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. Background Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS) are two important acute conditions to diagnose. Thrombotic microangiopathy (TMA) is a broad pathophysiologic process that leads to microangiopathic hemolytic anemia and thrombocytopenia, and involves capillary and small-vessel platelet aggregates. The most common cause is disseminated intravascular coagulation, which may be differentiated by abnormal coagulation. Clinically, a number of conditions present with microangiopathic hemolytic anemia and thrombocytopenia, including cancer, infection, transplantation, drug use, autoimmune disease, and pre-eclampsia and hemolysis, elevated liver enzymes and low platelet count syndrome in pregnancy. Despite overlapping clinical presentations, TTP and HUS have distinct pathophysiologies and treatment pathways. Objectives To present a consensus document from an International Working Group on TTP and associated thrombotic microangiopathies (TMAs). Methods The International Working Group has proposed definitions and terminology based on published information and consensus-based recommendations. Conclusion The consensus aims to aid clinical decisions, but also future studies and trials, utilizing standardized definitions. It presents a classification of the causes of TMA, and criteria for clinical response, remission and relapse of congenital and immune-mediated TTP. © 2016 International Society on Thrombosis and Haemostasis.

Thrombotic thrombocytopenic purpura or immune thrombocytopenia in a sickle cell/β+-thalassemia patient: a rare and challenging condition.

PubMed

Vlachaki, Efthymia; Agapidou, Aleka; Neokleous, Nikolaos; Adamidou, Despoina; Vetsiou, Evaggelia; Boura, Panagiota

2014-10-01

The diagnosis of thrombotic thrombocytopenic purpura is one of the possible diagnosis when a patient is admitted with unexpected micro-angiopathic hemolytic anemia and thrombocytopenia. The combination of sickle cell/β(+)-thalassemia and thrombotic thrombocytopenic purpura is rare and triggering. This article describes the poor outcome of a patient with sickle cell/β(+)-thalassemia presenting with gingival bleeding, severe thrombocytopenia and anemia. The patient had normal renal function, no neurological deficit and he was initially treated as immune thrombocytopenic purpura. He eventually died due to multi-organ failure and brain hemorrhage even though he had started plasma exchange sessions. The co-existence of thrombotic thrombocytopenic purpura and sickle cell anemia is making the diagnosis of the former difficult. Early and rapid intervention is critical to the outcome. Copyright © 2014 Elsevier Ltd. All rights reserved.

Current insights into thrombotic microangiopathies: Thrombotic thrombocytopenic purpura and pregnancy.

PubMed

von Auer, Charis; von Krogh, Anne-Sophie; Kremer Hovinga, Johanna A; Lämmle, Bernhard

2015-02-01

The complex relation between thrombotic thrombocytopenic purpura (TTP) and pregnancy is concisely reviewed. Pregnancy is a very strong trigger for acute disease manifestation in patients with hereditary TTP caused by double heterozygous or homozygous mutations of ADAMTS13 (ADisintegrin And Metalloprotease with ThromboSpondin type 1 domains, no. 13). In several affected women disease onset during their first pregnancy leads to the diagnosis of hereditary TTP. Without plasma treatment mother and especially fetus are at high risk of dying. The relapse risk during a next pregnancy is almost 100% but regular plasma transfusion starting in early pregnancy will prevent acute TTP flare-up and may result in successful pregnancy outcome. Pregnancy may also constitute a mild risk factor for the onset of acute acquired TTP caused by autoantibody-mediated severe ADAMTS13 deficiency. Women having survived acute acquired TTP may not be at very high risk of TTP relapse during an ensuing next pregnancy but seem to have an elevated risk of preeclampsia. Monitoring of ADAMTS13 activity and inhibitor titre during pregnancy may help to guide management and to avoid disease recurrence. Finally, TTP needs to be distinguished from the much more frequent hypertensive pregnancy complications, preeclampsia and especially HELLP (Hemolysis, Elevated Liver Enzymes, Low Platelet count) syndrome. © 2015 Elsevier Ltd. All rights reserved.

[Clopidogrel induced thrombotic thrombocytopenic purpura].

PubMed

Karkowski, L; Wolf, M; Lescampf, J; Coppérré, B; Veyradier, A; Ninet, J; Hot, A

2011-12-01

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder. Drug-induced TTP is uncommon and we report a TTP associated with the use of clopidogrel. We report a 50-year-old man who presented with acute myocardial infarction and received clopidogrel therapy. He developed acute TTP ten days after clopidogrel onset. Imputability of the drug was demonstrated during a reintroduction test. Deficiency of ADAMTS 13 was confirmed and autoantibodies against ADAMTS 13 were detected. Complete remission was obtained after 24 plasma exchange sessions and adjunction of corticosteroids. Drug-induced TTP are probably immunologic, as was demonstrated in our patient. Clinicians should be aware of this possible uncommon adverse effect of clopidogrel because prompt therapy is imperative for life saving. Copyright © 2011 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Thrombotic thrombocytopenic purpura possibly triggered by Graves’ disease

PubMed Central

Chitnis, Saurabh D; Mene-Afejuku, Tuoyo O; Aujla, Amandeep; Shady, Ahmed; Gil, Gaby S; Cativo, Eder Hans; Popescu-Martinez, Andrea

2017-01-01

Abstract Thrombotic thrombocytopenic purpura (TTP) is a part of a spectrum of thrombotic microangiopathy syndromes which are mainly characterized by platelet aggregation causing microangiopathic hemolytic anemia, thrombocytopenia and microvascular occlusion. In literature, very few cases expressing a direct association between pre-existing Grave’s disease and TTP have been described. A 37-year-old African–American woman with past medical history of Grave’s disease and polysubstance abuse who presented with complaints of dyspnoea at rest and chest pain was diagnosed to have TTP on further evaluation. Patient also showed severely elevated thyroid hormones and suppressed thyroid stimulating hormone levels indicating severe thyrotoxicosis. Initiation of prompt management of TTP and thyrotoxicosis led to a favorable patient outcome. In conclusion, patients presenting with thyrotoxicosis, thrombocytopenia and microangioapthic hemolytic anemia without an alternative cause should be treated and screened for TTP due to the high fatality associated with untreated or untimely detection of this disease. PMID:29744115

Cardiac troponin-I on diagnosis predicts early death and refractoriness in acquired thrombotic thrombocytopenic purpura. Experience of the French Thrombotic Microangiopathies Reference Center.

PubMed

Benhamou, Y; Boelle, P-Y; Baudin, B; Ederhy, S; Gras, J; Galicier, L; Azoulay, E; Provôt, F; Maury, E; Pène, F; Mira, J-P; Wynckel, A; Presne, C; Poullin, P; Halimi, J-M; Delmas, Y; Kanouni, T; Seguin, A; Mousson, C; Servais, A; Bordessoule, D; Perez, P; Hamidou, M; Cohen, A; Veyradier, A; Coppo, P

2015-02-01

Cardiac involvement is a major cause of mortality in patients with thrombotic thrombocytopenic purpura (TTP). However, diagnosis remains underestimated and delayed, owing to subclinical injuries. Cardiac troponin-I measurement (cTnI) on admission could improve the early diagnosis of cardiac involvement and have prognostic value. To assess the predictive value of cTnI in patients with TTP for death or refractoriness. The study involved a prospective cohort of adult TTP patients with acquired severe ADAMTS-13 deficiency (< 10%) and included in the registry of the French Reference Center for Thrombotic Microangiopathies. Centralized cTnI measurements were performed on frozen serum on admission. Between January 2003 and December 2011, 133 patients with TTP (mean age, 48 ± 17 years) had available cTnI measurements on admission. Thirty-two patients (24%) had clinical and/or electrocardiogram features. Nineteen (14.3%) had cardiac symptoms, mainly congestive heart failure and myocardial infarction. Electrocardiogram changes, mainly repolarization disorders, were present in 13 cases. An increased cTnI level (> 0.1 μg L(-1) ) was present in 78 patients (59%), of whom 46 (59%) had no clinical cardiac involvement. The main outcomes were death (25%) and refractoriness (17%). Age (P = 0.02) and cTnI level (P = 0.002) showed the greatest impact on survival. A cTnI level of > 0.25 μg L(-1) was the only independent factor in predicting death (odds ratio [OR] 2.87; 95% confidence interval [CI] 1.13-7.22; P = 0.024) and/or refractoriness (OR 3.03; 95% CI 1.27-7.3; P = 0.01). A CTnI level of > 0.25 μg L(-1) at presentation in patients with TTP appears to be an independent factor associated with a three-fold increase in the risk of death or refractoriness. Therefore, cTnI level should be considered as a prognostic indicator in patients diagnosed with TTP. © 2014 International Society on Thrombosis and Haemostasis.

[Haemolytic uremic syndrome and thrombotic thrombocytopenic purpura: classification based on molecular etiology and review of recent developments in diagnostics].

PubMed

Prohászka, Zoltán

2008-07-06

Haemolytic uremic syndrome and thrombotic thrombocytopenic purpura are overlapping clinical entities based on historical classification. Recent developments in the unfolding of the pathomechanisms of these diseases resulted in the creation of a molecular etiology-based classification. Understanding of some causative relationships yielded detailed diagnostic approaches, novel therapeutic options and thorough prognostic assortment of the patients. Although haemolytic uremic syndrome and thrombotic thrombocytopenic purpura are rare diseases with poor prognosis, the precise molecular etiology-based diagnosis might properly direct the therapy of the affected patients. The current review focuses on the theoretical background and detailed description of the available diagnostic possibilities, and some practical information necessary for the interpretation of their results.

A Case of Systemic Lupus Erythematosus developing Two years after Remission of Thrombotic Thrombocytopenic Purpura

PubMed Central

Myung, Seung-Jae; Yoo, Bin; Lee, Kyoo-Hyung; Yoo, Mi-Ran; Choi, Seung-Won; Yoo, Eun-Sil; Chi, Hyun-Sook; Moon, Hee-Bom

1996-01-01

We describe a 17-year-old male who presented with thrombotic thrombocytopenic purpura (TTP) and 2 years thereafter developed central nervous system lupus and nephritis. The association of TTP and systemic lupus erythematosus has been described, but the unusual sequence and chronological separation is very rare. PMID:8854658

A 14-Year Experience in the Management of Patients with Acquired Immune Thrombotic Thrombocytopenic Purpura in Northern Israel.

PubMed

Rinott, Nadav; Mashiach, Tatiana; Horowitz, Netanel A; Schliamser, Liliana; Sarig, Galit; Keren-Politansky, Anat; Dann, Eldad J

2015-01-01

Acquired idiopathic thrombotic thrombocytopenic purpura (I-TTP) is a life-threatening microangiopathic disorder usually treated with therapeutic plasma exchange (TPE). The current study assessed the role of rituximab in the treatment of complicated I-TTP. The sequence of TTP events was compared in a group of I-TTP patients treated with TPE and a cohort of refractory or relapsed patients who also received rituximab. This retrospective evaluation included 45 I-TTP patients, treated between January 2000 and October 2013, who underwent at least 3 TPE procedures and were followed up until December 2013 or death. Thirty-one patients with an uncomplicated course received TPE only. Fourteen patients had a complicated course due to either a primary refractory/exacerbated disease (n = 5) or relapse (n = 9) and received rituximab together with TPE. The median number of TPE procedures performed in the first TTP episode in the uncomplicated cohort and groups with primary refractory or relapsed TTP was 11, 27 and 45, respectively. The relapse rates per follow-up year in the uncomplicated I-TTP, primary refractory and relapsed I-TTP groups were 0.18, 0.2 and 0.6 episodes, respectively. After rituximab therapy this rate dropped to 0.2 per year in the relapsed subgroup. In conclusion, about a quarter of patients with I-TTP had a complicated course and experienced a major benefit from rituximab in terms of effectiveness and safety. © 2015 S. Karger AG, Basel.

The role of human leukocyte antigen DRB1-DQB1 haplotypes in the susceptibility to acquired idiopathic thrombotic thrombocytopenic purpura.

PubMed

Sinkovits, György; Szilágyi, Ágnes; Farkas, Péter; Inotai, Dóra; Szilvási, Anikó; Tordai, Attila; Rázsó, Katalin; Réti, Marienn; Prohászka, Zoltán

2017-02-01

The acquired form of idiopathic thrombotic thrombocytopenic purpura (TTP) is an autoimmune disease, in which the underlying ADAMTS13-deficiency is caused by inhibitory autoantibodies against the protease. Human leukocyte antigens (HLA), responsible for antigen presentation, play an important role in the development of antibodies. The loci coding HLA DR and DQ molecules are inherited in linkage as haplotypes. The c.1858C>T polymorphism of the PTPN22 gene, which codes a protein tyrosine phosphatase important in lymphocyte activation, predisposes to a number of autoimmune diseases. We determined the HLA-DRB1-DQB1 haplotypes and the PTPN22 c.1858C>T genotypes in 75 patients with acquired idiopathic TTP and in healthy controls, in order to assess the role of these genetic factors and their interactions in the susceptibility to TTP. We found that the carrier frequencies of the DRB1 ∗ 11-DQB1 ∗ 03 and DRB1 ∗ 15-DQB1 ∗ 06 haplotypes were higher, while those of the DRB1 ∗ 07-DQB1 ∗ 02 and DRB1 ∗ 13-DQB1 ∗ 06 haplotypes were lower in TTP patients. There was no difference in the overall frequency of the PTPN22 c.1858T allele between TTP patients and controls. In conclusion, we identified four HLA-DRB1-DQB1 haplotypes associated with an increased (DRB1 ∗ 11-DQB1 ∗ 03 and DRB1 ∗ 15-DQB1 ∗ 06) or a decreased (DRB1 ∗ 07-DQB1 ∗ 02 and DRB1 ∗ 13-DQB1 ∗ 06) susceptibility to acquired idiopathic TTP. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Evaluation of Plasma Platelet Microparticles in Thrombotic Thrombocytopenic Purpura.

PubMed

Tahmasbi, Leila; Karimi, Mehran; Kafiabadi, Sedigheh Amini; Nikougoftar, Mahin; Haghpanah, Sezaneh; Ranjbaran, Reza; Moghadam, Mohamad

2017-01-01

Platelet microparticles (PMPs) have a procoagulant activity about 50-100 times greater than active platelets due to high expression of negatively charged phospholipids on their surfaces. In this study, we evaluated microparticle immunophenotyping and also plasma PMPs level in patients with Thrombotic Thrombocytopenic Purpura (TTP) in Southern Iran. We had two study groups: 15 TTP patients and 15 healthy control group and PMPs from platelet concentrate (PC) at the 5 th day of storage. Microparticles were prepared in two steps, by low and high centrifugation followed by size confirmation via 'Dynamic Light Scattering (DLS)' Zetasizer. Immunophenotyping of PMPs was done via flow cytometry, using a FACS Calibur flow cytometer (BD, USA). PMPs counts were obtained using Partec-cyflow and Polysciences Microbeads (1 micron in diameter). Results were analyzed using FlowJo 7.6 (Treestar, USA) and Partec FlowMax software. Our results showed that the majority of microparticles in TTP patients and normal individuals were PMPs and also demonstrated that the plasma PMPs level in TTP patients was higher than the normal control group ( P -value<0.001). It seems that elevated PMPs level in TTP patients could be related to thrombotic events. Nevertheless, more studies are needed to confirm these results. © 2017 by the Association of Clinical Scientists, Inc.

Overweight individuals are at increased risk for thrombotic thrombocytopenic purpura.

PubMed

Nicol, Kathleen K; Shelton, Brent J; Knovich, Mary Ann; Owen, John

2003-11-01

Our understanding of the pathophysiology of thrombotic thrombocytopenic purpura, TTP, has increased dramatically in the past few years with the identification of the role of ADAMTS13. Nonetheless, risk factors for the development of acute TTP are few. Informally, obesity was felt to be common in patients with TTP and so a formal study was undertaken to further define this association. We report our data in 105 patients with classical TTP as defined by thrombocytopenia and microangiopathic hemolytic anemia. We found that marked obesity is a previously unrecognized risk factor with an associated odds ratio of 7.6. Interestingly, despite this increased risk, obesity might well be associated with lower mortality, although this did not reach statistical significance. Copyright 2003 Wiley-Liss, Inc.

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

Preclinical assessment of a new recombinant ADAMTS-13 drug product (BAX930) for the treatment of thrombotic thrombocytopenic purpura.

PubMed

Kopić, A; Benamara, K; Piskernik, C; Plaimauer, B; Horling, F; Höbarth, G; Ruthsatz, T; Dietrich, B; Muchitsch, E-M; Scheiflinger, F; Turecek, M; Höllriegl, W

2016-07-01

Essentials ADAMTS-13-deficiency is a cause of thrombotic thrombocytopenic purpura (TTP). Preclinical safety of recombinant human ADAMTS-13 (BAX930) was shown in animal models. Preclinical efficacy of BAX930 was shown in a mouse model of TTP. BAX930 showed advantageous efficacy over fresh frozen plasma, the current standard of care. Click to hear Dr Cataland and Prof. Lämmle present a seminar on Thrombotic Thrombocytopenic Purpura (TTP): new Insights in Pathogenesis and Treatment Modalities. Background Thrombotic thrombocytopenic purpura (TTP) is a rare blood disorder characterized by microthrombosis in small blood vessels of the body, resulting in a low platelet count. Baxalta has developed a new recombinant ADAMTS-13 (rADAMTS-13) product (BAX930) for on-demand and prophylactic treatment of patients with hereditary TTP (hTTP). Objectives To evaluate the pharmacokinetics, efficacy and safety of BAX930 in different species, by use of an extensive preclinical program. Methods The prophylactic and therapeutic efficacies of BAX930 were tested in a previously established TTP mouse model. Pharmacokinetics were evaluated after single intravenous bolus injection in mice and rats, and after repeated dosing in cynomolgus monkeys. Toxicity was assessed in rats and monkeys, safety pharmacology in monkeys, and local tolerance in rabbits. Results BAX930 was shown to be efficacious, as demonstrated by a stabilized platelet count in ADAMTS-13 knockout mice that were thrombocytopenic when treated. Prophylactic efficacy was dose-dependent and comparable with that achieved by treatment with fresh frozen plasma, the mainstay of hTTP treatment. Therapeutic efficacy was treatment interval-dependent. Safety pharmacology evaluation did not show any deleterious effects of BAX930 on cardiovascular and respiratory functions in monkeys. The compound's pharmacokinetics were similar and dose-proportional in mice, rats, and monkeys. BAX930 was well tolerated in rats, monkeys, and rabbits, even

[Acquired amegacaryocytic thrombocytopenic purpura hiding acute myeloid leukemia].

PubMed

Eddou, Hicham; Zinebi, Ali; Khalloufi, Abdelaziz; Sina, Mohammed; Mahtat, Mehdi; Doghmi, Kamal; Mikdame, Mohammed; Moudden, Mohammed Karim; Baaj, Mohammed El

2017-01-01

Acquired amegakaryocytic thrombocytopenic purpura is a very rare condition characterized by severe thrombocytopenia linked to the reduction or disappearance of megakaryocytes in the bone marrow. It may be primary idiopathic or secondary to many pathological conditions including hematologic disorders. We report the case of a 24-year-old patient admitted for haemorrhagic syndrome caused by immunological thrombocytopenic purpura. The diagnosis was acquired amegakaryocytosis after the failure of corticotherapy and the performance of myelography. The patient was treated with ciclosporin with rapid progression to acute myeloblastic leukemia. The progression of acquired amegakaryocytosis to acute leukemia is reported but it is generally not so rapid and above all it is preceded by myelodysplastic syndrome or medullary aplasia. This study highlights the importance of a close follow-up of these pathologies with a benign-like appearance.

Pegylated bovine carboxyhaemoglobin utilisation in a thrombotic thrombocytopenic purpura patient.

PubMed

Sam, C; Desai, P; Laber, D; Patel, A; Visweshwar, N; Jaglal, M

2017-08-01

To determine if pegylated bovine carboxyhaemoglobin can be utilised in a thrombotic thrombocytopenic purpura (TTP) patient. TTP is a condition characterized by thrombotic microangiopathy and has a high mortality rate when left untreated. Therapeutic plasma exchange is well established as the most effective and evidence-based treatment of TTP. The ability to administer plasma exchange therapy is limited in Jehovah's Witnesses who decline blood products due to religious beliefs. Pegylated bovine carboxyhaemoglobin is a novel oxygen transfer agent in development for the management of complications of ischaemia due to acute anaemia. Treatment was well tolerated, with grade 1 paresthesia of the right face and arm 1 h after the first infusion of Sanguinate, which spontaneously resolved and did not recur, and grade 1 cardiac troponin elevation after receiving the medication (with peak at 0·079 ng mL -1 ), but further workup with electrocardiogram and echocardiogram was unremarkable. By discharge on day 19, the patient's haemoglobin increased to 8·8 g dL -1 and platelet count to 221 000. We report the first case of TTP in a Jehovah's Witness that was successfully managed with the use of pegylated bovine carboxyhaemoglobin as an adjunct medication. © 2017 British Blood Transfusion Society.

ADAMTS13 test and/or PLASMIC clinical score in management of acquired thrombotic thrombocytopenic purpura: a cost-effective analysis.

PubMed

Kim, Chong H; Simmons, Sierra C; Williams, Lance A; Staley, Elizabeth M; Zheng, X Long; Pham, Huy P

2017-11-01

The ADAMTS13 test distinguishes thrombotic thrombocytopenic purpura (TTP) from other thrombotic microangiopathies (TMAs). The PLASMIC score helps determine the pretest probability of ADAMTS13 deficiency. Due to inherent limitations of both tests, and potential adverse effects and cost of unnecessary treatments, we performed a cost-effectiveness analysis (CEA) investigating the benefits of incorporating an in-hospital ADAMTS13 test and/or PLASMIC score into our clinical practice. A CEA model was created to compare four scenarios for patients with TMAs, utilizing either an in-house or a send-out ADAMTS13 assay with or without prior risk stratification using PLASMIC scoring. Model variables, including probabilities and costs, were gathered from the medical literature, except for the ADAMTS13 send-out and in-house tests, which were obtained from our institutional data. If only the cost is considered, in-house ADAMTS13 test for patients with intermediate- to high-risk PLASMIC score is the least expensive option ($4,732/patient). If effectiveness is assessed as measured by the number of averted deaths, send-out ADAMTS13 test is the most effective. Considering the cost/effectiveness ratio, the in-house ADAMTS13 test in patients with intermediate- to high-risk PLASMIC score is the best option, followed by the in-house ADAMTS13 test without the PLASMIC score. In patients with clinical presentations of TMAs, having an in-hospital ADAMTS13 test to promptly establish the diagnosis of TTP appears to be cost-effective. Utilizing the PLASMIC score further increases the cost-effectiveness of the in-house ADAMTS13 test. Our findings indicate the benefit of having a rapid and reliable in-house ADAMTS13 test, especially in the tertiary medical center. © 2017 AABB.

Differentiation of pernicious anemia from thrombotic thrombocytopenic purpura: The clinical value of subtle pathologic findings.

PubMed

Abbott, Daniel W; Friedman, Kenneth D; Karafin, Matthew S

2016-12-01

Thrombotic thrombocytopenic purpura (TTP) is a microangiopathic hemolytic anemia that requires emergent treatment with plasma exchange and is one of the most important conditions for which apheresis service professionals are consulted. Careful interpretation of initial laboratory values and the peripheral blood smear is a critical first step to determining the need for plasma exchange because other conditions can show deceptively similar red cell morphology, and ADAMTS13 levels are often not rapidly available. We report a case of a patient who was initially diagnosed with TTP and treated with plasma exchange based on preliminary laboratory data and a peripheral blood smear that contained bizarre microcytic red blood cells presumed to be schistocytes. The peripheral blood smear was later interpreted by the hematopathologist to be inconsistent with TTP, and further workup led to a diagnosis of severe vitamin B12 deficiency secondary to pernicious anemia. This case highlights the diagnostic complexity of thrombotic microangiopathies and the importance of a critical evaluation of the blood smear and presenting laboratory data when there is a concern for TTP. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Antiphospholipid syndrome with autoimmune hemolytic anemia which mimics thrombotic thrombocytopenic purpura].

PubMed

Karasawa, Naoki; Taniguchi, Yasuhiro; Hidaka, Tomonori; Katayose, Keiko; Kameda, Takuro; Side, Kotaro; Shimoda, Haruko; Nagata, Kenji; Kubuki, Yoko; Matsunaga, Takuya; Shimoda, Kazuya

2010-04-01

A 67-year-old woman was admitted to the hospital for lethargy, fever, hemolytic anemia, thrombocytopenia, and consciousness disturbance. Direct Coombs test was positive, and anti-cardiolipin beta2-glycoprotein I antibody was detected. She was diagnosed with antiphospholipid syndrome complicated with autoimmune hemolytic anemia (AIHA). She demonstrated variable consciousness disturbance, inability to distinguish right from left, dysgraphia and dyscalculia. Multiple cerebral infarctions, especially dominant cerebral hemisphere infarctions, were observed on magnetic resonance imaging. A ventilation-perfusion scan demonstrated the presence of a ventilation-perfusion mismatch in both lung fields, and multiple veinous embolisms in the right femoral, bilateral the great saphenous and popliteal veins. Therefore, pulmonary embolism and thrombophlebitis were diagnosed. Based on these findings, it was necessary to distinguish this diagnosis from thrombotic thrombocytopenic purpura (TTP). As ADAMTS-13 activity was within the normal range, TTP was denied. Thereafter, the patient was treated with 1 mg/kg of prednisolone for AIHA, 3 mg of warfarin, and 3500 units of low-molecular-weight heparin for thrombosis, and her condition improved.

Rituximab maintenance for relapsed refractory thrombotic thrombocytopenic purpura.

PubMed

Bhagirath, Vinai C; Kelton, John G; Moore, Jane; Arnold, Donald M

2012-12-01

Rituximab, an anti-CD20 chimeric monoclonal antibody, has been used successfully to treat patients with relapsed or refractory thrombotic thrombocytopenic purpura (TTP); however, the optimal dose and frequency and the role of rituximab maintenance remain uncertain. We describe a 45-year-old woman with chronic relapsing immune thrombocytopenia who responded to rituximab retreatment administered in four doses over the course of 12 months. Previously, she had received four doses of rituximab and sustained a remission for 19 months. During her latest TTP relapse, multiple treatments were administered including rituximab retreatment. After the first dose (375 mg/m2), she developed serum sickness requiring further doses to be deferred. Three subsequent doses were administered at 4-month intervals over the course of 12 months. ADAMTS13 activity was measured by von Willebrand factor (VWF) digestion. ADAMTS13 inhibition was measured by a modification of the VWF digestion assay and anti-ADAMTS13 antibodies were measured by enzyme-linked immunoassay (enzyme-linked immunosorbent assay, American Diagnostica). Clinical and laboratory remission were achieved after one dose of rituximab, with normalization of ADAMTS13 activity and disappearance of ADAMTS13 inhibitor. Three subsequent doses of rituximab were given without incident and the patient remained in remission after 3.5 years of follow-up (2.5 years since her last dose of rituximab). Maintenance dosing of rituximab should be considered in some patients with relapsing TTP. © 2012 American Association of Blood Banks.

Possible green tea-induced thrombotic thrombocytopenic purpura.

PubMed

Liatsos, George D; Moulakakis, Antonios; Ketikoglou, Ioannis; Klonari, Stella

2010-04-01

A case of a patient who developed thrombotic thrombocytopenic purpura (TTP) after consuming a weight-loss product containing green tea is reported. A 38-year-old, 68-kg Caucasian woman arrived at the emergency department with a one-week history of malaise, fatigue, and petechiae of the skin. She had no symptoms of infection and denied illegal drug use. Her medical history included hypothyroidism, for which she was treated with levothyroxine 150 microg daily for the past four years. She reported that she had been using a green tea preparation for the two months before admission to lose body weight. The daily preparation contained 200 mg of green tea extract 5:1, equivalent to 1 g of natural green tea. On clinical examination, the patient appeared acutely ill and was afebrile, with pallor, petechiae, and purpura of the extremities. Laboratory test results at the time of admission revealed that the patient had anemia and marked thrombocytopenia. A peripheral blood smear demonstrated a feature of microangiopathic hemolytic anemia. Immunoglobulin G autoantibodies against ADAM metallopeptidase with thrombospondin type 1 motif, 13 were detected. On hospital day 3, the patient appeared confused and exhibited aphasia that was initially transient but then recurrent. Brain computerized tomography did not exhibit focal pathology. Over the next few days, her neurologic symptoms subsided and her platelet count and hematocrit value gradually increased. Plasmapheresis was performed (12 procedures). Corticosteroid treatment was also initiated. After 20 days of hospitalization, the patient was discharged. A 38-year-old woman developed TTP after consuming a weight-loss product containing green tea extract for two months.

Twice-daily therapeutical plasma exchange-based salvage therapy in severe autoimmune thrombotic thrombocytopenic purpura: the French TMA Reference Center experience.

PubMed

Soucemarianadin, Myriam; Benhamou, Ygal; Delmas, Yahsou; Pichereau, Claire; Maury, Eric; Pène, Frédéric; Halimi, Jean-Michel; Presne, Claire; Thouret, Jean-Marc; Veyradier, Agnès; Coppo, Paul

2016-08-01

Daily therapeutic plasma exchange (TPE) and rituximab improved thrombotic thrombocytopenic purpura (TTP) prognosis. In the more severe cases, salvage therapies including twice-daily TPE and/or cyclophosphamide may be proposed and require evaluation. TTP was defined as a thrombotic microangiopathy (TMA) with severe (<10%) acquired ADAMTS13 deficiency. Among patients included in the French Reference Center for TMA registry, we considered those with a severe disease (i.e., unresponsive to daily TPE and rituximab) who received twice-daily TPE. Nineteen of 289 (6.6%) patients with TTP were treated by twice-daily TPE between 2008 and 2014. Twice-daily TPE was associated with rituximab in 16 cases. The median duration of twice-daily TPE treatment was 3 d (2-22 d). In 6 patients (31.6%), additional treatments (mainly pulses of cyclophosphamide) were performed because of a persistently refractory disease (4 cases) or an exacerbation (2 cases), despite twice-daily TPE. Only one patient (5.3%) died. The other 18 achieved a durable complete remission 25.5 d (13-68 d) after the first TPE. The median follow-up was 14.4 months (7 d-45 months). Twice-daily TPE may be an efficient strategy in the more severe TTP patients with a short-term life-threatening disease that could overcome their poor prognosis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Thrombotic microangiopathy].

PubMed

Beutel, G; Kielstein, J T; Ganser, A

2013-09-01

Thrombotic microangiopathy should be suspected every time the combination of microangiopathic hemolytic anemia without a coexisting cause, thrombocytopenia as well as renal and/or neurologic abnormalities occurs. The general term thrombotic microangiopathy includes different subtypes of the disease leading to abnormalities in multiple organ systems by endothelial injury and formation of platelet-rich thrombi in small vessels. The main types include thrombotic thrombocytopenic purpura in case of dominant neurologic abnormalities and the hemolytic uremic syndrome in case of acute kidney injury, respectively. Although these syndromes differ in their etiologies, clinical features, response to treatment, and prognosis, an early initiation of a direct therapeutic intervention frequently determines the clinical course of the patient. Irrespectively of the underlying etiology, plasma exchange is an essential component of acute therapeutic intervention while ongoing diagnostics are used to identify the definite treatment.

A case report of uncompensated alkalosis induced by daily plasmapheresis in a patient with thrombotic thrombocytopenic purpura.

PubMed

Nagai, Yoshiko; Itabashi, Mitsuyo; Mizutani, Mayuko; Ogawa, Tetsuya; Yumura, Wako; Tsuchiya, Ken; Nitta, Kosaku

2008-02-01

Plasmapheresis (PP) is widely known as the standard therapy for thrombotic thrombocytopenic purpura (TTP). Citrate is used as an anticoagulant in fresh frozen plasma, and the large amount of citrate infused during PP induces metabolic alkalosis. A 29-year-old woman was diagnosed with TTP associated with systemic lupus erythematosus, and was treated by daily PP in addition to a steroid, an immunosuppressant, vincristine, and cyclophosphamide. Uncompensated alkalosis caused by a combination of metabolic and respiratory alkalosis developed after artificial ventilation was discontinued. Her metabolic status improved after controlling her respiratory status and the activity of the TTP. Metabolic alkalosis is a common complication in TTP patients treated by frequent PP, but several factors that affect metabolic status may aggravate the alkalosis and induce uncompensated alkalosis.

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. © 2017 Wiley Periodicals, Inc.

Diagnosis and management of thrombotic thrombocytopenic purpura (TTP) in Australia: findings from the first 5 years of the Australian TTP/thrombotic microangiopathy registry.

PubMed

Blombery, P; Kivivali, L; Pepperell, D; McQuilten, Z; Engelbrecht, S; Polizzotto, M N; Phillips, L E; Wood, E; Cohney, S

2016-01-01

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening thrombotic microangiopathy (TMA). In 2009, the Australian TTP/TMA registry was established to collect data on patients presenting with TTP/TMA throughout Australia. To summarise information on the diagnosis and management of patients with TTP collected in the first 5 years (2009-2014) of the Australian TTP registry. Registry data from June 2009 to October 2014 were reviewed. Fifty-seven patients were identified with TTP (defined as ADAMTS13 activity <10%), accounting for 72 clinical episodes. ADAMTS13 inhibitor testing was performed in nine out of 57 patients (16%), reflecting the limited availability of accredited testing facilities. Sixty-seven out of 72 episodes were treated with therapeutic plasma exchange (PEx) using cryodepleted plasma (40% of episodes), fresh frozen plasma (36%) or a mixture (22%). Median exposure to plasma products was 55.9 L. PEx was commenced ≥2 days from stated diagnosis in 15% of episodes. Adverse reactions to PEx were common with documented allergic reactions (including life threatening) in 21% of episodes. Adjunctive immunosuppression was documented in 76% of episodes (corticosteroid 71% and rituximab 39%). Platelet transfusion was administered in 15% of episodes. Data from the Australian TTP/TMA registry suggest a heterogenous approach to the diagnosis and management of TTP in Australia over the assessed period. These observations highlight areas for improvement and standardisation of practice, including comprehensive diagnostic testing, more immediate access to PEx and a more uniform approach to adjunctive immunosuppression and supportive care. © 2015 Royal Australasian College of Physicians.

[Thrombotic microangiopathy in pregnancy complicated by acute hemorrhagic-necrotic pancreatitis during early puerperium].

PubMed

Redechová, S; Féderová, L; Hammerová, L; Filkászová, A; Horváthová, D; Redecha, M

2014-06-01

Authors in the article describe a case of a patient with thrombotic thrombocytopenic purpurain 37 weeks gestation complicated by acute severe hemorrhagic-necrotic pancreatitis during the early puerperium. Case report. Ist Department of gynaecology and obstetrics of the Comenius University Bratislava. 33-years-old patient in the 37 weeks gestation was admitted to our department with the signs of HELLP syndrome (hemolysis, elevated liver enzymes, low platelets). Due to the worsening clinical status, we have performed caesarean section. After the transient stabilization of the patient's clinical status, the hemolysis with severe thrombocytopenia reappeared. Based on the clinical signs of abdominal pain and computer tomography, the diagnosis of acute hemorrhagic-necrotic pancreatitis was set. The primary diagnosis was thrombotic thrombocytopenic purpura. Therefore, therapeutic plasma exchange was performed with consequent improvement of the patients clinical state. Normalization of the platelet count was achieved after 4.plasma exchanges. Consequently 5 plasma exchanges were performed. However, one month later, the disease relapsed. Therapeutic plasma exchanges were needed again (4x), with anti CD 20 administration. This therapy had good clinical outcome, without the need for further plasma exchanges. Thrombotic thrombocytopenic purpura is highly lethal disease. Early diagnosis, treatment, and multidisciplinary approach are essential.

ADAMTS13 Autoantibodies Cloned from Patients with Acquired Thrombotic Thrombocytopenic Purpura: 1. Structural and functional characterization in vitro

PubMed Central

Ostertag, Eric M.; Kacir, Stephen; Thiboutot, Michelle; Gulendran, Gayathri; Zheng, X. Long; Cines, Douglas B.; Siegel, Don L.

2016-01-01

BACKGROUND Acquired thrombotic thrombocytopenia purpura (TTP) is a life-threatening illness caused by autoantibodies that decrease the activity of ADAMTS13, the von Willebrand Factor cleaving protease. Despite efficacy of plasma exchange, mortality remains high and relapse is common. Improved therapies may come from understanding the diversity of pathogenic autoantibodies on a molecular/genetic level. Cloning comprehensive repertoires of patient autoantibodies can provide the necessary tools for studying immunobiology of disease and developing animal models. STUDY DESIGN AND METHODS Anti-ADAMTS13 antibodies were cloned from four patients with acquired TTP using phage display and characterized with respect to genetic origin, inhibition of ADAMTS13 proteolytic activity, and epitope specificity. Anti-idiotypic antisera raised to a subset of autoantibodies enabled comparison of their relatedness to each other and to polyclonal IgG in patient plasma. RESULTS Fifty-one unique antibodies were isolated comprising epitope specificities resembling the diversity found in circulating patient IgG. Antibodies directed to both the amino terminal domains and those requiring the ADAMTS13 cysteine-rich/spacer region for binding inhibited proteolytic activity, while those solely targeting carboxy-terminal domains were non-inhibitory. Anti-idiotypic antisera raised to a subset of antibody clones crossreacted with and reduced the inhibitory activity of polyclonal IgG from a set of unrelated patients. CONCLUSIONS Anti-ADAMTS13 autoantibodies isolated by repertoire cloning display the diversity of epitope specificities found in patient plasma and provide tools for developing animal models of acquired TTP. Shared idiotypes of inhibitory clones with circulating IgG from multiple patients suggest common features of pathogenic autoantibodies that could be exploited for developing more targeted therapies. PMID:27040144

Outcome of severe adult thrombotic microangiopathies in the intensive care unit.

PubMed

Pene, Frédéric; Vigneau, Cécile; Auburtin, Marc; Moreau, Delphine; Zahar, Jean-Ralph; Coste, Joël; Heshmati, Farhad; Mira, Jean-Paul

2005-01-01

Thrombotic microangiopathies, namely thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, are uncommon microvascular occlusive diseases. Despite the dramatic improvement in the outcome by exogenous plasma supply, either through plasma infusion or through plasma exchange, patients frequently require support in the intensive care unit. In the present study, we evaluated the outcome of a large cohort of patients with severe thrombotic microangiopathies. A retrospective multicenter study from January 1998 to June 2001. Fourteen French university hospital medical intensive care units. Sixty three adult patients with severe thrombotic microangiopathies. Of the 63 patients, 19 had a clinical presentation of thrombotic thrombocytopenic purpura, 18 had hemolytic uremic syndrome and 26 had combined neurologic and renal failures. Infections were the main etiology associated with thrombotic microangiopathies. The mortality rate was 35%. Of the survivors, all achieved complete remission. Whereas neurologic failure assessed through the Glasgow coma scale was an independent predictor of mortality [HR=0.845 (CI 95%: 0.759-0.940), P=0.002], renal impairment did not appear to be an adverse prognostic factor. The use of plasma exchange was independently associated with survival [HR=0.269 (CI 95%: 0.104-0.691), P=0.006]. Thrombotic microangiopathies with severe organ dysfunctions leading to hospitalization in the intensive care unit are associated with high mortality. Neurologic impairment appears to be the main adverse prognostic factor correlated to mortality, and the study confirms the importance of plasma exchange in the treatment of high-risk patients.

[Fatal thrombotic microangiopathy in the mother and fetus].

PubMed

Udvardy, M; Telek, B; Kiss, A; Flóra Nagy, M; Mikó, T; Rák, K

1990-04-14

The appearance of thrombotic microangiopathy (thrombotic thrombocytopenic purpura, haemolytic uraemic syndrome) could have been documented in a 23 years old pregnant woman, who had been treated previously for immune-thrombocytolytic purpura. The disturbing anamnestic data caused significant delay in correct diagnosis and in starting of fresh-frozen plasma therapy, so the woman and her fetus (in utero) had been died. The specific histological microangiopathic lesions could have been well documented by the autopsy of the mother, however no such alterations could have been detected in the fetus and placenta. This latter intriguing observation might be remarkable in the evaluation of several concepts dealing with the aetiopathogenesis of thrombotic microangiopathy. The short review of literature of thrombotic microangiopathy in pregnancy and puerperial period is also given.

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.

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

[Embolizing aortic valve endocarditis in the differential diagnosis of thrombotic thrombocytopenic purpura].

PubMed

Thomas, M; Heyll, A; Meckenstock, G; Vogt, M; Aul, C

1992-05-08

A 50-year-old man complained of lumbar pains, lack of energy, dysarthria and ataxic gait. Investigation revealed progressive anaemia (haemoglobin initially 10.5 g/dl, later 6.8 g/dl) and thrombocytopenia (initially 67,000/microliters, later 25,000/microliters). In addition he had unexplained pyrexia of up to 39.8 degrees C. Lactate dehydrogenase was 780 U/l and fragmented red cells were noted in the blood film. Because of suspicion of thrombotic thrombocytopenic purpura, treatment with fresh plasma by infusion was immediately initiated. On the third day of treatment he developed left ventricular failure; auscultation revealed a blowing early diastolic murmur over Erb's point together with a spindle-shaped early diastolic murmur over the right second intercostal space. Computed tomography of the skull showed recent haemorrhage into the left half of the cerebellum and an older right posterior infarct. The abdominal ultrasound scan suggested a haemorrhagic spleen infarct. In view of these findings the diagnosis was revised to embolizing aortic endocarditis with aortic reflux (confirmed by colour Doppler echo-cardiography). Aortic valve replacement was performed immediately, and the patient was treated with gentamycin 80 mg/d and teicoplanin 400 mg/d for four weeks. Postoperatively he was given 12 units of platelet concentrate and the platelet count remained stable thereafter (greater than 100,000/microliters). Splenectomy became necessary because the splenic haematoma increased in size during oral anticoagulant therapy. After a 6 week hospital stay the patient was discharged in good condition.

Cumulative Review of Thrombotic Microangiopathy, Thrombotic Thrombocytopenic Purpura, and Hemolytic Uremic Syndrome Reports with Subcutaneous Interferon β-1a.

PubMed

Ben-Amor, Ali-Frédéric; Trochanov, Anton; Fischer, Tanya Z

2015-05-01

Rare cases of thrombotic microangiopathy (TMA), manifested as thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS), have been reported with interferon β products. We performed a cumulative review of TMA cases recorded in a Global Safety Database for patients with multiple sclerosis who received subcutaneous interferon β-1a treatment. Search criteria were: all reported cases, serious and non-serious, from all sources (including non-health care professionals and clinical trial reports), regardless of event ranking and causality assessment by reporter or company. Data lock was May 3, 2014, with additional analysis of cases reported between August 1, 2014-November 30, 2014. Ninety-one patient cases (76.9% female) with 105 events were retrieved. Time to onset varied from 2 months to 14 years, and in 31.9% of patients the event occurred within 2 years of treatment initiation. Seven patients had a fatal outcome (five were secondary to other causes and two reported insufficient information). Forty-four patients recovered, 32 patients had not recovered at the time of the report, and in eight cases outcome was either not reported or unknown. Treatment was discontinued in 84.6% (77/91) of patients. In 67% (61/91) of patients, the reporter suspected a causal association between treatment and TMA/TTP-HUS. Risk factors and/or confounding factors were present in 45.1% (41/91) of patients. Early prodromal syndrome or specific patterns were not detected, although 54.9% (50/91) of cases contained insufficient information. Overall reporting rate of TMA/TTP-HUS was estimated as 7.2 per 100,000 patient-years. Reporting rates for human serum album (HSA)-containing and HSA-free formulations were 5.72 and 7.68 per 100,000 patient-years, respectively. No new signal relating specifically to increased frequency of TMA/TTP-HUS with HSA-free subcutaneous interferon β-1a was detected and no additional risk mitigation measures are required regarding the different

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

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

PubMed

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

2012-04-01

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

Outcomes in the treatment of thrombotic thrombocytopenic purpura with splenectomy: a retrospective cohort study.

PubMed

Outschoorn, Ubaldo Martinez; Ferber, Andres

2006-12-01

The mainstay of treatment for thrombotic thrombocytopenic purpura (TTP) is plasma exchange (PE), but the role of splenectomy is still undefined. The records of all patients with TTP at a single center over a 20-year period were retrospectively reviewed. Response to plasma exchange was determined. The outcome of patients treated with splenectomy in the setting of TTP was evaluated. Sixty-one patients had been treated for TTP. Thirty-nine patients (64%) achieved complete remission (CR) with PE, nineteen (31%) of these achieving sustained CR and seventeen (28%) with relapsed TTP. Twenty patients (33%) had PE refractory TTP and two patients (3%) had PE dependent TTP. During this time period, 10 patients (16%) underwent splenectomy, four patients (7%) for PE dependent TTP, three (5%) for relapsed TTP, and three (5%) for refractory TTP. All of the patients achieved CR after splenectomy. Two patients who had undergone splenectomy had subsequent relapses, both with previously relapsed TTP. In relapsed patients the relapse rate after splenectomy was 0.27 events per patient year compared to 0.6 events per patient year before splenectomy. Median follow-up after splenectomy was 19 months (range 0.13-90 months). In conclusion, relapses in TTP can be managed successfully with additional PE or with splenectomy. PE dependent or refractory TTP can be successfully treated with splenectomy.

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.

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

Clinical usefulness of a functional assay for the von Willebrand factor cleaving protease (ADAMTS 13) and its inhibitor in a patient with thrombotic thrombocytopenic purpura.

PubMed

Rick, M E; Austin, H; Leitman, S F; Krizek, D M; Aronson, D L

2004-02-01

Decreased von Willebrand factor cleaving protease activity (VWFCP, ADAMTS 13) leads to persistence of unusually large multimers of von Willebrand factor that bind to platelets, causing platelet aggregates, microangiopathic hemolysis, and thrombocytopenia in patients with thrombotic thrombocytopenic purpura (TTP). The clinical value of measuring ADAMTS 13 and its inhibitor is not fully defined; the case reported here illustrates the usefulness of the assay to help confirm the clinical diagnosis in a patient with other potential causes for thrombotic microangiopathy; the assay also helped in making treatment decisions. A patient with systemic lupus erythematosis (SLE) presented with fever and abdominal pain, thrombocytopenia, and anemia. Thrombotic microangiopathy was diagnosed by the appearance of schistocytes, decreasing platelet count, and evidence of hemolysis. ADAMTS 13 was decreased and an inhibitor was demonstrated in the patient's initial blood sample within 24 hr of admission. Plasma exchange was initiated, and serial assays showed increased ADAMTS 13 activity and decreased inhibitor after each plasma exchange; there was a rebound in inhibitor and a decrease in ADAMTS 13 activity prior to the next exchange that lessened over time. Increasing levels of protease activity correlated with clinical and laboratory improvement. Measurement of ADAMTS 13 activity and its inhibitor aided in the diagnosis of this complicated case of a patient with other potential causes for microangiopathic hemolysis. Subsequent levels correlated with the clinical course, and disappearance of the inhibitor indicated that long-term plasma exchange or other immunosuppressive treatment was not needed.

Defining the genetics of thrombotic microangiopathies.

PubMed

Vieira-Martins, Paula; El Sissy, Carine; Bordereau, Pauline; Gruber, Aurelia; Rosain, Jeremie; Fremeaux-Bacchi, Veronique

2016-04-01

The spectrum of the thrombotic microangiopathies (TMA) encompasses a heterogeneous group of disorders with hereditary and acquired forms. Endothelial cell injury in the microvasculature is common to all TMAs, whatever the pathophysiological process. In this review we describe genetic mutations characteristic of certain TMAs and review their contributions to disease. Recent identification of novel pathologic mutations has been enabled by exome studies. The monogenic forms of TMA are more frequently caused by recessive alterations in von Willebrand factor cleaving protease ADAMST13, leading to congenital thrombotic thrombocytopenic purpura, or cobalamine C and DGKE genes, leading to an atypical hemolytic-uremic syndrome (aHUS)-like TMA. aHUS, whether idiopathic or linked to a known complement amplifying condition, is a TMA that primarily affects kidney function. It often results from a combination of an underlying genetic susceptibility with environmental factors activating the alternative complement pathway. Pathogenic variants in at least five complement genes coding for complement factor H (CFH) complement factor I (CFI), MCP (CD46), C3 and complement factor B (CFB) have been demonstrated to increase the risk of developing aHUS, but several more genes have been implicated. A new challenge is to separate disease-associated genetic variants from the broader background of variants or polymorphisms present in all human genomes that are rare, potentially functional, but may or may not be pathogenic. Copyright © 2016 Elsevier Ltd. All rights reserved.

Acute disseminated melioidosis giving rise to pneumonia and renal abscesses complicated with thrombotic thrombocytopenic purpura in a post partum woman: a case report.

PubMed

Wijewickrama, Piyumi Sachindra Alwis; Weerakoon, Rohini

2017-11-29

Melioidosis is an established endemic infection in Sri Lanka, caused by Burkholderia pseudomallei, a gram negative bacterium distributed in saprophytes in soil and surface water. Main mode of transmission is via percutaneous inoculation. Pneumonia is the most common presentation in acute disease. We report a 33 year old previously healthy Sinhalese female with an occupational exposure to surface water in paddy fields, who was on postpartum day 6 following an uncomplicated pregnancy and delivery via an elective caesarian section. She presented with a 1 day history of breathlessness, preceded by a brief episode of fever. She had occasional right side coarse crackles and pitting oedema of both lower limbs. Shortly after admission, she developed type one respiratory failure needing invasive mechanical ventilation. Initial chest x-ray revealed slight obliteration of right medial diaphragmatic border while echocardiogram revealed moderate pulmonary hypertension. Computed tomography pulmonary angiogram excluded a pulmonary embolism, but revealed bilateral multi-lobar consolidation. Abdominal computed tomography demonstrated bilateral pyelonephritis with renal abscesses. As initial cultures were inconclusive, melioidosis antibody levels were done due to high degree of suspicion, which was found to be positive with a titer of 1:2560. A diagnosis of melioidosis was made based on the suggestive clinical picture, exposure history and the highly positive antibody level. She developed left side focal seizures together with thrombocytopenia and microangiopathic haemolytic anemia, suggestive of thrombotic thrombocytopenic purpura. Magnetic resonance imaging of brain was negative for cerebral abscesses but revealed extensive minute haemorrhagic foci throughout the cerebrum. Thus, the final diagnosis was acute melioidosis causing pneumonia and renal abscesses, complicated with thrombotic thrombocytopenic purpura and sepsis. She demonstrated dramatic response to high dose meropenem

Thrombotic microangiopathy associated with Valproic acid toxicity.

PubMed

Hebert, Sean A; Bohan, Timothy P; Erikson, Christian L; Swinford, Rita D

2017-08-03

Thrombotic microangiopathy (TMA) is a serious, sometimes life-threatening disorder marked by the presence of endothelial injury and microvascular thrombi. Drug-induced thrombotic microangiopathy (DI-TMA) is one specific TMA syndrome that occurs following drug exposure via drug-dependent antibodies or direct tissue toxicity. Common examples include calcineurin inhibitors Tacrolimus and Cyclosporine and antineoplastics Gemcitabine and Mitomycin. Valproic acid has not been implicated in DI-TMA. We present the first case of a patient meeting clinical criteria for DI-TMA following admission for valproic acid toxicity. An adolescent male with difficult to control epilepsy was admitted for impaired hepatic function while on valproic acid therapy. On the third hospital day, he developed severe metabolic lactic acidosis and multiorgan failure, prompting transfer to the pediatric intensive care unit. Progressive anemia and thrombocytopenia instigated an evaluation for thrombotic microangiopathy, where confirmed by concomitant hemolysis, elevated lactate dehydrogenase (LDH), low haptoglobin, and concurrent oliguric acute kidney injury. Thrombotic thrombocytopenic purpura was less likely with adequate ADAMTS13. Discontinuing valproic acid reversed the anemia, thrombocytopenia, and normalized the LDH and haptoglobin, supporting a drug-induced cause for the TMA. To the best of our knowledge, this is the first report of drug-induced TMA from valproic acid toxicity.

[Thrombotic microangiopathy in adults].

PubMed

Barrientos, Gonzalo J; Michelangelo, Hernán

2006-01-01

Thrombotic microangiopathic hemolytic anemias include thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS) and pregnancy associated thrombotic microangiopathy (TMA). Eight adult patients (four males and four females) with TMA who were treated between 2003 and 2004 at the Hospital Italiano de Buenos Aires were reviewed. The average age was 40. Clinical diagnosis of TMA was made on admission in four patients. During their stay in hospital, 4 patients developed HUS characteristics, three as TTP and one presented pregnancy associated TMA. All of them revealed thrombocytopenia and microangiophatic hemolytic anemia. Renal impairment was the third most frequent characteristic at presentation. The patients with TTP revealed the most severe condition. All patients received daily plasma exchange. Immunosuppressants were also used. Four patients recovered completely, 2 passed away, one remains with renal impairment and requires hemodialysis, and a colectomy was performed on one of them. The TMA syndromes are occlusive disorders associated to platelet microvascular thrombi. Systemic and renal circulations are primarily affected. TTP/HUS might represent an overlapping spectrum of idiopathic or secondary disease. Prompt recognition and treatment are vital, because high mortality occurs due to these disorders. Among the differential diagnosis of TMA we can refer to sepsis, neoplasms, systemic vasculitis, eclampsia and others. The mainstay treatments are daily plasma exchange and infusion with fresh frozen plasma. Improving the management of these diseases is required considering their high morbidity and mortality.

Postpartum plasma exchange in a woman with suspected thrombotic thrombocytopenic purpura (TTP) vs. hemolysis, elevated liver enzymes, and low platelet syndrome (HELLP): a case study.

PubMed

Myers, Linda

2010-01-01

The occurrence of a hypercoagulable state and decreasing concentration of ADAMTS 13 in late pregnancy and during the postpartum period increases the risk for a woman to develop life-threatening thrombotic thrombocytopenic purpura (TTP). This is also the time of great risk for the more common obstetric complications of preeclampsia; eclampsia; and hemolysis, elevated liver functions tests, low platelets (HELLP) syndrome. These conditions are associated with high maternal and perinatal mortality. Differential diagnosis may be difficult due to the overlapping of clinical and laboratory findings, including thrombocytopenia, microangiopathic hemolytic anemia, neurologic symptoms, and renal insufficiency, making it difficult or impossible to distinguish them from TTP. Management of microangiopathic disorders encountered during pregnancy differ; therefore, an accurate diagnosis is required. Outcomes of TTP without plasma exchange therapy (TPE) are almost uniformly fatal. Early recognition and management of symptoms with prompt and aggressive TPE is essential when TTP is suspected.

Effect of ADAMTS13 activity turnaround time on plasma utilization for suspected thrombotic thrombocytopenic purpura.

PubMed

Connell, Nathan T; Cheves, Tracey; Sweeney, Joseph D

2016-02-01

Thrombotic thrombocytopenic purpura (TTP) due to deficiency of the von Willebrand-cleaving protease ADAMTS13 is a hematologic emergency that requires prompt initiation of therapeutic plasma exchange (TPE). Long turnaround times (TATs) have precluded the use of pre-TPE measurement of ADAMTS13 activity for the initial diagnosis in most institutions. An in-house rapid TAT (r-TAT) assay for ADAMTS13 activity was implemented after 18 months of validation. In a quasi-experimental design using interrupted time series analysis, patterns of plasma utilization in patients with suspected TTP were assessed after implementation of this assay for ADAMTS13 activity and compared to utilization patterns for patients who received plasma exchange before r-TAT assay implementation designated the standard TAT period. In the 18 months after implementation of the r-TAT ADAMTS13 assay, there was a significant reduction in plasma utilization per patient suspected of having TTP (mean, 144.5 units vs. 63.3 units of plasma per patients suspected of having TTP; p = 0.002). The mean number of exchanges per patient and mean number of exchanges after achieving a platelet count of at least 150 × 10(9) /L were lower in the r-TAT cohort (p < 0.001 for both). There was no significant difference in 30-day mortality. Implementation of a rapid turnaround assay for ADAMTS13 resulted in a significant reduction in plasma utilization for patients with suspected TTP, without an increase in mortality. This study demonstrates that these data, provided in a timely fashion, can avoid unnecessary plasma exchange in patients who do not have TTP. © 2015 AABB.

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

PubMed

Hyla-Klekot, Lidia; Kucharska, Grazyna; Słonka, Karina

2013-03-01

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

Effect of rituximab on B cell phenotype and serum B cell-activating factor levels in patients with thrombotic thrombocytopenic purpura

PubMed Central

Becerra, E; Scully, M A; Leandro, M J; Heelas, E O; Westwood, J-P; De La Torre, I; Cambridge, G

2015-01-01

Autoantibodies inhibiting the activity of the metalloproteinase, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), underlie the pathogenesis of thrombotic thrombocytopenic purpura (TTP). Rituximab (RTX) combined with plasma-exchange (PEX) is an effective treatment in TTP. Patients can remain in remission for extended periods following PEX/RTX, and this is associated with continuing reduction in antibodies to ADAMTS13. Factors controlling B cell differentiation to autoantibody production, including stimulation through the B cell receptor and interactions with the B cell-activating factor (BAFF), may thus impact length of remission. In this cross-sectional study, we measured naive and memory B cell phenotypes [using CD19/immunoglobulin (Ig)D/CD27] following PEX/RTX treatment in TTP patients at B cell return (n = 6) and in 12 patients in remission 10–68 months post-RTX. We also investigated relationships among serum BAFF, soluble CD23 (sCD23– a surrogate measure of acquiring B memory (CD27+) phenotype) and BAFF receptor (BAFF-R) expression. At B cell return after PEX/RTX, naive B cells predominated and BAFF-R expression was reduced compared to healthy controls (P < 0·001). In the remission group, despite numbers of CD19+ B cells within normal limits in most patients, the percentage and absolute numbers of pre-switch and memory B cells remained low, with sCD23 levels at the lower end of the normal range. BAFF levels were correlated inversely with BAFF-R expression and time after therapy. In conclusion, the long-term effects of RTX therapy in patients with TTP included slow regeneration of memory B cell subsets and persistently reduced BAFF-R expression across all B cell subpopulations. This may reflect the delay in selection and differentiation of potentially autoreactive (ADAMTS13-specific) B cells, resulting in relatively long periods of low disease activity after therapy. PMID:25339550

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. © 2016 Wiley Periodicals, Inc.

Low ADAMTS-13 in plavix induced thrombotic thrombocytopenic purpura.

PubMed

Cao, Long Bao; Jones, Christopher; Movahed, Assad

2013-04-16

Thrombotic thrombocytopenia purpura (TTP) was first described in 1924 as a "pathologic alteration of the microvasculature, with detachment or swelling of the endothelium, amorphous material in the sub-endothelial space, and luminal platelet aggregation leading to compromise of the microcirculation". Ticlopidine induced TTP has been highly associated with autoimmune induced reduction in ADAMTS-13 activity. These findings, to a lesser extent, have also been found in clopidogrel induced TTP. We report a case of clopidogrel associated TTP in a patient that presented with acute stroke, renal failure, and non-ST elevation myocardial infarction.

Decreased prothrombotic effects of pegylated recombinant human megakaryocyte growth and development factor in thrombocytopenic state in a rat thrombosis model.

PubMed

Nishiyama, U; Kuwaki, T; Akahori, H; Kato, T; Ikeda, Y; Miyazaki, H

2005-02-01

Previous in vitro studies demonstrated that thrombopoietin (TPO) acts on platelets to activate a variety of intracellular signaling pathways and to enhance platelet sensitivity to multiple agonists. Little is known, however, about whether TPO exerts prothrombotic effects in vivo. The aim of this study was to examine the effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), a pegylated N-terminal domain of human TPO, in a rat model of venous thrombosis. A microthrombus was photochemically induced on the vessel wall of a mesenteric venule, but the vessel was not occluded by it. A single intravenous injection of PEG-rHuMGDF (3 microg kg(-1)) after the thrombus generation into normal rats enhanced the thrombus size, resulting in transient thrombotic occlusion in the majority of rats. Stimulatory effects on thrombus growth were also observed following administration of glycosylated recombinant human full-length TPO (6 microg kg(-1)). In rats rendered thrombocytopenic by total body irradiation, however, PEG-rHuMGDF, even at 300 microg kg(-1), did not induce a significant increase in thrombus size or thrombotic occlusion. Platelets from thrombocytopenic rats had decreased surface levels of c-Mpl and decreased sensitivity to PEG-rHuMGDF in an in vitro aggregation response. Thus, decreased prothrombotic effects of PEG-rHuMGDF in thrombocytopenic rats might be the result not only of low platelet counts but also of decreased platelet reactivity to PEG-rHuMGDF. These results indicate that PEG-rHuMGDF has little effect on venous thrombus formation in thrombocytopenic states associated with high endogenous TPO levels.

CD(+)(4)CD(+)(25) Treg cells in thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus patients.

PubMed

Huang, Hongdong; Sun, Weiming; Liang, Yumei; Long, Xi-Dai; Peng, Youming; Liu, Zhihua; Wen, Xiaojun; Jia, Meng

2014-09-01

CD(+)(4)CD(+)(25) Treg cells are of critical importance for maintenance of tolerance. The purpose of the this study was to observe the number of CD(+)(4)CD(+)(25) Treg cells in the patients with thrombotic thrombocytopenic purpura (TTP) associated with systemic lupus erythematosus (SLE), and to study pathogenesis of TTP with SLE. Seven patients with TTP associated with SLE and seven healthy volunteers were studied. The CD(+)(4)CD(+)(25) Treg cells were examined by flow cytometry. Clinical and laboratory data, such as urinary protein, serum creatinine, endothelial markers and immunologic serologics, were obtained from each patient and healthy volunteer. Glomerular injury was assessed by histopathology. Serum IL-2, IL-4, IL-6 and anti-endothelial cell antibody were analyzed by ELISA and anti-ADAMTS13 antibody were detected by Western blotting. CD(+)(4)CD(+)(25) Treg cells significantly decreased in TTP with SLE patients compared with controls (p < 0.05). CD(+)(4)CD(+)(25) Treg cells are negatively correlated with blood urea nitrogen, serum uric acid, supernatant IL-4, and proteinuria, and positively with estimated glomerular filtration rate (eGFR) in TTP with SLE patients. [Formula: see text] Treg cells gradually decreased as the severity of renal histology increased. Serum IL-2, IL-6, supernatant IL-4, anti-endothelial cell antibody, and anti-ADAMTS13 antibody significantly increased in TTP with SLE patients compared to those of the control groups (all p < 0.05). In contrast, serum levels of C3 were significantly decreased in TTP with SLE patients compared to those of the control groups (p < 0.05). CD(+)(4)CD(+)(25) Treg cells are not only lower in TTP with SLE patients, but also are correlated with disease severity in TTP with SLE patients.CD(+)(4)CD(+)(25)Treg cells may play an important role in the pathogenesis of TTP with SLE.

