Hema 🩸

Question 1

Which of the following genetic abnormalities is associated with acute promyelocytic leukemia?

a. T15;17
b. Inv 16
c. 16:16
d. 8:23

Answer 1

A. T15:17

Subtypes of AML are recognized due to the presence or absence of specific, recurrent cytogenetic, and/or genetic abnormalities. For example, the diagnosis of acute promyelocytic leukemia (APL) is based on the presence of either the t(15;17)(q22;q12) cytogenetic rearrangement or the PML-RARA fusion product of the translocation.

Question 2

A 67 year old male with known chronic myeloid leukemia presents to the emergency room for sudden onset severe abdominal pain radiating to the back. His lab workup shows 3x elevated lipase and amylase. Which tyrosine kinase inhibitor is the likely cause of his symptoms?

a. Dasatinib
b. Imatinib
c. Bosutinib
d. Nilotinib

Answer 2

Ans. D. Nilotinib

Question 3

Which infectious agent is associated with the development of lymphoplasmocytic lymphoma?

a. Epstein Barr Virus
b. Cytomegalovirus
c. Hepatitis B virus
d. Hepatitis C virus

Answer 3

Ans. D. Hepatitis C Virus

Question 4

Most common chemotherapeutic regimen for Hodgkin’s Lymphoma

a. ABVD
b. R-CHOP
c. ICE
d. GND

Answer 4

Ans. A. ABVD
The most common chemotherapy regimen used to treat HL in the United States is ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine). This regimen is given every other week, with each cycle including two treatments. In patients with low-risk, or favorable, disease, the use of four to six cycles of ABVD alone, without radiation therapy, results in progression-free and overall survival rates of 88-92% and 97-100%, respectively, at 5-7 years.

R-CHOP (Rituximab, Cyclophosphamide, Vincristine and Prednisone) is first line for non-hodgkin’s lymphoma. ICE (Ifosfamide, Carboplatin and Etoposide) and GND (Gemcitabine, Vinorelbine, Doxorubicin) are used as a salvage chemotherapy.

Question 5

A 64-year-old man is being evaluated for possible plasma cell dyscrasia. A bone marrow biopsy shows 20% clonal plasma cells. Which of the following additional findings fulfills a myeloma-defining event?

a. Serum calcium of 10.8 mg/dL (upper limit of normal 10.5 mg/dL)
b. Serum creatinine of 1.6 mg/dL with eGFR 55 mL/min
c. Hemoglobin of 11.2 g/dL (baseline 13.0 g/dL)
d. Spine MRI shows multiple 6–7 mm focal areas of abnormal marrow signal intensity

Answer 5

Ans. D. Spine MRI shows multiple 6–7 mm focal areas of abnormal marrow signal intensity

Symptomatic Multiple Myeloma
Clonal bone marrow plasma cells or biopsy-proven bony or extramedullary plasmacytomaª and any one or more of the following myeloma-defining events:
• Evidence of one or more indicators of end-organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:

• Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11 mg/dL)
• Renal insufficiency: creatinine clearance <40 mL/min* or serum creatinine > 177 umol/L (>2 mg/dL)
• Anemia: hemoglobin value of >20 g/L below the lower limit of normal, or a hemoglobin value <100 g/L
• Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT°
• Any one or more of the following biomarkers of malignancy:
• Clonal bone marrow plasma cell percentage* ≥60%
• Involved: uninvolved serum free light chain ratio” ≥100
• > 1 focal lesion on MRI studies

Question 6

56-year-old man in the ICU for septic shock from pneumonia begins to have oozing at venipuncture sites and bleeding around his central line. His laboratory results show a platelet count of 68 × 10⁹/L, a markedly elevated D-dimer, a prothrombin time prolonged by 4.5 seconds, and a fibrinogen level of 0.8 g/L. Using the ISTH scoring system for overt DIC, what is this patient’s total score?

a. 3
b. 4
c. 6
d. 7

Answer 6

Ans. C. 6

ISTH Criteria for Overt DIC. For the patient: Platelet Count - 1, Elevated D-dimer - 3, Prolonged PT - 1, Fibrinogen <1 - 6.

Question 7

A 29-year-old woman is brought to the emergency department 36 hours after an intentional ingestion of a large amount of paracetamol. She is confused, jaundiced, and has rapidly worsening encephalopathy. Her labs show: AST 6,800 U/L, ALT 7,500 U/L, INR 6.2, total bilirubin 9 mg/dL, platelets 210 × 10⁹/L, and fibrinogen 230 mg/dL.
The ICU team plans to place a central venous catheter and is concerned about her elevated INR. She is hemodynamically stable, not actively bleeding, and has no signs of DIC. Vitamin K has already been administered without improvement.

Which of the following is the most appropriate transfusion strategy to rapidly correct her coagulopathy prior to the procedure?

a. Fresh frozen plasma (FFP)
b. Cryoprecipitate
c. Four-factor prothrombin complex concentrate (4F-PCC)
d. Platelet transfusion

Answer 7

Ans. C. Four-factor prothrombin complex concentrate (4F-PCC)

Although treatment of bleeding with FFP was the standard approach to correcting hemostasis in patients with liver failure, the use of 4F-PCC is now favored due to lower volume, less increase in portal pressure, reduced risk of circulatory over- load, and other complications associated with FFP transfusion.

Question 8

A 32 year old female with known systemic lupus erythematosus comes in for heavy menstrual losses was advised blood transfusion.

On latest lab tests her hemoglobin was 5.5 g/L.
She had a transfusion reaction during the last admission, manifesting as itching, hives, swollen lips and difficulty breathing and transfusion was stopped. The hematology service requests for an IgA level, which turned out to be low.

