Anemias are characterized by a decrease and erythrocytoses by an increase of the red cell mass. In most clinical situations, changes in red cell mass are inferred from the hemoglobin concentration or hematocrit. Some red cell disorders are associated with compensated hemolysis without or with only slight anemia. Their clinical manifestations are evident not by the effects of anemia but by changes associated with catabolism of hemoglobin such as an increase in serum bilirubin and, if sustained, cholelithiasis, decreased haptoglobin, and usually chronic reticulocytosis. Some red cells disorders are only showcased by morphologic abnormalities as exemplified by hereditary elliptocytosis unaccompanied by hemolysis or anemia, or by cyanosis such as that seen with methemoglobinemia and sulfhemoglobinemia.
The anemias have their principal effect by decreasing the oxygen-carrying capacity of blood and their severity is most conveniently considered in terms of blood hemoglobin concentration; however, oxygen-carrying capacity of blood is also influenced by red cell and plasma volumes. Anemia may cause symptoms because of tissue hypoxia (eg, fatigue, dyspnea on exertion). Some manifestations are also caused by compensatory attempts to ameliorate hypoxia (eg, hyperventilation, tachycardia, and increased cardiac output). These manifestations are a function of the severity and rapidity of onset of the anemia. Tissue hypoxia sensing is ubiquitous and is signaled by an increased level of hypoxia-inducible transcription factors (HIFs) HIF-1 and HIF-2. HIFs upregulate transcription of many genes, in addition to the principal erythropoietic factor erythropoietin (EPO), that are involved in erythropoiesis, but also in angiogenesis, energy metabolism, and iron balance. The classification of anemia distinguishes whether the anemia is inherited or acquired and considers new kinetic and molecular findings. Some anemic disorders can be accompanied by nonerythroid pathologic indicators, such as mutated red cell enzyme aldolase, which is also associated with glycogen storage disease and developmental disability in addition to hemolytic anemia.
The erythrocytoses are often referred to as polycythemia. In this and related chapters, we have chosen to refer to polycythemia vera as simply polycythemia and other primary and secondary increases in red cell mass as erythrocytosis. Increased red cell mass has been variably termed either erythrocytosis or polycythemia; no clear consensus for either term has been achieved. Some interpret the meaning of polycythemia to imply that several hematopoietic lineages are increased—ie, erythrocytosis, neutrophilia, and thrombocytosis. In that case the only form of polycythemia, which includes erythrocytosis, is polycythemia vera. An editor of earlier editions of Williams Hematology, the late Allan Erslev, argued that the proper meaning of polycythemia is “too many cells in the blood.” This chapter will reserve the term polycythemia to mean polycythemia vera. The erythrocytoses are most conveniently expressed in terms of the packed red cell volume (hematocrit), because their clinical manifestations are primarily related to the expanded red cell mass and resulting increased viscosity of blood, and other specific features related to the pathophysiology stemming from a molecular causative defect (eg, thrombosis in polycythemia vera and Chuvash erythrocytosis [also Chuvash polycythemia], ...