[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. Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

A case of severe thrombotic thrombocytopenic purpura with concomitant Legionella pneumonia: review of pathogenesis and treatment.

PubMed

Talebi, Tony; Fernandez-Castro, Gustavo; Montero, Alberto J; Stefanovic, Alexandra; Lian, Eric

2011-09-01

Thrombotic thrombocytopenia purpura (TTP) is a severe multisystem disorder characterized by fever, microangiopathic hemolytic anemia, thrombocytopenia, neurologic symptoms, and impaired renal function. Platelet counts are usually diminished, whereas the bone marrow shows a large number of megakaryocytes indicating peripheral destruction and consumption of platelets. Coagulation studies in patients with TTP are normal or slightly elevated, which helps differentiate this entity from disseminated intravascular coagulation. The peripheral smear shows an abundance of schistocytes, reticulocytes, and, at times, nucleated red blood cells. Serum lactate dehydrogenase and indirect bilirubin are elevated as a result of mechanical destruction of red blood cells. Legionella pneumophila has been identified as a relatively common cause of both community-acquired and hospital-acquired pneumonia. An association between Legionella and TTP has only been cited once in the literature. Here we present a case of severe TTP with concurrent Legionella infection. Our patient presented with the classic clinical findings of TTP and an ADAMTS13 level of less than 5% associated with an inhibitor. After a 3-week treatment course with plasma exchange, steroids, and antibiotics, he had complete clinical recovery and his ADAMTS13 level increased to greater than 75%. (C) 2011 Lippincott Williams & Wilkins, Inc.

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

PubMed Central

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

2015-01-01

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

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. 2015 BMJ Publishing Group Ltd.

Genetics Home Reference: thrombotic thrombocytopenic purpura

MedlinePlus

... Resulting complications can include neurological problems (such as personality changes, headaches, confusion, and slurred speech), fever, abnormal ... form. The acquired form usually appears in late childhood or adulthood. Affected individuals may have a single ...

Low incidence of ADAMTS13 missense mutation R1060W in adult Egyptian patients with thrombotic thrombocytopenic purpura.

PubMed

El Sissy, Maha H; El Hafez, A Abd; El Sissy, A H

2014-01-01

Thrombotic thrombocytopenic purpura (TTP) is an acute life-threatening disorder, characterized by thrombocytopenia, microangiopathic hemolytic anemia, widespread microvascular thrombi and consequent clinical sequelae due to ischemic organ damage. TTP is most commonly associated with deficiency or inhibition of von Willebrand factor-cleaving protease (ADAMTS13) activity. ADAMTS13 mutations and polymorphisms have been reported in childhood congenital TTP, but their significance in adult-onset TTP is still under investigation. Two mutations stand out: the single base insertion 4143insA in exon 29 and the missense mutation R1060W in exon 24 have both been observed in several unrelated families, mainly in adult-onset TTP, and over a wide geographic area. Our objective in this study is to identify the prevalence of R1060W missense mutation in exon 24 ADAMTS13 in a sample of adult Egyptian TTP patients. Thirty-one adult-onset TTP patients were included in this study, with a male/female ratio of 1:4. Twenty-six cases (84%) presented with acute idiopathic TTP, 2 cases were drug abusers and 3 cases were pregnant. None of the study cases provided a history of suspicious TTP symptoms during childhood (2 cases gave a history of episodes of thrombocytopenia during childhood). All cases showed statistically significant decreased ADAMTS13 activity compared to normal controls (p < 0.001). The study revealed a high statistical difference regarding the ADAMTS13 inhibitor level in primary versus secondary cases (p = 0.003). None of our Egyptian cases or of the healthy normal controls are positive for exon 24 missense mutation. Larger studies and regional and national TTP registries are recommended. © 2013 S. Karger AG, Basel.

Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS): a 24-year clinical experience with 178 patients

PubMed Central

Levandovsky, Mark; Harvey, Danielle; Lara, Primo; Wun, Ted

2008-01-01

Background Thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome (TTP-HUS) are related and uncommon disorders with a high fatality and complication rate if untreated. Plasma exchange therapy has been shown to produce high response rates and improve survival in patients with many forms of TTP-HUS. We performed a retrospective cohort study of 178 consecutively treated patients with TTP-HUS and analyzed whether clinical or laboratory characteristics could predict for important short- and long-term outcome measures. Results Overall 30-day mortality was 16% (n = 27). 171 patients (96%) received plasma exchange as the principal treatment, with a mean of 8 exchanges and a mean cumulative infused volume of 42 ± 71 L of fresh frozen plasma. The rate of complete response was 65% or 55% depending on whether this was defined by a platelet count of 100,000/μl or 150,000/μl, respectively. The rate of relapse was 18%. The Clinical Severity Score did not predict for 30-day mortality or relapse. The time to complete response did not predict for relapse. Renal insufficiency at presentation was associated with a decreased risk of relapse, with each unit increase in serum creatinine associated with a 40% decreased odds of relapse. 72% of our cohort had an idiopathic TTP-sporadic HUS, while 17% had an underlying cancer, received a solid organ transplant or were treated with a mitomycin-based therapy. The estimated overall 5-year survival was 55% and was significantly better in those without serious underlying conditions. Conclusion Plasma exchange therapy produced both high response and survival rates in this large cohort of patients with TTP-HUS. The Clinical Severity Score did not predict for 30-day mortality or relapse, contrary to our previous findings. Interestingly, the presence of renal insufficiency was associated with a decreased risk of relapse. The most important predictor of mortality was the presence or absence of a serious underlying disorder. PMID

Reduced ADAMTS13 activity is associated with thrombotic risk in systemic lupus erythematosus.

PubMed

Martin-Rodriguez, S; Reverter, J C; Tàssies, D; Espinosa, G; Heras, M; Pino, M; Escolar, G; Diaz-Ricart, M

2015-10-01

Severe deficiency of ADAMTS13 activity leads to von Willebrand factor (VWF) ultralarge multimers with high affinity for platelets, causing thrombotic thrombocytopenic purpura. Other pathological conditions with moderate ADAMTS13 activity exhibit a thrombotic risk. We examined the ADAMTS13 activity in systemic lupus erythematosus (SLE) and its value as a thrombotic biomarker. ADAMTS13 activity, VWF antigen and multimeric structure, and vascular cell adhesion molecule 1 (VCAM-1) were measured in plasma samples from 50 SLE patients and 50 healthy donors. Disease activity (systemic lupus erythematosus disease activity index; SLEDAI) and organ damage (systemic lupus international collaborating clinics) scores, thrombotic events, antiphospholipid syndrome (APS) and antiphospholipid antibodies (aPLs) were registered. SLE patients showed decreased ADAMTS13 activity and high VWF levels compared with controls (66 ± 27% vs. 101 ± 8%, P < 0.01, and 325 ± 151% vs. 81 ± 14%, P < 0.001). VCAM-1 levels were higher in SLE patients (P < 0.05). Considering three groups of SLE patients depending on ADAMTS13 activity (>60%, 60-40% and <40%), comparative analysis showed significant association between ADAMTS13 activity and SLEDAI (P < 0.05), presence of aPLs (P < 0.001), APS (P < 0.01) and thrombotic events (P < 0.01). Reduced ADAMTS13 activity together with increased VWF levels were especially notable in patients with active disease and with aPLs. ADAMTS13 activity, in combination with other laboratory parameters, could constitute a potential prognostic biomarker of thrombotic risk in SLE. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

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. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Influenza-associated thrombotic microangiopathies.

PubMed

Bitzan, Martin; Zieg, Jakub

2017-09-07

Thrombotic microangiopathy (TMA) refers to phenotypically similar disorders, including hemolytic uremic syndromes (HUS) and thrombotic thrombocytopenic purpura (TTP). This review explores the role of the influenza virus as trigger of HUS or TTP. We conducted a literature survey in PubMed and Google Scholar using HUS, TTP, TMA, and influenza as keywords, and extracted and analyzed reported epidemiological and clinical data. We identified 25 cases of influenza-associated TMA. Five additional cases were linked to influenza vaccination and analyzed separately. Influenza A was found in 83%, 10 out of 25 during the 2009 A(H1N1) pandemic. Two patients had bona fide TTP with ADAMTS13 activity <10%. Median age was 15 years (range 0.5-68 years), two thirds were male. Oligoanuria was documented in 81% and neurological involvement in 40% of patients. Serum C3 was reduced in 5 out of 14 patients (36%); Coombs test was negative in 7 out of 7 and elevated fibrin/fibrinogen degradation products were documented in 6 out of 8 patients. Pathogenic complement gene mutations were found in 7 out of 8 patients tested (C3, MCP, or MCP combined with CFB or clusterin). Twenty out of 24 patients recovered completely, but 3 died (12%). Ten of the surviving patients underwent plasma exchange (PLEX) therapy, 5 plasma infusions. Influenza-mediated HUS or TTP is rare. A sizable proportion of tested patients demonstrated mutations associated with alternative pathway of complement dysregulation that was uncovered by this infection. Further research is warranted targeting the roles of viral neuraminidase, enhanced virus-induced complement activation and/or ADAMTS13 antibodies, and rational treatment approaches.

von Willebrand factor and its cleaving protease ADAMTS13 balance in coronary artery vessels: Lessons learned from thrombotic thrombocytopenic purpura. A narrative review.

PubMed

Morici, Nuccia; Cantoni, Silvia; Panzeri, Francesco; Sacco, Alice; Rusconi, Chiara; Stucchi, Miriam; Oliva, Fabrizio; Cattaneo, Marco

2017-07-01

Deficiency of the von Willebrand factor-cleaving protease ADAMTS13 is central to the pathophysiology of thrombotic thrombocytopenic purpura (TTP), a microangiopathic syndrome that presents as an acute medical emergency. In this review we will explore the evidence of a two-way relationship between TTP and ACS. Moreover, we will review the evidence emerged from epidemiological studies of an inverse relationship between the plasma levels of ADAMTS13 and the risk of ACS. Pubmed, MEDLINE and EMBASE, CINHAL, COCHRANE and Google Scholar databases were searched from inception to January 2017. The search yielded 43 studies representing 23 unique patient cases, 5 case series, 5 cohort studies and 10 case-control studies. Most ACS cases developing in the setting of TTP resolved with standard treatment of the underlying microangiopathy, with only a few requiring coronary invasive management. Antiplatelet therapy was not usually prescribed and all of the currently used P2Y 12 were felt to be a potential trigger for a TTP-like syndrome, although our review revealed that the occurrence of TTP in patients treated with new P2Y 12 antagonists is rare. Most studies confirmed the inverse association among ADAMTS13 levels and ACS. The heart is a definite target organ in TTP. The clinical spectrum of its involvement is probably influenced by local factors that add on to the systemic deficiency characteristic of TTP. It follows that patients with TTP should be carefully monitored for ACS events, especially when multiple risk factors for coronary disease exist. Copyright © 2017 Elsevier Ltd. All rights reserved.

Life-threatening postpartum hemolysis, elevated liver functions tests, low platelets syndrome versus thrombocytopenic purpura - Therapeutic plasma exchange is the answer.

PubMed

Nasa, Prashant; Dua, J M; Kansal, Sudha; Chadha, Geeta; Chawla, Rajesh; Manchanda, Manav

2011-04-01

The differential diagnosis of life-threatening microangiopathic disorders in a postpartum female includes severe preeclampsia-eclampsia, hemolysis, elevated liver functions tests, low platelets syndrome and thrombotic thrombocytopenic purpura. There is considerable overlapping in the clinical and laboratory findings between these conditions, and hence an exact diagnosis may not be always possible. However, there is considerable maternal mortality and morbidity associated with these disorders. This case underlines the complexity of pregnancy-related microangiopathies regarding their differential diagnosis, multiple organ dysfunction and role of therapeutic plasma exchange in their management.

Life-threatening postpartum hemolysis, elevated liver functions tests, low platelets syndrome versus thrombocytopenic purpura – Therapeutic plasma exchange is the answer

PubMed Central

Nasa, Prashant; Dua, J. M.; Kansal, Sudha; Chadha, Geeta; Chawla, Rajesh; Manchanda, Manav

2011-01-01

The differential diagnosis of life-threatening microangiopathic disorders in a postpartum female includes severe preeclampsia–eclampsia, hemolysis, elevated liver functions tests, low platelets syndrome and thrombotic thrombocytopenic purpura. There is considerable overlapping in the clinical and laboratory findings between these conditions, and hence an exact diagnosis may not be always possible. However, there is considerable maternal mortality and morbidity associated with these disorders. This case underlines the complexity of pregnancy-related microangiopathies regarding their differential diagnosis, multiple organ dysfunction and role of therapeutic plasma exchange in their management. PMID:21814380

Thrombotic Thrombocytopenic Purpura

MedlinePlus

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Acquired activated protein C resistance is associated with lupus anticoagulants and thrombotic events in pediatric patients with systemic lupus erythematosus.

PubMed

Male, C; Mitchell, L; Julian, J; Vegh, P; Joshua, P; Adams, M; David, M; Andrew, M E

2001-02-15

Acquired activated protein C resistance (APCR) has been hypothesized as a possible mechanism by which antiphospholipid antibodies (APLAs) cause thrombotic events (TEs). However, available evidence for an association of acquired APCR with APLAs is limited. More importantly, an association of acquired APCR with TEs has not been demonstrated. The objective of the study was to determine, in pediatric patients with systemic lupus erythematosus (SLE), whether (1) acquired APCR is associated with the presence of APLAs, (2) APCR is associated with TEs, and (3) there is an interaction between APCR and APLAs in association with TEs. A cross-sectional cohort study of 59 consecutive, nonselected children with SLE was conducted. Primary clinical outcomes were symptomatic TEs, confirmed by objective radiographic tests. Laboratory testing included lupus anticoagulants (LAs), anticardiolipin antibodies (ACLAs), APC ratio, protein S, protein C, and factor V Leiden. The results revealed that TEs occurred in 10 (17%) of 59 patients. Acquired APCR was present in 18 (31%) of 58 patients. Acquired APCR was significantly associated with the presence of LAs but not ACLAs. Acquired APCR was also significantly associated with TEs. There was significant interaction between APCR and LAs in the association with TEs. Presence of both APCR and LAs was associated with the highest risk of a TE. Protein S and protein C concentrations were not associated with the presence of APLAs, APCR, or TEs. Presence of acquired APCR is a marker identifying LA-positive patients at high risk of TEs. Acquired APCR may reflect interference of LAs with the protein C pathway that may represent a mechanism of LA-associated TEs. (Blood. 2001;97:844-849)

[Rituximab as effective therapy in very severe thrombotic thrombocytopenic purpura (TTP)].

PubMed

Illner, N; Wolf, G

2010-05-01

A 26-year-old woman was admitted from another hospital because of an increased serum creatinine (170 micromol/l). She was found to have a thrombocytopenia (14Gpt/l, WHO grade IV) with anaemia and a raised lactate dehydrogenase (25.45 micromol/l). The patient was in a reduced general state when admitted to this hospital. Her mucosal membranes were pale and she had moderate scleral icterus. During the first few hours she became clearly less alert but without motor or sensory deficits. Laboratory tests showed an increased total bilirubin (73 micromol, decreased haptoglobin (< 0.08 g/l), free hemoglobin was raised (20.7 micromol/l) and the blood smear showed 5.5% fragmentocytes. Direct and indirect Coombs tests were negative. Thrombotic thrombocytic purpura (TTP) was diagnosed. Daily plasmapheresis with fresh plasma replacement and administration of corticosteroids was initiated. ADAMTS13 activity (reported later) was < 2 % and antibodies against this protease were demonstrated. After initial improvement a motor and sensory aphasia occurred. Because of progressive thrombocytopenia, immunosuppression with a total of four doses of 375 mg/m(2)/bsa rituximab was undertaken (640 mg each), every seven days. Over the next two to three weeks the platelet count very slowly rose. The plasmapheresis was ended after a total of 65 sessions. Nine months after the last plasmapheresis the platelet count and renal functions were normal. Severe autoantibody TTP can be successfully treated by administering rituximanb, an anti-CD20 antibody, in addition to the standard treatment with plasmapheresis. Georg Thieme Verlag KG Stuttgart.New York.

Unusual Presentation of Chronic Idiopathic Thrombocytopenic Purpura

PubMed Central

Madhusudhanan, M.; Yusuff, Ali M.

2008-01-01

A snakebite victim presented with normal clotting profile and a low platelet count. A routine CBC in his past records (February 2004) showed a platelet count of 20,000/microlitre, but the patient was not symptomatic. We report a case of chronic idiopathic thrombocytopenic purpura, incidentally found in a patient presenting with snakebite. The patient also has acquired primary testicular failure. After the diagnosis the patient was on regular follow up. He caused trauma to the right external auditory canal and perforated his tympanic membrane. His left tympanic membrane was also scarred and retracted. Establishing a diagnosis of an ITP early is important so that the patient can take precaution to avoid undue trauma and monitor proper follow up. PMID:22567212

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

PubMed Central

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

2014-01-01

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

The efficacy of rituximab in the treatment of inhibitor-associated hemostatic disorders.

PubMed

Franchini, Massimo; Veneri, Dino; Lippi, Giuseppe; Stenner, Rachel

2006-08-01

Rituximab is a chimeric anti-CD20 monoclonal antibody active against normal and malignant B cells which has proven to be effective in the therapy of CD-20 positive lymphomas. Its B-cell cytotoxic action has also been exploited in many non-malignant autoimmune disorders in which it has been used with the aim of interfering with the production of pathologic antibodies. The present knowledge regarding the use of rituximab in antibody-associated disorders of hemostasis (i.e. idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, acquired hemophilia A, congenital hemophilia with inhibitors, acquired inhibitors against coagulation factors) is presented briefly in this review. The results suggest that rituximab can be useful in the treatment of disorders of hemostasis associated with inhibitor formation. Although collectively the number of patients treated is now quite substantial, most of the data are drawn from isolated case reports or descriptions of small, uncontrolled series. Large, prospective, randomized trials are, therefore, needed to confirm the positive, preliminary results.

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

Consensus opinion on diagnosis and management of thrombotic microangiopathy in Australia and New Zealand.

PubMed

Fox, Lucy C; Cohney, Solomon J; Kausman, Joshua Y; Shortt, Jake; Hughes, Peter D; Wood, Erica M; Isbel, Nicole M; de Malmanche, Theo; Durkan, Anne; Hissaria, Pravin; Blombery, Piers; Barbour, Thomas D

2018-06-01

Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. While TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all adults, urgent, empirical plasma exchange (PE) should be started within 4-8 h of presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 activity (a disintegrin and metalloprotease thrombospondin, number 13). A sodium citrate plasma sample should be collected for ADAMTS13 testing prior to any plasma therapy. In children, Shiga toxin-associated haemolytic uraemic syndrome due to infection with Escherichia coli (STEC-HUS) is the commonest cause of TMA, and is managed supportively. If TTP and STEC-HUS have been excluded, a diagnosis of aHUS should be considered, for which treatment is with the monoclonal complement C5 inhibitor, eculizumab. While early confirmation of aHUS is often not possible, except in the minority of patients in whom autoantibodies against factor H are identified, genetic testing ultimately reveals a complement-related mutation in a significant proportion of aHUS cases. The presence of other TMA-associated conditions (e.g. infection, pregnancy/postpartum and malignant hypertension) does not exclude TTP or aHUS as the underlying cause of TMA. © 2018 Asian Pacific Society of Nephrology.

Consensus opinion on diagnosis and management of thrombotic microangiopathy in Australia and New Zealand.

PubMed

Fox, Lucy C; Cohney, Solomon J; Kausman, Joshua Y; Shortt, Jake; Hughes, Peter D; Wood, Erica M; Isbel, Nicole M; de Malmanche, Theo; Durkan, Anne; Hissaria, Pravin; Blombery, Piers; Barbour, Thomas D

2018-06-01

Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. Although TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all adults, urgent, empirical plasma exchange (PE) should be started within 4-8 h of presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 (a disintegrin and metalloprotease thrombospondin, number 13) activity. A sodium citrate plasma sample should be collected for ADAMTS13 testing prior to any plasma therapy. In children, Shiga toxin-associated haemolytic uraemic syndrome due to infection with Escherichia coli (STEC-HUS) is the commonest cause of TMA, and is managed supportively. If TTP and STEC-HUS have been excluded, a diagnosis of aHUS should be considered, for which treatment is with the monoclonal complement C5 inhibitor, eculizumab. Although early confirmation of aHUS is often not possible, except in the minority of patients in whom auto-antibodies against factor H are identified, genetic testing ultimately reveals a complement-related mutation in a significant proportion of aHUS cases. The presence of other TMA-associated conditions (e.g. infection, pregnancy/postpartum and malignant hypertension) does not exclude TTP or aHUS as the underlying cause of TMA. © 2018 Royal Australasian College of Physicians.

Thrombocytopenic purpura in infectious mononucleosis-- A rare complication?

PubMed

Andrews, M V; Bart, J B

1975-01-01

We have presented an illustrative case of thrombocytopenic purpura complicating infectious mononucleosis. Steroid therapy appeared to be beneficial although spontaneous recovery cannot be excluded. The use of the Paul-Bunnell heterophil agglutination test is recommended for patients having idiopathic thrombocytopenic purpura to rule out subclinical infectious mononucleosis. It is suggested that this syndrome be treated with the expectancy of long-term remissions. Steroids appear to be of benefit. Platelet recovery is usually complete in less than 60 days. Splenectomy should not be considered until at least two months have passed. Chronic thrombocytopenia is an unlikely complication.

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.

Immune thrombocytopenic purpura in a child with acute lymphoblastic leukemia and mumps.

PubMed

Kurekci, A Emin; Atay, A Avni; Demirkaya, Erkan; Sarici, S Umit; Ozcan, Okan

2006-03-01

Immune thrombocytopenic purpura in childhood is characterized by a typical history of acute development of purpura and bruising in an otherwise healthy child. In children it usually follows a viral infection (eg, mumps, rubella) or immunization. We report for the first time a child with acute lymphoblastic leukemia who developed immune thrombocytopenic purpura due to mumps during the maintenance phase of acute lymphoblastic leukemia treatment.

Analyses of data of patients with Thrombotic Microangiopathy in the WAA registry.

PubMed

Mörtzell, M; Berlin, G; Nilsson, T; Axelsson, C G; Efvergren, M; Audzijoni, J; Griskevicius, A; Ptak, J; Blaha, M; Tomsova, H; Liumbruno, G M; Centoni, P; Newman, E; Eloot, S; Dhondt, A; Tomaz, J; Witt, V; Rock, G; Stegmayr, B

2011-10-01

Thrombotic Microangiopathy (TMA) is a histopathological feature of various diseases including thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. The aim of this study was to investigate the outcome and prognostic variables of TMA-patients. Data were consecutively retrieved from the WAA-apheresis registry (www.waa-registry.org) during 2003-2009. Included were all 120 patients (1237 procedures) who suffered from various forms of TMA, as registered by the ICD-10 code M31.1. Besides registry data, more extensive information was retrieved from the latest 64 patients. Adverse events of the TMA patients were compared to those of the other patients in the registry. The mean age was 46 years (range 11-85 years, 57% women). In 72% therapeutic apheresis was due to an acute indication while a long-term indication was present in 28%. Plasma exchange was performed by centrifugation and filtration technique (95% and 4%, respectively), and immunoadsorption in 1% of the patients. Only fresh frozen plasma was used as replacement fluid in 69% of procedures. Adverse events were more frequent than in the general apheresis population (10% versus 5%, RR 1.9, CI 1.6-2.3). No death occurred due to apheresis treatment. Three percent of the procedures were interrupted. Bronchospasm and/or anaphylactic shock were present in two patients and one patient suffered from TRALI. At admission 26% were bedridden and needed to be fed. The risk of dying during the treatment period was significantly higher if the patient also suffered from a compromising disease, such as cancer. There was an inverse correlation between the ADAMTS13 level and the antibody titer (r=-0.47, p=0.034). Patients with TMA have an increased risk for moderate and severe AE compared to the general apheresis population. Many patients were severely ill at admission. The prognosis is worse if the patient also has a severe chronic disease. Even slightly increased ADAMTS13-antibody titers seem to have a negative impact

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. © 2015 John Wiley & Sons Ltd.

Dental treatment in the era of new anti-thrombotic agents.

PubMed

Sahar-Helft, Sharonit; Chackartchi, Tali; Polak, David; Findler, Mordechai

2018-06-01

In recent years, there have been dramatic changes in anti-thrombotic treatment as a result of new anti-thrombotic agents, as well as changes in the indications for their use. As a consequence, dentists are encountering larger numbers of patients who are undergoing anti-thrombotic treatment and who have increased risk for bleeding. The current paper aims to review the literature regarding up-to-date anti-thrombotic treatment and provide information regarding their implications on dentistry. An online search was performed of the literature published between 2000 and 2016. Articles dealing with evidence-based clinical guidelines for anti-thrombotic treatments, as well as literature reporting the use of anti-thrombotic medications were included. The manuscripts were screened according to their relevance to dentistry as well as their treatment protocol guidelines. In total, 5,539 publications were identified: 56 of 554 evidence-based clinical guidelines were found that dealt with treatment protocols with anti-thrombotic agents; and 132 of 5,539 articles describe direct anti-thrombotic medications. Dental treatment includes a risk for bleeding. As a result of the increasing number of patients taking new-generation anti-thrombotic drugs, dentists must be up to date regarding the implications of such drugs on dental treatment as well as the practical means to achieve haemostasis. © 2017 FDI World Dental Federation.

The spectrum of renal thrombotic microangiopathy in lupus nephritis

PubMed Central

2013-01-01

Introduction Among various lupus renal vascular changes, thrombotic microangiopathy (TMA) presented with the most severe clinical manifestations and high mortality. The pathogenesis of TMA in systemic lupus erythematosus (SLE) was complicated. The aim of this study was to assess clinical manifestations, laboratory characteristics, pathological features and risk factors for clinical outcomes of lupus nephritis patients co-existing with renal TMA in a large cohort in China. Methods Clinical and renal histopathological data of 148 patients with biopsy-proven lupus nephritis were retrospectively analyzed. Serum complement factor H, A Disintegrin and Metalloprotease with Thrombospondin type I repeats 13 (ADAMTS-13) activity, antiphospholipid antibodies and C4d deposition on renal vessels were further detected and analyzed. Results In the 148 patients with lupus nephritis, 36 patients were diagnosed as co-existing with renal TMA based on pathological diagnosis. Among the 36 TMA patients, their clinical diagnoses of renal TMA were as followings: 2 patients combining with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome, 2 patients combining with anti-phospholipid syndrome, 2 patients with malignant hypertension, 1 patient with scleroderma and the other 29 patients presenting with isolated renal TMA. Compared with the non-renal TMA group, patients with renal TMA had significantly higher urine protein (7.09 ± 4.64 vs. 4.75 ± 3.13 g/24h, P = 0.007) and serum creatinine (159, 86 to 215 vs. 81, 68 to 112 μmol/l, P <0.001), higher scores of total activity indices (AI) (P <0.001), endocapillary hypercellularity (P <0.001), subendothelial hyaline deposits (P = 0.003), interstitial inflammation (P = 0.005), glomerular leukocyte infiltration (P = 0.006), total chronicity indices (CI) (P = 0.033), tubular atrophy (P = 0.004) and interstitial fibrosis (P = 0.018). Patients with renal TMA presented with poorer renal outcome (P = 0.005) compared with the non-TMA group

Malignant hypertension-associated thrombotic microangiopathy following cocaine use.

PubMed

Lamia, Rais; El Ati, Zohra; Ben Fatma, Lilia; Zouaghi, Karim; Smaoui, Wided; Rania, Khedher; Krid, Madiha; Ben Hmida, Fathi; Béji, Soumaya; Ben Moussa, Fatma

2016-01-01

Cocaine is one of the most commonly used illicit drugs with distribution and consumption throughout the world. Acute renal failure associated with rhabdomyolysis, direct vasoconstriction and hemodynamic alteration is well described in patients with cocaine intoxication. Cocaine use is associated with high blood pressure and may rarely induce malignant hypertension associated with thrombotic microangiopathy. We report the case of a patient who developed malignant hypertension associated with thrombotic microangiopathy after chronic consumption of cocaine. A kidney biopsy revealed thrombotic microangiopathy with fibrinoid necrosis of arterioles and glomerular tufts. He required dialysis sessions. Cocaine-mediated endothelial injury and platelet activation may play important pathogenetic roles in cocaine abusers who develop malignant hypertension associated with thrombotic microangiopathy. Clinicians need to be aware of this rare feature of cocaine intoxication.

Perioperative Care of a Patient with Refractory Idiopathic Thrombocytopenic Purpura Undergoing Total Knee Arthroplasty

PubMed Central

Gudimetla, Veera; Stewart, Andrew; Luscombe, Karen L; Charalambous, Charalambos P

2012-01-01

Idiopathic thrombocytopenic purpura (ITP) is an autoimmune disorder leading to low platelet count and an increased risk of bleeding. Major joint replacement surgery in a patient with ITP can be associated with severe postoperative bleeding. We present our experience of perioperative management in a patient with severe refractory chronic idiopathic thrombocytopenic purpura who successfully underwent a cemented total knee replacement. PMID:23269964

Coexisting Situs Inversus Totalis and Immune Thrombocytopenic Purpura.

PubMed

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

2016-01-01

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

[Thrombotic thrombocytopenia purpura in Martinique: Retrospective study between 2008 and 2015].

PubMed

Patient, M; Fuseau, P; Deligny, C

2017-08-01

Some studies suggest that thrombotic thrombocytopenic purpura (TTP) occurs more often in African Americans. However there is low evidence for this in the literature. The aim of our study was to describe the clinical and biological characteristics of TTP in the Afro-Caribbean population of Martinique. We retrospectively analysed all patients with TTP diagnosed at the Fort-de-France hospital between 2008, January 1st and 2015, December 31st. Diagnosis was confirmed if ADAMTS-13 activity was<10 %. Ten patients were included, corresponding to an average annual incidence of 3.2 cases/year/million individuals. None of the patient presented with the association of the five characteristic features of TTP. Microangiopathic haemolytic anaemia and severe peripheral thrombocytopenia (median: 13G/L) was the main presentation leading to diagnosis. There was no kidney involvement in 90 % of all patients, but severe neurological manifestations occurred in 70 %. Classical management including corticosteroids and plasma exchanges allowed clinical remission in 6 out of the 10 cases. If necessary, rituximab or cyclophosphamide was used. The overall survival rate was 90 %. In Martinique, the incidence of TTP is twice that reported in similar studies in France. Clinical manifestations seem to differ by more common and more severe neurological involvement. Mortality is low, in part, due to optimal care. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

An unusual occurrence of Kleine-Levin syndrome in a man with refractory immune thrombocytopenic purpura: a case report.

PubMed

Amirifard, Hamed; Barzkar, Farzaneh; Fazeli, Seyed Amirhossein; Hashemi, Seyed Mehdi

2015-04-01

Kleine-Levin syndrome is an extremely rare neurological entity characterized by recurrent episodes of hypersomnia which are sometimes associated with compulsive hyperphagia and behavioral changes. Autoimmunity has recently been proposed as a factor contributing to its pathogenesis. Immune thrombocytopenic purpura is a relatively common autoimmune disease showing a lot of complexity and uncertainty regarding its treatment regimens and its refractory nature in some cases. A 32-year-old Persian White man visited his private hematologist complaining of recent episodes of epistaxis and appearance of petechial lesions 24 hours after receiving a meningococcal vaccine. He had a history of immune thrombocytopenic purpura 13 years before his presentation. Based on his history and laboratory findings, his condition was diagnosed as a relapse of immune thrombocytopenic purpura and was managed accordingly. He did not respond to first-line corticosteroid regimens and later developed neurological symptoms as recurrent episodes of hypersomnia and hyperphagia. After a complete clinical and paraclinical evaluation and ruling out other possible conditions, he was given a diagnosis of Kleine-Levin syndrome. He was followed up for his immune thrombocytopenic purpura and received different treatment regimens none of which were adequately successful except intravenous immunoglobulin that was only temporarily effective. He has had 4 documented self-limited episodes of Kleine-Levin syndrome since his initial presentation. Immune thrombocytopenic purpura may be associated with meningococcal vaccination in adulthood. Responses to treatment in immune thrombocytopenic purpura vary among patients. Our patient only had a transient acceptable response to intravenous immunoglobulin while all other options failed to improve his platelet count. Concurrence of immune thrombocytopenic purpura and Kleine-Levin syndrome supports the role of autoimmunity as the proposed pathophysiological mechanism of

Management of Immune Thrombocytopenic Purpura: An Update

PubMed Central

Warrier, Rajasekharan; Chauhan, Aman

2012-01-01

Rapid strides have been made in the field of hematology, and advances in immune thrombocytopenic purpura (ITP) management are no exception. From idiopathic to immune, the changed nomenclature is itself a testimonial to the growing awareness and improvements in the management of ITP. We discuss the pathophysiology, clinical presentation, and current management of this common pediatric disorder and summarize current guidelines for ITP treatment. PMID:23049459

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

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

PubMed

Yousaf, Farhanah; 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.

Epsilon aminocaproic acid prevents bleeding in severely thrombocytopenic patients with hematological malignancies.

PubMed

Antun, Ana G; Gleason, Shannon; Arellano, Martha; Langston, Amelia A; McLemore, Morgan L; Gaddh, Manila; el Rassi, Fuad; Bernal-Mizrachi, Leon; Galipeau, Jacques; Heffner, Leonard T; Winton, Elliott F; Khoury, Hanna J

2013-11-01

Despite prophylactic platelet transfusions, bleeding remains a significant problem in thrombocytopenic patients. The antifibrinolytic agent epsilon aminocaproic acid (EACA) was administered to 44 chronically (median duration, 273 days) and severely (platelet count, 8 × 10(9)/L; range, 1 × 10(9)/L-19 × 10(9)/L) thrombocytopenic patients with hematological malignancies. Prophylactic EACA at a dose of 1 g twice daily was orally administered for a median duration of 47 days (range, 7 days-209 days) until the platelet count recovered to > 30; × 10(9) /L. Platelets were only transfused if bleeding occurred. While receiving EACA, 59% of the patients did not bleed, 25% had 19 episodes of spontaneously resolving minor bleeding that did not require platelet transfusion, and 16% received a median of 4 platelet transfusions (range, 1 transfusion-8 transfusions) for 1 major traumatic and 9 spontaneous grade 2 to grade 3 bleeding (based on the World Health Organization classification of idiopathic thrombocytopenic purpura). No EACA toxicities were noted, and venous thromboses were not observed. EACA is well tolerated and is associated with a low risk of major bleeding in patients with hematological malignancies who are experiencing chronic severe thrombocytopenia. © 2013 American Cancer Society.

Plasmapheresis in thrombotic microangiopathy-associated syndromes: review of outcome data derived from clinical trials and open studies.

PubMed

von Baeyer, Hans

2002-08-01

Current reimbursement policy of health insurance for therapeutic plasmapheresis requires proof of efficacy using the concept of evidence-based medicine. The aim of this paper is to review the outcome of plasmapheresis used to treat thrombotic microangiopathy (TMA)-associated syndromes in the last decade to provide scientific evidence to back up reimbursement applications. The strength of evidence of each reviewed study was assessed using the five levels of evidence criteria as defined by the American Society of Hematology in 1996 for assessment of the treatment of immune thrombocytopenia. The level Experimental indication was added for situations where only case reports or small series supported by pathophysiological reasoning are available. The definitions of evidence used in this paper are as follows: Level I, randomized clinical trial with low rates of error (p < 0.01); Level II, randomized clinical trial with high rates of error (p < 0.05); Level III, nonrandomized studies with concurrent control group; Level IV, nonrandomized studies with historical control group; Level V, case series without a control group or expert opinion; and Experimental, case reports and pathophysiological reasoning. The results of this analysis based on the published data is summarized as follows: The indication of plasmapheresis is assigned to Level IV evidence for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS); cancer/chemotherapy-associated TTP/HUS is assigned to Level V evidence; and TTP/HUS refractory to standard plasma exchange and post-bone marrow transplantation TTP/HUS are assigned to Experimental indication. For both subsets, protein A immunoadsorption is reportedly successful. The other TMA-associated syndromes, hemolysis elevated liver enzymes low platelets and HUS in early childhood, are no indication of plasmapheresis. Two randomized clinical trials were performed in order to demonstrate the superiority of plasma exchange/fresh frozen plasma (PEX

[Research Progress on Role of Inflammasome in Development of Thrombotic Diseases -Review].

PubMed

Wang, Jin-Xia; Liu, Ai-Fei; Li, Fang-Lin; Chen, Yi-Jian

2017-08-01

Inflammasome is a group of polyprotein complexes located in the cytoplasm, its activation can induce the maturation and release of proinflammatory cytokines IL-1β and IL-18, and promote the early atherosclerosis. In the recent years, it is found that the inflammasome is activated in thrombotic deseases, moveover, the activated inflammasome and its activation induced cytokines promote the occurrence and development of thrombolic deseases, and show the unfavaourable effect on prognosis. With further exploration on the mechanisms of thrombotic diseases, the relationship between the inflammasome and thrombotic diseases increasingly become a hot spot of research. This review focuses on the action mechanisms of inflammasome in thrombotic diseases.

How do we reduce plasma transfusion in Rhode Island?

PubMed

Nixon, Christian P; Tavares, Maria F; Sweeney, Joseph D

2017-08-01

Plasma transfusions are given to patients with coagulopathy, either prophylactically, before an invasive procedure; or therapeutically, in the presence of active bleeding; and as an exchange fluid in therapeutic plasma exchange for disorders such as thrombotic thrombocytopenic purpura. There is consensus that many prophylactic plasma transfusions are non-efficacious, and the misdiagnosis of thrombotic thrombocytopenic purpura results in unnecessary therapeutic plasma exchange. Beginning in 2001, programs to reduce plasma transfusion in the three major teaching hospitals in Rhode Island were initiated. The programs evolved through the establishment of guidelines, education for key prescribers of plasma, screening of plasma prescriptions, and engagement of individual prescribing physicians for out-of-guidelines prescriptions with modification or cancellation. Establishment of an in-house ADAMTS13 (ADAM metallopeptidase with thrombospondin type 1, motif 13) assay in 2013 was used to prevent therapeutic plasma exchange in patients with non-thrombotic thrombocytopenic purpura microangiopathy. Transfusion service data were gathered at the hospital level regarding blood component use, hospital data for discharges, inpatient mortality, and mean case-mix index, and, at the state level, for units of plasma shipped from the community blood center to in-state hospitals. Between 2006 and 2016, a reduction in plasma use from 11,805 to 2677 units (a 77% decrease) was observed in the three hospitals and was mirrored in the state as a whole. This decline was not associated with any increase in red blood cell transfusion. Inpatient mortality either declined or was unchanged. An active program focused on education and interdiction can achieve a large decrease in plasma transfusions without evidence of patient harm. © 2017 AABB.

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

PubMed

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

2016-12-31

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.

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

Expression of CD markers' in immune thrombocytopenic purpura: prognostic approaches.

PubMed

Behzad, Masumeh Maleki; Asnafi, Ali Amin; Jaseb, Kaveh; Jalali Far, Mohammad Ali; Saki, Najmaldin

2017-12-01

Immune Thrombocytopenic Purpura (ITP) is a common autoimmune bleeding disorder characterized by a reduction in peripheral blood platelet counts. In this disease, autoantibodies (Auto-Abs) are produced against platelet GPIIb/GPIIIa by B cells, which require interaction with T cells. In this review, the importance of B and T lymphocytes in ITP prognosis has been studied. Relevant literature was identified by a PubMed search (1990-2016) of English-language papers using the terms B and T lymphocyte, platelet, CD markers and immune thrombocytopenic purpura. T and B lymphocytes are the main immune cells in the body. Defective function causes disrupted balance of different subgroups of lymphocytes, and abnormal expression of surface markers of these cells results in self-tolerance dysfunction, as well as induction of Auto-Abs against platelet glycoproteins (PG). Given the role of B and T cells in production of autoantibodies against PG, it can be stated that the detection of changes in CD markers' expression in these cells can be a good approach for assessing prognosis in ITP patients. © 2017 APMIS. Published by John Wiley & Sons Ltd.

Management of adult patients with persistent idiopathic thrombocytopenic purpura following splenectomy: a systematic review.

PubMed

Vesely, Sara K; Perdue, Jedidiah J; Rizvi, Mujahid A; Terrell, Deirdra R; George, James N

2004-01-20

Treatment of chronic refractory idiopathic thrombocytopenic purpura is a dilemma because many patients have minimal symptoms, response to treatment is uncertain, and treatments may have serious adverse effects. To determine the effectiveness of treatments for adult patients with idiopathic thrombocytopenic purpura who have not responded to splenectomy. English-language reports from 1966 through 2003 that were retrieved from MEDLINE and Reference Update and bibliographies of retrieved articles. Articles reporting 5 or more total patients were reviewed to select eligible patients. Patients were eligible for inclusion if they were more than 16 years of age, had idiopathic thrombocytopenic purpura for more than 3 months, had a previous splenectomy, and had a platelet count less than 50 x 10(9) cells/L. Patients were assessed for platelet count response, bleeding complications, duration of follow-up, and death. Complete remission was defined as a normal platelet count with no treatment for more than 3 months and for the duration of follow-up. 90 articles with 656 patients treated with 22 therapies met selection criteria. Azathioprine, cyclophosphamide, and rituximab had the most reported complete responses, but they were reported in only 41 to 109 patients. Reported complete response rates ranged from 17% to 27%, but 36% to 42% of patients had no response with these 3 treatments. Most reports described only platelet count responses; bleeding outcomes were reported in only 63 patients (10%). Only 111 (17%) of the 656 eligible patients had pretreatment platelet counts of less than 10 x 10(9) cells/L. No treatment method was reported in more than 20 patients. Evidence for the effectiveness of any treatment for patients with idiopathic thrombocytopenic purpura and persistent severe thrombocytopenia after splenectomy is minimal. Potentially effective treatments must be evaluated by randomized, controlled trials to determine both benefit and safety.

[Acute renal failure secondary to hemolytic uremic syndrome in a pregnant woman with pre-eclampsia].

PubMed

García-Miguel, F J; Mirón Rodríguez, M F; Alsina Aser, M J

2009-02-01

Acute renal failure is a serious complication of pregnancy associated with a high rate of morbidity and mortality; the incidence is currently 1 per 10,000 pregnancies. The most common causes are gestational hypertension, bleeding, sepsis, and intrinsic renal disease. Other less common pregnancy-related syndromes, such as HELLP syndrome or thrombotic microangiopathy, may also lead to kidney failure. Hemolytic uremic syndrome and thrombotic thrombocytopenic purpura are forms of thrombotic microangiopathy and although neither is specific to pregnancy, the incidence of these entities rises during gestation. The classic symptoms are fever, hemolytic microangiopathic anemia, thrombopenia, neurologic dysfunction, and kidney abnormalities. When renal involvement is the predominant manifestation, the diagnosis is usually hemolytic uremic syndrome.

Rapid update on childhood immune thrombocytopenic purpure.

PubMed

Cole, Catherine H

2012-05-01

Most childhood immune thrombocytopenic purpure is benign, self-limiting and requires no therapy. However, questions remain: (i) to treat or not; (ii) bone marrow examination or not; and (iii) admit to hospital or not. These questions have dominated the literature and we still need a prospective large multi-centre study of these issues to determine a useful bleeding score, quality of life measure and a measure of parental anxiety. © 2011 The Author. Journal of Paediatrics and Child Health © 2011 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Nonbacterial thrombotic endocarditis presenting as intracerebral hemorrhage.

PubMed

Wigger, Olivier; Windecker, Stephan; Bloechlinger, Stefan

2016-12-01

Nonbacterial thrombotic endocarditis is a rare cause of valvular heart disease, most commonly associated with advanced malignancy. The morbidity of this kind of endocarditis lies in its tendency to embolize, while the valve function is usually preserved. The central nervous system is the most common site of embolization, leading to ischemic stroke. We report a case of nonbacterial thrombotic endocarditis complicated by intracerebral hemorrhage as the first manifestation of adenocarcinoma of the lung. The endocarditis led to severe aortic regurgitation. In view of the advanced stage of lung cancer, the patient refused further therapy. He passed away 3 weeks after first diagnosis of the adenocarcinoma.

A Case of HELLP Syndrome in a Patient with Immune Thrombocytopenic Purpura

PubMed Central

Ben, Sebastián; Rodríguez, Fabián; Severo, Carlos; Debat, Natalia

2010-01-01

We will describe the clinical case of a pregnant patient with chronic Immune Thrombocytopenic Purpura who develops preeclampsia syndrome with HELLP syndrome. These concomitant and independent conditions become complex, resulting in thrombocytopenia which creates diagnostic, prognostic and therapeutic inconveniences. PMID:20871821

Immune Thrombocytopenic Purpura Detected with Oral Hemorrhage: a Case Report

PubMed Central

Sugiura, Tsutomu; Yamamoto, Kazuhiko; Murakami, Kazuhiro; Horita, Satoshi; Matsusue, Yumiko; Nakashima, Chie; Kirita, Tadaaki

2018-01-01

Immune thrombocytopenic purpura (ITP) is an immune-mediated acquired disease found in both adults and children. It is characterized by transient or persistent decreases in the platelet count. We report a case of ITP detected based on oral hemorrhagic symptoms. The patient was a 79-year-old female with no significant past medical history. She presented with sudden onset of gingival bleeding and hemorrhagic bullae on the buccal mucosa. Gingival bleeding was difficult to control. Laboratory tests revealed severe thrombocytopenia with a platelet count as low as 2000/μL. Under a provisional diagnosis of a hematological disorder, she was referred to a hematologist. A peripheral smear showed normal-sized platelets. A bone marrow examination revealed increased numbers of megakaryocytes without morphologic abnormalities. The patient was diagnosed with ITP and treated with a combination of pulsed steroid therapy and high-dose immunoglobulin therapy. However, her severe thrombocytopenia was refractory to these treatments. Then, a thrombopoietin receptor agonist was begun as a second-line treatment. Her platelets rapidly increased, and no bleeding complications were reported. Because oral symptoms can be one of the initial manifestations of ITP, dentists should be familiar with the clinical appearance of ITP, and attention must be paid to detect and diagnose unidentified cases. PMID:29854891

Cerebral Venous Thrombosis after Intravenous Immunoglobulin Therapy in Immune Thrombocytopenic Purpura

PubMed Central

James, Joe; Shiji, P. V.; Radhakrishnan, Chandni

2017-01-01

A common misconception is that immune thrombocytopenic purpura (ITP) causes only bleeding diathesis. From this case vignette of a young male with ITP who had cerebral venous thrombosis, we highlight the importance of considering venous thrombosis in such patients when they present with focal cerebral signs. PMID:29307971

Long-term low-molecular-weight heparin and the post-thrombotic syndrome: a systematic review.

PubMed

Hull, Russell D; Liang, Jane; Townshend, Grace

2011-08-01

Post-thrombotic syndrome causes considerable morbidity. The Home-LITE study showed a lower incidence of post-thrombotic syndrome and venous ulcers after 3 months of treating deep vein thrombosis with the low-molecular-weight heparin tinzaparin versus oral anticoagulation. This systematic review examined whether long-term treatment of deep vein thrombosis using low-molecular-weight heparin, rather than oral anticoagulation, reduces development of post-thrombotic syndrome. We identified 9 articles comparing treatment of deep vein thrombosis using long-term low-molecular-weight heparin with any comparator, which reported outcomes relevant to the post-thrombotic syndrome assessed ≥ 3 months post-deep vein thrombosis. Pooled analysis of 2 studies yielded an 87% risk reduction with low-molecular-weight heparin in the incidence of venous ulcers at ≥ 3 months (P = .019). One study showed an overall odds ratio of 0.77 (P = .001) favoring low-molecular-weight heparin for the presence of 8 patient-reported post-thrombotic syndrome signs and symptoms. Pooled analysis of 5 studies showed a risk ratio for low-molecular-weight heparin versus oral anticoagulation of 0.66 (P < .0001) for complete recanalization of thrombosed veins. These results support the lower incidence of post-thrombotic syndrome and venous ulcers observed in Home-LITE. Long-term treatment with low-molecular-weight heparin rather than oral anticoagulation after a deep vein thrombosis may reduce or prevent development of signs and symptoms associated with post-thrombotic syndrome. Post-thrombotic syndrome and associated acute ulcers may develop more rapidly after deep vein thrombosis than previously recognized. Copyright © 2011 Elsevier Inc. All rights reserved.

Auricular chondritis and thrombotic microangiopathy: an unusual combination revealing systemic lupus erythematosus.

PubMed

Bellon, Nathalia; Anguel, Nadia; Vandendries, Christophe; Goujard, Cecile; Lambotte, Olivier

2013-07-01

Thrombotic microangiopathy is a severe disorder, which is a cause of stroke in young patients. Etiologic investigations are mandatory to diagnose underlying disease. Systemic lupus erythematosus is one of the diseases, which can be associated with thrombotic microangiopathy. Although lupus diagnosis is usually easy, relying on characteristic clinical manifestations, rare symptoms can be misinterpreted. We report here a case of polychondritis, which was the first manifestation of a lupus-associated thrombotic microangiopathy. Copyright © 2012 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

PREVALENCE OF POST-THROMBOTIC SYNDROME AFTER CARDIAC CATHETERIZATION

PubMed Central

Luceri, Michael J.; Tala, Joana A.; Weismann, Constance G.; Silva, Cicero T.; Faustino, E. Vincent S.

2015-01-01

BACKGROUND As the survival of children with cardiac disease increases, chronic complications of deep venous thrombosis from cardiac catheterization, particularly post-thrombotic syndrome, may be important to monitor for and treat, if needed. We aimed to determine the prevalence of this syndrome in children who underwent cardiac catheterization. PROCEDURE We conducted a cross-sectional study of children <18 years old at least 1 year from first catheterization through the femoral vein. We used the Manco-Johnson instrument, the only tool validated in children, to diagnose post-thrombotic syndrome. We defined the syndrome as a score ≥1. It was considered physically and functionally significant if the score was ≥1 in both physical and functional domains of the instrument. We also conducted ultrasonography to assess for thrombosis and valvular insufficiency. RESULTS We enrolled 62 children with a median age of 4 months during catheterization and a median of 5.4 years since catheterization. A total of 40 children had post-thrombotic syndrome (prevalence: 64.5%; 95% confidence interval: 51.3%–76.3%), the majority of which were mild. Presence of cyanotic congenital heart disease, total number of catheterizations, use of antithrombotic agents at any time after the first catheterization, age at first catheterization, or time since first catheterization was not associated with the syndrome. A total of 7 children (prevalence: 11.3%; 95% confidence interval: 3.2%–19.4%) had physically and functionally significant syndrome. None of the children had abnormalities on ultrasonography at the time of enrollment. CONCLUSIONS Post-thrombotic syndrome is a common complication after cardiac catheterization. Manifestations are usually mild and unlikely to require treatment. PMID:25663038

Impact of Hormone-Associated Resistance to Activated Protein C on the Thrombotic Potential of Oral Contraceptives: A Prospective Observational Study

PubMed Central

Müller, Jens; Sukhitashvili, Shorena; Welz, Julia; Kuhn, Walther C.; Oldenburg, Johannes; Rudlowski, Christian; Pötzsch, Bernd

2014-01-01

Introduction The increased thrombotic risk of oral contraceptives (OC) has been attributed to various alterations of the hemostatic system, including acquired resistance to activated protein C (APC). To evaluate to what extent OC-associated APC resistance induces a prothrombotic state we monitored plasma levels of thrombin and molecular markers specific for thrombin formation in women starting OC use. Elevated plasma levels of thrombin have been reported to characterize situations of high thrombotic risk such as trauma-induced hypercoagulability, but have not yet been studied during OC use. Patients and Methods Blood samples were collected prospectively from healthy women (n = 21) before and during three menstruation cycles after start of OC. APC resistance was evaluated using a thrombin generation-based assay. Plasma levels of thrombin and APC were directly measured using highly sensitive oligonucleotide-based enzyme capture assay (OECA) technology. Thrombin generation markers and other hemostasis parameters were measured additionally. Results All women developed APC resistance as indicated by an increased APC sensitivity ratio compared with baseline after start of OC (p = 0.0003). Simultaneously, plasma levels of thrombin, prothrombin fragment 1+2, and of thrombin-antithrombin complexes did not change, ruling out increased thrombin formation. APC plasma levels were also not influenced by OC use, giving further evidence that increased thrombin formation did not occur. Conclusions In the majority of OC users no enhanced thrombin formation occurs despite the development of APC resistance. It cannot be ruled out, however, that thrombin formation might occur to a greater extent in the presence of additional risk factors. If this were the case, endogenous thrombin levels might be a potential biomarker candidate to identify women at high thrombotic risk during OC treatment. Large-scale studies are required to assess the value of plasma levels of thrombin as

Defining the Thrombotic Risk in Patients with Myeloproliferative Neoplasms

PubMed Central

Vianello, Fabrizio; Battisti, Anna; Cella, Giuseppe; Marchetti, Marina; Falanga, Anna

2011-01-01

Polycythemia vera (PV) and essential thrombocythemia (ET) are two Philadelphia-negative myeloproliferative neoplasms (MPN) associated with an acquired mutation in the JAK2 tyrosine kinase gene. There is a rare incidence of progression to myelofibrosis and myeloid metaplasia in both disorders, which may or may not precede transformation to acute myeloid leukemia, but thrombosis is the main cause of morbidity and mortality. The pathophysiology of thrombosis in patients with MPN is complex. Traditionally, abnormalities of platelet number and function have been claimed as the main players, but increased dynamic interactions between platelets, leukocytes, and the endothelium do probably represent a fundamental interplay in generating a thrombophilic state. In addition, endothelial dysfunction, a well-known risk factor for vascular disease, may play a role in the thrombotic risk of patients with PV and ET. The identification of plasma markers translating the hemostatic imbalance in patients with PV and ET would be extremely helpful in order to define the subgroup of patients with a significant clinical risk of thrombosis. PMID:21623459

Overwork accelerates thrombotic reaction: implications for the pathogenesis of Karoshi.

PubMed

Otsui, Kazunori; Yamamoto, Junichiro; Inoue, Nobutaka

2018-02-01

Work-related stressors are potential causes of cardiovascular diseases (CVDs) and stroke; however, the pathophysiological mechanisms by which occupational stress induces and exacerbates CVDs remain unclear. The global thrombosis test (GTT) is a novel in vitro assay for evaluating both thrombotic reactions and subsequent thrombolysis. The time required to form an occlusive thrombus with the GTT, called as the occlusion time (OT), and the time to lyse the thrombus, the lysis time (LT), are markers of thrombotic and thrombolytic reactions, respectively. We investigated the impact of work-related stress on the thrombotic and thrombolytic reactions in 46 healthy medical residents. Off-duty or on-duty blood samples were collected on the mornings of non-work days or after the night duty on the emergent room respectively. The duration of sleep was significantly shorter during night duty than during off-duty nights [2.25 (1.0, 3.0) h vs. 6.0 (5.0, 7.0) h; p < 0.001]. Baseline OT was 310.3 (260.9, 437.7) s. whereas the on-duty OT was significantly shortened [284.2 (230.5, 355.8) s; p < 0.01]. LT was significantly prolonged during overwork conditions compared with off-duty conditions [1547 (1346, 1908) s vs. 1470 (1219, 1692) s; p < 0.05]. Overwork accelerates the thrombotic reactions. These reactions might explain the pathogenesis of overwork-related CVDs. The GTT is a good tool for evaluating of the level of fatigue.

[Thrombotic skin gangrene: A rare extra-intestinal manifestation of ulcerative colitis].

PubMed

Aounallah, A; Ghariani Fetoui, N; Ghariani, N; Korbi, M; Mokni, S; Boussofara, L; Saidi, W; Ksiaa, M; Ben Jazia, I; Guerfala, M; Sriha, B; Belajouza, C; Denguezli, M; Nouira, R

2017-02-01

Thrombotic cutaneous gangrene is a rare extra-intestinal manifestation of ulcerative colitis with a severe prognosis. A 35-year-old woman with a 7-year history of ulcerative colitis presented with extensive ecchymotic lesions that began a few hours earlier. On examination, she was febrile with multiple necrotic lesions. Skin biopsy showed multiple microthrombi in the dermal vessels. A diagnosis of thrombotic cutaneous gangrene was established. The patient was treated with heparin and systemic corticosteroids. The majority of cutaneous lesions showed improvement after 1 month. Thrombophlebitis of the left lower limb occurred subsequently. Thrombotic cutaneous gangrene is attributed to microvascular thrombosis, which arises from the hypercoagulability observed in ulcerative colitis. Complete blood and coagulation tests must be performed and early anticoagulation with heparin must be considered in order to prevent the progression of cutaneous infarction. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Enzymatic lipid oxidation by eosinophils propagates coagulation, hemostasis, and thrombotic disease

PubMed Central

Uderhardt, Stefan; Ackermann, Jochen A.; Fillep, Tobias; Hammond, Victoria J.; Willeit, Johann; Stark, Konstantin; Rossaint, Jan; Schubert, Irene; Mielenz, Dirk; Dietel, Barbara; Raaz-Schrauder, Dorette; Ay, Cihan; Thaler, Johannes; Heim, Christian; Collins, Peter W.; Schabbauer, Gernot; Mackman, Nigel; Voehringer, David; Nadler, Jerry L.; Lee, James J.; Massberg, Steffen; Rauh, Manfred; O’Donnell, Valerie B.

2017-01-01

Blood coagulation is essential for physiological hemostasis but simultaneously contributes to thrombotic disease. However, molecular and cellular events controlling initiation and propagation of coagulation are still incompletely understood. In this study, we demonstrate an unexpected role of eosinophils during plasmatic coagulation, hemostasis, and thrombosis. Using a large-scale epidemiological approach, we identified eosinophil cationic protein as an independent and predictive risk factor for thrombotic events in humans. Concurrent experiments showed that eosinophils contributed to intravascular thrombosis by exhibiting a strong endogenous thrombin-generation capacity that relied on the enzymatic generation and active provision of a procoagulant phospholipid surface enriched in 12/15-lipoxygenase–derived hydroxyeicosatetraenoic acid–phosphatidylethanolamines. Our findings reveal a previously unrecognized role of eosinophils and enzymatic lipid oxidation as regulatory elements that facilitate both hemostasis and thrombosis in response to vascular injury, thus identifying promising new targets for the treatment of thrombotic disease. PMID:28566277

[Thrombotic Microangiopathies].

PubMed

Schubert, Jörg; Dechant, Michael

2018-06-01

Thrombotic microangiopathies are almost devastating diseases leading to death at high frequency if untreated. They consist of at least five distinct entities, TTP, HUS, aHUS, TMA due to drug interference, systemic disease or post therapy TMA. Around 10 years ago there was only one established therapeutic approach as plasmapheresis. Meanwhile, there are new drugs been licensed or within licensing process. Patients with atypical HUS can be treated successfully by the Complement inhibitor Eculizumab. In addition, there is a new inhibitor of von-Willebrand-Polymerisation available. Caplacizumab provides a significantly better remission and decrease in TMA-related death. For therapy associated TMA as VOD/SOS Defibrotide could be established within a phase III study to significantly improve outcomes. In order to select these new medical approaches individual diagnostic parameters need to be established in order to rapidly distinguish between the TMA entities and start targeted therapy. © Georg Thieme Verlag KG Stuttgart · New York.

Rutosides for prevention of post-thrombotic syndrome.

PubMed

Morling, Joanne R; Yeoh, Su Ern; Kolbach, Dinanda N

2015-09-16

Post-thrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT) that is characterised by pain, swelling, and skin changes in the affected limb. One in three patients with DVT will develop post-thrombotic sequelae within five years. The current standard care for the prevention of PTS following DVT is elastic compression stockings. Rutosides are a group of compounds derived from horse chestnut (Aesculus hippocastanum), a traditional herbal remedy for treating oedema formation in chronic venous insufficiency (CVI). However, it is not known whether rutosides are effective and safe in the prevention of post-thrombotic syndrome. This is an update of the review first published in 2013. To determine the effectiveness and safety of rutosides for prevention of PTS in patients with DVT, compared to placebo, no intervention, or reference medication. For this update the Cochrane Vascular Group Trials Search Co-ordinator searched the Specialised Register (last searched September 2015) and the Cochrane Register of Studies (CRS) ((CENTRAL) 2015, Issue 8). Clinical trials databases were searched for details of ongoing and unpublished studies. We planned to include trials of rutosides versus any alternative (placebo, no intervention, or reference medication) in the prevention of PTS in patients with DVT. Two review authors independently assessed studies for inclusion and intended to extract information from the trials. No studies were identified comparing rutosides versus any alternative in the prevention of PTS. As there were no studies identified in this review there is currently insufficient evidence to determine the effectiveness and safety of rutosides for prevention of PTS in patients with DVT. Some studies suggest that rutosides may provide short-term relief of PTS symptoms. However, there is nothing published on their use as a preventative therapy for PTS. High quality randomised controlled trials of rutoside versus any alternative are required to

Rutosides for prevention of post-thrombotic syndrome.

PubMed

Morling, Joanne R; Yeoh, Su Ern; Kolbach, Dinanda N

2013-04-30

Post-thrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT) that is characterised by pain, swelling, and skin changes in the affected limb. One in three patients with DVT will develop post-thrombotic sequelae within five years. The current standard care for the prevention of PTS following DVT is elastic compression stockings. Rutosides are a group of compounds derived from horse chestnut (Aesculus hippocastanum), a traditional herbal remedy for treating oedema formation in chronic venous insufficiency (CVI). However, it is not known whether rutosides are effective and safe in the prevention of post-thrombotic syndrome. To determine the effectiveness and safety of rutosides for prevention of PTS in patients with DVT, compared to placebo, no intervention, or reference medication. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched October 2012) and CENTRAL (2012, Issue 9). Clinical trials databases were searched for details of ongoing and unpublished studies. We planned to include trials of rutosides versus any alternative (placebo, no intervention, or reference medication) in the prevention of PTS in patients with DVT. Two authors independently assessed studies for inclusion and intended to extract information from the trials. No studies were identified comparing rutosides versus any alternative in the prevention of PTS. As there were no studies identified in this review it is not possible to support the use of rutosides in the prevention of PTS. Some studies suggest that rutosides may provide short-term relief of PTS symptoms. However, there is nothing published on their use as a preventative therapy for PTS. High quality randomised controlled trials of rutoside versus any alternative are required to build the evidence base in this area.

