antiphospholipid symdrome aps. definition disorder of recurrent vascular thrombosis, pregnancy loss...
TRANSCRIPT
![Page 1: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/1.jpg)
Antiphospholipid symdrome
“APS”
![Page 2: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/2.jpg)
Definition
Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently raised levels of anti-phospholipid antibodies.
Primary: Occurs alone Secondary: Associated with other autoimmune
or rheumatic diseases
![Page 3: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/3.jpg)
Epidemiology of APLs
Prevalance : Unknown
Women : 60-80 %
Familial disease : Frequent
HLA-DQB
![Page 4: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/4.jpg)
Antiphospholipid Antibodies
Common findingsignificant proportion of healthy (esp. elderly)
populationmost never thrombosismay be transient
![Page 5: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/5.jpg)
Antiphospholipid Antibodies
Clinically significant antiphospholipid antibodies are not antiphospholipid antibodies
Antibodies against phospholipid-bound proteinse.g. 2 glycoprotein 1, prothrombin
![Page 6: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/6.jpg)
Anti-Phospholipid antibodies
Lupus Anti-coagulant Anti-cardiolipin antibody Anti-ß2 glycoprotein I antibody Anti-prothrombin False + serologic test for Syphillis
![Page 7: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/7.jpg)
Antiphospholipid syndrome
Association of a thrombotic tendencyvenous or arterial thrombosisrecurrent miscarriages
with the persistence of one or more antiphospholipid antibodiesconfirmed by two different tests, or IgG or IgM
by ELISA(LA,ACL)repeated after 6 week
![Page 8: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/8.jpg)
Lupus Anti-coagulant
Blocks In Vitro assembly of prothrombinase Prolongs
aPTTdRVVT(Russell viper venum time )KPC(Kaolin clotting )
![Page 9: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/9.jpg)
Anti-cardiolipin antibody
React with phospholipids such as cardiolipin Different immunoglobulin subclasses and
isotypes are associated with anti-cardiolipin antibodiesIgG, IgA, IgM (IgG 1-4)Increased levels of IgG acl incurs a greater risk of
thrombosis 85% concordance LA and ACL
![Page 10: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/10.jpg)
Anti-ß2 glycoprotein I antibody
Inhibitor of coagulation (phospholipid binded) Occurs alone in 11% Also known Apolipoprotein H Phospholipid bound inhibitor of coagulation and
platelet aggregation Inhibits contact activation of clotting Inhibits Prothrombin to Thrombin conversion Found in large percentage of primary and secondary
APS
![Page 11: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/11.jpg)
False + serologic test for Syphillis
Phospholipid dependant tests Syphillis antigen-cardiolipin
![Page 12: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/12.jpg)
Anti-prothrombin
Associated with higher risk of recurrent thrombosis
Risk independent of presence of ACL or LA
![Page 13: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/13.jpg)
Pathogenesis
![Page 14: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/14.jpg)
Mechanism of thrombosis
Antiphospholipid Ab :
Interference in cells of coagulation
Selective inhibition of protein C anticoagulant
pathway
![Page 15: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/15.jpg)
Interference in cells of coagulationAntiphospholipid Ab activation
Endothelial cell
Inducing :
Adhesion molecule,
Tissue Factor
Endothelin
TX A2
Monocyte
Expression :
TF
TXA2
Antiplatelet Ab
Aggregation vasoconstriction
Platelet activation
Thrombosis
![Page 16: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/16.jpg)
Mechanism of fetal lossAntiphospholipid Ab
Direct effect on throphoblast
Endothelial cell lesion of placental vessels
Competes with Annexin
Intraplacental thrombosis
Tissue hypoxia
Fetal loss
![Page 17: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/17.jpg)
Clinical manifestation
![Page 18: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/18.jpg)
Disease associations
![Page 19: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/19.jpg)
Clinical manifestation
Major : Vascular thrombosis Pregnancy morbidity
Minor : Hematologic :Thrombocytopenia,…Dermatologic : ( Livedo reticularis….)Neurologic : ( CVA ….)
