Sindrome da anticorpi antifosfolipidi: clinica e terapia. Vittorio Pengo Clinical Cardiology, Padova, Italy

Transcription

1 Sindrome da anticorpi antifosfolipidi: clinica e terapia Vittorio Pengo Clinical Cardiology, Padova, Italy

2 Revised Classification Criteria for the Antiphospholipid Syndrome J Thromb Haemost 2006;4: Clinical criteria 1. Vascular thrombosis One or more clinical episodes of arterial, venous, or small vessel thrombosis, in any tissue 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 evidence of inflammation in the vessel wall.

3 Pain in the right leg Lasting one month MC/ Male 18 yrs of age Proximal DVT LA (drvvt) + acl + (high titre) A-human-ß2GPI + No risk factors No associated autoimmune diseases Primary APS

4 MASSIVE POLMONARY EMBOLISM

5 PAPS MC/ Male18 yrs of age at presentation

6 PAPS MC/ Male18 yrs of age after 6 months Pulmonary artery pressure : 55 mmhg (CTPH)

7 APS most common features epilepsy pulmonary embolism Valvular Dysfunction Migrain like headaches Livedo -reticularis 14.2 arthralgia TIA /stroke Thrombocytopenia Fetal -loss DVT Euro-APS, 538 patients

8 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)

9 RA Thrombus

10 Arterial Thrombosis and APS Cerebral ischemia Stroke/TIA Dementia Epilepsy

11 CEREBRAL ISCHEMIA White matter

12 CEREBELLAR ISCHEMIA (female patient with objective vertigo)

13 Small ischemic areas in 45 years old male (B. L.) with cognitive disability

14 Multiple cerebral infarctions in 48 years old female ( N. C.) with hemiparesis and epilepsy

15 LIVEDO RETICULARIS Cerebral ischemia + livedo reticularis: Sneddon s syndrome

16 Pathogenesis Numerous recent studies have stressed a link between cerebral ischemia and cardiac valvular lesions. Cardiogenic stroke

17 CEREBRAL EMBOLUS

18 Marked focal thickening of the midportion of the posterior mitral valve leaflet Farzaneh-Far A, Arthr Rheum 2006

19 Multiple mitral valve thickening Clinical Cardiology, Padua

20 Libman-Sacks Endocarditis Moyssakis I, American Journal of Medicine 2007

21 APS most common features epilepsy pulmonary embolism Valvular Dysfunction Migrain like headaches Livedo -reticularis 14.2 arthralgia TIA /stroke Thrombocytopenia Fetal -loss DVT Euro-APS, 538 patients, in preparation

22 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

23 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 +

24 ANTERIOR DESCENDING CORONARY ARTERY THROMBOSIS NO ATHEROSCLEROSIS

25 All the previous slides referred to patients with triple positivity

26 High risk triple positive APS patients (n=160) 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) Pengo V, JTH 2010

27 High risk triple positive APS patients (n=160) Pengo V, JTH 2010

28 High risk triple positive APS patients (n=160) Pengo V, JTH 2010

29 High risk triple positive APS patients (n=160) Pengo V, JTH 2010

30 Vascular thrombosis in definite APS Often idiopathic Young subjects Triple positivity Often No risk factors Recurrence

31 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

32 CUTANEOUS NECROSIS

33 CUTANEOUS NECROSIS

34 Scansione TC: infarto surrenalico sinistro (freccia) della paziente n 2 Cutaneous biopsy of ear lobe showing a thrombus in dermal vessel (arrow)

35 Cutaneous lesions related to thrombi in microcirculation

36 Clinical criteria 2. Pregnancy morbidity a) One or more unexplained deaths of a morphologically normal fetus at or beyond the 10th week of gestation b) One or more premature births of a morphologically normal neonate at or before the 34th week of gestation (preeclampsia or eclampsia or severe placental insufficiency) c) Three or more unexplained consecutive spontaneous abortions before the 10th week of gestation (other causes excluded)

37 INTERVILLOUS PLACENTAL THROMBOSIS

38 PLACENTAL INFARCTION

39 APS treatment in pts with VTE VKA Intensity (INR ) Duration of treatment?

40 Canadian Trial on OAT in APS 114 pts with APL and thrombosis (76% venous) Randomization Warfarin INR years follow-up Warfarin INR Rec. TE 2 (3.4 %) Bleeding* 4+11 (19 %) Rec. TE 6 (10.7 %) Bleeding* 3+14 (25 %) (mean INR 2.3) (mean INR 3.3) *Major+minor Crowther et al., NEJM 2003; 349: 1133

41 WAPS Trial 109 pts with APL and thrombosis (68% venous) Randomization Warfarin INR years follow-up Warfarin INR 3-4 Rec. TE 5.5 % Bleeding* 14.6 % Rec. TE 11.1 % Bleeding* 27.8 % (mean INR 2.5) (mean INR 3.2) *Major+minor Finazzi et al., JTH 2005

42 Duration of treatment Provoked/unprovoked apl profile and titer Type of VTE (DVT/PE) Other (permanent) risk factors

43 Duration of treatment Long term if: 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

44 Duration of treatment Possible short term if: 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

45 Arterial thrombosis in APS VKA/antiplatelet drugs Intensity Duration of treatment VKA plus antiplatelet drugs Type and Titer of apl

46 Arterial thrombosis in APS Recommendations 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 ) (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

47 AORTIC ARCH SOFT PLAQUE

48 TREATMENT OF PREGNANT PATIENTS WITH APS Favourable outcome Kutteh et al, 1996 UH + LDA vs LDA 80% vs 40% (significant difference) Rai et al, 1997 UH + LDA vs LDA 71% vs 42% (significant difference) PATIENTS WITH PREVIOUS PREGNANCY MORBIDITY ALONE PROPHYLAXIS OF PREGNANCY LOSS Farquharson et al, 2002 LMWH + LDA vs LDA 78% vs 72% (no significant difference) ONE DAILY DOSE OF HEPARIN + LOW DOSE ASPIRIN

49 LOW DOSE ASPIRIN 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 ± No clinical trials There is agreement on full anticoagulation with UH or LMWH LDA is generally combined Tincani et al. Lupus. 2003;12: Ruitz-Irastorza et al. Ann NY Acad Sci. 2005; 1051:

50 SECOND LINE TREATMENT PROTOCOLS Triple positive patients Intravenous immunoglobulins (IVIG) Plasma exchange ± IVIG Immunoadsorption + IVIG