Anemia of Blood Loss

Acute blood loss

Chronic Blood Loss ( iron def. anemia because iron is

depleted )

RBC

Normochromic

normocytic.

Hypochromic microcytic

CAUSE

Trauma &

Hemorrhage

Hemolysis

Intravascular hemolysis

Extravascular hemolysis

Cuases

*trauma e . g by defective heart

valve, or valve prosthesis

*fixation of the complement

*exposure to Clostridia toxins

*(PNH)

*(G6PD) deficiency

*Immune-hemolytic anemia .

*Microangiopathichemolytic

anemia .

*Malaria

Most common in Hereditary

spherocytosis,

And sickle cell anemia

Symptoms

(1) Hemoglobinemia.

(2) Hemoglobinuria

(3) LDH is increased being

released from lysed RBCs .

((4) hemosidrinouria

(5) Massive hemolysis acute

tubular necrosis of the kidney

develops

(6) fanconi syndrome

(1) No hemoglobinemia or

hemoglobinuria seen

(2) Splenomegally(MORE)?

In both :

1-Decreased red cells life span . only 20 days

2-A compensatory increased erythropoiesis >>>

reticulocytosis

3-Retention of red cell destruction products

mainly iron & bilirubin >>

unconjugated, hyperbilirubinemia , jaundice

and formation of bilirubin-rich gallstones

(pigment )

+++

4-In severe hemolytic anemia extramedullary

hematopoiesis often develops in the spleen , liver

& lymph nodes .

5- The haptoglobin is always decreased

A 7-year-old girl is referred to your hematology

practice by her pediatrician after several

abnormal blood tests, which include an

increased mean corpuscular hemoglobin

concentration and increased red blood cell

osmotic fragility. You discover that one of the

child’s parents suffers from a genetic blood

disorder and you begin to suspect that the child

will most likely have to undergo surgery to treat

her disorder.

يا ترا شو نوع هاي العملية ؟؟؟؟؟؟؟

Hereditary Spherocytosis

Etiology autosomal dominant triat defect in the red blood cell membrane (usually spectrin or ankyrin) •In 25% of cases it is a severe autosomal recessive

Pathology Peripheral blood smear: Spherocytes (sphere-

shaped erythrocytes with no central pallor)

Clinical

Manifestations

Non specific: Splenomegaly; hemolytic

anemia, which can lead to jaundice ,

reticulocytosis , cholelithiasis ,

punctuated by aplastic crises

Lab findings: Increased erythrocyte osmotic

fragility, increased MCHC, normal MCV,

normal Hgb

Treatment

Splenectomy; folate supplementation

Note

Following splenectomy

(1) anemia will be corrected (because no spleen

to destroy RBCs).

(2) Spherocytes persist in peripheral blood .

(3) Appearance of Howell-Jolley bodies in

peripheral blood RBCs . The Howell-Jolley

body is a nuclear DNA remnant ,which is

normally removed by the spleen .

B-Vaccination against encapsulated organisms

like pneumococcus & H . influenza

and meningiococcalis also a must .

C-Supportive blood transfusion , especially

during aplastic crisis

An 8-year-old African American boy presents

to the emergency department complaining of

severe pain in both legs. The pain began after

the boy attended a pool party and spent much

of the day swimming. He reports that he has

suffered from severe bouts of back and chest

pain in the past owing to a pre-existing

medical condition. Routine laboratory studies

demonstrate a severe anemia. You place the

child on oxygen, begin aggressive intravenous

fluid hydration and call the blood bank to

prepare for a blood transfusion.

شو استفاد من الاكسجين ؟؟؟؟

Sickle Cell Anemia

Etiology * autosomal recessive

* point mutation at the 6th position of the β globin chain

* resulting in the production of Hgb S (96%)

Pathology Pathophysiology: Hgb S polymerizes in hypoxic environments (as

caused by infection, exercise, or dehydration), causing the RBC shape

to become distorted and more susceptible to hemolysis

Repeated episodes of sickling cause membrane damage the cell

accumulate calcium ,loose K water &then become irreversibly sickled

Clinical

Manifestations

1-Extravascular hemolysis >>>>> Reticulocytosis and hyperbilirubinemia and gall stones formation (

pigment ), spleen enlarged >> not specific

#extramedullary hematopoiesis >>bone marrow is hyperplastic >>

*cheek bones (chipmunk –like)

* hair on end or crew-cut appearance

# splanomegally in red pulp (500g)

2-Microvascular occlusion >> vaso occlusive crises

*Leg ulcers * autosplenectomy >> infections caused by pneumococci

& H. influenza ,Salmonella osteomyelitis , nasseria

* (Dactylitis)

* Acute chest syndrome : Triggered by pulmonary infections * CNS : seizures & strokes + septicemic & infective meningitis two leading causes of ischemia-related death *Aplastic crisis *

Treatment

Transfusions, fluid resuscitation, pain control, and oxygen during

hemolytic and vaso-occlusive crises; plasma exchange for severe vaso-

occlusive crises (ie, stroke, acute chest syndrome); hydroxyurea

(increases Hgb F levels) and bone marrow transplant for severe

disease

Note HbC : is another mutant β globin in which lysine residue instead of normal glutamic acid at position 6 . It is fairly common in USA the incidence is 1/1250 newborns are double heterozygotes they inherited HbS from one parent & HbC from the other parent i.e their hemoglobin is (HbSC)

