Objectives. Thrombotic Thrombocytopenic Purpura (TTP) and ADAMTS13 Testing. Disclosure
|
|
- Gerard Ray
- 5 years ago
- Views:
Transcription
1 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 Objectives The pathophysiology of thrombotic thrombocytopenic purpura (TTP) Laboratory characteristics of various tests Clinical applications of testing in diagnosis and management of patients with TTP 1
2 Thrombotic Microangiopathy (TMA) Clinical Presentation Hemolytic anemia Thrombocytopenia Organ damage Histologic Findings Schistocytosis Microvascular Thrombosis Pathophysiology Endothelial damage Coagulation abnormality deficiency Pathogenesis Compliment Shiga toxin dysfunction Other etiologies Differential Diagnosis of TMA TMA Thrombotic Thrombocytopenic Purpura (TTP) Severe Deficiency Hemolytic Uremic Syndrome Other Congenital TTP Immune mediated TTP (ittp) Infection-HUS E. Coli 0157: H7 Autoimmune diseases (e.g. catastrophic antiphospholipid syndrome) Primary ittp) Secondary (TTP) Complementmediated HUS DIC Autoimmune disorder (e.g., SLE, Sjogren syndrome,ra) Drugs (ticlodipine, quinine, simvastatin, trimethoprim,pegylated interferon ) Disseminated malignancy Infection (HIV) Infections Malignant hypertension Pregnancy (e.g. HELLP) Clinical Features of TTP Presenting features and clinical course ( ) N=65 No. (%) of patients History and physical examination Neurologic abnormalities 43 (66) Major abnormalities (eg. focal, Seizure, stroke and coma) 23 (35) Minor abnormalities (eg, confusion, headache) 20 (31) Fever 15 (23) Laboratory data (range) Hematocrit, percentage 25 (15-43) Platelet count, 10 3 /μl 16 (2-124) LDH, U/L 1613 ( ) Creatinine, μmol/l 97.2 ( ) Patients with the classic pentad (thrombocytopenia, microangiopathic hemolytic anemia, neurologic and renal abnormalities, fever) 3 (5) George, J. N. Blood, 2010, 116(20):
3 Clinical Diagnostic Criteria of TTP 1. Micro-angiopathic hemolytic anemia (MAHA) 2. Thrombocytopenia + With or without neurologic symptoms History of TTP Galbusera, M., M. Noris, et al. (2006). Seminars in thrombosis and hemostasis 32(2): Scully, M., et al. (2017). "Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies." Journal of thrombosis and haemostasis : JTH 15(2): Biology and Pathophysiology Von Willebrand Factor and J. Evan Sadler, Hematology 2015;2015:
4 Wild Type ADAMTS-13 and Mutations 1427aa Mutations Levy G G et al. Blood 2005;106:11-17 Anti- Autoantibody Epitopes Klaus et al r Patient Number N=25 Luken et al r N=7 Zheng et al r N=67 Johanna A. Kremer Hovinga, and Bernhard Lämmle Hematology 2012;2012: Laboratory Testing Activity Antigen Bethesda Titer Autoantibody Titer 4
5 AdamTS13 Activity Assays Full Native VWF Denature 1.5 M urea AdamTS13 Activation Residual BaCl 2 24 Hours VWF: Collagen Binding Activity VWF: Ristocetin Cofactor Activity VWF: Antibody Binding (IRMA) VWF: Multimer analysis VWF Peptide AdamTS13 Activation VWF-73aa or -78aa BaCl hour Detection FRET ELISA Mass spec. Most Frequently Used Assays Method Substrate, monoclonal or polyclonal antibodies Measurement of cleaved VWF Reference Blotting Purified (plasma-derived) VWF VWF western blot N Engl J Med 1998; 339: CBA Recombinant or plasma-derived VWF Collagen binding Thromb Haemost 1999; 82: FRET Fluorogenic VWF73 peptide (residues of VWF) Fluorescence resonance energy transfer (FRET) assay Br J Haematol 2005; 129: ELISA VWF78 peptide conjugated with HRP (Nterminus) and labelled with biotin (C-terminus) (HRP-VWF78-biotin) Recombinant VWF73 (residues of VWF) tagged with both GST and His (GST- VWF73-His) Streptavidin-agarose absorption J Thromb Haemost 2006; 4: and measurement of HRP activity in solution Anti-N10 MoAb and measurement Transfusion 2006; 46: 1444 of HRP activity 52. Mass Spec. Recombinant VWF73-His Mass spectrometry J Thromb Haemost Feb;4(2): Fluorescence Resonance Energy Transfer FRETS-VWF73 Assay Excitation at 340 nm Emission at 450 nm 1605 Substrate: Fluorescent and quenching agent labeled Peptide of VWF-73aa (A2 domain D 1596 to R 1668 ) Product: cleavage of substrate abolishes quenching effect permitting fluorescence to occur. Kokame, et al. Br J Haematol 2005:129 (1),
