Anemia

Dr.Kareemah Salem Alshurtan , MD

Assistant professors of Internal Medicine
Consultant of Adult Critical Care
 Definition: a decrease in the absolute number of
circulating RBCs; exact cutoffs vary from source to
source.

Men: Hb < 13 g/dL

WHO criteria for anemia Women: Hb < 12 g/dL
Pregnant women: Hb < 11 g/dL

Anemia : Revised WHO/National

Cancer Institute
Men: Hb < 14 g/dL
Women: Hb < 12 g/dL

American Society Men: Hb < 13.5 g/dL

of Hematology [3] Women: Hb < 12 g/dL

US National Health and Nutrition Examination Survey:

children aged 12–35 months: Hb < 11 g/dL
 Classification of anemia by
Severity Others
morphology
Microcytic anemia: Mild anemia: Time course: acute vs. chronic
• MCV :< 80 • Hb level > 10–11 g/dL
• Presentation: usually
asymptomatic; clinical features of
anemia may be present

Normocytic anemia: Moderate anemia: Inheritance: inherited vs. acquired

• MCV: 80–100 • Hb level: ∼ 7–10.9 g/dL

Classification
• Presentation: clinical features of
anemia may or may not be
present.

of Anemia: Macrocytic anemia:

• MCV : > 100
Severe anemia:
•
•
Hb level: ∼ 7–8 g/dL
Presentation: clinical features of
Etiology: primary vs. secondary

anemia typically present;

hemodynamic compromise may
be present.

RBC proliferation:
• Hypoproliferative
(decreased RBC production)
• Hyperproliferative
(increased RBC destruction or
blood loss)
Microcytic anemia Normocytic anemia: Macrocytic anemia:
Defective heme synthesis: Hemolytic anemia Megaloblastic anemia
1. Iron deficiency anemia (IDA): the most • Intrinsic defects • Vitamin B12 deficiency
common • Hemoglobinopathies • Folate deficiency
2. Lead poisoning • Sickle cell anemia • Medications
3. Sideroblastic anemia • HbC disease • Phenytoin
Defective globin chain: • Enzyme deficiencies • Sulfa drugs
1. Thalassemia • Pyruvate kinase deficiency • Trimethoprim
• G6PD deficiency • Hydroxyurea
• Membrane defects • MTX
• Paroxysmal nocturnal • 6-mercaptopurine
hemoglobinuria • Fanconi anemia
• Hereditary spherocytosis • Orotic aciduria
• Extrinsic defects Nonmegaloblastic anemia
• Autoimmune hemolytic anemia • Liver disease
• Microangiopathic hemolytic anemia • Alcohol use
• Macroangiopathic hemolytic anemia • Diamond-Blackfan anemia
• Infections • Myelodysplastic syndrome
• Mechanical destruction • Multiple myeloma
Nonhemolytic normocytic anemia • Hypothyroidism
• Blood loss
• Aplastic anemia
• Anemia of chronic kidney disease
• Iron deficiency anemia (early phase)
• Anemia of chronic disease (early phase)
• Dilutional anemia of pregnancy
Microcytic Anemia :

Iron deficiency anemia (IDA): Thalassemia:

• Special clinical manifestations: angular cheilosis, • Hemoglobinopathy disease .
atrophic glossitis, pica (consumption of • Special clinical manifestations:
nonnutritive substances such as ice, clay), • Chipmunk facies.
koilonychia (nail spooning), Plummer-Vinson • Pathologic fractures.
syndrome (iron deficiency anemia, esophageal • Hepatosplenomegaly (due to extramedullary hematopoiesis)
web & atrophic glossitis) • High-output CHF.
• Bilirubin gallstones.
• Causes: • Iron overload.
• Chronic bleeding (GI cancer, menstrual, parasites, NSAIDs,
etc.), • Peripheral blood smear typically shows microcytosis, nucleated erythrocytes,
and target cells.
• ↓ supply (malnutrition; ↓ absorption due to celiac
disease, Crohn’s, subtotal gastrectomy), • Active hemolysis:
• ↑ demand (pregnancy) • Increased lactate dehydrogenase (LDH).
• Increased unconjugated bilirubin.
• Work up for specific disease like celiac markers • Decreased haptoglobin levels.
Anti TTG, send for H. pylori test if you think about • Treatment :
GI bleeding due to peptic ulcer disease. • Supplemental folate
• Deferoxamine
• Genetic counseling
• stem cell transplant
 IDA vs anemia of chronic inflammation
Finding Type of Anemia
Inflammatory Anemia Iron Deficiency Anemia
MCV Normal (N) Low (↓)
Low (↓) Low (↓)
Serum iron
High (↑)
TIBC Normal (N)
Low (↓)
Transferrin saturation Normal (N)
<15 ng/mL (15 µg/L) (↓)
Ferritin Normal (N) or high ↑

Serum soluble transferrin

Normal Increased
receptor concentration
Stainable iron in bone
Present Absent
marrow
Macrocytic Anemia :

