Q 1:
Transfusion related acute lung injury is best defined as:
A. acute onset of chest pain within 1 h of transfusion, hypoxemia, (PaO 2 /FiO 2 < 300 mm Hg), bilateral infiltrates on chest radiography and absence of left heart failure
B. acute onset of chest pain within 6 h of transfusion, hypoxemia, (PaO 2 /FiO 2 < 300 mm Hg), bilateral infiltrates on chest radiography and absence of left heart failure
C. acute onset of pulmonary insufficiency within 1 h of transfusion, hypoxemia, (PaO 2 /FiO 2 < 300 mm Hg), bilateral infiltrates on chest radiography and absence of left heart failure
D. acute onset of pulmonary insufficiency within 6 h of transfusion, hypoxemia, (PaO 2 /FiO 2 < 300 mm Hg), bilateral infiltrates on chest radiography and absence of left heart failure
E. acute onset of pulmonary insufficiency within 6 h of transfusion, hypoxemia, (PaO 2 /FiO 2 < 300 mm Hg), hypercarbia (PaCO 2 > 50 mm Hg), bilateral infi ltrates on chest radiography and absence of left heart failure
Answer :
D
Pulmonary complications from blood transfusion comprise a spectrum of disease ranging in severity from mild pulmonary edema to transfusion related acute lung injury (TRALI).
Transfusion related acute lung injury is defi ned as acute respiratory compromise with the onset of dyspnea, hypoxia, and non-cardiogenic pulmonary edema within 6 h of transfusion.
All plasma-containing blood products (whole blood, RBC, platelets, FFP, cryoprecipitate and IVIG) have the potential to cause TRALI, and the incidence is cited as 1 in 5,000 transfusions.
It has been postulated that TRALI results from an immunogenic response that leads to pulmonary capillary endothelial damage, capillary leak and edema formation.
It is thought that donor antibodies react with the antigens on the recipient WBCs resulting in complement
activation. Granulocyte chemotaxin (C5a) attracts leukocytes to the pulmonary circulation and neutrophil lysosomal enzymes damage the capillary endothelium resulting in capillary
leak of fl uid into pulmonary alveoli.
The diagnosis of TRALI is based on clinical criteria and is made primarily after excluding other possible conditions. Proposed clinical criteria for the diagnosis of TRALI include:
(1) the acute onset of pulmonary insuffi ciency (within 6 h)
(2) hypoxemia, specifi cally PaO 2 /FiO 2 < 300 mm Hg
(3) bilateral fl uffy infi ltrates on chest radiography
(4) pulmonary artery wedge pressure ≤ 18 mm Hg
(5) the absence of left atrial hypertension.
Laboratory analysis of donor and recipient blood samples may further support the diagnosis.
If acute respiratory distress occurs during the transfusion, the transfusion should be stopped immediately.
The treatment is primarily supportive; oxygenation and ventilation must be maintained and mechanical ventilation implemented as necessary.
There is no supporting evidence for the use of corticosteroids or other anti-infl ammatory medications in the treatment of TRALI.
TRALI typically resolves after 48–96 h and does not cause permanent pulmonary damage.
Although rare, this is a potentially severe complication of blood product transfusions.
Although TRALI should be considered in any pediatric patient with the onset of acute pulmonary disease within 6 h following transfusion, the clinician should remember that other conditions may mimic TRALI.
- The diagnosis of acute intravascular volume overload (TACO: transfusion-associated circulatory
overload) should be considered in any child with underlying cardiac insuffi ciency.
- Hemolytic transfusion reactions, or anaphylaxis due to the transfusion of IgA-containing products to
a recipient with IgA defi ciency may also produce pulmonary manifestations.
- Several diagnoses, specifi c to the pediatric hematology-oncology population, may be confused with
TRALI and include :
-Acute chest syndrome in transfused patients with sickle cell anemi
- Diffuse alveolar hemorrhage during bone marrow recovery in a bone marrow
transplant patient, and acute respiratory distress occurring during granulocyte
transfusions.
-----------------------------------------------
Q 2:
1 unit of random donor platelets may increase platelet count by about
a) 1,000
b) 7 ,000
c) 20,000
d) 30,000
e) 50,000
Typically, one unit of platelets is transfused per 10 kg body weight. For infants and children, this will raise the platelet count by approximately 50,000/ m L.