6 Limitations of the Activity Assays Difference in low limit of quantification (LLQ) High coefficient variation (CV) at the lower end Discrepant results among different assays Various Interfering substances Static assay, which may be non-biological Discrepancy Among Different Assays Journal of Thrombosis and Haemostasis : The New WHO International Standard Pooled plasma from 38 normal healthy donors. 32 laboratories from 14 countries Using local pooled normal plasma preparations as calibrators. FRET (n = 18) or ELISA (n = 9). Combination of all results for activity gave an overall mean of 0.91 units/ml. The inter-laboratory variability (geometric coefficient of variation, GCV) was 12.4%. For estimates of antigen the combination of all results gave an overall mean of 0.92 units/ml with inter-laboratory variability (GCV) of 16.3%. Hubbard, A. R., A. B. Heath, et al. (2015). "Establishment of the WHO 1st International Standard, plasma (12/252): communication from the SSC of the ISTH." JTH 13(6):
7 Then New International Standard Does not Resolve Method/Laboratory Discrepancy L: Local Standard IS: International Standard Activity Assay Interference Free Hemoglobin Falsely low activity Falsely positive inhibitor Severe Hemolysis: Free hemoglobin inhibits activity. Studt JD, et al: Blood Free Hemoglobin Inhibitor Titer mg/dl BU 200 < >2 7
8 Bilirubin Meyer SC, et al: JTH 2007 Meyer, S. C., I. Sulzer, et al. (2007). JTH 5(4): EDTA AdamTS13 activity <5% Inhibitor screen (mixing study): Positive NPP expected= 53% Patient + NPP= <5% Titer: >16 BU EDTA negative control EDTA positive control Patient s sample Assays of Inhibitor Inhibitor Screen Assay: When activity <30%. Heat inactivation of residual activity Mix patient plasma with normal pooled plasma. Assess activity. Inhibitor Bethesda Titer Assay: Semiquantitative similar to FVIII inhibitor assay. 1 BU inhibits 50% activity in a 1:1 mix with normal pooled plasma. 8
9 The Antibody (e.g. IgG) Present in most patients with activity < 10% (90%) Mostly IgG antibody (Reiger M, et al: Blood 2005) High titer antibody is associated with worse prognosis (Ferrari S: Blood 2007) Low specificity: Positive in patients with autoimmune disorders. Up to 5-10% positivity in normal donors. Activity In Normal Adult and Pediatric Population Baseline AdamTS13 Levels in General Population Kokame, K. et al. J Thromb Haemost, (8): activity in Pediatric population is about 80% of adults Nguyen TC. et al. Haematologica
10 Activity Clinical Utility at the Initial Diagnosis of TTP Prevalence of Severe Deficiency (<10%) in Patients with an Acute On-set of TTP Author Design of study Positive Cases/Total (%) Furlan et al Retrospective 26/30 86* Tsai and Lian 1998 Retrospective 37/37 100* Veyradier et al Prospective, multicenter 47/66 71 Mori et al Retrospective? 12/18 66 Vesely et al Inception cohort, single center 16/48 33 Zhou et al Retrospective 34/34 100* Zheng et al Single center, prospective 16/20 80 Peyvandi et al Multicenter 48/ Matsumoto et al Multicenter 56/ Kremer Hovinga Multicenter 56/93 60 Matsumoto, et al Based on initial assessment 56/ Groot et al Retrospective 24/27 89* Kremer-Hovinga 2010 Inception cohort, single center 46/98 48 George et al Retrospective 51/ * Retrospective study with exclusion of cases of renal failure or other secondary TMA. Severe Deficiency Using VWF Collagen Binding Method is Highly Associated with TTP TMA Etiology activity < 5% activity 5%-50% activity >50% + inhibitor Total Idiopathic TTP HSCT and cyclosporine Cancer and chemotherapy Clopidogrel Pregnancy Other Total Zheng, X. L., et al. Blood, 2004, 103(11):
