TABLE OF CONTENTS
SECTION 1: ALTERATIONS IN HEMATOLOGIC FUNCTION ...................... Questions 1-85
SECTION 2: ALTERATIONS IN IMMUNE FUNCTION ........................... Questions 86-145
SECTION 3: ALTERATIONS IN CARDIOVASCULAR FUNCTION ........... Questions 146-210
SECTION 4: ALTERATIONS IN RENAL FUNCTION ............................ Questions 211-260
SECTION 5: ALTERATIONS IN GASTROINTESTINAL FUNCTION ................. Questions
261-300
,SECTION 1: ALTERATIONS IN HEMATOLOGIC FUNCTION (Questions 1-85)
1. A patient with hemophilia A (factor VIII deficiency) develops an inhibitor to factor VIII
after replacement therapy. Which of the following laboratory findings is most consistent
with this complication?
A) Prolonged prothrombin time (PT) that corrects with mixing
B) Prolonged activated partial thromboplastin time (aPTT) that does not correct with
mixing
C) Normal aPTT and prolonged bleeding time
D) Decreased factor VIII activity and decreased von Willebrand factor antigen
Answer: B
Rationale: The development of an inhibitor (neutralizing antibody) to factor VIII is a
serious complication of hemophilia A, occurring in approximately 20-30% of patients with
severe disease. Laboratory evaluation reveals a prolonged aPTT that does not correct when
the patient's plasma is mixed with normal plasma (immediate or after 2-hour incubation).
This lack of correction indicates the presence of an inhibitor rather than a factor deficiency.
In contrast, factor deficiencies correct with mixing studies because the normal plasma
supplies the missing factor. Option A is incorrect because PT is normal in hemophilia A
(intrinsic pathway defect). Option C is incorrect because aPTT is prolonged, not normal;
bleeding time is normal in hemophilia A. Option D is incorrect because von Willebrand
factor antigen is normal in hemophilia A; decreased VWF suggests von Willebrand disease.
2. A patient with myelodysplastic syndrome (MDS) has a bone marrow biopsy showing
increased blasts (12%) and ring sideroblasts. Which of the following genetic mutations is
most commonly associated with this phenotype?
,A) JAK2 V617F
B) BCR-ABL1
C) SF3B1
D) FLT3-ITD
Answer: C
Rationale: Ring sideroblasts are erythroid precursors with iron-laden mitochondria
forming a ring around the nucleus, visualized with Prussian blue staining. They are
characteristic of MDS with ring sideroblasts (MDS-RS). The SF3B1 gene, which encodes a
splicing factor, is mutated in over 80% of MDS-RS cases. SF3B1 mutations lead to aberrant
splicing of genes involved in iron metabolism, particularly downregulation of ABCB7,
which impairs mitochondrial iron export and results in ring sideroblast formation. Option
A (JAK2 V617F) is associated with myeloproliferative neoplasms such as polycythemia
vera, essential thrombocythemia, and primary myelofibrosis. Option B (BCR-ABL1) is the
hallmark of chronic myeloid leukemia (CML). Option D (FLT3-ITD) is commonly found in
acute myeloid leukemia (AML) and is associated with poor prognosis.
3. A patient with sickle cell disease (HbSS) develops acute chest syndrome after a vaso-
occlusive crisis. Which of the following pathophysiologic mechanisms contributes most
directly to the development of acute chest syndrome?
