Approach to Anemias

Verdah SabihHouse OfficerMU-2 BBH

DEFINITION: The World Health Organization (WHO) defines

anemia as a hemoglobin level <130 g/L(13 g/dL) in men and <120 g/L (12 g/dL) in women.

The critical elements of erythropoesis are used for the initial classification of anemia. EPO production Iron availability Proliferative capacity of the bone marrow Effective maturation of red cell precursors

HOW DO THE PATIENT PRESENTS…. most often recognized by abnormal screening

laboratory tests. less commonly present with advanced anemia

and its attendant signs and symptoms. Acute Anemia blood loss or hemolysis –

Hb/HCT does not reflect the volume of blood loss

Mild – No symptoms. Enhanced oxygen delivery by changes in pH and increased CO2

10-15% - hypotension and decreased organ perfusion >30% - postural hypotension, tachycardia >40% - hypovolemic shock: confusion, dyspnoea,

diaphoresis hypotension &tachycardia

Acute hemolysis Intravascular hemolysis: acute back pain, free

hemoglobin in plasma and urine, renal failure Moderate anemia S/S

Fatigue Loss of stamina Breathlessness Tachycardia on physical exertion Symptoms may not appear in young, healthy

patients until hemoglobin is 7-8 g/dL Diseases in which patient presents with

anemia Infections Rheumatoid Arthritis Cancer Lymphoproliferative disorders (CLL, B cell

neoplasm)

EVALUATION OF PATIENT…… HISTORY:

Is the patient bleeding?Actively? In past?

Is there evidence of hemolysis? Is the patient nutritionally deficient? Pica? medication review, toxin exposure Symptoms of known diseases causing anemia:

Gastric ulceration Rheumatoid arthritis Renal failure

Duration of symptoms: Hemoglobinopathies in longer duration

Treatment history Medications for pain, hematinics

Nutritional history family history of anemia

PHYSICAL EXAMINATION…. Build, nourishment Signs of disease Vitals – fever, tachycardia, blood pressure Pallor Koilonychia,hair loss, glossitis,stomatitis Jaundice(hemolysis) Lymphadenopathy Bone tenderness Petechiae CVS: forceful heartbeat, strong peripheral pulses,

and a systolic “flow” murmurs RESP: Dyspnoea Abdomen: Splenomegaly

HOW TO INVESTIGATE….. I. Complete blood

count (CBC) A. Red blood cell count

1. Hemoglobin 2. Hematocrit 3. Reticulocyte count

B. Red blood cell indices 1. Mean cell volume (MCV) 2. Mean cell hemoglobin

(MCH) 3. Mean cell hemoglobin

concentration (MCHC) 4. Red cell distribution

width (RDW)

C. White blood cell count 1. Cell differential 2. Nuclear segmentation

of neutrophils D. Platelet count E. Cell morphology/

Peripheral smear 1. Cell size 2. Hemoglobin content 3. Anisocytosis 4. Poikilocytosis 5. Polychromasia

Normal smear

Severe Iron defeciency anemiaAnisocytosis (size), Poikilocytosis (shape

MacrocytosisMacrocytes, Ovalocytes

ThallassemiaTarget cells

II. Iron supply studies A. Serum iron 50–150

µg/dL B. Total iron-binding

capacity 300–360 μg/dL

C. Serum ferritin(also an acute phase reactant) 15-20 µg/dL – Lack of

Iron stores Women: ~30 µg/dL Men: ~ 100 µg/dL 200 µg/dL – adequate

iron stores Serum Transferrin

saturation: 25-50%

III. Marrow examination

A. Aspirate 1. M/E ratioa 2. Cell morphology 3. Iron stain

B. Biopsy 1. Cellularity 2. Morphology

Normal iron stain

FURTHER INVESTIGATIONS……Microcytic anaemias

Haemoglobin electrophoresis Search for evidence of underlying infective, inflammatory or neoplastic disorder (blood cultures, ESR, C-reactive protein, ANA, CXR etc.)

Normocytic anaemias

Renal function, Haemolysis screen (if not already performed), Immunoglobulins and paraprotein screen, Search for evidence of underlying infective, inflammatory or neoplastic disorder

Macrocytic anaemias

Thyroid function tests, Liver function tests, Haemolysis screen (if not already performed)Serum Vit B12 & folic acid level

HOW TO CLASSIFY…..