Which of the following blood products is the best for this patient?

a. Washed RBC
b. Packed RBC
c. Irradiated PRBC
d. Whole Blood

Answer 8

Ans. A. Washed PRBC

Patients who are IgA deficient (<1% of the population) may be sensitized to this immunoglobulin isotype and may be at risk of anaphylactic reactions associated with plasma transfusion. As a precaution, individuals with severe IgA deficiency should therefore receive, where available, IgA-deficient plasma and washed cellular BCs. Patients who have anaphylactic or repeated allergic reactions to BCs should be tested for IgA deficiency. It should be noted that the importance, or even the reality, of such a transfusion-related allergic risk is currently debated.

Question 9

Which among the following is a cytokine that regulates macrophage and NK-cell activation?

a. IFN-alpha
b. IL-6
c. IFN-gamma
d. TNF-alpha

Answer 9

IFN-gamma attaches to the Type II interferon receptor of T-cells and NK cells to regulate macrophage and NK cell activation. They also induce class II histocompatibility antigens and Th1 T cell differentiation (vs another regulatory cytokine 1L-10, which inhibits differentiation of Th1 helper T cells)

IFN-alpha promotes antiviral activity and stimulates T-cell macrophages. It also has direct antitumor effects and are used therapeutically in viral and autoimmune conditions

TNF-alpha can cause fever, shock, anorexia through enhanced leukocyte cytotoxicity, enhanced NK-cell function, and proinflammatory cytokine induction

Question 10

For patients with systemic mastocytosis, which of the following supportive therapies can be offered to alleviate malabsorption?

a. Aspirin
b. Dexamethasone
c. Oral cromolyn sodium
d. Ranitidine

Answer 10

Ans. B. Dexamethasone

The management of SM is symptom control using a stepwise symptom/sign–directed approach. Medications include an H 1 antihistamine for flushing and pruritus, an H 2 antihistamine or proton pump inhibitor for gastric acid hypersecretion, oral cromolyn sodium for diarrhea and abdominal pain, and occasionally aspirin (in those who are known to be tolerant of NSAIDs) for severe flushing to block biosynthesis of prostaglandin D2.

Question 11

A 20 year old female with known Systemic lupus erythematosus had one abortion at 12 weeks age of gestation with morphologically normal fetus, and high titers of lupus anticoagulant repeated on 2 occasions 12 weeks apart. On review, the patient has already had previous deep vein thrombosis during her previous admission. She is not able to tolerate aspirin due to an allergic reaction. What is an appropriate approach to anticoagulation for this patient?

a. Warfarin alone, to target INR 2.0-3.0
b. Warfarin alone, to target INR 2.5-3.5
c. Warfarin alone, to target INR 3.0-4.0
d. Offer a DOAC, since the previous event was venous thrombosis

Answer 11

Ans. C. Warfarin alone, to target INR 3.0-4.0

Following the first thrombotic event, APS patients should be placed on vitamin K antagonists (VKAs) for life, aiming to achieve an international normalized ratio (INR) ranging from 2.0 to 3.0 in case of an unprovoked venous thrombosis. For patients with arterial thrombosis, the corresponding INR target should be 3.0–4.0 or 2.0–3.0 along with low-dose aspirin (LDA, 75–100 mg daily), depending on the thrombotic/hemorrhagic patient profile.

Question 12

Normal range of hemoglobin

Males
Females

Answer 12

Males: 135–174 g/L
(Anemia <130g/l)
(Polycythemia: >170 or hct >60)

Female: 120-150 g/L
(Anemia <120 g/l)
(Polycythemia >150 or hct >55)

Question 13

In a person whose reticulocyte count is 9%, hemoglobin 7.5 g/dL, hematocrit 23%, and MCV 75, what is the physiologic classification of anemia?

a. Hemolysis
b. Infiltration/fibrosis
c. Thalassemia
d. Drug toxicity

Answer 13

C. Thalassemia

RPI= retic count x (hgb/correctopn factor) / maturation time
= 9 x (7.5/15) / 2
= 2.25

RPI < 2.5 with microcytosis

Question 14

Stages of Iron deficiency

A) iron stores (serum ferritin) decrease but serum iron, TIBC, and red cell morphology are normal

B) iron stores depleted—serum iron decreases, TIBC increases, marrow iron stores absent, TSAT at 15-20%

C) first appearance of microcytic cells, TSAT <10-15%

Answer 14

A) Negative iron balance
B) iron deficiency erythropoiesis
C) Iron deficiency anemia

*absent marrow store: Ferritin <15 ug/L

Question 15

A man with elevated hemoglobin has increased RBC mass and elevated EPO. Arterial oxygen saturation is normal. He is a non-smoker. What is the next diagnostic step?

A. Measure carboxyhemoglobin
B. Measure hemoglobin oxygen affinity
C. JAK2 mutation testing
D. Bone marrow biopsy

Answer 15

B. Measure hemoglobin oxygen affinity

Question 16

Microcytic anemia

A) Iron and TSAT increased, RDW normal, target cells
B) Iron, TSAT and TIBC low, ferritin normal/high
C) iron, TSAT and ferritin low, TIBC high

Answer 16

A) Thalassemia
B) Anemia of inflammation
C) Iron deficiency

Question 17

Orally bioavailable EPO mimetics that act to increase the biological half-life of active hypoxia-inducible factor (HIF

Answer 17

roxadustat

Question 18

Goal pretransfusion hemoglobin in thalassemia

Answer 18

Hgb 9-10.5 g/dl with oral iron chelators (deferasirox and deferiprone, and IV deferoxamine)

Question 19

approved for treatment of transfusion-dependent thalassemia; works by binding transforming growth factor B superfamily ligands and reducing Smad2/3 signaling

Answer 19

Luspatercept

Question 20

Folic acid dose in pregnancy

W/out history of NTD
Prev history of NTD

Answer 20

W/o: 400 ug daily
W/ hx: 5mg daily

Question 21

What is the only acquired intracorpuscular hemolytic anemia?

