Transcription
Hi everyone, let's look over some review questions for Hematology.
Question one: A 51-year-old man presents to the ED complaining of increasing abdominal girth. He has a history of chronic alcoholism. Last year, he underwent emergency EGD for bleeding esophageal varices, which were subsequently banded. He said since his last admission, which was four months ago for ascites, he hasn't had any problems and only has had one drink per day. Paracentesis is performed. Which of the following would be the best test in the management of this patient? And it's a hematology question, so you can imagine this is going to be a he-man sir. Is it A) protein, B) partial thromboplastin time, C) platelet count, D) bleeding time, or E) hematocrit?
Okay, and the answer is A) protime. So, remember that the liver creates factors 2, 5, 7, and 10. So the protime is really measuring the activity of factor 7 because the protime is the direct coagulation site. So we could also measure partial thromboplastin time, but protein would be much more accurate.
Question 2: So, a 31-year-old woman, G2 P2, presents to the clinic complaining of fatigue that is beginning to interfere with her daily activities. She notes no change since her last pregnancy, which was a year ago via cesarean section due to failure of progress. That delivery was associated with significant bleeding that resulted in a four-day hospital stay and a transfusion. Her periods have returned, and she says she has a heavy flow, but this is normal for her. She takes iron along with a multivitamin. She is yoga at her local fitness club. On physical exam, you note a two to three-centimeter bruise on her right shin and petechiae on her left arm. A Pfannenstiel incision is noted along the lower abdomen. Bleeding studies indicate an elevated bleeding time, normal PT, normal PTT, and normal platelet count. Which of the following is most likely contributing to this patient's symptoms? Is it A) endometriosis, B) bleeding uterine fibroids, C) hemophilia A, D) von Willebrand's syndrome, or E) Bernard-Soulier syndrome?
Right, and the answer is D) von Willebrand's disease. So, there's nothing clinically that will separate this from Bernard-Soulier syndrome, but the question is which of the following is most likely. And von Willebrand's disease is a very common disease. Bernard-Soulier is rather uncommon. So, if we wanted to be sure which of the two they are, there's a test we can do. But first off, how do we know that's either von Willebrand's or Bernard-Soulier? Well, we got the fact that she's a heavy bleeder, she's got these petechiae, and she's got these bruises which are unexplained. And on her bleeding studies, she's got an elevated bleeding time, but she's got a normal platelet count and normal PT and a normal PTT. Bleeding time is managed by the platelets. So, if you have a defective platelet count or a defective platelet itself, if you have a quantitative or qualitative defect in platelets, you're going to have an elevated bleeding time. It has nothing to do with factors. So, bleeding time strictly has to do with platelets. If your bleeding time is elevated, something's wrong with your platelets, either how they are acting or in how many you have. So, we know there's a problem with platelets. Likewise, the platelet count is normal, so we know that we don't have too few platelets. So, we know that we have a qualitative defect in the platelets. And with the normal PT and normal PTT, we know that our factors are intact. So, now that we know we've got a qualitative defect in platelets, we're down to two diseases: von Willebrand's disease and Bernard-Soulier syndrome. And the question asks which of the following is most likely contributing to this patient's symptoms. So, the answer is von Willebrand's disease. If we wanted to differentiate between the two, we would use a ristocetin test. A ristocetin test basically simulates von Willebrand in the serum. And so, with Bernard-Soulier syndrome, since the defect is gp1b and there's a perfectly normal amount of von Willebrand's factor, adding the von Willebrand's factor is not going to change anything, so it'll be a defective test which continues to be defective. With von Willebrand's disease, since the platelet is essentially normal, that doesn't have von Willebrand's factor, when we add von Willebrand's factor, it will normalize. So, I'll have an abnormal test, but then it becomes normal when you add the von Willebrand's factor. If that confuses you, go back to the platelet bleeding section, and I describe that in greater detail. Oh, okay, I guess I have a diagram of it here. So, von Willebrand's disease versus Bernard-Soulier syndrome and your ristocetin platelet test.
Question 3: A 15-year-old male presents to the ED complaining of fatigue and malaise. He says he has had inconsistent, loose stools for the past week. He denies any other symptoms. Vitals are: blood pressure 115/75, heart rate of 94, respiration 16, temperature of 101.4. Physical reveals petechiae over both calves and minor, mild scleral icterus. He's stable. Routine labs are drawn: hemoglobin is 9.9, hematocrit is 29.9, white blood cells are 8.7, platelets are 141, sodium 139, potassium 3.5, chloride 103, bicarb 30, BUN 35, creatinine 2.1, and glucose 143. Both the total and indirect bilirubin are elevated. Schistocytes are noted on the peripheral smear. Which of the following is the best therapy in the management of this patient? Is it A) platelet transfusion, B) RBC transfusion, C) plasmapheresis, D) dialysis, or E) inpatient observation?
Right, so the answer here is C) plasmapheresis. So, this kid has TTP-HUS. He's got hemolytic uremic syndrome in addition to thrombotic thrombocytopenic purpura. How do we know that? There are a few hints in here. First of all, let's look at what signs of thrombotic thrombocytopenic purpura TTP. What it is, is it's associations of the platelets sticking together and causing these clots, which then can break red blood cells. It can break parts of the red blood cells off. That's what causes schistocyte red blood cells and causes it to spill out bilirubin. Of course, both of those things happen. So that's why he's got both schistocytes and elevated bilirubin. In addition to that, when you have all these thrombocytes, these platelets clumping together, and when you have TTP, that's what happens. Your platelet count actually goes down. Now, your massive platelets in your bloodstream is the same, but platelets are sticking together. So, when your platelets are being counted, the machine counts it as fewer because it counts pieces of platelets, not platelet mass. So, the platelet count is rather low, 141. And so that's what's causing the petechiae and any other bleeding symptoms. So, based on that, we know, and also the history of inconsistent, loose stools suggests a possible infection, namely Shigella. And Shigella shiga toxin is a prominent cause of hemolytic uremic syndrome. So, these two tend to happen in concert. They can happen separately, but they also tend to happen together. And what's happening here? So, you have the diarrhea, and then you've got the drop in platelet count with petechiae and elevated bilirubin, and then the low platelet count. And that's TTP-HUS. What do we do in TTP-HUS? We do plasmapheresis. If this kid were to only have hemolytic uremic syndrome, we wouldn't do anything. But because he's got TTP, we need to do plasmapheresis. I shouldn't say we wouldn't do anything for HUS. We would watch him. But because he has TTP, we need to do plasmapheresis. We don't do platelet transfusion in TTP. That would worsen things because the problem is not with the platelets.