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

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.

Post-thrombotic syndrome in children: a systematic review of frequency of occurrence, validity of outcome measures, and prognostic factors

PubMed Central

Goldenberg, Neil A.; Donadini, Marco P.; Kahn, Susan R.; Crowther, Mark; Kenet, Gili; Nowak-Göttl, Ulrike; Manco-Johnson, Marilyn J.

2010-01-01

Background Post-thrombotic syndrome is a manifestation of chronic venous insufficiency following deep venous thrombosis. This systematic review was conducted to critically evaluate pediatric evidence on frequency of occurrence, validity of outcome measures, and prognostic indicators of post-thrombotic syndrome. Design and Methods A comprehensive literature search of original reports revealed 19 eligible studies, totaling 977 patients with upper/lower extremity deep venous thrombosis. Calculated weighted mean frequency of post-thrombotic syndrome was 26% (95% confidence interval: 23–28%) overall, and differed significantly by prospective/non-prospective analysis and use/non-use of a standardized outcome measure. Results Standardized post-thrombotic syndrome outcome measures included an adaptation of the Villalta scale, the Clinical-Etiologic-Anatomic-Pathologic classification, and the Manco-Johnson instrument. Data on validity were reported only for the Manco-Johnson instrument. No publications on post-thrombotic syndrome-related quality of life outcomes were identified. Candidate prognostic factors for post-thrombotic syndrome in prospective studies included use/non-use of thrombolysis and plasma levels of factor VIII activity and D-dimer. Conclusions Given that affected children must endure chronic sequelae for many decades, it is imperative that future collaborative pediatric prospective cohort studies and trials assess as key objectives and outcomes the incidence, severity, prognostic indicators, and health impact of post-thrombotic syndrome, using validated measures. PMID:20595095

Complicated Lower Extremity Wound Caused by Immune Thrombocytopenic Purpura Leading to Hypercoagulable State: A Team Approach for Limb Salvage

PubMed Central

Simman, Richard; Haluschak, John; Jackson, Sarah

2010-01-01

This article describes a complicated lower extremity wound due to hypercoagulable state caused by immune thrombocytopenic purpura. A team approach was important to limb salvage. A literature review is included. PMID:24527141

Classical management of refractory adult immune (idiopathic) thrombocytopenic purpura.

PubMed

McMillan, R

2002-03-01

Treatment of chronic immune (idiopathic) thrombocytopenic purpura with corticosteroids and/or splenectomy results in safe platelet counts in over 70% of patients without additional treatment. Therapy of patients who are refractory to these two treatments may be difficult. The treatment approach to refractory ITP patients, described in this report, is arbitrarily divided into four levels: levels 1 through 3 represent treatments with increasing side effects; level 4 therapy may be tried when the others have failed. Patients undergoing these treatments may require concomitant intravenous gammaglobulin, high-dose corticosteroids or platelets, to maintain the platelet count in the setting of mucosal bleeding or severe thrombocytopenia. Copyright 2002, Elsevier Science Ltd. All rights reserved.

Antiphospholipid antibodies and non-thrombotic manifestations of systemic lupus erythematosus.

PubMed

İlgen, U; Yayla, M E; Ateş, A; Okatan, İ E; Yurteri, E U; Torgutalp, M; Keleşoğlu, A B D; Turgay, T M; Kınıklı, G

2018-04-01

Objectives The aim of this study was to investigate the association between antiphospholipid antibodies and non-thrombotic and non-gestational manifestations of systemic lupus erythematosus. Methods Systemic lupus erythematosus patients with persistently positive antiphospholipid antibodies or lupus anticoagulant were identified and grouped as systemic lupus erythematosus with antiphospholipid syndrome (SLE-APS), systemic lupus erythematosus with positive antiphospholipid antibodies/lupus anticoagulant without antiphospholipid syndrome (SLE-aPL), and systemic lupus erythematosus with negative aPLs (SLE-No aPL). Groups were compared in terms of non-thrombotic systemic lupus erythematosus manifestations and laboratory features retrospectively. Results A total of 150 systemic lupus erythematosus patients, 26 with SLE-APS, 25 with SLE-aPL, and 99 with SLE-No aPL, were identified. Livedo reticularis, neurologic involvement, and thrombocytopenia were more common in antiphospholipid antibody positive systemic lupus erythematosus cases. Malar rash, arthritis, and pleuritis were more common in the SLE-No aPL, SLE-APS, and SLE-aPL groups, respectively. Positivity rates and titers of specific antiphospholipid antibodies did not differ between the SLE-APS and SLE-aPL groups. Conclusions Presence of antiphospholipid syndrome or persistent antiphospholipid antibodies may be related to non-thrombotic and non-gestational systemic lupus erythematosus manifestations. Patients with systemic lupus erythematosus plus antiphospholipid syndrome and persistent antiphospholipid antibodies without antiphospholipid syndrome also differ in terms of systemic lupus erythematosus manifestations.

DRESS syndrome with thrombotic microangiopathy revealing a Noonan syndrome

PubMed Central

Bobot, Mickaël; Coen, Matteo; Simon, Clémentine; Daniel, Laurent; Habib, Gilbert; Serratrice, Jacques

2018-01-01

Abstract Rationale: The life-threatening drug rash with eosinophilia and systemic symptoms (DRESS) syndrome occurs most commonly after exposure to drugs, clinical features mimic those found with other serious systemic disorders. It is rarely associated with thrombotic microangiopathy. Patient concerns: We describe the unique case of a 44-year-old man who simultaneously experienced DRESS syndrome with thrombotic microangiopathy (TMA) after a 5 days treatment with fluindione. Diagnoses: Clinical evaluation leads to the discovery of an underlying lymphangiomatosis, due to a Noonan syndrome. Intervetions: The anticoagulant was withdrawn, and corticosteroids (1 mg/kg/day) and acenocoumarol were started. Outcomes: Clinical improvement ensued. At follow-up the patient is well. Lessons: The association of DRESS with TMA is a rare condition; we believe that the presence of the underlying Noonan syndrome could have been the trigger. Moreover, we speculate about the potential interrelations between these entities. PMID:29642153

Reduction of factor XII in antiphospholipid antibody-positive patients with thrombotic events in the rheumatology clinic.

PubMed

Takeishi, M; Mimori, A; Nakajima, K; Mimura, T; Suzuki, T

2003-02-01

Although rheumatological diagnosis often includes an assessment of antiphospholipid (aPL) antibodies, the significance of other prothrombotic factors has not been established in thrombotic patients who are not afflicted with either arteriosclerosis or vasculitis syndrome. We have observed both the presence of antiphospholipid antibodies and a reduction of factor XII in such patients. Our results identified both lupus anticoagulant-positive (50%) and anticardiolipin antibody-positive (58%) patients. In addition, 83% of patients showed factor XII antigen level reduction. Furthermore, 70% of aPL-positive thrombotic patients showed factor XII antigen level reduction. Only two cases had antiphospholipid antibody alone, and 4/12 showed just factor XII antigen reduction. Recently, it has been reported that the presence of antiphospholipid antibodies induces factor XII reduction, and that anti-factor XII autoantibody can be detected in thrombotic patients. However, our results indicate that there are smaller factor XII reductions in non-thrombotic controls who are positive for antiphospholipid antibodies. Furthermore, anti-factor XII autoantibody was not detected in patients with decreased factor XII levels. Kindred research suggested that in two patients there was a genetic component to factor XII reduction. We concluded that the presence of both antiphospholipid antibodies and reduced serum factor XII was observed in most thrombotic patients from our rheumatology clinic. It is therefore possible to consider that the coexistence of these prothrombotic factors can contribute to the onset of thrombosis.

Filter membrane-based automated therapeutic plasma exchange: a report of two cases from Nigeria.

PubMed

Arogundade, Fatiu A; Sanusi, Abubakr A; Akinbodewa, Akinwunmi A; Hassan, Muzamil O; Omotosho, Bolanle O; Balogun, Rasheed A; Akinsola, Adewale

2013-02-01

These case reports demonstrated the diagnostic dilemma encountered in patients with systemic lupus erythematosus and thrombotic thrombocytopenic purpura particularly in settings with limited diagnostic facilities and laboratory support. The similarities in the diagnostic criteria for both conditions make clear distinction as well as management decisions difficult. We present the difficulties encountered with both the diagnosis and the management of these two patients that were managed in our facility. Copyright © 2013 Wiley Periodicals, Inc.

Interaction between human blood platelets, viruses and antibodies. IV. Post-Rubella thrombocytopenic purpura and platelet aggregation by Rubella antigen–antibody interaction

PubMed Central

Myllylä, G.; Vaheri, A.; Vesikari, T.; Penttinen, K.

1969-01-01

A new method of measuring antibodies by observing sedimentation patterns of platelets has been compared with the complement fixation and haemagglutination inhibition techniques in ten cases of Rubella and seven cases of post-Rubella thrombocytopenic purpura. The method is based on the aggregation of platelets by the joint action of antibody and small size antigens. The platelet aggregation method gave exceptionally high titres in cases of post-Rubella thrombocytopenic purpura. Other serologic methods did not give these high titres. The hypothesis that small size virus antigen and antibody against it are both needed to induce thrombocytopenia during the recovery period is discussed. Large amounts of both may result in clinical symptoms. PMID:5814719

Pediatric post-thrombotic syndrome in children: Toward the development of a new diagnostic and evaluative measurement tool.

PubMed

Avila, M L; Brandão, L R; Williams, S; Ward, L C; Montoya, M I; Stinson, J; Kiss, A; Lara-Corrales, I; Feldman, B M

2016-08-01

Our goal was to conduct the item generation and piloting phases of a new discriminative and evaluative tool for pediatric post-thrombotic syndrome. We followed a formative model for the development of the tool, focusing on the signs/symptoms (items) that define post-thrombotic syndrome. For item generation, pediatric thrombosis experts and subjects diagnosed with extremity post-thrombotic syndrome during childhood nominated items. In the piloting phase, items were cross-sectionally measured in children with limb deep vein thrombosis to examine item performance. Twenty-three experts and 16 subjects listed 34 items, which were then measured in 140 subjects with previous diagnosis of limb deep vein thrombosis (70 upper extremity and 70 lower extremity). The items with strongest correlation with post-thrombotic syndrome severity and largest area under the curve were pain (in older children), paresthesia, and swollen limb for the upper extremity group, and pain (in older children), tired limb, heaviness, tightness and paresthesia for the lower extremity group. The diagnostic properties of the items and their correlations with post-thrombotic syndrome severity varied according to the assessed venous territory. The information gathered in this study will help experts decide which item should be considered for inclusion in the new tool. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cardiovascular risk factors are major determinants of thrombotic risk in patients with the lupus anticoagulant.

PubMed

Posch, Florian; Gebhart, Johanna; Rand, Jacob H; Koder, Silvia; Quehenberger, Peter; Pengo, Vittorio; Ay, Cihan; Pabinger, Ingrid

2017-03-10

Patients with the lupus anticoagulant (LA) are at an increased risk of thrombotic events, which in turn increase the risk of death. Understanding the determinants of thrombotic risk in patients with LA may pave the way towards targeted thromboprophylaxis. In the Vienna Lupus Anticoagulant and Thrombosis Study (LATS), we systematically evaluate risk factors for thrombotic events in patients with LA. We followed 150 patients (mean age: 41.3 years, female gender: n = 122 (81.3%), history of thrombosis or pregnancy complications: n = 111 (74.0%)), who tested repeatedly positive for LA until development of thrombosis, death, or censoring. The primary endpoint was a composite of arterial or venous thrombotic events (TEs). During a median follow-up of 9.5 years (range: 12 days-13.6 years) and 1076 person-years, 32 TEs occurred (arterial: n = 16, venous: n = 16; cumulative 10-year TE incidence: 24.3%). A prolonged lupus-sensitive activated partial thromboplastin time (aPTT-LA) (adjusted subdistribution hazard ratio (SHR) = 2.31, 95% CI: 1.07--5.02), diabetes (adjusted SHR = 4.39, 95% CI: 1.42-13.57), and active smoking (adjusted SHR = 2.31, 95% CI: 1.14-5.02) emerged as independent risk factors of both arterial and venous thrombotic risk. A risk model that includes a prolonged lupus-sensitive aPTT, smoking, and diabetes enabled stratification of LA patients into subgroups with a low, intermediate, and high risk of thrombosis (5-year TE risk of 9.7% (n = 77), 30.9% (n = 51), and 56.8% (n = 22). Long-term thrombotic risk in patients with LA is clustered within subjects harboring typical cardiovascular risk factors in addition to a prolonged lupus-sensitive aPTT, whereas patients with none of these risk factors represent a large subgroup with a low risk of thrombosis.

Six-month exercise training program to treat post-thrombotic syndrome: a randomized controlled two-centre trial

PubMed Central

Kahn, Susan R.; Shrier, Ian; Shapiro, Stan; Houweling, Adrielle H.; Hirsch, Andrew M.; Reid, Robert D.; Kearon, Clive; Rabhi, Khalil; Rodger, Marc A.; Kovacs, Michael J.; Anderson, David R.; Wells, Philip S.

2011-01-01

Background Exercise training may have the potential to improve post-thrombotic syndrome, a frequent, chronic complication of deep venous thrombosis. We conducted a randomized controlled two-centre pilot trial to assess the feasibility of a multicentre-based evaluation of a six-month exercise training program to treat post-thrombotic syndrome and to obtain preliminary data on the effectiveness of such a program. Methods Patients were randomized to receive exercise training (a six-month trainer-supervised program) or control treatment (an education session with monthly phone follow-ups). Levels of eligibility, consent, adherence and retention were used as indicators of study feasibility. Primary outcomes were change from baseline to six months in venous disease-specific quality of life (as measured using the Venous Insufficiency Epidemiological and Economic Study Quality of Life [VEINES-QOL] questionnaire) and severity of post-thrombotic syndrome (as measured by scores on the Villalta scale) in the exercise training group versus the control group, assessed by t tests. Secondary outcomes were change in generic quality of life (as measured using the Short-Form Health Survey-36 [SF-36] questionnaire), category of severity of post-thrombotic syndrome, leg strength, leg flexibility and time on treadmill. Results Of 95 patients with post-thrombotic syndrome, 69 were eligible, 43 consented and were randomized, and 39 completed the study. Exercise training was associated with improvement in VEINES-QOL scores (exercise training mean change 6.0, standard deviation [SD] 5.1 v. control mean change 1.4, SD 7.2; difference 4.6, 95% CI 0.54 to 8.7; p = 0.027) and improvement in scores on the Villalta scale (exercise training mean change −3.6, SD 3.7 v. control mean change −1.6, SD 4.3; difference −2.0, 95% CI −4.6 to 0.6; p = 0.14). Most secondary outcomes also showed greater improvement in the exercise training group. Interpretation Exercise training may improve post-thrombotic

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. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Can rotational thromboelastometry predict thrombotic complications in reconstructive microsurgery?

PubMed

Kolbenschlag, Jonas; Daigeler, Adrien; Lauer, Sarah; Wittenberg, Gerhard; Fischer, Sebastian; Kapalschinski, Nicolai; Lehnhardt, Marcus; Goertz, Ole

2014-05-01

Thrombotic occlusion of the microvascular pedicle is the major reason for flap loss. Thus, identifying patients who are at risk for such events is paramount. Rotational thromboelastometry (RTE) is widely used to detect coagulopathy and hypercoagulable states. The aim of our study was to assess its diagnostic value in reconstructive microsurgery. In all 181 patients undergoing free tissue transfer at our department between February 2010 and November 2011 preoperative RTE was performed. In addition, coagulation values as well as patient's demographic data, cause and localization of defect, type of flap and surgical revisions were recorded. The majority of patients was male (59.6%) with traumatic (59.7%) defects located on the lower extremity (60.3%). ALT was the most often used flap (35.9%). Preoperatively, 36.5% of patients had a hypercoagulable RTE (higher than physiological RTE values; intrinsic (ICPT) or extrinsic (ECPT) mean clot firmness (MCF) >72mm or functional fibrinogen (ICF) MCF >25mm). A total of 28 primary thrombosis of the microvascular pedicle occurred, 11 of those in-patients with a hypercoagulable state. Total flap loss rate because ofthrombosis was 7.7% (n = 14). Both a hypercoagulable RTE assay and a functional fibrinogen to platelet ratio (FPR) of >43 (MCF value of ICF divided by the MCF value of ICPT) were significant predictors of thrombotic flap loss when performing multivariate binary logistic regression, co-factoring for age, sex, and comorbidities (p = 0.036 and 0.003, respectively). RTE seems to be able to identify patients that are prone to thrombotic complications and might be used as a screening tool. Copyright © 2013 Wiley Periodicals, Inc.

Identification and Characterization of Anti-Platelet Antibodies in Idiopathic Thrombocytopenic Purpura Patients

PubMed Central

Aghabeigi, N; Lindsey, N; Zamani, A; Shishaeyan, B

2012-01-01

Background: The autoimmune disease known as Idiopathic (immune thrombocytopenic purpura thrombocytopenic purpura (ITP) is clinically defined by a low numbers of platelets in the circulation blood. This study aimed to isolate autoantibodies made against the platelet glycoproteins using platelets from healthy volunteers, to determine their specificity and further elucidate their effects on platelet function. Methods: This study used a phage display system to recognize Fab anti-platelet antibodies. Anti-platelet After isolation, the anti-platelet Fab-expressing phage was characterized by ELISA and Western blotting. The Fab-bearing phage pool obtained from five rounds of panning was analysed in order to determine its anti-platelet reactivity. Of the phage colonies obtained, 100 colonies of different sizes were randomly selected for reaction with whole platelets, using M13 phage as a negative control. Results: Twelve colonies of them had strong reactions against the whole platelet preparation, but only four colonies showed substantial reactivity against the lysed platelet preparation (lysate). Three of the four colonies showed three bands representing proteins with different molecular weights. The fourth colony showed only a single band. The final experiment to characterise the protein isolated from the phage library was a DNA gel agarose test. Conclusion: Each colony showed a DNA band that corresponded with the molecular size marker for 5.4 kbase pairs, and this suggested the presence of heavy and light antibody chains in the phage. PMID:23113135

Secondary thrombotic microangiopathy in two patients with Philadelphia-positive hematological malignancies treated with imatinib mesylate.

PubMed

Ojeda-Uribe, Mario; Merieau, Sylvain; Guillon, Marie; Aujoulat, Olivier; Hinschberger, Olivier; Eisenmann, Jean-Claude; Kenizou, David; Debliquis, Agathe; Veyradier, Agnès; Chantrel, François

2016-04-01

Drug-mediated thrombotic microangiopathy may cause life-threatening medical emergencies. Novel targeted therapies have dramatically changed the prognosis of a number of oncological diseases. Tyrosine kinase inhibitors of the Breakpoint Cluster Region-Abelson (BCR-ABL) oncoprotein are used in patients with chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia. Imatinib mesylate, which was the first anti-BCR-ABL tyrosine kinase inhibitor, has demonstrated a high tolerance profile and efficacy in these patients for many years. Good results have also been observed in patients with gastrointestinal stromal tumors. In this study, we describe two patients with Philadelphia chromosome-positive hematological malignancies who presented with secondary thrombotic microangiopathy that was most likely linked to the use of imatinib. Other potential causes of thrombotic microangiopathy were discarded, and the predisposing role of some comorbidities and potential short or long-term drug-drug interactions was assessed. The clinical and biological data were more indicative of atypical secondary hemolytic uremic syndrome in one of the cases and of secondary thrombotic microangiopathy with renal and cardiac impairment in the other, which is also categorized as secondary hemolytic uremic syndrome. The outcome was favorable after imatinib discontinuation and the treatment of severe cardiac and renal failures. © The Author(s) 2015.

Numerical Simulation of Thrombotic Occlusion in Tortuous Arterioles

PubMed Central

Feng, Zhi-Gang; Cortina, Miguel; Chesnutt, Jennifer KW; Han, Hai-Chao

2017-01-01

Tortuous microvessels alter blood flow and stimulate thrombosis but the physical mechanisms are poorly understood. Both tortuous microvessels and abnormally large platelets are seen in diabetic patients. Thus, the objective of this study was to determine the physical effects of arteriole tortuosity and platelet size on the microscale processes of thrombotic occlusion in microvessels. A new lattice-Boltzmann method-based discrete element model was developed to simulate the fluid flow field with fluid-platelet coupling, platelet interactions, thrombus formation, and thrombotic occlusion in tortuous arterioles. Our results show that vessel tortuosity creates high shear stress zones that activate platelets and stimulate thrombus formation. The growth rate depends on the level of tortuosity and the pressure and flow boundary conditions. Once thrombi began to form, platelet collisions with thrombi and subsequent activations were more important than tortuosity level. Thrombus growth narrowed the channel and reduced the flow rate. Larger platelet size leads to quicker decrease of flow rate due to larger thrombi that occluded the arteriole. This study elucidated the important roles that tortuosity and platelet size play in thrombus formation and occlusion in arterioles. PMID:29327739

Trichinella nativa outbreak with rare thrombotic complications associated with meat from a black bear hunted in Northern Ontario

USDA-ARS?s Scientific Manuscript database

Although trichinellosis is known to cause thrombotic disease, serious thrombotic events are rare and have previously not been shown to be associated with Trichinella nativa. Patient interviews and medical chart reviews were conducted on ten men who became ill following consumption of a common source...

The Lectin Pathway in Thrombotic Conditions-A Systematic Review.

PubMed

Larsen, Julie Brogaard; Hvas, Christine Lodberg; Hvas, Anne-Mette

2018-06-04

The lectin pathway of the complement system can activate the coagulation system in vitro, but the role of the lectin pathway in haemostatic activation and thrombosis in vivo is not clear. We performed a systematic review of the existing literature on associations between the lectin pathway and arterial and venous thrombosis, in accordance with the Assessing the Methodological Quality of Systematic Reviews guidelines. PubMed and Embase were searched from January 1990 to March 2017. We included original studies on human study populations investigating associations between the lectin pathway (protein serum levels, genotype or gene expression) and thrombotic conditions or laboratory coagulation markers. Exclusion criteria were case studies including fewer than five cases, conference abstracts or any other language than English. In total, 43 studies were included which investigated associations between the lectin pathway and cardiovascular thrombotic events (CVEs) ( n  = 22), ischaemic stroke ( n  = 9), CVE and stroke ( n  = 1) and other conditions (systemic lupus erythematosus [ n  = 6], sepsis-related coagulopathy [ n  = 3], pulmonary embolism [ n  = 1], asparaginase treatment [ n  = 1]). Studies on the lectin pathway and CVE risk reported discrepant results, as both high and low mannose-binding lectin (MBL) serum levels were found to correlate with increased CVE risk. In ischaemic stroke patients, occurrence of stroke as well as increased stroke severity and poor outcome were consistently associated with high serum MBL. For other thromboembolic conditions, only few studies were identified. In conclusion, lectin pathway activation may negatively influence outcome after ischaemic stroke and possibly contribute to CVE risk. Further research is warranted to elucidate the role of the lectin pathway in other thrombotic conditions. Schattauer GmbH Stuttgart.

[Evaluation of the antithrombotic strategy in low thrombotic risk patients who underwent aortic valve replacement with a bioprosthesis].

PubMed

Aceves-Velázquez, Eduardo; Vieyra-Herrera, Gerardo; Rodríguez-Chávez, Laura; Herrera-Alarcón, Valentín

2017-07-16

According to current guidelines, in patients without additional risk factors who have undergone aortic valve replacement with a bioprosthesis, anticoagulation in the first 3 months after surgery is still a matter of debate. According to current evidence, aspirin in low doses is a reasonable alternative to vitamin K antagonists (VKA). A comparison is made between the incidence of thrombotic and haemorrhagic complications in patients with low thrombotic risk who underwent aortic valve replacement with a bioprosthesis in the National Institute of Cardiology of Ignacio Chávez of Mexico. The hypothesis: aspirin as monotherapy has a beneficial effect compared to VKA. The studied patients were the low thrombotic risk patients who underwent aortic valve replacement with a bioprosthesis in the National Institute of Cardiology of Ignacio Chávez of Mexico from 2011 to 2015. The groups studied were: aspirin only, VKA only, and the combination of VKA plus aspirin. The patients were retrospectively followed-up for 12 months, and the thrombotic and haemorrhagic complications were documented. Of the 231 patients included in the study, only one patient in the VKA only group presented with a haemorrhagic complication. No thrombotic complications were observed. In the present study no thrombotic complications were observed in patients who did not receive anticoagulation in the first 3 months after an aortic valve replacement with a bioprosthesis after a follow up period of 12 months. This suggests that the use of aspirin only is safe during this period. Copyright © 2017 Instituto Nacional de Cardiología Ignacio Chávez. Publicado por Masson Doyma México S.A. All rights reserved.

Successful Treatment of Aggressive Mature B-cell Lymphoma Mimicking Immune Thrombocytopenic Purpura.

PubMed

Ono, Koya; Onishi, Yasushi; Kobayashi, Masahiro; Ichikawa, Satoshi; Hatta, Shunsuke; Watanabe, Shotaro; Okitsu, Yoko; Fukuhara, Noriko; Ichinohasama, Ryo; Harigae, Hideo

2018-03-30

A 55-year-old woman suffered from hemorrhagic tendency. She had severe thrombocytopenia without any hematological or coagulatory abnormalities, and a bone marrow examination revealed an increased number of megakaryocytes without any abnormal cells or blasts. No lymphadenopathy or hepatosplenomegaly was observed on computed tomography. She was initially diagnosed with immune thrombocytopenic purpura (ITP). None of the treatments administered for ITP produced a response. However, abnormal cells were eventually found during the third bone marrow examination. The pathological diagnosis was mature B-cell lymphoma. Rituximab-containing chemotherapy produced a marked increase in the patient's platelet count, and her lymphoma went into complete remission.

DRESS syndrome with thrombotic microangiopathy revealing a Noonan syndrome: Case report.

PubMed

Bobot, Mickaël; Coen, Matteo; Simon, Clémentine; Daniel, Laurent; Habib, Gilbert; Serratrice, Jacques

2018-04-01

The life-threatening drug rash with eosinophilia and systemic symptoms (DRESS) syndrome occurs most commonly after exposure to drugs, clinical features mimic those found with other serious systemic disorders. It is rarely associated with thrombotic microangiopathy. We describe the unique case of a 44-year-old man who simultaneously experienced DRESS syndrome with thrombotic microangiopathy (TMA) after a 5 days treatment with fluindione. Clinical evaluation leads to the discovery of an underlying lymphangiomatosis, due to a Noonan syndrome. The anticoagulant was withdrawn, and corticosteroids (1 mg/kg/day) and acenocoumarol were started. Clinical improvement ensued. At follow-up the patient is well. The association of DRESS with TMA is a rare condition; we believe that the presence of the underlying Noonan syndrome could have been the trigger. Moreover, we speculate about the potential interrelations between these entities.

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

Postinfluenza Vaccination Idiopathic Thrombocytopenic Purpura in Three Elderly Patients

PubMed Central

Nagasaki, Joji; Manabe, Masahiro; Ido, Kentaro; Ichihara, Hiroyoshi; Aoyama, Yasutaka; Ohta, Tadanobu; Furukawa, Yoshio; Mugitani, Atsuko

2016-01-01

The etiologies of secondary idiopathic thrombocytopenic purpura (ITP) include infection, autoimmune disease, and immunodeficiency. We report the cases of three elderly patients who developed ITP after receiving influenza vaccinations. The platelet count of an 81-year-old woman fell to 27,000/μL after she received an influenza vaccination. A 75-year-old woman developed thrombocytopenia (5,000 platelets/μL) after receiving an influenza vaccination. An 87-year-old woman whose laboratory test values included a platelet count of 2,000/μL experienced genital bleeding after receiving an influenza vaccination. After Helicobacter pylori (HP) eradication or corticosteroid treatment, all of the patients' platelet counts increased. Influenza vaccination is an underlying etiology of ITP in elderly patients. HP eradication or corticosteroid treatment is effective for these patients. Clinicians should be aware of the association between ITP and influenza vaccinations. PMID:26998369

[Thrombosis and post-thrombotic syndrome as a consequence of an accident].

PubMed

Wahl, U; Hirsch, T

2015-10-01

Phlebothromboses represent alarming complications in accident victims since they can cause fatal pulmonary embolisms. More than half of those affected also develop post-thrombotic syndrome in the course of the illness. In addition to making clinical assessments, the traumatologist should also have fundamental knowledge about diagnostic methods and be familiar with interpreting internal findings. Colour-coded duplex sonography plays a central role in diagnosing thrombosis and in assessing functional limitations. Further information can be gathered from various phlebological procedures. The expert evaluation of the immediate, as well as the long-term consequences of an accident frequently require leg swelling to be classified. It is not uncommon for post-thrombotic syndrome to be diagnosed for the first time during this process. An additional vascular appraisal is often required. An appreciation of social-medical and insurance-related aspects means a high degree of responsibility is placed on the expert.

Endovascular treatment of post-thrombotic and non-thrombotic iliofemoral venous outflow obstructions with self-expanding nitinol stents.

PubMed

Stuck, Anna K; Reich, Thomas; Engelberger, Rolf P; Sebastian, Tim; Kucher, Nils

2018-06-01

The aim of the study was to investigate venous patency and clinical outcomes for endovascular treatment of iliofemoral venous obstruction in patients with post-thrombotic syndrome (PTS) and non-thrombotic iliac vein lesion (NIVL) with dedicated self-expanding nitinol stents. Data were collected from the prospective Swiss Venous Stent Registry, enrolling consecutive patients with a standardized follow-up procedure since January 2008. Patency was evaluated by duplex sonography and clinical outcome by various scores including the Villalta score at baseline, three, six, and 12 months, and then annually after endovascular therapy. Overall, 93 patients (64 PTS, 29 NIVL) were analysed. Mean follow-up time was 20 ± 16 (range 3-70) months. A total of 11 (12 %) patients had a stent occlusion, all of which occurred in the PTS group, and 13 (14 %) patients had a symptomatic stent stenosis. Primary patency was 79 % (95 % CI 68-87 %) at 12 months and 72 % (95 % CI 59-82 %) at 24 months. In PTS patients, primary patency at 12 months was 75 % (95 % CI 61-84 %) vs. 89 % (95 % CI 63-97 %) in NIVL patients (p = 0.10). Secondary patency at 24 months was 94 % (95 % CI 84-98 %) in PTS and 100 % in NIVL, p = 0.19). Overall, 62 (67 %) patients were free from PTS at the latest follow-up with a Villalta score < 5 points. Predictive factors for the loss of primary patency were stents placed below the inguinal ligament (OR 2.59, 95 % CI, 0.99-6.84, p = 0.05). In symptomatic patients with chronic iliofemoral vein obstruction, endovascular therapy with self-expanding nitinol stents was associated with favourable patency rates and clinical improvement in the majority of patients.

Anti-Coagulant and Anti-Thrombotic Properties of Blacklip Abalone (Haliotis rubra): In Vitro and Animal Studies.

PubMed

Suleria, Hafiz Ansar Rasul; Masci, Paul P; Zhao, Kong-Nan; Addepalli, Rama; Chen, Wei; Osborne, Simone A; Gobe, Glenda C

2017-08-04

Sulphated polysaccharides with anti-thrombotic and anti-coagulant activities have been found in various marine biota. In this study, a previously characterised anti-thrombotic and anti-coagulant extract from blacklip abalone was fractionated by anion exchange chromatography (AEC), pooled (on a sulphated polysaccharide basis) and administered to Wistar rats via oral gavage (N = 8) for assessment as an oral therapeutic. To ensure that the preparation had anti-coagulant activity prior to oral administration, it was assessed in rat blood by thromboelastography (TEG) significantly increasing reaction (R) time (or time until clot formation). Following in vitro confirmation of anti-coagulant activity, 40 mg of the preparation was orally administered to rats with blood samples collected at 2, 4, and 6 h post-gavage. Assessment of all blood samples by TEG showed some prolongation of R time from 355 to 380 s after 4 h. Dosing of the post-gavage blood samples with the abalone preparation to confirm anti-thrombotic activity in vitro revealed residual anti-coagulant activity, further suggesting that oral administration did increase anti-coagulant potential in the collected blood but that bioavailability was low. Assessment of tissues and haematological parameters showed no obvious harmful effects of the abalone preparation in animals. In summary, even though oral administration of fractionated and pooled blacklip abalone extract to rats delayed clotting after 4 h, bioavailability of the preparation appeared to be low and may be more appropriate for intravenous administration as an anti-thrombotic or anti-coagulant therapeutic.

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

PubMed

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

2016-01-01

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. 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. 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). 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.

Differentiation of thrombus from pannus as the cause of acquired mechanical prosthetic heart valve obstruction by non-invasive imaging: a review of the literature.

PubMed

Tanis, Wilco; Habets, Jesse; van den Brink, Renee B A; Symersky, Petr; Budde, Ricardo P J; Chamuleau, Steven A J

2014-02-01

For acquired mechanical prosthetic heart valve (PHV) obstruction and suspicion on thrombosis, recently updated European Society of Cardiology guidelines advocate the confirmation of thrombus by transthoracic echocardiography, transesophageal echocardiography (TEE), and fluoroscopy. However, no evidence-based diagnostic algorithm is available for correct thrombus detection, although this is clinically important as fibrinolysis is contraindicated in non-thrombotic obstruction (isolated pannus). Here, we performed a review of the literature in order to propose a diagnostic algorithm. We performed a systematic search in Pubmed and Embase. Included publications were assessed on methodological quality based on the validated Quality Assessment of Diagnostic Accuracy Studies (QUADAS) II checklist. Studies were scarce (n = 15) and the majority were of moderate methodological quality. In total, 238 mechanical PHV's with acquired obstruction and a reliable reference standard were included for the evaluation of the role of fluoroscopy, echocardiography, or multidetector-row computed tomography (MDCT). In acquired PHV obstruction caused by thrombosis, mass detection by TEE and leaflet restriction detected by fluoroscopy were observed in the majority of cases (96 and 100%, respectively). In contrast, in acquired PHV obstruction free of thrombosis (pannus), leaflet restriction detected by fluoroscopy was absent in some cases (17%) and mass detection by TEE was absent in the majority of cases (66%). In case of mass detection by TEE, predictors for obstructive thrombus masses (compared with pannus masses) were leaflet restriction, soft echo density, and increased mass length. In situations of inconclusive echocardiography, MDCT may correctly detect pannus/thrombus based on the morphological aspects and localization. In acquired mechanical PHV obstruction without leaflet restriction and absent mass on TEE, obstructive PHV thrombosis cannot be confirmed and consequently, fibrinolysis

Association between Use of Exogenous Testosterone Therapy and Risk of Venous Thrombotic Events among Exogenous Testosterone Treated and Untreated Men with Hypogonadism.

PubMed

Li, Hu; Benoit, Karin; Wang, Wei; Motsko, Stephen

2016-04-01

Limited information exists about whether exogenous testosterone therapy is associated with a risk of venous thrombotic events. We investigated via cohort and nested case-control analyses whether exogenous testosterone therapy is associated with the risk of venous thrombotic events in men with hypogonadism. Databases were reviewed to identify men prescribed exogenous testosterone therapy and/or men with a hypogonadism diagnosis. Propensity score 1:1 matching was used to select patients for cohort analysis. Cases (men with venous thrombotic events) were matched 1:4 with controls (men without venous thrombotic events) for the nested case-control analysis. Primary outcome was defined as incident idiopathic venous thrombotic events. Cox regression and conditional logistic regression were used to assess HRs and ORs, respectively. Sensitivity analyses were also performed. A total of 102,650 exogenous testosterone treated and 102,650 untreated patients were included in cohort analysis after matching, and 2,785 cases and 11,119 controls were included in case-control analysis. Cohort analysis revealed a HR of 1.08 for all testosterone treated patients (95% CI 0.91, 1.27, p = 0.378). Case-control analysis resulted in an OR of 1.02 (95% CI 0.92, 1.13, p = 0.702) for current exogenous testosterone therapy exposure and an OR of 0.92 (95% CI 0.82, 1.03, p = 0.145) for past exogenous testosterone therapy exposure. These results remained nonstatistically significant after stratifying by exogenous testosterone therapy administration route and age category. Most sensitivity analyses yielded consistent results. No significant association was found between exogenous testosterone therapy and incidents of idiopathic or overall venous thrombotic events in men with hypogonadism. However, some discrepant findings exist for the association between injectable formulations and the risk of overall venous thrombotic events. Copyright © 2016 American Urological Association Education and Research

BK polyomavirus encephalitis in a patient with thrombotic microangiopathy after an allogeneic hematopoietic stem cell transplant.

PubMed

Jun, Jae-Bum; Choi, Yunsuk; Kim, Hawk; Lee, Sun Ho; Jeong, Joseph; Jung, Jiwon

2016-12-01

To date, only one case of BK polyomavirus (BKPyV) encephalitis combined with transplant-associated thrombotic microangiopathy has been reported in an hematopoietic stem cell transplantation (HCT) recipient. We report the case of an HCT recipient who developed thrombotic microangiopathy and subsequent BKPyV encephalitis. She died despite treatment with cidofovir, ciprofloxacin, and intravenous immunoglobulin without improvement in mental status. Early suspicion of BKPyV encephalitis in an HCT recipient presenting with altered mental status and hemorrhagic cystitis is important. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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.

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.

Marked improvement of thrombocytopenia in a murine model of idiopathic thrombocytopenic purpura by pegylated recombinant human megakaryocyte growth and development factor.

PubMed

Shibuya, Kazunori; Kuwaki, Tomoaki; Tahara, Emiko; Yuki, Chizuru; Akahori, Hiromichi; Kato, Takashi; Miyazaki, Hiroshi

2002-10-01

We examined the stimulatory effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production in male (NZW x BXSB) F(l) (W/B F(1)) mice, a murine model of idiopathic thrombocytopenic purpura. A cohort of 19- to 25-week-old, severely thrombocytopenic male W/B F(1) mice were given PEG-rHuMGDF at different dosing schedules. Before and at various times after therapy, platelet counts, reticulated platelets, platelet lifespan, and levels of platelet-associated immunoglobulin G were measured. Analysis of megakaryocytic cells was performed. Treatment of male W/B F(1) mice with PEG-rHuMGDF (30 microg/kg/day) three times per week for several weeks resulted in sustained thrombocytosis, accompanied by increased megakaryocytopoiesis in both the bone marrow and spleen. The degree of the platelet response to PEG-rHuMGDF varied between individual mice, likely reflecting the heterogeneity of the disease. Production of new platelets in response to PEG-rHuMGDF was manifested by an increase in reticulated platelets. Levels of platelet-associated immunoglobulin G decreased inversely during periods of thrombocytosis. PEG-rHuMGDF therapy also improved thrombocytopenia in male W/B F(1) mice refractory to splenectomy. Platelet lifespan was not affected by PEG-rHuMGDF. Male W/B F(1) mice treated with pegylated murine MGDF, a homologue of PEG-rHuMGDF, had persistent thrombocytosis for at least 7 months, suggesting that antiplatelet antibody production was not enhanced. PEG-rHuMGDF therapy potently stimulated platelet production, effectively ameliorating thrombocytopenia in a murine model of idiopathic thrombocytopenic purpura.

Antithrombocytopenic activity of carpaine and alkaloidal extract of Carica papaya Linn. leaves in busulfan induced thrombocytopenic Wistar rats.

PubMed

Zunjar, Vishwanath; Dash, Ranjeet Prasad; Jivrajani, Mehul; Trivedi, Bhavna; Nivsarkar, Manish

2016-04-02

The decoction of Carica papaya Linn. leaves is used in folklore medicine in certain parts of Malaysia and Indonesia for the treatment of different types of thrombocytopenia associated with diseases and drugs. There are several scientific studies carried out on humans and animal models to confirm the efficacy of decoction of papaya leave for the treatment of disease induced and drug induced thrombocytopenia, however very little is known about the bio-active compounds responsible for the observed activity. The aim of present study was to identify the active phytochemical component of Carica papaya Linn. leaves decoction responsible for anti-thrombocytopenic activity in busulfan-induced thrombocytopenic rats. Antithrombocytopenic activity was assessed on busulfan induced thrombocytopenic Wistar rats. The antithrombocytopenic activity of different bio-guided fractions was evaluated by monitoring blood platelet count. Bioactive compound carpaine was isolated and purified by chromatographic methods and confirmed by spectroscopic methods (LC-MS and 1D/2D-1H/13C NMR) and the structure was confirmed by single crystal X-ray diffraction. Quantification of carpaine was carried out by LC-MS/MS equipped with XTerra(®) MS C18 column and ESI-MS detector using 90:10 CH3CN:CH3COONH4 (6mM) under isocratic conditions and detected with multiple reaction monitoring (MRM) in positive ion mode. Two different phytochemical groups were isolated from decoction of Carica papaya leaves: phenolics, and alkaloids. Out of these, only alkaloid fraction showed good biological activity. Carpaine was isolated from the alkaloid fraction and exhibited potent activity in sustaining platelet counts upto 555.50±85.17×10(9)/L with no acute toxicity. This study scientifically validates the popular usage of decoction of Carica papaya leaves and it also proves that alkaloids particularly carpaine present in the leaves to be responsible for the antithrombocytopenic activity. Copyright © 2016 Elsevier

Anti-Coagulant and Anti-Thrombotic Properties of Blacklip Abalone (Haliotis rubra): In Vitro and Animal Studies

PubMed Central

Masci, Paul P.; Zhao, Kong-Nan; Addepalli, Rama; Chen, Wei; Osborne, Simone A.; Gobe, Glenda C.

2017-01-01

Sulphated polysaccharides with anti-thrombotic and anti-coagulant activities have been found in various marine biota. In this study, a previously characterised anti-thrombotic and anti-coagulant extract from blacklip abalone was fractionated by anion exchange chromatography (AEC), pooled (on a sulphated polysaccharide basis) and administered to Wistar rats via oral gavage (N = 8) for assessment as an oral therapeutic. To ensure that the preparation had anti-coagulant activity prior to oral administration, it was assessed in rat blood by thromboelastography (TEG) significantly increasing reaction (R) time (or time until clot formation). Following in vitro confirmation of anti-coagulant activity, 40 mg of the preparation was orally administered to rats with blood samples collected at 2, 4, and 6 h post-gavage. Assessment of all blood samples by TEG showed some prolongation of R time from 355 to 380 s after 4 h. Dosing of the post-gavage blood samples with the abalone preparation to confirm anti-thrombotic activity in vitro revealed residual anti-coagulant activity, further suggesting that oral administration did increase anti-coagulant potential in the collected blood but that bioavailability was low. Assessment of tissues and haematological parameters showed no obvious harmful effects of the abalone preparation in animals. In summary, even though oral administration of fractionated and pooled blacklip abalone extract to rats delayed clotting after 4 h, bioavailability of the preparation appeared to be low and may be more appropriate for intravenous administration as an anti-thrombotic or anti-coagulant therapeutic. PMID:28777290

A Systematic Review and Meta-analysis of Thrombotic Events Following Endovenous Thermal Ablation of the Great Saphenous Vein.

PubMed

Healy, Donagh A; Kimura, Shiori; Power, David; Elhaj, Abubaker; Abdeldaim, Yasser; Cross, Keith S; McGreal, Gerard T; Burke, Paul E; Moloney, Tony; Manning, Brian J; Kavanagh, Eamon G

2018-06-09

A systematic review and meta-analysis was performed to determine the incidence of thrombotic events following great saphenous vein (GSV) endovenous thermal ablation (EVTA). MEDLINE, Embase and conference abstracts were searched. Eligible studies were randomised controlled trials and case series that included at least 100 patients who underwent GSV EVTA (laser ablation or radiofrequency ablation [RFA]) with duplex ultrasound (DUS) within 30 days. The systematic review focused on the complications of endovenous heat induced thrombosis (EHIT), deep venous thrombosis (DVT), and pulmonary embolism (PE). The primary outcome for the meta-analysis was deep venous thrombotic events which were defined as DVT or EHIT Type 2, 3, or 4. Secondary outcomes for the meta-analysis were EHIT Type 2, 3, or 4, DVT and PE. Subgroup analyses were performed for both the RFA and EVLA groups. Pooled proportions were calculated using random effects modelling. Fifty-two studies (16,398 patients) were included. Thrombotic complications occurred infrequently. Deep venous thrombotic events occurred in 1.7% of cases (95% CI 0.9-2.7%) (25 studies; 10,012 patients; 274 events). EHIT Type 2, 3, or 4 occurred in 1.4% of cases (95% CI 0.8-2.3%) (26 studies; 10,225 patients; 249 events). DVT occurred in 0.3% of cases (95% CI = 0.2%-0.5%) (49 studies; 15,676 patients; 48 events). PE occurred in 0.1% of cases (95% CI = 0.1-0.2%) (29 studies; 8223 patients; 3 events). Similar results were found when the RFA and EVLA groups were analysed separately. Thrombotic events occur infrequently following GSV EVTA. Given the large numbers of procedures worldwide and the potential for serious consequences, further research is needed on the burden of these complications and their management. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Rutosides for treatment of post-thrombotic syndrome.

PubMed

Morling, Joanne R; Yeoh, Su Ern; Kolbach, Dinanda N

2015-09-16

Post-thrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT) that is characterised by pain, swelling, and skin changes in the affected limb. One in three patients with DVT will develop post-thrombotic sequelae within five years. Rutosides are a group of compounds derived from horse chestnut (Aesculus hippocastanum), a traditional herbal remedy for treating oedema formation in chronic venous insufficiency (CVI). However, it is not known whether rutosides are effective and safe in the treatment of PTS. This is an update of the review first published in 2013. To determine the effectiveness (improvement or deterioration in symptoms) and safety of rutosides for treatment of post-thrombotic syndrome (PTS) in patients with DVT compared to placebo, no intervention, elastic compression stockings (ECS) or any other treatment. For this update the Cochrane Vascular Group Trials Search Co-ordinator searched the Specialised Register (last searched September 2015) and the Cochrane Register of Studies (CRS) (CENTRAL (2015, Issue 8)). Clinical trials databases were searched for details of ongoing and unpublished studies. Two review authors (JM and DNK) independently assessed studies for inclusion. Studies were included to allow the comparison of rutosides versus placebo or no treatment, rutosides versus ECS, and rutosides versus any other treatment. Two review authors (JM and SEY) extracted information from the trials. Disagreements were resolved by discussion. Data were extracted using designated data extraction forms. The Cochrane risk of bias tool was used for all included studies to assist in the assessment of quality. Primary outcome measures were the occurrence of leg ulceration over time (yes or no) and any improvement or deterioration of post-thrombotic syndrome (yes or no). Secondary outcomes included reduction of oedema, pain, recurrence of deep venous thrombosis or pulmonary embolism, compliance with therapy, and adverse effects. All of the

[Gemcitabine-induced thrombotic microangiopathy: Can we improve screening and treatment?

PubMed

Charmetant, Xavier; Jolivot, Anne; Fournier, Thomas; Puthet, Jean-Charles; Cassier, Philippe; Lemoine, Sandrine; Juillard, Laurent

2017-06-01

Thrombotic microangiopathy is a rare but severe complication of treatment with gemcitabine. Its prevalence increases because gemcitabine's indications are growing. We report four cases, which presented with common clinical and biological manifestations, i.e. high blood pressure, proteinuria and increasing plasmatic creatinine level. However, severity was not similar, hemodialysis was inconstant. There is no consensus on treatment for this condition. Stopping gemcitabine is essential. Treatment was dispensed considering the severity of the presentation: plasma exchange therapy of variable outcome, and eculizumab, which was efficient when used. It's important to note that this syndrome includes common and frequent signs in patients receiving chemotherapies. But they must encourage the research of most specific signs, such as hypertension, mechanic hemolysis signs, proteinuria or hematuria, in order to recognize thrombotic microangiopathy as early as possible to treat it precociously, and to prevent additional gemcitabine injections. Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.

Immune Thrombocytopenia as a Consequence of Rocky Mountain Spotted Fever.

PubMed

Baldeo, Cherisse; Seegobin, Karan; Zuberi, Lara

2017-01-01

Primary immune thrombocytopenia (ITP) - also called idiopathic thrombocytopenic purpura or immune thrombocytopenic purpura - is an acquired thrombocytopenia caused by autoantibodies against platelet antigens. It is one of the more common causes of thrombocytopenia in otherwise asymptomatic adults. Rocky Mountain spotted fever (RMSF) is a potentially lethal, but curable, tick-borne disease. We present a case of ITP that was triggered by RMSF.

Systemic lupus erythematosus in a multiethnic cohort (LUMINA): XXVIII. Factors predictive of thrombotic events.

PubMed

Ho, K T; Ahn, C W; Alarcón, G S; Baethge, B A; Tan, F K; Roseman, J; Bastian, H M; Fessler, B J; McGwin, G; Vilá, L M; Calvo-Alén, J; Reveille, J D

2005-10-01

To determine the relationship between the presence of antiphospholipid (aPL) antibodies, hydroxychloroquine use and the occurrence of thrombotic events in patients with systemic lupus erythematosus (SLE). Four hundred and forty-two SLE patients from the LUMINA (Lupus in Minorities: Nature vs Nurture) cohort, a multiethnic (Hispanics from Texas, n = 99 and Puerto Rico, n = 36; African Americans, n = 172; and Caucasians, n = 135) cohort, were studied by generalized estimating equation (GEE) to determine the relationship between antiphospholipid (aPL) antibodies (measured as IgG and IgM aPL antibodies and/or the lupus anticoagulant) at enrolment or historically prior to enrolment, hydroxychloroquine use (ever) and the occurrence of thrombotic (central and/or peripheral, arterial and/or venous) events after adjusting for known and possible confounders [socioeconomic-demographic features, smoking, disease activity and damage, serum cholesterol levels, anti-oxidized low-density lipoprotein IgG and IgM antibodies, and high-sensitivity (hs) C-reactive protein]. Postanalysis correlation between aPL and anticardiolipin (aCL) assays was attempted by performing aCL assays on random samples of patients whose aPL status was known. A number of clinical variables were significant in the univariable analyses; however, in the multivariable GEE analyses, only smoking [odds ratio (OR) 2.777, 95% confidence interval (CI) 1.317-5.852] and disease activity as measured by the SLAM (Systemic Lupus Activity Measure) (OR 1.099; 95% CI 1.053-1.147) were significant. In particular, hydroxychloroquine use, which appeared to be protective against thrombotic events in the univariable analyses, was not retained in the multivariable analyses. aPL antibodies were not significant in either analysis. Few additional aPL-positive patients emerged from the validation study. Smoking and disease activity emerged as important determinants in the occurrence of thrombotic events in our patients. Comprehensive

Acute immune thrombocytopenic purpura as adverse reaction to oral polio vaccine (OPV).

PubMed

Jin, Cheng-qiang; Dong, Hai-xin; Sun, Zhuo-xiang; Zhou, Jian-wei; Dou, Cui-yun; Lu, Shu-hua; Yang, Rui-rui

2013-08-01

A case of acute immune thrombocytopenic purpura following oral polio vaccine (OPV) is reported. An 82-d-old infant developed purpura at the same day after the second dose of oral polio vaccine. Until the time of hospital admission, the male infant had been in good health and had not received any drugs, and the possible causes of this condition were excluded. His platelet count was 13×10(9)/L. Platelet-associated IgG was elevated, but the amount of megakaryocytes in bone marrow aspirates was within the normal range, suggesting immune mechanism-associated thrombocytopenia. The infant recovered with the proper treatment within 30 d. Attention should be paid to OPV-associated thrombocytopenia, though it seems to be less frequent than after natural infections.

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

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.

Risk of Vascular Thrombotic Events Following Discontinuation of Antithrombotics After Peptic Ulcer Bleeding.

PubMed

Kim, Seung Young; Hyun, Jong Jin; Suh, Sang Jun; Jung, Sung Woo; Jung, Young Kul; Koo, Ja Seol; Yim, Hyung Joon; Park, Jong Jae; Chun, Hoon Jai; Lee, Sang Woo

2016-04-01

To evaluate whether the risk of cardiovascular events increases when antithrombotics are discontinued after ulcer bleeding. Peptic ulcer bleeding associated with antithrombotics has increased due to the increase in the proportion of elderly population. Little is known about the long-term effects of discontinuing antithrombotics after peptic ulcer bleeding. The aim of this study was to evaluate whether the risk of cardiovascular events increases when antithrombotics are discontinued after ulcer bleeding. We reviewed the medical records of patients with ulcer bleeding who were taking antiplatelet agents or anticoagulants at the time of ulcer bleeding. Cox-regression model was used to adjust for potential confounders, and analyzed association between discontinuation of antithrombotic drugs after ulcer bleeding and thrombotic events such as ischemic heart disease or stroke. Of the 544 patients with ulcer bleeding, 72 patients who were taking antithrombotics and followed up for >2 months were analyzed. Forty patients discontinued antithrombotics after ulcer bleeding (discontinuation group) and 32 patients continued antithrombotics with or without transient interruption (continuation group). Thrombotic events developed more often in discontinuation group than in the continuation group [7/32 (21.9%) vs. 1/40 (2.5%), P=0.019]. Hazard ratio for thrombotic event when antithrombotics were continuously discontinued was 10.9 (95% confidence interval, 1.3-89.7). There were no significant differences in recurrent bleeding events between the 2 groups. Discontinuation of antithrombotics after peptic ulcer bleeding increases the risk of cardiovascular events. Therefore, caution should be taken when discontinuing antithrombotics after ulcer bleeding.

Mutation of the Kunitz-type proteinase inhibitor domain in the amyloid β-protein precursor abolishes its anti-thrombotic properties in vivo.

PubMed

Xu, Feng; Davis, Judianne; Hoos, Michael; Van Nostrand, William E

2017-07-01

Kunitz proteinase inhibitor (KPI) domain-containing forms of the amyloid β-protein precursor (AβPP) inhibit cerebral thrombosis. KPI domain-lacking forms of AβPP are abundant in brain. Regions of AβPP other than the KPI domain may also be involved with regulating cerebral thrombosis. To determine the contribution of the KPI domain to the overall function of AβPP in regulating cerebral thrombosis we generated a reactive center mutant that was devoid of anti-thrombotic activity and studied its anti-thrombotic function in vitro and in vivo. To determine the extent of KPI function of AβPP in regulating cerebral thrombosis we generated a recombinant reactive center KPI R13I mutant devoid of anti-thrombotic activity. The anti-proteolytic and anti-coagulant properties of wild-type and R13I mutant KPI were investigated in vitro. Cerebral thrombosis of wild-type, AβPP knock out and AβPP/KPI R13I mutant mice was evaluated in experimental models of carotid artery thrombosis and intracerebral hemorrhage. Recombinant mutant KPI R13I domain was ineffective in the inhibition of pro-thrombotic proteinases and did not inhibit the clotting of plasma in vitro. AβPP/KPI R13I mutant mice were similarly deficient as AβPP knock out mice in regulating cerebral thrombosis in experimental models of carotid artery thrombosis and intracerebral hemorrhage. We demonstrate that the anti-thrombotic function of AβPP primarily resides in the KPI activity of the protein. Copyright © 2017 Elsevier Ltd. All rights reserved.

Autoimmune conditions are associated with perioperative thrombotic complications in liver transplant recipients: A UNOS database analysis.

PubMed

Bezinover, Dmitri; Iskandarani, Khaled; Chinchilli, Vernon; McQuillan, Patrick; Saner, Fuat; Kadry, Zakiyah; Riley, Thomas R; Janicki, Piotr K

2016-05-21

End stage liver disease (ESLD) is associated with significant thrombotic complications. In this study, we attempted to determine if patients with ESLD, due to oncologic or autoimmune diseases, are susceptible to thrombosis to a greater extent than patients with ESLD due to other causes. In this retrospective study, we analyzed the UNOS database to determine the incidence of thrombotic complications in orthotopic liver transplant (OLT) recipients with autoimmune and oncologic conditions. Between 2000 and 2012, 65,646 OLTs were performed. We found 4,247 cases of preoperative portal vein thrombosis (PVT) and 1,233 cases of postoperative vascular thrombosis (VT) leading to graft failure. Statistical evaluation demonstrated that patients with either hepatocellular carcinoma (HCC) or autoimmune hepatitis (AIC) had a higher incidence of PVT (p = 0.05 and 0.03 respectively). Patients with primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and AIC had a higher incidence of postoperative VT associated with graft failure (p < 0.0001, p < 0.0001, p = 0.05 respectively). Patients with preoperative PVT had a higher incidence of postoperative VT (p < 0.0001). Multivariable logistic regression demonstrated that patients with AIC, and BMI ≥40, having had a transjugular intrahepatic portosystemic shunt, and those with diabetes mellitus were more likely to have preoperative PVT: odds ratio (OR)(1.36, 1.19, 1.78, 1.22 respectively). Patients with PSC, PBC, AIC, BMI ≤18, or with a preoperative PVT were more likely to have a postoperative VT: OR (1.93, 2.09, 1.64, 1.60, and 2.01, respectively). Despite the limited number of variables available in the UNOS database potentially related to thrombotic complications, this analysis demonstrates a clear association between autoimmune causes of ESLD and perioperative thrombotic complications. Perioperative management of patients at risk should include strategies to reduce the potential for these

[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.

Complete resolution of transplantation-associated thrombotic microangiopathy and hepatic veno-occlusive disease by defibrotide and plasma exchange.

PubMed

Beşişik, Sevgi Kalayoğlu; Oztürk, Gülistan Bahat; Calişkan, Yaşar; Sargin, Deniz

2005-03-01

Transplantation-associated thrombotic microangiopathy has been associated with significantly reduced survival following allogeneic bone marrow transplantation. We describe here the course of Transplantation-associated thrombotic microangiopathy and hepatic veno-occlusive disease, and response to plasma exchange therapy. A 19-year-old male patient underwent hematopoietic stem cell transplantation (HSCT) from his HLA-matched brother for lymphoblastic lymphoma in the first complete remission. Transplantation-associated thrombotic microangiopathy was diagnosed 17 days after transplantation. At that time, neurological abnormalities were not present. Cyclosporin A (CsA) was discontinued. Hematological stabilization was recorded. On day +20, abdominal distention, painful hepatomegaly and ascites complicated the clinical picture. With a high hepatic venous pressure gradient (18mmH20), veno-occlusive disease of the liver was diagnosed and defibrotide was started, which resulted in a dramatic cessation of pain and increase in urinary output. However, transplantation-associated thrombotic microangiopathy-related symptoms progressed and plasma exchange was instituted, which resulted in worsening of veno-occlusive disease symptoms. He was referred to the Intensive Care Unit due to respiratory compromise and was intubated. Plasma exchange was continued in order after hemofiltration. In three days, fever resolved, hemofiltration could be stopped, and ventilator dependence ended. After 19 aphereses, serum LDH level returned to normal and schistocytes were minimal on microscopic examination of the blood film. Platelet count increase was more gradual. Plasma exchange was discontinued. On the 40th day of defibrotide, all symptoms related with veno-occlusive disease were resolved and defibrotide was stopped. We think that our case is important to establish the relation and management strategy of these two small vessel complications of HSCT.

Systemic reactive angioendotheliomatosis-like syndrome in a steer presumed to be persistently infected with bovine viral diarrhea virus.

PubMed

Breshears, M A; Johnson, B J

2008-09-01

Unusual proliferative intravascular lesions were seen in multiple organs of a 2-year-old Corriente steer presumed to be persistently infected with bovine viral diarrhea virus (BVDV), based on widespread immunohistochemical detection of BVDV antigen. Proliferations of spindle cells, which were immunohistochemically positive for von Willebrand factor-related antigen, partially-to-completely occluded vessel lumens and were supported by cells that were immunohistochemically positive for smooth muscle actin. Distribution and character of the intraluminal proliferations are strikingly similar to those described in feline systemic reactive angioendotheliomatosis, a rare entity of unknown cause. The presence of occasional intravascular thrombi suggests that the proliferative vasculopathy was associated with an underlying thrombotic process with immunohistochemical similarities to thrombotic thrombocytopenic purpura of humans. Death of the steer was due to hemorrhage from a castration wound, which may indicate thrombocytopenia or platelet dysfunction. The role of persistent BVDV infection in the formation of the intravascular lesions is unknown.

Bilateral large subconjunctival haemorrhages unmasking immune thrombocytopenic purpura during retinopathy of prematurity screening.

PubMed

Chandra, Parijat; Kumawat, Devesh; Kumar, Vinod; Tewari, Ruchir

2017-10-04

Although thrombocytopenia is known to be associated with pathogenesis of retinopathy of prematurity (ROP), immune thrombocytopenic purpura (ITP) is rare in infancy and not reported to occur with ROP. A preterm infant with aggressive posterior ROP developed bilateral massive subconjunctival haemorrhage after scleral indentation during screening. On evaluation, the infant was found to have severe ITP. Following intravenous transfusion of platelets and immunoglobulin, platelet counts improved and subconjunctival haemorrhage resolved over time. This case highlights the unusual presentation of ITP and also discusses the association of thrombocytopenia with ROP. Ophthalmologists should get prompt haematological work-up of such occurrences. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Valsartan decreases platelet activity and arterial thrombotic events in elderly patients with hypertension.

