Clinical study of 9 patients with acquired thrombotic thrombocytopenic purpura
|
|
- Magnus Page
- 5 years ago
- Views:
Transcription
1 Journal of Clinical and Experimental Medicine VOL.1,ISS.3,DEC 2017,1-5 ONLINE ISSN: PRINT ISSN: DOI: /jocem Abstract: Clinical study of 9 patients with acquired thrombotic thrombocytopenic purpura Objective: To analyze the clinical features, treatment strategies and outcomes of patients with acquired thrombocytopenic purpura (TTP). Methods: The clinical data of 9 patients with acquired TTP were retrospectively analyzed. Using SPSS 13.0 software for data analysis. Results: There were 4 males and 5 females in 9 patients, with a median age of 43 (24-72) years. Five patients (55.56%) showed typical pentadia syndrome. Thrombocytopenia (100%), microangiopathy Anemia (100%), fever (88.89%) is more common, while the nervous system symptoms (77.78%) and kidney damage (55.56%) is relatively rare. Two patients were tested for plasma von Willebrand factor (ADAMTS13) activity, with activities of 2.4% and 4.4%, respectively. Four patients (44.44%) were treated effectively, and the effective rate of plasma exchange and plasma infusion was 55.56%. Five patients died without recurrence. The average age of onset of death was higher than that of the effective patients (52.2 ± VS ± 11.44), but the difference was not statistically significant (P = 0.081). Conclusion: Concurrent clinical fever, hemolysis and bleeding tendency need to consider the possibility of TTP. Detection of plasma ADAMTS13 activity contributes to the clinical diagnosis of TTP. Early diagnosis and timely application of plasma therapy can help control the disease. The prognosis of elderly patients is relatively poor. Hong Qu Pan Yu Central Hospital, GuangDong, China keywords: Purpura, thrombotic thrombocytopenia; von Willebrand factor lyase; clinical features; treatment Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA) characterized primarily by microvascular hemolytic anemia (MAHA), reduced platelet aggregation depletion, and organ damage caused by thrombosis (eg, the kidney, central nervous system, etc.). TTP has low incidence, high mortality and the presence of multiple system symptoms and misdiagnosis, missed diagnosis, leading to miss the best timing of treatment. Clinically, according to the genetic background it is divided into hereditary TTP and acquired TTP. The latter is divided into idiopathic and secondary according to whether there are obvious incentives. Most cases are idiopathic, no special cause can be found, the disease is easy to recurrent; secondary has a specific reason, having an increasing incidence in recent years,. We retrospectively analyzed the clinical features, treatment strategies and outcomes of 9 patients with acquired TTP, and the report is as follows. Cases and methods 1.General Information: 9 patients with acquired TTP were admitted to Panyu Central Hospital of Guangzhou from April 2010 to May TTP diagnosis of all patients was in line with the standard [1]. There were 4 males and 5 females, with a median age of 43 (24-72) years (Table 1). 2.Research Methods: All cases are in line with TTP diagnostic criteria. TTP diagnosis is based on five clinical features: reduced thrombocytopenia, microangiopathic hemolytic anemia (blood smears see broken red blood cells), nervous system abnormalities, renal damage and fever; diagnosis of TTP must have at least two criteria: microangiopathy hemolytic anemia and reduced thrombocytopenia, excluding other diseases that cause reduced thrombocytopenia and microangiopathic hemolytic anemia, such as antiphospholipid antibody syndrome and diffuse intravascular coagulation. changzhi212@163.com
2 2 VOL.1,ISS.3,DEC 2017,1-5 3.treatment programs 3.1 plasma treatment plasma infusion (PI) and (or) plasma exchange (PE). Plasma exchange volume 40-60ml / kg / d, when the patient improved symptoms it gradually adjusted to 1 time / qod, 2 times / W to 1 time / W. Plasma infusion ml / d, for 3-5 days, when the patient improved symptoms it gradually disabled. The median time to onset of plasma therapy was 2 (1-20) days, of which the median PE was 5 (1-10). 3.2 glucocorticoid treatment glucocorticoid choose methylprednisolone or prednisolone 1mg / (kg.d), or dexamethasone 10-20mg / d intravenous infusion, once every 5-14d, after stable condition the reduction and with a splash Nisong oral maintenance, specific reduction and maintenance of treatment programs is same with the diagnosis and treatment of immune thrombocytopenia [18]. 3.3 Immunosuppressant treatment 1 patient with systemic lupus erythematosus (SLE), combined with cyclophosphamide (CTX) 1.2g / w, a total of 1, due to the patients economic reasons to give up treatment, not to continue to use. 4. Efficacy: the efficacy standard reference [2-3] : 1 effective: normal platelet count, no clinical symptoms and signs; 2 some effective: PLT 50 * 10 ^ 9 / L or 1 times the basal value, no clinical symptoms and signs; 3 invalid: PLT <20 * 10 ^ 9 / L or less than 1 times, the increase in clinical symptoms; 4 recurrence: TTP clinical manifestations again after complete remission 30d. 5. Statistical analysis: The SPSS 13.0 software was used to analyze the data, and the independent sample t-test was used to compare the effective group with the death group. The difference was statistically significant at p <0.05. Other data use median representation. Results I.the clinical features 1. Causes: Nine patients with acquired TTP were acute onset, of which 3 cases co-exist autoimmune diseases, namely systemic lupus erythematosus, hyperthyroidism and immune thrombocytopenic purpura, 1 case of pulmonary infection, the rest 5 cases having no obvious incentive. 