rapid review questions

7/29/2019 Rapid Review Questions

1/11

A 10-year-old girl develops fever, epistaxis, and oliguria 5 days after attending a picnic at

which hamburgers and hot dogs are served. Physical examination shows scattered petechiae

and ecchymoses on the arms, chest, and back. Laboratory studies show:

Hemoglobin 9 g/dL

WBC count 8000/mm3

Platelet count 30,000/mm3

Prothrombin time (PT) 12 sec

Activated partial thromboplastin time (aPTT)35 secSerum blood urea nitrogen (BUN) 40 mg/dL

Serum creatinine 4 mg/dL

A peripheral smear shows fragmented RBCs. What is the most likely diagnosis?The patient

has HUS, which most commonly occurs in children. HUS is due to a toxin (Verotoxin) produced

by the 0157:H7 strain ofEscherichia coli, causing widespread endothelial cell damage at the

arteriolecapillary junction. E. coli often contaminates improperly cooked beef (e.g.,

hamburgers). Platelet thrombi develop at all the injury sites, causing consumption of platelets

and thrombocytopenia (epistaxis, petechiae, ecchymoses, easy bruising) as well as renal

failure (increased serum BUN and serum creatinine). RBCs that collide with the platelet

thrombi are damaged (fragmented RBCs or schistocytes), causing a hemolytic anemia

(microangiopathic hemolytic anemia; see Fig. 11-35 in Rapid Review Pathology, 3rd edition).

Option A (Aplastic anemia) is incorrect. Aplastic anemia is characterized by decreased

production of WBCs, RBCs, and platelets. Aplastic anemia is excluded in this patient, because

the WBC count is normal.

Option B (Disseminated intravascular coagulation (DIC)) is incorrect. In DIC, fibrin clots

are produced in the microcirculation that obstruct blood flow and consume coagulation

factors. Factors that are consumed in a fibrin clot are fibrinogen (factor I), prothrombin(factor II), and factors V and VIII. Since coagulating factors present in the final common

pathway are consumed (fibrinogen, prothrombin, factor V), there is prolongation of the PT

and aPTT (not present in this patient). Platelets are trapped in the fibrin clots leading to

thrombocytopenia. Fragmented RBCs (schistocytes) are present in the peripheral blood, due

to damage to RBCs by the fibrin clots. There are many overlapping features of DIC with HUS;

however, in the former disorder coagulation factors are consumed causing prolongation of the

PT and aPTT, while in the latter, platelets are consumed in the formation of platelet thrombi

and coagulation studies are normal.

Option D (Idiopathic thrombocytopenic purpura (ITP)) is incorrect. ITP is autoimmune

destruction of platelets, where IgG antibodies are directed against the GpIIb:IIIa fibrinogenreceptors on platelets. ITP is excluded in this patient because it is not associated with anemia

and renal failure.

Option E (Thrombotic thrombocytopenic purpura (TTP)) is incorrect. TTP occurs in

women and is uncommon in children. The pathophysiology of TTP and HUS is similar. TTP is a

disorder characterized by endothelial injury with the formation of platelet thrombi that

consume platelets, not coagulation factors; therefore, the PT and PTT are normal (not

prolonged).


2/11

The photograph shows characteristic leukocyte alterations in peripheral blood obtained from

a 23-year-old man with fever. Which of the following conditions is the most compatible with

these change

Streptococcal tonsillitis) is correct. The peripheral blood smear shows leukocyte

alterations that characterize acute bacterial infections, such as streptococcal tonsillitis. These

changes include the presence of band neutrophils (without segmentation) and of multilobed

neutrophils that show toxic granulation (prominent azurophilic granules) and cytoplasmic

vacuolization (phagolysosomes). When band neutrophils exceed 10% of the total leukocytes,

the term left shift is used, indicating that more immature cells in the neutrophil series are

being released from the bone marrow. These cells are released from the post-mitotic

neutrophil pool in the bone marrow due to the presence of interleukin-1 and tumor necrosis

factor-.