11 Severe Deficiency Using the New FRET method is Highly Associated with TTP 10% Kokame, K. et al. Br J Haematol 2005;129: Hassan, S. et al. Br J Haematol 2015; 171: Deficiency in Non-TTP Conditions Mild deficiency of (>10%): Uremia, Sepsis, chronic inflammation, DIC, pregnancy, post-operatively, liver disease (Mannucci PM, et al. Blood, 2001). Rare Non-TTP conditions with severe deficiency (<10%): Liver disease and cirrhosis Levels as low as 6% (Mannucci PM, et al. Blood, 2001). Alcoholic hepatitis < 5% (Uemura M, et al. Alcohol Lin Exp Res, 2005) Sepsis-induced DIC or severe sepsis < 5% (Ono T, et al. Blood 2006) Disseminated malignancy Mean was about 5% in 10 cases (Oleksowicz, et al. J Thrombo Haemost 1999) Timing of Activity Testing 11
12 Activity Before Each Plasma Exchange % of severe deficiency (<10%) 100% 89% 83% 78% 59% Pre-PE1 Wu, N., J. Liu, et al. (2015). Transfusion 55(1): TMA Diagnostic Algorithm If PLASMIC Score is >4, proceed with testing Modified from J. Evan Sadler Hematology 2015;2015: Association Between Patient Characteristics and Deficiency Using Multivariate Analysis. Coppo P, et al. (2010). PLoS ONE 5(4): e doi: /journal.pone
13 The Impact of Timely Results on Clinical Diagnosis and Management of Patients with TMA Suspected TMA pts Initial clinical and laboratory evaluation with available results TTP (7pts) Possible TTP (21 pts) Non-TTP (81) No PLEX Re-examine when results were available PLEX (7 pts) PLEX (21 pts) Continued PLEX Continued PLEX (7 pts) Continued PLEX (6 pts) Discontinued PLEX (15 pts) Mohamed Alsammak et al ISTH Abstract Benefit of Rapid Activity Turnaround Time on Plasma Utilization for Suspected TTP Outcome parameter Slow-TAT (n = 32) Rapid-TAT (n = 28) p value TAT (days), median (range) 9 (5-51) 1(<1-1) < Exchanged Total exchanges Exchanges per patient, mean (range) 14.1 (1-38) 5.3 (0-35) Total plasma units utilized Number of units of plasma per patient, mean (range) Plasma volume exchanged (ml) per patient per kg of body weight, mean (range) (13-386) ( ) 63.3 (0-425) ( ) day mortality 7 (21.9) 6 (21.4) Cost (18 months) $75/ unit of plasma and $2400/plasma exchange treatment Nathan Baseline T. Connell et al. $715,000 Transfusion 2015, , Connell, N.T., Transfusion, Utility of Testing in Assessing Prognosis of Congenital and Acquired TTP 13
14 Residual Plasmatic Activity of and Phenotype Severity in Congenital TTP Lotta LA, et al. Blood Jul 12;120(2): Studies activity Predictors of Outcome During the Acute Phase of Acquired TTP Design Outcomes (% of patients) Remission Activity Death Activity <10% 10% <10% 10% Vesely et al Prospective Zheng et al Prospective Mori et al Retrospective Coppo et al Retrospective NA 13 0 Raife et al Retrospective NA 8 18 Utility of Monitoring During Treatment 14
15 Poor Responder to Plasma Exchange (PE) due to Inhibitor Boosting Isonishi A, et al. Transfusion. 2015; 55: Shaded areas show normal ranges, and the vertical bars indicate values of mean ± SD. Utility of Testing in Assessing Risk of Relapse of Acquired TTP Activity at Time of Initial Diagnosis and Risk of Relapse N=136 N=47 The median follow-up= 7.5 years Johanna A. Kremer Hovinga et al. Blood 2010;115:
