ANTIPHOSPHOLIPID SYNDROME:  UPDATE ON PATHOGENESIS, DIAGNOSIS AND MANAGEMENT     Ricard Cervera, MD, PhD, FRCP    Departme...
ANTIPHOSPHOLIPID   SYNDROME    (1983-2011)
ANTIPHOSPHOLIPID        SYNDROME            Epidemiology• 20% of deep vein thrombosis• 10% of recurrent abortions• 30% of ...
ANTIPHOSPHOLIPID   SYNDROME  • DIAGNOSIS  • TREATMENT  • PATHOGENESIS
APS-2011:            DIAGNOSIS• Classical, unusual and silent clinical  manifestations• Catastrophic antiphospholipid     ...
ANTIPHOSPHOLIPID   SYNDROME  Clinical manifestations:Classical, unusual and silent       European Forum on             200...
ANTIPHOSPHOLIPID   SYNDROME  Clinical manifestations:Classical, unusual and silent           E U R O -P H O S P H O L IP I...
ANTIPHOSPHOLIPID   SYNDROME  Clinical manifestations:Classical, unusual and silent
ANTIPHOSPHOLIPID   SYNDROME  Clinical manifestations:Classical, unusual and silent            E U R O -P H O S P H O L IP ...
ANTIPHOSPHOLIPID   SYNDROME  Clinical manifestations:Classical, unusual and silent
ANTIPHOSPHOLIPID   SYNDROME  Clinical manifestations:Classical, unusual and silent
ANTIPHOSPHOLIPID   SYNDROME  Clinical manifestations:Classical, unusual and silent
ANTIPHOSPHOLIPID   SYNDROME  Clinical manifestations:Classical, unusual and silent
ANTIPHOSPHOLIPID   SYNDROME  Clinical manifestations:Classical, unusual and silent
ANTIPHOSPHOLIPID   SYNDROME  Clinical manifestations:Classical, unusual and silent
ANTIPHOSPHOLIPID   SYNDROME  Clinical manifestations:Classical, unusual and silent
ANTIPHOSPHOLIPID   SYNDROME  Clinical manifestations:Classical, unusual and silent
ANTIPHOSPHOLIPID SYNDROME      Clinical manifestations:    Classical, unusual and silent
ANTIPHOSPHOLIPID SYNDROME      Clinical manifestations:    Classical, unusual and silent
ANTIPHOSPHOLIPID SYNDROME      Clinical manifestations:    Classical, unusual and silent
ANTIPHOSPHOLIPID SYNDROME      Clinical manifestations:    Classical, unusual and silent
ANTIPHOSPHOLIPID   SYNDROME  Clinical manifestations:Classical, unusual and silent
JUGULAR V. THROMB.     STROKE                         PULMONARY EMBOLISMVALVE LESIONS BUDD-CHIARI            RENAL MICROAN...
2006J Thromb Haemostas 2006; 4:295-306
Revised criteria for APS Clinical criteria– Vascular thrombosis: > 1 episode– Pregnancy morbidity:   - Abortions (<10 sem....
Features of probable APS•   aPL-associated cardiac valve disease•   aPL-associated livedo reticularis•   aPL-associated th...
aPL-associatedcardiac valve disease
aPL-associated livedo     reticularis
aPL-associated nephropathy
aPL-associatedthrombocytopenia
Pre-Conference Workshop on CAPSand non-criteria APS manifestations        Smita Vaidya, Horacio Adrogué        Doruk Erkan...
APS NEPHROPATHY              RECOMMENDATIONS• 1. Routine performance of renal biopsy is not recommended in  APS.• 2. In AP...
HEART VALVE LESIONS              RECOMMENDATIONS1.In patients with APS and previous thrombosis, mainly witharterial involv...
THROMBOCYTOPENIA                 RECOMMENDATIONS• 1. Multicentric, international, prospective long-term follow-up  study o...
APS-2011:            DIAGNOSIS• Classical, unusual and silent clinical  manifestations• Catastrophic antiphospholipid     ...
CATASTROPHICANTIPHOSPHOLIPID SYNDROME        Epidemiology    CAPS: 1% of APS
European Forum on                  Antiphospholipid Antibodies      THE "CAPS" REGISTRY International Registry of Patients...
20031. Clinical evidence of vessel occlusions affecting 3 or more organs or    systems.2. Development of the manifestation...
2005•   Sensitivity                 90.3%•   Specificity                 99.4%•   Positive predictive value   99.4 %•   Ne...
Pre-Conference Workshop on CAPSand non-criteria APS manifestations        Smita Vaidya, Horacio Adrogué        Doruk Erkan...