A 10-month-old boy from Greece presents

with pallor and failure to thrive. During

physical

examination, you find that his spleen is enlarged and that he has an abnormal facial structure. You order a peripheral blood smear, which

shows a microcytic, hypochromic anemia with

target

cells. You begin to suspect that this child may

need blood transfusions for the rest of his life

10غالبا من نوع بيتا ...... لانها بينت عشهر

Thalassemias

α thalassemias are caused by deletions that remove one or more

of the α – globin gene loci on chromosome 16

Beta thalassemia : mutated not deleted on chromosome 11

Subtypes of a thalassemia

Minor (silent

carrier )

triat Major (HbH

disease )

Hydrops

Fetalis

Genotype 1 alpha allele

deleted

2 alpha allele

deleted

Cys : a -/a-

Trans : aa / --

مو موجود بسلايد بس

شرحنا

3 alpha allele

deleted

4 alpha allele

deleted

Symptoms no clinical

manifestations of

hemoglobinopathy

The patients have

mild to moderate

microcytic

hypochromic

anemia

Is a chronic

moderately

sever

hemolytic

anemia .

*This lack of

alfa chain

production is

incompatible

with life .

*Affected

fetuses die

either in utero

or shortly

after birth

Hemoglobin Contents

B chains

tetramer

HbH

* Hb

electrophoresis

reveals HbH

4%-30%

* has a high

affinity to

oxygen

Y chains

tetramer

Hb Bart

No treatment

needed

May need

observesion and

following

Blood

transfusion

Minor Intermedia major

Genotype B0 B or

B+ B

B+ B+ or

B+ B0

+++ alpha

minor

B+ B+

B0 BO

B+ B0

2 abnormal

Clinical

manifestation

asymptomatic &

anemia is mild if it

is present .

a milder

disease

* With transfusions alone the

survival into the second &

third decades is possible, but

gradually they develop iron

overload , hemochromatosis

>> Bronze – color of hand +it

is important cause of death

* heart failure

* ineffective erythropoiesis+

hemolytic anemia >> hair on

end as in the skull also there

is a delay of bone growth.

Growth retardation

*bone marrow hyperplasia

>> skeletal deformities

زي تبعون

sickle cell anemia * Extramedullary

hematopoiesis >>

splenomegaly ( up to

1500grams ) & hepatomegaly

Lap findings

/diagnosis

Postnatal

*Peripheral blood

shows microcytic

hypochromic red

and target cells

* electrophoresis :

increased Hb A2

5% (normal 2.5%)

, while Hb F 2%

may be normal or

increased .

*Peripheral blood shows

microcytic hypochromic red

,target cell and nucleated

RBCs

* reticulocytosis

* electrophoresis :

No HbA

Increased Hb A2 and HbF

How to differentiate between iron def. and thalassemia ?

There are many ways :

1) Ferritin : it is elevated in thalassemia and low in iron

def.

2) In thalassemia , much more anisocytosis ( so more

RDW )

3) Electrophoresis

4)

Hb A slightly

decreased

Diagnosis

prenatal

diagnosis of both forms of thalassemia can be made by DNA analysis at 12-14 weeks of gestation.

Treatment No treatment needed

transfusion and/or bone

marrow

transplantation

A 35-year-old African American man comes

to your office after noticing that his urine

has become tea colored. He tells you that he

has just returned from a trip to Africa

where he had taken primaquine to guard

against contracting malaria. Upon finding

Heinz bodies on his peripheral blood smear,

you suspect that his dark urine will likely

resolve on its own shortly. You reassure the

patient that his current condition is likely

related to the primaquine and recommend

no further testing.

Glucose 6- phosphate dehydrogenase (G6PD)

Etiology X-linked recessive disorder resulting in a deficiency of glucose-6-phosphate dehydrogenase

Pathophysiology G6PD is an enzyme involved in the production of NADPH in the

hexose

monophosphate shunt pathway. NADPH is necessary for reduced

glutathione, which protects

hemoglobin from oxidative damage. When G6PD is deficient,

reduced glutathione is absent.

Without reduced glutathione, hemoglobin is oxidized and forms

Heinz bodies in the RBC. Heinz

bodies cause damage to the RBC membrane damage RBC

membrane

----->intravascular hemolysis

Hienz bodies ↓RBC deformability---->goes to spleen and

removal of these heinz bodies by splenic macrophages

---->formation bite cells(bite of cytoplasm)

-phagocytosis of bite cells cause extravascular hemolysis

Clinical

Manifestation

Episodic hemolytic anemia with hemoglobinuria occurring with

ingestion of oxidant drugs

(eg, primaquine, quinidine, quinine, sulfonamides, anti-TB drugs) or

certain foods (ie, fava beans)

Clinically:-

-acute intravascular hemolysis is marked by:-

1-jaundice

2-Anemia

3-Hemoglobinemia

4-Hemoglobenuria

#begins after 2-3 days of taken oxidant agent

NO splenomegally or cholelithiasis in chronic hemolysis

Lap findings Avoid oxidant drugs

Treatment Increased malarial resistance is noted with G6PD deficiency

بتقدروا ما تدرسوا بس اصلا سهل ولازم نفهمه وتم ذكره هذا الموضوع تم ذكره بشكل غير مباشر

بالفيديوهات

african variant Mediterranean variant

Mildly reduced half-life of G6PD Markedly reduced half-life of

G6PD

Mild intravascular hemolysis with

oxidative

High intravascular hemolysis with

oxidative stress

A 30-year-old woman arrives at the emergency

room complaining of fatigue and dark-colored

urine. While obtaining the history of her present

illness, you learn that she has been recovering

from a recent bout of pneumonia, for which she

had been treated appropriately by her primary

care physician with a course of antibiotics.