16 Results at Remission and TTP Relapse Flora Peyvandi et al. Haematologica 2008;93:232-9 When to Order Testing and Result Interpretation TMA is suspected : Activity Inhibitor Screen Bethesda Titer During treatment Pre-PE testing may help to confirm TTP or a TTP that is refractory to PE. During remission activity or inhibitor titer to assess risk of relapse or verify the onset of a relapse. <10% is highly suggestive for TTP But higher activity does not exclude TTP Improvement of platelet count and activity indicate treatment response and approaching to remission. However, some patients could continue to have severe deficiency despite clinical remission. Persistent deficiency and positive titer may explain refractory TTP. Severe deficiency and positive inhibitor titer during remission indicate a risk of relapse. A sudden platelet count decline and activity <10%, in conjunction with other TMA features suggest TTP relapse. Summary The pathophysiology of in thrombotic thrombocytopenic purpura (TTP) Laboratory characteristics of various assays Clinical applications of testing in diagnosis and management of patients with TTP 16
17 Thank You 17
Thrombotic 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 informationClinical study of 9 patients with acquired thrombotic thrombocytopenic purpura
Journal of Clinical and Experimental Medicine VOL.1,ISS.3,DEC 2017,1-5 ONLINE ISSN: 2523-2835 www.jocem.org PRINT ISSN: 2521-0084 DOI:10.29422/jocem.2017.03.001 Abstract: Clinical study of 9 patients with
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 informationACTIFLUOR ADAMTS13 Activity *
ACTIFLUOR ADAMTS13 Activity * A Fluorescence Resonance Energy Transfer (FRET) assay for measuring ADAMTS13 activity in human plasma REF 812RUO 32 i 2 Cl8 C Sekisui Diagnostics, LLC 500 West Avenue, Stamford,
More informationCover Page. The handle holds various files of this Leiden University dissertation.
Cover Page The handle http://hdl.handle.net/1887/20119 holds various files of this Leiden University dissertation. Author: Lotta, Luca Andrea Title: Pathophysiology of thrombotic thrombocytopenic purpura
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 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 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 informationAcquired Idiopathic ADAMTS13 Activity Deficient Thrombotic Thrombocytopenic Purpura in a Population from Japan
Acquired Idiopathic ADAMTS13 Activity Deficient Thrombotic Thrombocytopenic Purpura in a Population from Japan Masanori Matsumoto 1, Charles L. Bennett 2, Ayami Isonishi 1, Zaina Qureshi 2, Yuji Hori 1,
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 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 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 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 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 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 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 informationThe utility of ADAMTS13 in differentiating TTP from other acute thrombotic microangiopathies: results from the UK TTP Registry
research paper The utility of ADAMTS13 in differentiating TTP from other acute thrombotic microangiopathies: results from the UK TTP Registry Sevda Hassan, 1 John-Paul Westwood, 2 Debra Ellis, 2 Chris
More informationAcquired Inhibitors of Coagulation
Acquired Inhibitors of Coagulation Christine L Kempton, MD, MSc Emory University Disclosures for In compliance with COI policy, ISTH requires the following disclosures to the session audience: Research
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 informationCover Page. The handle holds various files of this Leiden University dissertation.