Six units of platelets in the “standard” adult patient should raise the platelet count by about 30,000/ m L 1 h after the infusion.
Each unit of platelets typically raises the platelet count by approximately 5,000–10,000/ m L in adults.
--------------------
Q 3:
Free Erythrocyte Protoporphyrin is increased in the following conditions except :
A- Iron deficiency
B- Iron deficiency anemia.
C- Chronic lead poisoning.
D- Pyridoxine-responsive anemia
E- Anemia of chronic diseases.
Answer :
D
The Free Erythrocyte Protoporphyrin (FEO) test measures the non-complexed, non-heme protoporphyrin concentration in blood. This test alone is not sensitive enough to diagnose iron deficiency, but an elevated FEP in conjunction with a low MCV is suggestive.
A progressive, exponential increase in erythrocyte protoporphyrin concentration is observed at blood lead levels of 5 to 90 μg/dL.550 The
erythrocyte protoporphyrin level is an indicator of adverse metabolic effects. It is very effective as a screening test for severe lead poisoning, but it cannot be used to screen for blood lead levels below 40 to 50 μg/dL.
--------------------------
Q 4
Answer :
D
Pulmonary complications from blood transfusion comprise a spectrum of disease ranging in severity from mild pulmonary edema to transfusion related acute lung injury (TRALI).
Transfusion related acute lung injury is defi ned as acute respiratory compromise with the onset of dyspnea, hypoxia, and non-cardiogenic pulmonary edema within 6 h of transfusion.
All plasma-containing blood products (whole blood, RBC, platelets, FFP, cryoprecipitate and IVIG) have the potential to cause TRALI, and the incidence is cited as 1 in 5,000 transfusions.
It has been postulated that TRALI results from an immunogenic response that leads to pulmonary capillary endothelial damage, capillary leak and edema formation.
It is thought that donor antibodies react with the antigens on the recipient WBCs resulting in complement
activation. Granulocyte chemotaxin (C5a) attracts leukocytes to the pulmonary circulation and neutrophil lysosomal enzymes damage the capillary endothelium resulting in capillary
leak of fl uid into pulmonary alveoli.
The diagnosis of TRALI is based on clinical criteria and is made primarily after excluding other possible conditions. Proposed clinical criteria for the diagnosis of TRALI include:
(1) the acute onset of pulmonary insuffi ciency (within 6 h)
(2) hypoxemia, specifi cally PaO 2 /FiO 2 < 300 mm Hg
(3) bilateral fl uffy infi ltrates on chest radiography
(4) pulmonary artery wedge pressure ≤ 18 mm Hg
(5) the absence of left atrial hypertension.
Laboratory analysis of donor and recipient blood samples may further support the diagnosis.
If acute respiratory distress occurs during the transfusion, the transfusion should be stopped immediately.
The treatment is primarily supportive; oxygenation and ventilation must be maintained and mechanical ventilation implemented as necessary.
There is no supporting evidence for the use of corticosteroids or other anti-infl ammatory medications in the treatment of TRALI.
TRALI typically resolves after 48–96 h and does not cause permanent pulmonary damage.
Although rare, this is a potentially severe complication of blood product transfusions.
Although TRALI should be considered in any pediatric patient with the onset of acute pulmonary disease within 6 h following transfusion, the clinician should remember that other conditions may mimic TRALI.
- The diagnosis of acute intravascular volume overload (TACO: transfusion-associated circulatory
overload) should be considered in any child with underlying cardiac insuffi ciency.
- Hemolytic transfusion reactions, or anaphylaxis due to the transfusion of IgA-containing products to
a recipient with IgA defi ciency may also produce pulmonary manifestations.
- Several diagnoses, specifi c to the pediatric hematology-oncology population, may be confused with
TRALI and include :
-Acute chest syndrome in transfused patients with sickle cell anemi
- Diffuse alveolar hemorrhage during bone marrow recovery in a bone marrow
transplant patient, and acute respiratory distress occurring during granulocyte
transfusions.
-----------------------------------------------
Q 2:
1 unit of random donor platelets may increase platelet count by about
a) 1,000
b) 7 ,000
c) 20,000
d) 30,000
e) 50,000
Typically, one unit of platelets is transfused per 10 kg body weight. For infants and children, this will raise the platelet count by approximately 50,000/ m L.
