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Questions posted by pollbot in “NEET SS Clinical Hematology 2020 Telegram Group” will be added here for revision !!
Telegram group https://t.me/joinchat/Rw931hjbVbovJhZBvtni3Q
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1. Which of the following IV iron prepration can not be administered as single large dose of 1000 mg ?
1. Iron carboxymaltose
2. Iron isomaltoside
3. Iron sucrose
4. Low molecular weight iron dextranAnswer = [3] Iron sucrose is the right answer as maximum dose per infusion is 300 mg. Rest others can be administered in higher single doses. Iron carboxymaltose is most commonly used for single high dose administration in india.
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3. A 71-year-old woman presents with thirst, polyuria and back pain. Urgent radiography shows lytic lesions in the spine and vertebral collapse. FBC shows: WBC 9.8 x 109/l, Hb 94 g/l and platelet count 110 x 109/l. The blood film shows increased rouleaux formation and increased background staining. S.Creatinine is 1.2mg/dl and corrected plasma calcium is 3.2 mmol/l. The management should not include ?
/1. Steroids
/2. Hydration
/3. Sodium bicarbonate
/4. Zoledronic acidAnswer = [3] Sodium bicarbonate : Symptomatic patients whose serum calcium level exceeds 12 mg/dL or asymptomatic persons whose level exceeds 14 mg/dL should be immediately and aggressively treated with antihypercalcemic therapy: saline rehydration followed by loop diuretics, calcitonin, bisphosphonates, or denosumab. Glucocorticoids are a treatment option for hypercalcemia in patients with excessive vitamin D or endogenous overproduction of calcitriol secondary to lymphoma.
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4. A 43-year-old woman is receiving induction therapy with daunorubicin and all-trans-retinoic acid (ATRA) for acute promyelocytic leukemia. Eleven days after starting treatment she develops dyspnoea, fever, peripheral oedema and bilateral pleural effusions. Arterial oxygen saturation is found to be reduced. The specific management of this condition includes?
1. Blood cultures followed by broad spectrum antibiotics
2. Stop ATRA and no further readministration of ATRA
3. Leukapheresis
4. Stop ATRA and give corticosteroidsAnswer = [4] The condition describes differentiation syndrome which is seen during APML treatment by ATRA and correct management includes stopping ATRA and to give corticosteroids.
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8. In a Autosomal dominant HS patient the rbc membrane protein electrophoresis will most commonly show deficiency of ?
/1. Spectrin
/2. Ankyrin
/3. Both Ankyrin and Spectrin
/4. Band 3 proteinAnswer: MC genetic defect in AD HS is Ankyrin.
Ankyrin-1 plays a pivotal role in the stabilisation of the membrane, providing the main membrane binding site for the spectrin-based membrane skeleton. Since it links β spectrin to band 3, ankyrin deficiency leads to a proportional reduction in spectrin assembly on the membrane despite normal spectrin synthesis.
So the biochemical phenotype (ie rbc protein electrophoresis) of combined spectrin and ankyrin deficiency is the most common abnormality noted in about 40–65% of patients with hereditary spherocytosis.Note the “catch in Q” genetic defect or biochemical defect is being asked.
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Answer = Osmotic gradient ektacytometry measures RBC deformability under a defined shear stress as a function of suspending medium osmolality. The test is used to evaluate for inherited RBC membrane disorders, which are commonly responsible for hemolytic anemia, differentiating among hereditary spherocytosis (HS), hereditary elliptocytosis (HE) and pyropoikilocytosis (HPP), Southeast Asian ovalocytosis (SAO) and hereditary stomatocytosis (HSt).
Three distinct features of the osmotic gradient ektacytometry profiles are:
[1] Omin: Corresponds to the value of the hypotonic osmolality where 50 percent of the cells hemolyze in an osmotic fragility assay and provides information on the initial surface-to-volume ratio of the cell sample.
[2] EImax: Elongation index reaches a maximum near 300 mOsm/kg, suggesting that the normal red cell deforms optimally at the tonicity to which it is normally exposed. The value of EImax depends mostly on the cytoskeleton mechanics.
[3] Ohyp: The declining portion of the curve (the osmolality value where the cells are at half of the maximum elongation) correlates with the initial MCHC (intracellular viscosity) of the cell sample.
See in Image above !!
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Answer : Image A shows patient (red line) has an increased Omin (decreased surface-to-volume ratio), decreased EImax (decreased deformability), and decreased Ohyp (RBC dehydration), all consistent with the diagnosis of Hereditary Spherocytosis.
Answer : Image B shows patient (red line) has a decreased Omin (increased surface-to-volume ratio), normal EImax (normal deformability), and significantly decreased Ohyp (RBC dehydration), all consistent with the diagnosis of Heredtary Xerocytosis.
For comparison marked plot is given below :
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13. Iron chelation is indicated in transfusion dependent thalassemia when serum ferritin is ?
/1. > 200 microgm/L
/2. > 500 microgm/L
/3. > 1000 microgm/L
/4. > 2000 microgm/LAnswer is > 1000 microgm/L in “Transfusion dependent thalassemia”
Note that Cutoff to start Iron chelation in “Non Transfusion dependent thalassemia” is 800 microgm/L
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14. For iron overload disorders such as thalassemia the normal value of Liver iron concentration as measured by Liver MRI is taken as Values less than ??