Physical examination reveals an enlarged spleen

and

slight scleral icterus. You obtain a blood sample

and decide to order a direct Coomb test

Autoimmune Hemolytic Anemias

antibodies that recognize determinants on red cell membranes

causing hemolytic anemia

Warm antibody hemolytic

anemia

Cold antibody hemolytic anemia

IgG mediated IHA IgM or IgA mediated IHA

Caused by IgG or IgA antibody being active at 37 ˚C

Caused by low affinity IgM antibody that bind to RBCs membrane at low temperature below 30˚C

Occurs in (central parts of body)

hemolysis occurs in the hands & feet in cold weather (extremities)

Associated with: - Lupus - pt have anti-blood Ab -CLL (chronic lymphocytic lukemia) -methyl dopa which induce auto antibody against Rh blood group -penicillin or quinidine or cephaloceporines may act as hapten or opsonin( bind to RBC complex ) that enhance RBCs phagocytosis .

Associated with: •Mycoplasma pneumoniae (cold agglutination test)

• infectious mononucleosis (+ve haterophile

agglutination - Ab made against sheep blood) • CLL

دكتورة ذكرت هاد الموضوع بدون شرح .... بتقدروا ما تدرسوا

Paroxysmal nocturnal Hemoglobinuria(PNH):

Definition Intrinsic cause – intravascular hemolysis – acquired ( means

that the patient acquired the disease after birth ) not

congenital !

Pathophysiology note : How do cells in blood protect themselves from complement system? DAF (decay accelerating factor) and MIRL (membrane inhibitor of reactive lysis) are present in RBC, WBC and platelets. They block complement fixation in RBC. DAF decays C3 convertase. – - Protein called GPI (glycosylphophatidylinositol) anchors MIRL and DAF to cells للفهم مش مطلوب بالتفصيل هاد

mutation in gene of PIGA ( x –linked ) defect in myeloid stem

cell. >>> no synthesis of phosphatidylinositol glycan (PIG)

>>>so that GPI is absent in myeloid stem cells >>> red cells

that are sensitive to complement-mediated lysis>>>

Complement fixation lyses RBC, WBC and platelets

Clinical

presentation

Symptoms are seen paroxysmally at night because

breathing becomes swallow >>> retention co2 >> mild

acidosis >>>activates complement at night.

- Dark urine early morning

- Hemoglobinura, hemoglobinemia - Hemosiderinura seen

few days after hemolysis (after tubular cells slough off)

-

Venous thrombosis - due to release of clotting factors from

lysed platelets

Which is main cause of death in PNH

-infections

-Fe deficiency anemia (due to chronic loss of Hb in urine)

- Acute myeloid leukemia (10% of patients)

اخر تنتين مو مطلوبين

A 28-year-old woman presents to the hospital in labor

with her second child. As you prepare for

the delivery, you discover that this woman had

pregnancy complications associated with tearing

of the placenta during the delivery of her first child.

The mother and first child had been blood typed

for Rh antigen during their stay at the hospital and

records show that the mother is D-negative and

the first child was D-positive. Concerned, you decide

to administer anti-D IgG antiserum to the

mother during her delivery to prevent the possibility

of a serious hematologic complication for

the second child.

Erythroblastosis Fetalis

Etiology 1** blood group incompatibilty between mother & child

,when the fetus inherits red cell

antigenic determinant from the father ,that are foreign to

the mother

2** leakage of fetal red cells into maternal circulation &

transplacental passage of maternal

antibodies into the fetus

3**Rh antibodies are of IgG type that can pass through

the placenta , and induce hemolysis

of fetal RBCs

Clinical

manifestations

Severe fetal hemolytic anemia:

-- anemia , jaundice , increased unconjugated bilirubin

hepatosplenomegally

--kernicterus when bilirubin reaches 20 mg/dl or more

--hypoxic injury to the heart & liver

--circulatory & hepatic failure

severe cases may result in fetal heart failure with

generalized edema

or in a stillbirth

Treatment

1-Phototherapy ,

2- blood exchange transfusion

3-intravenous immunoglobulins injections

4- prophylactic ttt :Rhesus Immuglobulin

anti D antibodies to

the mother at 28 week of pregnancy & within 72 hours

before labor to Rh negative mother

with Rh positive neonate

5- Traumatic hemolytic anemia

RBCs get the appearance of : Schistocytes , burr cells or

helmet cells

Note : فقط للفهم

Schistocytes (broken RBC) (helmet cells)

- has mostly two acute angle and loss of about 50% of RBC;

contrast bite cells that have usually >2 acute angles and

almost entire volume of RBC is present.

#physical trauma in a variety of circumstances as:

1- Cardiac valve prostheses .