Option A (Acute myeloblastic leukemia) is incorrect. A peripheral blood smear from a

patient with acute myeloblastic leukemia would show myeloblasts containing rodlike

structures (Auer rods) in the cytoplasm and other immature myeloid elements.

Option B (Infectious mononucleosis) is incorrect. A peripheral blood smear from a patient

with infectious mononucleosis would show atypical lymphocytes, which have abundant

cytoplasm and enlarged nuclei with prominent nucleoli.

Option C (Invasive helminth infection) is incorrect. A peripheral blood smear from a

patient with invasive helminths (e.g., Strongyloides stercoralis) would show eosinophils, which

contain bright red granules in the cytoplasm that are larger than the azurophilic granules seen

in neutrophils.

Option E (Viral gastroenteritis) is incorrect. A peripheral blood smear from a patient withviral gastroenteritis would show absolute lymphocytosis (increased total lymphocyte count),

the leukocyte alteration that characterizes viral infections. Lymphocytes have round nuclei

and are usually surrounded by a thin rim of cytoplasm.


3/11

In which of the following clinical scenarios would the patient most likely have an increase in

the leukocyte shown in the photograph?

Option D (A 45-year-old woman has severe rheumatoid arthritis.) is correct.

Monocytosis is the primary leukocyte alteration in chronic inflammation (e.g., rheumatoid

arthritis). The photograph shows a monocyte with grayish-blue cytoplasm that contains many

fine azurophilic granules and nucleus that is horse-shoe shaped (this monocyte), round, or

kidney shaped.

Option A (A 4-year-old child has whooping cough.) is incorrect.Bordetella pertussis is the

cause of whooping cough. The lymphotoxin in this bacteria inhibits signal transduction bychemokine receptors which prevents lymphocytes from entering lymph nodes leading to

lymphocytosis. Lymphocyte counts are often >50,000/mm3 (lymphoid leukemoid reaction).

The photograph shows a small lymphocyte with scant cytoplasm surrounding a dark nucleus.

Option B (A 24-year-old man, who raises hogs, has a habit of eating raw bacon.) is

incorrect. This patient would most likely develop trichinosis, due to Trichinella spiralis. It is

contracted by eating raw or undercooked pork. The larvae penetrate muscle producing

muscle pain and tenderness. Invasive helminths produce eosinophilia (type I

hypersensitivity). The photograph shows an eosinophil with cytoplasm packed with reddish-

orange granules that do not cover the nucleus.

Option C (A 28-year-old man has a perforated acute appendicitis.) is incorrect. A

perforated acute appendicitis produces neutrophilic leukocytosis with left shift (e.g., band

neutrophils) and toxic granulation (prominent azurophilic granules).

Option E (A 56-year-old man with polycythemia vera has flushing of his face.) is

incorrect. In polycythemia, all cell lines except lymphocytes are increased. An increase in

basophils and mast cells causes the release of histamine, which produces flushing of the face

(called plethora), headaches, and pruritus after bathing. All of the myeloproliferative diseases

have basophilia.

A febrile 65-year-old man with prostate hyperplasia and urinary retention develops endotoxicshock. Within 24 hours, he has oozing of blood from all needle puncture sites, extensive

ecchymoses and petechiae, and gastrointestinal bleeding. Laboratory studies show a

hemoglobin of 9 g/dL, platelet count 75,000/mm3, prothrombin time (PT) 20 seconds, partial

thromboplastin time, activated partial thromboplastin time (aPTT) 50 sec, and a positive d-

dimer assay. What is the most likely diagnosis

Option C (Disseminated intravascular coagulation (DIC)) is correct. The endotoxins in

endotoxic shock (most often due to Escherichia coli sepsis) damage tissue, causing the release

of tissue thromboplastin. This activates the extrinsic coagulation system, causing DIC. Septic