Question 4: A 9-year-old presents to the clinic with his parents for an annual physical. You immediately notice that he appears pale and looks somewhat fatigued. His mom says his diet hasn't changed, but that he has been a bit more calm and he hasn't been playing football, even though he normally does this time of year. She attributes it to him growing up. On physical exam, you notice mild bruising on his left arm. He says he doesn't know how it got there. Routine labs are drawn: hemoglobin is 7.3, hematocrit 22.1, white blood cells 3.3, platelets 101, sodium 141, potassium 4.1, chloride 103, bicarb 28, BUN 15, creatinine 1.1, glucose 106. Peripheral smear is significant for myeloblasts. Which of the following is the next step in the management of this patient? Is it A) packed red blood cell transfusion, B) bone marrow biopsy, C) chest x-ray, D) iron supplementation, or E) referral to social services?
Okay, we get some time here, and the answer here is B) a bone marrow biopsy. So, this kid has pancytopenia. He's got low red blood cells, low white blood cells, and low platelets. That is an absolute indication in a child to get a bone marrow biopsy. And also because he's got myeloblasts too, that's also a big hint. So, when a kid has pancytopenia, you should be getting a bone marrow biopsy, and especially if he's got myeloblasts in his blood, you want to be checking the bone marrow because most likely this kid has either ALL or AML leukemia. Iron supplementation would not be useful here just because he has he hasn't changed his diet and he's got low white cells and low platelets too. If it were just low hemoglobin, then you'd probably get an iron study and possibly then looking to iron supplementation. And referral to social services is inappropriate here because again, there's a medical reason for him to have bruises. So, if there weren't a medical reason for him to have bruises, and perhaps bruises from different ages of bruises and for perhaps different like distinct shapes of bruises, then referral to social services may be useful. I want to go back real quick to question three. Another reason, I don't know if I talked about it, another reason that you know this kid has hemolytic uremic syndrome is because his creatinine is high. So that's uremia. His BUN and creatinine are both high. So.
Question 5: A 64-year-old man presents to the clinic for his annual physical. He denies any changes since his last year. He's 5'11", 175 pounds, maintains an optimal lipid profile, and exercises daily. Although he does say he enjoys a steak every couple days, he takes an aspirin and a multivitamin. He is current on all vaccinations and health maintenance procedures. Routine labs reveal hemoglobin 10, hematocrit of 30.2, white blood cells of 8.7, platelets of 364, MCV of 73, sodium of 140, potassium of 3.6, chloride of 98, bicarb 25, BUN of 2.1, creatinine of 1.4. The peripheral smear shows hypochromic red blood cells. Which of the following is the best next step in the management of this patient? Is it A) CT abdomen, B) stool guaiac test, C) colonoscopy, D) iron supplementation, or E) hold aspirin?
Right, the answer here is B) the stool guaiac test. Now, you might have been thinking this guy's got iron deficiency anemia, which is very possible. He's got hypochromic red blood cells, he's got anemia, and those are all possible. I mean, that's certainly possible that he's iron deficient anemia. As a matter of fact, I would say he does have iron deficiency anemia. It's very clear based on these clinical findings, on these lab findings. However, and I mean, you could do an iron study, but that wasn't one of the options. So, the question is, we're going to assume then because he's got hypochromic red blood cells, because he's got anemia, because he's got a low MCV, we're going to assume that the cause is iron deficiency anemia because the other cause, the other major cause, would be anemia of chronic disease, which is a low to normal MCV, or some of the congenital causes, which is not the case here. So, we know it's iron deficiency. So, what's the next best step? And this is a 64-year-old guy who's normally healthy, and look, he enjoys a steak every couple days, so he's probably getting enough iron in his diet. What do we do for this guy? What are we concerned of with any person that's older who is possibly losing blood, who is iron deficiency anemia but is getting enough iron in their diet? We're concerned of bleeding somewhere. And usually, when they're bleeding, if they notice it, it's going to be out of a wound or out of their stomach, out of their mouth, hematemesis. But if they're not noticing it, then it's probably from the backside, and that can be either hematochezia or it can be melena. And since he hasn't noticed any blood in his stool, what you would want to ask is, probably melena. So, what we want to do for this patient is do a stool guaiac test to see if there is any occult blood in the stool. If there is occult blood in the stool, then we want to do a colonoscopy to check and see if there's any lesion that's bleeding because that could possibly be colon cancer. Iron supplementation, of course, wouldn't be necessary here because he gets enough iron in his diet. We wouldn't want to jump right to colonoscopy because a stool guaiac test takes 20 seconds, it's cheap, and if the stool guaiac test is negative, you've pretty much ruled out colonoscopy. And since he gets his health maintenance tests on a regular, up-to-date basis, he's probably gotten a colonoscopy rather recently. So, there's no use in subjecting him to another one if there's no blood in the stool. And CT abdomen would not be useful in this case, and holding aspirin may be good if he had an ulcer, but there's no evidence of that here. So, the answer is a stool guaiac test.
A 29-year-old woman was seen in your clinic last week complaining of a painless, swollen, and enlarged lymph node, left cervical lymph node. She had also been experiencing two weeks of night sweats and had unintentionally lost 12 pounds over a couple of months. Excisional biopsy of the large left cervical lymph node was performed, and pathology reported the presence of Reed-Sternberg cells. Further workup was undertaken and indicated she had similar nodes on the right cervical side but none elsewhere. Which of the following is the best treatment for this patient? Is it A) localized radiation, B) cyclophosphamide, adriamycin, daunorubicin, and vincristine, C) rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, D) adriamycin, bleomycin, dan Christine, and dacarbazine, or E) cyclophosphamide and vincristine, doxorubicin, and dexamethasone?
Give you plenty of time to pause it here. Those are a lot of meds to look at. Okay, answer here is D. So, this is a patient with Hodgkin's lymphoma. We know it's Hodgkin's lymphoma because it has Reed-Sternberg cells. Remember, for the USMLE Step 2 and 3, you don't need to know how to look at pathology, but you need to know some of those pathology keywords, and Reed-Sternberg cells are one of them. So, this is a patient who has bilateral lymph nodes that have Hodgkin's lymphoma. So, because she's got them bilaterally, not just in one spot, we know that she's got stage two. And because there's none anywhere else, meaning none below the diaphragm, it's stage two, not stage three. So, this is stage 2B Hodgkin's lymphoma. Now, in stage one and two Hodgkin's lymphoma, you can use localized radiation. However, when you go towards B symptoms, when you get into the B symptoms, especially stage 2B, it's better to use chemotherapy because when you have B symptoms, it means there's probably some level of tumor cells in the blood. So, it's safer with most of the time, even with stage two, you do chemotherapy as well. With stage one, usually they do radiation. With stage two, it's kind of up in the air, but definitely if you have the B symptoms, then you're going to be using chemotherapy. How do we know what chemotherapy regimen to use in Hodgkin's lymphoma? It's always the ABVD regimen as far as you're concerned on the USMLE. Yes, there are oncologists who will use other regimens, but for the USMLE, you use the standard ABVD chemotherapy regimen for Hodgkin's lymphoma. ABVD, and that stands for Adriamycin, Bleomycin, Vincristine, and Dacarbazine.
