome but a lower prevalence of hematuria compared to non-DEP-HSPN. IgA, IgG and IgM antibody deposition was found in DEP-HSPN by histopathological examination. Proteinuria cleared in all 11 cases through treatment with steroids and/or immunosuppressive drugs. However, half of the DEP-HSPN patients continuously had hematuria after treatment. CONCLUSION: The early diagnosis and prompt initiation of immunosuppressive treatment based on renal biopsy are important for achieving favorable outcomes. PMID:27652838

  17. Henoch-Schönlein Purpura with Adalimumab Therapy for Ulcerative Colitis: A Case Report and Review of the Literature

    PubMed Central

    Donet, Jean A.; Cho-Vega, Jeong Hee; Sussman, Daniel A.; Deshpande, Amar R.

    2016-01-01

    Tumor necrosis factor-α (TNFα) inhibitor therapy has signified an important milestone in the fight against many rheumatological disorders and inflammatory bowel disease (IBD). Cutaneous adverse events caused by this class of medications are well known but relatively uncommon. Most reactions are mild and rarely warrant treatment withdrawal. Henoch-Schönlein purpura (HSP) is a disease with cutaneous vasculitis, arthritis, and gastrointestinal and renal involvement that is usually seen in children, though the worst complications are typically seen in adults. We present a case of HSP complicating adalimumab treatment in a patient with ulcerative colitis who had achieved endoscopic remission. We review similar cases reported in the literature and discuss the consequences of these autoimmune diseases. PMID:27529048

  18. Clinical features and outcomes of diffuse endocapillary proliferation Henoch-Schönlein purpura nephritis in children

    PubMed Central

    Fu, Haidong; Mao, Jianhua; Xu, Yanping; Gu, Weizhong; Zhu, Xiujuan; Liu, Aimin

    2016-01-01

    OBJECTIVE: To investigate the outcomes of childhood diffuse endocapillary proliferation Henoch-Schönlein purpura nephritis (DEP-HSPN) in response to early diagnosis and prompt treatment. METHODS: Eleven cases of DEP-HSPN in children were investigated in comparison to HSPN without diffuse endocapillary proliferation (non-DEP-HSPN). RESULTS: DEP-HSPN had a higher prevalence of nephrotic syndrome but a lower prevalence of hematuria compared to non-DEP-HSPN. IgA, IgG and IgM antibody deposition was found in DEP-HSPN by histopathological examination. Proteinuria cleared in all 11 cases through treatment with steroids and/or immunosuppressive drugs. However, half of the DEP-HSPN patients continuously had hematuria after treatment. CONCLUSION: The early diagnosis and prompt initiation of immunosuppressive treatment based on renal biopsy are important for achieving favorable outcomes.

  19. Joint effusions and purpura in multiply-transfused adult beta-thalassemia- clinical pointers to diagnosis of scurvy.

    PubMed

    Prakash, A; Pandey, A K

    2013-01-01

    Periodic transfusions and effective chelation have ensured that thalassemics survive in to adulthood but their life is punctuated by peculiar problems in adulthood. Three cases of scurvy are being reported presenting uniquely as purpura, right hip joint effusion and right knee joint effusion with haemorrhage in prepatellar and retropatellar bursae, respectively over an 18 month period (2009-2010). The first two cases did give a history of gum bleed. None had any coagulation disturbance or transfusion-transmitted infections or connective tissue disorder. All the three cases responded dramatically to vitamin C supplementation. It is imperative to keep in mind that recurrent blood transfusions are associated with a state of subclinical vitamin C deficiency and overt scurvy may manifest as cumulative number of transfusions increase, as in adult thalassemics. PMID:24899338

  20. Henoch-Schönlein Purpura with Adalimumab Therapy for Ulcerative Colitis: A Case Report and Review of the Literature.

    PubMed

    LaConti, Joseph J; Donet, Jean A; Cho-Vega, Jeong Hee; Sussman, Daniel A; Ascherman, Dana; Deshpande, Amar R

    2016-01-01

    Tumor necrosis factor-α (TNFα) inhibitor therapy has signified an important milestone in the fight against many rheumatological disorders and inflammatory bowel disease (IBD). Cutaneous adverse events caused by this class of medications are well known but relatively uncommon. Most reactions are mild and rarely warrant treatment withdrawal. Henoch-Schönlein purpura (HSP) is a disease with cutaneous vasculitis, arthritis, and gastrointestinal and renal involvement that is usually seen in children, though the worst complications are typically seen in adults. We present a case of HSP complicating adalimumab treatment in a patient with ulcerative colitis who had achieved endoscopic remission. We review similar cases reported in the literature and discuss the consequences of these autoimmune diseases. PMID:27529048

  1. Joint effusions and purpura in multiply-transfused adult beta-thalassemia- clinical pointers to diagnosis of scurvy.

    PubMed

    Prakash, A; Pandey, A K

    2013-01-01

    Periodic transfusions and effective chelation have ensured that thalassemics survive in to adulthood but their life is punctuated by peculiar problems in adulthood. Three cases of scurvy are being reported presenting uniquely as purpura, right hip joint effusion and right knee joint effusion with haemorrhage in prepatellar and retropatellar bursae, respectively over an 18 month period (2009-2010). The first two cases did give a history of gum bleed. None had any coagulation disturbance or transfusion-transmitted infections or connective tissue disorder. All the three cases responded dramatically to vitamin C supplementation. It is imperative to keep in mind that recurrent blood transfusions are associated with a state of subclinical vitamin C deficiency and overt scurvy may manifest as cumulative number of transfusions increase, as in adult thalassemics.

  2. A case of isotretinoin-induced purpura annularis telangiectodes of Majocchi and review of substance-induced pigmented purpuric dermatosis.

    PubMed

    Kaplan, Rachel; Meehan, Shane A; Leger, Marie

    2014-02-01

    IMPORTANCE Medications as well as chemical and food exposures have been causally linked to the development of pigmented purpuric dermatosis (PPD). We describe herein what is to our knowledge the first reported case of isotretinoin-induced PPD. OBSERVATIONS A woman in her 30s presented with purpura annularis telangiectodes of Majocchi on the lower extremities 2 months after initiating isotretinoin for the treatment of refractory nodulocystic acne. CONCLUSIONS AND RELEVANCE We believe isotretinoin was the most likely causative agent in this case because the lesions began after initiation of isotretinoin treatment and resolved shortly after its termination, and the pathologic findings were consistent with other described cases of drug-induced PPD. The lesions have continued to fade, and no new lesions have developed in a 3-month follow-up period. Drug-induced PPD is distinct from idiopathic PPD, and it is important to consider isotretinoin as a potential inciting agent.

  3. [Case of Henoch-Schönlein purpura nephritis successfully treated with tonsillectomy and steroid pulse therapy].

    PubMed

    Iwamoto, Mari; Wakabayashi, Mai; Hanada, Shigeru; Kobayashi, Namiko; Hata, Toshihiko; Ando, Ryoichi

    2009-01-01

    A 30-year-old Japanese man was admitted to our hospital because of fever, sore throat, abdominal pain, purpura skin lesion of the lower legs, and macrohematuria. On admission, his urine was positive (++) for protein; the sediment contained 100 red blood cells per high-power field, and the daily proteinuria level was 1.7 g. Renal biopsy was performed, and we diagnosed Henoch-Schönlein purpura nephritis (HSPN). Six months after the renal biopsy, the patient underwent a tonsillectomy. The pathological diagnosis of the resected tonsils was chronic tonsillitis. After tonsillectomy, the daily proteinuria had decreased to 0.1 g and the sediment contained only 10-19 red blood cells per high-power field. High-dose methylprednisolone therapy (500 mg/day for 3 days for three courses) was started two weeks after the tonsillectomy, followed by oral prednisolone at the initial dose of 30 mg on alternate days. The oral prednisolone was tapered gradually over 1 year. Antiplatelet drug (dipyridamole, 300 mg/day) and angiotensin II receptor antagonist (olmesartan, 10 mg/day) were also administered. This combination therapy resulted in a significant decrease in proteinuria and disappearance of microhematuria. The patient finally achieved clinical remission. Recent reports have shown that in patients with IgA nephropathy, combined tonsillectomy and methylprednisolone pulse therapy have an effect on clinical remission. In addition, it has been suggested that HSPN and IgA nephropathy represent a spectrum of clinical presentations of similar disorders. The result of this case indicated that this combination therapy had a favorable effect on clinical remission in adult patients with HSPN. PMID:19601558

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

    PubMed

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

    2013-12-01

    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.

  5. Haematology and neurology

    PubMed Central

    Austin, Steven; Cohen, Hannah; Losseff, Nick

    2007-01-01

    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. PMID:17369588

  6. Helicobacter pylori-associated immune thrombocytopenia.

    PubMed

    Franchini, Massimo; Veneri, Dino

    2006-03-01

    Idiopatic thrombocytopenic purpura (ITP), a disorder characterized by autoantibody-mediated platelet destruction, may be primary or secondary to various illnesses including lymphoproliferative, autoimmune, or infectious diseases. There are increasing data on the association between Helicobacter pylori infection and idiopathic thrombocytopenic purpura and the significant increase in platelet count after bacterial eradication. The aim of this review is to consider the studies so far published on Helicobacter pylori infection and idiopathic thrombocytopenic purpura in order to evaluate a possible pathogenic correlation between these two conditions. A review of the literature data show that Helicobacter pylori eradication in patients with idiopathic thrombocytopenic purpura is effective in increasing platelet count in approximately half of the cases. However, since the studies so far published are few, sometimes controversial and involve small series of patients, further controlled studies on larger numbers of patients with longer follow-up are needed to confirm these preliminary findings.

  7. The accuracy of platelet counting in thrombocytopenic blood samples distributed by the UK National External Quality Assessment Scheme for General Haematology.

    PubMed

    De la Salle, Barbara J; McTaggart, Paul N; Briggs, Carol; Harrison, Paul; Doré, Caroline J; Longair, Ian; Machin, Samuel J; Hyde, Keith

    2012-01-01

    A knowledge of the limitations of automated platelet counting is essential for the effective care of thrombocytopenic patients and management of platelet stocks for transfusion. For this study, 29 external quality assessment specimen pools with platelet counts between 5 and 64 × 10(9)/L were distributed to more than 1,100 users of 23 different hematology analyzer models. The same specimen pools were analyzed by the international reference method (IRM) for platelet counting at 3 reference centers. The IRM values were on average lower than the all-methods median values returned by the automated analyzers. The majority (~67%) of the automated analyzer results overestimated the platelet count compared with the IRM, with significant differences in 16.5% of cases. Performance differed between analyzer models. The observed differences may depend in part on the nature of the survey material and analyzer technology, but the findings have implications for the interpretation of platelet counts at levels of clinical decision making.

  8. Autoimmune progesterone dermatitis: Case report with history of urticaria, petechiae and palpable pinpoint purpura triggered by medical abortion.

    PubMed

    Mbonile, Lumuli

    2016-04-01

    Autoimmune progesterone dermatitis (APD) is a rare autoimmune response to raised endogenous progesterone levels that occur during the luteal phase of the menstrual cycle. Cutaneous, mucosal lesions and other systemic manifestations develop cyclically during the luteal phase of the menstrual cycle when progesterone levels are elevated. APD symptoms usually start 3 - 10 days before menstruation and resolve 1 - 2 days after menstruation ceases. A 30-year-old woman presented with urticaria, petechiae and palpable pinpoint purpura lesions of the legs, forearms, neck and buttocks 1 week prior to her menses starting and 2 months after a medical abortion. She was diagnosed with allergic contact dermatitis and topical steroids were prescribed. Her skin conditions did not improve and were associated with her menstrual cycle. We performed an intradermal test using progesterone, which was positive. She was treated with oral contraceptive pills and the symptoms were resolved. This is a typical case of APD triggered by increased sensitivity to endogenous progesterone induced a few months after medical abortion. PMID:27032848

  9. Suspects in the tale of lupus-associated thrombocytopenia

    PubMed Central

    Ziakas, P D; Routsias, J G; Giannouli, S; Tasidou, A; Tzioufas, A G; Voulgarelis, M

    2006-01-01

    Immunologically mediated thrombocytopenia is a frequent clinical manifestation in patients with systemic lupus erythematosus (SLE). Autoantibodies targeting platelet membrane glucoproteins have a central role in peripheral platelet destruction. Autoantibodies against thrombopoietin are also present in about one-third of patients, but their pathogenetic role is obscure. Thirty-eight serum samples from SLE patients were tested for anti-platelet antibodies, anti-thrombopoietin antibodies and levels of circulating thrombopoietin. Bone marrow histology was also assessed. Thirty-nine per cent of sera displayed anti-thrombopoietin antibodies and 29% had circulating anti-platelet antibodies. Anti-thrombopoietin antibodies were associated with lower thrombopoietin concentrations, and lower mean platelet values in long-term follow-up. Anti-platelet antibodies were present in about 40% of thrombocytopenic and non-thrombocytopenic individuals but were absent in patients who had recovered from thrombocytopenia, supporting their pathogenetic role. Both autoantibodies were absent in control sera from patients with rheumatoid arthritis and primary Sjögren’s syndrome. Decreased bone marrow cellularity, normal or low number of hypolobulated, pyknotic megakaryocytes and stromal alterations were prominent findings in thrombocytopenic SLE patients, suggesting a defect in megakaryopoiesis. These findings were not evident in specimens from patients with idiopathic thrombocytopenic purpura who had increased megakaryocytes, normal cellularity and absence of stromal alterations. In conclusion, peripheral destruction due to platelet autoantibodies, anti-thrombopoetin antibodies, lower effective circulating thrombopoetin and impaired compensatory response due to bone marrow damage interact in SLE and thrombocytopenia ensues. PMID:16792676

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

    ClinicalTrials.gov

    2005-06-23

    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

  11. Clinico-pathological association of Henoch-Schoenlein purpura nephritis and IgA nephropathy in children

    PubMed Central

    Mao, Song; Xuan, Xiaoyan; Sha, Yugen; Zhao, Sanlong; Zhu, Chunhua; Zhang, Aihua; Huang, Songming

    2015-01-01

    Objective: Henoch-Schonlein purpura nephritis (HSPN) and IgA nephropathy (IgAN) are similar syndromes. We aimed to determine whether the crescent formation/immunocomplex in glomeruli is associated with the differences of the biochemical indexes between HSPN and IgAN. Methods: We investigated the medical records of 137 HSPN cases and 41 IgAN cases from January 2009 to April 2014 in Nanjing Children’s Hospital of Nanjing Medical University. The clinical and pathological data were analyzed and compared between HSPN and IgAN. Results: HSPN patients had markedly higher levels of blood white blood cell (WBC), hemoglobulin (Hb) and platelet (PLT), lower levels of hematuria, blood nitrogen (BUN) and C4 compared with IgAN cases. Crescents formation and C3 deposition in the kidney did not affect these differences. Significantly lower levels of hematuria, blood IgG, IgM and C4 in HSPN compared with IgAN cases were observed among patients with IgG deposition. Markedly higher levels of WBC and Hb, lower levels of hematuria, creatinine (Cr), C4 in HSPN compared with IgAN cases were observed among patients with IgM deposition. No marked differences of the biochemical indexes were noted between HSPN and IgAN cases among patients with C1q deposition. Markedly higher levels of WBC and Hb, lower level of blood C4 in HSPN compared with IgAN cases were observed among patients with fibrogen deposition. Conclusions: The different levels of biochemical indexes at presentation between HSPN and IgAN may be associated with the deposition of IgG, IgM, C1q and fibrogen in the kidney. PMID:26045740

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

    SciTech Connect

    Beale, M.G.; Nash, G.S.; Bertovich, M.J.; MacDermott, R.P.

    1982-01-01

    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.

  13. [Clinico-pathological features and outcome in adult patients with Henoch-Schönlein purpura nephritis].

    PubMed

    Tsuruta, Yuki; Takei, Takashi; Takano, Mari; Sawara, Yukako; Aoki, Akiko; Eguchi, Aya; Kojima, Chiari; Moriyama, Takahito; Itabashi, Mitsuyo; Sugiura, Hidekazu; Tsukada, Misao; Ogawa, Tetsuya; Yoshida, Takumi; Uchida, Keiko; Tsuchiya, Ken; Nitta, Kosaku

    2010-01-01

    We examined the data of 24 patients with Henoch-Schönlein purpura nephritis (HSPN) over a 5-year follow-up period. Proteinuria, sediment RBC and CRP significantly decreased between the time of diagnosis and the end of the 5-year period. In the steroid usage group (n = 16), proteinuria was significantly higher, and crescent formation was significant higher at the time of diagnosis than in the non-steroid usage group (n = 8). However, there was no significant difference in the decrease in eGFR from the baseline at the end of the 5-year period between the two groups. Furthermore, to clarify the factors influencing the risk of renal function deterioration, we divided the patients into two groups, the (delta eGFR/pre eGFR) <0.25 group (n = 13) and (delta eGFR/pre eGFR) >0.25 group (n = 11), and compared the clinico-pathophysiological characteristics between the two groups. In the (delta eGFR/pre eGFR) >0.25 group, the ratio of glomerular obsolescence at the time of diagnosis was significantly higher than in the (delta eGFR/pre eGFR) <0.25 group. Glomerular obsolescence was identified as an independent risk factor for renal function deterioration. In this study, the prognosis of HSPN was related to glomerular obsolescence rather than to the disease activity. It may be necessary to consider the decrease in nephrons, in accordance with non-immunological glomerular obsolescence, in addition to immunological treatment to clarify the prognosis. PMID:20166542

  14. [Detection, diagnosis and analysis of the first case of neonatal alloimmune thrombocytopenia purpura associated with anti-HPA-5b in China].

    PubMed

    Zhou, Yan; Zhong, Zhou-Lin; Li, Li-Lan; Shen, Wei-Dong; Wu, Guo-Guang

    2014-04-01

    This study was aimed to investigate the detection and diagnosis of the neonatal alloimmune thrombocytopenia purpura (NAITP) caused by anti-HPA-5b antibody. The platelet count and clinical manifestation in the newborn were examined. The HPA-1-21bw genotypes of the newborn and her parents were detected by multiple-PCR and DNA sequencing. The HPA-specific antibody in the sera of newborn and her mother were detected and identified by flow cytometry (FCM) and monoclonal antibody-specific immobilization of platelet antigens (MAIPA). The results indicated that the clinical manifestations of the newborn were lighter. The HPA genotyping showed that the genotype of the newborn was HPA-5ab, while that of her mother and father were HPA-5aa and HPA-5ab, respectively. The antibody against the platelet of newborn's father existed in the newborn's mother sera. The HPA antibody of the mother was identified as anti-HPA-5b. It is concluded that the newborn with neonatal alloimmune thrombocytopenia purpura was caused by the antibody against HPA-5b.

  15. [Detection, diagnosis and analysis of the first case of neonatal alloimmune thrombocytopenia purpura associated with anti-HPA-5b in China].

    PubMed

    Zhou, Yan; Zhong, Zhou-Lin; Li, Li-Lan; Shen, Wei-Dong; Wu, Guo-Guang

    2014-04-01

    This study was aimed to investigate the detection and diagnosis of the neonatal alloimmune thrombocytopenia purpura (NAITP) caused by anti-HPA-5b antibody. The platelet count and clinical manifestation in the newborn were examined. The HPA-1-21bw genotypes of the newborn and her parents were detected by multiple-PCR and DNA sequencing. The HPA-specific antibody in the sera of newborn and her mother were detected and identified by flow cytometry (FCM) and monoclonal antibody-specific immobilization of platelet antigens (MAIPA). The results indicated that the clinical manifestations of the newborn were lighter. The HPA genotyping showed that the genotype of the newborn was HPA-5ab, while that of her mother and father were HPA-5aa and HPA-5ab, respectively. The antibody against the platelet of newborn's father existed in the newborn's mother sera. The HPA antibody of the mother was identified as anti-HPA-5b. It is concluded that the newborn with neonatal alloimmune thrombocytopenia purpura was caused by the antibody against HPA-5b. PMID:24763012

  16. Complement activation in relation to capillary leakage in children with septic shock and purpura.

    PubMed

    Hazelzet, J A; de Groot, R; van Mierlo, G; Joosten, K F; van der Voort, E; Eerenberg, A; Suur, M H; Hop, W C; Hack, C E

    1998-11-01

    To assess the relationship between capillary leakage and inflammatory mediators during sepsis, blood samples were taken on hospital admission, as well as 24 and 72 h later, from 52 children (median age, 3.3 years) with severe meningococcal sepsis, of whom 38 survived and 14 died. Parameters related to cytokines (interleukin 6 [IL-6] IL-8, plasma phospholipase A2, and C-reactive protein [CRP]), to neutrophil degranulation (elastase and lactoferrin), to complement activation (C3a, C3b/c, C4b/c, and C3- and C4-CRP complexes), and to complement regulation (functional and inactivated C1 inhibitor and C4BP) were determined. The degree of capillary leakage was derived from the amount of plasma infused and the severity of disease by assessing the pediatric risk of mortality (PRISM) score. Levels of IL-6, IL-8, C3b/c, C3-CRP complexes, and C4BP on admission, adjusted for the duration of skin lesions, were significantly different in survivors and nonsurvivors (C3b/c levels were on average 2.2 times higher in nonsurvivors, and C3-CRP levels were 1.9 times higher in survivors). Mortality was independently related to the levels of C3b/c and C3-CRP complexes. In agreement with this, levels of complement activation products correlated well with the PRISM score or capillary leakage. Thus, these data show that complement activation in patients with severe meningococcal sepsis is associated with a poor outcome and a more severe disease course. Further studies should reveal whether complement activation may be a target for therapeutical intervention in this disease.

