What is essential thrombocythemia?

- Essential thrombocythemia is a disorder where you have too many platelets or thrombocytes in your blood. It's one of our myeloproliferative disorders. So let's recall how this all begins. Platelets are first generated in the bone marrow and remember the bone marrow is located in the shaft of long bones like our femur and it all begins with this cell which is called a pleuripotent meaning with the ability to do many things so pleuri meaning plural, potent meaning ability, hematopoetic meaning relating to blood stem cell. A pleuripotent hematopoetic stem cell. This guy can then embark on two different types of lineages. This one down here we're not going to talk about, lymphoid stem cell because I've mentioned that before. But let's focus here, on they myeloid stem cell. Remember there are six different things that can come off a myeloid stem cell. And I won't talk about them in detail here but I'll just draw them out for reference. But our focus for this conversation will be on the sixth thing that can be made. And it follows this path here that begins with a megakaryoblast, a megakaryoblast. Which just means a cell that has a really big nucleus. So that's what karyo means, a really big nucleus. That will divide and mature into a megakaryocyte which will do this crazy thing where it will break into pieces like that so it just fractures and then produces a bunch of these little dudes right here which are just called thrombocytes or as you may recall, platelets. Thrombocytes or platelets. Remember platelets are for our clotting system. They make sure we don't bleed out when we sustain an injury. So for example, imagine we get poked right here or we're stabbed and then we start bleeding. Well our platelets here will then come on over and start aggregating, aggregating or start forming the early parts of a clot that will help close off this wound an then stop all that bleeding. Now another thing to remember about platelets is that over time they can get sheared as they pass through the vasculature and actually become messed up. So I'm trying to show these deformed platelets right here. So I'll drive that home and just write that they are deformed, if my drawing doesn't make sense. And they're no longer effective. We need to get rid of them. And so they go to the spleen. Our spleen right here will then act as a filter for the blood and destroy any deformed or unusual blood cells that are passing through. And that's kind of what happens for a platelet throughout it's lifetime. The problem with essential thrombocythemia is that you have a defect around here before you make the megakaryoblast, where your JAK 2 kinase, I'll write that here, it's JAK 2 kinases protein. It's a regulator protein that determines whether it's an appropriate time for a cell to divide and go forward with it's maturation. This protein is set in the on mode which just keeps telling megakaryoblasts, keep on dividing, keep on making these platelets. And so you end up with a bunch of platelets which can cause a variety of distinct things to happen to you which will then present as signs and symptoms of essential thrombocythemia. Now one of the earliest things that we know happens, so I'll write first here just because it's early. You can end up having what are called, thromboses which just mean clots which would make sense because you have a lot of platelets in your blood stream, I'll write plt for platelets and so these platelets will go around and make platelet plugs everywhere but there are three main places we notice them. First there's the head where you can end up having symptoms such as headache, dizziness or even weakness which can show up like a facial paralysis or even slurred speech which is not too different from a stroke which sure enough is what happens when you have a lot of platelet plugs that accumulate in your brain. The other two places your platelet plugs will predominately accumulate and I'll group these together. That includes your hands and your feet. And when these platelet plugs accumulate here, I'll draw an example in this hand right here. So this artery, kind of branches like this and let's say it goes to the tip of your thumb and then from there you need to have a return of the venous blood flow up this way but imagine you have platelets clotting over here and forming a plug and it makes it difficult for blood to flow from the arterial part to the venous part and so you end up not having oxygenated blood go to your tips of your fingers or your toes. That can manifest as two things, you can get some numbness or even burning. Now aside from thromboses, the next thing or the second thing that can happen is bleeding and that's because the presence of so many platelets in your blood stream will cause you to use up ingredients for clotting. Meaning that when you sustain a real injury and when you really need to clot, your platelets fail. Now this can manifest as a nose bleed or imagine if you were walking through a really crowded room and you just bump your thigh against a table or a chair, well you're not supposed to have an effect just from simply bumping your thigh on something but because you're not clotting, you can actually form a bruise and that can happen with even the most mild knock against a solid object. And lastly, remember that since platelets go to the spleen to be destroyed, if you have a lot of platelets coming here, your spleen is going to be kicked into overdrive,so it's going to be a lot bigger than what I've drawn right here. So you're going to get a mega spleen which we call splenomegaly. So those are some of the things we can look for if we suspect essential thrombocythemia. But how do we diagnose it? Well while this isn't one of the first line things you'd look for, sort of a slam dunk finding would be the presence of JAK 2 kinese mutation suggesting that we indeed have a myeloproliferative disorder. But a more specific thing to look for is the number of platelets that this patient has because if that number is greater than 450,000 for two or more months, then that's pretty suggestive. The other thing that's knows about essential thrombocythemia is that it's a diagnosis of exclusion which means you just have to make sure other disorders aren't present before you can conclude a patient has essential thrombocythemia. That means that you need to exclude things like other myeloproliferative disorders as well as causes of inflammation because that will cause the number of platelets to increase and there are a few other things I won't list here that could suggest why they have such a high count of platelets. And finally the last thing that you can do which is rarely done, is a bone marrow aspiration to check to see if there's a bunch of megakaryoblasts or cytes found in the bone marrow and then following the diagnosis, what can we do to treat essential thrombocythemia? Well the strategy for treatment depends on their risk. The risk for having bad outcomes related to thromboses or bleeding. If they're low risk, things like if they're young of age or they don't have very severe symptoms, than all they need is a mild anti-coagulant or something that prevents clotting like aspirin. Remember that one of the first things that happen when you have too many platelets in your circulation are thromboses. So aspirin will decrease the risk of having these clots or thromboses. Now if they're high risk, meaning that they're older or they've got other chronic diseases or if they have more severe symptoms, you can try a few things. First, you can give them hydroxyurea. Hydroxyurea is a drug that will decrease the production of megakaryoblasts. Another drug you can give is called, interferon alpha and this will work similarly to decrease the number of megakaryoblast that you have. But finally, in emergencies, if you've got excess bleeding or the patient is rather unstable, one of the things you can do is a procedure called, platelet phoresis. Platelet phoresis which is similar to dialysis where you filter the blood through a machine but in this case you are filtering the blood for excess platelets to decrease their risk of thromboses or bleeding or whatever else it is that initiated the emergency. Now most cases of essential thrombocythemia never get to be this bad. Most patients are actually in this low risk range and are treated on something pretty benign like aspirin but now that we've talked about all of these things here, now you're able to identify, think about how you'd diagnose or what you'd probably do to even treat essential thrombocythemia.