A   B    C
ANTIPHOSPHOLIPID   SYNDROME  • DIAGNOSIS  • TREATMENT  • PATHOGENESIS
APS-2011:         TREATMENT• High/moderate INR controversy• Heparin/aspirin for pregnancy  controversy• Treatment of catas...
APS-2011:        TREATMENT• High/moderate INR controversy• Heparin/aspirin for pregnancy  controversy• Treatment of catast...
n=100           oral       aspirin         none              anticoagulantevents             37           36             2...
APS-2011:        TREATMENT• High/moderate INR controversy• Heparin/aspirin for pregnancy  controversy• Treatment of catast...
APS - 2011:Heparin/aspirin for pregnancy controversy                S P E C IF IC S IT U A T IO N S :         A N T IP H O...
APS - 2011:Heparin/aspirin for pregnancy controversy              SPECIFIC SITUATIONS:          ANTIPHOSPHOLIPID SYNDROME ...
APS - 2011:Heparin/aspirin for pregnancy controversy               SPECIFIC SITUATIONS:           ANTIPHOSPHOLIPID SYNDROM...
APS-2011:        TREATMENT• High/moderate INR controversy• Heparin/aspirin for pregnancy  controversy• Treatment of catast...
CATASTROPHIC APS           Outcome       RECOVERY             50%Plasma exchange                  65%Anticoagulants       ...
CATASTROPHIC APS                 Triple Therapy                         TRATAMIENTO  PLASMA EXCHANGE                      ...
SB1                                                2006      160      140                  20%      120             53%   ...
Diapositiva 57SB1         The mortality rate wsfifty-three percent in the first period, before two thousand and one.      ...
SB3      p=0.025                 First period                  29%                              Second period           13...
Diapositiva 58SB3         When we use the logistic regression anlysis including age, precipitating factor and rate use of ...
ANTIPHOSPHOLIPID   SYNDROME  • DIAGNOSIS  • TREATMENT  • PATHOGENESIS
APS - 2011:    PATHOGENESIS• Role of infections• Peptide homology
APS - 2011:Role of infections      J Rheumatol 2000; 27:238-240
CATASTROPHIC APS       Precipitating Factors (I)INFECTIONS                 36 (24%)    Respiratory            15 (10%)    ...
APS - 2011:Role of infections
APS - 2011:Peptide homology  Arthritis & Rheumatism 2002 (in press)
APS - 2011:Peptide homology
APS - 2011:Peptide homology   J Clin Immunol 2003; 23: 377-383
APS - 2011:Peptide homology   J Clin Immunol 2003; 23: 377-383
MOLECULAR MIMICRY       J Clin Immunol 2004; 24: 12-23
J Clin Immunol 2004; 24: 12-23
J Clin Immunol 2004; 24: 12-23
EULAR PRIZE 2005 Yehuda Shoenfeld Pier Luigi Meroni  Ricard Cervera
Cervera ricard antiphospholipid syndrome update on pathogenesis diagnosis and management-torino gennaio
Cervera ricard antiphospholipid syndrome update on pathogenesis diagnosis and management-torino gennaio
Cervera ricard antiphospholipid syndrome update on pathogenesis diagnosis and management-torino gennaio
Cervera ricard antiphospholipid syndrome update on pathogenesis diagnosis and management-torino gennaio
Cervera ricard antiphospholipid syndrome update on pathogenesis diagnosis and management-torino gennaio
Cervera ricard antiphospholipid syndrome update on pathogenesis diagnosis and management-torino gennaio
Upcoming SlideShare
Loading in …5
×

Cervera ricard antiphospholipid syndrome update on pathogenesis diagnosis and management-torino gennaio

1,162 views

Published on

0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
1,162
On SlideShare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
69
Comments
0
Likes
1
Embeds 0
No embeds

No notes for slide

Cervera ricard antiphospholipid syndrome update on pathogenesis diagnosis and management-torino gennaio

  1. 1. ANTIPHOSPHOLIPID SYNDROME: UPDATE ON PATHOGENESIS, DIAGNOSIS AND MANAGEMENT Ricard Cervera, MD, PhD, FRCP Department of Autoimmune Diseases Hospital Clínic Barcelona
  2. 2. ANTIPHOSPHOLIPID SYNDROME (1983-2011)
  3. 3. ANTIPHOSPHOLIPID SYNDROME Epidemiology• 20% of deep vein thrombosis• 10% of recurrent abortions• 30% of cerebro-vascular accidents in <50 yr-olds NIH, 2001