Cover Page The handle http://hdl.handle.net/1887/20119 holds various files of this Leiden University dissertation. Author: Lotta, Luca Andrea Title: Pathophysiology of thrombotic thrombocytopenic purpura
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 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 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 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 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 informationPlatelets: Thrombotic Thrombocytopenic Purpura
Platelets: Thrombotic Thrombocytopenic Purpura James N. George, J. Evan Sadler, and Bernhard Lämmle Abnormalities of plasma von Willebrand factor (VWF) have been recognized to be associated with thrombotic
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 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 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 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 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 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 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 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 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 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 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 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 informationDiagnostic approach to microangiopathic hemolytic disorders
Received: 8 January 2017 Accepted: 3 March 2017 DOI: 10.1111/ijlh.12671 REVIEW ARTICLE Diagnostic approach to microangiopathic hemolytic disorders K. Kottke-Marchant Medical Director Hemostasis and Thrombosis
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 informationThrombotic Thrombocytopenic Purpura and ADAMTS-13: New Insights into Pathogenesis, Diagnosis, and Therapy
Thrombotic Thrombocytopenic Purpura and ADAMTS-13: New Insights into Pathogenesis, Diagnosis, and Therapy Janis Wyrick-Glatzel, MS, MT(ASCP) (University of Nevada Las Vegas, Las Vegas, NV) DOI: 10.1309/77KRKLJW0EA75T2R
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 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 informationTreating breakthrough bleeds: A new approach
Treating breakthrough bleeds: A new approach Using Bypassing Agents With HEMLIBRA Prophylaxis Indication HEMLIBRA is indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes
More informationThrombotic Thrombocytopenic Purpura From Platelet Aggregates to Plasma
Pathology Patterns Reviews Thrombotic Thrombocytopenic Purpura From Platelet Aggregates to Plasma Marisa B. Marques, MD, 1 Charles A. Mayfield, MD, PhD, 1 and Douglas P. Blackall, MD 2 Key Words: Thrombotic
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 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 informationUnderstanding of the pathophysiology
CMAJ Early release, published at www.cmaj.ca on October 17, 2016. Subject to revision. Review CME Thrombotic microangiopathies: a general approach to diagnosis and management Donald M. Arnold MD MSc, Christopher
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 informationresearch paper Summary
research paper Impact of severe ADAMTS13 deficiency on clinical presentation and outcomes in patients with thrombotic microangiopathies: the experience of the Harvard TMA Research Collaborative Pavan K.
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 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 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 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 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 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 informationAABB 2003 ANNUAL MEETING AWARD LECTURES
Blackwell Science, LtdOxford, UKTRFTransfusion0041-11322004 American Association of Blood BanksSeptember 200444913841392Original ArticleTHE OKLAHOMA TTP-HUS REGISTRYGEORGE AABB 2003 ANNUAL MEETING AWARD
More informationAccepted Manuscript. No more thrombotic thrombocytopenic purpura/hemolytic uremic syndrome please. Yeong-Hau H. Lien MD, PhD S (18)
Accepted Manuscript No more thrombotic thrombocytopenic purpura/hemolytic uremic syndrome please Yeong-Hau H. Lien MD, PhD PII: S0002-9343(18)30965-3 DOI: https://doi.org/10.1016/j.amjmed.2018.10.009 Reference:
More informationChallenges in Renal Apheresis. Mark E. Williams MD, FACP, FASN Director, Renal Apheresis Beth Israel Deaconess Medical Center Harvard Medical School
Challenges in Renal Apheresis Mark E. Williams MD, FACP, FASN Director, Renal Apheresis Beth Israel Deaconess Medical Center Harvard Medical School Outline Principles of Separation ASFA Guidelines Renal
