Studies on the pancytopenia of kala-azar.

1. The peripheral blood changes in uncomplicated kala-azar are those of pancytopenia; namely, anemia, leukopenia and thrombocytopenia. The red blood cell morphology is normal and there is very little evidence of increased erythrogenic activity. The leukopenia is due to a reduction in all types of cells, especially neutrophils. 2. When the disease is complicated by other infections the anemia is more severe and anisocytosis, poikilocytosis, and polychromatophilia may appear and normoblasts may occasionally be seen in the peripheral blood. Leukocytosis may develop, the leukopenia may persist or the syndrome of agranulocytosis may intervene. 3. As the duration of the disease increases, the spleen tends to become larger and the anemia, leukopenia and thrombocytopenia become progressively more severe. Leukopenia generally appears first, followed by anemia and finally thrombocytopenia. The degree of leukopenia, anemia and thrombocytopenia follow closely the degree of splenic enlargement. 4. The bone marrow in kala-azar is hyperplastic and infiltrated by reticulo-endothelial cells. In spite of this there appears to be an abundance of blood forming tissue, especially erythropoietic tissue. 5. Differential cell studies on preparations of sternal marrow reveal a marked reduction in the polymorphonuclear neutrophils and eosinophils. Myeloblasts, promyelocytes, neutrophilic myelocytes and metamyelocytes are present in approximately normal proportions as are the lymphocytes and monocytes. Plasma cells are somewhat increased. Erythroid cells, especially polychromatic normoblasts are numerous and the leukocyte-erythroid ratio is altered, more than the normal proportion of normoblasts being found. Megakaryocytes are present in normal or slightly reduced numbers. Staining abnormalities are noted in these cells and there is a striking reduction in platelet production. 6. During effective anti-leishmanial therapy parasitized reticulo-endothelial cells disappear and the percentage of reticulo-endothelial cells gradually diminishes as the polymorphonuclear neutrophils increase. There is a significant increase in the eosinophilic cells. Lymphocytes become more numerous and the plasma cells diminish in number. Nucleated red cells become less numerous and the leukocyte-erythroid ratio returns to normal. At the same time the proportion of orthochromatic normoblasts to polychromatic normoblasts increases. The relative number of megakaryocytes increases and platelet formation from the megakaryocytes is accelerated even beyond the normal. Huge groups of platelets are frequently seen in the marrow smears. A rise in platelets in the peripheral blood takes place late, after there has been a significant rise in hemoglobin and leukocytes. The three cellular elements are restored to normal in the peripheral blood in the same order as their reduction from normal. 7. Evidence is presented which contradicts the view that the pancytopenia is due to a crowding out of the bone marrow by reticulo-endothelial cells. 8. Certain similarities between the hematologic changes in this disease and those accompanying the hypersplenic syndromes are noted.