  4. 4. ANTIPHOSPHOLIPID SYNDROME • DIAGNOSIS • TREATMENT • PATHOGENESIS
  5. 5. APS-2011: DIAGNOSIS• Classical, unusual and silent clinical manifestations• Catastrophic antiphospholipid syndrome
  6. 6. ANTIPHOSPHOLIPID SYNDROME Clinical manifestations:Classical, unusual and silent European Forum on 2002 Antiphospholipid Antibodies
  7. 7. ANTIPHOSPHOLIPID SYNDROME Clinical manifestations:Classical, unusual and silent E U R O -P H O S P H O L IP I D P R O JE C T N e u ro lo g ic m a n ife s t a tio n s E n c e p h a lo p a th V e n o u s th ro m b o s is M u ltiin f d e m e n tia E p ile p s y T IA S tro k e M ig ra in e 0 5 10 15 20
  8. 8. ANTIPHOSPHOLIPID SYNDROME Clinical manifestations:Classical, unusual and silent
  9. 9. ANTIPHOSPHOLIPID SYNDROME Clinical manifestations:Classical, unusual and silent E U R O -P H O S P H O L IP ID P R O JE C T C a rd ia c m a n ifesta tio n s B y p a s s o c c lu s io n s A c u te m y o c a rd C h ro n ic m y o c a rd V e g e ta tio n s A n g in a M I V a lv e le s io n s 0 2 4 6 8 10
  10. 10. ANTIPHOSPHOLIPID SYNDROME Clinical manifestations:Classical, unusual and silent
  11. 11. ANTIPHOSPHOLIPID SYNDROME Clinical manifestations:Classical, unusual and silent
  12. 12. ANTIPHOSPHOLIPID SYNDROME Clinical manifestations:Classical, unusual and silent
  13. 13. ANTIPHOSPHOLIPID SYNDROME Clinical manifestations:Classical, unusual and silent
  14. 14. ANTIPHOSPHOLIPID SYNDROME Clinical manifestations:Classical, unusual and silent
  15. 15. ANTIPHOSPHOLIPID SYNDROME Clinical manifestations:Classical, unusual and silent
  16. 16. ANTIPHOSPHOLIPID SYNDROME Clinical manifestations:Classical, unusual and silent
  17. 17. ANTIPHOSPHOLIPID SYNDROME Clinical manifestations:Classical, unusual and silent
  18. 18. ANTIPHOSPHOLIPID SYNDROME Clinical manifestations: Classical, unusual and silent
  19. 19. ANTIPHOSPHOLIPID SYNDROME Clinical manifestations: Classical, unusual and silent
  20. 20. ANTIPHOSPHOLIPID SYNDROME Clinical manifestations: Classical, unusual and silent
  21. 21. ANTIPHOSPHOLIPID SYNDROME Clinical manifestations: Classical, unusual and silent
  22. 22. ANTIPHOSPHOLIPID SYNDROME Clinical manifestations:Classical, unusual and silent
  23. 23. JUGULAR V. THROMB. STROKE PULMONARY EMBOLISMVALVE LESIONS BUDD-CHIARI RENAL MICROANGIOPATHYFETAL MORBIDITY LIVEDO RETICULARIS DIGITAL ISCHEMIA LEG ULCERS “SYSTEMIC” ANTIPHOSPHOLIPID DVT SYNDROME
  24. 24. 2006J Thromb Haemostas 2006; 4:295-306
  25. 25. Revised criteria for APS Clinical criteria– Vascular thrombosis: > 1 episode– Pregnancy morbidity: - Abortions (<10 sem.): > 3 - Fetal death (>10 sem.): > 1 - Prematures (<28 sem.): > 1 Laboratory criteria– Anticardiolipin antibodies (IgG/IgM): > 2 determ.– Lupus anticaogulant: > 2 determ.– Anti-beta-2-glycoprotein I (IgG/IgM) : > 2 determ. Definite APS: 1 clínical criteria + 1 laboratory criteria
  26. 26. Features of probable APS• aPL-associated cardiac valve disease• aPL-associated livedo reticularis• aPL-associated thrombocytopenia• aPL-associated nephropathy
  27. 27. aPL-associatedcardiac valve disease
  28. 28. aPL-associated livedo reticularis
  29. 29. aPL-associated nephropathy
  30. 30. aPL-associatedthrombocytopenia
  31. 31. Pre-Conference Workshop on CAPSand non-criteria APS manifestations Smita Vaidya, Horacio Adrogué Doruk Erkan, Gerard Espinosa, Maria Tektonidou, Antonio Cabral Yehuda Shoenfeld, Emilio González Chair: Ricard Cervera April 13, 2010
  32. 32. APS NEPHROPATHY RECOMMENDATIONS• 1. Routine performance of renal biopsy is not recommended in APS.• 2. In APS patients with clinical and laboratory findings that suggest renal involvement (new onset of hypertension, proteinuria, hematuria or renal insufficiency), renal biopsy should be performed (Evidence level II).• 3. In patients with APS nephropathy, especially in SLE and in the absence of other causes associated with similar lesions, aPL testing is recommended (Evidence level II).• 4. In patients with APS nephropathy and persistently positive aPL, the diagnosis of APS should be considered, provided that other conditions resulting in similar renal lesions are excluded.