PubMed

Wu, Fang; Wang, Hong-Yan; Cai, Fan; Wang, Ling-Jie; Zhang, Feng-Ru; Chen, Xiao-Nan; Yang, Qian; Jiang, Meng-Hui; Wang, Xue-Feng; Shen, Wei-Feng

2015-01-20

Angiotensin type 1 receptor (AT 1 R) antagonists are extensively used for blood pressure control in elderly patients with hypertension. This study aimed to investigate the inhibitory effects of AT 1 R antagonist valsartan on platelet aggregation and the occurrence of cardio-cerebral thrombotic events in elderly patients with hypertension. Two-hundred and ten patients with hypertension and aged > 60 years were randomized to valsartan (n = 140) or amlodipine (n = 70) on admission. The primary endpoint was platelet aggregation rate (PAR) induced by arachidonic acid at discharge, and the secondary endpoint was the rate of thrombotic events including brain infarction and myocardial infarction during follow-up. Human aortic endothelial cells (HAECs) were stimulated by angiotensin II (Ang II, 100 nmol/L) with or without pretreatment of valsartan (100 nmol/L), and relative expression of cyclooxygenase-2 (COX-2) and thromboxane B 2 (TXB 2 ) and both p38 mitogen-activated protein kinase (p38MAPK) and nuclear factor-kB (NF-kB) activities were assessed. Statistical analyses were performed by GraphPad Prism 5.0 software (GraphPad Software, Inc., California, USA). PAR was lower after treatment with valsartan (11.49 ± 0.69% vs. 18.71 ± 2.47%, P < 0.001), associated with more reduced plasma levels of COX-2 (76.94 ± 7.07 U/L vs. 116.4 ± 15.89 U/L, P < 0.001) and TXB 2 (1667 ± 56.50 pg/ml vs. 2207 ± 180.20 pg/ml) (all P < 0.001). Plasma COX-2 and TXB 2 levels correlated significantly with PAR in overall patients (r = 0.109, P < 0.001). During follow-up (median, 18 months), there was a significantly lower thrombotic event rate in patients treated with valsartan (14.3% vs. 32.8%, P = 0.002). Relative expression of COX-2 and secretion of TXB 2 with concordant phosphorylation of p38MAPK and NF-kB were increased in HAECs when stimulated by Ang II (100 nmol/L) but were significantly decreased by valsartan pretreatment (100 nmol/L). AT 1 R antagonist valsartan decreases platelet

Predictors of thrombotic complications and mass effect exacerbation after pipeline embolization: The significance of adenosine diphosphate inhibition, fluoroscopy time, and aneurysm size.

PubMed

Raychev, Radoslav; Tateshima, Satoshi; Vinuela, Fernando; Sayre, Jim; Jahan, Reza; Gonzalez, Nestor; Szeder, Viktor; Duckwiler, Gary

2016-02-01

The mechanisms leading to delayed rupture, distal emboli and intraparenchymal hemorrhage in relation to pipeline embolization device (PED) placement remain debatable and poorly understood. The aim of this study was to identify clinical and procedural predictors of these perioperative complications. We conducted a retrospective review of consecutive patients who underwent PED placement. We utilized a non-commercial platelet aggregation method measuring adenosine diphosphate (ADP)% inhibition for evaluation of clopidogrel response. To our knowledge, this is the first study to test ADP in neurovascular procedures. Multivariable regression analysis was used to identify the strongest predictor of three separate outcomes: (1) thrombotic complications, (2) hemorrhagic complications, and (3) aneurysm mass effect exacerbation Permanent complication-related morbidity and mortality at 3 months was 6% (3/48). No specific predictors of hemorrhagic complications were identified. In the univariate analysis, the strongest predictors of thrombotic complications were: ADP% inhibition<49 (p=0.01), aneurysm size (p=0.04) and fluoroscopy time (p=0.002). In the final multivariate analysis, among all baseline variables, fluoroscopy time exceeding 52 min was the only factor associated with thrombotic complications (p=0.007). Aneurysm size≥18 mm was the single predictor of mass effect exacerbation (p=0.039). Procedural complexity, reflected by fluoroscopy time, is the strongest predictor of thrombotic complications in this study. ADP% inhibition is a reliable method of testing clopidogrel response in neurovascular procedures and values of <50% may predict thrombotic complications. Interval mass effect exacerbation after PED placement may be anticipated in large aneurysms exceeding 18 mm. © The Author(s) 2015.

Evaluation of 143 Cases of Immune Thrombocytopenic Purpura With Regards to Clinical Course and Response to Treatment

PubMed Central

Albayrak, Murat; Balcik, Ozlem Sahin; Aki, Sahika Zeynep; Gokmen, Ayla; Ceran, Funda; Yokus, Osman; Dagdas, Simten; Ayli, Meltem; Ozet, Gulsum

2010-01-01

Objective: Immune thrombocytopenic purpura (ITP) is also known as idiopathic thrombocytopenic purpura. Increased platelet destruction and insufficient platelet production are both responsible for its etiopathogenesis. ITP can be diagnosed after excluding other possible causes of thrombocytopenia. Materials and Methods: One hundred forty-three cases of chronic ITP that were monitored in a hematology clinic were retrospectively evaluated. All cases received first line treatment of 1 mg/kg/day prednisolone. Corticosteroid nonresponsive (CN) cases and corticosteroid-dependent (CD) cases underwent splenectomies. Results: The rate of CN/CD cases was found to be 53% (n=76). Sixty-six percent of these cases (n=50) underwent splenectomies. The ratio of non-responsive cases to relapse cases after splenectomy (SN/SR) was 30% (n=15). The total number of cases was 41, including those without splenectomy (n=26) and with SY/SR (n=15). Helicobacter pylori (Hp) eradication, immunosuppressive agents and danazol treatments were administered to patients (n=10, n=14 and n=4, respectively). Currently, 13 patients are being monitored without treatment. Fifteen patients who were non-responsive to Hp eradication treatment, immunosuppressive treatment or danazol treatment are still being monitored without any treatment. Conclusion: Optimal treatment is not available for splenectomy-resistant cases of ITP. The response rates for Hp eradication treatment, immunosuppressive treatments and anabolic agents are low. Therefore, larger studies with more patients are required using new agents, such as thrombopoietin (TPO) receptor agonists and anti-CD20 monoclonal antibodies. PMID:25610140

Analysis of National Trends in Hospital Acquired Conditions Following Major Urological Surgery Before and After Implementation of the Hospital Acquired Condition Reduction Program,,✰✰✰.

PubMed

Rude, Tope L; Donin, Nicholas M; Cohn, Matthew R; Meeks, William; Gulig, Scott; Patel, Samir N; Wysock, James S; Makarov, Danil V; Bjurlin, Marc A

2018-06-07

To define the rates of common Hospital Acquired Conditions (HACs) in patients undergoing major urological surgery over a period of time encompassing the implementation of the Hospital Acquired Condition Reduction program, and to evaluate whether implementation of the HAC reimbursement penalties in 2008 was associated with a change in the rate of HACs. Using American College of Surgeons National Surgical Quality Improvement Program (NSQIP) data, we determined rates of HACs in patients undergoing major inpatient urological surgery from 2005 to 2012. Rates were stratified by procedure type and approach (open vs. laparoscopic/robotic). Multivariable logistic regression was used to determine the association between year of surgery and HACs. We identified 39,257 patients undergoing major urological surgery, of whom 2300 (5.9%) had at least one hospital acquired condition. Urinary tract infection (UTI, 2.6%) was the most common, followed by surgical site infection (SSI, 2.5%) and venous thrombotic events (VTE, 0.7%). Multivariable logistic regression analysis demonstrated that open surgical approach, diabetes, congestive heart failure, chronic obstructive pulmonary disease, weight loss, and ASA class were among the variables associated with higher likelihood of HAC. We observed a non-significant secular trend of decreasing rates of HAC from 7.4% to 5.8% HACs during the study period, which encompassed the implementation of the Hospital Acquired Condition Reduction Program. HACs occurred at a rate of 5.9% after major urological surgery, and are significantly affected by procedure type and patient health status. The rate of HAC appeared unaffected by national reduction program in this cohort. Better understanding of the factors associated with HACs is critical in developing effective reduction programs. Copyright © 2018. Published by Elsevier Inc.

Coexistence of anti-β2-glycoprotein I domain I and anti-phosphatidylserine/prothrombin antibodies suggests strong thrombotic risk.

PubMed

Lee, Jee-Soo; Gu, JaYoon; Park, Hee Sue; Yoo, Hyun Ju; Kim, Hyun Kyung

2017-05-01

Highly specific assays for measuring antiphospholipid antibodies (aPLs) are required for accurate assessment of thrombotic risk. aPLs against β2-glycoprotein I domain I (anti-β2GPIdI) and against prothrombin complexed with phosphatidylserine (anti-PS/PT) have been recently identified as being associated with a hypercoagulable state. This study evaluated the synergism between anti-β2GPIdI and anti-PS/PT for predicting thrombotic events. A total of 180 patients with clinical suspicion of hypercoagulability were evaluated. The plasma levels of lupus anticoagulant (LA) and antibodies against anticardiolipin (anti-CL) (IgG and IgM), β2GPI (IgG and IgM), PS/PT (IgG and IgM), and β2GPI dI (IgG) were measured. IgG anti-β2GPIdI and LA were highly associated with thrombosis. Mean values and positivity rates of IgG anti-β2GPI dI and IgG anti-PS/PT were significantly higher in the triple-positive group (LA+, IgG anti-CL+, IgG anti-β2GPI+) than in the other groups. Interestingly, the thrombotic risk [odds ratio (OR) 24.400, 95% confidence interval (CI) 1.976-63.273, p<0.001] of the newly defined triple positive group (LA+, IgG anti-CL+, IgG anti-β2GPIdI+; OR 11.182, 95% CI 1.976-63.273, p=0.006) was more than twice that of the triple-positive group (LA+, IgG anti-CL+, IgG anti-β2GPI+). Double positivity for IgG anti-PS/PT and IgG anti-β2GPI also indicated significant thrombotic risk (OR 7.467, 95% CI 2.350-23.729, p=0.001). Furthermore, the thrombotic risk associated with double positivity for IgG anti-PS/PT and IgG anti-β2GPIdI was markedly elevated (OR 33.654, 95% CI 6.322-179.141, p<0.001). Our data suggest that simultaneous measurement of IgG anti-β2GPIdI and IgG anti-PS/PT may improve clinical decision-making for aPL-positive patients.

The pharmacokinetic and pharmacodynamic properties of site-specific pegylated genetically modified recombinant human interleukin-11 in normal and thrombocytopenic monkeys.

PubMed

Ma, Shan-Shan; Ho, Seong-Hyun; Ma, Su-Yong; Li, Yue-Juan; Li, Kai-Tong; Tang, Xiao-Chuang; Zhao, Guang-Rong; Xu, Song-Shan

2017-10-01

In order to improve the pharmacokinetic and pharmacodynamic properties of recombinant human interleukin-11 mutein (mIL-11) and to reduce the frequency of administration, we examined the feasibility of chemical modification of mIL-11 by methoxy polyethylene glycol succinimidyl carbonate (mPEG-SC). PEG-mIL-11 was prepared by a pH controlled amine specific method. Bioactivity of the protein was determined in a IL-11-dependent in vitro bioassay, its pharmacodynamic and pharmacokinetic properties were investigated by using normal and thrombocytopenic monkey models. N-terminus sequencing and peptide mapping analysis revealed that Lys33 is the PEGylated position for PEG-mIL-11. Bioactivity of PEG-mIL-11 assessed by B9-11 cell proliferation assay was comparable to that of mIL-11. More than 79-fold increase in area-under-the curve (AUC) and 26-fold increase in maximum plasma concentration (C max ) was observed in pharmacokinetic analysis. Single dose administration of the PEG-mIL-11 induced blood platelets number increase and the effect duration were comparable to that of 7 to 10 consecutive daily administration of mIL-11 to the normal and thrombocytopenic monkey models. PEG-mIL-11 is a promising therapeutic for thrombocytopenia. Copyright © 2017 Elsevier B.V. All rights reserved.

High-density lipoprotein from patients with coronary heart disease loses anti-thrombotic effects on endothelial cells: impact on arterial thrombus formation.

PubMed

Holy, Erik W; Besler, Christian; Reiner, Martin F; Camici, Giovanni G; Manz, Jasmin; Beer, Jürg H; Lüscher, Thomas F; Landmesser, Ulf; Tanner, Felix C

2014-11-01

Thrombus formation is determined by the balance between pro- thrombotic mediators and anti-thrombotic factors.High-density lipoprotein (HDL) from healthy subjects exerts anti-thrombotic properties. Whether this is also the case for HDL from patients with stable coronary heart disease (CHD) or acute coronary syndrome (ACS) is unknown.In human aortic endothelial cells in culture,HDL (50 µg/ml) from healthy subjects (HS) inhibited thrombin-induced tissue factor (TF) expression and activity, while HDL (50 µg/ml) from CHD and ACS patients did not. Similarly, only healthy HDL increased endothelial tissue factor pathway inhibitor (TFPI) expression and tissue plasminogen activator (tPA) release, while HDL from CHD and ACS patients had no effect. Healthy HDL inhibited thrombin-induced plasminogen activator inhibitor type 1 (PAI-1) expression, while HDL from ACS patients enhanced endothelial PAI-1 expression. Inhibition of nitric oxide (NO) formation with L-NAME (100 µmol/l) abolished the anti-thrombotic effects of healthy HDL on TF, TFPI, and tPA expression. The exogenous nitric oxide donor, DETANO, mimicked the effects of healthy HDL and counterbalanced the loss of anti-thrombotic effects of HDL from CHD and ACS patients in endothelial cells. In line with this observation, healthy HDL, in contrast to HDL from CHD and ACS patients, increased endothelial NO production. In the laser-injured carotid artery of the mouse, thrombus formation was delayed in animals treated with healthy HDL compared with mice treated with vehicle or HDL from patients with CHD or ACS. In conclusion, HDL from CHD and ACS patients loses the ability of healthy HDL to suppress TF and to increase TFPI and t-PA and instead enhances PAI-1 and arterial thrombus formation.

Risk factors for central venous catheter thrombotic complications in children and adolescents with cancer.

PubMed

Revel-Vilk, S; Yacobovich, J; Tamary, H; Goldstein, G; Nemet, S; Weintraub, M; Paltiel, O; Kenet, G

2010-09-01

The use of central venous catheters (CVCs) has greatly improved the quality of care in children with cancer, yet these catheters may cause serious infectious and thrombotic complications. The aim of this prospective registry study was to assess the host and CVC-related risk factors for CVC-created thrombotic complications. Patients undergoing CVC insertion for chemotherapy were followed prospectively for CVC complications. At the time of enrollment, demographic, clinical, and CVC-related data, and family history of thrombosis were collected. Survival and Cox regression analyses were performed. A total of 423 CVCs were inserted into 262 patients for a total of 76,540 catheter days. The incidence of CVC-related deep-vein thrombosis (DVT) was 0.13 per 1000 catheter-days (95% confidence interval [CI], 0.06-0.24). Insertion of peripherally inserted central catheters (PICCs) and insertion in an angiography suite significantly increased the risk of symptomatic CVC-related DVT. The incidence of CVC occlusion was 1.35 per 1000 catheter-days (95% CI, 1.1-1.63). Positive family history of thrombosis significantly increased the risk of CVC occlusion (hazard ratio [HR], 2.16; 95% CI, 1.2-3.8). The CVC-related risk factors were insertion of Hickman catheters, insertion in angiography suite, and proximal-tip location. Patients developing at least 1 episode of both CVC occlusion and infection had an increased risk for developing symptomatic CVC-related DVT (HR, 4.15; 95% CI, 1.2-14.4). Both patient-related and CVC-related factors are associated with higher risk of symptomatic thrombotic complications. These risk factors could be used in the clinical setting and in developing future studies for CVC thromboprophylaxis.

Anagrelide reduces thrombotic risk in essential thrombocythaemia vs. hydroxyurea plus aspirin.

PubMed

Dombi, Péter; Illés, Árpád; Demeter, Judit; Homor, Lajos; Simon, Zsofia; Karadi, Eva; Udvardy, Miklos; Egyed, Miklos

2017-02-01

To evaluate the reduction in thrombotic events (TE) in patients with essential thrombocythaemia (ET) treated with anagrelide versus hydroxyurea + aspirin (HU + ASA). A questionnaire was developed using 2008 WHO diagnostic criteria, and thrombotic risk factors were stratified according to Landolfi criteria. Through questionnaire completion, clinicians at Hungarian haematological centres entered data into the Hungarian MPN Registry on patients with myeloproliferative neoplasms. Based on ET registry data, TEs in anagrelide-treated patients (n = 139) were compared with HU + ASA-treated patients (n = 141). Patients were followed up for (median) 6 yr. TEs were reported in significantly fewer anagrelide-treated patients versus HU + ASA (15.1% versus 49.6%; P < 0.001). Numbers of major arterial and major venous events were similar between the groups, although there were over fivefold more minor arterial and minor venous events in the HU + ASA group (P < 0.001). While median age at diagnosis was older and length of follow-up shorter in the HU + ASA group (P < 0.05), this did not influence TE incidence; medication and TE before diagnosis only influenced TE incidence. Anagrelide significantly decreased the number of patients experiencing minor arterial and minor venous TEs versus HU + ASA over 6 yr. Risk of TE after diagnosis was significantly increased if the patient had TE before diagnosis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Rutosides for treatment of post-thrombotic syndrome.

PubMed

Morling, Joanne R; Yeoh, Su Ern; Kolbach, Dinanda N

2013-04-30

Post-thrombotic syndrome (PTS) is a long-term complication of deep venous thrombosis (DVT) that is characterised by pain, swelling, and skin changes in the affected limb. One in three patients with DVT will develop post-thrombotic sequelae within five years. Rutosides are a group of compounds derived from horse chestnut (Aesculus hippocastanum), a traditional herbal remedy for treating oedema formation in chronic venous insufficiency (CVI). However, it is not known whether rutosides are effective and safe in the treatment of PTS. To determine the effectiveness and safety of rutosides for treatment of PTS in patients with DVT compared to placebo, no intervention, elastic compression stockings (ECS) or any other treatment. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched October 2012) and CENTRAL (2012, Issue 9). Clinical trials databases were searched for details of ongoing and unpublished studies. Two authors (JM and DNK) independently assessed studies for inclusion. Studies were included to allow the comparison of rutosides versus placebo or no treatment, rutosides versus ECS, and rutosides versus any other treatment. Two authors (JM and SEY) extracted information from the trials. Disagreements were resolved by discussion. Data were extracted using designated data extraction forms. The Cochrane risk of bias tool was used for all included studies to assist in the assessment of quality. Primary outcome measures were the occurrence of leg ulceration over time (yes or no) and any improvement or deterioration of post-thrombotic syndrome (yes or no). Secondary outcomes included reduction of oedema, pain, recurrence of deep venous thrombosis or pulmonary embolism, compliance with therapy, and adverse effects. All of the outcome measures were analysed using Mantel-Haenzel fixed-effect model odds ratios. The unit of analysis was the number of patients. Ten reports of nine studies were identified

The association of JAK2V617F mutation and leukocytosis with thrombotic events in essential thrombocythemia.

PubMed

Hsiao, Hui-Hua; Yang, Ming-Yu; Liu, Yi-Chang; Lee, Ching-Ping; Yang, Wen-Chi; Liu, Ta-Chih; Chang, Chao-Sung; Lin, Sheng-Fung

2007-11-01

The Janus kinase 2 mutation, JAK2 (V617F), and megakaryocytic mutations, MPL (W515L/K), have been identified and correlated with a subtype of essential thrombocythemia (ET) patients. We investigated the frequency of mutations in ET patients and analyzed the relationship with their clinical features. Fifty-three ET patients were enrolled in the study. The amplification refractory mutation system was applied for the mutation survey of the JAK2V617F, while the polymerase chain reaction with sequencing was used for the mutation survey of MPLW515L/K. Thirty-five (66%) patients harboring the JAK2 (V617F) mutation, including 3 homozygous and 32 heterozygous changes, but no MPLW515L/K mutation, were found. During follow-up, 17 (32.1%) patients suffered from documented thrombotic events, with 15 having JAK2V617F mutations. Statistical analysis showed that patients with the JAK2 mutation had significantly higher leukocytes, hemoglobin level, and thrombotic event (p = 0.043, p = 0.001, and p = 0.029, respectively). Thrombotic events were also significantly correlated with leukocytosis and older age. The JAK2V617F mutation was noted in a certain population of ET patients and correlated with leukocytosis, high hemoglobin level, and thrombosis. Therefore, detection of the JAK2V617F mutation can affect not only the diagnosis, but also the management of ET patients.

Cluster-randomized, controlled trial of computer-based decision support for selecting long-term anti-thrombotic therapy after acute ischaemic stroke.

PubMed

Weir, C J; Lees, K R; MacWalter, R S; Muir, K W; Wallesch, C-W; McLelland, E V; Hendry, A

2003-02-01

Identifying the appropriate long-term anti-thrombotic therapy following acute ischaemic stroke is a challenging area in which computer-based decision support may provide assistance. To evaluate the influence on prescribing practice of a computer-based decision support system (CDSS) that provided patient-specific estimates of the expected ischaemic and haemorrhagic vascular event rates under each potential anti-thrombotic therapy. Cluster-randomized controlled trial. We recruited patients who presented for a first investigation of ischaemic stroke or TIA symptoms, excluding those with a poor prognosis or major contraindication to anticoagulation. After observation of routine prescribing practice (6 months) in each hospital, centres were randomized for 6 months to either control (routine practice observed) or intervention (practice observed while the CDSS provided patient-specific information). We compared, between control and intervention centres, the risk reduction (estimated by the CDSS) in ischaemic and haemorrhagic vascular events achieved by long-term anti-thrombotic therapy, and the proportions of subjects prescribed the optimal therapy identified by the CDSS. Sixteen hospitals recruited 1952 subjects. When the CDSS provided information, the mean relative risk reduction attained by prescribing increased by 2.7 percentage units (95%CI -0.3 to 5.7) and the odds ratio for the optimal therapy being prescribed was 1.32 (0.83 to 1.80). Some 55% (5/9) of clinicians believed the CDSS had influenced their prescribing. Cluster-randomized trials provide excellent frameworks for evaluating novel clinical management methods. Our CDSS was feasible to implement and acceptable to clinicians, but did not substantially influence prescribing practice for anti-thrombotic drugs after acute ischaemic stroke.

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

Pregnancy and Birth Outcomes among Women with Idiopathic Thrombocytopenic Purpura

PubMed Central

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

2016-01-01

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

The influence of the platelet count on the incidence of thrombotic and haemorrhagic complications in polycythaemia vera

PubMed Central

Dawson, Audrey A.; Ogston, D.

1970-01-01

In polycythaemia vera, those patients who have an elevated platelet count develop more thrombotic and more haemorrhagic complications than those with a normal count, even when the haematocrit is maintained by therapy within the normal range. PMID:5416508

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

PubMed

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.

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%).

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

Impact of optimal anticoagulation therapy on chronic venous ulcer healing in thrombophilic patients with post-thrombotic syndrome.

PubMed

Hinojosa, C A; Olivares-Cruz, S; Laparra-Escareno, H; Sanchez-Castro, S; Tamayo-Garcia, B; Anaya-Ayala, J E

2016-12-02

Post-thrombotic syndrome (PTS) is the long-term sequelae of deep venous thrombosis (DVT). PTS clinical manifestations include chronic leg pain, oedema, lipodermatosclerosis and ulcers. The objective of this study is to determine in patients with documented history of thrombophilias and DVT whether the number of previous thrombotic events and optimal anticoagulation therapy are associated with the time to venous ulcer healing following the start of compression therapy. Retrospective analysis performed in thrombophilic patients under the age of 50 years old with chronic venous ulcers secondary to DVT at the wound clinic in the National Institute of Medical Sciences and Nutrition 'Salvador Zubirán ' in Mexico City. Variables such as the number or episodes of thrombotic events, type of hypercoagulable disorder, optimal anticoagulation therapy with Warfarin monitored by therapeutic International Normalised Ratio (INR) (2-3) and compliance to compression therapy were examined. Patients that underwent superficial or perforator vein interruption or endovascular recanalisation of deep veins were excluded from the study. From a database of 29 patients with chronic venous ulcers followed in our clinic from January 1992 to September 2012, only 13 patients (61% female) met the inclusion criteria. Mean age±standard deviation (SD) was 32±12 years old. Of these, seven (54%) patients with suboptimal INR presented with an average of two previous thrombotic events and the remaining six (46%) patients with optimal INR only one event (p=0.28), the mean time to the clinical manifestation of a venous ulcer after the first episode of DVT was 39 months (range: 12-72) for patients with suboptimal INR and 82 months (range: 12-216) for those with optimal anticoagulation therapy (p=0.11). During the mean follow-up period of 52 months, all patients in optimal anticoagulation healed their ulcer; their mean time for wound healing was 44 months (range: 4-102). In the suboptimal INR group, only

Hematologic Complications of Pregnancy

PubMed Central

Townsley, Danielle M.

2013-01-01

Pregnancy induces a number of physiologic changes that affect the hematologic indices, either directly or indirectly. Recognizing and treating hematologic disorders that occur during pregnancy is difficult owing to the paucity of evidence available to guide consultants. This paper specifically reviews the diagnosis and management of benign hematologic disorders occurring during pregnancy. Anemia secondary to iron deficiency is the most frequent hematologic complication and is easily treated with oral iron formulations,; however care must be taken not to miss other causes of anemia, such as sickle cell disease. Thrombocytopenia is also a common reason for consulting the hematologist and distinguishing gestational thrombocytopenia from immune thrombocytopenia (ITP), preeclampsia, HELLP syndrome, or thrombotic thrombocytopenic purpura (TTP) is essential since the treatment differs widely. Occasionally the management of mother and infant involves the expeditious recognition of neonatal alloimmune thrombocytopenia (NAIT), a condition that is responsible for severe life-threatening bleeding of the newborn. Additionally, inherited and acquired bleeding disorders affect pregnant women disproportionately and often require careful monitoring of coagulation parameters in order to prevent bleeding in the puerperium. Finally, venous thromboembolism (VTE) during pregnancy is still largely responsible for mortality during pregnancy and the diagnosis, treatment options and guidelines for prevention of VTE during pregnancy are explored. PMID:23953339

Hematologic complications of pregnancy.

PubMed

Townsley, Danielle M

2013-07-01

Pregnancy induces a number of physiologic changes that affect the hematologic indices, either directly or indirectly. Recognizing and treating hematologic disorders that occur during pregnancy is difficult owing to the paucity of evidence available to guide consultants. This review discusses specifically the diagnosis and management of benign hematologic disorders occurring during pregnancy. Anemia secondary to iron deficiency is the most frequent hematologic complication and is easily treated with oral iron formulations; however, care must be taken not to miss other causes of anemia, such as sickle cell disease. Thrombocytopenia is also a common reason for consulting the hematologist, and distinguishing gestational thrombocytopenia from immune thrombocytopenia (ITP), preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), or thrombotic thrombocytopenic purpura (TTP) is essential since the treatment differs widely. Occasionally the management of mother and infant involves the expeditious recognition of neonatal alloimmune thrombocytopenia (NAIT), a condition that is responsible for severe life-threatening bleeding of the newborn. Additionally, inherited and acquired bleeding disorders affect pregnant women disproportionately and often require careful monitoring of coagulation parameters to prevent bleeding in the puerperium. Finally, venous thromboembolism (VTE) during pregnancy is still largely responsible for mortality during pregnancy, and the diagnosis, treatment options and guidelines for prevention of VTE during pregnancy are explored. Published by Elsevier Inc.

Thrombotic events associated with C1 esterase inhibitor products in patients with hereditary angioedema: investigation from the United States Food and Drug Administration adverse event reporting system database.

PubMed

Gandhi, Pranav K; Gentry, William M; Bottorff, Michael B

2012-10-01

To investigate reports of thrombotic events associated with the use of C1 esterase inhibitor products in patients with hereditary angioedema in the United States. Retrospective data mining analysis. The United States Food and Drug Administration (FDA) adverse event reporting system (AERS) database. Case reports of C1 esterase inhibitor products, thrombotic events, and C1 esterase inhibitor product-associated thrombotic events (i.e., combination cases) were extracted from the AERS database, using the time frames of each respective product's FDA approval date through the second quarter of 2011. Bayesian statistical methodology within the neural network architecture was implemented to identify potential signals of a drug-associated adverse event. A potential signal is generated when the lower limit of the 95% 2-sided confidence interval of the information component, denoted by IC₀₂₅ , is greater than zero. This suggests that the particular drug-associated adverse event was reported to the database more often than statistically expected from reports available in the database. Ten combination cases of thrombotic events associated with the use of one C1 esterase inhibitor product (Cinryze) were identified in patients with hereditary angioedema. A potential signal demonstrated by an IC₀₂₅ value greater than zero (IC₀₂₅ = 2.91) was generated for these combination cases. The extracted cases from the AERS indicate continuing reports of thrombotic events associated with the use of one C1 esterase inhibitor product among patients with hereditary angioedema. The AERS is incapable of establishing a causal link and detecting the true frequency of an adverse event associated with a drug; however, potential signals of C1 esterase inhibitor product-associated thrombotic events among patients with hereditary angioedema were identified in the extracted combination cases. © 2012 Pharmacotherapy Publications, Inc.

[Relationship between phenomenon of acquired activated protein C resistance and antiphospholipid antibodies in patients with systemic lupus erythematosus].

PubMed

Hu, Y Q; Chen, F P; Xie, Q Z

2001-10-28

To determine the occurrence of activated protein C resistance (APCR), to identify APCR is associated with thrombotic events (TEs), and acquired APCR is associated with the presence of antiphospholipid antibodies (APLAs) in 30 patients with systemic lupus erythematosus (SLE). Laboratory tests included dilute Russell's viper venom time assay for LA (dRVVT-LA), ELISA assay for ACL, APC sensitivity ratio, and factor V Leiden were detected by PCR-Mnl/I digestion. Acquired APCR was presented in 14(46.67%) of 30 patients. Factor V Leiden was not found in any patients. The incidence of TEs in the APCR-positive patients was significantly higher than that in the APCR-negative patients (42.85% vs 6.25%, P < 0.05). The incidence of TEs in the LA-positive patients was also significantly higher than that in the LA-negative patients (50% vs 11.1%, P < 0.05). The presence of either APCR or LAs is associated with one of the risk factors of TEs (P < 0.05). There is not a significant interaction between APCR and LAs in the association with TEs. Acquired APCR may not reflect the interference of LAs with the protein C pathway which may represent a mechanism of LA-associated TEs.

Cyclical thrombocytosis, acquired von Willebrand syndrome and aggressive non-melanoma skin cancers are common in patients with Philadelphia-negative myeloproliferative neoplasms treated with hydroxyurea.

PubMed

Verner, Emma; Forsyth, Cecily; Grigg, Andrew

2014-05-01

Abstract Cyclical thrombocytosis, acquired von Willebrand syndrome, aggressive non-melanoma skin cancers and other hydroxyurea complications have been reported in Philadelphia-negative myeloproliferative neoplasms (MPNs), but their incidence and clinical consequences have not been defined in a large cohort of patients. We conducted a retrospective analysis of 188 consecutive patients with MPNs specifically addressing the incidence of these complications. Cyclical thrombocytosis was documented in 29 patients (15%), the majority of whom were receiving hydroxyurea. Acquired von Willebrand syndrome was identified in 17 of the 84 screened patients (20%), but was not associated with any major bleeding complications. Non-melanoma skin cancers were reported in 51 patients (27%). Hydroxyurea-related fever occurred in nine of 149 patients (6%) who received hydroxyurea. Seventy-three patients (39%) experienced a total of 98 major thrombotic events, with the majority of these occurring prior to or within 3 months of the diagnosis. Cyclical thrombocytosis, acquired von Willebrand syndrome, aggressive non-melanoma skin cancers and other hydroxyurea-related complications are not infrequent in MPNs and have important clinical consequences for management.

Severe hemorrhage in children with newly diagnosed immune thrombocytopenic purpura

PubMed Central

Buchanan, George R.; Imbach, Paul; Bolton-Maggs, Paula H. B.; Bennett, Carolyn M.; Neufeld, Ellis J.; Vesely, Sara K.; Adix, Leah; Blanchette, Victor S.; Kühne, Thomas

2008-01-01

Controversy exists regarding management of children newly diagnosed with immune thrombocytopenic purpura (ITP). Drug treatment is usually administered to prevent severe hemorrhage, although the definition and frequency of severe bleeding are poorly characterized. Accordingly, the Intercontinental Childhood ITP Study Group (ICIS) conducted a prospective registry defining severe hemorrhage at diagnosis and during the following 28 days in children with ITP. Of 1106 ITP patients enrolled, 863 were eligible and evaluable for bleeding severity assessment at diagnosis and during the subsequent 4 weeks. Twenty-five children (2.9%) had severe bleeding at diagnosis. Among 505 patients with a platelet count less than or equal to 20 000/mm3 and no or mild bleeding at diagnosis, 3 (0.6%), had new severe hemorrhagic events during the ensuing 28 days. Subsequent development of severe hemorrhage was unrelated to initial management (P = .82). These results show that severe bleeding is uncommon at diagnosis in children with ITP and rare during the next 4 weeks irrespective of treatment given. We conclude that it would be difficult to design an adequately powered therapeutic trial aimed at demonstrating prevention of severe bleeding during the first 4 weeks after diagnosis. This finding suggests that future studies of ITP management should emphasize other outcomes. PMID:18698007

Idiopathic thrombocytopenic purpura diagnosed during the second decade of life.

PubMed

Lowe, Eric J; Buchanan, George R

2002-08-01

To retrospectively review our institutional experience of adolescents with idiopathic thrombocytopenic purpura (ITP). Medical record review of all patients diagnosed with ITP between the ages of 10 and 18 years seen at our center from January 1976 to March 2000. Data were collected from 126 patients. Of the evaluable 110 cases, 63 (57%) satisfied the criteria for chronic ITP, 30 (27%) for acute ITP, and 17 (15%) were uncertain. Sex distribution and mean ages were similar in all 3 groups. Platelet count at presentation was higher in patients with chronic ITP. Splenectomy was performed in 24 patients, with 17 (77%) of 22 having normal platelet counts at last follow-up. Outcome for the nonsplenectomized patients with chronic ITP included normalization of platelet count (n = 4), minimal or no bleeding without treatment (n = 29), treatment for ongoing symptoms (n = 5), and unknown (n = 1). Two patients died, 1 from intracranial hemorrhage and 1 from Escherichia coli sepsis and pulmonary hemorrhage. Patients 10 to 18 years of age with ITP are more likely than younger children to have chronic disease. Many patients with ITP recover without drug therapy or need for splenectomy. ITP in adolescents shares features of both childhood and adult ITP.

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.

Quiescent complement in nonhuman primates during E coli Shiga toxin-induced hemolytic uremic syndrome and thrombotic microangiopathy.

PubMed

Lee, Benjamin C; Mayer, Chad L; Leibowitz, Caitlin S; Stearns-Kurosawa, D J; Kurosawa, Shinichiro

2013-08-01

Enterohemorrhagic Escherichia coli (EHEC) produce ribosome-inactivating Shiga toxins (Stx1, Stx2) responsible for development of hemolytic uremic syndrome (HUS) and acute kidney injury (AKI). Some patients show complement activation during EHEC infection, raising the possibility of therapeutic targeting of complement for relief. Our juvenile nonhuman primate (Papio baboons) models of endotoxin-free Stx challenge exhibit full spectrum HUS, including thrombocytopenia, hemolytic anemia, and AKI with glomerular thrombotic microangiopathy. There were no significant increases in soluble terminal complement complex (C5b-9) levels after challenge with lethal Stx1 (n = 6) or Stx2 (n = 5) in plasma samples from T0 to euthanasia at 49.5 to 128 hours post-challenge. d-dimer and cell injury markers (HMGB1, histones) confirmed coagulopathy and cell injury. Thus, complement activation is not required for the development of thrombotic microangiopathy and HUS induced by EHEC Shiga toxins in these preclinical models, and benefits or risks of complement inhibition should be studied further for this infection.

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. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

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.

In vitro anti-thrombotic and anti-coagulant properties of blacklip abalone (Haliotis rubra) viscera hydrolysate.

PubMed

Suleria, Hafiz Ansar Rasul; Masci, Paul P; Addepalli, Rama; Chen, Wei; Gobe, Glenda C; Osborne, Simone A

2017-07-01

Abalone viscera contain sulphated polysaccharides with anti-thrombotic and anti-coagulant activities. In this study, a hydrolysate was prepared from blacklip abalone (Haliotis rubra) viscera using papain and bromelain and fractionated using ion exchange and size exclusion chromatography. Hydrolysates and fractions were investigated for in vitro thrombin inhibition mediated through heparin cofactor II (HCII) as well as anti-coagulant activity in plasma and whole blood. On the basis of sulphated polysaccharide concentration, the hydrolysate inhibited thrombin through HCII with an inhibitor concentration at 50% (IC50) of 16.5 μg/mL compared with 2.1 μg/mL for standard heparin. Fractionation concentrated HCII-mediated thrombin inhibition down to an IC50 of 1.8 μg/mL and improved anti-coagulant activities by significantly delaying clotting time. This study confirmed the presence of anti-thrombotic and anti-coagulant molecules in blacklip abalone viscera and demonstrated that these activities can be enriched with a simple chromatography regime. Blacklip abalone viscera warrant further investigation as a source of nutraceutical or functional food ingredients. Graphical abstract Schematic showing preparation of bioactive extracts and fractions from blacklip abalone.

Susoctocog Alfa: A Review in Acquired Haemophilia A.

PubMed

Burness, Celeste B; Scott, Lesley J

2016-05-01

Intravenous susoctocog alfa (Obizur(®)) is a recombinant, B-domain deleted, porcine sequence antihaemophilic factor VIII (FVIII) product that has recently been approved for the treatment of bleeding episodes in adults with acquired haemophilia A (AHA). Intravenous susoctocog alfa was an effective and generally well tolerated treatment for serious bleeding episodes in adult patients with AHA in a multinational, phase II/III trial (n = 28 evaluable). Patients received an initial dose of susoctocog alfa 200 U/kg, with subsequent dosages based on target FVIII trough levels and clinical assessments. All patients had a positive haemostatic response (based on predefined criteria) of the primary bleed 24 h after the first infusion of susoctocog alfa, with the bleed successfully controlled at the time of final dosing in 86 % of patients. The most frequently reported adverse reaction (incidence >5 %) was the development of inhibitory antibodies against susoctocog alfa (porcine FVIII). Overall, 25 % of antibody naive patients developed anti-susoctocog alfa antibodies during the study. No serious treatment-related adverse events, thrombotic events or allergic reactions were reported during the trial. In conclusion, intravenous susoctocog alfa is a useful addition to the limited treatment options available for the management of acute bleeding episodes in adults with AHA.

Opportunities for improvement in anti-thrombotic therapy and other strategies for the management of acute coronary syndromes: Insights from EPICOR, an international study of current practice patterns.

PubMed

Bueno, Héctor; Sinnaeve, Peter; Annemans, Lieven; Danchin, Nicolas; Licour, Muriel; Medina, Jesús; Pocock, Stuart; Sánchez-Covisa, Joaquín; Storey, Robert F; Jukema, J Wouter; Zeymer, Uwe; Van de Werf, Frans

2016-02-01

To describe international patterns and opportunities for improvement of pre- and in-hospital care of patients hospitalized for acute coronary syndromes (ACS), with special focus on anti-thrombotic therapy. EPICOR (long-tErm follow-uP of anti-thrombotic management patterns In acute CORonary syndrome patients), an international, cohort study, which enrolled 10,568 consecutive ACS survivors from 555 hospitals in 20 countries across Europe and Latin America (September 2010 to March 2011), prospectively registered detailed information on pre- and in-hospital management. Globally, 4738 (44.8%) were attended before hospitalization, 4241 (40.1%) had an ECG, 2119 (20%) received anti-platelet therapy and 101 STEMI patients (2%) fibrinolysis. In-hospital, 7944 patients (75.2%) received dual anti-platelet therapy, most often with clopidogrel (69.7%), and less with prasugrel (5.4%); 1705 (16.1%) had triple anti-platelet therapy, and 849 (8%) single anti-platelet therapy. STEMI patients more often received pre-hospital anti-thrombotics, and prasugrel, GP IIb/IIIa inhibitors and UFH in-hospital (all p < 0.001). More NSTE-ACS patients received clopidogrel, single anti-platelet therapy, and fondaparinux (all p < 0.001). As many as 33% of ACS patients were medically managed. A significant decreasing gradient was found between Northern, Southern and Eastern Europe and Latin America in use of more potent patterns of anti-platelet therapy, reperfusion therapy and invasive strategy. This large international study shows room for improvement in use of anti-thrombotic drugs and other strategies for optimal management of ACS, including pre-hospital ECG and anti-thrombotic therapy. Regional practice differences not based on evidence or conditioned by economic constraints should be reduced. © The European Society of Cardiology 2015.

Trichinella Nativa Outbreak With Rare Thrombotic Complications Associated With Meat From a Black Bear Hunted in Northern Ontario.

PubMed

Dalcin, Daniel; Zarlenga, Dante S; Larter, Nicholas C; Hoberg, Eric; Boucher, Daniel A; Merrifield, Samuel; Lau, Rachel; Ralevski, Filip; Cheema, Karamjit; Schwartz, Kevin L; Boggild, Andrea K

2017-05-15

Although trichinellosis is known to cause thrombotic disease, serious thrombotic events are rare and have not been previously associated with Trichinella nativa infection. Patient interviews and medical chart reviews were conducted on 10 men who became ill following consumption of a common source of black bear meat. Trichinella serology on patient sera as well as polymerase chain reaction (PCR) and larval identification of the meat samples was conducted. All 10 exposed individuals developed an acute illness clinically compatible with trichinellosis, characterized by fever, abdominal pain, and diarrhea, along with eosinophilia ranging from 0.9 × 109/L to 6.1 × 109/L. Within 2 weeks of the diarrheal illness, systemic symptoms developed in all exposed individuals characterized by fever, myalgia, periorbital edema, and fatigue. ST-elevation myocardial infarction and sinus venous tract thrombosis occurred as a complication of trichinellosis in 2 patients. Acute serology was nonreactive in all patients, though convalescent serology was reactive in 6 of 8 (75%) patients for whom sera was available. Multiplex PCR identified T. nativa from the bear meat, and was corroborated by microscopic larval identification. We report a 100% attack rate of T. nativa from bear meat among those who were exposed, and demonstrate that this species can cause serious thrombotic complications of trichinellosis in humans. Education of hunters and the public regarding the importance of proper preparation of wild game prior to ingestion is warranted. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com

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.

Endogenous pro-thrombotic biomarkers from the arm and leg may not have the same value.

PubMed

Lattimer, Christopher R; Kalodiki, Evi; Geroulakos, George; Hoppensteadt, Debra; Fareed, Jawed

2016-05-01

Assessments of endogenous pro-thrombotic biomarkers are performed invariably on arm blood. However, the commonest site for thrombosis is in the leg. A leg blood sample may reflect local pro-thrombotic processes more accurately than systemic arm blood. The aim was to determine whether pro-thrombotic biomarkers from standard venous arm samples differed significantly from leg samples. Concurrent blood samples were taken from an ankle/lower calf varicose vein and an ante-cubital vein in 24 patients awaiting laser treatment as well as age approximated and sex matched healthy controls without venous disease. The following assays were performed: thrombin-antithrombin (ng/ml), antithrombin (%) activity, microparticles (nM), fibrinogen (mg/dl), prothrombin fragment 1.2 (F1.2) (pM) and P-selectin (ng/ml). Expressed as median (inter-quartile range). Significant arm/leg differences were observed in thrombin-antithrombin, antithrombin, prothrombin fragment 1.2 and P-selectin. The legs of patients had significantly reduced antithrombin activity and P-selectin concentrations compared to their arms (leg: 101 (90-108) versus arm: 112 (99-126), P = 0.001 and leg: 42 (26-52) versus 45 (27-52), P = 0.044, respectively). Control leg samples had significantly increased thrombin-antithrombin and P-selectin compared to control arm samples (leg: 2.1 (0.9-3.2) versus arm: 0.8 (0.5-1.7), P = 0.015 and leg: 36 (24-50) versus arm: 30 (23-41), P = 0.007, respectively). However, the control legs had significantly reduced F1.2 (leg: 265 (230-333) versus arm: 299 (236-361), P = 0.028). No significant arm/leg differences were detected in the microparticle or fibrinogen levels. These findings indicate that venous arm blood is significantly different from venous leg blood in four out of six biomarkers studied. Recognition of local venous leg sampling as a site for investigation may unravel why the leg has a greater predisposition to thrombosis and lead the way towards an arm

Plasminogen activator inhibitor links obesity and thrombotic cerebrovascular diseases: The roles of PAI-1 and obesity on stroke.

PubMed

Chen, Rui; Yan, Jinchuan; Liu, Peijing; Wang, Zhongqun; Wang, Cuiping

2017-06-01

One of the global socioeconomic phenomena occurred during the last decades is the increased prevalence of obesity, with direct consequence on the risk of developing thrombotic disorders. As the physiological inhibitor of tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1) is well known for its role in fibrinolysis. More and more evidences have shown that PAI-1 involves in physiopathologic mechanisms of many diseases and metabolic disorder. Increased serum level of PAI-1 has been observed in obesity and it also contributes to the development of adipose tissue and then has effects on obesity. Meantime, obesity affects also the PAI-1 levels. These evidences indicate the complicated interaction between PAI-1 and obesity. Many clinic studies have confirmed that obesity relates to the stroke outcome although there are many contradictory results. Simultaneously, correlation is found between plasma PAI-1 and thrombotic cerebrovascular diseases. This article reviews contemporary knowledge regarding the complex interplay of obesity, PAI-1 and stroke.

Eculizumab for drug-induced de novo posttransplantation thrombotic microangiopathy: A case report.

PubMed

Safa, Kassem; Logan, Merranda S; Batal, Ibrahim; Gabardi, Steven; Rennke, Helmut G; Abdi, Reza

2015-02-01

De novo thrombotic microangiopathy (TMA) following renal transplantation is a severe complication associated with high rates of allograft failure. Several immunosuppressive agents are associated with TMA. Conventional approaches to managing this entity, such as withdrawal of the offending agent and/or plasmapheresis, often offer limited help, with high rates of treatment failure and graft loss. We herein report a case of drug induced de novo TMA successfully treated using the C5a inhibitor eculizumab in a renal transplant patient. This report highlights a potentially important role for eculizumab in settings where drug-induced de novo TMA is refractory to conventional therapies.

Awareness of antiplatelet resistance in patient with repeated episodes of thrombotic events

NASA Astrophysics Data System (ADS)

Dalimunthe, N. N.; Hamonangan, R.; Antono, D.; Prasetya, I.; Rusdi, L.

2018-03-01

Antiplatelet has been the cornerstones management of acute coronary syndrome. However, numbers of patients on these agents had episodes of adverse cardiovascular events. A 65-year-old woman post cardiac coronary bypass surgery on dual antiplatelet therapy, Aspirin, and Clopidogrel underwent several episodes of thrombotic events despite good adhered to thedailyantiplatelet regimen.These recurrent events had led to clinical suspicious of antiplatelet resistance. Platelet function test was performed which indicates a poor platelet response to Clopidogrel. Clopidogrelwas discontinued and Ticagrelor was prescribed together with Aspirin. During two months of follow up, there is no episode of chest discomfort.

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.

Synergy of combined tPA-edaravone therapy in experimental thrombotic stroke.

PubMed

Sun, Yu-Yo; Morozov, Yury M; Yang, Dianer; Li, Yikun; Dunn, R Scott; Rakic, Pasko; Chan, Pak H; Abe, Koji; Lindquist, Diana M; Kuan, Chia-Yi

2014-01-01

Edaravone, a potent antioxidant, may improve thrombolytic therapy because it benefits ischemic stroke patients on its own and mitigates adverse effects of tissue plasminogen activator (tPA) in preclinical models. However, whether the combined tPA-edaravone therapy is more effective in reducing infarct size than singular treatment is uncertain. Here we investigated this issue using a transient hypoxia-ischemia (tHI)-induced thrombotic stroke model, in which adult C57BL/6 mice were subjected to reversible ligation of the unilateral common carotid artery plus inhalation of 7.5% oxygen for 30 min. While unilateral occlusion of the common carotid artery suppressed cerebral blood flow transiently, the addition of hypoxia triggered reperfusion deficits, endogenous thrombosis, and attenuated tPA activity, leading up to infarction. We compared the outcomes of vehicle-controls, edaravone treatment, tPA treatment at 0.5, 1, or 4 h post-tHI, and combined tPA-edaravone therapies with mortality rate and infarct size as the primary end-points. The best treatment was further compared with vehicle-controls in behavioral, biochemical, and diffusion tensor imaging (DTI) analyses. We found that application of tPA at 0.5 or 1 h--but not at 4 h post-tHI--significantly decreased infarct size and showed synergistic (p<0.05) or additive benefits with the adjuvant edaravone treatment, respectively. The acute tPA-edaravone treatment conferred >50% reduction of mortality, ∼ 80% decline in infarct size, and strong white-matter protection. It also improved vascular reperfusion and decreased oxidative stress, inflammatory cytokines, and matrix metalloproteinase activities. In conclusion, edaravone synergizes with acute tPA treatment in experimental thrombotic stroke, suggesting that clinical application of the combined tPA-edaravone therapy merits investigation.

Synergy of Combined tPA-Edaravone Therapy in Experimental Thrombotic Stroke

PubMed Central

Sun, Yu-Yo; Morozov, Yury M.; Yang, Dianer; Li, Yikun; Dunn, R. Scott; Rakic, Pasko; Chan, Pak H.; Abe, Koji; Lindquist, Diana M.; Kuan, Chia-Yi

2014-01-01

Edaravone, a potent antioxidant, may improve thrombolytic therapy because it benefits ischemic stroke patients on its own and mitigates adverse effects of tissue plasminogen activator (tPA) in preclinical models. However, whether the combined tPA-edaravone therapy is more effective in reducing infarct size than singular treatment is uncertain. Here we investigated this issue using a transient hypoxia-ischemia (tHI)-induced thrombotic stroke model, in which adult C57BL/6 mice were subjected to reversible ligation of the unilateral common carotid artery plus inhalation of 7.5% oxygen for 30 min. While unilateral occlusion of the common carotid artery suppressed cerebral blood flow transiently, the addition of hypoxia triggered reperfusion deficits, endogenous thrombosis, and attenuated tPA activity, leading up to infarction. We compared the outcomes of vehicle-controls, edaravone treatment, tPA treatment at 0.5, 1, or 4 h post-tHI, and combined tPA-edaravone therapies with mortality rate and infarct size as the primary end-points. The best treatment was further compared with vehicle-controls in behavioral, biochemical, and diffusion tensor imaging (DTI) analyses. We found that application of tPA at 0.5 or 1 h – but not at 4 h post-tHI – significantly decreased infarct size and showed synergistic (p<0.05) or additive benefits with the adjuvant edaravone treatment, respectively. The acute tPA-edaravone treatment conferred >50% reduction of mortality, ∼80% decline in infarct size, and strong white-matter protection. It also improved vascular reperfusion and decreased oxidative stress, inflammatory cytokines, and matrix metalloproteinase activities. In conclusion, edaravone synergizes with acute tPA treatment in experimental thrombotic stroke, suggesting that clinical application of the combined tPA-edaravone therapy merits investigation. PMID:24911517

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

Regulatory T Cells in Patients with Idiopathic Thrombocytopenic Purpura.

PubMed

Akyol Erikçi, Alev; Karagöz, Bülent; Bilgi, Oğuz

2016-06-05

Immune thrombocytopenic purpura (ITP) is an immune-mediated bleeding disorder in which platelets are opsonized by autoantibodies and destroyed by an Fc receptor-mediated phagocytosis by the reticuloendothelial system within the spleen. Autoimmune processes are also considered in the pathogenesis of this disorder. CD4+CD25+FoxP3+ regulatory T (Treg) cells and CD8+CD28- Treg cells have roles in autoimmune diseases. We investigated these regulatory cells in ITP patients. We included 22 ITP patients and 16 age-matched healthy subjects. CD4+CD25+FoxP3+ Treg cells and CD8+CD28- cells were investigated by three-color flow cytometry. The ratios of these cell populations to total lymphocytes were calculated. Statistical analysis was carried out with the Mann-Whitney U test. CD4+CD25+ Treg cells were 9.69±3.70% and 12.99±5.58% in patients with ITP and controls, respectively. CD4+CD25highFoxP3+ cells were 27.72±19.74% and 27.55±23.98% in ITP patients and controls, respectively. The percentages of both of these cell types were not statistically significant when compared to the control group. We did not find any differences in ratios of CD4+CD25+FoxP3+ Treg cells or CD8+CD28- T cells in lymphocytes between patients and healthy subjects. We conclude that these circulatory cells are not different in ITP, but further studies are needed to explore the putative roles of these regulatory cells.

Proteasome inhibitor associated thrombotic microangiopathy.

PubMed

Yui, Jennifer C; Van Keer, Jan; Weiss, Brendan M; Waxman, Adam J; Palmer, Matthew B; D'Agati, Vivette D; Kastritis, Efstathios; Dimopoulos, Meletios A; Vij, Ravi; Bansal, Dhruv; Dingli, David; Nasr, Samih H; Leung, Nelson

2016-09-01

A variety of medications have been implicated in the causation of thrombotic microangiopathy (TMA). Recently, a few case reports have emerged of TMA attributed to the proteasome inhibitors (PI) bortezomib and carfilzomib in patients with multiple myeloma. The aim of this case series was to better characterize the role of PI in the etiology of drug-induced TMA. We describe eleven patients from six medical centers from around the world who developed TMA while being treated with PI. The median time between medication initiation and diagnosis of TMA was 21 days (range 5 days to 17 months). Median laboratory values at diagnosis included hemoglobin-7.5 g dL(-1) , platelet count-20 × 10(9) /L, LDH-698 U L(-1) , creatinine-3.12 mg dL(-1) . No patient had any other cause of TMA, including ADAMTS13 inhibition, other malignancy or use of any other medication previously associated with TMA. Nine patients had resolution of TMA without evidence of hemolysis after withdrawal of PI. Two patients had stabilization of laboratory values but persistent evidence of hemolysis despite medication withdrawal. One patient had recurrence of TMA with rechallenge of PI. There is a strong level of evidence that PI can cause DITMA. In evaluating patients with suspected TMA, PI use should be recognized as a potential etiology, and these medications should be discontinued promptly if thought to be the cause of TMA. Am. J. Hematol. 91:E348-E352, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Residual vein thrombosis and onset of post-thrombotic syndrome: influence of the 4G/5G polymorphism of plasminogen activator inhibitor-1 gene.

PubMed

Incalcaterra, Egle; Meli, Francesco; Muratori, Ida; Corrado, Egle; Amato, Corrado; Canino, Baldassare; Ferrara, Filippo

2014-03-01

Plasminogen activator inhibitor-1 (PAI-1) is the most important inhibitor of plasminogen activator. The functional 4G/5G polymorphism of the gene coding for PAI-1 may affect PAI-1 plasmatic activity, influencing the imbalance between coagulation and fibrinolysis cascades. In this prospective cohort analytic study, we investigated the role of this single nucleotide polymorphism in the persistence of thrombotic lesion and the occurrence of post-thrombotic syndrome. In a group of 168 patients with post-surgical deep vein thrombosis of the legs, we analyzed the 4G/5G polymorphism in the promoter of PAI-1 gene and plasmatic PAI-1 activity. Enrolled patients were divided in two groups: patients with 4G/5G polymorphism and increased PAI-1 activity (n=85) and patients without 4G/5G polymorphism and normal PAI-1 activity (n=83). All patients were treated according to current protocols and re-examined after 3, 12 and 36 months in order to evaluate the persistence of thrombotic lesion and the occurrence of post-thrombotic syndrome. We found a significantly increased PAI activity in carrier of the 4G allele, who experienced much more frequently a persistence of thrombosis after 3, 12 and 36 months and/or the development of post-thrombosis syndrome, in spite of the anticoagulant treatment. These data not only confirm the role played by PAI-1 activity and by the 4G/5G SNP of the PAI-1 gene, but also suggest that current therapeutic protocols, recommending the administration of low weight molecular heparin and oral anticoagulant for the treatment of deep vein thrombosis, could be non sufficient for patients genetically predisposed to a less efficient clot lysis. Copyright © 2013. Published by Elsevier Ltd.

Platelet receptors as therapeutic targets: Past, present and future.

PubMed

Jamasbi, Janina; Ayabe, Keng; Goto, Shinya; Nieswandt, Bernhard; Peter, Karlheinz; Siess, Wolfgang

2017-06-28

Anti-platelet drugs reduce arterial thrombosis after plaque rupture and erosion, prevent stent thrombosis and are used to prevent and treat myocardial infarction and ischaemic stroke. Some of them may also be helpful in treating less frequent diseases such as thrombotic thrombocytopenic purpura. The present concise review aims to cover current and future developments of anti-platelet drugs interfering with the interaction of von Willebrand factor (VWF) with glycoprotein (GP) Ibα, and directed against GPVI, GPIIb/IIIa (integrin α IIb β 3 ), the thrombin receptor PAR-1, and the ADP receptor P2Y 12 . The high expectations of having novel antiplatelet drugs which selectively inhibit arterial thrombosis without interfering with normal haemostasis could possibly be met in the near future.

[Treatment and results of therapy in chronic idiopathic thrombocytopenic purpura].

PubMed

Tasić, J; Milenović, M; Drasković, S; Vukicević, T; Macukanović, L; Kitić, Lj; Bakić, M

1994-01-01

Basic principles in the therapy of chronic idiopathic thrombocytopenic purpura are glucocorticoides and splenectomy. Other measures: Intravenous high doses gamma globulin therapy, attenuated androgenes, immunosupresive drugs and plasmaferesis are less effective. During the period of 1989-1992 we treated 34 patients. From 34 patients, 23 were women and 11 were men. We treated patients primarily by prednisolon approximaly for 2 - 4 weeks. Rarely we use doses of 3 mg/kg per day for short periods of time (5 to 10 days) or "pulse therapy" of 500 mg per day. Those doses may be effective in elevating platelet count if the response is poor. If response occurs, high dosages of steroides should be tareped to determine the amount that will maintain the platelet count in the range of 30x10(9)/l to 50x10(9)/l (to minimaze the toxic sade effects of steroides). If steroides are ineffective, we perform splenectomy. From 34 treated patients by glucocorticoides, in 16 we got remission and in 11 partial response. We discussed in detailes relationship duration of treatment with glucocorticoides and level of platelets, and also correlation duration of treatment with prognosis. From 6 splenectomized patients 3 were successful. In two patients we applied intravenous gamma globulin therapy and attenuated androgen successfuly. In one patients therapy with gamma globulin, immunosupresive drugs, androgen and other measures was ineffective. In one patients without splenectomy we administrated successfuly gamma globulin therapy and androgen for peroid of two years.

Platelet antibody in prolonged remission of childhood idiopathic thrombocytopenic purpura

DOE Office of Scientific and Technical Information (OSTI.GOV)

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.more » 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.« less

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. © 2010 John Wiley & Sons A/S.

E. coli derived Von Willebrand Factor-A2 domain FRET proteins that quantify ADAMTS13 activity

PubMed Central

Dayananda, Kannayakanahalli M.; Gogia, Shobhit; Neelamegham, Sriram

2010-01-01

The cleavage of the A2-domain of Von Willebrand Factor (VWF) by the metalloprotease ADAMTS13 regulates VWF size and platelet thrombosis rates. Reduction or inhibition of this enzyme activity leads to thrombotic thrombocytopenic purpura (TTP). We generated a set of novel molecules called VWF-A2 FRET proteins’, where variants of YFP (Venus) and CFP (Cerulean) flank either the entire VWF-A2 domain (175 amino acids) or truncated fragments (141, 113, 77 amino acids) of this domain. These proteins were expressed in E. coli in soluble form, and they exhibited Fluorescence/Förster Resonance Energy Transfer (FRET) properties. Results show that introduction of Venus/Cerulean itself did not alter the ability of VWF-A2 to undergo ADAMTS13 mediated cleavage. The smallest FRET protein, XS-VWF, detected plasma ADAMTS13 activity down to 10% of normal levels. Tests of acquired and inherited TTP could be completed within 30 min. VWF-A2 conformation changed progressively, and not abruptly, upon increasing urea concentration. While proteins with 77 and 113 VWF-A2 residues were cleaved in the absence of denaturant, 4M urea was required for the efficient cleavage of larger constructs. Overall, VWF-A2 FRET proteins can be applied both for the rapid diagnosis of plasma ADAMTS13 activity, and as a tool to study VWF-A2 conformation dynamics. PMID:21146487

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. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

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

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.

Curcuma oil ameliorates insulin resistance & associated thrombotic complications in hamster & rat

PubMed Central

Singh, Vishal; Jain, Manish; Misra, Ankita; Khanna, Vivek; Prakash, Prem; Malasoni, Richa; Dwivedi, Anil Kumar; Dikshit, Madhu; Barthwal, Manoj Kumar

2015-01-01

Background & objectives: Curcuma oil (C. oil) isolated from turmeric (Curcuma longa L.) has been shown to have neuro-protective, anti-cancer, antioxidant and anti-hyperlipidaemic effects in experimental animal models. However, its effect in insulin resistant animals remains unclear. The present study was carried out to investigate the disease modifying potential and underlying mechanisms of the C. oil in animal models of diet induced insulin resistance and associated thrombotic complications. Methods: Male Golden Syrian hamsters on high fructose diet (HFr) for 12 wk were treated orally with vehicle, fenofibrate (30 mg/kg) or C. oil (300 mg/kg) in the last four weeks. Wistar rats fed HFr for 12 wk were treated orally with C. oil (300 mg/kg) in the last two weeks. To examine the protective effect of C. oil, blood glucose, serum insulin, platelet aggregation, thrombosis and inflammatory markers were assessed in these animals. Results: Animals fed with HFr diet for 12 wk demonstrated hyperlipidaemia, hyperglycaemia, hyperinsulinaemia, alteration in insulin sensitivity indices, increased lipid peroxidation, inflammation, endothelial dysfunction, platelet free radical generation, tyrosine phosphorylation, aggregation, adhesion and intravascular thrombosis. Curcuma oil treatment for the last four weeks in hamsters ameliorated HFr-induced hyperlipidaemia, hyperglycaemia, insulin resistance, oxidative stress, inflammation, endothelial dysfunction, platelet activation, and thrombosis. In HFr fed hamsters, the effect of C. oil at 300 mg/kg was comparable with the standard drug fenofibrate. Curcuma oil treatment in the last two weeks in rats ameliorated HFr-induced hyperglycaemia and hyperinsulinaemia by modulating hepatic expression of sterol regulatory element binding protein 1c (SREBP-1c), peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC-1)α and PGC-1β genes known to be involved in lipid and glucose metabolism. Interpretation & conclusions: High

Curcuma oil ameliorates insulin resistance & associated thrombotic complications in hamster & rat.