  17. Targets and targeting.

    PubMed

    Will, E

    2001-08-01

    Using the vocabulary of ballistics in medicine for emphasis can result in misleading exaggeration and semantic confusion. The dual meaning of target as either aiming point (aim at) or outcome (aim to achieve) creates a muddle in the efforts to comply with quality assurance initiatives. Disentangling the two meanings allows new approaches to the clinical technology required in a modern health care environment. An example can be shown in new strategies for the management of renal anemia with iron and erythropoietin. The potential to shape outcome distributions through validated, preemptive intervention thresholds offers the predictable results required by patients and payers. Using the management of patient cohorts as a platform for outcomes creates no necessary conflict with individualized clinical care. Future guideline statements should include the likely characteristics of compliant outcome populations, as a prompt to clinical goals and as an indication of the necessary cost and effort of compliance with treatment standards. Overemphasis in language is no substitute for considered clinical methodology.

  18. Henoch-Schonlein Purpura in Children Hospitalized at a Tertiary Hospital during 2004-2015 in Korea: Epidemiology and Clinical Management

    PubMed Central

    Lee, Yong Hee; Kim, Yu Bin; Koo, Ja Wook

    2016-01-01

    Purpose To investigate the epidemiology, clinical manifestations, investigations and management, and prognosis of patients with Henoch-Schonlein purpura (HSP). Methods We performed a retrospective review of 212 HSP patients under the age of 18 years who were admitted to Inje University Sanggye Paik Hospital between 2004 and 2015. Results The mean age of the HSP patients was 6.93 years, and the ratio of boys to girls was 1.23:1. HSP occurred most frequently in the winter (33.0%) and least frequently in the summer (11.3%). Palpable purpura spots were found in 208 patients (98.1%), and gastrointestinal (GI) and joint symptoms were observed in 159 (75.0%) and 148 (69.8%) patients, respectively. There were 57 patients (26.9%) with renal involvement and 10 patients (4.7%) with nephrotic syndrome. The incidence of renal involvement and nephrotic syndrome was significantly higher in patients with severe GI symptoms and in those over 7 years old. The majority of patients (88.7%) were treated with steroids. There was no significant difference in the incidence of renal involvement or nephrotic syndrome among patients receiving different doses of steroids. Conclusion In this study, the epidemiologic features of HSP in children were similar to those described in previous studies, but GI and joint symptoms manifested more frequently. It is essential to carefully monitor renal involvement and progression to chronic renal disease in patients ≥7 years old and in patients affected by severe GI symptoms. It can be assumed that there is no direct association between early doses of steroids and prognosis. PMID:27738599

  19. [Treatment of thoracic and abdominal cavity perforation complicated by Henoch-Schonlein purpura nephritis in a patient with high-voltage electric burn].

    PubMed

    Zhang, Wei; Xie, Wei-guo; Min, Wei-xiong; Wang, De-yun; Zhang, Jia; Wan, Shi-yong

    2013-10-01

    A 55-year-old male patient suffered from severe high-voltage electric burn with an area of 20%TBSA full-thickness injury. The injury involved the distal end of left upper limb, right trunk, and whole abdominal wall. Fracture of the 7th-10th ribs was found in the right side of chest, with perforation of abdominal cavity, and bilateral pleural effusion was found. Part of the small intestine was necrotic and exposed. At the early stage, xeno-acellular dermal matrix was grafted after debridement of abdominal wound; peritoneal lavage was performed; negative pressure drainage was performed in orificium fistula of intestine for promoting the adhesion between perforated intestine and abdominal scar. Two orificium fistulas formed after closure of abdominal granulation wound by autologous skin grafting. Eschar of chest wall and denatured ribs were retained. The risk of infection of thoracic cavity was decreased by promoting the adhesion between lung tissue and chest wall. During the treatment, the patient was diagnosed with Henoch-Schonlein purpura nephritis by renal biopsy, with the symptoms of purpura in the lower limbs, heavy proteinuria, severe hypoalbuminemia, edema, etc. After control of kidney damage by immunosuppressive treatment instead of glucocorticoid, alleviation of the levels of proteinuria and blood albumin, free latissimus dorsi myocutaneous flap was excised to repair chest wall, and free skin graft was excised to repair intestinal fistula. After all the wounds were successfully covered, the patient was treated with glucocorticoid combined with immunosuppressants for more than 1 year. The patient was followed up for 3 years, and his renal function was completely recovered with satisfactory clinical outcome.

  20. Sputter target

    DOEpatents

    Gates, Willard G.; Hale, Gerald J.

    1980-01-01

    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. Potential of Serum and Urinary Matrix Metalloproteinase-9 Levels for the Early Detection of Renal Involvement in Children With Henoch-Schönlein Purpura

    PubMed Central

    Erol, Meltem; Yigit, Ozgul; Tasdemir, Mehmet; Bostan Gayret, Ozlem; Buke, Ovgu; Gunes, Aysegul; Hamilcikan, Sahin; Kasapcopur, Ozgur

    2016-01-01

    Background Matrix metalloproteinase-9 (MMP-9) is an enzyme implicated in the pathogenesis of renal diseases. Renal involvement is the principal cause of morbidity and mortality in children with Henoch-Schönlein purpura (HSP). Objectives The aim of this study was to evaluate whether serum and urinary MMP-9 levels are associated with renal involvement in HSP Patients and Methods We evaluated 40 children with HSP (patient group) and 27 healthy volunteer children (control group). The patient group was divided into two subgroups based on the presence or absence of nephritis. Nephritis was defined as the existence of hematuria and/or proteinuria. All anthropometric data, physical examination findings, blood pressure, and laboratory parameters were recorded. The serum and urine samples were analyzed to determine the MMP-9 levels three days after the initial phase of the disease. Results The mean age was 7.65 ± 3.41 (range 2 - 16) years in the patient group and 9.52 ± 3.91 (range 2 - 16) years in the control group. Henoch-Schonlein purpura nephritis (HSPN) was identified in eight patients. There was no significant difference in the serum MMP-9 levels between the HSPN subgroup and the controls (P > 0.05). However, there were significant differences in the urinary MMP-9 levels between the HSP subgroup and the control group (P < 0.05), with the urinary MMP-9 levels being significantly higher in patients in the HSP subgroup (P = 0.001). Further, the urinary MMP-9 levels were significantly higher in the patients with nephritis than in the patients without nephritis (P = 0.001) and the controls (P = 0.001). The optimal cut-off point (sensitivity; specificity) of the urinary MMP-9 level for the diagnosis of HSPN was 94.7 pg/mL. Conclusions The levels of MMP-9 in the urine were remarkably high in patients with HSPN. This non-invasive marker may therefore be an important indicator for the early diagnosis of nephritis in children with HSP.

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

    PubMed

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

    2011-07-01

    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.

  3. Characterization of the complications associated with plasma exchange for thrombotic thrombocytopaenic purpura and related thrombotic microangiopathic anaemias: a single institution experience

    PubMed Central

    McGuckin, S; Westwood, J-P; Webster, H; Collier, D; Leverett, D; Scully, M

    2014-01-01

    Background Plasma exchange (PEX) is a life-saving therapeutic procedure in patients with thrombotic thrombocytopaenic purpura (TTP) and other thrombotic microangiopathic anaemias (TMAs). However, it may be associated with significant complications, exacerbating the morbidity and mortality in this patient group. Study Design and Methods We reviewed all PEX procedures over a 72-month period, following the exclusive introduction of solvent–detergent double viral-inactivated plasma in high-volume users, such as TTP, in the United Kingdom (UK). We documented allergic reactions to plasma, citrate reactions, complications relating to central venous access insertion and venous thrombotic events (VTE) in 155 patient episodes and >2000 PEX procedures. Results The overall complication rate was low. Allergic plasma reactions occurred in 6·45% of the cohort with only one episode of acute anaphylaxis. Similarly, VTEs were 6·45%, not significantly greater than in medical patients receiving thromboprophylaxis, despite added potential risk factors in TTP. Citrate reactions were the most frequent complication documented, but toxicity was significantly reduced by administration of further calcium infusions during the PEX procedure. There were no serious central line infections and no catheter thrombosis. Conclusion Our data confirms that PEX continues to be a life-saving procedure in the acute TTP setting and, the procedure was not associated with an increased mortality and limited morbidity. PMID:24117855

  4. LIQUID TARGET

    DOEpatents

    Martin, M.D.; Salsig, W.W. Jr.

    1959-01-13

    A liquid handling apparatus is presented for a liquid material which is to be irradiated. The apparatus consists essentially of a reservoir for the liquid, a target element, a drain tank and a drain lock chamber. The target is in the form of a looped tube, the upper end of which is adapted to be disposed in a beam of atomic particles. The lower end of the target tube is in communication with the liquid in the reservoir and a means is provided to continuously circulate the liquid material to be irradiated through the target tube. Means to heat the reservoir tank is provided in the event that a metal is to be used as the target material. The apparatus is provided with suitable valves and shielding to provide maximum safety in operation.

  5. Purpura thrombopénique amégacaryocytaire acquis: penser au lupus érythémateux systémique

    PubMed Central

    Ernestho-ghoud, Indretsy Mahavivola; Rahamefy, Odilon; Ranaivo, Irina Mamisoa; Andrianarison, Malalaniaina; Ramarozatovo, Lala Soavina; Rabenja, Fahafahantsoa Rapelanoro

    2015-01-01

    L'amegacaryocytose acquise est exceptionnellement décrite au cours d'un Lupus Erythémateux Systémique (LES) à Madagascar. Nous rapportons la première observation d'un Purpura Thrombopénique Amegacaryocytaire Acquis (PTAA) simulant un Purpura Thrombopénique Idiopathique (PTI) révélateur d'un LES. Il s'agissait d'une femme de 24 ans, sans antécédents particuliers. Elle présentait un syndrome hémorragique avec une thrombopénie à 10 000/mm3. Le diagnostic de PTI était retenu avant l'hospitalisation. Elle avait reçu une corticothérapie mais ceci n’était pas suivi d'amélioration. A l'unité de Dermatologie, elle se plaignait d'une baisse de l'acuité visuelle. Elle était en bon état général. On retrouvait une tachycardie à 110 bpm, un érythème malaire en verspertilio typique et une pâleur cutanéo-muqueuse. Une hémorragie oculaire bilatérale était objectivée à l'examen ophtalmologique. Les examens paracliniques montraient une thrombopénie à 31000/mm3, une anémie microcytaire à 48g/dL. Les examens immunologiques étaient non réalisés. Un LES avec atteinte cutanée et hématologique était retenu. Un bolus de corticothérapie était administrée associée à une transfusion sanguine. L’évolution était marquée par l'apparition d'un signe d'engagement cérébral faisant suspecter un neurolupus. Le scanner cérébral révélait une hémorragie cérébrale avec une hydrocéphalie aigue traitée par un inhibiteur de l'anhydrase carbonique mais le neurolupus n’était pas écarté. L'anémie disparaissait par contre la thrombopénie s'aggravait à 16000/mm3. Le médullogramme montrait l'absence des mégacaryocytes. L’évolution était favorable à huit mois de suivi après un relais per os de la corticothérapie par la dose de 1 mg/kg/j à dose dégressive à huit mois de suivi. Les atteintes neurologiques, ophtalmologiques et hématologiques étaient compatible avec le diagnostic d'un LES. La persistance d'une thrombopénie doit

  6. Risk of long term renal impairment and duration of follow up recommended for Henoch-Schönlein purpura with normal or minimal urinary findings: a systematic review

    PubMed Central

    Narchi, H

    2005-01-01

    Background: The duration of follow up to assess the risk of long term renal impairment in Henoch-Schönlein purpura (HSP) without nephritic or nephrotic syndrome or renal failure on diagnosis remains undetermined. Aims: To undertake a systematic review of the literature to assess whether the risk of long term renal impairment without renal involvement on diagnosis could be estimated and to determine the time period when renal involvement is very unlikely after the diagnosis of HSP. Methods: Search of studies of unselected children with HSP, and available information on urinary findings, renal involvement, and long term renal function follow up. Studies of selected children with HSP nephropathy at diagnosis were excluded. Results: Twelve studies of 1133 children were reviewed. The follow up period ranged from 6 weeks to 36 years. Proteinuria and/or haematuria, which occurred in 34.2%, of which only one fifth were in association with nephritic or nephrotic syndrome, developed in 85% of cases within 4 weeks of the diagnosis of HSP, in 91% within 6 weeks, and in 97% within 6 months. Permanent renal impairment never developed after normal urinalysis; it occurred in 1.6% of those with isolated urinary abnormalities, and in 19.5% of those who developed nephritic or nephrotic syndrome. Conclusion: No long term renal impairment occurred after normal urinalysis. Even if urinalysis is normal at presentation, the testing should be continued for six months. There is no need to follow up after the first six months those whose urinalysis remains normal. PMID:15871983

  7. Tackling Targets.

    ERIC Educational Resources Information Center

    Further Education Unit, London (England).

    This document is designed to help British training and enterprise councils (TECs) and further education (FE) colleges develop and implement strategies for achieving the National Targets for Education and Training (NTET), which were developed by the Confederation of British Industry in 1992 and endorsed by the British government. The findings from…

  8. Target assembly

    DOEpatents

    Lewis, Richard A.

    1980-01-01

    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.

  9. Accelerator target

    DOEpatents

    Schlyer, D.J.; Ferrieri, R.A.; Koehler, C.

    1999-06-29

    A target includes a body having a depression in a front side for holding a sample for irradiation by a particle beam to produce a radioisotope. Cooling fins are disposed on a backside of the body opposite the depression. A foil is joined to the body front side to cover the depression and sample therein. A perforate grid is joined to the body atop the foil for supporting the foil and for transmitting the particle beam therethrough. A coolant is circulated over the fins to cool the body during the particle beam irradiation of the sample in the depression. 5 figs.

  10. Accelerator target

    DOEpatents

    Schlyer, David J.; Ferrieri, Richard A.; Koehler, Conrad

    1999-01-01

    A target includes a body having a depression in a front side for holding a sample for irradiation by a particle beam to produce a radioisotope. Cooling fins are disposed on a backside of the body opposite the depression. A foil is joined to the body front side to cover the depression and sample therein. A perforate grid is joined to the body atop the foil for supporting the foil and for transmitting the particle beam therethrough. A coolant is circulated over the fins to cool the body during the particle beam irradiation of the sample in the depression.

  11. [Current treatment of primary immune thrombocytopenia].

    PubMed

    Lozano, María L; Vicente, Vicente

    2014-05-01

    Primary immune thrombocytopenia, also termed immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by premature platelet destruction and impaired platelet production. Traditional treatment of ITP has predominantly consisted of immune suppression and/or modulation. However, the understanding of the immune mediated impairment of platelet production has led to the development of new treatments that target the thrombopoietin receptor, promoting formation of megakaryocytes and increasing platelet counts. Best practice for the management of ITP has not yet been established because data from comparative studies are lacking. While some disagreement might still remain among experts concerning therapy (when, who, and how should be treated), in recent years different evidence-based practice guidelines have been published to assist healthcare professionals in the diagnosis and treatment of ITP. This review describes the current treatment landscape of ITP.

  12. A Case of Microangiopathic Hemolytic Anemia after Myxoma Excision and Mitral Valve Repair Presenting as Hemolytic Uremic Syndrome

    PubMed Central

    Park, Young Joo; Kim, Sang Pil; Shin, Ho-Jin

    2016-01-01

    Microangiopathic hemolytic anemia occurs in a diverse group of disorders, including thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and prosthetic cardiac valves. Hemolytic anemia also occurs as a rare complication after mitral valve repair. In this report, we describe a case of microangiopathic hemolytic anemia following myxoma excision and mitral valve repair, which was presented as hemolytic uremic syndrome. PMID:27081450

  13. A Case of Microangiopathic Hemolytic Anemia after Myxoma Excision and Mitral Valve Repair Presenting as Hemolytic Uremic Syndrome.

    PubMed

    Park, Young Joo; Kim, Sang Pil; Shin, Ho-Jin; Choi, Jung Hyun

    2016-03-01

    Microangiopathic hemolytic anemia occurs in a diverse group of disorders, including thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and prosthetic cardiac valves. Hemolytic anemia also occurs as a rare complication after mitral valve repair. In this report, we describe a case of microangiopathic hemolytic anemia following myxoma excision and mitral valve repair, which was presented as hemolytic uremic syndrome. PMID:27081450

  14. [Autoimmune thrombocytopenia: diagnosis and treatment].

    PubMed

    Veneri, Dino; Franchini, Massimo

    2005-05-01

    Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disease characterized by an isolated, persistent thrombocytopenia in absence of known causes. In this review, we briefly analyze the most important diagnostic criteria of this autoimmune disorder, with particular consideration to differential diagnosis (false thrombocytopenia, congenital thrombocytopenia, acquired thrombocytopenia, pregnancy-associated thrombocytopenia) and to therapeutic options.

  15. Unusual presentations of Salmonella Typhi infections in children.

    PubMed

    Mittal, Sumit; Saxena, Ajit; Garg, Pankaj

    2009-01-01

    We report on three children with Salmonella typhi presenting with fever and urticaria, thrombocytopenic purpura and meningitis. We suggest that clinicians should consider S. typhi infection as a diagnosis even when the presenting features are more typical of other illnesses. PMID:19211418

  16. Thrombocytosis following thrombocytopenia in man

    PubMed Central

    Ogston, D.; Dawson, Audrey A.

    1969-01-01

    Observations are presented on the changes in the platelet count of patients during the treatment of Addisonian pernicious anaemia with vitamin B12, of thrombocytopenic purpura with prednisone, and of malignant disease with methotrexate. In each of these clinical situations, thrombocytopenia was succeeded, after a delay of a number of days, by a phase of thrombocytosis. PMID:5392350

  17. Dermatologic adverse events in pediatric patients receiving targeted anticancer therapies: a pooled analysis

    PubMed Central

    Pratilas, Christine A.; Sibaud, Vincent; Boralevi, Franck; Lacouture, Mario E.

    2015-01-01

    BACKGROUND The dermatologic adverse events (AEs) of various molecularly targeted therapies are well-described in adult cancer patients. Little has been reported on the incidence and clinical presentation of such AEs in pediatric patients with cancer. To address this gap, we analyzed the dermatologic AEs reported across clinical trials of targeted anticancer therapies in pediatric patients. METHODS We conducted an electronic literature search (PubMed, American Society of Clinical Oncology annual meetings’ abstracts, ClinicalTrials.gov, NCI’s Pediatric Oncology Branch webpage) to identify clinical trials involving targeted anticancer therapies that reported dermatologic AEs in their safety data. Studies were limited to the pediatric population, monotherapy trials (oncology), and English language publications. RESULTS Pooled data from 19 clinical studies investigating 11 targeted anticancer agents (alemtuzumab, rituximab, imatinib, dasatinib, erlotinib, vandetanib, sorafenib, cabozantinib, pazopanib, everolimus, and temsirolimus) were analyzed. The most frequently encountered dermatologic AEs were rash (127/660; 19%), xerosis (18/100; 18%), mucositis (68/402; 17%) and pruritus (12/169; 7%). Other AEs included pigmentary abnormalities of the skin/hair (13%), hair disorders (trichomegaly, hypertrichosis, alopecia and madarosis; 14%), urticaria (7%), palmoplantar erythrodysesthesia (7%), erythema, acne, purpura, skin fissures, other ‘unknown skin changes’, exanthem, infection, flushing, telangiectasia, and photosensitivity. CONCLUSION This study describes the dermatologic manifestations of targeted anticancer therapy-related AEs in the pediatric population. Since these AEs are often associated with significant morbidity, it is imperative that pediatric oncologists be familiar with their recognition and management, to avoid unnecessary dose modifications and/or termination, and to prevent impairments in patients’ quality of life. PMID:25683226

  18. Analytical modeling of laser pulse heating of embedded biological targets: An application to cutaneous vascular lesions

    NASA Astrophysics Data System (ADS)

    Mirkov, Mirko; Sherr, Evan A.; Sierra, Rafael A.; Lloyd, Jenifer R.; Tanghetti, Emil

    2006-06-01

    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

  19. Targeted therapies for cancer

    MedlinePlus

    ... page: //medlineplus.gov/ency/patientinstructions/000902.htm Targeted therapies for cancer To use the sharing features on ... cells so they cannot spread. How Does Targeted Therapy Work? Targeted therapy drugs work in a few ...

  20. Experience with IPNS targets

    SciTech Connect

    Carpenter, J.M.; Hins, A.G.

    1993-12-31

    Three targets have operated in the IPNS Neutron Scattering Facility. The first, a depleted Uranium target, served from 1981 until it was replaced in 1988 by the Enriched Uranium Booster Target. The Booster Target had operated for nearly three years when it suffered a cladding leak and was replaced with the retired depleted Uranium target. That target reached its end-of-life after less than one year`s further operation, and was replaced with an identical one newly assembled from spare components, which is still operating satisfactorily. This paper reviews the operating history of the IPNS targets and the findings reached during analysis of the failures. Similarities with ISIS target experience, preliminary conclusions and plans for providing spares and improved targets are discussed. We present some preliminary results from the hot cell examination of the failed depleted Uranium target.

  1. Electrically charged targets

    DOEpatents

    Goodman, Ronald K.; Hunt, Angus L.

