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Sample records for acquired thrombotic thrombocytopenic

  1. 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

  2. Acquired thrombotic thrombocytopenic purpura and atypical hemolytic uremic syndrome successfully treated with eculizumab

    PubMed Central

    Cottler-Fox, Michele; Motwani, Pooja

    2017-01-01

    Acquired idiopathic thrombotic thrombocytopenic purpura is a life-threatening disease with a mortality of up to 90%, if not promptly recognized and treated. We report a 64-year-old woman with this condition who presented with left-sided weakness and seizure-like activity preceded by headache and easy bruising. She did not achieve optimal response to plasma exchange, corticosteroids, rituximab, and vincristine. We initiated treatment with eculizumab, following which she had durable remission that continued for 30 months after discontinuation of the drug. We later found that our patient has homozygous deletion in two closely related genes, complement factor H–related 1 and complement factor H–related 3.

  3. Ribosomal and immune transcripts associate with relapse in acquired ADAMTS13-deficient thrombotic thrombocytopenic purpura.

    PubMed

    Edgar, Contessa E; Terrell, Deirdra R; Vesely, Sara K; Wren, Jonathan D; Dozmorov, Igor M; Niewold, Timothy B; Brown, Michael; Zhou, Fang; Frank, Mark Barton; Merrill, Joan T; Kremer Hovinga, Johanna A; Lämmle, Bernhard; James, Judith A; George, James N; Farris, A Darise

    2015-01-01

    Approximately 40% of patients who survive acute episodes of thrombotic thrombocytopenic purpura (TTP) associated with severe acquired ADAMTS13 deficiency experience one or more relapses. Risk factors for relapse other than severe ADAMTS13 deficiency and ADAMTS13 autoantibodies are unknown. ADAMTS13 autoantibodies, TTP episodes following infection or type I interferon treatment and reported ensuing systemic lupus erythematosus in some patients suggest immune dysregulation. This cross-sectional study asked whether autoantibodies against RNA-binding proteins or peripheral blood gene expression profiles measured during remission are associated with history of prior relapse in acquired ADAMTS13-deficient TTP. Peripheral blood from 38 well-characterized patients with autoimmune ADAMTS13-deficient TTP in remission was examined for autoantibodies and global gene expression. A subset of TTP patients (9 patients, 24%) exhibited a peripheral blood gene signature composed of elevated ribosomal transcripts that associated with prior relapse. A non-overlapping subset of TTP patients (9 patients, 24%) displayed a peripheral blood type I interferon gene signature that associated with autoantibodies to RNA-binding proteins but not with history of relapse. Patients who had relapsed bimodally expressed higher HLA transcript levels independently of ribosomal transcripts. Presence of any one potential risk factor (ribosomal gene signature, elevated HLA-DRB1, elevated HLA-DRB5) associated with relapse (OR = 38.4; p = 0.0002) more closely than any factor alone or all factors together. Levels of immune transcripts typical of natural killer (NK) and T lymphocytes positively correlated with ribosomal gene expression and number of prior episodes but not with time since the most recent episode. Flow cytometry confirmed elevated expression of cell surface markers encoded by these transcripts on T and/or NK cell subsets of patients who had relapsed. These data associate elevated ribosomal and

  4. 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

  5. Thrombotic thrombocytopenic purpura as an initial presentation of systemic lupus erythematosus with acquired ADAMTS 13 antibody

    PubMed Central

    Changcharoen, Bhisit; Bolger, Dennis Thomas

    2015-01-01

    We report a female patient presenting with headache, fatigue, ecchymoses and recent, excessive vaginal bleeding. Prompt review of the peripheral blood smear showed evidence of microangiopathic haemolytic anaemia (MAHA) and thrombocytopenia. Thrombotic thrombocytopenic purpura (TTP) was suspected. Plasma exchange and corticosteroids were started urgently. The patient responded favourably to the treatment. Subsequently, positive serological markers returned and were compatible with systemic lupus erythematosus (SLE). A disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13 (ADAMTS 13) activity was remarkably low with a positive inhibitory ADAMTS 13 antibody. Mycophenolate and hydroxychloroquine were started along with a prolonged course and taper of corticosteroids. These medications have been maintained with an excellent response in 14 months of follow-up. PMID:25701834

  6. Thrombotic Thrombocytopenic Purpura

    MedlinePlus

    ... make a normal ADAMTS13 enzyme. As a result, enzyme activity is lacking or changed. Acquired TTP is the ... the body makes antibodies (proteins) that block the activity of the ADAMTS13 enzyme. It's not clear what triggers inherited and acquired ...

  7. 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

  8. 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.

  9. FRETS-VWF73 rather than CBA assay reflects ADAMTS13 proteolytic activity in acquired thrombotic thrombocytopenic purpura patients.

    PubMed

    Mancini, I; Valsecchi, C; Lotta, L A; Deforche, L; Pontiggia, S; Bajetta, M; Palla, R; Vanhoorelbeke, K; Peyvandi, F

    2014-08-01

    Collagen-binding activity (CBA) and FRETS-VWF73 assays are widely adopted methods for the measurement of the plasmatic activity of ADAMTS13, the von Willebrand factor (VWF) cleaving-protease. Accurately assessing the severe deficiency of ADAMTS13 is important in the management of thrombotic thrombocytopenic purpura (TTP). However, non-concordant results between the two assays have been reported in a small but relevant percentage of TTP cases. We investigated whether CBA or FRETS-VWF73 assay reflects ADAMTS13 proteolytic activity in acquired TTP patients with non-concordant measurements. Twenty plasma samples with non-concordant ADAMTS13 activity results, <10% using FRETS-VWF73 and ≥20% using CBA, and 11 samples with concordant results, <10% using either FRETS-VWF73 and CBA assays, were analysed. FRETS-VWF73 was performed in the presence of 1.5 M urea. ADAMTS13 activities were also measured under flow conditions and the VWF multimer pattern was defined in order to verify the presence of ultra-large VWF due to ADAMTS13 deficiency. In FRETS-VWF73 assay with 1.5 M urea, ADAMTS13 activity significantly increased in roughly 50% of the samples with non-concordant results, whereas it remained undetectable in all samples with concordant measurements. Under flow conditions, all tested samples showed reduced ADAMTS13 activity. Finally, samples with non-concordant results showed a ratio of high molecular weight VWF multimers higher than normal. Our results support the use of FRETS-VWF73 over CBA assay for the assessment of ADAMTS13 severe deficiency and indicate urea as one cause of the observed differences.

  10. Acquired thrombotic thrombocytopenic purpura due to antibody-mediated ADAMTS13 deficiency precipitated by a localized Castleman's disease: a case report.

    PubMed

    Benevides, Thais Celi Lopes; Orsi, Fernanda Andrade; Colella, Marina Pereira; Percout, Priscila de Oliveira; Moura, Muriel Silva; Dias, Maria Almeida; Lins, Betina Diniz; Paula, Erich Vinicius de; Vassallo, Jose; Annichino-Bizzachi, Joyce

    2015-01-01

    Acquired ADAMTS13 inhibitor causing thrombotic thrombocytopenic purpura (TTP) may be precipitated by some infections, inflammatory diseases or neoplasia. We reported a case of refractory TTP precipitated by a newly diagnosed localized Castleman's disease (CD). TTP was initially treated with plasma exchange and immunosuppressive therapy with corticosteroids; however the treatment failed to promote sustained response. During hospitalization, an abdominal tumor was diagnosed and resected; the histological analysis revealed a CD of hyaline-vascular variant rich stroma. After tumor removal, the patient achieved a long-lasting clinical remission and normalized ADAMTS13 activity. This clinical case describes a novel association of acquired ADAMTS13 inhibitor and CD. The antibody to ADAMTS13 developed along with the systemic manifestation of CD and promptly disappeared after the resection of the tumor. There are reports of neoplasia-associated thrombotic microangiopathy however direct evidence of CD-dependent ADAMTS13 inhibitor had not yet been reported.

  11. The TITAN trial--assessing the efficacy and safety of an anti-von Willebrand factor Nanobody in patients with acquired thrombotic thrombocytopenic purpura.

    PubMed

    Holz, Josefin-Beate

    2012-06-01

    The Phase II TITAN trial is designed to assess the efficacy and safety of an anti-von Willebrand factor (vWF) Nanobody in patients with acquired thrombotic thrombocytopenic purpura (TTP). Nanobodies are a novel class of therapeutic proteins and are based on the smallest functional fragments of single-chain antibodies that occur naturally in the Camelidae family (Nanobody® and Nanobodies® are registered trademarks of Ablynx NV). With vWF implicated in the thrombotic process underlying TTP, an anti-vWF Nanobody may hold significant promise as adjunctive therapy to plasma exchange. Recruitment is currently ongoing, and aims to include a total of 110 patients from countries in Europe, the Middle East, Australia and Northern America.

  12. How I treat refractory thrombotic thrombocytopenic purpura

    PubMed Central

    Sayani, Farzana A.

    2015-01-01

    Acquired thrombotic thrombocytopenic purpura (TTP) is characterized by thrombocytopenia and microangiopathic hemolytic anemia (MAHA) without an obvious cause, and may include fever, mild renal failure, and neurologic deficits. It is characterized by a deficiency of the von Willebrand factor (VWF) cleaving enzyme, ADAMTS13 (a disintegrin and metalloproteinase, with a thrombospondin type 1 motif, member 13), resulting in formation of microthrombi in the high sheer environment of the microvasculature. This causes microvascular occlusion, MAHA, and organ ischemia. Diagnosis is based on the presence of clinical symptoms, laboratory aberrations consistent with MAHA, decreased ADAMTS13 activity, and possibly presence of anti-ADAMTS13 autoantibodies. Upfront treatment of acute TTP includes plasma exchange and corticosteroids. A significant number of patients are refractory to this treatment and will require further interventions. There are limited data and consensus on the management of the refractory TTP patient. Management involves simultaneously ruling out other causes of thrombocytopenia and MAHA, while also considering other treatments. In this article, we describe our management of the patient with refractory TTP, and discuss use of rituximab, increased plasma exchange, splenectomy, and immunosuppressive options, including cyclophosphamide, vincristine, and cyclosporine. We also review recent evidence for the potential roles of bortezomib and N-acetylcysteine, and explore new therapeutic approaches, including recombinant ADAMTS13 and anti-VWF therapy. PMID:25784681

  13. Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies.

    PubMed

    Scully, M; Cataland, S; Coppo, P; de la Rubia, J; Friedman, K D; Kremer Hovinga, J; Lämmle, B; Matsumoto, M; Pavenski, K; Sadler, E; Sarode, R; Wu, H

    2017-02-01

    Essentials An international collaboration provides a consensus for clinical definitions. This concerns thrombotic microangiopathies and thrombotic thrombocytopenic purpura (TTP). The consensus defines diagnosis, disease monitoring and response to treatment. Requirements for ADAMTS-13 are given.

  14. A rare combination of thrombotic thrombocytopenic purpura and antiphospholipid syndrome.

    PubMed

    Viner, Maya; Murakhovskaya, Irina

    2016-11-24

    Thrombocytopenia, in the setting of microangiopathic hemolytic anemia and thrombotic events, is characteristic of both thrombotic thrombocytopenic purpura and primary antiphospholipid syndrome. Clinically, it is difficult to distinguish between these two syndromes. We present a 41-year-old woman with chronic, relapsing thrombotic thrombocytopenic purpura in the presence of antiphospholipid antibodies. She had clinical manifestations of antiphospholipid syndrome without meeting laboratory criteria of the Sydney classification system. In the literature, there have only been nine cases of thrombotic thrombocytopenic purpura associated with primary antiphospholipid syndrome. Seven of the nine cases suffered from one or multiple strokes, a common feature in antiphospholipid syndrome, but an uncommon finding in thrombotic thrombocytopenic purpura. We introduce the possibility of an association between thrombotic thrombocytopenic purpura and the presence of antiphospholipid antibodies. Systematic testing of ADAMTS13 activity and anti-ADAMTS13 antibodies in patients who present with neurological symptoms and thrombocytopenia, in the presence of antiphospholipid antibodies, may help with the diagnosis of the rare thrombotic thrombocytopenic purpura-antiphospholipid syndrome combination.

  15. [Thrombotic Thrombocytopenic Purpura --Pathophysiology and Assays of ADAMTS13 Activity].

    PubMed

    Kato, Seiji; Fujimura, Yoshihiro

    2015-10-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder classified with a type of thrombotic microangiopathy (TMA). TTP is caused by a deficiency of von Willebrand factor-cleaving protease called ADAMTS13 (a disintegrin-like and metalloprotease with a thrombospondin type1 motif 13). Low ADAMTS13 levels result in increased ultra-large von Willebrand factor multimers (UL-VWFM), which induce platelet adhesion and thrombosis. Congenital TTP (Upshaw-Schulman syndrome: USS) is an inherited disorder of ADAMTS13, and the other more commonly is an acquired TTP caused by autoantibodies against ADAMTS13. This article reviews the progress of ADAMTS13 activity measurement and the resulting changes in the diagnosis and treatment of TTP.

  16. ADAMTS13 and von Willebrand factor in thrombotic thrombocytopenic purpura.

    PubMed

    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.

  17. Thrombotic thrombocytopenic purpura and other thrombotic microangiopathic hemolytic anemias: diagnosis and classification.

    PubMed

    Shenkman, Boris; Einav, Yulia

    2014-01-01

    Thrombotic microangiopathies (TMAs) include several diseases, most prominently are thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS). TMAs are characterized by profound thrombocytopenia, microangiopathic hemolytic anemia and organ ischemia. In most cases TTP results from deficiency of ADAMTS13, the von Willebrand factor-cleaving protease leading to increase of ultra-large von Willebrand factor (ULVWF) multimers. Congenital TTP is due to mutations in the gene of ADAMTS13 whereas acquired TTP is due to production of autoantibodies against ADAMTS13. In both cases severe deficiency of ADAMTS13 exists. However, the presence of ADAMTS13 activity does not rule out TTP. Diagnostic criteria of TTP are based on clinical features of neurologic and renal disfunction along with anemia and thrombocytopenia, low ADAMTS13 activity, and the presence of ULVWF. The standard treatment of TTP includes plasma exchange, protein A immunoabsobtion, immunosuppressive drugs, CD20 antibodies against B cells, and splenectomy. HUS is commonly caused by infection with Shiga-toxin produced by Escherichia coli. HUS is characterized by thrombocytopenia, anemia, renal impairment and diarrhea. Rarely, atypical HUS appears as a consequence of mutations related to the alternative pathway for the compliment system. Plasmapheresis in HUS is not efficient. Alternatively, plasma therapy and in some cases dialysis are used. TMA diseases may be associated with other infections, bone marrow transplantation, pregnancy, systemic vasculitis, and certain drugs.

  18. 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.

  19. Genetics Home Reference: thrombotic thrombocytopenic purpura

    MedlinePlus

    ... purpura also results from a reduction in ADAMTS13 enzyme activity; however, people with the acquired form do not ... activity of the enzyme. A lack of ADAMTS13 enzyme activity disrupts the usual balance between bleeding and clotting. ...

  20. 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

  1. Thrombotic thrombocytopenic purpura: three peripartum cases and diagnostic challenges.

    PubMed

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

    2013-01-01

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

  2. Thrombotic thrombocytopenic purpura: a syndrome of intravascular platelet consumption.

    PubMed Central

    Neame, P. B.; Hirsh, J.; Browman, G.; Denburg, J.; D'Souza, T. J.; Gallus, A.; Brain, M. C.

    1976-01-01

    In four of five patients with thrombotic thrombocytopenic purpura (TTP) in whom serial tests of hemostatic function were performed, severe thrombocytopenia, normal plasma fibrinogen concentrations and mildly increased concentrations of fibrinogen/fibrin degradation products were observed. Widespread platelet thrombi were found in arterioles and capillaries. Fibrin could be seen around some of the platelet clumps and was the main component in a small number of the thrombi in two patients. The observations show that TTP is a disorder in which intravascular platelet consumption results in disseminated platelet thrombosis. The coagulation system is apparently activated secondarily to platelet aggregation and variable quantities of fibrin are incorporated into the thrombi. Clinical improvement resulted from combined therapy with corticosteroids, heparin and drugs that suppress platelet function. Images FIG. 3 FIG. 4 FIG. 5 FIG. 6 PMID:1084215

  3. Thrombotic Thrombocytopenic Purpura: Three Peripartum Cases and Diagnostic Challenges

    PubMed Central

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

    2013-01-01

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

  4. 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.

  5. Successful treatment of an elderly frail patient with acquired idiopathic thrombotic thrombocytopenic purpura under close monitoring of ADAMTS13 activity and anti-ADAMTS13 antibody titers.

    PubMed

    Sano, Keigo; Yagi, Hideo; Hanamoto, Hitoshi; Fujita, Mariko; Iizuka, Takashi; Yamazaki, Keiko; Tsubaki, Kazuo

    2014-04-01

    A 68-year-old woman was admitted to the regional hospital because of hemolytic anemia, thrombocytopenia, and neurological abnormalities including unconsciousness. One week before admission, she suffered from diarrhea and subsequently passed out and hit her face on the ground. She was suspected of having TTP and was transferred to our hospital. We performed the assays of ADAMTS13 activity and anti-ADAMTS13 antibody titers, and confirmed the diagnosis of acquired idiopathic TTP with total deficiency of ADAMTS13 activity with its inhibitor. She was initially treated with plasma exchange combined with corticosteroids, however, we were forced to substitute plasma exchange with fresh frozen plasma infusion due to procedure-associated complications. The infusion of fresh frozen plasma was known as less effective and more likely to boost inhibitor titers compared to plasma exchange. In this circumstance, we could successfully switch the plasma therapy under close monitoring of ADAMTS13 activity and anti-ADAMTS13 antibody titers which precisely revealed the disease status of TTP in our patient, and eventually she achieved complete remission with normal level of ADAMTS13 activity and no inhibitor. Our experience suggested that the measurement of ADAMTS13 activity and inhibitor titer might be valuable not only for making the diagnosis but also for guiding treatment decisions by precise evaluating of disease status in patients with the acquired form of TTP.

  6. [A case of thrombotic thrombocytopenic purpura with systemic lupus erythematosus].

    PubMed

    Ogawa, Yayoi; Mukai, Masaya; Gotoh, Hideki; Tanaka, Satoshi; Takada, Akio; Takenouchi, Toshinao

    2006-10-01

    We described a case of thrombotic thrombocytopenic purpura (TTP) with systemic lupus erythematosus (SLE). A-60-year old woman was admitted to our hospital because of fever, disconsciousness, and general fatigue. 32 years ago, she was diagnosed as SLE with Raynaud's phenomenon, rash, photosensitivity, arthritis, lymphocytopenia, and ANA. Her SLE was well controlled with 10 mg predonisolone as a maintance dose until several weeks ago. On admission, severe thrombocytopenia (0.7x10(4)/microl) and other laboratory data revealed microangiopathic hemolytic anemia and renal dysfunction, Immediately after diagnosed as TTP, plasma exchange and corticosteroid therapy started. In spite of the treatment, disconsciousness progressed and systemic convulsion occurred and died 4 days after admission. Autopsied examination revealed diffuse microvascular hyalinized thrombi in heart, kidney, liver, spleen, and pancreas. Some microvascular thrombi were detected in lymph nodes, bone marrow, intestine. Pathological diagnosis of TTP was made on microvascular hyalinized platelet thrombi in organs. Von Willebrand factor-cleaving protease (VWF-CP) activity in plasma on set is less than 0.5 percent of normal and inhibitor for VWF-CP was detected. We here report a valuable case for analysis of pathogenesis in SLE-TTP.

  7. Thrombotic thrombocytopenic purpura: from platelet aggregates to plasma.

    PubMed

    Marques, Marisa B; Mayfield, Charles A; Blackall, Douglas P

    2004-06-01

    Thrombotic thrombocytopenic purpura (TTP) is a syndrome of severe thrombocytopenia and microangiopathic hemolytic anemia without an alternative explanation. Although some patients also have a combination of fever and neurologic and/or renal manifestations, these are not required for the diagnosis. Thus, plasmapheresis should start as soon as TTP is placed high in the differential diagnosis to prevent significant mortality. Histopathologically, TTP is characterized by widespread platelet thrombi in the microcirculation. Ultralarge von Willebrand factor (vWf) multimers found in the patient's plasma are the basis for the platelet thrombi. Recent evidence has linked the abnormal fragments of vWf with deficiency of a plasma enzyme named vWf-cleaving protease, or ADAMTS-13. While a small percentage of patients with TTP have a constitutional defect in this enzyme, many with the acute idiopathic form have an antibody to ADAMTS-13, affecting its ability to cleave vWf. The determination of the enzyme activity and the presence of its inhibitor have emerged as a potential tool in the diagnosis and prognosis of TTP. Furthermore, it helps to differentiate TTP from the hemolytic uremic syndrome, in which the level of ADAMTS-13 is expected to be normal or only slightly decreased.

  8. Platelet-delivered ADAMTS13 inhibits arterial thrombosis and prevents thrombotic thrombocytopenic purpura in murine models.

    PubMed

    Pickens, Brandy; Mao, Yingying; Li, Dengju; Siegel, Don L; Poncz, Mortimer; Cines, Douglas B; Zheng, X Long

    2015-05-21

    ADAMTS13 metalloprotease cleaves von Willebrand factor (VWF), thereby inhibiting platelet aggregation and arterial thrombosis. An inability to cleave ultralarge VWF resulting from hereditary or acquired deficiency of plasma ADAMTS13 activity leads to a potentially fatal syndrome, thrombotic thrombocytopenic purpura (TTP). Plasma exchange is the most effective initial therapy for TTP to date. Here, we report characterization of transgenic mice expressing recombinant human ADAMTS13 (rADAMTS13) in platelets and its efficacy in inhibiting arterial thrombosis and preventing hereditary and acquired antibody-mediated TTP in murine models. Western blotting and fluorescent resonance energy transfer assay detect full-length rADAMTS13 protein and its proteolytic activity, respectively, in transgenic (Adamts13(-/-)Plt(A13)), but not in wild-type and Adamts13(-/-), platelets. The expressed rADAMTS13 is released on stimulation with thrombin and collagen, but less with 2MesADP. Platelet-delivered rADAMTS13 is able to inhibit arterial thrombosis after vascular injury and prevent the onset and progression of Shigatoxin-2 or recombinant murine VWF-induced TTP syndrome in mice despite a lack of plasma ADAMTS13 activity resulting from the ADAMTS13 gene deletion or the antibody-mediated inhibition of plasma ADAMTS13 activity. These findings provide a proof of concept that platelet-delivered ADAMTS13 may be explored as a novel treatment of arterial thrombotic disorders, including hereditary and acquired TTP, in the presence of anti-ADAMTS13 autoantibodies.

  9. Risk Factors for Autoimmune Diseases Development After Thrombotic Thrombocytopenic Purpura.

    PubMed

    Roriz, Mélanie; Landais, Mickael; Desprez, Jonathan; Barbet, Christelle; Azoulay, Elie; Galicier, Lionel; Wynckel, Alain; Baudel, Jean-Luc; Provôt, François; Pène, Frédéric; Mira, Jean-Paul; Presne, Claire; Poullin, Pascale; Delmas, Yahsou; Kanouni, Tarik; Seguin, Amélie; Mousson, Christiane; Servais, Aude; Bordessoule, Dominique; Perez, Pierre; Chauveau, Dominique; Veyradier, Agnès; Halimi, Jean-Michel; Hamidou, Mohamed; Coppo, Paul

    2015-10-01

    Autoimmune thrombotic thrombocytopenic purpura (TTP) can be associated with other autoimmune disorders, but their prevalence following autoimmune TTP remains unknown. To assess the prevalence of autoimmune disorders associated with TTP and to determine risk factors for and the time course of the development of an autoimmune disorder after a TTP episode, we performed a cross sectional study. Two-hundred sixty-one cases of autoimmune TTP were included in the French Reference Center registry between October, 2000 and May, 2009. Clinical and laboratory data available at time of TTP diagnosis were recovered. Each center was contacted to collect the more recent data and diagnosis criteria for autoimmunity. Fifty-six patients presented an autoimmune disorder in association with TTP, 9 years before TTP (median; min: 2 yr, max: 32 yr) (26 cases), at the time of TTP diagnosis (17 cases) or during follow-up (17 cases), up to 12 years after TTP diagnosis (mean, 22 mo). The most frequent autoimmune disorder reported was systemic lupus erythematosus (SLE) (26 cases) and Sjögren syndrome (8 cases). The presence of additional autoimmune disorders had no impact on outcomes of an acute TTP or the occurrence of relapse. Two factors evaluated at TTP diagnosis were significantly associated with the development of an autoimmune disorder during follow-up: the presence of antidouble stranded (ds)DNA antibodies (hazard ratio (HR): 4.98; 95% confidence interval (CI) [1.64-15.14]) and anti-SSA antibodies (HR: 9.98; 95% CI [3.59-27.76]). A follow-up across many years is necessary after an acute TTP, especially when anti-SSA or anti-dsDNA antibodies are present on TTP diagnosis, to detect autoimmune disorders early before immunologic events spread to prevent disabling complications.

  10. Risk Factors for Autoimmune Diseases Development After Thrombotic Thrombocytopenic Purpura

    PubMed Central

    Roriz, Mélanie; Landais, Mickael; Desprez, Jonathan; Barbet, Christelle; Azoulay, Elie; Galicier, Lionel; Wynckel, Alain; Baudel, Jean-Luc; Provôt, François; Pène, Frédéric; Mira, Jean-Paul; Presne, Claire; Poullin, Pascale; Delmas, Yahsou; Kanouni, Tarik; Seguin, Amélie; Mousson, Christiane; Servais, Aude; Bordessoule, Dominique; Perez, Pierre; Chauveau, Dominique; Veyradier, Agnès; Halimi, Jean-Michel; Hamidou, Mohamed; Coppo, Paul

    2015-01-01

    Abstract Autoimmune thrombotic thrombocytopenic purpura (TTP) can be associated with other autoimmune disorders, but their prevalence following autoimmune TTP remains unknown. To assess the prevalence of autoimmune disorders associated with TTP and to determine risk factors for and the time course of the development of an autoimmune disorder after a TTP episode, we performed a cross sectional study. Two-hundred sixty-one cases of autoimmune TTP were included in the French Reference Center registry between October, 2000 and May, 2009. Clinical and laboratory data available at time of TTP diagnosis were recovered. Each center was contacted to collect the more recent data and diagnosis criteria for autoimmunity. Fifty-six patients presented an autoimmune disorder in association with TTP, 9 years before TTP (median; min: 2 yr, max: 32 yr) (26 cases), at the time of TTP diagnosis (17 cases) or during follow-up (17 cases), up to 12 years after TTP diagnosis (mean, 22 mo). The most frequent autoimmune disorder reported was systemic lupus erythematosus (SLE) (26 cases) and Sjögren syndrome (8 cases). The presence of additional autoimmune disorders had no impact on outcomes of an acute TTP or the occurrence of relapse. Two factors evaluated at TTP diagnosis were significantly associated with the development of an autoimmune disorder during follow-up: the presence of antidouble stranded (ds)DNA antibodies (hazard ratio (HR): 4.98; 95% confidence interval (CI) [1.64–15.14]) and anti-SSA antibodies (HR: 9.98; 95% CI [3.59–27.76]). A follow-up across many years is necessary after an acute TTP, especially when anti-SSA or anti-dsDNA antibodies are present on TTP diagnosis, to detect autoimmune disorders early before immunologic events spread to prevent disabling complications. PMID:26496263

  11. Takotsubo cardiomyopathy and thrombotic thrombocytopenic purpura preceding a lupus diagnosis: a case report.

    PubMed

    Georgiades, F; Demosthenous, S; Braimi, M; Tsitskari, T; Psarelis, S

    2015-11-01

    Takotsubo cardiomyopathy, a rare stress-related cardiomyopathy, has been observed in a few cases secondary to systemic lupus erythematosus (SLE). Herein, we report an unusual case where a postmenopausal woman presented initially with Takotsubo syndrome, later developed thrombotic thrombocytopenic purpura and cerebrovascular events, initially without clinical or laboratory features of SLE. During the course of her illness, she was found to satisfy four of the Systemic Lupus International Collaborating Clinics classification criteria for a SLE diagnosis. This unique presentation of our patient, initially with Takotsubo cardiomyopathy, the development of thrombotic thrombocytopenic purpura and cerebrovascular events preceding the diagnosis of SLE illustrates the importance of clinical observation and follow-up.

  12. 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

  13. Interactions of von Willebrand factor and ADAMTS13 in von Willebrand disease and thrombotic thrombocytopenic purpura.

    PubMed

    Budde, U; Schneppenheim, R

    2014-01-01

    The function of von Willebrand factor (VWF), a huge multimeric protein and a key factor in platelet dependent primary haemostasis, is regulated by its specific protease ADAMTS13. The ADAMTS13 dependent degradation of VWF to its proteolytic fragments can be visualized as a characteristic so-called triplet structure of individual VWF oligomers by multimer analysis. Lack of VWF high molecular weight multimers (VWF-HMWM) or their pathologically enhanced degradation underlies a particular type of von Willebrand disease, VWD type 2A with a significant bleeding tendency, and may also be observed in acquired von Willebrand syndrome due to cardiovascular disease. In these conditions multimer analysis is an obligatory and powerful tool for diagnosis of VWD. The opposite condition, the persistence of ultralarge VWF (UL-VWF) multimers may cause the microangiopathic life-threatening disorder thrombotic thrombocytopenic purpura (TTP). During the course of active TTP, UL-VWF is consumed in the hyaline thrombi formed in the microvasculature which will ultimately result in the loss of UL-VWF and VWF-HMWM. Therefore, VWF multimer analysis is not a valid tool to diagnose TTP in the active phase of disease but may be helpful for the diagnosis of TTP patients in remission.

  14. 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

  15. ADAMTS13 and anti-ADAMTS13 autoantibodies in thrombotic thrombocytopenic purpura - current perspectives and new treatment strategies.

    PubMed

    Tersteeg, Claudia; Verhenne, Sebastien; Roose, Elien; Schelpe, An-Sofie; Deckmyn, Hans; De Meyer, Simon F; Vanhoorelbeke, Karen

    2016-01-01

    A deficiency in ADAMTS13 (A Disintegrin And Metalloprotease with ThromboSpondin type-1 repeats, member 13) is associated with thrombotic thrombocytopenic purpura (TTP). Congenital TTP is caused by a defect in the ADAMTS13 gene resulting in decreased or absent enzyme activity; acquired TTP results from autoantibodies that either inhibit the activity or increase the clearance of ADAMTS13. Despite major progress in recent years in our understanding of the disease, many aspects around the pathophysiology of TTP are still unclear. Newer studies expanded the TTP field from ADAMTS13 and inhibitory antibodies to immune complexes, cloned autoantibodies, and a possible involvement of other proteases. Additionally, several new treatment strategies supplementing plasma-exchange and infusion are under investigation for a better and more specific treatment of TTP patients. In this review, we discuss the recent insights in TTP pathophysiology and describe upcoming therapeutic opportunities.

  16. Thrombotic thrombocytopenic purpura associated with metastatic gastric adenocarcinoma: successful management with plasmapheresis.

    PubMed

    Carr, D J; Kramer, B S; Dragonetti, D E

    1986-04-01

    A patient with metastatic gastric adenocarcinoma had progressive microangiopathic red blood cell changes, thrombocytopenia with increased marrow megakaryocytes, bleeding, altered mentation, and seizure. Coagulation parameters were inconsistent with disseminated intravascular coagulation; a clinical diagnosis of thrombotic thrombocytopenic purpura (TTP) was made. Plasmapheresis resulted in improvement on two separate occasions. The diagnosis of tumor-associated TTP should be considered in cancer patients. Plasmapheresis may be more effective than plasma transfusion alone in this syndrome, perhaps via removal of tumor-induced immune complexes from the circulation. Aggressive management of this complication seems justified in cancer patients for whom effective chemotherapy exists.

  17. Stroke due to typical thrombotic thrombocytopenic purpura treated successfully with intravenous thrombolysis and therapeutic plasma exchange

    PubMed Central

    Boattini, Matteo; Procaccianti, Gaetano

    2013-01-01

    We report a case of a 39-year-old man with expressive aphasia due to occlusion of the temporal stem of the left middle cerebral artery. Laboratory tests showed microangiopathic haemolytic anaemia and thrombocytopenia. A thrombotic thrombocytopenic purpura (TTP) was diagnosed, and thrombolytic therapy (TT) with alteplase followed by therapeutic plasma exchange (TPE) were performed with complete resolution of symptoms. The gold standard TTP treatment is TPE, and its delay can be lethal. The use of TT in TTP is controversial and has potential risks. This case shows a successful TT in a patient with typical TTP presenting as a stroke due to a large cerebral artery occlusion. PMID:23362068

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

    PubMed

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

    2013-11-01

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

  19. [Treatment of a pregnant patient after multiple trauma: rare combination with thrombotic thrombocytopenic purpura].

    PubMed

    Haffner, E; Pietsch, U; Fösel, T; Lindemann, W

    2013-02-01

    Multiple trauma during pregnancy is a relatively rare situation which poses a great challenge for the team in charge of treatment. A concomitant disease, such as thrombotic thrombocytopenic purpura (TTP) with thrombocytic coagulopathy increases the complexity of the treatment problems. This article describes the case of a 36-year-old pregnant woman referred to this hospital suffering from multiple trauma with severe liver rupture. Stabilization was achieved after an emergency Caesarean section and packing of the liver. Recurrent massive bleeding from the liver occurred after depacking and was treated successfully with recombinant factor VIIa. The concomitant TTP was treated by transfusion of fresh frozen plasma and corticosteroids. Rapid initiation of therapy was the goal to achieve hemostasis and prevent aggravation of the coagulation disorder and an unfavourable outcome despite severe thrombocytopenia.

  20. 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.

  1. Eculizumab refractory thrombotic thrombocytopenic purpura secondary to post-endoscopic retrograde cholangiopancreatography pancreatitis in a patient

    PubMed Central

    Malik, Faizan; Ali, Naveed; Ahsan, Irfan; Ghani, Ali Raza; Fidler, Christian

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a rare multisystem microvascular disorder, which is characterized by pentad of thrombocytopenia, microangiopathic hemolytic anemia, and organ dysfunction due to occlusive thrombi. The proposed pathophysiology involves an imbalance between unusually large von Willebrand factor multimers and the cleaving protease ADAMTS13. Acute pancreatitis is a well-described consequence of TTP, but TTP secondary to acute pancreatitis is a rare phenomenon. We present a patient who developed TTP due to post-ERCP pancreatitis with hematologic, cardiovascular, pulmonary, and renal complications and is the first case of this kind. Despite early initiation of therapy, the patient did not recover making it among the 10% of cases of TTP that prove fatal despite appropriate therapy. PMID:27987277

  2. The splenic autoimmune response to ADAMTS13 in thrombotic thrombocytopenic purpura contains recurrent antigen-binding CDR3 motifs.

    PubMed

    Schaller, Monica; Vogel, Monique; Kentouche, Karim; Lämmle, Bernhard; Kremer Hovinga, Johanna A

    2014-11-27

    Acquired thrombotic thrombocytopenic purpura (TTP) is the consequence of a severe ADAMTS13 deficiency resulting from autoantibodies inhibiting ADAMTS13 or accelerating its clearance. Despite the success of plasma exchange the risk of relapse is high. From 2 patients (A and B), splenectomized for recurrent episodes of acquired TTP, the splenic B-cell response against ADAMTS13 was characterized through generation of human monoclonal anti-ADAMTS13 autoantibodies (mAbs) by cloning an immunoglobulin G (IgG)4κ- and IgG4λ-Fab library using phage display technology and by Epstein-Barr virus transformation of switched memory B cells (CD19+/CD27+/IgG+). Sequence analysis of the anti-ADAMTS13 IgGs of both patients revealed that the VH gene use was limited in our patients to VH1-3 (55%), VH1-69 (17%), VH3-30 (7%), and VH4-28 (21%) and contained 8 unique and thus far not reported heavy-chain complementarity determining region 3 motifs, of which 4 were shared by the 2 patients. The discovery of several highly similar anti-ADAMTS13 autoantibodies in 2 unrelated TTP patients suggests that the autoimmune response is antigen driven, because the probability that such similar immunoglobulin rearrangements happen by chance is very low (< 10(-9)).

  3. Congenital thrombotic thrombocytopenic purpura caused by new compound heterozygous mutations of the ADAMTS13 gene.

    PubMed

    Rank, Cecilie Utke; Kremer Hovinga, Johanna; Taleghani, Magnus Mansouri; Lämmle, Bernhard; Gøtze, Jens Peter; Nielsen, Ove Juul

    2014-02-01

    Upshaw-Schulman syndrome (USS) is due to severe congenital deficiency of von Willebrand factor (VWF)-cleaving protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 domains, nr 13) activity resulting in the presence of unusually large forms of VWF in the circulation, causing intravascular platelet clumping and thrombotic microangiopathy. Our patient, a 26-year-old man, had attacks of thrombotic thrombocytopenic purpura (TTP) with thrombocytopenia and a urine dipstick positive for hemoglobin (4+), often as the only sign of hemolytic activity. He had ADAMTS13 activity of <1% of normal plasma without the presence of inhibitors of ADAMTS13. ADAMTS13 deficiency was caused by two new mutations of the ADAMTS13 gene: a deletion of a single nucleotide in exon17 (c. 2042 delA) leading to a frameshift (K681C fs X16), and a missense mutation in exon 25 (c.3368G>A) leading to p.R1123H. This case report confirms the importance of the analysis of the ADAMTS13 activity and its inhibitor in patients who have episodes of TTP, with a very low platelet count and sometimes without the classic biochemical signs of hemolysis.

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

    PubMed

    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.

  5. 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

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

    PubMed Central

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

    2013-01-01

    Background Thrombotic thrombocytopenic purpura is a rare, life-threatening disease characterised by microangiopathic haemolytic anaemia, thrombocytopenia and symptoms related to organ ischaemia, mainly involving the brain and the kidney. It is associated with a deficiency of ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor. The congenital form (Upshaw-Schulman syndrome) is rare and is associated with mutations of the ADAMTS13 gene on chromosome 9q34. The clinical symptoms of congenital thrombotic thrombocytopenic purpura are variable, with some patients developing their first episode during the neonatal period or childhood and others becoming symptomatic in adulthood. Materials and methods We describe a case of thrombotic thrombocytopenic purpura, who presented to our attention with a relapsing form of the disease: the first episode occurred at the age of 13 months. Phenotype and genotype tests were performed in the patient and his family. Results The undetectable level of ADAMTS13 in the patient was caused by two novel heterozygote missense mutations on the ADAMTS13 gene: one mutation is c.788C > T (p.Ser263Phe) on exon 7 and the second is c.3251G > A (p.Cys1084Tyr) on exon 25 of the ADAMTS13 gene. All the relatives who have been investigated were found to carry one of these missense mutations in a heterozygous state. Discussion Although Upshaw-Schulman syndrome is a rare disease, it should be considered in all children with thrombocytopenia and jaundice in the neonatal period. In fact, once a child is confirmed to carry mutations of the ADAMTS13 gene causing early thrombotic thrombocytopenic purpura, prophylactic treatment should be started to avoid recurrence of symptoms. Genotype tests of relatives would also be important for those women in the family who could be carriers of ADAMTS13 mutations, particularly during pregnancy. PMID:23058857

  7. Two Types of Renovascular Lesions in Lupus Nephritis with Clinical Thrombotic Thrombocytopenic Purpura.

    PubMed

    Sekine, Akinari; Hasegawa, Eiko; Hiramatsu, Rikako; Mise, Koki; Sumida, Keiichi; Ueno, Toshiharu; Yamanouchi, Masayuki; Hayami, Noriko; Suwabe, Tatsuya; Hoshino, Junichi; Sawa, Naoki; Takaichi, Kenmei; Ohashi, Kenichi; Fujii, Takeshi; Ubara, Yoshifumi

    2015-01-01

    Renovascular lesions of lupus nephritis (LN) were classified into five categories by D'Agati in Heptinstall's Pathology of the Kidney, with thrombotic microangiopathy (TMA) and clinical thrombotic thrombocytopenic purpura (TTP) being combined. We encountered 2 cases with histological LN (class III and lass V), and they presented with clinical features of TTP, such as acute renal failure, microangiopathic hemolytic anemia, thrombocytopenia, fever, and central neurologic symptoms. Immunosuppressive therapy with plasmapheresis was performed in both patients. Case 1 progressed to end-stage renal failure requiring dialysis and died, while case 2 responded to treatment. In case 1, small renal arteries showed positive mural staining for IgG and C3, while intraluminal material was negative for IgG and C3 [although it was positive for phosphotungstic acid-hematoxylin (PTAH), indicating fibrin deposition]. In case 2, small renal arteries showed mural staining for IgG, C1q, and C3, with the intraluminal material also being positive for these immunoglobulins, but negative for PTAH. These cases suggest that immunosuppressive therapy with plasmapheresis can control LN when intravascular thrombosis is related to immune complexes associated with activation of the early complement components C1q and C3. In contrast, immunosuppressive therapy with plasmapheresis may not be effective when intravascular thrombosis is unrelated to these factors and involves fibrin deposition. Accordingly, in LN patients with clinical features of TTP, we report two types of renovascular lesions, in addition to typical vascular change of TMA with no immune deposits seen in nonlupus patients.

  8. Thrombotic thrombocytopenic purpura misdiagnosed as autoimmune cytopenia: Causes of diagnostic errors and consequence on outcome. Experience of the French thrombotic microangiopathies reference centre.

    PubMed

    Grall, Maximilien; Azoulay, Elie; Galicier, Lionel; Provôt, François; Wynckel, Alain; Poullin, Pascale; Grange, Steven; Halimi, Jean-Michel; Lautrette, Alexandre; Delmas, Yahsou; Presne, Claire; Hamidou, Mohamed; Girault, Stéphane; Pène, Frédéric; Perez, Pierre; Kanouni, Tarik; Seguin, Amélie; Mousson, Christiane; Chauveau, Dominique; Ojeda-Uribe, Mario; Barbay, Virginie; Veyradier, Agnès; Coppo, Paul; Benhamou, Ygal

    2017-04-01

    Thrombotic thrombocytopenic purpura (TTP) has a devastating prognosis without adapted management. Sources of misdiagnosis need to be identified to avoid delayed treatment. We studied 84 patients with a final diagnosis of severe (<10%) acquired ADAMTS13 deficiency-associated TTP from our National database that included 423 patients, who had an initial misdiagnosis (20% of all TTP). Main diagnostic errors were attributed to autoimmune thrombocytopenia, associated (51%) or not (37%) with autoimmune hemolytic anemia. At admission, misdiagnosed patients were more frequently females (P = .034) with a history of autoimmune disorder (P = .017) and had organ involvement in 67% of cases; they had more frequently antinuclear antibodies (P = .035), a low/undetectable schistocyte count (P = .001), a less profound anemia (P = .008), and a positive direct antiglobulin test (DAT) (P = .008). In multivariate analysis, female gender (P = .022), hemoglobin level (P = .028), a positive DAT (P = .004), and a low schistocytes count on diagnosis (P < .001) were retained as risk factors of misdiagnosis. Platelet count recovery was significantly longer in the misdiagnosed group (P = .041) without consequence on mortality, exacerbation and relapse. However, patients in the misdiagnosed group had a less severe disease than those in the accurately diagnosed group, as evidenced by less organ involvement at TTP diagnosis (P = .006). TTP is frequently misdiagnosed with autoimmune cytopenias. A low schistocyte count and a positive DAT should not systematically rule out TTP, especially when associated with organ failure.

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

    PubMed

    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.

  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. Pregnancy-associated thrombotic thrombocytopenic purpura with anti-centromere antibody-positive Raynaud's syndrome.

    PubMed

    Watanabe, Ryu; Shirai, Tsuyoshi; Tajima, Yumi; Ohguchi, Hiroto; Onishi, Yasushi; Fujii, Hiroshi; Takasawa, Naruhiko; Ishii, Tomonori; Harigae, Hideo

    2010-01-01

    Thrombotic thrombocytopenic purpura (TTP), scleroderma renal crisis (SRC), and hemolysis, elevated liver enzyme levels, and a low platelet count (HELLP) syndrome display common symptoms that include microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. Therefore, it is important to distinguish between them because their treatments vary: however, the differential diagnosis is sometimes difficult. We report a 32-year-old woman who was referred to our department for further examination of microangiopathic hemolytic anemia, thrombocytopenia, and a slightly elevated serum creatinine level with anti-centromere antibody-positive Raynaud's syndrome in the early puerperal period. TTP, SRC, and HELLP syndrome were considered in the differential diagnosis, but the measurement of a disintegrin-like metalloprotease with thrombospondin type 1 motifs 13 (ADAMTS 13) activity and its inhibitor level led to the diagnosis of TTP. She was successfully treated by plasma exchange and high-dose prednisolone and angiotensin-converting enzyme inhibitor. If microangiopathic hemolytic anemia and thrombocytopenia are observed in perinatal women or patients with signs of systemic sclerosis, the measurement of ADAMTS13 activity and its inhibitor level are essential for diagnosis and therapeutic choice.

  12. Diffuse alveolar hemorrhage associated with thrombotic thrombocytopenic purpura after allogeneic bone marrow transplantation.

    PubMed

    Kalayoğlu Beşışık, Sevgi; Yenerel, Mustafa; Diz Küçükkaya, Reyhan; Çalışkan, Yaşar; Sargın, Deniz

    2004-12-05

    Alveolar hemorrhage is an early complication after bone marrow transplantation (BMT) and often associated with inflammatory pulmonary processes. We present a case of diffuse alveolar hemorrhage associated with BMT associated thrombotic thrombocytopenic purpura (BMT-TTP). An 18-years-old man with acute myeloid leukaemia (FAB; M5) underwent ABO incompatible BMT from his HLA-identical sister. On the 37th day of BMT, BMT-TTP was diagnosed with the occurrence of red cell fragmentation and rise in serum lactic dehydrogenase (LDH) level with severe sudden decrease in hemoglobin and platelet levels. Cyclosporine A (CsA) was ceased and plasma infusion with plasma exchange was started. On the 42nd day of BMT, the diagnosis of diffuse alveolar hemorrhage was made by the clinical, bronchoscopic and bronchoalveolar lavage fluid findings. Alveolar hemorrhage among patients with BMT-TTP has been scarce reported. These two complications may be regarded as related, as small vessel injury is a central feature in both and they may share aetiological and pathogenetic factors.

  13. 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.

  14. Renal thrombotic microangiopathies/thrombotic thrombocytopenic purpura in a patient with primary Sjögren's syndrome complicated with IgM monoclonal gammopathy of undetermined significance.

    PubMed

    Koga, Tomohiro; Yamasaki, Satoshi; Nakamura, Hideki; Kawakami, Atsushi; Furusu, Akira; Taguchi, Takashi; Eguchi, Katsumi

    2013-01-01

    Thrombotic microangiopathy (TMA)/thrombotic thrombocytopenic purpura (TTP) is a rare but potentially lethal condition requiring rapid recognition, diagnosis, and initiation of therapy. We experienced a case of a 61-year-old woman with primary Sjögren's syndrome (pSS) complicated with severe renal TMA/TTP following IgM monoclonal gammopathy of undetermined significance (MGUS). She was admitted to our hospital for further evaluation of hypergammaglobulinema, acute renal failure, and severe thrombocytopenia. She had been diagnosed with pSS 13 years prior to admission. Histological examination of her kidney revealed fibrin thrombi in the glomeruli and arterioles, a finding that is consistent with TMA/TTP. The patient was subsequently treated with plasma exchange, which resulted in a successful outcome without any complications. This rare case suggests that it is important to make a therapeutic decision based on appropriate and prompt pathological diagnosis.

  15. Splenectomy: Does it still play a role in the management of thrombotic thrombocytopenic purpura?

    PubMed Central

    Dubois, Luc; Gray, Daryl K.

    2010-01-01

    Background Plasma exchange is first-line therapy for patients with thrombotic thrombocytopenic purpura (TTP). Splenectomy is often indicated for patients with relapsing or refractory disease. Concerns exist about its efficacy and safety in these patients. We describe a series of patients whose TTP was treated with laparoscopic splenectomy. We also reviewed the literature in order to describe the use and safety of splenectomy for refractory or relapsing TTP. Methods We reviewed the charts of consecutive patients with TTP referred for splenectomy and searched MEDLINE for studies describing outcomes following splenectomy for relapsing or refractory TTP. Results In all, 5 patients were referred for relapsing TTP and underwent uneventful laparoscopic splenectomy. All 5 were in remission after more than 40 months of follow-up. We found 18 studies (87 patients) reporting the results of splenectomy for relapsing TTP and 15 studies (74 patients) involving patients who underwent splenectomy for refractory TTP. The aggregate complication (6% v. 10%) and mortality rates (1.2% v. 5%) were lower for patients who received treatment for relapsing versus refractory TTP. The rate of postsplenectomy relapse among patients with relapsing disease was 17%, whereas the nonresponse rate was 8% for patients with refractory TTP. There were no complications among the 22 laparoscopic cases reported. Conclusion Although the data supporting splenectomy for treatment of TTP are limited to case series with no control groups, they suggest that splenectomy is an option for patients with refractory or relapsing disease. When performed laparoscopically in patients with relapsing disease, splenectomy is associated with minimal morbidity and mortality. PMID:20858382

  16. Opana ER abuse and thrombotic thrombocytopenic purpura (TTP)-like illness: a rising risk factor in illicit drug users.

    PubMed

    Kapila, Aaysha; Chhabra, Lovely; Chaubey, Vinod K; Summers, Jeffery

    2014-03-03

    We report the case of a 22 year-old-woman who presented with upper extremity cellulitis secondary to an infiltration of illicit intravenous drug use. She confessed to the intravenous use of Opana ER (an extended release oral formulation of oxymorphone) which is an opioid drug approved only for oral use. She was found to have clinical evidence of profound thrombotic microangiopathy which resulted due to the intravenous use of Opana ER. She showed full clinical improvement after withholding drug and supportive clinical care. Recent report of Opana ER intravenous abuse was published from Tennessee county and has now been increasingly recognised as one of the causes of thrombocytopenia which mimicks clinically as thrombotic thrombocytopenic purpura. Physicians should be aware of this association as the lack of familiarity to this can pose serious management dilemmas for our patients (especially the polysubstance abusers).

  17. Adult-onset congenital thrombotic thrombocytopenic purpura caused by a novel compound heterozygous mutation of the ADAMTS13 gene.

    PubMed

    Krabbe, Johannes G; Kemna, Evelien W M; Strunk, Annuska L M; Jobse, Pieter A; Kramer, P A; Dikkeschei, L D; van den Heuvel, L P W J; Fijnheer, Rob; Verdonck, Leo F

    2015-10-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease, characterized by microangiopathic hemolytic anaemia and thrombocytopenia, resulting in neurologic and/or renal abnormalities. We report a 49-year-old patient with a history of thrombotic events, renal failure, and thrombocytopenia. Blood analysis demonstrated no ADAMTS13 activity in the absence of antibodies against ADAMTS13. The complete ADAMTS13 gene was sequenced, and two mutations were identified: one mutation on exon 24 (Arg1060Asp), which had previously been described, and a mutation on exon 27 (Met1260IlefsX34), which has not been reported. For these mutations, compound heterozygosity appears to be necessary to cause TTP, as family members of the patient display only one of the mutations and all displayed normal ADAMTS13 activity.

  18. Thrombotic Thrombocytopenic Purpura with Reversible Neurological Features: Brain Diffusion MRI with ADC Map, Spect and EEG Findings. A Case Report.

    PubMed

    Yerdelen, D; Göksel, B K; Yıldırım, T; Karataş, M; Karaca, S; Reyhan, M; Ozdoğu, H

    2006-11-30

    Although nervous system involvement is common in thrombotic thrombocytopenic purpura (TTP), abnormalities on computerized tomography, magnetic resonance imaging and electroencephalography are not encountered so frequently and if present, these abnormalities are often reversible. We describe a 39-year-old woman with recurring transient focal neurological findings found to have laboratory findings consistent with TTP. In cerebral diffusion weighted images (DWI), diffuse cortical hyperintensity was noted in right frontal lobe, but the ADC (apparent diffusion coefficient) map was normal. Electroencephalography demonstrated lateralized slowing and repeated DWI showed diffuse cortical hyperintensity in the right hemisphere. SPECT showed luxury perfusion in the right hemisphere areas. The patient's condition resolved with plasmapheresis. Our patient illustrates that diffuse hemispheric involvement can be seen in DWI and EEG, and SPECT may show luxury perfusion after resolution of neurological findings in TTP cases. To our knowledge, this is the first TTP case in which the ADC map was normal.

  19. Thrombotic thrombocytopenic purpura (TPP) successfully rescued by plasma exchange in the ICU: A report of two cases

    PubMed Central

    ZOU, XIULI; WU, TIEJUN; ZHANG, XIHONG; QU, AIJUN; TIAN, SUOCHEN

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disorder, which is characterized by thrombus formation in small blood vessels. The present study retrospectively analyzed the clinical data from two patients with severe TTP, who were treated successfully in the intensive care unit (ICU) at the Liaocheng People's Hospital in 2013. Comprehensive therapies were administered to the patients, including plasma exchange (PE), mechanical ventilation (case 1 only), steroid therapy, blood transfusion and anti-inflammatory treatment (case 2 only). The two patients returned to a stable state and were transferred back to the hematology department following PE. The positive outcome achieved for these patients suggests that early intervention involving bedside PE in the ICU may reduce the mortality rate of patients with severe TTP who have concurrent respiratory or circulatory failure and cannot be treated in the dialysis unit. PMID:27347058

  20. Efficacy of a rituximab regimen based on B cell depletion in thrombotic thrombocytopenic purpura with suboptimal response to standard treatment: Results of a phase II, multicenter noncomparative study.

    PubMed

    Benhamou, Ygal; Paintaud, Gilles; Azoulay, Elie; Poullin, Pascale; Galicier, Lionel; Desvignes, Céline; Baudel, Jean-Luc; Peltier, Julie; Mira, Jean-Paul; Pène, Frédéric; Presne, Claire; Saheb, Samir; Deligny, Christophe; Rousseau, Alexandra; Féger, Frédéric; Veyradier, Agnès; Coppo, Paul

    2016-12-01

    The standard four-rituximab infusions treatment in acquired thrombotic thrombocytopenic purpura (TTP) remains empirical. Peripheral B cell depletion is correlated with the decrease in serum concentrations of anti-ADAMTS13 and associated with clinical response. To assess the efficacy of a rituximab regimen based on B cell depletion, 24 TTP patients were enrolled in this prospective multicentre single arm phase II study and then compared to patients from a previous study. Patients with a suboptimal response to a plasma exchange-based regimen received two infusions of rituximab 375 mg m(-2) within 4 days, and a third dose at day +15 of the first infusion if peripheral B cells were still detectable. Primary endpoint was the assessment of the time required to platelet count recovery from the first plasma exchange. Three patients died after the first rituximab administration. In the remaining patients, the B cell-driven treatment hastened remission and ADAMTS13 activity recovery as a result of rapid anti-ADAMTS13 depletion in a similar manner to the standard four-rituximab infusions schedule. The 1-year relapse-free survival was also comparable between both groups. A rituximab regimen based on B cell depletion is feasible and provides comparable results than with the four-rituximab infusions schedule. This regimen could represent a new standard in TTP. This trial was registered at www.clinicaltrials.gov (NCT00907751). Am. J. Hematol. 91:1246-1251, 2016. © 2016 Wiley Periodicals, Inc.

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

    PubMed

    Karakus, Volkan; Deveci, Burak; Kurtoğlu, Erdal

    2013-06-01

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

  2. Idiopathic Relapsing Thrombotic Thrombocytopenic Purpura with Persistent ADAMTS13 Inhibitor Activity Treated Sequentially with Plasmapheresis, Rituximab, Cyclophosphamide and Splenectomy.

    PubMed

    Musa, Faisal; Baidas, Said

    2015-01-01

    We here describe a patient with an idiopathic thrombotic thrombocytopenic purpura (TTP) secondary to an ADAMTS13 inhibitor that continued to be dependent on plasmapheresis until the patient was treated with rituximab. TTP manifestations subsided with rituximab treatment in spite of a persistently low ADAMTS13 activity and continued a detectable inhibitor activity until the patient developed an intolerance to rituximab due to an allergic reaction when cyclophosphamide was added; this resulted in a normalization of ADAMTS13 activity and the disappearance of the inhibitor. Later, the patient developed an intolerance to rituximab due to a severe allergic reaction. Soon after stopping rituximab, the ADAMTS13 activity level dipped below 5% in addition to the appearance of the ADAMTS13 inhibitor. The patient had a splenectomy after rituximab and cyclophosphamide treatment; the medication was stopped based on several case reports of a complete remission of TTP after splenectomy. We believe that the reason TTP went into remission in our patient was because of rituximab treatment, in spite of both persistently low ADAMTS13 activity and a detectable inhibitor activity due to reducing the release of von Willebrand factor large multimers from the endothelial cells. We found that ADAMTS13 activity normalized and the inhibitor activity became undetectable when cyclophosphamide was added to rituximab. We suggest adding cyclophosphamide to rituximab for the treatment of patients with persistent ADAMTS13 inhibitors in order to prolong the remission period and lower the rate of relapse.

  3. Rituximab and intermediate-purity plasma-derived factor VIII concentrate (Koate®) as adjuncts to therapeutic plasma exchange for thrombotic thrombocytopenic purpura in patients with an ADAMTS13 inhibitor.

    PubMed

    Pandey, Soumya; Nakagawa, Mayumi; Rosenbaum, Eric R; Arnaoutakis, Konstantinos; Hutchins, Laura F; Makhoul, Issam; Milojkovic, Natasha; Cottler-Fox, Michele

    2015-02-01

    Thrombotic thrombocytopenic purpura (TTP) results from a congenital or acquired deficiency of the von Willebrand factor (vWF)-cleaving protease ADAMTS13. The disease can be fatal and hence treatment should be initiated promptly. Therapeutic plasma exchange (TPE) remains the standard treatment along with adjunct therapies including steroids and immunosuppressive drugs. Addition of rituximab to TPE has been shown to be beneficial in refractory/relapsing TTP; however, TPE results in removal of rituximab from the circulation requiring more frequent dosing of rituximab to achieve a favorable outcome. The intermediate-purity plasma-derived Factor VIII concentrate (FVIII) Koate® contains the highest amount of ADAMTS13 activity yet reported and has been used successfully in treating congenital TTP. Here we report our experience with addition of this FVIII concentrate to rituximab, corticosteroids and TPE in three TTP patients with an ADAMTS13 inhibitor to permit withholding TPE for 48 h after rituximab infusion.

  4. Systemic Lupus Erythematosus Presenting as Refractory Thrombotic Thrombocytopenic Purpura: A Diagnostic and Management Challenge. A Case Report and Concise Review of the Literature

    PubMed Central

    Abu-Hishmeh, Mohammad; Sattar, Alamgir; Zarlasht, Fnu; Ramadan, Mohamed; Abdel-Rahman, Aisha; Hinson, Shante; Hwang, Caroline

    2016-01-01

    Patient: Female, 34 Final Diagnosis: Refractory thrombotic thrombocytopenic purpura Symptoms: Fatigue Medication: — Clinical Procedure: Plasma exchange Specialty: Rheumatology • Hematology and Critical Care Objective: Rare co-existance of disease or pathology Background: Thrombotic thrombocytopenic purpura (TTP) is one of the thrombotic microangiopathic (TMA) syndromes, caused by severely reduced activity of the vWF-cleaving protease ADAMTS13. Systemic lupus erythematosus (SLE), on the other hand, is an autoimmune disease that affects various organs in the body, including the hematopoietic system. SLE can present with TMA, and differentiating between SLE and TTP in those cases can be very challenging, particularly in patients with no prior history of SLE. Furthermore, an association between these 2 diseases has been described in the literature, with most of the TTP cases occurring after the diagnosis of SLE. In rare cases, TTP may precede the diagnosis of SLE or occur concurrently. Case Report: We present a case of a previously healthy 34-year-old female who presented with dizziness and flu-like symptoms and was found to have thrombocytopenia, hemolytic anemia, and schistocytes in the peripheral smear. She was subsequently diagnosed with TTP and started on plasmapheresis and high-dose steroids, but without a sustained response. A diagnosis of refractory TTP was made, and she was transferred to our facility for further management. Initially, the patient was started on rituximab, but her condition continued to deteriorate, with worsening thrombocytopenia. Later, she also fulfilled the Systemic Lupus International Collaborating Clinics (SLICC) criteria for diagnosis of SLE. Treatment of TTP in SLE patients is generally similar to that in the general population, but in refractory cases there are few reports in the literature that show the efficacy of cyclophosphamide. We started our patient on cyclophosphamide and noticed a sustained improvement in the platelet

  5. Thrombotic thrombocytopenic purpura

    MedlinePlus

    ... level Mucus membrane biopsy Platelet count Urinalysis Von Willebrand factor assay Treatment You may have a treatment ... recover completely. But some people die of this disease, especially if it is not diagnosed right away. ...

  6. Citrate anticoagulation during plasma exchange in a patient with thrombotic thrombocytopenic purpura: short heparin-free hemodialysis helps to attenuate citrate load.

    PubMed

    Buturović-Ponikvar, Jadranka; Pernat, Andreja Marn; Ponikvar, Rafael

    2005-06-01

    The treatment of thrombotic thrombocytopenic purpura requires plasma exchange using fresh frozen plasma as a replacement solution once or even twice daily. If citrate anticoagulation is needed, the citrate load (both from fresh frozen plasma and citrate as an anticoagulant) can be significant, causing metabolic complications. The aim of our report is to present our experience with citrate anticoagulation in a patient with thrombotic thrombocytopenic purpura treated with daily membrane plasma exchange. Twenty-six plasma exchange procedures were performed during 20 days of treatment in a 46-year-old female. The blood flow was 98 +/- 8 mL/min; 4% trisodium citrate was infused into the arterial line (134 +/- 11 mL/h) and 1 M CaCl2 into the venous line (11.4 +/- 1.8 mL/h). Fresh frozen plasma (first 7 procedures) or cryo-poor plasma (19 procedures) were used as a replacement solution, 3176 +/- 536 mL per procedure. A total of 88,930 mL of plasma was exchanged. No serious side-effects occurred. iCa before plasma exchange was significantly higher than afterwards (1.23 +/- 0.12 vs. 1.12 +/- 0.12, P = 0.0047). Significant alkalosis occurred after three plasma exchanges (pH 7.64, bicarbonate 36.2 mmol/L), and was corrected by 3-h heparin-free hemodialysis with dialysate as follows: K 4.0 mmol/L, calcium 1.5 mmol/L, and bicarbonate set to 24 mmol/L. After dialysis, pH was 7.45 and bicarbonate 29.4 mmol/L. Another (2-h) heparin-free hemodialysis procedure was repeated after six plasma exchanges. Citrate anticoagulation can be safely performed in patients treated with plasma exchange once or twice daily. Periodically performed short heparin-free hemodialysis can correct metabolic alkalosis and attenuate the citrate load.

  7. Systemic Lupus Erythematosus Presenting as Refractory Thrombotic Thrombocytopenic Purpura: A Diagnostic and Management Challenge. A Case Report and Concise Review of the Literature.

    PubMed

    Abu-Hishmeh, Mohammad; Sattar, Alamgir; Zarlasht, Fnu; Ramadan, Mohamed; Abdel-Rahman, Aisha; Hinson, Shante; Hwang, Caroline

    2016-10-25

    BACKGROUND Thrombotic thrombocytopenic purpura (TTP) is one of the thrombotic microangiopathic (TMA) syndromes, caused by severely reduced activity of the vWF-cleaving protease ADAMTS13. Systemic lupus erythematosus (SLE), on the other hand, is an autoimmune disease that affects various organs in the body, including the hematopoietic system. SLE can present with TMA, and differentiating between SLE and TTP in those cases can be very challenging, particularly in patients with no prior history of SLE. Furthermore, an association between these 2 diseases has been described in the literature, with most of the TTP cases occurring after the diagnosis of SLE. In rare cases, TTP may precede the diagnosis of SLE or occur concurrently. CASE REPORT We present a case of a previously healthy 34-year-old female who presented with dizziness and flu-like symptoms and was found to have thrombocytopenia, hemolytic anemia, and schistocytes in the peripheral smear. She was subsequently diagnosed with TTP and started on plasmapheresis and high-dose steroids, but without a sustained response. A diagnosis of refractory TTP was made, and she was transferred to our facility for further management. Initially, the patient was started on rituximab, but her condition continued to deteriorate, with worsening thrombocytopenia. Later, she also fulfilled the Systemic Lupus International Collaborating Clinics (SLICC) criteria for diagnosis of SLE. Treatment of TTP in SLE patients is generally similar to that in the general population, but in refractory cases there are few reports in the literature that show the efficacy of cyclophosphamide. We started our patient on cyclophosphamide and noticed a sustained improvement in the platelet count in the following weeks. CONCLUSIONS Thrombotic thrombocytopenic purpura is a life-threatening hematological emergency which must be diagnosed and treated in a timely manner. Refractory cases of TTP have been described in the literature, but without clear evidence

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

    PubMed

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

    2013-06-01

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

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

    PubMed

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

    2015-10-13

    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.