PubMed

Singh, Vishal; Jain, Manish; Misra, Ankita; Khanna, Vivek; Prakash, Prem; Malasoni, Richa; Dwivedi, Anil Kumar; Dikshit, Madhu; Barthwal, Manoj Kumar

2015-06-01

Curcuma oil (C. oil) isolated from turmeric (Curcuma longa L.) has been shown to have neuro-protective, anti-cancer, antioxidant and anti-hyperlipidaemic effects in experimental animal models. However, its effect in insulin resistant animals remains unclear. The present study was carried out to investigate the disease modifying potential and underlying mechanisms of the C. oil in animal models of diet induced insulin resistance and associated thrombotic complications. Male Golden Syrian hamsters on high fructose diet (HFr) for 12 wk were treated orally with vehicle, fenofibrate (30 mg/kg) or C. oil (300 mg/kg) in the last four weeks. Wistar rats fed HFr for 12 wk were treated orally with C. oil (300 mg/kg) in the last two weeks. To examine the protective effect of C. oil, blood glucose, serum insulin, platelet aggregation, thrombosis and inflammatory markers were assessed in these animals. Animals fed with HFr diet for 12 wk demonstrated hyperlipidaemia, hyperglycaemia, hyperinsulinaemia, alteration in insulin sensitivity indices, increased lipid peroxidation, inflammation, endothelial dysfunction, platelet free radical generation, tyrosine phosphorylation, aggregation, adhesion and intravascular thrombosis. Curcuma oil treatment for the last four weeks in hamsters ameliorated HFr-induced hyperlipidaemia, hyperglycaemia, insulin resistance, oxidative stress, inflammation, endothelial dysfunction, platelet activation, and thrombosis. In HFr fed hamsters, the effect of C. oil at 300 mg/kg [ ] was comparable with the standard drug fenofibrate. Curcuma oil treatment in the last two weeks in rats ameliorated HFr-induced hyperglycaemia and hyperinsulinaemia by modulating hepatic expression of sterol regulatory element binding protein 1c (SREBP-1c), peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC-1)α and PGC-1β genes known to be involved in lipid and glucose metabolism. High fructose feeding to rats and hamsters led to the development of insulin

Sunitinib-Induced Acute Interstitial Nephritis in a Thrombocytopenic Renal Cell Cancer Patient.

PubMed

Azar, Ibrahim; Esfandiarifard, Saghi; Sinai, Pedram; Wazir, Ali; Foulke, Llewellyn; Mehdi, Syed

2017-01-01

Sunitinib, a multitargeted tyrosine kinase inhibitor (TKI), is currently the standard of care for patients with metastatic renal cell carcinoma. Renal adverse events associated with sunitinib include proteinuria, renal insufficiency secondary to focal segmental glomerulosclerosis (FSGS), and thrombotic microangiopathy. We describe the second reported instance of biopsy-proven sunitinib-induced acute interstitial nephritis (AIN), in a challenging case complicated by thrombocytopenia. The case illustrates the importance of early diagnosis and intervention in ensuring long-term recovery from renal complications. Four other cases of AIN reported along with inhibition of the vascular endothelial growth factor (VEGF) by either TKI (sunitinib and sorafenib) or antibodies (bevacizumab) suggest a possible class effect. Given our experience, we recommend monitoring renal function with VEGF inhibition, and in the case of renal failure in the setting of an unclear diagnosis, we recommend prompt biopsy.

Novel Thrombotic Function of a Human SNP in STXBP5 Revealed by CRISPR/Cas9 Gene Editing in Mice.

PubMed

Zhu, Qiuyu Martin; Ko, Kyung Ae; Ture, Sara; Mastrangelo, Michael A; Chen, Ming-Huei; Johnson, Andrew D; O'Donnell, Christopher J; Morrell, Craig N; Miano, Joseph M; Lowenstein, Charles J

2017-02-01

To identify and characterize the effect of a SNP (single-nucleotide polymorphism) in the STXBP5 locus that is associated with altered thrombosis in humans. GWAS (genome-wide association studies) have identified numerous SNPs associated with human thrombotic phenotypes, but determining the functional significance of an individual candidate SNP can be challenging, particularly when in vivo modeling is required. Recent GWAS led to the discovery of STXBP5 as a regulator of platelet secretion in humans. Further clinical studies have identified genetic variants of STXBP5 that are linked to altered plasma von Willebrand factor levels and thrombosis in humans, but the functional significance of these variants in STXBP5 is not understood. We used CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated 9) techniques to produce a precise mouse model carrying a human coding SNP rs1039084 (encoding human p. N436S) in the STXBP5 locus associated with decreased thrombosis. Mice carrying the orthologous human mutation (encoding p. N437S in mouse STXBP5) have lower plasma von Willebrand factor levels, decreased thrombosis, and decreased platelet secretion compared with wild-type mice. This thrombosis phenotype recapitulates the phenotype of humans carrying the minor allele of rs1039084. Decreased plasma von Willebrand factor and platelet activation may partially explain the decreased thrombotic phenotype in mutant mice. Using precise mammalian genome editing, we have identified a human nonsynonymous SNP rs1039084 in the STXBP5 locus as a causal variant for a decreased thrombotic phenotype. CRISPR/Cas9 genetic editing facilitates the rapid and efficient generation of animals to study the function of human genetic variation in vascular diseases. © 2016 American Heart Association, Inc.

Thrombus Extraction Catheters vs. Angiojet Rheolytic Thrombectomy in Thrombotic Lesions/SV Grafts

PubMed Central

Alexopoulos, Dimitrios; Davlouros, Periklis A

2012-01-01

Primary percutaneous coronary intervention, (pPCI), of native coronaries and saphenous vein grafts (SVGs), is the recommended reperfusion strategy for STEMI, and an early invasive approach is recommended for high risk patients with UA/NSTEMI. Although PCI effectively restores flow in the infarct related artery/culprit vessel in both situations, myocardial perfusion often remains suboptimal due to microvascular obstruction, partly attributed to distal embolization of thrombus. Hence, thrombectomy (manual or mechanical), prior to stenting may further reduce hard clinical end points in patients with ACS. This article discusses accumulated evidence regarding the safety and effectiveness of thrombectomy in culprit native coronaries and SVGs in such patients, as well as possible strategies for maximizing its benefits relative to the size of the thrombotic burden. PMID:22920486

Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations

PubMed Central

Salvadori, Maurizio; Bertoni, Elisabetta

2013-01-01

Hemolytic uremic syndrome (HUS) is a rare disease. In this work the authors review the recent findings on HUS, considering the different etiologic and pathogenetic classifications. New findings in genetics and, in particular, mutations of genes that encode the complement-regulatory proteins have improved our understanding of atypical HUS. Similarly, the complement proteins are clearly involved in all types of thrombotic microangiopathy: typical HUS, atypical HUS and thrombotic thrombocytopenic purpura (TTP). Furthermore, several secondary HUS appear to be related to abnormalities in complement genes in predisposed patients. The authors highlight the therapeutic aspects of this rare disease, examining both “traditional therapy” (including plasma therapy, kidney and kidney-liver transplantation) and “new therapies”. The latter include anti-Shiga-toxin antibodies and anti-C5 monoclonal antibody “eculizumab”. Eculizumab has been recently launched for the treatment of the atypical HUS, but it appears to be effective in the treatment of typical HUS and in TTP. Future therapies are in phases I and II. They include anti-C5 antibodies, which are more purified, less immunogenic and absorbed orally and, anti-C3 antibodies, which are more powerful, but potentially less safe. Additionally, infusions of recombinant complement-regulatory proteins are a potential future therapy. PMID:24255888

Acute Kidney Injury in Pregnancy.

PubMed

Jim, Belinda; Garovic, Vesna D

2017-07-01

Pregnancy-related acute kidney injury (AKI) has declined in incidence in the last three decades, although it remains an important cause of maternal and fetal morbidity and mortality. Pregnancy-related causes of AKI such as preeclampsia, acute fatty liver of pregnancy, HELLP (Hemolysis, Elevated Liver function tests, Low Platelets) syndrome, and the thrombotic microangiopathies (thrombotic thrombocytopenic purpura, atypical hemolytic-uremic syndrome [HUS]) exhibit overlapping features and often present as diagnostic dilemmas. Differentiating among these conditions may be difficult or impossible based on clinical criteria only. In difficult and rare cases, a renal biopsy may need to be considered for the exact diagnosis and to facilitate appropriate treatment, but the risks and benefits need to be carefully weighed. The use of eculizumab for the treatment of atypical HUS has demonstrated efficacy in early case reports. Non-pregnancy related causes such as volume depletion and pyelonephritis require early and aggressive resuscitative as well as antibiotic measures respectively. We will discuss in this review the various etiologies of AKI in pregnancy, current diagnostic approaches, and the latest treatment strategies. Given the recent trends of increasing maternal age at the time of pregnancy, and the availability of modern reproductive methods increase the risks of AKI in pregnancy in the coming years. Copyright © 2017 Elsevier Inc. All rights reserved.

Treating TTP/HUS with plasma exchange: a single centre's 25-year experience.

PubMed

Forzley, Brian R; Sontrop, Jessica M; Macnab, Jennifer J; Chen, Salina; Clark, William F

2008-10-01

Thrombotic thrombocytopenic purpura/Haemolytic uremic syndrome (TTP/HUS) is a thrombotic microangiopathy with a 6-month mortality rate of 16-29%. The present study described the clinical features, treatment regime and 6-month all-cause mortality rate of TTP/HUS patients at the London Health Sciences Centre (LHSC), Canada. Data for this retrospective cohort study were obtained from inpatient and outpatient records for all patients referred for plasma exchange therapy at LHSC, Canada between 1981 and 2006. Patients (n = 110) were categorized as: idiopathic primary (38%) or relapsed (16%), and secondary responsive (30%) or non-responsive (16%). Mortality data were available for all but three patients. The all-cause 6-month mortality rate was 19% overall and was 12% and 26% among idiopathic and secondary TTP/HUS patients, respectively. No mortality events occurred among the 17 idiopathic patients who relapsed. Relapsed patients had the least severe presenting characteristics, the fastest response time, and experienced significant improvement in the severity of clinical features between the first and final presentation. These findings suggest an excellent outcome for relapsed TTP/HUS patients. Patient education, surveillance, and aggressive plasma exchange therapy are hypothesized to improve the likelihood of survival: these hypotheses should be tested in a randomized controlled trial.

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

PubMed Central

Meyer, Oliver; Herzig, Eric; Salama, Abdulgabar

2012-01-01

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

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

Eltrombopag for the treatment of chronic idiopathic (immune) thrombocytopenic purpura (ITP).

PubMed

Boyers, D; Jia, X; Crowther, M; Jenkinson, D; Fraser, C; Mowatt, G

2011-05-01

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of eltrombopag for the treatment of adults with chronic idiopathic (immune) thrombocytopenic purpura (ITP), based on a review of the manufacturer's submission (MS) to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. ITP is an autoimmune disorder by which antibodies are formed against platelets with annual incidence rates in the UK/USA ranging from 1.13 to 6.62 cases per 100,000 adults. Eltrombopag increases the production of platelets at a rate that outpaces their destruction by the immune system, and has a UK marketing authorisation both for the treatment of adult ITP in splenectomised patients who are refractory to other treatments and as a second-line treatment for adult non-splenectomised patients for whom surgery is contraindicated. Both splenectomised and non-splenectomised patient groups were considered in the analysis. Two economic models were presented, one for a watch-and-rescue treatment scenario and the second for the long-term treatment of patients with more severe ITP. The submission's evidence was sourced from the relatively high-quality RAISE [RAndomized placebo-controlled Idiopathic thrombocytopenic purpura (ITP) Study with Eltrombopag] randomised controlled trial. The study indicated a statistically significant difference in favour of eltrombopag compared with placebo in the odds of achieving the primary outcome of a platelet count of between 50 and 400 × 109/l during the 6-month treatment period (odds ratio 8.2, 99% confidence interval 3.6 to 18.7). In the eltrombopag group, 50/83 (60%) non-splenectomised patients and 18/49 (37%) splenectomised patients achieved this outcome. Median duration of response for all patients was 10.9 weeks (splenectomised patients 6 weeks and non-splenectomised patients 13.4 weeks). Patients treated with eltrombopag required

Renal thrombotic microangiopathy caused by interferon beta-1a treatment for multiple sclerosis

PubMed Central

Mahe, Julien; Meurette, Aurélie; Moreau, Anne; Vercel, Caroline; Jolliet, Pascale

2013-01-01

Interferon beta-1a is available as an immunomodulating agent for relapsing forms of multiple sclerosis. Common side effects include flu-like symptoms, asthenia, anorexia, and administration site reaction. Kidney disorders are rarely reported. In this study we describe the case of a woman who has been undergoing treatment with interferon beta-1a for multiple sclerosis for 5 years. She developed a hemolytic-uremic syndrome with intravascular hemolysis in a context of severe hypertension. A kidney biopsy showed a thrombotic microangiopathy. This observation highlights an uncommon side effect of long-term interferon beta-1a therapy. Pathophysiological mechanisms leading to this complication might be explained by the antiangiogenic activity of interferon. PMID:23950639

Capnocytophaga canimorsus infection presenting with complete splenic infarction and thrombotic thrombocytopenic purpura: a case report.

PubMed

Brichacek, Michal; Blake, Peter; Kao, Raymond

2012-12-26

Animal bites are typically harmless, but in rare cases infections introduced by such bites can be fatal. Capnocytophaga canimorsus, found in the normal oral flora of dogs, has the potential to cause conditions ranging from minor cellulitis to fatal sepsis. The tendency of C. canimorsus infections to present with varied symptoms, the organism's fastidious nature, and difficulty of culturing make this a challenging diagnosis. Rarely, bacterial cytotoxins such as those produced by C. canimorsus may act as causative agents of TTP, further complicating the diagnosis. Early recognition is crucial for survival, and the variability of presentation must be appreciated. We present the first known case of C. canimorsus infection resulting in TTP that initially presented as splenic infarction. 72-year-old Caucasian male presented with a four-day history of abdominal pain, nausea, vomiting, diarrhea, and intermittent confusion. On presentation, vital signs were stable and the patient was afebrile. Physical examination was unremarkable apart from petechiae on the inner left thigh, and extreme diffuse abdominal pain to palpation and percussion along with positive rebound tenderness. Initial investigations revealed leukocytosis with left shift and thrombocytopenia, but normal liver enzymes, cardiac enzymes, lipase, INR and PTT. Abdominal CT demonstrated a non-enhancing spleen and hemoperitoneum, suggesting complete splenic infarction. Although the patient remained afebrile, he continued deteriorating over the next two days with worsening thrombocytopenia. After becoming febrile, he developed microangiopathic hemolytic anemia and hemodynamic instability, and soon after was intubated due to hypoxic respiratory failure and decreased consciousness. Plasma exchange was initiated but subsequently stopped when positive blood cultures grew a gram-negative organism. The patient progressively improved following therapy with piperacillin-tazobactam, which was switched to imipenem, then meropenem when Capnocytophaga was identified. There is a common misconception amongst practitioners that the presence of systemic infection excludes the possibility of TTP and vice versa. This case emphasizes that TTP may occur secondary to a systemic infection, thereby allowing the two processes to coexist. It is important to maintain a wide differential when considering the diagnosis of either TTP or C. canimorsus infection since delays in treatment may have fatal consequences.

Partial eNOS deficiency causes spontaneous thrombotic cerebral infarction, amyloid angiopathy and cognitive impairment.

PubMed

Tan, Xing-Lin; Xue, Yue-Qiang; Ma, Tao; Wang, Xiaofang; Li, Jing Jing; Lan, Lubin; Malik, Kafait U; McDonald, Michael P; Dopico, Alejandro M; Liao, Francesca-Fang

2015-06-24

Cerebral infarction due to thrombosis leads to the most common type of stroke and a likely cause of age-related cognitive decline and dementia. Endothelial nitric oxide synthase (eNOS) generates NO, which plays a crucial role in maintaining vascular function and exerting an antithrombotic action. Reduced eNOS expression and eNOS polymorphisms have been associated with stroke and Alzheimer's disease (AD), the most common type of dementia associated with neurovascular dysfunction. However, direct proof of such association is lacking. Since there are no reports of complete eNOS deficiency in humans, we used heterozygous eNOS(+/-) mice to mimic partial deficiency of eNOS, and determine its impact on cerebrovascular pathology and perfusion of cerebral vessels. Combining cerebral angiography with immunohistochemistry, we found thrombotic cerebral infarctions in eNOS(+/-) mice as early as 3-6 months of age but not in eNOS(+/+) mice at any age. Remarkably, vascular occlusions in eNOS(+/-) mice were found almost exclusively in three areas: temporoparietal and retrosplenial granular cortexes, and hippocampus this distribution precisely matching the hypoperfused areas identified in preclinical AD patients. Moreover, progressive cerebral amyloid angiopaphy (CAA), blood brain barrier (BBB) breakdown, and cognitive impairment were also detected in aged eNOS(+/-) mice. These data provide for the first time the evidence that partial eNOS deficiency results in spontaneous thrombotic cerebral infarctions that increase with age, leading to progressive CAA and cognitive impairments. We thus conclude that eNOS(+/-) mouse may represent an ideal model of ischemic stroke to address early and progressive damage in spontaneously-evolving chronic cerebral ischemia and thus, study vascular mechanisms contributing to vascular dementia and AD.

Thrombotic microangiopathy in marginal kidneys after sirolimus use.

PubMed

Pellé, Gaëlle; Xu, Ychen; Khoury, Noujoud; Mougenot, Béatrice; Rondeau, Eric

2005-12-01

The increasing shortage of cadaver donor kidneys has prompted the use of expanded or marginal donor kidneys, ie, from older donors or those with a history of hypertension or diabetes. These marginal kidneys may be especially susceptible to calcineurin inhibitor (CNI)-mediated vasoconstriction and nephrotoxicity. Recipients of renal transplants from marginal donors therefore require non-nephrotoxic immunosuppression. Some investigators have proposed using sirolimus, a novel and potent immunosuppressant, instead of CNIs. Moreover, another complication of solid-organ transplantation is thrombotic microangiopathy (TMA), which affects 3% to 14% of patients on immunosuppression therapy treated with CNIs. Therefore, it was suggested that CNIs may be substituted by sirolimus in patients with posttransplantation CNI-induced TMA. We report 3 patients who received marginal cadaveric kidneys and were administered maintenance immunosuppression with sirolimus, prednisone, and mycophenolate mofetil. They each developed de novo TMA despite never having been previously administered a CNI. In these cases, TMA occurred in marginal kidneys with possible endothelial injury before transplantation. Sirolimus may have prevented recovery from these injuries and thus may have promoted TMA in these marginal kidneys. The risk for such a vascular complication should be kept in mind in patients who receive marginal kidneys and are administered sirolimus, even when sirolimus is used without CNIs.

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.

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

PubMed Central

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. PMID:26057532

Cost of Purchased Versus Produced Plasma from Donor Recruitment Through Transfusion.

PubMed

Prioli, Katherine M; Pizzi, Laura T; Karp, Julie Katz; Galanis, Taki; Herman, Jay H

2016-10-01

Plasma is used to treat acquired coagulopathy or thrombotic thrombocytopenic purpura, or to reverse warfarin effect. Scant data are available, however, about its costs. To estimate total costs of plasma from production through administration, from the perspective of a US hospital blood donor center (BDC). Six sequential decision analytic models were constructed and informed by primary and secondary data on time, tasks, personnel, and supplies for donation, processing, and administration. Expected values of the models were summed to yield the BDC's total cost of producing, preparing, and transfusing plasma. Costs ($US 2015) are reported for a typical patient using three units of plasma. Models assume plasma was obtained from whole blood donation and transfused in an inpatient setting. Univariate sensitivity analyses were performed to test the impact of changing inputs for personnel costs and adverse event (AE) rates and costs. BDC production cost of plasma was $91.24/patient ($30.41/unit), a $30.16/patient savings versus purchased plasma. Administration and monitoring costs totaled $194.64/patient. Sensitivity analyses indicated that modifying BDC personnel costs during donation and processing has little impact on total plasma costs. However, the probability and cost of transfusion-associated circulatory overload (TACO) have a significant impact on costs. Plasma produced by our BDC may be less costly than purchased plasma. Though plasma processes have multiple tasks involving staff time, these are not the largest cost driver. Major plasma-related AEs are uncommon, but are the biggest driver of total plasma costs.

Factors associated with the effect of open splenectomy for immune thrombocytopenic purpura.

PubMed

Li, Ying; Zhang, Dawei; Hua, Fanli; Gao, Song; Wu, Yangjiong; Xu, Jianmin

2017-01-01

To assess the effect and complications of open splenectomy (OS) for immune thrombocytopenic purpura (ITP) and determine preoperative factors associated with surgical effect. This was a retrospective analysis of ITP patients who failed medical therapy and were treated with OS between 1997 and 2014 at the Jinshan Hospital, China. Follow-up was 60 months. Surgical effect was determined from platelet counts and bleeding episodes. Complications were assessed including bleeding episodes. Preoperative factors were identified by logistic regression analysis. Fifty-six patients (48.2 ± 16.2 yr old; 39 females) were included. Disease course was 31.2 ± 48.2 months; 91.1% patients had preoperative platelet count <20 × 10 9 /L. OS effect at 1 wk, 1 month, 1 yr, and 5 yrs was in 91.1%, 92.9%, 91.1%, and 89.3% patients, respectively. Pneumonia or lower extremity thrombosis occurred in 7.1% patients. Postoperative mild, moderate, and severe bleeding occurred in 33.9%, 50.0%, and 16.1% patients, respectively. No patients required blood transfusion. Mortality was zero. Larger spleen size associated with surgical effect at 1 wk, 1 month, and 1 yr, and lower preoperative minimum platelet count associated with effect at 5 yrs (P < 0.05). Open splenectomy is an effective treatment with less complications for the management of ITP. Lower preoperative minimum platelet count associated with successful OS at 5 yrs. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Thromboembolic complications following aminocaproic acid use in patients with hematologic malignancies.

PubMed

Juhl, Rebecca C; Roddy, Julianna V F; Wang, Tzu-Fei; Li, Junan; Elefritz, Jessica L

2018-02-09

Aminocaproic acid is frequently used in patients with hematologic malignancy that present with thrombocytopenia with or without hemorrhage. We conducted a retrospective study to evaluate the safety of aminocaproic acid in 109 patients with hematologic malignancies. Patients were included if aminocaproic acid had been administered for at least 24 hours for the prevention or treatment of thrombocytopenic hemorrhage. Our primary outcome was thromboembolic complications defined as arterial or venous thrombotic events objectively confirmed by imaging studies. Thromboembolic complications occurred in five patients (4.6%) and all were venous thromboses. Other than the underlying malignancy, these patients also had many concurrent risk factors including indwelling central venous catheters, which could have contributed to thromboses. In conclusion, in our population of patients with a variety of hematological malignancies, aminocaproic acid does not appear to be associated with a high incidence of thromboembolic complications.

Catastrophic antiphospholipid syndrome: a clinical review.

PubMed

Nayer, Ali; Ortega, Luis M

2014-01-01

Catastrophic antiphospholipid syndrome (CAPS) is a rare life-threatening autoimmune disease characterized by disseminated intravascular thrombosis resulting in multiorgan failure. Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO) and Web of Science have been searched. CAPS is due to antiphospholipid antibodies directed against a heterogeneous group of proteins that are associated with phospholipids. These autoantibodies activate endothelial cells, platelets, and immune cells, thereby promoting a proinflammatory and prothrombotic phenotype. Furthermore, antiphospholipid antibodies inhibit anticoagulants, impair fibrinolysis, and activate complements. Although CAPS can affect a variety of organs and tissues, the kidneys, lungs, central nervous system, heart, skin, liver, and gastrointestinal tract are most commonly affected. The systemic inflammatory response syndrome, likely to extensive tissue damage, accompanies CAPS. The most frequent renal manifestations are hypertension, proteinuria, hematuria, and acute renal failure.In the majority of patients with CAPS, a precipitating factor such as infection, surgery, or medication can be identified. Antiphospholipid antibodies such as lupus anticoagulant and antibodies against cardiolipin, β2-glycoprotein I, and prothrombin are serological hallmark of CAPS. Laboratory tests often reveal antinuclear antibodies, thrombocytopenia, and anemia. Despite widespread intravascular coagulation, blood films reveal only a small number of schistocytes. In addition, severe thrombocytopenia is uncommon. Histologically, CAPS is characterized by acute thrombotic microangiopathy. CAPS must be distinguished from other forms of thrombotic microangiopathies such as hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, and heparin-induced thrombocyt openia. CAPS is associated with high morbidity and mortality. Therefore, an aggressive multidisciplinary

Helicobacter pylori eradication in patients with chronic immune thrombocytopenic purpura

PubMed Central

Noonavath, Ravinder Naik; Lakshmi, Chandrasekharan Padma; Dutta, Tarun Kumar; Kate, Vikram

2014-01-01

AIM: To assess the effect of Helicobacter pylori (H. pylori) eradication on platelet counts in patients with chronic immune thrombocytopenic purpura (cITP). METHODS: A total of 36 cITP patients were included in the study. The diagnosis of H. pylori was done by rapid urease test and Giemsa staining of the gastric biopsy specimen. All H. pylori positive patients received standard triple therapy for 14 d and were subjected for repeat endoscopy at 6 wk. Patients who continued to be positive for H. pylori on second endoscopy received second line salvage therapy. All the patients were assessed for platelet response at 6 wk, 3rd and 6th months. RESULTS: Of the 36 patients, 17 were positive for H. pylori infection and eradication was achieved in 16 patients. The mean baseline platelet count in the eradicated patients was 88615.38 ± 30117.93/mm3 and platelet count after eradication at 6 wk, 3 mo and 6 mo was 143230.77 ± 52437.51/mm3 (P = 0.003), 152562.50 ± 52892.3/mm3 (P = 0.0001), 150187.50 ± 41796.68/mm3 (P = 0.0001) respectively and in the negative patients, the mean baseline count was 71000.00 ± 33216.46/mm3 and at 6 wk, 3rd and 6th month follow up was 137631.58 ± 74364.13/mm3 (P = 0.001), 125578.95 ± 71472.1/mm3 (P = 0.005), 77210.53 ± 56892.28/mm3 (P = 0.684) respectively. CONCLUSION: Eradication of H. pylori leads to increase in platelet counts in patients with cITP and can be recommended as a complementary treatment with conventional therapy. PMID:24944483

Long-Term Outcomes of Laparoscopic Splenectomy Versus Open Splenectomy for Idiopathic Thrombocytopenic Purpura

PubMed Central

Qu, Yikun; Xu, Jian; Jiao, Chengbin; Cheng, Zhuoxin; Ren, Shiyan

2014-01-01

The long-term outcomes of laparoscopic splenectomy (LS) versus open splenectomy (OS) in patients with idiopathic thrombocytopenic purpura (ITP) are not known. A retrospective analysis of 73 patients who underwent splenectomy (32 LS and 41 OS) for refractory ITP between April 2003 and June 2012 was conducted. LS was associated with shorter hospital stay (P = 0.01), less blood loss and blood transfusion during surgery, quicker resumption of oral diet (P < 0.0001), and earlier drain removal (P < 0.01). Conversion to OS was required in 4 patients (12.5%). Operation time was significantly longer in LS (P < 0.0001). Deep venous thrombosis (DVT) was observed in 1 patient after LS and in 4 patients after OS (P = 0.52). One patient died from intraperitoneal bleeding after OS, another patient developed pulmonary embolism. Median follow-up of 36 months was performed in LS group (29 of 32, 91%) and of 46 months in OS group (35 of 41, 85%), 25 patients (86%) in LS group and 32 (91%) in OS group reached sustained complete response (P = 0.792). Kaplan-Meier analysis showed that there was no significant difference in the relapse-free survival rate between the groups (P = 0.777). In conclusion, the long-term outcome of laparoscopic splenectomy is not different from that of open splenectomy for patients with ITP. PMID:24833154

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

Experimental acute thrombotic stroke in baboons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Del Zoppo, G.J.; Copeland, B.R.; Harker, L.A.

1986-11-01

To study the effects of antithrombotic therapy in experimental stroke, we have characterized a baboon model of acute cerebrovascular thrombosis. In this model an inflatable silastic balloon cuff has been implanted by transorbital approach around the right middle cerebral artery (MCA), proximal to the take-off of the lenticulostriate arteries (LSA). Inflation of the balloon for 3 hours in six animals produced a stereotypic sustained stroke syndrome characterized by contralateral hemiparesis. An infarction volume of 3.2 +/- 1.5 cm3 in the ipsilateral corpus striatum was documented by computerized tomographic (CT) scanning at 10 days following stroke induction and 3.9 +/- 1.9more » cm3 (n = 4) at 14 days by morphometric neuropathologic determinations of brain specimens fixed in situ by pressure-perfusion with 10% buffered formalin. Immediate pressure-perfusion fixation following deflation of the balloon was performed in 16 additional animals given Evans blue dye intravenously prior to the 3 hour MCA balloon occlusion. Light microscopy and transmission electron microscopy consistently confirmed the presence of thrombotic material occluding microcirculatory branches of the right LSA in the region of Evans blue stain, but not those of the contralateral corpus striatum. When autologous 111In-platelets were infused intravenously in four animals from the above group prior to the transient 3 hour occlusion of the right MCA, gamma scintillation camera imaging of each perfused-fixed whole brain demonstrated the presence of a single residual focus of 111In-platelet activity involving only the Evans blue-stained right corpus striatum. Focal right hemispheric activity was equivalent to 0.55 +/- 0.49 ml of whole blood, and the occlusion score derived from histologic examination of the microcirculation of the Evans blue-stained corpus striatum averaged 34.8 +/- 2.8.« less

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.

Thrombotic Microangiopathy in Haematopoietic Cell Transplantation: an Update

PubMed Central

Stavrou, Evi; Lazarus, Hillard M.

2010-01-01

Allogeneic hematopoietic cell transplantation (HCT) represents a vital procedure for patients with various hematologic conditions. Despite advances in the field, HCT carries significant morbidity and mortality. A rare but potentially devastating complication is transplantation-associated thrombotic microangiopathy (TA-TMA). In contrast to idiopathic TTP, whose etiology is attributed to deficient activity of ADAMTS13, (a member of the A Disintegrin And Metalloprotease with Thrombospondin 1 repeats family of metalloproteases), patients with TA-TMA have > 5% ADAMTS13 activity. Pathophysiologic mechanisms associated with TA-TMA, include loss of endothelial cell integrity induced by intensive conditioning regimens, immunosuppressive therapy, irradiation, infections and graft-versus-host (GVHD) disease. The reported incidence of TA-TMA ranges from 0.5% to 75%, reflecting the difficulty of accurate diagnosis in these patients. Two different groups have proposed consensus definitions for TA-TMA, yet they fail to distinguish the primary syndrome from secondary causes such as infections or medication exposure. Despite treatment, mortality rate in TA-TMA ranges between 60% to 90%. The treatment strategies for TA-TMA remain challenging. Calcineurin inhibitors should be discontinued and replaced with alternative immunosuppressive agents. Daclizumab, a humanized monoclonal anti-CD25 antibody, has shown promising results in the treatment of TA-TMA. Rituximab or the addition of defibrotide, have been reported to induce remission in this patient population. In general, plasma exchange is not recommended. PMID:21776339

Recurrent Thrombotic Events after Discontinuation of Vitamin K Antagonist Treatment for Splanchnic Vein Thrombosis: A Multicenter Retrospective Cohort Study.

PubMed

Riva, Nicoletta; Ageno, Walter; Poli, Daniela; Testa, Sophie; Rupoli, Serena; Santoro, Rita; Lerede, Teresa; Piana, Antonietta; Carpenedo, Monica; Nicolini, Alberto; Ferrini, Piera Maria; Martini, Giuliana; Mangione, Catello; Contino, Laura; Bonfanti, Carlo; Gresele, Paolo; Tosetto, Alberto

2015-01-01

It is generally recommended that patients with splanchnic vein thrombosis (SVT) should receive a minimum of 3 months of anticoagulant treatment. However, little information is available on the long-term risk of recurrent thrombotic events. The aim of this study was to evaluate the risk of venous and arterial thrombosis after discontinuation of vitamin K antagonist (VKA) in SVT patients. Retrospective information from a cohort of SVT patients treated with VKA and followed by 37 Italian Anticoagulation Clinics, up to June 2013, was collected. Only patients who discontinued VKA and did not receive any other anticoagulant drug were enrolled in this study. Thrombotic events during follow-up were centrally adjudicated. Ninety patients were included: 33 unprovoked SVT, 27 SVT secondary to transient risk factors, and 30 with permanent risk factors. During a median follow-up of 1.6 years, 6 venous and 1 arterial thrombosis were documented, for an incidence of 3.3/100 patient-years (pt-y). The recurrence rate was highest in the first year after VKA discontinuation (8.2/100'pt-y) and in patients with permanent risk factors (10.2/100'pt-y). Liver cirrhosis significantly increased the risk of recurrence. In conclusion, the rate of recurrent vascular complications after SVT is not negligible, at least in some patient subgroups.

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

The impact of a male or female thrombotic family history on contraceptive counseling: a cohort study.

PubMed

van Vlijmen, E F W; Veeger, N J G M; Middeldorp, S; Hamulyák, K; Prins, M H; Kluin-Nelemans, H C; Meijer, K

2016-09-01

Essentials It is unknown if a male or female thrombotic family history influences risk in female relatives. We assessed thrombotic risk in female relatives of male and female patients with thrombosis. A hormonally related female thrombotic family history further increases risk in female relatives. This information could be important in counseling women on contraceptive options. Click to hear Prof. Rosendaal's perspective on venous thrombosis: etiology, pathogenesis, and prognosis Background Women from thrombophilic families have increased risk of venous thromboembolism (VTE), which increases further during oral contraceptive (COC) use and pregnancy-postpartum. Whether this additional risk differs between relatives of male and female patients, or is different when that female patient had a hormonally related VTE (during COC use/pregnancy), is unknown. Methods One thousand five female relatives of consecutive patients with VTE from a family-based cohort were retrospectively followed for incident VTE from ages 15 to 50, first VTE, or study inclusion. Absolute and relative VTE risks adjusted for factors of patients (sex, age) and relatives (thrombophilia, COC use, pregnancy) were estimated in relatives of female and male patients and in relatives of female patients with and without hormonally related VTE. Results Absolute risk in relatives of female (0.32 [95% confidence interval [CI] 0.23-0.43]) vs. male patients (0.39 [95% CI 0.28-0.53]) was comparable. However, the heterogeneity analysis of risk estimates suggested that in relatives of female vs. male patients, the contribution of pregnancy-postpartum (hazard ratio [HR] 11.6 [95% CI 6.3-21.3] vs. HR6.6 [95% CI 2.8-15.2]) and, to a lesser extent, COC use (HR3.6 [95% CI 1.8-7.1] vs. HR2.7 [95% CI 1.5-5.0]) to the VTE risk differs. Absolute risk was significantly higher in relatives of female patients with hormonally related VTE (0.43 [95% CI 0.3-0.6]) vs. relatives of female patients without hormonally related VTE (0

Bleeding disorders in pregnant patients with rheumatic diseases.

PubMed

Rick, M E

1989-05-01

Although the bleeding disorders that occur in patients with rheumatic diseases are not different during pregnancy than at other times, their diagnosis and management are often different during pregnancy. In idiopathic thrombocytopenic purpura, for instance, antiplatelet antibodies may cross the placenta and cause life-threatening thrombocytopenia in the fetus while the mother is asymptomatic. Management of this disease has changed significantly in the past 5 years with the use of intravenous gammaglobulin which appears to lessen the degree of fetal as well as maternal thrombocytopenia when administered during the peripartum period. The utilization of plasmapheresis and plasma infusions for patients with thrombotic thrombocytopenic purpura has salvaged both the mother and the fetus in a disease which was fatal in more than 60 per cent of patients prior to their use. The outcome of pregnancy in this patient population has markedly improved with this treatment. The stimulus for the production of factor VIII inhibitors in the postpartum period is still not understood, but guidelines for management have changed, with the increased likelihood of decreasing the antibody and inducing tolerance with regimens including factor VIII, immunosuppressive agents and intravenous gammaglobulin in those patients who require treatment. The diagnosis of von Willebrand's disease during pregnancy is difficult because of the physiologic increase in von Willebrand factor during pregnancy; in this instance family studies may help in the diagnosis of this relatively common, autosomal dominant inherited disorder. Management now includes treatment with desmopressin as well as cryoprecipitate replacement therapy.

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

PubMed

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

2014-05-01

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.

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.

Impact of Helicobacter pylori Eradication Therapy on Platelet Counts in Patients With Chronic Idiopathic Thrombocytopenic Purpura

PubMed Central

Amiri, Mohamadreza

2016-01-01

This study was a before and after clinical evaluation of Helicobacter pylori eradication on platelet counts in a group of 23 patients with chronic Idiopathic (Autoimmune) thrombocytopenic purpura (CITP). H. pylori infection was identified in patients by a 13C-urea breath test and confirmed by an H. pylori stool antigen test. Eradication was conducted in patients testing positive. Infected (n = 10) and uninfected (n = 13) patient groups did not differ with respect to age, gender, history of previous splenectomy, treatment with anti-D, current treatment with corticosteroids, or initial platelet counts. H. pylori eradication was successful in eight infected CITP patients, with two patients not responsive to treatment. Compared to the uninfected group, patients in the infected group who responded to eradication therapy had significantly increased platelet counts after six months (56.2 ± 22.2 vs. 233 ± 85.6 ×103 million cells/L; P < 0.01), whereas platelet counts in the non-responding patients and uninfected group did not differ after this period of time. H. pylori eradication promotes significant platelet count improvement in patients with CITP. Thus, all patients with CITP should be tested and treated for H. pylori infections. PMID:26925898

JAK2 V617F, MPL, and CALR mutations in essential thrombocythaemia and major thrombotic complications: a single-institute retrospective analysis.

PubMed

Pósfai, Éva; Marton, Imelda; Király, Péter Attila; Kotosz, Balázs; Kiss-László, Zsuzsanna; Széll, Márta; Borbényi, Zita

2015-07-01

Thrombo-haemorrhagic events are the main cause of morbidity and mortality in essential thrombocythemia. The aim of this study was to estimate the incidence of thrombotic events and the impact of the JAK2V617F, MPL (W515L, W515K, W515R, W515A and S505N) and CALR (type-1, type-2) mutations on 101 essential thrombocythaemia patients (72 females and 29 males with a mean age of 61 years) diagnosed in a Southern Hungarian regional academic centre. The incidence of major thrombosis was 13.86 %. Sixty percent of the patients carried the JAK2V617F mutation. The MPL mutations were analysed by sequencing and the W515L was the only one we could identify with an incidence of 3.96 %. Type-2 CALR mutation could be identified in 3 cases among the patients who had JAK2/MPL-unmutated ET. Statistical analyses revealed that the JAK2V617F mutation was associated with significantly increased levels of platelet (p = 0.042), haemoglobin (p = 0.000), red blood cell (p = 0.000) and haematocrit (p = 0.000) and hepatomegaly (p = 0.045) at diagnosis compared to JAK2V617F negative counterparts, however there was no significant association between the JAK2V617F mutation status (relative risk: 1.297, 95 % CI 0.395-4.258; p = 0.668) and subsequent thrombotic complications. The impact of JAK2V617F, MPL W515L and CALR mutations on the clinical findings at the diagnosis of ET was obvious, but their statistically significant role in the prediction of thrombotic events could not be proven in this study. Our results indirectly support the concept that, besides the quantitative and qualitative changes in the platelets, the mechanisms leading to thrombosis are more complex and multifactorial.

A rare case of thrombotic microangiopathy triggered by acute pancreatitis.

PubMed

Singh, Kevin; Nadeem, Ahmed Jamal; Doratotaj, Behzad

2017-05-15

Thrombotic microangiopathy (TMA) occurring after acute pancreatitis is rarely described. Without prompt intervention, TMA can be, and often is, lethal, so prompt recognition is important. Here, we present a case of a 61-year-old woman with a history of alcohol misuse who presented with epigastric pain, nausea and vomiting after binge drinking. Elevated serum lipase and imaging were suggestive of acute-on-chronic pancreatitis. Although the patient's symptoms of acute pancreatitis subsided, her anaemia, thrombocytopenia and acute kidney injury worsened. A peripheral blood smear revealed schistocytes, prompting suspicion for TMA. Therapeutic plasma exchange (TPE) was promptly initiated and she completed 10 TPE sessions that improved her anaemia and serum creatinine and resolved the thrombocytopenia. Since TPE was effective and the ADAMTS13 assay revealed 55% activity in the absence of anti-ADAMTS13 IgG prior to initiation of therapy, a confident diagnosis of TMA caused by acute pancreatitis was made. There was no evidence of relapse 2 years later. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Recurrent Thrombotic Events after Discontinuation of Vitamin K Antagonist Treatment for Splanchnic Vein Thrombosis: A Multicenter Retrospective Cohort Study

PubMed Central

Riva, Nicoletta; Ageno, Walter; Poli, Daniela; Testa, Sophie; Rupoli, Serena; Santoro, Rita; Lerede, Teresa; Piana, Antonietta; Carpenedo, Monica; Nicolini, Alberto; Ferrini, Piera Maria; Martini, Giuliana; Mangione, Catello; Contino, Laura; Bonfanti, Carlo; Gresele, Paolo; Tosetto, Alberto

2015-01-01

It is generally recommended that patients with splanchnic vein thrombosis (SVT) should receive a minimum of 3 months of anticoagulant treatment. However, little information is available on the long-term risk of recurrent thrombotic events. The aim of this study was to evaluate the risk of venous and arterial thrombosis after discontinuation of vitamin K antagonist (VKA) in SVT patients. Retrospective information from a cohort of SVT patients treated with VKA and followed by 37 Italian Anticoagulation Clinics, up to June 2013, was collected. Only patients who discontinued VKA and did not receive any other anticoagulant drug were enrolled in this study. Thrombotic events during follow-up were centrally adjudicated. Ninety patients were included: 33 unprovoked SVT, 27 SVT secondary to transient risk factors, and 30 with permanent risk factors. During a median follow-up of 1.6 years, 6 venous and 1 arterial thrombosis were documented, for an incidence of 3.3/100 patient-years (pt-y). The recurrence rate was highest in the first year after VKA discontinuation (8.2/100'pt-y) and in patients with permanent risk factors (10.2/100'pt-y). Liver cirrhosis significantly increased the risk of recurrence. In conclusion, the rate of recurrent vascular complications after SVT is not negligible, at least in some patient subgroups. PMID:26508913

Multifaceted Role of Pneumolysin in the Pathogenesis of Myocardial Injury in Community-Acquired Pneumonia.

PubMed

Anderson, Ronald; Nel, Jan G; Feldman, Charles

2018-04-11

Pneumolysin (PLY), a member of the family of Gram-positive bacterial, cholesterol-dependent, β-barrel pore-forming cytolysins, is the major protein virulence factor of the dangerous respiratory pathogen, Streptococcus pneumoniae (pneumococcus). PLY plays a major role in the pathogenesis of community-acquired pneumonia (CAP), promoting colonization and invasion of the upper and lower respiratory tracts respectively, as well as extra-pulmonary dissemination of the pneumococcus. Notwithstanding its role in causing acute lung injury in severe CAP, PLY has also been implicated in the development of potentially fatal acute and delayed-onset cardiovascular events, which are now recognized as being fairly common complications of this condition. This review is focused firstly on updating mechanisms involved in the immunopathogenesis of PLY-mediated myocardial damage, specifically the direct cardiotoxic and immunosuppressive activities, as well as the indirect pro-inflammatory/pro-thrombotic activities of the toxin. Secondly, on PLY-targeted therapeutic strategies including, among others, macrolide antibiotics, natural product antagonists, cholesterol-containing liposomes, and fully humanized monoclonal antibodies, as well as on vaccine-based preventive strategies. These sections are preceded by overviews of CAP in general, the role of the pneumococcus as the causative pathogen, the occurrence and types of CAP-associated cardiac complication, and the structure and biological activities of PLY.

[Correlation between IgG subtypes and hematological diseases].

PubMed

Shao, Yuan-Yuan; Shao, Zong-Hong

2015-02-01

IgG is the main immunoglobulin, brings the immunolgic effects in body. The human IgG can be divided into four kinds; IgG1, IgG2, IgG3, IgG4, respectively. The structures of IgG1, IgG2, IgG3, IgG4 are different, therefore, their functions are also different. The defects, increase or imbalance of the IgG subtypes in autoimmune diseases, infectious diseases, cancer and other diseases are indicators of the immune response. IgG1, IgG2, IgG3 and IgG4 also play a different important roles in the disease progress. The analysis of IgG subtypes is beneficial to study the etiology, pathogenesis and prognosis of above menthioned deseases. This review briefly summarizes the characteristics of IgG subtypes in thrombotic thrombocytopenic purpura, autoimmune hemolytic anemia, hemophilia, lymphoma and leukemia.

Plasma exchange therapy in steroid-unresponsive relapses in patients with multiple sclerosis.

PubMed

Trebst, Corinna; Reising, Ansgar; Kielstein, Jan T; Hafer, Carsten; Stangel, Martin

2009-01-01

Plasma exchange (PE) is well established for conditions such as rapid progressive vasculitis associated with autoantibodies against neutrophil cytoplasmic antigens (ANCA), anti-glomerular basement membrane (GBM) antibody disease, or thrombotic thrombocytopenic purpura (TTP). Also, several neurological disorders, such as acute worsening in myasthenia gravis, Guillan-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP), can successfully be treated with PE. Only small case series have previously shown that PE is also effective in relapses in patients with multiple sclerosis (MS). We report our experiences of PE therapy in a series of 20 patients with 21 steroid unresponsive MS relapses. A marked-to-moderate clinical response with clear gain of function in 76% of patients with uni- or bilateral optic neuritis and in 87.5% of patients with relapses other than optic neuritis was observed. PE is an effective and well tolerated therapeutic option for steroid-unresponsive MS relapses.

New development of cardiac tamponade on underlying effusive–constrictive pericarditis: an uncommon initial presentation of scleroderma

PubMed Central

Subramanian, Stalin R; Akram, Rakhshanda; Velayati, Arash; Chadow, Hal

2013-01-01

A 40-year-old man with a medical history of hypertension was admitted for weight loss, generalised weakness, joint pains and mottling of fingertips. The initial laboratory data revealed microangiopathic haemolytic anaemia, thrombocytopenia and acute renal failure. Intravenous steroids were started for possible diagnosis of systemic lupus erythematosus based on admission assessment. Intravenous immunoglobulin and plasmapharesis were subsequently added to the treatment plan to cover thrombotic thrombocytopenic purpura while his autoimmune panel was pending. The echocardiogram study on day 2 revealed cardiac tamponade for which he underwent pericardiocentesis and right heart catheterisation. The atrial waveforms postpericardiocentesis demonstrated effusive–constrictive pericarditis. His clinical condition kept on deteriorating with reaccumulation of pericardial effusion and further complicated by hemoperitoneum and colonic obstruction. He had cardiorespiratory arrest on his fourth admission day and was not revived. Anti-Scl-70 antibody came back positive. Autopsy findings confirmed the presence of fibrinous pericarditis and hemoperitoneum. PMID:23853085

Anti-platelet and anti-thrombotic effect of a traditional herbal medicine Kyung-Ok-Ko.

PubMed

Kim, Tae-Ho; Lee, Kyoung Mee; Hong, Nam Doo; Jung, Yi-Sook

2016-02-03

Kyung-Ok-Ko (KOK), a traditional herbal prescription, contains six main ingredients; Rehmannia glutinosa var. purpurae, Lycium chinense, Aquillaria agallocha, Poria cocos, Panax ginseng, and honey. KOK has been widely taken as a traditional oriental medicine for improving blood circulation or age-related symptoms, such as dementia and stroke. However, the effect of KOK on platelet activity has not been clarified. To evaluate the effect of KOK on platelet function, we evaluated its effect on functional markers of platelet activation such as aggregation and shape change. As a mechanism study for the effect of KOK, we examined its effect on granule secretion, intracellular Ca(2+) increase, and PLCγ and Akt activation. To investigate the effect of orally administered KOK (0.5, 1, 2 g/kg), we examined its ex vivo effect on platelet aggregation in rat, and its in vivo anti-thrombotic effect in mice thromboembolism model. Furthermore, the effect of KOK on bleeding time was examined to estimate its potential side effect. KOK (0.3, 1, 3, 10 mg/ml) inhibited collagen-induced platelet aggregation and shape change in rat platelets in a concentration-dependent manner. The mechanism for the anti-platelet effect of KOK seems to involve the inhibition of ATP release, intracellular Ca(2+) elevation, and the phosphorylation of PLCγ and Akt. In rat ex vivo study, KOK (2 g/kg, p.o. for 1 day, and 0.5, 1, 2 g/kg, p.o. for 7 days) also had significant inhibitory effects on collagen-induced platelet aggregation. In addition, KOK showed a significant protective effect against thrombosis attack in mice. The prolongation of bleeding time by KOK was much less than that by ASA, suggesting a beneficial potential of KOK than ASA in view of side effect. These findings suggest that KOK elicits remarkable anti-platelet and anti-thrombotic effects with less side effect of bleeding, and therefore, it may have a therapeutic potential for the prevention of platelet-associated cardiovascular diseases

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

PubMed

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

2015-10-01

NF-κB essential modulator (NEMO) is a component of the IKK complex, which participates in the activation of the NF-κB pathway. Hypomorphic mutations in the IKBKG gene result in different forms of anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) in males without affecting carrier females. Here, we describe a hypomorphic and missense mutation, designated c.916G>A (p.D306N), which affects our patient, his mother, and his sister. This mutation did not affect NEMO expression; however, an immunoprecipitation assay revealed reduced ubiquitylation upon CD40-stimulation in the patient's cells. Functional studies have demonstrated reduced phosphorylation and degradation of IκBα, affecting NF-κB recruitment into the nucleus. The patient presented with clinical features of ectodermal dysplasia, immunodeficiency, and immune thrombocytopenic purpura, the latter of which has not been previously reported in a patient with NEMO deficiency. His mother and sister displayed incontinentia pigmenti indicating that, in addition to amorphic mutations, hypomorphic mutations in NEMO can affect females. Copyright © 2015 Elsevier Inc. All rights reserved.

Influence of the JAK2 V617F mutation and inherited thrombophilia on the thrombotic risk among patients with essential thrombocythemia

PubMed Central

De Stefano, Valerio; Za, Tommaso; Rossi, Elena; Fiorini, Alessia; Ciminello, Angela; Luzzi, Claudia; Chiusolo, Patrizia; Sica, Simona; Leone, Giuseppe

2009-01-01

It is uncertain whether the JAK2 V617F mutation increases the thrombotic risk in patients with essential thrombocythemia, and it is unknown whether inherited thrombophilia is an additive risk factor in mutated subjects. We studied 132 patients with essential thrombocythemia, 38 of them (29%) with a history of thrombosis. The JAK2 mutation was present in 83 (63%), and inherited thrombophilia in 7. The mutated patients <60 years had a relative risk (RR) for thrombosis at any time of 3.83 (95%CI 1.27–11.49) in comparison with wild-type patients; in those with both the mutation and thrombophilia the RR was 2.23 (95%CI 1.57–3.18) and 7.66 (95%CI 2.66–22.03) in comparison with mutated or wild-type patients without thrombophilia, respectively. During the follow-up, only the homozygotes for JAK2 V617F were more prone to thrombosis (RR 17.25, 95%CI 2.33–127.4). Among the patients >60 years, no increase in RR was associated with the JAK2 mutation. In conclusion, in the younger patients with ET the thrombotic risk is higher in the JAK2 V617F-mutated and is further increased by the presence of inherited thrombophilia. PMID:19336736

Acute cor pulmonale due to pulmonary tumour thrombotic microangiopathy from renal cell carcinoma.

PubMed

Story, Maria; Kwon, Sook Kyung; Robinson, Robert; Fortis, Spyridon

2017-06-28

We report the case of a previously healthy man who presented with subacute dyspnoea after a long drive. He developed hypoxic respiratory failure, thought secondary to a massive pulmonary embolism and was treated with tissue plasminogen activator but died in the hospital despite aggressive medical measures. Autopsy revealed pulmonary tumour thrombotic microangiopathy (PTTM) from papillary renal cell carcinoma. PTTM is a rare clinicopathological syndrome that clinically results in symptoms of dyspnoea and right heart failure. Pathologically, a localised paraneoplastic process evolves from tumour microemboli in the pulmonary arterioles, resulting in fibrocellular proliferation and narrowing of the vessels, causing subacute right heart failure. To our knowledge, this is the first case of PTTM due to papillary renal cell carcinoma. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Safety and efficacy of a 10% intravenous immunoglobulin preparation in patients with immune thrombocytopenic purpura: results of two international, multicenter studies.

PubMed

Kovaleva, Lidia; Apte, Shashikant; Damodar, Sharat; Ramanan, Vijay; Loriya, Svetlana; Navarro-Puerto, Jordi; Khojasteh, Ali

2016-12-01

To assess safety and efficacy of a 10% intravenous immunoglobulin in patients with primary immune thrombocytopenic purpura (ITP). ITP patients in two multicenter studies (Trials A/B) were treated with 2 g/kg Flebogamma ® 10% DIF (over 2-5 days) and were followed up to 1-3 months. 18 patients in Trial A and 58 in Trial B were enrolled (12 children in Trial B). The response rate (platelet count ≥50 × 10 9 /l) was 72.2% (Trial A) and 76.1/100% (adults/children; Trial B). Most patients improved bleedings (83.3% Trial A; 88.9% Trial B). Potential treatment-related adverse events were reported by 38.9% (Trial A) and 30.4/83.3% (adults/children; Trial B) of patients. All serious adverse events (five patients) resolved without sequelae. Flebogamma 10% DIF was effective and safe in patients with primary ITP.

A novel association of acquired ADAMTS13 inhibitor and acute dengue virus infection

PubMed Central

Rossi, Fernanda C.; Angerami, Rodrigo N.; de Paula, Erich V.; Orsi, Fernanda L.; Shang, Dezhi; del Guercio, Vânia M.; Resende, Mariângela R.; Annichino-Bizzacchi, Joyce M.; da Silva, Luiz J.; Zheng, X. Long; Castro, Vagner

2011-01-01

BACKGROUND Dengue is a mosquito-borne viral disease with an increasing incidence worldwide. Thrombocytopenia is a common finding in dengue virus (DV) infection; however, the underlying mechanisms remain unknown. CASE REPORT Here we provide the first evidence of a case of antibody formation against ADAMTS13 (ADAMTS13 inhibitor) in the course of a severe acute DV infection resulting in thrombotic microangiopathy (TMA). The patient presented with classical dengue symptoms (positive epidemiology, high fever, myalgia, predominantly in the lower limbs and lumbar region for 1 week) and, after 11 days of initial symptoms, developed TMA. Clinical and laboratorial investigation of dengue and TMA was performed. RESULTS The patient presented with ADAMTS13 inhibitor (IgG) during the acute phase of the disease, without anti-platelet antibodies detectable. Dengue infection had laboratorial confirmation. There were excellent clinical and laboratory responses to 11 serial plasma exchanges. Anti-ADAMTS13 inhibitor disappeared after remission of TMA and dengue resolution. No recurrence of TMA symptoms was observed after 2-year follow-up. CONCLUSIONS Although the real incidence of dengue-related TMA is unknown, this case provides the basis for future epidemiologic studies on acquired ADAMTS13 deficiency in DV infection. The prompt clinical recognition of this complication and early installment of specific therapy with plasma exchange are likely to improve the outcome of severe cases of dengue. PMID:19788513

A novel association of acquired ADAMTS13 inhibitor and acute dengue virus infection.

PubMed

Rossi, Fernanda C; Angerami, Rodrigo N; de Paula, Erich V; Orsi, Fernanda L; Shang, Dezhi; del Guercio, Vânia M; Resende, Mariângela R; Annichino-Bizzacchi, Joyce M; da Silva, Luiz J; Zheng, X Long; Castro, Vagner

2010-01-01

Dengue is a mosquito-borne viral disease with an increasing incidence worldwide. Thrombocytopenia is a common finding in dengue virus (DV) infection; however, the underlying mechanisms remain unknown. Here we provide the first evidence of a case of antibody formation against ADAMTS13 (ADAMTS13 inhibitor) in the course of a severe acute DV infection resulting in thrombotic microangiopathy (TMA). The patient presented with classical dengue symptoms (positive epidemiology, high fever, myalgia, predominantly in the lower limbs and lumbar region for 1 week) and, after 11 days of initial symptoms, developed TMA. Clinical and laboratorial investigation of dengue and TMA was performed. The patient presented with ADAMTS13 inhibitor (IgG) during the acute phase of the disease, without anti-platelet antibodies detectable. Dengue infection had laboratorial confirmation. There were excellent clinical and laboratory responses to 11 serial plasma exchanges. Anti-ADAMTS13 inhibitor disappeared after remission of TMA and dengue resolution. No recurrence of TMA symptoms was observed after 2-year follow-up. Although the real incidence of dengue-related TMA is unknown, this case provides the basis for future epidemiologic studies on acquired ADAMTS13 deficiency in DV infection. The prompt clinical recognition of this complication and early installment of specific therapy with plasma exchange are likely to improve the outcome of severe cases of dengue.

Discontinuation of antithrombotic therapy for a year or more in patients with continuous-flow left ventricular assist devices.

PubMed

Pereira, Naveen L; Chen, Dong; Kushwaha, Sudhir S; Park, Soon J

2010-10-01

The recommended anticoagulation regimen during continuous-flow axial left ventricular assist device (LVAD) support is aspirin and warfarin with a targeted international normalized ratio of 2.0-3.0. We report two patients in whom recurrent gastrointestinal bleeding during LVAD support necessitated discontinuation of this anti-thrombotic regimen for a year or more. Despite this, neither patients developed thrombotic complications during 29 patient-months of follow-up. An acquired von Willebrand factor (VWF) abnormality reflected by the absence or decreased abundance of the highest molecular weight multimers was demonstrated in both patients. The gold standard test for platelet function, light transmission platelet aggregometry was measured in one patient and was normal, indicative that the predominant abnormality in the coagulation profile of these patients is an acquired VWF syndrome. Clinical trials are required to address the question whether it is safe to discontinue anticoagulation in LVAD patients with acquired VWF abnormalities.

Clinical Aspects of Pregnancy and Delivery in Patients with Chronic Idiopathic Thrombocytopenic Purpura (ITP)

PubMed Central

Won, Young-Woong; Moon, Won; Yun, Yeong-Seop; Oh, Ho-Suk; Choi, Jung-Hye; Lee, Young-Yeul; Kim, In-Soon; Choi, Il-Young

2005-01-01

Background Idiopathic thrombocytopenic purpura (ITP) is a condition that often develops in young women and, consequently, physicians should frequently manage and monitor pregnant patients with this disorder. Methods We reviewed the charts of 30 women with chronic ITP delivered in 31 pregnancies from January 1995 to December 2003. Results Fifteen patients were diagnosed with ITP before pregnancy and sixteen patients were diagnosed during pregnancy. The mean platelet counts before pregnancy, during pregnancy, and at delivery were 70,040/mm3, 83,960/mm3, and 62,680/mm3, respectively. The symptoms of hemostatic impairment were not noted in most of the pregnancies (77%, 24/31). During pregnancy and at delivery, most of the women (61%, 19/31) received various kinds of treatment to raise platelet counts. At delivery, the most commonly used therapy was platelet transfusion (48.4%, 15/31). Seven pregnancies (22.6%) were treated with corticosteroids during pregnancy and at delivery. Five pregnancies (16.1%) were treated with IV IgG during pregnancy and at delivery. Fifteen deliveries (51.7%) were performed by cesarean section and fourteen (48.3%) with vaginal delivery. Bleeding was uncommon at delivery. There were no cases of infants with any clinical signs of hemorrhage. Conclusion Our current results suggest that ITP in pregnancy can proceed safely with low hemorrhagic risk in both infants and mothers, and that mothers with ITP can deliver healthy infants without serious hemorrhagic complications PMID:16134767

An increase in epicardial fat in women is associated with thrombotic risk.

PubMed

Basurto Acevedo, Lourdes; Barrera Hernández, Susana; Fernández Muñoz, María de Jesús; Saucedo García, Renata Patricia; Rodríguez Luna, Ana Karen; Martínez Murillo, Carlos

2018-01-29

A decrease in fibrinolytic activity and an increase in the thickness of the epicardial adipose tissue have been observed in patients with coronary artery disease. The aim of this study was to determine the association between epicardial adipose tissue and fibrinolytic activity by measuring the concentration of plasminogen activator inhibitor-1 (PAI-1). A cross-sectional study was conducted on 56 apparently healthy women aged 45 to 60 years. Anthropometric measurements and biochemical determinations were performed on all participants. The fibrinolytic activity was determined by measuring PAI-1 by ELISA. Epicardial thickness was assessed by transthoracic echocardiography. The concentration of PAI-1 was directly associated with the thickness of the epicardial adipose tissue (r=0.475, P=.001), body mass index (BMI), visceral adipose tissue, insulin resistance, glucose, and HDL-cholesterol. The multivariate regression analysis indicated that epicardial fat independently predicts the concentrations of PAI-1. Women with thicker epicardial adipose tissue have reduced fibrinolytic activity, and consequently greater thrombotic risk. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Acquired pendular nystagmus

PubMed Central

Kang, Sarah; Shaikh, Aasef G.

2017-01-01

Acquired pendular nystagmus is comprised of quasi-sinusoidal oscillations of the eyes significantly affecting gaze holding and clarity of vision. The most common causes of acquired pendular nystagmus include demyelinating disorders such as multiple sclerosis and the syndrome of ocular palatal tremor. However, several other deficits, such as pharmacological intoxication, metabolic and genetic disorders, and granulomatous disorders can lead to syndromes mimicking acquired pendular nystagmus. Study of the kinematic features of acquired pendular nystagmus has suggested a putative pathophysiology of an otherwise mysterious neurological disorder. Here we review clinical features of neurological deficits that co-occur with acquired pendular nystagmus. Subsequent discussion of the pathophysiology of individual forms of pendular nystagmus speculates on mechanisms of the underlying disease while providing insights into pharmacotherapy of nystagmus. PMID:28320194

Differences in microbiological profile between community-acquired, healthcare-associated and hospital-acquired infections.

