Transcription
Hematology. This session is for both clinical hematologists and those working in the laboratory. I would like, first, the laboratory staff, either biomedical scientists, medical lab technologists, or medical lab scientists, to comment on the blood film first, because they are the people, they are the gem people who report the blood film first. And if they think that this is a serious one or has some findings, they refer it to the clinical hematologist. Then the clinical hematologist will report the blood film as required by the exam, and then few questions, as we see in the exams. All right.
So, the first case. Right. So, this is a 35-year-old female who presented to the emergency department with progressive fatigue and tiredness, sent by GP to the emergency department. The full blood count shows hemoglobin of 110, white cell count of 21, and platelet count of 140. So, the biomedical scientist has made the blood film and he is going to report it now first. So, anyone who wants to report it first on the lab side, please. Actually, the screen is not visible to me. I don't know if I have some problem from my side. Is the screen visible to everyone? Or screen is visible but pixels are very much distorted. Like, sorry, visible, not clear. But not clear. Yes, visible now. This is at power 10. I will move to power 50. Yes, it's better. It's better now. It's better now. Anyone from the lab side who wants to comment on it first and then refer to clinical hematologist?
Um, so there are spherocytes along with that. Um, few atypical lymphocytes are seen. NRBC is there, and the lymphocytes got abundant cytoplasm. Can you please magnify it further? Okay, I will go through the blood film first at power 10 to give you an overview of the film. This was power 10. Now I will move to power 50, the oil lens. There are some stochocytes there, okay. So, let's see some other fields. Blast, stochocytes, thia, blasts. The atypical large L cells are seen. Are there nucleoplas? Like, not clear in the. Let's see some other block. We have. We'll add some more oil to that to get clear it. Like a monocytoid blast. There are some granules present here. The red dots. Hello. Hello. Yes, you can see. Yeah, can be seen in this. There is an Auer rod. Yes. M1. Uh, there is no M1, M2, M7 in the UK anymore. We do not use the old classification. Now we use the WHO 2022 classification in the UK.
This is another block. Right. As a, um, lab scientist, you have noticed blast and you are thinking this is acute leukemia, and you have referred the blood film to a clinical hematologist. So, I now, now I want a clinical hematologist to report this blood film for the purpose of FC path exam. Any clinical hematologist, sir? Can I? Yes, go ahead.
Okay. Um, so this is a peripheral smear showing normocytic, normochromic red blood cells and, um, uh, so the slide is not blurry and, um, uh, there are medium to large-sized atypical cells having a folded nuclei and two to three nucleoli, and slightly granular cytoplasm. Few of the cells show the presence of Auer rods. MH. And the, um, and also platelets are reduced on this smear. And, um, the fields which examined so far, I found only one or two platelets. And the features are suggestive of acute myeloid leukemia. Acute myeloid leukemia. Yes, sir. The features are suggestive. Most likely mono. Never say diagnosis on a blood film. You should say, the blood film findings are most likely consistent with acute myeloid leukemia, but we need to confirm that with flow cytometry and cytogenetics and genotyping. As there may be a lympho population hidden in the blood film which you, which we haven't seen. Maybe this is a T-cell or B-cell lymphoblastic leukemia. So, without flow, you cannot comment on the exact diagnosis. You always say, most likely this diagnosis, but we need to confirm that. And first, comment on the abnormal findings. You have seen multiple bloods. This blood film contains, uh, blasts, multiple blasts, which are large in size, having indentation in the form of fish mouth. Fish mouth indentation in the blasts are a feature of NPM1 mutation. Sir, NPM1 mutation. Yes, but it is not necessary that. Yes, go ahead. NPM1 has a cup-like, I have, but fish mouth, it doesn't look like a cup. This one, and we will see few others as well. So, I was saying that it is not necessary that in all NPM1, you will see the cup-like or fish mouth features, because NPM1 has multiple variants. So, there may be cells which are blast which have, which may have NPM1 variant mutation, but there is no cup shape or mouth shape or fish mouth shape appearance in them. But generally, it is considered that if it is a cup-shaped or mouth fish mouth shaped, then you think that this is, uh, NPM1. But that need to be confirmed on cytogenetic and karyotyping first. Like this one. This one is more prominent. But there are, like I mentioned, there are multiple NPM1 variants which will be having different features, not exactly cup shape. Right.