Answer 21

PNH

Question 22

What is the only inherited extracorpuscular hemolytic anemia?

Answer 22

Familial (atypical) HUS

Question 23

Which feature is NOT common to most patients with hemolytic disorder?

a. Increased MCV, MCH
b. Increased reticulocytes
c. Increased LDH
d. Increased haptoglobin

Answer 23

d. Increased haptoglobin → DECREASED haptoglobin

Question 24

the essential pathophysiologic process common to all HAs

Answer 24

Increased red cell turnover

• gold standard for proving that the life span of red cells is reduced—red cell survival study

Question 25

Young patient with jaundice and gallstones, CBC shows normocytic anemia with MCHC 38 and RDW 16. What is the main diagnostic test?

Answer 25

Osmotic fragility for hereditary spherocytosis MCHC >34 RDW >14 TX: splenectomy at age 4-6 years in severe cases, delay splenectomy until puberty in moderate cases, and avoid splenectomy in mild cases

Question 26

A patient’s PBS shows poikilocytosis with bite cells and Heinz bodies. Which would pose as a definite risk to this patient’s condition? a. Chloroquine b. Sulfasalazine c. Ciprofloxacin d. Dapsone

Answer 26

D. Dapsone G6PD deficiency

Question 27

Characterized by the presence of Donath-Landsteiner antibody

Answer 27

Paroxysmal Cold Hemoglobinuria (PCH)

Question 28

Characteristic MYD88 mutation

Answer 28

Waldenström macroglobinemia

Question 29

Characterized by triad of intravascular hemolysis, pancytopenia and a distinct tendency to venous thrombosis. Usually with hematuria and flow cytometry shows at least 5% of total red cells and at least 20% of total granulocytes are CD59 (-) What drug can be given?

Answer 29

Eculizumab- monoclonal antibody that binds to C5 *Paroxysmal Nocturnal Hemoglobinuria (PNH)

Question 30

Young adult presenting with pancytopenia and hypocellular marrow. PBS shows large erythrocytes and paucity of platelets and granulocytes. BMA shows mainly fat under the microscope with hematopoietic cells occupying <25%. What would be the most common early symptom for this patient?

Answer 30

Bleeding *Aplastic anemia

Question 31

The major prognostic determinant in Aplastic anemia is the blood count. What would define severe disease?

Answer 31

presence of 2 of three parameters: - ANC <500/uL - platelet count <20,000 - corrected reticulocyte count <1% (or absolute reticulocyte count <60,000/uL)

Question 32

Treatment for Aplastic anemia

Answer 32

- stem cell transplant for younger patients with compatible sibling donor If none, immunosuppression is the treatment of choice - standard regimen of ATG + cyclosporine - Eltrombopag as monotherapy for refractory aplastic anemia and in Not effective: Glucocorticoids G-CSF Hematopoietic growth factors

Question 33

In chronic anemia, when should iron chelators, deferoxamine and defarasirox be added to transfusion to avoid secondary hemochromatosis?

Answer 33

50th transfusion

Question 34

Pure red cell anemia with BMA showing red cells aplasia and giant pronormoblasts. What is the cause of the PRCA?

Answer 34

Parvovirus infection *Giant pronormoblast is the cytopathic sign of B19 Parvovirus infection

Question 34

MDS occurs as a late toxicity of cancer treatment. When is the latent period for the ff? DNA topoisomerase inhibitors Busulfan Procarbazine

Answer 34

2 years 5-7 years 5-7 years

Question 35

What are the three situations that cause microcytic erythrocytosis?

Answer 35

- B thalassemia trait (RDW is normal) - Hypoxic erythrocytosis - PV *JAK2 valine replaces phenylalanine

Question 36

Goal hemoglobin and hematocrit levels in PV

Answer 36

Men: Hgb <140; Hct <45% Women: Hgb <120; Hct <42%

Question 37

a phosphodiesterase inhibitor, can reduce the platelet count and, if tolerated, is preferable to hydroxyurea because it lacks marrow toxicity and is also protective against venous thrombosis in PV

Answer 37

Anagrelide

Question 38

In AML, blast count of !20% is required to establish the diagnosis of AML, except for AML with the recurrent genetic abnormalities:

Answer 38

t(15;17) [APL] t(8;21) [Myeloid sarcoma] inv(16) t(16;16)

Question 38

JAK2 inhibitor; Effective in PV withput myelofibrosis who are intolerant or refractory to hydroxyurea; also used for symptomatic splenomegaly

Answer 38

Ruxolitinib

Question 39

Abnormal rod-shaped granules that when present, AML is virtually certain

Answer 39

Auer rods MPO +

Question 40

Induction therapy in AML

Answer 40

Induction with Day 7 and 3. Regimen of cytarabine + anthracycline

Question 41

Defined by presence of BCR/ABL1 found in long arms of chromosome 9 and 22 known as Philadelphia chromosome

Answer 41

CML

Question 42

Which protease is deficient or has decreased activity in the idiopathic type of thrombotic thrombocytopenic purpura (TTP)? (HPIM21 P907) a. ADAMTS13 b. BoNTs c. MAC d. ZmpA

Answer 42

C. MAC

Question 43

Therapeutic options in CML A) TKI with lowest cardiovascular events B) Highest arterio-occlusive events C) Myelosuppression D) Diabetes, pancreatitis

Answer 43

A) Bosutinib B) Ponatinib C) Dasatinib and Omacetaxine mepesuccinate D) Nilotinib

Question 44

How is CNS leukemia diagnosed?

