Title: Understanding Anemia: Causes, Types, Clinical Features, and Diagnostic Investigations
Anemia is a condition characterized by a deficiency in the number or quality of red blood cells (RBCs) or hemoglobin in the blood, leading to reduced oxygen-carrying capacity. It is a prevalent global health issue affecting people of all ages, genders, and socioeconomic backgrounds. Understanding the causes, types, clinical features, and diagnostic investigations of anemia is crucial for effective management and treatment.
**Causes of Anemia:**
Anemia can result from various factors that disrupt the production, lifespan, or function of red blood cells. Some common causes include:
1. **Iron Deficiency:** Insufficient intake or absorption of iron, essential for hemoglobin synthesis, is a primary cause of anemia globally. It can stem from poor dietary intake, chronic blood loss (e.g., menstruation, gastrointestinal bleeding), or increased demand during pregnancy.
2. **Vitamin Deficiencies:** Deficiencies in vitamins such as vitamin B12 (cobalamin) or folate (vitamin B9) can impair RBC production, leading to megaloblastic anemia.
3. **Chronic Diseases:** Conditions like chronic kidney disease, inflammatory disorders (e.g., rheumatoid arthritis), and infections can disrupt erythropoiesis (RBC production) or accelerate RBC destruction, causing anemia.
4. **Hemolytic Disorders:** Inherited or acquired conditions that increase the breakdown (hemolysis) of red blood cells, such as sickle cell disease, thalassemia, or autoimmune hemolytic anemia, can result in anemia.
5. **Bone Marrow Disorders:** Diseases affecting the bone marrow, including leukemia, myelodysplastic syndromes, and aplastic anemia, can lead to decreased RBC production and anemia.
**Types of Anemia:**
Anemia is classified based on the underlying mechanism or etiology, leading to several types:
1. **Iron-Deficiency Anemia:** Characterized by low iron levels, resulting in decreased hemoglobin synthesis and microcytic (small-sized) RBCs.
2. **Megaloblastic Anemia:** Caused by impaired DNA synthesis in RBC precursors due to deficiencies in vitamin B12 or folate, leading to macrocytic (large-sized) RBCs.
3. **Hemolytic Anemia:** Occurs due to increased RBC destruction, either intravascularly (within blood vessels) or extravascularly (outside blood vessels), leading to various subtypes like autoimmune hemolytic anemia, hereditary spherocytosis, and sickle cell disease.
4. **Anemia of Chronic Disease:** Associated with chronic inflammation, infections, or malignancies, leading to impaired iron metabolism and decreased RBC production.
5. **Aplastic Anemia:** Results from bone marrow failure, leading to decreased production of all blood cell types, including RBCs.
**Clinical Features of Anemia:**
The clinical presentation of anemia can vary depending on its severity, underlying cause, and individual factors. Common clinical features include:
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Anemia; causes, types, laboratory investigations
1. RBC Disorders
ANEMIAS
Nawsherwan S Jabbary
Assis. Prof. and Consultant Hematopathologist
HMU-College of Medicine
Pathology Dept
nawsherwan.sadiq@hmu.edu.krd
2. Anemia
• Reduction of RBC mass or HGB
concentration.
• Symptoms reflect the rapidity of onset
• Pat. with acute hemorrhage/massive
hemolysis may exhibit symptoms of
hypovolemic shock.
• Slowly established anemia produce few
symptoms.
4. Differential Dx.Anemias –
Depending on MCV
Low MCV
Thalassemia
Iron def.
Lead Pois.
Sideroblastic
Normal MCV
Acute B. loss
Aplastic A.
Chronic Dis.
Hemoglobino
p-athies
Hemolysis
Iron def.
High MCV
Alcohol abuse
Aplastic A.
B12 def.
Folate def
Hemolysis
Hypothyroidism
Liver Ds
Myelodysplastic s
5. Anemia Symptoms physical exam
Fatigue
Decreased exercise tolerance
Dyspnea
Palpitations
Major sign is pallor of skin, and mucous
membranes
May develop tachycardia
Possible audible flow murmurs
Patients with hemolysis could present with
jaundice and splenomegaly.
