AN APPROACH TO THE ANEMIC PATIENT

Martin H. Ellis MD

Meir Hospital

2007

CASE PRESENTATION

• 67 y.o.male

• Chronic Lymphocytic leukemia for 4 years

• 1 week of weakness and dyspnea

6 mo agoNow

Wbc60 00072 000

Hb14.2 g/dL6.8 g/dL

Platelets192 K178 K

LAB DATA

Classification of anemia

• Etiologic– Decreased production– Increased destruction– Blood loss

• Morphologic– Microcytic hypochromic– Normocytic normochromic– Macrocytic

Approaching the diagnosis:First impressions

• Obvious clinical problems– Serious illness, overt bleeding

• Remainder of CBC– wbc, platelets

• MCV

Approaching the diagnosis:Isolated anemia, MCV low

• Iron deficiency– Elevated red cell distribution width

• Thalassemia– Normal red cell distribution width

• Anemia of chronic disease

• Lead poisoning

Approaching the diagnosis:Isolated anemia, MCV high

• B12, folate levels

• TSH

• Liver function tests

• Hemolytic parameters

• Consider bone marrow disorders

Approaching the diagnosis:Isolated anemia, MCV normal

• Mixed nutritional deficiencies– Dimorphic picture on smear

• Hemolysis

• Bone marrow disorders

• Anemia of chronic disease

• Chronic renal failure

• Acute bleeding

Approaching the diagnosis:Anemia with other cytopenias

• BM failure– Severe B12/FA deficiency– Aplastic anemia

• BM infiltration– Malignancies– Infections– Storage diseases

• Hypersplenism

BACK TO THE PATIENT…

• Background of CLL

• “Sudden” decrease in hemoglobin– Differential diagnosis

• Hemorrhage• Decreased production• Hemolysis

Aplastic anemia

• Pancytopenia with bone marrow hypocellularity

• Etiology:– Idiopathic – immune - T cell mediated– Constitutional (Fanconi anemia)– Radiation– Chemicals (benzene)– Drugs (cytotoxics, chloramphenicol, etc)– Infections (seronegative hepatitis, EBV)– Transfusion associated graft versus host disease

Aplastic anemia: diagnosis

• Clinical features– Abrupt or slow onset– Bleeding and anemia symptoms & signs

• Laboratory features– Pancytopenia (neutrophils < 500/µL, retic count <1%

& platelets , 20 000 /µL = severe AA)– Hypocellular/acellular bone marrow biopsy

BONE MARROW BIOPSIES

NORMOCELLULARAPLASTIC

Aplastic anemia: treatment

• Bone marrow transplant– For young patients– Sibling donors preferred– 80% cure rate

• Immunosuppression– Antithymocyte globulin + cyclosporine ± steroids– 70-80% response rate

Pure red cell aplasia (PRCA)

• Anemia, reticulocytopenia, absent red cell precursors in bone marrow

• Congenital– Diamond Blackfan anemia

• Acquired– Transient (parvovirus B19 in patients with hemolytic

anemia)– Paraneoplasatic (thymoma, CLL)– SLE, rheumatoid arthritis– Pregnancy– Drugs – new entity: anti EPO antibodies PRCA!

Paroxysmal nocturnal hemoglobinuria (PNH)

• Acquired mutation in PIG-A gene occurs at the stem cell level

• Results in reduced/absent GPI-linked cell surface membrane proteins (CD 55, CD 59)

• Red cells have enhanced sensitivity to circulating complement

• Bone marrow failure, hemolysis and thrombosis occur

HEMOLYTIC ANEMIA:DEFINITION

• Anemia caused by premature destruction of red blood cells

• Lifespan of erythrocyte reduced from its normal 120 days

NOTE: hemolysis = hemolytic anemia

CLASSIFICATION

SITE OF DESTRUCTION

• Extravascular vs Intravascular

SITE OF ERYTHROCYTE ABNORMALITY

• Membrane

• Cytoplasm

• Hemoglobin

• Extracorpuscular

EXTRACORPUSCULAR CAUSES

Immune hemolytic anemia• Autoantibodies of IgG or IgM subtype

• IgG reacts best at 37 C = “warm” antibody

• Ig M reacts below body temperature

= “cold” antibody

WARM AUTOIMMUNE HEMOLYTIC ANEMIA

CLINICAL FEATURES

• Females > males

• Pallor

• Jaundice

• Splenomegaly

• Occasional fulminant hemolysis-cardiovascular collapse

WARM AUTOIMMUNE HEMOLYTIC ANEMIA

• Causes:– Idiopathic

- Malignancies (lymphoma, CLL, other)

- Drugs (alpha methyl dopa, penicillin, quinidine)

- Collagen-vascular diseases (SLE)

• Laboratory features– Extravascular hemolysis

– Smear shows microspherocytes, polychromatophilia, basophilic stippling

WARM AUTOIMMUNE HEMOLYTIC ANEMIA

DIAGNOSTIC TEST

• Direct Coombs test

presence of antibody (or complement) on

RED CELLS

• Indirect Coombs test

presence of antibody in SERUM

DIRECT COOMBS TEST

Anti Human Globulin

Making the diagnosis in our patient

• Reticulocyte count– Beware… sometimes AIHA can occur without

reticulocytosis!!

• Biochemical parameters– LDH, indirect bilirubin, haptoglobin

• Direct Coombs test– Indirect Coombs less informative

• Bone marrow biopsy– Presence or absence of red cell precursors