  10. Thrombotic thrombocytopenic purpura - analysis of clinical features, laboratory characteristics and therapeutic outcome of 24 patients treated at a Tertiary Care Center in Saudi Arabia

    PubMed Central

    Iqbal, Shahid; Zaidi, Syed Z. A.; Motabi, Ibraheem H; Alshehry, Nawal Faiez; AlGhamdi, Mubarak S.; Tailor, Imran Khan

    2016-01-01

    Objective: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease. The primary aim was overall response rate (ORR) assessment in the treated patients Methods: This retrospective study included 24 patients treated during 2006-2015. TTP patients with microangiopathic hemolysis (MAHA) and thrombocytopenia were included. We analyzed clinical features, laboratory characteristics and treatment outcomes of 24 TTP patients treated at our tertiary care center (KFMC). Results: Twenty-four TTP patients (18 females; 6 males) had a mean age of 33.5±13.9 years; 22(91%) had neurologic features, 7(29%) fever, 10(42%) renal impairment; 4(20.83%) cardiac manifestations; 22(91.7%) had triad with additional neurologic abnormalities; only 2(8.2%) had pentad of TTP. Majority (54.16%) had idiopathic TTP. All patients received therapeutic plasma exchange (TPE); 23(95.8%) received adjunctive corticosteroids and 13(54.2%) received rituximab either due to refractoriness to TPE on ~day7, or earlier. Twenty-one out of 24 (87.5%) achieved complete remission (CR) without any subsequent relapse. At 22 months (median, range 1-113), 20 patients (83.3%) are alive at the time of report. Three patients died during acute episode because of sever disease or delayed treatment and one died in CR. Conclusion: TPE, steroids and or rituximab was very effective in preventing high risk of mortality and achieving durable CR in 87.5% of patients. More awareness is needed for early diagnosis and early referral to centers with appropriate tertiary care facilities.. PMID:28083052

  11. What Causes Thrombotic Thrombocytopenic Purpura?

    MedlinePlus

    ... is involved in blood clotting. Not having enough enzyme activity causes overactive blood clotting. In TTP, blood clots ... make a normal ADAMTS13 enzyme. As a result, enzyme activity is lacking or changed. "Inherited" means that the ...

  12. Living with Thrombotic Thrombocytopenic Purpura

    MedlinePlus

    ... skin causes petechiae. Paleness or jaundice (a yellowish color of the skin or whites of the eyes). Fatigue (feeling very tired and weak). Fever. A fast heart rate or shortness of breath. Headache, speech changes, confusion, coma, stroke , or seizure. A low amount ...

  13. The risk of venous thrombosis in individuals with a history of superficial vein thrombosis and acquired venous thrombotic risk factors.

    PubMed

    Roach, Rachel E J; Lijfering, Willem M; van Hylckama Vlieg, Astrid; Helmerhorst, Frans M; Rosendaal, Frits R; Cannegieter, Suzanne C

    2013-12-19

    Superficial vein thrombosis (SVT) increases the risk of venous thrombosis fourfold to sixfold. As most individuals with SVT do not develop venous thrombosis, additional risk factors may explain the risk of developing a venous thrombosis. In the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis study, we assessed the risk of venous thrombosis in individuals with previous SVT and a mild thrombotic risk factor (smoking or overweight/obesity), a strong risk factor (surgery, hospitalization, plaster cast immobilization, or malignancy), or a reproductive factor in women (oral contraception, postmenopausal hormone therapy, or pregnancy/puerperium). Individuals with previous SVT alone had a 5.5-fold (95% confidence interval [CI], 4.4-6.8) increased risk of venous thrombosis. This was 9.3 (95% CI, 7.2-12.1) combined with a mild thrombotic risk factor, 31.4 (95% CI, 14.6-67.5) with a strong risk factor, and 34.9 (95% CI, 19.1-63.8) in women with a reproductive risk factor. The highest separate risk estimates were found for SVT with surgery (42.5; 95% CI, 10.2-177.6), hospitalization (49.8; 95% CI, 11.9-209.2), or oral contraception (43.0; 95% CI, 15.5-119.3 in women). In conclusion, the risk of venous thrombosis is markedly increased in individuals with previous SVT who have an acquired thrombotic risk factor.

  14. Thrombocytopenic syndromes in pregnancy

    PubMed Central

    Yan, Matthew; Malinowski, Ann K

    2015-01-01

    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

  15. How Is Thrombotic Thrombocytopenic Purpura Diagnosed?

    MedlinePlus

    ... specializes in diagnosing and treating blood disorders. Medical History Your doctor will ask about factors that may affect TTP. For example, he or she may ask whether you: Have certain diseases or conditions, such as cancer, HIV, lupus, or infections (or whether you're pregnant). Have ...

  16. 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 ...

  17. Cancer-associated thrombotic microangiopathy

    PubMed Central

    Govind Babu, K; Bhat, Gita R

    2016-01-01

    Cancer-associated thrombotic microangiopathy refers to a group of disorders characterised by microvascular thrombosis, thrombocytopenia, and ischaemic end-organ damage. Haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura are the two major subtypes. It can be a manifestation of the malignancy itself or a complication of its therapy. The addition of several new drugs to the therapeutic armamentarium of cancer has brought to light several novel causative factors of this hitherto uncommon complication. This review covers the aetiology, pathogenesis, clinical manifestations, complications, and the management of cancer-associated thrombotic microangiopathy. Careful review of the patient’s medical records coupled with the correlation of clinical findings and laboratory reports can help clinch the diagnosis and institute appropriate treatment on time. PMID:27433282

  18. Pathogenesis of Thrombotic Microangiopathies

    PubMed Central

    Zheng, X. Long; Sadler, J. Evan

    2008-01-01

    Profound thrombocytopenia and microangiopathic hemolytic anemia characterize thrombotic microangiopathy, which includes two major disorders: thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). TTP has at least three types: congenital or familial, idiopathic, and nonidiopathic. The congenital and idiopathic TTP syndromes are caused primarily by deficiency of ADAMTS13, owing to mutations in the ADAMTS13 gene or autoantibodies that inhibit ADAMTS13 activity. HUS is similar to TTP, but is associated with acute renal failure. Diarrhea-associated HUS accounts for more than 90% of cases and is usually caused by infection with Shiga-toxin-producing Escherichia coli (O157:H7). Diarrhea-negative HUS is associated with complement dysregulation in up to 50% of cases, caused by mutations in complement factor H, membrane cofactor protein, factor I or factor B, or by autoanti-bodies against factor H. The incomplete penetrance of mutations in either ADAMTS13 or complement regulatory genes suggests that precipitating events or triggers may be required to cause thrombotic microangiopathy in many patients. PMID:18215115

  19. ADAMTS-13 in the Diagnosis and Management of Thrombotic Microangiopathies

    PubMed Central

    Sarig, Galit

    2014-01-01

    Thrombotic microangiopathies (TMAs) comprise a group of distinct disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and microvascular thrombosis. For many years distinction between these TMAs, especially between thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), remained purely clinical and hard to make. Recent discoveries shed light on different pathogenesis of TTP and HUS. Ultra-large von Willebrand factor (UL-VWF) platelet thrombi, resulting from the deficiency of cleavage protease which is now known as ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), were found to cause TTP pathology, while Shiga toxins or abnormalities in regulation of the complement system cause microangiopathy and thrombosis in HUS. TMAs may appear in various conditions such as pregnancy, inflammation, malignancy, or exposure to drugs. These conditions might cause acquired TTP, HUS, or other TMAs, or might be a trigger in individuals with genetic predisposition to ADAMTS-13 or complement factor H deficiency. Differentiation between these TMAs is highly important for urgent initiation of appropriate therapy. Measurement of ADAMTS-13 activity and anti-ADAMTS-13 antibody levels may advance this differentiation resulting in accurate diagnosis. Additionally, assessment of ADAMTS-13 levels can be a tool for monitoring treatment efficacy and relapse risk, allowing consideration of therapy addition or change. In the past few years, great improvements in ADAMTS-13 assays have been made, and tests with increased sensitivity, specificity, reproducibility, and shorter turnaround time are now available. These new assays enable ADAMTS-13 measurement in routine clinical diagnostic laboratories, which may ultimately result in improvement of TMA management. PMID:25386342

  20. Thrombotic thrombocytopenic purpura--possibilities of treatment and results.

    PubMed

    Gasparović, V; Mejić, S; Pisl, Z; Radonić, R; Radman, I

    2001-01-01

    Results of treatment of 13 patients fulfilling the criteria for TTP are presented. Thrombocytopenia was present in all patients (100%). Eleven of 13 patients (84.6%) had conciousness disorder, and seven of 13 patients (53.8%) had renal impairment. Immunosuppressive therapy with plasmapheresis and replacement of removed volume with fresh frozen plasma in a dosage of 25 ml/kg body weight resulted in statistically significant increase of platelet count (p = 0.0033), and significant improvement of consciousness as defined by increased Glasgow Coma Score (GCS) (p = 0.0524). In two patients, renal function recovered and, in one patient, hemodialysis was no longer needed. This improvement in a small patient group has no statistical significance.

  1. Breast Cancer-Associated Thrombotic Microangiopathy

    PubMed Central

    Regierer, Anne C.; Kuehnhardt, Dagmar; Schulz, Carsten-Oliver; Flath, Bernd; Jehn, Christian F.; Scholz, Christian W.; Possinger, Kurt; Eucker, Jan

    2011-01-01

    Background Thrombotic microangiopathy (TMA) is defined as thrombocytopenia and microangiopathic hemolytic anemia. Cancer-associated TMA, a rare but fatal condition, seems an entity distinct from classical thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS). Patients and Methods All patients with breast cancer-associated TMA treated at our institution between 2003 and 2008 were analyzed retrospectively. To elucidate pathophysiological mechanisms, we measured the serum activity of the metalloprotease ADAMTS13. Results 8 patients were identified. All showed bone marrow infiltration of breast cancer as well as thrombocytopenia, schistocytes, and hemolytic anemia. ADAMTS13 activity was mildly decreased in 4/6 patients (20–108%, normal range 30–120%), but none showed severely low levels as is characteristic of classical TTP. 6 patients were treated with anthracycline-containing fractionated chemotherapy, 5/6 patients experienced partial response. Overall survival was 13 months. Fractionated chemotherapy was well tolerated. Conclusions Cancer-associated TMA has an underlying mechanism different from classical TTP. While bone marrow infiltration might be of major relevance, ADAMTS13 deficiency seems to be an epiphenomenon. Fractionated chemotherapy resulted in higher remission rates and comparatively long survival. PMID:22419897

  2. Thrombotic Microangiopathy Syndrome in a Basic Underwater Demolition/SEAL Student.

    PubMed

    Croom, Daniel; Tracy, Heather

    2016-01-01

    Thrombotic microangiopathy (TMA) syndromes represent a spectrum of illnesses that share common clinical and pathologic features of microangiopathic hemolytic anemia, thrombocytopenia, and organ injury from pathologic small-vessel thrombosis. At least nine primary TMA syndromes have been described and classified based on common probable etiologies, diagnostic criteria, and treatments. The most recognized of the TMA syndromes include thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS). Advanced laboratory techniques are required to distinguish between these syndromes; however, all patients should initially be treated with plasma exchange for presumed ADAMTS13 deficiency-mediated TMA. The authors present a case of a TMA syndrome in a Navy SEAL (Sea, Air, Land) candidate.

  3. Thrombotic microangiopathic haemolytic anaemia and antiphospholipid antibodies

    PubMed Central

    Espinosa, G; Bucciarelli, S; Cervera, R; Lozano, M; Reverter, J; de la Red, G; Gil, V; Ingelmo, M; Font, J; Asherson, R

    2004-01-01

    Objective: To analyse the clinical and laboratory features of patients with thrombotic microangiopathic haemolytic anaemia (TMHA) associated with antiphospholipid antibodies (aPL). Methods: A computer assisted (PubMed) search of the literature was performed to identify all cases of TMHA associated with aPL from 1983 to December 2002. Results: 46 patients (36 female) with a mean (SD) age at presentation of TMHA of 34 (15) years were reviewed. Twenty eight (61%) patients had primary antiphospholipid syndrome (APS). TMHA was the first clinical manifestation of APS in 26 (57%) patients. The clinical presentations were haemolytic-uraemic syndrome (26%), catastrophic APS (23%), acute renal failure (15%), malignant hypertension (13%), thrombotic thrombocytopenic purpura (13%), and HELLP (haemolysis, elevated liver enzymes, and low platelet count in association with eclampsia) syndrome (4%). Lupus anticoagulant was detected in 86% of the episodes of TMHA, and positive anticardiolipin antibodies titres in 89%. Steroids were the most common treatment (69% of episodes), followed by plasma exchange (PE) (62%), anticoagulant or antithrombotic agents (48%), immunosuppressive agents (29%), and immunoglobulins (12%). Recovery occurred in only 10/29 (34%) episodes treated with steroids, and in 19/27 (70%) episodes treated with PE. Death occurred in 10/46 (22%) patients. Conclusions: The results emphasise the need for systematic screening for aPL in all patients with clinical and laboratory features of TMHA. The existence of TMHA in association with an APS forces one to rule out the presence of the catastrophic variant of this syndrome. PE is indicated as a first line of treatment for all patients with TMHA associated with aPL. PMID:15140782

  4. Hematopoietic cell transplantation-associated thrombotic microangiopathy: a review of pathophysiology, diagnosis, and treatment

    PubMed Central

    Rosenthal, Joseph

    2016-01-01

    Transplant-associated thrombotic microangiopathy (TA-TMA) is a multifactorial disorder caused by systemic vascular endothelial injury that can be triggered by several mechanisms during the transplant process. Thrombotic microangiopathy may affect multiple systems and occurs in ~30% of patients undergoing hematopoietic stem cell transplantation. A subgroup of patients with thrombotic microangiopathy develop TA-TMA, and the other may develop other thrombotic microangiopathic disorders such as thrombotic thrombocytopenic purpura, a condition with similar finding but different pathophysiology involving ADAMTS-13. The mortality rates in patients who develop severe TA-TMA are in excess of 80%. Recent investigations show that complement system activation in patients with TA-TMA is a very poor prognostic sign and implicates complement dysregulation as a key pathway in the pathogenesis of TA-TMA and its disease phenotype. The original diagnostic criteria for TA-TMA included hematologic and renal injury markers, which are limited in their ability to detect only advanced disease, and therefore may result in delayed TA-TMA diagnosis in transplant patients. A recent set of diagnostic criteria added markers of complement activation, proteinuria, and hypertension, with predicted improved detection of early TA-TMA. Supportive care that includes elimination of potentially toxic agents such as calcineurin inhibitors and sirolimus, adequate antimicrobial treatment, and maintaining adequate renal functions using renal replacement therapy may be sufficient for treatment of mild-to-moderate TA-TMA. Plasma exchange, which is a potentially curative therapy in thrombotic thrombocytopenic purpura, has no proven efficacy in TA-TMA. Blocking the complement system with eculizumab is currently the most effective treatment to circumvent the poor outcome in patients with severe TA-TMA. PMID:27621680

  5. Hematopoietic cell transplantation-associated thrombotic microangiopathy: a review of pathophysiology, diagnosis, and treatment.

    PubMed

    Rosenthal, Joseph

    2016-01-01

    Transplant-associated thrombotic microangiopathy (TA-TMA) is a multifactorial disorder caused by systemic vascular endothelial injury that can be triggered by several mechanisms during the transplant process. Thrombotic microangiopathy may affect multiple systems and occurs in ~30% of patients undergoing hematopoietic stem cell transplantation. A subgroup of patients with thrombotic microangiopathy develop TA-TMA, and the other may develop other thrombotic microangiopathic disorders such as thrombotic thrombocytopenic purpura, a condition with similar finding but different pathophysiology involving ADAMTS-13. The mortality rates in patients who develop severe TA-TMA are in excess of 80%. Recent investigations show that complement system activation in patients with TA-TMA is a very poor prognostic sign and implicates complement dysregulation as a key pathway in the pathogenesis of TA-TMA and its disease phenotype. The original diagnostic criteria for TA-TMA included hematologic and renal injury markers, which are limited in their ability to detect only advanced disease, and therefore may result in delayed TA-TMA diagnosis in transplant patients. A recent set of diagnostic criteria added markers of complement activation, proteinuria, and hypertension, with predicted improved detection of early TA-TMA. Supportive care that includes elimination of potentially toxic agents such as calcineurin inhibitors and sirolimus, adequate antimicrobial treatment, and maintaining adequate renal functions using renal replacement therapy may be sufficient for treatment of mild-to-moderate TA-TMA. Plasma exchange, which is a potentially curative therapy in thrombotic thrombocytopenic purpura, has no proven efficacy in TA-TMA. Blocking the complement system with eculizumab is currently the most effective treatment to circumvent the poor outcome in patients with severe TA-TMA.

  6. Acquired TTP: ADAMTS13 meets the immune system.

    PubMed

    Verbij, Fabian C; Fijnheer, Rob; Voorberg, Jan; Sorvillo, Nicoletta

    2014-11-01

    The majority of the patients affected by acquired thrombotic thrombocytopenic purpura (TTP) develop autoantibodies directed towards ADAMTS13 that interfere with its von Willebrand Factor (VWF) processing activity. B cell responses have been shown to primarily target the spacer domain of ADAMTS13 thereby prohibiting the binding of ADAMTS13 to the VWF A2 domain. In this review we summarize recent knowledge gained on the immune recognition and processing of ADAMTS13 by antigen-presenting cells (APCs). HLA-DRB1*11 has been identified as a risk factor for acquired TTP. Analysis of MHC class II/peptide complexes of ADAMTS13 pulsed dendritic cells have shown that the CUB2 domain derived peptide FINVAPHAR is preferentially presented on HLA-DRB1*11. Based on these findings we propose a model for the initiation of the autoimmune reactivity against ADAMTS13 in previously healthy individuals. We hypothesize that mimicry between a pathogen-derived peptide and the CUB2 derived FINVAPHAR-peptide might contribute to the onset of acquired TTP.

  7. Acute kidney injury in pregnancy: the thrombotic microangiopathies.

    PubMed

    Ganesan, Chitra; Maynard, Sharon E

    2011-01-01

    Acute kidney injury (AKI) is a rare but serious complication of pregnancy. Although prerenal and ischemic causes of AKI are most common, renal insufficiency can complicate several other pregnancy-specific conditions. In particular, severe preeclampsia/HELLP syndrome, acute fatty liver of pregnancy (AFLP) and thrombotic thrombocytopenic purpura (TTP) are all frequently complicated by AKI, and share several clinical features which pose diagnostic challenges to the clinician. In this article, we discuss the clinical and laboratory features, pathophysiology and treatment of these 3 conditions, with particular attention to renal manifestations. It is imperative to distinguish these conditions to make appropriate therapeutic decisions which can be lifesaving for the mother and fetus. Typically AFLP and HELLP improve after delivery of the fetus, whereas plasma exchange is the first-line treatment for TTP.

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

    PubMed Central

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

    2012-01-01

    Prevailing approaches to manage autoimmune thrombotic disorders, such as heparin-induced thrombocytopenia, antiphospholipid syndrome and thrombotic thrombocytopenic purpura, include immunosuppression and systemic anticoagulation, though neither provides optimal outcome for many patients. A different approach is suggested by the concurrence of autoantibodies and their antigenic targets in the absence of clinical disease, such as platelet factor 4 in heparin-induced thrombocytopenia and β2-glycoprotein-I (β2GPI) in antiphospholipid syndrome. The presence of autoantibodies in the absence of disease suggests that conformational changes or other alterations in endogenous protein autoantigens are required for recognition by pathogenic autoantibodies. In thrombotic thrombocytopenic purpura, the clinical impact of ADAMTS13 deficiency caused by autoantibodies likely depends on the balance between residual antigen, that is, enzyme activity, and demand imposed by local genesis of ultralarge multimers of von Willebrand factor. A corollary of these concepts is that disrupting platelet factor 4 and β2GPI conformation (or ultralarge multimer of von Willebrand factor oligomerization or function) might provide a disease-targeted approach to prevent thrombosis without systemic anticoagulation or immunosuppression. Validation of this approach requires a deeper understanding of how seemingly normal host proteins become antigenic or undergo changes that increase antibody avidity, and how they can be altered to retain adaptive functions while shedding epitopes prone to elicit harmful autoimmunity. PMID:22966172

  9. Circulating DNA and myeloperoxidase indicate disease activity in patients with thrombotic microangiopathies.

    PubMed

    Fuchs, Tobias A; Kremer Hovinga, Johanna A; Schatzberg, Daphne; Wagner, Denisa D; Lämmle, Bernhard

    2012-08-09

    Thrombotic microangiopathies (TMAs) are a group of life-threatening disorders characterized by thrombocytopenia, fragmentation of erythrocytes, and ischemic organ damage. Genetic disorders, autoimmune disease, and cancer are risk factors for TMAs, but an additional, unknown trigger is needed to bring about acute disease. Recent studies suggest that DNA and histones are released during inflammation or infection and stimulate coagulation, thrombosis, thrombocytopenia, and organ damage in mice. We show that extracellular DNA and histones as well as markers of neutrophils are present in acute TMAs. Analysis of plasma from TMA patients of different clinical categories revealed elevated levels of DNA-histone complexes and myeloperoxidase (MPO) from neutrophil granules as well as S100A8/A9, a heterocomplex abundant in neutrophil cytosol. During therapy of thrombotic thrombocytopenic purpura, a subtype of TMAs often associated with severe ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13) deficiency, plasma DNA and MPO were inversely correlated with platelet counts, and their levels indicated amelioration or exacerbation of the disease. ADAMTS13 deficiency together with increased levels of plasma DNA and MPO were characteristic for acute thrombotic thrombocytopenic purpura. A minor infection often precedes acute TMA and extracellular DNA and histones released during the inflammatory response could provide the second hit, which precipitates acute TMA in patients with pre-existing risk factors.

  10. 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.

  11. [The revolution of monoclonal antibodies in the treatment of thrombotic microangiopathy].

    PubMed

    Sauvètre, G; Grange, S; Froissart, A; Veyradier, A; Coppo, P; Benhamou, Y

    2015-05-01

    Thrombotic microangiopathies (TMA) define a syndrome characterized by the association of microangiopathic haemolytic anaemia with schistocytes, peripheral thrombocytopenia, and organ injury of variable severity. Thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uremic syndrome (HUS) are the main forms of TMA. Recent advances in the pathophysiology of those two diseases, which include in HUS the identification of a deregulation of the alternative complement pathway, and in TTP a severe deficiency in ADAMTS-13, allowed to develop specific, pathophysiology-based therapies. Therefore, rituximab and eculizumab tends to be increasingly used, and there is an urgent need to define consensual modes of administration at the international level, as well as common definitions of response evaluation and follow-up explorations.

  12. Acyclovir-induced thrombotic microangiopathy

    PubMed Central

    Goli, R.; Mukku, K. K.; Devaraju, S. B. R.; Uppin, M. S.

    2017-01-01

    Acyclovir is a commonly used antiviral drug. Acute kidney injury (AKI) due to intratubular crystal precipitation and interstitial nephritis is well known. Here we present a case of acyclovir induced AKI in a 61 year old male with herpes zoster, which presented like thrombotic microangiopathy with acute interstitial nephritis. This is the first case report on acyclovir causing thrombotic microaniopathy with partial improvement in renal function after plasmapharesis. PMID:28356666

  13. 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

  14. Wandering spleen: 'presentation in adolescent with high thrombotic risk'.

    PubMed

    Tchidjou, Hyppolite K; Castelluzzo, Maria A; Messia, Virginia; Luciani, Matteo; Monti, Lidia; Grimaldi, Chiara; Bernardi, Stefania; D'Argenio, Patrizia

    2014-07-01

    The term 'wandering spleen' refers to an abnormal hypermobility of the spleen, which may be congenital or acquired. The absence or abnormal laxity of splenic ligaments combined with an abnormally long and mobile vascular pedicle predispose to complications such as torsion of the splenic pedicle, infarction and splenic vein thrombosis. The clinical presentation of such disease is highly variable. In this case, we describe an asymptomatic case of wandering spleen in high thrombotic risk patients with cavernoma of splenic vein and infarction of the spleen. Physical examination was normal except the enlarged and no tender consistency spleen palpable at left iliac fossa. Ultrasonography revealed enlarged spleniform mass below its normal position suggesting vascular impairment and subsequently has been confirmed by colour Doppler ultrasound and computed tomography. The family history was positive for ischemic thrombotic vascular diseases and the screening for thrombotic risk has revealed hyperhomocysteinemia, thrombophilic homozygous gene mutations for factor V (H1299R) and MTHFR (C677T). For high thrombotic risk, prophylaxis postsplenectomy was suggested according to the international recommendations with subcutaneous low molecular weight heparin, associated with a preventive treatment with acetyl salicylic acid and folic acid along with B-vitamin. This case report may be helpful for clinicians involved in the care of splenectomized patients, because it has shown the importance of an appropriate pre and postoperative antithrombotic management to reduce as soon as possible the risk of thrombotic events in such patients after splenectomy.

  15. Immunodeficiency-associated thrombocytopenic purpura (IDTP). Response to splenectomy.

    PubMed

    Schneider, P A; Abrams, D I; Rayner, A A; Hohn, D C

    1987-10-01

    Immunodeficiency-associated thrombocytopenic purpura (IDTP) is a feature of the acquired immunodeficiency syndrome--related complex. Current therapeutic modalities for IDTP include splenectomy and the administration of corticosteroids or other agents. Empiric treatment of IDTP has been analogous to that for immunologic thrombocytopenic purpura (ITP). The present report reviews 15 patients who underwent splenectomy for IDTP, demonstrates the successful use of surgical therapy, and defines our indications for splenectomy in the treatment of this disorder. Thirteen of 15 patients had initially failed to respond to steroid therapy. Fourteen patients (93%) initially responded to splenectomy, with platelet counts increasing to 150 X 10(9)/L (150,000/mm3) or greater. A continuing complete response was achieved in nine patients (60%) following splenectomy. After postsurgical adjunctive therapy, durable remission was achieved in 73% (11/15) of the patients. Complications occurred in three patients, and there were no deaths. The mean follow-up was 12.4 months. Splenectomy may be performed in the treatment of IDTP with acceptable morbidity and likelihood of response.

  16. Scleroderma renal crisis or thrombotic thrombocytopenic purpura: seeing through the masquerade.

    PubMed

    Keeler, Emily; Fioravanti, Gloria; Samuel, Bensson; Longo, Santo

    2015-01-01

    SCLERODERMA: renal crisis (SRC), a somewhat rare but serious complication of systemic scleroderma, is one of only a few known rheumatologic emergencies; it presents in as many as 10% of patients with scleroderma. Before the use of angiotensin converting enzyme (ACE) inhibitors to treat SRC, the mortality rate for SRC was extremely high-as much as 90% after 1 year. However, the mortality rate has significantly improved with the early and aggressive use of ACE inhibitors. SRC typically includes acute renal failure and accelerated hypertension. Patients may report headache, changes in vision, fever, dyspnea, and encephalopathy. Laboratory study results can show elevated creatinine levels, thrombocytopenia, and microangiopathic hemolytic anemia (MAHA) with schistocytes on blood smear. Given this clinical and laboratory presentation, SRC can easily be mistaken for TTP in clinical practice, as we demonstrate in 2 presentations of similar cases of SRC, the first in a 36-year-old Caucasian woman and the second in a 54-year-old Caucasian woman. In both cases, SRC masqueraded as TTP, and both patients were almost mistakenly treated for TTP until the clinical picture changed and certain laboratory test and kidney biopsy results confirmed otherwise.

  17. Thrombotic risk of reduced ADAMTS13 activity in patients with antiphospholipid antibodies.

    PubMed

    Lee, Seung Jun; Kim, Ji-Eun; Han, Kyou-Sup; Kim, Hyun Kyung

    2016-12-01

    Antiphospholipid syndrome (APS) is an autoimmune disease in which antiphospholipid antibodies (aPLs) are generated. Previous studies show concurrence of APS and thrombotic thrombocytopenic purpura; therefore it is plausible to assume that anti-ADAMTS13 autoantibody is also involved in the pathophysiology of APS. We investigated the clinical significance of ADAMTS13 activity and anti-ADAMTS13 antibody in patients with aPLs. Two hundred and sixteen patients with positive lupus anticoagulant and/or anticardiolipin antibody were included. ADAMTS13 activity and anti-ADAMTS13 antibody were measured using fluorescence resonance energy-transfer technology and ELISA, respectively. Reduced ADAMTS13 activity was observed in 40.3% (87/216) of patients with aPLs. Although 33.8% (73/216) of patients were positive for anti-ADAMTS13 antibody, 41 of these 73 patients had normal levels of ADAMTS13 activity. Reduced ADAMTS13 activity was a significant risk factor for thrombotic events. Thrombotic events and age contributed to the reduced level of ADAMTS13 activity. Presence of anti-ADAMTS13 antibody did not show any association with the level of ADAMTS13 activity. Patients with autoimmune diseases tended to show higher levels of anti-ADAMTS13 antibody. Our findings suggest that reduced ADAMTS13 activity is a significant thrombotic risk factor in patients with aPLs irrespective of the presence of anti-ADAMTS13 antibody. Presence of anti-ADAMTS13 antibody is not seen with reduced activity and it tends to be increased in patients with autoimmune diseases.

  18. [Embolic stroke by thrombotic non bacterial endocarditis in an Antiphospholipid Syndrome patient].

    PubMed

    Graña, D; Ponce, C; Goñi, M; Danza, A

    2016-01-01

    The antiphospholipid syndrome (APS) is an acquired thrombophilia, considered a systemic autoimmune disorder. We report a patient with APS who presented multiple cerebral infarcts (stroke) as a complication of a thrombotic non bacterial endocarditis. We review the literature focused on the physiological mechanism that produce this disease and its complications. Clinical features and their prognostic value and the different therapeutic options were also studied.

  19. 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

  20. Thrombotic recurrences and bleeding events in APS vascular patients: a review from the literature and a comparison with the APS Piedmont Cohort.

    PubMed

    Bazzan, M; Vaccarino, A; Stella, S; Bertero, M T; Carignola, R; Montaruli, B; Roccatello, D; Shoenfeld, Y

    2013-06-01

    In APS vascular patients, thrombotic recurrences are more frequent than in non-APS thrombotic patients. To better define this clinical setting, a systematic review of the literature after 1999 was performed: 8 cohort studies (including the recent APS Piedmont Cohort) and 6 intervention studies were selected and evaluated. Thrombotic recurrences, bleeding events, therapeutic strategies, antiphospholipid (aPL) profile, inherited and acquired risk factors (when present) were calculated and compared. Emerging risk factors for thrombotic recurrences include withdrawal of oral anticoagulant therapy (OAT), high intensity OAT (INR range 3-4), aPL profile (triple positivity, Miyakis types 1 and 2a profiles) and association with inherited or acquired pro-thrombotic risk factors. Moreover, there are evidences that high risk (mainly for aPL profile) APS vascular patients have a high recurrence rate in spite of correct OAT treatment. Clinical trials in this clinical setting are needed.

  1. Case of twin pregnancy complicated by idiopathic thrombocytopenic purpura treated with intravenous immunoglobulin: Review of the literature.

    PubMed

    Zhao, W X; Yang, X F; Lin, J H

    2017-01-01

    Idiopathic thrombocytopenic purpura (ITP) is an acquired thrombocytopenia without other clear cause of thrombocytopenia. It is not common in a singleton pregnancy and less common in twin pregnancy. We report a 33-year-old ITP pluripara whose first pregnancy was uneventful. She carried twin pregnancy, complicated by recurrent very low platelets, and gave birth to preterm twins. This patient received multiple courses of intravenous immunoglobulin (IVIG) and showed a significant platelet count improvement with IVIG therapy.

  2. Autoimmune Hepatitis Associated with Immune Thrombocytopenic Purpura

    PubMed Central

    Ito, Akihiro; Yoshizawa, Kaname; Fujimori, Kazuya; Morita, Susumu; Shigeno, Takashi; Maejima, Toshitaka

    2017-01-01

    Although autoimmune hepatitis (AIH) is frequently complicated with chronic thyroiditis or other autoimmune disorders, reports on its association with immune thrombocytopenic purpura (ITP) are scarce. We herein describe a case of AIH associated with ITP. A 75-year-old Japanese woman was admitted to our hospital due to increased aminotransferase levels and severe thrombocytopenia. Elevated serum immunoglobulin G (IgG) was detected, and tests for platelet-associated IgG and anti-nuclear antibody were positive. Following the diagnosis of AIH-associated ITP, prednisolone treatment of 0.6 mg/kg/day resulted in a decrease in the aminotransferase levels and an increased platelet count. PMID:28090042

  3. Thrombophilia in 67 Patients With Thrombotic Events After Starting Testosterone Therapy.

    PubMed

    Glueck, Charles J; Prince, Marloe; Patel, Niravkumar; Patel, Jaykumar; Shah, Parth; Mehta, Nishi; Wang, Ping

    2016-09-01

    We compared thrombophilia in 67 cases (59 men and 8 women) with thrombotic events after starting testosterone therapy (TT) versus 111 patient controls having unprovoked venous thrombotic events without TT. In the 67 patients, thrombosis (47 deep venous thrombosis-pulmonary embolism, 16 osteonecrosis, and 4 ocular thrombosis) occurred 6 months (median) after starting TT. Cases differed from controls for factor V Leiden heterozygosity (16 of the 67 [24%] vs 13 [12%] of the 111, P = .038) and for lupus anticoagulant (9 [14%] of the 64 vs 4 [4%] of the 106, P = .019). After a first thrombotic event and continuing TT, 11 cases had a second thrombotic event, despite adequate anticoagulation, 6 of whom, still anticoagulated, had a third thrombosis. Screening for thrombophilia before starting TT should identify men and women at high risk for thrombotic events with an adverse risk-benefit ratio for TT. When TT is given to patients with familial and acquired thrombophilia, thrombosis may occur and recur in thrombophilic men despite anticoagulation.

  4. [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.

  5. Platelet antibodies in idiopathic thrombocytopenic purpura.

    PubMed Central

    Veenhoven, W A; Van der Schans, G S; Nieweg, H O

    1980-01-01

    An immunofluorescence (IF) technique for the detection of antibodies was applied to idiopathic thrombocytopenic purpura (ITP). Serum platelet antibodies were found in thirteen out of twenty-two patients (59 percent) with active disease, but in only four out of fifteen patients (27 percent) who had attained remission. Direct tests for platelet-associated IgG were positive in 36 and 44 percent of these patients respectively. In two cases IgM was observed on the patients' platelet membranes. C3 was not detedted on patients' platelets. Platelet-associated IgG was also found in several other disorders and its occurrence is not therefore diagnostic of ITP. In addition, serum platelet antibodies do not indicate specifically ITP as they may also be due to previous isoimmunization. Antibodies in the sera of patients with ITP generally did not fix Clq and in most cases bound to platelets only in the presence of EDTA. In contrast, isoantibodies often fixed Clq and they had equal affinity for platelets suspended in ACD or EDTA plasma. This was confirmed by quantitative data on IgG binding by platelets obtained by measuring 125-I-labelled protein A uptake. The simplicity of the IF technique permits its routine application and the technique may give useful information with respect to the nature of the antibodies. It must, however, be considered of limited value in the diagnosis of ITP. PMID:6991171

  6. Therapeutic splenectomy in immune thrombocytopenic purpura.

    PubMed

    Wani, N A; Parray, F Q

    2000-01-01

    The effects of splenectomy in 41 patients managed from 1982 to 1995 at Sher-i-Kashmir Institute of Medical Sciences, Srinagar (Jammu and Kashmir), India, were studied. Immune thrombocytopenic purpura (ITP) was the main indication for therapeutic splenectomy among all the hematologic disorders. The mean age was 30 years (range 7-64), and the male to female ratio was 1.05:1. The mean platelet count in the preoperative period was 31,751/mm(3) (range 4000-85,000). All patients presented with thrombocytopenia, i.e., platelet count of <100,000/mm(3). In addition, 5 patients presented with anemia, i.e., Hb <10 g%. Among the patients with thrombocytopenia, 30 patients presented with counts <50,000/mm(3) and 11 patients presented with counts between 50,000-100,000/mm(3). None of the patients presented with leukopenia. The morbidity observed was 15% and mortality was 2%. The response to splenectomy was complete for thrombocytopenia in 3 patients and partial in 5 patients; 4 patients failed to show any response. In anemic patients, 4 patients showed complete response and 1 patient showed no response. The prognosis was excellent in patients with platelet count >50,000/mm(3), age <50 years, no concomitant disease, and disease of shorter duration.

  7. Blood and marrow transplant clinical trials network toxicity committee consensus summary: thrombotic microangiopathy after hematopoietic stem cell transplantation.

    PubMed

    Ho, Vincent T; Cutler, Corey; Carter, Shelly; Martin, Paul; Adams, Roberta; Horowitz, Mary; Ferrara, James; Soiffer, Robert; Giralt, Sergio

    2005-08-01

    The syndrome of microangiopathic hemolysis associated with renal failure, neurologic impairment, or both is a recognized complication of hematopoietic stem cell transplantation. This entity is often called hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP), yet it is clear that the pathophysiology of transplant-associated HUS/TTP is different from that of classic HUS or TTP. Furthermore, the incidence of this syndrome varies from 0.5% to 76% in different transplant series, primarily because of the lack of a uniform definition. The toxicity committee of the Blood and Marrow Transplant Clinical Trials Network has reviewed the current literature on transplant-related HUS/TTP and recommends that it be henceforth renamed posttransplantation thrombotic microangiopathy (TMA). An operational definition for TMA based on the presence of microangiopathic hemolysis and renal and/or neurologic dysfunction is proposed. The primary intervention after diagnosis of TMA should be withdrawal of calcineurin inhibitors. Plasma exchange, although frequently used in this condition, has not been proven to be effective. In the absence of definitive trials, plasma exchange cannot be considered a standard of care for TMA. It is hoped that these positions will improve the identification and reporting of this devastating complication after hematopoietic stem cell transplantation and facilitate future clinical studies for its prevention and treatment.

  8. Targeted anti-thrombotic protein micelles

    PubMed Central

    Kim, Wookhyun; Haller, Carolyn; Dai, Erbin; Wang, Xiowei; Hagemeyer, Christoph E.; Liu, David R.; Peter, Karlheinz; Chaikof, Elliot L.

    2015-01-01

    Activated platelets provide a promising target for imaging inflammatory and thrombotic events along with site-specific delivery of a variety of therapeutic agents. Herein, we report the efficient design of multifunctional protein micelles bearing targeting and therapeutic proteins 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 efficient detection of thrombi. Inhibiting thrombus formation was subsequently accomplished by incorporating the catalytically active domain of thrombomodulin (TM) onto the micelle corona for local generation of activated protein C, which serves to inhibit thrombin formation. An effective strategy has been developed for preparation of protein micelles that can be targeted to sites of activated platelets with broad potential for treatment of acute thrombotic events. PMID:25504546

  9. Pernicious Anemia Associated Cobalamin Deficiency and Thrombotic Microangiopathy: Case Report and Review of the Literature

    PubMed Central

    Spinowitz, Bruce; Charytan, Chaim; Galler, Marilyn

    2017-01-01

    A 43-year-old Hispanic male without significant previous medical history was brought to emergency department for syncope following a blood draw to investigate a 40 lbs weight loss during the past 6 months associated with decreased appetite and progressive fatigue. The patient also reported a 1-month history of jaundice. On examination, he was hemodynamically stable and afebrile with pallor and diffuse jaundice but without skin rash or palpable purpura. Normal sensations and power in all extremities were evident on neurological exam. Presence of hemolytic anemia, schistocytosis, thrombocytopenia, and elevated lactate dehydrogenase (LDH) was suggestive of thrombotic thrombocytopenic purpura (TTP). However, presence of leukopenia, macrocytes, and an inadequate reticulocyte response to the degree of anemia served as initial clues to an alternative diagnosis. Two and one units of packed red blood cells were transfused on day 1 and day 3, respectively. In addition, one unit of platelets was transfused on day 2. Daily therapeutic plasma exchange (TPE) was initiated and continued until ADAMTS-13 result ruled out TTP. A low cobalamin (vitamin B12) level was evident at initial laboratory work-up and subsequent testing revealed positive intrinsic factor-blocking antibodies supporting a diagnosis of pernicious anemia with severe cobalamin deficiency. Hematological improvement was observed following vitamin B12 supplementation. The patient was discharged and markedly improved on day 9 with outpatient follow-up for cobalamin supplementation. PMID:28265287

  10. Pulmonary Endarterectomy in a Patient with Immune Thrombocytopenic Purpura

    PubMed Central

    Yıldızeli, Bedrettin; Yanartaş, Mehmed; Keskin, Sibel; Atagündüz, Işık; Altınay, Ece

    2015-01-01

    Immune thrombocytopenic purpura (ITP) patients are at high risk for bleeding complications regarding surgeries involving cardiopulmonary bypass. We report an ITP patient with chronic thromboembolic pulmonary hypertension who underwent uncomplicated pulmonary endarterectomy with receiving postoperative intravenous immunoglobulin (IVIG) therapy. The positive outcome of this case may suggest that pulmonary endarterectomy surgery is performed safely for ITP patients. PMID:26090264

  11. Thrombotic risk in the antiphospholipid syndrome.

    PubMed

    Lim, Wendy

    2014-10-01

    The antiphospholipid syndrome (APS) is characterized by venous or arterial thrombosis and/or pregnancy morbidity in patients with persistent presence of antiphospholipid antibodies (aPL). Patients who are diagnosed with APS are identified to have a high risk of recurrent thrombosis, which can occur despite anticoagulant therapy. The optimal type, intensity, and duration of anticoagulant therapy for the treatment of APS remain controversial issues, particularly for arterial thrombosis and recurrent thrombosis. Patients with persistently positive testing for lupus anticoagulant and elevated levels of anticardiolipin antibodies and anti-β2 glycoprotein I antibodies-known as triple positivity-appear to be at increased risk for thrombosis compared with patients who test positive for a single aPL. Recognizing that patients with APS may potentially have different thrombotic risk profiles may assist clinicians in assessing the risks, benefits, and optimal duration of anticoagulation. Future studies that delineate thrombotic risk in APS and evaluate current and novel anticoagulants as well as nonanticoagulant therapies are required.

  12. Multivessel Coronary Thrombosis in a Patient with Idiopathic Thrombocytopenic Purpura

    PubMed Central

    Yagmur, Julide; Cansel, Mehmet; Acikgoz, Nusret; Yagmur, Murat; Eyupkoca, Ferhat; Ermis, Necip; Akturk, Erdal

    2012-01-01

    A 49-year-old woman who had idiopathic thrombocytopenic purpura was admitted to our hospital with severe chest pain. Electrocardiography revealed inferolateral myocardial infarction. The patient underwent immediate coronary angiography, which revealed thrombi in the left coronary system. Percutaneous intervention was not indicated, because the thrombi had occluded the distal segments of multiple coronary arteries. Administration of tirofiban satisfactorily dissolved the thrombi. PMID:23304046

  13. 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

  14. Indicators of Acute and Persistent Renal Damage in Adult Thrombotic Microangiopathy

    PubMed Central

    Sucker, Christoph; Kuhr, Kathrin; Hollenbeck, Markus; Hetzel, Gerd R.; Burst, Volker; Teschner, Sven; Rump, Lars C.; Benzing, Thomas; Grabensee, Bernd; Kurschat, Christine E.

    2012-01-01

    Background Thrombotic microangiopathies (TMA) in adults such as thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are life-threatening disorders if untreated. Clinical presentation is highly variable and prognostic factors for clinical course and outcome are not well established. Methods We performed a retrospective observational study of 62 patients with TMA, 22 males and 40 females aged 16 to 76 years, treated with plasma exchange at one center to identify clinical risk factors for the development of renal insufficiency. Results On admission, 39 of 62 patients (63%) had acute renal failure (ARF) with 32 patients (52%) requiring dialysis treatment. High systolic arterial pressure (SAP, p = 0.009) or mean arterial pressure (MAP, p = 0.027) on admission was associated with acute renal failure. Patients with SAP>140 mmHg on admission had a sevenfold increased risk of severe kidney disease (OR 7.464, CI 2.097–26.565). MAP>100 mmHg indicated a fourfold increased risk for acute renal failure (OR 4.261, CI 1.400–12.972). High SAP, diastolic arterial pressure (DAP), and MAP on admission were also independent risk factors for persistent renal insufficiency with the strongest correlation for high MAP. Moreover, a high C-reactive protein (CRP) level on admission correlated with renal failure in the course of the disease (p = 0.003). At discharge, renal function in 11 of 39 patients (28%) had fully recovered, 14 patients (23%) remained on dialysis, and 14 patients (23%) had non-dialysis-dependent chronic kidney disease. Seven patients (11%) died. We identified an older age as risk factor for death. Conclusions High blood pressure as well as high CRP serum levels on admission are associated with renal insufficiency in TMA. High blood pressure on admission is also a strong predictor of sustained renal insufficiency. Thus, adult TMA patients with high blood pressure may require special attention to prevent persistent renal failure

  15. Complement-mediated thrombotic microangiopathy secondary to sepsis-induced disseminated intravascular coagulation successfully treated with eculizumab

    PubMed Central

    Abe, Tomohiro; Sasaki, Akira; Ueda, Taichiro; Miyakawa, Yoshitaka; Ochiai, Hidenobu

    2017-01-01

    Abstract Secondary thrombotic microangiopathies (TMAs) are induced by several underlying conditions; most are resolved by treating background disease. Eculizumab is a human monoclonal antibody that blocks the final stage of the complement system and effectively treats atypical hemolytic uremic syndrome (aHUS). In this report, we present a patient with TMA secondary to sepsis- induced coagulopathy, who was successfully treated with eculizumab. A 44-year-old woman, who had no special medical history or familial history of TMAs, was admitted on suspicion of septic shock. Physical examination revealed gangrene on her soles. Blood tests revealed a decreased platelet count, disseminated intravascular coagulation (DIC), renal dysfunction, hemolysis, and infection. Although the coagulation disorder improved with intensive care, the low platelet count, elevated lactate dehydrogenase levels, and renal dysfunction persisted. Our investigations subsequently excluded thrombotic thrombocytopenic purpura and Shiga toxin-producing Escherichia coli-induced HUS. Plasma exchange only improved lactate dehydrogenase levels. We clinically diagnosed this case as atypical HUS and started eculizumab treatment. The patient's platelet count increased, her renal dysfunction improved, and the gangrene on her feet was ameliorated. The patient was discharged without maintenance dialysis therapy after approximately 3 months. Subsequent tests revealed elevated serum levels of soluble C5b-9, and genetic testing revealed compound heterozygous c.184G > A (Val62Ile) and c.1204T > C (Tyr402His) single-nucleotide polymorphisms in complement factor H. We encountered a case of complement-mediated TMA accompanied by DIC, which was successfully treated with eculizumab. Further studies are necessary to support the optimal use of eculizumab for TMA with background diseases. PMID:28178155

  16. Thrombotic Microangiopathy in the Setting of HIV Infection: A Case Report and Review of the Differential Diagnosis and Therapy.

    PubMed

    Saab, Karim R; Elhadad, Sonia; Copertino, Dennis; Laurence, Jeffrey

    2016-08-01

    Before the modern era of HIV/AIDS therapeutics, which enabled a cascade of early recognition of infection, prompt initiation of effective antiretroviral therapies, and close follow-up, severe forms of microvascular clotting disorders known as thrombotic microangiopathies (TMAs) were frequent in the setting of advanced HIV disease. Their incidence was as high as 7% in the period 1984-1999, but fell dramatically, to <0.5%, by 2002. This profound change was predicated on one critical development: availability of new classes of anti-HIV drugs, enabling reduction and maintenance of HIV viral loads to undetectable levels. Another development in the period 1999-2002 related to TMA therapy: with recognition of autoantibodies against the von Willebrand factor cleaving protease ADAMTS13 as the etiology of most cases of one major form of TMA, thrombotic thrombocytopenic purpura, it permitted appropriate use of life-saving interventions based on plasma exchange and immune suppression. A more recent factor in TMA therapeutics was the 2011 approval by the US FDA and European EMA of eculizumab, a humanized monoclonal antibody against complement component C5, for the treatment of atypical hemolytic uremic syndrome, another major form of TMA. Despite these milestones, life- and organ-threatening TMAs still occur in untreated HIV disease and, to a much lesser extent, in those patients with suppressed viral loads. Confusion in terms of the differential diagnosis of these TMAs also impedes use of directed treatments. This report utilizes a case study of a young woman with advanced AIDS who presented with a severe TMA, characterized by coma and renal failure, to highlight the diagnostic and therapeutic challenges raised by complex hematologic conditions occurring in the setting of HIV.

  17. The utility of ADAMTS13 in differentiating TTP from other acute thrombotic microangiopathies: results from the UK TTP Registry.

    PubMed

    Hassan, Sevda; Westwood, John-Paul; Ellis, Debra; Laing, Chris; Mc Guckin, Siobhan; Benjamin, Sylvia; Scully, Marie

    2015-12-01

    Thrombotic microangiopathies (TMAs) are frequently difficult to differentiate clinically, and measurement of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) remains vital in thrombotic thrombocytopenic purpura (TTP) diagnosis. We retrospectively reviewed cases referred for ADAMTS13 testing, using UK TTP Registry screening data. Of a total 810 cases, 350 were confirmed as TTP. The 460 non-TTP cases comprised secondary TMAs (24·57%) and haemolytic uraemic syndrome (HUS) (27·17% aHUS, 2·83% Shiga-like toxin-producing E. coli [STEC]-HUS); the remainder were TMAs with no clear association, not TMAs, or had no confirmed diagnosis. ADAMTS13 levels were significantly lower in TTP than STEC-HUS, aHUS and other TMAs. TTP patients had significantly lower platelet count (15 × 10(9) /l; range 0-96) than aHUS (57 × 10(9) /l; range 13-145, P < 0·0001) or STEC-HUS (35 × 10(9) /l; range 14-106, P < 0·0001); they also had lower creatinine levels (92 μmol/l; range 43-374) than aHUS (255 μmol/l; range 23-941, P < 0·0001) and STEC-HUS (324 μmol/l; range 117-639, P < 0·0001). However, 12/34 (35·3%) aHUS patients had a platelet count <30 × 10(9) /l and 26/150 (17·3%) of TTP patients had a platelet count >30 × 10(9) /l; 23/150 (15·3%) of TTP patients had a creatinine level >150 μmol/l. This study highlights the wide variety of TMA presentations, and confirms the utility of ADAMTS13 testing in TTP diagnosis.

  18. Complement-mediated thrombotic microangiopathy secondary to sepsis-induced disseminated intravascular coagulation successfully treated with eculizumab: A case report.

    PubMed

    Abe, Tomohiro; Sasaki, Akira; Ueda, Taichiro; Miyakawa, Yoshitaka; Ochiai, Hidenobu

    2017-02-01

    Secondary thrombotic microangiopathies (TMAs) are induced by several underlying conditions; most are resolved by treating background disease. Eculizumab is a human monoclonal antibody that blocks the final stage of the complement system and effectively treats atypical hemolytic uremic syndrome (aHUS). In this report, we present a patient with TMA secondary to sepsis- induced coagulopathy, who was successfully treated with eculizumab.A 44-year-old woman, who had no special medical history or familial history of TMAs, was admitted on suspicion of septic shock. Physical examination revealed gangrene on her soles. Blood tests revealed a decreased platelet count, disseminated intravascular coagulation (DIC), renal dysfunction, hemolysis, and infection. Although the coagulation disorder improved with intensive care, the low platelet count, elevated lactate dehydrogenase levels, and renal dysfunction persisted. Our investigations subsequently excluded thrombotic thrombocytopenic purpura and Shiga toxin-producing Escherichia coli-induced HUS. Plasma exchange only improved lactate dehydrogenase levels. We clinically diagnosed this case as atypical HUS and started eculizumab treatment. The patient's platelet count increased, her renal dysfunction improved, and the gangrene on her feet was ameliorated. The patient was discharged without maintenance dialysis therapy after approximately 3 months. Subsequent tests revealed elevated serum levels of soluble C5b-9, and genetic testing revealed compound heterozygous c.184G > A (Val62Ile) and c.1204T > C (Tyr402His) single-nucleotide polymorphisms in complement factor H.We encountered a case of complement-mediated TMA accompanied by DIC, which was successfully treated with eculizumab. Further studies are necessary to support the optimal use of eculizumab for TMA with background diseases.

  19. Impact of severe ADAMTS13 deficiency on clinical presentation and outcomes in patients with thrombotic microangiopathies: the experience of the Harvard TMA Research Collaborative.

    PubMed

    Bendapudi, Pavan K; Li, Ang; Hamdan, Ayad; Uhl, Lynne; Kaufman, Richard; Stowell, Christopher; Dzik, Walter; Makar, Robert S

    2015-12-01

    The Harvard TMA Research Collaborative is a multi-institutional registry-based effort to study thrombotic microangiopathies (TMA). Laboratory and clinical parameters were recorded for 254 cases of suspected autoimmune thrombotic thrombocytopenic purpura (TTP). Patients with severe ADAMTS13 deficiency (activity ≤10%, N = 68) were more likely to be young, female and without a history of cancer treatment or transplantation. While all patients with severe deficiency were diagnosed with autoimmune TTP, those without severe deficiency frequently had disseminated intravascular coagulation, drug-associated TMA and transplant-related TMA. Patients with severe ADAMTS13 deficiency had superior overall survival at 360 d compared to those without severe deficiency (93·0% vs. 47·5%, P < 0·0001). Almost all patients with severe deficiency received therapeutic plasma exchange (TPE), but the use of TPE in patients with ADAMTS13 activity >10% varied significantly across the institutions in our consortium (13·2-63·8%, P < 0·0001). Nevertheless, 90-d mortality was not different in patients with ADAMTS13 activity >10% between the three hospitals (P = 0·98). Our data show that patients with severe ADAMTS13 deficiency represent a clinically distinct cohort that responds well to TPE. In contrast, TMA without severe ADAMTS13 deficiency is associated with increased mortality that may not be influenced by TPE.

  20. DRESS syndrome and thrombotic thrombocytopaenic purpura: are they related?

    PubMed Central

    Sandouk, Zahrae; Alirhayim, Zaid; Khoulani, Dania; Hassan, Syed

    2012-01-01

    A middle-aged man diagnosed with a drug reaction with eosinophilia and systemic symptom (DRESS) syndrome, secondary to phenytoin use, subsequently developed thrombotic thrombocytopaenic purpura. The patient improved with steroids and plasmapheresis. Their diagnosis can be challenging, and an early recognition and treatment are critical owing to their high mortality rates. Both diseases are thought to be of an autoimmune origin, and a potential relationship between them led to the consideration of the DRESS syndrome as an aetiology for thrombotic thrombocytopaenic purpura in this case. We concluded that two possibilities exist: some type of antibody developed during the clinical presentation of DRESS syndrome and subsequently resulted in an inhibition of a disintegrin and metalloproteinase with a thrombospondin type-1 motif, member 13 (ADAMTS13) leading to thrombotic thrombocytopaenic purpura, or perhaps this patient's autoimmune predisposition to thrombotic thrombocytopaenic purpura contributed to the drug reaction. PMID:23152183

  1. Hospital-acquired pneumonia and bacteremia caused by Legionella pneumophila in an immunocompromised patient.

    PubMed

    Lai, C-C; Tan, C-K; Chou, C-H; Hsu, H-L; Huang, Y-T; Liao, C-H; Hsueh, P-R

    2010-04-01

    The Legionella species is an important cause of communityand hospital-acquired pneumonia. Bacteremic pneumonia caused by L. pneumophila is rarely reported. We describe the first reported case of hospital-acquired pneumonia and bacteremia caused by L. pneumophila from Taiwan in a patient with idiopathic thrombocytopenic purpura who received steroid treatment. The patient was successfully treated with ceftazidime and clindamycin initially, followed by ciprofloxacin for 14 days. The blood isolate was further confirmed by 16S rDNA sequence analysis.

  2. 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.

  3. Thrombotic microangiopathy associated with monoclonal gammopathy.

    PubMed

    Ravindran, Aishwarya; Go, Ronald S; Fervenza, Fernando C; Sethi, Sanjeev

    2017-03-01

    Thrombotic microangiopathy (TMA) is a rare disease comprising of a diverse set of disorders linked by a common histologic finding of endothelial injury. Monoclonal immunoglobulins may act as a potential trigger in the pathogenesis of TMA. To determine the prevalence of monoclonal gammopathy and clinicopathological features of TMA associated with monoclonal immunoglobulin, we performed a retrospective study in adults (18 and older) with a clinical diagnosis of TMA. Of 146 patients with TMA, we detected monoclonal immunoglobulin in 20 patients (13.7%). Among patients 50 and older, the prevalence of monoclonal gammopathy was 21%, which is approximately five-fold higher than the 4.2% expected rate in this population. Fifteen patients had monoclonal gammopathy of undetermined significance, one had multiple myeloma, one with smoldering myeloma, two had POEMS syndrome, and one had T-cell lymphocytic leukemia. Renal biopsy was performed in 15 cases, of which six showed thrombi, 11 showed mesangiolysis, and all showed double contours along glomerular capillary walls. Acute tubular injury was present in 12 cases. Treatment options were varied and included therapeutic plasma exchange in 11 patients. Ten patients progressed to end-stage renal disease, of which two received kidney transplant. Thus, our study shows an unexpectedly high prevalence of monoclonal gammopathy in patients with TMA, suggesting a potential pathogenetic mechanism. This study underscores the importance of evaluating for a monoclonal gammopathy in patients with TMA as well as the potential for targeting the underlying hematologic disorder as an approach to treating TMA.

  4. A perspective on the measurement of ADAMTS13 in thrombotic thrombocytopaenic purpura.

    PubMed

    Pimanda, John E; Chesterman, Colin N; Hogg, Philip J

    2003-04-01

    The recent discovery of the von Willebrand Factor (vWF) cleaving protease (ADAMTS13) and the association of its deficiency with thrombotic thrombocytopaenic purpura (TTP) has generated both enormous interest and considerable confusion. Ultra large von Willebrand Factor (UL vWF) multimers are present in the plasmas of patients with chronic relapsing TTP in remission but disappear during an attack. This observation led to the recognition that UL vWF multimers precipitate the thrombotic occlusion of arterioles, a feature that characterizes TTP. Multiple mutations in ADAMTS13 are associated with congenital TTP and neutralizing autoantibodies have been demonstrated in the acquired TTP syndrome. Although a number of functional assays for this enzyme have been described, the more rigorously evaluated assays are difficult to perform outside a research laboratory. There is also an enduring uncertainty about the specificity of ADAMTS13 deficiency for the diagnosis of acquired TTP and a perception that the result does not alter patient management. The cloning of the ADAMTS13 gene has also raised the prospect of recombinant enzyme therapy for the treatment of TTP, and this has heightened the need for a simple assay. In this review, we evaluate the value of measuring this enzyme in the management of TTP.

  5. 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.

  6. Immune thrombocytopenic purpura might be an early hematologic manifestation of undiagnosed human immunodeficiency virus infection.

    PubMed

    Lai, Shih-Wei; Lin, Hsien-Feng; Lin, Cheng-Li; Liao, Kuan-Fu

    2017-03-01

    Little research focuses on the association between immune thrombocytopenic purpura and human immunodeficiency virus infection in Taiwan. This study investigated whether immune thrombocytopenic purpura might be an early hematologic manifestation of undiagnosed human immunodeficiency virus infection in Taiwan. We conducted a retrospective population-based cohort study using data of individuals enrolled in Taiwan National Health Insurance Program. There were 5472 subjects aged 1-84 years with a new diagnosis of immune thrombocytopenic purpura as the purpura group since 1998-2010 and 21,887 sex-matched and age-matched, randomly selected subjects without immune thrombocytopenic purpura as the non-purpura group. The incidence of human immunodeficiency virus infection at the end of 2011 was measured in both groups. We used the multivariable Cox proportional hazards regression model to measure the hazard ratio and 95 % confidence interval (CI) for the association between immune thrombocytopenic purpura and human immunodeficiency virus infection. The overall incidence of human immunodeficiency virus infection was 6.47-fold higher in the purpura group than that in the non-purpura group (3.78 vs. 0.58 per 10,000 person-years, 95 % CI 5.83-7.18). After controlling for potential confounding factors, the adjusted HR of human immunodeficiency virus infection was 6.3 (95 % CI 2.58-15.4) for the purpura group, as compared with the non-purpura group. We conclude that individuals with immune thrombocytopenic purpura are 6.47-fold more likely to have human immunodeficiency virus infection than those without immune thrombocytopenic purpura. We suggest not all patients, but only those who have risk factors for human immunodeficiency virus infection should receive testing for undiagnosed human immunodeficiency virus infection when they develop immune thrombocytopenic purpura.

  7. A Case of Immune Thrombocytopenic Purpura Secondary to Pulmonary Tuberculosis

    PubMed Central

    Meher, Lalit Kumar; Dalai, Siba Prasad; Nayak, Sachidananda; Tripathy, Sujit Kumar

    2016-01-01

    The haematological abnormalities associated with active pulmonary tuberculosis were known to human beings since decades but Immune Thrombocytopenic Purpura (ITP) secondary to pulmonary tuberculosis have been reported only in a couple of instances. We report a 27 year-old male patient who was admitted to our hospital with fever, shortness of breath, haematuria, epistaxis and generalized petechiae. The sputum positivity for Acid Fast Bacilli (AFB) and chest X-ray reports were suggestive of active pulmonary tuberculosis in our patient. Clinical and laboratory parameters including bone marrow aspiration cytology diagnosed the case to be ITP. Patient was put on Directly Observed Treatment and Short course (DOTS) category-1 Anti-Tuberculosis Therapy (ATT) and prednisone following which thrombocytopenia was corrected and there was complete recovery of the patient without recurrence of thrombocytopenia. PMID:27891382

  8. Thrombotic Microangiopathy Revealing Bone Metastases from an Ethmoid Sinus Carcinoma

    PubMed Central

    Morisse, Mony Chenda; Kontar, Loay; Bihan, Céline; Boone, Mathieu; Lachaier, Emma; Titeca-Beauport, Dimitri; Maizel, Julien; Chauffert, Bruno

    2016-01-01

    Cancer-related thrombotic microangiopathy (TMA) is a rare entity whose clinical and biological characteristics have been described in various tumors. Here we describe the first case of cancer-related TMA revealing diffuse bone metastases from an ethmoid sinus carcinoma. PMID:27721770

  9. Acquired hyperpigmentations*

    PubMed Central

    Cestari, Tania Ferreira; Dantas, Lia Pinheiro; Boza, Juliana Catucci

    2014-01-01

    Cutaneous hyperpigmentations are frequent complaints, motivating around 8.5% of all dermatological consultations in our country. They can be congenital, with different patterns of inheritance, or acquired in consequence of skin problems, systemic diseases or secondary to environmental factors. The vast majority of them are linked to alterations on the pigment melanin, induced by different mechanisms. This review will focus on the major acquired hyperpigmentations associated with increased melanin, reviewing their mechanisms of action and possible preventive measures. Particularly prominent aspects of diagnosis and therapy will be emphasized, with focus on melasma, post-inflammatory hyperpigmentation, periorbital pigmentation, dermatosis papulosa nigra, phytophotodermatoses, flagellate dermatosis, erythema dyschromicum perstans, cervical poikiloderma (Poikiloderma of Civatte), acanthosis nigricans, cutaneous amyloidosis and reticulated confluent dermatitis PMID:24626644

  10. Changes in splenic microcirculatory pathways in chronic idiopathic thrombocytopenic purpura.

    PubMed

    Schmidt, E E; MacDonald, I C; Groom, A C

    1991-09-15

    The spleen plays a central role in the pathogenesis of chronic idiopathic thrombocytopenic purpura (ITP); it produces massive quantities of antiplatelet antibodies, leading to accelerated phagocytosis of platelets. Lymphoid hyperplasia typically occurs in the spleen, characterized by large numbers of lymphatic nodules with active germinal centers. Whether changes in splenic microcirculatory pathways also occur is not known. We have studied this question by scanning electron microscopy of corrosion casts, comparing spleens removed from patients with ITP with normal spleens obtained from organ transplant donors. The casts demonstrate two major changes in microcirculatory pathways in ITP. Firstly, a striking proliferation of arterioles and capillaries is found in the white pulp and marginal zone (MZ), seen as extensive vascularization in 92.3% of lymphatic nodules (n = 191) versus 0.6% (n = 224) in normal spleens. Secondly, the marginal sinus, a series of flattened, anastomosing vascular spaces between the white pulp and MZ, is absent in 89.4% of lymphatic nodules versus 4.9% in normal spleens. The cause of these microcirculatory changes, which may not be exclusive to ITP, is presently unknown. Absence of the marginal sinus may affect distribution of blood flow through the MZ such that platelets spend increased amounts of time in the proximity of macrophages. In the presence of antiplatelet antibodies found in ITP spleens, this delayed transit would lead to greatly increased platelet destruction.

