Clinical Pathology(Heme)

Front 1

The increased HbF often present in patients with sickle cell disease is protective. How?
A. since there is no beta globin cells don't sickle as readily
B. HbF binds O2 with greater affinity than most other hemoglobins increasing RBC O2 delivery
C. HbF inhibits HbSS polymerization
D. A & B
E. A, B, C

Back 1

E. A, B, C.
Most patients with HbSS do not present at birth, but rather, most often at several months of age. Part of the reason is that HbF is at its highest in utero and immediately
post-partum, affording babies many protective benefits.
QCCP2, HbS

Front 2

What single etiology accounts for the majority of aplastic crises in children with sickle cell disease?
A. Salmonella
B. parvovirus B19
C. repeated microthrombotic episodes
D. low oxygen stress
E. high oxygen stress

Back 2

B. parvovirus B19.
Just like in patients with HbS disease, parvovirus is the most common cause of aplastic anemia, accounting for at least 70% of cases. Patients with sickle cell disease
have chronic thrombosis, which accounts for many of the other crises associated with sickle cell disease (acute chest, bone). Patients with HbSS are also at an increased
risk for infections, especially Salmonella.
QCCP2, HbS

Front 3

All of the following neurological conditions are associated with HbS disease, except:
A. meningitis
B. cerebral infarction
C. Lhermitte-Duclos
D. sensorineural hearing loss
E. moyamoya disease

Back 3

C. Lhermitte-Duclos.
Lhermitte-Duclos is a rare cerebellar tumor associated with Cowden syndrome, not HbS disease. Patients with sickle cell disease are at an increased risk of increased risk
of infection, especially with encapsulated bacteria due to autosplenectomy. There are several neurological manifestations of chronic thrombosis - TIAs, infarctions, and
hearing loss as well as moyamoya disease. Moyamoya is Japanese for “puff of smoke,” due to the characteristic diffuse expansion of contrast agent of cerebral
angiography, due to the vast collateral vascular network that develops secondary to arterial stenosis.
QCCP2, HbS

Front 4

All of the following nephropathies are associated with sickle cell disease, except:
A. papillary necrosis
B. renal infarction
C. thin basement membrane disease
D. pyelonephritis
E. renal medullary carcinoma

Back 4

C. thin basement membrane disease.
Thin basement membrane disease is a congenital disorders unrelated to sickle cell disease. There are 7 classic nephropathies of sickle cell disease, which, in addition to
the above, include gross hematuria, isosthenuria, and nephrotic syndrome.
QCCP2, HbS

Front 5

Which of the following complications of sickle cell disease occurs more frequently in patients with HbSC and HbS-beta thalassemia than in those with HbSS?
A. pre-eclampsia
B. chronic nonspecific hepatomegaly
C. hyperhemolytic crisis
D. priapism
E. proliferative retinopathy

Back 5

E. proliferative retinopathy.
For some reason, proliferative retinopathy occurs more commonly in HbSC and HbS-beta thalassemia than in HbSS.
QCCP2, HbS

Front 6

What is the effect of coinheritance of beta thalassemia on the HbS proportion in patients with HbS mutation?
A. decreased
B. no change
C. elevated
D. it depends
E. there is no HbS in HbS-beta thalassemia

Back 6

C. elevated.
The proportion of HbS in patients with HbS/beta thalassemia is increased to >50%, unlike in HbS/alpha thalassemia, where there is a decreased percentage of HbS. The
extent to which the HbS is decreased depends on the number of alpha globin genes detected.
QCCP2, HbS

Front 7

Which of the following hemoglobinopathies is associated with rod-shaped crystals?
A. HbS
B. HbC
C. HbSC
D. HbD
E. HbE

Back 7

B. HbC.
In addition to the rod-shaped crystals of hemoglobin, which results in the pencil cells of HbC, there are also abundant target cells, a nonspecific feature associated with
many hemoglobinopathies.
QCCP2, HbC

Front 8

This hemoglobinopathy is due to a fusion product of the delta and beta as well as a characteristic HbS proportion of less that 30%:
A. HbD
B. HbG
C. HbLepore
D. HbConstant Spring
E. HbE

Back 8

C. Hb L .
The unusual proportion of little HbS is due to confusion in reading the alkaline cellulose acetate gel where HbLepore and HbS comigrate.
QCCP2, HbLepore