Answer 44

5 or more cells/uL or leukemic blast cells were observed by morphology in cerebrospinal fluid *should receive intrathecal methotrexate at first LP

Question 45

What is the only ALL specific drug?

Answer 45

L-Asparaginase

Question 46

Preferred glucocorticoid on ALL because it penetrates the blood-brain barrier and also acts on resting leukemic blast cells

Answer 46

Dexamethasone

Question 47

What is the most important prognostic factor during therapy in ALL and is the most important parameter for treatment decisions?

Answer 47

MRD Minimal residual disease- detection of residual leukemic cells that are not recognizable by light microscopy

Question 48

One of the only types of leukemia not linked to radiation exposure but one of the most familial-associated malignancies

Answer 48

CLL

Question 49

Determine type of CML based immunophenotype A) CD5, CD19, CD23 +, Cyclin D1 - B) Cyclin D1 + C) CD10 +

Answer 49

A) CLL B) Mantle Cell lymphoma C) Follicular lymphoma

Question 50

The most common cancers seen in CLL

Answer 50

Skin Prostate Breast

Question 51

Transformation of CLL to an aggressive lymphoma, most commonly DLBCL

Answer 51

Richter’s transformation SUVs <5 R/O Richter SUVs >5 suspicious for Richter SUVs >/=10 very concerning *Excisional biopsy preferred mode of diagnosis

Question 52

What Stage of CLL describes the following: A) Lymphocytosis with lymphadenopathy B) <3 areas of lymphadenopathy C) Anemia or thrombocytopenia

Answer 52

A) RAI Intermediate risk B) Binet Stage B C) Rai High risk or Binet Stage C if Hgb <10 or plt <100

Question 53

A 67-year-old man is diagnosed with chronic lymphocytic leukemia (CLL) after routine blood work showed lymphocytosis. He is asymptomatic. Over the next 4 months, he is followed closely. Which of the following findings MOST clearly indicates the need to initiate therapy? A. Absolute lymphocyte count of 38 × 10⁹/L that has remained stable over 6 months B. Hemoglobin of 9.5 g/dL with a positive direct Coombs test that responds to steroids C. Cervical lymph nodes measuring 3 cm, unchanged in size for 1 year D. Progressive lymphocytosis with a 60% increase over 2 months E. Night sweats occurring intermittently for 2 weeks with concurrent pneumonia

Answer 53

D. Progressive lymphocytosis with a 60% increase over 2 months ** Spleen >6cm Lymph node >10 Lymphocytosis >50% B symptoms WITHOUT infection

Question 54

Lymphoma and related infection A) Malt lymphoma of Skin B) eyes C) small intestine D) Lymphoplasmacytic lymphoma E) Multicentric castleman’s disease and primary effusion lymphoma

Answer 54

A) Borrelia (BB=skin) B) C pssittaci C) C jejuni D) Hep C E) HHV 8

Question 55

On biopsy, there is a monotonous infiltration of medium-sized cells with round nuclei, multiple nucleoli, and basophilic cytoplasm with vacuoles. tingible body macrophages give rise to the classic “starry sky” appearance of this tumor

Answer 55

Burkitt’s Lymphoma

Question 56

Pathognomonic cytogenic finding is t(11,14) and usually overexpress cyclin

Answer 56

Mantle Cell lymphoma

Question 57

single most powerful predictor of survival and can substitute for staging for multiple myeloma

Answer 57

Serum B-microglobulin

Question 58

Which laboratory parameter and corresponding value is consistent with iron deficiency? a. Ferritin 100 μg/L b. Serum Iron 75 μg/dL c. TIBC 450 μg/dL d. Transferrin Saturation 30%

Answer 58

Answer: C. TIBC 450 μg/dL Source: HPIM 21st ed. Ch 97 p.750 Normal values of iron studies: serum iron 50-150 mcg/dL, TIBC 300-360 mcg/dL, TSat 25-50%, Ferritin (average value of 100 mcg/L in males, 30 mcg/L in females). Iron deficiency anemia is associated with ↓ iron, ↑TIBC, ↓TSat (<20%) and ↓Ferritin (<15 suggestive of absent iron stores, <30 is used due to higher sensitivity) The correct answer is: TIBC 450 μg/dL

Question 59

In a patient receiving oral iron therapy for iron deficiency anemia, which of the following laboratory parameters is expected to increase first? a. Ferritin b. Hemoglobin c. Mean Cell Volume d. Reticulocyte Count

Answer 59

Answer: D. Reticulocyte Count Source: HPIM 21st ed. Ch 97 p.752 Reticulocyte count begins to increase 4 to 7 days of treatment and peaks after 1 to 1 ½ weeks. The rest of the parameters begin to increase later. Significant increase in hemoglobin can begin after 2 weeks to 1 month of treatment The correct answer is: Reticulocyte Count

Question 60

Which parameter is the first to decrease in iron deficiency? a. Ferritin b. Hemoglobin c. Serum Iron d. Transferrin Saturation

Answer 60

Answer: A. Ferritin Source: HPIM 21st ed. Ch 97 p.749 Reduction in ferritin can occur as early as the stage of negative iron balance. The correct answer is: Ferritin