6. Laboratory Evaluation
• Reticulocyte count differentiates between
failure of RBC production (low retic) and
increased RBC destruction (increased retic)
or bleeding
• Peripheral blood smear provide clues to the
cause of the anemia:
• E.g : Spherocytes in immune hemolytic
anemia
7. Laboratory eval. Cont.
• Sickle and target cell in
hemoglobinopathies
• Tear drop cells and nucleated RBCs in
myelofibrosis and marrow infiltration
• Intracellular parasites in Malaria and
Babesiosis
• Pencil shape cells in severe iron deficiency
• Hypersegmented neutrophils in
megaloblastic anemia
• Immature blasts in leukemias
8. Laboratory eval.cont.
• MCV is important in anemia to differentiate
according to cell size
• Bone marrow analysis helpful in patients with low
retic count, provides information about causes of
anemia
9. Iron deficiency anemia
• Essentials of diagnosis
• CBC: Hb decreased, MCV, MCH both decreased
• Serum ferritin decrease, s. iron decreased, TIBC
increased
• Caused by bleeding in adults
unless proved otherwise
• Responds to iron therapy
10. Iron deficiency anemia
• Most common cause of anemia worldwide
• Average american diet contains 10-15mg of iron
per day (10% is absorbed).
• Iron Absorption in proximal small intestine
• Balanced daily iron absorption and loss at
1mg/day
11. Iron deficiency anemia
• Iron Bound to transferrin in plasma
• 60-75% found in Hgb
• Iron Stored as ferritin in the liver, spleen, BM and
muscle
• Pre-menopausal women could loose15mg of
iron per month, and need 900 mg/pregnancy
• Investigate GI blood loss in iron deficient men
and postmenopausal women
12. Iron deficiency anemia,
causes
• Most frequent cause of iron def. is blood
loss(Bleeding)
• Decreased iron absorption is rare, occasional
after gastric surgery
• Hemoglobinuria in traumatic hemolysis due to
prosthetic heart valve can cause IDA
• Frequent blood donors
13. Iron deficiency anemia-
symptoms
• In severe cases, skin and mucosal changes:
• Pallor
• Smooth tongue
• Brittle nails
• Dysphagia-esophageal webs (Plummer-Vinson
syndrome
• Pica ( ice, dirt)
14. • Early Iron storage depletion stage - no changes on RBC
morphology
• Decreased total serum iron concentration
• Increased total iron binding capacity (TIBC)
• Decreased ferritin levels
• Advanced iron deficiency affects RBC morphology:
microcytic - hypochromic cells,
target cells, pencil shaped cells
15. Megaloblastic anemia
• Results from block of synthesis of nucleotide
precursors of DNA
• Maturation of cell nucleus is arrested,
maturation of cytoplasm continues
• Most common causes:
• Vitamin B12 (Cobalamin) deficiency, more
common
• Folate deficiency
• Medications that inhibit DNA synthesis /
block folate metabolism
17. B12 deficiency
• B12 absorbed from animal protein in the diet
• Absorbed in the terminal ileum
• bound to intrinsic factor, a protein secreted by gastric
parietal cells
• B12 stored in the liver
• 3-4 years supply
• Daily losses 3-5 mcg, daily absorption 5mcg
• Dietary B12 deficiency is rare
• Ocuur in Vegans diet
18. B12 deficiency anemia-
causes
• Pernicious anemia:
• Autoimmune atrophy of gastric parietal cells
( most common)
• Gastrectomy
• Pancreatic insufficiency
• failure to inactivate competing binding
protein
19. B12 deficiency anemia- causes
• Bacterial overgrowth in the intestine
• Inflammatory bowel disease (crohn’s disease)
• Tapeworm infection
• Congenital Intrinsic Factor or Transcobalamin II
deficiency
20. Megaloblastic anemia
symptoms
• Often severe anemia at presentation
• Insidious onset
• Yellowish of skin
• pallor and jaundice
• Mucosal changes
• glossitis, anorexia, diarrhea
• B12 deficiency leads to complex neurologic
syndrome:
• paresthesias - early
• difficulty with balance - late
21. Laboratory findings
• Variable severity anemia
• MCV: 110-140 fl
• Peripheral smear
• large ovalocytes,
• hypersegmented neutrophils,
• and large platelets
• Hyper cellular bone marrow
• Increased bilirubin and lactate dehydrogenase
enzyme (LDH)
22. Anemia of chronic disease
• Occur in patients with:
• chronic inflammatory conditions (RA)
• Infections
• malignant (cancer)
• autoimmune diseases (SLE)
• Usually normocytic-normochromic
• occasionally microcytic
• Common causes:
• EPO deficiency (chronic renal failure)
• Direct inhibition of erythropoiesis
• Poor iron incorporation to developing Rbcs
• Shortened erythrocyte survival
23. Laboratory findings
• Low serum iron level
• TIBC is also reduced
• Transferrin saturation >10%
• Ferritin level normal or increased
• MCV normal or slightly reduced
24. Aplastic Anemia(AA)
• Essentials of Diagnosis (lab findings)
• Pancytopenia
• No abnormal cells seen
• Hypo cellular bone marrow
26. AA-Congenital causes
• Small proportion of the cases
• Defective genetic material (DNA ,gene
mutations, etc.)