/1) 3 mg/g dry wt of liver
/2) 5 mg/g dry wt of liver
/3) 7 mg/g dry wt of liver
/4) 10 mg/g dry wt of liverAnswer = Correct answer is Less than 3 mg/g dry wt of liver which is taken as cutoff for stopping iron chelation in thalassemia patients.
Note in normal healthy individuals the iron uncommonly exceeds a level of 2 mg/g dry wt of liver.
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16. In newborn screening program detection of Hb Barts in a range of 20-25% is suggestive of ?
[1] HbH disease
[2] Alpha thal silent carrier
[3] Alph thal trait
[4] Hb Barts hydrops fetalisAnswer = [1] HbH disease
HPLC at birth in alpha thal syndromes.
*Hb Bart’s hydrops fetalis syndrome: Hb Bart’s > 80%, a variable amount of Hb Portland and HbH present, No HbA
*HbH disease: HbH > 20% at birth
*α-thalassemia trait: Hb Bart’s in newborns 4-10% may be up to 20 %
*α-thalassemia silent carrier: Hb Bart’s in newborns is up to 2%
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18. An iron overload disorder presenting in adulthood with evidence of microcytic anemia, diabetes, peripheral retinal degeneration, dystonia, dementia, or dysarthria is s/o
1. Haemochromatosis type 3
2. Aceruloplasminemia
3. Juvenile haemochromatosis
4. Classical haemochromatosisAnswer = Aceruloplasminemia
Neurological expression is a key feature of the disease. Hereditary Aceruloplasminemia is the sole form of adult genetic iron overload in which excessive iron deposition occurs in the brain. Movement disorders can be present as well as psychiatric symptoms. Retinal degeneration is one of the consequences of the disease. -
19. X linked sideroblastic anemia is most common form of congenital sideroblastic anemia. The anemia in this disorder responds to :-
1. High dose pyridoxine
2. Low dose pyridoxine
3. High dose hydroxyurea
4. Low dose hydroxyureaAnswer = High dose pyridoxine
In more than half of the patients with XLSA, the anemia responds to high doses of pyridoxine. An initial dose of pyridoxine may be 50–100 mg, albeit higher doses have been reported and lower maintenance doses for responsive individuals may be effective. -
20. X linked sideroblastic anemia is caused by mutation in
[1] ALAS2
[2] ALAS1
[3] SLC25A38
[4] SLC19A2Answer = [1] ALAS2
X-linked sideroblastic anemia (XLSA) is the most common of the congenital SAs caused by mutation in Erythroid 5-aminolevulinate synthase (ALAS2) gene. -
21. Methyl Malonic Acid is raised in deficiency of ?
1. Vitamin B12
2. Folate
3. Both Vitamin B12 and Folate
4. None of these22. Elevated homocysteine is seen in deficiency of ?
1. Both Vitamin B12 and Folate
2. Vitamin B12
3. Folate
4. None of these23. Most sensitive for detection of Vitamin B12 deficiency is ?
1. Increased MMA
2. Low serum vitamin B12
3. Presence of clinical symptoms
4. Increased HomocysteineAnswer: Correct Answers are option [1] for Q 21, 22, 23
MMA (serum/urine) is increased only in def of B12 whereas Homocysteine is raised in various conditions including deficiency of B12 as well as Folate.
MMA is most sensitive test for detection of B12 deficiency.
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24. HoloTC (Holotranscobalamin) measures which of the following ??
1. Active B12
2. Inactive B12
3. Total B12
4. None of theseAnswer = [1]
When B12 deficiency is suspected, several circulating biomarkers can be used to confirm or dismiss the diagnosis.These markers include two direct markers (i.e., total B12 and active B12, which is referred to as holotranscobalamin (HoloTC)) and two metabolic markers (i.e., homocysteine (Hcy) and methylmalonic acid (MMA).
The determination of total B12 relies on the integral measurement of two B12 fractions:
[1] Biologically active HoloTC (i.e., B12 bound to transcobalamin)
[2] Biologically inactive holohaptocorrin (i.e., B12 bound to haptocorrin) -
25. Which of the following is true combination of causes leading to elavated Homocysteine (Hcy) ?
1. Deficiency of B12, Folate, Niacin
2. Deficiency of B12, Folate, B6
3. Deficiency of B12, Folate, Riboflavin
4. Deficiency of B12, Niacin, RiboflavinAnswer = [2] Homocysteine (Hcy)accumulates during B12 deficiency because of the diminished activity of methionine synthase, but Hcy can also increase due to folate deficiency, vitamin B6 deficiency, thyroid dysfunction, age, gender, and decreased glomerular filtration rate (GFR)
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26. Which of the following is not a cause of acquired sideroblastic anemia ?