PubMed

Cardoso, Teresa; Ribeiro, Orquídea; Aragão, Irene; Costa-Pereira, Altamiro; Sarmento, António

2013-01-01

Microbiological profiles were analysed and compared for intra-abdominal, urinary, respiratory and bloodstream infections according to place of acquisition: community-acquired, with a separate analysis of healthcare-associated, and hospital-acquired. Prospective cohort study performed at a university tertiary care hospital over 1 year. Inclusion criteria were meeting the Centers for Disease Control definition of intra-abdominal, urinary, respiratory and bloodstream infections. A total of 1035 patients were included in the study. More than 25% of intra-abdominal infections were polymicrobial; multi-drug resistant gram-negatives were 38% in community-acquired, 50% in healthcare-associated and 57% in hospital-acquired. E. coli was the most prevalent among urinary infections: 69% in community-acquired, 56% in healthcare-associated and 26% in hospital-acquired; ESBL producers' pathogens were 10% in healthcare-associated and 3% in community-acquired and hospital-acquired. In respiratory infections Streptococcus pneumoniae was the most prevalent in community-acquired (54%) and MRSA in healthcare-associated (24%) and hospital-acquired (24%). A significant association was found between MRSA respiratory infection and hospitalization in the previous year (adjusted OR = 6.3), previous instrumentation (adjusted OR = 4.3) and previous antibiotic therapy (adjusted OR = 5.7); no cases were documented among patients without risk factors. Hospital mortality rate was 10% in community-acquired, 14% in healthcare-associated and 19% in hospital-acquired infection. This study shows that healthcare-associated has a different microbiologic profile than those from community or hospital acquired for the four main focus of infection. Knowledge of this fact is important because the existing guidelines for community-acquired are not entirely applicable for this group of patients.

The Effects of Helicobacter pylori Eradication Therapy for Chronic Idiopathic Thrombocytopenic Purpura

PubMed Central

Hwang, Jae Jin; Lee, Dong Ho; Yoon, Hyuk; Shin, Cheol Min; Park, Young Soo; Kim, Nayoung

2016-01-01

Background/Aims The aim of this study was to evaluate the ability of Helicobacter pylori eradication treatment to increase platelet counts in Korean patients with chronic idiopathic thrombocytopenic purpura (ITP). Methods A total of 102 patients were evaluated against two criteria. First, those diagnosed with H. pylori infections in whom eradication was successful were assigned to the H. pylori-positive and -eradicated group (n=39), whereas those diagnosed with H. pylori infections in whom eradication failed were assigned to the H. pylori-positive and -non-eradicated group (n=3), and those without H. pylori infections were assigned to the H. pylori-negative group (n=60). Second, patients with complete remission in whom the platelet recovery effect was maintained over the average follow-up period of 6 months after eradication therapy were defined as the responder group (n=58), whereas those with partial or no response were defined as the nonresponder group (n=44). Results The platelet counts of the H. pylori-positive and -eradicated group were significantly increased 6 months after eradication therapy compared to those of the H. pylori-positive and -non-eradicated group and the H. pylori-negative group (43.2±29.1 to 155.3±68.7×103/μL vs 42.5±28.1 to 79.8±59.7×103/μL vs 43.1±28.9 to 81.2±62.2×103/μL; p=0.041). The eradication therapy success rate in the responder group was 100.0% (39/39), in contrast to the nonresponder group (0%, 0/3) (p<0.001). Conclusions H. pylori eradication therapy was related to increased platelet count, and successful eradication affected the increased platelet count in Korean patients with chronic ITP. PMID:26347517

Results of emergency surgery in patients with Moschowitz's disease refractory to hematological treatment: is splenectomy always advisable?

PubMed

Caronna, R; Cardi, M; Meloni, G; Mangioni, S; Spera, G; Benedetti, M; Frantellizzi, V; Layek, D; Catinelli, S; Schiratti, M; Chirletti, P

2005-01-01

Patients with thrombotic thrombocytopenic purpura (TTP), Moschowitz's disease, run a high risk of perioperative bleeding and need intensive hematologic support. In some patients, TTP is associated with cancer but the surgical role in these patients is still unclear. To illustrate the surgical problems and outcome we present the case histories of three patients with TTP observed in our emergency department. Two patients had TTP secondary to cancer and one patient with primary TTP (no evidence of neoplasia) had emergency operation for gastric hemorrhage, occlusion and TTP unresponsive to plasmapheresis. The first two patients who had not radical resection of cancer and no splenectomy, died for TTP complications. The third patient who underwent emergency splenectomy, had an uneventful postoperative course and TTP completely regressed. These case reports suggest that patients with TTP should be screened to rule out cancer. In patients with acute cancer-related complications emergency surgery should aim to resect the cancer. An associated splenectomy may increase the effectiveness of postoperative hematologic therapy.

Results of a 6-month survey of stool cultures for Escherichia coli O157:H7.

PubMed

Marshall, W F; McLimans, C A; Yu, P K; Allerberger, F J; Van Scoy, R E; Anhalt, J P

1990-06-01

Escherichia coli O157:H7 is a recently recognized enteric pathogen that causes acute hemorrhagic colitis. Although the infection is usually self-limited, it may be complicated by hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. At our institution, stool specimens are now routinely cultured for this organism. To determine the prevalence of E. coli O157:H7-associated diarrhea in our patient population, we surveyed all submitted stool cultures for 6 months for this organism. Specimens were screened for non-sorbitol fermenting E. coli and confirmed by slide-agglutination and immobilization testing. Of 2,164 specimens, 10 yielded E. coli O157:H7. It was the fourth most common bacterial stool pathogen found. Bloody diarrhea and abdominal pain were the most common symptoms of the infected patients. E. coli O157:H7 causes sporadic infections in our patient population and should be considered in the differential diagnosis of acute hemorrhagic colitis.

Thrombospondin-1 controls vascular platelet recruitment and thrombus adherence in mice by protecting (sub)endothelial VWF from cleavage by ADAMTS13

PubMed Central

Bonnefoy, Arnaud; Daenens, Kim; Feys, Hendrik B.; De Vos, Rita; Vandervoort, Petra; Vermylen, Jos; Lawler, Jack; Hoylaerts, Marc F.

2006-01-01

The function of thrombospondin-1 (TSP-1) in hemostasis was investigated in wild-type (WT) and Tsp1-/- mice, via dynamic platelet interaction studies with A23187-stimulated mesenteric endothelium and with photochemically injured cecum subendothelium. Injected calcein-labeled WT platelets tethered or firmly adhered to almost all A23187-stimulated blood vessels of WT mice, but Tsp1-/- platelets tethered to 45% and adhered to 25.8% of stimulated Tsp1-/- vessels only. Stimulation generated temporary endothelium-associated ultralarge von Willebrand factor (VWF) multimers, triggering platelet string formation in 48% of WT versus 20% of Tsp1-/- vessels. Injection of human TSP-1 or thrombotic thrombocytopenic purpura (TTP) patient-derived neutralizing anti-ADAMTS13 antibodies corrected the defective platelet recruitment in Tsp1-/- mice, while having a moderate effect in WT mice. Photochemical injury of intestinal blood vessels induced thrombotic occlusions with longer occlusion times in Tsp1-/- venules (1027 ± 377 seconds) and arterioles (858 ± 289 seconds) than in WT vessels (559 ± 241 seconds, P < .001; 443 ± 413 seconds, P < .003) due to defective thrombus adherence, resulting in embolization of complete thrombi, a defect restored by both human TSP-1 and anti-ADAMTS13 antibodies. We conclude that in a shear field, soluble or local platelet-released TSP-1 can protect unfolded endothelium-bound and subendothelial VWF from degradation by plasma ADAMTS13, thus securing platelet tethering and thrombus adherence to inflamed and injured endothelium, respectively. PMID:16204318

ADAMTS-13 rapidly cleaves newly secreted ultralarge von Willebrand factor multimers on the endothelial surface under flowing conditions.

PubMed

Dong, Jing-fei; Moake, Joel L; Nolasco, Leticia; Bernardo, Aubrey; Arceneaux, Wendy; Shrimpton, Corie N; Schade, Alicia J; McIntire, Larry V; Fujikawa, Kazuo; López, José A

2002-12-01

Thrombotic thrombocytopenic purpura (TTP) is a devastating thrombotic disorder caused by widespread microvascular thrombi composed of platelets and von Willebrand factor (VWF). The disorder is associated with a deficiency of the VWF-cleaving metalloprotease, ADAMTS-13, with consequent accumulation of ultralarge (UL) VWF multimers in the plasma. ULVWF multimers, unlike plasma forms of VWF, attach spontaneously to platelet GP Ibalpha, a component of the GP Ib-IX-V complex. We have found that ULVWF multimers secreted from stimulated endothelial cells (ECs) remained anchored to the endothelial surface where platelets and Chinese hamster ovary cells expressing the GP Ib-IX-V complex attached to form long beads-on-a-string structures in the presence of fluid shear stresses in both the venous (2.5 dyne/cm(2)) and arterial (20 and 50 dyne/cm(2)) ranges. Although measurement of the activity of the ADAMTS-13 VWF-cleaving metalloprotease in vitro requires prolonged incubation of the enzyme with VWF under nonphysiologic conditions, EC-derived ULVWF strings with attached platelets were cleaved within seconds to minutes in the presence of normal plasma (containing approximately 100% ADAMTS-13 activity) or in the presence of partially purified ADAMTS-13. By contrast, the strings persisted for the entire period of perfusion (10 minutes) in the presence of plasma from patients with TTP containing 0% to 10% ADAMTS-13 activity. These results suggest that cleavage of EC-derived ULVWF multimers by ADAMTS-13 is a rapid physiologic process that occurs on endothelial cell surfaces.

Acquired pendular nystagmus.

PubMed

Kang, Sarah; Shaikh, Aasef G

2017-04-15

Acquired pendular nystagmus is comprised of quasi-sinusoidal oscillations of the eyes significantly affecting gaze holding and clarity of vision. The most common causes of acquired pendular nystagmus include demyelinating disorders such as multiple sclerosis and the syndrome of ocular palatal tremor. However, several other deficits, such as pharmacological intoxication, metabolic and genetic disorders, and granulomatous disorders can lead to syndromes mimicking acquired pendular nystagmus. Study of the kinematic features of acquired pendular nystagmus has suggested a putative pathophysiology of an otherwise mysterious neurological disorder. Here we review clinical features of neurological deficits that co-occur with acquired pendular nystagmus. Subsequent discussion of the pathophysiology of individual forms of pendular nystagmus speculates on mechanisms of the underlying disease while providing insights into pharmacotherapy of nystagmus. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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

Code of Federal Regulations, 2012 CFR

2012-04-01

... 17 Commodity and Securities Exchanges 2 2012-04-01 2012-04-01 false Real estate operations acquired or to be acquired. 210.8-06 Section 210.8-06 Commodity and Securities Exchanges SECURITIES AND...-06 Real estate operations acquired or to be acquired. If, during the period for which income...

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

Code of Federal Regulations, 2013 CFR

2013-04-01

... 17 Commodity and Securities Exchanges 2 2013-04-01 2013-04-01 false Real estate operations acquired or to be acquired. 210.8-06 Section 210.8-06 Commodity and Securities Exchanges SECURITIES AND...-06 Real estate operations acquired or to be acquired. If, during the period for which income...

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

Code of Federal Regulations, 2014 CFR

2014-04-01

... 17 Commodity and Securities Exchanges 3 2014-04-01 2014-04-01 false Real estate operations acquired or to be acquired. 210.8-06 Section 210.8-06 Commodity and Securities Exchanges SECURITIES AND...-06 Real estate operations acquired or to be acquired. If, during the period for which income...

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

PubMed

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

2014-07-01

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

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

Code of Federal Regulations, 2011 CFR

2011-04-01

... 17 Commodity and Securities Exchanges 2 2011-04-01 2011-04-01 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. If...

[Changes of monocyte and monocyte-platelet aggregates in different subgroups of thrombotic events in patients with acute myocardial infarction during PCI].

PubMed

Wang, Sheng; Sun, Cuifang; Liao, Wang; Wu, Zhongwei; Wang, Yudai; Huang, Xiuxian; Lu, Sijia; Dong, Xiaoli; Shuai, Fujie; Li, Bin

2017-07-01

Objective To investigate the impact of thrombotic events on the alterations of monocyte and monocyte-platelet aggregates (MPAs) in patients with acute myocardial infarction (AMI) during percutaneous coronary intervention (PCI). Methods Blood was collected before PCI for flow cytometry. Monocyte subsets and MPAs were detected by four-color platform (CDl4-APC, CDl6-PE-Cy7, CD86-PE and CD41-Alexa Fluor R 488). According to the expression of the platelet surface marker CD41, the number of monocyte subsets and MPAs was analyzed using the fluorescent microspheres of absolute counting tube. The Wilcoxon rank sum test and receiver operating characteristic (ROC) curve analysis were performed. Results CD14 + CD16 ++ monocytes in intraprocedural thrombotic events (IPTE) group were significantly fewer than those in non-IPTE group, and the percentage in total mononuclear cells decreased. Compared with non-IPTE group, MPA binding ratio and monocyte subset MPA binding ratio were significantly higher in IPTE group. ROC analysis showed that MPA binding ratio and subgroup MPA binding ratio had a better predictive value for IPTE in patients with AMI. Conclusion The CD14 + CD16 ++ monocytes in IPTE group were significantly fewer than those in the non-IPTE group. MPA binding ratio and MPA binding ratio of monocyte subsets were significantly higher in the IPTE group than in the non-IPTE group, so they have a good predictive value for IPTE in patients with AMI.

[Telemedicine in thrombotic microangiopathies: A way forward in rare diseases requiring emergency care].

PubMed

Coppo, P; Corre, E; Rondeau, E; Benhamou, Y; Bachet, A; Stépanian, A; Veyradier, A

2016-08-01

Thrombotic microangiopathies (TMA) represent rare diseases requiring a high skill for their management that deserved in France the identification of a dedicated National reference center. TMA are short-term life-threatening diseases; however, with an adapted management, their prognosis can be excellent. It is therefore mandatory to recognize and treat them rapidly according to standard guidelines. Telemedicine is a specialized hub consisting of highly skilled staff trained in a specific domain of medicine. The telemedicine activity of a reference center is an important representative indicator of its expertise and recourse ability. It requires to be accurately evaluated and promoted. In this work, we report the French reference center for TMA telemedicine activity since its setting-up. TMA represent an interesting model of diseases that required a specific organization of telemedicine activity to adapt to clinicians demand, which includes particularly the need to answer resorts in real time 24/7. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Statins but Not Aspirin Reduce Thrombotic Risk Assessed by Thrombin Generation in Diabetic Patients without Cardiovascular Events: The RATIONAL Trial

PubMed Central

Macchia, Alejandro; Laffaye, Nicolás; Comignani, Pablo D.; Cornejo Pucci, Elena; Igarzabal, Cecilia; Scazziota, Alejandra S.; Herrera, Lourdes; Mariani, Javier A.; Bragagnolo, Julio C.; Catalano, Hugo; Tognoni, Gianni; Nicolucci, Antonio

2012-01-01

Background The systematic use of aspirin and statins in patients with diabetes and no previous cardiovascular events is controversial. We sought to assess the effects of aspirin and statins on the thrombotic risk assessed by thrombin generation (TG) among patients with type II diabetes mellitus and no previous cardiovascular events. Methodology/Principal Findings Prospective, randomized, open, blinded to events evaluation, controlled, 2×2 factorial clinical trial including 30 patients randomly allocated to aspirin 100 mg/d, atorvastatin 40 mg/d, both or none. Outcome measurements included changes in TG levels after treatment (8 to 10 weeks), assessed by a calibrated automated thrombogram. At baseline all groups had similar clinical and biochemical profiles, including TG levels. There was no interaction between aspirin and atorvastatin. Atorvastatin significantly reduced TG measured as peak TG with saline (85.09±55.34 nmol vs 153.26±75.55 nmol for atorvastatin and control groups, respectively; p = 0.018). On the other hand, aspirin had no effect on TG (121.51±81.83 nmol vs 116.85±67.66 nmol, for aspirin and control groups, respectively; p = 0.716). The effects of treatments on measurements of TG using other agonists were consistent. Conclusions/Significance While waiting for data from ongoing large clinical randomized trials to definitively outline the role of aspirin in primary prevention, our study shows that among diabetic patients without previous vascular events, statins but not aspirin reduce thrombotic risk assessed by TG. Trial Registration ClinicalTrials.gov NCT00793754 PMID:22470429

Infective and thrombotic complications of central venous catheters in patients with hematological malignancy: prospective evaluation of nontunneled devices.

PubMed

Worth, Leon J; Seymour, John F; Slavin, Monica A

2009-07-01

Central venous catheter (CVC)-related bloodstream infection (CR-BSI) is a significant complication in hematology patients. A range of CVC devices may be used, and risks for the development of complications are not uniform. The objectives of this study were to determine the natural history and rate of CVC-related complications and risk factors for CR-BSI and to compare device-specific complications in a hematology population. An observational cohort of patients with hematologic malignancy was prospectively studied following CVC insertion. Participants were reviewed until a CVC-related complication necessitated device removal, completion of therapy, death, or defined end-of-study date. The National Nosocomial Infection Surveillance definition for CR-BSI was used. Overall and device-specific rates of infective and noninfective complications were calculated and potential risk factors were captured. One hundred six CVCs (75 peripherally inserted central venous catheters [PICCs], 31 nontunneled CVCs) were evaluated in 66 patients, over 2,399 CVC days. Thrombosis occurred in 16 cases (15.1%), exit-site infection in two (1.9%), and CR-BSI in 18 (7.5 per 1,000 CVC days). No significant differences were found when complication rates in PICC and nontunneled devices were compared. An underlying diagnosis of acute myeloid leukemia was negatively associated with CR-BSI (odds ratio (OR) 0.14, p = 0.046), and a previous diagnosis of fungal infection was associated with infection (OR 22.82, p = 0.031). CR-BSI rates in our hematology population are comparable to prior reports. A low rate of exit-site infection and high proportion of thrombotic complications were observed. No significant differences in thrombotic or infective complications were evident when PICC and nontunneled devices were compared. PICC devices are a practical and safe option for management of hematology patients.

Plasma autoantibodies against platelet glycoprotein IIb/IIIa from patients with autoimmune thrombocytopenic purpura may recognize different antigenic determinants.

PubMed

Berchtold, P; Müller, D; Kouns, W C; Riederer, M A; Steiner, B

1998-10-01

Autoantibodies against platelet glycoprotein (GP) GPIIb/IIIa have been demonstrated in patients with autoimmune thrombocytopenic purpura. Recently, it has been shown that plasma autoantibodies from some patients bind to the cytoplasmic domain of GPIIIa. Our aim was to evaluate further the binding specificity of these plasma autoantibodies. From 7 patients with detectable plasma antibodies against intact GPIIb/IIIa, 1 showed strong antibody binding to a synthetic C-terminal peptide of GPIIIa. Ig class analysis of affinity purified anti-GPIIb/IIIa autoantibodies from this patient revealed an IgM antibody that reacted with intact GPIIb/IIIa as well as with recombinant GPIIb/IIIa lacking the C-terminal domains, and an IgG antibody that bound to intact GPIIb/IIIa but not to GPIIb/IIIa lacking the C-terminal region. These data indicate that this patient has at least 2 autoantibodies, an IgG directed against the cytoplasmic domain of GPIIIa and an IgM reacting with the extracellular part of GPIIIa. This may support the hypothesis that plasma IgG antibodies directed against the C-terminal domain of GPIIIa may be due to the exposition of cytoplasmic epitopes of GPIIIa as a result of increased cell lysis by IgM autoantibodies.

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

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

PubMed

Shimanovsky, Alexei; Patel, Devbala; Wasser, Jeffrey

2016-01-01

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

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

PubMed Central

Shimanovsky, Alexei; Patel, Devbala; Wasser, Jeffrey

2016-01-01

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

Investigation of celiac disease followed by immune thrombocytopenic purpura diagnosis in patients and comparison with literature

PubMed Central

Sarbay, Hakan; Kocamaz, Halil; Akin, Mehmet; Ozhan, Bayram

2017-01-01

OBJECTIVE: Celiac disease (CD) and Immune thrombocytopenic purpura (ITP) may occur together as a result of similar autoimmune mechanisms. The aim of this study was to assess the frequency of CD in a group of ITP patients and in the literature. METHODS: A total of 29 patients in Pamukkale University Faculty of Medicine Hospital Pediatric Hematology and Oncology Department with ITP were included in the study. Test was performed for the antibodies related to CD. Positive result for celiac antibodies was confirmed with biopsy. The results were compared with the literature. RESULTS: Of the study group, 13 patients (44.8%) were female and 16 (55.2%) were male. The mean age was 7.2±4.7 years and mean platelet count at the time of admission was 13,440±11,110/mm3 (range: 2000-41,000/mm3). Twelve patients (41.4%) were diagnosed as acute ITP, 6 patients (20.7%) as persistent ITP, and 11 patients (37.9%) as chronic ITP, according to the duration of thrombocytopenia. Antibody positivity was detected in 1 patient. Histological evaluation was compatible with CD. Results were compared with studies regarding the prevalence of CD in the population. No significant difference was found. CONCLUSION: Although it is not necessary to perform CD test in every case of ITP, the presence of differential diagnosis of CD is important to prevent unnecessary treatment, especially in ITP patients with growth retardation or malabsorption findings. PMID:28971174

12 CFR 583.1 - Acquire.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Acquire. 583.1 Section 583.1 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY DEFINITIONS FOR REGULATIONS AFFECTING SAVINGS AND LOAN HOLDING COMPANIES § 583.1 Acquire. The term acquire means to acquire, directly or indirectly...

Upper-Extremity Deep-Vein Thrombosis: A Retrospective Cohort Evaluation of Thrombotic Risk Factors at a University Teaching Hospital Antithrombosis Clinic.

PubMed

Stone, Rebecca H; Bress, Adam P; Nutescu, Edith A; Shapiro, Nancy L

2016-08-01

Upper-extremity deep-vein thrombosis (UEDVT) causes significant morbidity and mortality and is not well characterized in the existing literature, particularly in underrepresented minorities such as African Americans. To describe the characteristics of a cohort of patients with UEDVT seen at an urban academic medical center. This was a retrospective cohort study among patients with a confirmed UEDVT at the University of Illinois Hospital and Health Sciences System between 1996 and 2011. Patients were identified by ICD-9 code for UEDVT. Variables collected include thrombotic risk factors and outcomes, including recurrent thrombosis and bleeding. We identified 229 patients with UEDVT; 71% were African American, and 11% were diagnosed with sickle cell disease. The average number of UEDVT risk factors was 4.40 ± 1.5, the most common being central venous catheter (CVC) use (178, 78%). In the year following UEDVT, 13% experienced recurrent thrombosis, and 6% experienced major bleeding. Of 181 patients receiving warfarin after an UEDVT, 36% of international normalized ratio (INR) values were therapeutic. Patients with sickle cell disease had a lower proportion of INRs within the target range (25% vs 38%, P < 0.01), and were more likely to be lost to follow-up (67% vs 46%, P = 0.05) and experience a recurrent thrombotic event (29% vs 11%, P = 0.02). A CVC is the most common risk factor for UEDVT; however, patients with sickle cell disease demonstrate additional unique demographics and risk factors. Patients included in this underrepresented demographic cohort had a low quality of anticoagulation control, particularly those with sickle cell disease. © The Author(s) 2016.

Cost implications of intraprocedural thrombotic events and bleeding in percutaneous coronary intervention: Results from the CHAMPION PHOENIX ECONOMICS Study.

PubMed

Tamez, Hector; Généreux, Philip; Yeh, Robert W; Amin, Amit P; Fan, Weihong; White, Harvey D; Kirtane, Ajay J; Stone, Gregg W; Gibson, C Michael; Harrington, Robert A; Bhatt, Deepak L; Pinto, Duane S

2018-05-04

Despite improvements in percutaneous coronary intervention (PCI), intraprocedural thrombotic events (IPTE) and bleeding complications occur and are prognostically important. These have not been included in prior economic studies. PHOENIX ECONOMICS was a substudy of the CHAMPION PHOENIX trial, evaluating cangrelor during PCI. Hospital bills were reviewed from 1,171 patients enrolled at 22 of 63 US sites. Costs were estimated using standard methods including resource-based accounting, hospital billing data, and the Medicare fee schedule. Bleeding and IPTE, defined as abrupt vessel closure (transient or sustained), new/suspected thrombus, new clot on wire/catheter, no reflow, side-branch occlusion, procedural stent thrombosis or urgent need for CABG were identified. Costs were calculated according to whether a complication occurred and type of event. Multivariate analyses were used to estimate the incremental costs of IPTE and postprocedural events. IPTE occurred in 4.3% and were associated with higher catheterization laboratory and overall index hospitalization costs by $2,734 (95%CI $1,117, $4,351; P = 0.001) and $6,354 (95% CI $4,122, $8,586; P < 0.001), respectively. IPTE were associated with MI (35.4% vs. 3.6%; P < 0.001), out-of-laboratory stent thrombosis (4.2% vs. 0.1%; 0 = 0.005), ischemia driven revascularization (12.5% vs. 0.3%; P < 0.001), but not mortality (2.1% vs. 0.2%; P = 0.12) vs. no procedural thrombotic complication. By comparison, ACUITY minor bleeding increased hospitalization cost by $1,416 (95%CI = 312, $2,519; P = 0.012). ACUITY major bleeding increased cost of hospitalization by $7,894 (95%CI $4,154, $11,635; P < 0.001). IPTE and bleeding complications, though infrequent, are associated with substantial increased cost. These complications should be collected in economic assessments of PCI. © 2018 Wiley Periodicals, Inc.

Relationship between ADAMTS13 activity, von Willebrand factor antigen levels and platelet function in the early and late phases after TIA or ischaemic stroke.

PubMed

McCabe, Dominick J H; Murphy, Stephen J X; Starke, Richard; Harrison, Paul; Brown, Martin M; Sidhu, Paul S; Mackie, Ian J; Scully, Marie; Machin, Samuel J

2015-01-15

Reduced ADAMTS13 activity is seen in thrombotic thrombocytopenic purpura (TTP), and may lead to accumulation of prothrombotic ultra-large von Willebrand factor (ULVWF) multimers in vivo. ADAMTS13 activity and its relationship with VWF antigen (VWF:Ag) levels and platelet function in 'non-TTP related' TIA or ischaemic stroke has not been comprehensively studied. In this prospective pilot observational analytical case-control study, ADAMTS13 activity and VWF:Ag levels were quantified in platelet poor plasma in 53 patients in the early phase (≤ 4 weeks) and 34 of these patients in the late phase (≥ 3 months) after TIA or ischaemic stroke on aspirin. Data were compared with those from 22 controls not on aspirin. The impact of ADAMTS13 on platelet function in whole blood was quantified by measuring Collagen-ADP (C-ADP) and Collagen-Epinephrine closure times on a platelet function analyser (PFA-100(®)). Median ADAMTS13 activity was significantly reduced in the early phase (71.96% vs. 95.5%, P <0.01) but not in the late phase after TIA or stroke compared with controls (86.3% vs. 95.5%, P=0.19). There was a significant inverse relationship between ADAMTS13 activity and VWF:Ag levels in the early phase (r=-0.31; P=0.024), but not in the late phase after TIA or stroke (P=0.74). There was a positive correlation between ADAMTS13 activity and C-ADP closure times in early phase patients only, likely mediated via VWF:Ag levels. ADAMTS13 activity is reduced and VWF:Ag expression is increased within 4 weeks of TIA or ischaemic stroke onset, and can promote enhanced platelet adhesion and aggregation in response to stimulation with collagen and ADP via VWF-mediated pathways. These data improve our understanding of the dynamic haemostatic and thrombotic profiles of ischaemic cerebrovascular disease (CVD) patients, and are important in view of the potential future role that ADAMTS13 may have to play as an anti-thrombotic agent in CVD. Copyright © 2014 Elsevier B.V. All rights

Spontaneous acute subdural hematoma and intracerebral hemorrhage in a patient with thrombotic microangiopathy during pregnancy.

PubMed

Wayhs, Sâmia Yasin; Wottrich, Joise; Uggeri, Douglas Prestes; Dias, Fernando Suparregui

2013-01-01

Preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low-platelet count), and acute fatty liver of pregnancy are the main causes of thrombotic microangiopathy and evere liver dysfunction during pregnancy and represent different manifestations of the same pathological continuum. The case of a 35-week pregnant woman who was admitted to an intensive care unit immediately after a Cesarean section due to fetal death and the presence of nausea, vomiting, and jaundice is reported. Postpartum preeclampsia and acute fatty liver of pregnancy were diagnosed. The patient developed an acute subdural hematoma and an intracerebral hemorrhage, which were subjected to neurosurgical treatment. The patient died from refractory hemolytic anemia and spontaneous bleeding of multiple organs. Preeclampsia HELLP syndrome, and acute fatty liver of pregnancy might overlap and be associated with potentially fatal complications, including intracranial hemorrhage, as in the present case. Early detection and diagnosis are crucial to ensure management and treatment success.

Spontaneous acute subdural hematoma and intracerebral hemorrhage in a patient with thrombotic microangiopathy during pregnancy

PubMed Central

Wayhs, Sâmia Yasin; Wottrich, Joise; Uggeri, Douglas Prestes; Dias, Fernando Suparregui

2013-01-01

Preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low-platelet count), and acute fatty liver of pregnancy are the main causes of thrombotic microangiopathy and severe liver dysfunction during pregnancy and represent different manifestations of the same pathological continuum. The case of a 35-week pregnant woman who was admitted to an intensive care unit immediately after a Cesarean section due to fetal death and the presence of nausea, vomiting, and jaundice is reported. Postpartum preeclampsia and acute fatty liver of pregnancy were diagnosed. The patient developed an acute subdural hematoma and an intracerebral hemorrhage, which were subjected to neurosurgical treatment. The patient died from refractory hemolytic anemia and spontaneous bleeding of multiple organs. Preeclampsia, HELLP syndrome, and acute fatty liver of pregnancy might overlap and be associated with potentially fatal complications, including intracranial hemorrhage, as in the present case. Early detection and diagnosis are crucial to ensure appropriate management and treatment success. PMID:23917984

Complement C5-inhibiting therapy for the thrombotic microangiopathies: accumulating evidence, but not a panacea

PubMed Central

Brocklebank, Vicky

2017-01-01

Abstract Thrombotic microangiopathy (TMA), characterized by organ injury occurring consequent to severe endothelial damage, can manifest in a diverse range of diseases. In complement-mediated atypical haemolytic uraemic syndrome (aHUS) a primary defect in complement, such as a mutation or autoantibody leading to over activation of the alternative pathway, predisposes to the development of disease, usually following exposure to an environmental trigger. The elucidation of the pathogenesis of aHUS resulted in the successful introduction of the complement inhibitor eculizumab into clinical practice. In other TMAs, although complement activation may be seen, its role in the pathogenesis remains to be confirmed by an interventional trial. Although many case reports in TMAs other than complement-mediated aHUS hint at efficacy, publication bias, concurrent therapies and in some cases the self-limiting nature of disease make broader interpretation difficult. In this article, we will review the evidence for the role of complement inhibition in complement-mediated aHUS and other TMAs. PMID:28980670

Prevention and treatment of the post-thrombotic syndrome and of the chronic thromboembolic pulmonary hypertension.

PubMed

Pesavento, Raffaele; Prandoni, Paolo

2015-02-01

Post-thrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension (CTEPH) are late complications of venous thromboembolism. The purpose of this review is to present and discuss recently published studies that have improved our knowledge of PTS and CTEPH. The current understanding of the pathophysiology of PTS and CTEPH is discussed as well as the importance of chronic residual venous thrombosis, some polymorphisms of plasminogen activator inhibitor-1, and the current concept of misguided thrombus resolution. The surprising finding that elastic compression stockings may not be effective in preventing PTS and the novel medical treatment in CTEPH are discussed in detail. Novel direct oral anticoagulants show potential for prevention of PTS. No firm conclusions can be drawn on the efficacy of elastic stockings. Novel treatments of CTEPH for inoperable patients and those with persistent pulmonary hypertension after surgery have become available and further research on wider indication for their use is urgently needed.

Mice lacking the extracellular matrix protein MAGP1 display delayed thrombotic occlusion following vessel injury

PubMed Central

Werneck, Claudio C.; Vicente, Cristina P.; Weinberg, Justin S.; Shifren, Adrian; Pierce, Richard A.; Broekelmann, Thomas J.; Tollefsen, Douglas M.

2008-01-01

Mice lacking the extracellular matrix protein microfibril-associated glycoprotein-1 (MAGP1) display delayed thrombotic occlusion of the carotid artery following injury as well as prolonged bleeding from a tail vein incision. Normal occlusion times were restored when recombinant MAGP1 was infused into deficient animals prior to vessel wounding. Blood coagulation was normal in these animals as assessed by activated partial thromboplastin time and prothrombin time. Platelet number was lower in MAGP1-deficient mice, but the platelets showed normal aggregation properties in response to various agonists. MAGP1 was not found in normal platelets or in the plasma of wild-type mice. In ligand blot assays, MAGP1 bound to fibronectin, fibrinogen, and von Willebrand factor, but von Willebrand factor was the only protein of the 3 that bound to MAGP1 in surface plasmon resonance studies. These findings show that MAGP1, a component of microfibrils and vascular elastic fibers, plays a role in hemostasis and thrombosis. PMID:18281502

A Novel Quantitative Hemolytic Assay Coupled with Restriction Fragment Length Polymorphisms Analysis Enabled Early Diagnosis of Atypical Hemolytic Uremic Syndrome and Identified Unique Predisposing Mutations in Japan

PubMed Central

Yoshida, Yoko; Miyata, Toshiyuki; Matsumoto, Masanori; Shirotani-Ikejima, Hiroko; Uchida, Yumiko; Ohyama, Yoshifumi; Kokubo, Tetsuro; Fujimura, Yoshihiro

2015-01-01

For thrombotic microangiopathies (TMAs), the diagnosis of atypical hemolytic uremic syndrome (aHUS) is made by ruling out Shiga toxin-producing Escherichia coli (STEC)-associated HUS and ADAMTS13 activity-deficient thrombotic thrombocytopenic purpura (TTP), often using the exclusion criteria for secondary TMAs. Nowadays, assays for ADAMTS13 activity and evaluation for STEC infection can be performed within a few hours. However, a confident diagnosis of aHUS often requires comprehensive gene analysis of the alternative complement activation pathway, which usually takes at least several weeks. However, predisposing genetic abnormalities are only identified in approximately 70% of aHUS. To facilitate the diagnosis of complement-mediated aHUS, we describe a quantitative hemolytic assay using sheep red blood cells (RBCs) and human citrated plasma, spiked with or without a novel inhibitory anti-complement factor H (CFH) monoclonal antibody. Among 45 aHUS patients in Japan, 24% (11/45) had moderate-to-severe (≥50%) hemolysis, whereas the remaining 76% (34/45) patients had mild or no hemolysis (<50%). The former group is largely attributed to CFH-related abnormalities, and the latter group has C3-p.I1157T mutations (16/34), which were identified by restriction fragment length polymorphism (RFLP) analysis. Thus, a quantitative hemolytic assay coupled with RFLP analysis enabled the early diagnosis of complement-mediated aHUS in 60% (27/45) of patients in Japan within a week of presentation. We hypothesize that this novel quantitative hemolytic assay would be more useful in a Caucasian population, who may have a higher proportion of CFH mutations than Japanese patients. PMID:25951460

Acquired neuropathies.

PubMed

Lozeron, Pierre; Trocello, Jean-Marc; Kubis, Nathalie

2013-09-01

Acquired neuropathies represent most of the neuropathies encountered in clinical practice. Hundreds of causes have been identified even though up to 41% of patients are still classified as idiopathic (Rajabally and Shah in J Neurol 258:1431-1436, 1). Routine evaluation relies on comprehensive medical history taking, clinical examination, nerve conduction studies and laboratory tests. Other investigations such as nerve biopsy or nerve or muscle imaging are performed in specific settings. This review focuses on recent advances in acquired neuropathies.

Effects of multiple inherited and acquired thrombophilia on outcomes of in-vitro fertilization.

PubMed

Di Nisio, Marcello; Ponzano, Adalisa; Tiboni, Gianmario; Guglielmi, Maria Domenica; Rutjes, Anne Wilhelmina Saskia; Porreca, Ettore

2018-05-09

The effects of multiple inherited and acquired thrombophilic defects on the outcome of in-vitro fertilization (IVF) remain unexplored. The aim of this study was to evaluate the association between multiple thrombophilia and clinical outcomes in a large prospective cohort of women undergoing IVF. Consecutive women scheduled for IVF were eligible. The primary study outcome was live birth. Secondary outcomes included spontaneous abortion, clinical pregnancy, and symptomatic venous thromboembolism. 687 women with a mean age of 34.6 (±3.2) years were included. Overall, 22 women (3.2%) had two or more thrombophilic defects. The probability of live birth was not statistically significantly different between women with ≥2 thrombophilia (odds ratio [OR] 0.62; 95% confidence interval [CI], 0.18 to 2.11) or ≥1 thrombophilia (OR 0.67;95% CI, 0.41 to 1.09) and women without any thrombophilia. None of the individual inherited thrombophilia nor positivity to antiphospholipid antibodies or lupus anticoagulant were associated with live birth. Single positivity for lupus anticoagulant carried a more than threefold higher risk of abortion (OR 3.74; 95% CI, 1.30 to 10.75). There were no statistically significant associations between individual or multiple thrombophilic defects and clinical pregnancy or pregnancy test results. No woman had a history of venous thromboembolism and none developed a thrombotic event during the study. In women undergoing IVF, the presence of two or more thrombophilic defects was rare and showed no statistically significant associations with IVF outcomes. Copyright © 2018 Elsevier Ltd. All rights reserved.

Quantifying progression and regression of thrombotic risk in experimental atherosclerosis

PubMed Central

Palekar, Rohun U.; Jallouk, Andrew P.; Goette, Matthew J.; Chen, Junjie; Myerson, Jacob W.; Allen, John S.; Akk, Antonina; Yang, Lihua; Tu, Yizheng; Miller, Mark J.; Pham, Christine T. N.; Wickline, Samuel A.; Pan, Hua

2015-01-01

Currently, there are no generally applicable noninvasive methods for defining the relationship between atherosclerotic vascular damage and risk of focal thrombosis. Herein, we demonstrate methods to delineate the progression and regression of vascular damage in response to an atherogenic diet by quantifying the in vivo accumulation of semipermeable 200–300 nm perfluorocarbon core nanoparticles (PFC-NP) in ApoE null mouse plaques with [19F] magnetic resonance spectroscopy (MRS). Permeability to PFC-NP remained minimal until 12 weeks on diet, then increased rapidly following 12 weeks, but regressed to baseline within 8 weeks after diet normalization. Markedly accelerated clotting (53.3% decrease in clotting time) was observed in carotid artery preparations of fat-fed mice subjected to photochemical injury as defined by the time to flow cessation. For all mice on and off diet, an inverse linear relationship was observed between the permeability to PFC-NP and accelerated thrombosis (P = 0.02). Translational feasibility for quantifying plaque permeability and vascular damage in vivo was demonstrated with clinical 3 T MRI of PFC-NP accumulating in plaques of atherosclerotic rabbits. These observations suggest that excessive permeability to PFC-NP may indicate prothrombotic risk in damaged atherosclerotic vasculature, which resolves within weeks after dietary therapy.—Palekar, R. U., Jallouk, A. P., Goette, M. J., Chen, J., Myerson, J. W., Allen, J. S., Akk, A., Yang, L., Tu, Y., Miller, M. J., Pham, C. T. N., Wickline, S. A., Pan, H. Quantifying progression and regression of thrombotic risk in experimental atherosclerosis. PMID:25857553

Complement Activation on Platelets Correlates with a Decrease in Circulating Immature Platelets in Patients with Immune Thrombocytopenic Purpura

PubMed Central

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

2010-01-01

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 × 109/L) (p = 0.027) and thrombocytopenia (platelet count less than 100K/μl) (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 pharmacologic therapies, an enhanced response to splenectomy was noted (p <0.063). Thus, complement fixation may contribute to the thrombocytopenia of ITP by enhancing clearance of opsonized platelets from the circulation, and/or directly damaging platelets and megakaryocytes. PMID:19925495

Clinical feature and management of immune thrombocytopenic purpura in a tertiary hospital in Northwest Nigeria

PubMed Central

Hassan, Abdulaziz; Adebayo, Adeshola; Musa, Abubakar Umar; Suleiman, Aishatu Maude; Ibrahim, Ismaila Nda; Kusfa, Ibrahim Usman; Aminu, Mohammed Sirajo

2017-01-01

Background: Immune thrombocytopenic purpura (ITP) is a rare bleeding disorder that may remit spontaneously. Life-threatening bleeding may require transfusion support, steroids, and other immunosuppressive therapy or splenectomy. Objective: To review the clinical presentation and laboratory features of ITP at Ahmadu Bello University Teaching Hospital (ABUTH), Zaria, Nigeria. Subjects and Methods: A retrospective analytic study of case notes and bone marrow (BM) records of patients diagnosed with ITP at Haematology Department, ABUTH, Zaria, from January 1, 2004, to December 31, 2012. Results: There were nine cases (six females, three males), aged 6–20 (mean 11.11) years. The presentations were epistaxis 8 (88.9%), purpura 4 (44.4%), gum bleeding 4 (44.4%), menorrhagia 2 (22.2%), and intracranial hemorrhage (ICH) 1 (11.1%). Only 1 (11.1%) had clinical splenomegaly. Platelet count of <20 × 109/L was found in 4 (44.4%) while 6 (66.7%) had packed cell volume of <25%. All the nine cases had BM megakaryocytic hyperplasia. Six patients had blood transfusion support while 7 (77.8%) patients received oral prednisolone therapy with time to cessation of bleeding of 12–16 (mean of 8) weeks. One case had spontaneous remission while another had anti-D due to relapse after steroid therapy; this resulted in transient rise in platelet counts. None had other immunosuppressive therapy or splenectomy. Six (66.7%) cases were lost to follow-up after achieving remission and one died of ICH. Conclusion: ITP is not common in our center though its clinical presentations are varied. However, prednisolone and blood transfusion therapy are central to the management of these patients with favorable outcome. PMID:29269984

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.

Managing iliofemoral deep venous thrombosis of pregnancy with a strategy of thrombus removal is safe and avoids post-thrombotic morbidity.

PubMed

Herrera, Santiago; Comerota, Anthony J; Thakur, Subhash; Sunderji, Shiraz; DiSalle, Robert; Kazanjian, Sahira N; Assi, Zakaria

2014-02-01

Extensive deep venous thrombosis (DVT) during pregnancy is usually treated with anticoagulation alone, risking significant post-thrombotic syndrome (PTS) in young patients. Catheter-directed thrombolysis (CDT) and operative venous thrombectomy have been safely and effectively used in nonpregnant patients, demonstrating significant reduction in post-thrombotic morbidity. This report reviews short- and long-term outcomes of 13 patients with extensive DVT of pregnancy treated with a strategy of thrombus removal. From 1999 to 2013, 13 patients with iliofemoral DVT during pregnancy were offered CDT, pharmacomechanical thrombolysis (PMT), and/or venous thrombectomy. Gestational age ranged from 8 to 34 weeks. Fetal monitoring was performed throughout hospitalization. Radiation exposure was minimized with pelvic lead shields, focal fluoroscopy, and limited angiographic runs. Follow-up included objective vein evaluation using venous duplex and PTS assessment using the Villalta scale. CDT and/or PMT were used in 11 patients. Two patients underwent venous thrombectomy alone, and one patient had operative thrombectomy as an adjunct to CDT and PMT. Each patient had complete or near-complete thrombus resolution and rapid improvement in clinical symptoms. Eight of 11 having CDT or PMT underwent venoplasty and stenting of the involved iliac veins. Twelve of the 13 delivered healthy infants at term. One patient opted for termination of her pregnancy. Mean patient and gestational ages were 26 years and 26 weeks, respectively. Mean follow-up was 1.3 years, with only one recurrence. Duplex ultrasonography demonstrated patent veins in all but one patient and normal valve function in 10 patients. Eleven patients had Villalta scores <5 (considered normal), with a mean score of 0.7. Extensive DVT of pregnancy can be effectively and safely treated with a strategy of thrombus removal, resulting in a patent venous system, normal valve function in many, prevention of PTS, and reduction in

Targeting factor VIII expression to platelets for hemophilia A gene therapy does not induce an apparent thrombotic risk in mice.

PubMed

Baumgartner, C K; Mattson, J G; Weiler, H; Shi, Q; Montgomery, R R

2017-01-01

Essentials Platelet-Factor (F) VIII gene therapy is a promising treatment in hemophilia A. This study aims to evaluate if platelet-FVIII expression would increase the risk for thrombosis. Targeting FVIII expression to platelets does not induce or elevate thrombosis risk. Platelets expressing FVIII are neither hyper-activated nor hyper-responsive. Background Targeting factor (F) VIII expression to platelets is a promising gene therapy approach for hemophilia A, and is successful even in the presence of inhibitors. It is well known that platelets play important roles not only in hemostasis, but also in thrombosis and inflammation. Objective To evaluate whether platelet-FVIII expression might increase thrombotic risk and thereby compromise the safety of this approach. Methods In this study, platelet-FVIII-expressing transgenic mice were examined either in steady-state conditions or under prothrombotic conditions induced by inflammation or the FV Leiden mutation. Native whole blood thrombin generation assay, rotational thromboelastometry analysis and ferric chloride-induced vessel injury were used to evaluate the hemostatic properties. Various parameters associated with thrombosis risk, including D-dimer, thrombin-antithrombin complexes, fibrinogen, tissue fibrin deposition, platelet activation status and activatability, and platelet-leukocyte aggregates, were assessed. Results We generated a new line of transgenic mice that expressed 30-fold higher levels of platelet-expressed FVIII than are therapeutically required to restore hemostasis in hemophilic mice. Under both steady-state conditions and prothrombotic conditions induced by lipopolysaccharide-mediated inflammation or the FV Leiden mutation, supratherapeutic levels of platelet-expressed FVIII did not appear to be thrombogenic. Furthermore, FVIII-expressing platelets were neither hyperactivated nor hyperactivatable upon agonist activation. Conclusion We conclude that, in mice, more than 30-fold higher levels of

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. Copyright © 2016 Elsevier Inc. All rights reserved.

A new paradigm: Diagnosis and management of HSCT-associated thrombotic microangiopathy as multi-system endothelial injury

PubMed Central

Jodele, Sonata; Laskin, Benjamin L; Dandoy, Christopher E.; Myers, Kasiani C.; El-Bietar, Javier; Davies, Stella M.; Goebel, Jens; Dixon, Bradley P.

2015-01-01

Hematopoietic stem cell transplantation (HSCT)-associated thrombotic microangiopathy (TA-TMA) is now a well-recognized and potentially severe complication of HSCT that carries a high risk of death. In those who survive, TA-TMA may be associated with long-term morbidity and chronic organ injury. Recently, there have been new insights into the incidence, pathophysiology, and management of TA-TMA. Specifically, TA-TMA can manifest as a multi-system disease occurring after various triggers of small vessel endothelial injury, leading to subsequent tissue damage in different organs. While the kidney is most commonly affected, TA-TMA involving organs such as the lung, bowel, heart, and brain is now known to have specific clinical presentations. We now review the most up-to-date research on TA-TMA, focusing on the pathogenesis of endothelial injury, the diagnosis of TA-TMA affecting the kidney and other organs, and new clinical approaches to the management of this complication after HSCT. PMID:25483393

Acquired platelet function defect

MedlinePlus

... Some cases cannot be prevented. Alternative Names Acquired qualitative platelet disorders; Acquired disorders of platelet function Images ... Todd Gersten, MD, Hematology/Oncology, Florida Cancer Specialists & Research Institute, Wellington, FL. Review provided by VeriMed Healthcare ...

A mechanistic investigation of thrombotic microangiopathy associated with IV abuse of Opana ER.

PubMed

Hunt, Ryan; Yalamanoglu, Ayla; Tumlin, James; Schiller, Tal; Baek, Jin Hyen; Wu, Andrew; Fogo, Agnes B; Yang, Haichun; Wong, Edward; Miller, Peter; Buehler, Paul W; Kimchi-Sarfaty, Chava

2017-02-16

Since 2012, a number of case reports have described the occurrence of thrombotic microangiopathy (TMA) following IV abuse of extended-release oxymorphone hydrochloride (Opana ER), an oral opioid for long-term treatment of chronic pain. Here, we present unique clinical features of 3 patients and investigate IV exposure to the tablet's inert ingredients as a possible causal mechanism. Guinea pigs were used as an animal model to understand the hematopathologic and nephrotoxic potential of the inert ingredient mixture (termed here as PEO+) which primarily contains high-molecular-weight polyethylene oxide (HMW PEO). Microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury were found in a group of 3 patients following recent injection of adulterated extended-release oxymorphone tablets. Varying degrees of cardiac involvement and retinal ischemia occurred, with TMA evident on kidney biopsy. A TMA-like state also developed in guinea pigs IV administered PEO+. Acute tubular and glomerular renal injury was accompanied by nonheme iron deposition and hypoxia-inducible factor-1α upregulation in the renal cortex. Similar outcomes were observed following dosing with HMW PEO alone. IV exposure to the inert ingredients in reformulated extended-release oxymorphone can elicit TMA. Although prescription opioid abuse shows geographic variation, all physicians should be highly inquisitive of IV drug abuse when presented with cases of TMA.

Multicenter evaluation of signalment and comorbid conditions associated with aortic thrombotic disease in dogs.

PubMed

Winter, Randolph L; Budke, Christine M

2017-08-15

OBJECTIVE To assess signalment and concurrent disease processes in dogs with aortic thrombotic disease (ATD). DESIGN Retrospective case-control study. ANIMALS Dogs examined at North American veterinary teaching hospitals from 1985 through 2011 with medical records submitted to the Veterinary Medical Database. PROCEDURES Medical records were reviewed to identify dogs with a diagnosis of ATD (case dogs). Five control dogs without a diagnosis of ATD were then identified for every case dog. Data were collected regarding dog age, sex, breed, body weight, and concurrent disease processes. RESULTS ATD was diagnosed in 291 of the 984,973 (0.03%) dogs included in the database. The odds of a dog having ATD did not differ significantly by sex, age, or body weight. Compared with mixed-breed dogs, Shetland Sheepdogs had a significantly higher odds of ATD (OR, 2.59). Protein-losing nephropathy (64/291 [22%]) was the most commonly recorded concurrent disease in dogs with ATD. CONCLUSIONS AND CLINICAL RELEVANCE Dogs with ATD did not differ significantly from dogs without ATD in most signalment variables. Contrary to previous reports, cardiac disease was not a common concurrent diagnosis in dogs with ATD.

Haematological manifestations of lupus

PubMed Central

Fayyaz, Anum; Igoe, Ann; Kurien, Biji T; Danda, Debashish; James, Judith A; Stafford, Haraldine A; Scofield, R Hal

2015-01-01

Our purpose was to compile information on the haematological manifestations of systemic lupus erythematosus (SLE), namely leucopenia, lymphopenia, thrombocytopenia, autoimmune haemolytic anaemia (AIHA), thrombotic thrombocytopenic purpura (TTP) and myelofibrosis. During our search of the English-language MEDLINE sources, we did not place a date-of-publication constraint. Hence, we have reviewed previous as well as most recent studies with the subject heading SLE in combination with each manifestation. Neutropenia can lead to morbidity and mortality from increased susceptibility to infection. Severe neutropenia can be successfully treated with granulocyte colony-stimulating factor. While related to disease activity, there is no specific therapy for lymphopenia. Severe lymphopenia may require the use of prophylactic therapy to prevent select opportunistic infections. Isolated idiopathic thrombocytopenic purpura maybe the first manifestation of SLE by months or even years. Some manifestations of lupus occur more frequently in association with low platelet count in these patients, for example, neuropsychiatric manifestation, haemolytic anaemia, the antiphospholipid syndrome and renal disease. Thrombocytopenia can be regarded as an important prognostic indicator of survival in patients with SLE. Medical, surgical and biological treatment modalities are reviewed for this manifestation. First-line therapy remains glucocorticoids. Through our review, we conclude glucocorticoids do produce a response in majority of patients initially, but sustained response to therapy is unlikely. Glucocorticoids are used as first-line therapy in patients with SLE with AIHA, but there is no conclusive evidence to guide second-line therapy. Rituximab is promising in refractory and non-responding AIHA. TTP is not recognised as a criteria for classification of SLE, but there is a considerable overlap between the presenting features of TTP and SLE, and a few patients with SLE have concurrent

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. Copyright 2000 Wiley-Liss, Inc.

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. © 2015 John Wiley & Sons Ltd.

Antiphospholipid antibodies and antiphospholipid syndrome in patients presenting with immune thrombocytopenic purpura: a prospective cohort study.

PubMed

Diz-Küçükkaya, R; Hacihanefioğlu, A; Yenerel, M; Turgut, M; Keskin, H; Nalçaci, M; Inanç, M

2001-09-15

The pathogenetic role and the clinical importance of the presence of antiphospholipid antibodies (APAs) in patients with immune thrombocytopenic purpura (ITP) are not clear. In this study, the prevalence and clinical significance of APAs were investigated in patients with ITP. Eighty-two newly diagnosed ITP patients were prospectively studied. They were evaluated for the presence of lupus anticoagulant (LA) and immunoglobulin G/M anticardiolipin antibodies (ACAs). Thirty-one patients (37.8%) were APA positive at diagnosis. No statistically significant differences were found between the APA-positive and APA-negative groups regarding gender, initial platelet counts, or response to methylprednisolone therapy. After 5 years of follow-up, cumulative thrombosis-free survival of APA-positive (n = 31) and APA-negative (n = 51) ITP patients was 39% and 97.7%, respectively. A significant difference was found between these groups by log-rank test (P =.0004). In addition, LA was an important risk marker for the development of thrombosis in ITP patients. After a median follow-up of 38 months, 14 ITP patients (45%) who had APA positivity developed clinical features (thrombosis or fetal losses) of antiphospholipid syndrome (APS). There were no differences between the APA-positive patients with and without APS regarding the initial platelet counts, response to the therapy, or ACA positivity. The positivity rate for LA was significantly higher in those patients with ITP who developed APS (chi(2): P =.0036; relative risk 7.15; 95% confidence interval, 1.7-47). In conclusion, this study indicates that a significant proportion of patients initially presenting with ITP and APA positivity developed APS. In patients with ITP, the persistent presence of APAs is an important risk factor for the development of APS.

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

PubMed Central

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

2015-01-01

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

Therapeutic Suggestions for Chronic Subdural Hematoma Associated with Idiopathic Thrombocytopenic Purpura: A Case Report and Literature Review

PubMed Central

Takase, Hajime; Tatezuki, Junya; Ikegaya, Naoki; Yamamoto, Daisuke; Hashimoto, Mizuki; Takagi, Makoto; Mochimatsu, Yasuhiko; Kawahara, Nobutaka

2015-01-01

A 66-year-old woman who was previously diagnosed with idiopathic thrombocytopenic purpura (ITP) presented with mild right-sided hemiparesis and drowsiness. Head computed tomography (CT) imaging demonstrated a massive left chronic subdural hematoma (CSDH) with a midline shift. Because initial laboratory data showed a significantly decreased blood platelet count (0.3 × 104/mm3), medical treatments such as platelet transfusion, intravenous immunoglobulin (IVIG), and high-dose corticosteroid therapy, were initiated. She clinically and radiologically responded well to these treatments without any surgical intervention. In addition to presenting our case, we searched the PubMed and Ichushi Web databases to comprehensively illustrate clinical characteristics and treatment outcomes of similar cases. Including the present case, we found 19 reports and 23 cases of CSDH associated with ITP in the literature, and assessed 17 reports and 21 cases that were written in English and Japanese. None or mild neurological symptom were seen in 13 cases, and severe, such as coma and hemiparesis, were described in the younger 8 cases with significant difference. All except one were first treated with medical therapies. Most cases of the former group responded well to conservative therapy. On the other hand, most in the latter eventually needed surgical treatment in addition except recent two cases including the present case. CSDH associated with ITP is rarely described, and its management remains controversial. However, this report highlights multiple continuous medical treatments under strict observation and general care might be a useful alternative to avoid surgery in cases presenting with severe neurological deficits and extremely low platelet counts. PMID:28663980

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

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

Code of Federal Regulations, 2010 CFR

2010-04-01

... EXCHANGE COMMISSION FORM AND CONTENT OF AND REQUIREMENTS FOR FINANCIAL STATEMENTS, SECURITIES ACT OF 1933..., INVESTMENT ADVISERS ACT OF 1940, AND ENERGY POLICY AND CONSERVATION ACT OF 1975 Article 8 Financial Statements of Smaller Reporting Companies § 210.8-06 Real estate operations acquired or to be acquired. If...

Impact of chronic Immune Thrombocytopenic Purpura (ITP) on health-related quality of life: a conceptual model starting with the patient perspective

PubMed Central

Mathias, Susan D; Gao, Sue K; Miller, Kimberly L; Cella, David; Snyder, Claire; Turner, Ralph; Wu, Albert; Bussel, James B; George, James N; McMillan, Robert; Wysocki, Diane Kholos; Nichol, Janet L

2008-01-01

Background Immune thrombocytopenic purpura (ITP), a condition characterized by autoimmune-mediated platelet destruction and suboptimal platelet production, is associated with symptoms such as bruising, epistaxis, menorrhagia, mucosal bleeding from the gastrointestinal and urinary tracts and, rarely central nervous system bleeding. The aim of this research is to develop a conceptual model to describe the impact of ITP and its treatment on patients' health-related quality of life (HRQoL). Methods A literature search and focus groups with adult ITP patients were conducted to identify areas of HRQoL affected by ITP. Published literature was reviewed to identify key HRQoL issues and existing questionnaires used to assess HRQoL. Focus group transcripts were reviewed, and common themes were extracted by grouping conceptual categories that described the impact on HRQoL. Results The literature synthesis and themes from the focus group data suggest that decreased platelet counts, disease symptoms, and treatment side effects influence multiple domains of HRQoL for ITP patients. Key areas affected by ITP and its treatments include emotional and functional health, work life, social and leisure activities, and reproductive health. Conclusion ITP affects various areas of HRQoL. This conceptual model will help inform the evaluation of therapeutic strategies for ITP. PMID:18261217

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. Effective...

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. Effective...

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. Effective...

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. Effective...

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

PubMed

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

2007-12-01

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

Bilateral visual loss and cerebral infarction after spleen embolization in a trauma patient with idiopathic thrombocytopenic purpura: A case report.

PubMed

Wang, Wei-Ting; Li, Yu-Yu; Lin, Wan-Ching; Chen, Jen-Yin; Lan, Kuo-Mao; Sun, Cheuk-Kwan; Hung, Kuo-Chuan

2018-04-01

Splenic artery embolization (SAE) is a common procedure in trauma patients with blunt splenic injuries. We report a case of acute ischemic stroke following orthopedic surgery in a patient with post-SAE reactive thrombocytosis. A 37-year-old woman with idiopathic thrombocytopenic purpura (ITP) suffered from multiple trauma scheduled for open reduction and internal fixation for right tibial and left radius fracture five days after SAE. The patient did not have any thromboembolic complications, although the platelet counts increased from 43 × 10/L to 568 × 10/L within two days after SAE. Surgery was completed under general anesthesia with tracheal intubation without complications. The patient complained of visual loss followed by limb weakness on the fourth and eighth hour postoperatively. Magnetic resonance imaging (MRI) of head demonstrated ischemic change over bilateral basal ganglia, and occipital areas, suggesting the diagnosis of cortical blindness. To suppress platelet count and avoid platelet hyper-aggregation, anti-platelet drug (i.e., oral aspirin 100 mg daily), hydration, and hydroxyurea (i.e., 20 mg/kg daily) were used for the treatment of reactive thrombocytosis. Although right-sided hemiparesis persisted, the patient reported mild visual recovery. She was discharged four months after SAE with active rehabilitation. Our report highlights an increased risk of acute arterial thromboembolic events in patients with reactive thrombocytosis, especially those undergoing surgery.

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

Ocular Blood Flow Changes in Behçet Disease Patients with/without Thrombotic Disease

PubMed Central

Yüksel, Harun; Türkcü, Fatih M.; Hamidi, Cihat; Cingü, Abdullah K.; Çinar, Yasin; Şahin, Muhammed; Özkurt, Zeynep; Çaça, İhsan

2014-01-01

ABSTRACT In this study, the authors aimed to evaluate ocular blood flow changes in Behçet disease (BD) with and without thrombotic disease. Ninety eyes of 90 patients with a diagnosis of BD (30 eyes with active uveitis, 23 eyes with inactive uveitis, 25 eyes without ocular involvement, and 12 eyes without ocular involvement and with a history of thrombosis) and 30 eyes of 30 age- and sex-matched control patients without any systemic disease with a total of 120 eyes were evaluated. In all cases, ophthalmic, central retinal, and ciliary artery flow parameters were measured with colour Doppler ultrasonography (CDU). The ocular blood flow parameters of all vessels in patients with active uveitis were found to be affected. All the flow parameters in the CRAs of the study groups were significantly different from the control group (p < 0.001). Additionally, in non-ocular BD patients with thrombosis, blood flow parameters were affected more than the parameters in non-ocular BD patients without thrombosis and control patients. In conclusion, major haemodynamic changes were observed using CDU in the ophthalmic vessels of ocular Behçet patients. Also, CDU may detect ocular blood flow alterations before initial ocular clinical manifestations appear in BD patients PMID:27928286

Ocular Blood Flow Changes in Behçet Disease Patients with/without Thrombotic Disease.

PubMed

Yüksel, Harun; Türkcü, Fatih M; Hamidi, Cihat; Cingü, Abdullah K; Çinar, Yasin; Şahin, Muhammed; Özkurt, Zeynep; Çaça, İhsan

2014-01-01

In this study, the authors aimed to evaluate ocular blood flow changes in Behçet disease (BD) with and without thrombotic disease. Ninety eyes of 90 patients with a diagnosis of BD (30 eyes with active uveitis, 23 eyes with inactive uveitis, 25 eyes without ocular involvement, and 12 eyes without ocular involvement and with a history of thrombosis) and 30 eyes of 30 age- and sex-matched control patients without any systemic disease with a total of 120 eyes were evaluated. In all cases, ophthalmic, central retinal, and ciliary artery flow parameters were measured with colour Doppler ultrasonography (CDU). The ocular blood flow parameters of all vessels in patients with active uveitis were found to be affected. All the flow parameters in the CRAs of the study groups were significantly different from the control group ( p  < 0.001). Additionally, in non-ocular BD patients with thrombosis, blood flow parameters were affected more than the parameters in non-ocular BD patients without thrombosis and control patients. In conclusion, major haemodynamic changes were observed using CDU in the ophthalmic vessels of ocular Behçet patients. Also, CDU may detect ocular blood flow alterations before initial ocular clinical manifestations appear in BD patients.