2- Obstruction of vasculature called microangiopathic

hemolytic anemia (hemolysis in small blood vessel)

as in:

DIC , disseminated cancer, SLE , thrombotic

thrombocytopenic purpura (TTP),

malignant hypertension , hemolytic uremic syndrome

A 26-year-old pregnant woman presents to your office for a

checkup. She states that her pregnancy

has been proceeding smoothly, although she has been feeling

more tired than she expected. Her

physical examination is largely unremarkable except for

marked pallor. You order serum studies

and find that she has decreased hematocrit, decreased

ferritin, and increased total iron-binding

capacity. Her peripheral blood smear shows red blood cells

that are both microcytic and

hypochromic. You reassure her that these findings are most

likely associated with her pregnancy

status and recommend iron supplements.

Iron def. anemia

NOTE : مو مطالبين فيها

#↑RDW (RDW is like standard deviation of size of RBC; larger the

variation in RBC sizes, larger the RDW)

# ↑FEP (free erythrocyte protoporphyrin) As Fe is low but

protoporphyrin is normal, some protoporphyrin will be unbound to Fe

hence increasing the FEP.

A 57-year-old woman with a history of rheumatoid arthritis presents to your office complaining

of fatigue upon exertion. You note that she is pale and decide to send her for serum studies.

Laboratory results reveal an anemia as well as low serum iron levels, a low TIBC, and mildly increased serum ferritin levels. You tell the patient

your diagnosis and begin to discuss whether

treatment is necessary

CAD

A 46-year-old man presents to your office complaining of

weakness and a “pins and needles”

feeling in his extremities. You note that he is ataxic and has

decreased vibration and position

sense in both his arms and legs. Upon further examination,

you also observe that his tongue is

red and enlarged. When laboratory tests reveal a positive

Schilling test and a macrocytic anemia,

you question the patient’s diet habits, drinking habits, and

history of abdominal surgery.

Megalobastic anemia

هذه الجداول للفهم وحلوة وليست مطلوبة لكنها بتساعد

A 15-year-old girl presents to the emergency

department with a petechial rash, bleeding of the

oral mucosa, fatigue, and a history of recurrent sinus infections over the past 2 months. She does

remember having had a bad flu-like virus about 3

months ago that caused her to miss 4 days of

school. There is no hepatosplenomegaly on

examination. Laboratory tests reveal anemia,

neutropenia, and thrombocytopenia. There are no abnormal cell types seen on peripheral blood smear. You decide to admit the patient to the hospital

and you schedule a bone marrow biopsy

aplastic anemia

هذا الموضوع غيرمطلوب بشكل صريح ولكن يفضل الاطلاع عليه والاستزاد وتم شرحه

بالفيديوهات

Erythrocyte indices

Hb

anemia when Hemoglobin (Hb) level in blood is <13.5 grams/dl

in males & 12.5 grams/dl in females .

note : مو مطالبين فيها وليست للحفظ

How is anemia measured?

- Hb, Hct and RBC count (total RBC mass difficult to measure) All of

these measures are concentration dependent so have problems.

Ex – in pregnancy, blood volume increases making Hb and Hct

concentration low even though total amount might be same.

Immediately after gunshot wound and blood loss, Hb and Hct

concentration might be normal even though pt might have lost

lots of blood.

MCV : Mean corpuscular volume

the size of the red blood cells

متوسط حجم كريات الدم الحمراء

- Microcytic (mcv < 80 )

-macrocytic (mcv > 100 )

-normocytic (80 – 100)

MCH : mean corpuscular hemoglobin

quantifies the amount of hemoglobin per red blood cell. The normal values

for MCH are 29 ± 2 picograms (pg) per cell.

كمية الهيموغلوبيين بالخلية الوحدة

MCHC : mean corpuscular hemoglobin concentration

indicates the amount of hemoglobin per unit volume

NORMAL : 31-37 grams per deciliter (g/dL)

كمية الهيموغلوبين بالنسبة لوحدة الحجم

RDW : red cell distribution width

represents the coefficient of variation of the red blood cell volume

distribution (size) and is expressed as a percentage. The normal value for

RDW is 13 ± 1.5%.

للتعبير عن تنوع واختلاف بحجم الخلايا

فيديو شرح :

https://www.youtube.com/watch?v=QUHqYVK-Nhg

في حال كنتوا حاضرين الفيديوهات لا داعي له

قوانين مو مطلوبين ويمكن استنتاجهم من التعريف

Hematocrit or PCV : Packed cell volume

is the volume percentage (vol%) of red blood

NORMAL : 35-45%

موية او كريات الدم البيضاء يوجد فحوصات اخرى للدم ولكنها متعلقة بالامراض التابعة للصفائح الد

ولكن تم وضع ما يوجد ملاحظة الارقام الطبيعية تختلف من مصدر الى اخر ولكن قريبة من بعض

بالسلايدز

IRON STUDIES

Serum iron - measures the level of iron in the liquid part of your

blood.

Normal : 120 mg /dl in men and 100 mg /dl

الحديد ما بمشي لحاله بالدم فهون المقصود الحديد يلي رابط مع

Transferrin

Ferritin - measures the amount of stored iron in your body

Transferrin or total iron binding capacity (TIBC)

TIBC is a good indirect measurement of transferrin. Your body makes

transferrin in relationship to your need for iron; when iron stores are

low, transferrin levels increase, while transferrin is low when there is

too much iron. Usually about one third of the transferrin is being used

to transport iron. Because of this, your blood serum has considerable

extra iron-binding capacity, which is the unsaturated iron binding

capacity (UIBC). The TIBC equals UIBC plus the serum iron

measurement. Few laboratories measure UIBC.

