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]; Asra Firdous, M.B.B.S.[3]

Overview

Anemia is defined as a decrease in the oxygen-carrying capacity of the blood causing tissue hypoxia. It presents with a decrease in volume concentrations of hemoglobin (Hb), hematocrit, red blood cell indices like (MCV), and red blood cell count (RBC count). Anemia is defined as a hemoglobin concentration (Hb) of less than 12 g/dL in women and less than 13 g/dL in men, or alternatively, hematocrit of less than 36% in women and less than 40% in men.

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 ❑ Myelodysplastic syndrome ❑ 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

Diagnostic Work-up

Anemia Diagnostic work-up

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 Hypothyroidism ❑ 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) ❑ 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

Treatment

Anemia Treatment

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 ❑ Folic acid ❑ Iron chelation therapy ❑ 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 Aplastic anemia ❑ Blood transfusion ❑ Hematopoietic stem cell transplantation ❑ Erythropoietin ❑ Granulocyte colony-stimulating factor ❑ Immunosuppressive therapy ❑ Treat the underlying cause Leukemia ❑ Blood transfusion ❑ Chemotherapy ❑ Treat the underlying etiology

Abbreviations and Formula

MCV = mean cell volume RDW = Red blood cell distribution width TIBC = total iron binding capacity HEENT = head, eyes, ears, nose, and throat CNS = central nervous system WBC = white blood cells GI = gastrointestinal SLE = systemic lupus erythematosus EBV = epstein-barr virus HIV = human immunodeficiency virus IL-6 = interleukin 6 T3 = triiodothyronine T4 = thyroxine TSH = thyroid stimulating hormone LDH = lactate dehydrogenase DMSA = dimercaptosuccinic acid

Do's

• Investigating and treating the underlying cause is the crucial part of anemia management.
• Pregnant women must be screened for iron deficiency and folate deficiency.
• A well-balanced diet rich in iron and vitamins must be prescribed.
• In iron deficiency anemia, advice vitamin C rich diet like citrus fruits. Vitamin C helps in iron absorption.

Don'ts

• Due to the risk of iron overload, avoid excessive transfusion of blood.
• Do not give folic acid supplementation unless Vitamin B12 deficiency is ruled out.
• Avoid food items (e.g., coffee, tea, egg whites) in iron deficiency anemia as they decrease the absorption of iron in the body.