Transcription
Hey everybody, welcome to my channel, Medicos is Perfection Alice. We have been talking about anemia since the dawn of humanity. We have talked about microcytic anemia as well as macrocytic anemia. Currently, we are discussing normocytic anemia, and today's topic is aplastic anemia. So please grab some popcorn, and because it will be a very long video, I'd like to note something: aplastic anemia is supposedly a normocytic anemia; however, MCV is not really 80 to 100; it's usually more than that. So MCV is usually high, and we will discuss that soon.
Aplastic anemia: basically, your bone marrow has failed. So you have symptoms of anemia, of course; we know them: tired and pale, pale and tired, headache, angina, murmur, dyspnea on exertion. Those are normal symptoms of anemia. Also, since aplastic anemia will have pancytopenia, you'll get some bleeding and some infection: platelets, white blood cells. So basically, again, aplastic anemia: my bone marrow has failed me. And this is your nice little cute hematopoiesis. So we start with the multipotent stem cell; we have myeloid and lymphoid, and then we have erythrocytes, then neutrophils, basophils, and eosinophils. These three collectively are called granulocytes. Then we have the monocytes, then we have nice platelets, then the lymphocytes. These together are called granulocytes. So when we talk about granulocyte colony-stimulating factor, I'm talking about something that will stimulate the production of all of these cells.
So here is our hero: the mean corpuscular volume—microcytic, normocytic, or microcytic anemia, depending on the MCV. Okay, we are like suspecting that aplastic anemia will be normocytic. That's not exactly correct. The MCV in aplastic anemia is usually high. Why is that? I don't know, but probably because there is a very good association with myelodysplasia or MDS. An MDS has high MCV. That's just my prediction; don't take my word for it. Just know that aplastic anemia will have a high MCV. Also, there may be another reason. I've told you before that the cells, like the RBCs, when they are synthesized, they start big, and as they mature, they get smaller. So if you have a problem with your bone marrow, you cannot follow these steps, so you will end up with big cells. Okay, progenitor cells, precursor cells: so large cells will give you high MCV. That's another reason, or maybe like a probability.
What does aplastic anemia literally mean? "A" means no; "plastic" means synthesis, formation, creation, genesis. A plastic: no creation, no synthesis. Okay, so there is no synthesis of blood cells. Okay, what is anemia? "An" means no; "emia" means blood. Basically, it means you have no blood. It's like not completely accurate, but it's kind of okay. Aplastic anemia, let me tell you, is a misnomer; the name is incorrect. Okay, what's the correct name? Cytopenia. It's not just anemia, and cytopenia instead. So basically, aplastic anemia is a pancytopenia and a hypocellular bone marrow. Okay, so pancytopenia means anemia, leukopenia, thrombocytopenia, and the marrow itself has very few cells. Okay, notice that's different from MDS, myelodysplastic syndrome, where there is pancytopenia with a hypercellular marrow. And please know that anemia and aplastic anemia and MDS are closely associated; they can occur together.
