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 Now6 mo ago Wbc 6.8 g/dL14.2 g/dLHb 178 K192 KPlatelets 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, /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

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