Normal TIBC : 300-350 gm / dl

UIBC لم يتم ذكره بالمحاضرات ولكن معناه كمية Transferrin يلي

ماشية بالدم ومو رابطة باشي

Transferrin saturation: percentage of transferrin that is saturated

with iron.

Normal : 33%

كمية المواقع يلي موجودة عى البروتين ورابط معها الحديد

3 A 65-year-old man has experienced worsening fatigue

for the past 5 months. On physical examination, he is afebrile

and has a pulse of 91/min, respirations of 18/min, and blood pressure of

105/60 mm Hg. There is no organomegaly. A

stool sample is positive for occult blood. Laboratory findings

include hemoglobin of 5.9 g/dL, hematocrit of 18.3%, MCV

of 99 μm3, platelet count of 250,000/mm3, and WBC count of

7800/mm3. The reticulocyte concentration is 3.9%. No fibrin

split products are detected, and direct and indirect Coombs

test results are negative. A bone marrow biopsy specimen

shows marked erythroid hyperplasia. Which of the following

conditions best explains these findings?

A Aplastic anemia

B Autoimmune hemolytic anemia

C Chronic blood loss

D Iron deficiency anemia

E Metastatic carcinoma

A clinical study of patients who inherit mutations that

reduce the level of ankyrin, the principal binding site for spectrin,

in the RBC membrane cytoskeleton shows an increased

prevalence of chronic anemia with splenomegaly. For many

patients, it is observed that splenectomy reduces the severity

of anemia. This beneficial effect of splenectomy is most likely

related to which of the following processes?

A Decrease in opsonization of RBCs and lysis in

spleen

B Decrease in production of reactive oxygen species

by splenic macrophages

C Decrease in splenic RBC sequestration and lysis

D Increase in deformability of RBCs within splenic

sinusoids

E Increase in splenic storage of iron

4 During the past 6 months, a 25-year-old woman has

noticed a malar skin rash that is made worse by sun exposure.

She also has had arthralgias and myalgias. On physical examination,

she is afebrile and has a pulse of 100/min, respirations

of 20/min, and blood pressure of 100/60 mm Hg. There is erythema

of skin over the bridge of the nose. No organomegaly is

noted. Laboratory findings include positive serologic test results

for ANA and double-stranded DNA, hemoglobin of 8.1

g/dL, hematocrit of 24.4%, platelet count of 87,000/mm3, and

WBC count of 3950/mm3. The peripheral blood smear shows

nucleated RBCs. A dipstick urinalysis is positive for blood, but

there are no WBCs, RBCs, or casts seen on microscopic examination

of the urine. Which of the following laboratory findings

is most likely to be present?

A Decreased haptoglobin

B Decreased iron

C Decreased reticulocytosis

D Elevated D dimer

E Elevated hemoglobin F

F Elevated protoporphyrin

A 28-year-old woman has had a constant feeling of lethargy

since childhood. On physical examination, she is afebrile

and has a pulse of 80/min, respirations of 15/min, and blood

pressure of 110/70 mm Hg. The spleen tip is palpable, but

there is no abdominal pain or tenderness. Laboratory studies

show hemoglobin of 11.7 g/dL, platelet count of 159,000/

mm3, and WBC count of 5390/mm3. The peripheral blood

smear shows small round erythrocytes that lack a zone of central

pallor. An inherited abnormality in which of the following

RBC components best accounts for these findings?

A α-Globin chain

B β-Globin chain

C Carbonic anhydrase

D Glucose-6-phosphate dehydrogenase

E Heme with porphyrin ring

F Spectrin cytoskeletal protein

7 An 18-year-old woman from Copenhagen, Denmark,

has had malaise and a low-grade fever for the past week, along

with arthralgias. On physical examination, she appears very

pale, except for a bright red malar facial rash. She has a history

of chronic anemia, and spherocytes are observed on a peripheral

blood smear. Her hematocrit, which normally ranges

from 35% to 38%, is now 28%, and the reticulocyte count is very low.

The serum bilirubin level is 0.9 mg/dL. Which of the following events is

most likely to have occurred in this

patient?

A Accelerated extravascular hemolysis in the spleen

B Development of anti-RBC antibodies

C Disseminated intravascular coagulation

D Reduced erythropoiesis from parvovirus infection

E Superimposed dietary iron deficiency

6 A 13-year-old boy has the sudden onset of severe abdominal

pain and cramping accompanied by chest pain, nonproductive

cough, and fever. On physical examination, his

temperature is 39° C, pulse is 110/min, respirations are 22/min,

and blood pressure is 80/50 mm Hg. He has diffuse abdominal

tenderness, but no masses or organomegaly. Laboratory studies

show a hematocrit of 18%. The peripheral blood smear is shown

in the figure. A chest radiograph shows bilateral pulmonary infiltrates.

Which of the following is the most likely mechanism

for initiation of his pulmonary problems?