What are the causes of aplastic anemia, I mean, like aplastic pancytopenia, if you will? Constitutional, acquired, or iatrogenic. Constitutional, I mean like congenital, inherited: Fanconi anemia. And there is a huge difference between Fanconi anemia and Fanconi syndrome. Fanconi anemia is failure of bone marrow stem cells; Fanconi syndrome is failure of your proximal convoluted tubule of the kidney—huge difference. Also, other causes are: dyskeratosis congenita. Wow. Acquired causes can be idiopathic, which means we don't know—idiopathic pathology of the idiots, or we are idiots because we don't know the cause—just a joke. Or secondary: secondary to radiation, big-time drugs and toxins, such as what? Such as alkylating agents, antimetabolites, antimitotics, some antibiotics, anti-epileptics such as toye, carbamazepine, sulfa drugs, chlorpromazine, nonsteroidals, nifedipine, which is a calcium channel blocker. Toxins such as what? Toxin such as arsenic, such as benzene, such as gold. Quick recap of arsenic poisoning: you'll have sensorimotor polyneuropathy, aplastic anemia with pancytopenia, and basophilic stippling of the RBCs. Whenever you hear basophilic stippling, that doesn't mean stippling of the basophils—no, basophilic stippling of the red blood cells, which just mean like the RBC has some little cute basophilic dots like this. Okay. Viruses such as parvo B19, big-time hepatitis, HIV, and ABV, Epstein-Barr virus, which causes infectious mononucleosis, also known as mono. Immunological: many diseases; the basic mechanism is activation of the T cells, the T lymphocytes, which will secrete cytokines. The cytokines will destroy your myeloid cells—not the lymphoid, the myeloid stem cells. Also, there is a huge association with paroxysmal nocturnal hemoglobinuria as well as pregnancy. Note that the delivery of the baby will end this aplastic anemia; it's just like associated with pregnancy. How about iatrogenic? It causes intensive chemotherapy, such as treatment of cancer. So the patient has cancer; okay, you give them chemo; they end up with pancytopenia and aplastic anemia. That's terrible.
Okay, now to the mechanism of this disease: aplastic anemia. Okay, some of these cells, okay, have CD34; it's a cluster differentiation. These cells that have this cluster of differentiation are decreased; i.e., the primitive progenitors, the precursors are decreased; stem cells are decreased, probably because T lymphocytes or T cells will produce cytokines, which will destroy the myeloid—not the lymphoid; the lymphoid are intact; the myeloid are greatly affected. That's why you can get anemia, you can get leukopenia, you can get thrombocytopenia. Make sense? Symptoms and signs. Okay, first symptoms and signs are related to the pancytopenia. Please note that many patients with aplastic anemia look very well. So they look normal; they're laughing, and life is good, and everything is okay. But when you do the blood test, wow, all of their blood cells are decreased, maybe except for the lymphocytes. So signs and symptoms related to anemia: pale, tired, short of breath, lazy, headache, angina, murmur, pounding sensation in the ears. Why? Probably due to a hyperdynamic circulation. Anemia is one of the causes of a hyperdynamic circulation; blood is flowing very fast; it causes murmur and your heart pounding sensation in your ears. If you examine the cervix in a female or a rectum, both male and female, you can get some bleeding. Why? Maybe due to thrombocytopenia, which causes mucosal bleeding. Signs and symptoms of leukopenia or decreased white blood cells: infections and fever. Signs and symptoms of thrombocytopenia: thrombocytopenia; platelets are responsible for the primary phase of coagulation, so you will have mucosal or superficial bleeding. So you can have petechiae, with petechiae, which are less than three millimeters in diameter; purpura, which is three to ten millimeters; ten millimeters, of course, 10 millimeters equals one centimeter, of course; ecchymoses, which are more than one centimeter in diameter. The incidence of aplastic anemia is biphasic, so you will have prevalence here or increased peak incidence between ages 15 to 25 and over 60 years old patients.
Okay, clinical signs and symptoms related to the etiology: if you have Fanconi anemia, you will have short stature or stature and café au lait spots—café au lait, viva la flaunts. Also, if you have dyskeratosis congenita, you'll have peculiar nails and leukoplakia. If there is a telomerase defect, may be gene mutation; the gene is called TERT; you will end up with short telomeres, and the sign or the symptom will be early greying of hair. You have a young patient, and his or her hair is gray. Wow. What is the story of telomeres and telomerase? There is a big story. So telomeres are necessary for the cell to survive, i.e., cellular immortality. So normally, telomeres shorten with serial division of cells. So serial divisions make these telomeres shorter and these telomeres shorter and shorter and shorter. During serial so divisions will lead to senescence; the cells are getting old; you are getting old. Cancers, on the other hand, will have upregulated telomerase; upregulated too long telomerase will preserve these telomeres. Isn't that a good thing? It's a good thing if the cell is normal, but cancer cells are mutant, are mutated; preservation of these bad ugly cells is terrible. Preservation of these telomeres in cancer cells is bad; it will lead to immortality of your mutant cells; your cancer cells become immortal. Good luck with that. Of course, we are not making fun of any patients; I just want you to memorize it.
