Upload
lytu
View
249
Download
0
Embed Size (px)
Citation preview
Sindrome da anticorpi antifosfolipidi: clinica e terapia
Vittorio PengoClinical Cardiology, Padova, Italy
Clinical criteria
1. Vascular thrombosis
One or more clinical episodes of arterial, venous, or small vessel thrombosis, in anytissue or organ. Thrombosis must be confirmed by objective validated criteria (i.e.unequivocal findings of appropriate imaging studies or histopathology).For histopathologic confirmation, thrombosis should be present without significant evidenceof inflammation in the vessel wall.
Revised Classification Criteria for the Antiphospholipid Syndrome
J Thromb Haemost 2006;4:295-306
MC/ Male
18 yrs of age
Proximal DVT
LA (dRVVT) +
aCL + (high titre)
A-human-ß2GPI +
No risk factors
No associated autoimmune diseases
Pain in the right legLasting one month
Primary APS
APS most common features
38 .5
31 .3
27 .8
25 .3
23 .7
14 .2
14 .2
13
11 .8
9 .2
0 10 20 30 40 50
DVT
Fetal -loss
Thrombocytopenia
TIA /stroke
arthralgia
Livedo -reticularis
Migrain like headaches
Valvular Dysfunction
pulmonary embolism
epilepsy
Euro-APS, 538 patients
Other less common sites of venous thromboembolism in APS
•Venous thrombosis of the upper limbs •Retinal thrombosis •Cerebral vein thrombosis•Inferior vena cava thrombosis •Jugular vein thrombosis •Mesenteric vein thrombosis* •Budd-Chiari syndrome*•Portal vein*
*DD: myeloproliferative disorders (JAK2 mutation)
Pathogenesis
Numerous recent studies have stressed a link between cerebral ischemia and cardiac valvular lesions.
Cardiogenic stroke
Marked focal thickening of the midportion of the posterior mitral valve leaflet
Farzaneh-Far A, Arthr Rheum 2006
Libman-Sacks Endocarditis
Moyssakis I, American Journal of Medicine 2007Moyssakis I, American Journal of Medicine 2007
APS most common features
38 .5
31 .3
27 .8
25 .3
23 .7
14 .2
14 .2
13
11 .8
9 .2
0 10 20 30 40 50
DVT
Fetal -loss
Thrombocytopenia
TIA /stroke
arthralgia
Livedo -reticularis
Migrain like headaches
Valvular Dysfunction
pulmonary embolism
epilepsy
Euro-APS, 538 patients, in preparation
Other less common sites of arterial thromboembolism in APS
• Arterial thrombosis of the lower limbs • Myocardial infarction • Renal artery thrombosis • Retinal artery thrombosis • Mesenteric ischemia
THROMBOSIS IN THE LEFT RENAL ARTERY
PAPS
FP/ Female
13 yrs of age
Blood pressure 220/140 in the emergency room
LA (dRVVT) +
aCL + (high titre)
A-human-ß2GPI +
Characteristics
Age –yrs 41.1 ±
15.0
Female––no.(%) 113 (70.6)
APS-related event at diagnosis—no.(%)
VTE 76 (47.5)
Arterial Thrombosis 69 (43.1)
Obstetric complications 11 (6.9)
Catastrophic APS 4 (2.5)
High risk triple positive APS patients (n=160)
Pengo V, JTH 2010
• Often idiopathic• Young subjects• Triple positivity• Often No risk factors• Recurrence
Vascular thrombosis in definite APS
CATASTROPHIC APS
•Term proposed in 1992
•Accelerated form of APS with multiorgan thrombotic failure
•Around 50% mortality, it may show up ‘ex novo’
•Trigger: infection in many cases
•1% prevalence in APS
Scansione TC: infarto surrenalico sinistro (freccia) della paziente n°2