    1984-01-01

    Electrically chargeable laser targets and method for forming such charged targets in order to improve their guidance along a predetermined desired trajectory. This is accomplished by the incorporation of a small amount of an additive to the target material which will increase the electrical conductivity thereof, and thereby enhance the charge placed upon the target material for guidance thereof by electrostatic or magnetic steering mechanisms, without adversely affecting the target when illuminated by laser energy.

  2. Polarized internal target apparatus

    DOEpatents

    Holt, Roy J.

    1986-01-01

    A polarized internal target apparatus with a polarized gas target of improved polarization and density achieved by mixing target gas atoms with a small amount of alkali metal gas atoms, and passing a high intensity polarized light source into the mixture to cause the alkali metal gas atoms to become polarized which interact in spin exchange collisions with target gas atoms yielding polarized target gas atoms.

  3. Polarized internal target apparatus

    DOEpatents

    Holt, R.J.

    1984-10-10

    A polarized internal target apparatus with a polarized gas target of improved polarization and density (achieved by mixing target gas atoms with a small amount of alkali metal gas atoms, and passing a high intensity polarized light source into the mixture to cause the alkali metal gas atoms to become polarized which interact in spin exchange collisions with target gas atoms yielding polarized target gas atoms) is described.

  4. Magnetically attached sputter targets

    DOEpatents

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

    1994-02-15

    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.

  5. Magnetically attached sputter targets

    DOEpatents

    Makowiecki, Daniel M.; McKernan, Mark A.

    1994-01-01

    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.

  6. FLIR target screening

    NASA Technical Reports Server (NTRS)

    Aggarwal, R.

    1982-01-01

    Methods for the segmentation and recognition of individual targets sensed with forward looking infrared detectors are discussed. Particular attention is given to an adaptive multi-scenario target screener.

  7. High Power Cryogenic Targets

    SciTech Connect

    Gregory Smith

    2011-08-01

    The development of high power cryogenic targets for use in parity violating electron scattering has been a crucial ingredient in the success of those experiments. As we chase the precision frontier, the demands and requirements for these targets have grown accordingly. We discuss the state of the art, and describe recent developments and strategies in the design of the next generation of these targets.

  8. An actionable climate target

    NASA Astrophysics Data System (ADS)

    Geden, Oliver

    2016-05-01

    The Paris Agreement introduced three mitigation targets. In the future, the main focus should not be on temperature targets such as 2 or 1.5 °C, but on the target with the greatest potential to effectively guide policy: net zero emissions.

  9. Plasma sheath driven targets

    NASA Astrophysics Data System (ADS)

    Brownell, J. H.; Freeman, B. L.

    1980-02-01

    Plasma focus driven target implosions are simulated using hydrodynamic-burn codes. Support is given to the idea that the use of a target in a plasma focus should allow 'impedance matching' between the fuel and gun, permitting larger fusion yields from a focus-target geometry than the scaling laws for a conventional plasma focus would predict.

  10. Clinical uses of radiolabeled platelets

    SciTech Connect

    Datz, F.L.; Christian, P.E.; Baker, W.J.

    1985-12-01

    Platelets were first successfully radiolabeled in 1953. At that time, investigators were primarily interested in developing a technique to accurately measure platelet life span in both normal and thrombocytopenic patients. Studies using platelets labeled with /sup 51/Cr have shown shortened platelet survival times in a number of diseases including idiopathic thrombocytopenic purpura, coronary artery disease, and diabetes mellitus. More recently, labels such as /sup 111/In have been developed that allow in vivo imaging of platelets. Indium-111 platelets are being used to better understand the pathophysiology of atherosclerosis, thrombophlebitis, pulmonary embolism and clotting disorders, and to improve the clinical diagnosis of these diseases.

  11. CASP9 Target Classification

    PubMed Central

    Kinch, Lisa N.; Shi, Shuoyong; Cheng, Hua; Cong, Qian; Pei, Jimin; Mariani, Valerio; Schwede, Torsten; Grishin, Nick V.

    2011-01-01

    The Critical Assessment of Protein Structure Prediction round 9 (CASP9) aimed to evaluate predictions for 129 experimentally determined protein structures. To assess tertiary structure predictions, these target structures were divided into domain-based evaluation units that were then classified into two assessment categories: template based modeling (TBM) and template free modeling (FM). CASP9 targets were split into domains of structurally compact evolutionary modules. For the targets with more than one defined domain, the decision to split structures into domains for evaluation was based on server performance. Target domains were categorized based on their evolutionary relatedness to existing templates as well as their difficulty levels indicated by server performance. Those target domains with sequence-related templates and high server prediction performance were classified as TMB, while those targets without identifiable templates and low server performance were classified as FM. However, using these generalizations for classification resulted in a blurred boundary between CASP9 assessment categories. Thus, the FM category included those domains without sequence detectable templates (25 target domains) as well as some domains with difficult to detect templates whose predictions were as poor as those without templates (5 target domains). Several interesting examples are discussed, including targets with sequence related templates that exhibit unusual structural differences, targets with homologous or analogous structure templates that are not detectable by sequence, and targets with new folds. PMID:21997778

  12. Wake Shield Target Protection

    SciTech Connect

    Valmianski, Emanuil I.; Petzoldt, Ronald W.; Alexander, Neil B.

    2003-05-15

    The heat flux from both gas convection and chamber radiation on a direct drive target must be limited to avoid target damage from excessive D-T temperature increase. One of the possibilities of protecting the target is a wake shield flying in front of the target. A shield will also reduce drag force on the target, thereby facilitating target tracking and position prediction. A Direct Simulation Monte Carlo (DSMC) code was used to calculate convection heat loads as boundary conditions input into ANSYS thermal calculations. These were used for studying the quality of target protection depending on various shapes of shields, target-shield distance, and protective properties of the shield moving relative to the target. The results show that the shield can reduce the convective heat flux by a factor of 2 to 5 depending on pressure, temperature, and velocity. The protective effect of a shield moving relative to the target is greater than the protective properties of a fixed shield. However, the protective effect of a shield moving under the drag force is not sufficient for bringing the heat load on the target down to the necessary limit. Some other ways of diminishing heat flux using a protective shield are discussed.

  13. Petechial rash in children: a clinical dilemma.

    PubMed

    Barnetson, Laura; Heaton, Paul Anthony; Palmer, Sarah; Paul, Siba Prosad

    2016-05-01

    Children with a petechial rash commonly present to emergency departments. The rash can be associated with serious illnesses, such as invasive meningococcal disease (IMD), but is usually associated with less severe conditions. This article discusses the common and important causes of petechial rash, including IMD, viral illnesses, trauma, Henoch-Schönlein purpura and idiopathic thrombocytopenic purpura. It also analyses the National Institute for Health and Care Excellence (NICE) ( 2014 ) pathway for management of petechial rash in children and examines treatment of the various causes. The article includes two relevant case studies and discusses the role of emergency nurses. PMID:27165395

  14. Bar coded retroreflective target

    SciTech Connect

    Vann, C.S.

    2000-01-25

    This small, inexpensive, non-contact laser sensor can detect the location of a retroreflective target in a relatively large volume and up to six degrees of position. The tracker's laser beam is formed into a plane of light which is swept across the space of interest. When the beam illuminates the retroreflector, some of the light returns to the tracker. The intensity, angle, and time of the return beam is measured to calculate the three dimensional location of the target. With three retroreflectors on the target, the locations of three points on the target are measured, enabling the calculation of all six degrees of target position. Until now, devices for three-dimensional tracking of objects in a large volume have been heavy, large, and very expensive. Because of the simplicity and unique characteristics of this tracker, it is capable of three-dimensional tracking of one to several objects in a large volume, yet it is compact, light-weight, and relatively inexpensive. Alternatively, a tracker produces a diverging laser beam which is directed towards a fixed position, and senses when a retroreflective target enters the fixed field of view. An optically bar coded target can be read by the tracker to provide information about the target. The target can be formed of a ball lens with a bar code on one end. As the target moves through the field, the ball lens causes the laser beam to scan across the bar code.

  15. Bar coded retroreflective target

    DOEpatents

    Vann, Charles S.

    2000-01-01

    This small, inexpensive, non-contact laser sensor can detect the location of a retroreflective target in a relatively large volume and up to six degrees of position. The tracker's laser beam is formed into a plane of light which is swept across the space of interest. When the beam illuminates the retroreflector, some of the light returns to the tracker. The intensity, angle, and time of the return beam is measured to calculate the three dimensional location of the target. With three retroreflectors on the target, the locations of three points on the target are measured, enabling the calculation of all six degrees of target position. Until now, devices for three-dimensional tracking of objects in a large volume have been heavy, large, and very expensive. Because of the simplicity and unique characteristics of this tracker, it is capable of three-dimensional tracking of one to several objects in a large volume, yet it is compact, light-weight, and relatively inexpensive. Alternatively, a tracker produces a diverging laser beam which is directed towards a fixed position, and senses when a retroreflective target enters the fixed field of view. An optically bar coded target can be read by the tracker to provide information about the target. The target can be formed of a ball lens with a bar code on one end. As the target moves through the field, the ball lens causes the laser beam to scan across the bar code.

  16. Inertial Confinement fusion targets

    NASA Technical Reports Server (NTRS)

    Hendricks, C. D.

    1982-01-01

    Inertial confinement fusion (ICF) targets are made as simple flat discs, as hollow shells or as complicated multilayer structures. Many techniques were devised for producing the targets. Glass and metal shells are made by using drop and bubble techniques. Solid hydrogen shells are also produced by adapting old methods to the solution of modern problems. Some of these techniques, problems, and solutions are discussed. In addition, the applications of many of the techniques to fabrication of ICF targets is presented.

  17. Integrin Targeted MR Imaging.

    PubMed

    Tan, Mingqian; Lu, Zheng-Rong

    2011-01-19

    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 T(1), T(2), 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.

  18. HYDROGEN ISOTOPE TARGETS

    DOEpatents

    Ashley, R.W.

    1958-08-12

    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.

  19. Targeting the tumor microenvironment

    SciTech Connect

    Kenny, P.A.; Lee, G.Y.; Bissell, M.J.

    2006-11-07

    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.

  20. Infrared target array development

    NASA Astrophysics Data System (ADS)

    Scott, E. A.

    1980-04-01

    The US Army Yuma Proving Ground (USAYPG) was requested to develop and acquire a series of infrared targets with controllable thermal signatures to support the test and evaluation of the Target Acquisition Designation System/Pilot Night Vision System (TADS/PNVS) subsystems of the Advanced Attack Helicopter (AAH) Fire Control System. Prior to this development effort, no capability beyond the use of real-scene targets existed at USAYPG to provide thermally active targets with characteristic signatures in the infrared band. Three targets were acquired: (1) a detection target; (2) a recognition target; and (3) a laser scoring board. It is concluded that design goals were met and the system was delivered in time to perform its function. The system provides sufficient thermal realism and has advanced the state-of-the-art of infrared imaging system test and evaluation. It is recommended that the Field Equivalent Bar Target (FEBT) system be validated as a potential test standard and that environmentally 'hardened' targets be acquired for continued thermal sight testing.

  1. Target visibility for multiple maneuvering target tracking

    NASA Astrophysics Data System (ADS)

    Sabordo, Madeleine G.; Aboutanios, Elias

    2015-05-01

    We present a recursion of the probability of target visibility and its applications to analysis of track life and termination in the context of Global Nearest Neighbour (GNN) approach and Probability Hypothesis Density (PHD) filter. In the presence of uncertainties brought about by clutter; decisions to retain a track, terminate it or initialise a new track are based on probability, rather than on distance criterion or estimation error. The visibility concept is introduced into a conventional data-association-oriented multitarget tracker, the GNN; and a random finite set based-tracker, the PHD filter, to take into account instances when targets become invisible or occluded by obstacles. We employ the natural logarithmof the Dynamic Error Spectrum to assess the performance of the trackers with and without probability of visibility incorporated. Simulation results show that the performance of the GNN tracker with visibility concept incorporated is significantly enhanced.

  2. Gene targeting in livestock.

    PubMed

    Thomson, A J; Marques, M M; McWhir, J

    2003-01-01

    The development of nuclear transfer from tissue culture cells in livestock made it possible in principle to produce animals with subtle, directed genetic changes by in vitro modification of nuclear donor cells. In the short period since nuclear transfer was first performed, gene targeting in livestock has become a reality. Although gene targeting has immediate potential in biotechnology, it is unclear whether there are practical agricultural applications, at present. The first livestock targeting experiments have been directed at engineering animals either to render their organs immunologically compatible for human transplantation, or for improving the commercial production of recombinant proteins in the transgenic mammary gland. All successful examples of targeting have involved target loci that are expressed in the nuclear donor cell line. Two important barriers to the further development of this technology are adapting protocols for non-expressed genes and modifying procedures to enhance the lifespan of targeted cells in vitro. This review provides data that illustrate the difficulty in targeting non-expressed genes and discusses some of the practical issues associated with providing targeted nuclear donor cells that are competent for nuclear transfer.

  3. Knowing Your Learning Target

    ERIC Educational Resources Information Center

    Moss, Connie M.; Brookhart, Susan M.; Long, Beverly A.

    2011-01-01

    No matter what we decide students need to learn, not much will happen until students understand what they are supposed to learn during a lesson and set their sights on learning it. Crafting learning targets for each lesson and deliberately sharing them with students is one way to give students the direction they need. Targets that tell students…

  4. Methodology for target discrimination.

    PubMed

    McNolty, F; Clow, R

    1980-03-15

    The objective is to distinguish the true target from point-target imitators and from extended-target clutter in the exoatmospheric regime. Matched filters are carefully studied from the viewpoint of SNR enhancement and pulse recognition. The matched filter structure takes into account photon noise, modulation noise, generation-recombination (GR) noise, contact noise, and various thermal noise sources. A multicolor radiant-intensity structure for target discrimination is developed by analyzing the uncertainties in such target irradiance parameters as range, temperature, projected area, and emissivity. Bias terms, variances, and other statistical descriptors are derived. Certain statistical discrimination techniques are discussed that exploit the radiant-intensity format. Helstrom's method for processing radar signals is adapted to a fourchannel pulse-recognition system for which degradation due to arrival time delays and mismatched filters is discussed.

  5. Advanced Targeted Nanomedicine

    PubMed Central

    Arachchige, Mohan C M; Reshetnyak, Yana K.; Andreev, Oleg A.

    2015-01-01

    Targeted drug delivery has been the major topic in drug formulation and delivery. As nanomedicine emerges to create nano scale therapeutics and diagnostics, it is still essential to embed targeting capability to these novel systems to make them useful. Here we discuss various targeting approaches for delivery of therapeutic and diagnostic nano materials in view of search for more universal methods to target diseased tissues. Many diseases are accompanied with hypoxia and acidosis. Coating nanoparticles with pH Low Insertion Peptides (pHLIPs) increases efficiency of targeting acidic diseased tissues. It has been showing promising results to create future nanotheranostics for cancer and other diseases which are dominating in the present world. PMID:25615945

  6. Infrared Target Array Development

    NASA Astrophysics Data System (ADS)

    McIntire, Thomas O.; Scott, Edward A.

    1982-03-01

    A "life size" thermal target array has been developed to facilitate in-flight testing of airborne weapon systems containing night vision subsystems. This in-flight testing to measure the performance of the night vision subsystem and its effect on overall weapon system performance is essential to the test and evaluation process of the particular weapon under test. This measurement of subsystem performance is called the Modulation Transfer Function, or MTF. In addition, a laser designator subsystem is frequently incorporated in a precision guided munition weapon system. In the test and evaluation of the designator, such quantities as beam quality (energy distribution), beam divergence, and beam wander are of interest. The thermal targets may be used to evaluate armored weapon systems. The capability of providing carefully controlled and variable thermal signatures in a field test environment is considered unique. The thermal target array consists of three targets: A six bar recognition target, a two bar detection target, and a laser designator scoring board (cross-hair). The image dimensions of 2.3 meters by 2.3 meters were derived from an optimized threat envelope. The thermal signatures of the targets are controllable to within 0.3 C about a differential setpoint. This differential setpoint is measured between the active element and the target background (or "ambient"). Several differential temperature settings are available to the test officer: 1.25°C, 3°C, 5°C, 7.5°C, and 10°C. This paper reviews the thermal array test objectives, target array fabrication, methodology of target utilization, and representative results.

  7. Nuclear target development

    SciTech Connect

    Greene, J.P.; Thomas, G.E.

    1995-08-01

    The Physics Division operates a target development laboratory that produces thin foil targets needed for experiments performed at the ATLAS and Dynamitron accelerators. Targets are not only produced for the Physics Division but also for other divisions and occasionally for other laboratories and universities. In the past year, numerous targets were fabricated by vacuum evaporation either as self-supporting foils or on various substrates. Targets produced included Ag, Au, {sup 10,11}B, {sup 138}Ba, Be, {sup 12}C, {sup 40}Ca, {sup 116}Cd, {sup 155,160}Gd, {sup 76}Ge, In, LID, {sup 6}LiH, Melamine, Mg, {sup 142,150}Nd, {sup 58}Ni, {sup 206,208}Pb, {sup 194}Pt, {sup 28}Si, {sup 144,148}Sm, {sup 120,122,124}Sn, Ta, {sup 130}Te, ThF{sub 4}, {sup 46,50}Ti, TiH, U, UF{sub 4}, {sup 182}W and {sup 170}Yb. Polypropylene and aluminized polypropylene, along with metallized Mylar were produced for experiments at ATLAS. A number of targets of {sup 11}B of various thickness were made for the DEP 2-MeV Van de Graff accelerator. An increased output of foils fabricated using our small rolling mill included targets of Au, C, {sup 50}Cr, Cu, {sup 155,160}Gd, Mg, {sup 58}Ni, {sup 208}Pb, {sup 105,110}Pd. Sc, Ti, and {sup 64,66}Zn.

  8. IgA nephropathy and Henoch-Schoenlein purpura nephritis: aberrant glycosylation of IgA1, formation of IgA1-containing immune complexes, and activation of mesangial cells.

    PubMed

    Novak, Jan; Moldoveanu, Zina; Renfrow, Matthew B; Yanagihara, Takeshi; Suzuki, Hitoshi; Raska, Milan; Hall, Stacy; Brown, Rhubell; Huang, Wen-Qiang; Goepfert, Alice; Kilian, Mogens; Poulsen, Knud; Tomana, Milan; Wyatt, Robert J; Julian, Bruce A; Mestecky, Jiri

    2007-01-01

    IgA1 in the circulation and glomerular deposits of patients with IgA nephropathy (IgAN) is aberrantly glycosylated; the hinge-region O-linked glycans are galactose-deficient. The circulating IgA1 of patients with Henoch-Schoenlein purpura nephritis (HSPN) has a similar defect. This aberrancy exposes N-acetylgalactosamine-containing neoepitopes recognized by naturally occurring IgG or IgA1 antibodies resulting in formation of immune complexes. IgA1 contains up to six O-glycosylation sites per heavy chain; it is not known whether the glycosylation defect occurs randomly or preferentially at specific sites. We sought to define the aberrant glycosylation of a galactose-deficient IgA1 myeloma protein and analyze the formation of the immune complexes and their biological activities. Supplementation of serum or cord-blood serum with this IgA1 protein resulted in formation of new IgA1 complexes. These complexes stimulated proliferation of cultured human mesangial cells, as did the naturally-occurring IgA1-containing complexes from sera of patients with IgAN and HSPN. Uncomplexed IgA1 did not affect cellular proliferation. Using specific proteases, lectin Western blots, and mass spectrometry, we determined the O-glycosylation sites in the hinge region of the IgA1 myeloma protein and IgA1 proteins from sera of IgAN patients. The IgA1 myeloma protein had galactose-deficient sites at residues 228 and/or 230 and 232. These sites reacted with IgG specific to galactose-deficient IgA1. IgA1 from the IgAN patients had galactose-deficient O-glycans at the same residues. In summary, we identified the neoepitopes on IgA1 responsible for formation of the pathogenic immune complexes. These studies may lead to development of noninvasive diagnostic assays and future disease-specific therapy.

  9. STIS target acquisition

    NASA Technical Reports Server (NTRS)

    Kraemer, Steve; Downes, Ron; Katsanis, Rocio; Crenshaw, Mike; McGrath, Melissa; Robinson, Rich

    1997-01-01

    We describe the STIS autonomous target acquisition capabilities. We also present the results of dedicated tests executed as part of Cycle 7 calibration, following post-launch improvements to the Space Telescope Imaging Spectrograph (STIS) flight software. The residual pointing error from the acquisitions are < 0.5 CCD pixels, which is better than preflight estimates. Execution of peakups show clear improvement of target centering for slits of width 0.1 sec or smaller. These results may be used by Guest Observers in planning target acquisitions for their STIS programs.

  10. USGS aerial resolution targets.

    USGS Publications Warehouse

    Salamonowicz, P.H.

    1982-01-01

    It is necessary to measure the achievable resolution of any airborne sensor that is to be used for metric purposes. Laboratory calibration facilities may be inadequate or inappropriate for determining the resolution of non-photographic sensors such as optical-mechanical scanners, television imaging tubes, and linear arrays. However, large target arrays imaged in the field can be used in testing such systems. The USGS has constructed an array of resolution targets in order to permit field testing of a variety of airborne sensing systems. The target array permits any interested organization with an airborne sensing system to accurately determine the operational resolution of its system. -from Author

  11. Multiple tuberculous aneurysms of the aorta.

    PubMed

    Pierret, Charles; Tourtier, Jean-Pierre; Grand, Bertrand; Boddaert, Guillaume; Laurian, Claude; de Kerangal, Xavier

    2011-06-01

    Tuberculous aneurysms of the aorta are quite rare, but are exceptional when found in multiple locations. We report the case of multiple tuberculous aortic aneurysms of the thoracic and abdominal aorta in a 19-year-old female discovered when she consulted for thrombocytopenic purpura. The treatment for both locations included prolonged antituberculous therapy and surgical resection with cryopreserved aortic allograft patch for the reconstruction.