Megaloblastic anemia: Nonmegaloblastic anemia:

• Both vitamin B12 and folate are important in DNA synthesis.
• Liver disease: often macrocytic.
• Etiologies:
• Malnutrition (alcoholics, vegans), • Alcoholism: bone marrow suppression &
• Pernicious anemia (PA), (autoimmune disease against gastric parietal cells, with
polyglandular endocrine insufficiency and ↑ risk of gastric carcinoma),
macrocytosis independent of folate/B12 deficiency
• ↓ absorption (gastrectomy, Crohn’s disease), or cirrhosis
• ↑ competition (intestinal bacterial overgrowth, fish tapeworm)
• Low Folate :
• Reticulocytosis
• ↓ absorption, impaired metabolism (methotrexate, pyrimethamine,
trimethoprim; • Other causes: hypothyroidism; MDS; meds that
• ↑ requirement (chronic hemolytic anemia, pregnancy, malignancy, impair DNA synthesis (5-FU, hydroxyurea)
dialysis)

• Laboratory diagnosis:
• ↓ B12 or Folate
• Vit B12 : ↑ homocysteine and methylmalonic acid.
• Low folate : ↑ homocysteine but normal methylmalonic acid
• Anti-IF Antibody. (In PA)
• Pancytopenia due to ineffective erythropoiesis
• Intramedullary hemolysis. (high LDH, high indirect bilirubin and low haptoglobin)
• Peripheral blood smear: showed hypersegmented neutrophils.
Congenital Hemolytic Anemia :
Congenital: Glucose-6-phosphate dehydrogenase
Sickle Cell Disease (SCD) (G6PD) deficiency (bite cells and Heinz bodies)
• Structurally abnormal hemoglobin (HbS)
• Presentation :
• Chronic hemolysis
• Acute aplastic (parvovirus. B19)
• splenic sequestration crises.
• Vaso-occlusion & infarction:
• Acute chest syndrome & stroke (high mortality)
• pulmonary HTN,
• painful crises.
• splenic sequestration,
• renal papillary necrosis.
• aseptic necrosis,
• dactylitis (hand-foot syndrome),
• Priapism
Acquired: Autoimmune Hemolytic Anemia (AIHA):

General Diagnostic evaluation of hemolytic anemia

• Immune-mediated hemolysis is characterized by • ↑ reticulocyte count (RI >2%),
antibody binding to erythrocytes causing
• Autoimmune hemolysis: Coombs’ test = direct
complement-mediated and phagocyte-mediated
antiglobulin test (DAT)
destruction.
• Intravascular: ↑↑ LDH, ↓↓ haptoglobin;
• The laboratory hallmark of immune-mediated
hemoglobinemia, hemoglobinuria,
hemolysis is a positive direct antiglobulin
hemosiderinuria
(Coombs) test that detects either IgG or
complement (C3) on the erythrocyte surface. • Extravascular: splenomegaly
• Diagnosis: spherocytes on smear, positive • Family history of anemia; personal or family history
Coombs, splenomegaly of cholelithiasis
 • Asymptomatic
• Exertional dyspnea and fatigue
• Worsening of angina pectoris
Clinical • Pallor (e.g., on mucous
membranes, conjunctivae)
Features of • Growth impairment (chronic anemia)
Anemai / • Jaundice
Genral : • Splenomegaly
• Petechia & purpura
• Neurological manifestation
Clinical Features of Anemai / Accompanying Features :

Vary depending on underlying etiology Features of hyperdynamic state Features of extramedullary

hematopoiesis
• Clinical features of shock (if • Bounding pulses • Its may be present in certain
anemia is acute) • Tachycardia/palpitations severe, chronic forms of anemia
• Features of IDA: • Flow murmur (e.g., thalassemia, myelofibrosis).
• Pica (craving for ice or dirt), • Pulsatile sound in the ear • Hepatosplenomegaly
• Brittle nails • Possibly heart failure (anemia- • Paravertebral mass
• Angular cheilitis induced heart failure) • Widening of diploic spaces of
• Atrophic glossitis the skull
• Features of megaloblastic anemia:
• Oral sores
• Mucosal bleeding
• Paresthesias
• Ataxia
• Clinical features of hemolysis
• Signs of hemorrhage: e.g., GI
bleeding, menorrhagia
Diagnosis :
Approch of
Diagnosis :
 Microcytic Anemia Investigation :
Iron Profile • Peripheral blood smear (PBS)
• Reticulocyte count
Anemia Iron Ferritin TfS TIBC Reticulocyt RDW
e • Low reticulocyte count (< 2%): iron deficiency
anemia, thalassemia trait, anemia of chronic
disease, sideroblastic anemia, and lead poisoning
IDA ↓ ↓ ↓ ↑ ↓ ↑
• High reticulocyte count (> 2%): thalassemia