So, you have commented on the blood film and you have suggested flow cytometry and on the blood and bone marrow biopsy for this patient to confirm your diagnosis, right? So, the next question would be, what is the minimum genetic test requirement for any acute leukemia according to WHO 2022? Like, you have done bone marrow biopsy for a patient, what genetic test you would like to see in the patient in any leukemia patient? BCR-ABL1. Uh-huh. NPM1, FLT3. Okay. So, translocation 8;22, translocation 15;17. Mhm. AML. Yes. So, the BSH and the WHO 2022 guideline have mentioned that you need to send four things in any leukemia patient to reach a diagnosis and the prognostic classification. Karyotype, you have to see translocations on karyotyping. Molecular mutations by sending blood and bone marrow aspirate for NPM1, FLT3 ITD and TKD. Then you need FISH for 15;17, 8;21, and KMT2A. These are the, this was the third thing. The fourth one is NGS panel for a whole lot of mutations, ASXL1, BCOR, SRSF2, etcetera. There are quite a lot, 16, 17 mentioned in the guideline. So, whenever you do a bone marrow biopsy for a new leukemia patient, you send these things: FISH for 15;17, 8;21, KMT2A, karyotyping to know translocations, molecular for NPM1, FLT3 ITD and TKD, and NGS panel for the patient. And why do you send them? For treatment purpose, prognostication purposes, and it will tell you whether the patient has high-risk features or not, transplant is suitable for him in the future or not. Because if someone has TP53 mutation, he's a very bad risk person, even transplant will not cure him. All right.
So, this patient has, um, NPM1 mutation along with FLT3 ITD. What is the prognostic category of this patient? Standard. Standard? Are you sure, sir? It's a mutation and NPM1 and FLT3 is also mutated. Is this a standard category according to WHO 2022 guideline? This is intermediate category if you have NPM1 with FLT3. Yeah. Yes, sir. NPM1 is a good. FLT3 is bad. When both are, this is intermediate. If NPM1 alone is mutated and there is no FLT3, it is a standard category. And if it is NPM1 plus FLT3 mutation, then it is an intermediate risk category. For intermediate and worse category, our aim is to give a patient an intensive chemotherapy if he is fit for that, to bring him into remission and send him for allogeneic transplant. While standard risk category patients, they usually do better without transplant. Our aim is to give them intensive therapy and then maintenance if required. So, this patient has now NPM1 mutation, FLT3 mutation. He, the patient is 35-year-old female, fit, no comorbidities. What are your choices of chemotherapy for this patient? And what is the name of the regimen that you give to a patient of AML who is fit? Either it is daunorubicin and anthracycline, or it is like either FLAM based chemotherapy. Because this patient has FLT3 mutated, so you add midostaurin to these patients as well. Either daunorubicin or FLAM to this patient. And once in remission, then you, uh, send the patient for transplant.
So, this was NPM1, FLT3 mutated AML. There are multiple variants of NPM1. So, fish mouth and cup shape are not necessary to be present in all NPM1 mutated mutation. And always report the abnormality first in the report, and then your impression that this film is likely consistent with acute leukemia and suggestion that you need urgent flow for this patient and bone marrow biopsy including aspirate and trephine to confirm your diagnosis. Then this would complete your report. And in the morphology question of the part two, they usually ask what is the minimum genetic test criteria for leukemia? They can also ask what are the, um, CD34 negative AML? They can ask what is the prognostic classification of this AML? And what is the choice of treatment for this patient? Then you would mention both chemotherapy plus transplant in the future if it is intermediate or worse, and if it is standard, then just. They can give multiple questions in just one question. Are we allowed to keep NPM1 mutation on just morphology? No, no. As I mentioned to the candidate who was reporting the film, you cannot say on the blood film that this is AML or or this is NPM1 or 8;21. You just say, most likely consistent with, okay, okay, this diagnosis, but I need to confirm that on flow cytometry and bone marrow aspirate investigation. Because in the real life, when we see any blood film, we don't say that this is KMT2A AML or, um, 15;17 APML. We always say this is most likely suspicion. But then we send blood to the HMDS malignant diagnostic service or bone marrow aspirate to confirm our diagnosis. And once the diagnosis is confirmed, then we. So, never say on the blood film that this is the confirmed diagnosis. Some things are very clear, like if you are seeing myeloblasts in the blood film, then you would say there are myeloblasts. This is a hematological emergency. I would start ATRA for this patient, but I would send blood for PML-RAR alpha stain as well, which will give you results in one hour. And if PML-RAR alpha stain is positive, you are starting chemotherapy for the patient if the WBC count is more than 10.
