Transcription
Let's get on with our series about bleeding and coagulation disorders. In the first three videos, we have discussed platelets, platelets structure, and the arachidonic acid pathway. Today, we'll talk about thrombocytosis, or increased platelet count. Theoretically, it's more than 400,000, but clinically we don't care about thrombocytosis unless the platelet count is greater than 750,000 and symptomatic. So let's get started. [Music]
So here are the previous three videos in my series called bleeding and coagulation. I stopped adding videos to my hematology playlist because it's like, has 160 videos or something, so I started a new playlist called bleeding and coagulation. There is another reason to subscribe. Imagine places we start with the pluripotent, multiple pluripotent stem cells, and we have myeloid, lymphoid. Myeloid gives us the mega-karyoblast, which will give us the megakaryocytes. The megakaryocytes will give us some small pieces called platelets or thrombocytes, the cells of thrombosis. Normal platelet count is between 150,000 and 400,000 per microliter. The reason we don't care about thrombocytopenia unless it's less than 50,000, and the reason we don't care about thrombocytosis unless platelets are more than 750,000, it's not because we are evil people; it's because it's a curve like this, a normal distribution curve. So from here to here is the 150 to 400,000. Just because you're here doesn't mean you have thrombocytosis, and just because you're here doesn't mean you have thrombocytopenia. Let's say that your platelet count is 120; no, I'm not gonna worry about you; you're probably fine. I'm just asking you, do you have any symptoms? No, I don't. Just go home and follow up with me, provided that everything else is normal.
When Grandma comes and looks at her lab work and then says, "Okay, my son, I just read the lab results," whenever a patient tells you that he or she read the lab results, prepare yourself for a foolish question. "My platelet count is 600,000, and I'm so worried. Everything else is fine. The red blood cells are fine, the white blood cells are fine, the hemoglobin hematocrit values are fine." Grandma's asking, "Am I going to die?" I asked her one question, "Do you have any symptoms?" No. So go home, don't worry about it; it's just normal. I'm not making fun of patients like they ask foolish questions because they are not doctors. When I go to the mechanic, I ask foolish questions, like last day, his only your water pump is weak, so my question was, "Is it supposed to be strong?" I don't know, of course. I asked some questions about cars. Same way the patients ask dumb questions about medicine. Our job is to be like a nice person, a nice doctor, and to calm down and explain the normal distribution curve, explain that this is normal, explain that if she is asymptomatic, she'll be fine, and what I don't know that she can call you anytime, she can follow up with you and be the nicest guy ever. God help us.
Thrombocytosis is just more common in the elderly, but a younger person will ask you the same foolish question, except they will keep their teeth in. Platelets or thrombocytes, the cells of thrombosis. Decreased platelet count called thrombocytopenia. Increased platelet count, you can call thrombocytosis or thrombocythemia. So when I say essential thrombocytosis or essential thrombocythemia, they are synonymous; they are just the same. Platelets are synthesized from their magnificent parents, the megakaryocytes, made in the bone marrow. While leaving, they are squeezed into the sinusoids, and then they they just they are destroyed; they break down into pieces, thousands of pieces. Each piece is a platelet. Thrombocytosis or thrombocythemia, increased platelet count, theoretically more than 400,000, practically more than 750,000. Two types: we have primary or essential and secondary or reactive. Which one is more common? Secondary is more common. Cool. How about the primary, essential? As one of the myeloproliferative disorders, as we have discussed before, and myeloproliferative disorders are diseases of the elderly. It's very, very, very, very, very, very unlikely to have a myeloproliferative disorder in a three-and-a-half-year-old. That's why 100% of cases of thrombocytosis in infants is secondary. How about adults? Eighty percent of cases of thrombocytosis in adults are secondary; only 20% is primary.
I've talked about the myeloproliferative disorders before for a long period of time, but let's just review. These are the myeloproliferative disorders: the most important, CML, polycythemia vera, primary myelofibrosis, and essential thrombocytosis. All of these three have the JAK2 V617F mutation, which will lead to activation of the Janus kinase JAK2 kinase. Polycythemia vera: all cell lines are increased, especially the red blood cells. Essential thrombocytosis: all cell lines are increased, especially the platelets. Myeloproliferative neoplasm, and disease of the elderly, unlike Hodgkin's, which is a disease of the young, unlike Burkitt's, which is one of the non-Hodgkin's, also a disease of the young. All cell lines are affected, especially the platelets. If you do a bone marrow biopsy, guess what? It's hypercellular; it's working like crazy to increase all of these cell lines, especially the thrombosis. One of them is affected the most, as you know. All of them have rapid cell turnover. When you turn over the cells rapidly, you turn over the nucleus rapidly. The nucleus has purine, purine metabolism only in uric acid. Uric acid can cause gout and cause hyperuricemia, increase uric acid in the urine, causing uric acid stones, which are invisible on x-ray. That's why you need a CT scan. When the bone marrow is working like crazy and it's not sufficient, we need extra medullary hematopoiesis, leading to splenomegaly. All of them can transform into acute leukemia, sadly, and they can transform into each other. So a patient with essential thrombocytosis can end up with CML or can end up with polycythemia vera. Tell Grandma to follow up with you. Essential thrombocytosis again: leukocytosis, thrombocytosis, erythrocytosis, all of them lead to hyperviscosity syndrome, which relates to retinal vein thrombosis, visual disturbance, sluggish blood flow in the vasa nervorum, linked to neurological symptoms. Blood vessels are congested and engorged, which can lead to bleeding. This is hyperviscosity syndrome. For an unknown reason, essential thrombocytosis is more common in women than men. That's why I called Grandma Grandpa. There is clonal malignancy, increased number of platelets; they will increase the risk of thrombosis. These are thrombocytes, increased risk of bleeding, why? Because these platelets, it's a clonal malignancy, you'll end up with acquired von Willebrand disease, which I'll talk about. That's why we call essential thrombocythemia a JAK2 thrombocytosis. Platelets are high. Am I going to die? Yes, my dear, we all will die. I'm sorry. Follow up with me, and if you are asymptomatic and if it's controlled, you'll probably be fine. We'll give you some hydroxyurea and an anagrelide; you should be okay. And by the way, aspirin for your erythromelalgia.