A Chronic hypoxia of the pulmonary parenchyma

B Defects in the alternative pathway of complement

activation

C Extensive RBC adhesion to endothelium

D Formation of autoantibodies to alveolar basement

membrane

E Intravascular antibody-induced hemolysis

8 A clinical study of patients who inherit mutations that

reduce the level of ankyrin, the principal binding site for spectrin,

in the RBC membrane cytoskeleton shows an increased

prevalence of chronic anemia with splenomegaly. For many

patients, it is observed that splenectomy reduces the severity

of anemia. This beneficial effect of splenectomy is most likely

related to which of the following processes?

A Decrease in opsonization of RBCs and lysis in

spleen

B Decrease in production of reactive oxygen species

by splenic macrophages

C Decrease in splenic RBC sequestration and lysis

D Increase in deformability of RBCs within splenic

sinusoids

E Increase in splenic storage of iron

9 A 3-year-old boy from Sicily has a poor appetite and

is underweight for his age and height. Physical examination

shows hepatosplenomegaly. The hemoglobin concentration is

6 g/dL, and the peripheral blood smear shows severely hypochromic

and microcytic RBCs. The total serum iron level is

normal, and the reticulocyte count is 10%. A radiograph of the

skull shows maxillofacial deformities and expanded marrow

spaces. Which of the following is the most likely cause of this

child’s illness?

A Imbalance in α-globin and β-globin chain

production

B Increased fragility of erythrocyte membranes

C Reduced synthesis of hemoglobin F

D Relative deficiency of vitamin B12

E Sequestration of iron in reticuloendothelial cells

10 A 10-year-old child has experienced multiple episodes

of pneumonia and meningitis with septicemia since infancy.

Causative organisms include Streptococcus pneumoniae and

Haemophilus influenzae. On physical examination, the child

has no organomegaly and no deformities. Laboratory studies

show hemoglobin of 9.2 g/dL, hematocrit of 27.8%, platelet

count of 372,000/mm3, and WBC count of 10,300/mm3. A hemoglobin

electrophoresis shows 1% hemoglobin A2, 7% hemoglobin

F, and 92% hemoglobin S. Which of the following is

the most likely cause of the repeated infections in this child?

A Absent endothelial cell expression of adhesion

molecules

B Diminished hepatic synthesis of complement

proteins

C Impaired neutrophil production

D Loss of normal splenic function

E Reduced synthesis of immunoglobulins

11 A 32-year-old woman from Hanoi, Vietnam, gives birth

at 34 weeks’ gestation to a markedly hydropic stillborn male

infant. Autopsy findings include hepatosplenomegaly and

cardiomegaly, serous effusions in all body cavities, and generalized

hydrops. No congenital anomalies are noted. There

is marked extramedullary hematopoiesis in visceral organs.

Which of the following hemoglobins is most likely predominant

on hemoglobin electrophoresis of the fetal RBCs?

A Hemoglobin A1

B Hemoglobin A2

C Hemoglobin Bart’s

D Hemoglobin E

E Hemoglobin F

F Hemoglobin H

12 A 17-year-old girl has had a history of fatigue and weakness

for her entire life. She has not undergone puberty. On

physical examination, secondary sex characteristics are not

well developed. She has hepatosplenomegaly. CBC shows hemoglobin

of 9.1 g/dL, hematocrit of 26.7%, MCV of 66 μm3,

platelet count of 89,000/mm3, and WBC count of 3670/mm3.

The appearance of the peripheral blood smear is shown in the

figure. Additional laboratory findings include serum glucose

of 144 mg/dL, TSH of 6.2 mU/mL, and ferritin of 679 ng/mL.

A mutation in a gene encoding for which of the following is

most likely to be present in this girl?

A Ankyrin

B β-Globin

C G6PD

D HFE

E NADPH oxidase

13 A 12-year-old boy has a history of episodes of severe abdominal,

chest, and back pain since early childhood. On physical

examination, he is afebrile, and there is no organomegaly.

Laboratory studies show hemoglobin of 11.2 g/dL, platelet

count of 194,000/mm3, and WBC count of 9020/mm3. The peripheral

blood smear shows occasional sickled cells, nucleated

RBCs, and Howell-Jolly bodies. Hemoglobin electrophoresis

shows 1% hemoglobin A2, 6% hemoglobin F, and 93% hemoglobin

S. Hydroxyurea therapy is found to be beneficial in

this patient. An increase in which of the following is the most

likely basis for its therapeutic efficacy?

A Erythrocyte production

B Overall globin chain synthesis

C Oxygen affinity of hemoglobin

D Production of hemoglobin A

E Production of hemoglobin F

14 A 25-year-old woman has a 3-year history of arthralgias.

Physical examination shows no joint deformity, but she appears

pale. Laboratory studies show total RBC count of 4.7

million/mm3, hemoglobin of 12.5 g/dL, hematocrit of 37.1%,

platelet count of 217,000/mm3, and WBC count of 5890/mm3.

The peripheral blood smear shows hypochromic and microcytic

RBCs. Total serum iron and ferritin levels are normal.

Hemoglobin electrophoresis shows 93% hemoglobin A1 with

elevated hemoglobin A2 level of 5.8% and hemoglobin F level

of 1.2%. What is the most likely diagnosis?

A Anemia of chronic disease

B Autoimmune hemolytic anemia

C β-Thalassemia minor

D Infection with Plasmodium vivax E Iron deficiency anemia

15 A 23-year-old African-American man passes dark reddish

brown urine 3 days after taking an anti-inflammatory

medication that includes phenacetin. He is surprised, because

he has been healthy all his life and has had no major illnesses.

