Anemia resident survival guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: ; Chetan Lokhande, M.B.B.S [2]

Overview

Anemia is defined as a decrease in oxygen-carrying capacity of the blood . It is measured in unit volume concentrations of hemoglobin (Hb), red blood cell volume (MCV), red blood cell number (RBC count).

Causes

Life Threatening Causes

Life-threatening causes include conditions that may result in death or permanent disability within 24 hours if left untreated.

• Aplastic anemia
• Sickle cell anemia
• Hemolytic anemia
• Paroxysmal nocturnal hemoglobinuria
• Severe thalassemia
• Fanconi anemia
• Malaria
• Myelodysplastic syndrome
• Severe Hemorrhage
• Acute leukemia
• Disseminated intravascular coagulation (DIC)

Common causes

Common causes of anemia include:

• Hemolytic anemia
  • Hereditary spherocytosis and Hereditary elliptocytosis
  • Glucose 6 phosphate dehydrogenase deficiency
  • Sickle cell disease
  • Thalassemia
  • Drug induced hemolytic anemia
  • Prosthetic heart valves
  • Autoimmune hemolytic anemia
  • Alloimmune hemolytic anemia
  • Toxins (e.g., snake venom)

For a complete list of hemolytic anemia causes, click here

• Sideroblastic anemia
• Aplastic anemia

• Nutritional Anemia
  • Iron deficiency anemia
  • Megaloblastic anemia due to Vitamin B12 deficiency and Folate deficiency

• Infections
  • Helminth infections
  • Malaria
  • Babesiosis
  • Schistosomiasis
  • HIV
  • Tuberculosis
  • Septicemia

• Pregnancy
• Anemia of chronic disease
• Lead poisoning
• Liver disease
• Chronic renal disease
• Splenomegaly
• Bone marrow suppression
• Alcoholism

For a complete list of anemia causes, click here

Diagnosis

Characterise anemia symptoms ❑ Pallor ❑ Fatigue ❑ Weakness ❑ Dizziness ❑ Dyspnea on exertion

Ask about associated symptoms ❑ Jaundice ❑ Koilonychia ❑ Pica ❑ Back pain ❑ Chest pain ❑ Bone pain or Joint pain ❑ Dark urine ❑ Fever ❑ Chills ❑ Palpitations ❑ Numbness ❑ Tingling ❑ Ataxic gait ❑ Depression ❑ Sore tongue or tongue ulcers ❑ Mucosal bleeding ❑ Menorrhagia ❑ Abdominal pain ❑ Diarrhea ❑ Steatorrhea ❑ Weight loss ❑ Growth retardation ❑ Congenital abnormalities

Obtain a detailed history ❑ Age (causes of anemia varies with age) ❑ Gender (iron deficiency anemia is common in women of reproductive age ❑ Race (sickle cell anemia is common in black patients ❑ Past medical history (recurrent episodes, autoimmune diseases, chronic kidney disease, liver disease) ❑ Past surgical history (excessive blood loss, gastrectomy) ❑ Family history for hereditary anemia ❑ Menstrual history (menorrhagia) ❑ Dietary history (megaloblastic anemia, iron deficiency anemia) ❑ Medications/Poisoning ❑ History of blood transfusion ❑ Travel History (parasitic infections]])

Examine the patient Check vitals ❑ Temperature ❑ Pulse ❑ Blood pressure ❑ Respiratory rate Perform a general physical exam ❑ HEENT examination ❑ Pallor ❑ Jaundice ❑ Skin examination ❑ Pallor ❑ Pale nail beds and palmar creases ❑ Bruises ❑ Ulcers ❑ Nail defects ❑ Abnormal pigmentation ❑ Cardiovascular examination ❑ Tachycardia ❑ Systolic flow murmur ❑ Abdominal examination ❑ Signs of previous surgery ❑ Pulsations ❑ Abdominal distension (splenomegaly, hepatomegaly, ascites, malignancy) ❑ Rectal exam with Stool Guaiac for occult blood ❑ Pelvic Examination ❑ CNS examination (Vitamin B12 deficiency) ❑ Lymph nodes (infection, malignancy ❑ Extremities examination ❑ Edema (unilateral in malignancy) ❑ Leg ulcers ❑ Congenital abnormalities