Right. So, now we have another 40-year-old lady who is coming to the emergency department with easy bruising and two episodes of epistaxis. So, this is power 10. This is again a young lady who is coming to ED with easy bruising and two episodes of epistaxis. Looks like cold agglutinins. Cold agglutinins. Yes. Red cell agglutination. Yes. The coagulation profile shows prolonged APTT. Right. So, anyone? Sorry, PT is normal. PT is normal. APTT is prolonged. And the biomedical scientist has prepared the blood film. Is there anyone from the lab who wants to comment on this blood film and refer to hematology? Yeah, there are definitely cold agglutinins to some extent. That would account for the bleeding. Look at the neutrophils. Okay. So, this is power 10. I will move to power 50 to make it more clear. This is just oil movement. So, ignore this movement. But certainly, reheat this 37 in the block and rerun the sample. Okay. Definitely thrombocytopenia. Mhm. Is this patient on warfarin? The PT is normal. No, this patient is not on any anticoagulation. What is the ESR of this patient? We don't do usually ESR here. Why want? Why you want to know the ESR? That's not rouleaux. Definitely not rouleaux. There are many reactive lymphocytes. This could be some form of infection. Mycoplasma. Okay.
So, now you have commented on that that there are rouleaux and, um, there are some lymphoma cells as well. Yeah, that's right. You have now referred the blood to a clinical hematologist. Yeah, definitely would have sent this. And yeah, that's really abnormal blast cell. Maybe I need now a clinical hematologist to report this blood film for the exam purpose. E-port about exam purpose. Any hematologist, clinical hematologist, please. Uh, sir, may I? Yes. Okay. Do you want to hear the story again, or you are aware of the story? Um, this is a peripheral smear of a 40-year-old lady who came with a history of epistaxis and bruising, and, um, her APTT is prolonged. And, um, this is the peripheral smear showing red cell agglutination, and, um, there are atypical lymphoid cells seen which are medium to large in size, and the features are suggestive of some lymphoproliferative disorder. I would, uh, uh, investigate further by flow cytometry, bone marrow aspirate, and trephine biopsy. And lymph node biopsy. You're doing lymph node as well, and bone as well? For both, sir. Uh, because the history did not mention any lymphadenopathy, whether it was present or not. I have the patient has abdominal. The patient has abdominal pain only. The patient has abdominal pain and the spleen is 22 cm. Okay. I will go for, um, PET or CT for, um, lymph nodes, and, um, also I would go for bone marrow biopsy to see infiltration and also for immunohistochemistry to categorize this lymphoproliferative disorder. What are you thinking about? What this can be? So, does this patient need any workup for the serum protein electrophoresis or any B-lymphoproliferative disorder? Because they are, um, um, associated with, um, cold agglutinin diseases. Okay.
