00:00
Okay, now that we've been through the adventure of talking about normal hemostasis and
how we regulate hemostasis, let's talk about how we measure hemostasis because we're
going to need to know what's normal, what's abnormal, and whether our therapeutic
interventions are getting us to the right point. So, how do we measure this? Here's where
we are on our total roadmap. You can see we're about halfway done, so we're getting in to
the homestretch. Basic coagulation screening, we first have to look at platelet number and
it's not just the number in a complete blood count that's with CBC is, but the quality of the
platelets and their normal or abnormal function. So we have to do platelet function testing.
00:51
So, we also want to look at the coagulation cascade as part of our basic assessment. We
want to look at 2 times, the prothrombin time and the partial thromboplastin time and the PT
and PTT in a moment will become very clear, but we have 2 chemical laboratory
measurements. And finally, the D-dimer. Remember as we talked about breaking down a
fibrin platelet thrombus through the activity of plasmin and breaking off little fibrin
degradation products? We are actually forming something called a D-dimer that we can
measure to assess whether or not there is ongoing clotting or fibrinolysis and really
important for things like diagnosing potential pulmonary embolization. Okay, so those are
the kind of basic screening tests. Let's get down a little bit more into some details. Platelet
disorders. So we want to get a connotation on the number of platelets, and in general we
want to be above roughly 100,000 to 150,000 per microliter. So, the thrombocytopenia,
a decreased platelet count, has many many causes. Everything from marrow failure to
consumptive coagulopathy where we're clotting too much everywhere. We could also have
too many platelets, thrombocytosis. This can be reactive so it can be due to normal
processes. If we have an inflammatory response, the body responds by saying "We're under
attack, we need to make more of everything that's going to protect us including more
platelets." So a response to infection, injury, illness, or stress will actually cause the liver
to make more thrombocyte-increasing factors and thrombopoietin in particular and that
will cause us to have many more platelets. You can also have malignant diseases that are
also causing increased numbers of platelets and so these are classified as essential
thrombocythemia. It will be lead, obviously when you have too many platelets in this setting
you will become hypercoagulable. You have just too many platelets and the potential for
for them to be nonspecifically activated is something that you really have to very much be
aware of. One of the major mutations that drives thrombocythemia is a Janus kinase,
that's JAK2, and you'll hear about this in your patients. It's a tyrosine kinase that causes a
constitutive activation of the megakaryocytes in the bone marrow and we constantly crank
out too many platelets. So a JAK2, Janus kinase-tyrosine kinase mutation is detected in 30%
of patients with essential thrombocythemia. It's not enough just to count how many
platelets, too many or too few. We also have to say "Are they working appropriately?"
So, even though you have an adequate platelet count, if they don't clot appropriately we
have various ways of measuring that, then you will have bleeding problems. And this can
be congenital, you can be missing some of the receptors that normally are responsible for
platelet aggregation or platelet activation. Or you can have acquired defects. So NSAIDs,
you're all familiar with non-steroidal anti-inflammatory drugs such as aspirin, such as
naprosyn, such as ibuprofen and those will cause platelets to not function. In fact, we use
those intentionally for patients who might be a little hypercoagulable or otherwise have risk
for having a coagulation event. We say "Take an aspirin a day" because that will inhibit
platelet aggregation. But, if you have taken an aspirin a day and then you suddenly need
surgery, we may have to delay a bit until your platelets become functional. Okay.