Why is there hypercoagulability in antiphospholipid syndrome and at the same time the patient has lupus anticoagulants that even elevate the PTT level? Request

Well it's a question that troubles even many doctors, coagulation is like maths for them. They became doctors as they never liked maths and ended up in biology :)

Being a Rheumatologist I deal with fare share of my APLA syndromes and this did puzzle me for a long time.

The main answer

Now basically lupus antocoagulant (LA) is some kind of antiphospholipid antibody. In vivo, that is in body, phospholipids are bound to endothelial cells on vascular surface. While in vitro, in aPTT test you add phospholipids to drive intrinsic pathway.

Basically in the body this LA or antiphopsholipid antibody can bind to phospholipids (PL) on endothelial surface cells.

Normally endothelial cells do not ‘expose’ their PL. (They maintain their dignity of good flow :)

Some primary damage might ‘expose’ this phospholipids. As a result, these antibodies or LA might bind to them, activate endothelial cells, leads to lot of cascade of reactions, which makes this cell hyperactive and initiates coagulation at cell surface.

Basically , LA requires some cell surface bound phospholipids to initiate coagulation.

What happens to LA in aPTT test then ?

The test is done in vitro in a tube (see above image..yes the yellow tube one). So basically you add blood, calcium, some contact factor which simulates endothelial surface and external phospholipids. There is no real endothelial cell surface bound PL’s in a in vitro aPTT test.

The intrinisic pathway of coagulation can proceed, which doesnt necessary requires cell surface phospholipids.

But, Lupus anticoagulant, binds to these phospholipids without a real endothelial cell. The phospholipids are consumed. There is no endothelial cell activation and coagulation by LA, as it happens in body. The intrinisc pathway of coagulation cannot proceed at normal rate due to lack of phospholipids and aPTT in tube gets prolonged.

How do you know its LA prolonging it and not factor VIII ?

1. You add factor VIII or normal plasma with factor VIII - if it corrects its factor VIII deficiency.
2. You add lot of phospholipids - there is not enough LA to bind - free PL’s availaible for intrinsic pathway to go ahead, aPTT time corrects, becomes normal - you know its LA (voila :)

Hurray, you have got an answer. If you understood this much and otherwise happy with your life, go back relax and chill out. Spread this post. If you want to make you life more messy (as doctors normally do), read along.

Disclaimer :

No need to read below thing. I am just showing off my knowledge ;).

Don’t blame me if you got confused further :)

The problem is most medical people feel PT and aPTT test demonstrate what actually happens in body. In reality they don’t. In reality on tissue damage tissue factor is released, extrinisc pathway is initiated, initial thrombin formation later leads to amplification of coagulation by intrinisc pathway.

Now the way PT and apTT are designed, is to simulate only one pathway in vitro.

When you take a blood in tube and give lot of tissue factor, extrinsic pathway will dominate and hence you can detect any abnormalities in extrinisic pathway, this becomes PT test.

When you take blood in a tube with phospholipids, intrinsic pathway will dominate and hence you can detect abnormalities easily in intrinsic pathway, this becomes aPTT test.

Thus you simulate things to drive things on one road, extrinisc or intrinsic. In this way you can detect any roadblocks on either of them separately. In real life in body these pathways intersect. Extrinsic pathway starts and intrinisc pathway joins later.