Question 7: Gives us a 52-year-old male presenting to the clinic complaining of a progressive fatigue over the last year. He hasn't had any night sweats or unintentional weight loss. He's otherwise well. He hasn't had any change in diet and he hasn't noticed any bleeding. He had a colonoscopy about six months ago which showed a solitary polyp that was removed intraoperatively. Routine labs are unremarkable except for his white blood cell count of 15.6. Serum leukocyte alkaline phosphatase is low. Bone marrow biopsy is performed, and cytology reveals a translocation between chromosomes 9 and 22. Which of the following is likely the best therapy for this patient? Is it A) rituximab, B) imatinib, C) cytarabine and prednisone, D) interferon alpha 2b, or E) hydroxyurea?
All right, I'll give you some time to think about this one. You can pause here. All right, so the answer is B) imatinib. So, what do we have here? We've got an older guy who is coming in complaining of this progressive fatigue. Now, normally we worry about progressive fatigue because we think of bleeding, and bleeding would make us think of colon cancer. That would be our first go-to as far as things that could be really bad. Now, the good news is six months ago, we had this colonoscopy, which you should always be doing once you turn 50, get a colonoscopy, and it didn't show anything other than one polyp that was removed intraoperatively. And I probably could have added here that it was a benign polyp, but either way, we had six months ago the polyp removed. That was it. So, we don't really know where the bleeding is coming from. However, the first thing you should think of anytime somebody's got chronic fatigue, a progressive fatigue, is possibly anemia. Even though we don't know if there's any bleeding going on, it's possible that the patient might not notice any bleeding until we want to check for that first. And checking for anemia is as simple as getting a CBC. So, we get a CBC and we find out he doesn't have anemia, but he does have an elevated white count. So, that's interesting because he's otherwise well, he doesn't have any signs of infection. And anytime you have a patient with an elevated white count who has no other signs of infection, if you know he had signs consistent with pneumonia, we would expect a white blood cell count. But if you have an unexplained white blood cell count, then we want to know about those white cells because it's possible that there could be something going on here that is along the lines of a dyscrasia, like a cancer. So, we get something called a leukocyte alkaline phosphatase. Now, I could have ended this question and have said, which of the following is the best next lab to get, and a leukocyte alkaline phosphatase would have been answered. This is important because what leukocyte alkaline phosphatase tells us, or LAP, tells us is whether or not these elevated white count is just a leukemoid reaction, which is a normal spontaneous elevation in white cells, or if this is something more insidious going on. And what I like to think of it is as a leukocyte alkaline phosphatase is really the truth. What this is, it's a normal component of white cells that help you fight infection. And so, if the leukocyte alkaline phosphatase is high, that's normal. We would expect that if you have a high white count, you have a high leukocyte alkaline phosphatase because that's part of white cells. However, if it's low, that doesn't make any sense because if you have extra white blood cells, you would expect to have high leukocyte alkaline phosphatase. And in fact, in this patient, it is actually low. So, there's something wrong with those white cells, something about them is not normal, and we want to know what that is. So, we go ahead and do a bone marrow biopsy, and with the bone marrow biopsy, we do cytology to look at those blood cells, and what we find out is there's a translocation of chromosome 9 and 22. This is pathognomonic for chronic myelogenous leukemia. This is the Philadelphia chromosome translocation between chromosome 9 and 22. And so, the question then simply is, what's the best therapy for a patient with CML? And the answer is imatinib. Imatinib is a BCR-ABL fusion protein inhibitor. And that sounds like a lot, but if you remember Philadelphia chromosome, it's a fusion, that's what translocation is, and BCR-ABL is a fusion protein. This is what causes the CML. And what this drug does, it's actually a relatively new drug compared to some of these other ones, is that this blocks that fusion protein and therefore treats the CML. So, imatinib is the answer. Now, these other ones: rituximab, this is a monoclonal antibody that targets CD20, which is a cell surface protein on B cells, and this is something that we would use in, for instance, non-Hodgkin's lymphoma where we use the R-CHOP regimen. Cytarabine and prednisone would be appropriate for acute leukemias. AML, ALL can also be used for some lymphomas. This is also cytarabine is also called Ara-C, and that's simply an antimetabolite pyrimidine antimetabolite. It looks like cytosine, fools your cells into thinking it's cytosine, but really it's sort of a Trojan horse, and that helps with the acute leukemias. Interferon alpha 2b is really not used in chemotherapy. It's used for hepatitis C, chronic hepatitis C. And then hydroxyurea is also used as part of chemotherapy, but this is used for essential thrombocythemia. It can also be used for polycythemia vera. This is a ribonucleotide reductase inhibitor, so it helps to block the production of the building blocks for DNA. So, imatinib is, you should just associate the word imatinib with CML because that is the best drug. And remember that the Philadelphia chromosome is pathognomonic for CML.
Five-year-old boy complains of pain in his groin, and his mother has brought him into the ED. The child refuses to leave his mother's lap, as most kids in pain do. On physical exam, you notice an erect, painful penis, and the child is reluctant to let you touch it and cries during the examination. During your examination, the mother said that he was diagnosed with "some blood disorder" as a baby. Which of the following is the best initial step in the management of this patient? Is it A) oxygen and morphine, B) oxygen and acetaminophen, C) morphine, D) ethebenecid, or E) hydroxyurea?