Question 61

What is responsible for increased iron absorption that is seen among anemias associated with high levels of ineffective erythropoiesis? a. Erythroferrone b. Ferrireductase c. Hepcidin d. Hephaestin

Answer 61

A. Erythroferrone Source: HPIM 21st ed. Ch 97 p.749 Patients with anemias associated with high levels of ineffective erythropoiesis (e.g. thalassemia syndromes and MDS) absorb excess amounts of dietary iron. The molecular mechanism underlying this is the production of erythroferrone (ERFE) by developing erythroblasts. ERFE suppresses hepcidin production, and over time, this may lead to iron overload and tissue damage The correct answer is: Erythroferrone

Question 62

A 36-year-old man presents with fatigue, dark-colored urine in the morning, and abdominal pain. Laboratory evaluation reveals: moderate anemia, elevated LDH, undetectable haptoglobin, negative Coombs test and deficient CD55 and CD59 red cells on flow cytometry. What is the underlying pathophysiology for his anemia? a. Autoantibody mediated destruction of red blood cells b. Increased susceptibility to complement mediated reactions c. Oxidative cell damage due to an enzyme deficiency d. Primary deficiency in the red cell membrane cytoskeleton

Answer 62

B. Increased susceptibility to complement mediated reactions Source: HPIM 21st ed. Ch 100 p.789 Hemolytic anemia with evidence of CD55 and CD59 deficiency on red cells (can also be seen in granulocytes and monocytes), is confirmatory of Paroxysmal Nocturnal Hemoglobinuria. The deficiency of these proteins makes red cells highly susceptible to complement mediated hemolysis.

Question 63

Which blood smear finding is characteristic of myelodysplastic syndrome (MDS)? a. Basophilic stippling b. Howell-Jolly bodies c. Hypersegmented neutrophils d. Hyposegmented neutrophils

Answer 63

D. Hyposegmented neutrophils Source: HPIM 21st ed Ch 102 p.801 Pseudo-Pelger-Huët anomaly, characterized by hyposegmented neutrophils, is often seen in MDS. Hypersegmented neutrophils are more typical of megaloblastic anemia. Basophilic stippling represents precipitated or aggregated ribosomal RNA in red cells and is seen in several disorders, including lead poisoning and sideroblastic anemia. It can also be seen in some cases of MDS, but it is less characteristic than hyposegmented neutrophils. The presence of Howell-Jolly bodies often indicates splenic dysfunction or absence and is seen in post-splenectomy patients and patients with functional asplenia.

Question 64

At approximately what hematocrit level does blood viscosity begin to increase logarithmically, increasing the risk of hyperviscosity and thrombosis? a. Greater than 45% b. Greater than 55% c. Greater than 65% d. Greater than 75%

Answer 64

B. Hct >55%

Question 65

A 45-year-old woman is undergoing preoperative medical evaluation for an elective surgery to remove multiple uterine myomas. She was referred to a hematologist due to abnormalities on her work-up. The following are the results: hemoglobin 18.0 g/dL, hematocrit 60%, WBC 8.0 × 10⁹/L, platelet 260 × 10⁹/L, serum erythropoietin 55.62 mIU/mL (reference range: 2.59–18.50 mIU/mL). What is the most likely explanation for the findings? a. Autonomous erythropoietin production b. Constitutive activation of JAK STAT signaling pathway c. Mutation in the erythropoietin receptor d. Physiologic response to hypoxia

Answer 65

A. EPO secreting tumor

Question 66

A 54-year-old man presents to the clinic with complaints of burning pain, redness, and warmth in both feet. On examination, his feet are erythematous and warm to touch. Laboratory workup shows a hemoglobin of 175 g/L, hematocrit of 58%, WBC of 15 x 10⁹/L and platelet count of 630 x 10⁹/L. Additional testing for JAK V617F mutation was positive. What is the primary management for his symptoms? a. Hydroxyurea b. Pegylated Interferon c. Salicylates d. Therapeutic Phlebotomy

Answer 66

C. Salicylates Source: HPIM 21st ed Ch 103 p.804 The symptoms are consistent with erythromelalgia which is associated with thrombocytosis that is seen in various myeloproliferative neoplasms. Salicylates (e.g. Aspirin) is the primary medication for this.

Question 67

A 34-year-old woman presents with an incidental finding of thrombocytopenia (18,000/microliter). There are no signs or symptoms of bleeding from any site. No splenomegaly is found. Blood smear shows some large platelets. What is the appropriate management? a. Glucocorticoids b. Intravenous immunoglobulin c. Rh0(D) immune globulin d. Watch-and-wait

Answer 67

A. Glucocorticoids Source: HPIM 21st ed Ch 115 p. 907 Patients with platelet counts >30,000/microliter appear not to have increased mortality related to the thrombocytopenia, and are candidates for conservative watch-and-wait management. For those with much lower platelet counts (such as in this case) or with bleeding signs/symptoms, active treatment can be instituted with glucocorticoids as a first-line option, and IVIg and Rhogam as alternatives.

Question 68

A patient receiving heparin post-hip surgery shows a platelet count drop on post-operative day 10 and develops deep vein thrombosis. Which test is most appropriate to ascertain the cause of the new-onset problems? a. ADAMTS13 assay b. Bleeding time +/- clotting time c. ELISA for PF4 antibodies d. PTT with mixing study

Answer 68

C. ELISA for PF4 antibodies Source: HPIM 21st ed Ch 115 p. 906 The case describes heparin-induced thrombocytopenia (HIT), an immune-mediated condition where antibodies form against platelet factor 4 (PF4) bound to heparin. HIT (anti-heparin/PF4) antibodies can be detected using two types of assays. The most widely available is an enzyme-linked immunoassay (ELISA) with PF4/polyanion complex as the antigen.

