ANEMIA

Dr Amro Adas
Internal Medicine Specialist
-Hemoglobin levels < 13.5g/dl in men
-<12g/dL in women.
INDICATIONS FOR TRANSFUSION
 In severe cases (symptomatic patients, cardiovascular instability or continued
excessive blood loss) RBC transfusion is needed.
 Hb < 7
 In Ischemic Heart Disease Hb 8-9.
BLOOD TRANSFUSION SIDE EFFECTS
Immunologic side effects:
• Febrile non-hemolytic reaction - is the most common reaction, it is define by a rise in
body temperature>1 C and can present with chills.
• Acute hemolysis: most often occurs due to ABO incompatibility. Acute hemolysis may
present with hypotension, tachycardia, tachypnea, fever, chills, hemoglobinuria, chest
and flank pain, and discomfort at the infusion site.
• Anaphylaxis
• Transfusion related acute lung injury
• graft vs host
• post-transfusion purpura.

Non-immunologic side effects: volume overload, pulmonary edema, hypocalcemia and

infection transmission.
A 65-year-old female is brought to the ER due to symptomatic anemia and
hemoglobin 6 g/dl.
She is treated with 1 unit of blood. Shortly after the blood infusion is started the
patient
develops acute dyspnea, fever, chills, and flank pain. Urinalysis is positive for
hemoglobin.
Which of the following is the most correct statement?

1. This is a common side effect; antihistamines should be given and continue the
infusion
2. Stop the infusion immediately and return the blood unit to the blood bank
3. Sepsis due to urinary tract infection is the most common cause of these
symptoms
4. Hepatitis C infection of the unit of blood is the most common cause of these
symptoms
IRON DEFICIENCY ANEMIA
 Diminished red blood cell production
 MCV <80
 Hypochromic cells.
LABS IN IRON DEFICIENCY ANEMIA
 Low ferritin <10 ng/mL. (acute phase reactant)
 RBC count low.
 RDW high

 Serum Iron Low

 Total Iron Binding

Capacity High

Transferrin Sat Low

TREATMENT OF IDA
 Oral therapy with ferrous sulfate tablets is the most common method of therapy.

 Oral therapy should be continued 2-3 months after Hb and Htc have normalized.

 First markers improve:reticulocytes will be seen 2 weeks into treatment.

 Parenteral iron is used in patients with malabsorption, kidney disease, or an

intolerance to oral therapy.
ANEMIA OF CHRONIC DISEASE
 A defect in the ability to make use of iron sequestered in

stores within the reticuloendothelial system.

 Accompany any chronic inflammatory,

infectious, or neoplastic condition.

 The serum ferritin level is normal or elevated.

 The serum iron level and total iron binding capacity

(TIBC) are both low.

So transferrin sat almost normal.
SIDEROBLASTIC ANEMIA
 Trapped iron in the mitochondria of nucleated RBCs.

 Serum ferritin level is elevated. Transferrin

saturation is very high, and therefore the TIBC is

very low. The serum iron level is high. (everything high
except TIBC low)

 The most specific test is a Prussian Blue stain of RBCs

in the marrow that will reveal the ringed sideroblasts.

TREATMENT
 Remove the offending drug as appropriate.

 Some patients, especially those with Isoniazid-associated sideroblastic anemia,

will respond to pyridoxine therapy.

 Occasionally, sideroblastic anemia may be severe enough to warrant transfusion.

In refractory cases, BMT may be considered.
THALASSEMIA
TREATMENT OF THALASSEMIA
 Thalassemia traits of both the alpha and beta types do not require specific
treatment.

 Beta thalassemia major patients require blood transfusions once or twice a month.
The chronic transfusions lead to iron overload, which requires treatment with
deferasirox.

 Oral deferasirox is the standard of care. This is easier to give than deferoxamine,
which requires a subcutaneous pump.

 Splenectomy eliminates a major area of hemolysis. A small number of patients can be

treated with a bone marrow transplantation.
Which of the following is true regarding this
blood
smear?