Okay, lab results: complete blood count. How about, what do you think the RBC count will be? Decreased. Hemoglobin: decreased. Hematocrit: decreased. Why? It's anemia. MCV: I've told you, it's increased, probably due to myelodysplastic syndrome, and also because when you don't have cell divisions and your bone marrow failed, you will retain the big large cells, the progenitor cells, and you will end up with high MCV. How about reticulocytes? No, they are decreased. Why? Who produces reticulocytes? Mr. Bone marrow, and here Mr. Bone marrow has failed us. So no reticulocytes, no RBCs, and no baby RBCs. Fine. How about the peripheral smear? Peripheral smear may show immature myeloid cells. If it showed immature myeloid cells, probably there is MDS or leukemia as well. Wow. If it showed abnormal platelets, probably again MDS, myelodysplastic syndrome. Nucleated RBCs or teardrop cells: myelofibrosis. When your bone marrow is fibrous, it cries: teardrop red blood cells. Wow, even the bone marrow can be miserable. Bone marrow biopsy: aspiration of the bone marrow will yield what? Hypocellular bone marrow. Okay, it has failed us. Okay, instead of these cells, fat and stroma will replace the cells; the hematopoietic cells or hematopoietic cells are less than 25% of the bone marrow space; they are normally like larger or greater than that. Okay, no fibrous infiltration or malignant cells, because if there is fibrotic infiltration, it's probably a myelofibrosis; if there is malignant cells, it's probably something called myelofibrosis or malignant infiltration. The residual cells, those less than 25%, are normal in shape, so they are morphologically normal, so they are few but normal in shape. Okay, what will replace them? Fat and stroma. So in brief: hypocellular bone marrow, and it has a lot of fat and stroma. Megakaryocytes are usually absent. Pancytopenia: dry tap can be associated with myelofibrosis or myelofibrosis. Your bone marrow is fibrosis; you cannot aspirate it. Granuloma and the bone marrow can be drained infection leading to the bone marrow failure.
How to treat this ugly aplastic anemia? First: stop the offending drug or chemical, if there is any. Second: hematopoietic stem cell transplant, allograft. If you have a donor, you're a lucky person. What if you don't have a donor? Let's do some immunosuppression. I've told you that you have like T cells secreting cytokines destroying your myeloid cells, so we give antithymocyte globulin and cyclosporine as a form of immunosuppression; they are given together. Androgens may help; there is not enough evidence. How do androgens help? They upregulate the telomerase; telomerase will preserve the telomeres; telomeres; this will enhance the bone marrow activity, and our bone marrow is very lazy and has failed us; let's enhance and stimulate it. Symptomatic treatments: we can give epoetin alfa, packed red cell. Fine. Do not give whole blood. Why? Whole blood can contain some antibodies in the plasma, and your bone marrow has failed. Okay, and also we are taking immunosuppressive drugs, so please, plasma can contain antibodies that can destroy your life. Treat infections with broad-spectrum antibiotics such as ciprofloxacin. Give granulocyte colony-stimulating factor. Remember the granulocytes? Yes, those cells, white blood cells with granules. Yes, colony-stimulating factor: something to stimulate them.
Now to the fun part: question of the day. This is my fourteenth question. If you like previous ones, go to my Facebook page. So the question is: what's the drug that causes hyperesthesia, neuropathy, gingival hyperplasia, aplastic anemia, fetal anomalies, and the mechanism of action is blocking the sodium channel activation? A: is it methotrexate? B: aspirin? C: theophylline? D: phenytoin? E: atorvastatin? Let me know in the comments. Let's see who wins the prize, the quiz, and I'll see in the next section when we will continue our discussion on other causes of normocytic anemia.