  11. 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.

  12. 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.

  13. Pulmonary Tumor Thrombotic Microangiopathy: A New Paraneoplastic Syndrome?

    PubMed

    Carter, Corey A; Scicinski, Jan J; Lybeck, Harry E; Oronsky, Bryan T

    2016-01-01

    This report, based on data from a clinical case, proposes that pulmonary tumor thrombotic microangiopathy, an underdiagnosed cause of pulmonary hypertension and death in patients with adenocarcinoma, is a paraneoplastic syndrome (PNS). Clinicians in general must be alert to the presence or development of PNS that may precede, coincide with, follow, or herald the recurrence or the primary diagnosis of malignancy since early recognition facilitates prompt diagnosis and treatment.

  14. A systematic review of anti-thrombotic therapy in epistaxis.

    PubMed

    Musgrave, K M; Powell, J

    2016-12-01

    There is limited guidance available to clinicians regarding the management of antithrombotic therapy during epistaxis, whilst there has been an increase in the use of anticoagulation and antiplatelet therapy. In addition, the introduction of direct oral anticoagulants (DOACs), such as dabigatran and rivaroxaban, over the last decade has significantly increased the complexity of managing the anticoagulated epistaxis patient. We undertook a systemic literature review investigating potential management strategies for each class of anti-thrombotic therapy during epistaxis. A PubMED and Cochrane Library search was performed on 10/03/16 using, but not limited to, the search terms epistaxis, nosebleed, nose bleeding, nasal haemorrhage, nasal bleeding AND each of the following search terms: antithrombotic, anticoagulant, antiplatelet, aspirin, clopidogrel, warfarin, dabigatran, rivaroxaban, apixaban and tranexamic acid. This yielded 3815 results, of which 29 were considered relevant. Other sources such as national and international guidelines related to the management of anti-thrombotics were also utilised. We present the findings related to the management of each class of anti-thrombotic therapy during epistaxis. Overall we found a lack of evidence regarding this topic and further high quality research is needed. This is an area growing in complexity and the support of colleagues in Haematology and Cardiology is increasingly important.

  15. [Dental treatment and anti-thrombotic therapy. Part II: the era of new anti-thrombotic drugs].

    PubMed

    Chackartchi, T; Sachar Helft, S; Findler, M

    2014-01-01

    Surgical intra-oral treatment for patients under antithrombotic therapy presents a challenge for the dental team. Within the last few years evidence based systematic reviews established new clinical guidelines for wide groups of patients which need to use antithrombotic treatment. The expected increase in use of antithrombotic treatment forced the pharmaceutical industry to provide new treatments. The former anticoagulant and anti-platelets aggregation groups of drugs were limited to small variety of medication. The search for the new treatments with ideal properties led to newly invented groups of drugs. In this article we will describe the new advancements in anti-thrombotic treatments. The article will summarize the limited knowledge of surgical management of patients under the new anti-thrombotic medications and the recommended approach for oral surgical procedures.

  16. Extracellular ATP metabolism on vascular endothelial cells: A pathway with pro-thrombotic and anti-thrombotic molecules.

    PubMed

    Fuentes, Eduardo; Palomo, Iván

    2015-12-01

    Vascular endothelial contributes to the metabolism and interconversion of extracellular adenine nucleotides via ecto-ATPase/ADPase (CD39) and ecto-5'nucleotidase (CD73) activities. These enzymes collectively dephosphorylate ATP, ADP, and AMP with the production of additional adenosine. In the vascular system, adenine nucleotides (ATP and ADP) and nucleoside adenosine represent an important class of extracellular molecules involved in modulating the processes linked to vascular thrombosis exerting various effects in platelets. Yet, the mechanisms by which the extracellular ATP metabolism in the local environment trigger pro-thrombotic and anti-thrombotic states are yet to be fully elucidated. In this article, the relative contribution of extracellular ATP metabolism in platelet regulation is explored.

  17. 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.

  18. /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.

  19. Congenital and acquired ADAMTS13 deficiency: Two mechanisms, one patient.

    PubMed

    Ferrari, Barbara; Cairo, Andrea; Pontiggia, Silvia; Mancini, Ilaria; Masini, Luciano; Peyvandi, Flora

    2015-08-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening microangiopathy with a heterogeneous and largely unpredictable course. It is caused by ADAMTS13 deficiency, that can be either congenital or due to anti-ADAMTS13 autoantibodies development. ADAMTS13 deficiency is necessary but not always sufficient to cause acute clinical manifestations and trigger factors may be needed. We report the case of a woman diagnosed with congenital TTP in her adulthood, presenting with anti-ADAMTS13 autoantibodies in acute phase during ticlopidine consumption. Noteworthy, the two ADAMTS13 mutations identified in this patient are novel: one is a splice-site mutation located in intron 11 (c.1308+2_5delTAGG) and the other is a point missense mutation in exon 29 (c.4184T>C leading to p.Leu1395Pro substitution). Since congenital TTP is an extremely rare disease and drug-induced TTP is an uncommon side effect of treatment with ticlopidine, the simultaneous occurrence of both mechanisms of disease in one patient is exceptional. This case represents TTP as a multifactorial disease, with ADAMTS13 genetic abnormality and environmental exposures acting together in determining individual clinical phenotype.

  20. Predicting post-traumatic stress and health anxiety following a venous thrombotic embolism.

    PubMed

    Bennett, Paul; Patterson, Katie; Noble, Simon

    2016-05-01

    This research identified psychosocial factors associated with post-traumatic stress and health anxiety following a venous thrombotic embolism. In all, 158 participants, largely registered with a venous thrombotic embolism information website (Lifeblood: The Thrombosis Charity), completed an online survey. Post-traumatic symptom scores were linked to health threat, and not moderated by perceived control over risk for further venous thrombotic embolism. Health anxiety was associated with continuing symptoms and a negative emotional response to the venous thrombotic embolism. There is a need to intervene to reduce both short- and long-term distress in this population, ideally using a stepped-care model.

  1. Severe thrombotic events associated with dengue fever, Brazil.

    PubMed

    da Costa, Paulo Sérgio Gonçalves; Ribeiro, Geyza Machado; Junior, Cleber Soares; da Costa Campos, Lenilton

    2012-10-01

    Dengue fever has been a major problem in hospital settings in Brazil for the past 15 years. The main concern has been the severe forms, i.e., dengue hemorrhagic fever and dengue shock syndrome. Hemorrhagic events of different degrees have also been a major concern. We report five cases of large vein thrombotic events associated with the acute phase of dengue fever, including a previously non-reported case of mesenteric vein thrombosis. Complications such as these could have been overlooked in the diagnosis of dengue fever, given that the major concern is the hemorrhagic event.

  2. Pulmonary tumor thrombotic microangiopathy caused by prostate carcinoma

    PubMed Central

    Kuriyama, Keiko; Kinoshita, Tatsuya; Nagai, Keisuke; Hongyo, Hidenari; Kishimoto, Kentaro; Inoue, Atsuo; Takamura, Manabu; Choi, Soomi

    2016-01-01

    Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal malignancy-related condition that involves rapidly progressing hypoxia and pulmonary hypertension. We report a case of PTTM caused by prostate carcinoma, which was diagnosed before autopsy in an 81-year-old man. Computed tomography showed diffuse ground-glass opacities, consolidation, and small nodules in the peripheral regions of the lung. Autopsy showed adenocarcinoma cells embolizing small pulmonary arteries with fibrocellular intimal proliferation, which was consistent with PTTM caused by prostate carcinoma. PMID:27635254

  3. Relapsing thrombotic microangiopathy and intravenous sustained-release oxycodone

    PubMed Central

    Nataatmadja, Melissa; Divi, Dakshinamurthy

    2016-01-01

    Thrombotic microangiopathy (TMA) associated with injecting sustained-release oxymorphone, an opioid intended for oral use, has previously been reported. We report a case of TMA secondary to intravenous use of sustained-release oxycodone, and the first case to demonstrate relapsing disease due to persistent intravenous opioid use. In cases such as these, TMA is suspected to be due to a polyethylene oxide (PEO) coating found on these drugs, and the disease is likely due to a directly toxic effect of PEO to endothelial cells. We hypothesize that there are unidentified genetic predispositions causing some persons to be susceptible to developing this disease. PMID:27478601

  4. Incidence and interventions for post-thrombotic syndrome

    PubMed Central

    Sutter, Christopher; Tavri, Sidhartha; Patel, Indravadan

    2016-01-01

    Post-thrombotic syndrome (PTS) is a venous stress disorder that develops from long-term effects from a previous deep venous thrombosis (DVT). The morbidity associated with PTS may be significant and patients can present with edema, chronic pain, swelling, skin changes, and heaviness of the affected limb. PTS can eventually lead to a decreased quality of life and to a marked burden for the healthcare system. This article elaborates on clinical aspects of PTS including the pathophysiology, diagnostic work-up and management of the disease with a particular focus on endovascular options. PMID:28123982

  5. Thrombotic complications of implanted central venous access devices: prospective evaluation.

    PubMed

    Labourey, Jean-Luc; Lacroix, Philippe; Genet, Dominique; Gobeaux, François; Martin, Jean; Venat-Bouvet, Laurence; Lavau-Denes, Sandrine; Maubon, Antoine; Tubiana-Mathieu, Nicole

    2004-05-01

    Implanted venous access devices (IVAD) are routinely used in oncologic patients. Thrombotic complication is a source of morbidity. During one year 246 patients with different solid neoplastic diseases received IVAD for chemotherapy administration. Two hundred forty-nine IVAD were placed percutaneously or by surgical cutdown. IVAD were flushed immediately after implantation with 3-5 mL of heparinized saline (100 U/mL). No monthly flush was required. A prospective evaluation of thrombotic complications was realised. in event of catheter dysfunction and/or clinical symptoms of phlebitis, a catheter opacification and/or a Doppler ultrasonography were performed. Twenty-three catheter dysfunctions were noted, corresponding to 13 catheter occlusions. Twelve patients presented clinical symptoms of phlebitis. Eleven venous thrombosis were diagnosed in this group; 10 by echo-Doppler and one by scanography. A unvaried statistic analysis using Fisher's test was performed to detect risk factors. Two factors were identified: the position of catheter tip above T4 (p < 0.001) and mediastinal or cervical lymph nodes larger than 6 cm (p < 0.001). The first increased the risk of catheter occlusion and the second increased the risk of phlebitis.

  6. In vitro Anti-Thrombotic Activity of Extracts from Blacklip Abalone (Haliotis rubra) Processing Waste

    PubMed Central

    Suleria, Hafiz Ansar Rasul; Hines, Barney M.; Addepalli, Rama; Chen, Wei; Masci, Paul; Gobe, Glenda; Osborne, Simone A.

    2016-01-01

    Waste generated from the processing of marine organisms for food represents an underutilized resource that has the potential to provide bioactive molecules with pharmaceutical applications. Some of these molecules have known anti-thrombotic and anti-coagulant activities and are being investigated as alternatives to common anti-thrombotic drugs, like heparin and warfarin that have serious side effects. In the current study, extracts prepared from blacklip abalone (Haliotis rubra) processing waste, using food grade enzymes papain and bromelain, were found to contain sulphated polysaccharide with anti-thrombotic activity. Extracts were found to be enriched with sulphated polysaccharides and assessed for anti-thrombotic activity in vitro through heparin cofactor-II (HCII)-mediated inhibition of thrombin. More than 60% thrombin inhibition was observed in response to 100 μg/mL sulphated polysaccharides. Anti-thrombotic potential was further assessed as anti-coagulant activity in plasma and blood, using prothrombin time (PT), activated partial thromboplastin time (aPTT), and thromboelastography (TEG). All abalone extracts had significant activity compared with saline control. Anion exchange chromatography was used to separate extracts into fractions with enhanced anti-thrombotic activity, improving HCII-mediated thrombin inhibition, PT and aPTT almost 2-fold. Overall this study identifies an alternative source of anti-thrombotic molecules that can be easily processed offering alternatives to current anti-thrombotic agents like heparin. PMID:28042854

  7. Nanomedicine as a strategy to fight thrombotic diseases

    PubMed Central

    Varna, Mariana; Juenet, Maya; Bayles, Richard; Mazighi, Mikael; Chauvierre, Cédric; Letourneur, Didier

    2015-01-01

    This review highlights the preclinical and clinical research based on the use of nano- and micro-carriers in thrombolytic drug delivery. Ischemic heart and stroke caused by thrombosis are the main causes of death in the world. Because of their inactivation in the blood, high doses of thrombolytics are administered to patients, increasing the risk of intracranial hemorrhage. Preclinical research conducted with lipid, polymer or magnetic nanoparticles loaded with thrombolytic drugs showed an enhancement of thrombolysis and a reduction of undesirable side effects. Targeted nanocarriers exhibited an increased accumulation into clot. Clinical trials were already conducted with lipid-based microbubbles combined with ultrasound and thrombolytic drug and showed thrombolysis improvement. Future validation of nanosystems is awaited in clinic. This research opens new strategies for the management of thrombotic diseases. PMID:28031907

  8. Thrombotic manifestations in SAPHO syndrome. Review of the literature.

    PubMed

    Carranco-Medina, Tatiana Elizabeth; Hidalgo-Calleja, Cristina; Calero-Paniagua, Ismael; Sánchez-González, María Dolores; Quesada-Moreno, Alba; Usategui-Martín, Ricardo; Pérez-Garrido, Laura; Gómez-Castro, Susana; Montilla-Morales, Carlos Alberto; Martínez-González, Olga; Del Pino-Montes, Javier

    2015-01-01

    SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is a cluster of osteo-cutaneous manifestations that can lead to serious complications such as thrombosis of the subclavian vein or superior vena cava, mainly in patients with significant inflammatory involvement of the anterior-chest-wall. The objective of this study was to review the cases published in the medical literature related with the presence of thrombotic complications in patients diagnosed with SAPHO syndrome and to try to determine their possible pathogenic mechanism and risk factors. We analyzed 11 published reports of isolated clinical cases or case series, a total of 144 patients, which described a total of 15 cases of venous thrombosis. The clinical characteristics of these patients, evaluated to determine whether they meet the ASAS criteria for axial and peripheral spondyloarthritis, is analyzed the need for early diagnosis and treatment is highlighted.

  9. Heparin-induced thrombocytopenia with thrombotic sequelae: a review.

    PubMed

    Goor, Yoav; Goor, Odelia; Eldor, Amiram

    2002-08-01

    Heparin-induced thrombocytopenia (HIT) occurs in 1-5% of patients treated with heparin. The pathogenesis involves the formation of antibodies to heparin-platelet factor 4 complexes, and the major clinical sequelae are thrombotic. Diagnosis is based on a combination of clinical and laboratory data. Treatment consists of stopping heparin, but, insofar as the risk of thrombosis remains high, treatment by alternative antithrombotic agents is indicated. Most clinical experience has been with danaparoid sodium and hirudin. The use of low-molecular-weight heparins (LMWH) in subsequent HIT episodes has been described, but is not recommended, especially with the introduction of new agents, such as oral thrombin inhibitors and pentasaccharides, which are hoped to reduce the use of heparins and the occurrence of HIT.

  10. Thrombotic microangiopathy due to Viperidae bite: Two case reports

    PubMed Central

    Dineshkumar, T.; Dhanapriya, J.; Sakthirajan, R.; Thirumalvalavan, K.; Kurien, A. A.; Balasubramaniyan, T.; Gopalakrishnan, N.

    2017-01-01

    Snake bite is mainly an occupational hazard and causes serious health problems in rural India. Acute kidney injury (AKI) occurs in 5-30% cases. Renal pathologic findings include acute tubular necrosis, cortical necrosis, interstitial nephritis, glomerulonephritis, and vasculitis. Thrombotic microangiopathy (TMA) occurrence after a snake bite is reported rarely. Here, we present two patients who developed TMA after viper bite treated with hemodialysis and plasmapheresis. Renal biopsy showed fibrin thrombi in glomeruli and arterioles with cortical necrosis. One patient progressed to end-stage renal disease and other was lost to follow-up. TMA should be considered as a possible pathogenesis of AKI after snake bite. The role of plasma exchanges in snake bite TMA is yet to be defined. PMID:28356675

  11. Rapidly progressive lupus nephritis and concomitant thrombotic microangiopathy.

    PubMed

    Gharbi, Chems; Bourry, Edward; Rouvier, Philippe; Hacini, Sabria; Letaief, Ahmed; Baumelou, Alain; Izzedine, Hassane

    2010-10-01

    Although uncommon, thrombotic microangiopathy (TMA) is one of the most serious complications in patients with systemic lupus erythematosus. A 30-year-old black woman admitted to our hospital because of fever, fatigue, 'dark' urine and rapidly progressive renal failure was found to have systemic lupus erythematous and atypical hemolytic uremic syndrome. Kidney biopsy showed WHO class IV lupus nephritis with crescents and TMA. Hemodialysis was initiated for worsening renal failure. The patient was treated with corticosteroids, monthly pulse intravenous Cyclophosphamide, plasmapheresis and Rituximab on a weekly basis for 4 weeks. The patient's blood pressure was aggressively controlled using antihypertensive agents. Despite this extensive therapy, she remained dialysis dependent although hematological parameters returned to normal values.

  12. Hand-assisted laparoscopic splenectomy for idiopathic thrombocytopenic purpura during pregnancy.

    PubMed

    Iwase, K; Higaki, J; Yoon, H E; Mikata, S; Tanaka, Y; Takahashi, T; Hatanaka, K; Tamaki, T; Hori, S; Mitsuda, N; Kamiike, W

    2001-02-01

    A successful case of a hand-assisted laparoscopic splenectomy with low-pressure pneumoperitoneum for autoimmune thrombocytopenic purpura in a patient at 23 weeks' gestation is reported. Preoperative splenic arterial embolization was performed on the same day as the operation using painless contour embolic material and super-absorbent polymer microspheres. The abdominal wall retraction method first was applied to avoid the effects of pneumoperitoneum on systemic hemodynamic alterations. However, a sufficient surgical view could not be obtained, as the intra-abdominal organs were elevated because of the enlarged uterus. A surgical view with 4 to 6-mm Hg pneumoperitoneum was available for the hand-assisted splenectomy. The postoperative course was uneventful, and the patient vaginally delivered a healthy infant. A hand-assisted laparoscopic splenectomy with low-pressure pneumoperitoneum after splenic arterial embolization would be feasible for patients with autoimmune thrombocytopenic purpura during a relatively advanced pregnancy.

  13. Acute Thrombotic Mesenteric Ischemia: Primary Endovascular Treatment in Eight Patients

    SciTech Connect

    Gagniere, Johan; Favrolt, Gregory; Alfidja, Agaiecha; Kastler, Adrian; Chabrot, Pascal; Cassagnes, Lucie; Buc, Emmanuel; Pezet, Denis; Boyer, Louis

    2011-10-15

    Introduction: The purpose of this study was to evaluate our experience with initial percutaneous transluminal angioplasty (PTA) {+-} stenting as valuable options in the acute setting. Methods: Between 2003 and 2008, eight patients with abdominal angio-MDCT-scan proven thrombotic AMI benefited from initial PTA {+-} stenting. We retrospectively assessed clinical and radiological findings and their management. Seven patients presented thrombosis of the superior mesenteric artery, and in one patient both mesenteric arteries were occluded. All patients underwent initial PTA and stenting, except one who had balloon PTA alone. One patient was treated by additional in situ thrombolysis. Results: Technical success was obtained in all patients. Three patients required subsequent surgery (37.5%), two of whom had severe radiological findings (pneumatosis intestinalis and/or portal venous gas). Two patients (25%) died: both had NIDD, an ASA score {>=}4, and severe radiologic findings. Satisfactory arterial patency was observed after a follow-up of 15 (range, 11-17) months in five patients who did not require subsequent surgery, four of whom had abdominal guarding but no severe CT scan findings. One patient had an ileocecal stenosis 60 days after the procedure. Conclusions: Initial PTA {+-} stenting is a valuable alternative to surgery for patients with thrombotic AMI even for those with clinical peritoneal irritation signs and/or severe radiologic findings. Early surgery is indicated if clinical condition does not improve after PTA. The decision of a subsequent surgery must be lead by early clinical status reevaluation. In case of underlying atherosclerotic lesion, stenting should be performed after initial balloon dilatation.

  14. 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.

  15. Acquired Cystic Kidney Disease

    MedlinePlus

    ... They Work Kidney Disease A-Z Acquired Cystic Kidney Disease What is acquired cystic kidney disease? Acquired cystic kidney disease happens when a ... cysts. What are the differences between acquired cystic kidney disease and polycystic kidney disease? Acquired cystic kidney ...

  16. A Platelet Acquired Storage Pool Disorder Associated with Tamoxifen Therapy

    PubMed Central

    Nayak, Lalitha; Schmaier, Alvin H.

    2012-01-01

    The antiestrogenic drug tamoxifen, used in patients with breast cancer, is associated with an increase in arterial and venous thrombotic events, the mechanism of which is not clearly understood. We report a case of a lady who presented with new bruising and prolonged bleeding following a tooth extraction 4–6 weeks after starting tamoxifen. Investigations were consistent with an acquired platelet storage pool disorder. Repeat platelet function analysis was normal, performed 3 months after discontinuation of tamoxifen. We present a previously clinically unreported effect of tamoxifen on platelet function. PMID:23326738

  17. Level of IL-16 and Reticulated Platelets Percentage during the Clinical Course of Immune Thrombocytopenic Purpura in Children.

    PubMed

    Abd El-Glil, Reem R; Assar, Effat H

    2015-01-01

    Immune thrombocytopenic purpura (ITP) is an immune-mediated acquired disease with transient or persistent decrease of thrombocytes number in the blood. Cytokines play important roles in the immune regulation and are known to be deregulated in autoimmune diseases. This study aimed to investigate serum IL-16 levels in relation to reticulated platelets in children with ITP and platelet count. Twenty six children with ITP (11 with newly diagnosed ITP, 9 with persistent ITP and 6 with chronic ITP) and 12 age-matched healthy children controls were studied. Serum level of IL-16 and reticulated platelets count were assessed by Enzyme Linked Immunosorbent Assay (ELISA) and flow cytometry respectively. Serum IL-16 levels were significantly higher in patients as compared to controls (P < 0.001). Within patients, the levels were higher in newly diagnosed compared to persistent and chronic ITP (P < 0.01) and (P < 0.001) respectively. IL-16 levels were also significantly higher in persistent ITP compared to chronic ITP (P < 0.001). Reticulated platelets were also elevated in patients compared to controls and the increase was significant in newly diagnosed group (P < 0.05). Negative correlation was found between IL-16 level and reticulated platelets and platelets counts (r = -0.284, P = 0.028, r = 0.274 P = 0.25) respectively. It is concluded that IL-16 may be valuable in predicting the clinical course of pediatrics ITP. Measurement of reticulated platelets may provide significant information about thrombopoietic activity during the clinical course of ITP in children.

  18. Thrombotic Microangiopathy in Inverted Formin 2-Mediated Renal Disease.

    PubMed

    Challis, Rachel C; Ring, Troels; Xu, Yaobo; Wong, Edwin K S; Flossmann, Oliver; Roberts, Ian S D; Ahmed, Saeed; Wetherall, Michael; Salkus, Giedrius; Brocklebank, Vicky; Fester, Julian; Strain, Lisa; Wilson, Valerie; Wood, Katrina M; Marchbank, Kevin J; Santibanez-Koref, Mauro; Goodship, Timothy H J; Kavanagh, David

    2017-04-01

    The demonstration of impaired C regulation in the thrombotic microangiopathy (TMA) atypical hemolytic uremic syndrome (aHUS) resulted in the successful introduction of the C inhibitor eculizumab into clinical practice. C abnormalities account for approximately 50% of aHUS cases; however, mutations in the non-C gene diacylglycerol kinase-ε have been described recently in individuals not responsive to eculizumab. We report here a family in which the proposita presented with aHUS but did not respond to eculizumab. Her mother had previously presented with a post-renal transplant TMA. Both the proposita and her mother also had Charcot-Marie-Tooth disease. Using whole-exome sequencing, we identified a mutation in the inverted formin 2 gene (INF2) in the mutational hotspot for FSGS. Subsequent analysis of the Newcastle aHUS cohort identified another family with a functionally-significant mutation in INF2 In this family, renal transplantation was associated with post-transplant TMA. All individuals with INF2 mutations presenting with a TMA also had aHUS risk haplotypes, potentially accounting for the genetic pleiotropy. Identifying individuals with TMAs who may not respond to eculizumab will avoid prolonged exposure of such individuals to the infectious complications of terminal pathway C blockade.

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

    PubMed Central

    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/m2 (P75). A biochemical analysis showed 1×109 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

  20. 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.

  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

    2016-02-24

    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.

  2. Plateletpheresis for postsplenectomy rebound thrombocytosis in a patient with chronic immune thrombocytopenic purpura on romiplostim.

    PubMed

    Raval, Jay S; Redner, Robert L; Kiss, Joseph E

    2013-08-01

    Immune thrombocytopenic purpura (ITP) is an autoimmune disease in which IgG-coated platelets are removed from circulation by the spleen, and platelet production is impaired due to increased thrombopoietin (TPO) clearance. Romiplostim, a novel TPO-mimetic agent, is approved for patients with ITP that are unresponsive to traditional treatments. However, there is little experience when using this drug before splenectomy. We describe herein the case of a young female with chronic ITP who was treated with romiplostim, underwent splenectomy shortly thereafter, and required plateletpheresis for postoperative rebound thrombocytosis with concomitant neurologic symptoms.

  3. Severe Thrombocytopenic Purpura in a Child with Brucellosis: Case Presentation and Review of the Literature

    PubMed Central

    Perogiannaki, Aikaterini; Chaliasos, Nikolaos

    2017-01-01

    Brucellosis is still endemic and a significant public health problem in many Mediterranean countries, including Greece. It is a multisystemic disease with a broad spectrum of clinical manifestations including hematological disorders, such as anemia, pancytopenia, leucopenia, and thrombocytopenia. Thrombocytopenia is usually moderate and attributed to bone marrow suppression or hypersplenism. Rarely, autoimmune stimulation can cause severe thrombocytopenia with clinically significant hemorrhagic manifestations. We present the case of a girl with severe thrombocytopenic purpura as one of the presenting symptoms of Brucella melitensis infection. Treatment with intravenous immunoglobulin and the appropriate antimicrobial agents promptly resolved the thrombocyte counts. A review of similar published cases is also presented. PMID:28127481

  4. [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.

  5. A Hypereosinophilic Syndrome with Cardiac Involvement from Thrombotic Stage to Fibrotic Stage

    PubMed Central

    Kim, Nam Kyun; Kim, Chang-Yeon; Kim, Jae Hee; Jang, Se Yong; Bae, Myung Hwan; Lee, Jang Hoon; Yang, Dong Heon; Park, Hun Sik; Cho, Yongkeun

    2015-01-01

    Cardiac involvement is a major cause of morbidity and mortality in hypereosinophilic syndrome (HES). It is classified into 3 stages by the degree of eosinophils-mediated heart injury; acute necrotic stage, thrombotic stage, and fibrotic stage. Nonetheless, definitive evidence that each patient passes sequentially through these stages is lacking. We present a case of 48-year-old male patient with dyspnea and peripheral edema who underwent valve replacement surgery due to severe mitral regurgitation. After the valve replacement, HES with cardiac involvement in the thrombotic stage was diagnosed. In the follow-up study, the patient progressed into fibrotic stage of HES. PMID:26140152

  6. 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

  7. Management of thrombotic and cardiovascular disorders in the new millenium.

    PubMed

    Fareed, Jawed; Hoppensteadt, Debra A; Bick, Rodger L

    2003-04-01

    Anticoagulants and antithrombotic drugs have played a key role in the prophylaxis, treatment and surgica/interventional management of thrombotic and cardiovascular disorders. There are several newer drugs which are currently developed for the anticoagulant management of cardiovascular diseases in both the medical and surgical indications. These include the low molecular weight heparins (LMWHs), antithrombin agents such as the Hirudin, Hirulog and Argatroban and indirect and direct anti-Xa drugs, represented by Pentasaccharide (Arixtra) and DX 9065a, respectively. Several other agents such as the natural and recombinant anti-Xa drugs and anti-tissue factor agents are also developed. The antiplatelet agents include Clopidogrel, Cilostazol, Anplag and GP IIb/IIIa inhibitors. For the subcutaneous indications, unfractionated heparin is gradually replaced by the low molecular weight heparins (LMWHs). LMWHs such as the Enoxaparin and Dalteparin are commonly used for the management of acute coronary syndrome. These drugs have been approved for the treatment of unstable angina and are currently undergoing rigorous trials for interventional indications. Arixtra is also developed for various subcutaneous indications. However, it exhibits lower anticoagulant effects and may not be optimal for intravenous and interventional purposes. At a higher dosage when administered intravenously the LMWHs produce varying degrees of anticoagulation at relatively lower activated clotting times (150-200). Several studies in vascular and cardiovascular interventions have shown that even at a relatively lower anticoagulant level the LMWHs are as effective as unfractionated heparin at the recommended dosages which produce a relatively higher level of anticoagulation (ACT > 200 secs.). Thus, these agents are currently developed for interventional and surgical indications. It should be emphasized that different LMWHs produce different degrees of anticoagulation and should therefore be individually

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

    PubMed

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

    2016-10-01

    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.

  9. Spontaneous bilateral peripapillary, subhyaloid and vitreous hemorrhage with only minor platelet deficit in idiopathic thrombocytopenic purpura.

    PubMed

    Wan-Wei, Loo; Tengku-Norina, Tuan-Jaffar; Azma-Azalina, Ahmad-Alwi; Zulkifli, Abdul-Ghani; Zunaina, Embong

    2014-01-01

    A 45-year-old female with underlying idiopathic thrombocytopenic purpura (ITP) complained of acute onset of reduced vision and floaters, in both eyes, for 3 weeks. Visual acuity was 6/36 and 6/60 in the right eye and left eye, respectively. Ophthalmoscopy showed bilateral peripapillary, subhyaloid and vitreous hemorrhage. Hematological evaluation revealed moderate anemia (hemoglobin: 93 g/L) and mild thrombocytopenia (platelets: 120×10(9)/L). She was co-managed by a hematologist and ophthalmologists; she was treated medically. Follow-up care during the next 6 weeks revealed spontaneous, partially resolving hemorrhage, with improvement of visual acuity. The purpose of this case report is to highlight ophthalmic involvement of ITP in this patient, despite her only-mild thrombocytopenia, and her spontaneous recovery, despite her receiving only medical treatment.

  10. 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.

  11. Serum thrombopoietin levels in relation to disease status in patients with immune thrombocytopenic purpura.

    PubMed

    Kappers-Klunne, M C; de Haan, M; Struijk, P C; van Vliet, H H

    2001-12-01

    Pre- and post-treatment serum thrombopoietin (TPO) concentration was measured in 35 patients with immune thrombocytopenic purpura (ITP). Mean post-treatment levels were significantly lower (P = 0.02) than pretreatment and not different for treatment modality. No significant correlation between pre- or post-treatment TPO and platelet counts was demonstrable (R = -0.325, P = 0.056 and R = -0.227, P = 0.190 respectively). In patients with very low platelet counts (< or =20 x 10(9)/l), pretreatment serum TPO was significantly higher than in patients with higher counts (P = 0.033). The logarithm of the platelet turnover rate, measured in 15 patients, correlated with pretreatment TPO levels (R = 0.64). These findings suggest a contributory role for TPO in the mechanism of ITP.

  12. High-dose intravenous therapy with immune globulin before delivery for idiopathic thrombocytopenic purpura.

    PubMed Central

    Adderley, R. J.; Rogers, P. C.; Shaw, D.; Wadsworth, L. D.

    1984-01-01

    A 15-year-old girl with a 9-year history of idiopathic thrombocytopenic purpura resistant to high-dose steroid therapy and to splenectomy was admitted to hospital at 35 weeks' gestation with a platelet count of 10 X 10(9)/L. The bleeding time was normal, and measures of platelet aggregation were nearly so. Treatment with high intravenous doses of polyvalent immune globulin led to a rise in the platelet count to more than 110 X 10(9)/L within 5 days. An elective cesarean section was performed through the lower uterine segment with good hemostasis. After delivery the platelet count fell to its former level, but no postpartum bleeding occurred. There was a brief episode of thrombocytopenia in the infant, with some petechiae but no other hemorrhagic manifestations. No untoward effects of the immune globulin infusion were observed in either mother or daughter. PMID:6423252

  13. 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

  14. 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.

  15. High incidence of thrombotic complications early after liver transplantation for familial amyloidotic polyneuropathy.

    PubMed

    Bispo, Miguel; Marcelino, Paulo; Freire, António; Martins, Américo; Mourão, Luís; Barroso, Eduardo

    2009-02-01

    Early thrombotic complications are critical causes of in-hospital morbidity after orthotopic liver transplantation (OLT), potentially culminating in graft loss. The aim of this study was to retrospectively analyse these complications, trying to identify associated independent risk factors. This retrospective analysis included 223 OLTs performed on 213 patients, in a 30-month period. Eighty-six OLTs were performed on familial amyloidotic polyneuropathy (FAP) patients. Preoperative details (primary diagnosis and Child-Turcotte-Pugh classification, when applicable), surgical features (including type of arterial reconstruction), postoperative variables and outcome were analysed. The observation period ended 30 days post-OLT, until discharge or in-hospital death. Early thrombotic complications were diagnosed in 16 cases (7.2%), affecting mainly FAP patients (n = 12). Hepatic artery thrombosis (HAT) was the most frequent early thrombotic event (n = 12): incidence in FAP patients 11.6% (n = 10) versus incidence in non FAP patients 1.5% (n = 2), P = 0.001. By logistic regression analysis, FAP turned out to be an independent risk factor for early thrombotic complications, and specifically for HAT. The type of arterial reconstruction and other analysed surgical and medical factors did not influence early HAT occurrence. In conclusion, FAP was identified in this study as an independent risk factor for early HAT, a new datum not yet described in the literature.

  16. A Case of Locally Advanced Breast Cancer Complicated by Pulmonary Tumor Thrombotic Microangiopathy

    PubMed Central

    Kim, Hak Jin; Kwak, Mi Hyang; Kong, Sun-Young; Seong, Moon-Woo; Kang, Han-Sung; Lee, Keun Seok

    2012-01-01

    Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare, malignancy-related complication that causes marked pulmonary hypertension, right heart failure, and death. We report on a patient with locally advanced breast cancer whose course was complicated by fatal PTTM based on clinical and laboratory findings. PMID:23341791

  17. Thrombotic diseases in young women and the influence of oral contraceptives.

    PubMed

    Lidegaard, O

    1998-09-01

    The influence of oral contraceptive (OC) use in young women on the risk of development of venous thromboembolism, myocardial infarction, and thrombotic stroke was assessed through an analysis of nationwide register data from Denmark for 1980-93 and for 1994-95 from three ongoing case-control studies. All three diseases increased rapidly with increasing age; the arterial diseases increased almost exponentially, while the venous diseases increased more linearly. Venous thromboembolism was almost twice as prevalent as arterial complications in women 15-29 years old, while the number of arterial complications exceeded that of venous diseases by about 50% in women 30-44 years of age. Mortality from arterial diseases was 3.5 times higher than that from venous diseases among women under 30 years of age and 8.5 times higher than that from venous diseases in women 30-44 years old. The proportion of women with a significant disability was about 30% among those with an arterial complication; this proportion was 5% among women with venous thromboembolism. Users of OCs with second-generation progestogens had a 30% greater increased risk of thrombotic diseases, a 260% greater increased risk of thrombotic mortality, and a 220% greater increased risk of thrombotic disability than users of OCs with third-generation progestogens.

  18. Pulmonary tumor thrombotic microangiopathy with cor pulmonale due to desmoplastic small round cell tumor.

    PubMed

    Sadimin, Evita T; Collier, Adrienne G; Gaffney, Joseph W; Fyfe, Billie

    2012-04-01

    A 12-year-old boy presented acutely after an episode of syncope with perioral cyanosis. He died 19 hours after admission due to cor pulmonale as a complication of metastatic desmoplastic small round cell tumor in the lungs with associated tumor thrombotic microangiopathy.

  19. Renal thrombotic microangiopathy and FIP1L1/PDGFRα-associated myeloproliferative variant of hypereosinophilic syndrome

    PubMed Central

    Langlois, Anne Lyse; Shehwaro, Nathalie; Rondet, Claire; Benbrik, Youssef; Maloum, Karim; Gueutin, Victor; Rouvier, Philippe; Izzedine, Hassane

    2013-01-01

    We report a case of renal thrombotic microangiopathy (TMA) in a myeloproliferative variant of hypereosinophilic syndrome (HES) in a 24-year-old man which resolved with imatinib therapy. This is one of a few cases in the literature to date describing TMA in HES, suggesting that the pathogenesis of thrombosis is at least in part related to damage from activated eosinophils. PMID:27293571

  20. Renal thrombotic microangiopathy and FIP1L1/PDGFRα-associated myeloproliferative variant of hypereosinophilic syndrome.

    PubMed

    Langlois, Anne Lyse; Shehwaro, Nathalie; Rondet, Claire; Benbrik, Youssef; Maloum, Karim; Gueutin, Victor; Rouvier, Philippe; Izzedine, Hassane

    2013-08-01

    We report a case of renal thrombotic microangiopathy (TMA) in a myeloproliferative variant of hypereosinophilic syndrome (HES) in a 24-year-old man which resolved with imatinib therapy. This is one of a few cases in the literature to date describing TMA in HES, suggesting that the pathogenesis of thrombosis is at least in part related to damage from activated eosinophils.

  1. Role of Helicobacter pylori Eradication Therapy on Platelet Recovery in Chronic Immune Thrombocytopenic Purpura

    PubMed Central

    Sheema, Khan; Arshi, Naz; Farah, Naz; Imran, Sheikh

    2017-01-01

    Background. Idiopathic thrombocytopenic purpura (ITP) is a bleeding disorder in which the immune system destroys native platelets. In this condition an autoantibody is generated against a platelet antigen. ITP affects women more often than men and is more common in children than adults. Objective. To assess the effect of Helicobacter pylori eradication therapy (HPET) on platelet count in Helicobacter pylori associated chronic immune thrombocytopenic purpura (chronic ITP) in adult. Materials and Methods. It is an interventional prospective study conducted at Liaquat University of Medical and Health Sciences, Jamshoro, from 2014 to 2015. A set of 85 patients diagnosed with chronic ITP were included in the study via convenient sampling. Patients with platelets count < 100 × 109/L for >3 months were selected. They were posed to first-line investigations which comprised complete blood count (CBC) and peripheral blood smear examination followed by second-line tests including bone marrow examination and Helicobacter pylori stool specific antigen (HpSA-EIA). Standard H. pylori eradication therapy was offered and the patients were assessed at regular intervals for 6 months. Results. Of the 85 study patients, 32 (37.6%) were male and 53 (62.3%) were female. Mean ages of H. pylori positive and negative subjects were 43.89 ± 7.06 and 44.75 ± 7.91 years, respectively. Bone marrow examination confirmed the diagnosis and excluded other related BM disorders. H. pylori stool antigen (HpSA) was detected in 34 (40%) patients and hence regarded as H. pylori positive; the rest were negative. Treatment with eradication therapy significantly improved the mean platelet counts from 48.56 ± 21.7 × 109/l to 94.2 ± 26.8 × 109/l. Conclusion. We concluded that the anti-H. pylori eradication therapy improves blood platelet counts in chronic immune thrombocytopenia. PMID:28194178

  2. The scientific basis for evaluation and management of thrombotic disorders.

    PubMed

    Olcese, Vanessa A; Stirling, Michael; Lawson, Jeffrey

    2006-11-01

    The hemostatic mechanisms at work in the body involve a complex series of interactions between platelets, the endothelium, and the coagulation cascade. Much has been learned regarding the molecular mechanisms governing these intricate processes. The hypercoagulable state involves a disruption of the normal homeostatic equilibrium. This state may be either inherent or acquired. The prevention of associated thromboembolic complications requires therapeutic anticoagulation. A broader understanding of the factors contributing to these prothrombotic tendencies and the subtleties involved in their management provides the surgeon with another weapon in the armamentarium to promote better and safer patient outcomes.

  3. Acquired Idiopathic Generalized Anhidrosis.

    PubMed

    Gangadharan, Geethu; Criton, Sebastian; Surendran, Divya

    2015-01-01

    Acquired idiopathic generalized anhidrosis is a rare condition, where the exact pathomechanism is unknown. We report a case of acquired idiopathic generalized anhidrosis in a patient who later developed lichen planus. Here an autoimmune-mediated destruction of sweat glands may be the probable pathomechanism.

  4. LABORATORY-ACQUIRED MYCOSES

    DTIC Science & Technology

    laboratory- acquired mycoses . Insofar as possible, the etiological fungus, type of laboratory, classification of personnel, type of work conducted, and other...pertinent data have been listed in this study. More than 288 laboratory- acquired mycoses are described here, including 108 cases of

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

    PubMed

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

    2009-09-01

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

  6. Acquired inflammatory demyelinating neuropathies.

    PubMed

    Ensrud, E R; Krivickas, L S

    2001-05-01

    The acquired demyelinating neuropathies can be divided into those with an acute onset and course and those with a more chronic course. The acute neuropathies present as Guillain-Barré syndrome and include acute inflammatory demyelinating polyradiculoneuropathy (AIDP), Miller Fisher syndrome, acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and acute pandysautonomia. The chronic neuropathies are collectively known as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and include MADSAM (multifocal acquired demyelinating sensory and motor neuropathy, also know as Lewis-Sumner syndrome) and DADS (distal acquired demyelinating symmetric neuropathy) as variants. The clinical features, pathology, pathogenesis, diagnosis, treatment, rehabilitation, and prognosis of these neuropathies are discussed.

  7. Acquired color vision deficiency.

    PubMed

    Simunovic, Matthew P

    2016-01-01

    Acquired color vision deficiency occurs as the result of ocular, neurologic, or systemic disease. A wide array of conditions may affect color vision, ranging from diseases of the ocular media through to pathology of the visual cortex. Traditionally, acquired color vision deficiency is considered a separate entity from congenital color vision deficiency, although emerging clinical and molecular genetic data would suggest a degree of overlap. We review the pathophysiology of acquired color vision deficiency, the data on its prevalence, theories for the preponderance of acquired S-mechanism (or tritan) deficiency, and discuss tests of color vision. We also briefly review the types of color vision deficiencies encountered in ocular disease, with an emphasis placed on larger or more detailed clinical investigations.

  8. Effect of surgical and non-surgical periodontal debridement on vascular thrombotic markers in hypertensives

    PubMed Central

    Albush, Muhammad M.; Razan, Khattab K.; Raed, Al Dieri M.

    2013-01-01

    Background: Periodontal debridement has an impact on the vascular thrombotic markers in healthy individuals. This study aimed to investigate changes in several vascular thrombotic markers after surgical and non-surgical periodontal debridement in hypertensives with periodontitis. Materials and Methods: 40 hypertensives, 27 males and 13 females, 37-68 year old, mean 51.2 years, with moderate to severe periodontitis, were divided into two groups, (n = 20 for each); the first received comprehensive one session non-surgical periodontal debridement, (pockets 4-6 mm), while the second received comprehensive supragingival scaling with surgical debridement at one quadrant, (Pockets > 6 mm). Periodontal parameters included; plaque index (PI), gingival inflammation (GI), bleeding on probing (BOP), pocket probing depth (PPD). Vascular thrombotic tests included; platelets count (Plt), fibrinogen (Fib), Von Willebrand factor antigen activity (vWF:Ag), and D-dimers (DD). Results: PI, GI, BOP, PPD, decreased significantly (P = 0.001) after 6 weeks of periodontal debridement in both groups, while BOP and PPD remained higher in the surgical one (P < 0.05). Thrombotic vascular markers changes through the three-time intervals were significant in each group (P = 0.001), and time-group interception effect was significant for vWF:Ag (P = 0.005), while no significant differences between groups after treatment (P > 0.05). Conclusion: Periodontal debridement, surgical and non-surgical, improved the periodontal status in hypertensives. Periodontal treatment activated the coagulation system in hypertensives and recessed later while the treatment modality did not affect the degree of activation. PMID:24049332

  9. Is chronic HIV infection associated with venous thrombotic disease? A systematic review.

    PubMed

    Klein, S K; Slim, E J; de Kruif, M D; Keller, T T; ten Cate, H; van Gorp, E C M; Brandjes, D P M

    2005-04-01

    Infection with the human immunodeficiency virus (HIV) is still a major health problem world-wide. HIV infection has changed into a chronic infection with the chance of developing long-term complications. Vascular complications are frequently reported in the current literature. HIV and treatment by highly active antiretroviral therapy (HAART) are associated with many cardiovascular risk factors. An increased risk of arterial cardiovascular complications was found in a number of studies. However, data about the risk of venous thrombotic disease (VTE), including potentially fatal conditions as pulmonary embolism, were limited. In a systematic review of the literature, ten relevant epidemiological studies were identified that investigated the risk of venous thrombotic disease in HIV-infected patients. The incidence was increased two- to tenfold in comparison with a healthy population of the same age. However, these studies were mainly retrospective cohort studies that were prone to selection bias, confounding factors were not always mentioned and in all but three control populations were missing. An increased risk of venous thrombotic disease in HIV-infected patients could be explained by the presence of a hypercoagulable state, characterised by an increase in procoagulant factors, such as endothelial TF expression and thrombogenic properties of microparticles, and a decrease in anticoagulant factors, including AT III, HC II and the protein C pathway. Furthermore, the risk of VTE was associated with an increased risk of infections and autoimmune haemolytic anaemia, and was weakly associated with HAART. All together, quite some evidence pointed towards a relationship between HIV infection and venous thrombotic disease, but the association still needs to be established in properly designed epidemiological studies.

  10. BK virus encephalitis with thrombotic microangiopathy in an allogeneic hematopoietic stem cell transplant recipient.

    PubMed

    Lopes da Silva, R; Ferreira, I; Teixeira, G; Cordeiro, D; Mafra, M; Costa, I; Bravo Marques, J M; Abecasis, M

    2011-04-01

    BK virus (BKV) infection occurs most often in immunocompromised hosts, in the setting of renal or bone marrow transplantation. Hemorrhagic cystitis is the commonest manifestation but in recent years infections in other organ systems have been reported. We report an unusual case of biopsy-proven BKV encephalitis in a hematopoietic stem cell transplant patient who subsequently developed thrombotic microangiopathy. As far as we know, this is the first report of such an association in a transplant patient.

  11. FcγRIIa ligation induces platelet hypersensitivity to thrombotic stimuli.

    PubMed

    Berlacher, Mark D; Vieth, Joshua A; Heflin, Brittany C; Gay, Steven R; Antczak, Adam J; Tasma, Brian E; Boardman, Holly J; Singh, Navinderjit; Montel, Angela H; Kahaleh, M Bashar; Worth, Randall G

    2013-01-01

    Platelets are known for their important role in hemostasis, however their significance in other functions, including inflammation and infection, are becoming more apparent. Patients with systemic lupus erythematosus (SLE) are known to have circulating IgG complexes in their blood and are highly susceptible to thrombotic events. Because platelets express a single receptor for IgG, we tested the hypothesis that ligation of this receptor (FcγRIIa) induces platelet hypersensitivity to thrombotic stimuli. Platelets from SLE patients were considerably more sensitive to thrombin compared to healthy volunteers, and this correlated with elevated levels of surface IgG on SLE platelets. To test whether FcγRIIa ligation stimulated thrombin hypersensitivity, platelets from healthy volunteers were incubated with buffer or heat-aggregated IgG, then stimulated with increasing concentrations of thrombin. Interestingly, heat-aggregated IgG-stimulated platelets, but not buffer-treated platelets, were hypersensitive to thrombin, and hypersensitivity was blocked by an anti-FcγRIIa monoclonal antibody (mAb). Thrombin hypersensitivity was not due to changes in thrombin receptor expression (GPIbα or PAR1) but is dependent on activation of shared signaling molecules. These observations suggest that ligation of platelet FcγRIIa by IgG complexes induces a hypersensitive state whereby small changes in thrombotic stimuli may result in platelet activation and subsequent vascular complications such as transient ischemic attacks or stroke.

  12. Thrombotic events in patients with antiphospholipid syndrome treated with rivaroxaban: a series of eight cases.

    PubMed

    Signorelli, Flavio; Nogueira, Felipe; Domingues, Vinicius; Mariz, Henrique Ataide; Levy, Roger A

    2016-03-01

    The current treatment for antiphospholipid syndrome (APS) with thrombotic manifestation is long-term anticoagulation. Vitamin K antagonists (VKA) are usually the agents of choice. However, VKA limitations, such as unpredictable anticoagulation effects due to interaction with diet and other drugs, require regular monitoring. This may impact on patients' quality of life. Since the approval of new oral anticoagulants (NOAC) for non-valvular atrial fibrillation and deep vein thrombosis prevention, much has been speculated about its use in APS patients. We report here a series of eight APS patients with failure of thrombotic prevention during rivaroxaban use. All patients had venous thrombosis as the initial manifestation of APS, and two of them also had arterial manifestations. Three patients had triple antibody positivity. Five patients developed arterial events during the treatment with rivaroxaban. Until the results of ongoing trials of rivaroxaban for APS are presented, NOAC should not be recommended to APS patients. Our preliminary experience as well cases previously reported in the literature suggest that there is a high-risk group that is less protected with rivaroxaban, namely those with previous arterial thrombosis or triple positivity. VKA remains to be the mainstay treatment for thrombotic APS.

  13. Effect of the serotonin antagonist ketanserin on the hemodynamic and morphological consequences of thrombotic infarction

    SciTech Connect

    Dietrich, W.D.; Busto, R.; Ginsberg, M.D. )

    1989-12-01

    The effect of the serotonin (5-hydroxytryptamine, 5-HT) antagonist ketanserin on the remote hemodynamic consequences of thrombotic brain infarction was studied in rats. Treated rats received an injection of 1 mg/kg ketanserin 30 min before and 1 h following photochemically induced cortical infarction. Local CBF (LCBF) was assessed autoradiographically with ({sup 14}C)iodoantipyrine 4 h following infarction, and chronic infarct size was documented at 5 days. Thrombotic infarction led to significant decreases in LCBF within noninfarcted cortical regions. For example, mean LCBF was decreased to 63, 55, and 65% of control (nontreated normal rats) in ipsilateral frontal, lateral, and auditory cortices, respectively. In rats treated with ketanserin, significant decreases in LCBF were not documented within remote cortical areas compared with controls. In contrast to these hemodynamic effects, morphological analysis of chronic infarct size demonstrated no differences in infarct volume between treated (27 +/- 3 mm3) and nontreated (27 +/- 6 mm3) rats. These data are consistent with the hypothesis that 5-HT is involved in the widespread hemodynamic consequences of experimentally induced thrombotic infarction. Remote hemodynamic consequences of acute infarction can be inhibited without altering final infarct size.

  14. Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry.

    PubMed

    Baudo, Francesco; Collins, Peter; Huth-Kühne, Angela; Lévesque, Hervé; Marco, Pascual; Nemes, László; Pellegrini, Fabio; Tengborn, Lilian; Knoebl, Paul

    2012-07-05

    Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies to coagulation FVIII. Bleeding episodes at presentation are spontaneous and severe in most cases. Optimal hemostatic therapy is controversial, and available data are from observational and retrospective studies only. The EACH2 registry, a multicenter, pan-European, Web-based database, reports current patient management. The aim was to assess the control of first bleeding episodes treated with a bypassing agent (rFVIIa or aPCC), FVIII, or DDAVP among 501 registered patients. Of 482 patients with one or more bleeding episodes, 144 (30%) received no treatment for bleeding; 31 were treated with symptomatic therapy only. Among 307 patients treated with a first-line hemostatic agent, 174 (56.7%) received rFVIIa, 63 (20.5%) aPCC, 56 (18.2%) FVIII, and 14 (4.6%) DDAVP. Bleeding was controlled in 269 of 338 (79.6%) patients treated with a first-line hemostatic agent or ancillary therapy alone. Propensity score matching was applied to allow unbiased comparison between treatment groups. Bleeding control was significantly higher in patients treated with bypassing agents versus FVIII/DDAVP (93.3% vs 68.3%; P = .003). Bleeding control was similar between rFVIIa and aPCC (93.0%; P = 1). Thrombotic events were reported in 3.6% of treated patients with a similar incidence between rFVIIa (2.9%) and aPCC (4.8%).

  15. Acquired hypofibrinogenemia: current perspectives

    PubMed Central

    Besser, Martin W; MacDonald, Stephen G

    2016-01-01

    Acquired hypofibrinogenemia is most frequently caused by hemodilution and consumption of clotting factors. The aggressive replacement of fibrinogen has become one of the core principles of modern management of massive hemorrhage. The best method for determining the patient’s fibrinogen level remains controversial, and particularly in acquired dysfibrinogenemia, could have major therapeutic implications depending on which quantification method is chosen. This review introduces the available laboratory and point-of-care methods and discusses the relative advantages and limitations. It also discusses current strategies for the correction of hypofibrinogenemia. PMID:27713652

  16. Community-acquired pneumonia.

    PubMed

    Falguera, M; Ramírez, M F

    2015-11-01

    This article not only reviews the essential aspects of community-acquired pneumonia for daily clinical practice, but also highlights the controversial issues and provides the newest available information. Community-acquired pneumonia is considered in a broad sense, without excluding certain variants that, in recent years, a number of authors have managed to delineate, such as healthcare-associated pneumonia. The latter form is nothing more than the same disease that affects more frail patients, with a greater number of risk factors, both sharing an overall common approach.

  17. DNMT3B promoter polymorphism and risk of immune thrombocytopenic purpura in pediatric Egyptians.

    PubMed

    Shaheen, Iman A; Abukhalil, Reham E; Ali, Dina K; Afifi, Rasha A

    2012-10-01

    Idiopathic (immune) thrombocytopenic purpura (ITP) is a heterogeneous clinical disorder characterized by immune-mediated platelet destruction. Epigenetic changes in gene expression, including DNA methylation and histone modifications, might contribute to autoimmunity. Polymorphisms of the DNA methyltransferase 3B (DNMT3B) gene may influence DNMT3B activity on DNA methylation and increase the susceptibility to several diseases. The current study investigated the association between a single nucleotide polymorphism (SNP) in the promoter of DNMT3B gene and the risk for ITP in pediatric Egyptians. DNMT3B SNP was genotyped by PCR-restriction fragment length polymorphism in 71 pediatric ITP patients and 82 healthy controls matched for age and sex. The C/C wild genotype was not detected in ITP patients or in the controls. The frequencies of the T/T and C/T genotypes were 93.9 and 6.1% in the controls and 91.5 and 6.1% in ITP patients, respectively. There was no significant difference in either genotypes or allelic distribution between ITP patients and the controls. In conclusion, this polymorphism was almost equally distributed between ITP patients and the controls. These results demonstrated that this SNP may not be used as a stratification marker to predict the susceptibility to childhood ITP in Egypt.

  18. Long-term salvage therapy with cyclosporin A in refractory idiopathic thrombocytopenic purpura.

    PubMed

    Emilia, Giovanni; Morselli, Monica; Luppi, Mario; Longo, Giuseppe; Marasca, Roberto; Gandini, Giovanna; Ferrara, Leonardo; D'Apollo, Nicola; Potenza, Leonardo; Bertesi, Marcello; Torelli, Giuseppe

    2002-02-15

    Treatment of severe, chronic idiopathic thrombocytopenic purpura (ITP) refractory to most usual therapies is a difficult challenge. Little information exists on the clinical use of cyclosporin A (CyA) in the treatment of ITP. This report describes long-term treatment with CyA (median, 40 months) and follow-up (median, 36.8 months) in 12 adult patients with resistant ITP. CyA used in relatively low doses (2.5-3 mg/kg of body weight per day) led to a clinical improvement in 10 patients (83.3%). Five had a complete response (41.1%), 4 a complete response to maintenance therapy (33.3%), and one a partial response (8.3%). Two patients had no response. Most patients with a response (60%) had a long-term remission (mean, 28.6 months) after discontinuation of CyA. One patient had a relapse of ITP 4 years after CyA therapy was stopped. Side effects were moderate and transient, even in patients dependent on continued CyA treatment. CyA seems to represent reasonable salvage treatment in severe, potentially life-threatening, refractory ITP.

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

    PubMed

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

    2009-06-08

    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 >150×10(9)/L) or partial (platelet count between 50 and 150×10(9)/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.

  20. [Treatment of immune thrombocytopenic purpura in Pediatrics. Therapeutic efficacy of a regional intravenous immunoglobulin G].

    PubMed

    Buteler, C; Colombo, H; Gabosi, G; Manfredi, M J; Montero, S; Pasquali, M A; Rougier, C; Sisti, A M

    2001-01-01

    Immune thrombocytopenic purpura (ITP) is a bleeding disorder characterized by accelerated splenic removal of platelets opsonized with autoantibodies. Several different treatments have been tried in acute ITP patients, including intravenous immunoglobulin (IVIG) therapy. The aim of this paper was to assess the therapeutic efficacy, clinical tolerance and viral safety of Inmunoglobulina G Endovenosa-UNC, manufactured by Laboratorio de Hemoderivados, Cordoba National University, in the treatment of acute ITP patients. A prospective longitudinal study was carried out on 8 children, who were admitted to the Hospital de Niños de Córdoba, from July 1998 to June 1999. A dose of 1 g/Kg/day of Inmunoglobulina G Endovenosa-UNC was administered to those children whose platelet values remained < or = 20,000/mm3, 21 days after the first IVIG cycle. The observed results led us to conclude that Inmunoglobulina G Endovenosa-UNC is well tolerated and therapeutically effective in the treatment of acute ITP in children, with platelet values recovery, similar to those obtained with other IVIG. Moreover, it proved to be virally safe since the 8 patients were non reactive for viral markers of hepatitis B, hepatitis C and human immunodeficiency, 12 months after ending the treatment.

  1. Bleeding tendency and platelet function during treatment with romiplostim in children with severe immune thrombocytopenic purpura.

    PubMed

    Suntsova, Elena V; Demina, Irina M; Ignatova, Anastasia A; Ershov, Nikolay M; Trubina, Natalia M; Dobrynina, Juliya; Serkova, Irina V; Supik, Zhanna S; Orekhova, Ekaterina V; Hachatryan, Lili A; Kotskaya, Natalia N; Pshonkin, Aleksey V; Maschan, Aleksey A; Novichkova, Galina A; Panteleev, Mikhail A

    2017-03-07

    It has been suggested that platelet function in chronic immune thrombocytopenic purpura (ITP) may be abnormal. Thrombopoietin mimetics used for treatment can affect it, but the data remain limited. We investigated platelet function of 20 children diagnosed with severe ITP (aged 1-16 years, 12 females and eight males). Platelet functional activity in whole blood was characterized by flow cytometry before and after stimulation with SFLLRN plus collagen-related peptide. Levels of CD42b, PAC1, and CD62P, but not CD61 or annexin V, were significantly increased (P < 0.05) in resting platelets of patients before treatment compared with healthy donors. On average, PAC1 and CD62P in patients after activation were also significantly elevated, although some patients failed to activate integrins. Romiplostim (1-15 μg/kg/week s.c.) was prescribed to seven patients, with clinical improvement in six. Interestingly, one patient had clinical improvement without platelet count increase. Eltrombopag (25-75 mg/day p.o.) was given to four patients, with positive response in one. Others switched to romiplostim, with one stable positive response, one unstable positive response, and one non-responding. Platelet quality improved with romiplostim treatment, and their parameters approached the normal values. Our results suggest that platelets in children with severe ITP are pre-activated and abnormal, but improve with treatment.

  2. Life-Threatening Autoimmune Hemolytic Anemia and Idhiopatic Thrombocytopenic Purpura. Successful Selective Splenic Artery Embolization

    PubMed Central

    Molica, Matteo; Massaro, Fulvio; Annechini, Giorgia; Baldacci, Erminia; D’Elia, Gianna Maria; Rosati, Riccardo; Trisolini, Silvia Maria; Volpicelli, Paola; Foà, Robin; Capria, Saveria

    2016-01-01

    Selective splenic artery embolization (SSAE) is a nonsurgical intervention characterized by the transcatheter occlusion of the splenic artery and/or its branch vessels using metallic coils or other embolic devices. It has been applied for the management of splenic trauma, hypersplenism with portal hypertension, hereditary spherocytosis, thalassemia and splenic hemangioma. We hereby describe a case of a patient affected by idiopathic thrombocytopenic purpura (ITP) and warm auto-immune hemolytic anemia (AIHA) both resistant to immunosuppressive and biological therapies, not eligible for a surgical intervention because of her critical conditions. She underwent SSAE and achieved a hematologic complete response within a few days without complications. SSAE is a minimally invasive procedure to date not considered a standard option in the management of AIHA and ITP. However, following the progressive improvement of the techniques, its indications have been extended, with a reduction in morbidity and mortality compared to splenectomy in patients with critical clinical conditions. SSAE was a lifesaving therapeutic approach for our patient and it may represent a real alternative for the treatment of resistant AIHA and ITP patients not eligible for splenectomy. PMID:27158433

  3. 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

  4. 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

  5. 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.

  6. Acquired Brain Injury Program.

    ERIC Educational Resources Information Center

    Schwartz, Stacey Hunter

    This paper reviews the Acquired Brain Injury (ABI) Program at Coastline Community College (California). The ABI Program is a two-year, for-credit educational curriculum designed to provide structured cognitive retraining for adults who have sustained an ABI due to traumatic (such as motor vehicle accident or fall) or non-traumatic(such as…

  7. Laboratory evaluation of a bleeding patient.

    PubMed Central

    Wallerstein, R O

    1989-01-01

    Most causes of abnormal bleeding can be determined from a complete blood count including platelet count and bleeding, prothrombin, activated partial thromboplastin, and thrombin times. Occasionally, further evaluation is necessary, such as tests of factor XIII function, fibrinolysis, and vascular integrity. Possible diagnoses include disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, vitamin K deficiency, von Willebrand's disease, heparin-induced thrombocytopenia, acquired inhibitors of factor VIII, lupus anticoagulants, and coagulation disorders related to the acquired immunodeficiency syndrome. PMID:2660407

  8. Thrombotic Microangiopathy Care Pathway: A Consensus Statement for the Mayo Clinic Complement Alternative Pathway-Thrombotic Microangiopathy (CAP-TMA) Disease-Oriented Group.

    PubMed

    Go, Ronald S; Winters, Jeffrey L; Leung, Nelson; Murray, David L; Willrich, Maria A; Abraham, Roshini S; Amer, Hatem; Hogan, William J; Marshall, Ariela L; Sethi, Sanjeev; Tran, Cheryl L; Chen, Dong; Pruthi, Rajiv K; Ashrani, Aneel A; Fervenza, Fernando C; Cramer, Carl H; Rodriguez, Vilmarie; Wolanskyj, Alexandra P; Thomé, Stephan D; Hook, C Christopher

    2016-09-01

    Thrombotic microangiopathies (TMAs) comprise a heterogeneous set of conditions linked by a common histopathologic finding of endothelial damage resulting in microvascular thromboses and potentially serious complications. The typical clinical presentation is microangiopathic hemolytic anemia accompanied by thrombocytopenia with varying degrees of organ ischemia. The differential diagnoses are generally broad, while the workup is frequently complex and can be confusing. This statement represents the joint recommendations from a multidisciplinary team of Mayo Clinic physicians specializing in the management of TMA. It comprises a series of evidence- and consensus-based clinical pathways developed to allow a uniform approach to the spectrum of care including when to suspect TMA, what differential diagnoses to consider, which diagnostic tests to order, and how to provide initial empiric therapy, as well as some guidance on subsequent management.

  9. Hospital-acquired thrombocytopenia.

    PubMed

    McMahon, Christine M; Cuker, Adam

    2014-10-01

    The development of thrombocytopenia is common in hospitalized patients and is associated with increased mortality. Frequent and important causes of thrombocytopenia in hospitalized patients include etiologies related to the underlying illness for which the patient is admitted, such as infection and disseminated intravascular coagulation, and iatrogenic etiologies such as drug-induced immune thrombocytopenia, heparin-induced thrombocytopenia, posttransfusion purpura, hemodilution, major surgery, and extracorporeal circuitry. This review presents a brief discussion of the pathophysiology, distinguishing clinical features, and management of these etiologies, and provides a diagnostic approach to hospital-acquired thrombocytopenia that considers the timing and severity of the platelet count fall, the presence of hemorrhage or thrombosis, the clinical context, and the peripheral blood smear. This approach may offer guidance to clinicians in distinguishing among the various causes of hospital-acquired thrombocytopenia and providing management appropriate to the etiology.

