creation date: 2025-05-29 15:59
tags: Pathologies
Anemia
Background
Definition
Reduction of one of the following RBC measurements within the CBC:
- Hemoglobin concentration
- Hematocrit
- RBC count
Etiology
Diagnosis of etiology can be made using clinical features in addition to laboratory findings.
Microcytic anemia (MCV < 80 fL)
- Thalessemia
- Anemia of chronic disease
- Iron deficiency anemia
- Lead poisoning
- Sideroblastic anemia
Normocytic anemia (MCV 80-100 fL)
- Hemolytic anemia (incl. sickle cell anemia, autoimmune hemolysis, infections)
- Nonhemolytic anemia (incl. blood loss)
Macrocytic anemia (MCV >100 fL)
- Megaloblastic anemia (incl. B12 deficiency, folate deficiency)
- Nonmegaloblastic anemia (incl. liver disease, alcohol use)
Pathogenesis
The pathophysiology of anemia depends on the primary cause. However, the mechanism of anemia can be summarized into two components.
- Increased destruction of RBCs, either through blood loss or hemolysis
- Deficient or defective erythropoiesis
It must be noted that Hb is reported as a concentration of total blood volume. As such, imbalances between RBCs and plasma can result in anemia or falsely normal hemoglobin.
Clinical Presentation
Signs & Symptoms
Mild anemia is often asymptomatic and an incidental finding. However, anemia can manifest with:
- Exertional dyspnea
- Fatigue
- Angina pectoris (chest pain on exertion)
- Pallor
- Growth impairment (if anemia is chronic)
There may also be etiology specific features:
- Hemorrhage - eg. GI bleed, menorrhagia, shock
- Iron deficiency - pica, brittle nails, angular cheilitis, atrophic glossitis
- Megaloblastic - oral sores, mucosal bleed, paresthesia, ataxia
- Chronic - signs of extramedullary hematopoiesis (eg. hepatosplenomegaly)
History & Physical Exam
Acute blood loss should be identified and treated without diagnostic confirmation/workup.
Work-up for anemia discussed below.
Risk factors
Notable risk factors include:
- Inadequate dietary intake, malabsorption, increased requirements for nutrients such as iron, folate, and vitamin B12
- Chronic blood loss (eg. heavy menstrual bleeding)
- Chronic diseases
Diagnosis
Criteria
Anemia is diagnosed when:
- Hb < 120 g/L in women
- Hb < 130 g/L in men
It should be noted that clinical judgement should be used in assessment as cutoffs differ between populations and can be affected by a number of non-pathological processes (eg. pregnancy, aging, altitude)
Work-up
A complete blood count is used to confirm anemia, classify etiology, and assess severity. Further testing done based on MCV.
For microcytic anemia:
Iron deficiency anemia can be diagnosed with iron studies:
- Ferritin <11 mcg/L (female) or <24 mcg/L (male)
- Serum iron <9 mcmol/L (female) or <12 mcmol/L (male)
Note that ferritin is not sensitive and can present as normal/elevated in IDA.
Peripheral blood smear, reticulocyte count, and RDW are not routine due to non-specific findings.
Hemoglobin electrophoresis, bone marrow biopsy, and serum lead levels can be considered for specific etiologies.
For normocytic anemia:
Reticulocyte count for evalulation of bone marrow response.
Normal/low reticulocyte count (<2%) suggests ineffective/decreased RBC production (hypoproliferative anemia)
- Follow-up with iron studies, vitamin B12, folate levels
- Metabolic panel, LFTs, thyroid studies
- Bone marrow aspirate and biopsy if studies are normal
High reticulocyte count (>2%) suggests hemolysis or hemorrhage
- Assess for acute or chronic blood less and hemolysis (eg. bilirubin)
For macrocytic anemia:
Peripheral blood smear can find megaloblastic changes.
-
5 lobes of hypersegmented neutrophils suggests megaloblastic anemia
For megaloblastic anemia, investigate vitamin B12 and folate levels for deficiencies.
Borderline deficiencies can be confirmed with serum homocysteine and methylmalonic acid levels (both elevated in vit. B12 deficiency, only elevated homocysteine in folate deficiency). Consider bone marrow biopsy if investigations are normal.
For nonmegaloblastic anemia, obtain reticulocyte count.
- If normal/low (<2%): complete drug/alcohol use history, consider TSH/hepatic panel
- If high (>2%): consider blood loss/hemolysis
Differential
Differential includes all forms of anemia as discussed in above sections. Other diagnoses include:
- Pseudoanemia / physiological dilutional anemia of pregnancy - due to physiological increase in plasma volume leading to a relative decrease in hemoglobin and hematocrit
Red Flags / Complications
Pancytopenia can suggest more ominous diagnoses including:
- Acute leukemia
- Aplastic anemia
Other conditions that may also present with anemia includes:
There are also a number of complications that can occur with untreated anemia which include increased susceptibility to infection, worsening of symptoms, complications of the heart and lungs
Management
Lifestyle / Social
With nutrient deficiency forms of anemia, supplementation of said nutrient may be sufficient treatment, especially with low-severity.
For iron deficiency anemia, heme iron (Fe2+) rich foods such as
- Red meat
- Poultry
- Fish
and nonheme iron (Fe3+) rich foods such as - Legumes
- Lentils
- Tofu
- Spinach
paired with vitamin C (for conversion of ferrous to ferric iron) is recommended. Note that tea, coffee, calcium, and high-fibre can inhibit iron absorption.
Animal-based foods can also address vitamin B12 deficiency and green leafy vegetables and legumes can address folate deficiency.
For etiologies that result from some offending agent (eg. lead poisoning or iatrogenic), cessation of agent should be considered.
Pharmacological / Interventional
Treatment varies based on etiology. Supplementation are recommended for nutrient deficiency.
Oral iron supplementation:
- Ferrous sulfate, 325 mg daily or every other day (OTC or prescription)
- Continue for 3-6 months to replete iron stores
- Side effects: nausea, abdominal pain, constipation
IV iron therapy:
- If PO iron is not tolerated
Blood transfusion:
- Severe anemia with active bleeding or significant symptoms
Other interventions can mitigate anemia such as use of hormonal contraceptives to reduce menstrual blood loss.