Transcription
So, this is the first case. Uh, this is a 22-year-old lady who presented to the Medical Department with fever. Upon examination, uh, she has some lymphadenopathy as well. The, uh, biomedical scientist from the lab called you because he has seen some, uh, abnormal cells in the blood film. So, he wants to see you this blood film and take over the. So, anyone from the, um, attendees who is a volunteer, go for this case?
I can try. Okay. So, this is the power 10. I will go through the slide for a general view and then I will go to the 50 slide just to give you a hint. This case came in the, uh, paripath exam twice in Aro and it is very common in the short case of morphology. I will go to 50 power. The Red Cell morphology, HLS, and the white set for. Right. So, now you can report the blood P. This is the usual question in a report the blood P.
Okay. The blood film shows a presence of some atypical lymphoid cells with which are variable in size. Some are small in size and some are medium and having irregular nuclear contour. Nuclear contour and some have round nuclei, whereas the cytoplasm is also variable. And some of the large size cells, they show, um, abundant cytoplasm, a granular cytoplasm and scalloping, uh, around the RBCs. Whereas the neutrophils and the are preserved and the RBC morphology is unremarkable. And there is mild rocy opinion, uh, but, uh, I would suggest the close item. Why? Cloury to rule out whether they are reactive or they are clonal for the unin typing of these atypical info cells. The first thing which comes to my mind was infectious mononucleosis, keeping in view the patient age, young age, the presence of fever and lymphadenopathy. I don't know the status of split be because the chromatin of these atypical cell, it seems to be mature. It's not like the immature like which we do have in blast. And they have abundance cytoplasm which is scalping around the RBC. So, infectious mononucleosis came to my mind. So, that's why I advise cl cytometry to to differentiate from the malignant morphology.
And we, but you haven't, but you haven't seen any blast here. Sorry, any blast? You haven't seen any blast here. Yes, they don't look like blasty. In that cases, we do reactive. Yes. So, we do not send for phy. The blood film shows lymphocytosis, most of which are, um, atypical. They differ in size with basophilic cytoplasm and mature nuclei. The red cells and platelets are normal. The blood film is consistent with, uh, reactive nature. Further investigations are required to, uh, reach the final diagnosis.
Okay. We do not F the heterophile antibodies or monospot test or we just say, okay, too loud. Yes. So, this will be the next question. What investigation you will do? But to complete the report, you, you will write your findings. You will mention most probable consistency like this film is consistent with and, uh, suggestion, uh, to what investigation you would do next. So, the investigation you would do next will be the heterophile antibodies, that the monospot test, or you can asked for ABB specific antibodies. Yes, ABB serology or PCR. Um, we also do here, uh, HIV and hepatitis serology for such patient as well. And monosport test. And then the third question would be, what is the most likely diagnosis here, given the patient age and presentation? That is infectious mon, ABB induced viral infection. Most likely infectious mononucleosis. Yes, because the patient only presented with fever and FY. They did not mention any B symptom and the blood F does not show any immature blust and there is, um, scalloping around the RBC. This is the feature of reactive lymphy and they are BAS philic as well. There is no nuclear in. So, this case comes twice in thec exam. The, you don't mind, can you repeat, uh, the, okay, my final report that it that these, the presence of these atypical lymphocyst with, yes. In any report when they ask you report the blood fill, you will first write the findings in the blood film and you have to mention the most obvious finding first. This Blood film has lymphocytosis. You will see first that the blood film has, uh, lymphocytosis and few words about the lymphocytes, not, uh, much explanation about the lymphy because sometime you will address the GP. The blood F will be from the GP. The GP do not understand these things. So, only few words in the description of the cells. The blood film. This Blood film shows lymphocytosis. The lymphocytes are irregular in shape and size with nuclear maturity having basophilic cytoplasm. The red cells and platelets are normal. The blood fil is consistent with, uh, most likely. You will always write most likely or most probably because you have to confirm it on further investigation. You will not say that this is infectious, no nucleosis. You don't know. Maybe you do some test and it comes out something else. You will say the most likely or most probable diagnosis is consistent with, um, reactive nature. And then you will suggest investigations. You need to do further investigations to confirm your diagnosis. So, three parts, uh, description of the cells, most likely or most probable diagnosis, and what investigation you would do. So, this is the advice part. Then you will get, uh, five out of six marks or six out of six. Mon or in a further investigation, we can just say viral serology or we have to specify the viruses, whether it's HIV, hepatitis, or it's like, we, as I am suspecting because you are suspecting the, um, infectious mononucleosis, which is because of the epin bar virus. You can mention monosport test and EBV serology or PCR. And in such cases, um, because it is a transmittable disease, so we always do other viral serology as well, like heitis VC and the HIV. Okay. Thank you. Yeah. So, this was the first case. Now I would like anyone who has applied for the exam. Yes, I need a volunteer please.