Front 9

All of the following hemoglobins are unstable, except:
A. HbChesapeake
B. HbHasharon
C. HbKoln
D. HbZurich
E. HbHammersmith

Back 9

A. HbC .
HbChesapeake and HbDenver are Hb mutants with increased oxygen affinity, which can be demonstrated on a Hb:O2 dissociation graph. The remaining choices are all
hemoglobin mutations with decreased stability, which can present with hemolysis following oxidative stress.
QCCP2, Unstable and high oxygen affinity hemoglobin

Front 10

Which of the following ions is bound to hemoglobin in methemoglobin?
A. Ca++
B. Fe+++
C. Fe++
D. Mg++
E. Mn++

Back 10

B. Fe+++.
Iron in its oxidized ferric form, Fe+++ is bound to hemoglobin in methemoglobin, also known as hemiglobin (Hi). Methemoglobin has three letters before hemoglobin just
like the 3+ charge; ferric has an i in it like hemiglobin. Methemoglobin cannot bind oxygen like hemoglobin bound to the reduced ferrous form.
QCCP2, Methemoglobin

Front 11

What is the treatment of methemoglobinemia?
A. methylene blue
B. cyanide
C. desferroxamine
D. phenacetin
E. EDTA

Back 11

A. methylene blue.
Methylene blue reduces the 3+ ferric to 2+ ferrous form, thus converting hemiglobin, which can't bind oxygen, to hemoglobin, which can bind oxygen. Hemiglobin can be
used in the treatment of cyanide poisoning because hemiglobin binds cyanide with very high affinity. Desferroxamine and EDTA are chelating agents. Phenacetin can
cause an acquired methemoglobinemia.
QCCP2, Methemoglobin

Front 12

All of the following are part of the beta-globin cluster, except:
A. delta globin gene
B. beta globin gene
C. alpha globin gene
D. gamma globin gene
E. beta pseudogene

Back 12

C. alpha globin.
The beta globin genes are clustered together as a number of genes and pseudogenes on chromosome 11. Alpha globin is present as 2 genes on chromosome 16.
QCCP2, Thalassemia

Front 13

What's the most frequent genetic cause of beta° allele production?
A. nonsense mutations
B. promoter mutations
C. locus control region mutations
D. point mutations
E. 5' untranslated region mutations

Back 13

A. nonsense mutations.
Nonsense and frameshift mutations account for the majority of the mutations that lead to the loss of expression of beta-globin. beta° mutations produce no beta-globin,
while beta+ mutations lead to decreased beta-globin expression.
QCCP2, Thalassemia

Front 14

Which of the following genotypes is associated with alpha thalassemia trait?
A. --/-alpha
B. -alpha/-alpha
C. --/alphacsalpha
D. A & B
E. A, B, C

Back 14

D. A & B.
Alpha thalassemia trait manifests as 50% less HbA than wild type. It follows that the genotype of alpha thalassemia would show 1/2 the amount of alpha genes. There
are several possibilities whose frequency depends on ethnicity. The -alpha/-alpha genotype is more common in the African-American population, while the --/alpha alpha
genotype is seen more often in Asians. HbConstant Spring is an alpha mutation in the 5' UTR that results in the loss of alpha expression, therefore the --/alphaCSalpha
phenotype is HbH.
QCCP2, Thalassemia

Front 15

All of the following are considered “thalassemic indices,” except:
A. decreased RBC count
B. low MCV
C. lot Hct
D. normal to slightly increased RDW
E. MCV/RBC ratio <13

Back 15

A. decreased RBC count.
In fact, there is an increased RBC count perhaps responsive to the decreased hematocrit. All the other choices are recognized as consistent with thalassemia.
QCCP2, Clinical features

Front 16

What's the most common confounding factor that causes beta-thalassemia to be diagnosed as alpha-thalassemia based on hemoglobin electrophoresis?
A. concomitant sickle cell disease
B. concomitant sickle cell trait
C. concomitant congenital dyserythropoietic anemia
D. iron deficiency
E. hereditary elliptocytosis