And the answer here is A) oxygen and morphine. So, what does this kid have? I didn't want to give the race because the race always tips off the answer. This would probably be a Black child because most sickle cell cases in the US are in African Americans. Now, going from that, priapism is not uncommon in uncontrolled sickle cell patients. Even controlled sickle cell patients, it's not uncommon. So, this is exactly what this is: it's priapism. It's an erection that doesn't go away. And babies get erections, children get erections, you don't have to have puberty to get an erection. So, because the sickle cells have clotted or sickled in the vasculature of the penis, it's causing priapism. And so that's what's causing the pain. Priapism eventually becomes painful. And so, we want to treat this stem cell crisis as we would treat any stem cell crisis. And so, the first way we do that is to give oxygen. Oxygenation reduces sickling. Sickling is promoted by a low oxygen level. So, by giving oxygen, we reduce the sickling. Another thing that helps is morphine or any kind of opioid pain reliever. The reason that helps is because when you're in pain, you don't breathe as much, and so reducing that pain does help with reducing the sickling. So, we need oxygen and morphine. Acetaminophen wouldn't be good in an emergency case like this, although that can be used at home to reduce pain if you're not in any kind of crisis. Morphine alone, of course, wouldn't be enough. We want to give that oxygen. To acetaminophen, no. And hydroxyurea is given to help people with sickle cell disease to help them make hemoglobin F, which is normal, and thus reduce the amount of sickle cells. Eventually, after this medical treatment, you would need to do a drainage of the corpora cavernosa, which are the two spongy-like areas of the penis, sort of corpora cavernosa of the penis that hold the blood during erection, and you would just aspirate that blood out, and that would relieve the erection.
Question 9: A 60-year-old woman is recovering in the hospital status post cholecystectomy, day one. On routine lab work, you note that her calcium is elevated at 11.3. She denies any problems other than incision site pain. The incision is clean and well-dressed. Bone scans are performed and show lytic lesions of the skull. Which of the following is a necessary criterion that links the unexplained hypercalcemia and the x-ray findings into one diagnosis? Is it A) renal insufficiency, B) the presence of fatigue, weight loss, or night sweats, C) monoclonal spike on serum protein electrophoresis, D) greater than 10% plasma cells in peripheral circulation, or E) less than 10% plasma cells in peripheral circulation?
And the answer here is C) monoclonal spike on serum protein electrophoresis. So, anytime you have a patient with an unexplained hypercalcemia, one of the things, if it's an older patient, one of the things that should be on the forefront of your mind is multiple myeloma or just well, yeah, multiple myeloma. Now, sometimes a patient can have an elevated calcium level because of certain drugs they're taking, like if they're taking antacids or if they're taking certain diuretics. However, a very, very bad cause of hypercalcemia and a cause that you need to investigate if there is unexplained hypercalcemia is indeed multiple myeloma. So, that's why in this question, the bone scans were performed, and indeed lytic lesions were found, and that is suggestive of multiple myeloma. So, what is going to tie this all together? So, there's a plasma cell disorder continuum that I talked about, and on this continuum are monoclonal gammopathy of undetermined significance. That's basically where you've got these B cells that are releasing these releasing IgG's or whatever antibody it is, they're releasing antibodies, a clone of antibodies, and we really don't know why. There's really no other symptoms. Smoldering myeloma is when the patient has that M spike, but also on bone marrow, they've got 10% or more plasma cells in the bone marrow biopsy. So, the big difference between MGUS and smoldering myeloma is that in MGUS, the bone marrow biopsy has less than 10% plasma cells in the bone marrow. Smoldering myeloma has more than 10%, but both of them have the M spike. Neither of them, however, have the CRAB signs. And CRAB signs are signs indicative of actual multiple myeloma. So, C would be hypercalcemia and any symptoms related to hypercalcemia. R would be renal insufficiency. A would be anemia. And B would be bone lysis or lytic lesions. So, all patients with plasma cell disorders, plasma cell dyscrasias, have that M spike, even in the least severe, monoclonal gammopathy of undetermined significance, they have the M spike, even though they don't have the CRAB symptoms, and their bone marrow is normal. With smoldering myeloma, they have the greater than 10% plasma cells, similar to multiple myeloma, and they have the M spike, but they don't have the symptoms. With multiple myeloma, you've got all of it. You've got an M spike, you've got CRAB signs, and you've got greater than 10% cells on bone marrow. Look back on this. I said peripheral circulation, not bone marrow. Keep an eye on that. So, to these CRAB signs that distinguish multiple myeloma from MGUS or smoldering myeloma, but you have to have the M spike in order to have this disease at all, in order to have any of these plasma cell disorders. So, we already know that she's got the CRAB signs. So, the question now becomes, what's needed for diagnosis? Is it the M spike, or is it the plasma cells on bone marrow? You don't necessarily need to have greater than 10% plasma cells on bone marrow, but you do have to have that M spike. M spike is always needed to tie together CRAB signs and the plasma cell, the elevated plasma cells in the marrow, to tie it together to multiple myeloma. Hopefully, that was too confusing. Sorry if I made it confusing. Okay, so just reviewing how we treat this: with MGUS, it's just watching and waiting. One to two percent per year will go to multiple myeloma, but there's really no treatment we can do. With smoldering myeloma, there's a slightly greater progression to multiple myeloma, it's two percent per year. Go on multiple myeloma. You can consider referring these patients to a study group for investigative treatment. And for multiple myeloma, we use chemotherapy and autologous bone marrow transplant. And how do we what kind of chemo do we use? Well, of the patients who have multiple myeloma, if they're healthy, namely if they're under 70, don't have any comorbidities, we use CVAD. And CVAD is cyclophosphamide, then vincristine, adriamycin, and dexamethasone. After that point, we transplant them with an autologous bone marrow transplant. And after that, we have them on melphalan or thalidomide. Patients who are fragile, who wouldn't survive the bone marrow transplant or the CVAD chemotherapy, we just treat them with melphalan and thalidomide, and that will prolong their lifespan with the myeloma.
Question 10: A mom and dad bring their six-year-old son into the clinic because teachers have told them he appears tired and listless throughout the school day. They claim to be a very healthy vegan family. On physical exam, you note pallor, pale conjunctiva, and an uninterested child. Otherwise, unremarkable exam. Routine labs reveal hemoglobin of 8.3, hematocrit of 25.1, white blood cells of 7.2, platelets 341, iron studies are normal, MCV is 118. Peripheral smear notes polys segmented neutrophils. Which of the following labs would definitely confirm your diagnosis? Is it A) methylmalonic acid, B) homocysteine, C) thiamine levels, D) ionized calcium, or E) red cell distribution width?