2, clinical manifestations: 9 cases of acquired TTP in patients with first symptoms include fever, thrombocytopenia, fatigue, hemolytic anemia, neuropsychiatric symptoms, the above single or joint manifestations, in the effective treatment of progressive exacerbations or successive occurrence. Five cases showed "five joint" sign. Nine patients had thrombocytopenia and MAHA, one with hemorrhage concurrently, seven with neurological symptoms, eight with fever, and five with renal insufficiency (Table 2). II.laboratory tests 1. Hematology analysis: Nine cases of TTP patients have complete blood cell analysis data. HGB median 76 (43-93) g / L, 8 cases of moderate and severe anemia; PLT median 8 (2-17) * 10 ^ 9 / L; all 9 patients with peripheral blood smear, All detected broken red blood cells, the median was 4.4% (0.5% -13.0%), of which 3 patients with broken red blood cell count 3%. 2. Biochemical tests: The countable total bilirubin values of 8 patients, the median was 76.3 ( ) μmol / L, the normal reference value ( ) μmol / L; 6 patients with median LDH 1474 ( ) U / L, the normal reference value ( ) U / L, of which 4 cases (66.67%) patients with LDH> 1000U / L. The median creatinine was 157 ( ) μmol / L in 5 patients with renal dysfunction, the normal reference value was μmol / L, the median urea nitrogen was 11.6 ( ) μmol / L, the reference value is ( ) μmol / L. 3. Plasma ADAMTS13 activity and inhibitor test: ADAMTS13 was detected in 2 of 9 patients with TTP, with 1 activity of 4.4% and 1 activity of 2.4%, meanwhile, the test result of plasma ADAMTS13 inhibitor was weakly positive. III.treatment All 9 patients received glucocorticoid therapy, of which only 1 patient was treated with glucocorticoid alone and the remaining 8 patients were treated with PE or (and) PI or (and) immunosuppressant (cyclophosphamide). One patient was accompanied by systemic lupus erythematosus. CTX 1.2g / w was used for 1 time, and then the treatment was abandoned due to economic reasons. IV. the treatment results Five patients (55.56%) died, including 3 deaths in the
3 VOL.1,ISS.3,DEC 2017,1-5 3 hospital (1 failed due to plasma therapy) and 2 patients who abandoned treatment and died outside the hospital. One patient with glucocorticoid alone died; four of the eight patients receiving plasma therapy survived and four died (Table 3). There was no significant difference in age of onset, the total bilirubin level before treatment, body temperature, white blood cell count, hemoglobin, platelet count, serum creatinine and LDH (Table 4). Discussion TTP is a rare thrombotic microvascular disease characterized by multiple systemic lesions with a prevalence of about 3.7 / 1 million [4], with a prevalence of years and a male to female ratio of about 1: 2 [5]. Recent studies of FV Leiden anomaly [14] and tissue plasminogen activator activity (t-pa) reduction [15] have been linked to the development of TTP. However, the lack of vasopressin lyase (ADAMTS13) is a major pathological mechanism of TTP [6-9], but not all TTP patients detect abnormalities of ADAMTS13, especially TTP patients secondary to other diseases can seldom detect ADAMTS13 abnormalities [10]. In this study, only 2 patients were tested for ADAMTS13 activity due to the lack of detection means or reagents, and their activity was reduced. Therefore, ADAMTS13 activity measurement is an important auxiliary indicator in the diagnosis of TTP, rather than the only standard [11], but dynamic detection of ADAMTS13 activity can provide some reference for the disease. The diversity of TTP clinical manifestations. Among the patients with acquired TTP, thrombocytopenia (100%), microangiopathy hemolytic anemia (100%) and fever (88.89%) were more common, while neurological symptoms (77.78%) and renal damage (55.56% )were relatively rare. Five cases (55.56%) had a typical "five joint sign" performance. Therefore, TTP should be considered when patients have unexplained thrombocytopenia, hemolytic anemia and fever. In addition, patients with atypical clinical manifestations, broken red blood cells and elevated LDH can also assist in the early diagnosis of TTP. Since the introduction of PE therapy in clinical practice in the 1970s, the mortality rate of TTP has been gradually reduced from 90% to 10% -20% [17]. PE is still an important method for the treatment of this disease. It can effectively remove ADAMTS13 autoantibodies and excessive vwf multimers and supplement the normal ADAMTS13 for therapeutic purposes [12]. Plasma therapy was given in 8 patients (88.89%) in this group. The median time from onset to the PE treatment was 2 (1-20) days. The clinical symptoms were significantly improved in 4 patients. The median effective time was 3 (2-4) days. The mortality rate of patients receiving plasma therapy was 50%, much higher than the lowest reported international mortality rate (4%) [13]. Possible reasons include: 1 Among the 8 patients undergoing plasma therapy, 3 gave up follow-up treatment and 1 case of poor treatment; 2 due to delayed diagnosis, not timely PE treatment or insufficient replacement. In this study, plasma therapy combined with glucocorticoid therapy in patients without recurrence and death, the plasma and hormone dose, treatment time and the drug adjustment standard is based on the actual situation of the grass-roots hospitals and patients economic conditions, the effect seems encouraging. In summary, TTP is a rare clinical critically ill, clinical complex and diverse. When patients have unexplained manifestations of thrombocytopenia and hemolytic anemia, they are indications for the initiation of TTP treatment [16]. ADAMTS13 activity detection and related biochemical indicators of dynamic changes play a guiding role for the clinical evaluation of the disease development. The advent of PE has significantly increased the survival rate of patients with TTP, especially for the elderly, winning time for the patient's life, and new therapeutic approaches for TTP are also being actively explored, mainly focusing on inhibiting the collagen-vwf-platelet response axis and VWF antibody is expected for the treatment of TTP. However, for grass-roots medical units, primary medical staff's comprehensive understanding of the disease and its familiarity with clinical features are of crucial importance for the early diagnosis of TTP. Looking for TTP treatment guidelines and emergency procedures more suitable for primary health care workers remains to be confirmed by a large number of clinical studies.
