Drugs Used for Treatment of Anemia

Anemia

• Anemia is a decrease in number of red blood cells (RBCs) or less than the normal quantity of hemoglobin in the blood

• Hemoglobin (found inside RBCs) normally carries oxygen from the lungs to the tissues, so, anemia leads to hypoxia

• Anemia is the most common disorder of the blood

WHO Definition of Anemia 

WHO's Anemia Definition
Age or gender group	Hb threshold (g/dl)
Children (0.5–5.0 yrs.)	11
Children (5–12 yrs.)	11.5
Teens (12–15 yrs.)	12
Women, non-pregnant (>15 yrs.)	12
Women, pregnant	11
Men(>15yrs)	13

Types of Anemia

There are 3 main causes of anemia:

1. Blood loss
2. Decreased or faulty red blood cell production
3. Destruction of red blood cells

Anemia Caused by Blood Loss (Chronic Bleeding)

GIT

• Peptic ulcers
• Worms
• Hemorrhoids
• Gastritis 
• Cancer 

Drugs

• NSAIDs (Aspirin, Ibuprofen etc.)

Women

• Menorrhagia (Excessive menstrual bleeding )
• Multiple pregnancies
• Fibroids

Anemia Caused by Decreased or Faulty RBC Production

Bone marrow and stem cell problems

• Aplastic anemia (↓/absent stem cells)

Nutritional deficiencies

• Iron deficiency anemia
• Pernicious Anemia
• Vitamin B12 deficiency

Folic acid deficiency anemia

Chronic diseases

• Advanced kidney disease
• Hypothyroidism
• Cancer
• Infections
• Diabetes
• Old age
• Lead exposure

Anemia Caused by Destruction of RBCs
(Hemolytic Anemia)

• Sickle cell anemia 
• Hereditary spherocytosis 
• G6PD deficiency

Antibody mediated

• Warm & cold antibodies
• Rh disease
• Transfusion reaction

Mechanical trauma to RBCs

• Prosthetic heart valves
• Splenomegaly 
• Malaria

Classification According to Morphology of RBC

• Microcytic
• Macrocytic
• Normocytic

Microcytic Anemia (MCV<80)

   Heme synthesis defect 

• Iron deficiency anemia

   

    Globin synthesis defect 

• Thalassemia 

    

    Sideroblastic Anemia 

• Hereditary sideroblastic anemia
• Lead toxicity 

Macrocytic Anemia (MCV>100)

Megaloblastic anemia

• Vitamin B12 deficiency
• Folic acid deficiency
• Pernicious anemia
• Lack of intrinsic factor  (autoimmune condition targeting the parietal cells)
• Gastric bypass surgery
• Hypothyroidism
• Alcoholism commonly causes a macrocytosis  although not specifically anemia

Normocytic anemia (MCV 80-100)

• Acute blood loss
• Anemia of chronic disease
• Aplastic anemia (bone marrow failure)
• Hemolytic anemia

also read; Dengue Symptoms and Treatment

  Iron Deficiency Anemia

    Microcytic hypochromic anemia

        Iron deficiency is the most common cause of chronic anemia

    Causes

• Excessive menstruation (30 mg of iron in each menses)
• Pregnancy and breastfeeding
• GI bleed (occult mostly, peptic ulcer< carcinoma etc.)
• Worms 
• An iron-poor diet (esp. in infants, children, teens, vegetarians & poverty)
• Frequent blood donation
• Malabsorption (celiac disease, sprue, surgical removal of part of small intestine etc.)

    Signs and Symptoms

• Pallor
• Weakness, malaise
• Fatigue
• Dizziness
• Exertional dyspnea
• Body aches
• Tachycardia, ↑ cardiac output, vasodilation (CVS adaptations)
• Cardiac failure (extreme cases)

Blood CP

↓ RBCs

↓ Hb

↓ MCV

Peripheral film

• Microcytic (small cells)
• Hypochromic (pale and colorless) 
• Poikilocytosis (variation in shape)
• Anisocytosis (variation in size)

Investigations

    Blood CP with peripheral film

• Serum Ferritin - ↓
• Serum Iron - ↓
• Serum TIBC - ↑
• Serum Transferrin - ↑
• Bone marrow aspiration (Gold standard) - ↓ iron

    For Determining Cause

• Stool R/E (occult blood, worms etc.)
• Endoscopy
• Hb Electrophoresis

Iron Distribution in Normal Adults

• Iron is essential component of heme, responsible for transport of oxygen
• Hemoglobin
• Myoglobin 
• Enzymes 
• Transport (transferrin) 
• Storage (ferritin and other forms)

Sources

• Meat protein
• Vegetables 
• Grains

    Absorbtion

• Iron is absorbed in the duodenum and proximal jejunum
• Ferrous Iron( Fe2+) and heme are taken up by the divalent metal transporter, DMT1, efficiently transports ferrous iron across the luminal membrane of the intestinal enterocyte.