1. Copper poisoning
2. Lead poisoning
3. Copper deficiency
4. Isoniazid27. Which of the following is not true for paroxysmal cold hemoglobinuria ?
1. Postinfectious PCH doesn’t recurr
2. IgM against P antigen
3. Mostly postinfectious
4. IgG against P antigen28. Which of the following G6PD variant leads to chronic non spherocytic hemolytic anemia ?
1. Class I variant
2. Class II variant
3. Class III variant
4. Class IV variant -
Answers
26. Answer is [1]
Secondary causes of Sideroblastic Anemia (SA) include lead poisoning, medications which interfere with pyridoxine metabolism, and copper deficiency. Drugs that have been associated with the development of SA include ethanol, isoniazid, pyrazinamide, cycloserine, chloramphenicol, busulfan, melphalan, linezolid, and D-penicillamine. Copper deficiency is most often caused by malabsorption syndromes, total parental nutrition not supplemented with copper, or bowel resections. Overexposure to zinc can also lead to a deficiency of copper due to sequestration of copper in the intestinal epithelium and inhibition of copper absorption.Note >> Patients with copper deficiency also commonly develop neurologic symptoms in addition to the SA.
27. Answer is [2]
Paroxysmal cold hemoglobinuria (PCH) in children is a postinfectious disease which typically occurs after viral infections. The IgG antibody is directed against the P-antigen. Postinfectious PCH has no tendency to recur, in contrast to syphilis-associated PCH.28. Answer is [1]
Some G6PD variants (class 1 variants) cause chronic (not episodic) hemolysis, which can be called “chronic nonspherocytic hemolytic anemia.” With severe G6PD deficiency (class 2 variants), the anemia is often episodic and may be severe and life threatening (e.g., favism). -
29. Which of the following is not true for bernard soulier syndrome ?
1. Autosomal dominant
2. Macrothrombocytopenia
3. Adhesion defect
4. GPIb-IX-VAnswer = [1] The Bernard-Soulier syndrome (BSS) and Glanzmann thrombasthenia (GT) are rare autosomal recessive disorders of platelet adhesion and aggregation, respectively, and present as mucocutaneous bleeding in infancy or childhood. The BSS is due to deficiency or dysfunction of the platelet membrane receptor for VWF, the GPIb-IX-V complex.
30. Which of the following is not true for gray platelet syndrome ?
1. Autosomal recessive
2. Mild to moderate bleeding
3. Microthrombocytopenia
4. Alpha granule deficiencyAnswer = [3] The gray platelet syndrome is a rare autosomal recessive disorder due to platelet α-granule deficiency that causes mild to moderate bleeding, moderate macrothrombocytopenia, and platelets that have a gray appearance on Wright-stained blood smears.
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31. The value of vWF:RCO/ vWF:Ag ratio taken at cutoff to define vWD functional defect is ?
[1] 0.6
[2] 0.2
[3] 0.4
[4] 0.8Answer = 0.6 if vWF:RCO/ vWF:Ag ratio is 0.6 or less, then Type II vWD is a possibility and Type I is ruled out.
32. Low-dose ristocetin-induced platelet aggregation (LD-RIPA) will be positive in ?
[1] vWD type 2B and platelet-type vWD
[2] vWD type 2B
[3] vWD type 2B and vWD type 2M
[4] vWD type 2MAnswer = [1] vWD type 2B and platelet-type vWD both will show hyperresponsive ness to Low Dose Ristocetin.
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34. FEIBA is a factor bypass agent ie hemostatic agent used in hemophilia patients with inhibitors. Its components are ?
[1] Factor II, VII
[2] Factor II, VII, IX
[3] Factor II, VII, IX, X
[4] Factor II, VII, VIII, IXAnswer = [3] Factor II, VII, IX, X
FEIBA contains mainly non-activated factors II, IX, and X and mainly activated factor VII. It contains approximately equal unitages of factor VIII inhibitor bypassing activity and prothrombin complex factors.Bypassing agents are presently the standard of care for the treatment of bleeding episodes in patients with hemophilia and high‐titer inhibitors and are also used for bleed prevention. Bypassing agents available to patients are activated prothrombin complex concentrates recombinant factor VIIa and emicizumab (a bispecific antibody that mimics the function of FVIIIa in the intrinsic Xase complex).
Bypassing agents have been the primary therapeutic option for hemophilia patients with high responding inhibitors (titers ≥ 5.0 Bethesda Units). -
35. Which of the following is not a factor bypass agent. Factor bypass agents are standard of care for bleeding hemophilia pateints with inhibitor ?
[1] FEIBA
[2] rFVII
[3] Emicizumab
[4] IdracizumabAnswer = [4] Idracizumab
Idarucizumab, sold under the brand name Praxbind, is a monoclonal antibody used as a reversal agent for dabigatran. -
36. In the image below shows gel card test for PNH. The patients sample is put into tubes 4,5 and 6 (from left to right). The gel card test shows that patient:-
[1] Has PNH
[2] Doesn’t have PNH
[3] Inconclusive for PNH
[4] None of theseAnswer = [1] Has PNH
Explanation:
[Note the tube 1,2,3 From left to right which is done by using Blood from Normal person] Positive reactions of 3+ to 4+ (agglutinated cells forming a red line on the surface of the gel) indicate a normal red cell population with the presence of the corresponding DAF and MIRL antigens. This indicates a negative result for PNH and the PNH-ctl microtube must show a negative reaction (a compact button of cells on the bottom of the microtube).[Note the tube 4,5,6 From left to right which is done by using Blood from a PNH Patient] Negative reactions indicate the absence of the corresponding DAF and MIRL antigens. Cells lacking CD55 or CD59 do not agglutinate but form pellets at the bottom of the microtube. This indicates a positive result for PNH.