Anemia of chronic ↓ ↑ Normal to ↓ ↓ Normal • RDW: typically high in iron deficiency

disease ↓ anemia and sideroblastic anemia
• Hemoglobin electrophoresis:
• Normal hemoglobin A2: sideroblastic anemia, α-thalassemia trait
• Increased hemoglobin A2: β-thalassemia trait
Thalasemia Normal Normal Normal to Normal ↑ Normal • Other hemoglobinopathies (e.g., hemoglobin E, hemoglobin C)
to ↑ to ↑ ↑ to ↓ to ↑
• Bone marrow biopsy:
• Ringed sideroblasts on PBS (see sideroblastic
Sederoblastic anemia ↑ ↑ ↑ ↓ ↓ ↑ anemia, myelodysplastic syndromes)
• Unexplained thrombocytopenia, leukocytopenia, or pancytopenia
• Numerous immature forms of blood cells on CBC and/or PBS
Pregnancy Normal Normal ↓ ↑ Normal Normal • Serum lead level: consider in patients with basophilic
to ↓ stippling but no ringed sideroblasts on PBS .
Macrocytic Anemia Investigation :

Megaloblastic Anemia : Non - Megaloblastic Anemia :

• Vitamin B12 levels • Reticulocyte count:
• Folate level • Normal/low reticulocyte count (< 2%)
• Obtain a detailed drug and alcohol use history.
• Serum homocysteine and methylmalonic • Consider TSH, hepatic panel.
acid levels: obtain in patients with borderline • High reticulocyte count (> 2%)
serum vitamin B12 and/or folate levels • Reassess history for evidence of acute or chronic
• Normal methylmalonic blood loss.
acid but ↑ homocysteine levels: folate deficiency • Check hemolysis labs: ↓ haptoglobin, ↑ LDH, ↑
unconjugated bilirubin suggest a hemolytic anemia
• ↑ Methylmalonic acid,
normal/↑ homocysteine: vitamin B12 deficiency • Hemoglobin electrophoresis
• Bone marrow biopsy • Bone marrow biopsy
• Hypercellular marrow with dysplasia of all three cell
lines: myelodysplastic syndrome
• Hypocellular fat-filled marrow : aplastic anemia
• Absent or sparse erythroid precursors: pure red cell
aplasia
Normocytic anemia :
• Reticulocyte Count:
• Normal/low reticulocyte count (< 2%) indicates ineffective or
decreased RBC production(hypoproliferative anemia)
• Iron studies: to evaluate for iron deficiency anemia and/or anemia of chronic
disease (see microcytic anemia)
• Vitamin B12 and folate levels (see megaloblastic macrocytic anemia)
• Basic metabolic panel (BMP), LFTs, thyroid studies: if iron studies and vitamin B12 and folate levels
are normal
• Serum erythropoietin levels: consider if BUN and/or creatinine levels are abnormal [15]
• High reticulocyte count (> 2%)
• Reassess history for evidence of acute or chronic blood loss.
• Check hemolysis labs: ↓ haptoglobin, ↑ LDH, and ↑ unconjugated bilirubin suggest a hemolytic
anemia
• Bone marrow aspirate and biopsy: consider in hypoproliferative
anemia with normal nutritional assays and metabolic panels .
Additional diagnostics:
• Bone marrow biopsy: • Imaging:
• Indications • Not routinely indicated for the
include pancytopenia and/or workup of anemia unless bleeding
abnormal cells on is suspected
the CBC or peripheral blood • Consider endoscopy
smear (e.g., blasts) and/or colonoscopy in patients with
• Can be used to diagnose: anemia and positive FOBT.
• Aplastic anemia • Consider abdominal ultrasound to
• Myelodysplastic syndromes evaluate
• Myeloproliferative neoplasm for hypersplenism, liver disease, or
• Malignant invasion of the bone renal disease.
marrow • Consider CT and/or PET
scan if malignancy is suspected.
Management approach:
• Consider hospital admission or • Identify and treat the underlying causes
observation in: of anemia, e.g.:
• Acutely symptomatic anemia • Iron therapy for IDA
• Actively bleeding patient, as clinically • Hemostatic measures for acute hemorrhagic
indicated anemia
• Patients requiring blood transfusion • EPO for chronic kidney disease
• Anemia with WBC and/or platelet • Vitamin replenishment
count abnormalities • Megaloblastic anemia: e.g., Vitamin
• For hemodynamically unstable patients B12, folate
with acute blood loss: • Sideroblastic anemia: Vitamin B6
• Establish IV access. • Blood transfusion :
• Monitor the patient with serial blood pressures • Severe anemia in any patient: e.g., Hb ≤ 7 g/dL;
and continuous pulse oximetry. or Hb ≤ 8 g/dL in patients with perioperative or
• Consider indications for pRBC transfusion. cardiac risk factors
• Send type and screen with crossmatching. • Moderate anemia in high-risk or symptomatic
• Obtain blood for further workup of anemia patients.
prior to initiating transfusion. • Consider bone marrow transplantation in
• Identify and treat the underlying cause. select cases (e.g., aplastic anemia).
Thank you