  12. Nras in melanoma: targeting the undruggable target.

    PubMed

    Mandalà, Mario; Merelli, Barbara; Massi, Daniela

    2014-11-01

    RAS belongs to the guanosine 5'-triphosphate (GTP)-binding proteins' family, and oncogenic mutations in codons 12, 13, or 61 of RAS family occur in approximately one third of all human cancers with N-RAS mutations found in about 15-20% of melanomas. The importance of RAS signaling as a potential target in cancer is emphasized not only by the prevalence of RAS mutations, but also by the high number of RAS activators and effectors identified in mammalian cells that places the RAS proteins at the crossroads of several, important signaling networks. Ras proteins are crucial crossroads of signaling pathways that link the activation of cell surface receptors with a wide variety of cellular processes leading to the control of proliferation, apoptosis and differentiation. Furthermore, oncogenic ras proteins interfere with metabolism of tumor cells, microenvironment's remodeling, evasion of the immune response, and finally contributes to the metastatic process. After 40 years of basic, translational and clinical research, much is now known about the molecular mechanisms by which these monomeric guanosine triphosphatase-binding proteins promote cellular malignancy, and it is clear that they regulate signaling pathways involved in the control of cell proliferation, survival, and invasiveness. In this review we summarize the biological role of RAS in cancer by focusing our attention on the biological rational and strategies to target RAS in melanoma.

  13. Mitochondria-targeted antioxidants.

    PubMed

    Oyewole, Anne O; Birch-Machin, Mark A

    2015-12-01

    Redox homeostasis is maintained by the antioxidant defense system, which is responsible for eliminating a wide range of oxidants, including reactive oxygen species (ROS), lipid peroxides, and metals. Mitochondria-localized antioxidants are widely studied because the mitochondria, the major producers of intracellular ROS, have been linked to the cause of aging and other chronic diseases. Mitochondria-targeted antioxidants have shown great potential because they cross the mitochondrial phospholipid bilayer and eliminate ROS at the heart of the source. Growing evidence has identified mitochondria-targeted antioxidants, such as MitoQ and tiron, as potentially effective antioxidant therapies against the damage caused by enhanced ROS generation. This literature review summarizes the current knowledge on mitochondria-targeted antioxidants and their contribution to the body's antioxidant defense system. In addition to addressing the concerns surrounding current antioxidant strategies, including difficulties in targeting antioxidant treatment to sites of pathologic oxidative damage, we discuss promising therapeutic agents and new strategic approaches.

  14. Multiple shell fusion targets

    DOEpatents

    Lindl, J.D.; Bangerter, R.O.

    1975-10-31

    Multiple shell fusion targets for use with electron beam and ion beam implosion systems are described. The multiple shell targets are of the low-power type and use a separate relatively low Z, low density ablator at large radius for the outer shell, which reduces the focusing and power requirements of the implosion system while maintaining reasonable aspect ratios. The targets use a high Z, high density pusher shell placed at a much smaller radius in order to obtain an aspect ratio small enough to protect against fluid instability. Velocity multiplication between these shells further lowers the power requirements. Careful tuning of the power profile and intershell density results in a low entropy implosion which allows breakeven at low powers. For example, with ion beams as a power source, breakeven at 10-20 Terrawatts with 10 MeV alpha particles for imploding a multiple shell target can be accomplished.

  15. Target Heart Rate Calculator

    MedlinePlus

    ... My Saved Articles » My ACS » + - Text Size Target Heart Rate Calculator Compute your best workout Enter your age ... is your age? years. How to Check Your Heart Rate Right after you stop exercising, take your pulse: ...

  16. Liposomes for cardiovascular targeting.

    PubMed

    Levchenko, Tatyana S; Hartner, William C; Torchilin, Vladimir P

    2012-04-01

    Liposome-based pharmaceuticals used within the cardiovascular system are reviewed in this article. The delivery of diagnostic and therapeutic agents by plain liposomes and liposomes with surface-attached targeting antibodies or polyethylene glycol to prolong their circulation time and accumulation at vascular injuries, ischemic zones or sites of thrombi are also discussed. An overview of the advantages and disadvantages of liposome-mediated in vitro, ex vivo and in vivo targeting is presented, including discussion of the targeting of liposomes to pathological sites on the blood vessel wall and a description of liposomes that can be internalized by endothelial cells. Diagnostic liposomes used to target myocardial infarction and the relative importance of liposome size, targetability of immunoliposomes and prolonged circulation time on the efficiency of sealing hypoxia-induced plasma membrane damage to cardiocytes are discussed as a promising approach for therapy. The progress in the use of targeted liposomal plasmids for the transfection of hypoxic cardiomyocytes and myocardium is presented. Stent-mediated liposomal-based drug delivery is also reviewed briefly. PMID:22834079

  17. A Case Report of an Elderly Woman With Thrombocytopenia and Bilateral Lung Infiltrates

    PubMed Central

    Hashmi, Hafiz Rizwan Talib; Venkatram, Sindhaghatta; Diaz-Fuentes, Gilda

    2015-01-01

    Abstract Etiologies for diffuse alveolar hemorrhage are wide and range from infectious to vasculitis and malignant processes. Idiopathic thrombocytopenic purpura is an autoimmune disorder characterized by persistent thrombocytopenia, with a relatively indolent course in young patients, but a more complicated progression and high associated mortality in the older patients. Diffuse alveolar hemorrhage, complicating idiopathic thrombocytopenic purpura, is a very uncommon association, with only 2 reported cases in the literature. We present a 69-year-old healthy woman presenting with petechial rash, progressive dyspnea, and bilateral alveolar infiltrates. She was found to have idiopathic thrombocytopenic purpura associated with diffuse alveolar hemorrhage. The patient had an excellent response to high doses of pulse steroids and immunoglobulins. A high index of suspicion for noninfectious pulmonary diseases should be considered in patients with autoimmune diseases presenting with pulmonary infiltrates and hypoxia. Flexible bronchoscopy with sequential lavage is a relatively safe procedure in patients with coagulopathy and should be attempted to detect and confirm the diagnosis; absence of hemoptysis should not preclude the diagnosis. PMID:26683938

  18. Production Target Design Report

    SciTech Connect

    Woloshun, Keith Albert; Dale, Gregory E.; Olivas, Eric Richard

    2015-07-28

    The Northstar 99Mo production target, a cylindrical length of 100Mo rod, has evolved considerably since its first conception.  The cylinder was very early sliced into disks to increase the heat transfer area, first to 1 mm thick disks then to the current 0.5 mm thick.  The coolant was changed early in the target development from water to helium to eliminate corrosion and dissolution.  The diameter has increased from initially 6 mm to 12 mm, the current diameter of the test target now at ANL, to nominally 28 mm (26-30.6 mm, depending upon optimal beam spot size and shape).  The length has also changed to improve the production to cost ratio, so now the target is nominally 41 mm long (excluding coolant gaps between disks), and irradiated on both ends.  This report summarizes the current status of the plant target design.

  19. Burglar Target Selection

    PubMed Central

    Townsley, Michael; Bernasco, Wim; Ruiter, Stijn; Johnson, Shane D.; White, Gentry; Baum, Scott

    2015-01-01

    Objectives: This study builds on research undertaken by Bernasco and Nieuwbeerta and explores the generalizability of a theoretically derived offender target selection model in three cross-national study regions. Methods: Taking a discrete spatial choice approach, we estimate the impact of both environment- and offender-level factors on residential burglary placement in the Netherlands, the United Kingdom, and Australia. Combining cleared burglary data from all study regions in a single statistical model, we make statistical comparisons between environments. Results: In all three study regions, the likelihood an offender selects an area for burglary is positively influenced by proximity to their home, the proportion of easily accessible targets, and the total number of targets available. Furthermore, in two of the three study regions, juvenile offenders under the legal driving age are significantly more influenced by target proximity than adult offenders. Post hoc tests indicate the magnitudes of these impacts vary significantly between study regions. Conclusions: While burglary target selection strategies are consistent with opportunity-based explanations of offending, the impact of environmental context is significant. As such, the approach undertaken in combining observations from multiple study regions may aid criminology scholars in assessing the generalizability of observed findings across multiple environments. PMID:25866418

  20. Targeted assets risk analysis.

    PubMed

    Bouwsema, Barry

    2013-01-01

    Risk assessments utilising the consolidated risk assessment process as described by Public Safety Canada and the Centre for Security Science utilise the five threat categories of natural, human accidental, technological, human intentional and chemical, biological, radiological, nuclear or explosive (CBRNE). The categories of human intentional and CBRNE indicate intended actions against specific targets. It is therefore necessary to be able to identify which pieces of critical infrastructure represent the likely targets of individuals with malicious intent. Using the consolidated risk assessment process and the target capabilities list, coupled with the CARVER methodology and a security vulnerability analysis, it is possible to identify these targeted assets and their weaknesses. This process can help emergency managers to identify where resources should be allocated and funding spent. Targeted Assets Risk Analysis (TARA) presents a new opportunity to improve how risk is measured, monitored, managed and minimised through the four phases of emergency management, namely, prevention, preparation, response and recovery. To reduce risk throughout Canada, Defence Research and Development Canada is interested in researching the potential benefits of a comprehensive approach to risk assessment and management. The TARA provides a framework against which potential human intentional threats can be measured and quantified, thereby improving safety for all Canadians.

  1. Adequacy target in hemodialysis.

    PubMed

    Canaud, Bernard

    2004-01-01

    Over the last decade, the concept of dialysis adequacy has evolved to become a component of the optimal dialysis that includes quantitative and qualitative aspects. Current method used to assess dialysis efficacy in ESRD patients relies on a targeting approach using several vital indicators. Dialysis quality is a complex and evolutionary concept that has to be viewed in a quality assurance process to improve outcomes of ESRD patients. To simplify this assessment we propose a quantitative approach including several steps: the first step consists of selecting pertinent indicators (targets) tracking specific uremia metabolic abnormalities and defining suitable range values (target values); the second step consists of defining a method checking that targeted values are achieved on a regular basis; the third step consists of validating that targeted values offer the best survival to ESRD patients; the fourth step consists of correcting treatment prescription (treatment schedule) and implementation (effective treatment delivered) to improve treatment delivery and performances. Based on this approach, it is then possible to assess the efficacy of dialysis therapy both at the individual and at the dialysis unit level, that can be easily implemented in a computerized automatic control system. PMID:15599891

  2. High power density targets

    NASA Astrophysics Data System (ADS)

    Pellemoine, Frederique

    2013-12-01

    In the context of new generation rare isotope beam facilities based on high-power heavy-ion accelerators and in-flight separation of the reaction products, the design of the rare isotope production targets is a major challenge. In order to provide high-purity beams for science, high resolution is required in the rare isotope separation. This demands a small beam spot on the production target which, together with the short range of heavy ions in matter, leads to very high power densities inside the target material. This paper gives an overview of the challenges associated with this high power density, discusses radiation damage issues in targets exposed to heavy ion beams, and presents recent developments to meet some of these challenges through different projects: FAIR, RIBF and FRIB which is the most challenging. Extensive use of Finite Element Analysis (FEA) has been made at all facilities to specify critical target parameters and R&D work at FRIB successfully retired two major risks related to high-power density and heavy-ion induced radiation damage.

  3. The Sinuous Target

    SciTech Connect

    Zwaska, R.

    2015-06-01

    We report on the concept for a target material comprised of a multitude of interlaced wires of small dimension. This target material concept is primarily directed at high-power neutrino targets where the thermal shock is large due to small beam sizes and short durations; it also has applications to other high-power targets, particularly where the energy deposition is great or a high surface area is preferred. This approach ameliorates the problem of thermal shock by engineering a material with high strength on the micro-scale, but a very low modulus of elasticity on the meso-scale. The low modulus of elasticity is achieved by constructing the material of spring-like wire segments much smaller than the beam dimension. The intrinsic bends of the wires will allow them to absorb the strain of thermal shock with minimal stress. Furthermore, the interlaced nature of the wires provides containment of any segment that might become loose. We will discuss the progress on studies of analogue materials and fabrication techniques for sinuous target materials.

  4. Targeted assets risk analysis.

    PubMed

    Bouwsema, Barry

    2013-01-01

    Risk assessments utilising the consolidated risk assessment process as described by Public Safety Canada and the Centre for Security Science utilise the five threat categories of natural, human accidental, technological, human intentional and chemical, biological, radiological, nuclear or explosive (CBRNE). The categories of human intentional and CBRNE indicate intended actions against specific targets. It is therefore necessary to be able to identify which pieces of critical infrastructure represent the likely targets of individuals with malicious intent. Using the consolidated risk assessment process and the target capabilities list, coupled with the CARVER methodology and a security vulnerability analysis, it is possible to identify these targeted assets and their weaknesses. This process can help emergency managers to identify where resources should be allocated and funding spent. Targeted Assets Risk Analysis (TARA) presents a new opportunity to improve how risk is measured, monitored, managed and minimised through the four phases of emergency management, namely, prevention, preparation, response and recovery. To reduce risk throughout Canada, Defence Research and Development Canada is interested in researching the potential benefits of a comprehensive approach to risk assessment and management. The TARA provides a framework against which potential human intentional threats can be measured and quantified, thereby improving safety for all Canadians. PMID:23615063

  5. Cooled particle accelerator target

    DOEpatents

    Degtiarenko, Pavel V.

    2005-06-14

    A novel particle beam target comprising: a rotating target disc mounted on a retainer and thermally coupled to a first array of spaced-apart parallel plate fins that extend radially inwardly from the retainer and mesh without physical contact with a second array of spaced-apart parallel plate fins that extend radially outwardly from and are thermally coupled to a cooling mechanism capable of removing heat from said second array of spaced-apart fins and located within the first array of spaced-apart parallel fins. Radiant thermal exchange between the two arrays of parallel plate fins provides removal of heat from the rotating disc. A method of cooling the rotating target is also described.

  6. Targeted antithrombotic protein micelles.

    PubMed

    Kim, Wookhyun; Haller, Carolyn; Dai, Erbin; Wang, Xiowei; Hagemeyer, Christoph E; Liu, David R; Peter, Karlheinz; Chaikof, Elliot L

    2015-01-26

    Activated platelets provide a promising target for imaging inflammatory and thrombotic events along with site-specific delivery of a variety of therapeutic agents. Multifunctional protein micelles bearing targeting and therapeutic proteins were now obtained by one-pot transpeptidation using an evolved sortase A. Conjugation to the corona of a single-chain antibody (scFv), which binds to the ligand-induced binding site (LIBS) of activated GPIIb/IIIa receptors, enabled the efficient detection of thrombi. The inhibition of thrombus formation was subsequently accomplished by incorporating the catalytically active domain of thrombomodulin (TM) onto the micelle corona for the local generation of activated protein C, which inhibits the formation of thrombin. An effective strategy has been developed for the preparation of protein micelles that can be targeted to sites of activated platelets with broad potential for treatment of acute thrombotic events. PMID:25504546

  7. Setting reference targets

    SciTech Connect

    Ruland, R.E.

    1997-04-01

    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.

  8. Magnetized Target Fusion collaboration

    NASA Astrophysics Data System (ADS)

    Intrator, Thomas

    2004-11-01

    Magnetized Target Fusion (MTF) may be a low cost path to fusion, in a regime that is intermediate between magnetic and inertial fusion energy. It requires compression of a magnetized target plasma and consequent heating to fusion relevant conditions inside a converging flux conserver. We hope to demonstrate the physics basis for MTF, with a Field Reversed Configuration (FRC) target plasma to be translated axially to a compression region. We show recent and improved FRC formation data, example deformable liner implosions, and a conceptual design for the upcoming translation experiments, and describe a multi institution collaboration. The FRC is an elongated, compact toroid equilibrium that is extreme among magnetic configurations, and relaxed to a non force free state. There is high plasma beta, small toroidal field, cross-field diamagnetic current and flows, vanishing rotational transform, magnetic shear, helicity and anomalously large resistivity. Scientific issues include MTF with and without FRC's, and fundamental plasma physics beyond MHD, relevant to geophysical and astrophysical phenomena.

  9. Phoenix Color Targets

    NASA Technical Reports Server (NTRS)

    2008-01-01

    These images of three Phoenix color targets were taken on sols 1 and 2 by the Surface Stereo Imager (SSI) on board the Phoenix lander. The bottom target was imaged in approximate color (SSI's red, green, and blue filters: 600, 530, and 480 nanometers), while the others were imaged with an infrared filter (750 nanometers). All of them will be imaged many times over the mission to monitor the color calibration of the camera. The two at the top show grains 2 to 3 millimeters in size that were likely lifted to the Phoenix deck during landing. Each of the large color chips on each target contains a strong magnet to protect the interior material from Mars' magnetic dust.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  10. Targeted polypeptide degradation

    DOEpatents

    Church, George M.; Janse, Daniel M.

    2008-05-13

    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.

  11. Targeting peroxiredoxins against leukemia.

    PubMed

    Liu, Chuan-Xu; Zhou, Hu-Chen; Yin, Qian-Qian; Wu, Ying-Li; Chen, Guo-Qiang

    2013-01-15

    Peroxiredoxins (Prx), a family of small non-seleno peroxidases, are important regulators for cellular reactive oxygen species (ROS), which contribute to many signaling pathways and pathogenesis of diseases. Targeting redox homeostasis is being developed as a promising therapeutic strategy for many diseases such as cancers. This mini-review attempts to focus on our recent discoveries on adenanthin as the first natural molecule to specifically target the resolving cysteines of Prx I and Prx II and thus inhibit their peroxidase activities, and its role in differentiation induction in vitro and in vivo of acute myeloid leukemic cells.

  12. Foam encapsulated targets

    DOEpatents

    Nuckolls, John H.; Thiessen, Albert R.; Dahlbacka, Glen H.

    1983-01-01

    Foam encapsulated laser-fusion targets wherein a quantity of thermonuclear fuel is embedded in low density, microcellular foam which serves as an electron conduction channel for symmetrical implosion of the fuel by illumination of the target by one or more laser beams. The fuel, such as DT, is contained within a hollow shell constructed of glass, for example, with the foam having a cell size of preferably no greater than 2 .mu.m, a density of 0.065 to 0.6.times.10.sup.3 kg/m.sup.3, and external diameter of less than 200 .mu.m.

  13. Integrin Targeted Therapeutics

    PubMed Central

    Millard, Melissa; Odde, Srinivas; Neamati, Nouri

    2011-01-01

    Integrins are heterodimeric, transmembrane receptors that function as mechanosensors, adhesion molecules and signal transduction platforms in a multitude of biological processes. As such, integrins are central to the etiology and pathology of many disease states. Therefore, pharmacological inhibition of integrins is of great interest for the treatment and prevention of disease. In the last two decades several integrin-targeted drugs have made their way into clinical use, many others are in clinical trials and still more are showing promise as they advance through preclinical development. Herein, this review examines and evaluates the various drugs and compounds targeting integrins and the disease states in which they are implicated. PMID:21547158

  14. Targeting the tumor microenvironment

    PubMed Central

    Bournazou, Eirini; Bromberg, Jacqueline

    2013-01-01

    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. PMID:24058812

  15. Target chambers for gammashpere

    SciTech Connect

    Carpenter, M.P.; Falout, J.W.; Nardi, B.G.

    1995-08-01

    One of our responsibilities for Gammasphere, was designing and constructing two target chambers and associated beamlines to be used with the spectrometer. The first chamber was used with the early implementation phase of Gammasphere, and consisted of two spun-Al hemispheres welded together giving a wall thickness of 0.063 inches and a diameter of 12 inches.

  16. Target-Rich Environment

    ERIC Educational Resources Information Center

    Perna, Mark C.

    2005-01-01

    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…

  17. Target fragmentation in radiobiology

    NASA Technical Reports Server (NTRS)

    Wilson, John W.; Cucinotta, Francis A.; Shinn, Judy L.; Townsend, Lawrence W.

    1993-01-01

    Nuclear reactions in biological systems produce low-energy fragments of the target nuclei seen as local high events of linear energy transfer (LET). A nuclear-reaction formalism is used to evaluate the nuclear-induced fields within biosystems and their effects within several biological models. On the basis of direct ionization interaction, one anticipates high-energy protons to have a quality factor and relative biological effectiveness (RBE) of unity. Target fragmentation contributions raise the effective quality factor of 10 GeV protons to 3.3 in reasonable agreement with RBE values for induced micronuclei in bean sprouts. Application of the Katz model indicates that the relative increase in RBE with decreasing exposure observed in cell survival experiments with 160 MeV protons is related solely to target fragmentation events. Target fragment contributions to lens opacity given an RBE of 1.4 for 2 GeV protons in agreement with the work of Lett and Cox. Predictions are made for the effective RBE for Harderian gland tumors induced by high-energy protons. An exposure model for lifetime cancer risk is derived from NCRP 98 risk tables, and protraction effects are examined for proton and helium ion exposures. The implications of dose rate enhancement effects on space radiation protection are considered.

