Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (312 page)

   Haptoglobin: decreased.

Cold-Reactive AIHA and Cold Agglutinin Disease

   Anemia (severity depends on cold agglutinin titer) with anomalous high MCV and MCHC (artifacts due to RBC clumping at room temperature).

   Peripheral blood smear (PBS): RBC clumping.

   Reticulocyte count: high.

   Anticomplement (C3) Coombs test (positive). Anti-I antibodies are best detected using cord blood red cells.

   Cold agglutinin titers: elevated.

PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH)

   Definition

PNH is an acquired disorder of hematopoietic stem cells, characterized by intravascular hemolysis and hemoglobinuria. Only 25% of cases present with classical nocturnal and paroxysmal hemolysis. The clinical triad of intravascular hemolysis, venous thrombosis (the leading cause of death), and bone marrow failure is typical. The chronic intravascular hemolysis results in iron deficiency. There is a high risk of evolution into aplastic anemia, myelodysplastic syndrome, or AML. Clinically, the polymorphism of PNH can be roughly divided into two presentations:

   Classic PNH: hemolysis without bone marrow failure

   Aplastic anemia–PNH syndrome (AA-PNH): hemolysis with bone marrow failure

   When To Suspect Paroxysmal Nocturnal Hemoglobinuria

   Patients with Coombs-negative intravascular hemolysis, especially if concurrently iron deficient.

   Patients with hemoglobinuria.

   Patients with venous thrombosis involving unusual sites (mesenteric, hepatic, portal, cerebral, or dermal veins) and especially patients with otherwise unexplained Budd-Chiari syndrome. Such patients should also be investigated for the JAK2 V617F (see p. 1021) mutation if the etiology remains unclear.