Hi Amar. I will do it. Okay. Good. So, this is a 36-year-old lady who presented to the emergency department because of extreme tiredness. Uh, she cannot carry out the daily activities because of the lack of energy. She had blood test done and the, uh, lab called you because the hemoglobin is on lower side, 10.5. The white cell count is, uh, 5.4 and the pled count is on lower side as well, 114. The biomedical scientist is worried for the abnormal cells and high white cell count in the in the blood. So, this is power 10, just general overview of the blood cells. For, I will go to power 50 for sh for.
Okay. So, you can start reporting the blood film. The first question is, report the blood film. Yeah. I can see, uh, mononuclear cells, um, increase in number and these are medium to large in size and they have are like irregular nucleus with open chromatin. Some of the, uh, nucleus showing prominent nuclei as well. Uh, whereas the cytoplasm is moderate or adequate. Most of the cell showing a granular cytoplasm, but there are some inclusion. I can appreciate in the granular site, but, um, Frank or rods, I cannot appreciate. Some of the, uh, like blast cells showing indentation or irregular nuclei. Even I can, uh, like few nucleus showing cup shape nuclei as well. But, for my opinion, I can't say it is a prom myocytic. The, there is no abnormal bilobed, uh, appearance in the blast. Whereas in, uh, Red Cell, there is a anisocytosis. They are like, um, normochromic. Platelet are reduced. Um, I guess it's not like 140, but, uh, platelets are seen. Few neutr also. I can see few neutrophils. It's a like, uh, most probably like it's acute leukemia and I would advise bone marrow aspirate, refine, uh, flowcytometry and cytogenetics and molecular panel.
Okay. Yes, I agree with the blood reporting. Yeah. Uh, they have fish mouth appearance here. Yeah. Or or cup shape. Yeah. These are cup shape Bloss. Acute leukemia and you would do F investigation to confirm your diagnosis. Yes. Okay. So, what is the minimum genetic test that he would do in a new AML patient? B 2022. Yeah. I would, I would, I would like to know FLT3. I would like to know NPM and, uh, I guess, um, uh, one other is, uh, uh, which is, uh, translocation 166. I, I genetic. I just forgot it's NPM, FLT3 and, um, inversion 16 and translocation 166. There's one more. I just want to. And of course, it's not APML. So, I, I don't know whether I should write PML R R rank one and ranks like 821 translocation. I would also would like to see. So, this table is given in the BSH guideline. Remember it. It will be asked from you in the W or in the, uh, in this morphology question. It is, uh, there. There are four categories here. Will do, uh, FISH for inversion 16, 821 and, uh, KMT2A is the first category. Second category is stereotyping to know about any other transation. Third category is molecular NPM1 and FLT3 with ITD or TKD. This is the third category. The fourth category is NGS panel on any, um, suspected AC my leukemia. You will do this. Now, um, the examiner can ask you in this, um, this acute minor is, um, NPM1. Okay. And, uh, whether this is CD34 negative or positive? CD34 negative. NPM is the CD34 negative. Do you know any other acute leukemia who is CD34 negative? It is APML and mega carotic. KMT2A. KMT2A. So, the next question would be, um, what management you would do? This is a broad question and the examiner want to listen to your management of this patient. Yeah. Uh, in management, she is 36 year old. I would do baseline, um, CBC, renal, liver, viral and as well as the pregnancy test. And secondly, I would see the like blood counts and, uh, like if it's more than 50 or high, any symptoms for the leucocytosis, electrolyte, um, monitoring and, um, then if it's a likely abnormal electrod, then the PLS, uh, surveillance as well as the management. And, um, first is the supportive care, admission, supportive care, discussion of the diagnosis with the patient and, U, then probable further, uh, treatment discussion about the treatment and the, uh, this is like.
