[0:00]The anti-phospholipid syndrome is a disorder in which people have an accelerated incidence of thrombosis as well as recurrent pregnancy loss.
[0:10]And it's associated with the presence of these so-called anti-phospholipid antibodies, which are autoantibodies directed to cardiolipin, beta2 glycoprotein 1, or that prolong clotting test in a test tube, although they're prothrombotic in the patient.
[0:29]And we've studied this for a long time. And there's been many mechanisms proposed by which these antibodies might cause blood clots.
[0:37]One is activation of endothelial cells, one is activation of platelets, and there's others as well, uh, you know, activation of monocytes, activation of neutrophils.
[0:48]And probably all of these are involved to a different extent in different nations. Um, so we, uh, we sort of took a new look at platelets.
[0:59]And we have found that patients, many patients with this disorder have elevated levels of what we call procoagulant platelets.
[1:08]So procoagulant platelets are one form of an activated platelet. There's, there's a couple different forms.
[1:16]Some activated platelets express higher levels of integrands and they're more adhesive.
[1:23]Another population, a smaller population, express more of this negatively charged phospholipid on their surface and thereby support coagulation reactions.
[1:35]So, uh, so we found elevated levels of the procoagulant platelets in patients with antiphospholipid syndrome or APS.
[1:46]Um, and furthermore, uh, the circulating patients, we developed a model where we can incubate normal donor platelets from healthy people with sera from patients with APS.
[1:57]And we find that when we do that, that these normal donor platelets also assume a procoagulant form.
[2:06]And we can block that with available, uh, inhibitors of the complement pathway.
[2:14]And, uh, and then when we actually take these so-called procoagulant platelets, uh, and we isolate them and we just add them to normal human plasma.
[2:27]And we do the same thing with platelets from just healthy donors, we find that the platelets from patients with APS cause higher rates of thrombin generation than platelets from the normal donors.
[2:40]So they're clearly, uh, procoagulant, uh, we detect that both by functional activity as well as binding things that bind to negatively charged phospholipids.
[2:54]So, uh, finally we, we have a, again, we don't have a lot of patients, but from what we've done, we've found that, uh, that the presence of these the procoagulant platelets, which also have markers of complement activation on their surface.
[3:10]Um, their presence, those two things tend to correlate with a past history of thrombosis, more closely than do the clinical tests.
[3:22]currently existing clinical tests for the anti-phospholipid antibodies. So, we're always searching for better tests to try to define which patients, uh, with antiphospholipid syndrome have the highest risk of blood clots.
[3:42]Because the current, uh, guidelines suggest that all patients with APS, uh, receive blood thinners, anticoagulation, indefinitely for the rest of their life.
[3:52]Um, and we would like to be able to sort of fine-tune that recommendation a little better. So this certainly does not do that.
[4:02]But it may be a step in the right direction by, uh, potentially, uh, identifying a test that can be more predictive and also potentially, uh, we continue this work to better define the pathways by which these platelets are generated and maybe, uh, develop, uh, new therapies that can directly target these pathways rather than just, rather than just use anticoagulation.