  18. Enhanced target factor analysis.

    PubMed

    Rostami, Akram; Abdollahi, Hamid; Maeder, Marcel

    2016-03-10

    Target testing or target factor analysis, TFA, is a well-established soft analysis method. TFA answers the question whether an independent target test vector measured at the same wavelengths as the collection of spectra in a data matrix can be excluded as the spectrum of one of the components in the system under investigation. Essentially, TFA cannot positively prove that a particular test spectrum is the true spectrum of one of the components, it can, only reject a spectrum. However, TFA will not reject, or in other words TFA will accept, many spectra which cannot be component spectra. Enhanced Target Factor Analysis, ETFA addresses the above problem. Compared with traditional TFA, ETFA results in a significantly narrower range of positive results, i.e. the chance of a false positive test result is dramatically reduced. ETFA is based on feasibility testing as described in Refs. [16-19]. The method has been tested and validated with computer generated and real data sets.

  19. Cancer immunotherapy targeting neoantigens.

    PubMed

    Lu, Yong-Chen; Robbins, Paul F

    2016-02-01

    Neoantigens are antigens encoded by tumor-specific mutated genes. Studies in the past few years have suggested a key role for neoantigens in cancer immunotherapy. Here we review the discoveries of neoantigens in the past two decades and the current advances in neoantigen identification. We also discuss the potential benefits and obstacles to the development of effective cancer immunotherapies targeting neoantigens.

  20. Targets of curcumin

    PubMed Central

    Zhou, Hongyu; Beevers, Christopher S.; Huang, Shile

    2010-01-01

    Curcumin (diferuloylmethane), an orange-yellow component of turmeric or curry powder, is a polyphenol natural product isolated from the rhizome of the plant Curcuma longa. For centuries, curcumin has been used in some medicinal preparation or used as a food-coloring agent. In recent years, extensive in vitro and in vivo studies suggested curcumin has anticancer, antiviral, antiarthritic, anti-amyloid, antioxidant, and anti-inflammatory properties. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (such as nuclear factor-κB), growth factors (such as vascular endothelial cell growth factor), inflammatory cytokines (such as tumor necrosis factor, interleukin 1 and interleukin 6), protein kinases (such as mammalian target of rapamycin, mitogen-activated protein kinases, and Akt) and other enzymes (such as cyclooxygenase 2 and 5 lipoxygenase). Thus, due to its efficacy and regulation of multiple targets, as well as its safety for human use, curcumin has received considerable interest as a potential therapeutic agent for the prevention and/or treatment of various malignant diseases, arthritis, allergies, Alzheimer’s disease, and other inflammatory illnesses. This review summarizes various in vitro and in vivo pharmacological aspects of curcumin as well as the underlying action mechanisms. The recently identified molecular targets and signaling pathways modulated by curcumin are also discussed here. PMID:20955148

  1. Opportunity Spies Its Target

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This is a forward-looking view of the Meridiani Planum plains that lie between the Mars Exploration Rover Opportunity and its primary drive target, 'Endurance Crater.' The images in this image mosaic were taken by the rover's panoramic camera on sol 88.

  2. Right on Target

    ERIC Educational Resources Information Center

    Henderson, Nancy

    2008-01-01

    This article features the Target Community and Educational Services program, a salaried arrangement that allows students at McDaniel College to complete their studies while living with, and managing, clients with developmental disabilities. In what is believed to be the only arrangement of its kind in the U.S., full-time graduate students agree to…

  3. Targeted radionuclide therapy

    SciTech Connect

    Williams, Lawrence E.; DeNardo, Gerald L.; Meredith, Ruby F.

    2008-07-15

    Targeted radionuclide therapy (TRT) seeks molecular and functional targets within patient tumor sites. A number of agents have been constructed and labeled with beta, alpha, and Auger emitters. Radionuclide carriers spanning a broad range of sizes; e.g., antibodies, liposomes, and constructs such as nanoparticles have been used in these studies. Uptake, in percent-injected dose per gram of malignant tissue, is used to evaluate the specificity of the targeting vehicle. Lymphoma (B-cell) has been the primary clinical application. Extension to solid tumors will require raising the macroscopic absorbed dose by several-fold over values found in present technology. Methods that may effect such changes include multistep targeting, simultaneous chemotherapy, and external sequestration of the agent. Toxicity has primarily involved red marrow so that marrow replacement can also be used to enhance future TRT treatments. Correlation of toxicities and treatment efficiency has been limited by relatively poor absorbed dose estimates partly because of using standard (phantom) organ sizes. These associations will be improved in the future by obtaining patient-specific organ size and activity data with hybrid SPECT/CT and PET/CT scanners.

  4. Targeted radionuclide therapy

    PubMed Central

    Williams, Lawrence E.; DeNardo, Gerald L.; Meredith, Ruby F.

    2008-01-01

    Targeted radionuclide therapy (TRT) seeks molecular and functional targets within patient tumor sites. A number of agents have been constructed and labeled with beta, alpha, and Auger emitters. Radionuclide carriers spanning a broad range of sizes; e.g., antibodies, liposomes, and constructs such as nanoparticles have been used in these studies. Uptake, in percent-injected dose per gram of malignant tissue, is used to evaluate the specificity of the targeting vehicle. Lymphoma (B-cell) has been the primary clinical application. Extension to solid tumors will require raising the macroscopic absorbed dose by several-fold over values found in present technology. Methods that may effect such changes include multistep targeting, simultaneous chemotherapy, and external sequestration of the agent. Toxicity has primarily involved red marrow so that marrow replacement can also be used to enhance future TRT treatments. Correlation of toxicities and treatment efficiency has been limited by relatively poor absorbed dose estimates partly because of using standard (phantom) organ sizes. These associations will be improved in the future by obtaining patient-specific organ size and activity data with hybrid SPECT∕CT and PET∕CT scanners. PMID:18697529

  5. High purity tungsten targets

    NASA Technical Reports Server (NTRS)

    1975-01-01

    High purity tungsten, which is used for targets in X-ray tubes was considered for space processing. The demand for X-ray tubes was calculated using the growth rates for dental and medical X-ray machines. It is concluded that the cost benefits are uncertain.

  6. Tumor-Targeted Nanomedicines

    PubMed Central

    ElBayoumi, Tamer A.; Torchilin, Vladimir P.

    2009-01-01

    Purpose The efficacy of drug delivery systems can be enhanced by making them target-specific via the attachment of various ligands. We attempted to enhance tumor accumulation and therapeutic effect of doxorubicin-loaded long-circulating PEGylated liposomes (Doxil®, ALZA Corp.) by coupling to their surface the anti-cancer monoclonal antibody 2C5 (mAb 2C5) with nuclesome (NS)-restricted activity, that can recognize the surface of various tumor but not normal cells and specifically targets pharmaceutical carriers to tumor cells in vitro and in vivo. Following earlier in vitro results with various cancer cell lines, the mAb 2C5-liposomes were studied in vivo vs. plain and non-specific IgG-liposomes. Experimental design Antibody coupling to Doxil® was performed via the “post-insertion” technique. Using 111In-labeled liposomes, the tissue biodistribution and pharmacokinetic profile were studied, as well as their accumulation in tumors in mice was followed by the whole-body γ-scintigraphic imaging. Therapeutic efficacy of mAb 2C5-targeted Doxil® vs. non-specific IgG-modified and original Doxil® controls was followed by registering live tumor growth and determining tumor weights upon mice sacrifice. Results mAb2C5 antibody-targeted liposomes demonstrate enhanced accumulation in tumors, and the in vivo therapeutic activity of the mAb 2C5-Doxil® treatment was found to be significantly superior, resulting in final tumor weights of only 25-40% compared to all Doxil® control treatments, when tested against the subcutaneous primary murine tumors of 4T1 and C26 and human PC3 tumor in nude mice. Conclusions Our results demonstrate the remarkable capability of 2C5-targeted Doxil® to specifically deliver its cargo into various tumors significantly increasing the efficacy of therapy. PMID:19276264

  7. Correlation of TLR2 and TLR4 expressions in peripheral blood mononuclear cells to Th1- and Th2-type immune responses in children with henoch-schönlein purpura.

    PubMed

    Chang, Hong; Zhang, Qiu-Ye; Lin, Yi; Cheng, Na; Zhang, Shou-Qing

    2015-01-01

    We discussed the correlation of TLR2 (Toll-like receptor) and TLR4 expressions in peripheral blood mononuclear cells (PBMCs) to Th1- and Th2-type immune responses in children with Henoch-Schönlein Purpura (HSP). The role of TLR2 and TLR4 in the pathogenesis of HSP was analyzed. Sixty-four HSP children treated at our hospital from October 2011 to November 2012 were enrolled and divided into NHSPN group (complicated by renal impairment, 36 cases) and HSPN group (not complicated by renal impairment, 28 cases). In the meantime, 30 normal children receiving physical examination at our hospital were recruited as controls. Peripheral blood T cell subgroups and TLR2 and TLR4 expressions in PBMCs were detected by using flow cytometry; relative expression levels of TLR2 and TLR4 mRNA in PBMCs by real-time quantitative fluorescence PCR, and plasma levels of IFN-γ, IL-4 and IL-6 by ELISA method. Relative expression levels of TLR2 and TLR4 mRNAs in PBMCs and TLR2 and TLR4 protein expressions in children with HSP were significantly higher than those of the controls (P<0.01). The relative expression levels of TLR2 and TLR4 mRNAs in PBMCs and TLR2 and TLR4 protein expressions in HSPN group were obviously higher than those in NHSPN group (P<0.05; P<0.01; P<0.01; P<0.01); CD3(+) T cells and CD3(+)CD4(+) T cells in HSP group were significantly decreased, while CD3(+)CD8(+) T cells and CD3(+)HLADR(+) T activated cells were considerably increased (P<0.01); The plasma levels of IL-4 and IL-6 in HSP group were significantly higher than those of the normal controls (P<0.01, P<0.01); IFN-γ level in the former was much lower than in the control group (P<0.05); IFN-γ/IL-4 ratio in the former was also lower than that in the control (P<0.01); TLR2 and TLR4 expressions in HSP group showed significantly positive correlation with the plasma levels of IL-4 and IL-6 (P<0.01, P<0.05; P<0.01, P<0.01) and significantly negative correlation with IFN-γ/IL-4 ratio (P<0.01; P<0.01). TLR2 and TLR4

  8. Gene Targeting in Neuroendocrinology.

    PubMed

    Candlish, Michael; De Angelis, Roberto; Götz, Viktoria; Boehm, Ulrich

    2015-09-20

    Research in neuroendocrinology faces particular challenges due to the complex interactions between cells in the hypothalamus, in the pituitary gland and in peripheral tissues. Within the hypothalamus alone, attempting to target a specific neuronal cell type can be problematic due to the heterogeneous nature and level of cellular diversity of hypothalamic nuclei. Because of the inherent complexity of the reproductive axis, the use of animal models and in vivo experiments are often a prerequisite in reproductive neuroendocrinology. The advent of targeted genetic modifications, particularly in mice, has opened new avenues of neuroendocrine research. Within this review, we evaluate various mouse models used in reproductive neuroendocrinology and discuss the different approaches to generate genetically modified mice, along with their inherent advantages and disadvantages. We also discuss a variety of versatile genetic tools with a focus on their potential use in reproductive neuroendocrinology.

  9. Phoenix on Target

    NASA Technical Reports Server (NTRS)

    2008-01-01

    This topography map illustrates where NASA's Phoenix Mars Lander is targeted to land on May 25, 2008, based on expectations as of noon pacific time (3 p.m. eastern time), May 24, 2008.

    Phoenix is most likely to land at the cross-shaped target at the center of the red ellipse and least likely to land at the ellipse's edges. The ellipse is positioned over the northern arctic plains of Mars, and is approximately 70 kilometers (44 miles) long.

    The topography data was taken by NASA's Mars Global Surveyor. It shows exaggerated differences in the height of the terrain.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  10. Mitochondria-targeting particles

    PubMed Central

    Wongrakpanich, Amaraporn; Geary, Sean M; Joiner, Mei-ling A; Anderson, Mark E; Salem, Aliasger K

    2015-01-01

    Mitochondria are a promising therapeutic target for the detection, prevention and treatment of various human diseases such as cancer, neurodegenerative diseases, ischemia-reperfusion injury, diabetes and obesity. To reach mitochondria, therapeutic molecules need to not only gain access to specific organs, but also to overcome multiple barriers such as the cell membrane and the outer and inner mitochondrial membranes. Cellular and mitochondrial barriers can be potentially overcome through the design of mitochondriotropic particulate carriers capable of transporting drug molecules selectively to mitochondria. These particulate carriers or vectors can be made from lipids (liposomes), biodegradable polymers, or metals, protecting the drug cargo from rapid elimination and degradation in vivo. Many formulations can be tailored to target mitochondria by the incorporation of mitochondriotropic agents onto the surface and can be manufactured to desired sizes and molecular charge. Here, we summarize recently reported strategies for delivering therapeutic molecules to mitochondria using various particle-based formulations. PMID:25490424

  11. Targeting biodefense markets.

    PubMed

    Olinger, Gene Garrard

    2009-10-01

    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

  12. Method for forming targets

    DOEpatents

    Woerner, Robert L.

    1979-01-01

    Method for cryoinduced uniform deposition of cryogenic materials, such as deuterium-tritium (DT) mixtures, on the inner surface of hollow spherical members, such as inertially imploded targets. By vaporizing and quickly refreezing cryogenic materials contained within a hollow spherical member, a uniform layer of the materials is formed on the inner surface of the spherical member. Heating of the cryogenic material, located within a non-isothermal compact freezing cell, is accomplished by an electrical heat pulse, whereafter the material is quickly frozen forming a uniform layer on the inner surface of the spherical member. The method is not restricted to producing a frozen layer on only the inner surface of the innermost hollow member, but where multiple concentric hollow spheres are involved, such as in multiple shell targets for lasers, electron beams, etc., layers of cryogenic material may also be formed on the inner surface of intermediate or outer spherical members, thus providing the capability of forming targets having multiple concentric layers or shells of frozen DT.

  13. Apparatus for forming targets

    DOEpatents

    Woerner, Robert L.

    1980-01-01

    Apparatus and method for cryoinduced uniform deposition of cryogenic materials, such as deuterium-tritium (DT) mixtures, on the inner surface of hollow spherical members, such as inertially imploded targets. By vaporizing and quickly refreezing cryogenic materials contained within a hollow spherical member, a uniform layer of the materials is formed on the inner surface of the spherical member. Heating of the cryogenic material, located within a non-isothermal compact freezing cell, is accomplished by an electrical heat pulse, whereafter the material is quickly frozen forming a uniform layer on the inner surface of the spherical member. The method is not restricted to producing a frozen layer on only the inner surface of the innermost hollow member, but where multiple concentric hollow spheres are involved, such as in multiple shell targets for lasers, electron beams, etc., layers of cryogenic material may also be formed on the inner surface of intermediate or outer spherical members, thus providing the capability of forming targets having multiple concentric layers or shells of frozen DT.

  14. Targeting Inactive Enzyme Conformation

    PubMed Central

    Liu, Sijiu; Zeng, Li-Fan; Wu, Li; Yu, Xiao; Xue, Ting; Gunawan, Andrea M.; Ya-Qiu, Long; Zhang, Zhong-Yin

    2009-01-01

    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. PMID:19012396

  15. Follicular penetration and targeting.

    PubMed

    Lademann, Jürgen; Otberg, Nina; Jacobi, Ute; Hoffman, Robert M; Blume-Peytavi, Ulrike

    2005-12-01

    In the past, intercellular penetration was assumed to be the most important penetration pathway of topically applied substances. First hints that follicular penetration needs to be taken into consideration were confirmed by recent investigations, presented during the workshop "Follicular Penetration and Targeting" at the 4th Intercontinental Meeting of Hair Research Societies", in Berlin 2004. Hair follicles represent an efficient reservoir for the penetration of topically applied substances with subsequent targeting of distinct cell populations, e.g., nestin-expressing follicular bulge cells. The volume of this reservoir can be determined by differential stripping technology. The follicular penetration processes are significantly influenced by the state of the follicular infundibulum; recent experimental investigations could demonstrate that it is essential to distinguish between open and closed hair follicles. Topically applied substances can only penetrate into open hair follicle. Knowledge of follicular penetration is of high clinical relevance for functional targeting of distinct follicular regions. Human hair follicles show a hair-cycle-dependent variation of the dense neuronal and vascular network. Moreover, during hair follicle cycling with initiation of anagen, newly formed vessels occur. Thus, the potential of nestin-expressing hair follicle stem cells to form neurons and blood vessels was investigated.

  16. New targets for DBS.

    PubMed

    Benabid, Alim Louis; Torres, Napoleon

    2012-01-01

    The specific effect of DBS at high frequency, discovered during a VIM thalamotomy, was extended to the older targets of ablative neurosurgery such as the pallidum, for tremor in Parkinson's disease (PD), dyskinesias, essential tremor, as well as the internal capsule to treat psychiatric disorders (OCD). A second wave of targets came from basic research, enabled by the low morbidity, reversibility, and adaptability of DBS. This was the case for the subthalamic nucleus (STN) which improves the triad of dopaminergic symptoms, and the pedunculopontine nucleus (PPN) for gait disorders in PD. The new concepts of the role of basal ganglia in psychiatric disorders indicate the subgenual cortex CG 25 for severe resistant depression, the accumbens nucleus for depression, anorexia nervosa, and addiction, and the thalamus intralaminar nuclei for minimally conscious states. Serendipity and a scientific approach have provided several instances where targets have produced unexpected effects (such as STN in OCD), as well as limbic effects observed during attempts at VMH stimulation for obesity: this might offer a novel way to treat mild cognitive impairment, or memory deficits reported in Alzheimer's disease. While these might provide solutions for as yet unsolved problems, attention must be paid to ethical considerations. PMID:22166437

  17. Targeted Endoscopic Imaging

    PubMed Central

    Li, Meng; Wang, Thomas D

    2011-01-01

    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. PMID:19423025

  18. Radiation calibration targets

    NASA Technical Reports Server (NTRS)

    1997-01-01

    Several prominent features of Mars Pathfinder and surrounding terrain are seen in this image, taken by the Imager for Mars Pathfinder on July 4 (Sol 1), the spacecraft's first day on the Red Planet. Portions of a lander petal are at the lower part of the image. At the left, the mechanism for the high-gain antenna can be seen. The dark area along the right side of the image represents a portion of the low-gain antenna. The radiation calibration target is at the right. The calibration target is made up of a number of materials with well-characterized colors. The known colors of the calibration targets allow scientists to determine the true colors of the rocks and soils of Mars. Three bull's-eye rings provide a wide range of brightness for the camera, similar to a photographer's grayscale chart. In the middle of the bull's-eye is a 5-inch tall post that casts a shadow, which is distorted in this image due to its location with respect to the lander camera.

    A large rock is located at the near center of the image. Smaller rocks and areas of soil are strewn across the Martian terrain up to the horizon line.

    Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C.

  19. Palpable purpura with an unexpected outcome.

    PubMed

    Friesgaard Christensen, Anne; Clemmensen, Ole; Junker, Peter

    2013-01-01

    Scurvy is a potentially lethal condition caused by inadequate vitamin C intake. Hypovitaminosis of vitamin C causes vessel fragility and follicular hyperkeratosis that can lead to palpable purpuric skin lesions. In this case report, we aim to remind readers that scurvy still occurs in Western countries and that the clinical presentation may resemble vasculitis. PMID:23956916

  20. Event parameters - fixed target

    SciTech Connect

    Poskanzer, A.; Ritter, H.G.; Ludewigt, B.; Foley, K.; Borenstein, S.; Platner, E.; Love, W.; Keane, D.; Plasil, F.

    1984-06-15

    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.

  1. Targeting Breast Cancer Metastasis

    PubMed Central

    Jin, Xin; Mu, Ping

    2015-01-01

    Metastasis is the leading cause of breast cancer-associated deaths. Despite the significant improvement in current therapies in extending patient life, 30–40% of patients may eventually suffer from distant relapse and succumb to the disease. Consequently, a deeper understanding of the metastasis biology is key to developing better treatment strategies and achieving long-lasting therapeutic efficacies against breast cancer. This review covers recent breakthroughs in the discovery of various metastatic traits that contribute to the metastasis cascade of breast cancer, which may provide novel avenues for therapeutic targeting. PMID:26380552

  2. Non-Targeted Analysis Challenge (Non-targeted screening workshop)

    EPA Science Inventory

    This brief presentation is intended to motivate discussion of the "Non-Targeted Analysis Challenge" at the Advancing Non-Targeted Analyses of Xenobiotics in Environmental and Biological Media workshop held at the EPA RTP campus.

  3. Target Asteroids! Observing Targets for 2014 July through September

    NASA Astrophysics Data System (ADS)

    Hergenrother, Carl; Hill, Dolores

    2014-07-01

    Asteroids to be observed by the Target Asteroids! program during the period of July to September 2014 are presented. In addition to asteroids on the original Target Asteroids! list of easily accessible spacecraft targets, an effort has been made to identify other asteroids that are 1) brighter and easier to observe for small telescope users and 2) analogous to (101955) Bennu, the target asteroid of the OSIRIS-REx sample return mission.

  4. Target Asteroids! Observing Targets for 2014 April through June

    NASA Astrophysics Data System (ADS)

    Hergenrother, Carl; Hill, Dolores

    2014-04-01

    Asteroids to be observed by the Target Asteroids! program during the period of 2014 April through June are presented. In addition to asteroids on the original Target Asteroids! list of easily accessible spacecraft targets, an effort has been made to identify other asteroids that are 1) brighter and easier to observe for small telescope users and 2) analogous to 101955 Bennu, the target asteroid of the OSIRIS-REx sample return mission.