So, the examiner here would like your approach here. Uh, so if you have found this picture in the blood F, you will explain to the patient that we are suspecting, uh, hematological malignancy in in your blood P. So, we need further investigations to carry out, which include a bone marrow biopsy. And then you will give her a leaflet of bone marrow biopsy and explain how the procedure is done and and mention that it is an urgent one. The patient would say, "Whe, do I have acute leukemia?" The examiner would pretend as a patient would say, "Whether I have acute leukemia?" You would say, "At the moment, we cannot say with, uh, with 100% short that this is acute leukemia, but this is a suspicion that something is going on your blood F. That's why we want to do blood bone marrow biopsy to confirm that." And then once you have done your bone marrow biopsy and, uh, usually the, uh, flow cytometry is very quick. If you ask your HMDs, local HMDs, they will process this sample within 24 hours. So, you can mention to that we will, we will request our HMDs to expedite the procedures. And if there is a flow cytometry, which is consisted with acute leukemia, you will mention to the patient that we would need further investigations to to see your organ functions, like echocardiography, your liver function test, kidney function test, which are done normally, but ECG, chest X-ray, and lung function test will be done, uh, to see the fitness of the patient for the chemotherapy. Once the bone marrow biopsy confirm the acute leukemia, then you would do the breaking bad news with the patient and give her leaflet of acute myeloid leukemia and, um, offer her the treatment options, which are obviously the chemotherapy, but depending upon the patient status and comorbidities, you would decide, uh, whether to give her intensive chemotherapy or a non-intensive or single agent chemotherapy. She is 36, she is fit for intensive, uh, chemotherapy if she has no, uh, comorbidities and, U, you mentioned that you would exclude pregnancy as well because chemotherapy has larious effect on the pegnant. And after that, uh, once the patient agree for the chemotherapy, you will discuss the case in your MDT, present your case, present your treatment option, and if the MDT people agree, then you would proceed. Now, if this patient is fit, no comorbidities, no pregnancies, what intensive chemotherapy you would give to this patient? It is, um, 3 + 10, um, idarubicin and the cytosar. Yeah. What is 3+10? It's, um, um, idarubicin and the cytosar. A is three for three days and cytosar for the 10 days. Day one to day 10. Either flag and or du. Okay. And yes, and then, uh, according to the BSH guideline, standard of here is either du or like, but depending on CD33 or FLT3, you will choose milot. Milot. Okay. And then after two cycles of D, you will give her the high dose. Two cycles of high dose cab. And then I'm just interrupting you. Sorry. Uh, is it an intermediate dose AAS or it is a high dose? Because in some article I have read, it's now it's intermediate. A. The BSS guideline says high dose. Yeah. And once the patient is in remission after the first cycle, then you will request to your transplant colleagues whether this patient is fit for transplant or not. If this patient was not fit for intensive chemotherapy, what are the options you have? It's not fit for transplant. Not fit for transplant. Not fit for intensive therapy. What are the options? Then we can, after high dose, we can monitor patient. If she stays in remission, then after diagnosis. Yeah, you assess the patient. But she is after diagnosis and she's not like, then, then we can have option of Venetoclax and as a citadine. Okay. Is there any blast cut off for when is it's? I think, uh, 30%. But, uh, it is for, uh, because hypomethylating agent is can be given for up to 30% blast. It's, uh, if you are giving the ayine monotherapy, then the blush should be less than 30%. Less than 30%. Oh, so when is you have the option? So, this patient, white cell count was, uh, up to 60, almost, and you are giving Venetoclax. Would you be worried for anything? Tumor lysis syndrome? Okay. So, what you would do for tumor lysis syndrome? Uh, I would monitor electrolyte. I will first, like, before chemotherapy, I will hydrate the patient, monitor IO charting, input output and fluid, uh, balance and