More informationRisk factors of chronic renal failure after atypical Hemolytic Uremic Syndrome under plasmatherapy
Risk factors of chronic renal failure after atypical Hemolytic Uremic Syndrome under plasmatherapy Professeur Eric Rondeau Urgences néphrologiques et Transplantation rénale Hôpital Tenon, Paris WWA SFH
More informationSymposium. Acute Kidney Injury with Thrombocytopenia. Lalitha A V*, Suryanarayana G**, Sumithra S***
Symposium Acute Kidney Injury with Thrombocytopenia 10.21304/2018.0502.00372 Lalitha A V*, Suryanarayana G**, Sumithra S*** *Associate Professor, Head,PICU **, Fellow in PICU, *** Assistant Professor,
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 informationThrombotic thrombocytopenic purpura: Toward targeted therapy and precision medicine
Received: 3 August 2018 Accepted: 18 September 2018 DOI: 10.1002/rth2.12160 REVIEW ARTICLE Thrombotic thrombocytopenic purpura: Toward targeted therapy and precision medicine Paul Coppo MD, PhD 1,2,3 Adam
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 informationMicroangiopatia trombotica (MAT) e Sindrome emolitico-uremica atipica (SEUa): Basi patogenetiche, inquadramento diagnostico e principi del
Microangiopatia trombotica (MAT) e Sindrome emolitico-uremica atipica (SEUa): Basi patogenetiche, inquadramento diagnostico e principi del trattamento Vincenzo Montinaro U.O. Nefrologia Azienda Ospedaliera
More informationClinical Study Eculizumab Therapy Leads to Rapid Resolution of Thrombocytopenia in Atypical Hemolytic Uremic Syndrome
Hindawi Publishing Corporation Advances in Hematology Volume 214, Article ID 295323, 7 pages http://dx.doi.org/1.1155/214/295323 Clinical Study Therapy Leads to Rapid Resolution of Thrombocytopenia in
More informationHemolytic uremic syndrome
Hemolytic uremic syndrome Doyeun Oh Department of Internal Medicine CHA University School of Medicine Disclosures for Doyeun Oh Research Support/P.I. Employee Consultant Major Stockholder Speakers Bureau
More informationahus A PATIENT S GUIDE To learn more about ahus, visit Copyright 2011, Alexion Pharmaceuticals, Inc. All rights reserved.
To learn more about ahus, visit www.ahussource.com ahus A PATIENT S GUIDE Copyright 2011, Alexion Pharmaceuticals, Inc. All rights reserved. SOL 1169 BECOME EMPOWERED By learning more and taking control
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 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 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 informationHemostasis and thrombosis in patients with liver disease. Ton Lisman, Dept Surgery, UMC Groningen, The Netherlands
Hemostasis and thrombosis in patients with liver disease Ton Lisman, Dept Surgery, UMC Groningen, The Netherlands Importance of the liver in hemostasis Synthesis of Coagulation factors Fibrinolytic proteins
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 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 informationDiagnosis and Treatment of Common TMAs
Diagnosis and Treatment of Common TMAs K. Pavenski, MD FRCPC St. Michael s Hospital June 13, 2014 Disclosures I have a relevant conflict of interest - Alexion Pharmaceuticals Inc. Participated in advisory
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 informationRelapse Rate in Survivors of Acute Autoimmune Thrombotic Thrombocytopenic Purpura Treated with or without Rituximab
THIEME Cellular Haemostasis and Platelets 1743 Relapse Rate in Survivors of Acute Autoimmune Thrombotic Thrombocytopenic Purpura Treated with or without Rituximab Tanja Falter 1,2, Stephanie Herold 1,
More informationKeywords: caplacizumab; morbidity; mortality; purpura, thrombotic thrombocytopenic; von Willebrand factor. Introduction
Journal of Thrombosis and Haemostasis, 15: 1448 1452 DOI: 10.1111/jth.13716 BRIEF REPORT Caplacizumab reduces the frequency of major thromboembolic events, exacerbations and death in patients with acquired
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 informationDocument Title: Hemostasis: Platelet and Coagulation Disorders. Author(s): Joseph H. Hartmann (University of Michigan), DO 2012
Project: Ghana Emergency Medicine Collaborative Document Title: Hemostasis: Platelet and Coagulation Disorders Author(s): Joseph H. Hartmann (University of Michigan), DO 2012 License: Unless otherwise
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 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 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 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 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 information