4/11

shock is the most common cause of DIC. In DIC, fibrin clots are produced in the

microcirculation that obstruct blood flow and consume coagulation factors, causing bleeding

from needle puncture sites and the gastrointestinal tract. Factors that are normally consumed

in a fibrin clot are fibrinogen (factor I), prothrombin (factor II), and factors V and VIII. Since

coagulating factors present in the final common pathway are consumed (fibrinogen,

prothrombin, factor V), there is prolongation of the PT and aPTT. Platelets are trapped in the

fibrin clots leading to thrombocytopenia, which produces petechiae and ecchymoses. The

fibrinolytic system is activated (secondary fibrinolysis), and plasmin cleaves the fibrin strandsholding the fibrin clots together. Fibrin strands are held together by cross-links, and cleaved

fragments with cross-links are detected in the d-dimer assay, which is the most sensitive test

for diagnosing DIC.

Option A (Autoimmune thrombocytopenia) is incorrect. DIC is associated with fibrin clots,

multiple coagulation factor deficiencies, activation of the fibrinolytic system, and

thrombocytopenia. Therefore, conditions that produce thrombocytopenia, such as

autoimmune thrombocytopenia, do not explain all of the clinical and laboratory findings that

are present in DIC.

Option B (Circulating anticoagulant) is incorrect. Circulating anticoagulants are antibodies

that destroy coagulation factors (e.g., factor VIII), causing prolongation of the aPTT and/or PT.

However, these antibodies do not destroy platelets or produce fibrin clots that obstruct the

microcirculation as in DIC.

Option D (Primary fibrinolysis) is incorrect. Primary fibrinolysis is uncommon. It is usually

seen in the setting of radical prostatectomy and open heart surgery. Only the fibrinolytic

system is activated. Therefore, clinical findings are primarily those related to coagulation

factor deficiencies (e.g., fibrinogen, factor V, factor VIII). The platelet count is normal and d-

dimers are not present, because there are no fibrin clots.

Option E (Thrombotic thrombocytopenic purpura (TTP)) is incorrect. DIC is associated

with fibrin clots, multiple coagulation factor deficiencies, activation of the fibrinolytic system,

and thrombocytopenia. TTP is a disorder characterized by endothelial injury with the

formation of platelet thrombi that consume platelets, not coagulation factors; therefore, the

PT and PTT are normal (not prolonged).

A 22-year-old man has fever, fatigue, and a sore throat. Findings on physical examination

include exudative pharyngitis, hepatosplenomegaly, and painful generalized

lymphadenopathy. Laboratory findings show an increased WBC count, normal hemoglobin

concentration, and normal platelet count. The photograph shows one of many similar WBCs inthe peripheral blood of the patient. Which of the following laboratory studies would be most

useful in confirming the diagnosis in this patient?


5/11



Option E (A 56-year-old man with polycythemia vera has flushing of his face.) is correct.

In polycythemia, all cell lines except lymphocytes are increased. An increase in basophils and

mast cells causes the release of histamine, which produces flushing of the face (called

plethora), headaches, and pruritus after bathing. All of the myeloproliferative diseases have

basophilia. The basophil in the photograph shows the cytoplasm packed with large purple-

black granules that cover the nucleus.


cause of whooping cough. The lymphotoxin in this bacteria inhibits signal transduction by

chemokine receptors which prevents lymphocytes from entering lymph nodes leading to











Option E (A 45-year-old woman has severe rheumatoid arthritis.) is incorrect.


arthritis).


