title: Unresponsive thrombotic thrombocytopenic purpura in critically ill adults.
abstract: BACKGROUND
  The prognosis of thrombotic thrombocytopenic purpura (TTP) has considerably improved since the introduction of plasma exchange (PEX) therapy. However, unresponsive thrombotic thrombocytopenic purpura (Un-TTP) still carries high morbidity and mortality rates, indicating a need for early specific treatments.
  
  
  METHODS
  In a retrospective study including consecutive adults with TTP admitted between January 1997 and January 2011 in a teaching hospital intensive care unit (ICU), our objective here is to identify early clinical and laboratory features predicting Un-TTP. Patients who responded to plasma exchange and steroids (N = 49) were compared with patients with unresponsive TTP defined as requirement for other treatments, protracted course, or death (N = 37, 43 %).
  
  
  RESULTS
  Hospital mortality was 24.3 % in the Un-TTP group. Variables associated with Un-TTP on univariate logistic regression were older age, cardiac involvement, neurological involvement, higher anti-a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS13) immunoglobulin G (IgG) titer, lower platelet counts starting on day 2, higher Sequential Organ Failure Assessment (SOFA) scores starting on day 3, need for higher plasma volumes to obtain remission, and greater use of adjuvant treatments and life-sustaining interventions. Multivariate logistic regression identified four factors independently associated with Un-TTP: age over 60 years [odds ratio (OR) 7.90; 95 % confidence interval (95 % CI) 1.06-78.34], cardiac (OR 5.17; 95 % CI 1.63-16.39) or neurological (OR 8.04; 95 % CI 1.27-51.03) manifestations at diagnosis, and day 2 platelet count less than 15 G/l (OR 3.88; 95 % CI 1.30-11.62).
  
  
  CONCLUSIONS
  Therapeutic intensification starting on day 3 or even earlier in patients with the independent risk factors for unresponsive TTP identified in our study deserves evaluation in a multicenter prospective study.
authors.affiliation: Medical ICU, Saint-Louis Hospital and Université Paris-Diderot, Sorbonne Paris-Cité, 1 Avenue Claude Vellefaux, 75010, Paris, France. eric.mariotte@bch.aphp.fr
authors.forename: Eric
authors.initials: E
authors.lastname: Mariotte
authors.forename: Alice
authors.initials: A
authors.lastname: Blet
authors.forename: Lionel
authors.initials: L
authors.lastname: Galicier
authors.forename: Michael
authors.initials: M
authors.lastname: Darmon
authors.forename: Nathalie
authors.initials: N
authors.lastname: Parquet
authors.forename: Etienne
authors.initials: E
authors.lastname: Lengline
authors.forename: David
authors.initials: D
authors.lastname: Boutboul
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Canet
authors.forename: Richard
authors.initials: R
authors.lastname: Traineau
authors.forename: Benoît
authors.initials: B
authors.lastname: Schlemmer
authors.forename: Agnès
authors.initials: A
authors.lastname: Veyradier
authors.forename: Elie
authors.initials: E
authors.lastname: Azoulay
mesh_terms: D051722:ADAM Proteins / Q000276:immunology; D000071120:ADAMTS13 Protein; D000305:Adrenal Cortex Hormones / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D015415:Biomarkers; D015897:Comorbidity; D018450:Disease Progression; D005260:Female; D005602:France / Q000453:epidemiology; D006305:Health Status Indicators; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010951:Plasma Exchange; D011379:Prognosis; D011697:Purpura, Thrombotic Thrombocytopenic / Q000175:diagnosis* / Q000453:epidemiology / Q000628:therapy*; D012189:Retrospective Studies; D012307:Risk Factors; D013156:Splenectomy
chemical_list: D000305:Adrenal Cortex Hormones; D015415:Biomarkers; D007166:Immunosuppressive Agents; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
references.citation: Eur Neurol. 1998 Nov;40(4):220-4
references.pmid: 9813405
references.citation: Br J Haematol. 2000 Jun;109(3):496-507
references.pmid: 10886194
references.citation: Intensive Care Med. 2002 Nov;28(11):1619-24
references.pmid: 12415450
references.citation: N Engl J Med. 2006 May 4;354(18):1927-35
references.pmid: 16672704
references.citation: Haematologica. 2001 Aug;86(8):844-50
references.pmid: 11522541
references.citation: Haematologica. 2012 Aug;97(8):1181-6
references.pmid: 22580997
references.citation: J Thromb Haemost. 2003 Sep;1(9):2038-40; discussion 2040-5
references.pmid: 12941048
references.citation: Blood. 2007 Apr 1;109(7):2815-22
references.pmid: 17164349
references.citation: Expert Rev Cardiovasc Ther. 2003 Jul;1(2):243-55
references.pmid: 15030284
references.citation: Clin Cardiol. 2010 Apr;33(4):213-6
references.pmid: 20394041
references.citation: Ann Hematol. 2010 Jun;89(6):591-6
references.pmid: 20033409
references.citation: Kidney Int Suppl. 2009 Feb;(112):S52-4
references.pmid: 19180137
references.citation: Crit Care Med. 2012 Jan;40(1):104-11
references.pmid: 21926591
references.citation: Transfusion. 2008 Feb;48(2):382-92
references.pmid: 18028268
references.citation: Semin Thromb Hemost. 2005 Dec;31(6):700-8
references.pmid: 16388421
references.citation: Transfusion. 2008 Feb;48(2):349-57
references.pmid: 18028271
references.citation: Blood Transfus. 2010 Jul;8(3):203-10
references.pmid: 20671883
references.citation: Ann Surg. 1969 Apr;169(4):616-24
references.pmid: 5813186
references.citation: Br J Haematol. 2003 Feb;120(4):556-73
references.pmid: 12588343
references.citation: Br J Haematol. 2006 Jan;132(1):66-74
references.pmid: 16371021
references.citation: N Engl J Med. 1982 Dec 2;307(23):1432-5
references.pmid: 6813740
references.citation: Br J Haematol. 2012 Aug;158(3):323-35
references.pmid: 22624596
references.citation: Hematology Am Soc Hematol Educ Program. 2004;:407-23
references.pmid: 15561695
references.citation: JAMA. 1982 Mar 12;247(10):1433-6
references.pmid: 7199096
references.citation: Thromb Haemost. 1999 Nov;82(5):1382-5
references.pmid: 10595622
references.citation: Transfusion. 2009 May;49(5):873-87
references.pmid: 19210323
references.citation: J Thromb Haemost. 2005 Aug;3(8):1663-75
references.pmid: 16102032
references.citation: Transfusion. 2010 Dec;50(12):2753-60
references.pmid: 20576013
references.citation: Blood. 2003 Nov 1;102(9):3241-3
references.pmid: 12855569
references.citation: PLoS One. 2012;7(3):e33029
references.pmid: 22427934
references.citation: Crit Care Med. 2006 Aug;34(8):2127-33
references.pmid: 16763519
references.citation: Clin Lab. 2001;47(7-8):387-92
references.pmid: 11499801
references.citation: Br J Haematol. 2010 May;149(4):623-5
references.pmid: 20148878
references.citation: Swiss Med Wkly. 2003 Jun 14;133(23-24):325-32
references.pmid: 12923683
references.citation: Transfusion. 2012 Nov;52(11):2436-44
references.pmid: 22404639
references.citation: Blood. 2008 Jul 1;112(1):11-8
references.pmid: 18574040
references.citation: Blood. 2001 Sep 15;98(6):1765-72
references.pmid: 11535510