On physical examination, he is afebrile, and there are no remarkable

findings. CBC shows a mild normocytic anemia, but

the peripheral blood smear shows precipitates of denatured

globin (Heinz bodies) with supravital staining and scattered

“bite cells” in the population of RBCs. Which of the following

is the most likely diagnosis?

A α-Thalassemia minor

B β-Thalassemia minor

C Glucose-6-phosphate dehydrogenase deficiency

D Sickle cell trait

E Abnormal ankyrin in RBC cytoskeletal membrane

F Warm antibody autoimmune hemolytic anemia

16 Since childhood, a 30-year-old man has been easily

fatigued with minimal exercise. Laboratory studies show

hypochromic microcytic anemia. Hemoglobin electrophoresis

reveals decreased Hgb A1 with increased Hgb A2 and Hgb F.

His serum ferritin is markedly increased. Which of the following

mutations is most likely to be present in the β-globin gene of

this man?

A New stop codon

B Single base insertion, with frameshift

C Splice site

D Three-base deletion

E Trinucleotide repeat

مو مطلوب

17 A 16-year-old boy notes passage of dark urine. He has a history of multiple bacterial infections and venous thromboses for the past 10 years, including portal vein thrombosis in the previous year. On physical examination, his right leg is swollen and tender. CBC shows hemoglobin, 9.8 g/dL; hematocrit, 29.9%; MCV, 92 μm3; platelet count, 150,000/mm3; and WBC count, 3800/mm3 with 24% segmented neutrophils, 1% bands, 64% lymphocytes, 10% monocytes, and 1% eosinophils. He has a reticulocytosis, and his serum haptoglobin level is very low. A mutation affecting which of the following gene products is most likely to give rise to this clinical condition? A β-Globin chain B Factor V C Glucose-6-phosphate dehydrogenase D Phosphatidylinositol glycan A (PIGA) E Prothrombin G20210A F Spectrin 18 A 30-year-old, previously healthy man from Lagos, Nigeria, passes dark brown urine 2 days after starting the prophylactic antimalarial drug primaquine. On physical examination, he appears pale and is afebrile. There is no organomegaly. Laboratory studies show that his serum haptoglobin level is decreased. Which of the following is the most likely explanation of these findings? A Antibody-mediated hemolysis B Impaired DNA synthesis C Impaired globin chain synthesis D Increased susceptibility to complement-induced lysis E Mechanical fragmentation of RBCs as a result of vascular narrowing F Oxidative injury to hemoglobin G Reduced deformability of RBC membrane 19 A 34-year-old woman reports becoming increasingly tired for the past 5 months. On physical examination, she is afebrile

and has mild splenomegaly. Laboratory studies show a hemoglobin concentration of 10.7 g/dL and hematocrit of 32.3%. The peripheral blood smear shows spherocytes and rare nucleated RBCs. Direct and indirect Coombs test results are positive at

37° C, although not at 4° C. Which of the following underlying diseases is most likely to be diagnosed in this patient? A Escherichia coli septicemia B Hereditary spherocytosis C Infectious mononucleosis D Mycoplasma pneumoniae infection E Systemic lupus erythematosus 20 A 22-year-old woman has experienced malaise and a sore throat for 2 weeks. Her fingers turn white on exposure to cold. On physical examination, she has a temperature of

37.8° C, and the pharynx is erythematous. Laboratory findings include a positive monospot (heterophile antibody) test result. Direct and indirect Coombs test results are positive at

4° C, although not at 37° C. Which of the following molecules bound on the surfaces of the RBCs most likely accounts for these findings? A α2-Macroglobulin B Complement C3b C Fibronectin D Histamine E IgE 21 A 65-year-old man diagnosed with follicular non-Hodgkin lymphoma is treated with chemotherapy. He develops fever and cough of a week’s duration. On examination, there are bilateral pulmonary rales. A chest radiograph shows diffuse interstitial infiltrates. A sputum specimen is positive for cytomegalovirus. He develops scleral icterus and Raynaud phenomenon. Laboratory studies show hemoglobin, 10.3 g/dL; hematocrit, 41.3%; MCV, 101 μm3; WBC count, 7600/mm3; and platelet count, 205,000/ mm3. His serum total bilirubin is 6 mg/dL, direct bilirubin is 0.8 mg/dL, and LDH is 1020 U/L. Coombs test is positive. Which of the following is the most likely mechanism for his anemia? A Marrow aplasia caused by chemotherapy B Vitamin K deficiency caused by cytomegalovirus hepatitis