  33. 33. HEART VALVE LESIONS RECOMMENDATIONS1.In patients with APS and previous thrombosis, mainly witharterial involvement, a TTE is recommended (Evidence level II)2.1.With normal valves and in the absence of atheroscleroticfactors, follow up controls might not be necessary.2.2.If VHD exists, serial echocardiographic follow up controls arewarranted (1 prospective study) (Evidence level II)3.1.No attempt to treat VHD with curative intention isrecommended (Evidence level II)3.2. A trial of steroids might be considered in APS-related VHD(Evidence level IV)
  34. 34. THROMBOCYTOPENIA RECOMMENDATIONS• 1. Multicentric, international, prospective long-term follow-up study of patients with ITP (APIgG, aPL, LAC, anti-β2GP-I…), thrombosis being the primary outcome.• 2. International Registry of aPL-positive “ITP” patients (“Hematologic APS”).• 3. We suggest that TCP may be incorporated as an isolated clinical criteria for APS.
  35. 35. APS-2011: DIAGNOSIS• Classical, unusual and silent clinical manifestations• Catastrophic antiphospholipid syndrome
  36. 36. CATASTROPHICANTIPHOSPHOLIPID SYNDROME Epidemiology CAPS: 1% of APS
  37. 37. European Forum on Antiphospholipid Antibodies THE "CAPS" REGISTRY International Registry of Patients with Catastrophic APSwww.med.ub.es/MIMMUN/FORUM/CAPS.HTM
  38. 38. 20031. Clinical evidence of vessel occlusions affecting 3 or more organs or systems.2. Development of the manifestations simultaneously or in less than a week.3. Confirmation by histopathology of small vessel occlusion in at least one organ.4. Laboratory confirmation of the presence of aPL (LA and/or aCL). -Definite catastrophic APS: All 4 criteria. -Probable catastrophic APS: -1, 2 & 4 -1, 3 & 4 and the development of the third event in more than a week but less than a month, despite anticoagulation
  39. 39. 2005• Sensitivity 90.3%• Specificity 99.4%• Positive predictive value 99.4 %• Negative predictive value 91.1 %
  40. 40. Pre-Conference Workshop on CAPSand non-criteria APS manifestations Smita Vaidya, Horacio Adrogué Doruk Erkan, Gerard Espinosa, Maria Tektonidou, Antonio Cabral Yehuda Shoenfeld, Emilio González Chair: Ricard Cervera April 13, 2010
  41. 41. A B C
  42. 42. ANTIPHOSPHOLIPID SYNDROME • DIAGNOSIS • TREATMENT • PATHOGENESIS
  43. 43. APS-2011: TREATMENT• High/moderate INR controversy• Heparin/aspirin for pregnancy controversy• Treatment of catastrophic APS
  44. 44. APS-2011: TREATMENT• High/moderate INR controversy• Heparin/aspirin for pregnancy controversy• Treatment of catastrophic APS
  45. 45. n=100 oral aspirin none anticoagulantevents 37 36 23recurrences 7(19%)* 15(42%) 21(91%)median time 96* 75 48(months) p=0.0007
  46. 46. APS-2011: TREATMENT• High/moderate INR controversy• Heparin/aspirin for pregnancy controversy• Treatment of catastrophic APS
  47. 47. APS - 2011:Heparin/aspirin for pregnancy controversy S P E C IF IC S IT U A T IO N S : A N T IP H O S P H O L IP ID S Y N D R O M E T h e H o s p ita l C lín ic o f B a rc e lo n a E x p e rie n c e M E D IC A L T R E A T M E N T N o p re vio u s tre a tm e n t v io A s p irin 1 0 0 m g / d a y fro m 1 m o n th b e fo re a tte m p tin g c o n c e p tio n F a ilu re o f a s p irin in p re v io u s p re g n a n c y A s p irin p lu s L M W h e p a rin H is to ry o f th ro m b o s is A s p irin p lu s L M W h e p a rin P re d n is o n e d u rin g p re g n a n c y O n ly if re q u ire d fo r m e d ic a l c o m p lic a tio n s
