Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (311 page)

   Heterozygous individuals: no anemia.

   Other Considerations

   Stomatocytes may be seen on the peripheral blood smear (PBS) of many acquired disorders, such as alcoholism, liver disease, and drug-induced hemolytic anemias.

   
HEMOLYTIC EXTRINSIC RED BLOOD CELL DEFECTS

AUTOIMMUNE HEMOLYTIC ANEMIAS (AIHAS)

AIHAs anemias may be classified on the basis of the type of antibody present: warm (binding optimally at 37°C), cold (binding optimally at 4°C), or occasionally combined warm and cold antibodies. Each of these AIHAs may be idiopathic or secondary to other diseases.

   Definition

Warm-Reactive AIHAs

Warm-reactive AIHAs are due to the presence of IgG antibodies that react with RBC antigens at body temperature. About 60% are idiopathic, and the remaining 40% are the result of lymphomas, leukemias, other neoplasms, or autoimmune disorders such as SLE. They may also accompany HIV or other viral infections.

Cold-Reactive AIHAs and Cold Agglutinin Disease

These AIHAs result from the presence of IgM antibodies that react to polysaccharide antigens on the RBC surface at temperatures below that of the body’s. The antibodies fix complement.

Most of the chronic cases, for which the term
cold agglutinin disease
is commonly used, have an underlying B-cell neoplasm (CLL/small lymphocytic lymphoma [SLL], lymphomas, macroglobulinemia) as their etiology. Some cases are idiopathic. Acute cases either are the result of viral infections such as mycoplasma pneumonia and infectious mononucleosis or belong to a group known as paroxysmal cold hemoglobinuria. There are variable degrees of hemolysis; the disease can be intravascular or extravascular. The symptoms are exacerbated in cold weather; Raynaud phenomena are common, with vascular obstruction due to RBC clumps, cyanosis of exposed parts, and pallor. Splenomegaly is uncommon; the liver is the site for sequestering the coated RBCs.

   Laboratory Findings

Warm-Reactive AIHA

   Hb moderate to severe decrease, in the range of 7–10 g/dL.

   Reticulocytes: elevated in most cases.

   Indices: increased MCV due to reticulocytosis; increased MCHC reflects the presence of spherocytes.

   Peripheral blood smear (PBS): microspherocytes, polychromasia, and occasionally nucleated RBCs.

   Coombs test: direct IgG and C3d are positive. The warm antibodies are in most cases directed against IgG1 and less frequently against IgG3.

   Unconjugated bilirubin, LDH, urine, and fecal urobilinogen: elevated.