1. Low iron, low ferritin and high TIBC

2. High iron, low ferritin and high TIBC
3. Low iron, high ferritin and high TIBC
4. Normal iron, normal ferritin and
normal TIBC
5. Low iron, normal ferritin, low TIBC
A 75-year-old man with hypothyroidism, uncontrolled diabetes mellitus, and
renal failure
is evaluated in the clinic. 3 months ago he began hemodialysis treatment. He
receives
regular treatment with Erythropoietin, Atorvastatin, Insulin, Eltroxin. Iron
deficiency
anemia was found in the laboratory tests. He underwent a gastroscopy and
colonoscopy
with normal results.
What is the most likely cause of the anemia?

1. Uncontrolled (unbalanced) diabetes mellitus

2. Hypothyroidism
3. Treatment with Erythropoietin
4. Treatment with Atorvastatin and insulin
A 20-year-old female complaining of asthenia for the past two months. No fever or
nocturnal
hyperhidrosis. She reports of thalassemia minor in her family on her father’s side.
Her brother
and cousin suffer from hemophilia.
In laboratory tests: blood count hemoglobin 8 grams (reference values 12-15),
microcytosis.
Low ferritin - 10 micrograms/liter, high red cell distribution width (RDW).
Elevated total iron binding capacity - 400 microgram/deciliter.
Which of the following is the most likely diagnosis?

1. Thalassemia
2. Iron deficiency anemia
3. Anemia of chronic disease
4. Hemophilia
A 70 year old male patient presents to the office with weakness, fatigue
and arthritis.
On examination iron level is 40, ferritin is 250 and hemoglobin is 11.
Which of the following is the best next step?

1. Oral iron
2. Blood transfusion
3. Electrophoresis
4. Check markers for inflammatory disease
5. Bone marrow biopsy
A 30 year old female presents to the office for follow up. On examination
MCV is 72fL
and hemoglobin is 10.2g/dL, ferritin is low and iron is low.
Which of the following is the best next step?

1. Bone marrow aspiration

2. Oral iron
3. IV iron
4. RBC transfusion
5. Oral contraceptives
VITAMIN B12 (CYANOCOBALAMINE) DEFICIENCY

 Decreased absorption or intake of

vitamin B12 resulting in hematologic

and/or neurologic abnormalities.

- The combination of macrocytic anemia

and neurological symptoms in a
vegetarian patient warrants the
diagnosis of vitamin B12 deficiency
anemia.
 DIAGNOSIS OF MEGALOBLASTIC ANEMIA
 The WBCs have hyper segmented neutrophils with a mean lobe count >4.

 The reticulocyte count is reduced, although the bone marrow is hypercellular.

 Pancytopenia may occur.

 An elevated LDH, bilirubin, and iron level may occur and are due to

mild hemolysis of immature erythrocytes.

 If B12 level is low, it is enough to diagnose B12 def.
 Antibodies to intrinsic factor and parietal cells confirm pernicious anemia.
 An elevated methylmalonic acid level occurs with B12 deficiency and is useful if
the B12 level is equivocal. important
TREATMENT
- Oral (daily) and parenteral (monthly intramuscular or subcutaneous)
preparations.

 Parenteral route if neurologic manifestations of B12 deficiency.

 Treatment with cobalamin effectively stops progression of the deficiency process but
might not fully reverse more advanced neurologic effects.

 Folic acid replacement can correct the hematologic abnormalities of B12 deficiency,
but not the neurologic abnormalities.
 FOLIC ACID DEFICIENCY
- Decreased dietary intake is the most common

cause.

-The hematologic presentation of folic acid

deficiency is identical to B12 deficiency.

- Low red-blood-cell, folic-acid level.

-Treatment. Replace folic acid, almost always orally

LAST EXAM
A 50-year-old female with a history of total gastrectomy. She is asking regarding the need
for continued treatment with Vitamin B12 injections.
Which of the following recommendations is most correct and why?