So, this is kind of a flashback to Step 1. The answer is A) methylmalonic acid. So, it is vitamin B12 that is an enzyme for two different things. Homocysteine and folic acid combined to make methionine. And methylmalonic acid goes to methylmalonyl-CoA, which then uses vitamin B12 to convert to succinyl-CoA. Both succinyl-CoA and methionine both are needed for red blood cell growth, also white blood cells too are needed for maturation. So, if you don't have the vitamin B12, you're going to get backup products. So, you're going to have backup products of everything before this B12 because you don't have the B12 to convert it to succinyl-CoA or methionine, respectively. So, you're going to have backup of the methylmalonyl-CoA and homocysteine. Backup of methylmalonic acid. In laboratories, we can measure homocysteine. We often measure homocysteine. We also can measure methylmalonyl-CoA, or sorry, methylmalonic acid. Now, when you have a folate deficiency, you're going to have elevations of only homocysteine. When you have a vitamin B12 deficiency, you're going to have an elevation of both methylmalonic acid and homocysteine because in a folate deficiency, you don't have the folic acid to combine with the homocysteine. So, the homocysteine gets backed up because it doesn't have anything to react to. But the methylmalonyl-CoA is reacting into succinyl-CoA because of vitamin B12 is present. If you've got a B12 deficiency though, because both pathways use the B12, you're going to get a backup of both methylmalonic acid and homocysteine. So, if you were to order a homocysteine, yes, it would be elevated, and that could tell you you have a folate deficiency or a B12 deficiency, but you wouldn't be able to differentiate between the two. So, the methylmalonic acid level, the MMA level, is going to tell you specifically if the patient has a B12 deficiency. If the methylmalonic acid level is high, the patient has a B12 deficiency. You can bet that the patient, this same patient, would have an elevated homocysteine level too. But methylmalonic acid is indicative of a B12 deficiency. Any questions? Definitely right under the comments.
Okay, so this is continued from the last question. After an outpatient therapy, which of the following would you tell the parents? Is it A) your vegan diet is unhealthy and not appropriate for your son, B) consider adding tofu to his diet, C) your son needs to consume more foods like spinach and tomatoes, D) you should consider giving your son a multivitamin, particularly one that contains vitamin B12, or E) you should consider giving your son a multivitamin, particularly one that contains folate?
Based on what I explained from the last one, you'll probably figure out what this is. So, the answer here is D. So, since the vitamin B12 is the problem, we need to make sure he's getting B12. And that's possible for vegans because you can take a vitamin. I know over-the-counter pill vitamin that's got B12 in it, and that's really the major thing that's problematic in the diets of vegans. Also, calcium can be a problem, but vitamin B12 is really the only thing that's seriously problematic. Confronting parents is generally not advisable in most situations, and definitely beating them up about their vegan diet is not going to be something that they're going to be open towards. Tofu doesn't have a good amount of B12. B12 primarily comes from animal products. Your son needs to consume more foods like spinach and tomatoes. Spinach and tomatoes are sources of folate, and that's not a problem for vegans. As a matter of fact, they get plenty of folate. Folate is in vegetables, greens. And then you should consider giving your son a multivitamin, particularly one that contains folate. Again, not the problem here. Who would have a folate deficiency? Probably somebody who is taking certain medications or somebody who doesn't eat vegetables at all.
A 58-year-old black woman presents to your clinic complaining of pain in her proximal interphalangeal joints, metacarpophalangeal joints, as well as in both knees. She says that this has been going on for a couple of years but it's been getting worse gradually. It is worse when she wakes up. She has otherwise been reasonably healthy. She is not a smoker, and she has had a therapeutic hysterectomy 10 years ago for polycystic ovarian syndrome. She has not yet had her first colonoscopy. On labs, hemoglobin is 8.7, hematocrit 26.1, MCV is 87, ferritin is 165, which is high, serum iron is 90, which is normal, TIBC is 200, which is low, and saturation is 10%. Which of the following is the most likely reason for this woman's anemia? Is it A) iron deficiency, B) vitamin deficiency, C) chronic disease, D) occult blood loss, or E) thalassemia major?
And the answer here is C) chronic disease. So, even though I didn't tell you this, she appears to have rheumatoid arthritis based on the symmetry and the distribution of her joint pain, the fact that it's going on for a while, and she's reasonably healthy, and that it's worse when she wakes up. So, that is very suspicious for rheumatoid arthritis, although we don't know if she's got that. She's not diagnosed with that. Iron deficiency is unlikely given that her ferritin is normal, her serum iron is a little low, but that doesn't necessarily indicate iron deficiency. Her TIBC is low, that also goes against iron deficiency. So, what this is, is anemia of chronic disease. She's got a high ferritin and a low TIBC, which means that the cells are retaining ferritin, they're not incorporating it into hemoglobin. So, how do we remember all these? Okay, we have serum ferritin, which is the iron in your serum. There's not a lot of it, but you do have some iron in your serum, just like you have some sodium and potassium and sulfate in your serum. So, that's serum ferritin. Sorry, but I was just speaking of serum iron. Serum ferritin is where you hold, is the protein that holds onto iron because iron too is not soluble. The serum iron is the little amount of iron that is dissolved ionically in your serum. So, this is like sodium and potassium and chloride. You don't have a lot of iron because it's again, not very soluble. Serum ferritin is iron bound with protein and carried around in your serum. TIBC is your binding capacity. And then this is how the cells look. So, in iron deficiency, your serum ferritin is low. Why is it low? Because you don't have enough iron. Serum iron is of course also low because you don't have enough iron. So, both of these together, it's sort of your measurement of the patient's iron, and if they're both low, that points towards iron deficiency. TIBC in iron deficiency is high. What does TIBC mean? A good way to think of it is the TIBC goes up, this binding capacity goes up, the more your red blood cells are wanting to gain iron. If you have iron deficiency anemia, there's no problem with the red blood cells other than that you don't have enough iron. So, these cells are trying their hardest to get iron, but they can't because you don't have enough in your body. With thalassemia, you actually have a problem of the globin itself, so it has nothing to do with the iron. So, your serum ferritin, serum iron, and your TIBC are all totally normal. And you would notice thalassemia based on target cells and pyknocytes. It would also have a low MCV. Anemia of chronic disease is kind of the opposite of iron deficiency anemia. So, in anemia of chronic disease, you actually have enough iron, you may even have more than enough iron, but the problem is you're having a hard time incorporating that iron into your red blood cells. So, the serum ferritin is going to be high, serum iron is low, but the TIBC is going to be low because the cells are not cooperating with the addition of iron. It's similar in nature, but not in etiology, to sideroblastic anemia, where you have high storages, plenty of iron, either bound to ferritin or ionic, but your binding capacity is not enough to make up for it. So, with anemia of chronic disease, you're going to have a high serum ferritin, a normal serum iron, and a low TIBC.
Question 13: A 52-year-old man presents for annual physical and lab work. He has no complaints. Last year, his physical and lab work was unremarkable. He takes for Suva, statin, hydrochlorothiazide, aspirin, and a multivitamin. CMP is normal. Lipid studies reflect a well-controlled LDL and triglyceride level. CBC shows a hemoglobin of 9.1, hematocrit of 27.4, white blood cell of 3.6, and platelets of 324. Smear and differential shows 96% small, normal-appearing lymphocytes. Which of the following is the most likely diagnosis in this patient? Is it A) acute lymphocytic leukemia, B) acute myelogenous leukemia, C) chronic lymphocytic leukemia, D) chronic myelogenous leukemia, or E) subclinical multiple myeloma?