6/11

Option B (Heterophil antibody test) is correct. This patient has infectious mononucleosis,

which is caused by the Epstein-Barr virus (EBV). Infectious mononucleosis is usually

transmitted by saliva (kissing disease). The photograph shows atypical lymphocytes with

dark chromatin and abundant blue-gray cytoplasm. In mononucleosis, these are antigenically

stimulated T cells that are responding to B cells infected by the virus. Recall that EBV has

CD21 receptors on B cells and causes them to produce plasma cells that generate IgM

heterophile antibodies that are used to screen for the infection (87% sensitivity). The

heterophil antibodies that are specific for mononucleosis are IgM antibodies against horse,sheep, or bovine RBCs. Antibodies that are also useful diagnosing mono, particularly if the

heterophile antibody test is negative, are anti-viral capsid antigen antibodies and antibodies

against early antigen, both of which have >90% sensitivity and specificity.

Hepatosplenomegaly and painful generalized lymphadenopathy are invariably present in

mononucleosis.

Option A (Bone marrow aspiration) is incorrect. Bone marrow aspiration biopsies are

most often performed to rule out leukemias or primary disorders of the bone marrow (e.g.,

aplastic anemia, myelofibrosis).

Option C (Lymph node biopsy) is incorrect. A lymph node biopsy is usually performed

when a neoplastic process (e.g., malignant lymphoma, metastatic disease) is suspected. A

neoplastic process produces painless enlargement of lymph nodes, which is not present in this

case. This patient's painful lymphadenopathy indicates a benign, reactive process.

Option D (Serum antibody screening) is incorrect. Standard serum antibody screening

(indirect Coombs test) detects antibodies directed against Rh and other antigens that occur

normally on the surface of human RBCs. It does not detect the antibodies that are present in

infectious mononucleosis.

Option E (Serum transaminase tests) is incorrect. Tests for serum transaminases (e.g.,alanine aminotransferase) are useful in the diagnosis of hepatitis, which is invariably present

in patients with infectious mononucleosis. Thus, markedly increased levels of serum

transaminases would be expected in this patient, but they would not help diagnose the cause

of the hepatitis. The hepatitis in mononucleosis is self-limited and does not progress into

chronic hepatitis.

An Rh-positive 25-year-old woman with blood group O delivers an Rh-negative infant with

blood group A. The infant develops jaundice 8 hours after birth. An antibody screen of the

mother is negative. Laboratory studies show that the infant has a mild normocytic anemia and

an unconjugated hyperbilirubinemia. A direct Coombs test of the cord blood is positive. Aperipheral blood smear shows spherocytes. Which of the following is the most likely

diagnosis?

Option A (ABO hemolytic disease of the newborn) is correct. The most common cause of

jaundice within the first 24 hours after birth is ABO hemolytic disease of the newborn.

Individuals with blood group O normally have anti-A and anti-B antibodies of the IgM type as

well as anti-A,B antibodies of the IgG type. Therefore, ABO incompatibility occurs in pregnant

women who are blood group O and carrying fetuses with blood group A or blood group B.

Maternal anti-A,B-IgG antibodies cross the placenta and attach to the A or B antigens of the

fetal RBCs. Fetal macrophages in the spleen phagocytose and destroy the IgG-coated fetal


7/11

RBCs, causing the release of unconjugated bilirubin (macrophage end-produce of bilirubin

degradation) into the fetal blood and a mild hemolytic anemia. The unconjugated bilirubin is

removed by the mothers liver. In this neonate, the liver is unable to metabolize the increased

unconjugated bilirubin, causing jaundice within the first 24 hours. A direct Coombs test of the

RBCs is positive, because IgG antibodies coat the surface of the RBCs. The peripheral blood

contains numerous spherocytes, which are produced when splenic macrophages remove part

of the RBC membrane coated by the IgG antibodies rather than the entire RBC. In most cases,

an exchange transfusion is unnecessary in treating ABO hemolytic disease of the newborn,because the degree of anemia is not very severe and the level of unconjugated bilirubin is not

high enough to produce kernicterus.

Option B (Glucose-6-phosphate dehydrogenase (G6PD) deficiency) is incorrect. G6PD

deficiency is an X-linked recessive disorder that produces an intravascular hemolysis caused

by hydrogen peroxideinduced damage of RBC membranes and hemoglobin. G6PD deficiency

is not an antibody-mediated hemolysis; therefore, the direct Coombs test is negative, not

positive.