Question 69

Which vaccine has been mainly associated with VITT (vaccine-induced immune thrombocytopenia and thrombosis)? a. Ad26.COV2.S b. BNT162b2 c. ChAdOx1-S/nCoV-19 d. mRNA-1273

Answer 69

C. ChAdOx1-S/nCoV-19 Source: HPIM 21st ed Ch 115 p. 906 Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare adverse event associated mainly with adenoviral vector COVID-19 vaccines like ChAdOx1-S/nCoV-19 (AstraZeneca). It is characterized by thrombosis at unusual sites and thrombocytopenia, and involves antibodies against PF4-polyanion complexes, similar to HIT. The other options are other Covid-19 vaccines (Option A: J&J; Option B: Pfizer-BioNTech; Option D: Moderna).

Question 70

What is the function of ADAMTS13? a. It activates fibrinogen. b. It binds to factor VIII. c. It cleaves ultra-large VWF multimers. d. It stimulates platelet adhesion.

Answer 70

C

Question 71

How does inhibitor formation affect hemophilia management? a. Inhibitors increase the risk of delayed hypersensitivity reactions. b. Inhibitors neutralize clotting factors during subsequent infusions. c. Inhibitors deactivate platelets and may also lead to thrombocytopenia. d. Inhibitors paradoxically stimulate factor production, causing a surplus of ineffective coagulation factors.

Answer 71

B. Inhibitors neutralize clotting factors during subsequent infusions. Source: HPIM 21st ed Ch 116 p. 913 Factor replacement therapy in hemophilia may lead to the formation of inhibitors, which are alloantibodies against coagulation factors FVIII and FIX. These inhibitors neutralize coagulation factors, leading to ineffective factor replacement treatment.

Question 72

A man with hemophilia A has persistent bleeding despite therapeutic doses of FVIII infusion. Inhibitor assay shows 10 Bethesda Units (BU). What is the best treatment? a. DDAVP b. High-dose FVIII infusion c. Recombinant FVIIa infusion d. Tranexamic acid

Answer 72

C. Recombinant FVIIa infusion Source: HPIM 21st ed Ch 116 p. 913 Patients with hemophilia A who develop inhibitors can be classified as either low responders or high responders. Low responders (titer <5 BU) respond well to high doses of human FVIII. High-responder patients (initial inhibitor titer >5 BU, or an anamnestic response with increase in the antibody titer to >5 BU) do not respond to FVIII, and need to be treated with “bypass agents” [i.e. activated prothrombin complex concentrates (aPCCs) and recombinant activated factor VII (FVIIa)] as they activate coagulation downstream of the inhibited/absent factor or through a different pathway.

Question 73

A pregnant woman with known carrier status for hemophilia A has a Factor VIII level of 30%. What is the best peri-delivery plan? a. FVIII replacement during and after delivery b. IVIg infusion during and after delivery c. No treatment indicated d. Splenectomy before delivery

Answer 73

A. FVIII replacement during and after delivery Source: HPIM 21st ed Ch 116 p. 914 To prevent bleeding, FVIII should be raised to 50–70% for vaginal delivery. During pregnancy, FVIII levels increase approximately two- to threefold compared to nonpregnant women, whereas the FIX increase is less pronounced. After delivery, a rapid fall in the pregnancy-induced rise of maternal clotting factor levels occurs, resulting in an imminent risk of bleeding that can be prevented by infusion of factor concentrate to levels of 50–70% for 3 days for vaginal delivery and up to 5 days for cesarean delivery.

Question 74

What is the central mechanism in the pathophysiology of DIC? a. Abnormal fibrinolysis b. Consumption of coagulation factors c. Severe thrombocytopenia d. Uncontrolled thrombin generation

Answer 74

D. Uncontrolled thrombin generation Source: HPIM 21st ed Ch 116 p. 915 Uncontrolled thrombin generation is the first and central derangement that occurs in DIC. The rest of the choices are downstream and subsequent effects of this abnormality.

Question 75

A 68-year-old man is in the ICU for septic shock due to a community acquired pneumonia. On the 2nd hospital day, he develops petechiae and ecchymoses. Pertinent diagnostics: platelet count: 80,000/μL, PT: 18 seconds (control: 12.5 seconds), aPTT: 48 seconds (control: 34 seconds), fibrinogen: 90 mg/dL, D-dimer: markedly elevated. What is the most appropriate management for this case? a. Activated protein C b. Broad spectrum antibiotic c. Platelet concentrate transfusion d. Tranexamic Acid infusion

Answer 75

B. Broad spectrum antibiotic Source: HPIM 21st ed Ch 116 p. 917 Management of an overt DIC involves control and elimination of the underlying causes. For sepsis associated DIC, treatment of the microbial pathogen is the primary goal to control and resolve the DIC.