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37. Which of the following is true for routine antenatal anti-D prophylaxis in D negative pregnant mothers to prevent isoimmunisations ?
[1] 125 IU at 28 and 34 weeks of gestation
[2] 250 IU at 28 and 34 weeks of gestation
[3] 500 IU at 28 and 34 weeks of gestation
[4] 1000 IU at 28 and 34 weeks of gestationAnswer = [3]
All D negative pregnant women who have not been previously sensitised should be offered routine antenatal prophylaxis with anti‐D Ig (RAADP) either with a single dose regimen at around 28 weeks, or two‐dose regimen given at 28 and 34 weeks
(A) Two‐dose regimen = a minimum dose of anti‐D Ig 500 IU is recommended at 28 and 34 weeks.
(B) Single dose regimen = 1500 IU should be administered between 28 and 30 weeks. The single dose regimen may be more cost effective potentially enabling better compliance and providing logistic benefits.38. Which of the following is not used for estimation of fetomaternal hemorrhage (FMH) ?
[1] Kleihauer test
[2] Liley chart
[3] Flow cytometry based
[4] None of these39. Which of the following test is used to estimate fetal anemia in Rh isoimmunised pregnancy ?
[1] Amniocentesis and Liley Chart
[2] Middle cerebral artery flow
[3] Both of these
[4] None of the mentioned methodsAnswer 38 = [2]
Answer 39 = [3]
Kleihauer test is based on resistance of fetal Hb to alkali or acid denaturation as compared to adult Hb and is used to estimate fetal blood in maternal circulation ie it estimates FMH. This can also be done using flow cytometry method.
However Liley chart is used to estimate amount of fetal anemia in already isoimmunised pregnancy. Note that it needs repeated amniocentesis. Non invasive method for estimation of fetal anemia is by peak systolic velocity of middle cerebral artery. -
40. Which of the following is least likely to be positive for EBV ?
[1] Nodular Lymphocyte Predominant HL
[2] Mixed cellularity CHL
[3] Nodular Sclerosis CHL
[4] Lymphocyte depleted CHL41. Bone marrow involvement in Hodgkins Lymphoma is seen in what % of patients ?
[1] 5%
[2] 10%
[3] 20%
[4] 50%42. Brentuximab vedotin is antibody drug conjugate directed against CD30 and its common adverse effect is :-
[1] Nephropathy
[2] Neuropathy
[3] Pneumonitis
[4] Colitis43. Nivolumab used in relapse refractory Hodgkins Lymphoma is directed against ?
[1] PD-1
[2] CD15
[3] CD30
[4] PDL-1Correct ☑️ Answers are:-
40 = [1] NLPHL is least likely to be positive for EBV (<5%).
41 = [1] Bone marrow involvement in HL is seen in about 5% of cases.
42 = [2] BV related Neuropathy is seen in upto 50-60 % of the patients.
43 = [1] Nivolumab and Pembrolizumab are anti anti PD1 antibodies used in relapse refractory HLs.
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44. Which of the following statements regarding the use of Anti-Thymocyte globulin (ATG) in aplastic anemia are correct?
[1] Rabbit ATG is preferred over horse ATG
[2] The standard dose is 40 mg/Kg/day for 4-5 days
[3] It is the therapy of choice in children with aplastic anemia
[4] Lymphocytosis is usually associated with ATG therapy45. Which of the following is not used in used in treatment of Aplastic anemia ?
[1] Cyclosporine
[2] Ruxolitinib
[3] Eltrombopag
[4] Both B and C46. In a newly diagnosed case of Aplastic anemia the Hb is 6.5, TLC is 1200 / micro litres and neutrophil were 10% in the differential count and Platelet count is 15000 / micro litres. The Aplastic anemia will be classified as ?
[1] Non Severe AA
[2] Severe AA
[3] Very Severe AA
[4] Inadequate info47. “Triple Therapy” in Aplastic Anemia is referred to as combination of ?
[1] ATG + Cyclosporine + Danazol
[2] ATG + Eltrombopag + Danazol
[3] ATG + Cyclosporine + Eltrombopag
[4] Allo HSCT + Cyclosporine + Eltrombopag -
Answers for Q NO 44-47
44 = [2]
Antithymocyte globulin (ATG) is an antibody preparation derived from rabbits or horses hyperimmunized with human thymocytes, which is used to prevent or treat acute cellular rejection after solid organ transplantation and as a therapy of acute aplastic anemia. Antithymocyte globulin is a hyperimmune globulin preparation made from plasma of rabbits or horses that have been immunized with human thymocytes or T cells. ATG is given by infusion only and leads to a rapid decrease in circulating T cells and lymphopenia.
Brand Names = Thymoglobulin (rabbit ATG) and Atgam (horse ATG).
Rabbit ATG is more potent than horse ATG and is used to reduce acute Graft versus Host (aGVH) disease in recipients receiving ALLO HSCT.
In aplastic anemia Horse ATG is preffered over rabbit ATG.