electrolyte, calcium, phosphate, and, um, uric acid monitoring. And if it's, like, hyperemia, um, if it's hypocalcemia, hyposmia, then I would give, like, initially I would give a prophylactic Rasburicase. She's female, but I would check G6PD before Rasburicase. Usually we give, uh, prophylactic Rasburicase in a patient who is at risk of developing. Okay. With our rehydration and six hourly monitoring of the TLs bloods. And that's why the Venetoclax regimen is escalating regimen. Yes. You do not start with the full dose on the first day. You escalate it slowly and slowly. And it is mentioned in the guideline that the first course is given in the hospital. If patient is stable and there is no like, uh, is there any other complication apart from TLS? Because it's particularly mentioned the first course is given in the hospital and rest of the courses would be on, like, outpatient. First course is on admission and rest of the courses is like, can be given as outpatient. Yes. First course of any chemotherapy is given in the hospital because patient is new to it and they may develop, uh, any complication from that. So, that's then NPM1 mutation. What type of risk category is that? Favorable. Intermediate. Favorable. It is favorable. Okay. Would you check FLT3 with that? Yes. If it's positive with FLT3, then it will go into the intermediate category. NPM with FLT3 is intermediate. Okay. So, our hospital has U acute leukemia workup, PDF. I will share that in the group. Let's move. Amir is a like, um, there are like multiple predisposing factor for the TLS is patient like in this patient count is 60,000, not very high, not more than 100. Still patient can go into TLS with Venetoclax or it depends on the predisposing factor. If the patient has predisposing factor, he can go to TLS even with the small count as well. Yeah. No, my question is, is the, uh, any role of Venetoclax particularly for development of the TLS? Because it is mentioned in the like in when where the protocol is mentioned Venetoclax that a patient is might have a TLS. Is there anything with the particular with the Venetoclax that patient can go into the TLS or it's just like any other acute leukemia predisposing factor, high count patient can go into TLS? This Venetoclax itself has a side effect of developing TLS. Yes. Okay. High count plus if there is any renal problem or patient is dehydrated, patient is dehydrated, that can lead to increase incidence of TLS. Okay. Thank you. Sorry. So, when we start, when to CL, so we give prophylaxis for TLS as well. We, we start them both. If someone is at high risk of TLS, then we give them prophylactic Rasburicase. Like, uh, you may see patient of CL with 400, uh, white cell count or all whose count is almost 600, 700, and those patient, they are at risk of TLS. You give them, uh, prophylactic. But sometimes we give them treatment doses as well. If the count is 400, 500, so they are the very super high category of developing CL, uh, TLS, and we sometime give them treatment doses as well. Three treatment doses. Would you check G6PD in female or not? Or you give? Usually, usually do not check G6PD here because incidence is very low and it would take time to, uh, for the result to come out. So, is it like, uh, we need to mention? Because it in the guideline it is written that before Rasburicase, give a check G6PD. Yes. In the exam, you, you have to mention that and you have to mention to the examiner for the W as well. Okay. So, anyone for a third case? This was in the recent exam as well. Anyone? I will go for. Then if nobody's coming up. Okay. Right. So, the, this patient is 52-year-old who presented to ED because he is very unwell and, uh, he has high grade temperature, hypotensive, abnormal renal function test and liver function test. So, he was sent straight to IU for management. The biomedical scientist called you because he has seen a white cell count of, uh, 98 and he thinks that this is chronic myeloid leukemia. So, this is the blood film power 10, a general overview. The power 50 for, um, uh, I'm, can you move to the little bit, uh, on the body of the smear because you are on a thin side? If, okay, yes, it's, it's good. Now you can report the, yeah, smear shows increased number of, uh, uh, white cells, but and mainly it's neutrophils and and, um, I can see a few myosite, uh, left shift, but it's not a