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Perth Haematology :: Dr Steven Ward

Thrombosis

 

Antiphospholipid Syndrome (APS)

 

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Disorder characterised by:

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 Recurrent venous or arterial thrombosis

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Recurrent fetal loss

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Anti-phospholipid antibodies (aPL): antibodies to the phospholipid lining of cell membranes:

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Lupus Anticoagulant (LU)

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Anti-Cardiolipin Ab (aCL)

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Anti-β2-GlycoProtein 1 Ab (B2-GP1)

 

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Thrombocytopenia

 

 

Antiphospholipid Antibodies   

LU

Oval: LU

aCL

Oval: aCL

     B2GP1

Oval:      B2GP1

 

 

 

 

 

 

 

 

 

 

 

 

Primary APS: without other underlying causes

Secondary APS: associated with SLE, or other rheumatoid or autoimmune disorder.

Note: up to 5% of healthy individuals may have low levels of aPL antibodies.

 

Hypercoagulability leads to recurrent thrombosis in any organ or body system:

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Venous system: DVT

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CNS: CVA (mainly large or median branches rarely lacunar), sinus thrombosis

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Blood: thrombocytopenia, haemolysis

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Obstetric: pregnancy loss, eclampsia

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Pulmonary: PE, pulmonary hypertension

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Skin: livedo reticularis, purpura, infarcts / ulceration

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Cardiac: Libman-Sacks valve, MI

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Eye: amaurosis, retinal thrombosis

 

Frequency:

40% of patients with SLE; 24% of patients with DVT but not SLE; 5% of healthy individuals

More common in females

 

Diagnosis criteria

Need 1 clinical and 1 lab criterion

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Vascular thrombosis arterial or venous

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Recurrent miscarriage 1 or more > 10 weeks gestation, >3 if before 10 weeks, premature birth <34 weeks dur to eclampsia

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Lab: persisting (> 12 weeks): LU, aCL (mod to high titre) or mod to high titre B2GP1

 

Catastrophic APS: VTE in 3 > areas; onset simult or within 1 week; small vessle thrombosis in at least 1 organ; lab evidence of APL

 

Associations:

Autoimmune / rheumatic

%

 

Infection

%

SLE

25-50

 

Syphilis, Hep C, HIV HTLV-1

93

Sjogrens

42

 

Malaria, bacterial sepsis

 

Rheumatoid

33

 

 

 

ITP

30

 

Drugs

 

AIHA

?

 

Procainamide, quinidine

 

Psoriatic arthritis

28

 

Propanolol, hydralazine

 

Systemic Sclerosis scleroderma

25

 

Phenytoin, chlorpromazine

 

MCTD

22

 

IFN, quinine, amoxycillin, OCP

 

PMR

20

 

 

 

Behcet

20

 

 

 

 

Differential diagnosis other conditions which may be similar to APS

         DIC

         Infective endocarditis

         TTP

         Hypercoagulopathy cancer, oral contraceptive pill, genetic defects

         Atherosclerotic vascular disease, vasculitis

 

 

 

LABS

 

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aPL:

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aCL     IgG, high-titre  [low to moderate titre probably not related to thrombosis]

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B2-GP1 Ab  IgG high titre

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Lupus anticoagulant   strong link with thrombosis    

         

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False pos syphilis serology

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low-titre ANA

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low plats ; autoimmune haemolysis

 

Rx:

Controversial still

Remove any other risk factors for thrombosis: smoking, obesity, OCP, HT

Aspirin - ?unproven

Thrombosis: treat as usual warfarin INR 2.5-3 for 6m min for 1st clot; recurrent VTE INR 3-4

Steroids unproven

 

Catastrophic APS heparin / plasmapheresis / steroid / cyclophosphamide / IVIg

 

Look for underlying cause

 

 

 

 

aCL Tests

These are ELISA tests. Commonly IgG and IgM aCL are tested. IgA may also cause problems. The test is reported in Units grouped into negative (<5 ); low pos ( 5- 20); moderate pos (20-80) and high pos(>80). aCL Abs have been shown to react against B2GP1 bound to cardiolipin.

 

B2GP1 Antibody

ELISA test     

 

Lupus Anticoagulant Tests

Coagulation based tests.

APTT

Prolonged

50:50 APTT

Does not correct [mixing patient and normal plasma]

dRVVT

Prolonged  (screening test)

dRVVT + PL

Corrects the clotting time (Confirmatory Test)

 

dRVVT:

Uses platelet poor plasma

Warfarin will prolonged dRVVT

Heparin > 1U/mL may interfere

RVVT reacts directly with FX Xa-Va+PL = prothrombinase

 

                                                                                     II ------- IIa

 

 

                                                                             Fibrinogen --------Fibrin = Clot

 

 

LU ISTH criteria:

               Prolonged clot time in screening assay APTT-LA or dRVVT

               Mixing indicates presence of inhibitor [fails to correct APTT]

               Confirm by dependence of phospholipid (PL)

               No other coagulopathy (eg specific Factor deficiency or specific factor inhibitor)

 

 

WDP

Screening Tests:

               APTT

               50:50 APTT

               dRVVT                             35-45s (POS if prolonged)

 

Confrmatory Tests:

               dRVVT + PL                      NEG/EQUIV/POS