Back 16

D. iron deficiency.
The typical finding in beta thalassemia on hemoglobin electrophoresis is increased HbA2 (>2.5%) with normal HbF. In the case of concomitant Fe deficiency with beta
thalassemia in anemic patients, the HbA2 percentage may be normal, giving the appearance of alpha thalassemia. In that case, it is important to note that
electrophoresis should be repeated after ruling out iron deficiency and treatment if necessary.
QCCP2, Thalassemia

Front 17

How is beta-thalassemia major defined?
A. beta/beta+
B. beta/beta°
C. beta°/beta°
D. beta°/beta+
E. none of the above

Back 17

E. none of the above.
Admittedly, a trick question. Some of the genotypes above, most notably beta°/beta°, could be associated with beta thal major. However, the strict definition of beta
thalassemia major is clinical - dependence on transfusion.
QCCP2, Thalassemia

Front 18

What's the most common cause of warm autoimmune hemolytic anemia?
A. IgM anti-I
B. IgG anti-I
C. IgM anti-Rh
D. IgG anti-Rh
E. IgM anti-H

Back 18

D. IgG anti-D.
Broad specificity anti-Rh antibodies account for the majority of cases of warm autoimmune hemolytic anemia, while IgM anti-I is responsible for most cases of cold
autoagglutinins.
QCCP2, WAIHA

Front 19

All of the following antibodies are capable of fixing complement, except:
A. IgA
B. IgM
C. IgG1
D. IgD
E. IgG3

Back 19

D. IgD.
A subset of immunoglobulins are capable of binding to complement and lead to hemolysis. Of all the IgG subtypes, only IgG3 and IgG1 bind to complement. When IgG
binds, it tends to lead to extravascular hemolysis in the spleen.
QCCP2, WAIHA

Front 20

What's the specificity of the most common cause of cold autoagglutinins?
A. anti-i
B. anti-H
C. anti-Pr
D. anti-I
E. anti-IH

Back 20

D. anti-I.
Anti-I is associated with atypical (mycoplasmic) pneumonia and is the most common cause of cold IgM autoagglutinins, which can be either pathological or nonpathological.
QCCP2, Cold autoagglutinins

Front 21

What's the only reliable CBC index in the presence of cold agglutinins?
A. Hct
B. hemoglobin
C. RDW
D. platelets
E. reticulocyte index

Back 21

B. hemoglobin.
Due to the potential for cold autoagglutinins to react at or near room temperature, there is a substantial risk of agglutination in automated counters leading to aberrant results for most CB indices. Since hemoglobin is directly measured and unaffected by clumping, it can be reliably measured.
QCCP2, Cold autoagglutinins

Front 22

Which of the following reagents can be used to detect antibodies directed against the i antigen?
A. type O cord blood
B. type O adult blood
C. type A1 adult blood
D. A & B
E. A, B, C

Back 22

A. type O cord blood.
Remember, little i is a more immature glycoprotein on red cells which matures with branching to form the big I antigen. The formation of little i antigen is associated with EBV mononucleosis.
QCCP2, T4.10

Front 23

What is the most common modern presentation of paroxysmal cold hemoglobinuria?
A. older people with Reynaud syndrome
B. in children following a viral illness
C. older person several years following a syphilis infection
D. neonates with congenital syphilis
E. alcoholics with advanced cirrhosis

Back 23

B. in children following a viral illness.
Though originally described in syphilitics, the most common presentation nowadays is in children after viral (measles, mumps, VZV, EBV most commonly) infections.
QCCP2, Paroxysmal cold hemoglobinuria

Front 24

What description best fits the Donath-Landsteiner antibody?
A. IgM cold agglutinin/hemolysin
B. biphasic IgM hemolysin
C. IgG biphasic hemolysin
D. IgG warm agglutinin/ hemolysin
E. cold IgM agglutinin

Back 24

C. IgG biphasic hemolysin.
Donath-Landsteiner antibody is a biphasic anti-P IgG hemolysin described for its ability to bind to antigen and cold temperatures, such as at the periphery, but then to lyse when incubated at warm temperatures when the circulation brings the blood back to the central warmer areas.
QCCP2, Paroxysmal cold hemoglobinuria