1. No need for injections if the diet contains sufficient vitamin B12

2. Regular vitamin B12 injections are required due to a lack of pepsin secretion
3. Regular vitamin B12 injections are required due to a lack of somatostatin secretion
4. Regular vitamin B12 injections are required due to a lack of intrinsic factor secretion
A 75-year-old man is brought to the ER due to an episode of confusion. His
brain imaging
was normal. He has a history of gastric adenocarcinoma 15 years ago and had
a partial
gastrectomy. His labs reveal hemoglobins 8.2, MCV 111, WBC 2400.
What can be seen on this patient's bone marrow biopsy?

1. Change compatible with MDS

2. Megaloblastic changes
3. Fatty replacement of the bone marrow
4. Dry tap
5. Acute myeloid leukemia
LABORATORY FINDINGS IN HEMOLYSIS
 Normal to high MCV (high because reticulocytes are larger than older cells).

 The reticulocyte count is elevated.

 The LDH and indirect bilirubin are elevated.

 Hemoglobin or hemosiderin may be present in the urine when intravascular

hemolysis, as also low haptoglobin.
 SICKLE CELL DISEASE
- Autosomal recessive hereditary disease.

- Hemoglobin S is due to a substitution of a valine

for glutamic acid as the sixth amino acid of the beta

globin chain.

-The heterozygous form (trait) is present in 8% of

the African-American population, and the

homozygous form (disease) is present in 1 in
400 African-Americans.
DIAGNOSIS
 A sickle cell acute painful crisis can be precipitated by hypoxia, dehydration, acidosis, infection, and
fever (usually not associated with an increase in hemolysis or drop in hematocrit).

 When increased hemolysis occurs, another etiology such as concomitant glucose 6 phosphate
dehydrogenase deficiency (G6PD) or acute splenic sequestration should be considered.

 A sudden drop in hematocrit may also be caused by Parvovirus B19 infection or folate deficiency.

 Complications of SCD include splenic infarction, renal papillary necrosis, occlusion of the
retinal vessels, aseptic necrosis, osteomyelitis, dactylitis, stroke, priapism, acute chest
syndrome.
Treatment:

 An acute sickle cell pain crisis is treated with fluids, analgesics, and oxygen.

 Antibiotics are given with infection or even to patients with fever and leukocytosis even if a
definite site of infection has not been documented.

 Severe or life-threatening manifestations such as acute chest syndrome, CNS manifestations,

priapism, retinal symptoms and acute cardiac manifestations are managed with red blood
cell transfusions if the hematocrit is low, and exchange transfusion if the hematocrit is high.

 Chronic management includes folic acid replacement and vaccinations against Pneumococcus
and influenza.

 Hydroxyurea is used to decrease the frequency of the vaso-occlusive pain crisis.

 HEREDITARY SPHEROCYTOSIS
 A chronic mild hemolysis with spherocytes, jaundice, and splenomegaly from a
defect in the red cell membrane.

 An autosomal dominant disorder

 The mean corpuscular hemoglobin concentration

(MCHC) is elevated.
 Dx: osmotic fragility test , eosin-5 maleimide binding

test and SDS gel electrophoresis

-Bilirubin stones often occur, leading to cholelithiasis.

-Treatment: Supportive, possible splenectomy.

PAROXYSMAL NOCTURNAL HEMOGLOBINURIA
(PNH)
 A red cell membrane defect leading to intermittent dark urine and venous thrombosis and a chronic
form of hemolysis.

 The gold standard test is flow cytometry for

CD55 and CD59 on white and red cells.

It is a clonal stem-cell disorder and therefore

can progress into aplastic anemia and leukemia.

 Treatment:

- Eculizumab, folic acid, and filtered RBC transfusion.

-A definitive cure can be reached with

allogeneic bone marrow

transplantation.
LAST EXAM
A 25-year-old male presents to the ER with generalized weakness. On examination, he
is pale with conjunctival jaundice. Laboratory findings: anemia 7 gr/L (normal range:
13-16), bilirubin 8 mg/dL (normal range: 0.3-1.2), mostly indirect. A working diagnosis
is hemolysis. Results of the LDH and haptoglobin are pending. (The normal value range
for LDH is 120-200 U/L, and the normal value range for Haptoglobin is 40-160 mg/dL.)
Which of the following laboratory results supports the most likely diagnosis?

