Q. I have a question about forming the platelet plug. Where are the phospholipids that get exposed, and how does platelet aggregation affect that? If this is in the subendothelium why weren’t they exposed upon ripping or whatever caused the endothelial damage? Also, what is tissue factor?
A. The phospholipids you’re referring to are part of the platelet cell membrane. The platelet membrane contains many different kinds of phospholipids on its surface. This is important because many of the coagulation factors (for example, the factor Xa-Va complex) require a phospholipid surface to exert their effects. During platelet aggregation, some of the phospholipids undergo important changes, making them more available to the coagulation factors.
Here is how a platelet plug is formed:
1. The endothelium gets ripped up, which exposes subendothelial proteins (like collagen) to the blood.
2. The platelets see these subendothelial proteins, and they stick to them using von Willebrand factor (this step is called platelet adhesion).
3. As the platelets adhese, they flatten out and release their granules (which have a lot of functions, one of which is to attract other platelets).
4. Other platelets come to the adhesion site, and they stick down onto the platelets that are already there (this step is called aggregation).
5. Now the platelet plug is formed. One cool thing about the platelet plug – in addition to its function of plugging the hole in the vessel – is that the platelet membrane provides a phospholipid surface which is essential for many of the coagulation factors. In fact, when platelets aggregate, certain phospholipids in their membranes become even more available to be used by the coagulation factors.
Tissue factor is a separate thing. It is the substance that initiates the whole coagulation cascade in vivo. It’s present in different areas of the body (in the subendothelium, in some inflammatory cells, and perhaps even in little locked-up microparticles in the blood). It is not present in active form in the blood until it’s needed for coagulation. So when the endothelium is ripped up (or when inflammatory cells decide to release it, or when the little microparticles get a signal to open up), tissue factor is exposed to the blood, and it binds to factor VIIa, and the cascade proceeds along the extrinsic pathway.
A different kind of plug: the image of Claes Oldenberg’s giant three-way plug at the Tate was taken by jovike (http://www.flickr.com/photos/49503078599@N01/54082836/), under cc license.
Q. We learnt about a pretty rare disorder called thrombotic thrombocytopenic purpura (TTP) in which super-huge von Willebrand Factor (vWF) multimers are made which lead to occlusion of microcirculation. (more…)
Q. I have a question about von Willebrand Factor – where is it stored? All that I can gather is that it’s stored in ‘Weibel-Palade bodies’, but where are they? (more…)
Here’s a very good question about the diagnostic use of the bleeding time.
Q. I’m currently studying heme for boards and came across a practice questions that used platelet count, bleeding time, PT and PTT values to differentiate between certain diseases/problems. I was just wondering how in both Vitamin K deficiency and liver disease you can get an increase in PT and PTT but the bleeding time doesn’t change…I guess I figured that bleeding time would have to increase. Can you explain this to me?
A. Yeah, that does sound weird, you’d think the bleeding time would change – but actually, the bleeding time is only a measure of platelet function. It really has nothing to do with coagulation!
I kind of think of it like this: the platelet plug is the first thing to form, and that is enough to stop the bleeding from the incision made at the beginning of the test. The coagulation cascade happens next, and the status of that won’t be apparent in the bleeding time results. The patient might have some more bleeding later if their coagulation system is really screwed up…but the bleeding time assay will be done by then. In reality, it probably happens a little more concurrently than that (platelet plug is followed very closely by fibrin formation – the two probably even overlap a bit), but I think it’s a good way to remember the concept.
The same reasoning fits with the way that people with coagulation factor disorders bleed (as opposed to patients with platelet disorders). People with platelet abnormalities tend to bleed spontaneously into mucous membranes without much provocation (probably because they’re having a hard time forming that initial platelet plug) whereas patients with coagulation factor abnormalities, like hemophilia, tend to have deep, severe bleeds that happen after some time has elapsed (because they form the initial platelet plug okay, but they can’t seal it up with fibrin very well, so they end up bleeding later on).
Rudolf Virchow, a German pathologist in the 1800s, is considered by many to be “the father of pathology.” His famous Omnis cellula e cellula (“every cell originates from another existing cell like it”) theory, published in1858, rejected the then-prevalent belief that organisms could spontaneously arise from non-living matter (e.g., that maggots could spontaneously appear in decaying meat). (more…)
Queen Victoria reigned as British sovereign from 1837 until 1901. Britian enjoyed prosperity and growth under her monarchy, but her genetic legacy was another story. (more…)
Factor V Leiden is a genetic disorder in which patients have an increased tendency to form thromboses, or blood clots. (more…)
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