A) Increased nitric oxide production leading to vasodilation and pulmonary congestion
B) Intravascular hemolysis causing free hemoglobin scavenging of nitric oxide and
endothelial dysfunction
C) Bone marrow embolism from necrotic bone marrow
D) Pulmonary vasospasm due to cold exposure
Answer: B
, Rationale: Acute chest syndrome in sickle cell disease is a life-threatening complication
characterized by fever, respiratory symptoms, and new pulmonary infiltrates. The
pathogenesis is multifactorial, but intravascular hemolysis plays a central role. Free
hemoglobin released from lysed red blood cells scavenges nitric oxide (NO) with high
affinity, reducing NO bioavailability. This leads to endothelial dysfunction, increased
expression of adhesion molecules (VCAM-1, ICAM-1), and vasoconstriction. These changes
promote adhesion of sickled erythrocytes to the endothelium, further vaso-occlusion, and
ischemia-reperfusion injury in the pulmonary microvasculature. Option A is incorrect
because NO is decreased, not increased, in hemolytic states. Option C (bone marrow
embolism) is a less common mechanism and typically occurs in long bone infarcts, not as
the primary driver of acute chest syndrome. Option D is incorrect because cold exposure
triggers vaso-occlusive crises but is not the direct mechanism for acute chest syndrome.
4. A patient with chronic lymphocytic leukemia (CLL) develops autoimmune hemolytic
anemia (AIHA). Which of the following laboratory findings would most likely be present?
A) Elevated haptoglobin and normal LDH
B) Positive direct antiglobulin test (DAT) with anti-IgG and anti-C3d
C) Low reticulocyte count and elevated bilirubin
D) Schistocytes on peripheral smear and thrombocytopenia
Answer: B
Rationale: Autoimmune hemolytic anemia (AIHA) is a common complication of CLL,
occurring in approximately 10-15% of patients. The warm antibody type, mediated by IgG
antibodies, is the most common form in CLL. The direct antiglobulin test (DAT or Coombs
test) detects antibodies or complement proteins bound to the red blood cell surface. In
warm AIHA, the DAT is positive for IgG and often for C3d, indicating complement fixation.
Option A is incorrect because haptoglobin is consumed and therefore decreased in
hemolytic states, while LDH is elevated due to red blood cell lysis. Option C is incorrect
because reticulocyte count is typically elevated as the bone marrow compensates for
hemolysis; a low reticulocyte count in the setting of hemolysis would suggest bone marrow
suppression or aplastic crisis. Option D is incorrect because schistocytes and
SECTION 1: ALTERATIONS IN HEMATOLOGIC FUNCTION ...................... Questions 1-85
SECTION 2: ALTERATIONS IN IMMUNE FUNCTION ........................... Questions 86-145
SECTION 3: ALTERATIONS IN CARDIOVASCULAR FUNCTION ........... Questions 146-210
SECTION 4: ALTERATIONS IN RENAL FUNCTION ............................ Questions 211-260
SECTION 5: ALTERATIONS IN GASTROINTESTINAL FUNCTION ................. Questions
261-300
,SECTION 1: ALTERATIONS IN HEMATOLOGIC FUNCTION (Questions 1-85)
1. A patient with hemophilia A (factor VIII deficiency) develops an inhibitor to factor VIII
after replacement therapy. Which of the following laboratory findings is most consistent
with this complication?
A) Prolonged prothrombin time (PT) that corrects with mixing
B) Prolonged activated partial thromboplastin time (aPTT) that does not correct with
mixing
C) Normal aPTT and prolonged bleeding time
D) Decreased factor VIII activity and decreased von Willebrand factor antigen
Answer: B
Rationale: The development of an inhibitor (neutralizing antibody) to factor VIII is a
serious complication of hemophilia A, occurring in approximately 20-30% of patients with
severe disease. Laboratory evaluation reveals a prolonged aPTT that does not correct when
the patient's plasma is mixed with normal plasma (immediate or after 2-hour incubation).
This lack of correction indicates the presence of an inhibitor rather than a factor deficiency.
In contrast, factor deficiencies correct with mixing studies because the normal plasma
supplies the missing factor. Option A is incorrect because PT is normal in hemophilia A
(intrinsic pathway defect). Option C is incorrect because aPTT is prolonged, not normal;
bleeding time is normal in hemophilia A. Option D is incorrect because von Willebrand
factor antigen is normal in hemophilia A; decreased VWF suggests von Willebrand disease.