Order routine laboratory tests ❑ Complete Blood Count with WBC and platelets ❑ Red blood cell indices and morphology ❑ Reticulocyte count ❑ Peripheral blood smear

Microcytic anemia ❑ Iron deficiency ❑ Anemia of chronic disease ❑ Thalassemia ❑ Sideroblastic anemia ❑ Lead toxicity

Macrocytic anemia ❑ Megaloblastic bone marrow ❑ Vitamin B12 deficiency ❑ Folate deficiency ❑ Medications (hydroxyurea, zidovudine, methotrexate, chemotherapy agents) ❑ Nonmegaloblastic bone marrow ❑ Liver disease ❑ Hypothyroidism ❑ Alcohol abuse

Normocytic anemia ❑ Increased reticulocyte count ❑ Hemorrhage ❑ Blood loss ❑ Hemolytic anemia ❑ Decreased reticulocyte count ❑ Infections ❑ Aplastic anemia ❑ Leukemia ❑ Medications

Iron deficiency anemia ❑ Pregnancy ❑ Menorrhagia ❑ GI blood loss ❑ GI surgery ❑ Koilonychia ❑ Pica Thalassemia ❑ Resident of Mediterranean and Asia ❑ Chipmunk facies ❑ Skeletal deformity ❑ Hepatomegaly ❑ Splenomegaly Lead Poisoning ❑ House painted with chipped paint ❑ Wrist drop ❑ Foot drop ❑ Burtonian lines ❑ Basophilic stippling Sideroblastic anemia ❑ Alcohol abuse ❑ Isoniazid use ❑ Seborrheic dermatitis ❑ Vitamin B6 deficiency Anemia of chronic disease ❑ Signs and Symptoms of a chronic disease (SLE, chronic kidney disease, malignancy)

Vitamin B12 deficiency ❑ Vegan diet ❑ Gastrectomy ❑ Pernicious anemia ❑ Diphyllobothrium latum infection ❑ Crohn's disease ❑ Neurological deficit ❑ Psychological symptoms Folate deficiency ❑ Alcoholism ❑ Pregnancy and Lactation ❑ Medications (methotrexate, trimethoprim, phenytoin) ❑ Malnutrition ❑ Old age ❑ Glossitis ❑ Neural tube defects Liver disease ❑ Fever ❑ Jaundice ❑ Abdominal pain ❑ Pruritus Hypothyroidism ❑ Cold intolerance ❑ Weight gain ❑ Constipation ❑ Goiter ❑ Periorbital edema

Hemolytic anemia ❑ Family history of anemia ❑ African-American or African race ❑ Fava beans ❑ Medications ❑ Prosthetic heart valve ❑ Jaundice ❑ Hemoglobinuria ❑ Splenomegaly ❑ Gallstones Hemorrhage or Blood loss ❑ Hypotension ❑ Tachycardia Infections ❑ Travel History ❑ Fever Aplastic anemia ❑ History of radiation exposure ❑ Medications (benzene, chloramphenicol, alkylating agents) ❑ Viral infection (EBV, HIV) Leukemia ❑ Family history of cancer ❑ Chemotherapy ❑ Exposure to radiation, pesticide, insecticide ❑ Petechiae ❑ Bleeding ❑ Recurrent infections ❑ Weight loss ❑ Anorexia ❑ Hepatosplenomegaly ❑ Lymphadenopathy

