Blood Disease: Understanding Anemia

Presenting Problems in Blood Disease

• Anemia is a condition where hemoglobin levels fall below the normal range for age and sex.
• Factors like pregnancy (increased plasma volume) and altitude affect hemoglobin levels.
• Pregnancy lowers the reference range for normal hemoglobin to above 105 g/L at 28 weeks.
• Mean cell volume (MCV) may increase by 5 fL in pregnancy.
• Gestational thrombocytopenia (low platelet count) is a usually benign condition.
• Altitude also affects hemoglobin levels; this must be considered when assessing anemia.

Learning Objectives

• Define, classify, and identify causes of anemia.
• Describe the clinical presentation of anemia.
• Outline the investigation and approach to diagnosing anemia.
• Identify causes of iron deficiency anemia (IDA), investigate, and diagnose.
• Explain iron absorption, regulation, and distribution in the body.
• Differentiate between anemia diagnosis and treatment.

Clinical Features of Anemia

• Clinical features of anemia reflect diminished oxygen supply to tissues.
• They depend on the degree of anemia, the speed of development.
• The presence of cardio-respiratory disease influences anemia symptoms.
• Rapid onset anemia (like blood loss) results in more pronounced symptoms than gradually developing anemia.

History

• Iron deficiency anemia is the most common global anemia type.
• Thorough gastrointestinal (GI) history is needed, looking for blood loss symptoms.
• Menorrhagia (heavy menstrual bleeding) is a common cause of anemia in menstruating women.
• Dietary history must assess iron and folate intake, especially in pregnancy and rapid growth periods.

Past, Family, and Drug History

• Past medical history may reveal conditions linked to anemia (e.g., rheumatoid arthritis, GI surgery).
• Family history can suggest hereditary anemias (e.g., hemoglobinopathies, spherocytosis).
• Drug history can identify medications that may cause blood loss or hemolysis.

Physical Examination

• General physical exam findings for anemia are supplemented with findings related to the cause.
• Example: Right iliac fossa mass suggests potential cancer.
• Associated conditions might include jaundice (hemolytic anemia), neurological signs (vitamin B12 deficiency), and leg ulcers (sickle-cell anemia).
• Absence of specific symptoms doesn't rule out undiagnosed pathology.

Causes of Anemia:

• Decreased or ineffective marrow production.
  • Lack of iron, vitamin B12, or folate
  • Hypoplasia
  • Malignant cell invasion
  • Renal failure
• Peripheral causes.
  • Blood loss
  • Haemolysis
  • Hypersplenism

Investigation of Anemia

• Anemia investigation often relies on red blood cell size (MCV).
• Low MCV suggests iron deficiency or thalassemia.
• High MCV suggests vitamin B12 or folate deficiency.
• Normal MCV might indicate acute blood loss or anemia of chronic disease.
• The reticulocyte count differentiates between red blood cell production failure and increased destruction.

Iron Deficiency Anemia: Prevalence

• Approximately 30% of the global population has anemia, with half experiencing iron deficiency anemia.

Iron Importance

• Iron is crucial for fundamental processes, including oxygen and electron transport and respiration.
• Iron-containing heme proteins are essential, including hemoglobin, myoglobin, cytochromes, peroxidases, and catalase.
• Many Kreb cycle factors contain or depend on Iron.

Iron Absorption

• Normal mixed diets offer 10-20 mg of daily iron.
• Iron exists in inorganic or organic forms (e.g., meat, vegetables, beans, milk is low in iron).
• Only 5-10% of ingested iron is absorbed.
• Iron is released from protein compounds by stomach acid and enzymes in the small intestine.
• Duodenum and jejunum are the primary absorption sites.

Iron Absorption Regulation

• Intestinal mucosal cells regulate iron uptake.
• Body iron stores influence mucosal iron.
  • High stores prevent absorption.
  • Low stores promote absorption.
• Mucosal cells shed into the lumen when iron stores are high.

Iron Excretion

• No physiological iron excretion pathway.
• Iron loss happens via:
  • Intestinal cell shedding
  • Urine
  • Nails, hair shedding
  • Menstruation
• Daily losses (~1 mg) are compensated by absorption.