The answer here is C) chronic lymphocytic leukemia. So, you kind of have an idea that this is a lymphocyte problem because when you look at the differential, it's 96% lymphocytes, and that's not usually how it goes. Lymphocytes are a lot lower than that in normal blood, but these are small and normal-appearing lymphocytes. So, they appear to be lymphocytes that are normal and doing what they're supposed to do. That would not be the case in acute lymphocytic leukemia. In acute lymphocytic leukemia, if you saw anything in the differential in the peripheral bloodstream, they would be blasts, they would be abnormal lymphocytes. With chronic leukemia, you have a leukemia, yes, but you've got rather normal cells coming out. And so, if you see anything in the peripheral blood, you're going to see normal-appearing, rather normal-appearing cells. So, because it's lymphocytes, then we know it's chronic lymphocytic leukemia. There are normal-appearing lymphocytes, and the white blood cell count of 3.6, of course, pushes us towards chronic lymphocytic leukemia as well. If you did a leukocyte alkaline phosphatase, you would indeed have a low leukocyte alkaline phosphatase, indicating that these are not lymphocytes that are responding as a leukemoid reaction. Subclinical multiple myeloma would be like MGUS or smoldering myeloma, and that's not the case here. In that case, we'd have an elevated calcium, and that's not shown here.
Three years later, he presents to your clinic, still relatively healthy, but complaining of severe swollen cervical and axillary lymph nodes. He has also lost ten pounds since his last visit six months ago, which he says was unintentional. On physical exam, axillary and cervical nodes are palpable and firm, non-tender, bilaterally. Which of the following chemotherapeutics is the likely best medical management and treatment of this patient? Is it A) fludarabine, B) imatinib, C) adriamycin, D) vincristine, or E) bleomycin?
And the answer here is A) fludarabine. So, fludarabine is the best therapy in the treatment of chronic lymphocytic leukemia as far as you're concerned for the USMLE. Now, again, you may work under heme oncologists, we use different drugs, but fludarabine is the traditionally used drug for the treatment of CLL as of 2013. So, that's the one you should be, that's the one you should associate with CLL. And we only treat CLL when it becomes symptomatic. So, notice back three years ago when he first came, he didn't have any other symptoms, so we kept a watchful eye on it. Once he starts developing symptoms, it is then indicated, and those symptoms can be like these symptoms like he's got down here, or it can be the swollen lymph nodes, then we begin treating him with fludarabine.
Question 15: A 58-year-old woman is admitted for left-sided substernal chest pain. EKG reveals ST elevation in leads II, III, and aVF. Cardiac enzymes are significantly elevated. The pain started only 45 minutes ago, therefore she's administered TPA. She is admitted to the ICU for post-MI care and is recovering comfortably. Heparin has been initiated for protocol. On day three of admission, her CBC comes back with a hemoglobin of 12.1, hematocrit of 35.8, white blood cell of 10.8, and platelets of 32. Which of the following is the most likely cause of the thrombocytopenia? Is it A) thrombotic thrombocytopenic purpura, B) myocardial infarction, C) tissue plasminogen activator (TPA), D) concomitant leukemia, or E) heparin?
And I will say you might put it here that the smear was unremarkable. Peripheral smear unremarkable. Answer here is E) heparin. So, heparin has a tendency, but doesn't frequently cause thrombocytopenia. So, it's heparin-induced thrombocytopenia. And there are other drugs that can cause thrombocytopenia as well. Heparin is the most well-known, perhaps because it's a drug that works with things like platelets work with. I don't know, but heparin-induced thrombocytopenia is something to keep in the back of your mind in any patient that you're starting on heparin. So, the platelets are 32, and that is definitely low. Anytime it gets below 150 or so, you should definitely be thinking of some kind of thrombocytopenia from something. TTP is very unlikely here, primarily because heparin was initiated, and now all of a sudden her platelets are 32. But thrombotic thrombocytopenia, thrombotic thrombocytopenic purpura, TTP would also be accompanied by other signs, namely schistocytes, bilirubin, and so forth. Myocardial infarction does not itself cause thrombocytopenia. TPA also does not itself cause thrombocytopenia. Concomitant leukemia, probably not the case because she's got a normal hemoglobin. And the most obvious, most logical explanation would be heparin-induced thrombocytopenia.
Same patient. Which of the following is the best next step in the management of this patient? Is it A) platelet transfusion, B) discontinue heparin, C) start prednisone, D) exchange transfusion, or E) watch and wait?
And the answer is B) discontinue heparin. So, don't quote me here, but from what I know, patients who have had heparin in heparin-induced thrombocytopenia can be given the low molecular weight heparins. But it is highly, highly, highly, highly discouraged. I've never had a patient with heparin-induced thrombocytopenia personally, so I've never run into that. But from what I know, I want to know the low molecular weight heparin they were created to reduce the incidence of heparin-induced thrombocytopenia. But I have heard that if I have heard both. I have heard some doctors say that if a patient has HIT, you shouldn't give them low molecular weight heparins. But the prevailing knowledge that I've heard is that low molecular weight heparins can be given if the patient has had heparin-induced thrombocytopenia. I'll get back to you and I'll type that in under the description on this. That's a good question that just came to mind.
Question 17: A 24-year-old woman presents to the ED complaining of fever and shaking chills. BP 108/71, heart rate 105, respirations 18, temperature 102.2. Well, waiting in her ED bed unattended for probably a long time if it's like most of the EDs I know, her blood pressure drops to 81/49. Aggressive bolus fluids are started, and her blood pressure stabilizes. The RN notes, however, blood oozing from puncture sites as well as around the Foley catheter. Routine labs return: hemoglobin of 13.2, hematocrit of 39.2, white blood cells of 16.2, platelets...
Of 52 peripheral smear so fragrant fragmented red blood cells. PT and PTT are both elevated. Plasma fibrinogen is 59. Which of the following is the best next step in the management of this patient? A transfuse packed red blood cells. B transfuse platelets. C IV ampicillin and IV gentamicin. D IV vancomycin and aztreonam. E platelet transfusion, parenteral vitamin K, and IV ampicillin.