  10. Desmosomes in acquired disease

    PubMed Central

    Stahley, Sara N.; Kowalczyk, Andrew P.

    2015-01-01

    Desmosomes are cell-cell junctions that mediate adhesion and couple the intermediate filament cytoskeleton to sites of cell-cell contact. This architectural arrangement functions to integrate adhesion and cytoskeletal elements of adjacent cells. The importance of this robust adhesion system is evident in numerous human diseases, both inherited and acquired, that occur when desmosome function is compromised. This review focuses on autoimmune and infectious diseases that impair desmosome function. In addition, we discuss emerging evidence that desmosomal genes are often misregulated in cancer. The emphasis of our discussion is placed on how human diseases inform our understanding of basic desmosome biology, and in turn, how fundamental advances in the cell biology of desmosomes may lead to new treatments for acquired diseases of the desmosome. PMID:25795143

  11. Desmosomes in acquired disease.

    PubMed

    Stahley, Sara N; Kowalczyk, Andrew P

    2015-06-01

    Desmosomes are cell-cell junctions that mediate adhesion and couple the intermediate filament cytoskeleton to sites of cell-cell contact. This architectural arrangement integrates adhesion and cytoskeletal elements of adjacent cells. The importance of this robust adhesion system is evident in numerous human diseases, both inherited and acquired, which occur when desmosome function is compromised. This review focuses on autoimmune and infectious diseases that impair desmosome function. In addition, we discuss emerging evidence that desmosomal genes are often misregulated in cancer. The emphasis of our discussion is placed on the way in which human diseases can inform our understanding of basic desmosome biology and in turn, the means by which fundamental advances in the cell biology of desmosomes might lead to new treatments for acquired diseases of the desmosome.

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

    PubMed

    Zimmerman, Jacquelyn; Norsworthy, Kelly J; Brodsky, Robert

    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.

  13. 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

  14. Detection of expression of IL-18 and its binding protein in Egyptian pediatric immune thrombocytopenic purpura.

    PubMed

    Shaheen, Iman A; Botros, Shahira K A; Morgan, Dalia S

    2014-01-01

    Immune thrombocytopenic purpura (ITP) is an autoimmune disorder, characterized by dysfunctional cellular immunity including the presence of activated platelet specific autoreactive T cells that recognize and respond to autologous platelet antigens. Autoreactive T cells drive the generation of platelet reactive autoantibodies by B cells as well as T-cytotoxic cell-mediated lysis of platelets. Interleukin-18 (IL-18) is a mediator of T helper type 1 cell responses synergistically with IL-12 that initiate and promote host defense and inflammation. IL-18 has a specific binding protein (IL-18BP) which belongs to the immunoglobulin superfamily. In the present study, serum level and messenger RNA( mRNA) expression of IL-18 as well as IL-18BP mRNA expression were measured in peripheral blood mononuclear cells (PBMNCs) of 100 Egyptian pediatric patients with ITP (70 acute and 30 chronic). In addition to this, we recruited 80 healthy volunteers in order to investigate the possible association between the imbalance of IL-18 and IL-18 BP expressions and the pathogenesis of ITP. IL-18 serum level and mRNA expression were not elevated in cases more than in the control group, but IL-18 mRNA was higher in chronic cases when compared to the acute ones (p=0.031) and there was a good negative correlation between the platelet count and serum IL-18. IL-18 BP m-RNA was slightly elevated in cases more than in the control group (95% Confidence interval=1.15-2.01). Our results were not supportive for previous findings of elevated IL18/BP mRNA ratio in ITP patients. This could be referred to the fact that autoimmune diseases are complex genetic disorders, therefore further studies on polymorphisms affecting IL-18 gene expression as well as kinetics of IL-18 expression are required to evaluate the role of interleukin 18 and its binding protein in the pathogenesis of ITP.

  15. 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.

  16. Mycophenolate mofetil (MMF) for the treatment of steroid-resistant idiopathic thrombocytopenic purpura.

    PubMed

    Hou, Ming; Peng, Jun; Shi, Yan; Zhang, Chunqing; Qin, Ping; Zhao, Chuanli; Ji, Xuebin; Wang, Xueyong; Zhang, Maohong

    2003-06-01

    The treatment of chronic idiopathic thrombocytopenic purpura (ITP) is difficult in those unresponsive to corticosteroids and/or splenectomy. We attempted to induce durable response in 21 patients with refractory ITP by applying mycophenolate mofetil (MMF) (1.5-2.0 g/d), a novel immunosuppressive agent. Overall response rate was 62% (13 of 21), including 24% (five of 21) in complete response (CR), 29% (six of 21) in partial response (PR), and 10% (two of 21) in minor response (MR). The response rates for non-splenectomized and splenectomized ITP patients were 64% (nine of 14) and 57% (four of seven), respectively (P > 0.05). 39% (five of 13) responders relapsed as a result of dose reduction or withdraw of MMF, and 61% (eight of 13) responders maintained their effectiveness for a median of 24 wk. Sustained response was observed in three patients in whom MMF was withdrawn. MMF was well tolerated with only slight nausea and diarrhea recorded in 3 of 21 cases. No premature withdrawal was found in this study. CD3+ peripheral blood mononuclear cells (PBMC) and CD19+ PBMC were significantly reduced 12 wk after MMF administration in the responders. Platelet-associated antibodies against glycoproteins GPIIb/IIIa were detected in 13 of 21 (62%) patients before MMF treatment, and antibody levels were significantly decreased in responders 12 wk after MMF administration. This suggested that MMF might correct the immunologic abnormalities underlying the destruction of circulating platelets in ITP. We conclude that MMF could be used as a second-line agent for the treatment of steroid-resistant ITP before or after splenectomy and thereby is worth of further evaluation in randomized studies.

  17. 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.

  18. The oxidative modification of von Willebrand factor is associated with thrombotic angiopathies in diabetes mellitus.

    PubMed

    Oggianu, Laura; Lancellotti, Stefano; Pitocco, Dario; Zaccardi, Francesco; Rizzo, Paola; Martini, Francesca; Ghirlanda, Giovanni; De Cristofaro, Raimondo

    2013-01-01

    The thrombogenic activity of Von Willebrand factor (VWF) is proportional to its molecular size and inversely related to its proteolysis by ADAMTS-13. Oxidation of VWF severely impairs its proteolysis by the metalloprotease. This study was aimed at assessing in patients with type 1 and type 2 diabetes whether protein carbonyls, marker of oxidative stress, are associated with both the level and oxidation status of VWF as well as with micro- and macroangiopathic complications. Eighty-three diabetic patients (41 type 1 and 42 type 2 diabetic subjects) and their respective eighty-three healthy controls were studied after verifying the availability, through institutional databases, of clinical biochemistry records spanning at least 3 years. VWF and protein carbonyls were measured by immunoassays, whereas VWF multimers were studied by SDS-agarose gel electrophoresis. Type 2 diabetic subjects had higher levels of VWF antigen (VWF:ag), VWF activity (VWF:act) and plasma proteins' carbonyls compared to both their controls and type 1 diabetic subjects. Moreover, high molecular weight VWF multimers and specific VWF-bound carbonyls were significantly increased in subjects with micro- and macro-angiopathic complications. In both type 1 and type 2 diabetic subjects, ADAMTS-13 activity was in the normal range. In a multivariable analysis, only VWF-bound carbonyls were significantly associated with any form of thrombotic angiopathy in the entire group of T1- and T2 diabetic patients. These data provide first evidence that not only high VWF levels but also its oxidation status and the presence of high molecular weight VWF multimers that are not observed in SDS-agarose gel electrophoresis of normal subjects are associated with thrombotic angiopathies in diabetes mellitus. These findings may help identify diabetic patients particularly at risk for these complications and elucidate a new pathophysiological mechanism of thrombotic angiopathies in this clinical setting.

  19. The Oxidative Modification of Von Willebrand Factor Is Associated with Thrombotic Angiopathies in Diabetes Mellitus

    PubMed Central

    Pitocco, Dario; Zaccardi, Francesco; Rizzo, Paola; Martini, Francesca; Ghirlanda, Giovanni; De Cristofaro, Raimondo

    2013-01-01

    The thrombogenic activity of Von Willebrand factor (VWF) is proportional to its molecular size and inversely related to its proteolysis by ADAMTS-13. Oxidation of VWF severely impairs its proteolysis by the metalloprotease. This study was aimed at assessing in patients with type 1 and type 2 diabetes whether protein carbonyls, marker of oxidative stress, are associated with both the level and oxidation status of VWF as well as with micro- and macroangiopathic complications. Eighty-three diabetic patients (41 type 1 and 42 type 2 diabetic subjects) and their respective eighty-three healthy controls were studied after verifying the availability, through institutional databases, of clinical biochemistry records spanning at least 3 years. VWF and protein carbonyls were measured by immunoassays, whereas VWF multimers were studied by SDS-agarose gel electrophoresis. Type 2 diabetic subjects had higher levels of VWF antigen (VWF:ag), VWF activity (VWF:act) and plasma proteins’ carbonyls compared to both their controls and type 1 diabetic subjects. Moreover, high molecular weight VWF multimers and specific VWF-bound carbonyls were significantly increased in subjects with micro- and macro-angiopathic complications. In both type 1 and type 2 diabetic subjects, ADAMTS-13 activity was in the normal range. In a multivariable analysis, only VWF-bound carbonyls were significantly associated with any form of thrombotic angiopathy in the entire group of T1- and T2 diabetic patients. These data provide first evidence that not only high VWF levels but also its oxidation status and the presence of high molecular weight VWF multimers that are not observed in SDS-agarose gel electrophoresis of normal subjects are associated with thrombotic angiopathies in diabetes mellitus. These findings may help identify diabetic patients particularly at risk for these complications and elucidate a new pathophysiological mechanism of thrombotic angiopathies in this clinical setting. PMID:23383177

  20. Dynamic Shear Stress Regulation of Inflammatory and Thrombotic Pathways in Baboon Endothelial Outgrowth Cells

    PubMed Central

    Hinds, Monica T.; Nerem, Robert M.

    2013-01-01

    Endothelial outgrowth cells (EOCs) have garnered much attention as a potential autologous endothelial source for vascular implants or in tissue engineering applications due to their ease of isolation and proliferative ability; however, how these cells respond to different hemodynamic cues is ill-defined. This study investigates the inflammatory and thrombotic response of baboon EOCs (BaEOCs) to four hemodynamic conditions using the cone and plate shear apparatus: steady, laminar shear stress (SS); pulsatile, nonreversing laminar shear stress (PS); oscillatory, laminar shear stress (OS); and net positive, pulsatile, reversing laminar shear stress (RS). In summary, endothelial nitric oxide synthase (eNOS) mRNA was significantly upregulated by SS compared to OS. No differences were found in the mRNA levels of the inflammatory markers intercellular adhesion molecule-1 (ICAM-1), E-selectin, and vascular cell adhesion molecule-1 (VCAM-1) between the shear conditions; however, OS significantly increased the number of monocytes bound when compared to SS. Next, SS increased the anti-thrombogenic mRNA levels of CD39, thrombomodulin, and endothelial protein-C receptor (EPCR) compared to OS. SS also significantly increased CD39 and EPCR mRNA levels compared to RS. Finally, no significant differences were detected when comparing pro-thrombotic tissue factor mRNA or its activity levels. These results indicate that shear stress can have beneficial (SS) or adverse (OS, RS) effects on the inflammatory or thrombotic potential of EOCs. Further, these results suggest SS hemodynamic preconditioning may be optimal in increasing the efficacy of a vascular implant or in tissue-engineered applications that have incorporated EOCs. PMID:23406430

  1. Thrombotic microangiopathy: An unusual cause of renal failure in rheumatoid arthritis

    PubMed Central

    Sakthirajan, R.; Dhanapriya, J.; Dineshkumar, T.; Gopalakrishnan, N.; Murugan, S.; Balasubramaniyan, T.

    2017-01-01

    Rheumatoid arthritis (RA) is one of the commonest rheumatological diseases. Renal involvement is not common but can occur as a result of chronic inflammation as part of disease process or drug toxicity. Thrombotic microangiopathy (TMA) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ failure of variable severity. Only a few cases of TMA in patients with RA were reported to date. We describe a 45-year-old female patient with RA who presented with oliguria and edema. Renal biopsy showed TMA with patchy cortical necrosis. She improved with hemodialysis and plasmapheresis. PMID:28182045

  2. Surgical experience with thrombotic and fibrotic forms of non-tropical eosinophilic endomyocardial disease.

    PubMed

    Arvay, A; Lengyel, M; Mészáros, R; Palik, I

    1985-10-01

    Surgical treatment in 8 cases of non-tropical eosinophilic endomyocardial diseases with (4 patients) and without (4 patients) eosinophilia is reported. Follow-up results (1 to 4 years) in the 6 survivors, including hemodynamic re-study, were excellent even in patients operated on in the thrombotic stage (3) or with hypereosinophilia (2), or with dominant right ventricular involvement (3). Two-dimensional echocardiography gave the correct description of the pathologic stage and ventricular involvement in 6 of the 8 cases before catheterization.

  3. Recanalization of Aged Venous Thrombotic Occlusions with the Aid of a Rheolytic System: An Experimental Study

    SciTech Connect

    Vicol, Calin; Dalichau, Harald

    1996-04-15

    Purpose: The suitability of a rheolytic system for recanalization of aged venous thrombotic occlusions was tested in an animal experiment. Methods: The system consists of a flush-suction catheter and a high-pressure liquid pump. Thrombosis was experimentally induced in 13 venous segments of 10 adult goats. Results: After a mean period of 12 days, a complete thrombectomy using the flush-suction system was achieved in 12 cases. No complications such as perforation or dissection were observed. Conclusion: This system seems to be an appropriate device for percutaneous transluminal venous thrombectomy, even in older occlusions.

  4. Suction Thrombectomy of Thrombotic Occlusion of the Subclavian Artery in a Case of Takayasu's Arteritis

    SciTech Connect

    Purkayastha, Sukalyan; Jayadevan, E.R.; Kapilamoorthy, T.R.; Gupta, A.K. E-mail: gupta@sctimst.ac.in

    2006-04-15

    Takayasu's arteritis, also known as pulseless disease, is a chronic inflammatory arteritis affecting large vessels, predominantly the aorta and its main branches. Vessel inflammation leads to wall thickening, fibrosis, stenosis, and thrombus formation. Percutaneous removal of arterial thrombus with the use of several devices has been reported, with mixed results. We present a case of Takayasu's arteritis with thrombotic occlusion of the subclavian artery in which pulsed urokinase injection and suction thrombectomy were used to revascularize a threatened limb and to establish the sole arterial supply to the brain.

  5. Eculizumab for rescue of thrombotic microangiopathy in PM-Scl antibody-positive autoimmune overlap syndrome

    PubMed Central

    Thomas, Christie P.; Nester, Carla M.; Phan, Andrew C.; Sharma, Manisha; Steele, Amanda L.; Lenert, Petar S.

    2015-01-01

    A 46-year-old female with interstitial lung disease presented with proximal muscle weakness, worsening hypertension, microangiopathic hemolysis, thrombocytopenia and deteriorating renal function. She had no sclerodactyly, but had abnormal capillaroscopy. She tested positive for PM-Scl antibodies, and a renal biopsy showed an acute thrombotic microangiopathy consistent with scleroderma renal crisis (SRC). She failed to respond to corticosteroids, plasmapheresis and renin–angiotensin pathway inhibitors. She recovered quickly with the anti-C5 antibody, eculizumab. She had no genetic abnormalities associated with atypical hemolytic uremic syndrome except a DNA variant of unknown significance in C3. This case suggests that eculizumab may be effective for SRC. PMID:26613027

  6. Platelets miRNA as a Prediction Marker of Thrombotic Episodes

    PubMed Central

    Dzieciol, Malgorzata

    2016-01-01

    The blood platelets are crucial for the coagulation physiology to maintain haemostatic balance and are involved in various pathologies such as atherosclerosis and thrombosis. The studies of recent years have shown that anucleated platelets are able to succeed protein synthesis. Additionally, mRNA translation in blood platelets is regulated by miRNA molecules. Recent works postulate the possibility of using miRNAs as biomarkers of atherosclerosis and ischemic episodes. This review article describes clinical studies that presented blood platelets miRNAs expression profile changes in different thrombotic states, which suggest use of these molecules as predictive biomarkers. PMID:28042196

  7. Cardiovascular thrombotic events in arthritis trials of the cyclooxygenase-2 inhibitor celecoxib.

    PubMed

    White, William B; Faich, Gerald; Borer, Jeffrey S; Makuch, Robert W

    2003-08-15

    To determine whether the cyclooxygenase-2 (COX-2) inhibitor celecoxib affects cardiovascular thrombotic risk, we analyzed the incidence of cardiovascular events for celecoxib, placebo, and nonsteroidal anti-inflammatory drugs (NSAIDs) in the entire controlled, arthritis clinical trial database for celecoxib. The primary analysis used the Antiplatelet Trialists' Collaboration end points, which include: (1) cardiovascular, hemorrhagic, and unknown deaths, (2) nonfatal myocardial infarction, and (3) nonfatal stroke. Other secondary thrombotic events were also examined. Separate analyses were performed for all patients and for those not taking aspirin. Data from all controlled, completed arthritis trials of > or =4 weeks duration, including 13 new drug application studies and 2 large post-marketing trials (CLASS and SUCCESS) were included for analyses. Patients were randomized to celecoxib at doses from 100 to 400 mg twice daily (18,942 patients; 5,668.2 patient-years of exposure), diclofenac 50 to 75 mg twice daily, ibuprofen 800 mg thrice daily, naproxen 500 mg twice daily (combined NSAID exposure of 11,143 patients; 3,612.2 patient-years), or placebo (1,794 subjects; 199.9 subject-years). Data from a long-term uncontrolled trial with 5,209 patients (6,950 patients-years) treated with celecoxib were included in a supplemental analysis. The entire 15-trial database was searched for possible serious thrombotic events as well as to identify all deaths. For these patients, detailed clinical data were obtained and reviewed by 2 of the investigators (WBW and JSB), who were independently and blinded to exposure, to classify the event as primary, secondary, or neither. All analyses were done using the intent-to-treat population, and time-to-event analyses were performed using per-patient data. To examine heterogeneity of results among studies, tests of interaction were performed using the Cox model. Incidences of the primary and secondary events were not significantly

  8. Ischemic colitis as a manifestation of thrombotic microangiopathy following bone marrow transplantation.

    PubMed

    Komeno, Yukiko; Ogawa, Seishi; Ishida, Tateru; Takeuchi, Kengo; Tsujino, Shiho; Kurokawa, Mineo; Aoki, Katsunori; Kanda, Yoshinobu; Chiba, Shigeru; Motokura, Toru; Fukayama, Masashi; Hirai, Hisamaru

    2003-12-01

    Thrombotic microangiopathy (TMA) is a microvascular disorder characterized by platelet aggregation and hemolytic anemia. In the setting of bone marrow transplantation (BMT), ischemic colitis due to TMA is difficult to differentiate from acute graft-versus-host disease. We report a 32-year-old man who presented ischemic colitis due to TMA after unrelated BMT for myelodysplastic syndrome. He suffered from treatment-resistant bloody diarrhea, and died of renal failure and Aspergillus pleuritis on day 253 post-BMT. Autopsy revealed endothelial injuries of arterioles and ischemic changes in the intestines and kidneys. Clinical and pathological characteristics of ischemic colitis due to BMT-associated TMA are described.

  9. Acquired Factor V Inhibitor

    PubMed Central

    Hirai, Daisuke; Yamashita, Yugo; Masunaga, Nobutoyo; Katsura, Toshiaki; Akao, Masaharu; Okuno, Yoshiaki; Koyama, Hiroshi

    2016-01-01

    Inhibitors directed against factor V rarely occur, and the clinical symptoms vary. We herein report the case of a patient who presented with a decreased factor V activity that had decreased to <3 %. We administered vitamin K and 6 units of fresh frozen plasma, but she thereafter developed an intracerebral hemorrhage. It is unclear whether surgery >10 years earlier might have caused the development of a factor V inhibitor. The treatment of acquired factor V inhibitors is mainly the transfusion of platelet concentrates and corticosteroids. Both early detection and the early initiation of the treatment of factor V inhibitor are thus considered to be important. PMID:27746446

  10. Risk factors, management and primary prevention of thrombotic complications related to the use of central venous catheters.

    PubMed

    Linnemann, Birgit; Lindhoff-Last, Edelgard

    2012-09-01

    An adequate vascular access is of importance for the treatment of patients with cancer and complex illnesses in the intensive, perioperative or palliative care setting. Deep vein thrombosis and thrombotic occlusion are the most common complications attributed to central venous catheters in short-term and, especially, in long-term use. In this review we will focus on the risk factors, management and prevention strategies of catheter-related thrombosis and occlusion. Due to the lack of randomised controlled trials, there is still controversy about the optimal treatment of catheter-related thrombotic complications, and therapy has been widely adopted using the evidence concerning lower extremity deep vein thrombosis. Given the increasing use of central venous catheters in patients that require long-term intravenous therapy, the problem of upper extremity deep venous thrombosis can be expected to increase in the future. We provide data for establishing a more uniform strategy for preventing, diagnosing and treating catheter-related thrombotic complications.

  11. [Acquired coagulant factor inhibitors].

    PubMed

    Nogami, Keiji

    2015-02-01

    Acquired coagulation factor inhibitors are an autoimmune disease causing bleeding symptoms due to decreases in the corresponding factor (s) which result from the appearance of autoantibodies against coagulation factors (inhibitor). This disease is quite different from congenital coagulation factor deficiencies based on genetic abnormalities. In recent years, cases with this disease have been increasing, and most have anti-factor VIII autoantibodies. The breakdown of the immune control mechanism is speculated to cause this disease since it is common in the elderly, but the pathology and pathogenesis are presently unclear. We herein describe the pathology and pathogenesis of factor VIII and factor V inhibitors. Characterization of these inhibitors leads to further analysis of the coagulation process and the activation mechanisms of clotting factors. In the future, with the development of new clotting examination method (s), we anticipate that further novel findings will be obtained in this field through inhibitor analysis. In addition, detailed elucidation of the coagulation inhibitory mechanism possibly leading to hemostatic treatment strategies for acquired coagulation factor disorders will be developed.

  12. TNF-alpha and annexin A2: inflammation in thrombotic primary antiphospholipid syndrome.

    PubMed

    Bećarević, Mirjana

    2016-12-01

    Antiphospholipid syndrome (APS) is characterized by thromboses and/or pregnancy losses. Laboratory criterion for the diagnosis of APS is the presence of antiphospholipid antibodies (anticardiolipin, anti-beta2-glycoprotein I (aβ2gpI) and lupus anticoagulant). On the one hand, the latest classification criteria for the diagnosis of APS emphasized that thrombotic manifestations of the syndrome should be without any signs of an inflammatory process, while on the other hand, some recent reports have suggested that APS is a "pro-inflammatory state." This article is focused on the importance of TNF-alpha and annexin A2 (anxA2) for patients with vascular (thrombotic) manifestations of the primary APS. The classic antithrombotic and antiplatelet therapy does not protect APS patients from the development of recurrent thrombosis. Therefore, an urgent need for the introduction of new therapeutic approaches in the treatment of APS patients is obvious. This review provides a rationale for the necessity for the use of immunomodulatory medications that could interfere with β2gpI binding to its receptor(s), such as anxA2, and/or inhibit TNF-alpha activity.

  13. Shape optimization of pulsatile ventricular assist devices using FSI to minimize thrombotic risk

    NASA Astrophysics Data System (ADS)

    Long, C. C.; Marsden, A. L.; Bazilevs, Y.

    2014-10-01

    In this paper we perform shape optimization of a pediatric pulsatile ventricular assist device (PVAD). The device simulation is carried out using fluid-structure interaction (FSI) modeling techniques within a computational framework that combines FEM for fluid mechanics and isogeometric analysis for structural mechanics modeling. The PVAD FSI simulations are performed under realistic conditions (i.e., flow speeds, pressure levels, boundary conditions, etc.), and account for the interaction of air, blood, and a thin structural membrane separating the two fluid subdomains. The shape optimization study is designed to reduce thrombotic risk, a major clinical problem in PVADs. Thrombotic risk is quantified in terms of particle residence time in the device blood chamber. Methods to compute particle residence time in the context of moving spatial domains are presented in a companion paper published in the same issue (Comput Mech, doi: 10.1007/s00466-013-0931-y, 2013). The surrogate management framework, a derivative-free pattern search optimization method that relies on surrogates for increased efficiency, is employed in this work. For the optimization study shown here, particle residence time is used to define a suitable cost or objective function, while four adjustable design optimization parameters are used to define the device geometry. The FSI-based optimization framework is implemented in a parallel computing environment, and deployed with minimal user intervention. Using five SEARCH/ POLL steps the optimization scheme identifies a PVAD design with significantly better throughput efficiency than the original device.

  14. The Unravelling of the Genetic Architecture of Plasminogen Deficiency and its Relation to Thrombotic Disease

    PubMed Central

    Martin-Fernandez, Laura; Marco, Pascual; Corrales, Irene; Pérez, Raquel; Ramírez, Lorena; López, Sonia; Vidal, Francisco; Soria, José Manuel

    2016-01-01

    Although plasminogen is a key protein in fibrinolysis and several mutations in the plasminogen gene (PLG) have been identified that result in plasminogen deficiency, there are conflicting reports to associate it with the risk of thrombosis. Our aim was to unravel the genetic architecture of PLG in families with plasminogen deficiency and its relationship with spontaneous thrombotic events in these families. A total of 13 individuals from 4 families were recruited. Their genetic risk profile of thromboembolism was characterized using the Thrombo inCode kit. Only one family presented genetic risk of thromboembolism (homozygous carrier of F12 rs1801020 and F13A1 rs5985). The whole PLG was tested using Next Generation Sequencing (NGS) and 5 putative pathogenic mutations were found (after in silico predictions) and associated with plasminogen deficiency. Although we can not find genetic risk factors of thrombosis in 3 of 4 families, even the mutations associated with plasminogen deficiency do not cosegregated with thrombosis, we can not exclude plasminogen deficiency as a susceptibility risk factor for thrombosis, since thrombosis is a multifactorial and complex disease where unknown genetic risk factors, in addition to plasminogen deficiency, within these families may explain the thrombotic tendency. PMID:27976734

  15. [Testing system design and analysis for the execution units of anti-thrombotic device].

    PubMed

    Li, Zhelong; Cui, Haipo; Shang, Kun; Liao, Yuehua; Zhou, Xun

    2015-02-01

    In an anti-thrombotic pressure circulatory device, relays and solenoid valves serve as core execution units. Thus the therapeutic efficacy and patient safety of the device will directly depend on their performance. A new type of testing system for relays and solenoid valves used in the anti-thrombotic device has been developed, which can test action response time and fatigue performance of relay and solenoid valve. PC, data acquisition card and test platform are used in this testing system based on human-computer interaction testing modules. The testing objectives are realized by using the virtual instrument technology, the high-speed data acquisition technology and reasonable software design. The two sets of the system made by relay and solenoid valve are tested. The results proved the universality and reliability of the testing system so that these relays and solenoid valves could be accurately used in the antithrombotic pressure circulatory equipment. The newly-developed testing system has a bright future in the aspects of promotion and application prospect.

  16. CFD-based Thrombotic Risk Assessment in Kawasaki Disease Patients with Coronary Artery Aneurysms

    NASA Astrophysics Data System (ADS)

    Sengupta, Dibyendu; Kung, Ethan; Kahn, Andrew; Burns, Jane; Marsden, Alison

    2012-11-01

    Coronary aneurysms occur in 25% of untreated Kawasaki Disease (KD) patients and put patients at increased risk for myocardial infarction and sudden death. Clinical guidelines recommend using aneurysm diameter >8 mm as the arbitrary criterion for treating with anti-coagulation therapy. This study uses patient-specific modeling to non-invasively determine hemodynamic parameters and quantify thrombotic risk. Anatomic models were constructed from CT angiographic image data from 5 KD aneurysm patients and one normal control. CFD simulations were performed to obtain hemodynamic data including WSS and particle residence times (PRT). Thrombosis was clinically observed in 4/9 aneurysmal coronaries. Thrombosed vessels required twice as many cardiac cycles (mean 8.2 vs. 4.2) for particles to exit, and had lower mean WSS (1.3 compared to 2.8 dynes/cm2) compared to vessels with non-thrombosed aneurysms of similar max diameter. 1 KD patient in the cohort with acute thrombosis had diameter < 8 mm. Regions of low WSS and high PRT predicted by simulations correlated with regions of subsequent thrombus formation. Thrombotic risk stratification for KD aneurysms may be improved by incorporating both hemodynamic and geometric quantities. Current clinical guidelines to assess patient risk based only on aneurysm diameter may be misleading. Further prospective study is warranted to evaluate the utility of patient-specific modeling in risk stratifying KD patients with coronary aneurysms. NIH R21.

  17. Transluminal Attenuation Gradient for Thrombotic Risk Assessment in Kawasaki Disease Patients with Coronary Artery Aneurysms

    NASA Astrophysics Data System (ADS)

    Grande Gutierrez, Noelia; Kahn, Andrew; Burns, Jane; Marsden, Alison

    2014-11-01

    Kawasaki Disease (KD) can result in coronary aneurysms in up to 25% of patients if not treated early putting patients at risk of thrombus formation, myocardial infarction and sudden death. Clinical guidelines for administering anti-coagulation therapy currently rely on anatomy alone. Previous studies including patient specific modeling and computer simulations in KD patients have suggested that hemodynamic data can predict regions susceptible to thrombus formation. In particular, high Particle Residence Time gradient (PRTg) regions have shown to correlate with regions of thrombus formation. Transluminal Attenuation Gradient (TAG) is determined from the change in radiological attenuation per vessel length. TAG has been used for characterizing coronary artery stenoses, however this approach has not yet been used in aneurysmal vessels. The aim of this study is to analyze the correlation between TAG and PRTg in KD patients with aneurysms and evaluate the use of TAG as an index to quantify thrombotic risk. Patient specific anatomic models for fluids simulations were constructed from CT angiographic image data from 3 KD aneurysm patients and one normal control. TAG values for the aneurysm patients were markedly lower than for the non-aneurysmal patient (mean -18.38 vs. -2). In addition, TAG values were compared to PRTg obtained for each patient. Thrombotic risk stratification for KD aneurysms may be improved by incorporating TAG and should be evaluated in future prospective studies.

  18. ADAMTS13 Endopeptidase Protects against Vascular Endothelial Growth Factor Inhibitor-Induced Thrombotic Microangiopathy.

    PubMed

    Erpenbeck, Luise; Demers, Melanie; Zsengellér, Zsuzsanna K; Gallant, Maureen; Cifuni, Stephen M; Stillman, Isaac E; Karumanchi, S Ananth; Wagner, Denisa D

    2016-01-01

    Thrombotic microangiopathy (TMA) is a life-threatening condition that affects some, but not all, recipients of vascular endothelial growth factor (VEGF) inhibitors given as part of chemotherapy. TMA is also a complication of preeclampsia, a disease characterized by excess production of the VEGF-scavenging soluble VEGF receptor 1 (soluble fms-like tyrosine kinase 1; sFlt-1). Risk factors for VEGF inhibitor-related TMA remain unknown. We hypothesized that deficiency of the VWF-cleaving ADAMTS13 endopeptidase contributes to the development of VEGF inhibitor-related TMA. ADAMTS13(-/-) mice overexpressing sFlt-1 presented all hallmarks of TMA, including thrombocytopenia, schistocytosis, anemia, and VWF-positive microthrombi in multiple organs. Similar to VEGF inhibitor-related TMA in humans, these mice exhibited severely impaired kidney function and hypertension. In contrast, wild-type mice overexpressing sFlt-1 developed modest hypertension but no other features of TMA. Recombinant ADAMTS13 therapy ameliorated all symptoms of TMA in ADAMTS13(-/-) mice overexpressing sFlt-1 and normalized BP in wild-type mice. ADAMTS13 activity may thus be a critical determinant for the development of TMA secondary to VEGF inhibition. Administration of recombinant ADAMTS13 may serve as a therapeutic approach to treat or prevent thrombotic complications of VEGF inhibition.

  19. Anti-thrombotic effect of rutin isolated from Dendropanax morbifera Leveille.

    PubMed

    Choi, Jun-Hui; Kim, Dae-Won; Park, Se-Eun; Lee, Hyo-Jeong; Kim, Ki-Man; Kim, Kyung-Je; Kim, Myung-Kon; Kim, Sung-Jun; Kim, Seung

    2015-08-01

    Dendropanax morbifera H. Lev. is well known in Korean traditional medicine for improvement of blood circulation. In this study, rutin, a bioflavonoid having anti-thrombotic and anticoagulant activities was isolated from a traditional medicinal plant, D. morbifera H. Lev. The chemical characteristics of rutin was studied to be quercetin 3-O-α-l-rhamnopyranosyl-(1-6)-β-d-glucopyranoside using high performance liquid chromatography mass spectrometry (HPLC-MS), proton nuclear magnetic resonance ((1)H NMR) and carbon-13 nuclear magnetic resonance ((13)C NMR). Turbidity and fibrin clotting studies revealed that rutin reduces fibrin clot in concentration dependent manner. Rutin was found to prolong activated partial thromboplastin time (aPTT), prothrombin time (PT) and closure time (CT). Furthermore, it decreased the activity of pro-coagulant protein, thrombin. In vivo study showed that rutin exerted a significant protective effect against collagen and epinephrine (or thrombin) induced acute thromboembolism in mice. These results suggest that rutin has a potent to be an anti-thrombotic agent for cardiovascular diseases.

  20. Acquired epidermodysplasia verruciformis.

    PubMed

    Rogers, Heather D; Macgregor, Jennifer L; Nord, Kristin M; Tyring, Stephen; Rady, Peter; Engler, Danielle E; Grossman, Marc E

    2009-02-01

    Epidermodysplasia verruciformis (EV) is a rare autosomal recessive genodermatosis with an increased susceptibility to specific human papillomavirus (HPV) genotypes. Classically, this viral infection leads to the development of tinea versicolor-like macules on the trunk, neck, arms, and face during childhood, and over time, these lesions can progress to squamous cell carcinoma. More recently, an EV-like syndrome has been described in patients with impaired cell-mediated immunity. We describe two cases of EV-like syndrome in HIV-positive patients, review all previously reported cases of EV in patients with impaired cell-mediated immunity, introduce the term "acquired epidermodysplasia verruciformis" to describe EV developing in the immunocompromised host and examine the limited treatment options for these patients.

  1. AIDS: acquired immunodeficiency syndrome.

    PubMed Central

    Gilmore, N. J.; Beaulieu, R.; Steben, M.; Laverdière, M.

    1983-01-01

    Acquired immunodeficiency syndrome, or AIDS, is a new illness that occurs in previously healthy individuals. It is characterized by immunodeficiency, opportunistic infections and unusual malignant diseases. Life-threatening single or multiple infections with viruses, mycobacteria, fungi or protozoa are common. A rare neoplasm, Kaposi's sarcoma, has developed in approximately one third of patients with AIDS. More than 800 cases of AIDS have been reported in North America, over 24 of them in Canada. The majority of patients are male homosexuals, although AIDS has also developed in abusers of intravenously administered drugs, Haitian immigrants, individuals with hemophilia, recipients of blood transfusions, prostitutes, and infants, spouses and partners of patients with AIDS. The cause of AIDS is unknown, but the features are consistent with an infectious process. Early diagnosis can be difficult owing to the nonspecific symptoms and signs of the infections and malignant diseases. Therefore, vigilance by physicians is of utmost importance. PMID:6342737

  2. AIDS: acquired immunodeficiency syndrome *

    PubMed Central

    Gilmore, N.J.; Beaulieu, R.; Steben, M.; Laverdière, M.

    1992-01-01

    Acquired immunodeficiency syndrome, or AIDS, is a new illness that occurs in previously healthy individuals. It is characterized by immunodeficiency, opportunistic infections and unusual malignant diseases. Life-threatening single or multiple infections with viruses, mycobacteria, fungi or protozoa are common. A rare neoplasm, Kaposi's sarcoma, has developed in approximately one third of patients with AIDS. More than 800 cases of AIDS have been reported in North America, over 24 of them in Canada. The majority of patients are male homosexuals, although AIDS has also developed in abusers of intravenously administered drugs, Haitian immigrants, individuals with hemophilia, recipients of blood transfusions, prostitutes, and infants, spouses and partners of patients with AIDS. The cause of AIDS is unknown, but the features are consistent with an infectious process. Early diagnosis can be difficult owing to the nonspecific symptoms and signs of the infections and malignant diseases. Therefore, vigilance by physicians is of the utmost importance. PMID:1544049

  3. Role of xanthine oxidoreductase in the anti-thrombotic effects of nitrite in rats in vivo.

    PubMed

    Kramkowski, K; Leszczynska, A; Przyborowski, K; Kaminski, T; Rykaczewska, U; Sitek, B; Zakrzewska, A; Proniewski, B; Smolenski, R T; Chabielska, E; Buczko, W; Chlopicki, S

    2016-01-01

    The mechanisms underlying nitrite-induced effects on thrombosis and hemostasis in vivo are not clear. The goal of the work described here was to investigate the role of xanthine oxidoreductase (XOR) in the anti-platelet and anti-thrombotic activities of nitrite in rats in vivo. Arterial thrombosis was induced electrically in rats with renovascular hypertension by partial ligation of the left renal artery. Sodium nitrite (NaNO2, 0.17 mmol/kg twice daily for 3 days, p.o) was administered with or without one of the XOR-inhibitors: allopurinol (ALLO) and febuxostat (FEB) (100 and 5 mg/kg, p.o., for 3 days). Nitrite treatment (0.17 mmol/kg), which was associated with a significant increase in NOHb, nitrite/nitrate plasma concentration, resulted in a substantial decrease in thrombus weight (TW) (0.48 ± 0.03 mg vs. vehicle [VEH] 0.88 ± 0.08 mg, p < 0.001) without a significant hypotensive effect. The anti-thrombotic effect of nitrite was partially reversed by FEB (TW = 0.63 ± 0.06 mg, p < 0.05 vs. nitrites), but not by ALLO (TW = 0.43 ± 0.02 mg). In turn, profound anti-platelet effect of nitrite measured ex vivo using collagen-induced whole-blood platelet aggregation (70.5 ± 7.1% vs. VEH 100 ± 4.5%, p < 0.05) and dynamic thromboxaneB2 generation was fully reversed by both XOR-inhibitors. In addition, nitrite decreased plasminogen activator inhibitor-1 concentration (0.47 ± 0.13 ng/ml vs. VEH 0.62 ± 0.04 ng/ml, p < 0.05) and FEB/ALLO reversed this effect. In vitro the anti-platelet effect of nitrite (1 mM) was reversed by FEB (0.1 mM) under hypoxia (0.5%O2) and normoxia (20%O2). Nitrite treatment had no effect on coagulation parameters. In conclusion, the nitrite-induced anti-platelet effect in rats in vivo is mediated by XOR, but XOR does not fully account for the anti-thrombotic effects of nitrite.

  4. Acquired aplastic anemia.

    PubMed

    Keohane, Elaine M

    2004-01-01

    Acquired aplastic anemia (AA) is a disorder characterized by a profound deficit of hematopoietic stem and progenitor cells, bone marrow hypocellularity, and peripheral blood pancytopenia. It primarily affects children, young adults, and those over 60 years of age. The majority of cases are idiopathic; however, idiosyncratic reactions to some drugs, chemicals, and viruses have been implicated in its etiology. An autoimmune T-cell reaction likely causes the stem cell depletion, but the precise mechanism, as well as the eliciting and target antigens, is unknown. Symptoms vary from severe life-threatening cytopenias to moderate or non-severe disease that does not require transfusion support. The peripheral blood typically exhibits pancytopenia, reticulocytopenia, and normocytic or macrocytic erythrocytes. The bone marrow is hypocellular and may exhibit dysplasia of the erythrocyte precursors. First line treatment for severe AA consists of hematopoietic stem cell transplantation in young patients with HLA identical siblings, while immunosuppression therapy is used for older patients and for those of any age who lack a HLA matched donor. Patients with AA have an increased risk of developing paroxysmal nocturnal hemoglobinuria (PNH), myelodysplastic syndrome (MDS), or acute leukemia. Further elucidation of the pathophysiology of this disease will result in a better understanding of the interrelationship among AA, PNH, and MDS, and may lead to novel targeted therapies.

  5. Acquired spatial dyslexia.

    PubMed

    Siéroff, E

    2015-08-10

    Acquired spatial dyslexia is a reading disorder frequently occurring after left or right posterior brain lesions. This article describes several types of spatial dyslexia with an attentional approach. After right posterior lesions, patients show left neglect dyslexia with errors on the left side of text, words, and non-words. The deficit is frequently associated with left unilateral spatial neglect. Severe left neglect dyslexia can be detected with unlimited exposure duration of words or non-words. Minor neglect dyslexia is detected with brief presentation of bilateral words, one in the left and one in the right visual field (phenomenon of contralesional extinction). Neglect dyslexia can be explained as a difficulty in orienting attention to the left side of verbal stimuli. With left posterior lesions, spatial dyslexia is also frequent but multiform. Right neglect dyslexia is frequent, but right unilateral spatial neglect is rare. Attentional dyslexia represents difficulty in selecting a stimulus, letter or word among other similar stimuli; it is a deficit of attentional selection, and the left hemisphere plays a crucial role in selection. Two other types of spatial dyslexia can be found after left posterior lesions: paradoxical ipsilesional extinction and stimulus-centred neglect dyslexia. Disconnections between left or right parietal attentional areas and the left temporal visual word form area could explain these deficits. Overall, a model of attention dissociating modulation, selection control, and selection positioning can help in understanding these reading disorders.

  6. Adjunctive therapies to reduce thrombotic events in patients with a history of myocardial infarction: role of vorapaxar

    PubMed Central

    Farag, Mohamed; Patel, Hiten; Gorog, Diana A

    2015-01-01

    Acute myocardial infarction (AMI) is generally attributed to coronary atherothrombotic disease. Platelet activation is essential for thrombus formation and is thus an important target for pharmacological intervention to prevent and treat AMI. Despite contemporary treatment with dual antiplatelet therapy, including acetylsalicylic acid and adenosine diphosphate receptor antagonists, patients with prior AMI remain at increased risk of future thrombotic events. This has stimulated the search for more potent antithrombotic agents. Among these is the oral protease-activated receptor-1 antagonist vorapaxar, which represents a new oral antiplatelet agent to reduce thrombotic risk in patients with atherothrombotic disease. The TRACER and the TRA 2°P-TIMI 50 trials concluded that vorapaxar in addition to standard therapy reduced ischemic adverse cardiac events. A remarkable benefit was observed in patients with stable atherosclerotic disease, particularly those with a previous history of AMI. Although favorable effects were seen in reduction of adverse cardiac events, this was associated with excess major and intracranial bleeding, particularly in patients at high risk of bleeding and those with a history of stroke or transient ischemic attack. Currently, the lack of a reliable individualized risk stratification tool to assess patients for thrombotic and bleeding tendencies in order to identify those who might gain most net clinical benefit has led to limited use of vorapaxar in clinical practice. Vorapaxar may find a niche as an adjunct to standard care in patients at high risk of thrombotic events and who are at low risk of bleeding. PMID:26229441

  7. Swine Model of Thrombotic Caval Occlusion Created by Autologous Thrombus Injection with Assistance of Intra-caval Net Knitting

    PubMed Central

    Shi, Wan-Yin; Wu, Shuang; Hu, Lan-Yue; Liu, Chang-Jian; Gu, Jian-Ping

    2015-01-01

    To evaluate the feasibility of a swine model of thrombotic inferior vena cava (IVC) occlusion (IVCO) created by autologous thrombus injection with assistance of intra-caval net knitting. Sixteen pigs were included and divided into two groups: Group A (n = 10), IVCO model created by knitting a caval net followed by autologous thrombus injection; Group B (n = 6), control model created by knitting a net and normal saline injection. Venography was performed to assess each model and the associated thrombotic occlusion. The vessels were examined histologically to analyse the pathological changes postoperatively. IVCO model was successfully created in 10 animals in Group A (100%). Immediate venography showed extensive clot burden in the IVC. Postoperative venography revealed partial caval occlusion at 7 days, and complete occlusion coupled with collateral vessels at 14 days. Histologically, Group A animals had significantly greater venous wall thickening, with CD163-positive and CD3-positive cell infiltration. Recanalization channels were observed at the margins of the thrombus. By contrast, no thrombotic occlusion of the IVC was observed in Group B. The thrombotic IVCO model can be reliably established in swine. The inflammatory reaction may contribute to the caval thrombus propagation following occlusion. PMID:26680253

  8. A case of tacrolimus-associated thrombotic microangiopathy after ABO-blood-type-incompatible renal transplantation.

    PubMed

    Takeda, Asami; Ohtsuka, Yasuhiro; Horike, Keij; Inaguma, Daizyo; Goto, Norihiko; Watarai, Yoshihiko; Uchida, Kazuharu; Morozumi, Kunio

    2011-07-01

    De novo thrombotic microangiopathy(TMA) is most commonly triggered by calcineurin inhibitors (CNI) and the prognosis is less severe than with recurrent TMA. However, it is difficult to distinguish de novo TMA from CNI toxicity and acute antibody-mediated rejection(AMR) soon after renal transplantation. We present a case of tacrolimus-associated TMA soon after ABO blood type incompatible renal transplantation that was difficult to differentiate from acute AMR. On day 9 his urine output decreased dramatically and the Scr level increased. His anti-blood type A antibody titer increased to ×16 postopratively and the tacrolimus trough level was higher than in our immunosuppressive regimen. Although we gave priority to anti-AMR treatment, adequate dose adjustment of tacrolimus after tacrolimus nephrotoxicity was diagnosed from graft biopsy could correct allograft dysfunction.

  9. Nonbacterial Thrombotic Endocarditis in a Patient with Bowel Infarction due to Mesenteric Vein Thrombosis

    PubMed Central

    Kim, Hyue Mee; Lee, Hak Seung; Jung, Ji-Hyun; Kim, Chee Hae; Oh, Sooyeon; Kim, Jung Ho; Zo, Joo-Hee

    2014-01-01

    Ante mortem cases of venous thrombosis in patients with nonbacterial thrombotic endocarditis (NBTE) have not yet been reported. We describe a rare case of NBTE in a patient with mesenteric vein thrombosis. A healthy 37-year-old man with abdominal pain and fever underwent emergency small bowel resection due to bowel ischemia resulting from mesenteric vein thrombosis. Transthoracic echocardiography revealed multiple mobile masses attached to the anterior leaflet of the mitral valves and their chordae tendineae. On suspicion of infective endocarditis, the cardiac masses were excised through open-heart surgery. However, pathologic reviews were compatible with NBTE. The patient was stable after the cardiac surgery and was treated with warfarin. Laboratory and imaging findings regarding his hypercoagulable condition were all negative. PMID:24876861

  10. Non-Bacterial Thrombotic Endocarditis in a Patient with Rheumatoid Arthritis

    PubMed Central

    Choi, Jung-Hye; Park, Jeong-Eun; Kim, Jang-Young

    2016-01-01

    Rheumatoid arthritis (RA) is frequently associated with various extra-joint complications. Although rare, thromboembolic complications are associated with high morbidity and mortality. We experienced a very rare case of nonbacterial thrombotic endocarditis (NBTE) and subsequent embolic stroke in a patient with RA. A 72-year-old male with a 15-year history of RA suddenly developed neurologic symptoms of vomiting and dizziness. Brain magnetic resonance imaging revealed recently developed multiple cerebellar and cerebral lacunar infarctions. Echocardiography showed a pulsating mitral valve vegetation involving the posterior cusp of the mitral valve leaflet, which was confirmed as NBTE. Immediate anti-coagulation therapy was started. The NBTE lesion disappeared in follow-up echocardiography after 4 weeks of anti-coagulation treatment. PMID:27275182

  11. Thrombocytosis: Diagnostic Evaluation, Thrombotic Risk Stratification, and Risk-Based Management Strategies

    PubMed Central

    Bleeker, Jonathan S.; Hogan, William J.

    2011-01-01

    Thrombocytosis is a commonly encountered clinical scenario, with a large proportion of cases discovered incidentally. The differential diagnosis for thrombocytosis is broad and the diagnostic process can be challenging. Thrombocytosis can be spurious, attributed to a reactive process or due to clonal disorder. This distinction is important as it carries implications for evaluation, prognosis, and treatment. Clonal thrombocytosis associated with the myeloproliferative neoplasms, especially essential thrombocythemia and polycythemia vera, carries a unique prognostic profile, with a markedly increased risk of thrombosis. This risk is the driving factor behind treatment strategies in these disorders. Clinical trials utilizing targeted therapies in thrombocytosis are ongoing with new therapeutic targets waiting to be explored. This paper will outline the mechanisms underlying thrombocytosis, the diagnostic evaluation of thrombocytosis, complications of thrombocytosis with a special focus on thrombotic risk as well as treatment options for clonal processes leading to thrombocytosis, including essential thrombocythemia and polycythemia vera. PMID:22084665

  12. Venous and arterial thrombotic risks with thalidomide: evidence and practical guidance

    PubMed Central

    Palladino, Carmela

    2012-01-01

    Oral immunomodulatory drugs (IMiDs), namely thalidomide, lenalidomide and pomalidomide, interfere with several pathways important for disease progression. Today they play a crucial role in the treatment of multiple myeloma patients, and have considerably improved myeloma outcomes. These agents, and thalidomide in particular, are associated with higher rates of thromboembolic events, both venous and arterial. Individual risk factors for thromboembolic events include advanced age, previous history of thromboembolism, an indwelling central venous catheter, comorbid conditions (e.g. infections, diabetes, cardiac disease, obesity), current or recent immobilization, recent surgery and inherited thrombophilic abnormalities. Cancer therapy and cancer itself also increase the risk of thromboembolic events. The aim of this review is to help clinicians to define the risk of thrombotic events in patients treated with thalidomide and thus to provide practical recommendations to manage thromboprophylaxis in these patients. PMID:25083240

  13. Endovascular therapy for advanced post-thrombotic syndrome: Proceedings from a multidisciplinary consensus panel

    PubMed Central

    Vedantham, Suresh; Kahn, Susan R; Goldhaber, Samuel Z; Comerota, Anthony J; Parpia, Sameer; Meleth, Sreelatha; Earp, Diane; Williams, Rick; Sista, Akhilesh K; Marston, William; Rathbun, Suman; Magnuson, Elizabeth A; Razavi, Mahmood K; Jaff, Michael R; Kearon, Clive

    2016-01-01

    Patients with advanced post-thrombotic syndrome (PTS) and chronic iliac vein obstruction suffer major physical limitations and impairment of health-related quality of life. Currently there is a lack of evidence-based treatment options for these patients. Early studies suggest that imaging-guided, catheter-based endovascular therapy can eliminate iliac vein obstruction and saphenous venous valvular reflux, resulting in reduced PTS severity; however, these observations have not been rigorously validated. A multidisciplinary expert panel meeting was convened to plan a multicenter randomized controlled clinical trial to evaluate endovascular therapy for the treatment of advanced PTS. This article summarizes the findings of the panel, and is expected to assist in developing a National Institutes of Health-sponsored clinical trial and other studies to improve the care of patients with advanced PTS. PMID:27247235

  14. The post thrombotic syndrome: Ignore it and it will come back to bite you.

    PubMed

    ten Cate-Hoek, Arina J; Henke, Peter K; Wakefield, Thomas W

    2016-03-01

    Post thrombotic syndrome (PTS) is a very common chronic complication of deep venous thrombosis (DVT), as three out of ten patients with lower extremity DVT will develop PTS. The possibility to identify patients at risk is limited. Diagnosis is challenging, because there is no gold standard diagnostic method. Progress in diagnostic options may therefore change future diagnostic strategies. The better understanding of pathophysiologic processes that underlie PTS may stimulate the development of treatment modalities and improve and diversify management options. The quest for adequate preventive strategies and treatment is important because PTS has a detrimental effect on patients' quality of life and is associated with increased healthcare as well as societal costs. The problem of PTS prevention is therefore clearly relevant to patients, doctors as well as policy makers.

  15. Thrombotic microangiopathies and acute kidney injury induced by artificial termination of pregnancy.

    PubMed

    Wu, H; Zou, H B; Xu, Y; Zhang, L

    2014-01-01

    Thrombotic microangiopathy (TMA) is a rare, but potentially lethal condition requiring rapid recognition, diagnosis and initiation of therapy. Here, we present two cases of women with hemolytic anemia, thrombocytopenia and acute kidney injury shortly after surgical termination of pregnancy. Histological examination of their kidneys revealed endothelial cell swelling and luminal stenosis or fibrin-containing thrombi in the glomeruli and arterioles, which support the diagnosis of TMA. The patients were treated with hemodialysis, plasma infusion and corticosteroids with or without immunosuppressive agents. Three weeks after treatment, one patient was cured and symptoms of the other patient markedly improved. Reporting of more cases of TMA associated with surgical termination of pregnancy will provide further insights into this rare disease, possibly aiding in identifying risk factors and improving time to clinical diagnosis, treatment and prognosis.

  16. [Thrombotic microangiopathy and intravascular hemolysis in pregnancy-induced hypertension. The lie of HELLP syndrome].

    PubMed

    Díaz de León-Ponce, Manuel Antonio; Briones-Garduño, Jesús Carlos; Meneses-Calderón, José; Moreno-Santillán, Armando Alberto

    2006-01-01

    We reviewed the literature regarding pregnancy-induced hypertension and its relation with thrombotic microangiopathy and intravascular hemolysis (TMIH). In the present work we described the background, frequency, mortality, clinical picture, classification, diagnosis, complications and treatment. In addition, we analyzed Weinstein's report of 1982, and we concluded that the reported data of the HELLP syndrome is not conclusive because the presence of TMIH is not demonstrable in his group of patients. Also, we retrospectively reviewed the medical charts from three Intensive Care Units from two specialized gyneco-obstetrics hospitals and from one General Hospital. From all the patients with pregnancy-induced hypertension and who developed TMIH confirmed clinically and by laboratory findings, we described the incidence of acute renal failure and the mortality in this group of patients.

  17. Acquired reactive perforating collagenosis

    PubMed Central

    Fei, Chengwen; Wang, Yao; Gong, Yu; Xu, Hui; Yu, Qian; Shi, Yuling

    2016-01-01

    Abstract Background: Reactive perforating collagenosis (RPC) is a rare form of transepithelial elimination, in which altered collagen is extruded through the epidermis. There are 2 types of RPC, acquired RPC (ARPC) and inherited RPC, while the latter is extremely rare. Here we report on 1 case of ARPC. Methods: A 73-year-old female was presented with strongly itchy papules over her back and lower limbs for 3 months. She denied the history of oozing or vesiculation. A cutaneous examination showed diffusely distributed multiple well-defined keratotic papules, 4 to 10 mm in diameter, on the bilateral lower limbs and back as well as a few papules on her chest and forearm. Scratching scars were over the resolved lesions while Koebner phenomenon was negative. The patient had a history of type 2 diabetes for 15 years. Laboratory examinations showed elevated blood glucose level. Skin lesion biopsy showed a well-circumscribed area of necrosis filled with a keratotic plug. Parakeratotic cells and lymphocytic infiltration could be seen in the necrosed area. In dermis, sparse fiber bundles were seen perforating the epidermis. These degenerated fiber bundles were notarized as collagen fiber by elastic fiber stain, suggesting a diagnosis of RPC. Results: Then a diagnosis of ARPC was made according to the onset age and the history of diabetes mellitus. She was treated with topical application of corticosteroids twice a day and oral antihistamine once a day along with compound glycyrrhizin tablets 3 times a day. And the blood glucose was controlled in a satisfying range. Two months later, a significant improvement was seen in this patient. Conclusion: Since there is no efficient therapy to RPC, moreover, ARPC is considered to be associated with some systemic diseases, the management of the coexisting disease is quite crucial. The patient in this case received a substantial improvement due to the control of blood glucose and application of compound glycyrrhizin tablets. PMID

  18. Treatable high homocysteine alone or in concert with five other thrombophilias in 1014 patients with thrombotic events.

    PubMed

    Glueck, Charles J; Smith, Domonique; Gandhi, Niral; Hemachandra, Kailash; Shah, Parth; Wang, Ping

    2015-10-01

    In 1014 patients with thrombotic events, we determined how often treatable high serum homocysteine alone, or in concert with five other thrombophilias, was associated with thrombotic events. We studied 1014 outpatients sequentially referred for evaluation of thrombotic events, all having six measures of thrombophilia--three PCR (methylenetetrahydrofolate reductase C677T-A1298C, factor V Leiden G506A, prothrombin G20210A), and three serologic (factors VIII, XI, homocysteine). Of the 1014 patients, 198 (20%) had atherothrombosis, 199 (20%) ocular vascular thrombosis, 211 (21%) osteonecrosis, 180 (18%) pseudotumor cerebri, and 123 (12%) recurrent miscarriage. In 434 of 1014 (43%) patients, all six thrombophilic measures were normal. High homocysteine, present in 126 of 1014 patients (12.4%), was the sole thrombophilia in 50 (5%), accompanied only by methylenetetrahydrofolate reductase homozygosity-compound heterozygosity in 22 (2.2%), and accompanied by other thrombophilias in 54 (5%). Patients were more likely than 110 healthy controls to have high homocysteine (12 vs. 5%; P = 0.02) and high factor VIII (21 vs. 7%; P = 0.0003). On treatment for a median of 18 months with L-methyl folate (5 mg), vitamin B6 (100 mg), and vitamin B12 (2 mg/day), in 74 homocysteinemic patients, median homocysteine fell from 15.6 to 10.0 μmol/l (P < 0.0001), and in 56 (76%), homocysteine fell to normal on treatment. When homocysteinemia was the sole thrombophilia, normalization of homocysteine was accompanied by freedom from new thrombotic events in 38 of 41 patients (93%). In evaluation of 1014 patients with thrombotic events, 126 (12%) had treatable high serum homocysteine, and in 50 (5%), high homocysteine was the sole treatable thrombophilia.

  19. Thicker carotid intima-media thickness and increased plasma VEGF levels suffered by post-acute thrombotic stroke patients

    PubMed Central

    Yueniwati, Yuyun; Darmiastini, Ni Komang; Arisetijono, Eko

    2016-01-01

    Background and objectives Atherosclerosis causes reduction of the oxygen supply to structures in the far arterial wall, provoking the release of factors that drive angiogenesis of vasa vasorum, including VEGF. Other studies have revealed the inflammatory response in atherosclerosis and the role of platelet factor 4 (PF4) as an anti-angiogenic chemokine through the inhibition of VEGF. This cross-sectional study aims at measuring the effect of atherosclerosis assessed through carotid intima-media thickness (CIMT) against plasma VEGF levels in patients with post-acute thrombotic stroke. Materials and methods CIMT was assessed sonographically using GE Logiq S6 with 13 MHz frequency linear probe. VEGF-A plasma levels were measured using enzyme-linked immunosorbent assay (ELISA) method. Differences among variables were compared statistically. The data were analyzed using Pearson correlation. Results A total of 25 patients with post-acute thrombotic stroke were identified in days 7 to 90. CIMT thickening was indicated in 88% of patients (1.202 ± 0.312 mm), while an increase in plasma VEGF was identified in all patients (178.28 ± 93.96 ng/mL). There was no significant correlation between CIMT and plasma VEGF levels in patients with post-acute thrombotic stroke (p=0.741). A significant correlation was recognized between CIMT and total cholesterol (p=0.029) and low-density lipoprotein (p=0.018). Conclusion There were no significant correlations between CIMT and plasma VEGF levels in patients with post-acute thrombotic stroke. However, plasma VEGF increased in patients with thrombotic stroke. CIMT measurement is a promising noninvasive modality to assess the vascular condition of patients with stroke and diabetes, while plasma VEGF cannot specifically assess vascular condition as it can be triggered by ischemic conditions in tissues of the whole body. PMID:28008280

  20. Multidrug resistance-1 in T lymphocytes and natural killer cells of adults with idiopathic thrombocytopenic purpura: effect of prednisone treatment.

    PubMed

    López-Karpovitch, Xavier; Graue, Gerardo; Crespo-Solís, Erick; Piedras, Josefa

    2008-07-01

    High P-glycoprotein-mediated multidrug resistance-1 (P-gp/MDR1) activity in lymphocytes from idiopathic thrombocytopenic purpura (ITP) patients may affect disease outcome. ITP treatment includes glucocorticoids that are substrates of P-gp; hence, P-gp functional activity and antigenic expression were assessed by flow cytometry in T and natural killer (NK) cells from ITP patients before and after prednisone therapy. Herein, patients' T and NK cells did not show increased MDR1 functional activity, whereas P-gp antigenic expression was significantly enhanced in both therapy-free and prednisone-treated patients. Prednisone treatment did not significantly modify the function and expression of MDR1 in T and NK cells of ITP patients.

  1. Low-dose vincristine in the treatment of corticosteroid-refractory idiopathic thrombocytopenic purpura (ITP) in non-splenectomized patients.

    PubMed Central

    Cervantes, F.; Montserrat, E.; Rozman, C.; Diumenjo, C.; Feliu, E.; Grañena, A.

    1980-01-01

    Eight non-splenectomized patients with corticosteroid-refractory idiopathic thrombocytopenic purpura (ITP) were treated with low-dose vincristine (1 mg/week up to a total dose of 4 mg). Complete remission was achieved in 2 cases and partial remission in 3. Bleeding stopped in one patient who failed to remit. No statistical relationship was found between the response to vincristine and the duration of the disease or the corticosteroid-therapy. Side effects were only observed in one patient. By comparing these results with those reported in the literature, it can be inferred that low-dose vincristine may be useful in the management of corticosteroid-refractory ITP. PMID:7194478

  2. Simultaneous reactivation of herpes simplex virus and varicella-zoster virus in a patient with idiopathic thrombocytopenic purpura.

    PubMed

    Nikkels, A F; Frère, P; Rakic, L; Fassotte, M; Evrard, B; De Mol, P; Piérard, G E

    1999-01-01

    Simultaneous reactivation of distinct Herpesviridae with development of clinical manifestations is exceptional. We report a 48-year-old woman suffering from idiopathic thrombocytopenic purpura. As the disease remained refractory to corticosteroids, immunoglobulins and splenectomy, a cure of vinblastine was administered. An atypical stomatitis developed few days later. Immunohistochemistry on a Tzanck smear and a biopsy evidenced a Herpes simplex virus type 1 (HSV-1) infection. The patient presented simultaneously a single necrotic lesion on the abdomen. Immunohistochemistry on a skin biopsy revealed the presence of the varicella-zoster virus (VZV) gE, gB and IE63 proteins. Intravenous aciclovir was initiated. The present case of simultaneous clinical infections by HSV-I and VZV underlines the importance of complementary viral identification testing in the event of unusual clinical presentations.

  3. 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.

  4. Hereditary Thrombophilia and thrombotic events in pregnancy: single-center experience.

    PubMed

    Coriu, L; Ungureanu, R; Talmaci, R; Uscatescu, V; Cirstoiu, M; Coriu, D; Copaciu, E

    2014-01-01

    Pregnancy is a normal physiological state that predisposes to thrombosis, determined by hormonal changes in the body. These changes occur in the blood flow (venous stasis), changes in the vascular wall (hypotonia, endothelial lesion) and changes in the coagulation factors (increased levels of factor VII, factor VIII, factor X, von Willebrand factor) and decreased activity levels of natural anticoagulants (protein C, protein S). In this study, we tried to determine a possible association between thrombosis and inherited thrombophilia in pregnant women. This is a retrospective study of 151 pregnant women with a history of complicated pregnancy: maternal thrombosis and placental vascular pathology (intrauterine growth restriction, preeclampsia, recurrent pregnancy loss), who were admitted in our hospital during the period January 2010 to July 2014. We performed genetic analyses to detect the factor V Leiden mutation, the G20210A mutation in the prothrombin gene, the C677T mutation and the A1298C mutation in methylenetetrahydrofolate reductase (MTHFR) gene. The risk of thrombosis in patients with factor V Leiden is 2.66 times higher than the patients negative for this mutation (OR 2.66 95% CI 0.96-7.37 P=0.059). We did not find any statistical association with mutations in the MTHFR gene. Pregnant women with a family history of thrombosis present a 2.18-fold higher risk of thrombosis (OR 2.18 CI 0.9-5.26 P=0.085). Of 151 pregnant women, thrombotic events occurred in 24 patients: deep vein thrombosis, pulmonary embolism, cerebral venous sinus thrombosis and ischemic stroke. The occurrence of thrombotic events was identified in the last trimester of pregnancy, but especially postpartum. Thrombosis in pregnancy is a redoubtable complication requiring an excellent cooperation between the obstetrician and anesthesiologist.