So, the blood film contains multiple cold agglutinins, and there are multiple atypical lymphocytes. Some are small in size, some are large in size with minimum, some have minimum cytoplasm, and some have abundant cytoplasm. I was looking for any Howell-Jolly bodies, but I couldn't see because this patient had splenomegaly as well. So, difficult to comment on the red cell and size and shape because of the agglutination due to the presence of atypical lymphocytes and cytokines. There is a suspicion that this patient has a lymphoma. This patient needs, um, blood to be sent for flow cytometry and further investigation to find out the cause of abnormal lymphocytes, which can be either bone marrow biopsy if cytopenias are present, because I haven't given you the full blood count, or a lymph node biopsy on imaging if there is any lymphadenopathy. For now, which condition gives you cold agglutinins? Plasmas. Lymphomas. Waldenstrom's macroglobulinemia. So, Waldenstrom's macroglobulinemia and, um, Mycoplasma infection. And infectious mononucleosis. Yeah, but the lymphocytes are not typical for the infectious causes of cold hemaglobulin disease. And on further investigation to simplify it for you, MYD88 is negative. We have received the flow, and the flow is CD5 negative, CD20 negative, CD23 negative, CD10 negative, CD11c negative. It may be marginal zone. Marginal zone. I have given you the hint that this patient has splenomegaly, and the flow cytometry does not fit with Waldenstrom's. Does not fit with CLL. Yes, sir. So, most likely you ruled out MBL and MCL as well. Yeah. So, most likely consistent with marginal zone lymphoma. And we are still waiting for. I was going to ask a little question. That you said on morphology description that there are cold agglutinins on the periphery. Can we say this is cold agglutinins or just agglutination of this red cell agglutination? Not cold agglutinins. I just wanted to ask another question. That you said patient was bleeding. That can be due to acquired hemophilia like thing when immunoglobulin raised causes decreased factors. Yes. So, this was this would be the next question in the FC path exam. Why this patient is bleeding? Because this patient contains paraproteins, and paraprotein is a cause of acquired von Willebrand syndrome. Yes, acquired von Willebrand syndrome. And acquired von Willebrand syndrome leads to bleeding in the patient. Any condition with paraproteinemia has a tendency to lead to acquired von Willebrand syndrome. Acquired von Willebrand syndrome has a lot of causes, and one of the cause is paraprotein. So, Waldenstrom's has paraprotein. You can see von Willebrand syndrome with Waldenstrom's as well. But in multiple myeloma, in marginal zone lymphoma as well. In multiple myeloma, you can see Factor 10 deficiency as well, but von Willebrand syndrome is also common in multiple myeloma. Would you expect to see some plasma cells there? Though? Yes, I, I'm searching for that if there is any plasma cell present in the film or not. But I had seen few plasma cells in this. All right.
So, what is the treatment option for splenic marginal zone lymphoma? Splenectomy can be done. Do you have any other option? Uh, sir, hepatitis C profile should be done. Yes, it is commonly associated with hepatitis C. And what else? You can give interferon treatment. Interferon. What does the BSH guideline say? This is the, um, polarized lymphoma cell. Post-clinic marginal zone lymphoma. It has projections on both ends, which is a feature of splenic marginal zone only. These projections. And these. So, if the patient is not symptomatic, you do not give any treatment. But if the patient is symptomatic, you start with either rituximab or bendamustine plus rituximab for this splenic marginal zone lymphoma. Sir, may I ask a question? That I often thought so that as patient is CD20 negative, but CD11c is positive. I think so. How can it be used in this lymphoma? The marginal zone lymphoma cells, they are CD20 positive. They are not negative. Oh, okay. Okay. Sorry. Dr. What about these granular lymphocytes? Can be present if there is coexistent infection with that. But the majority of the lymphocytes were, um, small lymphocytes with minimum cytoplasm, and they were lymphoma cells. Then the flow cytometry was according to the splenic marginal zone. Right. Thank you.
Right. Now, again, we have a 35-year-old male who was referred by the CHP because of the abnormal high white cell count. The white cell count is 50,000. There's a marked shift of myeloid series up to the level of blast. You can see you can appreciate all the, um, myeloid cells in it. Neutrophils, promyelocytes, myelocytes, metamyelocytes. This is at power 10. And just in clusters. I'm going to the oil immersion to see to give you an overview of the film. And now power 50. This looks like a CML. Not seeing any visible fields in it. So, we have here b-form. White. I think myeloproliferative disorder would be a better term. Here. Somebody says B-cell. Yeah. Mhm. With basophilia. You see ML plus basophilia. The blast percentage is 11%. There is no accelerated phase in the UK anymore. Either it is a chronic phase or it is a blast phase. Treat as AML. AML in chronic phase. Yes, this is a CML and chronic phase. But I want you to report it for the purpose of FC path exam. How would you report this blood film?