Front 25

Which describes the best way to detect cryoglobulins?
A. run serum electrophoresis at 4°C
B. clot blood at 4°C then immediately subject serum to electrophoresis
C. incubate serum at 4°C with non-specific IgM, subject immunoprecipitate to electrophoresis
D. clot blood at 37°C, store serum for 3 days at 4°C, collect precipitate and subject to electrophoresis
E. spin down unclotted blood at 37°C, store supernatant at 4°C, subject precipitate to electrophoresis

Back 25

D. clot blood at 37°C, store serum 3 days at 4°C, collect precipitate and subject to electrophoresis.
We need serum, not plasma, so choice E is out. Choice C wouldn't produce anything except native serum with a lot of IgM. Choices A and B also wouldn't be much different from normal serum. The cryoglobulins must be cold-precipitated from serum, then subjected to electrophoresis.
QCCP2, Cryoglobulinemia

Front 26

Which of the following types of cryoglobulins are most commonly associated with Waldenstrom macroglobulinemia?
A. type I
B. type II
C. type III
D. types II and III
E. type IV

Back 26

A. type I.
Type I is due to monoclonal cryoglobulins, which fits best with a monoclonal IgM gammopathy, such as Waldenstrom macroglobulinemia. Type II cryoglobulins are a mix of polyclonal and monoclonal (which is usually an IgM anti-IgG) and are the most common (mostly due to SLE and HCV). Type III is a mix of two different polyclonal processes.
QCCP2, Cryoglobulins

Front 27

All of the following are associated with the clinical presentation of cryoglobulinemia, except:
A. palpable purpura
B. petechiae
C. arthralgias
D. glomerulonephritis
E. anemia

Back 27

B. petechiae.
Petechiae are a sign of microvascular bleeding due to either platelet or small vessel defects, not associated with cryoglobulinemia. The palpable purpura is very common and reflects an underlying leukocytoclastic vasculitis.
QCCP2, Cryoglobulinemia

Front 28

What is the most common renal manifestation of cryoglobulinemia?
A. minimal change
B. membranous glomerulopathy
C. post-infectious glomerulonephritis
D. membranoproliferative glomerulonephritis, type I
E. membranoproliferative glomerulonephritis, type II

Back 28

E. membranoproliferative glomerulonephritis, type II.
Renal disease commonly affects patients with cryoglobulinemia and usually presents several years after initial symptoms of disease. Clinically, it can manifest as a nephrotic or nephritic syndrome with severe hypocomplementemia. The dense deposits of type II MPGN have the ultrastructural feature of subendothelial immune complexes with a fibrillary pattern.
QCCP2, Cryoglobulinemia

Front 29

What is typically the earliest laboratory evidence of an iron-deficiency anemia?
A. decreased transferrin
B. decreased ferritin
C. decreased serum iron
D. increased zinc protoporphyrin
E. decrease in hemoglobin

Back 29

B. decreased ferritin.
Usually, decreased ferritin is the most sensitive indication of a possible iron-deficiency anemia. This is followed by the rest of the choices presented, with a decrease in hemoglobin being a later manifestation of iron deficiency anemia. It is important to note that ferritin is an acute phase response protein and that, in patients with decreased hepatic clearance, the levels could be increased.
QCCP2, Iron deficiency anemia

Front 30

Which of the following patterns is most consistent with iron-deficiency anemia?
A. increased soluble serum transferrin receptor, zinc protoporphyrin, free erythrocyte protoporphyrin, and decreased ferritin
B. decreased soluble serum transferrin receptor, zinc protoporphyrin, free erythrocyte protoporphyrin, and increased ferritin
C. increased soluble serum transferrin receptor, decreased zinc protoporphyrin, free erythrocyte protoporphyrin, and ferritin
D. decreased soluble serum transferrin receptor, zinc protoporphyrin, free erythrocyte protoporphyrin, and ferritin
E. increased soluble serum transferrin receptor, zinc protoporphyrin, free erythrocyte protoporphyrin, and ferritin

Back 30

A. increased serum soluble transferrin receptor, zinc protoporphyrin, free erythrocyte protoporphyrin, and decreased ferritin.
The pattern most consistent with iron-deficient anemia would be decreased serum Fe, ferritin, with increased TIBC, ZPP, FEP, and serum soluble transferrin receptor. It is important to note that many of the tests are nonspecific and false negative results are common due to confounding comorbidities, such as a chronic inflammatory state or hepatic insufficiency.
QCCP2, Iron deficiency anemia