  5. Future therapeutic directions for factor Xa inhibition in the prophylaxis and treatment of thrombotic disorders.

    PubMed

    Turpie, Alexander G G

    2003-11-15

    The targeted mechanism of factor Xa inhibition has been studied extensively, initially as prophylaxis for venous thromboembolism (VTE) in the orthopedic surgical setting. Future therapeutic directions for selective factor Xa inhibition in the management of other thrombotic diseases are discussed. Thromboembolic diseases can occur in the venous or arterial sides of the circulatory system. Factor Xa inhibition is a targeted approach to anticoagulation that resulted from significant advances in our understanding of the coagulation cascade. The factor Xa inhibitor fondaparinux has been studied extensively in the orthopedic surgical setting for the prophylaxis of VTE. Current investigations that are under way or completed evaluate the efficacy and safety of fondaparinux for the management of various thrombotic diseases. The future development of fondaparinux resides primarily in three therapeutic areas: prevention of VTE, treatment of VTE, and treatment of acute coronary syndromes. For the prevention of VTE, fondaparinux has been studied as extended prophylaxis following hip fracture surgery (PENTHIFRA Plus), for use in high-risk abdominal surgical patients (PEGASUS and APOLLO), and for use in medical patients (ARTEMIS). Studies evaluating fondaparinux for the treatment of VTE are part of the large MATISSE clinical program (MATISSE DVT and MATISSE PE). Fondaparinux was investigated in phase 2 studies for the treatment of acute coronary syndromes, including acute ST-segment myocardial infarction (PENTALYSE) and unstable angina (PENTUA). Encouraging data from these trials are the basis for phase 3 programs in this area (MICHELANGELO). The orthopedic prophylactic and nonorthopedic clinical programs for fondaparinux in the management of thrombosis support the concept that targeted inhibition of coagulation is an effective advance in antithrombotic therapy.

  6. Combined assessment of thrombotic and haemorrhagic risk in acute medical patients.

    PubMed

    La Regina, Micaela; Orlandini, Francesco; Marchini, Francesca; Marinaro, Alessia; Bonacci, Rosanna; Bonanni, Paola; Corsini, Francesca; Ceraudo, Anna Maria; Pacetti, Edoarda; Scuotri, Lucia; Costabile, Davide; Dentali, Francesco

    2016-01-01

    Acute medical patients have a high risk of venous thromboembolic events (VTE). Unfortunately, the fear of bleeding complications limits the use of antithrombotic prophylaxis in this setting. To stratify the VTE and haemorrhagic risk, two clinical scores (PADUA, IMPROVE) have recently been developed. However, it is not clear how many patients have a concomitant high VTE and haemorrhagic risk and what is the use of prophylaxis in this situation. To clarify these issues we performed a prospective cohort study enrolling consecutive patients admitted to internal medicine. Patients admitted to internal medicine (January to December 2013) were included. VTE and haemorrhagic risk were evaluated in all the included patients. Use and type of anti-thrombotic prophylaxis was recorded. A total of 1761 patients (mean age 77.6 years) were enrolled; 76.8% (95% CI 74.7-78.7) were at high VTE risk and 11.9% (95% CI 10.4-13.5) were at high haemorrhagic risk. Anti-thrombotic prophylaxis was used in 80.5% of patients at high VTE risk and in 6.5% at low VTE risk (p<0.001), and in 16.6% at high haemorrhagic risk and in 72.5% at low haemorrhagic risk (p<0.001). Prophylaxis was used in 20.4% at both high VTE and haemorrhagic risk and in 88.9% at high VTE risk but low haemorrhagic risk. At multivariate-analysis, use of prophylaxis appeared highly influenced by the VTE risk (OR 68.2, 95% CI 43.1 - 108.0). In conclusion, many patients admitted to internal medicine were at high risk of VTE. Since almost 90% of them were at low haemorrhagic risk, pharmacological prophylaxis may be safely prescribed in most of these patients.

  7. Activation of Blood Coagulation in Two Prototypic Autoimmune Skin Diseases: A Possible Link with Thrombotic Risk.

    PubMed

    Cugno, Massimo; Tedeschi, Alberto; Borghi, Alessandro; Bucciarelli, Paolo; Asero, Riccardo; Venegoni, Luigia; Griffini, Samantha; Grovetti, Elena; Berti, Emilio; Marzano, Angelo Valerio

    2015-01-01

    Coagulation activation has been demonstrated in two prototypic autoimmune skin diseases, chronic autoimmune urticaria and bullous pemphigoid, but only the latter is associated with increased thrombotic risk. Two markers of coagulation activation (prothrombin fragment F1+2 and fibrin fragment D-dimer) were measured by immunoenzymatic methods in plasma samples from 30 patients with active chronic autoimmune urticaria, positive for autologous serum skin test, 30 patients with active bullous pemphigoid and 30 healthy subjects. In skin biopsies, tissue factor expression was evaluated by both immunohistochemistry and in situ hybridization. F1+2 and D-dimer levels were higher in active chronic autoimmune urticaria (276.5±89.8 pmol/L and 5.56±4.40 nmol/L, respectively) than in controls (145.2±38.0 pmol/L and 1.06±0.25 nmol/L; P=0.029 and P=0.011) and were much higher in active bullous pemphigoid (691.7±318.7 pmol/L and 15.24±9.09 nmol/L, respectively) (P<0.0001). Tissue factor positivity was evident in skin biopsies of both disorders with higher intensity in bullous pemphigoid. F1+2 and D-dimer, during remission, were markedly reduced in both disorders. These findings support the involvement of coagulation activation in the pathophysiology of both diseases. The strong systemic activation of coagulation in bullous pemphigoid may contribute to increase the thrombotic risk and provides the rationale for clinical trials on anticoagulant treatments in this disease.

  8. 16 CFR 801.2 - Acquiring and acquired persons.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 1 2013-01-01 2013-01-01 false Acquiring and acquired persons. 801.2 Section 801.2 Commercial Practices FEDERAL TRADE COMMISSION RULES, REGULATIONS, STATEMENTS AND INTERPRETATIONS UNDER THE HART-SCOTT-RODINO ANTITRUST IMPROVEMENTS ACT OF 1976 COVERAGE RULES § 801.2...

  9. 16 CFR 801.2 - Acquiring and acquired persons.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Acquiring and acquired persons. 801.2 Section 801.2 Commercial Practices FEDERAL TRADE COMMISSION RULES, REGULATIONS, STATEMENTS AND INTERPRETATIONS UNDER THE HART-SCOTT-RODINO ANTITRUST IMPROVEMENTS ACT OF 1976 COVERAGE RULES § 801.2...

  10. 16 CFR 801.2 - Acquiring and acquired persons.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 1 2012-01-01 2012-01-01 false Acquiring and acquired persons. 801.2 Section 801.2 Commercial Practices FEDERAL TRADE COMMISSION RULES, REGULATIONS, STATEMENTS AND INTERPRETATIONS UNDER THE HART-SCOTT-RODINO ANTITRUST IMPROVEMENTS ACT OF 1976 COVERAGE RULES § 801.2...

  11. 16 CFR 801.2 - Acquiring and acquired persons.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 1 2014-01-01 2014-01-01 false Acquiring and acquired persons. 801.2 Section 801.2 Commercial Practices FEDERAL TRADE COMMISSION RULES, REGULATIONS, STATEMENTS AND INTERPRETATIONS UNDER THE HART-SCOTT-RODINO ANTITRUST IMPROVEMENTS ACT OF 1976 COVERAGE RULES § 801.2...

  12. 16 CFR 801.2 - Acquiring and acquired persons.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Acquiring and acquired persons. 801.2 Section 801.2 Commercial Practices FEDERAL TRADE COMMISSION RULES, REGULATIONS, STATEMENTS AND INTERPRETATIONS UNDER THE HART-SCOTT-RODINO ANTITRUST IMPROVEMENTS ACT OF 1976 COVERAGE RULES § 801.2...

  13. Nonbacterial thrombotic endocarditis with embolic cerebral vascular accidents in a patient with advanced, recurrent clear cell carcinoma of the ovary: A case report.

    PubMed

    Liang, Lusha W; Perez, Alexander R; Cangemi, Nicholas A; Young, Robert J; Makker, Vicky

    2016-04-01

    •Nonbacterial thrombotic endocarditis can occur in ovarian clear cell carcinoma.•We report on NBTE-associated embolic cerebrovascular infarcts in advanced OCCC.•Further NBTE-associated embolic events can be prevented with anticoagulant therapy.

  14. Radiolabeled anti-tissue factor antibody (AP-1) for imaging thrombotic disease by PET

    SciTech Connect

    Joshi, V.; Meinken, G.; Srivastava, S.

    1995-05-01

    The objective of this study was to develop and test radioimmunoconjugates of AP-1, an anti-tissue factor (TF) MAb, for PET imaging of vessel wall injury or associated thrombotic disease. Recently, anti rabbit MAb AP-1 was shown to prevent thrombosis following vascular injury in a rabbit model. In the represent study of AP-1 was conjugated with the conventional DTPA dianhydride (DTPA-DA) and with 4-isothiocyanato-cyclohexyl-EDTA (4-ICE) (2 to 2.5 ligands per MAb). Labeling with {sup 57}Co was done by adding {sup 57}CoCl{sub 2} in 0.1 N HCl to 500 {mu}g of conjugate in 0.1 M NaHCO{sub 3} containing 0.12 M acetate. The reaction mixture (pH {approximately} 5.5) was allowed to stand at room temperature for 8 h, and then purified by size exclusion HPLC following EDTA chase (10 {mu}l of 0.1 M EDTA, pH 7.0, 10 min). Labeling efficiencies were >90%. When incubated with mouse serum these conjugates showed similar stability ({approximately}3% activity loss for 4-ICE vs 6% for DTPA-DA at 24 h). The inhibition of tissue factor procoagulant activity was determined for the {sup 67}Co labeled conjugates using a two stage clotting assay. In the first stage, clotting times were determined using serial dilutions of reconstituted TF standards to check linearity. In the second stage, clotting times were determined for {sup 67}Co labeled AP-1 conjugates at various dilutions (1 ng to 1 {mu}g/mL) in presence of 150 ng/ml of TF. Results were compared with those obtained using unlabeled conjugates and the native AP-1. Neither conjugation with chelators nor radiolabelling affected the TF activity of AP-1. These conjugates labeled with {sup 66}Co (t l/1 17.5 h, {beta}{sup +} emission) should prove effective for PET imaging of vessel wall injury or thrombotic disease in our previously established rabbit model. Based on our previous data with other MAbs, the 4-ICE conjugate is expected to provide better biodistribution.

  15. Potential influences of complement factor H in autoimmune inflammatory and thrombotic disorders.

    PubMed

    Ferluga, Janez; Kouser, Lubna; Murugaiah, Valarmathy; Sim, Robert B; Kishore, Uday

    2017-04-01

    Complement system homeostasis is important for host self-protection and anti-microbial immune surveillance, and recent research indicates roles in tissue development and remodelling. Complement also appears to have several points of interaction with the blood coagulation system. Deficiency and altered function due to gene mutations and polymorphisms in complement effectors and regulators, including Factor H, have been associated with familial and sporadic autoimmune inflammatory - thrombotic disorders, in which autoantibodies play a part. These include systemic lupus erythematosus, rheumatoid arthritis, atypical haemolytic uremic syndrome, anti-phospholipid syndrome and age-related macular degeneration. Such diseases are generally complex - multigenic and heterogeneous in their symptoms and predisposition/susceptibility. They usually need to be triggered by vascular trauma, drugs or infection and non-complement genetic factors also play a part. Underlying events seem to include decline in peripheral regulatory T cells, dendritic cell, and B cell tolerance, associated with alterations in lymphoid organ microenvironment. Factor H is an abundant protein, synthesised in many cell types, and its reported binding to many different ligands, even if not of high affinity, may influence a large number of molecular interactions, together with the accepted role of Factor H within the complement system. Factor H is involved in mesenchymal stem cell mediated tolerance and also contributes to self-tolerance by augmenting iC3b production and opsonisation of apoptotic cells for their silent dendritic cell engulfment via complement receptor CR3, which mediates anti-inflammatory-tolerogenic effects in the apoptotic cell context. There may be co-operation with other phagocytic receptors, such as complement C1q receptors, and the Tim glycoprotein family, which specifically bind phosphatidylserine expressed on the apoptotic cell surface. Factor H is able to discriminate between self and

  16. Recurrent pseudotumor cerebri in childhood: a case of neuro-Behçet disease complicated with thrombotic risk factors.

    PubMed

    Yilmaz, Sanem; Serdaroglu, Gul; Unver, Hale; Akcay, Ayfer; Gokben, Sarenur; Tekgul, Hasan

    2011-07-01

    Pseudotumor cerebri with or without venous sinus thrombosis is a rare clinical presentation of Behçet disease in childhood. We present here a case of childhood pseudotumor cerebri without a previous diagnosis of Behçet disease. The detailed history and physical examination of the case led to the diagnosis of neuro-Behçet disease. The investigation of predisposition to thrombosis revealed heterozygous factor V Leiden mutation along with the high lipoprotein(a) level. The symptoms resolved dramatically by treatment with the combination of immunosuppression and anticoagulation with regard to the detected factor V Leiden mutation and high lipoprotein(a) level. After a symptom-free period of 9 months, the cerebral vein thrombosis recurred. We present this case to draw attention to this rare cause of pseudotumor cerebri in childhood and to emphasize the importance of additional thrombotic risk factors regarding the potential recurrence of thrombotic events in Behçet disease.

  17. Thrombotic events in MYH9 gene-related autosomal macrothrombocytopenias (old May-Hegglin, Sebastian, Fechtner and Epstein syndromes).

    PubMed

    Girolami, Antonio; Antonio, Girolami; Vettore, Silvia; Silvia, Vettore; Bonamigo, Emanuela; Emanuela, Bonamigo; Fabris, Fabrizio; Fabrizio, Fabris

    2011-11-01

    Congenital macrothrombocytopenia are a group of disorders which may be due to mutations in the MYH9 gene. This gene linked to chromosome 22 encodes for the nonmuscle heavy chain IIA that is expressed in platelets and in other tissues. In the past these disorders were known as May-Hegglin anomaly, Sebastian, Fechtner and Epstein syndromes. The main common feature is the presence of thrombocytopenia with large platelets. The evaluation of all reported cases indicates that thrombotic events appear to occur only in patients with May Hegglin variants. Whether this is due to the higher prevalence of this variant as compared with the others or to a specific difference is still unknown. However, the occurrence of thrombotic events in only one of these conditions may be used as a new tentative differentiability feature.

  18. [Characteristic of fatal thrombotic complications based on the materials from the Thanatology Department of Forensic Medicine Bureau of the Rostov region, for 2004-2007].

    PubMed

    Berezovskiĭ, D P; Kolkutin, V V; Kovtunov, V V; Kornienko, I V

    2009-01-01

    The authors report statistical data on the spectrum and frequency of fatal thrombotic complications based on the analysis of materials available from the regional bureau of forensic medical examination collected in the period from 2004 to 2007. All lethal cases are categorized in terms of the patients' age, gender, time and clinical characteristics of the injury, time of surgical intervention. Results of the analysis indicate the necessity of examination of fatal cases of thrombotic complications following a standardized protocol.

  19. Anti-thrombotic effect of a novel formula from Corni fructus with malic acid, succinic acid and citric acid.

    PubMed

    Zhang, Qi-Chun; Zhao, Yue; Bian, Hui-Min

    2014-05-01

    Our previous investigation had confirmed the inhibition of platelet aggregation of a novel Corni fructus-derived formula composed of malic acid, succinic acid and citric acid with a ratio of 3:2:2. The present study was to further evaluate the anti-thrombotic effect of the formula in vivo. Mice of acute pulmonary thromboembolism, and rats of arterial thrombosis were used to determine the anti-thrombotic effect of the formula. Histology analysis of endothelium was conducted with hematoxylin and eosin stain. TXB2 , 6-K-PGF1α , cAMP, cGMP and NO in rat plasma were determined. In vitro assay of αIIbβ3 and phosphorylation of ERK1/2 were performed in ADP-treated platelet. The formula significantly reduced the recovery time and mortality rate of mice with acute pulmonary thromboembolism. Remarkably extended occlusion time, decreased thrombus weight and more integrated endothelium were observed in rat with the formula. Enhanced 6-K-PGF1α , cGMP and NO, but not TXB2 and cAMP, were demonstrated in rat plasma with treatment of the formula. Finally, the formula was shown to inhibit αIIbβ3 expression and activation of ERK1/2 in platelet. The formula shows positive anti-thrombotic effect. The direct interference on ADP activated signaling in platelet and regulation of endothelium function are two primary pathways involved in the action on thrombosis.

  20. Two cases of kidney transplantation-associated thrombotic microangiopathy successfully treated with eculizumab.

    PubMed

    Ikeda, Takashi; Okumi, Masayoshi; Unagami, Kohei; Kanzawa, Taichi; Sawada, Anri; Kawanishi, Kunio; Omoto, Kazuya; Ishida, Hideki; Tanabe, Kazunari

    2016-07-01

    Transplantation-associated thrombotic microangiopathy (TA-TMA) is relatively rare and requires immediate intervention to avoid irreversible organ damage or death; however, consensus regarding the treatment approach is lacking. Atypical haemolytic uraemic syndrome (aHUS) is a rare disease caused by dysregulation of the alternative complement pathway resulting in TMA. aHUS is histologically similar to TA-TMA; approximately 60% of TA-TMA patients have complement dysregulation. Eculizumab, a humanized anti-C5 monoclonal antibody, inhibits terminal membrane-attack complex formation and TMA progression. Eculizumab has been successfully used to treat aHUS post-transplant. We present two cases of kidney TA-TMA due to unknown causes, suspected antibody-mediated rejection, or calcineurin inhibitor (CNI)-related toxicity that developed on day 1 or 2 post-kidney transplantation. Low platelet count and haemoglobin level with red cell fragments were detected. Despite steroid pulse, plasma exchange (PE), and intravenous immunoglobulin therapy, TA-TMA did not improve; therefore, eculizumab was administered despite no genetic testing. Laboratory data, including renal function, improved immediately. TA-TMA treatment primarily involves PE initiation or CNI discontinuation; eculizumab can be used to safely treat TA-TMA and then be ceased in the short term. Therefore, eculizumab administration might be beneficial for kidney TA-TMA as early as the diagnosis of refractory to PE.

  1. Thrombotic microangiopathy caused by oral contraceptives in a kidney transplant recipient.

    PubMed

    Shirai, Hiroyuki; Yashima, Jun; Tojimbara, Tamotsu; Honda, Kazuho

    2016-07-01

    Thrombotic microangiopathy (TMA) after kidney transplantation has various aetiologies, including acute antibody-mediated rejection, bacterial or viral infection and immunosuppressive drugs, particularly calcineurin inhibitors. We present the case of a 28-year-old woman who developed TMA 30 months after the transplantation of an ABO-incompatible kidney from a living unrelated donor. The patient developed a sudden onset of allograft renal dysfunction and became uremic. She was transferred to our institution from a community hospital with strongly suspected acute allograft rejection. Intensive treatments for both T- and B-cell mediated acute rejection, including steroid pulse therapy, double-filtration plasmapheresis, antithymocyte globulin (1.5 mg/kg × 14 days) and rituximab (100 mg), were initiated during haemodialysis. However, her renal allograft function did not improve. Histopathological analysis 8 days after the treatment indicated TMA, despite the absence of apparent acute T-cell- or acute antibody-mediated rejection. There were no symptoms of infectious diseases, such as intestinal haemorrhagic colitis or viral infection. We concluded that the use of oral contraceptives, which had been initiated 3 weeks before TMA onset for the treatment of irregular vaginal bleeding, was the aetiologic agent.

  2. Neurological Dysfunction Associated with Antiphospholipid Syndrome: Histopathological Brain Findings of Thrombotic Changes in a Mouse Model

    PubMed Central

    Ziporen, Lea; Polak-Charcon, Sylvia; Korczyn, D. Amos; Goldberg, Iris; Afek, Arnon; Kopolovic, Juri; Chapman, Joab

    2004-01-01

    The aim of this work was to study the pathological processes underlying neurological dysfunctions displayed by BALB/C mice induced with experimental antiphospholipid syndrome (APS), as we have previously reported. Experimental APS was induced in female BALB/C mice by immunization with a pathogenic monoclonal anticardiolipin (aCL) antibody, H-3 (n=10), or an irrelevant immunoglobulin in controls (n=10). Mice immunized with H-3 developed clinical and neurological manifestations of APS, including: embryo resorption, thrombocytopenia neurological defects and behavioral disturbances. In mouse sera, the titer of various autoantibodies were elevated, including: anti-phospholipids (aPLs), anti-2 glycoprotein-I (β2GPI), anti-endothelial cell antibodies (AECA) and low titer of anti-dsDNA antibodies. Five months after APS induction, mice were sacrificed and brain tissue specimens were processed for hematoxylin and eosin (H&E), immunofluorescence staining and transmission electron microscopy (TEM). H&E staining of cortical tissue derived from all APS mice revealed mild inflammation, localized mainly in the meninges. Prominent IgG deposits in the large vessel walls and perivascular IgG leakage were observed by immunofluorescence. No large thrombi were observed in large vessels. However, EM evaluation of cerebral tissue revealed pathological changes in the microvessels. Thrombotic occlusion of capillaries in combination with mild inflammation was the main finding and may underlie the neurological defects displayed by mice with APS. PMID:15154615

  3. De novo thrombotic microangiopathy after non-renal solid organ transplantation.

    PubMed

    Verbiest, Annelies; Pirenne, Jacques; Dierickx, Daan

    2014-11-01

    Thrombotic microangiopathy (TMA) is a rare but serious complication of organ transplantation. This article presents the first literature review on TMA following non-renal solid organ transplantation (SOT). Ischemia-reperfusion, immunosuppressive drugs, acute interfering disease and a relative deficiency of the von Willebrand factor (vWF) cleaving protease (ADAMTS13) appear to play a major role in its pathogenesis. De novo TMA occurs in 4.0% of liver and 2.3% of lung transplant recipients, whereas the incidence remains unknown after intestinal transplantation. The median time of onset is 2, 37 and 8 weeks after liver, lung and intestinal transplantations respectively, with a three month survival of about 70%. In heart transplantation TMA is rare, occurrence is late and prognosis is poor. In TMA early after liver transplantation an elevated vWF/ADAMTS13 ratio may show diagnostic value. Early withdrawal of calcineurin inhibitors (CNI) proves to be lifesaving. Conversion to another CNI and rechallenge after resolution are generally safe, except after heart transplantation. The value of plasma exchange therapy remains controversial.

  4. Thrombotic risk assessment in antiphospholipid syndrome: the role of new antibody specificities and thrombin generation assay.

    PubMed

    Sciascia, Savino; Baldovino, Simone; Schreiber, Karen; Solfietti, Laura; Radin, Massimo; Cuadrado, Maria J; Menegatti, Elisa; Erkan, Doruk; Roccatello, Dario

    2016-01-01

    Antiphospholipid syndrome (APS) is an autoimmune condition characterized by the presence of antiphospholipid antibodies (aPL) in subjects presenting with thrombosis and/or pregnancy loss. The currently used classification criteria were updated in the international consensus held in Sidney in 2005. Vascular events seem to result of local procoagulative alterations upon triggers influence (the so called "second-hit theory"), while placental thrombosis and complement activation seem to lead to pregnancy morbidity. The laboratory tests suggested by the current classification criteria include lupus anticoagulant, a functional coagulation assay, and anticardiolipin and anti-β2-glycoprotein-I antibodies, generally detected by solid phase enzyme-linked immunosorbent assay. The real challenge for treating physicians is understanding what is the actual weight of aPL in provoking clinical manifestations in each case. As thrombosis has a multi-factorial cause, each patient needs a risk-stratified approach. In this review we discuss the role of thrombotic risk assessment in primary and secondary prevention of venous and arterial thromboembolic disease in patients with APS, focusing on new antibody specificities, available risk scoring models and new coagulation assays.

  5. Compression stockings to prevent post-thrombotic syndrome: a role for anticoagulation clinics?

    PubMed

    Wittkowsky, Ann K; Nutescu, Edith A; Devine, Emily Beth

    2008-12-01

    Anticoagulation clinics are increasingly used to manage oral anticoagulant therapy in patients with venous thromboembolic disease (VTE). Such clinics may be in a position to assume greater responsibility for other aspects of the long-term management of VTE, including prevention of post-thrombotic syndrome (PTS). Current guidelines suggest use of graduated elastic compression stockings with a pressure of 30-40 mm Hg at the ankle for 2 years following the diagnosis of deep vein thrombosis (DVT) to prevent PTS. A survey of anticoagulation clinic providers was conducted to determine to what extent patients with DVT are prescribed compression stockings and by whom, and the degree of compression and duration of therapy prescribed. Survey results show a very low rate of use of compression stockings in patients with DVT, and limited adherence to current recommendations for strength and duration of use. We believe that healthcare providers practicing in anticoagulation clinics should be encouraged to expand their scope of practice into a more comprehensive model of antithrombosis care, including prevention of PTS. By doing so, the extent of use of compression stockings might be increased, and adherence to current guidelines for strength and duration of compression might be improved.

  6. Left atrial strain: a new predictor of thrombotic risk and successful electrical cardioversion

    PubMed Central

    González-Alujas, Teresa; Valente, Filipa; Aranda, Carlos; Rodríguez-Palomares, José; Gutierrez, Laura; Maldonado, Giuliana; Galian, Laura; Teixidó, Gisela; Evangelista, Artur

    2016-01-01

    Background Left atrial deformation (LAD) parameters are new markers of atrial structural remodelling that seem to be affected in atrial fibrillation (AF) and atrial flutter (AFL). This study aimed to determine whether LAD can identify patients with a higher risk of thrombosis and unsuccessful electrical cardioversion (ECV). Methods Retrospective study including 56 patients with AF or AFL undergoing ECV, with previous transthoracic (TTE) and transoesophageal echocardiography (TEE) studies. Echocardiographic parameters analysed were as follows: left ventricle function, left atrium (LA) dimensions, LAD parameters (positive and negative strain peaks), left atrial appendage (LAA) filling and emptying velocities and the presence of thrombi. Strain values were analysed according to thrombotic risk and success of ECV. Results Lower mean values of peak-positive strain (PPS) in patients with prothrombotic velocities (<25 cm/s) and a higher incidence of thrombi in LAA were observed compared with those with normal velocities. Multivariate analysis revealed PPS normalised by LA maximum volume indexed by body surface area (BSA) to be associated with prothrombotic risk (odds ratio 0.000 (95% CI: 0.000–0.243), P 0.017), regardless of CHADs2VASC score. Peak-negative strain normalised by LA volumes indexed by BSA were associated with unsuccessful ECV. Conclusions Atrial deformation parameters identify AF and AFL patients with a high risk of thrombosis and unsuccessful ECV. Therefore, these new parameters should be included in anticoagulation management and rhythm vs rate control strategies. PMID:27249551

  7. The Role of Complement Inhibition in Thrombotic Angiopathies and Antiphospholipid Syndrome.

    PubMed

    Erkan, Doruk; Salmon, Jane E

    2016-03-05

    Antiphospholipid syndrome (APS) is characterized by thrombosis (arterial, venous, small vessel) and/or pregnancy morbidity occurring in patients with persistently positive antiphospholipid antibodies (aPL). Catastrophic APS is the most severe form of the disease, characterized by multiple organ thromboses occurring in a short period and commonly associated with thrombotic microangiopathy (TMA). Similar to patients with complement regulatory gene mutations developing TMA, increased complement activation on endothelial cells plays a role in hypercoagulability in aPL-positive patients. In mouse models of APS, activation of the complement is required and interaction of complement (C) 5a with its receptor C5aR leads to aPL-induced inflammation, placental insufficiency, and thrombosis. Anti-C5 antibody and C5aR antagonist peptides prevent aPL-mediated pregnancy loss and thrombosis in these experimental models. Clinical studies of anti-C5 monoclonal antibody in aPL-positive patients are limited to a small number of case reports. Ongoing and future clinical studies of complement inhibitors will help determine the role of complement inhibition in the management of aPL-positive patients.

  8. Endocardial Endothelial Dysfunction Progressively Disrupts Initially Anti then Pro-Thrombotic Pathways in Heart Failure Mice

    PubMed Central

    Schoner, Amanda; Tyrrell, Christina; Wu, Melinda; Gelow, Jill M.; Hayes, Alicia A.; Lindner, Jonathan R.; Thornburg, Kent L.; Hasan, Wohaib

    2015-01-01

    Objective An experimental model of endocardial thrombosis has not been developed and endocardial endothelial dysfunction in heart failure (HF) is understudied. We sought to determine whether disruption of the endothelial anti-coagulant activated protein C (APC) pathway in CREBA133 HF mice promotes endocardial thrombosis in the acute decompensated phase of the disease, and whether alterations in von Willebrand factor (vWF) secretion from HF endocardium reduces thrombus formation as HF stabilizes. Approach and results Echocardiography was used to follow HF development and to detect endocardial thrombi in CREBA133 mice. Endocardial thrombi incidence was confirmed with immunohistochemistry and histology. In early and acute decompensated phases of HF, CREBA133 mice had the highest incidence of endocardial thrombi and these mice also had a shorter tail-bleeding index consistent with a pro-thrombotic milieu. Both APC generation, and expression of receptors that promote APC function (thrombomodulin, endothelial protein C receptor, protein S), were suppressed in the endocardium of acute decompensated HF mice. However, in stable compensated HF mice, an attenuation occurred for vWF protein content and secretion from endocardial endothelial cells, vWF-dependent platelet agglutination (by ristocetin), and thrombin generation on the endocardial surface. Conclusions CREBA133 mice develop HF and endocardial endothelial dysfunction. Attenuation of the anti-coagulant APC pathway promotes endocardial thrombosis in early and acute decompensated phases of HF. However, in stable compensated HF mice, disruptions in endothelial vWF expression and extrusion may actually reduce the incidence of endocardial thrombosis. PMID:26565707

  9. Type I interferon causes thrombotic microangiopathy by a dose-dependent toxic effect on the microvasculature

    PubMed Central

    Kavanagh, David; Jury, Alexa; Williams, Jac; Scolding, Neil; Bellamy, Chris; Gunther, Claudia; Ritchie, Diane; Gale, Daniel P.; Kanwar, Yashpal S.; Challis, Rachel; Buist, Holly; Overell, James; Weller, Belinda; Flossmann, Oliver; Blunden, Mark; Meyer, Eric P.; Krucker, Thomas; Evans, Stephen J. W.; Campbell, Iain L.; Jackson, Andrew P.; Chandran, Siddharthan

    2016-01-01

    Many drugs have been reported to cause thrombotic microangiopathy (TMA), yet evidence supporting a direct association is often weak. In particular, TMA has been reported in association with recombinant type I interferon (IFN) therapies, with recent concern regarding the use of IFN in multiple sclerosis patients. However, a causal association has yet to be demonstrated. Here, we adopt a combined clinical and experimental approach to provide evidence of such an association between type I IFN and TMA. We show that the clinical phenotype of cases referred to a national center is uniformly consistent with a direct dose-dependent drug-induced TMA. We then show that dose-dependent microvascular disease is seen in a transgenic mouse model of IFN toxicity. This includes specific microvascular pathological changes seen in patient biopsies and is dependent on transcriptional activation of the IFN response through the type I interferon α/β receptor (IFNAR). Together our clinical and experimental findings provide evidence of a causal link between type I IFN and TMA. As such, recombinant type I IFN therapies should be stopped at the earliest stage in patients who develop this complication, with implications for risk mitigation. PMID:27663672

  10. Intestinal thrombotic microangiopathy following reduced-intensity umbilical cord blood transplantation.

    PubMed

    Narimatsu, H; Kami, M; Hara, S; Matsumura, T; Miyakoshi, S; Kusumi, E; Kakugawa, Y; Kishi, Y; Murashige, N; Yuji, K; Masuoka, K; Yoneyama, A; Wake, A; Morinaga, S; Kanda, Y; Taniguchi, S

    2005-09-01

    Thrombotic microangiopathy (TMA) is a significant complication after hematopoietic stem-cell transplantation (HSCT); however, there is little information on it following reduced-intensity cord blood transplantation (RI-CBT). We reviewed the medical records of 123 adult patients who received RI-CBT at Toranomon Hospital between January 2002 and August 2004. TMA was diagnosed in seven patients based on intestinal biopsy (n = 6) or autopsy results (n = 1). While these patients showed some clinical symptoms such as diarrhea and/or abdominal pain, mental status alterations or neurological disorders were not observed in any of them. Laboratory results were mostly normal at the onset of TMA; >2% fragmented erythrocytes (n = 1), <10 mg/dl haptoglobin (n = 1), and >200 IU/dl lactic dehydrogenase (LD) (n = 4). On endoscopic examination, TMA lesions, consisting of ulcers, erosions, and diffuse exfoliation, were distributed spottily from terminal ileum to rectum. Intestinal graft-versus-host disease (GVHD) and cytomegalovirus (CMV) colitis were confirmed in five and four patients, respectively. With therapeutic measures including supportive care (n = 4), fresh frozen plasma (n = 1), and a reduction of immunosuppressive agents (n = 1), TMA improved in four patients. The present study demonstrates that intestinal TMA is a significant complication after RI-CBT. Since conventional diagnostic criteria can overlook TMA, its diagnosis requires careful examination of the gastrointestinal tract using endoscopy with biopsy.

  11. Transcutaneous oxygen tension in patients with post-thrombotic leg ulcers: treatment with intermittent pneumatic compression.

    PubMed

    Kolari, P J; Pekanmäki, K; Pohjola, R T

    1988-02-01

    Transcutaneous oxygen tension (TcPO2) and the effect of intermittent pneumatic compression on tissue oxygenation were studied in 10 patients with post-thrombotic leg ulcers. Oxygen tension was measured near the edge of the leg ulcer before and after 60 min of intermittent compression at 50 mmHg. The control group consisted of nine subjects with no evidence of peripheral vascular disease. The mean TcPO2 for the controls was 59.7 (SEM2.9) mmHg and for the study group 26.2 (SEM7.0) mmHg before treatment and 42.7 (SEM6.4) mmHg after treatment (p less than 0.005). Oxygen tension increased in nine patients in the study group. The change in TcPO2 correlated highly significantly (r = 0.912, p less than 0.002) with the reduction of oedema and the inverse change of skin temperature. The results suggest that intermittent pneumatic compression decreases interstitial fluid volume and venous stasis, both of which may lead to increased tissue oxygenation.

  12. DNMT3B 579G>T promoter polymorphism and the risk for idiopathic thrombocytopenic purpura in a Chinese population.

    PubMed

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

    2009-01-01

    Epigenetics may influence the expression of numerous genes, which might contribute to autoimmune diseases. DNA methylation is mediated by DNA methyltransferases, especially DNA methyltransferase 3B (DNMT3B). Polymorphisms of the DNMT3B gene may influence DNMT3B activity on DNA methylation and increase the susceptibility to several diseases. The current study investigated the association between DNMT3B 579G>T and the risk for idiopathic thrombocytopenic purpura (ITP). The DNMT3B 579G>T polymorphisms were analyzed by PCR-RFLP. There was no significant difference in genotype and allele distribution between the ITP patient and the controls (p = 0.722 and 0.667, respectively). Similar results were observed between the 2 groups when stratified by age and disease course, including acute in childhood, chronic in childhood, acute in adult and chronic in adult. Importantly, this study showed a statistical difference in the distribution of SNP of DNMT3B between Chinese and Koreans or Americans. It is shown that the SNP of DNMT3B 579G>T may not be used on its own as a marker to predict the susceptibility to ITP in a Chinese population and that DNMT3B 579G>T promoter SNP varies from one ethnic population to another.

  13. 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.

  14. Thrombocytopenia in pregnancy: do the time of diagnosis and delivery route affect pregnancy outcome in parturients with idiopathic thrombocytopenic purpura?

    PubMed

    Yuce, T; Acar, D; Kalafat, E; Alkilic, A; Cetindag, E; Soylemez, F

    2014-12-01

    The objective of this study was to investigate the determining effects of diagnosis time on pregnancy outcomes in a population of pregnant women with idiopathic thrombocytopenic purpura (ITP). Records of all the pregnant women with thrombocytopenia were evaluated. Those with a confirmed diagnosis of ITP were included in the study. Main outcome measures were antenatal thrombocyte count, postpartum haemorrhage rate, and route of delivery. Foetal outcomes such as foetal thrombocyte count, haemorrhage, and birth weight were also reported as secondary outcome measures. Time of diagnosis either antenatal or preconception did not significantly alter the investigated parameters. Delivery route had no impact on complication rates. Time of diagnosis also did not affect treatment modality. ITP is rare disorder accounting for less than 5 % of all pregnant thrombocytopenias. Time of diagnosis does not affect maternal-foetal outcomes or treatment modality unless diagnosis is made during labour. Compared to gestational thrombocytopenia, treatment rates may differ but treatment modalities remain the same and the effort put into making the differential should be weighed against maternal stress factors for lengthy laboratory evaluation as long as the thrombocytopenia is of pure nature without any systemic involvement.

  15. Clinical Features and Treatment Outcomes of Primary Immune Thrombocytopenic Purpura in Hospitalized Children Under 2-Years Old

    PubMed Central

    Farhangi, H; Ghasemi, A; Banihashem, A; Badiei, Z; Jarahi, L; Eslami, G; Langaee, T

    2016-01-01

    Background Immune thrombocytopenic purpura (ITP) is the most prevalent cause of thrombocytopenia in children. Despite the importance of ITP in children under 2-years old, only a few publications are available in the literature.ITP usually presents itself as isolated thrombocytopenia and mucocutaneous bleeding. Materials and Methods This study was conducted on 187 under 2-year-old children diagnosed with ITP and treated at Dr. Sheikh Hospital from 2004 to 2011.In this retrospective study, clinical symptoms, laboratory findings, history of viral infections, vaccination history, and treatment efficacy in children under 2-years old with ITP were investigated.Patients were followed for one year after being discharged from the hospital. Results The risk of the disease developing into chronic form was higher in older children (0.001). ITP in children under 3-months old was significantly associated with vaccination (p=0.007). There was no significant differences between male and female patients in regards to newly diagnosed ITP, persistent, and chronic disease status (p = 0.21). No significant difference in bleeding symptoms was observed between patients under 3-months old and 3 to 24-months old (p=0.18). Conclusion Infantile ITP respond favorably to treatment. The risk of the disease developing into chronic form is higher in 3-to-24-month-old children compared to under-three-month olds. PMID:27222699

  16. New developments in idiopathic thrombocytopenic purpura (ITP): cooperative, prospective studies by the Intercontinental Childhood ITP Study Group.

    PubMed

    Imbach, Paul; Kühne, Thomas; Zimmerman, Sherri

    2003-12-01

    Based on 6 years of experience with worldwide cooperation of investigators in the field of hematology, the International Childhood ITP Study Group (ICIS) has provided a long-term concept for prospective studies and new, evidence-based definitions of idiopathic thrombocytopenic purpura (ITP). Structured interactions between the cooperating investigators, the ICIS board, the writing committees, an expert panel, and the central operative office are summarized in the Rules of the ICIS. Preliminary experience shows high acceptance of the activities of the ICIS by participants from many countries. There is good cooperation, resulting in analyses and publication of results. New areas of focus for ICIS include the formation of an expert panel, regular meetings, and publication of results from current studies. Long-term financial resources must be found. ICIS is looking back on 6 constructive years of international cooperation resulting in new or confirmatory evidence regarding the demographics, diagnosis, natural history, and management of childhood ITP. New structures and cooperation must be identified to continue this productive endeavor.

  17. Dysplastic changes in idiopathic thrombocytopenic purpura and the effect of corticosteroids to increase dysplasia and cause hyperdiploid macropolycytes.

    PubMed

    Olcay, L; Yetgin, S; Okur, H; Erekul, S; Tuncer, M

    2000-10-01

    This study evaluates the dysplastic hematological changes in nine patients with idiopathic thrombocytopenic purpura (ITP) in 11 attacks, before and after corticosteroid treatment. The pretreatment blood smears of patients with ITP, displayed more neutrophils with bizarre nuclei (P < 0.001), Döhle or Döhle-like inclusions (P < 0. 01), irregular distribution of granules (P < 0.05), hypo-agranulation (P < 0.05), pseudo-Pelger-Huet-like cells (P < 0. 01), and nuclei with chromatine clumping (P < 0.01) than the normal children. The eosinophils of ITP patients were also dysplastic, before treatment. The pretreatment diameter of the neutrophils and the percentage of macropolycytes were greater than those of the patients with viral infections and normal group (P < 0.05 for all). The percentage of neutrophils with bizarre nuclei and nuclei with chromatine clumping and the diameter of neutrophils and macropolycyte percentage increased with corticosteroid therapy (P < 0.01, < 0.01, < 0.01, and < 0.05, respectively). The neutrophil diameter, percentage of macropolycytes, and number of neutrophils with bizarre nuclei decreased within 1-4 weeks after the therapy was stopped. In the neutrophils of two patients, diploidy and hyperdiploidy were established before and on the last day of therapy, respectively, and diploidy reversed after therapy was stopped. In conclusion, ITP patients display dysplastic findings in both neutrophils and eosinophils before treatment and corticosteroids cause transient significant increase in some of the dysplastic changes in neutrophils.

  18. Enumeration of feline platelets in ethylenediamine tetra-acetic acid anticoagulated blood with the ADVIA 2120 system and two manual methods: Leucoplate and Thrombo-TIC.

    PubMed

    Tvedten, Harold W; Ljusner, Jessika; Lilliehöök, Inger E

    2013-07-01

    A manual method (Thrombo-TIC; Bioanalytic GmbH, Umkirch/Freiburg, Germany) was advertised to disaggregate platelet clumps and to make human platelets spherical to improve platelet enumeration. The current study's hypothesis was that this method would perform better than current methods for feline blood anticoagulated with ethylenediamine tetra-acetic acid (EDTA), which often contains platelet aggregates. Platelet concentrations (PLTs) were determined in 21 feline blood samples by 3 methods. Thrombo-TIC was compared to the manual method (Leucoplate; Sobioda, Montbonnot-Saint-Martin, France) currently used in the authors' laboratory along with an ADVIA 2120 (Siemens AG, Eschborn, Germany) optical platelet concentration. Feline blood samples often contained platelet aggregates. ADVIA flagged for platelet aggregates in 11 of the 21 feline blood samples, and examination of blood smear revealed platelet aggregates in 14 of the 21 samples. The hemocytometers displayed more platelet aggregates with the Thrombo-TIC method than with Leucoplate. The method giving the greatest PLT was considered most accurate. The Leucoplate median PLT (238 × 10(9)/1) was greater than Thrombo-TIC (202 × 10(9)/1) or ADVIA (157 × 10(9)/1). Intra-assay precision was determined for the 3 methods using the 21 feline blood samples. Median Thrombo-TIC and Leucoplate precision (7.4% and 7.3% coefficient of variation [CV], respectively) were similar and not much worse than ADVIA (5.9% CV). The Thrombo-TIC method did not appear to perform better than the current manual method (Leucoplate). Leucoplate appeared least affected by platelet aggregation in feline blood. The ADVIA automated PLT appeared to be most negatively affected by platelet aggregation. The Thrombo-TIC method did not appear to prevent platelet aggregation in feline EDTA blood samples and, thus, is not recommended for such use.

  19. Portal vein thrombosis relevance on liver cirrhosis: Italian Venous Thrombotic Events Registry.

    PubMed

    Violi, Francesco; Corazza, Roberto Gino; Caldwell, Stephen Hugh; Perticone, Francesco; Gatta, Angelo; Angelico, Mario; Farcomeni, Alessio; Masotti, Michela; Napoleone, Laura; Vestri, Annarita; Raparelli, Valeria; Basili, Stefania

    2016-12-01

    Portal vein thrombosis may occur in cirrhosis; nevertheless, its prevalence, and predictors are still elusive. To investigate this issue, the Italian Society of Internal Medicine undertook the "Portal vein thrombosis Relevance On Liver cirrhosis: Italian Venous thrombotic Events Registry" (PRO-LIVER). This prospective multicenter study includes consecutive cirrhotic patients undergoing Doppler ultrasound examination of the portal area to evaluate the prevalence and incidence of portal vein thrombosis over a 2-year scheduled follow-up. Seven hundred and fifty-three (68 % men; 64 ± 12 years) patients were included in the present analysis. Fifty percent of the cases were cirrhotic outpatients. Viral (44 %) etiology was predominant. Around half of the patients had a mild-severity disease according to the Child-Pugh score; hepatocellular carcinoma was present in 20 %. The prevalence of ultrasound-detected portal vein thrombosis was 17 % (n = 126); it was asymptomatic in 43 % of the cases. Notably, more than half of the portal vein thrombosis patients (n = 81) were not treated with anticoagulant therapy. Logistic step-forward multivariate analysis demonstrated that previous portal vein thrombosis (p < 0.001), Child-Pugh Class B + C (p < 0.001), hepatocellular carcinoma (p = 0.01), previous upper gastrointestinal bleeding (p = 0.030) and older age (p = 0.012) were independently associated with portal vein thrombosis. Portal vein thrombosis is a frequent complication of cirrhosis, particularly in patients with moderate-severe liver failure. The apparent undertreatment of patients with portal vein thrombosis is a matter of concern and debate, which should be addressed by planning interventional trials especially with newer oral anticoagulants. Clinicaltrials.gov identifier NCT01470547.

  20. A high-throughput sequencing test for diagnosing inherited bleeding, thrombotic, and platelet disorders

    PubMed Central

    Simeoni, Ilenia; Stephens, Jonathan C.; Hu, Fengyuan; Deevi, Sri V. V.; Megy, Karyn; Bariana, Tadbir K.; Lentaigne, Claire; Schulman, Sol; Sivapalaratnam, Suthesh; Vries, Minka J. A.; Westbury, Sarah K.; Greene, Daniel; Papadia, Sofia; Alessi, Marie-Christine; Attwood, Antony P.; Ballmaier, Matthias; Baynam, Gareth; Bermejo, Emilse; Bertoli, Marta; Bray, Paul F.; Bury, Loredana; Cattaneo, Marco; Collins, Peter; Daugherty, Louise C.; Favier, Rémi; French, Deborah L.; Furie, Bruce; Gattens, Michael; Germeshausen, Manuela; Ghevaert, Cedric; Goodeve, Anne C.; Guerrero, Jose A.; Hampshire, Daniel J.; Hart, Daniel P.; Heemskerk, Johan W. M.; Henskens, Yvonne M. C.; Hill, Marian; Hogg, Nancy; Jolley, Jennifer D.; Kahr, Walter H.; Kelly, Anne M.; Kerr, Ron; Kostadima, Myrto; Kunishima, Shinji; Lambert, Michele P.; Liesner, Ri; López, José A.; Mapeta, Rutendo P.; Mathias, Mary; Millar, Carolyn M.; Nathwani, Amit; Neerman-Arbez, Marguerite; Nurden, Alan T.; Nurden, Paquita; Othman, Maha; Peerlinck, Kathelijne; Perry, David J.; Poudel, Pawan; Reitsma, Pieter; Rondina, Matthew T.; Smethurst, Peter A.; Stevenson, William; Szkotak, Artur; Tuna, Salih; van Geet, Christel; Whitehorn, Deborah; Wilcox, David A.; Zhang, Bin; Revel-Vilk, Shoshana; Gresele, Paolo; Bellissimo, Daniel B.; Penkett, Christopher J.; Laffan, Michael A.; Mumford, Andrew D.; Rendon, Augusto; Freson, Kathleen; Ouwehand, Willem H.; Turro, Ernest

    2016-01-01

    Inherited bleeding, thrombotic, and platelet disorders (BPDs) are diseases that affect ∼300 individuals per million births. With the exception of hemophilia and von Willebrand disease patients, a molecular analysis for patients with a BPD is often unavailable. Many specialized tests are usually required to reach a putative diagnosis and they are typically performed in a step-wise manner to control costs. This approach causes delays and a conclusive molecular diagnosis is often never reached, which can compromise treatment and impede rapid identification of affected relatives. To address this unmet diagnostic need, we designed a high-throughput sequencing platform targeting 63 genes relevant for BPDs. The platform can call single nucleotide variants, short insertions/deletions, and large copy number variants (though not inversions) which are subjected to automated filtering for diagnostic prioritization, resulting in an average of 5.34 candidate variants per individual. We sequenced 159 and 137 samples, respectively, from cases with and without previously known causal variants. Among the latter group, 61 cases had clinical and laboratory phenotypes indicative of a particular molecular etiology, whereas the remainder had an a priori highly uncertain etiology. All previously detected variants were recapitulated and, when the etiology was suspected but unknown or uncertain, a molecular diagnosis was reached in 56 of 61 and only 8 of 76 cases, respectively. The latter category highlights the need for further research into novel causes of BPDs. The ThromboGenomics platform thus provides an affordable DNA-based test to diagnose patients suspected of having a known inherited BPD. PMID:27084890

  1. [Renal thrombotic microangiopathy and antiphospholipid syndrome nephropathy in a patient with lupus nephritis].

    PubMed

    Sakamaki, Yusuke; Konishi, Konosuke; Hashiguchi, Akinori; Tomita, Shigeki; Kubota, Eiji; Itoh, Hiroshi; Hayashi, Koichi

    2016-01-01

    The patient was a 48-year-old Japanese woman diagnosed as having systemic lupus erythematosus at the age of 21 years when she presented with fever and an erythematous skin rash on her face and extremities. Prednisolone was initiated at that time. Thirteen days before admission to our hospital, she was referred to us by her family physician. Upon admission, blood tests showed pancytopenia, hypocomplementemia, and renal dysfunction, as well as the presence of lupus anticoagulant. Urinalysis showed abundant proteinuria and heavy microscopic hematuria. After performing a renal biopsy, we initiated immunosuppressive therapy and an anticoagulant. On the 22nd hospital day, microangiopathic hemolytic anemia appeared with the progression of thrombocytopenia and renal failure, and the patient subsequently underwent ten sessions of plasma exchange. After the commencement of the plasma exchange, her general condition improved. Her renal dysfunction, however, continued to progress, and hemodialysis was started on the 36th hospital day. The light microscopy showed severe endo- and extra-capillary proliferative glomerulonephritis with abundant crescents, and massive thrombi in the capillary lumen of the glomeruli. The arterioles contained occlusive hyaline materials. An immunofluorescence study showed granular staining of immunoglobulins and complements along the glomerular capillary wall. An electron microscopy examination revealed the presence of electron-dense deposits in the subepithelial and intramembranous areas of the glomeruli, but subendothelial deposits were absent. For cases with lupus nephritis (LN), immunosuppressive therapy based on corticosteroid remains the mainstay of treatment. However, immunosuppression alone may be insufficient when antiphospholipid antibody syndrome and thrombotic microangiopathy (TMA) are also present, and other treatment modalities including antiplatelet therapy, anticoagulation, and plasma exchange are likely to be necessary, as

  2. [Remote results of veno-venous bypass operations in post-thrombotic disease].

    PubMed

    Pokrovsky, A V; Ignat'ev, I M; Gradusov, E G

    2016-01-01

    The present study was aimed at analyzing the remote results of the operation of cross-over autovenous bypass at terms varying from 2 to 28 years in a total of 68 patients presenting with unilateral post-thrombotic occlusive lesions of iliac veins and in 12 patients operated on for obstruction of the femoral vein (saphenopopliteal bypass grafting). The obtained findings showed that a decisive factor of successful cross-over bypass grafting was a sufficient diameter of the autovenous transplant (not less than 7-8 mm). It was determined that in 70.6% of patients the cross-over bypass grafts become dilated with time and thus provide adequate outflow of blood from the affected extremity. Studies of the phlebodynamics in the diseased limb under the conditions of an open and cross-clamped shunt demonstrated that in 72% of patients the main function on carrying out venous return is performed by a cross-over shunt. Some shunts (20.7%) undergo pathological transformation in the form of deforming ectasias and cicatricial stenosis, which in many cases deteriorates the conditions of the outflow of blood and requires secondary surgical correction of the shunts. These operations were successfully performed in patients in the remote terms. Patency of the grafts at 15 years of follow up amounted to 79.6%. There was significant improvement of the outcomes of the bypassing operation observed in application of distal arteriovenous fistulas. A permanent clinical effect was achieved in 74.4% of patients with the functioning shunts. Patency of the saphenopopliteal shunts within the follow-up terms up to 12 years amounted to 91.7%. The remote results showed their reliable function and improvement of the regional phlebodynamics. It was determined that the shunts could function for a long time, not undergoing pathological ectasia. Forty-eight patients during dynamic follow up were subjected to operations on superficial and perforant veins with predominant application of minimally invasive

  3. The genetic fingerprint of susceptibility for transplant-associated thrombotic microangiopathy

    PubMed Central

    Zhang, Kejian; Zou, Fanggeng; Laskin, Benjamin; Dandoy, Christopher E.; Myers, Kasiani C.; Lane, Adam; Meller, Jaroslav; Medvedovic, Mario; Chen, Jenny; Davies, Stella M.

    2016-01-01

    Transplant-associated thrombotic microangiopathy (TA-TMA) occurs frequently after hematopoietic stem cell transplantation (HSCT) and can lead to significant morbidity and mortality. There are no data addressing individual susceptibility to TA-TMA. We performed a hypothesis-driven analysis of 17 candidate genes known to play a role in complement activation as part of a prospective study of TMA in HSCT recipients. We examined the functional significance of gene variants by using gene expression profiling. Among 77 patients undergoing genetic testing, 34 had TMA. Sixty-five percent of patients with TMA had genetic variants in at least one gene compared with 9% of patients without TMA (P < .0001). Gene variants were increased in patients of all races with TMA, but nonwhites had more variants than whites (2.5 [range, 0-7] vs 0 [range, 0-2]; P < .0001). Variants in ≥3 genes were identified only in nonwhites with TMA and were associated with high mortality (71%). RNA sequencing analysis of pretransplantation samples showed upregulation of multiple complement pathways in patients with TMA who had gene variants, including variants predicted as possibly benign by computer algorithm, compared with those without TMA and without gene variants. Our data reveal important differences in genetic susceptibility to HSCT-associated TMA based on recipient genotype. These data will allow prospective risk assessment and intervention to prevent TMA in highly susceptible transplant recipients. Our findings may explain, at least in part, racial disparities previously reported in transplant recipients and may guide treatment strategies to improve outcomes. PMID:26603840

  4. Renal thrombotic microangiopathy in patients with systemic lupus erythematosus and the antiphospholipid syndrome.

    PubMed

    Hughson, M D; Nadasdy, T; McCarty, G A; Sholer, C; Min, K W; Silva, F

    1992-08-01

    Current studies indicate that a thrombotic microangiopathy (TMA) identifies patients with systemic lupus erythematosus (SLE) who are at high risk of progressing to end-stage renal disease. We have observed two patients with SLE and one patient with a primary antiphospholipid syndrome (APS) who developed acute renal insufficiency with thrombocytopenia. Renal biopsies showed a TMA characterized by thrombi or by cellular and mucoid intimal hyperplasia of small arteries and arterioles. No arterial or arteriolar immune-complex deposits were detected by immunofluorescent or electron microscopy. Biopsies from one SLE patient and the APS patient showed no immune-complex glomerular disease. Both had serum antiphospholipid antibodies (aPL). aPL were not detected in the serum of the other SLE patient who had an active lupus nephritis. Acute renal failure and thrombocytopenia resolved in each case following treatment by plasmapheresis or prednisone and heparin. None of the patients were initially treated with cytotoxic drugs. As more knowledge is gained, the accurate identification of renal vascular lesions in SLE or related diseases could influence renal prognosis and choice of therapy. The cases reported here provide further evidence that a TMA can cause acute renal failure independent of lupus nephritis. TMA should be distinguished from other forms of renal vascular disease, particularly a noninflammatory lupus microangiopathy, which is probably mediated by subendothelial immune-complex deposits. The absence of immunoglobulin deposits in vessels involved by a TMA indicates that microvascular thrombosis is promoted by mechanisms other than those usually attributed to immune-complex disease. Phospholipid reactive antibodies may be pathogenetic in some cases.

  5. Plasmapheresis Is Associated With Better Renal Outcomes in Lupus Nephritis Patients With Thrombotic Microangiopathy

    PubMed Central

    Li, Qiu-Yu; Yu, Feng; Zhou, Fu-De; Zhao, Ming-Hui

    2016-01-01

    Abstract The aim of this study was to evaluate the efficacy of plasmapheresis in patients with lupus nephritis-combined thrombotic microangiopathy (TMA) in a Chinese cohort. Clinical and therapeutic data of patients with lupus nephritis–combined TMA were collected retrospectively. A comparison between those with and without plasmapheresis was performed. Seventy patients with renal biopsy-proven TMA in lupus nephritis were treated with conventional combined corticosteroid and immunosuppressive agents as induction therapy, 9 of the 70 patients received additional plasmapheresis. The plasmapheresis group presented with more severe SLE and renal activity indices, including a significant higher ratio of neurologic disorder (P = 0.025), lower level of platelet count (P = 0.009), higher value of serum creatinine (P = 0.038), higher percentage of anti-cardiolipin antibodies positive (P = 0.001), and higher Systemic Lupus Erythematosus Disease Activity Index scores (P = 0.012), than that of the nonplasmapheresis group. However, the plasmapheresis group had a significant higher rate of remission and a lower ratio of treatment failure than that of the nonplasmapheresis group (P = 0.03). As the baseline data were significantly different between the 2 groups, the propensity score match was further designed to avoid retrospective bias. After re-analysis, the plasmapheresis group still had a significant higher rate of remission and a lower ratio of treatment failure than that of the nonplasmapheresis group (P = 0.018). More importantly, the plasmapheresis group had significant less composite endpoints than that of the nonplasmapheresis group (P = 0.005). Our study suggested that additional plasmapheresis on conventional induction therapy may benefit patients with lupus nephritis-combined TMA, which warrants further explorations. PMID:27149490

  6. Predictors for the development of post-thrombotic syndrome in patients with primary lower limb deep venous thrombosis: A case-control study.

    PubMed

    Siddiqui, Nadeem A; Sophie, Ziad; Zafar, Farhan; Soares, Delvene; Naz, Iram

    2017-02-01

    Introduction Post-thrombotic syndrome is a common and debilitating sequelae of lower limb deep venous thrombosis. Very little awareness is present about the risk factors and about the diagnosis, prevention, and treatment of this condition. Objective The objective of this study is to identify the predictors of post-thrombotic syndrome after lower limb deep venous thrombosis. Materials and methods A case-control study was conducted on all adult patients who were admitted with lower limb deep venous thrombosis at our institution from January 2005 to June 2012. These patients were scheduled for a research clinic visit, which included informed consent, data collection, and physical examination. Patients found to have post-thrombotic syndrome served as cases and those without post-thrombotic syndrome served as controls. Villalta scoring system was used to diagnose the post-thrombotic syndrome and then to assess the severity of the condition in both the groups. Cox regression risk factor analysis was performed to identify the predictors of post-thrombotic syndrome. Results Out of the 125 patients examined, 49 were found to have post-thrombotic syndrome. Risk factors found to be significant were body mass index of more than 35 kg/m(2) ( n = 13, p = 0.003), history of immobilization ( n = 19, p = 0.003), one or more hypercoagable disorders ( n = 32, p = 0.02), iliofemoral deep venous thrombosis ( n = 18, p = 0.001), complete obstruction on ultrasound ( n = 26, p = 0.016), unstable range of international normalized ratio ( n = 23, p = 0.041) and non-compliance for the use of compressions stockings ( n = 14, p = 0.001). On multivariate analysis, one or more hypercoagable disorder, iliofemoral deep venous thrombosis, and non-compliance to the use of compression stockings were found to be independent risk factors for the development of post-thrombotic syndrome. Conclusion One or more hypercoagable disorders, iliofemoral

  7. Musicality: instinct or acquired skill?

    PubMed

    Marcus, Gary F

    2012-10-01

    Is the human tendency toward musicality better thought of as the product of a specific, evolved instinct or an acquired skill? Developmental and evolutionary arguments are considered, along with issues of domain-specificity. The article also considers the question of why humans might be consistently and intensely drawn to music if musicality is not in fact the product of a specifically evolved instinct.

  8. Duplicated Information Acquired by Libraries.

    ERIC Educational Resources Information Center

    White, Carl M.

    The object of this study is to make a start toward determining the extent of duplicated information that is being acquired in spite of customary precautions to avoid it. Referring to a specific case, the percentages in Table II show the frequency of appearance in five other works of 19 items in Mitchell's "Encyclopedia of American Politics." While…

  9. Acquired aplastic anemia in children.

    PubMed

    Hartung, Helge D; Olson, Timothy S; Bessler, Monica

    2013-12-01

    This article provides a practice-based and concise review of the etiology, diagnosis, and management of acquired aplastic anemia in children. Bone marrow transplantation, immunosuppressive therapy, and supportive care are discussed in detail. The aim is to provide the clinician with a better understanding of the disease and to offer guidelines for the management of children with this uncommon yet serious disorder.

  10. 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

  11. Ten years of cerebral venous thrombosis: male gender and myeloproliferative neoplasm is associated with thrombotic recurrence in unprovoked events.

    PubMed

    Lim, H Y; Ng, C; Donnan, G; Nandurkar, H; Ho, Prahlad

    2016-10-01

    Cerebral venous thrombosis (CVT) is a rare venous thrombotic event. We review our local experience in the management of CVT in comparison to other venous thromboembolism (VTE) with specific focus on risk factors for thrombotic recurrence. Retrospective evaluation of consecutive CVT presentations from January 2005 to June 2015, at two major tertiary hospitals in Northeast Melbourne, Australia. This population was compared to a separate audit of 1003 consecutive patients with DVT and PE. Fifty-two patients (30 female, 22 male) with a median age of 40 (18-83) years, presented with 53 episodes of CVT. Twenty-nine episodes (55 %) were associated with an underlying risk factor, with hormonal risk factors in females being most common. The median duration of anticoagulation was 6 months with 11 receiving life-long anticoagulation. Eighty-one percent had residual thrombosis on repeat imaging, which was not associated with recurrence at the same or distant site. Nine (17 %) had CVT-related haemorrhagic transformation with two resultant CVT-related deaths (RR 22.5; p = 0.04). All three VTE recurrences occured in males with unprovoked events (RR 18.2; p = 0.05) who were subsequently diagnosed with myeloproliferative neoplasm (MPN). Compared to the non-cancer VTE population, non-cancer CVT patients were younger, had similar rate of provoked events and VTE recurrence, although with significantly higher rate of MPN diagnosis (RR 9.30 (2.29-37.76); p = 0.002) CVT is a rare thrombotic disorder. All recurrences in this audit occurred in male patients with unprovoked events and subsequent diagnosis of MPN, suggesting further evaluation for MPN may be warranted in patients with unprovoked CVT.

  12. Molecular basis of inherited antithrombin deficiency in Portuguese families: identification of genetic alterations and screening for additional thrombotic risk factors.

    PubMed

    David, Dezsö; Ribeiro, Sofia; Ferrão, Lénia; Gago, Teresa; Crespo, Francisco

    2004-06-01

    Antithrombin (AT), the most important coagulation serine proteases inhibitor, plays an important role in maintaining the hemostatic balance. Inherited AT deficiency, mainly characterized by predisposition to recurrent venous thromboembolism, is transmitted in an autosomal dominant manner. In this study, we analyzed the underlying genetic alterations in 12 unrelated Portuguese thrombophilic families with AT deficiency. At the same time, the modulating effect of the FV Leiden mutation, PT 20210A, PAI-1 4G, and MTHFR 677T allelic variants, on the thrombotic risk of AT deficient patients was also evaluated. Three novel frameshift alterations, a 4-bp deletion in exon 4 and two 1-bp insertions in exon 6, were identified in six unrelated type I AT deficient families. A novel missense mutation in exon 3a, which changes the highly conserved F147 residue, and a novel splice site mutation in the invariant acceptor AG dinucleotide of intron 2 were also identified in unrelated type I AT deficient families. In addition to these, two previously reported missense mutations changing the AT reactive site bond (R393-S394) and leading to type II-RS deficiency, and a previously reported cryptic splice site mutation (IVS4-14G-->A), were also identified. In these families, increased thrombotic risk associated with co-inheritance of the FV Leiden mutation and of the PAI-1 4G variant was also observed. In conclusion, we present the first data regarding the underlying genetic alterations in Portuguese thrombophilic families with AT deficiency, and confirm that the FV Leiden mutation and probably the PAI-1 4G variant represent additional thrombotic risk factors in these families.

  13. Thrombotic microangiopathy in Interferon Beta treated multiple sclerosis patients: Review of literature and report of two new cases.

    PubMed

    Vosoughi, Reza; Marriott, James J

    2014-05-01

    Beta interferons (IFN-β) were the first approved disease modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) and are still the most-widely prescribed medications for this disease. Despite good overall long-term safety data with prolonged use of this group of drugs, they can rarely cause serious and sometimes life threatening adverse effects. In this article we report two cases of thrombotic microangiopathy occurring during prolonged use of IFN-β and review the available literature on this topic.