Option C (Hereditary spherocytosis) is incorrect. Hereditary spherocytosis is an

autosomal dominant disorder caused by a defect in ankyrin in the cell membrane. Hereditary

spherocytosis is not an antibody-mediated hemolysis; therefore, the direct Coombs test is

negative, not positive.

Option D (Pyruvate kinase deficiency) is incorrect. Pyruvate kinase deficiency is an

autosomal recessive hemolytic anemia. In pyruvate kinase deficiency, RBCs have no adenosine

triphosphate, causing dehydration of the RBCs due to damage to the RBC membrane. The

RBCs have spiny protuberances from the surface. Splenic macrophages remove the damaged

RBCs causing a hemolytic anemia with jaundice. Pyruvate kinase deficiency is not an

antibody-mediated hemolysis; therefore, the direct Coombs test is negative, not positive.

Option E (Rh hemolytic disease of the newborn) is incorrect. Rh hemolytic disease of the

newborn occurs when Rh-positive infants are born to Rh-negative (D-antigen negative)

mothers. The neonate, in this case, is Rh negative.



Option A (A 4-year-old child has whooping cough.) is correct.Bordetella pertussis is the





8/11

The photograph shows a small lymphocyte with scant cytoplasm surrounding a dark nucleus.










Option D (A 45-year-old woman has severe rheumatoid arthritis.) is incorrect.


arthritis).





have basophilia.

A few weeks after an upper respiratory infection, a 10-year-old boy has several bouts of

epistaxis associated with nonpruritic lesions on the skin (see photograph). The skin lesions

are nonpalpable and do not blanch under digital pressure. There is no evidence of

lymphadenopathy or hepatosplenomegaly on physical examination. Hemoglobin and WBC

counts are normal. WBC morphology is normal. The platelet count is 25,000/mm

3

. Which ofthe following is the most likely cause of the platelet abnormality?

Option A (Antibodies directed against a platelet receptor) is correct. The patient has

idiopathic thrombocytopenic purpura (ITP), which is caused by IgG antibodies that are

directed against glycoprotein IIb/IIIa fibrinogen receptors on the surface of platelets (type II

hypersensitivity reaction). Splenic macrophages with receptors for IgG phagocytose destroy

the platelets leading to thrombocytopenia. The lesions shown in the photograph are

petechiae, which are defined as pinpoint areas of hemorrhage into the subcutaneous tissue.

Petechiae and epistaxis are common signs of a platelet disorder. ITP is the most common

cause of thrombocytopenia in children and is treated with corticosteroids. The prognosis is


9/11

excellent.

Option B (Deficiency of von Willebrand factorcleaving protease) is incorrect. A

deficiency of von Willebrand factorcleaving protease in endothelial cells is found in

thrombotic thrombocytopenic purpura (TTP), an uncommon cause of thrombocytopenia in

women. It is characterized by endothelial damage at the arteriole-capillary junctions

throughout the body. This exposes von Willebrand factor (vWF), which is a platelet adhesion

factor that is normally synthesized by endothelial cells. Platelets have GpIb receptors thatadhere to the exposed vWF. Following adhesion, there is platelet aggregation and the

formation of platelet thrombi at all of these injury sites. Consumption of platelets in these

thrombi is sufficient enough to produce thrombocytopenia. TTP produces a classic pentad of

fever, thrombocytopenia, microangiopathic hemolytic anemia with schistocytes (platelet

thrombi damage RBCs), central nervous system dysfunction, and renal failure.

Option C (Immunocomplex vasculitis involving small vessels) is incorrect.

Immunocomplex vasculitis involving small vessels damages the vessels and causes multifocal

areas of subcutaneous hemorrhage (purpura or ecchymoses). The acute inflammatory

reaction causes the affected tissue to swell causing the lesions to be palpable; hence, the term

palpable purpura as an identifying feature of small vessel vasculitis.