  5. Target Asteroids! Observing Targets for 2014 October through December

    NASA Astrophysics Data System (ADS)

    Hergenrother, Carl; Hill, Dolores

    2014-10-01

    Asteroids to be observed by the Target Asteroids! program during the period of October to December 2014 are presented. In addition to asteroids on the original Target Asteroids! list of easily accessible spacecraft targets, an effort has been made to identify other asteroids that are 1) brighter and easier to observe for small telescope users and 2) analogous to (101955) Bennu, the target asteroid of the OSIRIS-REx sample return mission.

  6. Targeting adipose tissue

    PubMed Central

    2012-01-01

    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 γ (PPARγ) 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

  7. Molecular and cellular targets.

    PubMed

    Bode, Ann M; Dong, Zigang

    2006-06-01

    Carcinogenesis is a multistage process consisting of initiation, promotion, and progression stages and each stage may be a possible target for chemopreventive agents. A significant outcome of these investigations on the elucidation of molecular and cellular mechanisms is the explication of signal transduction pathways induced by tumor promoters in cancer development. The current belief today is that cancer may be prevented or treated by targeting specific cancer genes, signaling proteins, and transcription factors. The molecular mechanisms explaining how normal cells undergo neoplastic transformation induced by tumor promoters are rapidly being clarified. Accumulating research evidence suggests that many of dietary factors, including tea compounds, may be used alone or in combination with traditional chemotherapeutic agents to prevent or treat cancer. The potential advantage of many natural or dietary compounds seems to focus on their potent anticancer activity combined with low toxicity and very few adverse side effects. This review summarizes some of our recent work regarding the effects of the various tea components on signal transduction pathways involved in neoplastic cell transformation and carcinogenesis. PMID:16688728

  8. Molecular and Cellular Targets

    PubMed Central

    Bode, Ann M.; Dong, Zigang

    2008-01-01

    Carcinogenesis is a multistage process consisting of initiation, promotion and progression stages and each stage may be a possible target for chemopreventive agents. A significant outcome of these investigations on the elucidation of molecular and cellular mechanisms is the explication of signal transduction pathways induced by tumor promoters in cancer development. The current belief today is that cancer may be prevented or treated by targeting specific cancer genes, signaling proteins and transcription factors. The molecular mechanisms explaining how normal cells undergo neoplastic transformation induced by tumor promoters are rapidly being clarified. Accumulating research evidence suggests that many of dietary factors, including tea compounds, may be used alone or in combination with traditional chemotherapeutic agents to prevent or treat cancer. The potential advantage of many natural or dietary compounds seems to focus on their potent anticancer activity combined with low toxicity and very few adverse side effects. This review summarizes some of our recent work regarding the effects of the various tea components on signal transduction pathways involved in neoplastic cell transformation and carcinogenesis. PMID:16688728

  9. Targeted therapy for sarcomas

    PubMed Central

    Forscher, Charles; Mita, Monica; Figlin, Robert

    2014-01-01

    Sarcomas are tumors of mesenchymal origin that make up approximately 1% of human cancers. They may arise as primary tumors in either bone or soft tissue, with approximately 11,280 soft tissue tumors and 2,650 bone tumors diagnosed each year in the United States. There are at least 50 different subtypes of soft tissue sarcoma, with new ones described with ever-increasing frequency. One way to look at sarcomas is to divide them into categories on the basis of their genetic make-up. One group of sarcomas has an identifiable, relatively simple genetic signature, such as the X:18 translocation seen in synovial sarcoma or the 11:22 translocation seen in Ewing’s sarcoma. These specific abnormalities often lead to the presence of fusion proteins, such as EWS-FLI1 in Ewing’s sarcoma, which are helpful as diagnostic tools and may become therapeutic targets in the future. Another group of sarcomas is characterized by complex genetic abnormalities as seen in leiomyosarcoma, osteosarcoma, and undifferentiated sarcoma. It is important to keep these distinctions in mind when contemplating the development of targeted agents for sarcomas. Different abnormalities in sarcoma could be divided by tumor subtype or by the molecular or pathway abnormality. However, some existing drugs or drugs in development may interfere with or alter more than one of the presented pathways. PMID:24669185

  10. Liquid Hydrogen: Target, Detector

    SciTech Connect

    Mulholland, G.T.; Harigel, G.G.

    2004-06-23

    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.

  11. Magnetized Target Fusion

    NASA Technical Reports Server (NTRS)

    Griffin, Steven T.

    2002-01-01

    Magnetized target fusion (MTF) is under consideration as a means of building a low mass, high specific impulse, and high thrust propulsion system for interplanetary travel. This unique combination is the result of the generation of a high temperature plasma by the nuclear fusion process. This plasma can then be deflected by magnetic fields to provide thrust. Fusion is initiated by a small traction of the energy generated in the magnetic coils due to the plasma's compression of the magnetic field. The power gain from a fusion reaction is such that inefficiencies due to thermal neutrons and coil losses can be overcome. Since the fusion reaction products are directly used for propulsion and the power to initiate the reaction is directly obtained from the thrust generation, no massive power supply for energy conversion is required. The result should be a low engine mass, high specific impulse and high thrust system. The key is to successfully initiate fusion as a proof-of-principle for this application. Currently MSFC is implementing MTF proof-of-principle experiments. This involves many technical details and ancillary investigations. Of these, selected pertinent issues include the properties, orientation and timing of the plasma guns and the convergence and interface development of the "pusher" plasma. Computer simulations of the target plasma's behavior under compression and the convergence and mixing of the gun plasma are under investigation. This work is to focus on the gun characterization and development as it relates to plasma initiation and repeatability.

  12. A Note on Inflation Targeting.

    ERIC Educational Resources Information Center

    Lai, Ching-chong; Chang, Juin-jen

    2001-01-01

    Presents a pedagogical graphical exposition to illustrate the stabilizing effect of price target zones. Finds that authorities' commitment to defend a price target zone affects the public's inflation expectations and, in turn, reduces actual inflation. (RLH)

  13. Characterization of solid hydrogen targets

    SciTech Connect

    Fujiwara, M.C.; Bailey, J.M.; Beer, G.A.

    1995-12-01

    In experiments using the TRIUMF solid hydrogen target systems, knowledge of target thickness and uniformity is often essential in order to extract physical parameters from the data. We have characterized the thickness and uniformity of frozen targets using the energy loss of alpha particles. An accuracy of about 5% was achieved, a limit imposed by the uncertainty in the stopping powers. Details of the method are described and the thickness calibration of the target is presented.

  14. ORION laser target diagnostics.

    PubMed

    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

    2012-10-01

    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

  15. Electromagnetic targeting of guns

    SciTech Connect

    Pogue, E.W.; Boat, R.M.; Holden, D.N.; Lopez, J.R.

    1996-10-01

    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.

  16. Polarized tritium target development

    SciTech Connect

    Jones, C.E.; Fedchak, J.A.; Kowalczyk, R.S.

    1995-08-01

    Work began on the development of a completely sealed polarized tritium target for experiments at CEBAF. Because of the similarities between optical pumping of tritium and hydrogen, all prototype work is done with hydrogen. We constructed a test station for filling glassware with hydrogen, where we can dissociate molecular hydrogen and monitor the purity of the gas. A simple two-cell glass system was constructed, consisting of a region in which the molecular hydrogen is dissociated with an RF discharge and a region where the atoms can be optically pumped. So far, a clean discharge was obtained in the glassware. With this system, we plan to investigate ways to eliminate the discharge from the optical pumping region and test the quality of the discharge once the pumping cell is coated with drifilm.

  17. ORION laser target diagnosticsa)

    NASA Astrophysics Data System (ADS)

    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.

    2012-10-01

    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.

  18. ORION laser target diagnostics.

    PubMed

    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

    2012-10-01

    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.

  19. ORION laser target diagnostics

    SciTech Connect

    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.; and others

    2012-10-15

    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.

  20. Target detection portal

    DOEpatents

    Linker, Kevin L.; Brusseau, Charles A.

    2002-01-01

    A portal apparatus for screening persons or objects for the presence of trace amounts of target substances such as explosives, narcotics, radioactive materials, and certain chemical materials. The portal apparatus can have a one-sided exhaust for an exhaust stream, an interior wall configuration with a concave-shape across a horizontal cross-section for each of two facing sides to result in improved airflow and reduced washout relative to a configuration with substantially flat parallel sides; air curtains to reduce washout; ionizing sprays to collect particles bound by static forces, as well as gas jet nozzles to dislodge particles bound by adhesion to the screened person or object. The portal apparatus can be included in a detection system with a preconcentrator and a detector.

  1. Targeting HER2

    PubMed Central

    Wong, Karen J; Baidoo, Kwamena E; Nayak, Tapan K; Regino, Celeste AS; Garmestani, Kayhan; Brechbiel, Martin W

    2010-01-01

    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 γ-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. PMID:20716957

  2. Rotating Target Development for SNS Second Target Station

    SciTech Connect

    McManamy, Thomas J; Rennich, Mark J; Crawford, Roy K; Geoghegan, Patrick J; Janney, Jim G

    2010-01-01

    A rotating target for the second target station (STS) at SNS has been identified as an option along with a mercury target. Evaluation of the rotating target alternative for STS has started at 1.5 MW which is considered an upper bound for the power. Previous preconceptual design work for a 3 MW rotating target is being modified for the lower power level. Transient thermal analysis for a total loss of active water cooling has been done for a simplified 2D model of the target and shielding monolith which shows that peak temperatures are well below the level at which tungsten vaporization by steam could exceed site boundary dose limits. Design analysis and integration configuration studies have been done for the target-moderator-reflector assembly which maximizes the number of neutron beam lines and provides for replacement of the target and moderators. Target building hot cell arrangement for this option will be described. An option for operation in rough vacuum without a proton beam window using Ferro fluid seals on a vertical shaft is being developed. A full scale prototypic drive module based on the 3 MW preconceptual design has been fabricated and successfully tested with a shaft and mock up target supplied by the ESS-Bilbao team. Overall planning leading to decision between mercury and the rotating target in 2011 will be discussed

  3. Split-target neutronics and the MLNSC spallation target system

    SciTech Connect

    Russell, G.J.; Ferguson, P.D.; Pitcher, E.J.; Court, J.D.

    1996-12-31

    The Manuel Lujan, Jr., Neutron Scattering Center (MLNSC) at the Los Alamos National Laboratory is one of four operating Short-Pulse Spallation Sources worldwide. The MLNSC target system (composed of targets, moderators, and reflectors) was first installed in 1985. The target system employs a split tungsten spallation target with a void space in between (the flux-trap gap); this target system will be upgraded in 1998. The ability to efficiently split a spallation target allowed us to introduce the concept of flux-trap moderators and ultimately the notion of backscattering and upstream moderators. The upgraded MLNSC target system will employ both flux-trap and upstream/backscattering moderators to simultaneously service 16 neutron flight paths with high-intensity neutron beams for materials science research.

  4. Design of ligand-targeted nanoparticles for enhanced cancer targeting

    NASA Astrophysics Data System (ADS)

    Stefanick, Jared F.

    Ligand-targeted nanoparticles are increasingly used as drug delivery vehicles for cancer therapy, yet have not consistently produced successful clinical outcomes. Although these inconsistencies may arise from differences in disease models and target receptors, nanoparticle design parameters can significantly influence therapeutic efficacy. By employing a multifaceted synthetic strategy to prepare peptide-targeted nanoparticles with high purity, reproducibility, and precisely controlled stoichiometry of functionalities, this work evaluates the roles of polyethylene glycol (PEG) coating, ethylene glycol (EG) peptide-linker length, peptide hydrophilicity, peptide density, and nanoparticle size on tumor targeting in a systematic manner. These parameters were analyzed in multiple disease models by targeting human epidermal growth factor receptor 2 (HER2) in breast cancer and very late antigen-4 (VLA-4) in multiple myeloma to demonstrate the widespread applicability of this approach. By increasing the hydrophilicity of the targeting peptide sequence and simultaneously optimizing the EG peptide-linker length, the in vitro cellular uptake of targeted liposomes was significantly enhanced. Specifically, including a short oligolysine chain adjacent to the targeting peptide sequence effectively increased cellular uptake ~80-fold using an EG6 peptide-linker compared to ~10-fold using an EG45 linker. In vivo, targeted liposomes prepared in a traditional manner lacking the oligolysine chain demonstrated similar biodistribution and tumor uptake to non-targeted liposomes. However, by including the oligolysine chain, targeted liposomes using an EG45 linker significantly improved tumor uptake ~8-fold over non-targeted liposomes, while the use of an EG6 linker decreased tumor accumulation and uptake, owing to differences in cellular uptake kinetics, clearance mechanisms, and binding site barrier effects. To further improve tumor targeting and enhance the selectivity of targeted

  5. Unintended events following immunization with MMR: a systematic review.

    PubMed

    Jefferson, Tom; Price, Deirdre; Demicheli, Vittorio; Bianco, Elvira

    2003-09-01

    Public debate over the safety of the trivalent measles, mumps and rubella (MMR) vaccine and the drop in vaccination rates in several countries persists despite its almost universal use and accepted effectiveness. We carried out a systematic review to assess the evidence of unintended effects (beneficial or harmful) associated with MMR and the applicability of systematic reviewing methods to the field of safety evaluation. Eligible studies were comparative prospective or retrospective on healthy individuals up to 15 years of age, carried out or published by 2003. We identified 120 articles satisfying our inclusion criteria and included 22. MMR is associated with a lower incidence of upper respiratory tract infections, a higher incidence of irritability, similar incidence of other adverse effects compared to placebo and is likely to be associated with benign thrombocytopenic purpura (TP), parotitis, joint and limb complaints and aseptic meningitis (mumps Urabe strain-containing MMR). Exposure to MMR is unlikely to be associated with Crohn's disease, ulcerative colitis, autism or aseptic meningitis (mumps Jeryl-Lynn strain-containing MMR). The design and reporting of safety outcomes in MMR vaccine studies, both pre- and post-marketing, are largely inadequate. The evidence of adverse events following immunization with MMR cannot be separated from its role in preventing the target diseases.

  6. Clinical application of partial splenic embolization.

    PubMed

    Guan, Yong-Song; Hu, Ying

    2014-01-01

    Partial splenic embolization (PSE) is one of the intra-arterial therapeutic approaches of diseases. With the development of interventional radiology, the applications of PSE in clinical practice are greatly extended, while various materials are developed for embolization use. Common indications of PSE include hypersplenism with portal hypertension, hereditary spherocytosis, thalassemia, autoimmune hemolytic anemia, splenic trauma, idiopathic thrombocytopenic purpura, splenic hemangioma, and liver cancer. It is also performed to exclude splenic artery aneurysms from the parent vessel lumen and prevent aneurysm rupture, to treat splenic artery steal syndrome and improve liver perfusion in liver transplant recipients, and to administer targeted treatment to areas of neoplastic disease in the splenic parenchyma. Indicators of the therapeutic effect evaluation of PSE comprise blood routine test, changes in hemodynamics and in splenic volume. Major complications of PSE include the pulmonary complications, severe infection, damages of renal and liver function, and portal vein thrombosis. The limitations of PSE exist mainly in the difficulties in selecting the arteries to embolize and in evaluating the embolized volume.

  7. Fecal microbiota transplantation broadening its application beyond intestinal disorders.

    PubMed

    Xu, Meng-Que; Cao, Hai-Long; Wang, Wei-Qiang; Wang, Shan; Cao, Xiao-Cang; Yan, Fang; Wang, Bang-Mao

    2015-01-01

    Intestinal dysbiosis is now known to be a complication in a myriad of diseases. Fecal microbiota transplantation (FMT), as a microbiota-target therapy, is arguably very effective for curing Clostridium difficile infection and has good outcomes in other intestinal diseases. New insights have raised an interest in FMT for the management of extra-intestinal disorders associated with gut microbiota. This review shows that it is an exciting time in the burgeoning science of FMT application in previously unexpected areas, including metabolic diseases, neuropsychiatric disorders, autoimmune diseases, allergic disorders, and tumors. A randomized controlled trial was conducted on FMT in metabolic syndrome by infusing microbiota from lean donors or from self-collected feces, with the resultant findings showing that the lean donor feces group displayed increased insulin sensitivity, along with increased levels of butyrate-producing intestinal microbiota. Case reports of FMT have also shown favorable outcomes in Parkinson's disease, multiple sclerosis, myoclonus dystonia, chronic fatigue syndrome, and idiopathic thrombocytopenic purpura. FMT is a promising approach in the manipulation of the intestinal microbiota and has potential applications in a variety of extra-intestinal conditions associated with intestinal dysbiosis.

  8. Successful plasma exchange combined with rituximab therapy in aggressive APS-related cutaneous necrosis.

    PubMed

    Costa, Rubens; Fazal, Salman; Kaplan, Robert B; Spero, Joel; Costa, Ricardo

    2013-03-01

    Antiphospholipid antibody syndrome (APS) is a systemic autoimmune disorder characterized by venous and/or arterial thrombosis or recurrent fetal loss associated with the presence of antiphospholipid antibodies and/or a lupus anticoagulant. The skin appears to be an important target organ and many cases of APS may present with skin manifestations. These lesions may be manifold and may take the form of livedo reticularis, livedo racemosa, ulcerations, digital gangrene, subungeal splinter hemorrhages, superficial venous thrombosis, thrombocytopenic purpura, pseudovasculitic manifestations, extensive cutaneous necrosis, or primary anetoderma. We report a case of fulminant APS-related cutaneous necrosis. A 38-year-old Caucasian male with a past history of APS, multiple deep vein thrombi/pulmonary emboli, presented with necrotic lesions on his right upper and right lower extremities. Initially, baseline anticoagulation was increased without improvement. Subsequently, plasma exchange was initiated on a daily schedule. Furthermore, rituximab 1,000 mg IV was administered on days 1 and 15. After six consecutive daily sessions of plasma exchange, there was significant regression of the necrotic lesions. After a 22-day hospital stay, the patient was discharged to home on fondaparinux. The patient presented approximately 2 months later after missing follow-up appointments. At the time, his initial lesions looked remarkably improved.

  9. Role of Siglec-7 in Apoptosis in Human Platelets

    PubMed Central

    Nguyen, Kim Anh; Hamzeh-Cognasse, Hind; Palle, Sabine; Anselme-Bertrand, Isabelle; Arthaud, Charles-Antoine; Chavarin, Patricia; Pozzetto, Bruno; Garraud, Olivier; Cognasse, Fabrice

    2014-01-01

    Background Platelets participate in tissue repair and innate immune responses. Sialic acid-binding immunoglobulin-like lectins (Siglecs) are well-characterized I-type lectins, which control apoptosis. Methodology/Principal Findings We characterized the expression of Siglec-7 in human platelets isolated from healthy volunteers using flow cytometry and confocal microscopy. Siglec-7 is primarily expressed on α granular membranes and colocalized with CD62P. Siglec-7 expression was increased upon platelet activation and correlated closely with CD62P expression. Cross-linking Siglec-7 with its ligand, ganglioside, resulted in platelet apoptosis without any significant effects on activation, aggregation, cell morphology by electron microscopy analysis or secretion. We show that ganglioside triggered four key pathways leading to apoptosis in human platelets: (i) mitochondrial inner transmembrane potential (ΔΨm) depolarization; (ii) elevated expression of pro-apoptotic Bax and Bak proteins with reduced expression of anti-apoptotic Bcl-2 protein; (iii) phosphatidylserine exposure and (iv), microparticle formation. Inhibition of NAPDH oxidase, PI3K, or PKC rescued platelets from apoptosis induced by Siglec-7 recruitment, suggesting that the platelet receptors P2Y1 and GPIIbIIIa are essential for ganglioside-induced platelet apoptosis. Conclusions/Significance The present work characterizes the role of Siglec-7 and platelet receptors in regulating apoptosis and death. Because some platelet pathology involves apoptosis (idiopathic thrombocytopenic purpura and possibly storage lesions), Siglec-7 might be a molecular target for therapeutic intervention/prevention. PMID:25230315

  10. An autoantibody epitope comprising residues R660, Y661, and Y665 in the ADAMTS13 spacer domain identifies a binding site for the A2 domain of VWF

    PubMed Central

    Pos, Wouter; Crawley, James T. B.; Fijnheer, Rob; Voorberg, Jan; Lane, David A.