Management

Iron deficiency anemia ❑ Iron studies ❑ Decreased serum ferritin ❑ Decreased serum iron ❑ Increased total iron binding capacity ❑ Increased serum transferrin/ total iron binding capacity ❑ Increased transferrin saturation ❑ Increased RDW ❑ Elevated erythrocyte (RBC) zinc protoporphyrin ❑ Iron stain (prussian blue stain) on bone marrow aspirate Thalassemia ❑ Elevated lactate dehydrogenase (LDH) ❑ Low haptoglobin ❑ Hyperbilirubinemia ❑ Abnormal bands on hemoglobin electrophoresis ❑ Target cells on peripheral blood smear Lead Poisoning ❑ Basophilic stippling of red blood cells ❑ Elevated venous blood lead levels Sideroblastic anemia ❑ Iron studies ❑ Increased serum ferritin ❑ Increased serum iron ❑ Decreased total iron binding capacity ❑ Increased transferrin ❑ Prussian Blue stain of RBC in bone marrow, shows ringed sideroblasts ❑ Bone marrow aspiration and biopsy Anemia of chronic disease ❑ Iron studies ❑ Normal or Increased serum ferritin ❑ Decreased serum iron ❑ Decreased transferrin ❑ Normal or low-normal percent saturation of transferrin ❑ Increased cytokines (e.g., IL-6, interferon-gamma) ❑ Increased acute phase reactants (e.g., fibrinogen, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)) ❑ Rheumatologic assays or Serological tests (e.g., anti-nuclear antibody, rheumatoid factor, anti-CCP, anti-dsDNA)

Vitamin B12 deficiency ❑ Decreased serum B12 levels ❑ Increased serum homocysteine levels ❑ Increased serum methylmalonic acid levels ❑ Anti-IF antibodies ❑ Anti-parietal cell antibodies ❑ Peripheral blood smear ❑ Multisegmented neutrophils ❑ Anisocytosis ❑ Poikilocytosis Folate deficiency ❑ Decreased serum folate levels ❑ Decreased RBC folate levels ❑ Increased homocysteine levels ❑ Normal methylmalonic acid levels ❑ Peripheral blood smear ❑ Multisegmented neutrophils ❑ Anisocytosis ❑ Poikilocytosis Liver disease ❑ Liver function tests ❑ Albumin ❑ Total protein ❑ Bilirubin ❑ ALP (alkaline phosphatase), ALT (alanine transaminase), AST (aspartate aminotransferase), and GGT (gamma-glutamyl transpeptidase) ❑ LDH (lactate dehydrogenase) ❑ Prothrombin time Hypothroidism ❑ Low serum T3,T4 levels ❑ Low or elevated serum TSH levels

Hemolytic anemia ❑ Elevated total bilirubin ❑ Elevated LDH ❑ Direct antiglobulin test (DAT) (Coomb's test) ❑ Indirect antiglobulin test (indirect Coombs' test)<br ❑ Osmotic fragility test ❑ Urine hemosiderin ❑ Urine hemoglobin ❑ Peripheral blood smear ❑ Schistocytes ❑ Spherocytes ❑ Target cells ❑ Bite cells ❑ Sickle shaped RBC ❑ Degmacytes Hemorrhages or Bleeding ❑ Complete blood count ❑ Bleeding time ❑ Prothrombin time (PT) and the activated partial thromboplastin time (aPTT) ❑ Coagulation factors ❑ Serum fibrinogen ❑ Serum D-dimer ❑ Ultrasonography Infections ❑ CBC with differentials ❑ Blood smear for malaria ❑ Blood culture and sensitivity ❑ Gram stain ❑ Urine culture and sensitivity Aplastic anemia ❑ Pancytopenia ❑ Bone marrow biopsy ❑ Hypocellular bone marrow with increased adipose tissue and decreased hematopoietic cells in the marrow space ❑ Normal maturation of all cell lines Leukemia ❑ Bone marrow biopsy ❑ Complete blood count ❑ Thrombocytopenia ❑ Leucocytosis or Leucopenia ❑ Absolute basophilia and eosinophilia ❑ Neutrophilia or Neutropenia Low or elevated leukocyte alkaline phosphatase