Six units of platelets in the “standard” adult patient should raise the platelet count by about 30,000/ m L 1 h after the infusion.
Each unit of platelets typically raises the platelet count by approximately 5,000–10,000/ m L in adults.
--------------------
Q 3:
Free Erythrocyte Protoporphyrin is increased in the following conditions except :
A- Iron deficiency
B- Iron deficiency anemia.
C- Chronic lead poisoning.
D- Pyridoxine-responsive anemia
E- Anemia of chronic diseases.
Answer :
D
The Free Erythrocyte Protoporphyrin (FEO) test measures the non-complexed, non-heme protoporphyrin concentration in blood. This test alone is not sensitive enough to diagnose iron deficiency, but an elevated FEP in conjunction with a low MCV is suggestive.
A progressive, exponential increase in erythrocyte protoporphyrin concentration is observed at blood lead levels of 5 to 90 μg/dL.550 The
erythrocyte protoporphyrin level is an indicator of adverse metabolic effects. It is very effective as a screening test for severe lead poisoning, but it cannot be used to screen for blood lead levels below 40 to 50 μg/dL.
--------------------------
Q 4
You
are seeing a 9-year-old boy for a health supervision visit. He was treated for
acute lymphoblastic leukemia at 4 years of age and has been off therapy and in
remission for almost 2 years.
Of
the following, the MOST important site to examine for potential relapse in this
boy is (are):
A. hips
B. liver
C. lymph
nodes
D. testes
E. tonsils
Answer
D
Answer
D
The
most common site of relapse of acute lymphoblastic leukemia (ALL) is the bone
marrow, but relapses in the central nervous system and the testes also are
important. Because more than 95% of treated children attain an initial
remission, most treatment failures are due to later relapses.
All
boys who have ALL must undergo testicular examination during routine health
supervision visits. Testicular relapse presents with painless testicular
enlargement that most often is unilateral and frequently is missed by the child
and parents. Both central nervous system and testicular relapse occur when the
bone marrow remains in remission.
-----
Q 5
Answer
E
-----
Q 5
A
15-month-old boy develops fatigue and pallor. Physical examination results are
otherwise normal. Laboratory studies reveal: hemoglobin, 2.9 g/dL (29 g/L);
white blood cell count, 6,400/cu mm (6.4 x 109/L); differential count, 43%
neutrophils, 49% lymphocytes, and 8% monocytes; platelets, 298,000/cu mm (298 x
109/L); mean corpuscular volume, 72 fL; reticulocyte count, 0.1% (1 x 10-3);
indirect bilirubin, 0.2 mg/dL (3.42 mcmol/L); and fetal hemoglobin, 2% (normal
for age.
Of
the following, the MOST likely diagnosis is:
A. anemia
of chronic disease
B. Diamond-Blackfan
anemia
C. Fanconi
anemia
D. iron
deficiency anemia
E. transient
erythroblastopenia of childhood
Answer
E
Transient
erythroblastopenia of childhood (TEC) is the most common form of pure red blood
cell aplasia in children. This acquired disorder occurs in previously healthy
children who present with severe anemia. Its pathophysiology is not understood,
although many have presumed a viral etiology. Most patients are between 1 and 3
years of age. The average hemoglobin at presentation is 5.7 g/dL (57 g/L).
White blood cell and platelet counts are usually normal, but neutropenia is
common. The anemia is normocytic and normochromic, and hemoglobin F levels are
normal for age. Severe erythroid hypoplasia is evident in the bone marrow
unless spontaneous recovery already is occurring, in which case erythroid
hyperplasia precedes the reticulocytosis and recovery. All patients recover,
with 60% requiring a transfusion for support until recovery. The recommendation
is to observe patients and provide transfusion if there is a risk of
cardiovascular compromise. No other therapy is indicated.
TEC
must be distinguished from Diamond-Blackfan anemia (DBA), a much more serious
disorder. Both dominant and autosomal recessive patterns of inheritance have
been reported for DBA, but 75% of cases are sporadic, suggesting that they are
acquired due to new mutations or to variable penetrance. A defect of the
erythroid stem cell is most likely responsible for the disorder. Pallor usually
is recognized at or soon after birth. Approximately 25% of patients demonstrate
physical anomalies, most commonly of the head and face. Hemoglobin levels
average 4 g/dL (40 g/L) at diagnosis. Macrocytosis is frequent, and
reticulocytes are decreased or absent. White blood cell counts are usually
normal. Although platelet counts also generally are normal, thrombocytopenia
may be noted at some point in 25% of patients. Elevated hemoglobin F levels,
increased titers of red blood cell membrane “i” antigen, and higher mean
corpuscular volumes are consistent with more “fetal-like” erythropoiesis. Bone
marrow examination usually reveals erythroid hypoplasia. Red blood cell
adenosine deaminase levels often are elevated.