    2010-01-01

    In the majority of patients with acquired thrombotic thrombocytopenic purpura (TTP), antibodies are directed toward the spacer domain of ADAMTS13. We have previously shown that region Y658-Y665 is involved. We now show that replacement of R660, Y661, or Y665 with alanine in ADAMTS13 reduced/abolished the binding of 2 previously isolated human monoclonal antibodies and polyclonal antibodies derived from plasma of 6 patients with acquired TTP. We investigated whether these residues also influenced cleavage of short von Willebrand factor (VWF) fragment substrate VWF115. An ADAMTS13 variant (R660A/Y661A/Y665A, ADAMTS13-RYY) showed a 12-fold reduced catalytic efficiency (kcat/Km) arising from greatly reduced (> 25-fold) binding, demonstrated by surface plasmon resonance. The influence of these residue changes on full-length VWF was determined with denaturing and flow assays. ADAMTS13-RYY had reduced activity in both, with proteolysis of VWF unaffected by autoantibody. Binding of ADAMTS13-RYY mutant to VWF was, however, similar to normal. Our results demonstrate that residues within Y658-Y665 of the ADAMTS13 spacer domain that are targeted by autoantibodies in TTP directly interact with a complementary exosite (E1660-R1668) within the VWF A2 domain. Residues R660, Y661, and Y665 are critical for proteolysis of short VWF substrates, but wider domain interactions also make important contributions to cleavage of full-length VWF. PMID:20032502

  11. Fecal microbiota transplantation broadening its application beyond intestinal disorders

    PubMed Central

    Xu, Meng-Que; Cao, Hai-Long; Wang, Wei-Qiang; Wang, Shan; Cao, Xiao-Cang; Yan, Fang; Wang, Bang-Mao

    2015-01-01

    Intestinal dysbiosis is now known to be a complication in a myriad of diseases. Fecal microbiota transplantation (FMT), as a microbiota-target therapy, is arguably very effective for curing Clostridium difficile infection and has good outcomes in other intestinal diseases. New insights have raised an interest in FMT for the management of extra-intestinal disorders associated with gut microbiota. This review shows that it is an exciting time in the burgeoning science of FMT application in previously unexpected areas, including metabolic diseases, neuropsychiatric disorders, autoimmune diseases, allergic disorders, and tumors. A randomized controlled trial was conducted on FMT in metabolic syndrome by infusing microbiota from lean donors or from self-collected feces, with the resultant findings showing that the lean donor feces group displayed increased insulin sensitivity, along with increased levels of butyrate-producing intestinal microbiota. Case reports of FMT have also shown favorable outcomes in Parkinson’s disease, multiple sclerosis, myoclonus dystonia, chronic fatigue syndrome, and idiopathic thrombocytopenic purpura. FMT is a promising approach in the manipulation of the intestinal microbiota and has potential applications in a variety of extra-intestinal conditions associated with intestinal dysbiosis. PMID:25574083

  12. Liquid film target impingement scrubber

    DOEpatents

    McDowell, William J.; Coleman, Charles F.

    1977-03-15

    An improved liquid film impingement scrubber is provided wherein particulates suspended in a gas are removed by jetting the particle-containing gas onto a relatively small thin liquid layer impingement target surface. The impingement target is in the form of a porous material which allows a suitable contacting liquid from a pressurized chamber to exude therethrough to form a thin liquid film target surface. The gas-supported particles collected by impingement of the gas on the target are continuously removed and flushed from the system by the liquid flow through each of a number of pores in the target.

  13. Foveal target repetitions reduce crowding.

    PubMed

    Sayim, Bilge; Greenwood, John A; Cavanagh, Patrick

    2014-01-01

    Crowding is the limitation of peripheral vision by clutter. Objects that are easily identified when presented in isolation are hard to identify when presented flanked by similar close-by objects. It is often assumed that the signal of a crowded target is irretrievably lost because it is combined with the signals of the flankers. Here, we asked whether a target signal can be enhanced (or retrieved) by items presented far outside the crowding region. We investigated whether remote items matching a peripheral, crowded target enhanced discrimination compared to remote items not matching the target. In Experiment 1, we presented the remote item at different locations in the visual field and found that, when presented in the fovea, a matching remote item improved target discrimination compared to a nonmatching remote item. In Experiment 2, we varied stimulus onset asynchronies between target and remote items and found a strong effect when the remote item was presented simultaneously with the target. The effect diminished (or was absent) with increasing temporal separation. In Experiment 3, we asked whether semantic knowledge of a target was sufficient to improve target discrimination and found that this was not the case. We conclude that crowded target signals are not irretrievably lost. Rather, their accurate recognition is facilitated in the presence of remote items that match the target. We suggest that long-range grouping mechanisms underlie this "uncrowding" effect.

  14. Targeting tumor acidity

    NASA Astrophysics Data System (ADS)

    Reshetnyak, Yana K.; Engelman, Donald M.; Andreev, Oleg A.

    2012-02-01

    One of the main features of solid tumors is extracellular acidity, which correlates with tumor aggressiveness and metastatic potential. We introduced novel approach in targeting of acidic tumors, and translocation of cell-impermeable cargo molecules across cellular membrane. Our approach is based on main principle of insertion and folding of a polypeptide in lipid bilayer of membrane. We have identified family of pH Low Insertion Peptides (pHLIPs), which are capable spontaneous insertion and folding in membrane at mild acidic conditions. The affinity of peptides of pHLIP family to membrane at low pH is several times higher than at neutral pH. The process of peptides folding occurs within milliseconds. The energy released in a result of folding (about 2 kcal/mol) could be used to move polar cargo across a membrane, which is a novel concept in drug delivery. pHLIP peptides could be considered as a pH-sensitive single peptide molecular transporters and conjugated with imaging probes for fluorescence, MR, PET and SPECT imaging, they represent a novel in vivo marker of acidity. The work is supported by NIH grants CA133890 and GM073857 to OAA, DME, YRK.

  15. Epigenomes as therapeutic targets.

    PubMed

    Hamm, Christopher A; Costa, Fabricio F

    2015-07-01

    Epigenetics is a molecular phenomenon that pertains to heritable changes in gene expression that do not involve changes in the DNA sequence. Epigenetic modifications in a whole genome, known as the epigenome, play an essential role in the regulation of gene expression in both normal development and disease. Traditional epigenetic changes include DNA methylation and histone modifications. Recent evidence reveals that other players, such as non-coding RNAs, may have an epigenetic regulatory role. Aberrant epigenetic signaling is becoming to be known as a central component of human disease, and the reversible nature of the epigenetic modifications provides an exciting opportunity for the development of clinically relevant therapeutics. Current epigenetic therapies provide a clinical benefit through disrupting DNA methyltransferases or histone deacetylases. However, the emergence of next-generation epigenetic therapies provides an opportunity to more effectively disrupt epigenetic disease states. Novel epigenetic therapies may improve drug targeting and drug delivery, optimize dosing schedules, and improve the efficacy of preexisting treatment modalities (chemotherapy, radiation, and immunotherapy). This review discusses the epigenetic mechanisms that contribute to the disease, available epigenetic therapies, epigenetic therapies currently in development, and the potential future use of epigenetic therapeutics in a clinical setting.

  16. Using the Nova target chamber for high-yield targets

    SciTech Connect

    Pitts, J.H.

    1987-09-28

    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.

  17. The target effect: visual memory for unnamed search targets.

    PubMed

    Thomas, Mark D; Williams, Carrick C

    2014-01-01

    Search targets are typically remembered much better than other objects even when they are viewed for less time. However, targets have two advantages that other objects in search displays do not have: They are identified categorically before the search, and finding them represents the goal of the search task. The current research investigated the contributions of both of these types of information to the long-term visual memory representations of search targets. Participants completed either a predefined search or a unique-object search in which targets were not defined with specific categorical labels before searching. Subsequent memory results indicated that search target memory was better than distractor memory even following ambiguously defined searches and when the distractors were viewed significantly longer. Superior target memory appears to result from a qualitatively different representation from those of distractor objects, indicating that decision processes influence visual memory.

  18. Facility target insert shielding assessment

    SciTech Connect

    Mocko, Michal

    2015-10-06

    Main objective of this report is to assess the basic shielding requirements for the vertical target insert and retrieval port. We used the baseline design for the vertical target insert in our calculations. The insert sits in the 12”-diameter cylindrical shaft extending from the service alley in the top floor of the facility all the way down to the target location. The target retrieval mechanism is a long rod with the target assembly attached and running the entire length of the vertical shaft. The insert also houses the helium cooling supply and return lines each with 2” diameter. In the present study we focused on calculating the neutron and photon dose rate fields on top of the target insert/retrieval mechanism in the service alley. Additionally, we studied a few prototypical configurations of the shielding layers in the vertical insert as well as on the top.

  19. Multiple target laser ablation system

    DOEpatents

    Mashburn, Douglas N.

    1996-01-01

    A laser ablation apparatus and method are provided in which multiple targets consisting of material to be ablated are mounted on a movable support. The material transfer rate is determined for each target material, and these rates are stored in a controller. A position detector determines which target material is in a position to be ablated, and then the controller controls the beam trigger timing and energy level to achieve a desired proportion of each constituent material in the resulting film.

  20. Multiple target laser ablation system

    DOEpatents

    Mashburn, D.N.

    1996-01-09

    A laser ablation apparatus and method are provided in which multiple targets consisting of material to be ablated are mounted on a movable support. The material transfer rate is determined for each target material, and these rates are stored in a controller. A position detector determines which target material is in a position to be ablated, and then the controller controls the beam trigger timing and energy level to achieve a desired proportion of each constituent material in the resulting film. 3 figs.

  1. Summary of Recent Target Studies

    SciTech Connect

    Bieniosek, F.; O'Day, S.

    1993-02-04

    This report describes recent measurements that have been performed with the new target stack (Fig. 1). Highlights of these measurements are: (1) Pbar yields of nickel and powdered rhenium are comparable to that of copper. (2) Enhancement of pbar yield at the interface between copper and aluminum disks in the target stack has been observed. This effect occurs only when the lens is focused near the upstream edge of the target. (3) The target density depletion study in powdered rhenium showed an apparent yield reduction on the time scale of a single proton pulse, accompanied by release of airborne radioactive material.

  2. Data Mining for Target Marketing

    NASA Astrophysics Data System (ADS)

    Levin, Nissan; Zahavi, Jacob

    Targeting is the core of marketing management. It is concerned with offering the right product/service to the customer at the right time and using the proper channel. In this chapter we discuss how Data Mining modeling and analysis can support targeting applications. We focus on three types of targeting models: continuous-choice models, discrete-choice models and in-market timing models, discussing alternative modeling for each application and decision making. We also discuss a range of pitfalls that one needs to be aware of in implementing a data mining solution for a targeting problem.

  3. Target engagement in lead generation.

    PubMed

    Durham, Timothy B; Blanco, Maria-Jesus

    2015-03-01

    The pharmaceutical industry is currently facing multiple challenges, in particular the low number of new drug approvals in spite of the high level of R&D investment. In order to improve target selection and assess properly the clinical hypothesis, it is important to start building an integrated drug discovery approach during Lead Generation. This should include special emphasis on evaluating target engagement in the target tissue and linking preclinical to clinical readouts. In this review, we would like to illustrate several strategies and technologies for assessing target engagement and the value of its application to medicinal chemistry efforts.

  4. Guidance system for laser targets

    DOEpatents

    Porter, Gary D.; Bogdanoff, Anatoly

    1978-01-01

    A system for guiding charged laser targets to a predetermined focal spot of a laser along generally arbitrary, and especially horizontal, directions which comprises a series of electrostatic sensors which provide inputs to a computer for real time calculation of position, velocity, and direction of the target along an initial injection trajectory, and a set of electrostatic deflection means, energized according to a calculated output of said computer, to change the target trajectory to intercept the focal spot of the laser which is triggered so as to illuminate the target of the focal spot.

  5. Targets and Secondary Beam Extraction

    NASA Astrophysics Data System (ADS)

    Noah, Etam

    2014-02-01

    Several applications make use of secondary beams of particles generated by the interaction of a primary beam of particles with a target. Spallation neutrons, bremsstrahlung photon-produced neutrons, radioactive ions and neutrinos are available to users at state-of-the-art facilities worldwide. Plans for even higher secondary beam intensities place severe constraints on the design of targets. This article reports on the main targetry challenges and highlights a variety of solutions for targetry and secondary beam extraction. Issues related to target station layout, instrumentation at the beam-target interface, safety and radioprotection are also discussed.

  6. Validation of ion channel targets.

    PubMed

    Gerlach, Aaron C; Antonio, Brett M

    2015-01-01

    A prerequisite for a successful target-based drug discovery program is a robust data set that increases confidence in the validation of the molecular target and the therapeutic approach. Given the significant time and resource investment required to carry a drug to market, early selection of targets that can be modulated safely and effectively forms the basis for a strong portfolio and pipeline. In this article we present some of the more useful scientific approaches that can be applied toward the validation of ion channel targets, a molecular family with a history of clinical success in therapeutic areas such as cardiovascular, respiratory, pain and neuroscience.

  7. Targeted Nanotechnology for Cancer Imaging

    PubMed Central

    Toy, Randall; Bauer, Lisa; Hoimes, Christopher; Ghaghada, Ketan B.; Karathanasis, Efstathios

    2014-01-01

    Targeted nanoparticle imaging agents provide many benefits and new opportunities to facilitate accurate diagnosis of cancer and significantly impact patient outcome. Due to the highly engineerable nature of nanotechnology, targeted nanoparticles exhibit significant advantages including increased contrast sensitivity, binding avidity and targeting specificity. Considering the various nanoparticle designs and their adjustable ability to target a specific site and generate detectable signals, nanoparticles can be optimally designed in terms of biophysical interactions (i.e., intravascular and interstitial transport) and biochemical interactions (i.e., targeting avidity towards cancer-related biomarkers) for site-specific detection of very distinct microenvironments. This review seeks to illustrate that the design of a nanoparticle dictates its in vivo journey and targeting of hard-to-reach cancer sites, facilitating early and accurate diagnosis and interrogation of the most aggressive forms of cancer. We will report various targeted nanoparticles for cancer imaging using X-ray computed tomography, ultrasound, magnetic resonance imaging, nuclear imaging and optical imaging. Finally, to realize the full potential of targeted nanotechnology for cancer imaging, we will describe the challenges and opportunities for the clinical translation and widespread adaptation of targeted nanoparticles imaging agents. PMID:25116445

  8. Therapeutic Targeting of Telomerase

    PubMed Central

    Jäger, Kathrin; Walter, Michael

    2016-01-01

    Telomere length and cell function can be preserved by the human reverse transcriptase telomerase (hTERT), which synthesizes the new telomeric DNA from a RNA template, but is normally restricted to cells needing a high proliferative capacity, such as stem cells. Consequently, telomerase-based therapies to elongate short telomeres are developed, some of which have successfully reached the stage I in clinical trials. Telomerase is also permissive for tumorigenesis and 90% of all malignant tumors use telomerase to obtain immortality. Thus, reversal of telomerase upregulation in tumor cells is a potential strategy to treat cancer. Natural and small-molecule telomerase inhibitors, immunotherapeutic approaches, oligonucleotide inhibitors, and telomerase-directed gene therapy are useful treatment strategies. Telomerase is more widely expressed than any other tumor marker. The low expression in normal tissues, together with the longer telomeres in normal stem cells versus cancer cells, provides some degree of specificity with low risk of toxicity. However, long term telomerase inhibition may elicit negative effects in highly-proliferative cells which need telomerase for survival, and it may interfere with telomere-independent physiological functions. Moreover, only a few hTERT molecules are required to overcome senescence in cancer cells, and telomerase inhibition requires proliferating cells over a sufficient number of population doublings to induce tumor suppressive senescence. These limitations may explain the moderate success rates in many clinical studies. Despite extensive studies, only one vaccine and one telomerase antagonist are routinely used in clinical work. For complete eradication of all subpopulations of cancer cells a simultaneous targeting of several mechanisms will likely be needed. Possible technical improvements have been proposed including the development of more specific inhibitors, methods to increase the efficacy of vaccination methods, and

  9. Therapeutic Targeting of Telomerase.

    PubMed

    Jäger, Kathrin; Walter, Michael

    2016-01-01

    Telomere length and cell function can be preserved by the human reverse transcriptase telomerase (hTERT), which synthesizes the new telomeric DNA from a RNA template, but is normally restricted to cells needing a high proliferative capacity, such as stem cells. Consequently, telomerase-based therapies to elongate short telomeres are developed, some of which have successfully reached the stage I in clinical trials. Telomerase is also permissive for tumorigenesis and 90% of all malignant tumors use telomerase to obtain immortality. Thus, reversal of telomerase upregulation in tumor cells is a potential strategy to treat cancer. Natural and small-molecule telomerase inhibitors, immunotherapeutic approaches, oligonucleotide inhibitors, and telomerase-directed gene therapy are useful treatment strategies. Telomerase is more widely expressed than any other tumor marker. The low expression in normal tissues, together with the longer telomeres in normal stem cells versus cancer cells, provides some degree of specificity with low risk of toxicity. However, long term telomerase inhibition may elicit negative effects in highly-proliferative cells which need telomerase for survival, and it may interfere with telomere-independent physiological functions. Moreover, only a few hTERT molecules are required to overcome senescence in cancer cells, and telomerase inhibition requires proliferating cells over a sufficient number of population doublings to induce tumor suppressive senescence. These limitations may explain the moderate success rates in many clinical studies. Despite extensive studies, only one vaccine and one telomerase antagonist are routinely used in clinical work. For complete eradication of all subpopulations of cancer cells a simultaneous targeting of several mechanisms will likely be needed. Possible technical improvements have been proposed including the development of more specific inhibitors, methods to increase the efficacy of vaccination methods, and

  10. Tritium target fabrication for the rotating target neutron source

    NASA Astrophysics Data System (ADS)

    Adair, H. L.; Kobisk, E. H.; Byrum, B. L.

    1982-09-01

    The Isotope Research Materials Laboratory (IRML) of the Oak Ridge National Laboratory (ORNL) prepares tritium targets that are used to produce an intense beam of 14.5 MeV neutrons by the 13H( 12H, 01n) 24He reaction. The intense beams of 14.5 MeV neutrons are used in programs involving cancer research, materials evaluation, and materials identification. Many of the tritium targets prepared by IRML for the past four years have been used in support of the Rotating Target Neutron Source (RTNS) programs at the Lawrence Livermore National Laboratory (LLNL). The tritium targets are prepared by the vacuum evaporation of titanium from a rod-fed electron beam gun. The resulting vapor-condensed titanium layers are exposed to a tritium atmosphere to form titanium tritide. A summary of tritium target development at IRML with an emphasis on the RTNS programs is presented.

  11. Dual targeting of peroxisomal proteins

    PubMed Central

    Ast, Julia; Stiebler, Alina C.; Freitag, Johannes; Bölker, Michael

    2013-01-01

    Cellular compartmentalization into organelles serves to separate biological processes within the environment of a single cell. While some metabolic reactions are specific to a single organelle, others occur in more than one cellular compartment. Specific targeting of proteins to compartments inside of eukaryotic cells is mediated by defined sequence motifs. To achieve multiple targeting to different compartments cells use a variety of strategies. Here, we focus on mechanisms leading to dual targeting of peroxisomal proteins. In many instances, isoforms of peroxisomal proteins with distinct intracellular localization are encoded by separate genes. But also single genes can give rise to differentially localized proteins. Different isoforms can be generated by use of alternative transcriptional start sites, by differential splicing or ribosomal read-through of stop codons. In all these cases different peptide variants are produced, of which only one carries a peroxisomal targeting signal. Alternatively, peroxisomal proteins contain additional signals that compete for intracellular targeting. Dual localization of proteins residing in both the cytoplasm and in peroxisomes may also result from use of inefficient targeting signals. The recent observation that some bona fide cytoplasmic enzymes were also found in peroxisomes indicates that dual targeting of proteins to both the cytoplasm and the peroxisome might be more widespread. Although current knowledge of proteins exhibiting only partial peroxisomal targeting is far from being complete, we speculate that the metabolic capacity of peroxisomes might be larger than previously assumed. PMID:24151469

  12. A high yield neutron target

    NASA Technical Reports Server (NTRS)

    Alger, D. L.; Steinberg, R.; Weisenbach, P.

    1974-01-01

    Target, in cylinder form, rotates rapidly in front of beam. Titanium tritide film is much thicker than range of accelerated deutron. Sputtering electrode permits full use of thick film. Stream of high-velocity coolant provides efficient transfer of heat from target.

  13. Projectile penetration into representative targets

    NASA Astrophysics Data System (ADS)

    Stone, George W.

    1994-10-01

    The differential equation representing the penetration of a 'hard' projectile into semi-infinite, homogeneous target materials is solved for several generic combinations of the target material/projectile characteristics. A 'hard' projectile is defined as one that does not change size or shape and does not lose mass during the penetration process. The target materials evaluated range from the structurally 'soft' materials (liquids) to structurally 'hard' materials (armor plate) with viscous and fluid dynamic drag considered. The solutions to the differential equation(s) are expanded in series form to demonstrate the underlying parameters governing projectile penetration and the way they interact to limit penetration in a given target material. It is shown that the fundamental parameter governing projectile penetration into structurally 'firm' materials is the initial kinetic energy of the projectile divided by the frontal area of the projectile and the inherent structural characteristic of the target. Experimental data on the penetration of steel spheres into ballistic gelatin and for armor piercing bullets into armor plate materials are used to verify the characteristics of the solutions to the equation of motion for the projectile and to demonstrate how penetration can vary with projectile size and target characteristics. The penetration equation for a single 'hard' target material is used to develop a solution for the penetration of multilayered 'hard' target materials.

  14. Dual targeting of peroxisomal proteins.

    PubMed

    Ast, Julia; Stiebler, Alina C; Freitag, Johannes; Bölker, Michael

    2013-10-18

    Cellular compartmentalization into organelles serves to separate biological processes within the environment of a single cell. While some metabolic reactions are specific to a single organelle, others occur in more than one cellular compartment. Specific targeting of proteins to compartments inside of eukaryotic cells is mediated by defined sequence motifs. To achieve multiple targeting to different compartments cells use a variety of strategies. Here, we focus on mechanisms leading to dual targeting of peroxisomal proteins. In many instances, isoforms of peroxisomal proteins with distinct intracellular localization are encoded by separate genes. But also single genes can give rise to differentially localized proteins. Different isoforms can be generated by use of alternative transcriptional start sites, by differential splicing or ribosomal read-through of stop codons. In all these cases different peptide variants are produced, of which only one carries a peroxisomal targeting signal. Alternatively, peroxisomal proteins contain additional signals that compete for intracellular targeting. Dual localization of proteins residing in both the cytoplasm and in peroxisomes may also result from use of inefficient targeting signals. The recent observation that some bona fide cytoplasmic enzymes were also found in peroxisomes indicates that dual targeting of proteins to both the cytoplasm and the peroxisome might be more widespread. Although current knowledge of proteins exhibiting only partial peroxisomal targeting is far from being complete, we speculate that the metabolic capacity of peroxisomes might be larger than previously assumed.