  14. Rituximab therapy for chonic and refractory immune thrombocytopenic purpura: a long-term follow-up analysis

    PubMed Central

    Garcia-Chavez, Jaime; Montiel-Cervantes, Laura; Esparza, Miriam García-Ruiz; Vela-Ojeda, Jorge

    2007-01-01

    The aim of this study was to evaluate the long-term response to rituximab in patients with chronic and refractory immune thrombocytopenic purpura (ITP). Adults with ITP fail to respond to conventional therapies in almost 30% of cases, developing a refractory disease. Rituximab has been successfully used in these patients. We used rituximab at 375 mg/m2, IV, weekly for a total of four doses in 18 adult patients. Complete remission (CR) was considered if the platelet count was >100 × 109/l, partial remission (PR) if platelets were >50 × 109/l, minimal response (MR) if the platelet count was >30 × 109/l and <50 × 109/l, and no response if platelet count remained unchanged. Response was classified as sustained (SR) when it was stable for a minimum of 6 months. Median age was 43.5 years (range, 17 to 70). Median platelet count at baseline was 12.5 × 109/l (range, 3.0 to 26.3). CR was achieved in five patients (28%), PR in five (28%), MR in four (22%), and two patients were classified as therapeutic failures (11%). Two additional patients were lost to follow-up. The median time between rituximab therapy and response was 14 weeks (range, 4 to 32). SR was achieved in 12 patients (67%). There were no severe adverse events during rituximab therapy. During follow-up (median, 26 months; range, 12 to 59), no other immunosuppressive drugs were used. In conclusion, rituximab therapy is effective and safe in adult patients with chronic and refractory ITP. Overall response rate achieved is high, long term, and with no risk of adverse events. PMID:17874322

  15. Association of interleukin-(IL)10 haplotypes and serum IL-10 levels in the progression of childhood immune thrombocytopenic purpura.

    PubMed

    Tesse, Riccardina; Del Vecchio, Giovanni Carlo; De Mattia, Domenico; Sangerardi, Maria; Valente, Federica; Giordano, Paola

    2012-08-15

    Derangement of genetic and immunological factors seems to have a pivotal role in the pathophysiology of immune thrombocytopenic purpura (ITP). We investigated interleukin(IL)-10 genetically determined expression in children with an acute progression of ITP (n=41) compared to young patients with chronic ITP (n=44) and healthy controls (n=60), and attempted to correlate IL-10 production with the course of the disease. We genotyped our study population for three single nucleotide polymorphisms at positions -1082 (A/G), -819 (C/T) and -592 (C/A) in the promoter region of the IL-10 gene. IL-10 levels were measured by enzyme-linked immunoassay. The IL-10 production in our study population was significantly higher in patients carrying the GCC haplotype than those bearing ACC and ATA haplotypes (6.9 ± 1.5 vs 3.6 ± 0.8 vs 3.3 ± 0.3, p=0.03). The serum concentration of IL-10 was significantly higher in patients with an acute course of their disease, who mainly carried the GCC haplotype (92%), compared to chronic subjects, bearing the non-GCC haplotypes, and controls [17 pg/mL (1.7-18) vs 3.5 pg/mL (0.6-11) vs 3 pg/mL (1-7), p<0.01)]. Our findings show that patients carrying the GCC-high producer IL-10 haplotype have an acute development of ITP and that IL-10 levels might represent a useful predictive biomarker of the disease course.

  16. Analysis of clinical effects and mechanism of recombinant human interleukin-11 with glucocorticoids for treatment of idiopathic thrombocytopenic purpura

    PubMed Central

    Wu, Xifeng; Wang, Lijuan; Sun, Lin; Li, Tantan; Ran, Xuehong

    2017-01-01

    The aim of the present study was to evaluate the effectiveness and safety of recombinant human interleukin-11 (IL-11) with glucocorticoids for treatment of adult idiopathic thrombocytopenic purpura (ITP) and the regulatory effect on immune mechanisms. A total of 80 patients with initial diagnosis of ITP admitted to our hospital were selected. Patients were randomly divided into the control group and observation group, with 40 cases each. The control group received glucocorticoids treatment, and the observation group received IL-11 and glucocorticoids. The treatment effects were compared. The total effective rate and effective degree of the observation group was higher than in the control group and the difference was statistically significant (P<0.05); comparing the incidence of complications of the two groups, there was no statistical difference (P>0.05). In the observation group, onset time was reduced, platelet recovery level increased and platelet antibody positive rate decreased, and the differences were statistically significant (P<0.05). The total treatment course was shorter and recurrence rate was lower in the observation group compared with the control group, and the differences were statistically significant (P<0.05). The percentage of CD4+CD25+ regulatory T cells decreased in the two groups after treatment, and was more pronounced in the observation group. The difference was statistically significant (P<0.05). In conclusion, IL-11 with glucocorticoids for the treatment of adult ITP is safe and effective, and may be associated with decreased percentage of CD4+CD25+ regulatory T cells. PMID:28352325

  17. Nursing home-acquired pneumonia.

    PubMed

    El Solh, Ali A

    2009-02-01

    Nursing home-acquired pneumonia (NHAP) was first described in 1978. Since then there has been much written regarding NHAP and its management despite the lack of well-designed studies in this patient population. The most characteristic features of patients with NHAP are the atypical presentation, which may lead to delay in diagnosis and therapy. The microbial etiology of pneumonia encompasses a wide spectrum that spans microbes recovered from patients with community-acquired pneumonia to organisms considered specific only to nosocomial settings. Decision to transfer a nursing home patient to an acute care facility depends on a host of factors, which include the level of staffing available at the nursing home, patients' advance directives, and complexity of treatment. The presence of risk factors for multidrug-resistant pathogens dictates approach to therapy. Prevention remains the cornerstone of reducing the incidence of disease. Despite the advance in medical services, mortality from NHAP remains high.

  18. Occupationally Acquired American Cutaneous Leishmaniasis

    PubMed Central

    Felinto de Brito, Maria Edileuza; Andrade, Maria Sandra; de Almeida, Éricka Lima; Medeiros, Ângela Cristina Rapela; Werkhäuser, Roberto Pereira; de Araújo, Ana Isabele Freitas; Brandão-Filho, Sinval Pinto; Paiva de Almeida, Alzira Maria; Gomes Rodrigues, Eduardo Henrique

    2012-01-01

    We report two occupationally acquired cases of American cutaneous leishmaniasis (ACL): one accidental laboratory autoinoculation by contaminated needlestick while handling an ACL lesion sample, and one acquired during field studies on bird biology. Polymerase chain reaction (PCR) assays of patient lesions were positive for Leishmania, subgenus Viannia. One isolate was obtained by culture (from patient 2 biopsy samples) and characterized as Leishmania (Viannia) naiffi through an indirect immunofluorescence assay (IFA) with species-specific monoclonal antibodies (mAbs) and by multilocus enzyme electrophoresis (MLEE). Patients were successfully treated with N-methyl-glucamine. These two cases highlight the potential risks of laboratory and field work and the need to comply with strict biosafety procedures in daily routines. The swab collection method, coupled with PCR detection, has greatly improved ACL laboratory diagnosis. PMID:23227369

  19. [Acquired disorders of color vision].

    PubMed

    Lascu, Lidia; Balaş, Mihaela

    2002-01-01

    This article is a general view of acquired disorders of color vision. The revision of the best known methods and of the etiopathogenic classification is not very important in ophthalmology but on the other hand, the detection of the blue defect advertise and associated ocular pathology. There is a major interest in serious diseases as multiple sclerosis, AIDS, diabetes melitus, when the first ocular sign can be a defect in the color vision.

  20. Comparison of cardiovascular thrombotic events in patients with osteoarthritis treated with rofecoxib versus nonselective nonsteroidal anti-inflammatory drugs (ibuprofen, diclofenac, and nabumetone).

    PubMed

    Reicin, Alise S; Shapiro, Deborah; Sperling, Rhoda S; Barr, Eliav; Yu, Qinfen

    2002-01-15

    Aspirin, nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), and specific cyclooxygenase-2 (COX-2) inhibitors each have distinctive effects on COX-1-mediated thromboxane biosynthesis, the major determinant of platelet aggregation. It is unclear whether these effects are associated with differences in thrombogenic risks. To compare the risk for thrombotic cardiovascular events among patients receiving rofecoxib, nonselective NSAIDs, and placebo, cardiovascular safety was assessed in 5,435 participants in 8 phase IIB/III osteoarthritis trials. The median treatment exposure was 31/2 months. The primary end point assessed was the risk of any arterial or venous thrombotic cardiovascular adverse event (AE). A second analysis assessed differences in the Anti-Platelet Trialists' Collaboration (APTC) events, a cluster end point that consists of the combined incidence of (1) cardiovascular, hemorrhagic, and unknown death; (2) myocardial infarction; and (3) cerebrovascular accident. Similar rates of thrombotic cardiovascular AEs were reported with rofecoxib, placebo, and comparator nonselective NSAIDs (ibuprofen, diclofenac, or nabumetone). In trials that compared rofecoxib with NSAIDs, the incidence of thrombotic cardiovascular AEs was 1.93/100 patient-years in the rofecoxib treatment group compared with 2.27/100 patient-years in the combined nonselective NSAID group. In trials that compared rofecoxib with placebo, the incidence of thrombotic cardiovascular AEs was 2.71/100 patient-years in the rofecoxib group compared with 2.57/100 patient-years in the placebo group. Consistent with the risks of cardiovascular AEs, similar rates of APTC events were reported with rofecoxib, placebo, and comparator nonselective NSAIDs. Thus, in the rofecoxib osteoarthritis development program, there was no difference between rofecoxib, comparator nonselective NSAIDs, and placebo in the risks of cardiovascular thrombotic events.

  1. Novel anti-thrombotic agent for modulation of protein disulfide isomerase family member ERp57 for prophylactic therapy

    PubMed Central

    Cui, Guozhen; Shan, Luchen; Guo, Lin; Chu, Ivan Keung; Li, Guohui; Quan, Quan; Zhao, Yun; Chong, Cheong Meng; Zhang, Zaijun; Yu, Pei; Hoi, Maggie Pui Man; Sun, Yewei; Wang, Yuqiang; Lee, Simon MingYuen

    2015-01-01

    Protein disulfide isomerase (PDI) family members including PDI and ERp57 emerge as novel targets for anti-thrombotic treatments, but chemical agents with selectivity remain to be explored. We previously reported a novel derivative of danshensu (DSS), known as ADTM, displayed strong cardioprotective effects against oxidative stress-induced cellular injury in vitro and acute myocardial infarct in vivo. Herein, using chemical proteomics approach, we identified ERp57 as a major target of ADTM. ADTM displayed potent inhibitory effects on the redox activity of ERp57, inhibited the adenosine diphosphate (ADP)-induced expressions of P-selectin and αIIbβ3 integrin, and disrupted the interaction between ERp57 and αIIbβ3. In addition, ADTM inhibited both arachidonic acid (AA)-induced and ADP-induced platelet aggregation in vitro. Furthermore, ADTM significantly inhibited rat platelet aggregation and thrombus formation in vivo. Taken together, ADTM represents a promising candidate for anti-thrombotic therapy targeting ERp57. PMID:26037049

  2. Anti-inflammatory and anti-thrombotic effects of zingerone in a rat model of myocardial infarction.

    PubMed

    Hemalatha, K L; Stanely Mainzen Prince, P

    2016-11-15

    Myocardial infarction continues to be a major public health problem. Reduction in mortality rate and prevention of myocardial infarction are of utmost importance. Inflammation and thrombosis play an important role in the pathogenesis of myocardial infarction. The anti-inflammatory and anti-thrombotic effects of zingerone were evaluated in isoproterenol induced myocardial infarcted rats. Rats were pretreated with zingerone (6mg/kg body weight) daily for 14 days and were then induced myocardial infarction with isoproterenol (100mg/kg body weight) on 15th and 16th day. Isoproterenol induced myocardial infarcted rats showed significant (P<0.05) increase in the levels/ activities of cardiac troponin-I (cTnI), high sensitive C-reactive protein (Hs CRP), lysosomal hydrolases in the serum and concentration of heart lysosomal lipid peroxidation (LPO) products. RT-PCR study revealed over expression of myocardial tumour necrosis factor - alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) genes in the myocardial infarcted rats. Histopathology of heart and coronary artery revealed marked inflammation and coronary thrombosis. Zingerone pretreatment significantly (P<0.05) decreased serum cTnI, Hs CRP, lysosomal hydrolases and heart lysosomal LPO and down regulated myocardial TNF-α, IL-1β and IL-6 genes and prevented coronary thrombosis in isoproterenol induced myocardial infarcted rats. The observed effects of zingerone could be attributed to its anti-inflammatory and anti-thrombotic properties.

  3. A single-institution, 20-year prospective experience with an affordable Fc-receptor blockade method to treat patients with chronic, refractory autoimmune thrombocytopenic purpura.

    PubMed

    Estrada-Gómez, Roberto; Vargas-Castro, Olga; Oropeza-Borges, Mabel; González-Carrillo, Martha L; Pérez-Romano, Beatriz; Ruiz-Argüelles, Guillermo J

    2007-01-01

    In a 20-year period in a single institution, 34 patients with chronic, refractory autoimmune thrombocytopenic purpura were prospectively treated with ex vivo anti-D opsonized autologous red blood cells. All patients had received previous treatment with steroids and/or immunosuppressive agents, and 11 had been splenectomized. Twenty one patients had an increase in the platelet count; in five cases, the increase was more than 50 x 10(9)/L platelets and in 16 the increase was more than 100 x 10(9)/L platelets. Early responses were observed in 20 patients and late responses in seven, whereas seven patients (20%) did not respond at all. Nine of the 20 individuals who achieved an ER had a subsequent drop in the platelet count; however, only three had a drop below 50 x 10(9)/L. When last censored, of the 34 patients, 24 (70%) had a platelet count above 50 x 10(9)/L. The 84-month thrombocytopenia-free (over 50 x 10(9)/L platelets) status of the whole group is 70%, whereas the 84-month complete remission (over 100 x 10(9)/L platelets) status of the whole group is 50%. It is concluded that the use of ex vivo anti-D opsonized red blood cells may represent another, substantially cheaper treatment of patients with chronic, refractory, autoimmune thrombocytopenic purpura.

  4. Treatment with liposome-encapsulated clodronate as a new strategic approach in the management of immune thrombocytopenic purpura in a mouse model.

    PubMed

    Alves-Rosa, F; Stanganelli, C; Cabrera, J; van Rooijen, N; Palermo, M S; Isturiz, M A

    2000-10-15

    Immune thrombocytopenic purpura (ITP) is an autoimmune disease related to the presence of elevated levels of platelet-associated immunoglobulin, or autoantibodies. In recent years the importance of macrophage Fc gamma receptors in the uptake of platelets in ITP has been confirmed. Although in patients with ITP the platelet destruction occurs in liver and spleen, in this present experimental mouse model the liver was the principal organ of sequestration of sensitized platelets. The uptake in the spleen, bone marrow, lung, and kidneys was negligible and not different from that in control animals. In addition, the trapped platelets did not return to circulation, and new cells derived from the platelet-storage pool or new thrombocytogenesis were necessary to restore the platelet count. The depletion of splenic and hepatic murine macrophages by liposome-encapsulated clodronate (lip-clod) was studied as a new strategy for ITP treatment. Lip-clod inhibits, in a dose-dependent manner, the antibody-induced thrombocytopenia. Moreover, lip-clod treatment rapidly restored (24 hours) the platelet count in thrombocytopenic animals to hematologic safe values, and despite additional antiplatelet antiserum treatment, mice were able to maintain this level of platelets at least up to 48 hours. The bleeding times in lip-clod-treated animals was not different from those in controls, demonstrating that the hemostasis was well controlled in these animals. The results presented in this study demonstrate that lip-clod treatment can be effective in the management of experimental ITP. (Blood. 2000;96:2834-2840)

  5. Acquired Upper Extremity Growth Arrest.

    PubMed

    Gauger, Erich M; Casnovsky, Lauren L; Gauger, Erica J; Bohn, Deborah C; Van Heest, Ann E

    2016-09-29

    This study reviewed the clinical history and management of acquired growth arrest in the upper extremity in pediatric patients. The records of all patients presenting from 1996 to 2012 with radiographically proven acquired growth arrest were reviewed. Records were examined to determine the etiology and site of growth arrest, management, and complications. Patients with tumors or hereditary etiology were excluded. A total of 44 patients (24 boys and 20 girls) with 51 physeal arrests who presented at a mean age of 10.6 years (range, 0.8-18.2 years) were included in the study. The distal radius was the most common site (n=24), followed by the distal humerus (n=8), metacarpal (n=6), distal ulna (n=5), proximal humerus (n=4), radial head (n=3), and olecranon (n=1). Growth arrest was secondary to trauma (n=22), infection (n=11), idiopathy (n=6), inflammation (n=2), compartment syndrome (n=2), and avascular necrosis (n=1). Twenty-six patients (59%) underwent surgical intervention to address deformity caused by the physeal arrest. Operative procedures included ipsilateral unaffected bone epiphysiodesis (n=21), shortening osteotomy (n=10), lengthening osteotomy (n=8), excision of physeal bar or bone fragment (n=2), angular correction osteotomy (n=1), and creation of single bone forearm (n=1). Four complications occurred; 3 of these required additional procedures. Acquired upper extremity growth arrest usually is caused by trauma or infection, and the most frequent site is the distal radius. Growth disturbances due to premature arrest can be treated effectively with epiphysiodesis or osteotomy. In this series, the specific site of anatomic growth arrest was the primary factor in determining treatment. [Orthopedics. 201x; xx(x):xx-xx.].

  6. The inhibition of acquired fear.

    PubMed

    Izquierdo, Iván; Cammarota, Martín; Vianna, Mónica M R; Bevilaqua, Lía R M

    2004-01-01

    A conditioned stimulus (CS) associated with a fearsome unconditioned stimulus (US) generates learned fear. Acquired fear is at the root of a variety of mental disorders, among which phobias, generalized anxiety, the posttraumatic stress disorder (PTSD) and some forms of depression. The simplest way to inhibit learned fear is to extinguish it, which is usually done by repeatedly presenting the CS alone, so that a new association, CS-"no US", will eventually overcome the previously acquired CS-US association. Extinction was first described by Pavlov as a form of "internal inhibition" and was recommended by Freud and Ferenczi in the 1920s (who called it "habituation") as the treatment of choice for phobic disorders. It is used with success till this day, often in association with anxiolytic drugs. Extinction has since then been applied, also successfully and also often in association with anxiolytics, to the treatment of panic, generalized anxiety disorders and, more recently, PTSD. Extinction of learned fear involves gene expression, protein synthesis, N-methyl-D-aspartate (NMDA) receptors and signaling pathways in the hippocampus and the amygdala at the time of the first CS-no US association. It can be enhanced by increasing the exposure to the "no US" component at the time of behavioral testing, to the point of causing the complete uninstallment of the original fear response. Some theorists have recently proposed that reiteration of the CS alone may induce a reconsolidation of the learned behavior instead of its extinction. Reconsolidation would preserve the original memory from the labilization induced by its retrieval. If true, this would of course be disastrous for the psychotherapy of fear-motivated disorders. Here we show that neither the CS nor retrieval cause anything remotely like reconsolidation, but just extinction. In fact, our findings indicate that the reconsolidation hypothesis is essentially incorrect, at least for the form of contextual fear most

  7. Foodborne listeriosis acquired in hospitals.

    PubMed

    Silk, Benjamin J; McCoy, Morgan H; Iwamoto, Martha; Griffin, Patricia M

    2014-08-15

    Listeriosis is characterized by bacteremia or meningitis. We searched for listeriosis case series and outbreak investigations published in English by 2013, and assessed the strength of evidence for foodborne acquisition among patients who ate hospital food. We identified 30 reports from 13 countries. Among the case series, the median proportion of cases considered to be hospital-acquired was 25% (range, 9%-67%). The median number of outbreak-related illnesses considered to be hospital-acquired was 4.0 (range, 2-16). All patients were immunosuppressed in 18 of 24 (75%) reports with available data. Eight outbreak reports with strong evidence for foodborne acquisition in a hospital implicated sandwiches (3 reports), butter, precut celery, Camembert cheese, sausage, and tuna salad (1 report each). Foodborne acquisition of listeriosis among hospitalized patients is well documented internationally. The number of listeriosis cases could be reduced substantially by establishing hospital policies for safe food preparation for immunocompromised patients and by not serving them higher-risk foods.

  8. Bejel: acquirable only in childhood?

    PubMed

    Rothschild, Bruce M; Rothschild, Christine; Naples, Virginia; Billard, Michel; Panero, Barbara

    2006-10-01

    Bejel clearly has a long history in the Middle East and the Sudan, but was it transmitted to Europe? As the major manifestation of bejel is presence of periosteal reaction in 20-40% of afflicted populations, absence of significant population frequency of periosteal reaction in Europe would exclude that diagnosis. Examination of skeletal populations from continental Europe revealed no significant periosteal reaction at the time of and immediately subsequent to the Crusades. Thus, there is no evidence for bejel in Europe, in spite of clear contact (the mechanism of bejel transmission in children) between warring groups, at least during the Crusades. This supports the hypothesis that bejel is a childhood-acquired disease and apparently cannot be contracted in adulthood.

  9. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.10 Acquire. Acquire means to obtain cranberries by any means whatsoever for the purpose of handling cranberries....

  10. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.10 Acquire. Acquire means to obtain cranberries by any means whatsoever for the purpose of handling cranberries....

  11. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.10 Acquire. Acquire means to obtain cranberries by any means whatsoever for the purpose of handling cranberries....

  12. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.10 Acquire. Acquire means to obtain cranberries by any means whatsoever for the purpose of handling cranberries....

  13. 7 CFR 926.10 - Acquire.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... REQUIREMENTS APPLICABLE TO CRANBERRIES NOT SUBJECT TO THE CRANBERRY MARKETING ORDER § 926.10 Acquire. Acquire means to obtain cranberries by any means whatsoever for the purpose of handling cranberries....

  14. Acquired haemophilia in recipients of depot thioxanthenes.

    PubMed

    Stewart, A J; Manson, L M; Dasani, H; Beddall, A; Collins, P; Shima, M; Ludlam, C A

    2000-11-01

    We present two cases in which the occurrence of acquired haemophilia is associated with the use of depot preparations of the thioxanthenes zuclopenthixol and flupenthixol. These drugs have not previously been implicated in the aetiology of acquired haemophilia.

  15. Common femoral endovenectomy in conjunction with iliac vein stenting to improve venous inflow in severe post-thrombotic obstruction.

    PubMed

    Verma, Himanshu; Tripathi, Ramesh K

    2017-01-01

    Post-thrombotic syndrome secondary to iliofemoral deep venous thrombosis is a significant contributor to advanced chronic venous insufficiency. Iliac vein stenting is a standard procedure to treat iliocaval obstruction. In cases with obstruction extending across the groin, venous inflow for an iliac vein stent may be poor and compromise results of iliac vein stenting. Treatment options include extension of stents across the inguinal ligament that may have limitations in improving inflow only from only one vessel. Endovenectomy in this scenario becomes an attractive option with or without iliac vein stenting to provide outflow to the profunda vein, which otherwise is "axially transformed" in chronic iliofemoral deep venous thrombosis. We describe a technique of endovenectomy in combination with iliac vein stenting to establish a patent outflow tract for profunda and femoral veins. Accompanying also is a video demonstration of endovenectomy that will help viewers understand more technical aspects of the procedure.

  16. [Post thrombotic syndrome: are elastic stockings on their last legs? The role of compression in prevention and treatment].

    PubMed

    ten Cate-Hoek, Arina J

    2015-01-01

    Post thrombotic syndrome (PTS) is a common chronic complication of deep venous thrombosis (DVT). PTS has a negative impact on quality of life. Patients with a more serious form of this syndrome have increased rates of sick leave and incur increased medical costs. The underlying processes leading to PTS are not yet fully understood. Pressure increases in the deep-venous system, resulting in venous hypertension. Venous hypertension is the cause of the most important symptoms of PTS: pain, oedema and skin abnormalities. Compression therapy reduces oedema and pain in patients in the acute phase following DVT. Based on convincing results from randomised trials, elastic compression therapy was recommended for patients with DVT for many years, in order to prevent venous hypertension and PTS. Recent studies have led to discussion on the added value of elastic compression.

  17. Pulmonary Tumor Thrombotic Microangiopathy Caused by a Parotid Tumor: Early Antemortem Diagnosis and Long-term Survival

    PubMed Central

    Toyonaga, Haruka; Tsuchiya, Michiko; Sakaguchi, Chikara; Ajimizu, Hitomi; Nakanishi, Yosuke; Nishiyama, Seiya; Morikawa, Noboru; Hayashi, Yasuyuki; Nagasaka, Yukio; Yasui, Hiroshi

    2017-01-01

    Pulmonary tumor thrombotic microangiopathy (PTTM) is a high-mortality disease that is difficult to diagnose clinically. Our patient was an 80-year-old woman who came to us due to symptoms of increasing dyspnea. A clinical evaluation showed that she had hypoxemia and pulmonary arterial hypertension without any abnormalities in the major pulmonary arteries, bronchi, or alveoli. A lung perfusion scan showed multiple wedge-shaped perfusion defects. Further examination revealed adenocarcinoma in her right parotid gland with metastasis to the submandibular lymph nodes. We diagnosed her to have PTTM caused by a parotid tumor. The patient survived for 11 months with chemotherapy. An early antemortem diagnosis by minimally invasive examinations will help PTTM patients to survive longer. PMID:28050002

  18. Acquiring Evolving Technologies: Web Services Standards

    DTIC Science & Technology

    2016-06-30

    2006 Carnegie Mellon University Acquiring Evolving Technologies : Web Services Standards Harry L. Levinson Software Engineering Institute Carnegie...Acquiring Evolving Technologies : Web Services Standards 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 2 Acquiring Evolving Technologies : Web Services Standards © 2006 Carnegie Mellon University Acquiring

  19. Neutrophil Protease Cleavage of Von Willebrand Factor in Glomeruli - An Anti-thrombotic Mechanism in the Kidney.

    PubMed

    Tati, Ramesh; Kristoffersson, Ann-Charlotte; Manea Hedström, Minola; Mörgelin, Matthias; Wieslander, Jörgen; van Kooten, Cees; Karpman, Diana

    2017-02-01

    Adequate cleavage of von Willebrand factor (VWF) prevents formation of thrombi. ADAMTS13 is the main VWF-cleaving protease and its deficiency results in development of thrombotic microangiopathy. Besides ADAMTS13 other proteases may also possess VWF-cleaving activity, but their physiological importance in preventing thrombus formation is unknown. This study investigated if, and which, proteases could cleave VWF in the glomerulus. The content of the glomerular basement membrane (GBM) was studied as a reflection of processes occurring in the subendothelial glomerular space. VWF was incubated with human GBMs and VWF cleavage was assessed by multimer structure analysis, immunoblotting and mass spectrometry. VWF was cleaved into the smallest multimers by the GBM, which contained ADAMTS13 as well as neutrophil proteases, elastase, proteinase 3 (PR3), cathepsin-G and matrix-metalloproteinase 9. The most potent components of the GBM capable of VWF cleavage were in the serine protease or metalloprotease category, but not ADAMTS13. Neutralization of neutrophil serine proteases inhibited GBM-mediated VWF-cleaving activity, demonstrating a marked contribution of elastase and/or PR3. VWF-platelet strings formed on the surface of primary glomerular endothelial cells, in a perfusion system, were cleaved by both elastase and the GBM, a process blocked by elastase inhibitor. Ultramorphological studies of the human kidney demonstrated neutrophils releasing elastase into the GBM. Neutrophil proteases may contribute to VWF cleavage within the subendothelium, adjacent to the GBM, and thus regulate thrombus size. This anti-thrombotic mechanism would protect the normal kidney during inflammation and could also explain why most patients with ADAMTS13 deficiency do not develop severe kidney failure.

  20. An NO Donor Approach to Neuroprotective and Procognitive Estrogen Therapy Overcomes Loss of NO Synthase Function and Potentially Thrombotic Risk

    PubMed Central

    VandeVrede, Lawren; Abdelhamid, Ramy; Qin, Zhihui; Choi, Jaewoo; Piyankarage, Sujeewa; Luo, Jia; Larson, John; Bennett, Brian M.; Thatcher, Gregory R. J.

    2013-01-01

    Selective estrogen receptor modulators (SERMs) are effective therapeutics that preserve favorable actions of estrogens on bone and act as antiestrogens in breast tissue, decreasing the risk of vertebral fractures and breast cancer, but their potential in neuroprotective and procognitive therapy is limited by: 1) an increased lifetime risk of thrombotic events; and 2) an attenuated response to estrogens with age, sometimes linked to endothelial nitric oxide synthase (eNOS) dysfunction. Herein, three 3rd generation SERMs with similar high affinity for estrogen receptors (ERα, ERβ) were studied: desmethylarzoxifene (DMA), FDMA, and a novel NO-donating SERM (NO-DMA). Neuroprotection was studied in primary rat neurons exposed to oxygen glucose deprivation; reversal of cholinergic cognitive deficit was studied in mice in a behavioral model of memory; long term potentiation (LTP), underlying cognition, was measured in hippocampal slices from older 3×Tg Alzheimer's transgenic mice; vasodilation was measured in rat aortic strips; and anticoagulant activity was compared. Pharmacologic blockade of GPR30 and NOS; denudation of endothelium; measurement of NO; and genetic knockout of eNOS were used to probe mechanism. Comparison of the three chemical probes indicates key roles for GPR30 and eNOS in mediating therapeutic activity. Procognitive, vasodilator and anticoagulant activities of DMA were found to be eNOS dependent, while neuroprotection and restoration of LTP were both shown to be dependent upon GPR30, a G-protein coupled receptor mediating estrogenic function. Finally, the observation that an NO-SERM shows enhanced vasodilation and anticoagulant activity, while retaining the positive attributes of SERMs even in the presence of NOS dysfunction, indicates a potential therapeutic approach without the increased risk of thrombotic events. PMID:23976955

  1. An NO donor approach to neuroprotective and procognitive estrogen therapy overcomes loss of NO synthase function and potentially thrombotic risk.

    PubMed

    VandeVrede, Lawren; Abdelhamid, Ramy; Qin, Zhihui; Choi, Jaewoo; Piyankarage, Sujeewa; Luo, Jia; Larson, John; Bennett, Brian M; Thatcher, Gregory R J

    2013-01-01

    Selective estrogen receptor modulators (SERMs) are effective therapeutics that preserve favorable actions of estrogens on bone and act as antiestrogens in breast tissue, decreasing the risk of vertebral fractures and breast cancer, but their potential in neuroprotective and procognitive therapy is limited by: 1) an increased lifetime risk of thrombotic events; and 2) an attenuated response to estrogens with age, sometimes linked to endothelial nitric oxide synthase (eNOS) dysfunction. Herein, three 3(rd) generation SERMs with similar high affinity for estrogen receptors (ERα, ERβ) were studied: desmethylarzoxifene (DMA), FDMA, and a novel NO-donating SERM (NO-DMA). Neuroprotection was studied in primary rat neurons exposed to oxygen glucose deprivation; reversal of cholinergic cognitive deficit was studied in mice in a behavioral model of memory; long term potentiation (LTP), underlying cognition, was measured in hippocampal slices from older 3×Tg Alzheimer's transgenic mice; vasodilation was measured in rat aortic strips; and anticoagulant activity was compared. Pharmacologic blockade of GPR30 and NOS; denudation of endothelium; measurement of NO; and genetic knockout of eNOS were used to probe mechanism. Comparison of the three chemical probes indicates key roles for GPR30 and eNOS in mediating therapeutic activity. Procognitive, vasodilator and anticoagulant activities of DMA were found to be eNOS dependent, while neuroprotection and restoration of LTP were both shown to be dependent upon GPR30, a G-protein coupled receptor mediating estrogenic function. Finally, the observation that an NO-SERM shows enhanced vasodilation and anticoagulant activity, while retaining the positive attributes of SERMs even in the presence of NOS dysfunction, indicates a potential therapeutic approach without the increased risk of thrombotic events.

  2. [Pathogenesis of thrombotic and hemorrhagic complications in myeloproliferative and myelodysplastic syndromes].

    PubMed

    Vlădăreanu, Ana-Maria; Popov, Viola; Bumbea, H; Ciufu, Cristina; Vasilache, Veronica; Petre, Anca; Onisâi, Minodora

    2011-01-01

    Chronic myeloproliferative disorders (CMD) and Myelodisplastic Syndromes (MDS) represents a group of clonal pluripotent stem-cell pathologies. During their natural history, the clinical picture reveals both thrombosis and hemorrhage. The thrombosis could affect the microvessels, and also the large vessels, including even less usual territories (suprahepatic veins, porta vein, pulmonary vein). There are many factors contributing to thrombosis in myeloproliferative chronic disorders--the associated comorbidities, the numeric alterations of blood elements and also the disorders of the platelet's function. Thus, there were described quantitative and qualitative anomalies of platelet's receptors: GP Ib, GP IIb/IIIa, GP IV, GP VI, thrombopoietin receptor of the platelet cMPL, the increase of platelet activation; the increase of P selectin and thrombospondin and the increase on GP IIb/IIIa expression--they were all correlated with thrombosis. An important role has been attributed to JAK2 mutation, which affects the platelet receptor for thrombopoietin cMPL. Regarding the hemorrhage in chronic myeloproliferative syndrome, it is favored by many disorders in platelet's function, such as: the decrease of von Willebrand factor's receptor of the platelet, which leads to acquired Bernard Soulier syndrome; quantitative and qualitative disorders of dense granules of the platelet, decrease of the secretion and platelet aggregation after epinephrine, ADP and collagen stimulation. It was also described the acquired von Willebrand syndrome, most frequently type 2.

  3. Corticomotoneuronal function and hyperexcitability in acquired neuromyotonia.

    PubMed

    Vucic, Steve; Cheah, Benjamin C; Yiannikas, Con; Vincent, Angela; Kiernan, Matthew C

    2010-09-01

    Acquired neuromyotonia encompasses a group of inflammatory disorders characterized by symptoms reflecting peripheral nerve hyperexcitability, which may be clinically confused in the early stages with amyotrophic lateral sclerosis. Despite a clear peripheral nerve focus, it remains unclear whether the ectopic activity in acquired neuromyotonia receives a central contribution. To clarify whether cortical hyperexcitability contributes to development of clinical features of acquired neuromyotonia, the present study investigated whether threshold tracking transcranial magnetic stimulation could detect cortical hyperexcitability in acquired neuromyotonia, and whether this technique could differentiate acquired neuromyotonia from amyotrophic lateral sclerosis. Cortical excitability studies were undertaken in 18 patients with acquired neuromyotonia and 104 patients with amyotrophic lateral sclerosis, with results compared to 62 normal controls. Short-interval intracortical inhibition in patients with acquired neuromyotonia was significantly different when compared to patients with amyotrophic lateral sclerosis (averaged short interval intracortical inhibition acquired neuromyotonia 11.3 +/- 1.9%; amyotrophic lateral sclerosis 2.6 +/- 0.9%, P < 0.001). In addition, the motor evoked potential amplitudes (acquired neuromyotonia 21.0 +/- 3.1%; amyotrophic lateral sclerosis 38.1 +/- 2.2%, P < 0.0001), intracortical facilitation (acquired neuromyotonia -0.9 +/- 1.3%; amyotrophic lateral sclerosis -2.3 +/- 0.6%, P < 0.0001), resting motor thresholds (acquired neuromyotonia 62.2 +/- 1.6%; amyotrophic lateral sclerosis 57.2 +/- 0.9%, P < 0.05) and cortical silent period durations (acquired neuromyotonia 212.8 +/- 6.9 ms; amyotrophic lateral sclerosis 181.1 +/- 4.3 ms, P < 0.0001) were significantly different between patients with acquired neuromyotonia and amyotrophic lateral sclerosis. Threshold tracking transcranial magnetic stimulation established corticomotoneuronal integrity

  4. 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.

  5. Association of CD4+CD25+FoxP3+ regulatory T cells with natural course of childhood chronic immune thrombocytopenic purpura

    PubMed Central

    Son, Bo Ra

    2015-01-01

    Purpose The purpose of this study was to determine the frequency of CD4+CD25+FoxP3+ regulatory T cells (Treg) in the peripheral blood of patients with childhood chronic immune thrombocytopenic purpura (ITP) exhibiting thrombocytopenia and spontaneous remission. The findings of this study indicate the possibility of predicting spontaneous recovery and pathogenesis of childhood chronic ITP. Methods Eleven children with chronic ITP (seven thrombocytopenic and four spontaneous remission cases; mean age, 8.8 years; range, 1.7-14.9 years) were enrolled in this study. Five healthy children and eight healthy adults were included as controls. The frequency of Treg was evaluated by flow cytometry in the peripheral blood. Results In this study, four patients (36%) achieved spontaneous remission within 2.8 years (mean year; range, 1.0-4.4 years). The frequency of Treg was significantly lower in patients with persisting thrombocytopenia (0.13%±0.09%, P<0.05), than that in the patients with spontaneous remission (0.30%±0.02%), healthy adults controls (0.55%±0.44%), and healthy children controls (0.46%±0.26%). A significantly positive correlation was found between the frequency of Treg and the platelet count in children. Conclusion These data suggest that a lower frequency of Treg contributes to the breakdown of self-tolerance, and may form the basis for future development of specific immunomodulatory therapies. Furthermore, Treg frequency has prognostic implication toward the natural course and long-term outcomes of childhood chronic ITP. PMID:26124848

  6. Associative Learning Through Acquired Salience

    PubMed Central

    Treviño, Mario

    2016-01-01

    Most associative learning studies describe the salience of stimuli as a fixed learning-rate parameter. Presumptive saliency signals, however, have also been linked to motivational and attentional processes. An interesting possibility, therefore, is that discriminative stimuli could also acquire salience as they become powerful predictors of outcomes. To explore this idea, we first characterized and extracted the learning curves from mice trained with discriminative images offering varying degrees of structural similarity. Next, we fitted a linear model of associative learning coupled to a series of mathematical representations for stimulus salience. We found that the best prediction, from the set of tested models, was one in which the visual salience depended on stimulus similarity and a non-linear function of the associative strength. Therefore, these analytic results support the idea that the net salience of a stimulus depends both on the items' effective salience and the motivational state of the subject that learns about it. Moreover, this dual salience model can explain why learning about a stimulus not only depends on the effective salience during acquisition but also on the specific learning trajectory that was used to reach this state. Our mathematical description could be instrumental for understanding aberrant salience acquisition under stressful situations and in neuropsychiatric disorders like schizophrenia, obsessive-compulsive disorder, and addiction. PMID:26793078

  7. Inherited or acquired metabolic disorders.

    PubMed

    Eichler, Florian; Ratai, Eva; Carroll, Jason J; Masdeu, Joseph C

    2016-01-01

    This chapter starts with a description of imaging of inherited metabolic disorders, followed by a discussion on imaging of acquired toxic-metabolic disorders of the adult brain. Neuroimaging is crucial for the diagnosis and management of a number of inherited metabolic disorders. Among these, inherited white-matter disorders commonly affect both the nervous system and endocrine organs. Magnetic resonance imaging (MRI) has enabled new classifications of these disorders that have greatly enhanced both our diagnostic ability and our understanding of these complex disorders. Beyond the classic leukodystrophies, we are increasingly recognizing new hereditary leukoencephalopathies such as the hypomyelinating disorders. Conventional imaging can be unrevealing in some metabolic disorders, but proton magnetic resonance spectroscopy (MRS) may be able to directly visualize the metabolic abnormality in certain disorders. Hence, neuroimaging can enhance our understanding of pathogenesis, even in the absence of a pathologic specimen. This review aims to present pathognomonic brain MRI lesion patterns, the diagnostic capacity of proton MRS, and information from clinical and laboratory testing that can aid diagnosis. We demonstrate that applying an advanced neuroimaging approach enhances current diagnostics and management. Additional information on inherited and metabolic disorders of the brain can be found in Chapter 63 in the second volume of this series.

  8. 17 CFR 210.8-06 - Real estate operations acquired or to be acquired.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Real estate operations acquired or to be acquired. 210.8-06 Section 210.8-06 Commodity and Securities Exchanges SECURITIES AND... Statements of Smaller Reporting Companies § 210.8-06 Real estate operations acquired or to be acquired....

  9. Acquired immune deficiency syndrome: review.

    PubMed

    Scully, C; Cawson, R A; Porter, S R

    1986-07-19

    Acquired immunodeficiency syndrome (AIDS) is reviewed for dental practitioners, with an emphasis on oral findings; the clinical course, diagnosis, reporting, treatment, prognosis, transmission, and epidemiology are also covered. HIV infection has an incubation period that may be associated with glandular fever, a prodrome called AIDS-Related Complex (ARC) characterized by lymphadenopathy, low fever, weight loss, night sweats, diarrhea, oral candidosis, nonproductive cough and recurrent infections. AIDS is characterized by opportunistic infections. Over 50% present with pneumocystis carinii pneumonia, 21% with Kaposi's sarcoma, and 6% have both. The AIDS virus causes direct neurological symptoms in some cases. Oral candidosis (thrush) in a young male without a local cause such as xerostomia or immune suppression is strongly suggestive of AIDS. Other oral manifestations are severe herpes simplex, varicella-zoster, Epstein-Barr virus, cytomegalovirus, venereal warts, aphthous ulceration, mycobacterial oral ulcers, oral histoplasmosis, sinusitis and osteomyelitis of the jaw. Hairy leukoplakia, usually seen on the lateral border of the tongue, is probably caused by Epstein-Barr virus. Kaposi's sarcoma, an endothelial cell tumor, is characteristic of AIDS, and in 50% of patients is oral or perioral. Cervical lymph node enlargement will be seen in those with ARC as well as AIDS. No guidelines have been issued by the Department of Health and Social Security for dental surgeons in the UK for reporting AIDS cases. Although HIV virions have been isolated from saliva, there are no known incidents of transmission via saliva. HIV is less likely to be transmitted by needle stick injuries than, for example hepatitis B (25% risk), especially if the blood is from a carrier rather than a full blown AIDS case.

  10. Clinicopathological associations of acquired erythroblastopenia

    PubMed Central

    Gunes, Gursel; Malkan, Umit Yavuz; Yasar, Hatime Arzu; Eliacik, Eylem; Haznedaroglu, Ibrahim Celalettin; Demiroglu, Haluk; Sayinalp, Nilgun; Aksu, Salih; Etgul, Sezgin; Aslan, Tuncay; Goker, Hakan; Ozcebe, Osman Ilhami; Buyukasik, Yahya

    2015-01-01

    Introduction: Acquired erythroblastopenia (AE) is a rare clinical situation. It is characterized by the reduction of erythroid precursors in the bone marrow together with the low reticulocyte counts in the peripheral blood. Background: Main secondary causes of AE are drugs, Parvovirus B19 and other infectious reasons, lymphoid and myeloid neoplasia, autoimmune diseases, thymoma and pregnancy. The aim of this study is to assess the frequencies and clinical associations of AE via analyzing 12340 bone marrow samples in a retrospective manner. Material and method: Bone marrow aspirations which were obtained from patients who applied to Hacettepe University Hematology Clinic between 2002 and 2013, were analyzed retrospectively. Results: Thirty four erythroblastopenia cases were found. Patients ranged in age from 16 to 80 years with a median of 38 years. Fifteen patients were men (44%) and nineteen were women (56%). In these patients, detected causes of erythroblastopenia were MDS, idiopathic pure red cell aplasia (PRCA), parvovirus infection, post chemotherapy aplasia, plasma proliferative diseases, copper deficiency due to secondary amyloidosis, fever of unknown origin, hemophagocytic syndrome, enteric fever and legionella pneumonia. We found that between those reasons the most common causes of erythroblastopenia are MDS (17.7%) and idiopathic PRCA (17.7%). Discussion: As a result, erythroblastopenia in the bone marrow may be an early sign of MDS. In those AE cases possibility of being MDS must be kept in mind as it can be mistaken for PRCA. Conclusion: To conclude, in adults MDS without excess blast is one of the most common causes of erythroblastopenia in clinical practice and in case of erythroblastopenia the presence of MDS should be investigated. PMID:26885236

  11. Idiopathic thrombocytopenic purpura (ITP)

    MedlinePlus

    Blood tests will be done to check your platelet count . A bone marrow aspiration or biopsy may also be done. ... the disease usually goes away without treatment. Some children ... the platelet count in about half of people. However, other drug ...

  12. Cryptosporidiosis in the acquired immune deficiency syndrome.

    PubMed

    Cooper, D A; Wodak, A; Marriot, D J; Harkness, J L; Ralston, M; Hill, A; Penny, R

    1984-10-01

    Cryptosporidiosis was found in a patient with the acquired immune deficiency syndrome. The microbiological and morphological features of this newly recognized opportunistic infection are distinctive and diagnostic.

  13. Successful Revascularization of an LCx CTO Lesion by Retrograde Approach From an Acute Thrombotic SVG Without Protection Device in an ACS Patient.

    PubMed

    Lin, Mei Mei; Wang, Ji Hung

    2016-05-25

    We describe a patient who underwent coronary artery bypass grafting (CABG) surgery with the presentation of acute coronary syndrome (ACS). The diagnostic coronary angiogram showed acute thrombotic and occluded saphenous vein graft (SVG) and proximal right coronary artery (RCA) drug eluting stent (DES) instent restenosis (ISR) with chronic total occlusion (CTO). Our strategy was to recanalize the native left circumflex coronary artery (LCx) CTO instead of SVG or RCA instent CTO. After heparinization for 5 days, the LCx antegrade approach and the retrograde approach from left anterior descending coronary artery (LAD) septal branches were first attempted but failed, and the LCx CTO was successfully revascularized retrogradely via the acute thrombotic SVG without an embolic protection device (EPD).

  14. Acute Thrombotic Occlusion of the Popliteal Artery following Knee Dislocation: A Case Report of Management, Local Unit Practice, and a Review of the Literature

    PubMed Central

    Hindi, Fadi; Ettles, Callum; Pemberton, Mark

    2017-01-01

    Arterial complications following traumatic knee injury are relatively rare but mandate timely recognition and treatment to avoid significant comorbidity and medicolegal ramifications. In this report we describe a case of acute thrombotic occlusion of the popliteal artery occurring after knee dislocation, successfully repaired by intimal fixation and a limited venous patch reconstruction. We present a review of local practice in screening vascular injuries following knee dislocation, aligned with a review of the literature and considerations for practice. PMID:28246569

  15. Acute Thrombotic Occlusion of the Popliteal Artery following Knee Dislocation: A Case Report of Management, Local Unit Practice, and a Review of the Literature.

    PubMed

    Godfrey, Anthony Dean; Hindi, Fadi; Ettles, Callum; Pemberton, Mark; Grewal, Perbinder

    2017-01-01

    Arterial complications following traumatic knee injury are relatively rare but mandate timely recognition and treatment to avoid significant comorbidity and medicolegal ramifications. In this report we describe a case of acute thrombotic occlusion of the popliteal artery occurring after knee dislocation, successfully repaired by intimal fixation and a limited venous patch reconstruction. We present a review of local practice in screening vascular injuries following knee dislocation, aligned with a review of the literature and considerations for practice.

  16. Thrombotic complications in adult patients with lymphoma: a meta-analysis of 29 independent cohorts including 18 018 patients and 1149 events.

    PubMed

    Caruso, Vanesa; Di Castelnuovo, Augusto; Meschengieser, Susana; Lazzari, Maria A; de Gaetano, Giovanni; Storti, Sergio; Iacoviello, Licia; Donati, Maria Benedetta

    2010-07-01

    Thrombotic complications in hematologic malignancies have important clinical implications. In this meta-analysis we sought to obtain accurate estimates of the thrombotic risk in lymphoma patients. Articles were searched in electronic databases and references. Eighteen articles were identified (29 cohorts, 18 018 patients and 1149 events). Pooled incidence rates (IRs) were calculated by the use of a method based on the exact maximum likelihood binomial distribution. The global IR of thrombosis was 6.4% (95% confidence interval [CI] 6.0%-6.8%). The global IRs of venous or arterial events were 5.3% (95% CI, 5.0%-5.7%) and 1.1% (95% CI, 0.9%-1.2%), respectively. The IR of thrombosis observed in subjects with non-Hodgkin lymphoma (NHL) was 6.5% (95% CI, 6.1%-6.9%), significantly greater than that observed for patients with Hodgkin lymphoma (4.7%; 95% CI, 3.9%-5.6%). Within NHL, patients with high-grade disease had a greater risk of events (IR 8.3%; 95% CI, 7.0%-9.9%) than low-grade disease (IR 6.3%; 95% CI, 4.5%-8.9%). This meta-analysis shows that the IR of thrombosis in lymphoma patients is quite high, especially in those with NHL at an advanced stage of the disease. These results may help better defining lymphoma populations at high thrombotic risk, to whom prophylactic approaches could be preferentially applied.

  17. Comparative incidence of a first thrombotic event in purely obstetric antiphospholipid syndrome with pregnancy loss: the NOH-APS observational study.

    PubMed

    Gris, Jean-Christophe; Bouvier, Sylvie; Molinari, Nicolas; Galanaud, Jean-Philippe; Cochery-Nouvellon, Eva; Mercier, Erik; Fabbro-Peray, Pascale; Balducchi, Jean-Pierre; Marès, Pierre; Quéré, Isabelle; Dauzat, Michel

    2012-03-15

    The incidence of thrombosis in the purely obstetric form of antiphospholipid syndrome is uncertain. We performed a 10-year observational study of 1592 nonthrombotic women who had experienced 3 consecutive spontaneous abortions before the 10th week of gestation or 1 fetal death at or beyond the 10th week of gestation. We compared the frequencies of thrombotic events among women positive for antiphospholipid Abs (n = 517), women carrying the F5 6025 or F2 rs1799963 polymorphism (n = 279), and women with negative thrombophilia screening results (n = 796). The annual rates of deep vein thrombosis (1.46%; range, 1.15%-1.82%), pulmonary embolism (0.43%; range, 0.26%-0.66%), superficial vein thrombosis (0.44%; range, 0.28%-0.68%), and cerebrovascular events (0.32%; range, 0.18%-0.53%) were significantly higher in aPLAbs women than in the other groups despite low-dose aspirin primary prophylaxis. Women carrying 1 of the 2 polymorphisms did not experience more thrombotic events than women who screened negative for thrombophilia. Lupus anticoagulant was a risk factor for unprovoked proximal and distal deep and superficial vein thrombosis and women in the upper quartile of lupus anticoagulant activity had the highest risk. Despite data suggesting that aPLAbs may induce pregnancy loss through nonthrombotic mechanisms, women with purely obstetric antiphospholipid syndrome are at risk for thrombotic complications.

  18. Acquiring and Managing Electronic Journals. ERIC Digest.

    ERIC Educational Resources Information Center

    Curtis, Donnelyn; Yue, Paoshan

    Electronic journals are both a blessing and a curse for libraries. To be meaningful in the current information environment--to meet users' ever-increasing demands--libraries must acquire as many appropriate full text resources as possible, as quickly as possible, and make them easy to use. This Digest provides tips for acquiring and providing…

  19. Acquired idiopathic generalized anhidrosis: case report.

    PubMed

    Brantley, Elise I; Mutasim, Diya F; Heaton, Charles

    2011-01-01

    We report a case of acquired idiopathic generalized anhidrosis (AIGA) in a 56-year-old white woman. Acquired idiopathic generalized anhidrosis is an exceedingly rare group of heterogeneous disorders that has been almost exclusively reported in young Japanese males. Our case is unique in that AlGA may be underrecognized in this patient population.

  20. Immune Complex Mediated Glomerulonephritis with Acute Thrombotic Microangiopathy following Newly Detected Hepatitis B Virus Infection in a Kidney Transplant Recipient.

    PubMed

    Salter, Tracey; Burton, Hannah; Douthwaite, Sam; Newsholme, William; Horsfield, Catherine; Hilton, Rachel

    2016-01-01

    Hepatitis B virus (HBV) presents a risk to patients and staff in renal units. To minimise viral transmission, there are international and UK guidelines recommending HBV immunisation for patients commencing renal replacement therapy (RRT) and HBV surveillance in kidney transplant recipients. We report the case of a 56-year-old male who was immunised against HBV before starting haemodialysis. He received a deceased donor kidney transplant three years later, at which time there was no evidence of HBV infection. After a further six years he developed an acute kidney injury; allograft biopsy revealed an acute thrombotic microangiopathy (TMA) with glomerulitis, peritubular capillaritis, and C4d staining. Due to a "full house" immunoprofile, tests including virological screening were undertaken, which revealed acute HBV infection. Entecavir treatment resulted in an improvement in viral load and kidney function. HBV genotyping demonstrated a vaccine escape mutant, suggesting "past resolved" infection that reactivated with immunosuppression, though posttransplant acquisition cannot be excluded. This is the first reported case of acute HBV infection associated with immune complex mediated glomerulonephritis and TMA. Furthermore, it highlights the importance of HBV surveillance in kidney transplant recipients, which although addressed by UK guidelines is not currently practiced in all UK units.

  1. Architecture of fibrin network inside thrombotic material obtained from the right atrium and pulmonary arteries: flow and location matter.

    PubMed

    Mazur, Piotr; Sobczyński, Robert; Ząbczyk, Michał; Babiarczyk, Paulina; Sadowski, Jerzy; Undas, Anetta

    2013-01-01

    Pulmonary embolectomy is a treatment option in selected patients with high-risk pulmonary embolism (PE). Efficiency of thrombus degradation in PE largely depends on the architecture of its fibrin network, however little is known about its determinants. We present the case of a 56-year-old woman with high-risk PE and proximal deep-vein thrombosis, whose thrombotic material removed during embolectomy from the right atrium and pulmonary (lobar and segmental) arteries has been studied using scanning electron microscopy (SEM). SEM images showed that distally located thrombi are richer in densely-packed fibrin fibers and contain more white cells and less erythrocytes than the proximal ones and the atrial thrombus. Fibrin fibers alignment along the flow vector was observed in the thrombi removed from high-velocity flow pulmonary arteries, and not in the atrial thrombus. The content of denser fibrin network and platelet aggregates was increased in segmental thromboemboli. Our findings describe the relation between thrombus architecture and location, and might help to elucidate thrombus resistance to anticoagulant therapy in some PE patients.

  2. Immune Complex Mediated Glomerulonephritis with Acute Thrombotic Microangiopathy following Newly Detected Hepatitis B Virus Infection in a Kidney Transplant Recipient

    PubMed Central

    Burton, Hannah; Douthwaite, Sam; Newsholme, William; Horsfield, Catherine

    2016-01-01

    Hepatitis B virus (HBV) presents a risk to patients and staff in renal units. To minimise viral transmission, there are international and UK guidelines recommending HBV immunisation for patients commencing renal replacement therapy (RRT) and HBV surveillance in kidney transplant recipients. We report the case of a 56-year-old male who was immunised against HBV before starting haemodialysis. He received a deceased donor kidney transplant three years later, at which time there was no evidence of HBV infection. After a further six years he developed an acute kidney injury; allograft biopsy revealed an acute thrombotic microangiopathy (TMA) with glomerulitis, peritubular capillaritis, and C4d staining. Due to a “full house” immunoprofile, tests including virological screening were undertaken, which revealed acute HBV infection. Entecavir treatment resulted in an improvement in viral load and kidney function. HBV genotyping demonstrated a vaccine escape mutant, suggesting “past resolved” infection that reactivated with immunosuppression, though posttransplant acquisition cannot be excluded. This is the first reported case of acute HBV infection associated with immune complex mediated glomerulonephritis and TMA. Furthermore, it highlights the importance of HBV surveillance in kidney transplant recipients, which although addressed by UK guidelines is not currently practiced in all UK units. PMID:27800206

  3. Association of FXII 5'UTR 46C>T polymorphism with FXII activity and risk of thrombotic disease.

    PubMed

    Rasighaemi, Parisa; Kazemi, Ahmad; Ala, Fereidun; Jazebi, Mohammad; Razmkhah, Farnaz

    2010-03-05

    AMAÇ: Thrombotic diseases are caused by genetic and environmental factors. There are a number of well-characterized genetic defects that lead to increased risk of thrombosis. Results from previous studies have indicated that FXII is involved in the pathogenesis of thrombophilic diseases. However, the results in this regard are highly controversial. One of the most important determinants of Plasma FXII level is 46CgT polymorphism in the FXII gene. In the present study, the risk of thrombophilic diseases related to this polymorphism was investigated in a case-control study. YÖNTEMLER: Yüz altmış denek incelenmiştir: 120 hastaya trombofili (96’sı tromboembolizm, 24’ü arteriyel tromboz) tanısı konmuş olup 40 hasta yaş ve cinsiyet açısından eşleştirilmiştir. Her bir denek için, FXII aktivite düzeyi, FXII’den yoksun plazma ile tek adımlı pıhtılaşma testi kullanarak ölçülmüş ve 46CγT polimorfizmi, (RFLP) yöntemi ile genotiplenmiştir.

  4. Ex vivo diffusion tensor imaging and neuropathological correlation in a murine model of hypoxia-ischemia-induced thrombotic stroke.

    PubMed

    Shereen, Ahmed; Nemkul, Niza; Yang, Dianer; Adhami, Faisal; Dunn, R Scott; Hazen, Missy L; Nakafuku, Masato; Ning, Gang; Lindquist, Diana M; Kuan, Chia-Yi

    2011-04-01

    Diffusion tensor imaging (DTI) is a powerful method to visualize white matter, but its use in patients with acute stroke remains limited because of the lack of corresponding histologic information. In this study, we addressed this issue using a hypoxia-ischemia (HI)-induced thrombotic model of stroke in adult mice. At 6, 15, and 24  hours after injury, animals were divided into three groups for (1) in vivo T2- and diffusion-weighted magnetic resonance imaging, followed by histochemistry, (2) ex vivo DTI and electron microscopy, and (3) additional biochemical or immunochemical assays. The temporal changes of diffusion anisotropy and histopathology were compared in the fimbria, internal capsule, and external capsule. We found that HI caused a rapid reduction of axial and radial diffusivities in all three axonal bundles. A large decrease in fractional anisotropy, but not in axial diffusivity per se, was associated with structural breakdown of axons. Furthermore, the decrease in radial diffusivity correlated with swelling of myelin sheaths and compression of the axoplasma. The gray matter of the hippocampus also exhibited a high level of diffusion anisotropy, and its reduction signified dendritic degeneration. Taken together, these results suggest that cross-evaluation of multiple DTI parameters may provide a fuller picture of axonal and dendritic injury in acute ischemic stroke.

  5. Presence of antiphospholipid antibody is a risk factor in thrombotic events in patients with antiphospholipid syndrome or relevant diseases.

    PubMed

    Habe, Koji; Wada, Hideo; Matsumoto, Takeshi; Ohishi, Kohshi; Ikejiri, Makoto; Matsubara, Kimiko; Morioka, Tatsuhiko; Kamimoto, Yuki; Ikeda, Tomoaki; Katayama, Naoyuki; Nobori, Tsutomu; Mizutani, Hitoshi

    2013-03-01

    Antiphospholipid antibodies (aPL) including lupus anticoagulant (LA), anticardiolipin antibodies (aCL) IgG and aCL-β2-glycoprotein I (β2GPI) complex IG are causative factors for thrombotic event (THE). We retrospectively investigated relationships between aPLs and THE in 458 patients suspected of having antiphospholipid syndrome. THEs were observed in 232 of 458 patients, including 148 cases of venous thrombosis, 59 of arterial thrombosis, 18 of microthrombosis, and 20 of complications of pregnancy. The frequency of THE was significantly high in patients positive for LA and/or aPL. In patients with autoimmune disease (AID), the frequency of THE was significantly high in patients with any types of aPLs. Additionally, risk of THE was significantly increased in patients with more than two types of aPLs. Prolonged activated partial thromboplastin time indicated a high risk for THE. However, neither thrombocytopenia nor AID was a risk for THE. In conclusion, the presence of aPL is an indicator for high risk of THE in patients in whom THE was suspected. However, the risk of THE in aPL-positive patients varied among patients with different underlying diseases.

  6. Evaluation of sensory and in vitro anti-thrombotic properties of traditional Greek yogurts derived from different types of milk.

    PubMed

    Megalemou, Kalliopi; Sioriki, Eleni; Lordan, Ronan; Dermiki, Maria; Nasopoulou, Constantina; Zabetakis, Ioannis

    2017-01-01

    Given that fermented dairy products exhibit high bioactivities against cardiovascular diseases (CVDs), the anti-thrombotic properties, fatty acid profiles and sensory properties of cow, goat and ewe derived Greek yogurts have been assessed and compared. The total lipids (TL), total polar lipids (TPL), total neutral lipids (TNL) were obtained and the polar lipid fractions were further separated by thin layer chromatography (TLC). These lipid samples (TL, TPL and TLC fractions) were subsequently assessed for their biological activity against atherosclerosis based on the in vitro inhibition of Platelet Activating Factor (PAF)-induced platelet aggregation. The fatty acid compositions of all yogurts were analyzed by Gas Chromatography with flame ionization detector (GC-FID). Goat yogurt lipids have been found to exert more potent inhibitory activity (i.e. lower IC50 values in both TL and TPL samples) in contrast to the corresponding fractions of cow and ewe yogurts. The observed sensory data indicates that ewe yogurt was the most palatable of all three Greek yogurts.

  7. Improvement in Gemcitabine-Induced Thrombotic Microangiopathy with Rituximab in a Patient with Ovarian Cancer: Mechanistic Considerations.

    PubMed

    Murugapandian, Sangeetha; Bijin, Babitha; Mansour, Iyad; Daheshpour, Sepehr; Pillai, Biju G; Thajudeen, Bijin; Salahudeen, Abdulla K

    2015-01-01

    Gemcitabine is a potent and widely used anticancer drug. We report a case of gemcitabine-induced thrombotic microangiopathy (GCI-TMA), a known but not widely recognized complication of gemcitabine use, and our experience of treating GCI-TMA with rituximab. A 74-year-old woman was referred to our clinic for an evaluation of worsening renal function. She has recently been treated for ovarian cancer (diagnosed in 2011) with surgery (tumor debulking and bilateral salpingo-oophorectomy) along with cisplatin chemotherapy in 2012, followed by carboplatin/doxorubicin in 2013 and recent therapy for resistant disease with gemcitabine. Laboratory tests showed anemia, normal platelets and elevated lactate dehydrogenase. A peripheral smear revealed numerous schistocytes, and a kidney biopsy showed acute as well as chronic TMA. The patient continued on gemcitabine therapy, and treatment with plasma exchange was started. Since there was no response to treatment even after 5 sessions of plasma exchange, one dose of rituximab was given, which was associated with a drop in the creatinine level to 2 mg/dl. The pathogenesis of renal injury could be the effect of direct injury to the endothelium mediated by cytokines. Usual treatment includes withdrawing the drug and initiation of treatment with plasmapheresis with or without steroids. In cases resistant to plasmapheresis, treatment with rituximab can be tried. The mechanism of action of rituximab might be due to the reduced production of B-cell-dependent cytokines that drive endothelial dysfunction by depleting B cells. Patients receiving gemcitabine chemotherapy should be monitored for the development of TMA, and early treatment with plasma exchange along with rituximab might benefit these patients who already have a bad prognosis.

  8. Improvement in Gemcitabine-Induced Thrombotic Microangiopathy with Rituximab in a Patient with Ovarian Cancer: Mechanistic Considerations

    PubMed Central

    Murugapandian, Sangeetha; Bijin, Babitha; Mansour, Iyad; Daheshpour, Sepehr; Pillai, Biju G.; Thajudeen, Bijin; Salahudeen, Abdulla K.