Cutaneous biopsy of ear lobe showing a thrombus in dermal vessel (arrow)
Clinical criteria
2. Pregnancy morbidity
a) One or more unexplained deaths of a morphologicallynormal fetus at or beyond the 10th week of gestation
b) One or more premature births of a morphologicallynormal neonate at or before the 34th week of gestation(preeclampsia or eclampsia or severe placental insufficiency)
c) Three or more unexplained consecutive spontaneousabortions before the 10th week of gestation (other causesexcluded)
Canadian Trial on OAT in APS
114 pts with APL and thrombosis (76% venous)
Randomization
WarfarinINR 2-3 2.7 years follow-up
Bleeding*4+11 (19 %)
Bleeding*3+14 (25 %)
Rec. TE2 (3.4 %)
Rec. TE6 (10.7 %)
Crowther et al., NEJM 2003; 349: 1133
WarfarinINR 3.1-4
(mean INR 2.3) (mean INR 3.3)
*Major+minor
WAPS Trial
109 pts with APL and thrombosis (68% venous)
Randomization
WarfarinINR 2-3 3.6 years follow-up
Bleeding*14.6 %
Bleeding*27.8 %
Rec. TE5.5 %
Rec. TE11.1 %
Finazzi et al., JTH 2005
WarfarinINR 3-4
(mean INR 2.5) (mean INR 3.2)
*Major+minor
Duration of treatment
• Provoked/unprovoked• aPL profile and titer• Type of VTE (DVT/PE)• Other (permanent) risk factors
Duration of treatment
• Provoked/unprovoked• aPL profile and titer• Type of VTE (DVT/PE)• Other risk factors
• Unprovoked• aPL profile:triple positivity• VTE was PE• Other thrombophilia• Associated autoimmune
disease
Long term if:
Duration of treatment
• Type of VTE (DVT/PE)• aPL profile and titer• Provoked/unprovoked• Other risk factors
• VTE was Provoked• aPL profile: single positivity• Other thrombophilias are
absent• No associated autoimmune
disease
Possible short term if:
Arterial thrombosis in APS
• VKA/antiplatelet drugs• Intensity• Duration of treatment• VKA plus antiplatelet drugs• Type and Titer of aPL
Arterial thrombosis in APSRecommendations from observational studies
“Because of the high risk of recurrence and consequent disability or death, stroke in APS should be treated with long-term OAT, target INR 2.5 (range 2.0-3.0) (level III evidence) ...
… Whether additional therapy with aspirin is efficacious is not known …
… Extracerebral arterial thrombosis in APS will also warrant consideration for long-term OAT …”
Br Soc Haemat Guidelines on APS Br J Haemat 2000; 109:704
TREATMENT OF PREGNANT PATIENTS WITH APS ____________________________________
PATIENTS WITH PREVIOUSPREGNANCY MORBIDITY ALONE
ONE DAILY DOSE OF HEPARIN
+LOW DOSE ASPIRIN
PROPHYLAXIS OF PREGNANCY LOSS
Favourable outcomeKutteh et al, 1996UH + LDA vs LDA 80% vs 40%
(significant difference)
Rai et al, 1997UH + LDA vs LDA 71% vs 42%
(significant difference)
Farquharson et al, 2002LMWH + LDA vs LDA 78% vs 72%
(no significant difference)
TREATMENT OF PREGNANT PATIENTS WITH APS ____________________________________
PATIENTS WITH PREVIOUS VASCULAR THROMBOSIS ALONE OR ASSOCIATED
TO PREVIOUS PREGNANCY MORBIDITY
THROMBOSIS PROPHYLAXIS
+PROPHYLAXIS OF PREGNANCY LOSS
FULL DOSE HEPARIN±
LOW DOSE ASPIRIN
• No clinical trials• There is agreement on full
anticoagulation with UH or LMWH
• LDA is generally combined
• Tincani et al. Lupus. 2003;12: 524-9.
• Ruitz-Irastorza et al. Ann NY Acad Sci. 2005; 1051: 606-12.