  15. Spinning targets for laser fusion

    SciTech Connect

    Baldwin, D.E.; Ryutov, D.D.

    1995-09-01

    Several techniques for spinning the ICF targets up prior to or in the course of their compression are suggested. Interference of the rotational shear flow with Rayleigh-Taylor instability is briefly discussed and possible consequences for the target performance are pointed out.

  16. The proteome targets of intracellular targeting antimicrobial peptides.

    PubMed

    Shah, Pramod; Hsiao, Felix Shih-Hsiang; Ho, Yu-Hsuan; Chen, Chien-Sheng

    2016-04-01

    Antimicrobial peptides have been considered well-deserving candidates to fight the battle against microorganisms due to their broad-spectrum antimicrobial activities. Several studies have suggested that membrane disruption is the basic mechanism of AMPs that leads to killing or inhibiting microorganisms. Also, AMPs have been reported to interact with macromolecules inside the microbial cells such as nucleic acids (DNA/RNA), protein synthesis, essential enzymes, membrane septum formation and cell wall synthesis. Proteins are associated with many intracellular mechanisms of cells, thus protein targets may be specifically involved in mechanisms of action of AMPs. AMPs like pyrrhocoricin, drosocin, apidecin and Bac 7 are documented to have protein targets, DnaK and GroEL. Moreover, the intracellular targeting AMPs are reported to influence more than one protein targets inside the cell, suggesting for the multiple modes of actions. This complex mechanism of intracellular targeting AMPs makes them more difficult for the development of resistance. Herein, we have summarized the current status of AMPs in terms of their mode of actions, entry to cytoplasm and inhibition of macromolecules. To reveal the mechanism of action, we have focused on AMPs with intracellular protein targets. We have also included the use of high-throughput proteome microarray to determine the unidentified AMP protein targets in this review.

  17. Targeting polymer therapeutics to bone.

    PubMed

    Low, Stewart A; Kopeček, Jindřich

    2012-09-01

    An aging population in the developing world has led to an increase in musculoskeletal diseases such as osteoporosis and bone metastases. Left untreated many bone diseases cause debilitating pain and in the case of cancer, death. Many potential drugs are effective in treating diseases but result in side effects preventing their efficacy in the clinic. Bone, however, provides a unique environment of inorganic solids, which can be exploited in order to effectively target drugs to diseased tissue. By integration of bone targeting moieties to drug-carrying water-soluble polymers, the payload to diseased area can be increased while side effects decreased. The realization of clinically relevant bone targeted polymer therapeutics depends on (1) understanding bone targeting moiety interactions, (2) development of controlled drug delivery systems, as well as (3) understanding drug interactions. The latter makes it possible to develop bone targeted synergistic drug delivery systems.

  18. TARGETING POLYMER THERAPEUTICS TO BONE

    PubMed Central

    Low, Stewart; Kopeček, Jindřich

    2012-01-01

    An aging population in the developing world has led to an increase in musculoskeletal diseases such as osteoporosis and bone metastases. Left untreated many bone diseases cause debilitating pain and in the case of cancer, death. Many potential drugs are effective in treating diseases but result in side effects preventing their efficacy in the clinic. Bone, however, provides an unique environment of inorganic solids, which can be exploited in order to effectively target drugs to diseased tissue. By integration of bone targeting moieties to drug-carrying water-soluble polymers, the payload to diseased area can be increased while side effects decreased. The realization of clinically relevant bone targeted polymer therapeutics depends on (1) understanding bone targeting moiety interactions, (2) development of controlled drug delivery systems, as well as (3) understanding drug interactions. The latter makes it possible to develop bone targeted synergistic drug delivery systems. PMID:22316530

  19. Targeted marketing and public health.

    PubMed

    Grier, Sonya A; Kumanyika, Shiriki

    2010-01-01

    Targeted marketing techniques, which identify consumers who share common needs or characteristics and position products or services to appeal to and reach these consumers, are now the core of all marketing and facilitate its effectiveness. However, targeted marketing, particularly of products with proven or potential adverse effects (e.g., tobacco, alcohol, entertainment violence, or unhealthful foods) to consumer segments defined as vulnerable raises complex concerns for public health. It is critical that practitioners, academics, and policy makers in marketing, public health, and other fields recognize and understand targeted marketing as a specific contextual influence on the health of children and adolescents and, for different reasons, ethnic minority populations and other populations who may benefit from public health protections. For beneficial products, such understanding can foster more socially productive targeting. For potentially harmful products, understanding the nature and scope of targeted marketing influences will support identification and implementation of corrective policies.

  20. Targeted marketing and public health.

    PubMed

    Grier, Sonya A; Kumanyika, Shiriki

    2010-01-01

    Targeted marketing techniques, which identify consumers who share common needs or characteristics and position products or services to appeal to and reach these consumers, are now the core of all marketing and facilitate its effectiveness. However, targeted marketing, particularly of products with proven or potential adverse effects (e.g., tobacco, alcohol, entertainment violence, or unhealthful foods) to consumer segments defined as vulnerable raises complex concerns for public health. It is critical that practitioners, academics, and policy makers in marketing, public health, and other fields recognize and understand targeted marketing as a specific contextual influence on the health of children and adolescents and, for different reasons, ethnic minority populations and other populations who may benefit from public health protections. For beneficial products, such understanding can foster more socially productive targeting. For potentially harmful products, understanding the nature and scope of targeted marketing influences will support identification and implementation of corrective policies. PMID:20070196

  1. Targeting ion transport in cancer

    PubMed Central

    Oosterwijk, E.; Gillies, R. J.

    2014-01-01

    The metabolism of cancer cells differs substantially from normal cells, including ion transport. Although this phenomenon has been long recognized, ion transporters have not been viewed as suitable therapeutic targets. However, the acidic pH values present in tumours which are well outside of normal limits are now becoming recognized as an important therapeutic target. Carbonic anhydrase IX (CAIX) is fundamental to tumour pH regulation. CAIX is commonly expressed in cancer, but lowly expressed in normal tissues and that presents an attractive target. Here, we discuss the possibilities of exploiting the acidic, hypoxic tumour environment as possible target for therapy. Additionally, clinical experience with CAIX targeting in cancer patients is discussed. PMID:24493755

  2. Type of Cancer Treatment: Targeted Therapy

    Cancer.gov

    Information about the role that targeted therapies play in cancer treatment. Includes how targeted therapies work against cancer, who receives targeted therapies, common side effects, and what to expect when having targeted therapies.

  3. Molecularly targeted therapies for recurrent glioblastoma: current and future targets

    PubMed Central

    Lau, Darryl; Magill, Stephen T.; Aghi, Manish K.

    2016-01-01

    Object Glioblastoma is the most aggressive and diffusely infiltrative primary brain tumor. Recurrence is expected and is extremely difficult to treat. Over the past decade, the accumulation of knowledge regarding the molecular and genetic profile of glioblastoma has led to numerous molecularly targeted therapies. This article aims to review the literature and highlight the mechanisms and efficacies of molecularly targeted therapies for recurrent glioblastoma. Methods A systematic search was performed with the phrase “(name of particular agent) and glioblastoma” as a search term in PubMed to identify all articles published up until 2014 that included this phrase in the title and/or abstract. The references of systematic reviews were also reviewed for additional sources. The review included clinical studies that comprised at least 20 patients and reported results for the treatment of recurrent glioblastoma with molecular targeted therapies. Results A total of 42 articles were included in this review. In the treatment of recurrent glioblastoma, various targeted therapies have been tested over the past 10–15 years. The targets of interest include epidermal growth factor receptor, vascular endothelial growth factor receptor, platelet-derived growth factor receptor, Ras pathway, protein kinase C, mammalian target of rapamycin, histone acetylation, and integrins. Unfortunately, the clinical responses to most available targeted therapies are modest at best. Radiographic responses generally range in the realm of 5%–20%. Progression-free survival at 6 months and overall survival were also modest with the majority of studies reporting a 10%–20% 6-month progression-free survival and 5- to 8-month overall survival. There have been several clinical trials evaluating the use of combination therapy for molecularly targeted treatments. In general, the outcomes for combination therapy tend to be superior to single-agent therapy, regardless of the specific agent studied

  4. Auditory target detection in reverberation

    NASA Astrophysics Data System (ADS)

    Zurek, Patrick M.; Freyman, Richard L.; Balakrishnan, Uma

    2004-04-01

    Measurements and theoretical predictions of auditory target detection in simulated reverberant conditions are reported. The target signals were pulsed 13-octave bands of noise and the masker signal was a continuous wideband noise. Target and masker signals were passed through a software simulation of a reverberant room with a rigid sphere modeling a listener's head. The location of the target was fixed while the location of the masker was varied in the simulated room. Degree of reverberation was controlled by varying the uniform acoustic absorption of the simulated room's surfaces. The resulting target and masker signals were presented to the listeners over headphones in monaural-left, monaural-right, or binaural listening modes. Changes in detection performance in the monaural listening modes were largely predictable from the changes in target-to-masker ratio in the target band, but with a few dB of extra masking in reverberation. Binaural detection performance was generally well predicted by applying Durlach's [in Foundations of Modern Auditory Theory (Academic, New York, 1972)] equalization-cancellation theory to the direct-plus-reverberant ear signals. Predictions in all cases were based on a statistical description of room acoustics and on acoustic diffraction by a sphere. The success of these detection models in the present well-controlled reverberant conditions suggests that they can be used to incorporate listening mode and source location as factors in speech-intelligibility predictions.

  5. Aided targeting system simulation evaluation

    NASA Technical Reports Server (NTRS)

    Demaio, Joe; Becker, Curtis

    1994-01-01

    Simulation research was conducted at the Crew Station Research and Development Facility on the effectiveness and ease of use of three targeting systems. A manual system required the aviator to scan a target array area with a simulated second generation forward looking infrared (FLIR) sensor, locate and categorize targets, and construct a target hand-off list. The interface between the aviator and the system was like that of an advanced scout helicopter (manual mode). Two aided systems detected and categorized targets automatically. One system used only the FLIR sensor and the second used FLIR fused with Longbow radar. The interface for both was like that of an advanced scout helicopter aided mode. Exposure time while performing the task was reduced substantially with the aided systems, with no loss of target hand-off list accuracy. The fused sensor system showed lower time to construct the target hand-off list and a slightly lower false alarm rate than the other systems. A number of issues regarding system sensitivity and criterion, and operator interface design are discussed.

  6. Targeted biopharmaceuticals for cancer treatment.

    PubMed

    Zhou, Lufang; Xu, Ningning; Sun, Yan; Liu, Xiaoguang Margaret

    2014-10-01

    Cancer is a complex invasive genetic disease that causes significant mortality rate worldwide. Protein-based biopharmaceuticals have significantly extended the lives of millions of cancer patients. This article reviews the biological function and application of targeted anticancer biopharmaceuticals. We first discuss the specific antigens and core pathways that are used in the development of targeted cancer therapy. The innovative monoclonal antibodies, non-antibody proteins, and small molecules targeting these antigens or pathways are then reviewed. Finally, the current challenges in anticancer biopharmaceuticals development and the potential solutions to address these challenges are discussed.

  7. Versatile cold atom target apparatus

    SciTech Connect

    Goetz, Simone; Hoeltkemeier, Bastian; Hofmann, Christoph S.; Litsch, Dominic; DePaola, Brett D.; Weidemueller, Matthias

    2012-07-15

    We report on a compact and transportable apparatus that consists of a cold atomic target at the center of a high resolution recoil ion momentum spectrometer. Cold rubidium atoms serve as a target which can be operated in three different modes: in continuous mode, consisting of a cold atom beam generated by a two-dimensional magneto-optical trap, in normal mode in which the atoms from the beam are trapped in a three-dimensional magneto-optical trap (3D MOT), and in high density mode in which the 3D MOT is operated in dark spontaneous optical trap configuration. The targets are characterized using photoionization.

  8. A variable optical target simulator

    NASA Technical Reports Server (NTRS)

    Kulas, C. E.; Crosswhite, E. D.

    1979-01-01

    A crucial experiment, relative to determining the ability of an imaging seeker to track a target and generate accurate terminal guidance, requires an optical device which can provide imagery that grows in size as a real-time estimate of true missile flight conditions. The basic components of an Optical Contrast TV Imaging Seeker are reviewed to establish the need for an optical target simulator. An optomechanical device called a Variable Optical Target Simulator (VOTS) which generates end game scene situations is discussed. The organization of optical components and their control for providing an image which grows in size as a linear estimate of real world situations is presented.

  9. Backlighting prospects for ICF targets

    SciTech Connect

    Rupert, V.; Matthews, D.; Ahlstrom, H.; Attwood, D.; Price, R.; Coleman, L.; Manes, K.; Slivinsky, V.

    1981-01-01

    High energy x-ray backlighters are necessary to diagnose the implosion symmetry and stability of intermediate and high density targets. Synchronization requirements between the target irradiating pulse and the radiograph place severe constraints on the type of x-ray sources which can be used and favors laser irradiated backlighters. Data gathered on line emitters as a function of laser pulselength, wavelength and intensity in the 5 to 10 keV region are used to determine which diagnostic instruments will be feasible for ICF target experiments, and the requirements for backlighter irradiation.

  10. Development of targeted radiotherapy systems

    NASA Astrophysics Data System (ADS)

    Ferro, Guillermina; Murphy, Consuelo A.; Villarreal, José E.; Pedraza, Martha; García, Laura; Tendilla, José I.; Paredes, Lydia

    2001-10-01

    Conventional or external beam radiotherapy, has been a viable alternative for cancer treatment. Although this technique is effective, its use is limited if the patient has multiple malignant lesions (metastases). An alternative approach is based on the design of radiopharmaceuticals that, to be administered in the patient, are directed specifically toward the target cell producing a selective radiation delivery. This treatment is known as targeted radiotherapy. We have summarized and discussed some results related to our investigations on the development of targeted radiotherapy systems, including aspects of internal dosimetry.

  11. Cavitation in a Mercury Target

    SciTech Connect

    West, C.D.

    2000-09-01

    Recent theoretical work on the formation of bubble nucleation centers by energetic particles leads to some reasonably credible calculations of the maximum negative pressure that might be sustained without bubble formation in the mercury target of the Spallation Neutron Source.

  12. Strategically targeting MYC in cancer

    PubMed Central

    Posternak, Valeriya; Cole, Michael D.

    2016-01-01

    MYC is a major driver of cancer cell growth and mediates a transcriptional program spanning cell growth, the cell cycle, metabolism, and cell survival. Many efforts have been made to deliberately target MYC for cancer therapy. A variety of compounds have been generated to inhibit MYC function or stability, either directly or indirectly. The most direct inhibitors target the interaction between MYC and MAX, which is required for DNA binding. Unfortunately, these compounds do not have the desired pharmacokinetics and pharmacodynamics for in vivo application. Recent studies report the indirect inhibition of MYC through the development of two compounds, JQ1 and THZ1, which target factors involved in unique stages of transcription. These compounds appear to have significant therapeutic value for cancers with high levels of MYC, although some effects are MYC-independent. These approaches serve as a foundation for developing novel compounds to pharmacologically target MYC-driven cancers. PMID:27081479

  13. Targeted cytokines for cancer immunotherapy.

    PubMed

    Lode, H N; Reisfeld, R A

    2000-01-01

    Targeting of cytokines into the tumor microenvironment using antibody-cytokine fusion proteins, called immunocytokines, represents a novel approach in cancer immunotherapy. This article summarizes therapeutic efficacy and immune mechanisms involved in targeting interleukin-2 (IL-2) to neuroectodermal tumors using ganglioside GD2-specific antibody-IL-2 fusion protein (ch14.18-IL-2). Treatment of established melanoma metastases with ch14.18-IL-2 resulted in eradication of disease followed by a vaccination effect protecting mice from lethal challenges with wild-type tumor calls. In a syngeneic neuroblastoma model, targeted IL-2 was effective in the amplification of a weak memory immune response previously induced by IL-12 gene therapy using an engineered linear version of this heterodimeric cytokine. These findings show that targeted IL-2 may provide an effective tool in cancer immunotherapy and establish the missing link between T cell-mediated vaccination and objective clinical responses.

  14. Inertial-confinement-fusion targets

    SciTech Connect

    Hendricks, C.D.

    1982-08-10

    Much of the research in laser fusion has been done using simple ball on-stalk targets filled with a deuterium-tritium mixture. The targets operated in the exploding pusher mode in which the laser energy was delivered in a very short time (approx. 100 ps or less) and was absorbed by the glass wall of the target. The high energy density in the glass literally exploded the shell with the inward moving glass compressing the DT fuel to high temperatures and moderate densities. Temperatures achieved were high enough to produce DT reactions and accompanying thermonuclear neutrons and alpha particles. The primary criteria imposed on the target builders were: (1) wall thickness, (2) sphere diameter, and (3) fuel in the sphere.

  15. Targeting ubiquitination for cancer therapies

    PubMed Central

    Morrow, John Kenneth; Lin, Hui-Kuan; Sun, Shao-Cong; Zhang, Shuxing

    2015-01-01

    Ubiquitination, the structured degradation and turnover of cellular proteins, is regulated by the ubiquitin–proteasome system (UPS). Most proteins that are critical for cellular regulations and functions are targets of the process. Ubiquitination is comprised of a sequence of three enzymatic steps, and aberrations in the pathway can lead to tumor development and progression as observed in many cancer types. Recent evidence indicates that targeting the UPS is effective for certain cancer treatment, but many more potential targets might have been previously overlooked. In this review, we will discuss the current state of small molecules that target various elements of ubiquitination. Special attention will be given to novel inhibitors of E3 ubiquitin ligases, especially those in the SCF family. PMID:26630263

  16. "Cavitation in a Mercury Target"

    SciTech Connect

    West, C.D.

    2000-09-06

    Recent theoretical work on the formation of bubble nucleation centers by energetic particles leads to some reasonably credible calculations of the maximum negative pressure that might be sustained without bubble formation in the mercury target of the Spallation Neutron Source.

  17. Strategically targeting MYC in cancer.

    PubMed

    Posternak, Valeriya; Cole, Michael D

    2016-01-01

    MYC is a major driver of cancer cell growth and mediates a transcriptional program spanning cell growth, the cell cycle, metabolism, and cell survival. Many efforts have been made to deliberately target MYC for cancer therapy. A variety of compounds have been generated to inhibit MYC function or stability, either directly or indirectly. The most direct inhibitors target the interaction between MYC and MAX, which is required for DNA binding. Unfortunately, these compounds do not have the desired pharmacokinetics and pharmacodynamics for in vivo application. Recent studies report the indirect inhibition of MYC through the development of two compounds, JQ1 and THZ1, which target factors involved in unique stages of transcription. These compounds appear to have significant therapeutic value for cancers with high levels of MYC, although some effects are MYC-independent. These approaches serve as a foundation for developing novel compounds to pharmacologically target MYC-driven cancers. PMID:27081479

  18. SCF ubiquitin ligase targeted therapies

    PubMed Central

    Skaar, Jeffrey R.; Pagan, Julia K.; Pagano, Michele

    2015-01-01

    Summary The recent clinical successes of inhibitors of the proteasome for the treatment of cancer have highlighted the therapeutic potential of this protein degradation system. Proteasome inhibitors prevent the degradation of numerous proteins, so increased specificity could be achieved by inhibiting the components of the ubiquitin-proteasome system that target specific subsets of proteins for degradation. F-box proteins are the substrate-targeting subunits of SKP1-CUL1-F-box protein (SCF) ubiquitin ligase complexes. Through the degradation of a plethora of diverse substrates, SCF ubiquitin ligases control a large number of processes at the cellular and organismal levels, and their misregulation is implicated in many pathologies. SCF ligases are characterized by a high specificity for their substrates, so they represent promising drug targets. However, the potential for therapeutic manipulation of SCF complexes remains an underdeveloped area. This review will explore and discuss potential strategies to target SCF-mediated biology to treat human diseases. PMID:25394868

  19. Nanomedicine: Swarming towards the target

    NASA Astrophysics Data System (ADS)

    Wang, Yucai; Brown, Paige; Xia, Younan

    2011-07-01

    A system comprising 'signalling' and 'receiving' modules -- where the receiving module circulating in the bloodstream is directed to the tumour by a cascade triggered by the signalling module -- improves the targeting effect of a nanomedicine.

  20. Gene targeting with retroviral vectors

    SciTech Connect

    Ellis, J.; Bernstein, A. )

    1989-04-01

    The authors have designed and constructed integration-defective retroviral vectors to explore their potential for gene targeting in mammalian cells. Two nonoverlapping deletion mutants of the bacterial neomycin resistance (neo) gene were used to detect homologous recombination events between viral and chromosomal sequences. Stable neo gene correction events were selected at a frequency of approximately 1 G418/sup r/ cell per 3 x 10/sup 6/ infected cells. Analysis of the functional neo gene in independent targeted cell clones indicated that unintegrated retroviral linear DNA recombined with the target by gene conversion for variable distances into regions of nonhomology. In addition, transient neo gene correction events which were associated with the complete loss of the chromosomal target sequences were observed. These results demonstrated that retroviral vectors can recombine with homologous chromosomal sequences in rodent and human cells.