C Megaloblastic anemia caused by folate deficiency D Extravascular hemolysis caused by cold agglutinins E Iron deficiency caused by metastases to colon 22 A 29-year-old woman has had fatigue with dizziness for the past 5 months. On physical examination, she has an erythematous malar rash. She has no lymphadenopathy, but there is a palpable spleen tip. She is afebrile. Laboratory studies show hemoglobin, 8.9 g/dL; hematocrit, 27.8%; MCV, 103 μm3; RBC distribution width index, 22; WBC count, 8650/mm3; platelet count, 222,000/mm3; and reticulocyte count, 3.3%. The peripheral blood smear shows polychromasia, but no schistocytes. Her serum total bilirubin is 3.2 mg/dL with direct bilirubin 0.8 mg/dL, and haptoglobin is 5 mg/dL. Antinuclear antibody and anti–double-stranded DNA tests are positive. What additional laboratory test finding is she most likely to have? A D-dimer 10 μg/mL B Increased RBC osmotic fragility C Positive Coombs test D Serum cobalamin (vitamin B12) 50 pg/mL E Serum ferritin 240 ng/mL 23 A 29-year-old rugby player takes part in a particularly contentious game between New Zealand and South Africa. He is the forward prop in the scrums, hitting hard and being hit hard by other players. He feels better after downing several pints of beer following the game, but notes darker urine. Urinalysis is positive for blood. Which of the following pathogenic mechanisms underlies change in the color of urine? A Complement lysis B Intravascular disruption C Osmotic fragility D Sinusoidal sickling E Splenic sequestration 24 In an epidemiologic study of anemias, the findings show that there is an increased prevalence of anemia in individuals of West African ancestry. By hemoglobin electrophoresis, some individuals within this region have increased hemoglobin S levels. The same regions also have a high prevalence of an infectious disease. Which of the following infectious agents is most likely to be endemic in the region where such anemia shows increased prevalence?

A Borrelia burgdorferi B Clostridium perfringens C Cryptococcus neoformans D Plasmodium falciparum E Treponema pallidum F Trypanosoma brucei 25 An infant is born at 34 weeks’ gestation to a 28-year-old woman, G3, P2. At birth, the infant is observed to be markedly hydropic and icteric. A cord blood sample is taken, and direct Coombs test result is positive for the infant’s RBCs. Which of the following is the most likely mechanism for the findings in this infant? A Hemolysis of antibody-coated cells B Hematopoietic stem cell defect C Impaired globin synthesis D Mechanical fragmentation of RBCs E Oxidative injury to hemoglobin F Reduced deformability of RBC membranes bancrofti 27 A 33-year-old previously healthy man with persistent fever and heart murmur is diagnosed with infective endocarditis. He receives a high dosage of a cephalosporin antibiotic during the next 10 days. He now has increasing fatigue. On physical examination he has tachycardia and scleral icterus. Laboratory studies show a hemoglobin level of 7.5 g/dL, platelet count of 261,000/mm3, and total WBC count of 8300/ mm3. The direct Coombs test is positive. The periperal blood smear shows reticulocytosis. Which of the following is the most likely cause for his anemia? A Dietary nutrient deficiency B Disseminated intravascular coagulopathy C Immune-mediated hemolysis D Infection with parvovirus E Inherited hemoglobinopathy F RBC cytoskeletal protein disorder 29 A 54-year-old, previously healthy man has experienced minor fatigue on exertion for the past 9 months. On physical examination, there are no remarkable findings. Laboratory

studies show hemoglobin of 11.7 g/dL, hematocrit of 34.8%, MCV of 73 μm3, platelet count of 315,000/mm3, and WBC count of 8035/mm3. Which of the following is the most sensitive and cost-effective test that the physician should order to help to determine the cause of these findings? A Bone marrow biopsy B Hemoglobin electrophoresis C Serum ferritin D Serum haptoglobin E Serum iron F Serum transferrin 30 A 73-year-old man takes no medications and has had no prior major illnesses or surgeries. For the past year, he has become increasingly tired and listless. Physical examination shows that he appears pale but has no hepatosplenomegaly and no deformities. CBC shows hemoglobin, 9.7 g/dL; hematocrit, 29.9%; MCV, 69.7 mm3; RBC count, 4.28 million/mm3; platelet count, 331,000/mm3; and WBC count, 5500/mm3. His peripheral blood smear is shown in the figure. Which of the following is the most likely underlying condition causing this patient’s findings? A Autoimmune hemolytic anemia B Chronic alcohol abuse C β-Thalassemia major D Hemophilia A E Occult malignancy F Vitamin B12 deficiency

31 A clinical study is performed using adult patients diagnosed with peptic ulcer disease, chronic blood loss, and hypochromic microcytic anemia. Their serum ferritin levels average 5 to 7 ng/mL. The rate of duodenal iron absorption in this study group is found to be much higher than in a normal control group. After treatment with omeprazole and clarithromycin, study group patients have hematocrits of 40% to 42%, MCV of 82 to 85 μm3, and serum ferritin of 30 to 35 ng/ mL. Measured rates of iron absorption in the study group after therapy are now decreased to the range of the normal controls. Which of the following substances derived from liver is most likely to have been decreased in the study group patients before therapy, and returned to normal after therapy? A Divalent metal transporter-1 (DMT-1) B Hemosiderin C Hepcidin D HLA-like transmembrane protein E Transferrin 32 A 39-year-old man has experienced chronic fatigue and weight loss for the past 3 months. There are no remarkable findings on physical examination. Laboratory studies show hemoglobin, 10.0 g/dL; hematocrit, 30.3%; MCV, 91 μm3; platelet count, 240,000/mm3; WBC count, 7550/mm3; serum iron 80 μg/dL; total iron-binding capacity, 145 μg/dL; and serum ferritin, 565 ng/mL. Serum erythropoetin levels are low for the level of Hb and hepcidin levels are elevated. Which of the following is the most likely diagnosis? A Anemia of chronic disease B Aplastic anemia C Iron deficiency anemia D Megaloblastic anemia E Microangiopathic hemolytic anemia F Thalassemia minor هون في كمان اسئلة :