prominent feature. Myosite peak is not observed, but the neutrophil shows prominent aerophilic granules. And, um, red cells are, um, um, hypochromic on this smear. Red cells are hypochromic and, um, and isocytosine, but there I can appreciate the platelets. It's maybe it's in a within normal range. So, my, uh, conclusion is reactive neutrophil leucocytosis. The probably infection. I would suggest D-dimer, CRP and, uh, monitoring of count, um, in, like, for the next few weeks. In next weeks, monitoring of counts. Okay. So, why it is not a CML? Because I cannot see any basophils. I cannot see myosite peak and there is evidence of infection, inflammation. He admitted. So, at this point in time, I would not go for, uh, any further investigation in the lines of CML. Okay. And what, why not it is a typical neutrophilic chronic neutrophil leukemia? Leukemia? Yeah, but it could be the possibility. But, as patient is having, uh, clinically is correlating with, uh, reactive neutrocytosis, so right now I will, um, observe the count, let the patient is, um, stabilize or improve, and then we can, uh, go for if it's a persistent count and, with basophilia, then I can go for CML. If it's persistently high. Don't say like that in the exam that it is a possibility. This is not chronic neutrophilic leukemia. Chronic neutrophilic leukemia has a separate criteria. Yeah. For that, you cannot diagnose it on blood. Their nuts are mature. They are not that toxic granulitic and it has a specific criteria. I think the neutrophil, neutrophil should be more than 96%. 80%, I guess. Yes. And and they are all mature neutrophils. Yeah. This one has many band forms, B forms, and and they are toxic granulitic as well. In CNL, they are not. Okay. What is the mutation associated with CNL? No, I don't remember mutation with C. Tsf, csf3r. Yeah. Yes, this is a. They usually ask in the wife about that. If they come to a leukemoid reaction, know, so usually the questions asked from us in the exam were report blood, how to differentiate from CML, and what investigation you would like to do next. So, the patient at this point, uh, at this point with this history, would you mention about investigation for CML? I think no. This patient is separate. This patient is. So, you have to send the sepsis related investigations. You haven't seen any basophils here, mylo sites here, and you're not suspecting CML here. You haven't seen any blast here. The myeloid peak, you haven't seen here. There is no need of doing CML investigations and no need to do investigations for CNL. So, Dr., in this peripheral F reporting, we just say the peripheral finding consistent as. Should we mention these points that there is no basophilia, no mosite peak, and this findings are consistent with the react, most likely reactive neutrophilia with toxic granulation, and would advise for CRP, your blood culture, or urine culture, that's it. Yeah. Then they are done already. This Blood film shows neutrophilic leucocytosis. Neutrophils are having toxic granulations. The, uh, red cells are hypochromic with a slightly increase in split count. The blood frame is consistent with, uh, leukemoid reaction, most likely secondary to infection. Um, further investigation would include, uh, investigations related to sepsis. Thank you. Yes. Then the next part in the in the exam would be, uh, how to differentiate, uh, like what are the differential diagnosis? This can be a question as well. You can write, uh, leukemoid reaction, CML, CNL, but the leukemoid reaction will be the first one. And then if they mention how to differentiate the differential diagnosis or what is the most likely diagnosis, then you will only mention leukemoid reaction because they don't have CML feature. They don't have CNL feature. Yeah. And sometime, um, uh, a question can come with similar picture but less, uh, less granulations and they would have mentioned somewhere in the in the history that the patient came to day unit for a procedure, then that is GSF induced neutrophilia. So, going through the history is very important. They give you a lot of tips. So, the second last ISE. Any volunteer? If there is, uh, no one is volunteering, then I would continue. I. Okay. So, this Blood film is a GP blood film, which means the bloods are taken in the GP surgery and sent to the Hospital from, uh, 70-year-old man. The, the biomedical