  48. 48. APS - 2011:Heparin/aspirin for pregnancy controversy SPECIFIC SITUATIONS: ANTIPHOSPHOLIPID SYNDROME The Hospital Clínic of Barcelona Experience n:137(78%) 100 n=63 (81%) 90 ABORTION/FETAL DEATH 80 LIVEBORN 70 60 50 40 30 n=14 (19%) n=39 (22%) 20 10 0 Before After treatment treatment
  49. 49. APS - 2011:Heparin/aspirin for pregnancy controversy SPECIFIC SITUATIONS: ANTIPHOSPHOLIPID SYNDROME The Hospital Clínic of Barcelona Experience RESULTS (V) Normal liveborn AAS before conception (n=59 patients) patients) 52 cases (88.1% ) AAS after conception (n=18 patients) patients) 11 cases (61.1% ) p=0.01 OR (IC):4.7 (1.3-16.2) (1.3-
  50. 50. APS-2011: TREATMENT• High/moderate INR controversy• Heparin/aspirin for pregnancy controversy• Treatment of catastrophic APS
  51. 51. CATASTROPHIC APS Outcome RECOVERY 50%Plasma exchange 65%Anticoagulants 63%Steroids 54%IV Gammaglobulins 50%Cyclophosphamide 41%AC+St+Pl/IV-GG 70%AC+St+Pl/IV-GG+Cyclo 50% (p=0.02) CAPS Registry, 2011
  52. 52. CATASTROPHIC APS Triple Therapy TRATAMIENTO PLASMA EXCHANGE STEROIDS ANTICOAGULATION+/- IV IMMUNOGLOBULINS Infections SIRS Asherson RA, Cervera et al. Medicine (Baltimore) 2001; 80:355-376
  53. 53. SB1 2006 160 140 20% 120 53% 100 Died 80 33% Survived 60 40 20 0 1992-2000 2001-2005 p=0.005 Year of Diagnosis
  54. 54. Diapositiva 57SB1 The mortality rate wsfifty-three percent in the first period, before two thousand and one. whilst the mortality rate was thirty-three percent from 2001. In other word the mortality decresed twenty percent from two thounsand and one with a p statistically significant. What does depend on? sbucciarelli; 05/03/2006
  55. 55. SB3 p=0.025 First period 29% Second period 13% AC+CS+PE and/or IVIG
  56. 56. Diapositiva 58SB3 When we use the logistic regression anlysis including age, precipitating factor and rate use of combinated therapy The precipitanting factor dissapeared. the mortality decrease in the second period was associated with the age and the higher rate use of combinated treatment. Likely the age is a statistical factor, because there is a little difference between two age.This difference is not enough for explaining so significant reduction of mortality Therefore the main reason for explaining the mortality decrese was the higher use rate of combinated therapy In other word the reduction of twenty percent of mortality from two thounsand and one depends on the higher use rate of combinated treatment wit AC+CS+PE and/or IVIG. sbucciarelli; 05/03/2006
  57. 57. ANTIPHOSPHOLIPID SYNDROME • DIAGNOSIS • TREATMENT • PATHOGENESIS
  58. 58. APS - 2011: PATHOGENESIS• Role of infections• Peptide homology
  59. 59. APS - 2011:Role of infections J Rheumatol 2000; 27:238-240
  60. 60. CATASTROPHIC APS Precipitating Factors (I)INFECTIONS 36 (24%) Respiratory 15 (10%) Cutaneous 6 (4%) Urinary 6 (4%) Gastrointestinal 3 (2%) Sepsis 2 (1%) Other 4 (3%) CAPS Registry, 2011
  61. 61. APS - 2011:Role of infections
  62. 62. APS - 2011:Peptide homology Arthritis & Rheumatism 2002 (in press)
  63. 63. APS - 2011:Peptide homology
  64. 64. APS - 2011:Peptide homology J Clin Immunol 2003; 23: 377-383
  65. 65. APS - 2011:Peptide homology J Clin Immunol 2003; 23: 377-383
  66. 66. MOLECULAR MIMICRY J Clin Immunol 2004; 24: 12-23
  67. 67. J Clin Immunol 2004; 24: 12-23
  68. 68. J Clin Immunol 2004; 24: 12-23
  69. 69. EULAR PRIZE 2005 Yehuda Shoenfeld Pier Luigi Meroni Ricard Cervera

×