So, this peripheral smear is showing, um, all the myeloid series starting from, um, blast, promyelocyte, myelocyte, metamyelocyte, and mature neutrophils, band, and mature neutrophils are seen along with that. These NRBCs are present. Platelets are adequate. A few basophils are also appreciated in the smear. The red blood cells are normocytic, normochromic, and most likely the peripheral film is suggestive of CML in a chronic phase. So, I would like to go for, uh, the cytogenetics and flow and for, uh, PCR for translocations 9;22 on PCR and for PCR abl protein. So, where is the? So, where is the basophil? I'm sorry to get you. Oh, so we can see one basophil in this. This is. The blood film shows leukocytosis with a myeloid peak containing lymphocytes, myelocytes, basophils, eosinophils, NRBCs, and neutrophils, most likely consistent with chronic myeloid leukemia. Needs blood for flow and BCR-ABL transcript mutation and bone marrow biopsy if there is. If there is a question, that when we advise the patient of CML, PCR for the first time, do we go for qualitative PCR and then before initiation of treatment, we go for quantitative? Or which test we go for quantitative? Quantitative PCR is first. Okay. Quantitative. Right. And, uh, if the patient has cryptic, cryptic translocations, then what do we do? Translocations of what? Uh, sir, cryptic translocation. Cryptic abnormalities. Which one? Like, for example, are you talking about? Yes, sir. Major chromosomal proteins. Major cryptic proteins. Aneuploidy 19 is chromosome 17. Those ones. Um, no, sir. I'm talking about if it is not translocation 2;10, if it's not BCR of size, not, not yes, not appreciated on the conventional, not on the conventional probe of PCR, then what do we do next? Atypical transcripts. We haven't come across any such case where we couldn't quantitate the BCR transcripts. There are typical transcripts like e13 to e34. There are atypical as well. FISH is the, uh, answer for such cryptic lesions, cryptic mutations that are not carried by the conventional PCR. So, it is written in the 17th edition of, um, 2017 edition of WHO, but these are very rare. I think they will not be mentioned in 2022. We haven't come across. I think. May I ask something? I think that cryptic translocations are not detected on the conventional karyotype of cytogenetics, but they can be detected by FISH. But I had a question that you told the cytogenetics and flow cytometry. What would flow cytometry do in CML? So, this question is also on my mind that what is the role of flow cytometry? What will be the result of flow cytometry in case of CML? Yes, I ask question. Yes, yes. So, when you do a bone marrow biopsy or when you are confirming the diagnosis, whether these are only the myeloid series of the patient, then flow cytometry is a part of the bone marrow aspirate and biopsy, and we do flow cytometry for all our leukemia cases, whether they are chronic or not chronic. Just to make sure there is only one disease in this patient, which is CML, because there are cases where we have seen CLL with a small phenotype of CML as well, or CML with a small phenotype of CLL as well. The dual diagnosis patients. We have many patients who have dual diagnosis, CLL-CML, CML-CLL, Waldenstrom's-CLL, Waldenstrom's-CML as well. So, we do flow cytometry for all of our leukemia patients or myeloma patients, just to make sure there is no dual diagnosis, and that you told that there are 11% blast. We can see those blasts are really myeloid or maybe lymphoid. And if they are lymphoid, then even 11% lymphoid blast will categorize this case into blast phase. Blast phase. Um, when the counts are, the blasts are about 20%, you treat it as AML. The accelerated phase where the blasts were between 10 to 20, they have been out now. Like we have only chronic phase or blast phase. Blast phase are treated as AML because the blasts are usually about. If there are, if there are lymphoblasts, then 2022 classification says that if there are lymphoblasts, then even less than 20% blasts are blast phase. Yes, that is correct. WHO 2022 mentions like that. But these are not lymphoblasts. All of them are granular. They are all myeloid cells. So, we do flow cytometry in all our patients just to make sure we are not dealing with a dual diagnosis, we are dealing with a single diagnosis, and we do have multiple cases where there are dual diagnosis, and we keep an eye on them in both our clinics according to their diagnosis, because if they are carrying CLL, they can come up at any time or they can go in transformation at any time. So, we cannot ignore that. All right.
So, we have talked about the transcripts and major chromosomal abnormalities in these patients. What prognostic score do you use for CML? So, called the. What is the latest one? Euro. ELTS. The ELTS scoring system is the latest that we use here in the UK for, for CML patients. All right. Now, this patient is a young patient, 35-year-old, who had a white cell count of 40,000. You have done the cytoreduction and you have got the diagnosis as well. BCR-ABL is present. What treatment would you like to offer to this patient? Okay. So, he is a high-risk ELTS patient. His ELTS score is coming into high risk. What TKI would you offer him? Nilotinib. Sir, Nilotinib. Visually start with Nilotinib. If there is no contraindication for starting the Nilotinib. What are the contraindications for any pleural or pericardial disease? Is a contraindication for Nilotinib. So, any patient who has cardiac disease, cardiomyopathy, pulmonary hypertension, or, um, lung abnormalities, you do not offer them. The chronic myeloid leukemia came up in the part two exam twice in the viva, and they asked everything about CML, starting from findings on the blood film to transcripts, major chromosomal abnormalities, what drugs you would give, side effects of the drugs, if there is T315I mutation, what is the option of a drug, if there is a mutation present, when would you do TKD mutation in CML patient, and what is TFR treatment pre-remission? So, be ready. This can be a question in the paper form as well, or this can be a question in the viva. And in the viva, the patient is usually young. They want to know, they want to know fertility preservation in both male and female, and pregnancy test in the female. Right.
