Q. Can you write a post about antiphospholipid syndrome? I could not find good source which explains its pathophysiology and laboratory results.
A. First, before we get into the antiphospholipid syndrome, we need to talk about antiphospholipid antibodies. As you might expect from their name, antiphospholipid antibodies are autoantibodies in the patient’s plasma that are directed against various phospholipids (there are lots of phospholipid surfaces in the body – including the phospholipid surface upon which the coagulation factors interact). There are a bunch of different types of antiphospholipid antibodies, including anticardiolipin antibodies, anti-ÃŽÂ²2-glycoprotein antibodies, and the so-called lupus anticoagulants (which were discovered in patients with lupus).
In addition to binding to various phospholipid surfaces in the body, these autoantibodies also just happen to bind to the phospholipid part of the PTT reagent (and sometimes, the PT reagent). Then there’s not enough usable reagent in the test tube, and the patient’s specimen doesn’t clot! The coagulation tests are therefore falsely prolonged.
Antiphospholipid antibodies are sometimes called “inhibitors”Â because they appear to inhibit coagulation in the test tube. But here’s a weird thing: in the body, they can be associated with thrombosis!
You may be asking yourself: how do you get these antiphospholipid antibodies? And are they dangerous?
It turns out there are different answers for different patients. Children, for example, sometimes develop antiphospholipid antibodies after an infection. In this setting, the risk of thrombosis is only slightly increased; it’s usually not a big deal clinically. Adults sometimes develop antiphospholipid antibodies as part of an autoimmune disorder like lupus (in fact, antiphospholipid antibodies – in whatever clinical setting – are often called “lupus inhibitors”Â because of this association). In these patients, the risk of thrombosis is moderately increased. Finally, elderly adults may develop antiphospholipid antibodies in association with drugs. This is virtually always a harmless event with no increased risk of thrombosis.
Okay, so here’s where we get to the antiphospholipid antibody syndrome part. This term is used when a patient with an antiphospholipid antibody has thromboses or pregnancy-related complications (like recurrent miscarriage, pre-term labor, or pre-eclampsia). This syndrome is a serious thing. In a small number of patients, the thromboses can be widespread, leading to multi-organ system damage and death. The term is reserved for patients who are symptomatic; you wouldn’t use the term in patients who have an antiphospholipid antibody but no symptoms.
So what would you do if you think your patient might have an antiphospholipid antibody? Well, you’d need to confirm this suspicion with laboratory tests. First, order a PTT (in fact, that’s how a lot of these patients get picked up – they present with an abnormally prolonged PTT in the face of clinical evidence of thrombosis).
Then, order up a mixing study. Remember what a mixing study is? You do this test when you have a patient with a prolonged PTT and you want to know why. It’s performed by taking the patient’s (probably abnormal) plasma and mixing it with some pooled (hopefully normal) plasma – then running the PTT on this new mixed sample. If the new PTT value is within the normal range (if it “corrects”Â), then you know the pooled human plasma must have supplied something to the patient’s plasma to make it clot normally. (The “something”Â is usually a coagulation factor that the patient is missing.) If the new PTT value is still abnormal (if it’s still prolonged, and doesn’t “correct”Â), then you know that even though you added a bunch of normal plasma to the mix, the patient’s plasma still couldn’t clot normally. There must be some other problem with the patient’s plasma. (The “other problem”Â is usually an inhibitor.)
One caveat: some antiphospholipid antibodies do not prolong the PTT. It all depends on the particular PTT reagent your lab is using (some reagents are just more easily swayed by the antiphospholipid antibodies). So if you really feel your patient may have an antiphospholipid antibody, you shouldn’t stop investigating that possibility just because the PTT comes back normal! There are plenty of fancy lab tests that can be done to detect antiphospholipid antibodies. Just call your friendly neighborhood pathologist and see what he/she has to offer.
Med student here at U Missouri. just want to say thanks for many of your entries. Just found them and they are very helpful!
This is a phenomenal and accessible description of the antiphospholipid antibody syndrome. Kudos on your superlative contributions.
Thanks a lot
Thank you so much for this entry. Wonderful explanation; better than anything I could find in my medical school texts/lectures.
Thanks for the explanation. Still want to know. Why are people with lupus antibodies present with thrombosis instead of bleeding invivo? Thank you.
Hi Ayuba –
The exact interaction between the antiphospholipid antibodies and the components of the coagulation system is not well worked out. Certainly platelets have a phospholipid surface – so the antibodies likely interact with platelets and somehow induce a thrombotic state. There may be other interactions with the endothelium as well that we don’t fully understand. Great question! Wish there was a more definitive answer.
Thanks. I’m a resident in Haematology and you contributed alot to my understanding of the speciality. You really are a gift to us. Keep on with the good works. Really appreciate.
Gracias! you make the difficult so fun and easy:) I read your post everyday now before I begin my study schedule.
In APLA syndrome where there is not much chance for clotting how does thrombosis occur???( thrombosis is due to platelet aggregation as to my knowledge)
Superab way of explanation.
1.apart from ACL n lupus which r APL antibody r then any other APL antibody.
2.pathophysiology of formation of APL in children , adults n elderly
3. If PTT reagent any specific reagent to be used to do the test.