All right, answer here is C, IV ampicillin and IV gentamicin. So now that we've got fluids started because this patient has DIC, disseminated intravascular coagulation, we need to get the underlying cause fixed. So one of the most common underlying causes, I'll say the two most underlying causes are sepsis and trauma. So because she's got a fever, that makes us think that it's likely sepsis. So we want to give empiric antibiotics. And whenever you think of empiric antibiotics, you should take IV ampicillin and anti-air, sorry, IV ampicillin and IV gentamicin. IV vancomycin and aztreonam doesn't quite have the broad coverage as ample gent.
So this is DIC, and DIC has all the features of TTP and all the features of ITP. However, in addition, DIC has an elevated PT and elevated PTT because you're getting faster consumption. So that's what sets DIC apart. Also, what sets DIC apart is that it's commonly got a noticeable trigger, so shock, trauma, pregnancy, abruption of the placenta, so forth. So IV ampicillin and ID gentamicin. Now, if this woman were pregnant and she didn't have the temperature, then I would go ahead and say that the best next step would be to stabilize her as best you can and deliver her either by cesarean, probably certainly by cesarean section. Okay, all that plasma fibrinogen tells you is that you are forming a lot of clots because fibrinogen is a factor too. You've got a low fibrinogen.
Question 18. A 65-year-old woman presents to the clinic complaining of intermittent changes of vision. She says that various points throughout the day, she will have prolonged episodes of darkening in her vision visual field. Physical exam: few pupils are equally round and reactive to light and accommodation. Sclera is normal. Normal on fundoscopy. The retina appears healthy. On Snell and eye test, vision is 20/30 in both her left and right eye, which is down from 20/20 last year. There is some gingival bleeding. Dentition is not compromised. Hearing is intact bilaterally. Hepato-megaly is noted to percussion. Patient reports no history of excessive drinking. She's on no medications. Which of the following is the next best step in the management of this patient? A bone marrow biopsy. B tissue plasminogen activator. C serum protein electrophoresis. D plasmapheresis. E referral to ophthalmology.
Think of what you suspect, what disease, what rare disease you expect suspect in this patient. Okay, the answer here is C, serum protein electrophoresis. So we're putting all these together. If she's got decreases in her vision and her visual acuity, which can be basically equated to blurry, she's got bleeding, and she's got enlargement of her visceral organs, those are all associated with Waldenstrom's macroglobulinemia. And with Waldenstrom's macroglobulinemia, it's very similar to multiple myeloma in as much as you have a clonal plasma cell proliferating and creating antibodies. Now, serum protein electrophoresis measures proteins, of which antibodies are sort of protein. Measures proteins in the blood. So it measures them from big to small. And then if it goes up on this amount here on your Y-axis, it means there's more of it. And then as you go down the, as you go down the axis, the X-axis, they're bigger and bigger and bigger. So you've got your albumin, your alpha-1 antitrypsin, alpha-1 binding globulin, transport, and down here alpha-2, you've got alpha-2 globulin, alpha-2 macroglobulin, down to your beta, you've got transferrin, beta-lipoprotein, and then your gamma. Remember gamma globulin, so you've got your antibodies. So when you have a patient who's got multiple myeloma or monoclonal gammopathy of undetermined significance, you have a spike in the gamma region. That's why it's called monoclonal gammopathy because you have a lot of gamma things, which are antibodies. So you have an M spike in the gamma region, and that's your M spike, your M-guts, or multiple myeloma. If you have the other symptoms with Waldenstrom's macroglobulinemia, rather than making IgG, which is what you make in multiple myeloma, you're making IgM. And IgM is slightly bigger. And so you're going to have your quote-unquote M spike, similar to how you have it in multiple myeloma. You're going to have it a little bit closer to your Y-axis. So that's meaning it's a bigger protein. And so you're going to have it between the beta and the gamma region. And so because you have that M spike closer, I mean, we know it's bigger, we know it's IgM, and so we know it's Waldenstrom's macroglobulinemia, in addition to, of course, all the other symptoms that the patient has that differentiate it from, differentiate it from multiple myeloma. But this confirms that it's Waldenstrom's macroglobulinemia. And the thing about IgM is that IgM can form these big polymers, and these polymers can sludge up the blood. And that's what's actually causing the vision. Also causes the organomegaly and so forth. So serum protein electrophoresis is the best way to diagnose Waldenstrom's macroglobulinemia, which this patient has many symptoms consistent with.
Question 19. A 43-year-old man presents with a painless swollen mass on his left jaw. He is otherwise healthy. He does not smoke or drink and he works as an accountant. Physical exam reveals a non-tender and large left sub-submandibular lymph node. Excisional biopsy is performed and reveals immunoblastic and centroblastic B-cells. No Reed-Sternberg cells are present. Workup is continued with a whole-body PET which suspiciously shows lesions on what, what I'm, what I wanted to write there, which shows suspicious lesions on a right submandibular node as well as on a left mesenteric node. A diagnosis of stage 3A diffuse large cell lymphoma is made. Which of the following regimens is most appropriate for this patient? A rituximab, bleomycin, doxorubicin, vincristine, and prednisone. B rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. C Adriamycin, bleomycin, and vincristine, and dacarbazine. D bleomycin, vinblastine, and prednisone. E fludarabine.
Okay, give you some time to look through all these drugs and the answer closet if you want. The answer is B, rituximab, cyclophosphamide, hydroxy-doxorubicin, which is the same as saying doxorubicin, it's just the longer name, then vincristine, and prednisone. So this is a non-Hodgkin's lymphoma. I put a ton of jargon in this, a ton of pathology jargon, a ton of anatomical jargon, a ton of information you didn't need to know. Basically, the only information you need to know is that he's got a non-tender and large lymph node that was biopsied and showed that it had, that it had lymphoma and it wasn't Hodgkin's lymphoma because no Reed-Sternberg cells were present, and that he has stage 3 lymphoma, non-Hodgkin's lymphoma. So I told you right at the end, a diagnosis of stage 3A diffuse large cell, diffuse large cell lymphoma is made. So basically, I told you this patient has stage 3A non-Hodgkin's lymphoma. What do you give them? And you should know that non-Hodgkin's lymphoma, all the time, you give them R-CHOP. R-CHOP is rituximab, cyclophosphamide, hydroxy-doxorubicin, vincristine, which is known by its trade name of Oncovin, and prednisone. That's always what we use in NHL. As far as your current concern for the USMLE, notice down here, ABVD makes an appearance. Adriamycin, bleomycin, vincristine, and dacarbazine. That's what we use in Hodgkin's lymphoma. Fludarabine down here makes an appearance. That's what we use for CLL. With symptoms, the other ones I just made up. So remember R-CHOP for NHL.