The standard dose of horse ATG in APLASTIC ANEMIA is 40 mg/Kg/day for 4-5 days.45 = [2]
46 = [3]
The modified Camitta criteria are used to assess severity of AA (If Absolute neutrophil count in diagnosed AA patient is less than 200 / micoro litre than it is called as Very severe AA (See image below)
47 = [3] ATG + Cyclosporine + Eltrombopag
Triple Therapy in Aplastic anemia consists of two immunosuppressive agents ie ATG + CYCLOSPORINE along with Eltrombopag (stem cell stimulant) -
48. Which of the following inherited bone marrow failure syndrome is associated with pulmonary fibrosis ?
[1] Fanconi Anaemia
[2] Dyskeratosis Congenita
[3] Shwachman Diamond syndrome
[4] Severe Congenital Neutropenia49. Which of the following is NOT seen in diamond blackfen anemia ?
[1] Short stature
[2] Hypotelorism
[3] Abnormal thumbs
[4] Cardiac Septal defect50. Which of the following bis NOT true for Fanconi Anemia ?
[1] Mostly AR inheritance
[2] Chromosomal breakage analysis positive
[3] 50% patient progress to MDS/AML if untreated.
[4] Physical stigmata absent in upto 30% pateint. -
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Q51-60 = Based on adverse events of chemotherapeutic agents !
51. Which of the following is not a adverse event with L-Asparginase administration ?
[1] Pancreatitis
[2] Hepatitis
[3] Neuritis
[4] Hypersensitivity52. Which of the following is implicated in increased thrombotic risk in ALL induction therapy ?
[1] L-Asparginase
[2] Prednisolone
[3] Both A and B
[4] None of these53. Major dose limiting toxicity of vincristine ?
[1] Neutropenia
[2] Thrombocytopenia
[3] Neurotoxicity
[4] Diarrhoea54. Which of the following is implicated in cardiotoxicity ?
[1] Vinblastine
[2] Doxorubicin
[3] L-Asparginase
[4] All of these55. PRES during ALL induction therapy is attributed mainly as adverse effect of ?
[1] Prednisolone
[2] L-Asparginase
[3] Doxorubicin
[4] Vincristine -
Answer 51 = [3]
Drug = L-Asparginase
Source = Purified from Escherichia coli and/or Erwinia chrysanthemi.
Mechanism = Tumor cells lack asparagine synthetase and thus require exogenous sources of L-Asparagine. L-Asparaginase hydrolyzes circulating L-Asparagine to aspartic acidand ammonia. Depletion of the essential amino acid L-Asparagine results in rapid inhibition of protein synthesis. Cytotoxicity of drug correlates well with inhibition of protein synthesis.
Adverse reactions:-
Hypersensitivity reaction.
Mild elevation in LFTs/Hepatitis.
Increased risk of both bleeding and clotting (Hypercoagulability).
Pancreatitis develops in up to 10% of patients.
Severe neurotoxicity resembles ammonia toxicity (rare) – Not Neuritis
NOTE>>> Contraindicated in patients with either active pancreatitis or a history of pancreatitis. If pancreatitis develops while on therapy, L-Asparaginase should be stopped immediately.Answer 52 = [3] Both (see above for L-Asp)
Corticosteroids also induce hypercoagulable state. -
Answer 53 = [3] Neurotoxicity
Vincristine
Source = Plant alkaloid derived from the periwinkle plant Catharanthus roseus.
Mechanism = Cell cycle–specific with activity in the mitosis (M) phase. Inhibits tubulin polymerization, disrupting formation of microtubule assembly during mitosis. This results in an arrest in cell division, ultimately leading to cell death.
Adverse events:-
Neurotoxicity = Most commonly observed dose-limiting toxicity. Clinical manifestations are variable, and include peripheral neuropathy (paresthesias, paralysis, and loss of deep tendon reflexes), autonomic nervous system dysfunction (orthostasis, sphincter problems, and paralytic ileus), cranial nerve palsies, ataxia, cortical blindness, seizures, and coma. Bone, back, limb, jaw, and parotid gland pain may also occur.
Constipation, abdominal pain, and paralytic ileus are common. -
Answer 54 = [2] Dxorubicin
Doxorubicin (Anthracycline)
Myelosuppression = Dose-limiting toxicity with leukopenia more common than thrombocytopenia or anemia.
Cardiotoxicity = Cummulative Dose-limiting toxicity
[1] Acute form presents within the first 2–3 days as arrhythmias and/or conduction abnormalities, EKG changes, pericarditis, and/or myocarditis.
[2] Chronic form results in a dose-dependent, dilated cardiomyopathy associated with congestive heart failure. Risk increases when cumulative doses are greater than 450 mg/m2.
The basic mechanisms of cardiotoxicity may involve direct pathways for reactive oxygen species generation and topoisomerase 2 as well as other indirect pathways. -
Answer 55 = [1] Prednisolone
Posterior reversible encephalopathy syndrome (PRES) is a severe, life-threatening neurological disorder clinically presenting with various symptoms such as headache, visual disturbances, and epileptic seizures.
PRES is characterized by usually bilateral cerebral (parieto-occipital lobe) vasogenic edema in computed tomography (CT) and magnetic resonance imaging (MRI) scans and occurs most commonly in patients with uncontrolled hypertensive blood pressure.