    2015-01-01

    Gemcitabine is a potent and widely used anticancer drug. We report a case of gemcitabine-induced thrombotic microangiopathy (GCI-TMA), a known but not widely recognized complication of gemcitabine use, and our experience of treating GCI-TMA with rituximab. A 74-year-old woman was referred to our clinic for an evaluation of worsening renal function. She has recently been treated for ovarian cancer (diagnosed in 2011) with surgery (tumor debulking and bilateral salpingo-oophorectomy) along with cisplatin chemotherapy in 2012, followed by carboplatin/doxorubicin in 2013 and recent therapy for resistant disease with gemcitabine. Laboratory tests showed anemia, normal platelets and elevated lactate dehydrogenase. A peripheral smear revealed numerous schistocytes, and a kidney biopsy showed acute as well as chronic TMA. The patient continued on gemcitabine therapy, and treatment with plasma exchange was started. Since there was no response to treatment even after 5 sessions of plasma exchange, one dose of rituximab was given, which was associated with a drop in the creatinine level to 2 mg/dl. The pathogenesis of renal injury could be the effect of direct injury to the endothelium mediated by cytokines. Usual treatment includes withdrawing the drug and initiation of treatment with plasmapheresis with or without steroids. In cases resistant to plasmapheresis, treatment with rituximab can be tried. The mechanism of action of rituximab might be due to the reduced production of B-cell-dependent cytokines that drive endothelial dysfunction by depleting B cells. Patients receiving gemcitabine chemotherapy should be monitored for the development of TMA, and early treatment with plasma exchange along with rituximab might benefit these patients who already have a bad prognosis. PMID:26266248

  9. Bleeding Risk during Treatment of Acute Thrombotic Events with Subcutaneous LMWH Compared to Intravenous Unfractionated Heparin; A Systematic Review

    PubMed Central

    Costantino, Giorgio; Ceriani, Elisa; Rusconi, Anna Maria; Podda, Gian Marco; Montano, Nicola; Duca, Piergiorgio; Cattaneo, Marco; Casazza, Giovanni

    2012-01-01

    Background Low Molecular Weight Heparins (LMWH) are at least as effective antithrombotic drugs as Unfractionated Heparin (UFH). However, it is still unclear whether the safety profiles of LMWH and UFH differ. We performed a systematic review to compare the bleeding risk of fixed dose subcutaneous LMWH and adjusted dose UFH for treatment of venous thromboembolism (VTE) or acute coronary syndromes (ACS). Major bleeding was the primary end point. Methods Electronic databases (MEDLINE, EMBASE, and the Cochrane Library) were searched up to May 2010 with no language restrictions. Randomized controlled trials in which subcutaneous LMWH were compared to intravenous UFH for the treatment of acute thrombotic events were selected. Two reviewers independently screened studies and extracted data on study design, study quality, incidence of major bleeding, patients’ characteristics, type, dose and number of daily administrations of LMWH, co-treatments, study end points and efficacy outcome. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using the random effects model. Results Twenty-seven studies were included. A total of 14,002 patients received UFH and 14,635 patients LMWH. Overall, no difference in major bleeding was observed between LMWH patients and UFH (OR = 0.79, 95% CI 0.60–1.04). In patients with VTE LMWH appeared safer than UFH, (OR = 0.68, 95% CI 0.47–1.00). Conclusion The results of our systematic review suggest that the use of LMWH in the treatment of VTE might be associated with a reduction in major bleeding compared with UFH. The choice of which heparin to use to minimize bleeding risk must be based on the single patient, taking into account the bleeding profile of different heparins in different settings. PMID:22984525

  10. Assessment of Novel Anti-thrombotic Fusion Proteins for Inhibition of Stenosis in a Porcine Model of Arteriovenous Graft

    PubMed Central

    Terry, Christi M.; Zhuplatov, Ilya; He, Yuxia; Wun, Tze-Chein; Kim, Seong-Eun; Cheung, Alfred K.

    2015-01-01

    Background Hemodialysis arteriovenous synthetic grafts (AVG) provide high volumetric blood flow rates shortly after surgical placement. However, stenosis often develops at the vein-graft anastomosis contributing to thrombosis and early graft failure. Two novel fusion proteins, ANV-6L15 and TAP-ANV, inhibit the tissue factor/factor VIIa coagulation complex and the factor Xa/factor Va complex, respectively. Each inhibitor domain is fused to an annexin V domain that targets the inhibitor activity to sites of vascular injury to locally inhibit thrombosis. This study’s objective was to determine if these antithrombotic proteins are safe and effective in inhibiting AVG stenosis. Methods A bolus of either TAP-ANV or ANV-6L15 fusion protein was administered intravenously immediately prior to surgical placement of a synthetic graft between the external jugular vein and common carotid artery in a porcine model. At surgery, the vein and artery were irrigated with the anti-thrombotic fusion protein. Control animals received intravenous heparin. At 4 weeks, MRI was performed to evaluate graft patency, the pigs were then euthanized and grafts and attached vessels were explanted for histomorphometric assessment of neointimal hyperplasia at the vein-graft anastomosis. Blood was collected at surgery, immediately after surgery and at euthanasia for serum metabolic panels and coagulation chemistries. Results No acute thrombosis occurred in the control group or in either experimental group. No abnormal serum chemistries, activated clotting times or PT, PTT values were observed after treatment in experimental or control animals. However, at the vein-graft anastomosis, there was no difference between the control and experimental groups in cross-sectional lumen areas, as measured on MRI, and no difference in hyperplasia areas as determined by histomorphometry. These results suggest that local irrigation of TAP-ANV or ANV-6L15 intra-operatively was as effective in inhibiting acute graft

  11. Pre-activated blood platelets and a pro-thrombotic phenotype in APP23 mice modeling Alzheimer's disease.

    PubMed

    Jarre, Andrea; Gowert, Nina S; Donner, Lili; Münzer, Patrick; Klier, Meike; Borst, Oliver; Schaller, Martin; Lang, Florian; Korth, Carsten; Elvers, Margitta

    2014-09-01

    Platelet activation and thrombus formation play a critical role in primary hemostasis but also represent a pathophysiological mechanism leading to acute thrombotic vascular occlusions. Besides, platelets modulate cellular processes including inflammation, angiogenesis and neurodegeneration. On the other hand, platelet activation and thrombus formation are altered in different diseases leading to either bleeding complications or pathological thrombus formation. For many years platelets have been considered to play a role in neuroinflammatory diseases such as Alzheimer's disease (AD). AD is characterized by deposits of amyloid-β (Aβ) and strongly related to vascular diseases with platelets playing a critical role in the progression of AD because exposure of platelets to Aβ induces platelet activation, platelet Aβ release, and enhanced platelet adhesion to collagen in vitro and at the injured carotid artery in vivo. However, the molecular mechanisms and the relation between vascular pathology and amyloid-β plaque formation in the pathogenesis of AD are not fully understood. Compelling evidence is suggestive for altered platelet activity in AD patients. Thus we analyzed platelet activation and thrombus formation in aged AD transgenic mice (APP23) known to develop amyloid-β deposits in the brain parenchyma and cerebral vessels. As a result, platelets are in a pre-activated state in blood of APP23 mice and showed strongly enhanced integrin activation, degranulation and spreading kinetics on fibrinogen surfaces upon stimulation. This enhanced platelet signaling translated into almost unlimited thrombus formation on collagen under flow conditions in vitro and accelerated vessel occlusion in vivo suggesting that these mice are at high risk of arterial thrombosis leading to cerebrovascular and unexpectedly to cardiovascular complications that might be also relevant in AD patients.

  12. De novo post-transplant thrombotic microangiopathy localized only to the graft in autosomal dominant polycystic kidney disease with thrombophilia

    PubMed Central

    Rolla, Davide; Fontana, Iris; Ravetti, Jean Louis; Marsano, Luigina; Bellino, Diego; Panaro, Laura; Ansaldo, Francesca; Mathiasen, Lisa; Storace, Giulia; Trezzi, Matteo

    2015-01-01

    Introduction: Thrombotic microangiopathy (TMA) is a serious complication of renal transplantation and is mostly related to the prothrombotic effect of calcineurin inhibitors (CNIs). A subset of TMA (29%-38%) is localized only to the graft. Case 1: A young woman suffering from autosomal dominant polycystic kidney disease (ADPKD) underwent kidney transplant. After 2 months, she showed slow renal deterioration (serum creatinine from 1.9 to 3.1 mg/dl), without hematological signs of hemolytic-uremic syndrome (HUS); only LDH enzyme transient increase was detected. Renal biopsy showed TMA: temporary withdraw of tacrolimus and plasmapheresis was performed. The renal function recovered (serum creatinine 1.9 mg/dl). From screening for thrombophilia, we found a mutation of the Leiden factor V gene. Case 2: A man affected by ADPKD underwent kidney transplantation, with delay graft function; first biopsy showed acute tubular necrosis, but a second biopsy revealed TMA, while no altered hematological parameters of HUS was detected. We observed only a slight increase of lactate dehydrogenase (LDH) levels. The tacrolimus was halved and plasmapheresis was performed: LDH levels normalized within 10 days and renal function improved (serum creatinine from 9 to 2.9 mg/dl). We found a mutation of the prothrombin gene. Only a renal biopsy clarifies the diagnosis of TMA, but it is necessary to pay attention to light increasing level of LDH. Conclusion: Prothrombotic effect of CNIs and mTOR inhibitor, mutation of genes encoding factor H or I, anticardiolipin antibodies, vascular rejection, cytomegalovirus infection are proposed to trigger TMA; we detected mutations of factor II and Leiden factor V, as facilitating conditions for TMA in patients affected by ADPKD. PMID:26693501

  13. Plasmapheresis Is Associated With Better Renal Outcomes in Lupus Nephritis Patients With Thrombotic Microangiopathy: A Case Series Study.

    PubMed

    Li, Qiu-Yu; Yu, Feng; Zhou, Fu-De; Zhao, Ming-Hui

    2016-05-01

    The aim of this study was to evaluate the efficacy of plasmapheresis in patients with lupus nephritis-combined thrombotic microangiopathy (TMA) in a Chinese cohort.Clinical and therapeutic data of patients with lupus nephritis-combined TMA were collected retrospectively. A comparison between those with and without plasmapheresis was performed.Seventy patients with renal biopsy-proven TMA in lupus nephritis were treated with conventional combined corticosteroid and immunosuppressive agents as induction therapy, 9 of the 70 patients received additional plasmapheresis. The plasmapheresis group presented with more severe SLE and renal activity indices, including a significant higher ratio of neurologic disorder (P = 0.025), lower level of platelet count (P = 0.009), higher value of serum creatinine (P = 0.038), higher percentage of anti-cardiolipin antibodies positive (P = 0.001), and higher Systemic Lupus Erythematosus Disease Activity Index scores (P = 0.012), than that of the nonplasmapheresis group. However, the plasmapheresis group had a significant higher rate of remission and a lower ratio of treatment failure than that of the nonplasmapheresis group (P = 0.03). As the baseline data were significantly different between the 2 groups, the propensity score match was further designed to avoid retrospective bias. After re-analysis, the plasmapheresis group still had a significant higher rate of remission and a lower ratio of treatment failure than that of the nonplasmapheresis group (P = 0.018). More importantly, the plasmapheresis group had significant less composite endpoints than that of the nonplasmapheresis group (P = 0.005).Our study suggested that additional plasmapheresis on conventional induction therapy may benefit patients with lupus nephritis-combined TMA, which warrants further explorations.

  14. Haemostaseome-associated SNPs: has the thrombotic phenotype a greater influence than ethnicity? GMT study from Aquitaine including Basque individuals.

    PubMed

    Freyburger, Geneviève; Labrouche, Sylvie; Hubert, Christophe; Bauduer, Frédéric

    2015-01-01

    The Genetic Markers for Thrombosis (GMT) study compared the relative influence of ethnicity and thrombotic phenotype regarding the distribution of SNPs implicated in haemostasis pathophysiology ("haemostaseome"). We assessed 384 SNPs in three groups, each of 480 subjects: 1) general population of Aquitaine region (Southwestern France) used as control; 2) patients with venous thromboembolism from the same area; and 3) autochthonous Basques, a genetic isolate, who demonstrate unusual characteristics regarding the coagulation system. This study sought to evaluate i) the value of looking for a large number of genes in order to identify new genetic markers of thrombosis, ii) the value of investigating low risk factors and potential preferential associations, iii) the impact of ethnicity on the characterisation of markers for thrombosis. We did not detect any previously unrecognised SNP significantly associated with thrombosis risk or any preferential associations of low-risk factors in patients with thrombosis. The sum of ϰ² values for our 110 significant SNPs demonstrated a smaller genetic distance between patients and controls (321 cumulated ϰ² value) than between Basques and controls (1,570 cumulated ϰ² value). Hence, our study confirms the genetic particularity of Basques especially regarding a significantly lower expression of the non-O blood group (p< 0.0004). This is mitigated by a higher prevalence of factor II Leiden (p< 0.02) while factor V Leiden prevalence does not differ. Numerous other differences covering a wide range of proteins of the haemostaseome may result in an overall different genetic risk for venous thromboembolism.

  15. Effect of immunoglobulin G (IgG) interchain disulfide bond cleavage on efficacy of intravenous immunoglobulin for immune thrombocytopenic purpura (ITP).

    PubMed

    Machino, Y; Ohta, H; Suzuki, E; Higurashi, S; Tezuka, T; Nagashima, H; Kohroki, J; Masuho, Y

    2010-12-01

    Intravenous immunoglobulin (IVIG) has been used widely to treat immune thrombocytopenic purpura (ITP), but the mechanisms of its action remain unclear. We investigated the affinity for Fcγ receptors (FcγRs) and the thrombocytopenia-ameliorating effect of S-sulfonated gammaglobulin (SGG) and S-alkylated gammaglobulin (AGG), in comparison with unmodified gammaglobulin (GG), in a mouse ITP model. Cleavage of immunoglobulin (Ig)G interchain disulfide bonds by either S-sulfonation or S-alkylation did not decrease the affinity for FcγRIIA (CD32A) and FcγRIIB (CD32B), but did decrease the affinity for FcγRIA (CD64A) and FcγRIIIA (CD16A), presumably because of changes in H-chain configuration. The interchain disulfide bond cleavage decreased the affinity much more for mouse FcγRIV than for mouse FcγRIIB. The ability of AGG to ameliorate ITP was greatly diminished, while SGG, whose disulfide bonds are reconstituted in vivo, was as effective as GG. These results suggest that the interchain disulfide bonds are important for therapeutic effect. It is also suggested that the interaction of IVIG with the inhibitory receptor FcγRIIB is insufficient for effective amelioration of ITP and that, at least in this model, direct binding of IVIG to FcγRIIIA is also required.

  16. 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.

  17. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group.

    PubMed

    Rodeghiero, Francesco; Stasi, Roberto; Gernsheimer, Terry; Michel, Marc; Provan, Drew; Arnold, Donald M; Bussel, James B; Cines, Douglas B; Chong, Beng H; Cooper, Nichola; Godeau, Bertrand; Lechner, Klaus; Mazzucconi, Maria Gabriella; McMillan, Robert; Sanz, Miguel A; Imbach, Paul; Blanchette, Victor; Kühne, Thomas; Ruggeri, Marco; George, James N

    2009-03-12

    Diagnosis and management of immune thrombocytopenic purpura (ITP) remain largely dependent on clinical expertise and observations more than on evidence derived from clinical trials of high scientific quality. One major obstacle to the implementation of such studies and in producing reliable meta-analyses of existing data is a lack of consensus on standardized critical definitions, outcome criteria, and terminology. Moreover, the demand for comparative clinical trials has dramatically increased since the introduction of new classes of therapeutic agents, such as thrombopoietin receptor agonists, and innovative treatment modalities, such as anti-CD 20 antibodies. To overcome the present heterogeneity, an International Working Group of recognized expert clinicians convened a 2-day structured meeting (the Vicenza Consensus Conference) to define standard terminology and definitions for primary ITP and its different phases and criteria for the grading of severity, and clinically meaningful outcomes and response. These consensus criteria and definitions could be used by investigational clinical trials or cohort studies. Adoption of these recommendations would serve to improve communication among investigators, to enhance comparability among clinical trials, to facilitate meta-analyses and development of therapeutic guidelines, and to provide a standardized framework for regulatory agencies.

  18. Molecular mimicry by Helicobacter pylori CagA protein may be involved in the pathogenesis of H. pylori-associated chronic idiopathic thrombocytopenic purpura.

    PubMed

    Takahashi, Toru; Yujiri, Toshiaki; Shinohara, Kenji; Inoue, Yusuke; Sato, Yutaka; Fujii, Yasuhiko; Okubo, Masashi; Zaitsu, Yuzuru; Ariyoshi, Koichi; Nakamura, Yukinori; Nawata, Ryouhei; Oka, Yoshitomo; Shirai, Mutsunori; Tanizawa, Yukio

    2004-01-01

    The eradication of Helicobacter pylori often leads to platelet recovery in patients with chronic idiopathic thrombocytopenic purpura (cITP). Although this clinical observation suggests the involvement of H. pylori, little is known about the pathogenesis of cITP. We initially examined the effect of H. pylori eradication on platelet counts in 20 adult Japanese cITP patients. Then, using platelet eluates as the probe in immunoblot analyses, we examined the role of molecular mimicry in the pathogenesis of cITP. Helicobacter pylori infection was detected in 75% (15 of 20) of cITP patients. Eradication was achieved in 13 (87%) of the H. pylori-positive patients, seven (54%) of which showed increased platelet counts within the 4 months following treatment. Completely responsive patients also showed significant declines in platelet-associated immunoglobulin G (PAIgG) levels. Platelet eluates from 12 (nine H. pylori-positive and three H. pylori-negative) patients recognized H. pylori cytotoxin-associated gene A (CagA) protein, and in three completely responsive patients, levels of anti-CagA antibody in platelet eluates declined after eradication therapy. Cross-reactivity between PAIgG and H. pylori CagA protein suggests that molecular mimicry by CagA plays a key role in the pathogenesis of a subset of cITP patients.

  19. 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.

  20. 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.

  1. [Interaction of anti-thrombotic and anti-inflammatory activities of commonly used traditional Chinese medicine for promoting blood circulation and removing blood stasis revealed by network pharmacology analysis].

    PubMed

    Lü, Ming; Wang, Tai-yi; Tian, Xiao-xuan; Shi, Xin-hui; Fan, Guan-wei; Zhang, Yan; Zhu, Yan

    2015-09-01

    Chinese traditional patent medicine for promoting blood circulation and removing blood stasis(PBCRBS) originated from traditional Chinese medicine theory and had approved efficacy and safety standards. However, its compatibility regularity and anti-thrombotic mechanism is not clear. To analyze the compatibility regularity and anti-thrombotic mechanism of Chinese traditional patent medicine for PBCRBS, a statistical and bioinformatics analysis was carried out using traditional Chinese medicine inheritance support system (TICMISS, V2.0) and ingenuity pathway analysis (IPA). The compatibility regularity analysis shows that the most commonly used herb combinations are Danshen (Salvia miltiorrhiza Bge.), Chuanxiong (Ligusticum chuanxiong Hort.) and Honghua (Carthamustinctorius L.). The anti-thrombotic mechanism analysis reveals that 25 ingredients have an effect on 29 thrombosis related molecules which 23 molecules are related to inflammation response. Furthermore, there are 5 inflammation molecules (NOS2, PTGS2, IL6, TNF, IL1β) served as major targets. At the same time, Danshen, Chuangxiong and Honghua mainly used as sovereign herb or minister herb in the application of cardiovascular and cerebrovascular diseases. Therefore, Chinese traditional patent medicine for PBCRBS probably has an effect on anti-thrombotic activity through inhibiting the inflammatory response. In summary, the most commonly used herb combinations of Chinese traditional patent medicine for PBCRBS are Danshen, Chuanxiong and Honghua. Inhibiting inflammatory response, especially inflammation related molecules (NOS2, PTGS2, IL6, TNF and IL1β), is probably a new starting point to clarify the anti-thrombotic mechanism of Chinese patent medicine for PBCRBS.

  2. A Prospective Open-label Pilot Study of Fluvastatin on Pro-inflammatory and Pro-thrombotic Biomarkers in Antiphospholipid Antibody Positive Patients

    PubMed Central

    Erkan, Doruk; Willis, Rohan; Murthy, Vijaya L.; Basra, Gurjot; Vega, JoAnn; Ruiz Limón, Patricia; Carrera, Ana Laura; Papalardo, Elizabeth; Martínez-Martínez, Laura Aline; González, Emilio B.; Pierangeli, Silvia S.

    2014-01-01

    Objective: To determine if pro-inflammatory and pro-thrombotic biomarkers are differentially upregulated in persistently antiphospholipid antibody (aPL)-positive patients, and to examine the effects of fluvastatin on these biomarkers. Methods: Four groups of patients (age 18-65) were recruited: a) Primary Antiphospholipid Syndrome (PAPS); b) Systemic Lupus Erythematosus (SLE) with APS (SLE/APS); c) Persistent aPL positivity without SLE or APS (Primary aPL); and d) Persistent aPL positivity with SLE but no APS (SLE/aPL). The frequency-matched control group, used for baseline data comparison, was identified from a databank of healthy persons. Patients received fluvastatin 40 mg daily for three months. At three months, patients stopped the study medication and they were followed for another three months. Blood samples for 12 pro-inflammatory and pro-thrombotic biomarkers were collected monthly for six months. Results: Based on the comparison of the baseline samples of 41 aPL-positive patients with 30 healthy controls, 9/12 (75%) biomarkers (interleukin [IL]-6, IL1β, vascular endothelial growth factor [VEGF], tumor necrosis factor [TNF]-□α, interferon [IFN]-α, inducible protein-10 [IP10], soluble CD40 ligand [sCD40L], soluble tissue factor [sTF], and intracellular cellular adhesion molecule [ICAM]-1) were significantly elevated. Twenty-four patients completed the study; fluvastatin significantly and reversibly reduced the levels of 6/12 (50%) biomarkers (IL1β, VEGF, TNFα, IP10, sCD40L, and sTF). Conclusion: Our prospective mechanistic study demonstrates that pro-inflammatory and pro-thrombotic biomarkers, which are differentially upregulated in persistently aPL-positive patients, can be reversibly reduced by fluvastatin. Thus, statin-induced modulation of the aPL effects on target cells can be a valuable future approach in the management of aPL-positive patients. PMID:23933625

  3. [Hospital-acquired urinary tract infections].

    PubMed

    Adukauskiene, Dalia; Cicinskaite, Ilona; Vitkauskiene, Astra; Macas, Andrius; Tamosiūnas, Ramūnas; Kinderyte, Aida

    2006-01-01

    Urinary tract infections are responsible for 40-60% of all hospital-acquired infections. Increased age of patients and comorbid diseases render hospitalized patients more susceptible to infection. Almost 80% of hospital-acquired urinary tract infections are associated with urinary catheters, and only 5-10% of urinary infections are caused by invasive manipulations in the urogenital tract. Pathogens of hospital-acquired urinary tract infections are frequently multi-resistant, and antibiotic therapy can only be successful when the complicating factors are eliminated or urodynamic function is restored. For treatment of complicated hospital-acquired urinary tract infections, the antibiotics must exhibit adequate pharmacodynamic and pharmacokinetic properties: high renal clearance of unmetabolized form with good antimicrobial activity in both acidic and alkaline urine. For selection of empirical treatment of hospital-acquired urinary tract infections, it is necessary to evaluate localization of infection, its severity, possible isolates, and the most frequent pathogens in the department where patient is treated. The best choice for the starting the antimicrobial therapy is the cheapest narrow-spectrum effective antibiotic in the treatment of urinary tract infection until microbiological evaluation of pathogens will be received. Adequate management of urinary tract infections lowers the rate of complications, requirements for antibacterial treatment, selection of multi-resistant isolates and is cost effective.

  4. Variable eculizumab clearance requires pharmacodynamic monitoring to optimize therapy for thrombotic microangiopathy after hematopoietic stem cell transplantation

    PubMed Central

    Jodele, Sonata; Fukuda, Tsuyoshi; Mizuno, Kana; Vinks, Alexander A.; Laskin, Benjamin L.; Goebel, Jens; Dixon, Bradley P.; Chima, Ranjit S; Hirsch, Russel; Teusink, Ashley; Lazear, Danielle; Lane, Adam; Myers, Kasiani C.; Dandoy, Christopher E.; Davies, Stella M.

    2015-01-01

    Thrombotic microangiopathy (TMA) after hematopoietic stem cell transplant (HSCT) associated with terminal complement activation, as measured by elevated plasma terminal complement (sC5b-9) concentrations, has a very high mortality. The complement inhibitor eculizumab may be a therapeutic option for HSCT-associated TMA. We examined the pharmacokinetics and pharmacodynamics (PK/PD) of eculizumab in children and young adult HSCT recipients with TMA and activated complement to determine drug dosing requirements for future efficacy trials. We analyzed prospectively collected laboratory samples and clinical data from 18 HSCT recipients with high-risk TMA presenting with complement activation who were treated with eculizumab. We measured eculizumab serum concentrations, total hemolytic complement activity (CH50), and plasma sC5b-9 concentrations. Population PK/PD analyses correlated eculizumab concentrations with complement blockade and clinical response and determined inter-individual differences in PK parameters. We also compared transplant survival in patients treated with eculizumab (n=18) to patients with the same high-risk TMA features who did not receive any targeted therapy during a separate prospective observational study (n=11). In the PK analysis, we found significant inter-patient variability in eculizumab clearance, ranging from 16 to 237 mL/hr/70kg in the induction phase. The degree of complement activation measured by sC5b-9 concentrations at the start of therapy, in addition to actual body weight, were significant determinants of eculizumab clearance and disease response. Sixty one percent of treated patients had complete resolution of TMA and were able to safely discontinue eculizumab without disease recurrence. Overall survival was significantly higher in treated subjects compared to untreated patients (56% versus 9%, p=0.003). Complement blocking therapy is associated with improved survival in HSCT patients with high-risk TMA who historically have

  5. 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...

  6. 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

  7. Cost of hospital-acquired infection.

    PubMed

    Hassan, Mahmud; Tuckman, Howard P; Patrick, Robert H; Kountz, David S; Kohn, Jennifer L

    2010-01-01

    The authors assessed the costs of hospital-acquired infections using rigorous econometric methods on publicly available data, controlling for the interdependency of length of stay and the incidence of hospital acquired infection, and estimated the cost shares of different payers. They developed a system of equations involving length of stay, incidence of infection, and the total hospital care cost to be estimated using simultaneous equations system. The main data came from the State of New Jersey UB 92 for 2004, complimented with data from the Annual Survey of Hospitals by the American Hospital Association and the Medicare Cost Report of 2004. The authors estimated that an incidence of hospital acquired infection increases the hospital care cost of a patient by $10,375 and it increases the length of stay by 3.30 days, and that a disproportionately higher portion of the cost is attributable to Medicare. They conclude that reliable cost estimates of hospital-acquired infections can be made using publicly available data. Their estimate shows a much larger aggregate cost of $16.6 billion as opposed to $5 billion reported by the Centers for Disease Control and Prevention but much less than $29 billion as reported elsewhere in the literature.

  8. 7 CFR 989.17 - Acquire.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 8 2012-01-01 2012-01-01 false Acquire. 989.17 Section 989.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN...

  9. How Did Light Acquire a Velocity?

    ERIC Educational Resources Information Center

    Lauginie, Pierre

    2013-01-01

    We discuss how light acquired a velocity through history, from the ancient Greeks to the early modern era. Combining abstract debates, models of light, practical needs, planned research and chance, this history illustrates several key points that should be brought out in science education.

  10. Sexually acquired Salmonella Typhi urinary tract infection.

    PubMed

    Wielding, Sally; Scott, Gordon

    2016-05-01

    We report a case of isolated urinary Salmonella enterica serotype Typhi in an HIV-positive man who has sex with men. He was clinically well and blood and stool cultures were negative, indicating that this may have been a sexually acquired urinary tract infection.

  11. Acquired nasal deformities in fighter pilots.

    PubMed

    Schreinemakers, Joyce R C; van Amerongen, Pieter; Kon, Moshe

    2010-07-01

    Fighter pilots may develop slowly progressive deformities of their noses during their flying careers. The spectrum of deformities that may be acquired ranges from soft tissue to osseous changes. The main cause is the varying pressure exerted by the oxygen mask on the skin and bony pyramid of the nose during flying.

  12. 7 CFR 989.17 - Acquire.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 8 2013-01-01 2013-01-01 false Acquire. 989.17 Section 989.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN...

  13. 7 CFR 989.17 - Acquire.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Acquire. 989.17 Section 989.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN...

  14. 7 CFR 989.17 - Acquire.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 8 2014-01-01 2014-01-01 false Acquire. 989.17 Section 989.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; FRUITS, VEGETABLES, NUTS), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN...

  15. 7 CFR 989.17 - Acquire.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 8 2011-01-01 2011-01-01 false Acquire. 989.17 Section 989.17 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and Orders; Fruits, Vegetables, Nuts), DEPARTMENT OF AGRICULTURE RAISINS PRODUCED FROM GRAPES GROWN...

  16. Eye Movement Correlates of Acquired Central Dyslexia

    ERIC Educational Resources Information Center

    Schattka, Kerstin I.; Radach, Ralph; Huber, Walter

    2010-01-01

    Based on recent progress in theory and measurement techniques, the analysis of eye movements has become one of the major methodological tools in experimental reading research. Our work uses this approach to advance the understanding of impaired information processing in acquired central dyslexia of stroke patients with aphasia. Up to now there has…

  17. Group Treatment in Acquired Brain Injury Rehabilitation

    ERIC Educational Resources Information Center

    Bertisch, Hilary; Rath, Joseph F.; Langenbahn, Donna M.; Sherr, Rose Lynn; Diller, Leonard

    2011-01-01

    The current article describes critical issues in adapting traditional group-treatment methods for working with individuals with reduced cognitive capacity secondary to acquired brain injury. Using the classification system based on functional ability developed at the NYU Rusk Institute of Rehabilitation Medicine (RIRM), we delineate the cognitive…

  18. Acquiring a Second Language for School.

    ERIC Educational Resources Information Center

    Collier, Virginia P.

    1995-01-01

    This report offers a conceptual model for use with language minority children who are entering a new school when they must acquire the language of the majority student population. The model has four development components or processes: sociocultural, linguistic, academic, and cognitive. These four components are described in detail. Research is…

  19. Acquired immunodeficiency syndrome with subacute sclerosing panencephalitis.

    PubMed

    Gowda, Vykuntaraju K N; Sukanya, V; Shivananda

    2012-11-01

    A 7-year-old boy with acquired immunodeficiency syndrome, receiving antiretroviral drugs for 2 years, presented with a recent onset of myoclonic jerks and cognitive deterioration. On examination, he manifested myoclonic jerks once every 10-15 seconds. His electroencephalogram indicated periodic complexes, and his cerebrospinal fluid tested positive for measles antibodies.

  20. 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 Central

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

    2011-01-01

    On 11th 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 50×109/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

  1. Inherited, congenital and acquired disorders by hemostasis (vascular, platelet & plasmatic phases) with repercussions in the therapeutic oral sphere

    PubMed Central

    Arrieta-Blanco, Juan J.; Martínez-López, Federico; Oñate-Cabrerizo, Daniel; Cabrerizo-Merino, Maria C.

    2014-01-01

    The hemostasis alterations, either congenital or hereditary origin, and acquired, are circumstances that hinder oral care to patients who suffer them and also generates in the professional who has to attend, high stress. Bleeding control once established and dental treatment planning, both in the aspect of preparation, as the realization of the odonto-stomatological therapeutic, has suffered updates that do need to remember certain aspects of the care of these patients. But we must not forget that the hematologist or internist who controls the patient’s medical condition, is a cornerstone for the planning and implementation of treatment plans. We must also remember that, in certain circumstances, treatment should be performed in a hospital setting. In this review, we aim to provide the odonto-stomatologist guidance on how to address the problem and provide simple and updated guidelines to apply in the treatment of these people. Key words:Hemostasis disorder, oral care protocols, haemorrhagic and thrombotic disorders, haemophilia, von willebrand disease, desmopressin, purple, thrombocytopenia, thrombocytopathies. PMID:24121923

  2. [Acquired paraneoplastic hypertrichosis lanuginosa associated with scleroderma].

    PubMed

    Valda Rodriguez, L; Torrico Velasco, J; Zeballos Vasconcellos, R

    1990-01-01

    Acquired hypertrichosis lanuginosa is universally recognized as an individual disease and seldom reported as a genuine paraneoplastic manifestation. We report the case of a 30-year old woman with acquired hypertrichosis lanuginosa. Due to the finding of a cervical lymph node metastasis, she was investigated for an internal neoplasm, but the original tumour could not be found by the usual methods. A bronchogenic carcinoma was discovered at autopsy. Beside hypertrichosis, this patient had other disorders not described in the literature as associated with that disease, viz.: progressive systemic scleroderma, fissured and hyperpigmented tongue, thrombocytopenia, galactorrhoea, axillary and pubic alopecia and overcurvature of toe nails. A review of similar cases in the literature provided clinical arguments in favour of the hormonal origin of this paraneoplastic hypertrichosis.

  3. Acquired portosystemic collaterals: anatomy and imaging.

    PubMed

    Leite, Andréa Farias de Melo; Mota, Américo; Chagas-Neto, Francisco Abaeté; Teixeira, Sara Reis; Elias Junior, Jorge; Muglia, Valdair Francisco

    2016-01-01

    Portosystemic shunts are enlarged vessels that form collateral pathological pathways between the splanchnic circulation and the systemic circulation. Although their causes are multifactorial, portosystemic shunts all have one mechanism in common-increased portal venous pressure, which diverts the blood flow from the gastrointestinal tract to the systemic circulation. Congenital and acquired collateral pathways have both been described in the literature. The aim of this pictorial essay was to discuss the distinct anatomic and imaging features of portosystemic shunts, as well as to provide a robust method of differentiating between acquired portosystemic shunts and similar pathologies, through the use of illustrations and schematic drawings. Imaging of portosystemic shunts provides subclinical markers of increased portal venous pressure. Therefore, radiologists play a crucial role in the identification of portosystemic shunts. Early detection of portosystemic shunts can allow ample time to perform endovascular shunt operations, which can relieve portal hypertension and prevent acute or chronic complications in at-risk patient populations.

  4. Clinical laboratory data: acquire, analyze, communicate, liberate.

    PubMed

    Azzazy, Hassan M E; Elbehery, Ali H A

    2015-01-01

    The availability of portable healthcare devices, which can acquire and transmit medical data to remote experts would dramatically affect healthcare in areas with poor infrastructure. Smartphones, which feature touchscreen computer capabilities and sophisticated cameras, have become widely available with over billion units shipped in 2013. In the clinical laboratory, smartphones have recently brought the capabilities of key instruments such as spectrophotometers, fluorescence analyzers and microscopes into the palm of the hand. Several research groups have developed sensitive and low-cost smartphone-based diagnostic assay prototypes for testing cholesterol, albumin, vitamin D, tumor markers, and the detection of infectious agents. This review covers the use of smartphones to acquire, analyze, communicate, and liberate clinical laboratory data. Smartphones promise to dramatically improve the quality and quantity of healthcare offered in resource-limited areas.

  5. Subcortical infarction resulting in acquired stuttering.

    PubMed

    Ciabarra, A M; Elkind, M S; Roberts, J K; Marshall, R S

    2000-10-01

    Stuttering is an uncommon presentation of acute stroke. Reported cases have often been associated with left sided cortical lesions, aphasia, and difficulties with other non-linguistic tests of rhythmic motor control. Three patients with subcortical lesions resulting in stuttering are discussed. In one patient the ability to perform time estimations with a computerised repetitive time estimation task was characterised. One patient had a pontine infarct with clinical evidence of cerebellar dysfunction. A second patient had a left basal ganglionic infarct and a disruption of timing estimation. A third patient had a left subcortical infarct and a mild aphasia. These findings expand the reported distribution of infarction that can result in acquired stuttering. Subcortical mechanisms of speech control and timing may contribute to the pathophysiology of acquired stuttering.

  6. Recognising and managing community-acquired pneumonia.

    PubMed

    Gibson, Vanessa

    2015-11-18

    Pneumonia remains a significant cause of morbidity and mortality in the UK and yet the seriousness of the disease is underestimated. Pneumonia can be life-threatening because the delicate tissues of the alveoli and pulmonary capillaries are susceptible to damage from the inflammatory response. This damage leads to consolidation that prevents the diffusion of oxygen and carbon dioxide, and this in turn can lead to respiratory failure. This article summarises guidance on the diagnosis and management of community-acquired pneumonia, and also includes information on the prevention of pneumonia. This information should be valuable to nurses working in a variety of clinical areas since patients with community-acquired pneumonia are encountered in primary, intermediate, secondary and critical care.

  7. Acquired versus familial demyelinative neuropathies in children.

    PubMed

    Miller, R G; Gutmann, L; Lewis, R A; Sumner, A J

    1985-01-01

    The electrophysiologic differences between chronic acquired demyelinative neuropathy and the demyelinative form of Charcot-Marie-Tooth disease have recently been reported. The present report extends these observations to include the genetically determined demyelinating neuropathies seen in metachromatic leukodystrophy, Krabbe's leukodystrophy, and Cockayne's syndrome. The electrophysiologic features of metachromatic leukodystrophy (five patients), Krabbe's (four patients), and Cockayne's syndrome (three patients) were all similar. There was uniform slowing of conduction (both in different nerves and in different nerve segments), and conduction block was not seen. These findings are consistent with a uniform degree of demyelination in multiple nerves and throughout the entire length of individual axons. Thus, uniform slowing of nerve conduction constitutes strong evidence for a familial demyelinative neuropathy, as opposed to the multifocal slowing seen in acute and chronic acquired demyelinative neuropathy.

  8. Acquired portosystemic collaterals: anatomy and imaging*

    PubMed Central

    Leite, Andréa Farias de Melo; Mota Jr., Américo; Chagas-Neto, Francisco Abaeté; Teixeira, Sara Reis; Elias Junior, Jorge; Muglia, Valdair Francisco

    2016-01-01

    Portosystemic shunts are enlarged vessels that form collateral pathological pathways between the splanchnic circulation and the systemic circulation. Although their causes are multifactorial, portosystemic shunts all have one mechanism in common-increased portal venous pressure, which diverts the blood flow from the gastrointestinal tract to the systemic circulation. Congenital and acquired collateral pathways have both been described in the literature. The aim of this pictorial essay was to discuss the distinct anatomic and imaging features of portosystemic shunts, as well as to provide a robust method of differentiating between acquired portosystemic shunts and similar pathologies, through the use of illustrations and schematic drawings. Imaging of portosystemic shunts provides subclinical markers of increased portal venous pressure. Therefore, radiologists play a crucial role in the identification of portosystemic shunts. Early detection of portosystemic shunts can allow ample time to perform endovascular shunt operations, which can relieve portal hypertension and prevent acute or chronic complications in at-risk patient populations. PMID:27777479

  9. Brucella abortus Infection Acquired in Microbiology Laboratories

    PubMed Central

    Fiori, Pier Luigi; Mastrandrea, Scilla; Rappelli, Paola; Cappuccinelli, Piero

    2000-01-01

    We report an outbreak of laboratory-acquired Brucella abortus infection originating in the accidental breakage of a centrifuge tube. A total of 12 laboratory workers were infected (attack rate of 31%), with an incubation time ranging from 6 weeks to 5 months. Antibody titers were evaluated weekly in all personnel exposed, allowing the diagnosis of the infection in most cases before the onset of clinical symptoms, so that specific therapy could be administrated. PMID:10790142

  10. Acquiring Secure Systems Through Information Economics

    DTIC Science & Technology

    2015-05-01

    Introduction “For all future weapons systems that DoD will acquire or procure, DoD will mandate specific cybersecurity standards for weapons...systems to meet. Acquisition and procurement policy and practice will be updated to promote effective cybersecurity throughout a system’s life cycle...physical damage or injury Motivating Contractor Efforts - Contractors have different priorities than the DOD when it comes to cybersecurity - Classic

  11. Earth Knowledge Acquired by Middle School Students

    NASA Technical Reports Server (NTRS)

    Ride, Sally

    2008-01-01

    Earth Knowledge Acquired by Middle School Students (EarthKAM), an education activity, allows middle school students to program a digital camera on board the International Space Station to photograph a variety of geographical targets for study in the classroom. Photos are made available on the web for viewing and study by participating schools around the world. Educators use the images for projects involving Earth Science, geography, physics, and social science.

  12. Acquired Antibiotic Resistance Genes: An Overview

    PubMed Central

    van Hoek, Angela H. A. M.; Mevius, Dik; Guerra, Beatriz; Mullany, Peter; Roberts, Adam Paul; Aarts, Henk J. M.

    2011-01-01

    In this review an overview is given on antibiotic resistance (AR) mechanisms with special attentions to the AR genes described so far preceded by a short introduction on the discovery and mode of action of the different classes of antibiotics. As this review is only dealing with acquired resistance, attention is also paid to mobile genetic elements such as plasmids, transposons, and integrons, which are associated with AR genes, and involved in the dispersal of antimicrobial determinants between different bacteria. PMID:22046172

  13. Acquired ciliary circumscribed grey hair (ACCG).

    PubMed

    Romero, A G; Calatayud, J C

    2001-12-01

    Grey-haired areas usually occur due to aging or inheritance. A case is described of abrupt occurrence of a focal circumscribed grey-hair in the eyebrow region (a single hair) in a 27-year-old woman. The phenomenon was named acquired ciliary circumscribed grey-hair (ACCG). Qualitative and semiquantitative findings were obtained by microanalytical studies. In addition to morphological differences from control hair, the ACCG hair showed a high percentage of sulfur (99.8%) and absence of oligoelements.

  14. Rare presentation of spontaneous acquired diaphragmatic hernia.

    PubMed

    Gupta, Shweta; Bali, Roseleen Kaur; Das, Kamanasish; Sisodia, Anula; Dewan, R K; Singla, Rupak

    2011-01-01

    Spontaneous acquired diaphragmatic hernia without any apparent history of trauma is a very rare condition and is very difficult to diagnose. We present a case of a 21-year-old male who presented with abdominal pain for one month and four episodes of vomiting for one day. Clinical suspicion, chest radiography with nasogastric tube in situ and computed tomography (CT) confirmed the diagnosis. The diaphragmatic defect was repaired surgically. The patient had an uneventful post-operative recovery.

  15. The pathophysiology of acquired premature ejaculation.

    PubMed

    McMahon, Chris G; Jannini, Emmanuele A; Serefoglu, Ege C; Hellstrom, Wayne J G

    2016-08-01

    The second Ad Hoc International Society for Sexual Medicine (ISSM) Committee for the Definition of Premature Ejaculation defined acquired premature ejaculation (PE) as a male sexual dysfunction characterized by a the development of a clinically significant and bothersome reduction in ejaculation latency time in men with previous normal ejaculatory experiences, often to about 3 minutes or less, the inability to delay ejaculation on all or nearly all vaginal penetrations, and the presence of negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy. The literature contains a diverse range of biological and psychological etiological theories. Acquired PE is commonly due to sexual performance anxiety, psychological or relationship problems, erectile dysfunction (ED), and occasionally prostatitis and hyperthyroidism, consistent with the predominant organic etiology of acquired PE, men with this complaint are usually older, have a higher mean BMI and a greater incidence of comorbid disease including hypertension, sexual desire disorder, diabetes mellitus, chronic prostatitis, and ED compared to lifelong, variable and subjective PE.

  16. The pathophysiology of acquired premature ejaculation

    PubMed Central

    Jannini, Emmanuele A.; Serefoglu, Ege C.; Hellstrom, Wayne J. G.

    2016-01-01

    The second Ad Hoc International Society for Sexual Medicine (ISSM) Committee for the Definition of Premature Ejaculation defined acquired premature ejaculation (PE) as a male sexual dysfunction characterized by a the development of a clinically significant and bothersome reduction in ejaculation latency time in men with previous normal ejaculatory experiences, often to about 3 minutes or less, the inability to delay ejaculation on all or nearly all vaginal penetrations, and the presence of negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy. The literature contains a diverse range of biological and psychological etiological theories. Acquired PE is commonly due to sexual performance anxiety, psychological or relationship problems, erectile dysfunction (ED), and occasionally prostatitis and hyperthyroidism, consistent with the predominant organic etiology of acquired PE, men with this complaint are usually older, have a higher mean BMI and a greater incidence of comorbid disease including hypertension, sexual desire disorder, diabetes mellitus, chronic prostatitis, and ED compared to lifelong, variable and subjective PE. PMID:27652216

  17. 48 CFR 1845.502-70 - Contractor-acquired property.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Contractor-acquired... Possession of Contractors 1845.502-70 Contractor-acquired property. All contractor-acquired property must be... contractor-acquired. (2) Submission of DD Form 1419, DOD Industrial Plant Requisition, or equivalent...

  18. Length of stay, hospitalization cost, and in-hospital mortality in US adult inpatients with immune thrombocytopenic purpura, 2006–2012

    PubMed Central

    An, Ruopeng; Wang, Peizhong Peter

    2017-01-01

    Purpose In this study, we examined the length of stay, hospitalization cost, and risk of in-hospital mortality among US adult inpatients with immune thrombocytopenic purpura (ITP). Methods We analyzed nationally representative data obtained from Nationwide/National Inpatient Sample database of discharges from 2006 to 2012. Results In the US, there were an estimated 296,870 (95% confidence interval [CI]: 284,831–308,909) patient discharges recorded for ITP from 2006 to 2012, during which ITP-related hospitalizations had increased steadily by nearly 30%. The average length of stay for an ITP-related hospitalization was found to be 6.02 days (95% CI: 5.93–6.10), which is 28% higher than that of the overall US discharge population (4.70 days, 95% CI: 4.66–4.74). The average cost of ITP-related hospitalizations was found to be US$16,594 (95% CI: US$16,257–US$16,931), which is 48% higher than that of the overall US discharge population (US$11,200; 95% CI: US$11,033–US$11,368). Gender- and age-adjusted mortality risk in inpatients with ITP was 22% (95% CI: 19%–24%) higher than that of the overall US discharge population. Across diagnosis related groups, length of stay for ITP-related hospitalizations was longest for septicemia (7.97 days, 95% CI: 7.55–8.39) and splenectomy (7.40 days, 95% CI: 6.94–7.86). Splenectomy (US$25,262; 95% CI: US$24,044–US$26,481) and septicemia (US$18,430; 95% CI: US$17,353–US$19,507) were associated with the highest cost of hospitalization. The prevalence of mortality in ITP-related hospitalizations was highest for septicemia (11.11%, 95% CI: 9.60%–12.63%) and intracranial hemorrhage (9.71%, 95% CI: 7.65%–11.77%). Conclusion Inpatients with ITP had longer hospital stay, bore higher costs, and faced greater risk of mortality than the overall US discharge population. PMID:28176930

  19. The Case of a Zebra That Was Misdiagnosed as a Horse: Pulmonary Tumor Thrombotic Microangiopathy, a New Paraneoplastic Syndrome, Mimicking PD-1-Induced Pneumonitis

    PubMed Central

    Carter, Corey A.; Browning, Robert; Oronsky, Bryan T.; Scicinski, Jan J.; Brzezniak, Christina

    2016-01-01

    A case report of a 47-year-old woman with triple-negative breast cancer on a clinical trial called PRIMETIME (NCT02518958) who received the anti-PD-1 inhibitor nivolumab and the experimental anticancer agent RRx-001 is presented. Although initially diagnosed and treated for anti-PD-1-induced pneumonitis, clinical and radiological abnormalities triggered further investigation, leading to the diagnosis of pulmonary tumor thrombotic microangiopathy (PTTM). This example highlights the importance of exercising due diligence in determining immune-related adverse events and suggests that PD-1-induced pneumonitis should be a diagnosis of exclusion rather than a diagnosis by default. A case history and review of the literature are presented for PTTM, which we propose to define as a paraneoplastic syndrome. PMID:26933422

  20. AngioJet rheolytic thrombectomy for thrombotic myocardial injury in a 15-year-old cystic fibrosis patient during lung transplantation.

    PubMed

    Hayes, Don; Schell, Randall M; Plunkett, Mark D; Gurley, John C; Hoopes, Charles W

    2012-08-01

    We report on an acute myocardial injury caused by thrombotic emboli during off-pump bilateral sequential lung transplantation in a 15-year-old female patient with end-stage cystic fibrosis. A few minutes after reperfusion of the right (second sequential) allograft, the patient developed hemodynamic collapse, including hypotension, acute akinesis of the anterior and lateral myocardial walls, and severe mitral regurgitation. Thrombus was noted within the left atrium and ventricle on intraoperative transesophageal echocardiogram. After emergent cannulation for cardiopulmonary bypass, the patient underwent left cardiac catheterization with AngioJet rheolytic thrombectomy and removal of the clot from the distal left anterior descending coronary artery. Reperfusion was established without the need for stent placement or further intervention. The patient required short-term life support with venoarterial extracorporeal membrane oxygenation.

  1. The Case of a Zebra That Was Misdiagnosed as a Horse: Pulmonary Tumor Thrombotic Microangiopathy, a New Paraneoplastic Syndrome, Mimicking PD-1-Induced Pneumonitis.

    PubMed

    Carter, Corey A; Browning, Robert; Oronsky, Bryan T; Scicinski, Jan J; Brzezniak, Christina

    2016-01-01

    A case report of a 47-year-old woman with triple-negative breast cancer on a clinical trial called PRIMETIME (NCT02518958) who received the anti-PD-1 inhibitor nivolumab and the experimental anticancer agent RRx-001 is presented. Although initially diagnosed and treated for anti-PD-1-induced pneumonitis, clinical and radiological abnormalities triggered further investigation, leading to the diagnosis of pulmonary tumor thrombotic microangiopathy (PTTM). This example highlights the importance of exercising due diligence in determining immune-related adverse events and suggests that PD-1-induced pneumonitis should be a diagnosis of exclusion rather than a diagnosis by default. A case history and review of the literature are presented for PTTM, which we propose to define as a paraneoplastic syndrome.

  2. Computed tomographic observations pertinent to intracranial venous thrombotic and occulsive disease in childhood: state of the art, some new data, and hypotheses

    SciTech Connect

    Segall, H.D.; Ahmadi, J.; McComb, J.G.; Zee, C.S.; Becker, T.S.; Han, J.S.

    1982-05-01

    Selected topics are discussed and new observations recorded regarding computed tomographic (CT) evaluation of intracranial venous thrombotic and occlusive disease in childhood. High density of the vein of Galen and adjacent venous sinuses (relative to brain) can be seen normally in children. A number of potential pitfalls in the diagnosis of superior sagittal sinus thrombosis are also disclosed. A case of cavernous sinus thrombosis with abnormal CT changes is included. In addition, the normal CT appearance of the cavernous sinus is described. In some cases, filling defects occur which appear to correlate with normal cranial nerves. An unusual case of venous sinus occlusion by neoplasm (sarcoma) is presented. Finally, new findings in the Sturge-Weber syndrome are analyzed. Enhancement of the brain in this condition may have its basis in altered circulation resulting from fundamental venous abnormalities.

  3. Acquired prosopagnosia without word recognition deficits.

    PubMed

    Susilo, Tirta; Wright, Victoria; Tree, Jeremy J; Duchaine, Bradley

    2015-01-01

    It has long been suggested that face recognition relies on specialized mechanisms that are not involved in visual recognition of other object categories, including those that require expert, fine-grained discrimination at the exemplar level such as written words. But according to the recently proposed many-to-many theory of object recognition (MTMT), visual recognition of faces and words are carried out by common mechanisms [Behrmann, M., & Plaut, D. C. ( 2013 ). Distributed circuits, not circumscribed centers, mediate visual recognition. Trends in Cognitive Sciences, 17, 210-219]. MTMT acknowledges that face and word recognition are lateralized, but posits that the mechanisms that predominantly carry out face recognition still contribute to word recognition and vice versa. MTMT makes a key prediction, namely that acquired prosopagnosics should exhibit some measure of word recognition deficits. We tested this prediction by assessing written word recognition in five acquired prosopagnosic patients. Four patients had lesions limited to the right hemisphere while one had bilateral lesions with more pronounced lesions in the right hemisphere. The patients completed a total of seven word recognition tasks: two lexical decision tasks and five reading aloud tasks totalling more than 1200 trials. The performances of the four older patients (3 female, age range 50-64 years) were compared to those of 12 older controls (8 female, age range 56-66 years), while the performances of the younger prosopagnosic (male, 31 years) were compared to those of 14 younger controls (9 female, age range 20-33 years). We analysed all results at the single-patient level using Crawford's t-test. Across seven tasks, four prosopagnosics performed as quickly and accurately as controls. Our results demonstrate that acquired prosopagnosia can exist without word recognition deficits. These findings are inconsistent with a key prediction of MTMT. They instead support the hypothesis that face

  4. [Iris heterochromia in acquired Horner's syndrome].

    PubMed

    Beynat, J; Soichot, P; Bidot, S; Dugas, B; Creuzot-Garcher, C; Bron, A

    2007-09-01

    Horner's syndrome (HS) is related to an interruption of the oculosympathetic nerve pathway. The classic clinical findings associated with this condition are ptosis, miosis, and enophthalmos. Heterochromia is typically described in congenital HS, but it is an uncommon finding in acquired HS. We report a case of post-traumatic HS associated with heterochromia. A literature review indicates that this type of heterochromia may be related to a reduction in the number of iris melanocytes. This mechanism may be the same in the physiological iris color modifications in adulthood.

  5. [Acquired immunodeficiency syndrome in pediatric patients].

    PubMed

    Molina Moguel, J L; Ruiz Illezcas, R; Forsbach Sánchez, S; Carreño Alvarez, S; Picco Díaz, I

    1990-12-01

    The object of this study was to determine how many of the patients treated at the Pediatric Odontology Clinic, a branch of the Maxillo-Facial Surgery Service at the Veinte de Noviembre Regional Hospital, ISSSTE, are VIH-positive of show serious manifestations of Acquired Immuno-Deficiency Syndrome (AIDS). For such purpose, 100 pediatric patients suffering from different systemic or local diseases were evaluated, the most common being hematological alterations. Results evidenced the presence of VIH in the blood of five of the pediatric subjects, all suffering from Hemophilia.

  6. Origins of species: acquired genomes and individuality

    NASA Technical Reports Server (NTRS)

    Margulis, L.

    1993-01-01

    Entire genomes with their accompanying protein synthetic systems are transferred throughout the biosphere primarily as bacteria and protists which become symbionts as they irreversibly integrate into pre-existing organisms to form more complex individuals. Individualization is stabilized by simultaneous transmission of once-separate heterologous genetic systems. The origin of new species is hypothesized to correlate with the acquisition, integration and subsequent inheritance of such acquired microbial genomes. These processes were recognized by Mereschkovsky ("Symbiogenesis" in Russian, 1909) and by Wallin ("Symbionticism", see p. 181, this issue).

  7. Common acquired causes of thrombosis in children.

    PubMed

    Tolbert, Jaszianne; Carpenter, Shannon L

    2013-08-01

    Compared to adults, venous thromboembolism in the pediatric population is a rare event. Cancer, cardiac disease, antiphospholipid antibodies, and indwelling catheters are established risk factors for thromboembolism in children. We examined the literature related to thrombophilia in children, childhood cancer and thrombosis, cardiac disease and thrombosis, and antiphospholipid antibody syndrome in children. Citations in identified articles yielded additional articles for review. We found that studies of acquired thrombophilia in children are limited. Current treatment for thromboembolism in children is based on adult data therefore optimal treatment in this population remains unclear.

  8. Acquired Congenital Malalignment of the Great Toenails

    PubMed Central

    Decker, Ashley; Scher, Richard K.; Avarbock, Andrew

    2016-01-01

    Congenital malalignment is the lateral deviation of the nail plate along the longitudinal axis due to the lateral rotation of the nail matrix. The nail plate grows out in ridges caused by repeated microtrauma to the nail. Common complications include onychomycosis, Pseudomonas infection and acute or chronic paronychia. Treatment options range from conservative management to surgical options including realignment and nail matrixectomy. Congenital malalignment usually presents in infancy or childhood, but we present two cases of acquired malalignment occurring in the teenage years. PMID:27171597

  9. Oxidation of Met1606 in von Willebrand factor is a risk factor for thrombotic and septic complications in chronic renal failure.

    PubMed

    De Filippis, Vincenzo; Lancellotti, Stefano; Maset, Fabio; Spolaore, Barbara; Pozzi, Nicola; Gambaro, Giovanni; Oggianu, Laura; Calò, Lorenzo A; De Cristofaro, Raimondo

    2012-03-01

    CKD (chronic kidney disease) is a life-threatening pathology, often requiring HD (haemodialysis) and characterized by high OS (oxidative stress), inflammation and perturbation of vascular endothelium. HD patients have increased levels of vWF (von Willebrand factor), a large protein (~240 kDa) released as UL-vWF (ultra large-vWF polymers, molecular mass ~20000-50000 kDa) from vascular endothelial cells and megakaryocytes, and responsible for the initiation of primary haemostasis. The pro-haemostatic potential of vWF increases with its length, which is proteolytically regulated by ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin motifs 13), a zinc-protease cleaving vWF at the single Tyr1605-Met1606 bond, and by LSPs (leucocyte serine proteases), released by activated PMNs (polymorphonuclear cells) during bacterial infections. Previous studies have shown that in vitro oxidation of Met1606 hinders vWF cleavage by ADAMTS-13, resulting in the accumulation of UL-vWF that are not only more pro-thrombotic than shorter vWF oligomers, but also more efficient in binding to bacterial adhesins during sepsis. Notably, HD patients have increased risk of developing dramatic cardiovascular and septic complications, whose underlying mechanisms are largely unknown. In the present study, we first purified vWF from HD patients and then chemically characterized its oxidative state. Interestingly, HD-vWF contains high carbonyl levels and increased proportion of UL-vWF polymers that are also more resistant to ADAMTS-13. Using TMS (targeted MS) techniques, we estimated that HD-vWF contains >10% of Met1606 in the sulfoxide form. We conclude that oxidation of Met1606, impairing ADAMTS-13 cleavage, results in the accumulation of UL-vWF polymers, which recruit and activate platelets more efficiently and bind more tightly to bacterial adhesins, thus contributing to the development of thrombotic and septic complications in CKD.

  10. Influence of the JAK2 V617F Mutation and Inherited Thrombophilia on the Thrombotic Risk among Patients with Myeloproliferative Disorders

    PubMed Central

    TEVET, Mihaela; IONESCU, Razvan; DRAGAN, Cornel; LUPU, Anca Roxana

    2015-01-01

    Background: A number of studies showed that the JAK2 V617F mutation increases the thrombotic risk in patients with myeloproliferative disorders (MPN) while others did not reveal this correlation, and it is unknown whether inherited thrombophilia is an additive risk factor in mutated subjects. Our aim was to clarify the contribution of JAK2 V617F to a hypercoagulable state, as well as its interaction with other thrombophilic factors in patients with thrombosis and myeloproliferative disorders. Method: We studied 192 patients with myeloproliferative disorders, 90 with Essential thrombocytemia (ET), 42 with Polycythemia vera (PV) and 60 with Primary or idiopathic myelofibrosis (PMI). From these patients a subgroup of only 62 patients underwent laboratory screening for thrombophilia. Results: The JAK2 V617F mutation was present in 62.8% patients with myeloproliferative disorders, 97.6% with PV, 54.5 % with ET and 53.44% patients with PMI. The mutated patients had a relative risk (RR) for thrombosis at any time of 2.94 in comparison with "wild-type" patients which was 0.93; in those patients having both the mutation and thrombophilia the RR was 3.56 (95% CI 2.41-7.34) compared to patients with neither the mutation nor thrombophilia, suggesting an additive interaction between the two risk factors. Conclusion: In patients with myeloproliferatives neoplasias, the thrombotic risk is higher in the JAK2 V617F-mutated subgroup and it is further increased by the presence of inherited thrombophilia (especially by the presence of mutated F V Leiden and lupus anticoagulant). PMID:26225146

  11. Acquired and congenital coronary artery abnormalities.

    PubMed

    Young, Ming-Lon; McLeary, Michael; Chan, Kak-Chen

    2017-01-01

    Sudden unexpected cardiac deaths in approximately 20% of young athletes are due to acquired or congenital coronary artery abnormalities. Kawasaki disease is the leading cause for acquired coronary artery abnormalities, which can cause late coronary artery sequelae including aneurysms, stenosis, and thrombosis, leading to myocardial ischaemia and ventricular fibrillation. Patients with anomalous left coronary artery from the pulmonary artery can develop adequate collateral circulation from the right coronary artery in the newborn period, which remains asymptomatic only to manifest in adulthood with myocardial ischaemia, ventricular arrhythmias, and sudden death. Anomalous origin of coronary artery from the opposite sinus occurs in 0.7% of the young general population aged between 11 and 15 years. If the anomalous coronary artery courses between the pulmonary artery and the aorta, sudden cardiac death may occur during or shortly after vigorous exercise, especially in patients where the anomalous left coronary artery originates from the right sinus of Valsalva. Symptomatic patients with evidence of ischaemia should have surgical correction. No treatment is needed for asymptomatic patients with an anomalous right coronary artery from the left sinus of Valsalva. At present, there is no consensus regarding how to manage asymptomatic patients with anomalous left coronary artery from the right sinus of Valsalva and interarterial course. Myocardial bridging is commonly observed in cardiac catheterisation and it rarely causes exercise-induced coronary syndrome or cardiac death. In symptomatic patients, refractory or β-blocker treatment and surgical un-bridging may be considered.

  12. Software for Acquiring Image Data for PIV

    NASA Technical Reports Server (NTRS)

    Wernet, Mark P.; Cheung, H. M.; Kressler, Brian

    2003-01-01

    PIV Acquisition (PIVACQ) is a computer program for acquisition of data for particle-image velocimetry (PIV). In the PIV system for which PIVACQ was developed, small particles entrained in a flow are illuminated with a sheet of light from a pulsed laser. The illuminated region is monitored by a charge-coupled-device camera that operates in conjunction with a data-acquisition system that includes a frame grabber and a counter-timer board, both installed in a single computer. The camera operates in "frame-straddle" mode where a pair of images can be obtained closely spaced in time (on the order of microseconds). The frame grabber acquires image data from the camera and stores the data in the computer memory. The counter/timer board triggers the camera and synchronizes the pulsing of the laser with acquisition of data from the camera. PIVPROC coordinates all of these functions and provides a graphical user interface, through which the user can control the PIV data-acquisition system. PIVACQ enables the user to acquire a sequence of single-exposure images, display the images, process the images, and then save the images to the computer hard drive. PIVACQ works in conjunction with the PIVPROC program which processes the images of particles into the velocity field in the illuminated plane.

  13. [HIV infection and acquired immunodeficiency syndrome].

    PubMed

    Takamatsu, J

    1997-05-01

    On June 4, 1981, MMWR published a report about Pneumocystis carinii pneumonia in homosexual men in Los Angeles. This was the first published report. A years later, this disease was named acquired immunodeficiency syndrome (AIDS). In the following year, Montangier et al in France discovered the causative agent, which they called lymphadenopathy virus (LAV), now known as human immunodeficiency virus (HIV). In 1985, solid-phase enzymeimmunoassay for the detection of the antibody to HIV was developed. Since then, other new techniques for the identification of HIV infection have been become available. These include more sensitive methods (for example; polymerase chain reaction techniques). Although these techniques facilitate early and definite diagnosis of infection, these tests may fail to detect the antibody in sera during window period of infection or overdiagnose infection in sera contaminated with genes not related to HIV. Although preventing blood exposure is the primary means of preventing occupationally acquired human immunodeficiency virus (HIV) infection, appropriate post-exposure management is an important element of workplace safety. Information suggesting that zidovudine (ZDV) postexposure prophylaxis (PEP) may reduce the risk for HIV transmission after occupational exposure to HIV infected blood prompted a Public Health Service (PHS) interagency working group, with expert consultation, and recommendations on PEP and management of occupational exposure to HIV in relation to these findings were discussed.

  14. Treatment of community-acquired pneumonia.

    PubMed

    Lee, Young R; Houngue, Coovi; Hall, Ronald G

    2015-01-01

    Community-acquired pneumonia is the sixth leading cause of death in the USA. Adherence to the 2007 Infectious Diseases Society of America/American Thoracic Society community-acquired pneumonia guidelines has been associated with improved clinical outcomes. However, choice between guideline-recommended treatments is at the discretion of the prescribing clinician. This review is intended to discuss the characteristics of these treatment options including dosing frequency, dose adjustment for renal/hepatic dysfunction, serious/common adverse events, drug interactions, lung penetration, pharmacokinetic-pharmacodynamic target and effect of obesity to help guide antimicrobial selection. An increasing portion of patients are receiving expanded empiric coverage for methicillin-resistant Staphylococcus aureus as recommended by the American Thoracic Society and Infectious Diseases Society of America for healthcare-associated pneumonia. However, this expanded coverage may not be achieving the desired improvements in clinical outcomes. We expect this increasingly diverse spectrum of patients with pneumonia to eventually result in the merger of these two guidelines to include all patients with pneumonia.

  15. Clinicopathological correlation of acquired hyperpigmentary disorders.

    PubMed

    Patel, Anisha B; Kubba, Raj; Kubba, Asha

    2013-01-01

    Acquired pigmentary disorders are group of heterogenous entities that share single, most significant, clinical feature, that is, dyspigmentation. Asians and Indians, in particular, are mostly affected. Although the classic morphologies and common treatment options of these conditions have been reviewed in the global dermatology literature, the value of histpathological evaluation has not been thoroughly explored. The importance of accurate diagnosis is emphasized here as the underlying diseases have varying etiologies that need to be addressed in order to effectively treat the dyspigmentation. In this review, we describe and discuss the utility of histology in the diagnostic work of hyperpigmentary disorders, and how, in many cases, it can lead to targeted and more effective therapy. We focus on the most common acquired pigmentary disorders seen in Indian patients as well as a few uncommon diseases with distinctive histological traits. Facial melanoses, including mimickers of melasma, are thoroughly explored. These diseases include lichen planus pigmentosus, discoid lupus erythematosus, drug-induced melanoses, hyperpigmentation due to exogenous substances, acanthosis nigricans, and macular amyloidosis.