So, the fourth case is again a 50-year-old male with progressive anemia, thrombocytopenia, and fatigue. He has abdominal discomfort as well, and the ED doctor has found a very large spleen in this patient. Uh, sir, pardon me. What were the, um, again, was it bicytopenia? So, the patient has progressive cytopenia, anemia, and thrombocytopenia. Okay. And progressive fatigue as well. Right. And on clinical examination, the patient has, uh, abdominal discomfort due to large spleen in this patient as well. Something is moving on the slide. Is this a cursor or no? Sometimes when I put the oil, so the previous 10x, they become, um, blottable. This is at power 10. Power 50. Dr. Amir, what stage of the patient? Sorry. Patient is 56-year-old. Has the patient been on chemotherapy? No. Patient is not on any chemotherapy. Patient has just progressive fatigue and anemia, thrombocytopenia with large spleen. Hard-looking cells. Are there any lymphocytes? No. No, it's only cytopenias and splenomegaly that is the abnormal findings in this patient. [Music] [Music] [Music] That. [Music] Where a teardrop cell can be appreciated in this field along with some polychromasia and spherocytosis. Mhm. Let us see. Yes, he looks like he has thrombocytopenia as well, and the field does not contain any white cells. This is the only white cell. Something like aplastic leukemia. Sorry. Aplastic anemia. Something like that. M. In aplastic anemia. Aplastic anemia can be diagnosed. [Music] On. This is true. This patient has many teardrop cells and, uh, a myeloproliferative disorder. Myelofibrosis. Any leukemia picture, sir? What about the monocyte count? There are. I saw. Yes, I saw a lymphocyte having granular cytoplasm, but I can't see again. Let me again. A bit reactive. There is a pseudopod. Right. So, up till now, we have seen anisocytosis and many B12 like. Sorry. What about B12? B12 folate and iron studies? They are normal. Okay. Teardrop. So, whenever there is tear dropping, fragmented RBCs can be seen. Yes. Whenever there is tear dropping, Howell-Jolly bodies, and patient has splenomegaly with progressive cytopenia, the top differential that comes in mind is myelofibrosis. Myelofibrosis. We cannot make a diagnosis on, on the blood film that this is myelofibrosis, because the criteria of myelofibrosis diagnosis is on bone marrow biopsy. The major criteria, the minor criteria is on blood film and blood tests. So, if you ask me that what is the, um, LDH of this patient? LDH of this patient is high, 1000. So, according to BMB criteria, patient should have bone marrow fibrosis grade 3 or 4. According to BMB criteria, progressive anemia, unexplained anemia, teardrop cells, constitutional symptoms, and yes, splenomegaly. So, because of progressive anemia, teardrop cells, you would suspect that this patient has likely, um, most likely consistent with myelofibrosis. You need to do a bone marrow biopsy for this patient to confirm your diagnosis. Because of the cytopenias, you could not see many findings on the blood film, but there is teardrop cells and Howell-Jolly bodies, which is likely consistent with myelofibrosis. P-dropping is a feature of either iron deficiency anemia or myelofibrosis. This patient does not seem to have iron deficiency anemia because the red cells are normally, usually, um, more severe teardrops, poikilocytes in myelofibrosis, occasionally blasts as well. Yes. So, because of the cytopenias, you need to see the whole blood film for the NRBCs, dysplastic neutrophils, and blasts. This can be big. Yes. Pseudopods look like a nuclear eye here, but look like a blast. Right. So, suspected case of myelofibrosis in this one.