So we have two types of thrombocytosis: primary, which is one of the myeloproliferative disorders, known as essential thrombocytosis, and secondary or reactive thrombocytosis, which is the most common subtype, secondary to what? To another disease, and it will depend in kids, probably acute infection, why? Because, as you know, acute infection has interleukin 6, and interleukin 6 stimulates thrombopoietin production, and thrombopoietin will promote poiesis of thrombocytes. Chronic inflammation, same thing. I'll sex tissue damage, why? Because platelets' job is to form a plug when the tissue is damaged, and you have lots of injuries, yeah, platelets are gonna be high. It's a net feedback. Malignancy, hemolytic anemia will lead to increased EPO, and by the way, EPO looks like TPO; the cells are confused, and it will increase the number of platelets. Thalassemias, same thing. In adults, acute infection, chronic inflammation, same thing. In looking six tissue damage, this is the freaking job of the platelet. Malignancy, because malignancy leads to anemia, anemia increases EPO. EPO looks like TPO, which will increase platelet production. Also, malignancy has interleukin 6 as a cytokine. Remember, multiple myeloma had interleukin 6 overactivity, so this will lead to increased TPO. TPO deficiency, why? It will cause anemia; anemia causes increased EPO. This is inappropriate EPO production, which will lead to secondary thrombocytosis. Post-surgery, and this is a famous term for surgeons, it's called post-operative thrombocytosis. When a cancer patient developed thrombocytosis, usually it carries poor prognosis, so it's musical. We have thrombocytosis, poor prognosis. Spurious causes of thrombocytosis: what the spurious mean? It means fake; it means false; it's not an actual thrombocytosis; there's just some artifact or stuff that looks like platelet and incorrectly counted as platelets by the stupid machine called the analyzer. That's why you should use your brain, do a peripheral smear, look at the cells dead in the eye by yourself manually, and don't depend on the stupid analyzer. So, for example, cryoglobulinemia, globulin is needle-like; it looks like this. As you know, platelets are biconvex; the analyzer is stupid; it's a freaking computer, so, oh yeah, I will count it as platelet, wrong. Bacteria, I don't know why, but for some reason the machine is confused. Fragments of leukemic cells, because platelets are fragments of the megakaryocytes too, so both of them are fragments; the machine is confused. Never trust a lab technician with patients' lives, please; they are my friends; they watch these videos, but please don't trust me with your car; okay, I'll probably put the engine in the back. How to avoid this spurious, pseudo thrombocytosis? By doing the peripheral smear or by repeating the test; hopefully the stupid machine will not be confused twice.
Symptoms of thrombocytosis: most of the time is asymptomatic. That's why I asked Grandma, "Are you symptomatic?" She said no; I sent her home. Primary thrombocytosis symptoms include erythromelalgia, thrombosis, bleeding; it's the evil myeloproliferative disorder. Thrombocytosis is not the same as thrombophilia. Thrombophilia is one of the Virchow's triad: we had endothelial injury, we had blood stasis, and we had hypercoagulability. Hypercoagulability is another thrombophilia; it's not the same as thrombocytosis. Don't believe your professors. How to diagnose thrombocytosis? We need a peripheral smear and a bone marrow biopsy, especially in case of the primary myeloproliferative, essential thrombocytosis. Cool. How to treat thrombocytosis? No symptoms, no treatment, hashtag sent her home. Secondary thrombocytosis: if a spleen because when you have lots of platelets, and as friends, antiplatelet maybe it can help. Primary thrombocytosis with symptoms: we have aspirin; we can use hydroxyurea; it's a cyto-reducing drug. I love this name; cyto means cell, reducing the production; it will reduce the number of these stupid thrombocytes. And anagrelide, if you have the JAK2 kinase mutation, use ruxolitinib, which is a tyrosine kinase inhibitor. Any drug that ends in -nib is a tyrosine kinase inhibitor, and as you know, the JAK kinase, it's JAK2 kinase, so it's a kinase; that's why we need a kinase inhibitor, such as the amazing ruxolitinib. Who names these things?
Quick summary: thrombocytosis, clinically speaking, is more than 750,000. If it's primary, usually in an elderly, or me, not usually, almost always it's myeloproliferative, JAK2 kinase, thrombosis and bleeding, more common in women, hashtags send her home, don't send her home if she's symptomatic. Secondary depends, can be kids or adults, infection or inflammation, malignancy, TPO deficiency, and post-operative. Please don't forget TPO deficiency because it will lead to anemia; anemia will increase the EPO; EPO looks like TPO; you will end up with thrombocytosis. You guys are awesome; thank you for watching. If you really like Grandma, follow me on Facebook; I have lots of cases there. We have 85 plus vignettes on my Facebook page. Just Google Facebook Medicosis, and you're fire. Please subscribe. See you next time. Be safe, stay happy, and study hard. It's Medicosis Perfecti's nails, where medicine makes perfect sense.