1. LDH 1200 U/L, haptoglobin 200

2. LDH 100 U/L, haptoglobin 200
3. LDH 1200 U/L, haptoglobin 10
4. LDH 100 U/L, haptoglobin 40
A 43-year-old female patient completed treatment with Penicillin V due to
pharyngitis and
was admitted due to extreme weakness. On examination: pallor and jaundice.
Laboratory tests: hemoglobin 8 g/dL, MCV 94, reticulocytosis, increased LDH,
indirect
hyperbilirubinemia, positive Coombs test.
Which of the following is the most likely diagnosis?

1. Hemolytic anemia
2. Megaloblastic anemia
3. Aplastic anemia
4. Acute upper gastrointestinal bleeding
A 25 year old male presents to the ER with weakness and jaundice. He took
cotrimoxazole
for the last week. On examination his LDH and bilirubin are elevated and
haptoglobin is
decreased. Which of the following is the most likely diagnosis?

1. G6PD
2. Hereditary spherocytosis
3. Sickle cell anemia
4. Iron deficiency anemia
5. Paroxysmal nocturnal hemoglobinuria
HEMOLYTIC UREMIC SYNDROME
 A syndrome characterized by acute renal failure, microangiopathic hemolytic
anemia, and thrombocytopenia.
 No fever or confusion.
 Preceded by history of diarrhea, often hemorrhagic,.
 Escherichia coli O157:H7 is the most frequent, although not only, etiologic
serotype.
 Treatment of HUS is mainly supportive.
THROMBOTIC THROMBOCYTOPENIC
PURPURA (TTP)
 Thrombocytopenia, hemolysis (microangiopathic hemolytic anemia), and
thrombosis.
 Pathogenesis of TTP is associated with a mutation in ADAMTS13 which leads to
large von Willebrand factor molecules.

 Treatment:
-The mainstay of treatment for patients with TTP is plasma exchange. (daily until
the platelet count is normal and signs of hemolysis are resolved for at least 2
days.
-The addition of rituximab to initial therapy decreases the duration of
plasmapheresis and relapses.
-Caplacizumab, an anti-VWF nanobody, decreases mortality and burden of care
when used in patients with ADAMTS13 <10% or with a high clinical probability of
disease.(important)
HUS AND TTP BLOOD FILM
 Schistocytes are fragmented RBCs

due to microangiopathic hemolysis

Causes:
-HUS, TTP
-DIC (Disseminated intravascular

Coagulation

DIC has high INR and PTT but TTP, HUS

Has normal INR and PTT
 S
 Atypical HUS is a diagnosis of exclusion, it

is considered likely when ADAMTS13 is not

deficient and when no etiologic pathogen is
found. (No E Coli).

 Eculizumab may be given for cases

of atypical HUS.
DISSEMINATED INTRAVASCULAR COAGULATION DIC
 Causes: bacterial sepsis, malignancy, and obstetric complications.

 Clinical findings
-Bleeding
-Hypercoagulability.
-Platelet count is low, fibrinogen low, PT aPTT and INR high, D dimer high
-.A blood smear will show schistocytes (due to microangiopathic hemolytic anemia).

-Treatment with fresh frozen plasma (FFP) and/or platelets is indicated in case of active
bleeding or a high risk of bleeding. Cryoprecipitate is given in case of very low
fibrinogen level, <100mg/dL.
A 53-year-old female patient, has underlying AIDS. Was admitted to the emergency
room
due to dizziness, and instability in gait for two days. On her physical examination -
confused, depressed consciousness, multiple petechiae on the abdomen and arms.
On the initial laboratory investigation: hemoglobin 7 g%, thrombocytopenia 17,000
with cell fragments in the smear, creatinine 2.5 mg/dL, BUN 55 mg/dL.
What is the most appropriate treatment for the patient's condition at this stage?