Note >>> Greater than 90% of patients demonstrate involvement of the parietooccipital lobes, but lesion can also be present in the frontal lobe basal ganglia, cerebellum, and brainstem.
Steroids directly or indirectly causing acute HTN may lead to PRES. -
56. Cerebellar toxicity is associated with ?
[1] Cytosar (ARA C)
[2] Cyclophosphamide
[3] Idarubicin
[4] All of these57. Which of the following is done to prevent High Dose Methotrexate Toxicity ?
[1] Leucovorin Rescue
[2] Urine Alkalinisation
[3] Both of the above
[4] None of these58. Glucarpidase is an FDA-approved intravenous drug for the treatment of elevated levels of
[1] Cytosar
[2] Cyclophosphamide
[3] Methotrexate
[4] Doxorubicin59. Dose limiting toxicity of Cisplatin is ?
[1] Nephrotoxicity
[2] Myelosupression
[3] Neurotoxicity
[4] Ototoxicity60. Pancreatitis is associated with which of the following ?
[1] Doxorubicin
[2] L-Asparginase
[3] Vincristine
[4] Cyclophosphamide -
Answer 56 = [1] = CYTOSAR (ARA C) = Cytarabine
Cytarabine
Source = Deoxycytidine analog originally isolated from the sponge Cryptotethya crypta.
Mechanism = Incorporation of ara-CTP into DNA resulting in chain termination and inhibition of DNA synthesis and function. Cell cycle–specific with activity in the S-phase.
Toxicity:-
Myelosuppression is dose-limiting.
Neurotoxicity = Cerebellar ataxia, lethargy, and confusion. Neurotoxicity develops in up to 10% of patients. Onset usually 5 days after drug treatment and lasts up to 1 week. In most cases, CNS toxicities are mild and reversible. Risk factors for neurotoxicity include high-dose therapy, age older than 40, and abnormal renal and/or liver function. -
Answer 57 = [3]
Answer 58 = [3]
Methotrexate
Cell cycle–specific antifolate analog, active in S-phase of the cell cycle.Mechanism:- Antifolate
Inhibition of dihydrofolate reductase (DHFR) resulting in depletion of critical reduced folates.
Inhibition of de novo thymidylate synthesis.
Inhibition of de novo purine synthesis.
Incorporation of dUTP into DNA resulting in inhibition of DNA synthesis and function.Toxicity:-
Myelosuppression is dose-limiting toxicity
Mucositis can also be dose-limiting toxicity.
Renal toxicity results from the intratubular precipitation of methotrexate and its metabolites.
Poorly defined pneumonitis characterized by fever, cough, and interstitial pulmonary infiltrates.Preventing toxicity:-
[1] Hydration = With high-dose therapy it is important to vigorously hydrate the patient with with NS and Sodium bicarbonate should be included in the IV fluid to ensure that the urine pH is greater than 7.0 at the time of drug infusion and ideally for up to 48–72 hours after drug is given.
[2] Rescue with leucovorin or L-leucovorin, the active isomer of leucovorin, should begin at 24 hours after drug infusion.
[3] Glucarpidase (Antidote) is indicated for the treatment of toxic plasma methotrexate concentrations in patients with delayed drug clearance due to impaired renal function. -
Answer 57 = [3]
Answer 58 = [3]
Methotrexate
Cell cycle–specific antifolate analog, active in S-phase of the cell cycle.Mechanism:- Antifolate
Inhibition of dihydrofolate reductase (DHFR) resulting in depletion of critical reduced folates.
Inhibition of de novo thymidylate synthesis.
Inhibition of de novo purine synthesis.
Incorporation of dUTP into DNA resulting in inhibition of DNA synthesis and function.Toxicity:-
Myelosuppression is dose-limiting toxicity
Mucositis can also be dose-limiting toxicity.
Renal toxicity results from the intratubular precipitation of methotrexate and its metabolites.
Poorly defined pneumonitis characterized by fever, cough, and interstitial pulmonary infiltrates.Preventing toxicity:-
[1] Hydration = With high-dose therapy it is important to vigorously hydrate the patient with with NS and Sodium bicarbonate should be included in the IV fluid to ensure that the urine pH is greater than 7.0 at the time of drug infusion and ideally for up to 48–72 hours after drug is given.
[2] Rescue with leucovorin or L-leucovorin, the active isomer of leucovorin, should begin at 24 hours after drug infusion.
[3] Glucarpidase (Antidote) is indicated for the treatment of toxic plasma methotrexate concentrations in patients with delayed drug clearance due to impaired renal function. -
Answer 59 = [1]
CISPLATIN
Class = Platinum analog
Mechanism = Covalently binds to DNA with preferential binding to the N-7 position of guanine and adenine to produce cross-links.
Toxicity
Nephrotoxicity = Dose-limiting toxicity in up to 35%–40% of patients. Effects on renal function are dose-related and usually observed at 10–20 days after therapy.
Neurotoxicity usually in the form of peripheral sensory neuropathy. Paresthesias and numbness in a classic stocking-glove pattern. Tends to occur after several cycles of therapy and risk increases with cumulative doses.Prevention of Nephrotoxicity
Patients must be hydrated before, during, and postdrug administration. -
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Q61-70 Basics of stem cell transplantation.