4 4 VOL.1,ISS.3,DEC 2017,1-5 Table 1 Summary of clinical data in 9 cases of acquired thrombocytopenic purpura patients no. item gender male female female female male male female male female age Body tempreture( ) WBC(*10^9/L) Hb (g/l) Plt(*10^9/L) LDH(U/L) Creatinine (umol/l) Urea nitrogen (umol/l) TB(umol/L) DB(umol/L) IB(umol/L) Ferr Re% Broken red blood cells (%) ADAMTS13 ADAMTS13 Not checked Not checked Not checked Not checked Not checked activity 2.4% Not checked Not checked 4.4% Table 2 the clinical manifestations of 9 cases of acquired thrombocytopenic purpura patients Clinical manifestations cases(%) Bleeding 6(66.67%) Cerebral hemorrhage 2(22.22%) Skin ecchymosis 3(33.33%) Menstrual volume increased 1(11.11%) Microvascular hemolytic anemia 9(100%) Neuropsychiatric symptoms 7(77.78%) Consciousness indifferent, unconscious 2(22.22%) Looking, convulsions 4(44.44%) Headache, vomiting 1(11.11%) fever 8(88.89%) Renal insufficiency 5(55.56%) Table 3 the treatment and outcome of 9 cases of thrombotic thrombocytopenic purpura patients [cases (%)] treatment method cases effective died Glucocorticoids 1 0(0) 1(100.00%) Glucocorticoids + plasma exchange + plasma infusion Glucocorticoids + plasma exchange + plasma infusion + immunosuppressants Plasma exchange + plasma infusion 3 1(33.33%) 2(66.67%) 1 0(0) 1(100%) 4 3(75.00%) 1(25.00%) Table 4 the comparison of clinical features when onset of patients with thrombotic thrombocytopenic purpura with different treatment results (± s) Clinical indicators effective group (4 cases) death group (5 cases) P value age(year) 32.25± ± body temperature( ) 39.1± ± WBC(*10^9/L) 39.8± ± HGB(g/L) 75± ± PLT(*10^9/L) 10.25± ± Total bilirubin Creatinine Urea nitrogen 78.78± ± ± ± ± ± LDH(U/L) ± ± References: [1] Chinese Society of Hematology, Department of Thrombosis and Hemostasis. Chinese expert consensus on diagnosis and treatment of Thrombotic thrombocytopenic purpura (2012 Edition) [J] Journal of Hematology, 2012,33 (11): [2] Zhan X, Streiff MB, King KE,et al. Thrombotic thrombocytopenic purpura at the Johns Hopkins Hospital from 1992 to 2008: clinical outcomes and risk factors for relapse[j]. Transfusion,2010,50(4): [3] Gurkan E, Baslamisli F, Guvenc B, et al. Thrombotic thrombocytopenic prupura in southern Turkey: a single-center experience of 29 cases[j]. Clin Lab Haematol,2003,120(4): [4] Allford SL,Hunt BJ,Rose P,et al.guidelines on the diagnosis and management of the thrombotic microangiopathic haemolytic anaemias[j].br J Haematol,2003,120(4):
5 VOL.1,ISS.3,DEC 2017,1-5 5 [5] George JN,Terrell DR,Swisher KK,et al.lessons learned from the Oklahoma syndrome registry[j].j Clin Apher,2008,23(4): [6] Zheng X,Chung D,Takayama TK,et al.structure of von Willebrand factor- cleaving protease (ADAMTS13),a metalloprotease involed in thrombotic thrombocytopenic purpura[j].j Bio Chem,2001,276(44): [7] Fujikawa K,Suzuki H,MeMullen B,et al.purification of human von Willebrand factor-cleaving protease and its identification as a new member of the metalloproteinase family [J].Blood, 2001,98(6): [8] Soejima K,Mimura N,Hirashima M,et al.a novel human metalloprotease synthesized in the liver and secreted into the blood:possibly,the von Willebrand factor cleaving protease?[j].j Biochem,2001,130(4): [9] SADLER J E.Von Willebrand factor,adamts13,and thrombotic thrombocytopenic purpura [J].Blood,112(1): [10] KREMER HOVINGA J A,LAMMLE B.Role of ADAMTS13 in the pathogenesis,diagnosis,and treatment of thrombotic thrombocytopenic purpura [J].Hematology Am Soc Hematol Educ Program,2012,2012: [11] George JN.How I treat patients with thrombotic thrombocytopenic purpura:2010[j].blood,2010,116(20): [12] MATSUMOTO M.Anti-ADAMTS13 autoantibodies in patientis with thrombotic thrombocytopenic purpura[j].nihon Rinsho Meneki Gakkai Kaishi,2013,36(2): [13] Zhan H,Streiff MB,King KE,et al.thrombotic thrombocytopenic purpura at the Johns Hopkins Hospital from 1992 to 2008: clinical outcomes and risk factors for relapse[j]. Transfusion,2010,50(4): [14] RAIFE TJ,LENTZ SR,ATKINSON BS,et al.faclor V Leiden;a genetic risk factor for thrombotic Microangiopathy in patients with normal von Willebrand factor-clearing protease activity[j]. Blood,2002,99(2); [15] HOIRISCH-CLAPAUCH S,NARDI AE.A role for tissue plasminogen activator in thrombotic thrombocytopenic purpura[j].med Hypotheses,2014,83(6): [16] YANG Yan,DONG Chun-xia,YANG Lin-hua.Thrombotic thrombocytopenic purpura research[j].chinese Jurnal of Thrombosis and Hemostasis,2016,22(1): [17] Bandarenko N,Brecher ME,United States Thrombotic THrombocytopenic Purpura Apheresis Study Group (US TTP ASG);multicenter survey and retrospective analysis of current efficacy of therapeutic plasma exchange[j].j Clin Apher,1998,13(3): [18] Chinese Society of Hematology, Department of Thrombosis and Hemostasis. Chinese expert consensus on diagnosis and treatment of adult primary immune thrombocytopenia [J] Journal of Hematology, 2011,32 (3):
Journal of Clinical and Experimental Medicine
Journal of Clinical and Experimental Medicine www.jocem.org Volume 1 Issue 3 DEC 2017 Editor-in-chief R.F Deng Deputy-Editors-in-Chief W.H. Chen X.R. XU Y.J. ZHANG X.R. WANG Y.G. HUANG L.X.SU Editor staff
More informationBeyond Plasma Exchange: Targeted Therapy for Thrombotic Thrombocytopenic Purpura
Beyond Plasma Exchange: Targeted Therapy for Thrombotic Thrombocytopenic Purpura Kristen Knoph, PharmD, BCPS PGY2 Pharmacotherapy Resident Pharmacy Grand Rounds April 25, 2017 2016 MFMER slide-1 Objectives
More informationThrombotic Thrombocytopenic
The Treatment of TTP and the Prevention of Relapses GERALD APPEL, MD Professor of Clinical Medicine Columbia University College of Physicians and Surgeons NY-Presbyterian Hospital New York, New York Thrombotic
More information* Renal insufficiencies
Thrombotic Thrombocytopenic Purpura Behzad Poopak, DCLS PhD. Tehran medical Branch Islamic Azad university bpoopak@yahoo.com Case Summary Ms. X, a 35-year year-old woman Complained of weakness, low grade
More informationWhat is meant by Thrombotic Microangiopathy (TMA)?