Iron Distribution in the Body

• Total body iron ranges from 3.5 to 2.5 g.
• Most is in hemoglobin (~65-70%).
• Storage iron includes ferritin and hemosiderin within reticuloendothelial systems (bone marrow, spleen, liver) and also in liver cells.
• Tissue iron is found in iron-containing enzymes and myoglobin.
• Plasma iron is a small fraction (~0.1%) delivered by transferrin to tissues.

Iron Deficiency Anemia: Blood Loss

• Gastrointestinal (GI) blood loss is the common explanation in men and post-menopausal women.
• This includes occult cancers, gastritis, ulcers, inflammatory bowel disease.
• Hookworm and schistosomiasis are prevalent causes in developing countries for GI blood loss.
• Chronic NSAID use exacerbates GI blood loss.

Iron Deficiency Anemia: Other Causes

• Menstruation, pregnancy, and breastfeeding lead to increased iron needs and decreased stores, especially in women.
• Poor dietary iron intake, especially in developing countries, is another major cause during infancy, pregnancy, and adolescence.
• Malabsorption (e.g., celiac disease) impedes iron absorption.

Iron Deficiency Anemia: Investigations

• Plasma ferritin is vital for confirming iron deficiency.
• Subnormal ferritin levels indicate deficiency; however, raised ferritin might exist in liver disease or acute inflammation.
• Plasma iron and total iron-binding capacity (TIBC) measure iron availability and are influenced by multiple factors beyond iron stores.
• Transferrin levels are lowered by malnutrition and raised by pregnancy.
• Transferrin saturation (% of TIBC occupied by iron) is less specific but can suggest deficiency.
• Bone marrow aspirate and staining are diagnostic in complex cases.

Iron Deficiency Anemia: Investigation of Cause

• Investigating the causes depends on patient's age, sex, and symptoms.
• Men over 40/post-menopausal women with normal conditions need upper/lower GI tract endoscopy or barium studies.
• Coeliac disease suspicion warrants antigliadin/anti-endomysium antibody tests and duodenal biopsy.
• Stool and urine analyses are useful in tropical regions to check for parasites.

Iron Deficiency Anemia: Clinical Findings

• Early anemia presents without obvious findings.
• As anemia progresses, symptoms emerge like:
  • Pallor
  • Fatigue
  • Reduced exercise capacity
  • Shortness of breath
• Severe cases exhibit mucosal changes:
  • Mouth soreness (glossitis, smooth tongue).
  • Spooned nails (koilonychia)
  • Pica (unusual cravings).
• Organomegaly is unusual with IDA.

Iron Deficiency Anemia: Blood Picture

• Reduced hemoglobin and packed cell volume (PCV).
• Reduced mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC).
• Leucocytes and platelets are usually normal.
• Peripheral blood film shows hypochromic, microcytic red blood cells.
• Bone marrow aspirate shows depleted iron stores.

Iron Deficiency Anemia: Diagnosis

• Diagnosing IDA involves evaluating hematologic parameters.
• Reduced serum iron.
• Increased total iron-binding capacity.
• Reduced transferrin saturation (S. iron/TIBC)
• Reduced serum ferritin.
• Bone marrow iron depletion (Prussian blue stain).

Iron Deficiency Anemia: Differential Diagnosis

• Other hypochromic anemias possible causes, such as thalassemia, sideroblastic anemia, lead poisoning, and chronic disease anemia are differentiated.
  • Thalassemia involves iron studies and haemoglobin electrophoresis
  • Sideroblastic anemia involves bone marrow iron staining.
  • Lead poisoning assesses history, blood film, and urine lead levels.
  • Chronic disease anemia involves iron studies.

Iron Deficiency Anemia: Management

• Oral ferrous sulphate (200 mg 8 hourly) is the primary therapy.
• Treatment duration is 3-6 months.
• Patients intolerant to ferrous sulfate can switch to ferrous gluconate.
• Parenteral iron (iron sorbitol) is needed only in cases of malabsorption or intolerance.
• Body weight and hemoglobin levels help estimate iron stores.
• Monitor haemoglobin levels, daily 7-10 days expected rise.

Iron Deficiency Anemia: Conclusion

• Comprehensive assessment and management for IDA address blood loss, nutritional deficiencies, and malabsorption.