scientist called you because he noticed that the white cell count is 150 and, uh, he is worried for acute leukemia. You call the patient and the patient says that I have just tiredness and nothing else. So, this is the power 10. This is the power 50. Mhmm. For. For. Okay. So, now you can report the blood film. The blood film findings should in mark have scanty to moderate amount of ucular cytoplasm. The nuclear chromatin is condensed, mature, and there are no nucleoli. And some smut cells are also seen. There seems to be a mild anemia and the platelet count seems to be a bit on lower side. And the findings are consistent with, uh, lymphoproliferative disorder and would advise admission and bone marrow biopsy. Bone marrow aspirate and fine biopsy followed by flow cytometry on peripheral blood for confirmation of diagnosis. Why would you admit this patient? For for further workup? As you, you have to do the bone marrow. Send the flow cytometry. And he's having chest tightness. To see whether he has to go for echocardiography or ECG. No, I said just tightness, not chest tightness. Okay. I thought it was just tightness. [Music] So, you're suspecting proliferation of disorder in this patient? Yes. What investigation you would advise? What advice you would give to the GP? To send him to the hematology and for advice for bone marrow biopsy and flow cytometry on peripheral blood for immunophenotyping. The GP cannot do bone marrow biopsy. Why are you telling him that bone marrow biopsy? Okay, then I'll only tell him to send the patient, refer the patient to hematology. So, we usually ask them that we will, we will need the blood sample from this patient for flow cytometry to confirm the diagnosis and, uh, referral of the patient to, uh, hematology assessment unit. So, you don't take sample when the patient will come to you, or you will ask the GP to send further sample? The GP will send the samples further. Or usually we call the patient with such high count and ask, ask the patient how is he, if he can come to hematology assessment unit today or tomorrow, then they usually come there and then we further investigate the patient. The blood film shows leukocytosis. The white cells are mature. There is no blast in the blood film. The platelet count is on lower side and red cells are okay. Consistent with lymphoproliferative dis, uh, disorder. The patient would need further investigation like cytometry for the confirmation of diagnosis. Please send the patient, uh, to the hematology assessment area or hematology department for review. You will not advise bone marrow, bone marrow of assessment. Yeah, because if you are suspecting, ative, FL will tell you the diagnosis. What flow cytometry you are expecting here? Um, B NHL. And I would expecting this patient could have positive for CD19, CD5. I'm not sure whether it's mantle or it's because the morphology is not classic of classical of CLL. It could be CLL, it could be mantle. Not sure whether it's CLL or it's mantle. So, it is CD5 positive and CD23 positive, 43 positive and 20 positive and C. Okay. And when would you treat this patient? Um, um, if the patient is symptomatic, he is having cytopenias and which are not related to autoimmune hemolytic anemia or some underlying etiology other than the CLL. If there is increase in size of lymphadenopathy and if there is the doubling time is is more than six months and there is increase in size of spleen or liver, then you will think of. Otherwise, you will observe. If patient is asymptomatic, you will observe him six monthly and note down his CBCs. Yes. If patient develop massive splenomegaly or bone marrow failure or if the lymphocyte counts, uh, doubling time is less than 6 months or the symp persistent B symptoms or progressive B symptoms, then we treat. What are the bad prognostic features and CLL? The bad prognosis include the increase doubling time and the presence of TP53, CD38, Zap70. High TLC count and plus, I think, persistent. I don't remember any mutation. Molecular. TP53. Presence of TP53 is associated with bad prognosis. CD38 and Zap70 and IgHV unmutated is also bad. What about Notch1? Notch1 is also bad prognostic marker. SF3B1? Sorry, sorry. Which one? SF3B1. Sfb31. SF3B1 and BIRC3. They're also associated with bad prognosis. Yes, they are associated with bad prognosis. And which system do you use for