  16. The Acquired Immunodeficiency Syndrome: current status.

    PubMed Central

    Quagliarello, V.

    1982-01-01

    A recently recognized syndrome of acquired immunodeficiency (Acquired Immunodeficiency Syndrome-AIDS) has arisen since June 1981. It has received international attention. The clinical spectrum consists of repeated opportunistic infections, rare malignancies, and autoimmune phenomena, occurring in previously healthy adults with no history of an immunologic disorder. The population subset at risk for this syndrome appears to be predominantly homosexual American males and intravenous drug abusers with rare cases being reported in heterosexuals, hemophiliacs, and foreign patients, especially Haitians. The immunologic aberrancy in all patients described appears limited to T-lymphocyte hyporesponsiveness and imbalance of T-helper and suppressor cells. This disordered immunoregulation is a consistent finding in all reported cases and appears to predispose to the opportunistic infections and malignancies which have been associated with a 40 percent mortality. The underlying factor responsible for the immunoregulatory defect is unknown but possible etiologies include a transmissible infectious agent, drug use, chronic antigen stimulation, and spermatozoa exposure. Treatment of the associated infections and malignancies has been a frustrating endeavor as many patients respond incompletely or relapse soon after successful treatment course. Preventive measures, including patient education, physician awareness, and immunomodulating agents, are discussed. PMID:6134399

  17. [Clinical cases of acquired coagulation inhibitors].

    PubMed

    Yamane, T; Hino, M; Ota, K; Akahori, M; Hirai, M; Inoue, T; Mugitani, A; Tatsumi, N

    2000-12-01

    The acquired coagulation factor inhibitors are classified into alloantibodies, which appear in association with supplementary treatment for congenital coagulation factor deficiency, and autoantibodies, which are spontaneously produced. We report here 2 cases of acquired factor VIII inhibitor and 1 case of factor V inhibitor. Case 1: A 52-year-old woman noted swelling of the right parotid region in March 1988. Though contrast examination was scheduled, she was admitted for detailed examination due to a markedly prolonged coagulation time. An APTT correction test suggested that decreased factor VIII activity was due to the presence of an inhibitor. Since antinuclear antibody and SS-A antibody were positive and infiltration by lymphocytes in the salivary gland acini in a lip biopsy specimen was detected, Sjögren's syndrome was diagnosed. Case 2: A 33-year-old woman had normal delivery of her second child in February 1998. In June 1998, she suffered slight contusion in the left lower limb. The affected site became swollen and painful, making walking difficult. Since both upper limbs became markedly swollen after 1 week, she visited our hospital. Prolonged APTT and a marked decrease in factor VIII activity were observed. Factor VIII inhibitor titer was high at 19 Bethesda units. Case 3: A 64-year-old man had had asymptomatic macroscopic hematuria since the beginning of August 1998 but was placed under observation since no abnormal findings were observed on various imaging tests. However, he was admitted to Osaka City General Medical Center because of vesicular tamponade. Factor V activity was markedly decreased to 1.0%. PT correction test suggested that decreased factor V activity was due to the presence of an inhibitor. The underlying disease could not be determined in this case. In patients with acquired coagulation inhibitors, bleeding symptoms are reported to be mild in many cases, and severe bleeding is rare. However, cases of death without severe bleeding or

  18. ACECARD. Acquire CoOmmodities Easily Card

    SciTech Connect

    Soler, E.E.

    1996-09-01

    Acquire Commodities Easily Card (AceCard) provides an automated end-user method to distribute company credit card charges to internal charge numbers. AceCard will allow cardholders to record card purchases in an on-line order log, enter multiple account distributions per order that can be posted to the General Ledger, track orders, and receipt information, and provide a variety of cardholder and administrative reports. Please note: Customers must contact Ed Soler (423)-576-6151, Lockheed Martin Energy Systems, for help with the installation of the package. The fee for this installation help will be coordinated by the customer and Lockheed Martin and is in addition to cost of the package from ESTSC. Customers should contact Sandy Presley (423)-576-4708 for user help.

  19. Acquire CoOmmodities Easily Card

    SciTech Connect

    Soler, E. E.

    1998-05-29

    Acquire Commodities Easily Card (AceCard) provides an automated end-user method to distribute company credit card charges to internal charge numbers. AceCard will allow cardholders to record card purchases in an on-line order log, enter multiple account distributions per order that can be posted to the General Ledger, track orders, and receipt information, and provide a variety of cardholder and administrative reports. Please note: Customers must contact Ed Soler (423)-576-6151, Lockheed Martin Energy Systems, for help with the installation of the package. The fee for this installation help will be coordinated by the customer and Lockheed Martin and is in addition to cost of the package from ESTSC. Customers should contact Sandy Presley (423)-576-4708 for user help.

  20. Stereotypic movement disorder after acquired brain injury.

    PubMed

    McGrath, Cynthia M; Kennedy, Richard E; Hoye, Wayne; Yablon, Stuart A

    2002-05-01

    Stereotypic movement disorder (SMD) consists of repetitive, non-functional motor behaviour that interferes with daily living or causes injury to the person. It is most often described in patients with mental retardation. However, recent evidence indicates that this condition is common among otherwise normal individuals. This case study describes a patient with new-onset SMD occurring after subdural haematoma and brain injury. SMD has rarely been reported after acquired brain injury, and none have documented successful treatment. The current psychiatric literature regarding neurochemistry, neuroanatomy, and treatment of SMD are reviewed with particular application to one patient. Treatment options include serotonin re-uptake inhibitors, opioid antagonists and dopamine antagonists. SMD has been under-appreciated in intellectually normal individuals, and may also be unrecognized after brain injury. Further investigation is needed in this area, which may benefit other individuals with SMD as well.

  1. Innate and acquired bacteriophage-mediated immunity

    PubMed Central

    Barr, Jeremy J.; Youle, Merry; Rohwer, Forest

    2013-01-01

    We recently described a novel, non-host-derived, phage-mediated immunity active at mucosal surfaces, the main site of pathogen entry in metazoans. In that work, we showed that phage T4 adheres to mucus glycoproteins via immunoglobulin-like domains displayed on its capsid. This adherence positions the phage in mucus surfaces where they are more likely to encounter and kill bacteria, thereby benefiting both the phage and its metazoan host. We presented this phage-metazoan symbiosis based on an exclusively lytic model of phage infection. Here we extend our bacteriophage adherence to mucus (BAM) model to consider the undoubtedly more complex dynamics in vivo. We hypothesize how mucus-adherent phages, both lytic and temperate, might impact the commensal microbiota as well as protect the metazoan epithelium from bacterial invasion. We suggest that BAM may provide both an innate and an acquired antimicrobial immunity. PMID:24228227

  2. Acquired immunodeficiency syndrome and health care professionals.

    PubMed

    Menon, V; Bharucha, K

    1994-01-01

    As health care professionals, we face a grave risk of acquiring HIV infection in the course of our work. But how many of us really know the precautions to be applied in the hospital set up in dealing with HIV infected patients? A knowledge, attitude and practice (KAP) study was conducted in Pune hospitals to assess the current status. Among the results 65% servants had not heard of AIDS, 85% nursing staff did not apply the Universal Safety Precautions (USP) approach, 13.5% resident thought that the HIV was not transmitted by blood, 30% consultants would avoid contact with an HIV positive patient. This study has shown that definite lacunae exist in knowledge specific to the particular population in question. A proposal for an education programme which is target specific and one of constant renewal is sought.

  3. Signal regulators of systemic acquired resistance

    PubMed Central

    Gao, Qing-Ming; Zhu, Shifeng; Kachroo, Pradeep; Kachroo, Aardra

    2015-01-01

    Salicylic acid (SA) is an important phytohormone that plays a vital role in a number of physiological responses, including plant defense. The last two decades have witnessed a number of breakthroughs related to biosynthesis, transport, perception and signaling mediated by SA. These findings demonstrate that SA plays a crictical role in both local and systemic defense responses. Systemic acquired resistance (SAR) is one such SA-dependent response. SAR is a long distance signaling mechanism that provides broad spectrum and long-lasting resistance to secondary infections throughout the plant. This unique feature makes SAR a highly desirable trait in crop production. This review summarizes the recent advances in the role of SA in SAR and discusses its relationship to other SAR inducers. PMID:25918514

  4. Acquired Localized Hypertrichosis Induced by Rivastigmine

    PubMed Central

    Imbernón-Moya, Adrian; Podlipnik, Sebastian; Burgos, Fernando; Vargas-Laguna, Elena; Aguilar-Martínez, Antonio; Fernández-Cogolludo, Eva; Gallego-Valdes, Miguel Angel

    2016-01-01

    Hypertrichosis is the excessive hair growth in any area of the skin surface. Acquired localized hypertrichosis may be secondary to multiple causes and there is a secondary form due to several drugs, which is usually reversible with discontinuation of the causative agent. Rivastigmine is a reversible and competitive inhibitor of acetylcholinesterase and butyrylcholinesterase used for symptomatic treatment of Alzheimer dementia and Parkinson's disease. It has an adequate safety profile and cutaneous side effects are unusual. Irritant contact dermatitis, allergic dermatitis, baboon syndrome, and cutaneous rash due to rivastigmine have been reported. We report on a Caucasian 80-year-old male with personal history of Alzheimer's disease. The patient started therapy with oral rivastigmine one month prior to clinical presentation of localized hypertrichosis on both forearms. Norgalanthamine has been shown to promote hair growth activity via the proliferation of dermal papilla. Acetylcholinesterase inhibitors can induce hair growth. PMID:27073702

  5. Treatment of the acquired von Willebrand syndrome.

    PubMed

    Budde, Ulrich; Scheppenheim, Sonja; Dittmer, Rita

    2015-12-01

    Acquired von Willebrand syndrome (aVWS) accounts for 22% of patients with abnormal von Willebrand factor. Most patients with known pathophysiological mechanisms suffer from cardiovascular, myeloproliferative and lymphoproliferative disorders. Less frequent associations are of autoimmune origin, due to hyperfibrinolysis, adsorption to tumor cells, reduced synthesis and prolonged circulation. The mechanisms leading to aVWS is hitherto not known in patients with liver and kidney diseases, drug use, glycogen storage disease, virus infections and at least 18 other disease entities. Diagnosis is complicated by the battery of tests needed, and their inherent rather low sensitivity and specificity for aVWS. Thus, even in acute bleeding situations it may take days until a firm diagnosis is settled and specific therapies can be initiated. The main aim is to shed more light onto this, compared with inherited von Willebrand disease, rare disease which affects at least 2-3% of the older population.

  6. Intensive care unit-acquired weakness.

    PubMed

    Horn, J; Hermans, G

    2017-01-01

    When critically ill, a severe weakness of the limbs and respiratory muscles often develops with a prolonged stay in the intensive care unit (ICU), a condition vaguely termed intensive care unit-acquired weakness (ICUAW). Many of these patients have serious nerve and muscle injury. This syndrome is most often seen in surviving critically ill patients with sepsis or extensive inflammatory response which results in increased duration of mechanical ventilation and hospital length of stay. Patients with ICUAW often do not fully recover and the disability will seriously impact on their quality of life. In this chapter we discuss the current knowledge on the pathophysiology and risk factors of ICUAW. Tools to diagnose ICUAW, how to separate ICUAW from other disorders, and which possible treatment strategies can be employed are also described. ICUAW is finally receiving the attention it deserves and the expectation is that it can be better understood and prevented.

  7. Severe acquired anaemia in Africa: new concepts.

    PubMed

    van Hensbroek, Michael B; Jonker, Femkje; Bates, Imelda

    2011-09-01

    Severe anaemia is common in Africa. It has a high mortality and particularly affects young children and pregnant women. Recent research provides new insights into the mechanisms and causes of severe acquired anaemia and overturns accepted dogma. Deficiencies of vitamin B12 and vitamin A, but not of iron or folic acid, are associated with severe anaemia. Bacterial infections and, in very young children, hookworm infections are also common in severe anaemia. Irrespective of the aetiology, the mechanism causing severe anaemia is often red cell production failure. Severe anaemia in Africa is therefore a complex multi-factorial syndrome, which, even in an individual patient, is unlikely to be amenable to a single intervention. Policies and practices concerning anaemia diagnosis, treatment and prevention need to be substantially revised if we are to make a significant impact on the huge burden of severe anaemia in Africa.

  8. Acquiring case adaptation knowledge: A hybrid approach

    SciTech Connect

    Leake, D.B.; Kinley, A.; Wilson, D.

    1996-12-31

    The ability of case-based reasoning (CBR) systems to apply cases to novel situations depends on their case adaptation knowledge. However, endowing CBR systems with adequate adaptation knowledge has proven to be a very difficult task. This paper describes a hybrid method for performing case adaptation, using a combination of rule-based and case-based reasoning. It shows how this approach provides a framework for acquiring flexible adaptation knowledge from experiences with autonomous adaptation and suggests its potential as a basis for acquisition of adaptation knowledge from interactive user guidance. It also presents initial experimental results examining the benefits of the approach and comparing the relative contributions of case learning and adaptation learning to reasoning performance.

  9. Acquired immunodeficiency syndrome: Ga-67 citrate imaging

    SciTech Connect

    Woolfenden, J.M.; Carrasquillo, J.A.; Larson, S.M.; Simmons, J.T.; Masur, H.; Smith, P.D.; Shelhamer, J.H.; Ognibene, F.P.

    1987-02-01

    All gallium-67 citrate scans obtained in patients with acquired immunodeficiency syndrome (AIDS) at the Clinical Center, National Institutes of Health (Bethesda, Md.) were retrospectively analyzed and correlated with the results of bronchoscopy, chest radiography, and endoscopy. There were 164 scans of 95 patients. Twenty scans were from patients with Pneumocystis carinii pneumonia; 19 were abnormal, for a sensitivity of 95%. Ga-67 uptake tended to be less in patients receiving therapy for P. carinii pneumonia. Chest radiographs were normal at least initially in three patients with abnormal scans and P. carinii pneumonia. Unusually prominent colonic activity was associated with infection in some patients. No lesions of Kaposi sarcoma showed tracer uptake. Gallium scanning is useful for detecting P. carinii pneumonia and other opportunistic infections in patients with AIDS, but it is not useful for localizing Kaposi sarcoma.

  10. Guidelines for prevention of hospital acquired infections

    PubMed Central

    Mehta, Yatin; Gupta, Abhinav; Todi, Subhash; Myatra, SN; Samaddar, D. P.; Patil, Vijaya; Bhattacharya, Pradip Kumar; Ramasubban, Suresh

    2014-01-01

    These guidelines, written for clinicians, contains evidence-based recommendations for the prevention of hospital acquired infections Hospital acquired infections are a major cause of mortality and morbidity and provide challenge to clinicians. Measures of infection control include identifying patients at risk of nosocomial infections, observing hand hygiene, following standard precautions to reduce transmission and strategies to reduce VAP, CR-BSI, CAUTI. Environmental factors and architectural lay out also need to be emphasized upon. Infection prevention in special subsets of patients - burns patients, include identifying sources of organism, identification of organisms, isolation if required, antibiotic prophylaxis to be used selectively, early removal of necrotic tissue, prevention of tetanus, early nutrition and surveillance. Immunodeficient and Transplant recipients are at a higher risk of opportunistic infections. The post tranplant timetable is divided into three time periods for determining risk of infections. Room ventilation, cleaning and decontamination, protective clothing with care regarding food requires special consideration. Monitoring and Surveillance are prioritized depending upon the needs. Designated infection control teams should supervise the process and help in collection and compilation of data. Antibiotic Stewardship Recommendations include constituting a team, close coordination between teams, audit, formulary restriction, de-escalation, optimizing dosing, active use of information technology among other measure. The recommendations in these guidelines are intended to support, and not replace, good clinical judgment. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments. PMID:24701065

  11. Community-Acquired Pneumonia in Latin America.

    PubMed

    Iannella, Hernán A; Luna, Carlos M

    2016-12-01

    Community-acquired pneumonia (CAP) is associated with significant morbidity and mortality in Latin America and the Caribbean (LAC) region. Poverty, socioeconomic factors, and malnutrition influence the incidence and outcome of CAP in LAC. In LAC, Streptococcus pneumoniae is the most frequent microorganism responsible for CAP, (incidence: 24-78%); the incidence of atypical microorganisms is similar to other regions of the world. Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) is a growing problem in the LAC region, with the Caribbean being the second most affected area worldwide after Sub-Saharan Africa. Pneumococcal pneumonia remains the most common cause of CAP in HIV-infected patients, but Pneumocystis jirovecii and tuberculosis (TB) are also common in this population. The heterogeneity of the health care systems and social inequity between different countries in LAC, and even between different settings inside the same country, is a difficult issue. TB, including multidrug-resistant TB, is several times more common in South American and Central American countries compared with North America. Furthermore, hantaviruses circulating in the Americas (new world hantaviruses) generate a severe respiratory disease called hantavirus pulmonary syndrome, with an associated mortality as high as 50%. More than 30 hantaviruses have been reported in the Western Hemisphere, with more frequent cases registered in the southern cone (Argentina, Chile, Uruguay, Paraguay, Bolivia, and Brazil). Respiratory viruses (particularly influenza) remain an important cause of morbidity and mortality, particularly in the elderly. Low rates of vaccination (against influenza as well as pneumococcus) may heighten the risk of these infections in low- and middle-income countries.

  12. Acute kidney injury in a patient with hemolytic anemia and thrombocytopenia.

    PubMed

    Breunig, Michael; Lalama, Miguel; Rivard, Gabrielle; Kashiwagi, Deanne; Cornell, Lynn

    2016-11-01

    Atypical hemolytic uremic syndrome (HUS) is clinically difficult to distinguish from HUS and thrombotic thrombocytopenic purpura. Atypical HUS results from dysregulation of complement activation causing thrombotic microangiopathy affecting multiple organ systems. Atypical HUS is associated with high morbidity and mortality, making early recognition and appropriate therapy necessary to improve patient outcomes.

  13. HUS AND TTP

    PubMed Central

    Trachtman, Howard

    2013-01-01

    SYNOPSIS This review will describe the epidemiology, pathophysiology, presentation, clinical causes, treatment, and long-term prognosis of pediatric patients who present with thrombotic microangiopathy (TMA). The focus will be on hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP), the most common phenotypes of TMA. PMID:24237985

  14. Preschoolers Acquire General Knowledge by Sharing in Pretense

    ERIC Educational Resources Information Center

    Sutherland, Shelbie L.; Friedman, Ori

    2012-01-01

    Children acquire general knowledge about many kinds of things, but there are few known means by which this knowledge is acquired. In this article, it is proposed that children acquire generic knowledge by sharing in pretend play. In Experiment 1, twenty-two 3- to 4-year-olds watched pretense in which a puppet represented a "nerp" (an unfamiliar…

  15. 19 CFR 148.38 - Sale of articles acquired abroad.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 2 2013-04-01 2013-04-01 false Sale of articles acquired abroad. 148.38 Section... § 148.38 Sale of articles acquired abroad. An article brought in under the $800 or $1,600 exemption for articles acquired abroad for personal or household use and subsequently sold is not dutiable or subject...

  16. 19 CFR 148.38 - Sale of articles acquired abroad.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Sale of articles acquired abroad. 148.38 Section... § 148.38 Sale of articles acquired abroad. An article brought in under the $800 or $1,600 exemption for articles acquired abroad for personal or household use and subsequently sold is not dutiable or subject...

  17. 19 CFR 148.38 - Sale of articles acquired abroad.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 2 2011-04-01 2011-04-01 false Sale of articles acquired abroad. 148.38 Section... § 148.38 Sale of articles acquired abroad. An article brought in under the $800 or $1,600 exemption for articles acquired abroad for personal or household use and subsequently sold is not dutiable or subject...

  18. 19 CFR 148.38 - Sale of articles acquired abroad.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 2 2012-04-01 2012-04-01 false Sale of articles acquired abroad. 148.38 Section... § 148.38 Sale of articles acquired abroad. An article brought in under the $800 or $1,600 exemption for articles acquired abroad for personal or household use and subsequently sold is not dutiable or subject...

  19. 7 CFR 770.8 - Use of acquired land.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 7 2014-01-01 2014-01-01 false Use of acquired land. 770.8 Section 770.8 Agriculture... SPECIAL PROGRAMS INDIAN TRIBAL LAND ACQUISITION LOANS § 770.8 Use of acquired land. (a) General. Subject to § 770.5(d) land acquired with loan funds, or other property serving as the security for a...

  20. 43 CFR 4110.1-1 - Acquired lands.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Acquired lands. 4110.1-1 Section 4110.1-1 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT... and Preference § 4110.1-1 Acquired lands. Where lands have been acquired by the Bureau of...

  1. 30 CFR 879.14 - Management of acquired land.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Management of acquired land. 879.14 Section 879... ABANDONED MINE LAND RECLAMATION ACQUISITION, MANAGEMENT, AND DISPOSITION OF LANDS AND WATER § 879.14 Management of acquired land. Land acquired under this part may be used for any lawful purpose that...

  2. 7 CFR 770.8 - Use of acquired land.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 7 2013-01-01 2013-01-01 false Use of acquired land. 770.8 Section 770.8 Agriculture... SPECIAL PROGRAMS INDIAN TRIBAL LAND ACQUISITION LOANS § 770.8 Use of acquired land. (a) General. Subject to § 770.5(d) land acquired with loan funds, or other property serving as the security for a...

  3. 43 CFR 4110.1-1 - Acquired lands.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Acquired lands. 4110.1-1 Section 4110.1-1 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT... and Preference § 4110.1-1 Acquired lands. Where lands have been acquired by the Bureau of...

  4. 43 CFR 4110.1-1 - Acquired lands.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Acquired lands. 4110.1-1 Section 4110.1-1 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT... and Preference § 4110.1-1 Acquired lands. Where lands have been acquired by the Bureau of...

  5. 30 CFR 879.14 - Management of acquired land.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Management of acquired land. 879.14 Section 879... ABANDONED MINE LAND RECLAMATION ACQUISITION, MANAGEMENT, AND DISPOSITION OF LANDS AND WATER § 879.14 Management of acquired land. Land acquired under this part may be used for any lawful purpose that...

  6. 7 CFR 770.8 - Use of acquired land.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 7 2012-01-01 2012-01-01 false Use of acquired land. 770.8 Section 770.8 Agriculture... SPECIAL PROGRAMS INDIAN TRIBAL LAND ACQUISITION LOANS § 770.8 Use of acquired land. (a) General. Subject to § 770.5(d) land acquired with loan funds, or other property serving as the security for a...

  7. 43 CFR 4110.1-1 - Acquired lands.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Acquired lands. 4110.1-1 Section 4110.1-1 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT... and Preference § 4110.1-1 Acquired lands. Where lands have been acquired by the Bureau of...

  8. 30 CFR 879.14 - Management of acquired land.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Management of acquired land. 879.14 Section 879... ABANDONED MINE LAND RECLAMATION ACQUISITION, MANAGEMENT, AND DISPOSITION OF LANDS AND WATER § 879.14 Management of acquired land. Land acquired under this part may be used for any lawful purpose that...

  9. 30 CFR 879.14 - Management of acquired land.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Management of acquired land. 879.14 Section 879... ABANDONED MINE LAND RECLAMATION ACQUISITION, MANAGEMENT, AND DISPOSITION OF LANDS AND WATER § 879.14 Management of acquired land. Land acquired under this part may be used for any lawful purpose that...

  10. Circulating Immune Complexes of IgA Bound to Beta 2 Glycoprotein are Strongly Associated with the Occurrence of Acute Thrombotic Events

    PubMed Central

    Martínez-Flores, José A.; Serrano, Manuel; Pérez, Dolores; de la Cámara A, Gómez; Lora, David; Morillas, Luis; Ayala, Rosa; Paz-Artal, Estela; Morales, José M.

    2016-01-01

    Aim: Antiphospholipid syndrome (APS) is characterized by recurrent thrombosis and/or gestational morbidity in patients with antiphospholipid autoantibodies (aPL). Over recent years, IgA anti-beta2-glycoprotein I (B2GPI) antibodies (IgA aB2GPI) have reached similar clinical relevance as IgG or IgM isotypes. We recently described the presence of immune complexes of IgA bounded to B2GPI (B2A-CIC) in the blood of patients with antecedents of APS symptomalology. However, B2A-CIC's clinical associations with thrombotic events (TEV) have not been described yet. Methods: A total of 145 individuals who were isolate positive for IgA aB2GPI were studied: 50 controls without any APS antecedent, 22 patients with recent TEV (Group-1), and 73 patients with antecedents of old TEV (Group-2). Results: Mean B2A-CIC levels and prevalence in Group-1 were 29.6 ± 4.1 AU and 81.8%, respectively, and were significantly higher than those of Group-2 and controls (p < 0.001). In a multivariable analysis, positivity of B2A-CIC was an independent variable for acute thrombosis with a 22.7 odd ratio (confidence interval 5.1 –101.6, 95%, p < 0.001). Levels of B2A-CIC dropped significantly two months after the TEV. B2A-CIC positive patients had lower platelet levels than B2A-CIC-negative patients (p < 0.001) and more prevalence of thrombocytopenia (p < 0.019). Group-1 had no significant differences in C3 and C4 levels compared with other groups. Conclusion: B2A-CIC is strongly associated with acute TEV. Patients who did not develop thrombosis and were B2A-CIC positive had lower platelet levels, which suggest a hypercoagulable state. This mechanism is unrelated to complement-fixing aPL. B2A-CIC could potentially select IgA aB2GPI-positive patients at risk of developing a thrombotic event. PMID:27063992

  11. Free radicals mediate systemic acquired resistance.

    PubMed

    Wang, Caixia; El-Shetehy, Mohamed; Shine, M B; Yu, Keshun; Navarre, Duroy; Wendehenne, David; Kachroo, Aardra; Kachroo, Pradeep

    2014-04-24

    Systemic acquired resistance (SAR) is a form of resistance that protects plants against a broad spectrum of secondary infections. However, exploiting SAR for the protection of agriculturally important plants warrants a thorough investigation of the mutual interrelationships among the various signals that mediate SAR. Here, we show that nitric oxide (NO) and reactive oxygen species (ROS) serve as inducers of SAR in a concentration-dependent manner. Thus, genetic mutations that either inhibit NO/ROS production or increase NO accumulation (e.g., a mutation in S-nitrosoglutathione reductase [GSNOR]) abrogate SAR. Different ROS function additively to generate the fatty-acid-derived azelaic acid (AzA), which in turn induces production of the SAR inducer glycerol-3-phosphate (G3P). Notably, this NO/ROS→AzA→G3P-induced signaling functions in parallel with salicylic acid-derived signaling. We propose that the parallel operation of NO/ROS and SA pathways facilitates coordinated regulation in order to ensure optimal induction of SAR.

  12. Acquiring synaesthesia: insights from training studies

    PubMed Central

    Rothen, Nicolas; Meier, Beat

    2014-01-01

    Synaesthesia denotes a condition of remarkable individual differences in experience characterized by specific additional experiences in response to normal sensory input. Synaesthesia seems to (i) run in families which suggests a genetic component, (ii) is associated with marked structural and functional neural differences, and (iii) is usually reported to exist from early childhood. Hence, synaesthesia is generally regarded as a congenital phenomenon. However, most synaesthetic experiences are triggered by cultural artifacts (e.g., letters, musical sounds). Evidence exists to suggest that synaesthetic experiences are triggered by the conceptual representation of their inducer stimuli. Cases were identified for which the specific synaesthetic associations are related to prior experiences and large scale studies show that grapheme-color associations in synaesthesia are not completely random. Hence, a learning component is inherently involved in the development of specific synaesthetic associations. Researchers have hypothesized that associative learning is the critical mechanism. Recently, it has become of scientific and public interest if synaesthetic experiences may be acquired by means of associative training procedures and whether the gains of these trainings are associated with similar cognitive benefits as genuine synaesthetic experiences. In order to shed light on these issues and inform synaesthesia researchers and the general interested public alike, we provide a comprehensive literature review on developmental aspects of synaesthesia and specific training procedures in non-synaesthetes. Under the light of a clear working definition of synaesthesia, we come to the conclusion that synaesthesia can potentially be learned by the appropriate training. PMID:24624072

  13. Transfusion-acquired AIDS in Taiwan.

    PubMed

    Yao, C; Wang, W W; Chung, Y M; Su, Y L; Liu, C Y; Chen, Y M

    1996-01-01

    Human immunodeficiency virus type 1 (HIV-1) can be transmitted through blood transfusion. The first transfusion-acquired immunodeficiency syndrome (AIDS) patient in Taiwan was a 46-year-old woman who received two units of whole blood during a hysterectomy at a provincial hospital in 1985. In 1991, she experienced a herpes zoster infection. In March 1993, she had extensive herpetic gingivostomatitis and another herpes zoster attack, and was treated at the same hospital. Two months later, she had oral candidiasis and was treated at a medical center. She was not tested for HIV-1 infection until she developed Pneumocystis carinii pneumonia in June 1993. In February 1994, and developed cytomegalovirus retinitis and died 6 months later. Donor blood given to the patients during the hysterectomy was HIV-1 positive. The donor's HIV infection was discovered in 1991 and he died of AIDS in 1993. As blood centers in Taiwan did not start screening for HIV-1 until January 1988, it is urgently recommended that any individual who received a blood transfusion between 1984 and 1987 in Taiwan and who currently experiences repeated episodes of opportunistic infections have an HIV-1 blood test. The receipt of a blood transfusion between 1984 and 1987 should be listed by the Department of Health as an indication for HIV-1 screening.

  14. [Thoracic manifestations of AIDS (acquired immunodeficiency syndrome)].

    PubMed

    Bernasconi, A; Zompatori, M; Chiodo, F; Costigliola, P; Ricchi, E; Colangeli, V; Canini, R; Gavelli, G

    1989-11-01

    AIDS (acquired immunodeficiency syndrome) seems to be related to human immunodeficiency virus (HIV) and is characterized by severe T-helpers lymphocyte dysfunction. Many of the AIDS patients (47-70%) develop pulmonary manifestations, both infectious and neoplastic, in the course of their disease. In the Department of Infectious Diseases of our Hospital are studied many patients HIV+. Every year 246 seropositive new patients have been discovered. Among them we have studied 25 subjects with respiratory disease, by chest radiographs; successively, according to clinical picture, we have performed thoracic computed tomography, Gallium scintigraphy, fiberoptic bronchoscopy with transbronchial biopsy (TBB), bronchoalveolar lavage (BAL); the majority of these patients (68%) had AIDS, only 28% had ARC and 4% had PGL. In our experience, the diagnosed diseases were mainly infections (92%), and most frequently (52%) due to Pneumocystis carinii, alone or in association with other etiologic agents. We have not found pathognomonic radiographic abnormalities, but chest X-ray evaluated with clinical and laboratory data, may often be useful to obtain diagnostic indications and in order to determine a more specific and aggressive diagnostic approach.

  15. Mycobacterial disease, immunosuppression, and acquired immunodeficiency syndrome.

    PubMed Central

    Collins, F M

    1989-01-01

    The mycobacteria are an important group of acid-fast pathogens ranging from obligate intracellular parasites such as Mycobacterium leprae to environmental species such as M. gordonae and M. fortuitum. The latter may behave as opportunistic human pathogens if the host defenses have been depleted in some manner. The number and severity of such infections have increased markedly with the emergence of the acquired immunodeficiency syndrome (AIDS) epidemic. These nontuberculous mycobacteria tend to be less virulent for humans than M. tuberculosis, usually giving rise to self-limiting infections involving the cervical and mesenteric lymph nodes of young children. However, the more virulent serovars of M. avium complex can colonize the bronchial and intestinal mucosal surfaces of healthy individuals, becoming virtual members of the commensal gut microflora and thus giving rise to low levels of skin hypersensitivity to tuberculins prepared from M. avium and M. intracellulare. Systemic disease develops when the normal T-cell-mediated defenses become depleted as a result of old age, cancer chemotherapy, or infection with human immunodeficiency virus. As many as 50% of human immunodeficiency virus antibody-positive individuals develop mycobacterial infections at some time during their disease. Most isolates of M. avium complex from AIDS patients fall into serotypes 4 and 8. The presence of these drug-resistant mycobacteria in the lungs of the AIDS patient makes their effective clinical treatment virtually impossible. More effective chemotherapeutic, prophylactic, and immunotherapeutic reagents are urgently needed to treat this rapidly increasing patient population. PMID:2680057

  16. Community-acquired pneumonia among smokers.

    PubMed

    Almirall, Jordi; Blanquer, José; Bello, Salvador

    2014-06-01

    Recent studies have left absolutely no doubt that tobacco increases susceptibility to bacterial lung infection, even in passive smokers. This relationship also shows a dose-response effect, since the risk reduces spectacularly 10 years after giving up smoking, returning to the level of non-smokers. Streptococcus pneumoniae is the causative microorganism responsible for community-acquired pneumonia (CAP) most frequently associated with smoking, particularly in invasive pneumococcal disease and septic shock. It is not clear how it acts on the progress of pneumonia, but there is evidence to suggest that the prognosis for pneumococcal pneumonia is worse. In CAP caused by Legionella pneumophila, it has also been observed that smoking is the most important risk factor, with the risk rising 121% for each pack of cigarettes smoked a day. Tobacco use may also favor diseases that are also known risk factors for CAP, such as periodontal disease and upper respiratory viral infections. By way of prevention, while giving up smoking should always be proposed, the use of the pneumococcal vaccine is also recommended, regardless of the presence of other comorbidities.

  17. Gastrointestinal Manifestations of the Acquired Immunodeficiency Syndrome

    PubMed Central

    Rodgers, Vance D.; Kagnoff, Martin F.

    1987-01-01

    In addition to abnormalities in systemic immune function, patients with the acquired immunodeficiency syndrome (AIDS) and the pre-AIDS syndromes have significant abnormalities in the distribution of T-cell subsets in the intestinal tract. Such immune deficits predispose such patients to opportunistic infections and tumors, many of which involve the gastrointestinal tract. For example, Candida albicans often causes stomatitis and esophagitis. Intestinal infections with parasites (Cryptosporidium, Isospora belli, Microsporidia) or bacteria (Mycobacterium avium-intracellulare) are associated with severe diarrhea and malabsorption, whereas viruses like cytomegalovirus and herpes simplex virus cause mucosal ulcerations. Clinically debilitating chronic diarrhea develops in many AIDS patients for which no clear cause can be identified. Enteric pathogens like Salmonella and Campylobacter can be associated with bacteremias. Kaposi's sarcoma and lymphoma involving the intestinal tract are now well-recognized complications of AIDS. Although AIDS is not associated with a pathognomonic liver lesion, opportunistic infections and Kaposi's sarcoma or lymphoma may involve the liver. ImagesFigure 3.Figure 4.Figure 5.Figure 6.Figure 7. PMID:3825111

  18. Biomarkers in Pediatric Community-Acquired Pneumonia

    PubMed Central

    Principi, Nicola; Esposito, Susanna

    2017-01-01

    Community-acquired pneumonia (CAP) is an infectious disease caused by bacteria, viruses, or a combination of these infectious agents. The severity of the clinical manifestations of CAP varies significantly. Consequently, both the differentiation of viral from bacterial CAP cases and the accurate assessment and prediction of disease severity are critical for effectively managing individuals with CAP. To solve questionable cases, several biomarkers indicating the etiology and severity of CAP have been studied. Unfortunately, only a few studies have examined the roles of these biomarkers in pediatric practice. The main aim of this paper is to detail current knowledge regarding the use of biomarkers to diagnose and treat CAP in children, analyzing the most recently published relevant studies. Despite several attempts, the etiologic diagnosis of pediatric CAP and the estimation of the potential outcome remain unsolved problems in most cases. Among traditional biomarkers, procalcitonin (PCT) appears to be the most effective for both selecting bacterial cases and evaluating the severity. However, a precise cut-off separating bacterial from viral and mild from severe cases has not been defined. The three-host protein assay based on C-reactive protein (CRP), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), plasma interferon-γ protein-10 (IP-10), and micro-array-based whole genome expression arrays might offer more advantages in comparison with former biomarkers. However, further studies are needed before the routine use of those presently in development can be recommended. PMID:28218726

  19. Identification of acquired DNA in Neisseria lactamica.

    PubMed

    van Passel, Mark W J; Bart, Aldert; Luyf, Angela C M; van Kampen, Antoine H C; van der Ende, Arie

    2006-09-01

    Anomalous DNA (aDNA) in prokaryotic genomes, identified by its aberrant nucleotide composition, generally represents horizontally acquired DNA. Previous studies showed that frequent DNA transfer occurs between commensal Neisseriae and Neisseria meningitidis. Currently, it is unknown whether aDNA regions are also transferred between these species. The genome of Neisseria lactamica strain 892586 was assessed by a strategy that enables the selective isolation of aDNA, using endonucleases with recognition sites that are overrepresented in aDNA. Of eight regions with aDNA, five displayed similarity to virulence-associated meningococcal sequences. Of three aDNA fragments with limited or no similarity to neisserial sequences, one encodes a novel putative autotransporter/adhesin. The remaining two fragments are adjacent in the N. lactamica genome, and encode a novel putative ATPase/subtilisin-like protease operon. A similar operon is present in the genomes of different respiratory tract pathogens. The identification of aDNA from N. lactamica with similarity to meningococcal aDNA shows that genetic exchange between the Neisseriae is not limited to the neisserial core genome. The discovery of aDNA in N. lactamica similar to a locus in other pathogens substantially expands the neisserial gene pool.

  20. Natural and acquired macrolide resistance in mycobacteria.

    PubMed

    Doucet-Populaire, F; Buriánková, K; Weiser, J; Pernodet, J-L

    2002-12-01

    The genus Mycobacterium contains two of the most important human pathogens, Mycobacterium tuberculosis and Mycobacterium leprae, the etiologic agents of tuberculosis and leprosy, respectively. Other mycobacteria are mostly saprophytic organisms, living in soil and water, but some of them can cause opportunistic infections. The increasing incidence of tuberculosis as well as infections with non-tuberculous mycobacteria (NTM) in AIDS patients has renewed interest in molecular mechanisms of drug resistance in these pathogens. Mycobacteria show a high degree of intrinsic resistance to most common antibiotics. For instance, species from the M. tuberculosis complex (MTC) are intrinsically resistant to macrolides. Nevertheless, some semi-synthetic macrolides as the erythromycin derivatives clarithromycin, azithromycin and most recently the ketolides, are active against NTM, particularly Mycobacterium avium, and some of them are widely used for infection treatment. However, shortly after the introduction of these new drugs, resistant strains appeared due to mutations in the macrolide target, the ribosome. The mycobacterial cell wall with its specific composition and structure is considered to be a major factor in promoting the natural resistance of mycobacteria to various antibiotics. However, to explain the difference in macrolide sensitivity between the MTC and NTM, the synergistic contribution of a specific resistance mechanism might be required, in addition to possible differences in cell wall permeability. This mini-review summarizes the current knowledge on the natural and acquired macrolide resistance in mycobacteria, gives an overview of potential mechanisms implicated in the intrinsic resistance and brings recent data concerning a macrolide resistance determinant in the MTC.

  1. [Acquired and congenital heart diseases during pregancy].

    PubMed

    De Feo, Stefania; Iacovoni, Attilio; Faggiano, Pompilio

    2012-05-01

    Heart diseases are the leading cause of maternal morbidity and mortality. The number of patients with congenital heart diseases reaching childbearing age, as well as the proportion of women with acquired conditions, such as ischemic heart disease, becoming pregnant is constantly increasing. All women with known heart disease should have pre-pregnancy counseling, to assess maternal and fetal risk. Women at moderate or high risk should be under the care of a specialist prenatal team with experience in managing women with heart disease during pregnancy. Conditions that are considered at particularly high risk (mortality >10%) include Marfan syndrome with dilated aortic root, severe left ventricular dysfunction, severe left heart obstructive lesions, and pulmonary hypertension. Peripartum cardiomyopathy is a rare and potentially fatal disease related to pregnancy and the postnatal period that presents with symptoms of congestion and/or hypoperfusion and may rapidly progress to acute and life-threatening heart failure. However, the majority of women with heart disease can tolerate pregnancy; therefore an adequate multidisciplinary approach with the gynecologist, anesthesiologist and cardiologist should be advocated in order to reduce maternal and fetal risks associated with pregnancy.

  2. The complex pathophysiology of acquired aplastic anaemia.

    PubMed

    Zeng, Y; Katsanis, E

    2015-06-01

    Immune-mediated destruction of haematopoietic stem/progenitor cells (HSPCs) plays a central role in the pathophysiology of acquired aplastic anaemia (aAA). Dysregulated CD8(+) cytotoxic T cells, CD4(+) T cells including T helper type 1 (Th1), Th2, regulatory T cells and Th17 cells, natural killer (NK) cells and NK T cells, along with the abnormal production of cytokines including interferon (IFN)-γ, tumour necrosis factor (TNF)-α and transforming growth factor (TGF)-β, induce apoptosis of HSPCs, constituting a consistent and defining feature of severe aAA. Alterations in the polymorphisms of TGF-β, IFN-γ and TNF-α genes, as well as certain human leucocyte antigen (HLA) alleles, may account for the propensity to immune-mediated killing of HSPCs and/or ineffective haematopoiesis. Although the inciting autoantigens remain elusive, autoantibodies are often detected in the serum. In addition, recent studies provide genetic and molecular evidence that intrinsic and/or secondary deficits in HSPCs and bone marrow mesenchymal stem cells may underlie the development of bone marrow failure.

  3. Male body image following acquired brain injury.

    PubMed

    Howes, Hannah; Edwards, Stephen; Benton, David

    2005-02-01

    The purpose of this study was to investigate body image concerns and psycho-emotional health in males with acquired brain injury (ABI). Using a between subjects study of 25 males with ABI and 25 matched controls, variables were analysed using correlations and 2 x 2 analyses of variance (ANOVAs) with head injury and injury type as independent variables. Body image and psycho-emotional health were evaluated using self-report questionnaires. Disability and cognitive impairment were measured using a mixture of self-report, cognitive testing and clinical notes. Results indicated that males with ABI had significantly lower self-esteem and body dissatisfaction on a number of items relating to physical and sexual functioning. There were significant differences in body image between stroke and TBI, but there was no corresponding relationship with psycho-emotional health. These body image differences might be explained by age. The finding that ABI has a negative effect on body image and that this relates to psycho-emotional health should be investigated further, perhaps being included in future rehabilitation strategies.

  4. The inheritance of acquired epigenetic variations.

    PubMed

    Jablonka, Eva; Lamb, Marion J

    2015-08-01

    There is evidence that the functional history of a gene in one generation can influence its expression in the next. In somatic cells, changes in gene activity are frequently associated with changes in the pattern of methylation of the cytosines in DNA; these methylation patterns are stably inherited. Recent work suggests that information about patterns of methylation and other epigenetic states can also be transmitted from parents to offspring. This evidence is the basis of a model for the inheritance of acquired epigenetic variations. According to the model, an environmental stimulus can induce heritable chromatin modifications which are very specific and predictable, and might result in an adaptive response to the stimulus. This type of response probably has most significance for adaptive evolution in organisms such as fungi and plants, which lack distinct segregation of the soma and germ line. However, in all organisms, the accumulation of specific and random chromatin modifications in the germ line may be important in speciation, because these modifications could lead to reproductive isolation between populations. Heritable chromatin variations may also alter the frequency and distribution of classical mutations and meiotic recombination. Therefore, inherited epigenetic changes in the structure of chromatin can influence neo-Darwinian evolution as well as cause a type of "Lamarckian" inheritance.

  5. In vivo models of cortical acquired epilepsy

    PubMed Central

    Chauvette, Sylvain; Soltani, Sara; Seigneur, Josée; Timofeev, Igor

    2015-01-01

    The neocortex is the site of origin of several forms of acquired epilepsy. Here we provide a brief review of experimental models that were recently developed to study neocortical epileptogenesis as well as some major results obtained with these methods. Most of neocortical seizures appear to be nocturnal and it is known that neuronal activities reveal high levels of synchrony during slow-wave sleep. Therefore, we start the review with a description of mechanisms of neuronal synchronization and major forms of synchronized normal and pathological activities. Then, we describe three experimental models of seizures and epileptogenesis: ketamine-xylazine anesthesia as feline seizure triggered factor, cortical undercut as cortical penetrating wound model and neocortical kindling. Besides specific technical details describing these models we also provide major features of pathological brain activities recorded during epileptogenesis and seizures. The most common feature of all models of neocortical epileptogenesis is the increased duration of network silent states that up-regulates neuronal excitability and eventually leads to epilepsy. PMID:26343530

  6. Acquired immunodeficiency syndrome in older African Americans.

    PubMed

    Funnyé, Allen S; Akhtar, Abbasi J; Biamby, Gisele

    2002-04-01

    The purpose of this study was to determine if older African Americans are disproportionately affected by acquired immunodeficiency syndrome (AIDS), and to review the clinical impact of AIDS and the importance of prevention and treatment efforts. A review of the literature and statistics was obtained using Medline and the AIDS Public Information Data Set offered by the Centers for Disease Control and Prevention. Twenty-seven percent of the U.S. population is above the age of 50, and the number of AIDS cases in this group is growing, with African Americans accounting for the highest proportion of cases and deaths. Testing for HIV may be delayed and symptoms attributed to other illnesses. Though 5% of new cases occur in those over 50, prevention programs, testing, and the perception of risk by providers may be insufficient. There are few research studies on HIV treatment in older patients and no specific guidelines for antiretroviral treatments available. Although death rates for AIDS has been declining, adults over 50 still have the highest mortality rate. Co-morbid conditions, such as heart disease and hypertension, may require taking multiple drugs, which may complicate treatment. Increasing heterosexual transmission rates and a lack of information on HIV reinforces the need for specific prevention programs targeted toward older African Americans.

  7. In vivo models of cortical acquired epilepsy.

    PubMed

    Chauvette, Sylvain; Soltani, Sara; Seigneur, Josée; Timofeev, Igor

    2016-02-15

    The neocortex is the site of origin of several forms of acquired epilepsy. Here we provide a brief review of experimental models that were recently developed to study neocortical epileptogenesis as well as some major results obtained with these methods. Most of neocortical seizures appear to be nocturnal and it is known that neuronal activities reveal high levels of synchrony during slow-wave sleep. Therefore, we start the review with a description of mechanisms of neuronal synchronization and major forms of synchronized normal and pathological activities. Then, we describe three experimental models of seizures and epileptogenesis: ketamine-xylazine anesthesia as feline seizure triggered factor, cortical undercut as cortical penetrating wound model and neocortical kindling. Besides specific technical details describing these models we also provide major features of pathological brain activities recorded during epileptogenesis and seizures. The most common feature of all models of neocortical epileptogenesis is the increased duration of network silent states that up-regulates neuronal excitability and eventually leads to epilepsy.

  8. Acquired prosopagnosia: structural basis and processing impairments.

    PubMed

    Davies-Thompson, Jodie; Pancaroglu, Raika; Barton, Jason

    2014-01-01

    Cognitive models propose a hierarchy of parallel processing stages in face perception, and functional neuroimaging shows a network of regions involved in face processing. Reflecting this, acquired prosopagnosia is not a single entity but a family of disorders with different anatomic lesions and different functional deficits. One classic distinction is between an apperceptive variant, in which there is impaired perception of facial structure, and an associative/amnestic variant, in which perception is relatively intact, with subsequent problems matching perception to facial memories, because of either disconnection or loss of those memories. These disorders also have to be distinguished from people-specific amnesia, a multimodal impairment, and prosop-anomia, in which familiarity with faces is preserved but access to names is disrupted. These different disorders can be conceived as specific deficits at different processing stages in cognitive models, and suggests that these functional stages may have distinct neuroanatomic substrates. It remains to be seen whether a similar anatomic and functional variability is present in developmental prosopagnosia.

  9. Octaploidy in idiopathic thrombocytopenic purpura

    PubMed Central

    Makroo, R. N.; Chowdhry, Mohit; Mishra, Manoj; Srivastava, Priyanka; Fauzdar, Ashish

    2011-01-01

    We report a case of an elderly 68-year-old male who presented in our hospital with chief complaints of petechial rashes and ecchymosis over extremities and bleeding from the oral cavity since 3–4 days prior to hospitalization. He saw a physician before coming to our hospital and received one dose of IV methylprednisolone and oral wysolone. He had come to our hospital for further management. Bone marrow karyotyping was done and chromosomal analysis revealed two cell lines. Eighty percent of the cells analyzed revealed apparently normal male karyotype. However, 20% cells analyzed revealed a total of 184 chromosomes, suggesting octaploidy. PMID:22346001

  10. Late endovascular removal of Günther-Tulip inferior vena cava filter and stent reconstruction of chronic post-thrombotic iliocaval obstruction after 4753 days of filter dwell time: a case report with review of literature.

    PubMed

    Doshi, Mehul Harshad; Narayanan, Govindarajan

    2016-12-01

    Chronic post-thrombotic obstruction of the inferior vena cava (IVC) or iliocaval junction is an uncommon complication of long indwelling IVC filter. When such an obstruction is symptomatic, endovascular treatment options include stent placement with or without filter retrieval. Filter retrieval becomes increasingly difficult with longer dwell times. We present a case of symptomatic post-thrombotic obstruction of the iliocaval junction related to Günther-Tulip IVC filter (Cook Medical Inc, Bloomington, IN) with dwell time of 4753 days, treated successfully with endovascular filter removal and stent reconstruction. Filter retrieval and stent reconstruction may be a treatment option in symptomatic patients with filter-related chronic IVC or iliocaval junction obstruction, even after prolonged dwell time.

  11. Community-Acquired Legionella pneumophila Pneumonia

    PubMed Central

    Viasus, Diego; Di Yacovo, Silvana; Garcia-Vidal, Carolina; Verdaguer, Ricard; Manresa, Frederic; Dorca, Jordi; Gudiol, Francesc; Carratalà, Jordi

    2013-01-01

    Abstract Legionella pneumophila has been increasingly recognized as a cause of community-acquired pneumonia (CAP) and an important public health problem worldwide. We conducted the present study to assess trends in epidemiology, diagnosis, clinical features, treatment, and outcomes of sporadic community-acquired L. pneumophila pneumonia requiring hospitalization at a university hospital over a 15-year period (1995–2010). Among 3934 nonimmunosuppressed hospitalized patients with CAP, 214 (5.4%) had L. pneumophila pneumonia (16 cases were categorized as travel-associated pneumonia, and 21 were part of small clusters). Since the introduction of the urinary antigen test, the diagnosis of L. pneumophila using this method remained stable over the years (p = 0.42); however, diagnosis by means of seroconversion and culture decreased (p < 0.001 and p = 0.001, respectively). The median age of patients with L. pneumophila pneumonia was 58.2 years (SD 13.8), and 76.4% were male. At least 1 comorbid condition was present in 119 (55.6%) patients with L. pneumophila pneumonia, mainly chronic heart disease, diabetes mellitus, and chronic pulmonary disease. The frequency of older patients (aged >65 yr) and comorbidities among patients with L. pneumophila pneumonia increased over the years (p = 0.06 and p = 0.02, respectively). In addition, 100 (46.9%) patients were classified into high-risk classes according to the Pneumonia Severity Index (groups IV–V). Twenty-four (11.2%) patients with L. pneumophila pneumonia received inappropriate empirical antibiotic therapy at hospital admission. Compared with patients who received appropriate empirical antibiotic, patients who received inappropriate therapy more frequently had acute onset of illness (p = 0.004), pleuritic chest pain (p = 0.03), and pleural effusion (p = 0.05). The number of patients who received macrolides decreased over the study period (p < 0.001), whereas the number of patients who received levofloxacin increased (p

  12. [Acquired pendular nystagmus after pontine hemorrhage].

    PubMed

    Yokota, J; Kosaka, K; Yoshimoto, Y; Amakusa, T

    1999-12-01

    A 60-year-old hypertensive woman had a pontine hemorrhage that caused slight right hemiplegia, deep sensory disturbance on her right side and dysarthria. Three months after the stroke, she was transferred to our hospital for rehabilitation. Approximately 6 months later, she gradually began to complain of the visual oscillation. Continual, unceasing conjugate vertical/rotatory eye movements were observed. Fixation was momentary at best because of an inability to dampen the spontaneous eye movements. Electrooculography (EOG) showed bilateral vertical/rotatory sinusoidal eye movements of 2.5 Hz frequency and 10- to 35-degree amplitude. Both vertical and horizontal optokinetic nystagmus were absent. Caloric stimulation did not evoke any responses bilaterally. There were no rhythmical movements at similar frequencies in other parts of the body such as palatal myoclonus. MRI revealed not only hematoma mainly at the dorsal pontine tegmentum but also hypertrophy of the inferior olive nucleus, suggesting disruption of the central tegmental tract. Lesions of this tract may be one cause of pendular nystagmus. Several drug therapies were investigated for the nystagmus. There was no response to baclofen 15 mg. Trihexyphenidyl 4 mg was discontinued because of drug-induced hallucinations. Tiapride 600 mg and phenobarbital 90 mg were each slightly effective in reducing both frequency and amplitude of nystagmus. Treatment with clonazepam 1 mg resulted in the striking disappearance of nystagmus. She was aware of this and no longer experienced oscillopsia. Despite the visual benefit, however, the patient did not wish to continue this drug because of drowsiness and muscle relaxation. The potential long-term therapeutic application of clonazepam should be further investigated. To our knowledge, there have been no reports of successful treatment in acquired pendular nystagmus with clonazepam. Therefore, based on this favorable experience, it is suggested that clonazepam should be added

  13. Nursing home-acquired pneumonia. Treatment options.

    PubMed

    Marrie, T J; Slayter, K L

    1996-05-01

    Nursing home-acquired pneumonia (NHAP) is a diagnostic and therapeutic challenge, and antimicrobial therapy represents only 1 facet of the treatment of this disease. The nursing home population consists of a mixture of well, frail and dependent elderly. For some residents, supportive care may be the best therapeutic option. A variety of antimicrobial regimens have been proposed for the empirical therapy of NHAP; however, there are still very few data from controlled clinical trials that assess outcome. The clinical trials that have been completed support the concept that an early switch from intravenous to oral therapy can be successfully used to treat pneumonia affecting frail, often seriously ill, groups of patients. Annual influenza vaccine should be offered to all nursing home residents. This practice is about 50% effective in preventing hospitalisation and pneumonia, and about 80% effective in preventing death. The same level of evidence is not available to support the use of pneumococcal vaccine in this group; however, current practice suggests that all nursing home residents receive this vaccine on admission and once every 6 years thereafter. Frequently, knowledge about pneumonia is not applied as optimally as should be done. Care maps have been shown to reduce length of stay and shorten the time from emergency room entry until administration of antibiotic therapy by up to 3 hours. Areas for urgent research attention in patients with NHAP are: (a) proper studies to define the microbiological aetiology of NHAP (this requires bronchoscopy with sampling of the distal airways using a protected bronchial brush); (b) randomised controlled clinical trials of sufficient size to determine whether one antibiotic regimen is superior to another (currently most trials are designed to show that the agent under study is equivalent to a currently used agent); and (c) end-of-life decision making in the nursing home population.

  14. Chapter 22: Hereditary and acquired angioedema.

    PubMed

    Georgy, Mary S; Pongracic, Jacqueline A

    2012-01-01

    Hereditary angioedema (HAE) is an autosomal dominant disorder defined by a deficiency of functional C1 esterase inhibitor (C1-INH). Acquired angioedema (AAE) is caused by either consumption (type 1) or inactivation (type 2) of CI-INH. Both HAE and AAE can be life-threatening. The screening test for both conditions is complement component C4, which is low to absent at times of angioedema or during quiescent periods. A useful test to differentiate HAE from AAE is C1q protein, which is normal in HAE and low in AAE. There are three types of HAE: type 1 HAE is most common, occurring in ∼85% of patients and characterized by decreased production of C1-INH, resulting in reduced functional activity to 5-30% of normal. In type 2, which occurs in 15% of cases, C1-INH is detectable in normal or elevated quantities but is dysfunctional. Finally, type 3, which is rare and almost exclusively occurs in women, is estrogen dependent and associated with normal CI-INH and C4 levels. One-third of these patients have a gain-of-function mutation in clotting factor XII leading to kallikrein-driven bradykinin production. Although the anabolic steroid, danazol, is useful in increasing the concentration of C4 and reducing the episodes of angioedema in HAE and AAE, it has expected adverse effects. Fortunately, disease-specific therapies are available and include C1-INH enzyme for i.v. infusion either acutely or empirically, ecallantide, an inhibitor of kallikrein, and icatibant, a bradykinin B2-receptor antagonist, both approved for acute angioedema and administered, subcutaneously.

  15. Impact of lactobacilli on orally acquired listeriosis

    PubMed Central

    Archambaud, Cristel; Nahori, Marie-Anne; Soubigou, Guillaume; Bécavin, Christophe; Laval, Laure; Lechat, Pierre; Smokvina, Tamara; Langella, Philippe; Lecuit, Marc; Cossart, Pascale

    2012-01-01

    Listeria monocytogenes is a foodborne pathogen that crosses the intestinal barrier and disseminates within the host. Here, we report a unique comprehensive analysis of the impact of two Lactobacillus species, Lactobacillus paracasei CNCM I-3689 and Lactobacillus casei BL23, on L. monocytogenes and orally acquired listeriosis in a gnotobiotic humanized mouse model. We first assessed the effect of treatment with each Lactobacillus on L. monocytogenes counts in host tissues and showed that each decreases L. monocytogenes systemic dissemination in orally inoculated mice. A whole genome intestinal transcriptomic analysis revealed that each Lactobacillus changes expression of a specific subset of genes during infection, with IFN-stimulated genes (ISGs) being the most affected by both lactobacilli. We also examined microRNA (miR) expression and showed that three miRs (miR-192, miR-200b, and miR-215) are repressed during L. monocytogenes infection. Treatment with each Lactobacillus increased miR-192 expression, whereas only L. casei association increased miR-200b and miR-215 expression. Finally, we showed that treatment with each Lactobacillus significantly reshaped the L. monocytogenes transcriptome and up-regulated transcription of L. monocytogenes genes encoding enzymes allowing utilization of intestinal carbon and nitrogen sources in particular genes involved in propanediol and ethanolamine catabolism and cobalamin biosynthesis. Altogether, these data reveal that the modulation of L. monocytogenes infection by treatment with lactobacilli correlates with a decrease in host gene expression, in particular ISGs, miR regulation, and a dramatic reshaping of L. monocytogenes transcriptome. PMID:23012479

  16. Retinal vascular occlusion: a window to diagnosis of familial and acquired thrombophilia and hypofibrinolysis, with important ramifications for pregnancy outcomes

    PubMed Central

    Dixon, Stephan G; Bruce, Carl T; Glueck, Charles J; Sisk, Robert A; Hutchins, Robert K; Jetty, Vybhav; Wang, Ping

    2016-01-01

    Aim Our specific aim was to document the pathoetiologic importance of thrombophilia among females presenting with severe ischemic retinal vein (RVO) or retinal artery (RAO) occlusion, without typical risk factors, and to emphasize that the ophthalmologists’ diagnosis of thrombophilia has important diagnostic and therapeutic downstream ramifications for nonocular thrombosis, including reproductive outcomes. Methods We evaluated familial and acquired thrombophilia in 60 females with RVO (central RVO, n=52; branch RVO, n=8) and 16 with RAO (central RAO, n=11; branch RAO, n=5). They were referred by retinologists, without typical risk factors for RVO/RAO and/or severe ocular ischemic presentation. We focused on extraocular thrombotic events, particularly pregnancy complications, including unexplained spontaneous abortion, pre-eclampsia–eclampsia. Thrombophilia measurements in the 76 females were compared with 62 healthy normal females without ocular vascular occlusions (OVOs). Results The 76 females with OVO were more likely than 62 normal female controls to have high homocysteine (24% vs 0%, P<0.0001), high anticardiolipin antibody (immunoglobulin M, 17% vs 3%, P=0.012), high (>150%) factor VIII (42% vs 11%, P<0.0001), and high (>150%) factor XI (22% vs 4%, P=0.004). Of the 76 females, 26 (34%) had ≥1 spontaneous abortion; 17 (22%) had ≥2 spontaneous abortions and/or pre-eclampsia–eclampsia. Compared to 62 healthy female controls, these 17 females with pregnancy complications had high homocysteine (29% vs 0%, P=0.0003), high anticardiolipin antibody immunoglobulin M (24% vs 3%, P=0.02), high factor VIII (38% vs 11%, P=0.02), and were marginally more likely to be heterozygous for the factor V Leiden mutation (19% vs 3%, P=0.058). Conclusion In females lacking typical risk factors for retinal vascular occlusion or severely ischemic presentation, by diagnosing thrombophilia as an etiology for OVO, the ophthalmologist opens a window to family screening and

  17. Elevated total plasma homocysteine and 667C{r_arrow}T mutation of the 5,10-methylenetetrahydrofolate reductase gene in thrombotic vascular disease

    SciTech Connect

    De Franchis, R.; Sebastio, G.; Andria, G.

    1996-07-01

    Moderate elevation of total plasma homocysteine (tHcy) has been reported as an independent risk factor for thrombotic vascular disease, a well-known multifactorial disorder. Possible genetic causes of elevated tHcy include defects of the sulfur-containing amino acids metabolism due to deficiencies of cystathionine {Beta}-synthase, of 5,10-methylenetetrahydrofolate reductase (MTHFR), and of the enzymes of cobalamin metabolism. An impaired activity of MTHFR due to a thermolabile form of the enzyme has been observed in {le}28% of hyperhomocysteinemic patients with premature vascular disease. More recently, the molecular basis of such enzymatic thermolability has been related to a common mutation of the MTHFR gene, causing a C-to-T substitution at nt 677 (677C{r_arrow}T). This mutation was found in 38% of unselected chromosomes from 57 French Canadian individuals. The homozygous state for the mutation was present in 12% of these subjects and correlated with significantly elevated tHcy. Preliminary evidence indicates that the frequency of homozygotes for the 677C{r_arrow}T mutation may vary significantly in populations from different geographic areas. 5 refs., 2 tabs.

  18. Early surgery for hospital-acquired and community-acquired active infective endocarditis.

    PubMed

    Shibata, Toshihiko; Sasaki, Yasuyuki; Hirai, Hidekazu; Fukui, Toshihiro; Hosono, Mitsuharu; Suehiro, Shigefumi

    2007-06-01

    Active infective endocarditis (IE) is classified into two groups; hospital acquired IE (HIE) and IE other than HIE, which was defined as community-acquired IE (CIE). Eighty-two patients underwent surgical treatment for active IE. Seventy-one cases were CIE group and eleven were HIE. There were six patients with native valve endocarditis and five cases of prosthetic valve endocarditis in the HIE group. We compared the surgical outcome of both types of active IE retrospectively. The preoperative status of the patients in the HIE group was more critical than that in the CIE group. Streptococcus spp. were the major micro-organisms in the CIE group (39%), while 82% of the HIE cases were caused by Staphylococcus spp. All Staphylococcus organisms in the HIE group were methicillin resistant. There were 10 hospital deaths, three in the CIE group and seven in the HIE group. Operative mortality in the HIE group was significantly higher than in the CIE group (63.6% vs. 4.2%, P<0.001). The outcome of early operation was satisfactory for active CIE, but poor for HIE. These types of active IE should be considered separately.

  19. [Report of 2 cases with acquired von Willebrand disease and one with acquired hemophilia A].

    PubMed

    Martínez-Murillo, C; Quintana González, S; Ambriz Fernández, R; Domínguez García, V; Rodríguez Moyado, H; Arias Aranda, A; Collazo Jaloma, J; Gutiérrez Romero, M

    1995-01-01

    We report three patients with acquired inhibitors against F VIII:C/F vW:Ag complex. Two patients had acquired hemophilia A. The three patients presented with bleeding diathesis. Case 1 was a 19 years old woman with Graves-Basedow disease; case 2 was a 40 years old woman with systemic lupus erythematosus of four years; and case 3 a 38 years old woman who had had rheumatoid arthritis for five years and was in her 3d month postpartum. The F VIII:C level was below 8 U/dL in all cases. The F vW:Ag, ristocetin cofactor and platelet aggregation with ristocetin were diminished in the two cases with von Willebrand. Inhibitor to F VIII:C was 50, 38 and 20 Bethesda units, respectively, for cases 1, 2 and 3. The three patients showed clinical response to DDAVP and cryoprecipitates with partial response in laboratory tests. All patients responded to corticosteroid treatment, but immunosuppressive treatment was necessary in case 3.

  20. 33 CFR 211.2 - Authority to acquire real estate.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... PROJECTS Real Estate; General § 211.2 Authority to acquire real estate. (a) Congressional authority... of the Army to acquire real estate for river and harbor improvements, flood control projects and allied purposes, is based upon enactments of the Congress authorizing the particular projects...