What is meant by Thrombotic Microangiopathy (TMA)? Thrombotic Microangiopathy (TMA) is a group of disorders characterized by injured endothelial cells, microangiopathic hemolytic anemia (MAHA), with its
More informationPresentation Outline. Disease Background Previous research on platelet recovery rate Goal of our study Methods Results Limitations Conclusions
Platelet Recovery Rate at Day 5 of Therapeutic Plasma Exchange for Acquired Thrombotic Thrombocytopenic Purpura Can Aid in Identifying Risk of Disease Exacerbation Suzanne Zhou, Yara A. Park, Marian A.
More informationDR V PHILIP CLINICAL HAEMATOLOGY UNIT CHRIS HANI BARAGWANATH ACADEMIC HOSPITAL
DR V PHILIP CLINICAL HAEMATOLOGY UNIT CHRIS HANI BARAGWANATH ACADEMIC HOSPITAL Rare but fatal disease if unrecognized and untreated Incidence about 1: 1 million in the USA Female preponderance of 2:1 Part
More informationThrombotic thrombocytopenic purpura: a look at the future
Thrombotic thrombocytopenic purpura: a look at the future Andrea Artoni, MD Ph.D. Angelo Bianchi Bonomi Hemophilia and Thrombosis Center IRCCS Ca Granda Ospedale Maggiore Policlinico Milan, Italy andrea.artoni@policlinico.mi.it
More informationThrombotic Thrombocytopenic Purpura and the Role of ADAMTS-13
Thrombotic Thrombocytopenic Purpura and the Role of ADAMTS-13 Mark Cunningham,MD Director, Hematology Laboratory Department of Pathology University of Kansas Medical Center College of American Pathologists
More informationObjectives. Thrombotic Thrombocytopenic Purpura (TTP) and ADAMTS13 Testing. Disclosure
Thrombotic Thrombocytopenic Purpura (TTP) and Testing Dong Chen MD PhD Special Coagulation Laboratory Mayo Clinic-Rochester 2018 Disclosure Chair, CAP Coagulation Resource Committee Mayo Medical Laboratory
More informationHemolytic uremic syndrome: Investigations and management
Hemolytic uremic syndrome: Investigations and management SAWAI Toshihiro M.D., Ph.D. Department of Pediatrics, Shiga University of Medical Science Otsu, JAPAN AGENDA TMA; Thrombotic micro angiopathy STEC-HUS;
More informationAtypical Hemolytic Uremic Syndrome: When the Environment and Mutations Affect Organ Systems. A Case Report with Review of Literature
Atypical Hemolytic Uremic Syndrome: When the Environment and Mutations Affect Organ Systems. A Case Report with Review of Literature Mouhanna Abu Ghanimeh 1, Omar Abughanimeh 1, Ayman Qasrawi 1, Abdulraheem
More informationNew insights in thrombotic microangiopathies : TTP and ahus
New insights in thrombotic microangiopathies : TTP and ahus Dr Catherine LAMBERT Hematology Cliniques universitaires Saint-Luc Catherine.lambert@uclouvain.be New insights in thrombotic microangiopathies
More informationDRUG NAME: Eculizumab Brand(s): Soliris DOSAGE FORM/ STRENGTH: 10 mg/ml (300 mg per vial)
Preamble: A confirmed diagnosis of atypical hemolytic uremic syndrome (ahus) is required for eculizumab funding. The information below is to provide clinicians with context for how a diagnosis of ahus
More informationLet`s go for the diagnosis! Yazeed Toukan, MD Pediatric Pulmonary Institute, Ruth Rappaport Children`s Hospital July 2016
Let`s go for the diagnosis! Yazeed Toukan, MD Pediatric Pulmonary Institute, Ruth Rappaport Children`s Hospital July 2016 Case report 20 months old girl Israeli Arab Muslim family, consanguineous marriage
More informationHEME 10 Bleeding Disorders
HEME 10 Bleeding Disorders When injury occurs, three mechanisms occur Blood vessels Primary hemostasis Secondary hemostasis Diseases of the blood vessels Platelet disorders Thrombocytopenia Functional
More informationThrombotic thrombocytopenic purpura: 2008 Update
MEDICAL GRAND ROUNDS CME CREDIT MARK A. CROWTHER, MD Director, Division of Hematology, McMaster University, Hamilton, Ontario, Canada JAMES N. GEORGE, MD Hematology-Oncology Section, Department of Medicine,
More information1) unexplained microangiopathic hemolytic anemia (Coombs negative anemia),
Ravi Sarode, MD Consensus Process The TTP-CC subcommittee developed 7 key questions Sent to the 7 speakers for electronic voting in Yes or No format Will be published in JCA soon Q.1 Untreated TTP carries
More informationBleeding and Thrombotic Disorders. Kristine Krafts, M.D.
Bleeding and Thrombotic Disorders Kristine Krafts, M.D. Bleeding and Thrombotic Disorders Bleeding disorders von Willebrand disease Hemophilia A and B DIC TTP/HUS ITP Thrombotic disorders Factor V Leiden
More informationMost Common Hemostasis Consults: Thrombocytopenia
Most Common Hemostasis Consults: Thrombocytopenia Cindy Neunert, MS MSCS Assistant Professor, Pediatrics CUMC Columbia University TSHNA Meeting, April 15, 2016 Financial Disclosures No relevant financial
More informationA 60 year old woman with altered mental status and thrombotic microangiopathy. Josh Veatch
A 60 year old woman with altered mental status and thrombotic microangiopathy Josh Veatch Previously healthy 60 year old woman 2 3 months of fatigue following a URI, transient episodes being out of it
More informationTMA in HUS and TTP: new insights
TMA in HUS and TTP: new insights Daan Dierickx University Hospitals Leuven, Department of Hematology, Belgium 20th Annual Meeting Belgian Society on Thrombosis and Haemostatis Antwerpen, 22 th November
More informationTHROMBOTIC MICROANGIOPATHY. Jun-Ki Park 7/19/11
THROMBOTIC MICROANGIOPATHY Jun-Ki Park 7/19/11 TMAs are microvascular occlusive disorders characterized by systemic or intrarenal aggregation of platelets, thrombocytopenia, and mechanical injury to erythrocytes.