61. Which of the following is a low expression HLA antigen ?
[1] HLA A
[2] HLA B
[3] HLA DRB1
[4] HLA DQB162. 8/8 Match Donor excludes matching at which of the following HLA Loci ?
[1] HLA A
[2] HLA B
[3] HLA DRB1
[4] HLA DQB163.10/10 Match Donor excludes matching at which of the following HLA Loci ?
[1] HLA A
[2] HLA DRB1
[3] HLA DQB1
[4] HLA DPB1Answers
61 = [4]
62 = [4]
63 = [4]
HLA matching is the most relevant factor when choosing a donor.
HLA antigens are either “high expression” such as HLA‐A, B, C (class I), DRB1 (class II), or “low expression” such as DQB1, DPB1, and DRB3/4/5 (all class II).
The “high expression” antigens play a pivotal role in the transplant setting because of high antigen density on the cells.
HLA matching at the allele level of HLA‐A, B, C and DRB1 (8 alleles) is done to see for 8/8 match.
HLA matching at the allele level of HLA‐A, B, C DRB1 and DQB1 (10 alleles) is done to see for 10/10 match.Read Basics of HLA Typing here [READ]
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64. In Allo HSCT the donor derived T cells mediate:-
[1] Engraftment
[2] Immune reconstitution
[3] Graft vs host disease
[4] All of theseAnswer = [4]
The CD34+ cell dose is the primary determinant of successful engraftment. However, other components (in particular, the Tcells) play pivotal roles in transplant outcomes.T-cells mediate the following four immunological processes:
1 Engraftment
2 Immune reconstitution to prevent infection
3 Graft versus tumor (GvT) effect to prevent relapse
4 Graft versus host disease (GvHD) -
65. Which of the following can be a source of hematopoietic stem cells for HSCT ?
[1] Bone marrow
[2] Peripheral blood
[3] Umbilical cord blood
[4] All of these66. Fastest or earliest engraftment is seen with which of these sources of hematopoietic stem cells ?
[1] Bone marrow
[2] Peripheral blood
[3] Umbilical cord blood
[4] Same time to engraftment in all theseAnswers
65 = [4]
66 = [2]
Initial allogeneic transplants were done using bone marrow grafts. However the currently used sources of hematopoietic grafts are:
1 Peripheral blood (PB)
2 Bone marrow (BM)
3 UCBNOTE >> PB grafts are NOW more commonly used. Main advantages of using PB grafts are faster and more secure and early engraftment and immune reconstitution, and less relapses (via GvT effect). However chronic GvHD (cGvHD) rates are higher as compared to BM grafts.
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67. In BMT setting, recipient with blood group O and donor with blood group A, B or AB is regarded as ?
[1] Minor mismatch
[2] Major mismatch
[3] Compatible
[4] None of theseAnswer = [2]
ABO blood type matching is not required for a successful transplant. However, ABO mismatching can result in complications.
Donor/recipient matching are either compatible or mismatched (major, minor or bi‐directional).
Major and bi‐directional (major and minor) mismatches are best avoided, if possible.
ABO major mismatch carries risk of two complications:
[1] Acute hemolysis
[2] Delayed erythroid engraftment and pure red cell aplasiaABO minor mismatch carries risk of following complications:
[1] Passenger lymphocyte syndrome (PLS)
[2] Delayed hemolysis -
68. Target CD34+ ve cells in peripheral blood (PB) graft in Allo HSCT is ?
[1] >/= 4 X 10^6/kg
[2] >/= 6 X 10^6/kg
[3] >/= 8 X 10^6/kg
[4] >/= 10 X 10^6/kgAnswer = [1]
The recommended CD34+ cell dose in a PB graft is at least 4×10^6 CD34+ cells/kg of recipient weight, while a dose of<2×106 CD34+ cells/kg is discouraged to avoid risk of engraftment failure.Also remember = The recommended cell dose in a BM graft is 4 X 10^8 TNC((total nucleated cells)/kg of recipient weight for hematologic malignancies.
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69. Which if the following is best donor for a CMV seronegative recipient ?
[1] CMV Seropositive
[2] CMV Seronegative
[3] Both have same outcome
[4] None of the aboveAnswer = [2]
CMV remains dormant in leukocytes and can be re‐activated when the host becomes immunocompromised. For a CMV negative patient, ideally, a CMV negative donor should be used, whenever possible to prevent CMV disease in post transplant period.
For patients who are CMV positive, either CMV negative or positive donor can be used. Some centers prefer to use CMV positive donors for CMV positive patients
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70. Which of the following factor has impact on transplant outcomes ?
[1] CMV status
[2] Gender of donor
[3] Age of donor
[4] All of theseAnswer = [4]
HLA matching is the most relevant factor when choosing a donor. However, the following factors have also role transplant outcomes
1 CMV status of the donor and patient
2 ABO blood matching
3 Age/Gender of the donor
4 Weight discrepancy between the donor and the patient -
71. Glucksberg-Seattle criteria (GSC) is used for grading of :-
[1] Acute GVHD
[2] Chronic GVHD
[3] Engraftment syndrome
[4] Graft vs Leukemia effectAnswer = [1] Acute graft-versus-host disease (AGVHD) severity is usually graded (grades 0-IV) by the pattern of organ involvement using the classic Glucksberg-Seattle criteria (GSC).