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

PubMed

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

2012-04-19

The assessment of rare adverse events following vaccination may not be possible within a single country due to an insufficiently large denominator population. In 2008 a European consortium (VAESCO) was funded to perform collaborative vaccine safety studies. To help assess the feasibility of multi-country collaboration England and Denmark, who have established vaccine safety research infrastructures, undertook to work to a common protocol and share results and data to estimate the risk of a known true adverse event, thrombocytopenic purpura (TP) following measles-mumps-rubella (MMR) vaccination. TP is a known rare reaction to MMR and therefore provided an opportunity to assess whether two countries would produce similar results when working collaboratively. Despite some initial problems with ensuring data were comparable, the two countries gave very similar estimates of the relative incidence in the 6 weeks after vaccination and a pooled relative incidence estimate of 2.13 (95% confidence interval 1.55-2.94) and attributable risk of 1 in 50,000 doses. Both countries used hospital admissions for TP and the analysis was performed using the self controlled case series method which is particularly suited to collaborative studies because of its implicit control for individual level confounding. The study therefore shows the potential for vaccine safety collaborations across Europe to detect true associations through use of common protocols and sharing of results or data. Copyright © 2011 Brighton Collaboration. Published by Elsevier Ltd.. All rights reserved.

Mechanisms of smooth muscle antibody production: a clinical study in children with infections, haemolytic syndromes, and idiopathic thrombocytopenic purpura.

PubMed Central

Kanakoudi-Tsakalidis, F; Cassimos, C; Papastavrou-Mavroudi, T; Akoglu, T; Toh, B H; Yildiz, A; Osung, O; Holborow, E J; Sotelo, J

1979-01-01

Sera from 530 children suffering from various diseases and from 64 controls were tested for smooth muscle autoantibodies (SMA) by indirect immunofluorescence. A high incidence of SMA (51-86%) was found in patients with viral and bacterial infections (viral hepatitis, infectious mononucleosis, measles, mumps, chickenpox, typhoid fever, and brucellosis), independently of liver invovlvement, and in patients with acute haemolytic anaemia due to G-6-PD deficiency (48%). By contrast, the incidence of SMA from patients with beta-thalassaemia major and idiopathic thrombocytopenic purpura was no higher than in the controls. The discrepancy in incidence in haemolytic anaemias due to different causes may reflect the effect of endogenous and extrinsic agents. In the viral infections, SMA were mainly of the IgM class and gave an 'SMA-V' staining pattern. In bacterial infections (typhoid fever and brucellosis), SMA were either IgG only or IgM and IgG, and the staining pattern was also mainly 'SMA-V'. In infections which affect or may affect the liver (viral hepatitis, infectious mononucleosis, typhoid fever, and brucellosis), SMA was present at high titres (1:80-1:320), whereas in infections not affecting the liver (measles, mumps, and chickenpox) the titres were lower (less than or equal to 1:80). In most patients SMA occurred transiently and without apparent pathogenetic significance. The antigen against which infection-induced SMA is directed is not actin; its nature has yet to be identified. PMID:575362

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.

Venous thrombotic events in hospitalized children and adolescents with inflammatory bowel disease.

PubMed

Nylund, Cade M; Goudie, Anthony; Garza, Jose M; Crouch, Gary; Denson, Lee A

2013-05-01

Adults with inflammatory bowel disease (IBD) have an increased risk of venous thrombotic events (TEs). We sought to evaluate the risk for TE in children and adolescents with IBD using a large population database. The triennial Healthcare Cost and Utilization Project Kids' Inpatient Database was used in a retrospective cohort study of hospitalized children in the United States across 1997, 2000, 2003, 2006, and 2009. Billing codes were used to identify discharges with Crohn disease, ulcerative colitis, pulmonary embolism, deep vein thrombosis, thrombophlebitis, thrombosis of intracranial venous sinus, Budd-Chiari syndrome, and portal vein thrombosis. A logistic regression model was fitted to quantify the increased risk of TE in children with IBD, while adjusting for other risk factors of thrombosis. The total weighted number of pediatric discharges was 7,448,292, and 68,394 (0.92%) were identified with IBD. The incidence of any TE in a hospitalized child or adolescent with IBD was 117.9/10,000 with a relative risk (95% confidence interval) of 2.36 (2.15-2.58). The adjusted odds ratio for any TE in a patient with IBD without surgery was 1.22 (1.08-1.36). Risk factors for TE among patients with IBD include older age, central venous catheter, parenteral nutrition, and an identified hypercoagulable condition. There is an increasing trend of TE in both the IBD and non-IBD patients. Hospitalized children and adolescents with IBD are at increased risk for TE. Conservative methods of TE prevention including hydration, mobilization, or pneumatic devices should be considered in hospitalized patients with IBD.

7 CFR 926.10 - Acquire.

Code of Federal Regulations, 2010 CFR

2010-01-01

... of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements and... 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. Effective...

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. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Measurement of utility values in the UK for health states related to immune thrombocytopenic purpura.

PubMed

Szende, Agota; Brazier, John; Schaefer, Caroline; Deuson, Robert; Isitt, John J; Vyas, Paresh

2010-08-01

To measure utility values associated with immune (idiopathic) thrombocytopenic purpura (ITP), as perceived by the United Kingdom (UK) general public. A multi-step process, including clinical trial data, literature review, and patient focus group, was used to develop ITP health states valued in a web survey. Six ITP health states were defined based on platelet levels, risk of bleeding and key adverse events/disease complications. Clinical trial data on bleeding and ITP-specific quality of life data were key sources for developing health-state descriptions. 359 respondents, randomly selected from a managed web panel in the UK, completed the web-based Time Trade-Off survey. Wilcoxon signed-rank test was used to compare differences between each pair of health states. Sample characteristics (mean age: 47.9 +/- 16.9 years; 54% female) were comparable to the UK general population. ITP health states were valued as significantly worse than perfect health. Experiencing bleeding episodes was a more important driver than low platelet levels in valuing a health state to be worse. Substantial disutilities were associated with surviving an intracranial haemorrhage. Mean (SD) utility values for each ITP health state are: HS1: platelets >or=50 x 10(9)/L, no outpatient bleed: 0.863 +/- 0.15; HS2: platelets >or=50 x 10(9)/L, outpatient bleed: 0.734 +/- 0.19; HS3: platelets <50 x 10(9)/L, no outpatient bleed: 0.841 +/- 0.19; HS4: platelets <50 x 10(9)/L, outpatient bleed: 0.732 +/- 0.19; HS5: intracranial haemorrhage (2-6 months): 0.038 +/- 0.46; HS6: steroid treatment adverse events: 0.758 +/- 0.20. Potential limitations relate to web user population characteristics and lack of comparative testing of web-based TTO methods. Results provide evidence that the UK general population associate substantial loss of value living with ITP, suggesting an important role for new ITP treatments. Utility values based on these health states may be useful in future cost-effectiveness studies of

Hospital-acquired pneumonia

MedlinePlus

... pneumonia; HCAP Patient Instructions Pneumonia in adults - discharge Images Hospital-acquired pneumonia Respiratory system References Chastre J, Luyt C-E. Ventilator-associated pneumonia. In: Broaddus ...

Children Acquire Emotion Categories Gradually

ERIC Educational Resources Information Center

Widen, Sherri C.; Russell, James A.

2008-01-01

Some accounts imply that basic-level emotion categories are acquired early and quickly, whereas others imply that they are acquired later and more gradually. Our study examined this question for fear, happiness, sadness, and anger in the context of children's categorization of emotional facial expressions. Children (N=168, 2-5 years) first labeled…

Ensuring the profitability of acquired physician practices.

PubMed

Ortiz, J P

1997-01-01

Healthcare organizations are aggressively acquiring physician group practices to create primary care networks and broaden their managed care market penetration. However, few are realizing a positive return on investment after acquisition. The odds that acquired practices will be profitable can be improved if healthcare organizations plan carefully by establishing separate acquiring entities, setting clear goals for the practices, forming skilled management teams with strong physician leadership to manage the acquired practices, and carefully structuring their physician incentive compensation plans.

Clinical use of a rapid collagen binding assay for von Willebrand factor cleaving protease in patients with thrombotic thrombocytopenic purpura.

PubMed

Rick, Margaret E; Moll, Stephan; Taylor, Mark A; Krizek, Dennis M; White, Gilbert C; Aronson, David L

2002-10-01

A simple collagen binding assay (CBA) for measuring activity of the von Willebrand factor cleaving protease in clinical samples is described, and results of fifty masked plasmapheresis samples rom patients with TTP/HUS and other diseases are presented. There was 97.5% concordance between the CBA and a multimer gel assay. The CBA identified low protease activity in 78% of patients who had a clinical syndrome consistent with TTP/HUS and in 2 of 10 sick controls, giving it a positive predictive value of 0.94. The heterogeneity regarding the presence or absence of vWF protease activity in patients with TTP/HUS was confirmed by finding a low negative predictive value of 0.50 with the CBA. The CBA detected inhibitors of the protease in 26 of 29 patients (90%) with TTP/HUS and low protease activity levels. The CBA is a useful clinical assay for examining von Willebrand factor protease activity and detecting inhibitors against the protease.

An update on acquired nystagmus.

PubMed

Rucker, Janet C

2008-01-01

Proper evaluation and treatment of acquired nystagmus requires accurate characterization of nystagmus type and visual effects. This review addresses important historical and examination features of nystagmus and current concepts of pathogenesis and treatment of gaze-evoked nystagmus, nystagmus due to vision loss, acquired pendular nystagmus, peripheral and central vestibular nystagmus, and periodic alternating nystagmus.

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 format...

Health-related quality of life of immune thrombocytopenic purpura patients: results from a web-based survey.

PubMed

Snyder, Claire F; Mathias, Susan D; Cella, David; Isitt, John J; Wu, Albert W; Young, Joan

2008-10-01

To assess the health-related quality of life (HRQOL) of immune thrombocytopenic purpura (ITP) patients. This was a cross-sectional, descriptive study comparing ITP patients' HRQOL to age and gender matched controls. ITP patients from the Platelet Disorder Support Association were recruited until 1000 surveys had been completed. Controls were randomly sampled from the Harris Interactive Online Panel. ITP patients and controls completed a one-time web-based survey, including a comprehensive HRQOL assessment. ITP patients completed the SF-36, the EQ-5D, and the ITP-Patient Assessment Questionnaire (ITP-PAQ). Controls completed the SF-36 and EQ-5D only. ITP patients' SF-36 and EQ-5D scores were compared to controls in unadjusted and adjusted analyses. Associations between splenectomy status, duration of illness, and platelet count with ITP patients' HRQOL scores were also examined. This analysis included 1002 ITP patients and 1031 controls. ITP patients scored worse on seven of eight SF-36 domains and the Physical and Mental Summary scores (all p < 0.05) and on the EQ-5D visual analog scale (65.5 vs. 82.3; p = 0.002). ITP patients who had undergone splenectomy had similar SF-36 and EQ-5D scores to non-splenectomy patients but scored significantly worse on 5 of 10 ITP-PAQ scales: Bother, Psychological, Fear, Social Activity, and Work (all p < 0.05). ITP patients diagnosed within the past 5 years had worse Bother and Overall Quality of Life scores than less recently diagnosed patients but were similar on other ITP-PAQ scales. Lower platelet count was consistently associated with worse ITP-PAQ scores and had weaker associations with SF-36 and EQ-5D scores. ITP was associated with consistent and statistically significant deficits on generic HRQOL measures. The ITP-PAQ demonstrated differences based on disease severity and treatments. The self-selection bias in the two samples limits the generalizability of the results to all patients with ITP. Further research is needed in

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

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.

Aspirin Is Associated with Improved Survival in Severely Thrombocytopenic Cancer Patients with Acute Myocardial Infarction.

PubMed

Feher, Attila; Kampaktsis, Polydoros N; Parameswaran, Rekha; Stein, Eytan M; Steingart, Richard; Gupta, Dipti

2017-02-01

Patients with hematologic malignancies are at risk for severe thrombocytopenia (sTP). The risk and benefit of aspirin are not known in thrombocytopenic cancer patients experiencing acute myocardial infarction (AMI). Medical records of patients with hematologic malignancies diagnosed with AMI at Memorial Sloan Kettering Cancer Center during 2005-2014 were reviewed. sTP was defined as a platelet count <50,000 cells per µL within 7 days of AMI. Of 118 patients with hematologic malignancies who had AMI, 58 (49%) had sTP. Twenty-five patients (43%) with sTP received aspirin as a treatment for AMI. Compared with patients without sTP with AMI, patients with sTP with AMI were less likely to receive aspirin (83% vs. 43%; p  = .0001) and thienopyridine treatment (27% vs. 3%; p  = .0005). During median follow-up of 3.7 years after AMI, survival was lower in patients with sTP than in those with no sTP (23% vs. 50% at 1 year; log rank p  = .003). Patients with sTP who received aspirin for AMI had improved survival compared with those who did not (92% vs. 70% at 7 days, 72% vs. 33% at 30 days, and 32% vs. 13% at 1 year; log rank p  = .008). In multivariate regression models, aspirin use was associated with improved 30-day survival both in the overall patient cohort and in sTP patients. No fatal bleeding events occurred. Major bleeding was not associated with sTP or aspirin use. Treatment of AMI with aspirin in patients with hematologic malignancies and sTP is associated with improved survival without increase in major bleeding. The Oncologist 2017;22:213-221 Implications for Practice: In patients with hematologic malignancies and acute myocardial infarction with severe thrombocytopenia (platelet count < 50,000 cells/µL), guideline-recommended medical therapy is often withheld because of the fear of major bleeding. In this study, aspirin therapy was associated with improved survival without an increase in major bleeding in this high-risk patient cohort. �

Compression stockings significantly improve hemodynamic performance in post-thrombotic syndrome irrespective of class or length.

PubMed

Lattimer, Christopher R; Azzam, Mustapha; Kalodiki, Evi; Makris, Gregory C; Geroulakos, George

2013-07-01

Graduated elastic compression (GEC) stockings have been demonstrated to reduce the morbidity associated with post-thrombotic syndrome. The ideal length or compression strength required to achieve this is speculative and related to physician preference and patient compliance. The aim of this study was to evaluate the hemodynamic performance of four different stockings and determine the patient's preference. Thirty-four consecutive patients (40 legs, 34 male) with post-thrombotic syndrome were tested with four different stockings (Mediven plus open toe, Bayreuth, Germany) of their size in random order: class 1 (18-21 mm Hg) and class II (23-32 mm Hg), below-knee (BK) and above-knee thigh-length (AK). The median age, Venous Clinical Severity Score, Venous Segmental Disease Score, and Villalta scale were 62 years (range, 31-81 years), 8 (range, 1-21), 5 (range, 2-10), and 10 (range, 2-22), respectively. The C of C0-6EsAs,d,pPr,o was C0 = 2, C2 = 1, C3 = 3, C4a = 12, C4b = 7, C5 = 12, C6 = 3. Obstruction and reflux was observed on duplex in 47.5% legs, with deep venous reflux alone in 45%. Air plethysmography was used to measure the venous filling index (VFI), venous volume, and time to fill 90% of the venous volume. Direct pressure measurements were obtained while lying and standing using the PicoPress device (Microlab Elettronica, Nicolò, Italy). The pressure sensor was placed underneath the test stocking 5 cm above and 2 cm posterior to the medial malleolus. At the end of the study session, patients stated their preferred stocking based on comfort. The VFI, venous volume, and time to fill 90% of the venous volume improved significantly with all types of stocking versus no compression. In class I, the VFI (mL/s) improved from a median of 4.9 (range, 1.7-16.3) without compression to 3.7 (range, 0-14) BK (24.5%) and 3.6 (range, 0.6-14.5) AK (26.5%). With class II, the corresponding improvement was to 4.0 (range, 0.3-16.2) BK (18.8%) and 3.7 (range, 0.5-14.2) AK (24

Risk Factors for and Management of MPN-Associated Bleeding and Thrombosis.

PubMed

Martin, Karlyn

2017-10-01

The Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) are characterized by both thrombotic and bleeding complications. The purpose of this review is to describe the risk factors associated with bleeding and thrombosis in MPN, as well as to review prevention strategies and management of these complications. Well-described risk factors for thrombotic complications include older age and history of prior thrombosis, along with traditional cardiovascular and venous thromboembolic risk factors. More recently, JAK2 V617F mutation has been found to carry an increased risk of thrombotic complications, whereas CALR has a lower risk than JAK2 mutation. Factors associated with an increased risk of bleeding in MPN include a prior history of bleeding, acquired von Willebrand syndrome, and primary myelofibrosis. Recent findings suggest that thrombocytosis carries a higher risk of bleeding than thrombosis in MPN, and aspirin may exacerbate this risk of bleeding, particularly in CALR-mutated ET. Much of the management of MPN focuses on predicting risk of bleeding and thrombosis and initiating prophylaxis to prevent complications in those at high risk of thrombosis. Emerging evidence suggests that sub-populations may have bleeding risk that outweighs thrombotic risk, particularly in setting of antiplatelet therapy. Future work is needed to better characterize this balance. At present, a thorough assessment of the risks of bleeding and thrombosis should be undertaken for each patient, and herein, we review risk factors for and management of these complications.

Community-acquired bacterial meningitis.

PubMed

van de Beek, Diederik; Brouwer, Matthijs; Hasbun, Rodrigo; Koedel, Uwe; Whitney, Cynthia G; Wijdicks, Eelco

2016-11-03

Meningitis is an inflammation of the meninges and subarachnoid space that can also involve the brain cortex and parenchyma. It can be acquired spontaneously in the community - community-acquired bacterial meningitis - or in the hospital as a complication of invasive procedures or head trauma (nosocomial bacterial meningitis). Despite advances in treatment and vaccinations, community-acquired bacterial meningitis remains one of the most important infectious diseases worldwide. Streptococcus pneumoniae and Neisseria meningitidis are the most common causative bacteria and are associated with high mortality and morbidity; vaccines targeting these organisms, which have designs similar to the successful vaccine that targets Haemophilus influenzae type b meningitis, are now being used in many routine vaccination programmes. Experimental and genetic association studies have increased our knowledge about the pathogenesis of bacterial meningitis. Early antibiotic treatment improves the outcome, but the growing emergence of drug resistance as well as shifts in the distribution of serotypes and groups are fuelling further development of new vaccines and treatment strategies. Corticosteroids were found to be beneficial in high-income countries depending on the bacterial species. Further improvements in the outcome are likely to come from dampening the host inflammatory response and implementing preventive measures, especially the development of new vaccines.

[Fegelers syndrome, acquired port-wine stain or acquired capillary malformation: three cases and a literature review].

PubMed

Freysz, M; Cribier, B; Lipsker, D

2013-05-01

Port-wine stains or capillary malformations are generally congenital. Very few cases of acquired port-wine stains in adults have been described, and these occur particularly after trauma. We report three cases of acquired port-wine stains and we performed a review of the literature using the keywords "port-wine stain", "capillary malformation", "angioma" and "acquired" in the Medline database PubMed. All relevant articles were included. Two male patients and one female patient consulted for one or more angiomatous lesions, located respectively on the upper rear part of the right thigh (case 1), the left leg (case 2) and the right side of the face, skull and chest (case 3). Each patient's skin biopsy was consistent with port-wine stain. The three patients asserted the acquired nature of the lesions: the male patients were respectively 17 and 38 years old, and the female patient was 11 years old. No causative factors were evident preceding the lesion, and there was no family history of port-wine stain. The topography was systematic in patients 2 and 3. The lesions were light red in patient 1, dark red in patient 2 and pale pink in patient 3. The remainder of the physical examination was unremarkable, except for benign angiokeratoma of the scrotum in case 1 and pigmented leucoderma-type macules in case 3. LITERATURE RESULTS: Sixty-six cases of acquired port-wine stains were reported in the literature. The average age was 25 years (3-69) with a sex-ratio of 0.88. Generally, no causative factor was given. However, trauma (30.5%), estrogenic impregnation (16.5%), and more rarely, medication, solar damage, frostbite, cluster headache, herpes zoster and acoustic neuroma were reported as causatives factors. Acquired port-wine stain is rare. Although often idiopathic, it can result from spinal trauma, which must be explored if suggested by the history. In our series, the clinical presentation suggested a latent congenital vascular malformation of late onset, in particular in

Use of Belatacept as Alternative Immunosuppression in Three Renal Transplant Patients with De Novo Drug-Induced Thrombotic Microangiopathy

PubMed Central

Cicora, Federico; Paz, Marta; Mos, Fernando; Roberti, Javier

2013-01-01

Thrombotic microangiopathy (TMA), a severe complication of renal transplantation, is a pathological process involving microvascular occlusion, thrombocytopenia, and microangiopathic hemolytic anemia. It generally appears within the first weeks after transplantation, when immunosuppressive drugs are used at high doses. De novo TMA may also be drug-induced when calcineurin inhibitors or proliferation signal inhibitors are used. We report three cases of de novo drug-induced TMA in renal transplant patients who were managed by replacing calcineurin inhibitors or proliferation signal inhibitors with belatacept, a primary maintenance immunosuppressive drug, which blocks the CD28 costimulation pathway, preventing the activation of T lymphocytes. To identify the cause of TMA, we ruled out HUS, hepatitis C serology, HIV serology, parvovirus B19, cytomegalovirus, anti-HLA antibodies, and prolonged activated partial thromboplastin time. We suspect that the TMA was caused by the calcineurin inhibitors or proliferation signal inhibitors. Belatacept treatment was initiated at a dose of 10 mg/kg on days 1, 5, 14, 28, 60, and 90; maintenance treatment was 5 mg/kg once a month for 1 year. Belatacept, in combination with other agents, prevented graft rejection in three patients. PMID:24198835

Innate Effector-Memory T-Cell Activation Regulates Post-Thrombotic Vein Wall Inflammation and Thrombus Resolution.

PubMed

Luther, Natascha; Shahneh, Fatemeh; Brähler, Melanie; Krebs, Franziska; Jäckel, Sven; Subramaniam, Saravanan; Stanger, Christian; Schönfelder, Tanja; Kleis-Fischer, Bettina; Reinhardt, Christoph; Probst, Hans Christian; Wenzel, Philip; Schäfer, Katrin; Becker, Christian

2016-12-09

Immune cells play an important role during the generation and resolution of thrombosis. T cells are powerful regulators of immune and nonimmune cell function, however, their role in sterile inflammation in venous thrombosis has not been systematically examined. This study investigated the recruitment, activation, and inflammatory activity of T cells in deep vein thrombosis and its consequences for venous thrombus resolution. CD4 + and CD8 + T cells infiltrate the thrombus and vein wall rapidly on deep vein thrombosis induction and remain in the tissue throughout the thrombus resolution. In the vein wall, recruited T cells largely consist of effector-memory T (T EM ) cells. Using T-cell receptor transgenic reporter mice, we demonstrate that deep vein thrombosis-recruited T EM receive an immediate antigen-independent activation and produce IFN-γ (interferon) in situ. Mapping inflammatory conditions in the thrombotic vein, we identify a set of deep vein thrombosis upregulated cytokines and chemokines that synergize to induce antigen-independent IFN-γ production in CD4 + and CD8 + T EM cells. Reducing the number of T EM cells through a depletion recovery procedure, we show that intravenous T EM activation determines neutrophil and monocyte recruitment and delays thrombus neovascularization and resolution. Examining T-cell recruitment in human venous stasis, we show that superficial varicose veins preferentially contain activated memory T cells. T EM orchestrate the inflammatory response in venous thrombosis affecting thrombus resolution. © 2016 American Heart Association, Inc.

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…

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

Platelet participation in the pathogenesis of dermonecrosis induced by Loxosceles gaucho venom.

PubMed

Tavares, F L; Peichoto, M E; Marcelino, J R; Barbaro, K C; Cirillo, M C; Santoro, M L; Sano-Martins, I S

2016-06-01

Loxosceles gaucho spider venom induces in vitro platelet activation and marked thrombocytopenia in rabbits. Herein, we investigated the involvement of platelets in the development of the dermonecrosis induced by L. gaucho venom, using thrombocytopenic rabbits as a model. L. gaucho venom evoked a drop in platelet and neutrophil counts 4 h after venom injection. Ecchymotic areas at the site of venom inoculation were noticed as soon as 4 h in thrombocytopenic animals but not in animals with initial normal platelet counts. After 5 days, areas of scars in thrombocytopenic animals were also larger, evidencing the marked development of lesions in the condition of thrombocytopenia. Histologically, local hemorrhage, collagen fiber disorganization, and edema were more severe in thrombocytopenic animals. Leukocyte infiltration, predominantly due to polymorphonuclears, was observed in the presence or not of thrombocytopenia. Thrombus formation was demonstrated by immunohistochemistry at the microvasculature, and it occurred even under marked thrombocytopenia. Taken together, platelets have an important role in minimizing not only the hemorrhagic phenomena but also the inflammatory and wound-healing processes, suggesting that cutaneous loxoscelism may be aggravated under thrombocytopenic conditions. © The Author(s) 2015.

Corpus callosum demyelination associated with acquired stuttering.

PubMed

Decker, Barbara McElwee; Guitar, Barry; Solomon, Andrew

2018-04-21

Compared with developmental stuttering, adult onset acquired stuttering is rare. However, several case reports describe acquired stuttering and an association with callosal pathology. Interestingly, these cases share a neuroanatomical localisation also demonstrated in developmental stuttering. We present a case of adult onset acquired stuttering associated with inflammatory demyelination within the corpus callosum. This patient's disfluency improved after the initiation of immunomodulatory therapy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A 43-year-old woman with unexplained elevation of hCG.

PubMed

Johnson, Lisa M; Gniadek, Thomas J; Cohn, Claudia S; Bachowski, Gary; Karger, Amy B

2018-05-01

This case report investigates an unusual hCG result in a woman who is not pregnant. A 43-year-old woman was admitted for recurrence of thrombotic thrombocytopenic purpura (TTP) and therapeutic plasma exchange (TPE) was initiated. Prior to transitioning the patient from TPE to immunosuppressive therapy, a serum qualitative hCG test was performed and was positive. Several etiologies for elevated hCG were considered and investigated, including heterophile antibody interference, endogenous hCG from pituitary or malignancy, and exogenous hCG. Retrospective measurement of hCG levels in remnant samples, including a sample obtained prior to TPE initiation, demonstrated that the hCG elevation occurred with plasma administration for TPE. Further investigation with the American Red Cross confirmed that a plasma donor was unknowingly pregnant and in the latter half of the first trimester at the time of donation, when hCG levels peak. In plasma recipients with unexplained hCG elevation, passive transfer of hCG from plasma should be considered in the differential diagnosis. Retrospective measurement of hCG in remnant samples obtained prior to plasma exchange can assist in confirming the source. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Clinical application of a rapid method using agarose gel electrophoresis and Western blotting to evaluate von Willebrand factor protease activity.

PubMed

Kirzek, D M; Rick, M E

2001-03-01

A method for evaluating the activity of the von Willebrand factor (vWF) protease is described, and a clinical application is illustrated. The procedure utilizes gel electrophoresis, Western blotting, and luminographic detection methods to evaluate the distribution of vWF multimers before and after incubation of clinical samples under conditions that favor proteolysis by this enzyme. Physiologically, the high-molecular-weight multimers of vWF are cleaved by the vWF protease under conditions of high shear stress in parts of the arterial circulation; cleavage of vWF multimers is also observed after exposure of vWF to denaturing agents in vitro and thus can serve as a laboratory test for the activity of the protease. vWF protease activity is decreased or absent in patients with thrombotic thrombocytopenic purpura due to an inhibiting autoantibody, and this leads to high levels of noncleaved vWF and to life-threatening thrombosis, thrombocytopenia and anemia. The assay evaluates the activity of the protease by assessing the cleavage of vWF multimers after patient plasmas are incubated in vitro under denaturing conditions. With the use of these electrophoresis and Western blotting techniques, patient plasmas can be rapidly assessed for the activity of the vWF protease which may aid in the treatment strategy for these patients.

[Clinical efficacy of electric stimulation of crural muscles in comprehensive treatment of post-thrombotic disease].

PubMed

Ryzhkin, V V; Lobastov, K V; Vorontsova, A V; Schastlivtsev, I V; Barinov, V E; Naumov, E K; Laberko, L A

The purpose of the study was to evaluate clinical efficacy of electromyostimulation (EMS) of the crural muscles as part of comprehensive therapy for post-thrombotic disease in patients with residual venous obstruction in the femoropopliteal segment. We carried out a prospective comparative clinical study enrolling patients having endured a fist episode of clinically unprovoked venous thrombosis of the femoropopliteal segment and completed the standard 6-month course of anticoagulant therapy and presenting with ultrasonographic signs of complete recanalization of the proximal venous segments (stenosis of 20% and more from the vessel's initial diameter), as well as scoring 5 points and more by the Villalta scale. The study included a total of 60 patients (38 men and 22 women, mean age 58.5±11.4 years) subdivided into two groups consisting of 30 patients each. Patients of both the Study and Control Groups underwent comprehensive therapy including wearing a compression knee sock (23-32 mmHg), a course phlebotrophic drugs, and dosed walking (not less than 5,000 steps a day). The Study Group patients were additionally subjected to daily electrical stimulation of the crural muscles with the "Veinoplus VI" unit (three 30-minute sessions a day). The duration of the follow up amounted to 12 months. The criteria for assessing therapeutic efficacy were as follows: severity of the disease by the VCSS and Villalta scales, quality of life as assessed by the CIVIQ-20 questionnaire, and lack of relapses of the venous thrombus. Clinical and instrumental assessment of the patients' condition was carried out monthly, with the disease's severity and quality of life assesses each 6 months. Relapses of venous thrombosis were registered in 7 (23.3%) patients from the Control Group and were not observed in patients undergoing EMS (p=0.011). In 5 cases, thrombosis was asymptomatic and in 4 cases it was presented by reocclusion of the involved venous segments. Patients of the Study Group

Myelofibrosis and acquired hemophilia A: a case report.

PubMed

Wrobel, Marie; Comio, Emilie; Gay, Valerie; Baroudi, Noureddine; Meyer, Pascal; Chuniaud-Louche, Christine; Hacini, Maya; Pica, Gian Matteo

2016-05-07

Myelofibrosis and acquired hemophilia A is a rare association. To the best of our knowledge only one case of myelofibrosis and acquired hemophilia A has been previously described. A 66-year-old Caucasian man diagnosed with myelofibrosis evolving in acute myeloid leukemia was referred to us for postoperative bleeding. Hemostatic studies showed prolonged activated partial thromboplastin time, decreased factor VIII coagulation, and a high factor VIII inhibitor titer; these findings led to a diagnosis of acquired hemophilia A for which he was treated with methylprednisolone and recombinant activated factor VII on admission. Due to a lack of response he was subsequently treated with rituximab combined with activated prothrombin complex concentrates. Furthermore, he received azacytidine to treat the underlying hematological malignancies. Immunosuppressive rituximab therapy resolved acquired hemophilia A with marked efficacy. Rapid and accurate diagnosis, effective hemostatic therapy, and timely treatment for underlying disease are important in the management of acquired hemophilia A secondary to hematological malignancy.

14 CFR 1274.402 - Contractor acquired property.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Contractor acquired property. 1274.402 Section 1274.402 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION COOPERATIVE AGREEMENTS WITH COMMERCIAL FIRMS Property § 1274.402 Contractor acquired property. As provided in § 1274.923...

Acquired dyslexia in a Turkish-English speaker.

PubMed

Raman, Ilhan; Weekes, Brendan S

2005-06-01

The Turkish script is characterised by completely transparent bidirectional mappings between orthography and phonology. To date, there has been no reported evidence of acquired dyslexia in Turkish speakers leading to the naïve view that reading and writing problems in Turkish are probably rare. We examined the extent to which phonological impairment and orthographic transparency influence reading disorders in a native Turkish speaker. BRB is a bilingual Turkish-English speaker with deep dysphasia accompanied by acquired dyslexia in both languages. The main findings are an effect of imageability on reading in Turkish coincident with surface dyslexia in English and preserved nonword reading. BRB's acquired dyslexia suggests that damage to phonological representations might have a consequence for learning to read in Turkish. We argue that BRB's acquired dyslexia has a common locus in chronic underactivation of phonological representations in Turkish and English. Despite a common locus, reading problems manifest themselves differently according to properties of the script and the type of task.

Isolated acquired factor VII deficiency: review of the literature.

PubMed

Mulliez, Sylvie M N; Devreese, Katrien M J

2016-04-01

Isolated acquired factor VII (FVII) deficiency is a rare haemorrhagic disorder. We report what is currently known about the pathogenesis, clinical features, diagnosis, treatment and prognosis of acquired FVII deficiency. We performed a literature search and included all articles published between 1980 and August 2015. Acquired FVII deficiency has been reported in 42 patients. There are well-established clinical diseases associated with acquired FVII deficiency, most notably infections, malignancy and haematological stem cell transplantation. The exact pathogenesis of the diseases is still unknown, but different pathophysiological hypotheses have been suggested. The clinical manifestation of acquired FVII deficiency varies greatly in severity; asymptomatic course as well as severe life-threatening bleeding diathesis and fatal bleedings have been described.

Acquired Cystic Kidney Disease

MedlinePlus

... care provider about when to begin screening. Eating, Diet, and Nutrition No specific diet will prevent or delay acquired ... Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition Blood Diseases Diagnostic Tests La información de la ...

26 CFR 1.9002-6 - Acquiring corporation.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 13 2012-04-01 2012-04-01 false Acquiring corporation. 1.9002-6 Section 1.9002... (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9002-6 Acquiring corporation. Section 5... a corporation by another corporation in a distribution or transfer described in section 381(a) of...

26 CFR 1.9002-6 - Acquiring corporation.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 26 Internal Revenue 13 2014-04-01 2014-04-01 false Acquiring corporation. 1.9002-6 Section 1.9002... (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9002-6 Acquiring corporation. Section 5... a corporation by another corporation in a distribution or transfer described in section 381(a) of...

26 CFR 1.9002-6 - Acquiring corporation.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 26 Internal Revenue 13 2013-04-01 2013-04-01 false Acquiring corporation. 1.9002-6 Section 1.9002... (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9002-6 Acquiring corporation. Section 5... a corporation by another corporation in a distribution or transfer described in section 381(a) of...

26 CFR 1.9002-6 - Acquiring corporation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 13 2011-04-01 2011-04-01 false Acquiring corporation. 1.9002-6 Section 1.9002... (CONTINUED) INCOME TAXES (CONTINUED) General Actuarial Valuations § 1.9002-6 Acquiring corporation. Section 5... a corporation by another corporation in a distribution or transfer described in section 381(a) of...

Connectionist neuropsychology: uncovering ultimate causes of acquired dyslexia.

PubMed

Woollams, Anna M

2014-01-01

Acquired dyslexia offers a unique window on to the nature of the cognitive and neural architecture supporting skilled reading. This paper provides an integrative overview of recent empirical and computational work on acquired dyslexia within the context of the primary systems framework as implemented in connectionist neuropsychological models. This view proposes that damage to general visual, phonological or semantic processing abilities are the root causes of different forms of acquired dyslexia. Recent case-series behavioural evidence concerning pure alexia, phonological dyslexia and surface dyslexia that supports this perspective is presented. Lesion simulations of these findings within connectionist models of reading demonstrate the viability of this approach. The commitment of such models to learnt representations allows them to capture key aspects of performance in each type of acquired dyslexia, particularly the associated non-reading deficits, the role of relearning and the influence of individual differences in the premorbid state of the reading system. Identification of these factors not only advances our understanding of acquired dyslexia and the mechanisms of normal reading but they are also relevant to the complex interactions underpinning developmental reading disorders.

The predictive value of markers of fibrinolysis and endothelial dysfunction in the post thrombotic syndrome. A systematic review.

PubMed

Rabinovich, Anat; Cohen, Jacqueline M; Kahn, Susan R

2014-06-01

The post thrombotic syndrome (PTS) develops in 20-40% of deep venous thrombosis (DVT) patients. Risk factors for PTS have not been well elucidated. Identification of risk factors would facilitate individualised risk assessment for PTS. We conducted a systematic review to determine whether biomarkers of fibrinolysis or endothelial dysfunction can predict the risk for PTS among DVT patients. Studies were identified by searching the electronic databases PubMed, EMBASE, Scopus and Web of science. We included studies published between 1990 and 2013, measured biomarker levels in adult DVT patients, and reported rates of PTS development. Fourteen studies were included: 11 investigated the association between D-dimer and PTS; three examined fibrinogen; two measured von Willebrand factor; one measured plasminogen activator inhibitor-1; one assessed ADAMTS-13 (A Disintegrin and Metalloprotease with Thrombospondin type 1 repeats) and one measured factor XIII activity. Studies varied with regards to inclusion criteria, definition of PTS, time point and method of biomarker measurement. We were unable to meta-analyse results due to marked clinical heterogeneity. Descriptively, a significant association with PTS was found for D-dimer in four studies and factor XIII in one study. Further prospective research is needed to elucidate whether these markers might be useful to predict PTS development.

26 CFR 1.9002-6 - Acquiring corporation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Acquiring corporation. 1.9002-6 Section 1.9002... (CONTINUED) INCOME TAXES General Actuarial Valuations § 1.9002-6 Acquiring corporation. Section 5(d) of the... corporation by another corporation in a distribution or transfer described in section 381(a) of the Code the...

19 CFR 148.33 - Articles acquired abroad.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 19 Customs Duties 2 2010-04-01 2010-04-01 false Articles acquired abroad. 148.33 Section 148.33... Articles acquired abroad. (a) Exemption. Each returning resident is entitled to bring in free of duty and..., Harmonized Tariff Schedule of the United States (19 U.S.C. 1202), articles for his personal or household use...

19 CFR 148.33 - Articles acquired abroad.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 19 Customs Duties 2 2012-04-01 2012-04-01 false Articles acquired abroad. 148.33 Section 148.33... Articles acquired abroad. (a) Exemption. Each returning resident is entitled to bring in free of duty and..., Harmonized Tariff Schedule of the United States (19 U.S.C. 1202), articles for his personal or household use...

19 CFR 148.33 - Articles acquired abroad.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 19 Customs Duties 2 2014-04-01 2014-04-01 false Articles acquired abroad. 148.33 Section 148.33... Articles acquired abroad. (a) Exemption. Each returning resident is entitled to bring in free of duty and..., Harmonized Tariff Schedule of the United States (19 U.S.C. 1202), articles for his personal or household use...

19 CFR 148.33 - Articles acquired abroad.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 19 Customs Duties 2 2011-04-01 2011-04-01 false Articles acquired abroad. 148.33 Section 148.33... Articles acquired abroad. (a) Exemption. Each returning resident is entitled to bring in free of duty and..., Harmonized Tariff Schedule of the United States (19 U.S.C. 1202), articles for his personal or household use...

19 CFR 148.33 - Articles acquired abroad.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 19 Customs Duties 2 2013-04-01 2013-04-01 false Articles acquired abroad. 148.33 Section 148.33... Articles acquired abroad. (a) Exemption. Each returning resident is entitled to bring in free of duty and..., Harmonized Tariff Schedule of the United States (19 U.S.C. 1202), articles for his personal or household use...

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 to...

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 to...

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 to...

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 to...

Clinical features of dog- and bat-acquired rabies in humans.

PubMed

Udow, Sean J; Marrie, Ruth Ann; Jackson, Alan C

2013-09-01

Clinical differences in rabies due to canine and bat rabies virus variants have been noted, but no detailed studies have been reported to support these observations. Using the Morbidity and Mortality Weekly Report and PubMed, we identified 142 case reports of rabies from North America, South America, Europe, Africa, and Asia. We systematically abstracted 126 selected data elements and compared clinical features and investigation results in dog- and bat-acquired cases of rabies. Survivors and cases acquired from aerosolized viral exposure or tissue/organ transplant were excluded (n = 20). Of 122 cases, 49 (40.2%) were dog-acquired and 54 (44.3%) were bat-acquired. Bat-acquired cases of rabies were more often misdiagnosed and lacked a bite history. Encephalopathy, hydrophobia, and aerophobia were more common in dog-acquired rabies. Abnormal cranial nerve, motor, and sensory examinations, tremor, myoclonus, local sensory symptoms, symptoms at the exposure site, and local symptoms in the absence of a bite or scratch were more common in patients with bat-acquired rabies, as was increased cerebrospinal fluid protein (P = .031). Patients with paralytic rabies had longer survival times than those with encephalitic rabies, and also had shorter incubation periods if they had received postexposure prophylaxis. Clinical differences in dog- and bat-acquired rabies may reflect differences in the route of viral spread of rabies virus variants in the nervous system, although certain variants could cause more severe dysfunction in neuronal subpopulations. Recognition that bat-acquired rabies may present with different clinical manifestations than dog-acquired rabies may help improve the early diagnosis of rabies.

Connectionist neuropsychology: uncovering ultimate causes of acquired dyslexia

PubMed Central

Woollams, Anna M.

2014-01-01

Acquired dyslexia offers a unique window on to the nature of the cognitive and neural architecture supporting skilled reading. This paper provides an integrative overview of recent empirical and computational work on acquired dyslexia within the context of the primary systems framework as implemented in connectionist neuropsychological models. This view proposes that damage to general visual, phonological or semantic processing abilities are the root causes of different forms of acquired dyslexia. Recent case-series behavioural evidence concerning pure alexia, phonological dyslexia and surface dyslexia that supports this perspective is presented. Lesion simulations of these findings within connectionist models of reading demonstrate the viability of this approach. The commitment of such models to learnt representations allows them to capture key aspects of performance in each type of acquired dyslexia, particularly the associated non-reading deficits, the role of relearning and the influence of individual differences in the premorbid state of the reading system. Identification of these factors not only advances our understanding of acquired dyslexia and the mechanisms of normal reading but they are also relevant to the complex interactions underpinning developmental reading disorders. PMID:24324241

Preschoolers acquire general knowledge by sharing in pretense.

PubMed

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 kind of animal). For instance, in one scenario, the nerp ate and disliked a carrot. When subsequently asked generic questions about real nerps, children's responses suggested that they had learned general facts (e.g., nerps dislike carrots). In Experiment 2, thirty-two 4- to 5-year-olds learned from scenarios lacking pretend speech or sound effects. The findings reveal a long overlooked means by which children can acquire generic knowledge. © 2012 The Authors. Child Development © 2012 Society for Research in Child Development, Inc.

Aquatic Toxicity Information Retrieval Data Base (ACQUIRE). Data file

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

The purpose of Acquire is to provide scientists and managers quick access to a comprehensive, systematic, computerized compilation of aquatic toxicity data. Scientific papers published both nationally and internationally on the toxicity of chemicals to aquatic organisms and plants are collected and reviewed for ACQUIRE. Independently compiled data files that meet ACQUIRE parameter and quality assurance criteria are also included. Selected toxicity test results and related testing information for any individual chemical from laboratory and field aquatic toxicity effects are included for tests with freshwater and marine organisms. The total number of data records in ACQUIRE is now over 105,300.more » This includes data from 6000 references, for 5200 chemicals and 2400 test species. A major data file, Acute Toxicity of Organic Chemicals (ATOC), has been incorporated into ACQUIRE. The ATOC file contains laboratory acute test data on 525 organic chemicals using juvenile fathead minnows.« less

Epidemiology of acquired aplastic anaemia in Pakistan.

PubMed

Ehsan, Ayesha; Shah, Shahida Amjad Riaz; Ibrahim, Tayyaba

2011-01-01

Acquired aplastic anaemia is a rare disease which results in morbidity and mortality at a young age. This study was carried out to determine the clinical presentation, haematological parameters and association factors of acquired aplastic anaemia in a cohort of Pakistani patients. This was a cross-sectional study conducted at Haematology Department, Shaikh Zayed Hospital, Lahore over 7 years from June 2000 to July 2007. Eighty-two patients of acquired aplastic anaemia were enrolled in the study by non-probability purposive sampling. Their diagnosis was confirmed by complete blood count, bone marrow aspirate and trephine biopsy. The cohort was classified on the basis of severity and the epidemiological, clinical and haematological parameters were analysed. Of the 82 enrolled patients of acquired aplastic anaemia, 49 (59.8%) were males and 33 (40.2%) were females. Mean age of the patients was 27.93 +/- 18.7 years with a range of 1-80 years. The male to female ratio was 1.48:1. Bone marrow cellularity was less than 25 % in 31 (38.0%) cases and between 25-30% in 51 (62%) of patients. Most of the cases were clinically severe aplastic anaemia (68%). In 62 (76%) of the cases no association factors predisposing to aplastic anaemia could be identified. Acquired Aplastic anaemia is a disease of all ages. In the second decade and the elderly predominantly severe clinical stages were seen. Males presented at a younger age while females presented at all ages with a somewhat similar incidence. No association factors of Aplastic Anaemia could be identified in majority of the patients.

Role of Cannabinoid CB2 Receptor Gene (CNR2) Polymorphism in Children with Immune Thrombocytopenic Purpura in Beni-Suef Governorate in Egypt.

PubMed

Ezzat, Dina A; Hammam, Amira A; El-Malah, Waleed M; Khattab, Rasha A; Mangoud, Eman M

2017-01-01

The cannabinoid system is involved in the immune regulation by modulation of Th cells type 1 and 2. It is composed of the CB2 receptor which is expressed at 10 to 100 folds greater levels on immune cells than the CB1 receptors. The CB2 is encoded by the cannabinoid CB receptor gene (CNR2) gene. This study aims to investigate the polymorphism in CNR2 gene variation rs 35761398 (Q63R) in Egyptian children with immune thrombocytopenic purpura and to investigate the relation between this gene polymorphism and either the susceptibility to or the chronicity of the disease. Forty children diagnosed as ITP were included in this study and 20 healthy children as normal control. CNR2 gene was investigated in those children by PCR RFLP technique (restriction fragment length polymorphism). CNR2 genotyping revealed that 45% of ITP patients had the QR heterotype, 50% had the RR homotype and 5% had QQ, the wild type with significantly higher frequency of homomutant genotype in comparison to controls. The relative odds ratio suggested a double risk for developing ITP in RR homotype (OR 2.152). A significant overpresentation of the RR genotype and of R allele was observed in the chronic patients (P=0.002 and 0.003, respectively). The associated risk to develop chronic ITP increased more than two folds for the RR homotype (OR=2.854). In conclusion, this study confirms the role of CNR2 Q63R polymorphism in the susceptibility to ITP in children and chronicity of the disease. Copyright© by the Egyptian Association of Immunologists.

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

Length of stay, hospitalization cost, and in-hospital mortality in US adult inpatients with immune thrombocytopenic purpura, 2006-2012.

PubMed

An, Ruopeng; Wang, Peizhong Peter

2017-01-01

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). We analyzed nationally representative data obtained from Nationwide/National Inpatient Sample database of discharges from 2006 to 2012. 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%). Inpatients with ITP had longer hospital stay, bore higher costs, and faced greater risk of mortality than the overall US discharge population.

[Diagnostics and antimicrobial therapy of severe community-acquired pneumonia].

PubMed

Sinopalnikov, A I; Zaitsev, A A

2015-04-01

In the current paper authors presented the latest information concerning etiology of severe community-acquired pneumonia. Most cases are caused by a relatively small number ofpathogenic bacterial and viral natures. The frequency of detection of various pathogens of severe community-acquired pneumonia may vary greatly depending on the region, season and clinical profile of patients, availability of relevant risk factors. Authors presented clinical characteristics of severe community-acquired pneumonia and comparative evaluation of a number of scales to assess the risk of adverse outcome of the disease. Diagnosis of severe community-acquired pneumonia includes the following: collecting of epidemiological history, identification of pneumonia, detection of sepsis and identification of multiple organ dysfunction syndrome, detection of acute respiratory failure, assessment of comorbidity. Authors gave recommendations concerning evaluation of the clinical manifestations of the disease, the use of instrumental and laboratory methods for diagnosis of severe community-acquired pneumonia. To select the mode of antimicrobial therapy is most important local monitoring antimicrobial resistance of pathogens. The main criteria for the effectiveness of treatment are to reduce body temperature, severe intoxication, respiratory and organ failure.

Extensive Drug Resistance Acquired During Treatment of Multidrug-Resistant Tuberculosis

PubMed Central

Cegielski, J. Peter; Dalton, Tracy; Yagui, Martin; Wattanaamornkiet, Wanpen; Volchenkov, Grigory V.; Via, Laura E.; Van Der Walt, Martie; Tupasi, Thelma; Smith, Sarah E.; Odendaal, Ronel; Leimane, Vaira; Kvasnovsky, Charlotte; Kuznetsova, Tatiana; Kurbatova, Ekaterina; Kummik, Tiina; Kuksa, Liga; Kliiman, Kai; Kiryanova, Elena V.; Kim, HeeJin; Kim, Chang-ki; Kazennyy, Boris Y.; Jou, Ruwen; Huang, Wei-Lun; Ershova, Julia; Erokhin, Vladislav V.; Diem, Lois; Contreras, Carmen; Cho, Sang Nae; Chernousova, Larisa N.; Chen, Michael P.; Caoili, Janice Campos; Bayona, Jaime; Akksilp, Somsak; Calahuanca, Gloria Yale; Wolfgang, Melanie; Viiklepp, Piret; Vasilieva, Irina A.; Taylor, Allison; Tan, Kathrine; Suarez, Carmen; Sture, Ingrida; Somova, Tatiana; Smirnova, Tatyana G.; Sigman, Erika; Skenders, Girts; Sitti, Wanlaya; Shamputa, Isdore C.; Riekstina, Vija; Pua, Kristine Rose; Therese, M.; Perez, C.; Park, Seungkyu; Norvaisha, Inga; Nemtsova, Evgenia S.; Min, Seonyeong; Metchock, Beverly; Levina, Klavdia; Lei, Yung-Chao; Lee, Jongseok; Larionova, Elena E.; Lancaster, Joey; Jeon, Doosoo; Jave, Oswaldo; Khorosheva, Tatiana; Hwang, Soo Hee; Huang, Angela Song-En; Gler, M. Tarcela; Dravniece, Gunta; Eum, Seokyong; Demikhova, Olga V.; Degtyareva, Irina; Danilovits, Manfred; Cirula, Anda; Cho, Eunjin; Cai, Ying; Brand, Jeanette; Bonilla, Cesar; Barry, Clifton E.; Asencios, Luis; Andreevskaya, Sofia N.; Akksilp, Rattanawadee

2014-01-01

Background. Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance. Methods. To assess the GLC's impact, we followed adults with pulmonary MDR tuberculosis from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping. We compared the frequency and predictors of acquired resistance to second-line drugs (SLDs) in 9 countries that volunteered to participate, 5 countries that met GLC criteria, and 4 countries that did not apply to the GLC. Results. In total, 832 subjects were enrolled. Of those without baseline resistance to specific SLDs, 68 (8.9%) acquired extensively drug-resistant (XDR) tuberculosis, 79 (11.2%) acquired fluoroquinolone (FQ) resistance, and 56 (7.8%) acquired resistance to second-line injectable drugs (SLIs). The relative risk (95% confidence interval [CI]) of acquired resistance was lower at GLC-approved sites: 0.27 (.16–.47) for XDR tuberculosis, 0.28 (.17–.45) for FQ, and 0.15 (.06–.39) to 0.60 (.34–1.05) for 3 different SLIs. The risk increased as the number of potentially effective drugs decreased. Controlling for baseline drug resistance and differences between sites, the odds ratios (95% CIs) were 0.21 (.07–.62) for acquired XDR tuberculosis and 0.23 (.09–.59) for acquired FQ resistance. Conclusions. Treatment of MDR tuberculosis involves substantial risk of acquired resistance to SLDs, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards. PMID:25057101

Acquired factor VII deficiency associated with acute myeloid leukemia.

PubMed

Anoun, Soumaya; Lamchahab, Mouna; Oukkache, Bouchra; Qachouh, Maryam; Benchekroun, Said; Quessar, Asmaa

2015-04-01

Isolated acquired factor VII deficiency is a rare coagulopathy. It has been reported in 31 patients with malignancy, sepsis, postoperatively, aplastic anemia, and during bone marrow transplantation. We discuss, through a new case of acquired factor VII deficiency, the characteristics of this disease when it is associated with acute myeloid leukemia. Acquired factor VII deficiency in hematological diseases can be caused by intensive chemotherapy, infections, or hepatic dysfunction. The best treatment in developing countries remains corticosteroids associated with plasma exchange, frozen plasma, and antibiotics.

27 CFR 6.45 - Assistance in acquiring license.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Assistance in acquiring license. 6.45 Section 6.45 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS âTIED-HOUSEâ Unlawful Inducements Furnishing Things of Value § 6.45 Assistance in acquiring license. Any...

Rethinking responsibility in offenders with acquired paedophilia: punishment or treatment?

PubMed

Gilbert, Frédéric; Focquaert, Farah

2015-01-01

This article reviews the current neurobiological literature on the aetiology of developmental and acquired paedophilia and examines what the consequences could be in terms of responsibility and treatment for the latter. Addressing the question of responsibility and punishment of offenders with acquired paedophilia from a neurobiological perspective is controversial. Consequently it is essential to avoid hasty conclusions based strictly on neurobiological abnormality justifications. This study establishes a distinction between developmental and acquired paedophilia. The article investigates whether offenders who fulfil the diagnosis of acquired paedophilia should be held fully responsible, particularly in cases where the offender's conduct appears to result from volitionally controlled behaviour that is seemingly incompatible with a neurological cause. Moreover, the article explores how responsibility can be compromised when offenders with acquired paedophilia have (partially) preserved moral knowledge despite their sexual disorder. The article then examines the option of offering mandatory treatment as an alternative to imprisonment for offenders with acquired paedophilia. Furthermore, the article addresses the ethical issues related to offering any form of quasi-coercive treatment as a condition of release. This study concludes that decisions to fully or partially excuse an individual who fulfil the diagnosis of acquired paedophilia should take all relevant information into account, both neurobiological and other environmental evidence, and should proceed on a careful case by case analysis before sentencing or offering treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

A case of palpable purpura and nephropathy: Occam's Razor or Hickam's Dictum.

PubMed

Mandhadi, Ranadeep; Kodumuri, Vamsi; Arora, Rohit; Puneet Singh, Param; Adigopula, Shashi; Chua, Serafin

2013-01-01

Vasculitis causing palpable purpura, nephropathy, and hematologic abnormalities is a well-known entity. However, sometimes, vasculitis may not be the primary cause but is part of a systemic disease. Literature suggests that infections like HIV can induce nephropathy and antineutrophilic cytoplasmic antibody-positive vasculitis, which is different from the well-known entity of "antineutrophilic cytoplasmic antibody-associated vasculitis." We present a 46-year-old female patient with a history of intravenous drug abuse who reported with a rash, swelling, and palpable purpura of the lower extremities. Peripheral smear showed no evidence of disseminated intravascular coagulation or thrombotic thrombocytopenic purpura; metabolic profile showed acute kidney injury. She was found to be HIV- and hepatitis C-positive. Immunologic workup was positive for both MPO and PR3 antineutrophilic cytoplasmic antibodies and negative for cryoglobulins; complement levels were low. Skin biopsy showed leukocytoclastic vasculitis but kidney biopsy was negative for any immunologic involvement; it showed only glomerulosclerosis. Thus, it was thought that nephropathy and vasculitis, in this case, are two distinct pathologic processes, both induced by infection (HIV and/or hepatitis C). The patient responded to low-dose steroid therapy. She was later started on the definitive therapy, the highly active antiretroviral therapy regimen. This case illustrates the fact that low-dose steroids can still be a good alternative in acute situations in patients at risk from immunosuppression.

Cerebral Venous Sinus Thrombosis Due to Low-molecular-weight Heparin-induced Thrombocytopenia.

PubMed

Gleichgerrcht, Ezequiel; Lim, Ming Y; Turan, Tanya N

2017-11-01

Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication of heparin exposure. A limited number of studies have reported cerebral venous sinus thrombosis (CVST) as the presenting thrombotic event induced by HIT, only one of which occurred with exposure to low-molecular-weight heparin (LMWH), with death as outcome. Here, we present a unique case of LMWH-induced HIT leading to CVST but resulting in good clinical outcome. A 52-year-old woman received subcutaneous LMWH for deep vein thrombosis prophylaxis while in rehabilitation following kyphoplasty for spinal fracture related to recent trauma. On postoperative day 15, she developed acute onset altered mental status with significant agitation and nonsensical speech and was found to have brain imaging findings suggestive of CVST. Work-up revealed a drop in platelets associated with HIT, which did not improve off heparin products and with steroids, requiring intravenous immunoglobulin therapy, likely due to an overlapping immune thrombocytopenic purpura. Patient was managed on an argatroban drip until platelet count normalized and was able to transition to warfarin. Her clinical outcome was very favorable with near-normal neurological exam except for subtle cognitive changes. This unique case of LMWH-induced HIT leading to CVST but resulting in good clinical outcome highlights the importance of linking CVST with HIT and of establishing the need for early alternative antithrombotic therapeutic strategies.

Cyclosporin A Impairs the Secretion and Activity of ADAMTS13 (A Disintegrin and Metalloprotease with Thrombospondin Type 1 Repeat)*

PubMed Central

Hershko, Klilah; Simhadri, Vijaya L.; Blaisdell, Adam; Hunt, Ryan C.; Newell, Jordan; Tseng, Sandra C.; Hershko, Alon Y.; Choi, Jae Won; Sauna, Zuben E.; Wu, Andrew; Bram, Richard J.; Komar, Anton A.; Kimchi-Sarfaty, Chava

2012-01-01

The protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat) cleaves multimers of von Willebrand factor, thus regulating platelet aggregation. ADAMTS13 deficiency leads to the fatal disorder thrombotic thrombocytopenic purpura (TTP). It has been observed that cyclosporin A (CsA) treatment, particularly in transplant patients, may sometimes be linked to the development of TTP. Until now, the reason for such a link was unclear. Here we provide evidence demonstrating that cyclophilin B (CypB) activity plays an important role in the secretion of active ADAMTS13. We found that CsA, an inhibitor of CypB, reduces the secretion of ADAMTS13 and leads to conformational changes in the protein resulting in diminished ADAMTS13 proteolytic activity. A direct, functional interaction between CypB (which possesses peptidyl-prolyl cis-trans isomerase (PPIase) and chaperone functions) and ADAMTS13 is demonstrated using immunoprecipitation and siRNA knockdown of CypB. Finally, CypB knock-out mice were found to have reduced ADAMTS13 levels. Taken together, our findings indicate that cyclophilin-mediated activity is an important factor affecting secretion and activity of ADAMTS13. The large number of proline residues in ADAMTS13 is consistent with the important role of cis-trans isomerization in the proper folding of this protein. These results altogether provide a novel mechanistic explanation for CsA-induced TTP in transplant patients. PMID:23144461

Cyclosporin A impairs the secretion and activity of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat).

PubMed

Hershko, Klilah; Simhadri, Vijaya L; Blaisdell, Adam; Hunt, Ryan C; Newell, Jordan; Tseng, Sandra C; Hershko, Alon Y; Choi, Jae Won; Sauna, Zuben E; Wu, Andrew; Bram, Richard J; Komar, Anton A; Kimchi-Sarfaty, Chava

2012-12-28

The protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeat) cleaves multimers of von Willebrand factor, thus regulating platelet aggregation. ADAMTS13 deficiency leads to the fatal disorder thrombotic thrombocytopenic purpura (TTP). It has been observed that cyclosporin A (CsA) treatment, particularly in transplant patients, may sometimes be linked to the development of TTP. Until now, the reason for such a link was unclear. Here we provide evidence demonstrating that cyclophilin B (CypB) activity plays an important role in the secretion of active ADAMTS13. We found that CsA, an inhibitor of CypB, reduces the secretion of ADAMTS13 and leads to conformational changes in the protein resulting in diminished ADAMTS13 proteolytic activity. A direct, functional interaction between CypB (which possesses peptidyl-prolyl cis-trans isomerase (PPIase) and chaperone functions) and ADAMTS13 is demonstrated using immunoprecipitation and siRNA knockdown of CypB. Finally, CypB knock-out mice were found to have reduced ADAMTS13 levels. Taken together, our findings indicate that cyclophilin-mediated activity is an important factor affecting secretion and activity of ADAMTS13. The large number of proline residues in ADAMTS13 is consistent with the important role of cis-trans isomerization in the proper folding of this protein. These results altogether provide a novel mechanistic explanation for CsA-induced TTP in transplant patients.

Dyspnoea after antiplatelet agents: the AZD6140 controversy.

PubMed

Serebruany, V L; Stebbing, J; Atar, D

2007-03-01

Recent randomised studies suggest that experimental oral reversible platelet P2Y12 receptor inhibitor, AZD6140, causes dyspnoea. This also raises similar concerns about the parent compound, and another adenosine triphosphate (ATP) analogue (AR-69931MX or cangrelor), which is currently in Phase 3 trial in patients undergoing coronary interventions. We analysed package inserts, and available clinical trials safety data for antiplatelet agents with regard to the incidence of dyspnoea. We found that dyspnoea is a very rare complication of the presently approved platelet inhibitors, mostly caused by underlying disease, rather than antiplatelet therapy per se. The main reasons for respiratory distress after oral (AZD6140), and intravenous (cangrelor) agents may be the development of mild asymptomatic thrombotic thrombocytopenic purpura, fluid retention and dyspnoea because of the reversible nature of these drugs. Also, these agents are ATP analogues, which rapidly metabolise to adenosine, a well-known bronchoprovocator causing dyspnoea as well. In summary, dyspnoea is seldom considered, there are no treatment algorithms when it does occur, plausible mechanisms exist and despite these plausible mechanisms, the true cause of dyspnoea in these exposed individuals is unknown. Additional pulmonary function testing, immunological investigations and platelet receptor studies are urgently needed to determine the cause of dyspnoea after AZD6140, and to point out how such serious adverse reactions can be prevented, or at least minimised, raising potential concerns about this drug.

Role of Investigating Thrombophilic Disorders in Young Stroke

PubMed Central

Ng, Kay W. P.; Loh, Pei K.; Sharma, Vijay K.

2011-01-01

Our knowledge about various inherited and acquired causes of thrombophilic disorders has increased significantly during the past decade. Technology for various diagnostic tests for these rare disorders has matched the rapid advances in our understanding about the thrombophilic disorders. Inherited thrombophilic disorders predispose young patients for various venous or arterial thrombotic and thromboembolic episodes. Our understanding has also improved about various gene-gene and gene-environment interactions and their impact on the resultant heterogenous clinical manifestations. We describe various thrombophilic disorders, their diagnostic tests, pathogenic potential in isolation or with other concurrent inherited/acquired defects and possible therapeutic and prophylactic strategies. Better understanding, optimal diagnostic and screening protocols are expected to improve the diagnostic yield and help to reduce morbidity, disability, and mortality in relatively younger patients harbouring these inherited and acquired thrombophilic disorders. PMID:21331344

A single-center prospective study on the safety of plasma exchange procedures using a double-viral-inactivated and prion-reduced solvent/detergent fresh-frozen plasma as the replacement fluid in the treatment of thrombotic microangiopathy.