More informationPLASMA EXCHANGE J MANION NEPEAN HOSPITAL
PLASMA EXCHANGE J MANION NEPEAN HOSPITAL PLASMA The fluid portion of blood Normally approx 5% body weight or 3.5L in 70kg male Clots on standing unless anticoagulated Common plasma proteins are albumin,
More informationThings to never miss in the office. Brett Houston MD FRCPC (PYG-5, hematology) Leonard Minuk MD FRCPC
Things to never miss in the office Brett Houston MD FRCPC (PYG-5, hematology) Leonard Minuk MD FRCPC Presenter Disclosure Faculty / Speaker s name: Brett Houston / Leonard Minuk Relationships with commercial
More informationmonoclonal gammopathy of undetermin Citation Rheumatology international, 33(1),
NAOSITE: Nagasaki University's Ac Title Author(s) Renal thrombotic microangiopathies/ in a patient with primary Sjögren's monoclonal gammopathy of undetermin Koga, Tomohiro; Yamasaki, Satoshi; Atsushi;
More informationLAMA SHATAT TTP, ITP, DIC
TTP, ITP, DIC Reduction in platelet number (thrombocytopenia) constitutes an important cause of generalized bleeding. A count less than 100,000 platelets/μl is generally considered to constitute thrombocytopenia.
More informationSoliris (eculizumab) DRUG.00050
Market DC Soliris (eculizumab) DRUG.00050 Override(s) Prior Authorization Approval Duration 1 year Medications Soliris (eculizumab) APPROVAL CRITERIA Paroxysmal Nocturnal Hemoglobinuria I. Initiation of
More informationDr. Rai Muhammad Asghar Associate Professor Head of Pediatric Department Rawalpindi Medical College
Dr. Rai Muhammad Asghar Associate Professor Head of Pediatric Department Rawalpindi Medical College AN APPROACH TO BLEEDING DISORDERS NORMAL HEMOSTASIS After injury, 3 processes halt bleeding Vasoconstriction
More informationRituximab Can Be Combined With Daily Plasma Exchange to Achieve Effective B-Cell Depletion and Clinical Improvement in Acute Autoimmune TTP
Coagulation and Transfusion Medicine / REFRACTORY ACUTE AUTOIMMUNE TTP Rituximab Can Be Combined With Daily Plasma Exchange to Achieve Effective B-Cell Depletion and Clinical Improvement in Acute Autoimmune
More informationThe importance of thrombocytopenia and its causes
SYSMEX EDUCATIONAL ENHANCEMENT AND DEVELOPMENT NO 4 2017 SEED HAEMATOLOGY The importance of thrombocytopenia and its causes Key words: Thrombocytopenia, thrombocytopenic, low levels of platelets What is
More informationBleeding Disorders.2 MS Abdallah Awidi Abbadi.MD. FRCP.FRCPath Feras Fararjeh MD
Bleeding Disorders.2 MS4.25.02.2019 Abdallah Awidi Abbadi.MD. FRCP.FRCPath Feras Fararjeh MD Email: abdalla.awidi@gmail.com Case 6: GT 18 yr old female was admitted with pallor, abdominal pain and gum
More informationCoagulation Disorders. Dr. Muhammad Shamim Assistant Professor, BMU
Coagulation Disorders Dr. Muhammad Shamim Assistant Professor, BMU 1 Introduction Local Vs. General Hematoma & Joint bleed Coagulation Skin/Mucosal Petechiae & Purpura PLT wound / surgical bleeding Immediate
More informationTTP and ADAMTS13: When Is Testing Appropriate?
TTP and ADAMTS13: When Is Testing Appropriate? Pier Mannuccio Mannucci and Flora Peyvandi A. Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Medicine and Medical Specialities, University
More informationSara K. Vesely, James N. George, Bernhard Lämmle, Jan-Dirk Studt, Lorenzo Alberio, Mayez A. El-Harake, and Gary E. Raskob
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS ADAMTS13 activity in thrombotic thrombocytopenic purpura hemolytic uremic syndrome: relation to presenting features and clinical outcomes in
More informationHUS and TTP Testing. Kenneth D. Friedman, M.D. Director, Hemostasis Reference Lab BloodCenter of Wisconsin, Milwaukee WI
HUS and TTP Testing Kenneth D. Friedman, M.D. Director, Hemostasis Reference Lab BloodCenter of Wisconsin, Milwaukee WI Disclosures Relevant Financial Relationships Consultant: Ablynx, Bayer, CSL Behring,
More informationHeme (Bleeding and Coagulopathies) in the ICU
Heme (Bleeding and Coagulopathies) in the ICU General Topics To Discuss Transfusions DIC Thrombocytopenia Liver and renal disease related bleeding Lack of evidence in managing critical illness related
More informationApproccio morfologico alle microangiopatie trombotiche
Approccio morfologico alle microangiopatie trombotiche Gina Zini Polo Oncologia e Ematologia Policlinico A. Gemelli Università Cattolica S. Cuore - Roma 1 Thrombotic microangiopathies Occlusive microangiopathic
More informationBehzad Poopak, DCLS PhD
Behzad Poopak, DCLS PhD Test Report Name Age Critical Low HEMATOLOGY Activated Partial Thromboplastin Time, Plasma Critical High - 150 sec Units Fibrinogen 60 - mg/dl INR (International Normalizing
More informationSome renal vascular disorders
Some renal vascular disorders Introduction Nearly all diseases of the kidney involve the renal blood vessels secondarily We will discuss: -Hypertension (arterionephrosclerosis in benign HTN & hyperplastic
More informationCaplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura
Original Article Treatment for Acquired Thrombotic Thrombocytopenic Purpura M. Scully, S.R. Cataland, F. Peyvandi, P. Coppo, P. Knöbl, J.A. Kremer Hovinga, A. Metjian, J. de la Rubia, K. Pavenski, F. Callewaert,
More informationClinical Presentation and Follow-up of Eighteen Patients with Thrombotic Thrombocytopenic Purpura Received in: March 2007 Accepted in: 14/1/2010
Clinical Presentation and Follow-up of Eighteen Patients with Thrombotic Thrombocytopenic Purpura Received in: March 2007 Accepted in: 14/1/2010 Dr. Ahmed Khudair Yaseen Elmeshhedany * Dr. Ahmed Abdulmajeed
More informationAppendix to Notification Letter for rituximab and eltrombopag dated 20 February 2014
Appendix to Notification Letter for rituximab and eltrombopag dated 20 February 2014 The notification letter which contains details of the decision to widen the restriction criteria for rituximab and eltrombopag
More informationWhen a patient presents with TMA, identify the underlying cause for the appropriate diagnosis... IS IT TTP OR IS IT ahus?