Others
![Page 20: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/20.jpg)
Vascular thrombosis
Sporadic In < 50 years Unrelated to antibody level Recurrent Venous : Deep vein thrombosis of the leg Arterial : Stroke Small vessel : Kidneys & Skin
![Page 21: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/21.jpg)
Pregnancy morbidity Unexplained fetal death
Unexplained spontaneous abortion
Premature birth before the 34th weeks of gestation
Others : Fetal distress , preclampsia , post partum thrombotic accident , HELLP syndrome , fetal growth disorder
![Page 22: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/22.jpg)
Hematologic
Thrombocytopenia : Mild to moderate(100,000 – 150,000 )
APL a/b in 70-82% of SLE and thrombocytopenia 30 – 40% with ITP ITP therefore may be associated with thrombosis
Hemolytic anemia : Positive combs test
![Page 23: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/23.jpg)
Dermatologic Raynoud phenomen Livedo reticularis Superficial
thrombophelebitis Leg ulcer Cutaneous necrosis Splinter hemorrhage Acrocyanosis
![Page 24: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/24.jpg)
Livedo reticularis
![Page 25: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/25.jpg)
Livedo reticularis with necrotic finger tipsin Antiphospholipid syndrome
![Page 26: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/26.jpg)
Neurologic Migraine headache Stroke & TIA Chorea Memory loss Dementia Multiple sclerosis-like syndrome Transverse myelitis Seizure Non focal neurologic symptoms Guillene-barre
![Page 27: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/27.jpg)
Others Libman-sacks endocarditis
Valvular insufficiency
Pulmonary hypertension
Renal failure
![Page 28: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/28.jpg)
Laboratory tests
![Page 29: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/29.jpg)
Laboratory tests
Anti cardiolipin ( ACL ) & Lupus anti coagulant ( LA ) test : for people suspected of having APS
Anti B2GP1 : for people with signs of APS but normal ACL & LA tests
Platelet , ANA , ESR , Urinalysis : for patient with SLE
![Page 30: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/30.jpg)
Drug induced APLa
![Page 31: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/31.jpg)
Drug induced APS
Phenytoin , Hydralazine , Chlorpromazine , Procainamide
IgM isotype of antiphospholipid Ab
Antiphospholipid no related to B2GP1
Thrombosis and Thrombocytopenia
![Page 32: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/32.jpg)
DIAGNOSIS
![Page 33: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/33.jpg)
Diagnosis
Definite APS is considered to be persist if
at least one of the clinical and one of the
laboratory criteria are presented
![Page 34: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/34.jpg)
Vascular thrombosis :
One or more clinical episode of arterial , venous or small-vessel thrombosis in any tissue or organ and Thrombosis confirmed by imaging or Doppler
studies or histopathology , with the exception of superficial venous thrombosis
Histopathologic confirmation with thrombosis in the absence of inflammation in the vessel wall
![Page 35: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/35.jpg)
Pregnancy morbidity
Unexplained fetal death : After the 10th weeks of gestation (one or more)
Unexplained spontaneous abortion : before the 10th weeks of gestation (3 or more)
Premature birth before the 34th weeks of gestation (one or more)
![Page 36: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/36.jpg)
Laboratory criteria ACL Ab
IgG and/or IgM isotype in blood Medium or high titer on two or more occasions at
least six weeks apart Measured by standard ELISA for B2GP1
dependent L.A Ab
Present in plasma on two or more occasions at least six weeks apart,
![Page 37: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/37.jpg)
Diseases association
![Page 38: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/38.jpg)
Disease associations
Long list of associated diseasesSLE
Main GroupsAutoimmuneInfections and drugsNeoplasmsGeneticOther
![Page 39: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/39.jpg)
![Page 40: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/40.jpg)
Non-Autoimmune causes for positive Antiphosphospholipid Ab tests
Assay Antibody type Causes
ELISA B2GP1 independent Syphlis,lyme Leptospirosis, HIV
B2GP1 dependent Advanced age Drug Lymphoproliferative Hyperimmunoglobulin M
LA Either HIV , Drugs
![Page 41: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/41.jpg)
Catastrophic APS
![Page 42: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/42.jpg)
Catastrophic vascular occulsion syndrome
Multiple vascular of medium and small arteries that occurring over a period of day
Risk factors : Infection, Drugs, Small surgery, Anticoagulant withdrawal, Post partum period
Often history of SLE or PAPS Stroke , Cardiac , Hepatic , Adrenal , Renal and
Intestinal infarction , Peripheral gangrene , Thrombocytopenia , Hemolytic anemia , Hypertension
Biopsy : Non-inflammatory vascular occlusion 50% mortality
![Page 43: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/43.jpg)
Treatment
![Page 44: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/44.jpg)
Treatment-General
Thrombotic therapyHeparinWafarin
Pregnancy – controversialSC heparin and/or Aspirin
Immunosuppresion – rarely used Treat associated condition eg.SLE Risk factor modification eg.smoking , OCP
![Page 45: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/45.jpg)
APS treatment Asymptomatic Positive antiphospholipid
Ab : no treatment
Venous thrombosis :
Peripheral venous thrombosis : INR = 2 Proximal thrombosis , Budd-chiari
syndrome , Cavernous or sagittal sinus thrombosis , Pulmonary emboli : INR =3
Arterial Thrombosis : INR = 3
![Page 46: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/46.jpg)
APS treatment First pregnancy, Single pregnancy loss
< 10th week : Low dose Aspirin
Recurrent fetal loss , loss after 10th week : Heparin 5000 U bid throughout pregnancy Discontinue 6-12 weeks postpartum
Recurrent fetal loss , loss after 10th week +Thrombosis : Heparin 5000 U bid throughout pregnancy and Warfarin postpartum
![Page 47: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/47.jpg)
Treatment-Other
Plasmapharesis IVIG Experimental – fibrinolytics, prostacyclin anti-
cytokines
![Page 48: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/48.jpg)
Treatment - CAPS
Uncontrolled data to suggest intensive treatment betters outcome(70% recovery)AnticoagulationSteroidsPlasmapharesis or IVIGTreatment of any precipitant eg. InfectionCytotoxics (if indicated eg.Active SLE )
![Page 49: Antiphospholipid symdrome APS. Definition Disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently](https://reader033.vdocuments.site/reader033/viewer/2022061305/55145cbd550346284e8b56c6/html5/thumbnails/49.jpg)