PubMed

Vendramin, Chiara; McGuckin, Siobhan; Alwan, Ferras; Westwood, John-Paul; Thomas, Mari; Scully, Marie

2017-01-01

Patients presenting with acute episodes of thrombotic microangiopathies (TMAs) require urgent access to plasma exchange (PEX). OctaplasLG, a solvent/detergent fresh-frozen plasma product that has undergone viral inactivation and prion reduction step, has been used in our institution since 2013, replacing Octaplas. We prospectively reviewed 981 PEX procedures where OctaplasLG was the replacement fluid in 90 patients admitted acutely with a TMA presentation within our institution from January 1, 2013, to December 31, 2015. We recorded citrate toxicities, plasma reactions, viral transfer, complications related to central venous catheter, and venous thrombotic events (VTEs). Citrate toxicities were 5.4%, plasma reactions were 2%, and all were classified as Grade 1 or 2. VTE had an incidence of 12.2%, although 50% of the episodes occurred in early remission when patients were not receiving PEX. No line insertions complications were recorded. Line-associated infections were 2.2%. Hepatitis B and C serology and human immunodeficiency virus (HIV) were checked on admission. There were four patients who may have had passive transient transfer of hepatitis B antibodies from pooled plasma. No hepatitis C or HIV viral transfer was documented after treatment and no seroconversion was detected after treatment. Our data have demonstrated that the incidence of complications during PEX is low and using OctaplasLG is comparable to the low incidence of reactions. No cases of anaphylaxis, transfusion-related acute lung injury, or fatal plasma reactions were seen. There was no evidence of viral transmission or seroconversion after treatment. © 2016 AABB.

Naturally acquired microchimerism

PubMed Central

GAMMILL, HILARY S.; NELSON, J. LEE

2010-01-01

Bi-directional transplacental trafficking occurs routinely during the course of normal pregnancy, from fetus to mother and from mother to fetus. In addition to a variety of cell-free substances, it is now well recognized that some cells are also exchanged. Microchimerism refers to a small number of cells (or DNA) harbored by one individual that originated in a genetically different individual. While microchimerism can be the result of iatrogenic interventions such as transplantation or transfusion, by far the most common source is naturally acquired microchimerism from maternal-fetal trafficking during pregnancy. Microchimerism is a subject of much current interest for a number of reasons. During pregnancy, fetal microchimerism can be sought from the mother’s blood for the purpose of prenatal diagnosis. Moreover, studies of fetal microchimerism during pregnancy may offer insight into complications of pregnancy, such as preeclampsia, as well as insights into the pathogenesis of autoimmune diseases such as rheumatoid arthritis which usually ameliorates during pregnancy. Furthermore, it is now known that microchimerism persists decades later, both fetal microchimerism in women who have been pregnant and maternal microchimerism in her progeny. Investigation of the long-term consequences of fetal and maternal microchimerism is another exciting frontier of active study, with initial results pointing both to adverse and beneficial effects. This review will provide an overview of microchimerism during pregnancy and of current knowledge regarding long-term effects of naturally acquired fetal and maternal microchimerism. PMID:19924635

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 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 IN...

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 IN...

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 IN...

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 IN...

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 IN...

Enhancing global vaccine pharmacovigilance: Proof-of-concept study on aseptic meningitis and immune thrombocytopenic purpura following measles-mumps containing vaccination

PubMed Central

Perez-Vilar, Silvia; Weibel, Daniel; Sturkenboom, Miriam; Black, Steven; Maure, Christine; Castro, Jose Luis; Bravo-Alcántara, Pamela; Dodd, Caitlin N.; Romio, Silvana A.; de Ridder, Maria; Nakato, Swabra; Molina-León, Helvert Felipe; Elango, Varalakshmi; Zuber, Patrick L.F.

2017-01-01

New vaccines designed to prevent diseases endemic in low and middle-income countries (LMICs) are now being introduced without prior record of utilization in countries with robust pharmacovigilance systems. To address this deficit, our objective was to demonstrate feasibility of an international hospital-based network for the assessment of potential epidemiological associations between serious and rare adverse events and vaccines in any setting. This was done through a proof-of-concept evaluation of the risk of immune thrombocytopenic purpura (ITP) and aseptic meningitis (AM) following administration of the first dose of measles-mumps-containing vaccines using the self-controlled risk interval method in the primary analysis. The World Health Organization (WHO) selected 26 sentinel sites (49 hospitals) distributed in 16 countries of the six WHO regions. Incidence rate ratios (IRR) of 5.0 (95% CI: 2.5-9.7) for ITP following first dose of measles-containing vaccinations, and of 10.9 (95% CI: 4.2-27.8) for AM following mumps-containing vaccinations were found. The strain-specific analyses showed significantly elevated ITP risk for measles vaccines containing Schwarz (IRR: 20.7; 95% CI: 2.7-157.6), Edmonston-Zagreb (IRR: 11.1; 95% CI: 1.4-90.3), and Enders´Edmonston (IRR: 8.5; 95% CI: 1.9-38.1) strains. A significantly elevated AM risk for vaccines containing the Leningrad-Zagreb mumps strain (IRR: 10.8; 95% CI: 1.3-87.4) was also found. This proof-of-concept study has shown, for the first time, that an international hospital-based network for the investigation of rare vaccine adverse events, using common standardized procedures and with high participation of LMICs, is feasible, can produce reliable results, and has the potential to characterize differences in risk between vaccine strains. The completion of this network by adding large reference hospitals, particularly from tropical countries, and the systematic WHO-led implementation of this approach, should permit the

Ultrasound of Inherited vs. Acquired Demyelinating Polyneuropathies

PubMed Central

Zaidman, Craig M.; Harms, Matthew B.; Pestronk, Alan

2013-01-01

Introduction We compared features of nerve enlargement in inherited and acquired demyelinating neuropathies using ultrasound. Methods We measured median and ulnar nerve cross-sectional areas in proximal and distal regions in 128 children and adults with inherited (Charcot-Marie Tooth-1 (CMT-1) (n=35)) and acquired (Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) (n=55), Guillaine-Barre Syndrome (GBS) (n=21) and Multifocal Motor Neuropathy (MMN) (n=17)) demyelinating neuropathies. We classified nerve enlargement by degree and number of regions affected. We defined patterns of nerve enlargement as: none- no enlargement; mild-nerves enlarged but never more than twice normal; regional- nerves normal at at least one region and enlarged more than twice normal at atleast one region; diffuse- nerves enlarged at all four regions with atleast one region more than twice normal size. Results Nerve enlargement was commonly diffuse (89%) and generally more than twice normal size in CMT-1, but not (p<0.001) in acquired disorders which mostly had either no, mild or regional nerve enlargement (CIDP (64%), GBS (95%), and MMN (100%)). In CIDP, subjects treated within three months of disease onset had less nerve enlargement than those treated later. Discussion Ultrasound identified patterns of diffuse nerve enlargement can be used to screen patients suspected of having CMT-1. Normal, mildly, or regionally enlarged nerves in demyelinating polyneuropathy suggests an acquired etiology. Early treatment in CIDP may impede nerve enlargement. PMID:24101129

Thrombotic safety of prothrombin complex concentrate (Beriplex P/N) for dabigatran reversal in a rabbit model.

PubMed

Herzog, Eva; Kaspereit, Franz J; Krege, Wilfried; Doerr, Baerbel; van Ryn, Joanne; Dickneite, Gerhard; Pragst, Ingo

2014-09-01

In vivo animal data have shown prothrombin complex concentrate (PCC) to be effective in preventing bleeding induced by excessive plasma levels of the direct thrombin inhibitor dabigatran. This animal model study was designed to determine the risk of thrombosis associated with administration of a PCC (Beriplex P/N) to reverse dabigatran-induced bleeding. Anesthetized rabbits were treated with initial 0, 75, 200 or 450 μg kg(-1) dabigatran boluses followed by continuous infusions to maintain elevated plasma dabigatran levels. At 15 min after the start of dabigatran administration, PCC doses of 0, 50 or 300 IU kg(-1) were administered. Thereafter, coagulation in an arteriovenous (AV) shunt was evaluated and histopathologic examination for thrombotic changes performed. Venous thrombosis was also assessed in a modified Wessler model. At the suprapharmacologic dose of 300 IU kg(-1), PCC increased thrombus weight during AV shunting, but this effect could be prevented by dabigatran at all tested doses. AV shunt occlusion after PCC administration was delayed by 75 μg kg(-1) dabigatran and abolished by progressively higher dabigatran doses. High-dose treatment with 300 IU kg(-1) PCC resulted in histologically evident low-grade pulmonary thrombi; however, that effect could be blocked by dabigatran in a dose-dependent manner (p=0.034). In rabbits treated with high-dose PCC, dabigatran inhibited thrombus formation during venous stasis. PCC effectively reversed dabigatran-induced bleeding. In this animal study, thrombosis after PCC administration could be prevented in the presence of dabigatran. PCC reversed dabigatran-induced excessive bleeding while retaining protective anticoagulatory activity of dabigatran. Copyright © 2014. Published by Elsevier Ltd.

Aggressive behaviour of inpatients with acquired brain injury.

PubMed

Visscher, Ada J M; van Meijel, Berno; Stolker, Joost J; Wiersma, Jan; Nijman, Henk

2011-12-01

To study the prevalence, nature and determinants of aggression among inpatients with acquired brain injury. Patients with acquired brain injury often have difficulty in controlling their aggressive impulses. A prospective observational study design. By means of the Staff Observation Aggression Scale-Revised, the prevalence, nature and severity of aggressive behaviour of inpatients with acquired brain injury was assessed on a neuropsychiatric treatment ward with 45 beds. Additional data on patient-related variables were gathered from the patients' files. In total, 388 aggressive incidents were recorded over 17 weeks. Of a total of 57 patients included, 24 (42%) patients had engaged in aggressive behaviour on one or more occasions. A relatively small proportion of patients (n=8; 14%) was found to be responsible for the majority of incidents (n=332; 86%). The vast majority of aggression incidents (n=270; 70%) were directly preceded by interactions between patients and nursing staff. In line with this, most incidents occurred at times of high contact intensity. Aggressive behaviour was associated with male gender, length of stay at the ward, legal status and hypoxia as the cause of brain injury. Aggression was found to be highly prevalent among inpatients with acquired brain injury. The results suggest that for the prevention of aggression on the ward, it may be highly effective to develop individually tailored interventions for the subgroup with serious aggression problems. Insight into the frequency, nature and determinants of aggressive behaviour in inpatients with acquired brain injury provides nurses with tools for the prevention and treatment of aggressive behaviour. © 2011 Blackwell Publishing Ltd.

A case of acquired port wine stain: an association with repeated sunburn?

PubMed

Seremet, Sila; Benar, Elif B; Afsar, Fatma Sule; Calli, Aylin; Ulusarac, Ozlem

2016-10-01

Unlike congenital port wine stain (PWS), an acquired PWS is a rare vascular lesion that develops later in life. Although solar damage is associated with acquired PWS, there is no reported case of acquired PWS after sunburn in the literature. We report a case of a 54-year-old man diagnosed with acquired PWS possibly caused by repeated sunburn. We recommended laser treatment to our patient; however, the patient did not chose to receive any treatment. Our case demonstrates a possible rare occurrence of an acquired PWS after sunburn with larger lesions and more diffuse distribution. For this reason, our case differs from other acquired PWS cases. © 2016 The International Society of Dermatology.

26 CFR 1.472-7 - Inventories of acquiring corporations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 26 Internal Revenue 6 2014-04-01 2014-04-01 false Inventories of acquiring corporations. 1.472-7 Section 1.472-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Inventories § 1.472-7 Inventories of acquiring corporations...

26 CFR 1.472-7 - Inventories of acquiring corporations.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 6 2012-04-01 2012-04-01 false Inventories of acquiring corporations. 1.472-7 Section 1.472-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Inventories § 1.472-7 Inventories of acquiring corporations...

26 CFR 1.471-9 - Inventories of acquiring corporations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 26 Internal Revenue 6 2014-04-01 2014-04-01 false Inventories of acquiring corporations. 1.471-9 Section 1.471-9 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Inventories § 1.471-9 Inventories of acquiring corporations...

26 CFR 1.471-9 - Inventories of acquiring corporations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 6 2010-04-01 2010-04-01 false Inventories of acquiring corporations. 1.471-9 Section 1.471-9 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Inventories § 1.471-9 Inventories of acquiring corporations. For...

26 CFR 1.472-7 - Inventories of acquiring corporations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 6 2010-04-01 2010-04-01 false Inventories of acquiring corporations. 1.472-7 Section 1.472-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Inventories § 1.472-7 Inventories of acquiring corporations. For...

26 CFR 1.471-9 - Inventories of acquiring corporations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 6 2011-04-01 2011-04-01 false Inventories of acquiring corporations. 1.471-9 Section 1.471-9 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Inventories § 1.471-9 Inventories of acquiring corporations...

26 CFR 1.472-7 - Inventories of acquiring corporations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 6 2011-04-01 2011-04-01 false Inventories of acquiring corporations. 1.472-7 Section 1.472-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Inventories § 1.472-7 Inventories of acquiring corporations...

26 CFR 1.471-9 - Inventories of acquiring corporations.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 6 2012-04-01 2012-04-01 false Inventories of acquiring corporations. 1.471-9 Section 1.471-9 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Inventories § 1.471-9 Inventories of acquiring corporations...

26 CFR 1.472-7 - Inventories of acquiring corporations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 26 Internal Revenue 6 2013-04-01 2013-04-01 false Inventories of acquiring corporations. 1.472-7 Section 1.472-7 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Inventories § 1.472-7 Inventories of acquiring corporations...

26 CFR 1.471-9 - Inventories of acquiring corporations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 26 Internal Revenue 6 2013-04-01 2013-04-01 false Inventories of acquiring corporations. 1.471-9 Section 1.471-9 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Inventories § 1.471-9 Inventories of acquiring corporations...

Recurrent and acquired tracheoesophageal fistulae (TEF)-Minimally invasive management.

PubMed

Nazir, Zafar; Khan, Muhammad Arif Mateen; Qamar, Javaria

2017-10-01

Recurrent and acquired fistulae are a serious complication of congenital esophageal atresia and tracheoesophageal fistula (TEF) repair and foreign body ingestion (FBI) (e.g., button battery). We report our experience with a minimally invasive approach to recurrent and acquired TEF. Medical records of patients referred for management of recurrent and acquired TEF between 2003 and 2015 were reviewed retrospectively. Patients underwent endoscopic procedures (de-epithelization of fistulous tract and fibrin tissue adhesive-Tisseel R ) under general anesthesia. Nine children (7 male, 2 female) with age range 3months to 3years (mean 1.5year) were managed. TEF closed spontaneously in four patients, whereas in 5 patients the TEF closed after combined endoscopic procedure. Three patients required repeat endoscopic procedures. Follow-up ranged between 7months to 10years (mean 4.2years). Active observation and repeat combined endoscopic procedures are safe alternatives to open surgical repair of acquired and recurrent TEF. Level IV study. Copyright © 2017 Elsevier Inc. All rights reserved.

33 CFR 211.2 - Authority to acquire real estate.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Authority to acquire real estate..., DEPARTMENT OF DEFENSE REAL ESTATE ACTIVITIES OF THE CORPS OF ENGINEERS IN CONNECTION WITH CIVIL WORKS PROJECTS Real Estate; General § 211.2 Authority to acquire real estate. (a) Congressional authority...

33 CFR 211.2 - Authority to acquire real estate.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Authority to acquire real estate..., DEPARTMENT OF DEFENSE REAL ESTATE ACTIVITIES OF THE CORPS OF ENGINEERS IN CONNECTION WITH CIVIL WORKS PROJECTS Real Estate; General § 211.2 Authority to acquire real estate. (a) Congressional authority...

33 CFR 211.2 - Authority to acquire real estate.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Authority to acquire real estate..., DEPARTMENT OF DEFENSE REAL ESTATE ACTIVITIES OF THE CORPS OF ENGINEERS IN CONNECTION WITH CIVIL WORKS PROJECTS Real Estate; General § 211.2 Authority to acquire real estate. (a) Congressional authority...

33 CFR 211.2 - Authority to acquire real estate.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 3 2013-07-01 2013-07-01 false Authority to acquire real estate..., DEPARTMENT OF DEFENSE REAL ESTATE ACTIVITIES OF THE CORPS OF ENGINEERS IN CONNECTION WITH CIVIL WORKS PROJECTS Real Estate; General § 211.2 Authority to acquire real estate. (a) Congressional authority...

33 CFR 211.27 - Method of acquiring Federal jurisdiction.

Code of Federal Regulations, 2010 CFR

2010-07-01

... PROJECTS Federal Jurisdiction over Real Estate § 211.27 Method of acquiring Federal jurisdiction... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Method of acquiring Federal jurisdiction. 211.27 Section 211.27 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY...

[Acquired angioedema – clinical characteristic of the patients diagnosed in 2012-2016 with acquired C1 inhibitor deficiency].

PubMed

Stobiecki, Marcin; Czarnobilska, Ewa; Obtułowicz, Krystyna

Acquired angioedema is a rare disease caused by a deficiency of C1 esterase inhibitor with recurrent swelling symptoms. It may occur in the course of lymphoproliferative disorders or autoimmune diseases. Symptoms resemble hereditary angioedema, and the only differentiating features is negative family history, late onset of symptoms and accompanying lymphoproliferative disorder. The aim of the study was to analyze the cases of acquired angioedema. The retrospective analysis of 341 patients from the registry of patients with C1 inhibitor deficiency. Results: We identified 4 patients among 119 with HAE (3.57%) diagnosed in this same period of time 2012-2016 who fulfilled the criteria of acquired edema. In two cases the primary reason of angioedema was lymphoproliferive disease, in two monoclonal gammapathy of unknown reason. We analyzed also the results of laboratory tests C4, C1 inhibitor, C1q. In all cases the face was dominated localization. After the treatment of primary lymphoproliferive disease, in two cases, we observed total remission of angioedema. Only one patient with gammapathy require treatment with C1 inhibitor during the attacks. In these case we observed both plasma deriver, and recombinant C1 inhibitor were effective.

Elevated total plasma homocysteine and 667C{r_arrow}T mutation of the 5,10-methylenetetrahydrofolate reductase gene in thrombotic vascular disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

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, causingmore » 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.« less

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

Hemati, Zeinab; Kiani, Davood

2016-04-01

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. 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. 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. 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.

Blocking neutrophil diapedesis prevents hemorrhage during thrombocytopenia

PubMed Central

Hillgruber, Carina; Pöppelmann, Birgit; Weishaupt, Carsten; Steingräber, Annika Kathrin; Wessel, Florian; Berdel, Wolfgang E.; Gessner, J. Engelbert; Ho-Tin-Noé, Benoît

2015-01-01

Spontaneous organ hemorrhage is the major complication in thrombocytopenia with a potential fatal outcome. However, the exact mechanisms regulating vascular integrity are still unknown. Here, we demonstrate that neutrophils recruited to inflammatory sites are the cellular culprits inducing thrombocytopenic tissue hemorrhage. Exposure of thrombocytopenic mice to UVB light provokes cutaneous petechial bleeding. This phenomenon is also observed in immune-thrombocytopenic patients when tested for UVB tolerance. Mechanistically, we show, analyzing several inflammatory models, that it is neutrophil diapedesis through the endothelial barrier that is responsible for the bleeding defect. First, bleeding is triggered by neutrophil-mediated mechanisms, which act downstream of capturing, adhesion, and crawling on the blood vessel wall and require Gαi signaling in neutrophils. Second, mutating Y731 in the cytoplasmic tail of VE-cadherin, known to selectively affect leukocyte diapedesis, but not the induction of vascular permeability, attenuates bleeding. Third, and in line with this, simply destabilizing endothelial junctions by histamine did not trigger bleeding. We conclude that specifically targeting neutrophil diapedesis through the endothelial barrier may represent a new therapeutic avenue to prevent fatal bleeding in immune-thrombocytopenic patients. PMID:26169941

Trade-offs between acquired and innate immune defenses in humans

PubMed Central

McDade, Thomas W.; Georgiev, Alexander V.; Kuzawa, Christopher W.

2016-01-01

Immune defenses provide resistance against infectious disease that is critical to survival. But immune defenses are costly, and limited resources allocated to immunity are not available for other physiological or developmental processes. We propose a framework for explaining variation in patterns of investment in two important subsystems of anti-pathogen defense: innate (non-specific) and acquired (specific) immunity. The developmental costs of acquired immunity are high, but the costs of maintenance and activation are relatively low. Innate immunity imposes lower upfront developmental costs, but higher operating costs. Innate defenses are mobilized quickly and are effective against novel pathogens. Acquired responses are less effective against novel exposures, but more effective against secondary exposures due to immunological memory. Based on their distinct profiles of costs and effectiveness, we propose that the balance of investment in innate versus acquired immunity is variable, and that this balance is optimized in response to local ecological conditions early in development. Nutritional abundance, high pathogen exposure and low signals of extrinsic mortality risk during sensitive periods of immune development should all favor relatively higher levels of investment in acquired immunity. Undernutrition, low pathogen exposure, and high mortality risk should favor innate immune defenses. The hypothesis provides a framework for organizing prior empirical research on the impact of developmental environments on innate and acquired immunity, and suggests promising directions for future research in human ecological immunology. PMID:26739325

[Familial occurrence of acquired heart valve defect].

PubMed

Schieche, M

1975-09-15

A report is given on a family examination, issuing from 213 persons with an acquired valvular defect for the establishment of further cases on altogether 783 relations of the direct line. In 19 families other 21 patients with an acquired valvular defect were found; this corresponds to a share of 2.7 % of the relations examined and 8.1% of the families affected, respectively. The result repays the expenditure and, apart from this, leads to an essential furthering of the confidence between physician, patient and family as the smallest social unity for prophylaxis, diagnostics, therapy and metaphylaxis of chronic diseases.

GETTING LOST: TOPOGRAPHIC SKILLS IN ACQUIRED AND DEVELOPMENTAL PROSOPAGNOSIA

PubMed Central

Lee, Edison; Pancaroglu, Raika; Burles, Ford; Duchaine, Brad; Iaria, Giuseppe; Barton, Jason J S

2016-01-01

Previous studies report that acquired prosopagnosia is frequently associated with topographic disorientation. Whether this is associated with a specific anatomic subtype of prosopagnosia, how frequently it is seen with the developmental variant, and what specific topographic function is impaired to account for this problem are not known. We studied ten subjects with acquired prosopagnosia from either occipitotemporal or anterior temporal lesions and seven with developmental prosopagnosia. Subjects were given a battery of topographic tests, including house and scene recognition, the road map test, a test of cognitive map formation, and a standardized self-report questionnaire. House and/or scene recognition were frequently impaired after either occipitotemporal or anterior temporal lesions in acquired prosopagnosia. Subjects with occipitotemporal lesions were also impaired in cognitive map formation: an overlap analysis identified right fusiform and parahippocampal gyri as a likely correlate. Only one subject with acquired prosopagnosia had mild difficulty with directional orientation on the road map test. Only one subject with developmental prosopagnosia had difficulty with cognitive map formation, and none were impaired on the other tests. Scores for house and scene recognition correlated most strongly with the results of the questionnaire. We conclude that topographic disorientation in acquired prosopagnosia reflects impaired place recognition, with a contribution from poor cognitive map formation when there is occipitotemporal damage. Topographic impairments are less frequent in developmental prosopagnosia. PMID:26874939

45 CFR 7.4 - Option to acquire foreign rights.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Option to acquire foreign rights. 7.4 Section 7.4... Option to acquire foreign rights. In any case where it is determined that all domestic rights should be...-wide regulations issued thereunder, that the Government shall reserve an option to require the...

34 CFR 7.4 - Option to acquire foreign rights.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Option to acquire foreign rights. 7.4 Section 7.4 Education Office of the Secretary, Department of Education EMPLOYEE INVENTIONS § 7.4 Option to acquire... issued thereunder, that the Government shall reserve an option to require the assignment of such rights...

[Topical problems of empiric therapy of community-acquired pneumonia in outpatient practice].

PubMed

Stepanova, I I; Chorbinskaya, S A; Baryshnikonva, G A; Nikiforova, N V; Pokutniy, N F; Zverkov, I V; Maslovskyi, L V; Kotenko, K V

2016-01-01

Community-acquired pneumonia is one of prevalent infectious respiratory diseases. Adequate treatment of community-acquired pneumonia, with consideration of the disease severity and microbial resistence, remains extremely topical. The article covers contemporary views of community-acquired pneumonia treatment standards. The authors described results of personal research aimed to study antibacterial treatment for community-acquired pneumonia on outpatient basis over 2004-2012, evaluated correspondence of the treatment to the national clinical recommendations.

Life Experiences and the Acquired Capability for Suicide in Incarcerated Men

PubMed Central

Smith, Phillip N.; Selwyn, Candice; D’Amato, Darcey; Granato, Stephani; Kuhlman, Shane; Mandracchia, Jon T.

2016-01-01

Suicide is a leading cause of death in US prisons. Prisoners may be at risk for suicide due to their greater likelihood of experiencing events that promote the acquired capability for suicide. The current study examined the associations of 10 domains of life experiences with the acquired capability for suicide in 399 male prisoners. All life experience domains were associated with acquired capability with certain domains evidencing relatively stronger relations. Results support that aggression, thrill seeking, suicidal thoughts and behaviors, and accidental injury may be particularly important to the development of the acquired capability for suicide in prisoners. PMID:27050295

Acquired Acrodermatitis Enteropathica: A Case Study

PubMed Central

Stelzer, John W; Esplin, Nathan; Farooq, Ahsan; Karasik, Olga

2017-01-01

We present a case of severe acquired acrodermatitis enteropathica in a vegan adult female with multiple underlying comorbidities. Acquired acrodermatitis enteropathica or zinc-deficiency dermatitis is the most common diagnosis than many practitioners realize with up to 10% of the patients in developed nations with the risk of zinc deficiency. The condition can be difficult to diagnose due to many similarly-presenting conditions. Furthermore, comorbid conditions in the patients can serve as confounders to the diagnosis. The symptoms are often extremely distressing for the patients, though the treatment is simple and clinical improvement occurs rapidly with appropriate care. We recommend a high index of suspicion to practitioners as well as a low-threshold for initiating treatment in the patients with any clinical symptoms of the condition. PMID:29152424

Post-thrombotic syndrome after central venous catheter removal in childhood cancer survivors: A prospective cohort study.

PubMed

Polen, E; Weintraub, M; Stoffer, C; Jaffe, D H; Burger, A; Revel-Vilk, S

2015-02-01

Although the use of central venous catheters (CVCs) has greatly improved the quality of care of children with cancer, these catheters increase the risk of deep vein thrombosis (DVT) and the potential long-term complication of post-thrombotic syndrome (PTS). We aimed to study PTS post-CVC removal using physical, functional and health related quality of life (HRQoL) domains in childhood cancer and bone marrow transplantation (BMT) survivors. We conducted a prospective study in a cohort of childhood cancer and BMT survivors post-CVC use. Participants were evaluated for PTS with the Modified Villalta Score (MVS) and the Manco-Johnson Instrument (MJI). HRQoL was assessed using the PedsQL™ questionnaire. A total of 158 children were enrolled at a median of 41 (4-149) months from CVC removal. Signs and symptoms of PTS were present in 34% (95% confidence interval [CI] 27-43%) (MVS criteria) and 30.5% (95% CI 23.1-37.8%) (MJI criteria). Diagnosis of PTS was associated with history of CVC occlusion, history of CVC-related DVT and the use of ≥2 CVCs. The presence of signs and symptoms of PTS was a predictor for low HRQoL tested by the PedsQL™ Total Scale scores and Physical Health Summary scores. PTS post-CVC removal in pediatric cancer survivors is not a rare event. The association between PTS and the history of CVC occlusion confirms earlier findings, and suggests that CVC occlusion may indicate asymptomatic DVT. PTS is also associated with lower HRQoL scores highlighting the need to study preventive measures, especially for high risk groups. Pediatr Blood Cancer 2015;62:285-290. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

Acquiring 4D Thoracic CT Scans Using Ciné CT Acquisition

NASA Astrophysics Data System (ADS)

Low, Daniel

One method for acquiring 4D thoracic CT scans is to use ciné acquisition. Ciné acquisition is conducted by rotating the gantry and acquiring x-ray projections while keeping the couch stationary. After a complete rotation, a single set of CT slices, the number corresponding to the number of CT detector rows, is produced. The rotation period is typically sub second so each image set corresponds to a single point in time. The ciné image acquisition is repeated for at least one breathing cycle to acquire images throughout the breathing cycle. Once the images are acquired at a single couch position, the couch is moved to the abutting position and the acquisition is repeated. Post-processing of the images sets typically resorts the sets into breathing phases, stacking images from a specific phase to produce a thoracic CT scan at that phase. Benefits of the ciné acquisition protocol include, the ability to precisely identify the phase with respect to the acquired image, the ability to resort images after reconstruction, and the ability to acquire images over arbitrarily long times and for arbitrarily many images (within dose constraints).

Intensive Care Unit–Acquired Weakness: Implications for Physical Therapist Management

PubMed Central

Moss, Marc; Quan, Dianna; Schenkman, Margaret

2012-01-01

Patients admitted to the intensive care unit (ICU) can develop a condition referred to as “ICU-acquired weakness.” This condition is characterized by profound weakness that is greater than might be expected to result from prolonged bed rest. Intensive care unit–acquired weakness often is accompanied by dysfunction of multiple organ systems. Individuals with ICU-acquired weakness typically have significant activity limitations, often requiring physical assistance for even the most basic activities associated with bed mobility. Many of these individuals have activity limitations months to years after hospitalization. The purpose of this article is to review evidence that guides physical rehabilitation of people with ICU-acquired weakness. Included are diagnostic criteria, medical management, and prognostic indicators, as well as criteria for beginning physical rehabilitation, with an emphasis on patient safety. Data are presented indicating that rehabilitation can be implemented with very few adverse effects. Evidence is provided for appropriate measurement approaches and for physical intervention strategies. Finally, some of the key issues are summarized that should be investigated to determine the best intervention guidelines for individuals with ICU-acquired weakness. PMID:22282769

Rehabilitation of discourse impairments after acquired brain injury

PubMed Central

Gindri, Gigiane; Pagliarin, Karina Carlesso; Casarin, Fabíola Schwengber; Branco, Laura Damiani; Ferré, Perrine; Joanette, Yves; Fonseca, Rochele Paz

2014-01-01

Language impairments in patients with acquired brain injury can have a negative impact on social life as well as on other cognitive domains. Discourse impairments are among the most commonly reported communication deficits among patients with acquired brain damage. Despite advances in the development of diagnostic tools for detecting such impairments, few studies have investigated interventions to rehabilitate patients presenting with these conditions. Objective The aim of this study was to present a systematic review of the methods used in the rehabilitation of discourse following acquired brain injury. Methods The PubMed database was searched for articles using the following keywords: "rehabilitation", "neurological injury", "communication" and "discursive abilities". Results A total of 162 abstracts were found, but only seven of these met criteria for inclusion in the review. Four studies involved samples of individuals with aphasia whereas three studies recruited samples of individuals with traumatic brain injury. Conclusion All but one article found that patient performance improved following participation in a discourse rehabilitation program. PMID:29213880

Community acquired Pseudomonas pneumonia in an immune competent host.

PubMed

Gharabaghi, Mehrnaz Asadi; Abdollahi, Seyed Mojtaba Mir; Safavi, Enayat; Abtahi, Seyed Hamid

2012-05-26

Pseudomonas aeruginosa is an uncommon cause of community-acquired pneumonia in immune-competent hosts. It is commonly seen in patients with structural lung abnormality such as cystic fibrosis or in immune compromised hosts. Here, the authors report a case of community-acquired Pseudomonas pneumonia in a 26-year old healthy man who presented with 8-week history of malaise and cough.

[Study of prognostic factors and prevalence of post-thrombotic syndrome in patients with deep vein thrombosis in Spain].

PubMed

Ordi, Josep; Salmerón, Luis; Acosta, Fernando; Camacho, Isabel; Marín, Núria

2016-01-15

The prevalence of post-thrombotic syndrome (PTS) in Spain is not known accurately at present. The main objective of this study was to determine the prevalence of PTS and the possible prognostic factors related to its development and impact on quality of life. This was an observational, multicenter, cross-sectional and retrospective study of patients who had suffered a deep vein thrombosis (DVT) between March 2010 and March 2011. The Villalta scale was applied as a standardized assessment of PTS at the enrollment visit. According to the score, distribution was: patients with PTS (score>4) and patients without PTS (score ≤4). Subsequently, DVT data and risk factors were collected retrospectively. The quality of life of patients was evaluated. In total 511 patients with DVT were enrolled, of which 7 patients were excluded as they did not meet the inclusion/exclusion criteria. The prevalence of PTS was 53%, with 56.2% having a mild character, 20.6% moderate, and 23.2% severe. The presence of risk factors for DVT including immobilization, hormonal therapy and obesity was significantly higher in patients with PTS than in patients without PTS. There were not significant differences in the location of the DVT. The perception of patients about their health was significantly worse in patients with DVT. The prevalence of PTS in patients with DVT is very high. The presence of risk factors for DVT clearly contributes to a greater predisposition to suffering PTS in an average time of 2 years. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Method for distributed object communications based on dynamically acquired and assembled software components

NASA Technical Reports Server (NTRS)

Sundermier, Amy (Inventor)

2002-01-01

A method for acquiring and assembling software components at execution time into a client program, where the components may be acquired from remote networked servers is disclosed. The acquired components are assembled according to knowledge represented within one or more acquired mediating components. A mediating component implements knowledge of an object model. A mediating component uses its implemented object model knowledge, acquired component class information and polymorphism to assemble components into an interacting program at execution time. The interactions or abstract relationships between components in the object model may be implemented by the mediating component as direct invocations or indirect events or software bus exchanges. The acquired components may establish communications with remote servers. The acquired components may also present a user interface representing data to be exchanged with the remote servers. The mediating components may be assembled into layers, allowing arbitrarily complex programs to be constructed at execution time.

Acquired pit of the optic nerve: a risk factor for progression of glaucoma.

PubMed

Ugurlu, S; Weitzman, M; Nduaguba, C; Caprioli, J

1998-04-01

To examine acquired pit of the optic nerve as a risk factor for progression of glaucoma. In a retrospective longitudinal study, 25 open-angle glaucoma patients with acquired pit of the optic nerve were compared with a group of 24 open-angle glaucoma patients without acquired pit of the optic nerve. The patients were matched for age, mean intraocular pressure, baseline ratio of neuroretinal rim area to disk area, visual field damage, and duration of follow-up. Serial optic disk photographs and visual fields of both groups were evaluated by three independent observers for glaucomatous progression. Of 46 acquired pits of the optic nerve in 37 eyes of 25 patients, 36 pits were located inferiorly (76%) and 11 superiorly (24%; P < .001). Progression of optic disk damage occurred in 16 patients (64%) in the group with acquired pit and in three patients (12.5%) in the group without acquired pit (P < .001). Progression of visual field loss occurred in 14 patients (56%) in the group with acquired pit and in six (25%) in the group without pit (P=.04). Bilateral acquired pit of the optic nerve was present in 12 patients (48%). Disk hemorrhages were observed more frequently in the group with acquired pit (10 eyes, 40%) compared with the group without pit (two eyes, 8%; P=.02). Among patients with glaucoma, patients with acquired pit of the optic nerve represent a subgroup who are at increased risk for progressive optic disk damage and visual field loss.

Solithromycin for the treatment of community-acquired bacterial pneumonia.

PubMed

Viasus, Diego; Ramos, Oscar; Ramos, Leidy; Simonetti, Antonella F; Carratalà, Jordi

2017-01-01

Community-acquired pneumonia is a major public health problem worldwide. In recent years, there has been an increase in the frequency of resistance to the antimicrobials such as β-lactams or macrolides which have habitually been used against the causative pathogens. Solithromycin, a next-generation macrolide, is the first fluoroketolide with activity against most of the frequently isolated bacteria in community-acquired pneumonia, including typical and atypical bacteria as well as macrolide-resistant Streptococcus pneumoniae. Areas covered: A detailed assessment of the literature relating to the antimicrobial activity, pharmacokinetic/pharmacodynamic properties, efficacy, tolerability and safety of solithromycin for the treatment of community-acquired bacterial pneumonia Expert commentary: Recent randomized controlled phase II/III trials have demonstrated the equivalent efficacy of oral and intravenous solithromycin compared with fluoroquinolones in patients with lower mild-to-moderate respiratory infections, and have shown that systemic adverse events are comparable between solithromycin and alternative treatments. However, studies of larger populations which are able to identify infrequent adverse events are now needed to confirm these findings. On balance, current data supports solithromycin as a promising therapy for empirical treatment in adults with community-acquired bacterial pneumonia.

Clinical role of Cefixime in community-acquired infections.

PubMed

Dreshaj, Sh; Doda-Ejupi, T; Tolaj, I Q; Mustafa, A; Kabashi, S; Shala, N; Geca, Nj; Aliu, A; Daka, A; Basha, N

2011-01-01

Cefixime is an oral third generation cephalosporin, frequently used in respiratory tract infections (RTI) in the pediatric population. However, in some publications cefixime has demonstrated poor efficacy against staphylococci and streptococci. of this study was to evaluate the efficacy of cefixime in the treatment of community-acquired infections in a country where parenteral third generation cephalosporins have been used for a long time. The present study was designed to assess the clinical efficacy, bacteriological eradication rates and tolerability of cefixime in children with community-acquired upper RTI (URTI), lower RTI (LRTI) and uncomplicated urinary tract infections (UTI). The study was prospective, open, and included 89 patients, from 6 months to 28 years, of both sexes, with the diagnosis of community-acquired URTI, LRTI and UTI. The treatment with cefixime was successful in 30/30 (100%) patients suffering from acute otitis media (AOM), in 10/12 (83.3%) with acute sinusitis, in 12/12 patients (100%) with pneumonia, in 31/35 (88.57) with uncomplicated UTI. The antibiotic was well tolerated. In 10 days treatment we recorded one case (1.3%) with acute gastroenteritis and two cases (2.6%) of maculopapular rash. Side-effects were transient and disappeared after finishing therapy in all three of the cases. Community-acquired infections, such as AOM, LRTI and UTI, caused by susceptible pathogens, can be treated with cefixime, as a good choice for a successful clinical response.

Patients' Hand Washing and Reducing Hospital-Acquired Infection.

PubMed

Haverstick, Stacy; Goodrich, Cara; Freeman, Regi; James, Shandra; Kullar, Rajkiran; Ahrens, Melissa

2017-06-01

Hand hygiene is important to prevent hospital-acquired infections. Patients' hand hygiene is just as important as hospital workers' hand hygiene. Hospital-acquired infection rates remain a concern across health centers. To improve patients' hand hygiene through the promotion and use of hand washing with soap and water, hand sanitizer, or both and improve patients' education to reduce hospital-acquired infections. In August 2013, patients in a cardiothoracic postsurgical step-down unit were provided with individual bottles of hand sanitizer. Nurses and nursing technicians provided hand hygiene education to each patient. Patients completed a 6-question survey before the intervention, at hospital discharge and 1, 2, and 3 months after the intervention. Hospital-acquired infection data were tracked monthly by infection prevention staff. Significant correlations were found between hand hygiene and rates of infection with vancomycin-resistant enterococci ( P = .003) and methicillin-resistant Staphylococcus aureus ( P = .01) after the intervention. After the implementation of hand hygiene interventions, rates of both infections declined significantly and patients reported more staff offering opportunities for and encouraging hand hygiene. This quality improvement project demonstrates that increased hand hygiene compliance by patients can influence infection rates in an adult cardiothoracic step-down unit. The decreased infection rates and increased compliance with hand hygiene among the patients may be attributed to the implementation of patient education and the increased accessibility and use of hand sanitizer. ©2017 American Association of Critical-Care Nurses.

Acquired Large Calcified Unruptured Sinus of Valsalva Aneurysm.

PubMed

Park, Sang-Hyun; Seol, Sang-Hoon; Seo, Guang-Won; Song, Pil-Sang; Kim, Dong-Kie; Kim, Ki-Hun; Kim, Doo-Il

2015-11-01

Acquired aneurysms of the sinus of Valsalva are rare. They are caused by infections such as tuberculosis, syphilis and endocarditis, as well as atherosclerosis and traumatic injury. They may be asymptomatic and incidentally discovered. We present a rare case of a large acquired calcified unruptured aneurysm of the right coronary sinus of Valsalva that was compressing the right ventricular outflow tract. Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Community-Acquired Acute Kidney Injury: A Nationwide Survey in China.

PubMed

Wang, Yafang; Wang, Jinwei; Su, Tao; Qu, Zhen; Zhao, Minghui; Yang, Li

2017-05-01

This study aimed to describe the burden of community-acquired acute kidney injury (AKI) in China based on a nationwide survey about AKI. Cross-sectional and retrospective study. A national sample of 2,223,230 hospitalized adult patients from 44 academic/local hospitals in Mainland China was used. AKI was defined according to the 2012 KDIGO AKI creatinine criteria or an increase or decrease in serum creatinine level of 50% during the hospital stay. Community-acquired AKI was identified when a patient had AKI that could be defined at hospital admission. The rate, cause, recognition, and treatment of community-acquired AKI were stratified according to hospital type, latitude, and economic development of the regions in which the patients were admitted. All-cause in-hospital mortality and recovery of kidney function at hospital discharge. 4,136 patients with community-acquired AKI were identified during the 2 single-month snapshots (January 2013 and July 2013). Of these, 2,020 (48.8%) had cases related to decreased kidney perfusion; 1,111 (26.9%), to intrinsic kidney disease; and 499 (12.1%), to urinary tract obstruction. In the north versus the south, more patients were exposed to nephrotoxins or had urinary tract obstructions. 536 (13.0%) patients with community-acquired AKI had indications for renal replacement therapy (RRT), but only 347 (64.7%) of them received RRT. Rates of timely diagnosis and appropriate use of RRT were higher in regions with higher per capita gross domestic product. All-cause in-hospital mortality was 7.3% (295 of 4,068). Delayed AKI recognition and being located in northern China were independent risk factors for in-hospital mortality, and referral to nephrology providers was an independent protective factor. Possible misclassification of AKI and community-acquired AKI due to nonstandard definitions and missing data for serum creatinine. The features of community-acquired AKI varied substantially in different regions of China and were closely

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. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Enhancing global vaccine pharmacovigilance: Proof-of-concept study on aseptic meningitis and immune thrombocytopenic purpura following measles-mumps containing vaccination.

PubMed

Perez-Vilar, Silvia; Weibel, Daniel; Sturkenboom, Miriam; Black, Steven; Maure, Christine; Castro, Jose Luis; Bravo-Alcántara, Pamela; Dodd, Caitlin N; Romio, Silvana A; de Ridder, Maria; Nakato, Swabra; Molina-León, Helvert Felipe; Elango, Varalakshmi; Zuber, Patrick L F

2018-01-08

New vaccines designed to prevent diseases endemic in low and middle-income countries (LMICs) are now being introduced without prior record of utilization in countries with robust pharmacovigilance systems. To address this deficit, our objective was to demonstrate feasibility of an international hospital-based network for the assessment of potential epidemiological associations between serious and rare adverse events and vaccines in any setting. This was done through a proof-of-concept evaluation of the risk of immune thrombocytopenic purpura (ITP) and aseptic meningitis (AM) following administration of the first dose of measles-mumps-containing vaccines using the self-controlled risk interval method in the primary analysis. The World Health Organization (WHO) selected 26 sentinel sites (49 hospitals) distributed in 16 countries of the six WHO regions. Incidence rate ratios (IRR) of 5.0 (95% CI: 2.5-9.7) for ITP following first dose of measles-containing vaccinations, and of 10.9 (95% CI: 4.2-27.8) for AM following mumps-containing vaccinations were found. The strain-specific analyses showed significantly elevated ITP risk for measles vaccines containing Schwarz (IRR: 20.7; 95% CI: 2.7-157.6), Edmonston-Zagreb (IRR: 11.1; 95% CI: 1.4-90.3), and Enders'Edmonston (IRR: 8.5; 95% CI: 1.9-38.1) strains. A significantly elevated AM risk for vaccines containing the Leningrad-Zagreb mumps strain (IRR: 10.8; 95% CI: 1.3-87.4) was also found. This proof-of-concept study has shown, for the first time, that an international hospital-based network for the investigation of rare vaccine adverse events, using common standardized procedures and with high participation of LMICs, is feasible, can produce reliable results, and has the potential to characterize differences in risk between vaccine strains. The completion of this network by adding large reference hospitals, particularly from tropical countries, and the systematic WHO-led implementation of this approach, should permit the

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.

A successful renal transplantation for renal failure after dasatinib-induced thrombotic thrombocytopenic purpura in a patient with imatinib-resistant chronic myelogenous leukaemia on nilotinib.

PubMed

Martino, Suella; Daguindau, Etienne; Ferrand, Christophe; Bamoulid, Jamal; Hayette, Sandrine; Nicolini, F-E; Capellier, G; Deconinck, Eric; Larosa, Fabrice

2013-01-01

Second-generation tyrosine kinase inhibitors (TKI2) often induce molecular remission, and prolonged survival with a better tolerance in imatinib-resistant chronic myelogenous leukaemia (CML) patients. We report the case of a CML in first chronic phase who was diagnosed in August 2003 in a young 24 year-old Caucasian woman. Our patient received first imatinib and then dasatinib and nilotinib. Imatinib was well tolerated and she developed TTP/HUS on dasatinib without documented evolution of CML and finally obtained MR5.0 with nilotinib and without any side effect. This case also illustrates the absence of cross-resistance and side-effects between the different TKIs and the feasibility of kidney transplantation associated with a nilotinib treatment of CML allowing a continuing MR5.0 and no further side effects.

Free Reading: A Powerful Tool for Acquiring a Second Language

ERIC Educational Resources Information Center

Priya, J.; Ponniah, R. Joseph

2013-01-01

The paper claims that free reading is a crucial ingredient in acquiring a second or foreign language. It contributes to the development of all measures of language competence which include grammar, vocabulary, spelling, syntax, fluency and style. The review supports the claim that readers acquire language subconsciously when they receive…

Acquired Aplastic Anemia in Children

PubMed Central

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

2013-01-01

SYNOPSIS 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. PMID:24237973

Intensive care unit-acquired weakness.

PubMed

Griffiths, Richard D; Hall, Jesse B

2010-03-01

Severe weakness is being recognized as a complication that impacts significantly on the pace and degree of recovery and return to former functional status of patients who survive the organ failures that mandate life-support therapies such as mechanical ventilation. Despite the apparent importance of this problem, much remains to be understood about its incidence, causes, prevention, and treatment. Review from literature and an expert round-table. The Brussels Round Table Conference in 2009 convened more than 20 experts in the fields of intensive care, neurology, and muscle physiology to review current understandings of intensive care unit-acquired weakness and to improve clinical outcome. Formal electrophysiological evaluation of patients with intensive care unit-acquired weakness can identify peripheral neuropathies, myopathies, and combinations of these disorders, although the correlation of these findings to weakness measurable at the bedside is not always precise. For routine clinical purposes, bedside assessment of neuromuscular function can be performed but is often confounded by complicating factors such as sedative and analgesic administration. Risk factors for development of intensive care unit-acquired weakness include bed rest itself, sepsis, and corticosteroid exposure. A strong association exists between weakness and long-term ventilator dependence; weakness is a major determinant of patient outcomes after surviving acute respiratory failure and may be present for months, or indefinitely, in the convalescence phase of critical illness. Although much has been learned about the physiology and cell and molecular biology of skeletal and diaphragm dysfunction under conditions of aging, exercise, disuse, and sepsis, the application of these understandings to the bedside requires more study in both bench models and patients. Although a trend toward greater immobilization and sedation of patients has characterized the past several decades of intensive care

Forest abovegroundbiomass mapping using spaceborne stereo imagery acquired by Chinese ZY-3

NASA Astrophysics Data System (ADS)

Sun, G.; Ni, W.; Zhang, Z.; Xiong, C.

2015-12-01

Besides LiDAR data, another valuable type of data which is also directly sensitive to forest vertical structures and more suitable for regional mapping of forest biomass is the stereo imagery or photogrammetry. Photogrammetry is the traditional technique for deriving terrain elevation. The elevation of the top of a tree canopy can be directly measured from stereo imagery but winter images are required to get the elevation of ground surface because stereo images are acquired by optical sensors which cannot penetrate dense forest canopies with leaf-on condition. Several spaceborne stereoscopic systems with higher spatial resolutions have been launched in the past several years. For example the Chinese satellite Zi Yuan 3 (ZY-3) specifically designed for the collection of stereo imagery with a resolution of 3.6 m for forward and backward views and 2.1 m for the nadir view was launched on January 9, 2012. Our previous studies have demonstrated that the spaceborne stereo imagery acquired in summer has good performance on the description of forest structures. The ground surface elevation could be extracted from spaceborne stereo imagery acquired in winter. This study mainly focused on assessing the mapping of forest biomass through the combination of spaceborne stereo imagery acquired in summer and those in winter. The test sites of this study located at Daxing AnlingMountains areas as shown in Fig.1. The Daxing Anling site is on the south border of boreal forest belonging to frigid-temperate zone coniferous forest vegetation The dominant tree species is Dhurian larch (Larix gmelinii). 10 scenes of ZY-3 stereo images are used in this study. 5 scenes were acquired on March 14,2012 while the other 5 scenes were acquired on September 7, 2012. Their spatial coverage is shown in Fig.2-a. Fig.2-b is the mosaic of nadir images acquired on 09/07/2012 while Fig.2-c is thecorresponding digital surface model (DSM) derived from stereo images acquired on 09/07/2012. Fig.2-d is the

Leukocyte- and endothelial-derived microparticles: a circulating source for fibrinolysis

PubMed Central

Lacroix, Romaric; Plawinski, Laurent; Robert, Stéphane; Doeuvre, Loïc; Sabatier, Florence; Martinez de Lizarrondo, Sara; Mezzapesa, Anna; Anfosso, Francine; Leroyer, Aurelie S.; Poullin, Pascale; Jourde, Noémie; Njock, Makon-Sébastien; Boulanger, Chantal M.; Anglés-Cano, Eduardo; Dignat-George, Françoise

2012-01-01

Background We recently assigned a new fibrinolytic function to cell-derived microparticles in vitro. In this study we explored the relevance of this novel property of microparticles to the in vivo situation. Design and Methods Circulating microparticles were isolated from the plasma of patients with thrombotic thrombocytopenic purpura or cardiovascular disease and from healthy subjects. Microparticles were also obtained from purified human blood cell subpopulations. The plasminogen activators on microparticles were identified by flow cytometry and enzyme-linked immunosorbent assays; their capacity to generate plasmin was quantified with a chromogenic assay and their fibrinolytic activity was determined by zymography. Results Circulating microparticles isolated from patients generate a range of plasmin activity at their surface. This property was related to a variable content of urokinase-type plasminogen activator and/or tissue plasminogen activator. Using distinct microparticle subpopulations, we demonstrated that plasmin is generated on endothelial and leukocyte microparticles, but not on microparticles of platelet or erythrocyte origin. Leukocyte-derived microparticles bear urokinase-type plasminogen activator and its receptor whereas endothelial microparticles carry tissue plasminogen activator and tissue plasminogen activator/inhibitor complexes. Conclusions Endothelial and leukocyte microparticles, bearing respectively tissue plasminogen activator or urokinase-type plasminogen activator, support a part of the fibrinolytic activity in the circulation which is modulated in pathological settings. Awareness of this blood-borne fibrinolytic activity conveyed by microparticles provides a more comprehensive view of the role of microparticles in the hemostatic equilibrium. PMID:22733025

Is solvent/detergent plasma better than standard fresh-frozen plasma? A systematic review and an expert consensus document

PubMed Central

Marietta, Marco; Franchini, Massimo; Bindi, M. Lucia; Picardi, Francesco; Ruggeri, Matteo; De Silvestro, Giustina

2016-01-01

Background Only a few studies have compared solvent/detergent plasma (SD-plasma) to standard fresh-frozen plasma (FFP) in terms of efficacy and safety. Materials and methods A systematic review was performed in order to develop a consensus document on the use of SD-plasma. Moreover, a pharmacoeconomic study was performed in order to assess whether the use of SD-plasma can be cost-effective with respect to the use of FFP. A multidisciplinary panel used the systematic review and the GRADE methodology to develop evidence-based recommendations on this topic. Results Based on moderate to very low quality evidence, the panel developed the following consensus statements: (i) the panel suggested that SD-plasma is safer than FFP; (ii) the panel could not express for or against a greater efficacy of SD-plasma as compared to FFP; (iii) the panel suggested that in patients undergoing liver transplantation SD-plasma can be preferred over FFP; (iv) the panel suggested that SD-plasma can be preferred over FFP in patients with thrombotic thrombocytopenic purpura undergoing plasma-exchange procedures; (v) the panel could not recommend for or against preferring SD-plasma over FFP in critical care patients; and (vi) the panel suggested that the use of SD-plasma can be cost-effective with respect to the use of FFP. Discussion Data from additional randomised studies are needed to establish more definitive guidelines on the use of SD-plasma. PMID:27136429

Two approaches to the clinical dilemma of treating TTP with therapeutic plasma exchange in patients with a history of anaphylactic reactions to plasma.

PubMed

Sidhu, Davinder; Snyder, Edward L; Tormey, Christopher A

2017-06-01

Thrombotic thrombocytopenic purpura (TTP) is a rare but serious disease caused by autoantibody-mediated deficiency in von Willebrand factor (VWF) cleaving protease, ADAMTS-13. The primary acute treatment is therapeutic plasma exchange (TPE). However, some patients can develop allergic/anaphylactic reactions to the replacement (i.e., donor) plasma over time. Two potential treatment strategies for patients with TTP who demonstrate severe allergic reactions to plasma used for exchange were examined. Two patients with TTP exacerbations who developed severe allergic reactions to donor plasma were identified. One patient's TPE was re-initiated with Octaplas, a lot-batched solvent and detergent treated, type-specific, pooled donor plasma product. The other patient was exchanged with primarily albumin, followed by slow incremental exposures to donor plasma to mitigate exposures and allergic risks. Both patients were assessed for anaphylaxis. Both treatment strategies were successful in preventing any further clinically significant allergic/anaphylactic reactions and facilitated both patients' TTP remissions. Based on our experience with two similar patients with TTP exacerbations and history of anaphylactic reactions to plasma during TPE, we have identified two possible treatment protocols to achieve remission in this clinical dilemma. Substituting Octaplas for standard plasma or, alternatively, using albumin with slowly increasing amounts of standard plasma may help to mitigate the risk of further anaphylactic adverse events. J. Clin. Apheresis 32:158-162, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

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. Copyright © 2012 Cognitive Science Society, Inc.

Value-based purchasing and hospital acquired conditions: are we seeing improvement?

PubMed

Spaulding, Aaron; Zhao, Mei; Haley, D Rob

2014-12-01

To determine if the Value-Based Purchasing Performance Scoring system correlates with hospital acquired condition quality indicators. This study utilizes the following secondary data sources: the American Hospital Association (AHA) annual survey and the Centers for Medicare and Medicaid (CMS) Value-Based Purchasing and Hospital Acquired Conditions databases. Zero-inflated negative binomial regression was used to examine the effect of CMS total performance score on counts of hospital acquired conditions. Hospital structure variables including size, ownership, teaching status, payer mix, case mix, and location were utilized as control variables. The secondary data sources were merged into a single database using Stata 10. Total performance scores, which are used to determine if hospitals should receive incentive money, do not correlate well with quality outcome in the form of hospital acquired conditions. Value-based purchasing does not appear to correlate with improved quality and patient safety as indicated by Hospital Acquired Condition (HAC) scores. This leads us to believe that either the total performance score does not measure what it should, or the quality outcome measurements do not reflect the quality of the total performance scores measure. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A rare case of acquired lymphangioma circumscriptum of the penis.

PubMed

Adikari, S; Philippidou, M; Samuel, M

2017-02-01

Acquired lymphangioma circumscriptum is a rare occurrence on the penis. We report a case of a 47-year-old man who presented with a single lesion of acquired lymphangioma circumscriptum on the penis resembling genital warts. We report the case to increase awareness of this rare condition which may mimic sexually transmitted infections such as genital warts.

Rocky Mountain spotted fever acquired in Florida, 1973-83.

PubMed Central

Sacks, J J; Janowski, H T

1985-01-01

From 1973 to 1983, 49 Florida residents were reported with confirmed Rocky Mountain spotted fever (RMSF), 25 of whom were considered to have had Florida-acquired disease. Although there was no history of tick exposure for six of these 25 persons, all had contact with dogs or outdoor activities during the incubation period. The tick vectors of RMSF are widely distributed throughout Florida. We conclude that RMSF, although rare in Florida, can be acquired in the state. PMID:4061716

The inferior impact of antibody-mediated rejection on the clinical outcome of kidney allografts that develop de novo thrombotic microangiopathy.

PubMed

Wu, Kaiyin; Budde, Klemens; Schmidt, Danilo; Neumayer, Hans-Hellmut; Lehner, Lukas; Bamoulid, Jamal; Rudolph, Birgit

2016-02-01

Antibody-mediated rejection (AMR) can induce and develop thrombotic microangiopathy (TMA) in renal allografts. A definitive AMR (dAMR) co-presents three diagnostic features. A suspicious AMR (sAMR) is designated when one of the three features is missing. Thirty-two TMA cases overlapping with AMR (AMR+ TMA) were studied, which involved 14 cases of sAMR+ TMA and 18 cases of dAMR+ TMA. Thirty TMA cases free of AMR features (AMR- TMA) were enrolled as control group. The ratio of complete response to treatment was similar between AMR- TMA and AMR+ TMA group (23.3% vs. 12.5%, p = 0.33), or between sAMR+ TMA and dAMR+ TMA group (14.3% vs. 11.1%, p = 0.79). At eight yr post-transplantation, the death-censored graft survival (DCGS) rate of AMR- TMA group was 62.8%, which was significantly higher than 28.0% of AMR+ TMA group (p = 0.01), but similar between sAMR+ TMA and dAMR+ TMA group (30.0% vs. 26.7%, p = 0.92). Overall, the intimal arteritis and the broad HLA (Human leukocyte antigens) mismatches were closely associated with over time renal allograft failure. The AMR+ TMA has inferior long-term graft survival, but grafts with sAMR+ TMA or dAMR+ TMA have similar characteristics and clinical courses. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Acquired Elastotic Hemangioma: Case Series and Comprehensive Literature Review

PubMed Central

Hinds, Brian R

2017-01-01

Background Acquired elastotic hemangioma is a benign vascular proliferation that typically presents as an asymptomatic red plaque on a sun-exposed site of an adult. Material and Methods The PubMed database was used to search the following words: acquired, angioma, arm, basal, carcinoma, cell, elastosis, elastotic, exposed, forearm, hemangioma, solar, sun, and vascular. The relevant papers and reference cited generated by the search were reviewed. The features from a case series of 11 patients with acquired elastotic hemangioma are presented. In addition, a comprehensive review of the characteristics of this unique hemangioma—not only in our 11 patients but also in the previously reported 34 individuals with this lesion—is provided. Results Acquired elastotic hemangioma, reported in 45 patients (24 women and 21 men), typically appeared as an asymptomatic solitary red plaque in sun-exposed areas—most commonly the forearm--of adults aged 50 years or older. The pathology shows a proliferation of vascular channels—surrounded and intertwined by intense solar elastosis--in the upper dermis, located parallel to the overlying epidermis, and separated from it by a zone of normal-appearing superficial papillary dermis. There was extensive solar elastosis surrounding and between the new blood vessels; some of the endothelial cells protrude (in a hob-nail pattern) into the vessel lumen. The clinical differential diagnosis includes basal cell carcinoma and the pathologic differential diagnosis includes other benign, malignant, and reactive vascular lesions. Ultraviolet radiation may contribute to the pathogenesis of this hemangioma since it occurs on sun-exposed sites. There was no recurrence of the lesion following either excision or observation. Conclusions The possibility of acquired elastotic hemangioma should be considered by clinicians when they encounter an older individual with a new red plaque on a sun-exposed site that clinically appears to be a superficial

Development and Validation of a Practical Two-Step Prediction Model and Clinical Risk Score for Post-Thrombotic Syndrome.

PubMed

Amin, Elham E; van Kuijk, Sander M J; Joore, Manuela A; Prandoni, Paolo; Cate, Hugo Ten; Cate-Hoek, Arina J Ten

2018-06-04

 Post-thrombotic syndrome (PTS) is a common chronic consequence of deep vein thrombosis that affects the quality of life and is associated with substantial costs. In clinical practice, it is not possible to predict the individual patient risk. We develop and validate a practical two-step prediction tool for PTS in the acute and sub-acute phase of deep vein thrombosis.  Multivariable regression modelling with data from two prospective cohorts in which 479 (derivation) and 1,107 (validation) consecutive patients with objectively confirmed deep vein thrombosis of the leg, from thrombosis outpatient clinic of Maastricht University Medical Centre, the Netherlands (derivation) and Padua University hospital in Italy (validation), were included. PTS was defined as a Villalta score of ≥ 5 at least 6 months after acute thrombosis.  Variables in the baseline model in the acute phase were: age, body mass index, sex, varicose veins, history of venous thrombosis, smoking status, provoked thrombosis and thrombus location. For the secondary model, the additional variable was residual vein obstruction. Optimism-corrected area under the receiver operating characteristic curves (AUCs) were 0.71 for the baseline model and 0.60 for the secondary model. Calibration plots showed well-calibrated predictions. External validation of the derived clinical risk scores was successful: AUC, 0.66 (95% confidence interval [CI], 0.63-0.70) and 0.64 (95% CI, 0.60-0.69).  Individual risk for PTS in the acute phase of deep vein thrombosis can be predicted based on readily accessible baseline clinical and demographic characteristics. The individual risk in the sub-acute phase can be predicted with limited additional clinical characteristics. Schattauer GmbH Stuttgart.

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.

25 CFR 243.7 - How can a non-Native acquire live reindeer?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false How can a non-Native acquire live reindeer? 243.7 Section 243.7 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FISH AND WILDLIFE REINDEER IN ALASKA § 243.7 How can a non-Native acquire live reindeer? If you are a non-Native who wants to acquire live Alaskan reindeer, you must apply to us in...