Guidelines on the investigation and management of the APL syndrome Dr Wan Zaidah Abdullah BJH : (Revised of !991 guidelines by the Haemostasis and thrombosis task force of the BSH )

Definition  APL antibodies comprise of a family of antibodies reactive with epitopes on proteins which are themselves complexed with negatively chaarged PL.  Thus many APL antibodies require B2GP I, aPL binding plasma proteins with weak anticoagulant activity.  (read on the mechanism)

APS-definition  Arterial or venous thrombosis  Rec miscarriages  In whom the blood tests for APL antibody (ACL and LA) are persistently positive plus other causes and contributory factors are considered.

Other features  Thrombocytopenia  Livedo reticularis  Sterile endocarditis with embolism  Young arterial stroke and MI  Catastrophic APS- high fatality due to extensive microvascular thrombosis

Pathogenesis  Pr C resistance  Vascular endothelial dysfunction  Impaired fibrinolytic activity  Thrombosis in the utero-placental vasculature  Multifactorial  Auto-immune

Cont  ? Familial  Incidental aPL: antibodies in healthy subjects ? Predict future thrombosis ( need to exclude infection, drugs- chlorpromazine and autoimmune dzs)  * Low risk of VTE and arterial dzs in drug induced APL

Diagnosis difficulty ?????  May be made delayed especially after anticoagulant therapy has been instituted in active situation (started B4 persistence of the presence of antibody is demonstrated particularly LA)  Clinical assoc with APL antibodies- primary and secondary

Indication for lab testing  Spont VTE  Rec VTE even in the presence of underlying risk factors  Peripheral artery occlusive dzs at a young age (<50 years)*  Autoimmnue dzs- the finding will influence the use of prophylactic measures at time of particular risk)  Rec abortion 3 or more- even in 3 rd trimester  Early severe PE or severe placental insufficiency ( + anti-Ro antibodies to be done to detect FHB)

Pregnant patient  Under regulated of APL antibodies and therefore best done at early pregnancy or preconceptually when possible.

Lab Ix LA- coagulation assay Solid phase immunoassay B2 GP I (recent)- correlate strongly with thrombotic clinical events) Must do both. (LA and ACL )

Lab test Coagulation assays for LA

Criteria for the presence of LA  1. Prolongaton of a PL dependent coagulation test  2. Evidence of inhibitor demonstrated by mixing tests  3. Confirmation of the PL dependent nature of inhibitor  4. Exclude factor deficiency

LA test  Screening- sensitive test  Confirmatory tests- often performed using diff reagents in the same type of tests  Bcoz of heterogenous nature of APL, > 1 test is used for detection of LA  PT and TT are important tests  LA- interfere in coagulation factor assays, suspect when unexpected combined factor def.

Procedures used to detect LA  Screening  APTT  DRVVT  KCT  TTI  Confirmation tests  Mixing tests  PL dependent nature by plt neutralization procedures:  -LA insensitive tests  -Hexagonal phase lipids  -High concentration PL

Preanalytical variables  Follow samples collection for other haemostatic tests: minimal venous stasus, rapid draw nd immediate anticoagulation.  Prepared plasma within 1 hr post collection at RT 2000g for 15 min, with minimization of plt contamination esp after freezing the samples.( Repeating centrifugation- 5 min)

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