YOU HAVE REACHED THE DIAGNOSIS NOW TREAT IT!.... Iron deficiency anemia: Transfusions: Only if there is hemodynamic

compromise or acute hemorrhage Oral:150-200 mg of iron daily 1 hour before meal

in divided doses (ferrous sulfate, ferrous gluconate) Continue for:

14 days + (Hb required level – Hb current level) x 4 half of the dose 6 – 9 months to restore iron

reserve Absorption

is enhanced: vit C(250 mg before taking iron), meat, orange juice, fish

is inhibited: cereals, tea, milk

Parentral iron subsitution:Bad oral iron tolerance (nausea, diarrhoea) &Necessity of quick management (CHD, CHF) 50 - 100 mg daily I.v only in hospital (risk of anaphylactic shock) I.m in outpatient department Total dose by iv infusion: iron to be injected (mg) = (15 - Hb g ) x body

weight (kg) x 3Iron dextran (IV or IM)Ferric gluconate (IV)iron sucrose (IV)Ferumoxytol(in adults with CKD)

ANEMIA OF CHRONIC DISEASE: Treat the underlying disorder (if possible) Transfusion rarely indicated Darbepoietin/EPO Goal is to not exceed hemoglobin values of 12

g/Dl THALASSEMIA: Thalassemia trait: None indicated β-Thalassemia intermedia, β-thalassemia major,

&Hgb H: Chronic transfusion Splenectomy Treatment for iron overload Management of complications, including leg

ulcers,pulmonary hypertension, gallstones, aplasia

SIDEROBLASTIC ANEMIAS: Hereditary:

fairly stable anemia. Iron overload develops in all patients because of inc. iron absorption.

Treat iron overload with phelebotomy or chelation. Acquired:

Iron overload does not respond to treatment with pyridoxine

Reversible: alcohol, isoniazid, and chloramphenicol removal of the drug

Lead poisoning: edetate disodium (EDTA) chelation

ANEMIA OF RENAL INSUFFICIENCY OR FAILURE: subcutaneous or IV ESA(erythropoietin or

darbepoietin) Goal is to maintain Hct between 33% and 36%

(Hgb between 11 and 12 g/dL) Iron therapy indicated for ferritin levels below 100

mg/L APLASTIC ANEMIA:

Withdraw the offending agent (if identified) Support with transfusions as needed; mild forms of

disease may not need definitive treatment Bone marrow transplantation (BMT) is the

treatment of choice in all patients under the age of 45 years with severe aplastic anemia when there is a human leukocyte antigen–matched donor

Immunosuppression with antithymocyte globulin plus cyclosporine plus corticosteroids is used when BMT not possible

PURE RED CELL APLASIA: Initial treatment is supportive with transfusions, if

needed Cases caused by parvovirus infection may respond to

IV immune globulin Cases caused by thymoma may respond to tumor

removal Immunosuppressive drugs are used in refractory

cases (e.g.corticosteroids, cyclosporine, cyclophosphamide)

MEGALOBLASTIC ANEMIA: Intramuscular vitamin B12 injections are usually the

initial treatment of choice for pernicious anemia Oral vitamin B12 can be equally effective in raising

serum levels. Must be given in very large doses (1–2 mg/day) in patients with pernicious anemia

Lower oral doses (250 μg/day) may be sufficient to treat food-cobalamin malabsorption

FOLATE DEFICIENCY: oral folic acid (1–2 mg/day is usually sufficient)

MYELODYSPLASTIC SYNDROMES: Supportive care Careful blood count monitoring with transfusion

support Iron overload can occur with repeated

transfusions---- Iron chelation Growth factor support with Erythropoietin

(EPO)& Granulocyte colony-stimulating factor Allogeneic stem cell transplantation Only

curative approach to treatment Hypomethylating agents (azacitidine or

decitabine) Lenalidomide Conventional chemotherapy (cytarabine based)

IMMUNE HEMOLYTIC ANEMIA Initial: Support with blood transfusions plus

prednisone 1 mg/kg/day with or without IV immune globulin (IgG)

Splenectomy: If refractory to prednisone Immunosuppressives and/or cytotoxic agents: If

refractory to splenectomy and prednisone G6PD deficiency

Supportive Sickle cell disorders (SS, Sβ-thal, SC)

Pain crises: Hydration and analgesics (avoid meperidine); transfusion usually not needed

Acute chest syndrome: Antibiotics, oxygen, exchange transfusion

Stroke: Exchange transfusion Hematopoietic cell transplantation may be

potentially curative,

REFRENCES…. Harrison's Principles of Internal Medicine, 19E The Johns Hopkins Internal Medicine Board

Review, 4th Edition