Option D (Infiltrative bone marrow disease with destruction of megakaryocytes) is

incorrect. Infiltrative bone marrow disease with destruction of megakaryocytes commonly

occurs in leukemia, myelofibrosis, and metastatic disease to the bone marrow. In all these

conditions, immature WBCs and nucleated RBCs are present in the peripheral blood.

Option E (Vessel damage due to a toxin produced by Escherichia coli) is incorrect. The

O157:H7 strain ofE. coli produces a toxin that damages small vessels causing hemolytic

uremic syndrome. It is usually contracted by eating undercooked beef products (e.g., steak,

hamburgers). Findings are very similar to what has been described for TTP; except, the toxinis responsible for injury at the arteriole-capillary junctions that initiates platelet thrombus

formation and consumption of platelets.

An afebrile blood group O, Rh negative (O) 75-year-old man has a massive lower

gastrointestinal bleed from sigmoid diverticulosis. He has to be transfused with blood group

O, Rh positive (O+) blood, because no group O, Rh negative (O) blood is currently available in

the blood banks in the area. He states that he has been transfused once in the past without any

problems. In the pretransfusion workup, the patient has a negative antibody screen and a

compatible major crossmatch with 4 units of group O, Rh positive (O+) blood. Midway through

infusion of the third unit of blood he develops fever, headache, and tachycardia. The

transfusion is stopped and a transfusion workup in the blood bank exhibits the following on aposttransfusion specimen of patient blood:

Patient temperature: 103o F (39.4 C)

Patient blood pressure: 130/86 mm Hg

Patient pulse: 130 beats/minute

Patient plasma: clear

Patient antibody screen:negative

Patient direct Coombs: negative

Patient urine: negative dipstick for blood


10/11

Which of the following best explains the mechanism for the transfusion reaction?

Option E (Patient anti-HLA antibodies are directed against donor leukocytes) is correct.

The patient has a febrile transfusion reaction. In these reactions, the recipient has anti-human

leukocyte antigen (HLA) antibodies directed against foreign HLA antigens on donor

leukocytes (type II hypersensitivity reaction). Destruction of the donor leukocytes releasespyrogens causing fever as well as other findings such as chills, headache, and flushing.

Option A (Delayed hemolytic transfusion reaction) is incorrect. The antibody screen and

direct Coombs test are both negative. This excludes the presence of IgG antibodies in the

serum attaching to foreign antigens on donor RBCs. This would lead to phagocytosis and

destruction of the RBCs by splenic macrophages (extravascular hemolysis) and unconjugated

hyperbilirubinemia, with a possibility of developing jaundice.

Option B (Error in the major crossmatch) is incorrect. Although errors in crossmatching

blood do occur, they are extremely rare. Furthermore, an error would not explain the

correlation of fever with infusion of the blood.

Option C (Hemolytic transfusion reaction related to receiving Rh positive blood) is

incorrect. The patient had a negative antibody screen prior to his transfusions, which

excludes the presence of preexisting anti-D antibodies. Receiving D antigen positive blood

would not result in the immediate development of antibodies leading to a hemolytic anemia.

However, it is likely, that in the future, he would have to receive D antigen negative blood,

because of anti-D antibodies from D antigen positive transfusions.

Option D (Histamine-related transfusion reaction) is incorrect. The patient does not have

an allergic type of transfusion reaction, which involves the release of histamine from mastcells leading to itching, flushing, and hives (type I hypersensitivity reaction).




correct. This patient would most likely develop trichinosis, due to Trichinella spiralis. It is






11/11






perforated acute appendicitis produces neutrophilic leukocytosis with left shift (e.g., bandneutrophils) and toxic granulation (prominent azurophilic granules).

Option D (A 45-year-old woman has severe rheumatoid arthritis.) is incorrect.


arthritis).





have basophilia.

rapid review questions

Documents