When a patient presents with TMA, identify the underlying cause for the appropriate diagnosis... IS IT TTP OR IS IT ahus? ADAMTS13 activity >5% RULES OUT a diagnosis of severe ADAMTS13 deficiency (TTP)
More informationUnusual association of lupus and thrombotic thrombocytopenic purpura like syndrome: clinical experience of a rare presentation
Abdellatif et al. J Unexplored Med Data 2018;3:5 DOI: 10.20517/2572-8180.2017.26 Journal of Unexplored Medical Data Case Report Open Access Unusual association of lupus and thrombotic thrombocytopenic
More informationRituximab as first-line treatment for acquired thrombotic thrombocytopenic purpura
Clinical Note Rituximab as first-line treatment for acquired thrombotic thrombocytopenic purpura Journal of International Medical Research 2017, Vol. 45(3) 1253 1260! The Author(s) 2017 Reprints and permissions:
More informationCase Report ISSN:
Case Report ISSN: 2581-6756 N-Acetylcysteine for Refractory Acquired Thrombotic Thrombocytopenic Purpura: New Dosage Approaches Ignacio Español 1, Juan Diego Leal 1, José Ros 2, José Sanmartín 2, María
More informationManagement of thrombotic thrombocytopenic purpura without plasma exchange: the Jehovah s Witness experience
EXCEPTIONAL CASE REPORT Management of thrombotic thrombocytopenic purpura without plasma exchange: the Jehovah s Witness experience James N. George, 1,2 Steven A. Sandler, 3 and Joanna Stankiewicz 3 1
More informationDr. E.SUDHA (Fellow in Pediatric Nephrology) DEPT OF PEDIATRIC NEPHROLOGY & DIALYSIS Dr.MEHTA CHILDRENS HOSPITAL
Dr. E.SUDHA (Fellow in Pediatric Nephrology) DEPT OF PEDIATRIC NEPHROLOGY & DIALYSIS Dr.MEHTA CHILDRENS HOSPITAL CASE HISTORY 4 yrs old previously well boy Born to 2 nd degree consanguinity Fever x 5 days
More informationCase report 24 th Summer School of Internal Medicine 2015
Case report 24 th Summer School of Internal Medicine 2015 Goldmannová D., Horák P., Skácelová M. IIIrd Internal Clinic - endocrinology, diabetology, rheumatology, nephrology University hospital Olomouc,
More informationIndex. Note: Page numbers of article titles are in boldface type.
Note: Page numbers of article titles are in boldface type. A Abdominal tumors, in children, 530 531 Alkalinization, in tumor lysis syndrome, 516 Allopurinol, in tumor lysis syndrome, 515 Anaphylaxis, drug
More informationEDUCATIONAL COMMENTARY PLATELET DISORDERS
EDUCATIONAL COMMENTARY PLATELET DISORDERS Educational commentary is provided through our affiliation with the American Society for Clinical Pathology (ASCP). To obtain FREE CME/CMLE credits click on Earn
More informationRenal failure and thrombocytopaenia? Don t forget TTP/HUS. Jonathan Wala Nephrologist
Renal failure and thrombocytopaenia? Don t forget TTP/HUS Jonathan Wala Nephrologist Thrombotic microangiopathies Disorders characterized by: thrombocytopaenia microangiopathic haemolytic anaemia (MAHA)
More informationResults of the TITAN study for Caplacizumab
Results of the TITAN study for Webcast presentation 17th June 2014 Nanobodies - Inspired by nature Forward looking statements Certain statements, beliefs and opinions in this presentation are forward-looking,
More informationAswanth P. Reddy, Ujjwal Gupta, and Jonathan S. Harrison. University of Connecticut, Farmington, Connecticut, USA
CASE REPORT Rituximab in Relapsing acquired Thrombotic Thrombo cytopenic Purpura: Experience and Evidence 1 2 1* Aswanth P. Reddy, Ujjwal Gupta, and Jonathan S. Harrison 1 University of Connecticut, Farmington,
More informationAcute Immune Thrombocytopenic Purpura (ITP) in Childhood
Acute Immune Thrombocytopenic Purpura (ITP) in Childhood Guideline developed by Robert Saylors, MD, in collaboration with the ANGELS team. Last reviewed by Robert Saylors, MD September 22, 2016. Key Points
More informationBBTS Advanced Clinical and laboratory case studies. Therese Callaghan
BBTS 2017 Advanced Clinical and laboratory case studies Therese Callaghan Disclaimer Nothing to disclose A 52 year old man with history of paranoid schizophrenia presents to A&E with history of abdominal
More informationDiagnosis and Treatment of Thrombotic Thrombocytopenic Purpura: A Single Institution Experience
J Med Sci 2012;32(3):121-127 http://jms.ndmctsgh.edu.tw/3203121.pdf Copyright 2012 JMS Diagnosis and Treatment of Thrombotic Thrombocytopenic Purpura: A Single Institution Experience Ping-Ying Chang 1,
More informationThrombotic Microangiopathies
Thrombotic Microangiopathies ASH/San Antonio Breast Cancer Symposium Review James N. George March 14, 2015 Thrombotic Microangiopathies (TMA): Everything you need to know from 5 patient stories Thrombotic
More informationCyclosporine or steroids as an adjunct to plasma exchange in the treatment of immune-mediated thrombotic thrombocytopenic purpura
REGULAR ARTICLE Cyclosporine or steroids as an adjunct to plasma exchange in the treatment of immune-mediated thrombotic thrombocytopenic purpura Spero R. Cataland, 1 Peter J. Kourlas, 2 Shangbin Yang,
More informationPaolo Gresele Dipartimento di Medicina, Sezione di Medicina Interna e Cardiovascolare, Università di Perugia
Le sindromi trombotiche microangiopatiche: il ruolo del laboratorio Paolo Gresele Dipartimento di Medicina, Sezione di Medicina Interna e Cardiovascolare, Università di Perugia Microangiopatie trombotiche:
More informationCase Report Ciprofloxacin-Induced Thrombotic Thrombocytopenic Purpura: A Case of Successful Treatment and Review of the Literature
Case Reports in Critical Care Volume 2015, Article ID 143832, 4 pages http://dx.doi.org/10.1155/2015/143832 Case Report Ciprofloxacin-Induced Thrombotic Thrombocytopenic Purpura: A Case of Successful Treatment
More informationTTP, Sickle Cell Disease, and the role of von Willebrand factor
TTP, Sickle Cell Disease, and the role of von Willebrand factor José A. López Puget Sound Blood Center University of Washington Seattle, WA Disclosures No conflicts to disclose. Thrombotic Thrombocytopenic
More informationIndex. Note: Page numbers of article titles are in boldface type.