Question 76

A 45-year-old man with chronic liver disease receives a transfusion of 1 unit packed red blood cells. Approximately one hour into the transfusion, he develops a low-grade fever of 38°C without chills, hypotension, rash, or respiratory symptoms. The fever resolves with administration of an antipyretic. No evidence of infection or hemolysis was noted. Which is the most appropriate step to prevent this reaction in the future? a. Perform a crossmatch with extended antigen typing b. Pre-medicate with the use of paracetamol c. Transfuse a leukocyte reduced blood product d. Transfused a washed blood product

Answer 76

C. Transfuse a leukocyte reduced blood product Source: HPIM 21st ed Ch 113 p.894 This is a case of febrile non hemolytic transfusion reaction. The most appropriate preventive measure for this is to use leukodepleted products. The fever is mediated by cytokines which are produced by the white blood cells that are present in the blood unit. By performing leukodepletion (or leukoreduction), 99% of the white blood cells are removed from the unit which significantly reduces the likelihood of producing fever mediated by cytokines.

Question 77

A 65-year-old man presents with left sided weakness. He is on warfarin 2.5 mg daily for a valvular heart disease and chronic atrial fibrillation. CT scan shows an acute intracerebral hemorrhage in the right basal ganglia. The latest PT-INR is 15.0. He is hemodynamically stable and weighs 65 kg. Which is an appropriate reversal strategy for this case? a. Conservative management for now, no reversal warranted b. Transfuse 4 units of cryoprecipitate c. Transfuse 4 units of fresh frozen plasma d. Transfuse 4 units of fresh whole blood

Answer 77

C. Transfuse 4 units of fresh frozen plasma Source: HPIM 21st ed Ch 113 p.889 table 113-4 This is a case of an acute intracerebral hemorrhage that is primarily due to a severe coagulopathy brought about by Warfarin. For major bleeding, the appropriate reversal strategy is administering prothrombin complex concentrate (PCC), in setting where it is not available (i.e. Philippines), fresh frozen plasma is an appropriate alternative. Vitamin K is also given as an adjunctive measure.

Question 78

Which patient is most likely to warrant a platelet concentrate transfusion? a. A 21-year-old asymptomatic woman with immune thrombocytopenia; platelet count 10 x 10⁹/L b. A 38-year-old woman for elective craniectomy; platelet count 75 x 10⁹/L c. A 55-year-old asymptomatic man, with acute myeloid leukemia s/p cycle induction chemotherapy; platelet count 50 x 10⁹/L d. A 60-year-old man for elective open cholecystectomy; platelet count 65 x 10⁹/L

Answer 78

B. A 38-year-old woman for elective craniectomy; platelet count 75 x 109/L Source: HPIM 21st ed Ch 113 p.889 table 113-4 For individuals with asymptomatic thrombocytopenia that is not due to ITP, TTP or DIC, the threshold for prophylactic transfusion is a platelet count of <10 x 109/L. For patients undergoing major elective surgery, the usual threshold to transfuse is a platelet count of <50 x 109/L. Some exceptions to this include neurosurgical procedure or those involving the posterior orbit, for this kind of surgery, a higher platelet count is necessary (>80-100 x 109/L) to prevent major bleeding in a highly enclosed compartment.

Question 79

Which of the following characterizes transfusion related acute lung injury? a. It is mediated by anti HLA class II antibodies that are present in the blood product b. It presents with a cardiogenic pulmonary edema within 6 hours of transfusion c. The transfusion of blood product from a male donor is a risk factor d. Treatment involves administering corticosteroids

Answer 79

A. It is mediated by anti HLA class II antibodies that are present in the blood product Source: HPIM 21st ed Ch 113 p.894 TRALI is mediated by anti HLA class II antibodies and produces a non cardiogenic pulmonary edema. An established risk factor is a donor from a multiparous female. Treatment is purely supportive if this occurs.

Question 80

A 53-year-old woman with advanced-stage diffuse large B-cell lymphoma achieved complete remission following systemic immunochemotherapy. After completing treatment, she developed persistent numbness and tingling in her hands and feet. What is the mechanism of action of the medication responsible for this? a. Anti-metabolite b. Anti-tumor antibiotic c. Direct DNA intercalating agent d. Mitotic spindle inhibitor

Answer 80

D. Mitotic spindle inhibitor Source: HPIM 21st ed Ch 73 p.543 Neuropathy is a common adverse effect that can be seen with Vincristine, which is a common chemotherapy agent used for lymphoma as part of the R-CHOP regimen. It is a mitotic spindle inhibitor.

Question 81

Which hallmark of cancer is best illustrated by a mutation in the p53 gene? a. Avoiding immune destruction b. Evading growth suppressors c. Inducing angiogenesis d. Resisting cell death

Answer 81

B. Evading growth suppressors Source: HPIM 21st ed Ch 72 p.509 p53 is a major tumor suppressor involved in halting cell cycle progression. Loss of its function allows cells to evade growth suppression. It also contributes to resisting cell death, but its hallmark role is in growth suppression.

Question 82

Which genetic abnormality is associated with a favorable prognosis in AML? a. complex karyotype b. FLT3-ITD c. inv(16) d. TP53 mutation

Answer 82

C. inv(16) Source: HPIM 21st ed Ch 104 p.811 inv(16) and t(8;21) are associated with favorable prognosis in AML. FLT3-ITD and TP53 mutations indicate poor outcomes. Patients with complex karyotype (presence of 3 or more abnormalities) also have a very poor prognosis.

Question 83

A 67-year-old male patient is diagnosed with AML after presenting with anemia, thrombocytopenia, and splenomegaly. On further probing, he recalls being given melphalan and prednisone for his multiple myeloma 5 years ago. Which chromosome is most likely to be affected in his disease? a. Chromosome 5 b. Chromosome 11 c. Chromosome 16 d. Chromosome 22

Answer 83

A. Chromosome 5 Source: HPIM 21st ed Ch 104 p.810 Alkylating agent–associated AML occurs 4–6 years after exposure, and is associated with multilineage dysplasia and monosomy/aberrations in chromosomes 5 and 7. Topoisomerase II inhibitor–associated AML occurs 1–3 years after exposure, and is associated with monocytic features and aberrations involving chromosome 11q23.