Iron deficiency anemia ❑ Iron supplements ❑ Erythropoietin ❑ Blood transfusion Thalassemia ❑ Blood transfusion ❑ Bone marrow transplant ❑ Gene therapy Lead poisoning ❑ Chelation therapy ❑ DMSA/Succimer ❑ Ethylenediaminetetraacetic acid (EDTA) ❑ British anti-Lewisite (BAL)/Dimercaprol Sideroblastic anemia ❑ Pyridoxine, thiamine and folic acid ❑ Iron chelators ❑ Blood transfusion Anemia of chronic disease ❑ Iron supplements ❑ Erythropoietin ❑ Blood transfusion ❑ Treat the underlying cause

Vitamin B12 deficiency ❑ Vitamin B12 supplementation ❑ Folic acid supplementation ❑ Treat the cause of vitamin B12 deficiency Folate deficiency ❑ Folic acid supplementation (rule out vitamin B12 deficiency before starting folic acid supplementation) ❑ Vitamin B12 supplementation (if vitamin B12 deficiency is present) ❑ Treat the cause of folate deficiency Liver disease ❑ Treat the underlying cause Hypothyroidism ❑ Thyroid hormone replacement therapy

Hemolytic anemia ❑ Blood transfusion ❑ Erythropoietin ❑ Immunosuppression Bleeding or Hemorrhage ❑ Emergency bleeding control ❑ Discontinue antiplatelet and anticoagulation therapy ❑ Blood transfusion ❑ Treat the underlying cause Infection ❑ Antibiotics ❑ Treat the underlying cause Leukemia ❑ Blood transfusion ❑ Chemotherapy ❑ Treat the underlying etiology

Management

INDICATIONS FOR TESTING Fatigue, weakness, pallor, dizziness, fainting

Check routine Labs, CBC , smear and reticulocyte count and index

Diagnosed as anemia if Hgb in males < 13g / dl and in females if Hgb < 12g / dl Check whether corrected reticulocyte index ≥ 2.5

If No Check RBC indices

If Yes then

Normal MCV / MCHC Normocytic Normochromic

Low MCV / MCHC Microcytic Hypochromic

High MCV Macrocytic

Check peripheral smear

↓ EPO production or improper response to EPO

Maturation defect

Maturation defect

Fragmented cells on peripheral smear

No fragmented cells on peripheral smear

*Bone marrow disorder Inflammation *Autoimmune disease *Chronic renal disease *Critical illness *Chronic endocrine disorders *Aplastic anemia *Pure red cell aplasia

*Iron deficiency *Chronic disease *Thalassemia (Hemoglobinopathies) *Sideroblastic anemia *Lead toxicity

*Folate, B12 deficiency (Megaloblastic Anemia) * Drug effect *Excessive alcohol use *Hypothyroidism

Suggests hemolytic process *Metabolic defect *Hemoglobinopathies (eg, sickle cell) *Autoimmune destruction *Splenic sequestration *RBC membrane defect *Intravascular hemolysis See Hemolytic Anemia

Suspect hemorrhage and acute blood loss

Abnormal peripheral smear

If yes then work up based on smear bone marrow biopsy may be necessary

If no

ORDER Iron and Iron Binding Capacity and Ferritin check B12, Folate levels

Start Vit B12,Folate If low

Low / normal TIBC Normal / high ferritin Low / normal iron

High TIBC Low iron Low ferritin

Inflammation / Chronic Disease Consider Biopsy in this case

Iron Deficiency anemia

Abbreviations and Formula

MCV = mean cell volume MCHC = mean cell hemoglobin concentration TIBC = total iron binding capacity

Reticulocyte correction for anemia:

Retic Count % x Hgb / Htc x Maturation time correction

Do's

• Before evaluating for anemia, ask about the following:
  • Any medical condition that could be associated
  • Duration of anemia
  • Ethnicity and race
  • Any medication use
  • Occupational history
• Determine if there is anything that shows evidence of:
  • Decreased red cell production
  • Increased red cell destruction
  • Bleeding
  • Bone marrow suppression
  • Nutritional deficiency

• Do a detailed physical examination and keep a high level of suspicion