Index Note: Page numbers of article titles are in boldface type. A Acute lung injury (ALI) transfusion-related, 363 372. See also Transfusion-related acute lung injury (TRALI) ALI. See Acute lung injury
More informationPathology note 8 BLEEDING DISORDER
Pathology note 8 BLEEDING DISORDER Slide75 ( Types of clotting factors deficiency): Today we will talk about public public factor deficiency it could be acquired or inherited, acquired diseases are more
More informationPREGNANCY ASSOCIATED THROMBOTIC THROMBOCYTOPENIC PURPURA AND ACUTE KIDNEY INJURY
VII, 2013, 2 33 A, PREGNANCY ASSOCIATED THROMBOTIC THROMBOCYTOPENIC PURPURA AND ACUTE KIDNEY INJURY M. Lubomirova Clinic of Nephrology, University Hospital Aleksandrovska So a : ( ), /HELLP, (AFLP) (TTP)
More informationThrombotic Microangiopathies (TMA) / TTP/HUS/αHUS Pathology & Molecular. Genetics
Thrombotic Microangiopathies (TMA) / TTP/HUS/αHUS Pathology & Molecular Genetics Helen Liapis, M.D. Senior Consultant Arkana Labs Professor of Pathology & Immunology. retired Washington University School
More informationTHE MULTIPLE FACETS OF THROMBOTIC MICROANGIOPATHIES
THE MULTIPLE FACETS OF THROMBOTIC MICROANGIOPATHIES Summary of Presentations from the Alexion-Sponsored Symposium, held at the 19 th EHA Congress, Milan, Italy, on 12 th June 2014 Chairperson Pier Mannuccio
More informationLong-term follow-up of idiopathic thrombotic thrombocytopenic purpura treated with rituximab
Long-term follow-up of idiopathic thrombotic thrombocytopenic purpura treated with rituximab Jens Marcus Chemnitz, Jens Uener, Michael Hallek, Christof Scheid To cite this version: Jens Marcus Chemnitz,
More informationNaser Al-Husban * and Oqba Al-Kuran
Al-Husban and Al-Kuran Journal of Medical Case Reports (2018) 12:147 https://doi.org/10.1186/s13256-018-1692-1 CASE REPORT Open Access Post-Partum Thrombotic Thrombocytopenic Purpura (TTP) in a Patient
More informationThrombotic thrombocytopenic purpura
The Intensive Care Society 2011 Thrombotic thrombocytopenic purpura J Thachil Thrombocytopenia is the most common coagulation problem in intensive care units with an incidence of up to 60% in some studies.
More informationDepartment of Clinical Haematology. Diagnosis and management of thrombotic thrombocytopenic purpura (TTP): Summary
Diagnosis and management of thrombotic thrombocytopenic purpura (TTP): Summary Suspected TTP Investigations Further Investigations Blood Products URGENT treatment Suspect TTP if MAHA and thrombocytopenia
More informationThrombocytopenia: a practial approach
Thrombocytopenia: a practial approach Dr. med. Jeroen Goede FMH Innere Medizin, Medizinische Onkologie, Hämatologie FAMH Hämatologie Chefarzt Hämatologie Kantonsspital Winterthur Outline Introduction and
More informationTherapeutic dilemma in the management of a patient with the clinical picture of TTP and severe B 12 deficiency
Walter et al. BMC Hematology (2015) 15:16 DOI 10.1186/s12878-015-0036-2 CASE REPORT Therapeutic dilemma in the management of a patient with the clinical picture of TTP and severe B 12 deficiency Kara Walter
More informationAssociation Between Thrombotic Microangiopathy and Reduced ADAMTS13 Activity in Malignant Hypertension
Association Between Thrombotic Microangiopathy and Reduced ADAMTS13 Activity in Malignant Hypertension Bert-Jan H. van den Born, Niels V. van der Hoeven, Evelyn Groot, Peter J. Lenting, Joost C.M. Meijers,
More informationPrimary causes: Complement dysregulation (50% of non-shiga toxin-producing E. coli ) Secondary causes:
General department INTRODUCTION The hemolytic uremic syndrome (HUS): microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury One of the main causes of acute kidney injury in children
More informationA Rational Approach to Evaluation of Thrombotic Microangiopathy
A Rational Approach to Evaluation of Thrombotic Microangiopathy An Algorithmic Approach C. Christopher Hook, MD for the Complement Alternative Pathway Thrombotic Micro- Angiopathy (CAP-TMA) Disease-Oriented
More informationAnemia (3).ms4.25.Oct.15 Hemolytic Anemia. Abdallah Abbadi
Anemia (3).ms4.25.Oct.15 Hemolytic Anemia Abdallah Abbadi Case 3 24 yr old female presented with anemia syndrome and jaundice. She was found to have splenomegaly. Hb 8, wbc 12k, Plt 212k, retics 12%, LDH
More informationPlatelet Disorders. By : Saja Al-Oran
Platelet Disorders By : Saja Al-Oran Introduction The platelet arise from the fragmentation of the cytoplasm of megakaryocyte in the bone marrow. circulate in the blood as disc-shaped anucleate particles
More informationAssessing thrombocytopenia in the intensive care unit: The past, present, and future
Assessing thrombocytopenia in the intensive care unit: The past, present, and future Ryan Zarychanski MD MSc FRCPC Sections of Critical Care and of Hematology, University of Manitoba Disclosures FINANCIAL
More informationR. Coward has documented that he has received cooperative grants from Takeda and Novo Nordisk
R. Coward has documented that he has received cooperative grants from Takeda and Novo Nordisk Advances in our understanding of the pathogenesis of glomerular thrombotic microangiopathy Lindsay Keir Richard
More informationA 23 year old Caucasian male presented with shortness of breath, hypertension, bloody sputum, and a history of drug abuse (confirmed by urinalysis).