NOTE >> International Bone Marrow Transplant Registry (IBMTR) developed a new Severity Index by regrouping the patterns of organ involvement into five Indexes (0-D) that appeared more predictive of transplant-related mortality (TRM) and transplant failure (TF, relapse or TRM).72. Acute GVHD grading and staging in based on all of the following EXCEPT?
[1] Liver enzyme levels
[2] Serum bilirubin
[3] % of skin involvement
[4] Daily stool volumesAnswer = [1] Acute graft‐versus‐host disease (GvHD) is a frequent complication of allogeneic haemopoietic stem cell transplantation (HSCT) and donor lymphocyte infusions (DLI). First‐line treatment of acute GvHD is based on corticosteroids, and produce sustained responses in 50–80% of patients depending on the initial severity.
The original grading system for acute GvHD was proposed by Glucksberg et al (1974) and identified five categories of patients (grades 0, I, II, III, IV). It is known as the Glucksberg‐Seattle criteria (GSC) and it is based on the degree of skin, liver and gut involvement (skin rash, total serum bilirubin and diarrhoea volume), together with a subjective assessment of clinical status.73. Ann Arbor biomarker risk score for Acute GVHD is based on estimation of levels of :-
[1] TNFR1
[2] REG3 Alpha
[3] ST2
[4] All of theseAnswer = [4] All of these: Ann Arbor biomarker risk score for Acute GVHD is based on concentrations of three recently validated biomarkers (TNFR1, ST2, and REG3α) to create an algorithm that computed the probability of NRM six months after GVHD onset for individual patients.
74. Drug of choice (First line agent) for treatment of acute GVHD is ?
[1] Steroid
[2] Methotrexate
[3] Ruxolitinib
[4] CyclosporineAnswer = [1] Acute graft‐versus‐host disease (GvHD) is a frequent complication of allogeneic haemopoietic stem cell transplantation (HSCT) and donor lymphocyte infusions (DLI). First‐line treatment of acute GvHD is based on corticosteroids, and produce sustained responses in 50–80% of patients depending on the initial severity.
75. Drug of choice (First line agent) for treatment of chronic GVHD is ?
[1] Cyclosporine
[2] Steroid
[3] Ruxolitinib
[4] Methotrexate
Answer = [B] Steroid -
Q76.
Answer = is Factor VIII deficiency
For details of mixing studies and how to use aged/adsrobed plasma: Read Here (Click) -
77. Which of the following Hb types coelute with HbA2 in HPLC ?
[1] HbE
[2] HbD Iran
[3] Hb Lepore
[4] All of these
Answer = [4] All of theseHb E, Hb D Iran and Hb Lepore all coelute with HbA2.
The table below shows conditions in which HBA2 window will show increased area or increased concentration.
NOTE if HbA2 is =/> 10% then diagnosis other than Beta Thal trait should be considered
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78. In Hb Electrophroresis (Alkaline gel) the band of Hb Lepore coincides with ?
[1] HbS
[2] HbD
[3] HbG
[4] All of the above
Answer = [4] All of the aboveHemoglobin electrophoresis
Cellulose acetate at alkaline pH is initial procedure.
Separation is largely determined by electrical charge.
At this pH Hb is negatively charged and moves toward the positively charged anode.CO MIGRATING Hb
[1] Group A – A, M, some unstable Hbs
[2] Group F – F
[3] Group S – S, D, G, Lepore
[4] Group C – C, E, A2, O Arab
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Answer 80 = [B] Factor H
Answer 81 = [B] EculizumabAtypical HUS
Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by intravascular hemolysis, thrombocytopenia, and acute kidney failure.
Hemolytic uremic syndrome (HUS) is one of the disease processes that belong to thrombotic microangiopathies (TMAs)CLASSIFICATION
[1] Typical HUS (ie, STEC-HUS) follows a gastrointestinal infection with STEC
[2] aHUS is associated primarily with mutations or autoantibodies leading to dysregulated complement activation.Note = Among the 30% to 50% of patients with aHUS who have no detectable complement defect, some have either impaired diacylglycerol kinase ε (DGKε) activity, cobalamin C deficiency, or plasminogen deficiency.
In aHUS, mutations have been reported in 5 central complement proteins [Factor H, MCP (CD46), Factor I, C3, Factor B]. Most of these mutations lead to impaired regulation of alternative pathway activation. Most commonly involved gene is of Factor H (25-30% of cases)
TREATMENT OPTIONS
Historically, aHUS had a poor prognosis with about 50% of all patients progressing to end-stage renal disease (ESRD).Prior to the introduction of eculizumab, plasma infusion or plasma exchange (PI/PE) was the standard of care by supplying the normal/functional complement inhibitory molecules, but they do not address the underlying pathology.
Eculizumab, a terminal complement inhibitor that binds to C5 with high affinity, blocks the generation of proinflammatory C5a and C5b-9. Approved in 2011 in the United States, it is the drug of choice for the treatment of aHUS; immediate treatment with eculizumab is strongly recommended when the diagnosis of aHUS is confirmed.
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