staging of CLL? You two, uh, system. The Rai and the Bennet. Okay. Right. Thank you. And all right. So, this is the last case. And I need someone for the, who is an exam candidate. Um, okay, Amir, I will do it. Is there anyone else who wants to go ahead before Shahim? Captain Ala is on the top in the list. Dr. SK and Faiz Mansuri. I can do that. Okay. Good. Yes. So, this is a 32-year-old boy, a male, um, who presented to, uh, emergency department with, uh, tiredness and bruising on the body. So, the bloods were taken from the patient and the biomedical scientist called you, uh, because he has seen some abnormal cells, uh, in the blood film and, uh, increase white cell count. White cell count is, uh, 30. So, he asked you to come down to the lab and see the blood film. Apparently, this is power 10, uh, general overview of the blood film. This is power 15 now. And these are the cells. E. E. E. E. Okay. You can report the blood film now. This marked fragmentation in the red blood cells, occasional nucleated red blood cells, and the abnormal promyelocytes. Few blast cells. The cytoplasm of these abnormal promyelocytes are intensely granular. And findings are compatible with APL. And there are many blast cells as well. Okay. So, you think that this is the, uh, APML looks like. So, how would you compile your report for the examiner? So, fragmented dead cells, nucleated dead cells, prominent abnormal promyelocytes, with the the cytoplasm containing granules of these abnormal promyelocytes contain, uh, the cytoplasm of these abnormal promyelocytes contain granules. There are few, there are many blast cells as well, which have a high nuclear to cytoplasmic ratio, with a copious amount of cytoplasm as well, containing granules. Findings are compar, consistent with acute leukemia. Features favor acute promyelocytic leukemia. I would advise urgent immunophenotyping, translocation 1517, and DIC analysis, and an urgent referral to hematology assessment unit.
So, the blood film contains leucocytosis with many, uh, leukemic precursors. Most of them are granular, some of them are bilobed, which is consistent with acute leukemia, most likely acute promyelocytic leukemia. This is a hematology emergency. It would need, uh, emergent assessment of the patient, investigation, and initiation of the treatment. So, you are the hematology registrar. You have to tell the examiner that you know that this is an emergency. You have to do everything now. You cannot say refer to hematology. No, if you are called about such blood film in the night, you do not say refer to hematology. You go to the hospital at 3:00 a.m. in the morning to see the patient and to see the blood film by yourself and to explain to the patient what is what. We are expecting. Yeah. We usually bluelight the patient even at home. You bring him to. We usually bluelight the patient if even if he is at home, you bring him to the ward. Yeah. So, the examiner relies on your words that you have written or you have said in the W. They do not know what you are doing in the hospital. They will guess it from whatever you say or you write in the paper. If you mention this is hematological emergency, which would need, uh, emergent assessment of the patient, admission, explanation of the probable diagnosis, and initiation of treatment, it means, uh, you have dealt APML in in your experience. Okay. What investigations should be done for this case to confirm the diagnosis? So, I will send the blood urgently to HMDs for FISH analysis of 1517 and obviously the cytometric analysis. These are the urgent investigations. I will send, uh, full blood count, DIC profile, which includes PT, fibrinogen, and D-dimers. And I would do all the baseline virology. And, no, I mean, mention investigations to confirm profile. Those full blood count, renal profile would have been been done by the ED for you. As a hematologist, to confirm the diagnosis, you will send blood to HMDs for PML RAR stain, which usually takes 1 hour to process. And yes, I will speak to someone with the HMDs as well, to that the, and I will preemptively tell them that a sample would be coming. So, which we suspecting APL, so kindly report it in. As you will not tell the HMDs that a sample is coming. You will hand-deliver the sample if it is in your hospital. All the tertiary hospital, hospital, all the tertiary hospital have