Question 84

hich laboratory abnormalities are commonly seen in acute promyelocytic leukemia at the time of diagnosis and can be life-threatening? a. Hypocalcemia b. Hypofibrinogenemia c. Metabolic acidoses d. Severe neutrophilia

Answer 84

B. Hypofibrinogenemia Source: HPIM 21st ed Ch 104 p.813 APL often presents with DIC-associated minor hemorrhage but may have significant gastrointestinal bleeding, intrapulmonary hemorrhage, or intracranial hemorrhage. Hypofibrinogenemia and prolonged prothrombin time are prominent abnormalities associated with this DIC-like presentation in APL.

Question 85

Which is true regarding the clinical features of chronic myeloid leukemia (CML)? a. Most patients with CML present in the accelerated phase. b. All cases of classical CML present with the Philadelphia chromosome [t(9;22)(q34.1;q11.2)]. c. Splenomegaly is the most common physical finding. d. Thrombocytopenia is a common presenting symptom, while thrombocytosis is rare.

Answer 85

C. Splenomegaly is the most common physical finding. Source: HPIM 21st ed Ch 105 p.819-821 Around 90% of CML cases present in the indolent or chronic phase. The Ph chromosome is detectable in only ~90% of cases. The remaining 10% of cases may have complex translocations that involve chromosomes 9 and 22, and one or more additional chromosomes. Splenomegaly is the most common physical finding (20-70% of patients), while hepatomegaly is less common (5-10% of patients). Thrombocytosis is much more common, and thrombocytopenia is rare and suggestive of a worse prognosis.

Question 86

A 60-year-old man with leukocytosis, thrombocytosis, anemia, and splenomegaly is found to have BCR-ABL1 positivity. What is the most appropriate initial therapy? a. Ibrutinib b. Imatinib c. Methotrexate d. Rituximab

Answer 86

B. Imatinib Source: HPIM 21st ed Ch 105 p.821 The findings are diagnostic of chronic myeloid leukemia (CML). Imatinib is a first-line tyrosine kinase inhibitor for BCR-ABL1-positive CML. Ibrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor and is used primarily in the treatment of lymphoid malignancies such as chronic lymphocytic leukemia and mantle cell lymphoma. Methotrexate is a drug used in the treatment of numerous diseases, including acute leukemias. Rituximab is a monoclonal antibody that is used in the treatment of CD20-positive malignancies.

Question 87

A 64-year-old man with sepsis is admitted for urgent diagnostic upper GI endoscopy because of melena. He is afebrile but hypotensive. His platelet count is 28,000/µL. According to standard platelet transfusion thresholds, what is the most appropriate platelet target before the procedure? Choices: A. ≥10,000/µL B. ≥20,000/µL C. ≥50,000/µL D. ≥80,000/µL

Answer 87

C. ≥50,000/µL Platelet transfusion thresholds (classic board values): • ≤5,000/µL – prophylaxis (no fever/infection) • ≤10,000-20,000/µL – if fever or infection • ≤50,000/µL – surgery, DIC, endoscopy, invasive procedures • ≤80,000–100,000/µL – neurosurgery or eye surgery

Question 88

How does Drug-induced thrombocytopenia due to heparin differs from that seen with other drugs

Answer 88

1) thrombocytopenia not usually severe, rarely <20,000 2) markedly increase risk of thrombosis than bleeding

Question 89

What are the 4t’s in HIT?

Answer 89

- thrombocytopenia - timing of plt count drop (after exposure to heparin for 5–14 days or if prev exposure (<100days) before 5 days) - thrombosis - other cause not evident * Rarely, thrombocytopenia and thrombosis begin several days after all heparin has been stopped (termed delayed-onset HIT

Question 90

A patient develops a generalized rash involving >2/3 of the body within 5 minutes of plasma transfusion, followed by hypotension. Diagnosis? Choices: A. Minor allergic reaction B. Severe allergy C. Anaphylaxis D. GVHD

Answer 90

C. Anaphylaxis Timing rule: • <2/3 body, 2–3 h → Minor allergy • 2/3 body, 2–3 h → Severe allergy • Immediate + shock → Anaphylaxis

Question 91

A patient develops acute dyspnea 4 hours after transfusion. CXR shows pulmonary edema. JVP is elevated, BNP is high. Diagnosis? A. TRALI B. TACO C. FNHTR D. Severe allergy

Answer 91

Answer: B. TACO Differentiator: • TACO → ↑JVP, ↑BNP, fluid overload • TRALI → normal JVP, inflammatory Mnemonic: 💧 “TACO is TOO MUCH volume” *due to donor anti-HLA class II

Question 92

What is recommended to be started in TTP individuals with diagnostic ADAMTS13 levels (usually <10%)?

Answer 92

Caplacizumab (antiVWF nanobody) and Rituximab * additionally for rituximab, in patients with evidence of an inhibitor, given potential side effects and costs

Question 93

What is the most common and earliest finding in vitamin K–deficient patients?

Answer 93

Prolonged PT due to the short half-life of FVII, and occurs before prolongation of the aPTT. Parenteral administration of 10 mg of vitamin K is sufficient to restore normal levels of clotting factor within 8–10 h

Question 94

The amount of iron needed by an individual patient is calculated by the following formula

Answer 94

Body weight (kg) x 2.3 x (15 – patient’s hemoglobin, g/dL) + 500 or 1000 mg (for stores)