Pharmacokinetics

• Normally, only a small amount of iron is lost from the body each day – 1mg
• So dietary requirements are small and easily fulfilled by the iron available in a wide variety of foods
• Nearly all of the iron used to support hematopoiesis is recovered from catalysis of the Hb, in dying or damaged erythrocytes
• However, iron requirements can exceed normal dietary supplies and iron deficiency can develop in special populations  i.e.
• ↑ iron requirement (e.g. growing children, pregnant women)
• ↑ iron loss (e.g. menstruating women)

Transport and Storage

• Intestinal iron is stored as Ferritin or ferrous iron is transported across basolatteral membrane by transporter known as ferroportin and oxidized to ferric iron (Fe3+) by a ferroxidase. 

    Excess iron can be stored in 

• GI epithelial cell, 
• Macrophages
• Hepatocytes 

Iron Deficiency Anemia

Oral Preparations:

• Ferrous sulphate,
• Ferrous gluconate 
• Ferrous fumerate

Parenteral:

• Iron dextran,
• Iron sucrose complex
• Sodium ferric gluconate complex

Toxicity

    Acute overdose

• Necrotizing gastroenteritis, 
• Abdominal pain
• Bloody diarrhea 
• Shock, lethargy

    Chronic overdose

• Hemochromatosis, with damage to heart, liver, pancreas and other organs,
• Organ failure and death.

Acute Iron Toxicity

  Management

• young children who accidentally ingest iron tablets,  as few as 10 tablets 
• Whole bowel irrigation should be performed to flush out unabsorbed pills. 
• Deferoxamine, iron-chelating compound, can be given systemically to bind iron that has already been absorbed and to promote its excretion in urine and feces.
• Appropriate supportive therapy for gastrointestinal bleeding, metabolic acidosis, and shock must also be provided.

Chronic Iron Toxicity

• Chronic iron toxicity (iron overload), also known as hemochromatosis, results when excess iron is deposited in the
• heart, liver, pancreas, and other organs. It can lead to organ failure and death. It most commonly occurs in patient with inherited hemochromatosis, a disorder characterized by excessive iron absorption, and in patients who receive many red cell transfusions over a long period of time (eg, patients with thalassemia major).
• Chronic iron overload in the absence of anemia is most efficiently treated by intermittent phlebotomy. One unit of blood can be removed every week or so until all of the excess iron is removed. 

Iron chelation therapy using

• parenteral deferoxamine 
• oral iron chelator deferasirox is approved for treatment of iron overload.
• Iron chelators
• Deferoxamine: for acute iron Poisoning, acquired or inherited hemochromatosis, Given sub-cutaneously or I/M
• A/E: hypotension, acute respiratory distress, with long infusions
• Deferasirox: for hemochromatosis not treated by phlebotomy

Megaloblastic Anemia

    Causes

• Deficiency of Vitamin B12 &  folic acid
• The most common causes of vitamin B12 deficiency are pernicious anemia, partial or total gastrectomy, and
• conditions that affect the distal ileum, such as malabsorption syndromes,
• inflammatory bowel disease, or
• small bowel resection.

    Vitamin B12

• Cobalt containing  vitamin , synthesized only by bacteria 
• Cyanocobalamin
• Hydroxycobalamin ( long half life)
• A cofactor required for essential enzymatic reactions that form tetrahydrofolate
• Convert homocysteine to methionine
• Metabolize methylmalonyl Co-A
• Treatment: parenteral vit B12 

    Folic Acid 

• A precursor of an essential  donor of methyl groups used for synthesis of amino acids, purines, deoxynucleotide.

    Uses:

• Megaloblastic anemia due to folic acid def.
• Prevention of congenital neural tube defects

Large amounts can partially compensate for vit B12 def and put pts. with unrecognized B12 def at risk of neurological consequences that is not compensated by folic acid

Erythropoietin

• Erythropoietin 
• Anemia of renal failure
• Through activation of receptors on erythroid progenitors in the bone marrow, erythropoietin stimulates the production of red cells and increases their release from the bone marrow.
• Recombinant human erythropoietin (epoetin alfa) is routinely used for the anemia associated with renal failure and is sometimes effective for patients with other forms of anemia (eg, primary bone marrow disorders or anemias secondary to cancer chemotherapy or HIV treatment, bone marrow transplantation, AIDS, or cancer)
• Intravenous or subcutaneous
• Darbepoetin alfa , a glycosylated form of erythropoietin, has a much longer half-life
• Methoxy polyethylene glycol-epoetin beta is a long-lasting form of erythropoietin that can be administered once or twice a month.
• The most common complications of erythropoietin therapy are hypertension and thrombosis.

        Thank you 

By Dr Shah Faisal Tabani 

MBBS | Khyber Medical College Peshawar Pakistan