• Fanconi’s anemia(most common)
• Schwachmann-Diamond syndrome
• Dyskeratosis congenita
27. Hemolytic anemias
General
• Premature loss of RBCs by hemolysis either:
• Reticulocytosis
• as a compensatory response of a normal
bone marrow
• Only other condition causing reticulocytosis
in anemia is blood loss
29. Sickle cell anemia
essential Dx.
• Sickled cells on blood smear
• Positive family history and lifelong history of hemolytic anemia
• Recurrent painful episodes
• Hemoglobin S present on
Hgb electrophoresis
In addition to
general findings
Of hemolytic anemia
31. Sickle cell anemia lab
findings
• Sickling tests is positive
• Confirmatory test-
• hemoglobin electrophoresis showing
• 85-98% Hgb S present
• No Hgb A present in homozygous
• Variable amount of Hgb F present
32. Sickle cell trait
• Patients with heterozygous genotype (AS)
• Clinically normal
• Acute painful episodes under extreme conditions only
• Hematologically normal, no anemia, normal RBCs
• Screening test-positive, Hgb electrophoresis will show
40% Hgb S
• No treatment is necessary.
33. Thalassemia
• Hemoglobinopathies
• Hereditary reduction in the synthesis of globin
chain
• alpha or beta
• Hypochromic -microcytic anemia because of
defective hemoglobinization of RBCs
• Often confused with iron deficiency, decreased
MCV
34. Thalassemia
• Most common inherited hemolytic disorder
• Defective Hgb caused by decreased production of
at least one globin chain
• Common in persons of Mediterranean
• Alpha thalassemia due to:
• gene deletion causing decreased alpha globin chain
• Beta thalassemia caused by:
• point mutations, leading to reduced or absent beta-globin
chain synthesis
35. Essentials of diagnosis
lab findings
• Microcytosis out of proportion to the degree
of anemia
• Positive family Hx or lifelong personal Hx of
microcytic anemia
• Microcytes, and target cells in blood smear
• In beta-thalassemia minor elevated levels of
Hgb A2 and in major Hgb F is increased
36. Alpha thalassemia
• Three alpha globin gene present-silent carrier
• Two alpha globin gene present-trait
• only mild microcytic anemia
• Only one alpha globin chain present, Hgb H
disease(thalassemia minor or intermedia)
• Pallor and splenomegaly present.
• All four alpha globin gene deletion- affected
fetus is stillborn (hydrops fetalis)
37. B-Thalassemia
• B-Thalassemia minor clinically
asymptomatic
• microcytosis, mild anemia
• B-thalassemia Intermediate produce
• moderate hemolysis or
• severe anemia
• main complication iron overload (non transfusion dependent
38. Signs and Symptoms
• B-Thalassemia major (Cooley’s anemia)
homozygous
• normal at birth
• after 6 months develop severe anemia(need transfusion)
• growth failure
• bone deformities
• pathologic fractures
• and hepatosplenomegaly
39. B-Thalassemia major
• Improved with blood transfusion,
• but iron overload develops(hemosiderosis), deposits in
• heart(heart failure),
• liver(cirrhosis),
• and endocrine glands (endocrinopathies)
40. Laboratory findings
• Alpha thalassemia trait: mild anemia, RBC count
normal, microcytes, hypochromia, occasional
target cells
• Hgb H disease: more marked hemolytic anemia,
RBC morphology includes all trait changes and
poikilocytosis
41. G6PD deficiency
• X-linked recessive disorder
• Episodic hemolysis in response to oxidant
drugs or infection
• Reduced levels of glucose-6-phosphate
dehydrogenase between hemolytic episodes
• Commonly found in people of African,
Mediterranean, Sephardic Jews and Chinese
descents
42. G6PD deficiency
• Most female carriers are asymptomatic
• Clinical problems arise only when the affected
individual is exposed to oxidative stress
(infections, drugs )
43. QUESTIONS
-Classify anemia according to cell size with 3
examples for each
-Lab findings of aplastic anemia
-Causes of IDA
-Lab findings of IDA
-Causes of megaloblastic anemia
-Lab findings of megaloblastic anemia
-Lab findings of anemia of chronic diseases
-Lab findings of sickle cell anemia
-Lab findings of thalassemia