Now, again, what is the prognostic score used for myelofibrosis? It goes back. Yeah. Good. Thank you. So, DIPSS is the score that we use for myelofibrosis. Yes. Let's say this patient, before that, what are the secondary causes of bone marrow fibrosis? They are metastatic bone marrow and, uh, acute megakaryoblastic leukemia and anemia. No, sorry. No. Metastasis and, yes, inflammatory disorders. Graft-versus-host disease. The new BMB guidelines have given a table as a cause of secondary myelofibrosis, which can be asked in the viva or in the morphology question. They have categorized it as infection like HIV, TB, leishmaniasis, autoimmune disorders like hematological causes like AML, leukemia, monocytosis, MDS, CML, metastatic cancer, drugs like roxithromycin, and graft-versus-host disease, and radiation. So, they all can lead to bone marrow fibrosis. So, let's say this patient's DIPSS score is intermediate, intermediate one. What are the options of therapy you have for this patient? This patient is now symptomatic because of the progressive anemia, fatigue, abdominal pain, and you want to treat him, and his DIPSS score came out as intermediate one. What are the options of treatment? Interferon or hydroxyurea. If JAK2 is positive, then JAK2 inhibitor, ruxolitinib. Mhm. Yeah. You can give, um, anything to this patient because the guidelines have changed. Previously, we used to give ruxolitinib for high DIPSS score, but now you can give it at low DIPSS score as well. You can give. You can start with ruxolitinib. If not available, then interferon. If not available, then hydroxyurea. Or always say, if there is any trial in your hospital or nearby hospital, you will enroll the patient in the trial, because every tertiary hospital in the UK has some trial running. We always mention in the answer if the patient is agreeable, we can enroll the patient. All right.
What is the side effect associated with ruxolitinib if you stop it suddenly? And rebound of symptoms. There is a term called SIRS, systemic inflammatory response syndrome. Usually that is associated with ruxolitinib if you stop it suddenly. And what about nilotinib? If what is the side effect with nilotinib? It's again a JAK inhibitor. It causes hypophosphatemia and causes encephalopathy. So, those who are going for part one or part two, remember the common side effects of these drugs. They can be asked because you will be consenting the patient for these side effects as well when you are starting the medication. If you know them, it's better. They can be asked in the MCQ question in part one and in the viva question or as a one-mark question in the paper. So, the last question is from parasites. This patient has just returned from Argentina or Argentine and is now complaining of difficulties following. All right. So, this is at power 10 for the exam purpose. If someone is coming from South America complaining of fever or difficulties swallowing, what do you think in your mind? Trypanosomiasis. Okay. Let's see if we have Trypanosoma here or not. [Music] [Music] Yeah, could see Trypanosoma. Could see. Yeah, we have Trypanosoma here. See the. What did you say? Did you say cruzi? Cruzi? [Music] Yeah, another one. But there is some artifact. Trypanosoma is quite clear, isn't it? Yes. Uh, let's see if we have any other one. This one, maybe this two. Yeah. And make it big. Nothing. Infection. Wow. See the tail. Yeah. So, these are Trypanosoma. So, my microbiologist has told me that Trypanosoma cruzi is C-shaped and causes Chagas disease, and it has a small kinetoplast which is somewhere at the tip here. It's not visible here. This one is nuclear. While Trypanosoma brucei, which causes African trypanosomiasis, sleeping sickness syndrome, is S-shaped, causes sleeping sickness and what else? But they have the kinetoplast as well, I think. But they would not ask us in FC path exam this much detail. If you say this is Trypanosoma, and according to the area from South America, most likely this is cruzi because it's C-shaped. C-shaped. This is enough. Trypanosoma is common in the FC morphology exam. Every now and then, they would give either Leishmania or Plasmodium, or they would give Trypanosoma cases. So, what is the treatment options for Trypanosoma? Allopurinol or diethylcarbamazine is for the worms. For the Trypanosoma, I don't have any clinical experience with Trypanosoma, but this is just for exam purpose. The treatment options are either pentamidine or nifurtimox or benznidazole. So, if you just cram few drug names for the worms, malaria, and Trypanosoma treatment, that is enough because you need to see them only during the exam purpose. I think rest of your life, you are not supposed to deal with them. So, this was the last case of Trypanosoma. And do you have any questions before we wonder? Thank you very much. Has you enjoyed that? Welcome. Um, so this was session 10. They are free sessions. If you want to donate, these are my account numbers. And if you want to give me a copy, this is the link. I will share in the group. Subscribe the channel and thank you. Have a nice rest of the weekend and see you next week. Thank you. Thank you very much. What's the channel's name? Thank you. Thank you. Thank you.