1. Plasma exchange
2. Imuran
3. Methylprednisolone pulse therapy
4. Eculizumab
A 73-year-old female patient was hospitalized due to a urinary tract infection.
Growth of Escherichia coli in blood and urine cultures. The patient receives prophylactic
heparin. The next day, the patient vomited once with traces of fresh blood. On her
examination: blood pressure was 80/50, regular pulse of 110 per minute, new
neurological
symptoms, and the appearance of ecchymoses and petechiae on the skin. On the
laboratory tests: increased D-Dimer, increased INR, low platelets, and fibrinogen
decreased. On brain CT, new small ischemic infarcts.
Which of the following is the most likely diagnosis?

1. Bleeding secondary to prophylactic heparin

2. DIC - Disseminated Intravascular Coagulation
3. Idiopathic thrombocytopenia
4. Allergic reaction to the antibiotic treatment
A 35-year-old man is presenting to the ER due to jaundice and abdominal
pain that
extends to the back and started in the last few hours. In the laboratory –
WBC 13K, 4% reticulocytes, MCHC 50 (increased), LDH 500, Bilirubin 11,
direct bilirubin 8,
normal liver functions. On abdominal US, gallstones were seen, without
signs of
inflammation.
What other finding shall we expect?

1. Small RBCs with no central pallor

2. Increased Amylase
3. Hypercellular bone marrow
4. Low Iron
A 45-year-old woman, usually healthy, has been suffering from a cough and
sub-febrile
fever for about 10 days. She went to her family doctor, who recommended
treatment with amoxicillin, and after 4 days of treatment, there was only a
slight improvement.
She now presented to the emergency room due to a new weakness. Vital
signs are normal. On examination, she is slightly pale, has soft crackles on
lung auscultation, regular and fast heart sounds, soft, non-tender abdomen,
and mild rash with non-palpable purpura on the extremities. In the
laboratory:
Count - new anemia 8.5, MCV 110, leukocytes 5k, platelets 145k.
Chemistry - creatinine 1 (base), sodium 145, potassium 4, total bilirubin 1.9 of
which 0.3 direct, AST 55, ALT 35, LDH 350. On chest X-ray, reticular
interstitial infiltrates are seen bilaterally.
which of the following tests would most likely assist in the diagnosis?

1. G6PD levels
2. Coombs test
3. Serology for Parvo B19
4. ADAMTS13 levels
5. Measurement of platelet factor 4 complex
A 18 year old female from Sudan is brought to the ER with fever 38.9,
heart rate 120
and blood pressure 90/60, arterial oxygen saturation is 88% and
hematocrit is 32%.
On blood smear the following finding is seen.
Which of the following is the immediate treatment in this patient?

1. Exchange transfusion
2. Penicillin
3. Blood transfusion
4. IVIG
5. Plasmaphersis
An 18-year-old male arrives at the ER with several days of intermittent bloody
diarrhea.
On the day of admission, he also noticed diffuse skin petechiae. On
evaluation –
hemolytic anemia, thrombocytopenia, and renal failure.
Which of the following is the most likely diagnosis?

1. Dysentery with secondary anemia due to blood loss

2. Hemolytic-uremic syndrome
3. Immune thrombocytopenic purpura
4. Hereditary spherocytosis
A 40-year-old male arrives to the ER with confusion and fever of 38.6"C. On
examination-
Hemodynamically and respiratory-stable, no nuchal rigidity. Labs- WBC 6,400,
hemoglobin 8.8 g/dl, MCV 90, platelets 60,000, total bilirubin 3.4 mg/dl,
indirect bilirubin 3 mg/dl, creatinine 1.9 mg/dl. Peripheral blood smear image
is given
below. Which of the following is the most appropriate treatment?

1. Steroids and IVIG

2. Empiric broad spectrum antibiotics
3. Plasma exchange
4. One unit of blood after cross and match
5. Urgent dialysis
80 years old female is brought to the ER due to sepsis. On laboratory tests
the following
findings are seen: platelet count- 20,000 prolonged PT and aPTT, fibrinogen
70mg/dL
and d-dimer is elevated. Treatment is initiated with platelets and fresh frozen
plasma.
Which of the following should be added to the therapy?

1. Heparin
2. Tranexamic acid
3. Aminocaproic acid
4. Cryoprecipitate
5. Phlebotomy