2. A patient with myelodysplastic syndrome (MDS) has a bone marrow biopsy showing
increased blasts (12%) and ring sideroblasts. Which of the following genetic mutations is
most commonly associated with this phenotype?
,A) JAK2 V617F
B) BCR-ABL1
C) SF3B1
D) FLT3-ITD
Answer: C
Rationale: Ring sideroblasts are erythroid precursors with iron-laden mitochondria
forming a ring around the nucleus, visualized with Prussian blue staining. They are
characteristic of MDS with ring sideroblasts (MDS-RS). The SF3B1 gene, which encodes a
splicing factor, is mutated in over 80% of MDS-RS cases. SF3B1 mutations lead to aberrant
splicing of genes involved in iron metabolism, particularly downregulation of ABCB7,
which impairs mitochondrial iron export and results in ring sideroblast formation. Option
A (JAK2 V617F) is associated with myeloproliferative neoplasms such as polycythemia
vera, essential thrombocythemia, and primary myelofibrosis. Option B (BCR-ABL1) is the
hallmark of chronic myeloid leukemia (CML). Option D (FLT3-ITD) is commonly found in
acute myeloid leukemia (AML) and is associated with poor prognosis.
3. A patient with sickle cell disease (HbSS) develops acute chest syndrome after a vaso-
occlusive crisis. Which of the following pathophysiologic mechanisms contributes most
directly to the development of acute chest syndrome?
A) Increased nitric oxide production leading to vasodilation and pulmonary congestion
B) Intravascular hemolysis causing free hemoglobin scavenging of nitric oxide and
endothelial dysfunction
C) Bone marrow embolism from necrotic bone marrow
D) Pulmonary vasospasm due to cold exposure
Answer: B
, Rationale: Acute chest syndrome in sickle cell disease is a life-threatening complication
characterized by fever, respiratory symptoms, and new pulmonary infiltrates. The
pathogenesis is multifactorial, but intravascular hemolysis plays a central role. Free
hemoglobin released from lysed red blood cells scavenges nitric oxide (NO) with high
affinity, reducing NO bioavailability. This leads to endothelial dysfunction, increased
expression of adhesion molecules (VCAM-1, ICAM-1), and vasoconstriction. These changes
promote adhesion of sickled erythrocytes to the endothelium, further vaso-occlusion, and
ischemia-reperfusion injury in the pulmonary microvasculature. Option A is incorrect
because NO is decreased, not increased, in hemolytic states. Option C (bone marrow
embolism) is a less common mechanism and typically occurs in long bone infarcts, not as
the primary driver of acute chest syndrome. Option D is incorrect because cold exposure
triggers vaso-occlusive crises but is not the direct mechanism for acute chest syndrome.
4. A patient with chronic lymphocytic leukemia (CLL) develops autoimmune hemolytic
anemia (AIHA). Which of the following laboratory findings would most likely be present?
A) Elevated haptoglobin and normal LDH
B) Positive direct antiglobulin test (DAT) with anti-IgG and anti-C3d
C) Low reticulocyte count and elevated bilirubin
D) Schistocytes on peripheral smear and thrombocytopenia
Answer: B
Rationale: Autoimmune hemolytic anemia (AIHA) is a common complication of CLL,
occurring in approximately 10-15% of patients. The warm antibody type, mediated by IgG
antibodies, is the most common form in CLL. The direct antiglobulin test (DAT or Coombs
test) detects antibodies or complement proteins bound to the red blood cell surface. In
warm AIHA, the DAT is positive for IgG and often for C3d, indicating complement fixation.
Option A is incorrect because haptoglobin is consumed and therefore decreased in
hemolytic states, while LDH is elevated due to red blood cell lysis. Option C is incorrect
because reticulocyte count is typically elevated as the bone marrow compensates for
hemolysis; a low reticulocyte count in the setting of hemolysis would suggest bone marrow
suppression or aplastic crisis. Option D is incorrect because schistocytes and