Unlike
TEC, DBA does not remit spontaneously. Corticosteroids are useful. Fewer than
5% of patients respond rapidly and enter a steroid-independent remission, up to
60% respond but remain steroid-dependent, up to 20% eventually may be able to
discontinue steroids, fewer than 5% respond only to very large doses of
steroids and become transfusion-dependent, and 30% to 40% fail to respond to
corticosteroids. Approximately 15% of patients die. Bone marrow transplantation
can be effective. There also appears to be a small but increased risk of
leukemia among children who have DBA.
One
feature that helps to distinguish TEC from DBA is age, with only 20% of TEC
patients being younger than 1 year of age and more than 90% of children who
have DBA being diagnosed by 1 year. The presence of associated physical
anomalies, elevated hemoglobin F, macrocytosis, increased red blood cell “i”
antigen, and elevated red blood cell adenosine deaminase support a diagnosis of
DBA.
Other forms of pure red blood cell aplasia in children are very rare. The
anemia of chronic disease usually is associated with an obvious underlying
disorder and rarely is profound. Fanconi anemia seldom presents with anemia in
the first year, and usually physical anomalies, pancytopenia, and macrocytosis
are evident. Severe iron deficiency would be expected to be microcytic.
--
Q 6
--
Q 6
In
examining a 4-year-old girl who is new to your practice, you discover that she
has rudimentary thumbs and is well below the 5th percentile for both weight and
height. You also observe irregular hyperpigmentation on the trunk and
anogenital areas.
Of
the following, the MOST likely hematologic disorder associated with these
findings is:
A. acute
lymphoblastic leukemia
B. Bloom
syndrome
C. Diamond-Blackfan
anemia
D. Fanconi
anemia
E. thrombocytopenia
and absent radii (TAR) syndrome
Answer
D
Answer
D
Approximately 80% of
patients who have Fanconi anemia exhibit congenital anomalies. Recognizing
these anomalies is important because the aplastic anemia usually is not evident
until 4 to 14 years of age. Pancytopenia at birth is unusual. Among the
anomalies are hyperpigmentation (60% of patients); short stature (57%); upper
limb anomalies (48%) that include absent, hypoplastic, supernumerary, or bifid
thumbs and aplasia of the first metacarpal or the radius; hypogonadism (40%);
and microcephaly (27%). Almost 20% of affected patients manifest a variety of
other skeletal anomalies. The only potential cure for this autosomal recessive
disorder is bone marrow transplantation, and early diagnosis allows for better
donor identification and patient preparation. It is also important to make the
diagnosis to enable parents to use prenatal diagnosis for future children.
----------------------------
Q 7
Dyskeratosis
congenita is a rare inherited bone marrow failure syndrome in which aplastic
anemia complicates 50% of cases and in which there is a predisposition to
malignancies. The inheritance is complex. Skin and nail changes often appear
during childhood. Skeletal abnormalities, which include osteoporosis, avascular
necrosis, abnormal bone trabeculation, scoliosis, and mandibular hypoplasia,
are seen in 20% of cases. The skin and nail abnormalities are distinct from the
changes seen in Fanconi anemia.
Thrombocytopenia
and absent radii (TAR) syndrome is also known as congenital amegakaryocytic
thrombocytopenia. The classic finding of absent radii with thumbs present
differentiates it from Fanconi anemia. Anomalies of hands, shoulders, and lower
limbs also may be seen. TAR presents with isolated thrombocytopenia in the
neonate, but 45% of patients ultimately develop aplastic anemia. Inheritance is
complex but usually autosomal recessive.
Diamond-Blackfan
anemia, or congenital hypoplastic anemia, is associated with physical
abnormalities in approximately 25% of patients. Anomalies include a typical
facies, micrognathia, flattening of the thenar eminences, and triphalangeal thumbs.