A 23 year old Caucasian male presented with shortness of breath, hypertension, bloody sputum, and a history of drug abuse (confirmed by urinalysis). He was found to have severe kidney injury requiring
More informationHematologic Disorders. Assistant professor of anesthesia
Preoperative Evaluation Hematologic Disorders Dr M.Razavi Assistant professor of anesthesia Anemia Evaluation needs to consider the extent and type of surgery, the anticipated blood loss, and the patient's
More informationCase Report A Case of Thrombotic Thrombocytopenia Purpura Associated with Systemic Lupus Erythematosus: Diagnostic Utility of ADAMTS-13 Activity
SAGE-Hindawi Access to Research Autoimmune Diseases Volume 2011, Article ID 483642, 6 pages doi:10.4061/2011/483642 Case Report A Case of Thrombotic Thrombocytopenia Purpura Associated with Systemic Lupus
More informationNot So Benign Hematology Aplastic anemia, Paroxysmal Nocturnal Hemoglobinuria, atypical Hemolytic Uremic Syndrome, Thrombotic Thrombocytopenic Purpura
Not So Benign Hematology Aplastic anemia, Paroxysmal Nocturnal Hemoglobinuria, atypical Hemolytic Uremic Syndrome, Thrombotic Thrombocytopenic Purpura Robert A. Brodsky, MD Johns Hopkins Family Professor
More informationKeeping track of your numbers
Keeping track of your numbers If you have relapsed or refractory multiple myeloma, keeping track of your numbers can help you take an active role in your care. It s also one way you and your doctor can
More informationSchematic Of Heparin Induced Thrombocytopenia Platelet Count
Schematic Of Heparin Induced Thrombocytopenia Platelet Count Normal IgG and IgG2 differentially inhibit HIT antibody-dependent platelet activation that platelet counts were lower in FcγRIIA 131RR patients
More informationRituximab prophylaxis to prevent thrombotic thrombocytopenic purpura relapse: outcome and evaluation of dosing regimens
REGULAR ARTICLE Rituximab prophylaxis to prevent thrombotic thrombocytopenic purpura relapse: outcome and evaluation of dosing regimens John-Paul Westwood, 1 Mari Thomas, 1 Ferras Alwan, 1 Vickie McDonald,
More informationRayos Prior Authorization Program Summary
Rayos Prior Authorization Program Summary FDA APPROVED INDICATIONS AND DOSAGE FDA-Approved Indications: 1 Agent Indication Dosage Rayos (prednisone delayedrelease tablet) as an anti-inflammatory or immunosuppressive
More informationPostoperative Thrombotic Thrombocytopenic Purpura After Open Heart Operations
Postoperative Thrombotic Thrombocytopenic Purpura After Open Heart Operations Darin J. Saltzman, MD, PhD, Jae C. Chang, MD, Juan C. Jimenez, MD, John G. Carson, MD, Amir Abolhoda, MD, Richard S. Newman,
More informationHematologic changes in systemic diseases. Chittima Sirijerachai
Hematologic changes in systemic diseases Chittima Sirijerachai Systemic diseases Infection Renal diseases Liver diseases Connective tissue diseases Malignancy Anemia of chronic disease (ACD) Chronic infections:
More informationDefinition Chronic autoimmune disease The body s immune system starts attacking itself Can affect most organs and tissues in the body Brain, lungs, he
LIVING WITH SYSTEMIC LUPUS ERYTHEMATOSUS Stacy Kennedy, M.D.,M.B.A. Rowan Diagnostic Clinic Salisbury, N.C. May 11, 2013 Agenda What is lupus Who is affected Causes of lupus Symptoms and organ involvement
More informationThrombotic thrombocytopenic purpura at presentation of juvenile systemic lupus erythematosus patients
CASE REPORT Thrombotic thrombocytopenic purpura at presentation of juvenile systemic lupus erythematosus patients ABSTRACT Lucia M. A. Campos 1, Maria Silvia Spadoni 2, Cintia M. Michelin 3, Adriana A.
More informationMedical Policy. MP Eculizumab (Soliris) Related Policies None. Last Review: 01/24/2019 Effective Date: 04/25/2019 Section: Prescription Drug
Medical Policy Last Review: 01/24/2019 Effective Date: 04/25/2019 Section: Prescription Drug Related Policies None DISCLAIMER Our medical policies are designed for informational purposes only and are not
More informationThrombotic microangiopathy and indications for therapeutic plasma exchange
SPIN DOCTORS:APHERESIS FOR HEMATOLOGISTS Thrombotic microangiopathy and indications for therapeutic plasma exchange Jill Adamski 1 1 Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona,
More informationISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI CLINICAL RESEARCH CENTER ALDO E FOR CELE RARE DACCO DISEASES ALDO E CELE DACCO
ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI CENTRO MARIO DI NEGRI RICERCHE INSTITUTE CLINICHE FOR PHARMACOLOGICAL PER LE MALATTIE RESEARCH RARE CLINICAL RESEARCH CENTER ALDO E FOR CELE RARE DACCO DISEASES
More informationSafety and Efficacy of Eculizumab in Pediatric Patients With ahus, With or Without Baseline Dialysis
SP281 Safety and Efficacy of Eculizumab in Pediatric Patients With ahus, With or Without Baseline Johan Vande Walle, 1 Larry A. Greenbaum, 2 Camille L. Bedrosian, 3 Masayo Ogawa, 3 John F. Kincaid, 3 Chantal
More informationNon-immune acquired haemolytic anaemias. Dr.Maysem
Non-immune acquired haemolytic anaemias Dr.Maysem Causes of Non-immune acquired haemolytic anaemias. Infections Infections can cause haemolysis in a variety of ways: -They may precipitate an acute haemolytic
More informationEffect of under filling tube
Effect of under filling tube 2 What constitutes underfilling? A 4.5ml vacutainer collection tube should contain at least 4ml of blood Less than that could give falsely prolonged clotting times ALSO be
More informationLong-Term Outcomes After Successful Treatment of TTP
Long-Term Outcomes After Successful Treatment of TTP Spero R. Cataland, M.D. Assoc. Professor of Clinical Internal Medicine Division of Hematology Ohio State University Historical Perspective Prior to
More information