Heme-Onc Grand Rounds Holland Haynie, MD

Friday September 24, 2004

Hemolytic Anemia

Twenty percent of American children will have anemia before the age of 18

Five percent of all anemia’s are hemolytic

A hemolytic process can be indirectly associated with:

- Reticulocytosis

- ↑ Bilirubin

- ↑ LDH

- ↓ Haptoglobin

Differential Diagnosis of Hemolytic Anemia

Cellular Defects

– Membrane Defects

Hereditary spherocytosis

Hereditary elliptocytosis

Paroxysmal nocturnal

hemoglobinuria

– Enzyme Deficiencies

Pyruvate kinase deficiency

G6PD deficiency

– Hemoglobin Abnormalities

Sickle Cell Disease

Thalassemias (microcytic)

Extracellular Defects – Autoimmune Hemolytic

Anemia

– MAHA

DIC, TTP, HUS

ECMO

Prosthetic Heart Valves

Burns/Thermal

– Hypersplenism

– Plasma Factors

Liver Disease

Abetalipoproteinemia

Infections

Wilson Disease

Laboratory Evaluation

Complete Blood Count with Differential

Blood smear – Macro/Microcytosis, Anisocytosis

– Poikilocytosis

– Hyper/Hypochromia, Polychromasia

– Inclusions

Reticulocyte count – Usually elevated due to compensation for increased

destruction

– CRC=%Retics x patient HCT/normal HCT

– CRC > 1.5 shows adequate compensation

Laboratory Evaluation

AST, LDH – Can be elevated from release of intracellular enzymes

Haptoglobin

DAT

Urinalysis

Bilirubin

Confirmatory Studies – G6PD assay

– Osmotic Fragility

– Membrane protein studies

Hereditary Spherocytosis

+ Family hx, smear, osmotic fragility studies most useful for Dx

Normal MCV & MCH, MCHC (>36) ~50% of cases, retic count (avg 10%), bili (~50% of cases)

Peripheral smear: spherocytes (up to 80% of cases), polychromasia, occasionally nucleated RBCs

Abnormal osmotic fragility test -- increased fragility

Hereditary Elliptocytosis

Morphology of RBCs most important for Dx

Typically 15-70% of erythrocytes are elliptical (length >1.5x diameter)

In most pts, there is no hemolysis, and hematologic values are NL.

+ hemolysis in 10% of pts with Hgb and retic count, may see erythroid hyperplasia in the marrow

G-6-PD Deficiency Hemoglobinemia & hemoglobinuria occur 24-28 hrs after ingestion of oxidant substance

Degree of hemolysis depends on the antioxidant effect of substance, amount ingested, and severity of deficiency

“Bite cells” and Heinz bodies on smear during this time—disappear 3-4 days

Quantitative enzyme assay for Dx

Pyruvate Kinase Deficiency

Broad spectrum of findings ranging from completely compensated hemolytic state to severe anemia.

Besides erythrocyte PK activity, mostly nonspecific lab findings: anemia, hyperbilirubinemia, serum LDH, haptoglobin

NL osmotic fragility

Smear: polychromatophilic erythrocytes, maybe a few spiculated erythrocytes

Microangiopathic HA

Direct damage to RBC membrane (e.g DIC, TTP, HUS, vasculitis, burns)

Clinical features of underlying disease process + anemia, thrombocytopenia.

Labs: typical findings of hemolysis-- Hgb, LDH, bili, retic count

Smear: RBC fragments

Autoimmune Hemolytic Anemia: Lab evaluation

- CBC - Low Hgb (often <7 gm/dL)

- Reticulocytosis

- UA - Intravascular=>normal

- Extravascular=>Hemoglobinuria

- Blood chemistry - Unconjugated hyperbilirubinemia

- Elevated LDH, AST

- Low haptoglobin

- Direct antiglobulin test (Coombs) - Presence of antibodies and/or complements

- PBS - Spherocytosis, Schistocytes

- Polychromasia (due to reticulocytosis)

- BMA - Intense erythroid hyperplasia

Autoimmune Hemolytic Anemia

Incidence – 1:80,000

Classification – Primary: idiopathic

– associated with Secondary: a systemic disease

Pathophysiology – Warm-reactive

IgG autoantibody, ? complement

Extravascular hemolysis: splenomegaly, jaundice and anemia

– Cold-reactive

IgM autoantibody, + complement, often follow an infection (mycoplasma)

Intravascular hemolysis: hemoglobinemia, hemoglobinuria and anemia

– Paroxysmal cold hemoglobinurea

Autoimmune Hemolytic Anemia: Clinical presentation

Anemia

– Weakness, SOB, dizziness, pallor, tachycardia,

systolic flow murmur

Jaundice

Dark urine

Abdominal pain

Fever

Secondary Autoimmune Hemolytic Anemia: Etiologies

– Autoimmune disease SLE, other autoimmune cytopenia (Evans syndrome)

– Malignancy May present prior to making underlying diagnosis

– Infection Viral-like syndrome: mycoplasma, EBV, measles, varicella

Acute bacterial infection: removal of sialic acid from T antigen on RBC

– Drugs PCN, erythromycin, probenecid, tylenol, ibuprophen

Autoimmune Hemolytic Anemia: Treatment

Symptomatic: – Maintain good UOP, avoid cold stimuli (blood warmer),

Transfusions – CV compromise

– Find “least incompatible” blood

– Caution with IVH: slow tranfusion rate, hyrdrate

Corticosteroids – Best primary therapy (specially IgG mediated)

IVIG – Blockage of reticuloendothelial system (children have poor response)

Exchange transfusion – Better for IgM antibodies

Splenectomy – Better response in IgG autoantibodies

Aggressive medical therapy for refractory disease (danazol, cyclosporine,…)

In Conclusion…

Hemolytic anemia may present like a viral

illness

Autoimmune Hemolytic Anemia is DAT

positive

Be sure to exclude other causes of

hemolytic anemia (infection, malignancy,

systemic autoimmune disease,

medications)