HMDs. Yeah. Yeah, but no, not always you have an HMDs locally. Like we used to call them. We used to be based in and we had to call Leeds HMDs. Okay. Okay. Okay. Right. That's fine. FISH takes 6 hours. So, it is a second-line investigation. Third one is the PCR, which is the gold standard test. It takes 48 hours. So, if you are in hour, you can send the sample or blue light the sample to HMDs or PML RAR stain. They will tell you the result within 1 hour. FISH will take 6 hours and PCR would take, uh, 48 hours. This is to confirm the diagnosis. But you will not wait for the result. If you are suspecting APML, on the blood film, you have to start the treatment for the patient after explaining the diagnosis to the patient, probable diagnosis to the right. What is the risk category of this particular patient? He is a high risk or low risk AP? He is high risk. And why is that? Leukocyte count. White cell count. What is the cut off to consider as a high? Exactly. Remember, maybe it was 144. I don't exactly remember, or maybe that is for CMML. You were talking about was 30. For APML, it is 10. More than 10, it is high risk. Less than 10, it is low risk. Okay. So, let's say this patient is in DIC. What are your targets for the blood components or the blood value? So, if I will transfuse, to keep the PT and APT in a normal range, uh, and, uh, fibrinogen below 1.5. I, if it's above 1.5, I will give cryoprecipitate. And platelets needs to be kept above 50. So, I will give platelets as well if it's below 50. So, platelets below 50. PT and APT raised. PT and APT raised. And fibrinogen above 1.5. These are the cut offs. Okay. All right. So, you think this is APML. It is a high-risk category and patient is not in the DIC at the moment. And you have informed the patient that we are suspecting APML in your case and you need treatment. What is the treatment option for this patient? The urgent treatment is when you see the patient, you start him with dexamethasone and ATRA with 45 mg per meter squared BT dose. And that's the urgent management for the. And for the chemotherapy, since since he's high risk, I'll go for ATRA plus idarubicin induction chemo. And then I, and I will then console. Yeah. Okay. So, why are you giving dexamethasone? To prevent differentiation syndrome. He's high. He's high risk. So, probably WBC count may increase further and he can go. Okay. Right. Good. The patient says that, doctor, is there any side effect of ATRA that you are giving me? Retinoic acid. So, do you know any side effects of retinoic acid? Teratogenicity and obviously differentiation syndrome. [Music] Mhm. Long QT interval is for E. I don't exactly remember with this ATRA. ATRA can cause electrolyte abnormalities. Electrolyte abnormalities. Yeah. Yeah. And electrolyte abnormalities can lead to prolonged QT interval. So, other than electrolyte abnormalities and differentiation syndrome, do you know any other side effect? In kids, it can cause pseudotumor cerebri with raised intracranial pressure. Hepatotoxicity. Yeah. It can lead to pancreatitis, B necrosis as well. Okay. What is differentiation syndrome? Sorry, my kid is crying. I have to leave. Well, the differentiation syndrome is basically when your white cell count increases, it goes into maturation. And this may lead to, uh, increased, you know, third spacing of the fluid in the form of pleural effusion, weight gain, ascites. Okay. What you would do if the patient develop differentiation syndrome? Dexamethasone and IV fluids. And we need to stop ATRA. Okay. No IV fluids. If you, if the patient has developed a weight gain and infusion. And other than ATRA, do you know anything else, uh, which can develop syndrome? This is the last question. Not really. I don't know. Yeah. So, arsenic, IDH inhibitor, like anidb, gilteritinib, monalisa, they can, they all lead to differentiation syndrome. Okay. All right. So, this was the last case. Many people ask on the the Facebook and on personal messages that they are going for part two exam. We need W as well. That's why I increased the number of questions. Anything else before we stop here? Nothing. Um, can you repeat poor risk, uh, molecular in CLL? Notch1, SF3B1, and which was the third one? It's a BIRC3. Okay. Thank you. So, uh, next, we will meet on Tuesday for part two and Monday for part one. See you later. Take care. Bye-bye everyone.