Okay, so here's your chemo cheat sheet. So for ALL, we use doxorubicin and vincristine, prednisone, and sometimes methotrexate intrathecally. So doxorubicin, vincristine, and prednisone are all part of the intravenous chemotherapy. And if there's CNS symptoms, which there usually is, methotrexate is administered. For any AML, we use cytarabine. We also use doxorubicin. So if the patient has the M3 variant of AML, which can present with DIC, then we also add on all-trans-retinoic acid, which helps the M3 cancerous cells progress. For CLL, we use fludarabine or chlorambucil. Older patients tend to do a little better with chlorambucil, but fludarabine is the drug of choice for the USMLE. For CML, we use imatinib. Remember, imatinib is the BCR-ABL fusion protein inhibitor. And so that is going to take care of that disgusting byproduct, progeny of the Philadelphia chromosome 8;22 translocation. For multiple myeloma, we use VAD, it's like vincristine, Adriamycin, and dexamethasone, followed by an autologous bone marrow transplant. Those are in the young, healthy patients who can tolerate bone marrow transplant. When you see that before the bone marrow transplant, if they're old, they're weak, they're sick, they've got some kind of pre-existing condition that excludes them from a bone marrow transplant, particularly if they're over the age of 70, then we're going to treat them palliatively with melphalan or thalidomide. Hodgkin's, we use ABVD. That's Adriamycin, bleomycin, vincristine, and dacarbazine. And for non-Hodgkin's lymphoma, we give them R-CHOP, rituximab, cyclophosphamide, hydroxy-doxorubicin, vincristine, otherwise known as Oncovin, and prednisone. And in some, sometimes you may see the USMLE just put CHOP. It might just give you cyclophosphamide, hydroxy-doxorubicin, vincristine, prednisone. That's okay too. But make sure if rituximab along with CHOP is on there, you choose that one instead. But if rituximab is not on the CHOP and you don't have any other choices, then that's okay too.
Question 20. A 19-year-old woman has been admitted to the hospital for chest pain and shortness of breath. On workup, she has a three-centimeter thrombosis in her left common femoral vein. CT scan confirms the presence of pulmonary embolism, and treatment is initiated. Heparin is initiated. On history, she takes oral contraceptives and yesterday morning she had returned on a 10-hour flight from a vacation in Japan. Which of the following congenital factors would confer upon her the highest risk of deep venous thrombosis? A Factor V Leiden. B Protein S deficiency. C Prothrombin G20210A mutation. D Lupus anticoagulant. E Protein C deficiency.
You have to kind of think back to that chart I showed you. This is important. It's not necessarily the most common one, but it is the most severe one if you have it. One answer is B, protein S deficiency. So you should know that protein S deficiency, although it is the most rare, or approximately the most rare hypercoagulability disorder, inherited hypercoagulability disorder, it does result in a 32-fold relative risk of venous thromboembolism. So protein S embolism, or so sorry, protein S deficiency, protein C deficiency, antithrombin 3 deficiency, they're the bad ones. Factor V Leiden, the prothrombin mutation, they're not as big a deal. Lupus anticoagulant is problematic too, but again, to a lesser degree. Now, all of these, without maybe the exception of protein C, protein S, and antithrombin 3, mostly Factor V Leiden, the prothrombin mutation, and the lupus anticoagulant, they're really not a problem in and of themselves. The problem is when you start combining them with other risk factors. So you're taking estrogen replacement, you're taking a birth control, you're pregnant, you're sitting on an airplane or on a train for a long period of time, you just got surgery, you're bedridden, you had trauma, you've got renal disease, you're 90. All of those factors increase your risk of coagulation. So this woman had a prop, has protein S deficiency. Perhaps she knows that. Hopefully she didn't, otherwise she would have been taking steps. Hopefully she wasn't on OCPs that she knew she was protein S deficient. But anytime you have any of these, these diseases, you want to go out of your way to stay away from these symptoms, these factors, I should say. So they just have a multiplicative effect upon.
Okay, back to chemo drugs. So chemo drugs and their major adverse effects. I just want to point those out here so you can pause it here and do the association. They're not lined up with the correct adverse effect, but try and see if you can match the number to the letter. I'll pause it here and then we'll go on. Okay, so vincristine and vinblastine cause peripheral neuropathy. Cyclophosphamide causes hemorrhagic cystitis and can cause bladder cancer. So cisplatin and carboplatin, they cause hearing impairment and nephrotoxicity. Doxorubicin and daunorubicin, they cause cardiotoxicity. Bleomycin causes pulmonary fibrosis. And dexamethasone with any steroid causes fluid retention. And then methotrexate, 5-fluorouracil, 6-mercaptopurine, because they are antimetabolites, they cause myelosuppression.
Okay, I can't take credit for this. This is Chemo Man, found this on online at medsource.blogspot.com. But you can like put, you can put this into like some kind of something that you can remember this with. So it's useful, I think. Okay, so see, there's the V's for vincristine and then blastine. And there's the B's for bleomycin and the D for doxorubicin. That's like the heart there. Then the C's are the C's of cisplatin and carboplatin. And then there it is again as the kidneys. Also remember that you can give mesna to mitigate some of the effects of cyclophosphamide. Oh, and then I put this together for you. I'm not going to talk about all of this. I just want to go over a little bit. This is the, just a review of platelet type, the platelet cycle, and then the coagulation stabilization of the platelet clot. So we get our immature clot, our then aggregated clot, and then the mature coagulated clot. So what I really want to point out since I haven't really talked about these are the drugs that are used in these drugs are used primarily in anticoagulating people. And so there's the GP IIb/IIIa inhibitors, which remember is a, sorry, that's a typo, that should be IIb/IIIa inhibitor. IIb/IIIa. So abciximab, eptifibatide. They both block GP IIb/IIIa. And then clopidogrel, prasugrel, and ticagrelor. They decrease the action of ADP. Both of these will reduce the recruitment and the aggregation of platelets to one another. So they're considered antiplatelet drugs. The other ones that that block clots from forming in the coagulation cascade are considered anticoagulants. And so that would be heparin and warfarin. Remember, heparin inhibits antithrombin 3. Warfarin inhibits the vitamin K factors. And we also have the low molecular weight heparins too. Anything that blocks the the platelet cycle, so platelets from adhering to one another, is going to increase the bleeding time. Remember the ristocetin test for discerning von Willebrand's, Bernard-Soulier, Glanzmann's thrombasthenia, and of course any platelet disease is superficial bleeding. With factor disease, the way we discern these are by measuring the factor levels, but we're going to have a hint based on the fact that we will have a prolonged PT and or prolonged PTT, normal bleeding time. And then this is deep bleeding like hemarthrosis, etc. And that is all I've got for you.