Bloom
syndrome is a rare chromosomal breakage syndrome in which several skeletal
anomalies may be found; the major hematologic risk is development of leukemia
and other malignancies. Only mild anemia is typical.
----------------------------
Q 7
You
diagnose severe factor VIII deficiency hemophilia in a 3-year-old boy who has
no family history of hemophilia. The parents want to understand the disorder
better.
Of
the following, a TRUE statement is that:
A. family
history is negative in 30% of cases
B. identification
of female carriers is difficult
C. it
is a sex-linked recessive disorder with variable penetrance
D. moderate
hemophilia (factor VIII levels of 1% to 5%) is most common
E. prenatal
diagnosis is possible in only 25% of families
Answer
A
Providing genetic counseling to families that have severe factor VIII deficiency hemophilia (hemophilia A) has greatly improved, but it is limited by the absence of any family history in 30% of newly diagnosed children. This is due primarily to the strong predisposition of the factor VIII gene to mutate.
Approximately 50% to 60% of patients who have hemophilia have the severe form of the disease, with factor VIII levels of less than 1%. Patients who have moderate and mild hemophilia (factor VIII levels of 1% to 5% and greater than 5%, respectively) have different genetic defects.
---
Q 8:
A medical student asks you the difference between prothrombin time (PT) and partial thromboplastin time (PTT).
Answer
A
Providing genetic counseling to families that have severe factor VIII deficiency hemophilia (hemophilia A) has greatly improved, but it is limited by the absence of any family history in 30% of newly diagnosed children. This is due primarily to the strong predisposition of the factor VIII gene to mutate.
Approximately 50% to 60% of patients who have hemophilia have the severe form of the disease, with factor VIII levels of less than 1%. Patients who have moderate and mild hemophilia (factor VIII levels of 1% to 5% and greater than 5%, respectively) have different genetic defects.
---
Q 8:
A medical student asks you the difference between prothrombin time (PT) and partial thromboplastin time (PTT).
Which
of the following statements is TRUE?:
A. Only
the PTT is prolonged by heparin
B. Only
the PTT is prolonged in hemophilia and von Willebrand disease
C. The
International Normalized Ratio is derived from the PTT
D. The
PTT is preferred for monitoring coumarin dosage
E. The
PTT measures all the components of the PT except factor V
Answer:
B
Answer:
B
The
partial thromboplastin time (PTT) and prothrombin time (PT) are important
screening tests in the evaluation of children who have bleeding disorders. The
PTT measures all the factors in the pathway except factor VII. The PTT not only
measures more factors than the PT, but it measures those most commonly involved
in coagulopathies, such as factor VIII, which is involved in von Willebrand
disease and factor VIII deficiency hemophilia (hemophilia A).
The PTT also measures
factor IX and helps to identify patients who have factor IX deficiency
hemophilia (hemophilia B). Circulating antiphospholipid antibodies (“lupus”
anticoagulant) are more likely to prolong the PTT. Finally, the PTT is much
more sensitive to prolongation from heparin.
Normal
ranges for the PTT vary among laboratories but usually are in the range of 20
to 35 seconds for both children and adults. The PTT is prolonged in newborns,
particularly in preterm infants. The PTT usually remains normal until the level
of an affected factor falls below 30%, with a normal value arbitrarily set at
100% and the normal range approximately 50% to 150%.
The
PT measures factor VII as well as the factors common to both the PT and PTT
(factors X, V, II, and fibrinogen). The PT usually is in the range of 10 to 13
seconds and typically becomes prolonged when the level of involved factor is
below 40%. Prolongation of the PT in the presence of a normal PTT usually
reflects isolated factor VII deficiency. The PT is more useful in monitoring
the effect of coumarin-type anticoagulants. Although these drugs prolong both
tests, the PT reflects changes more rapidly. The half-life of factor VII, at 4
to 6 hours, is much shorter than the other coagulation factors. Therefore,
changes in factor VII levels induced by the coumarins are reflected most
quickly by the PT.
The
International Normalized Ratio (INR) is derived from the PT compared with
control values and using an international sensitivity index that corrects for
variation in the sensitivity of the varying reagents used to perform the PT.
The INR provides a value that reduces interlaboratory variation due to both techniques
and reagents used. For this reason, coumarin-induced anticoagulation is
assessed using the INR.
Deficiency
of factor XIII is not associated with prolongation of either the PTT or the PT.
