The Spleen and Haemolytic Disorders

Abstract

The spleen is frequently found to play a significant role in the destruction of red cells in haemolytic diseases: currently the mechanisms most convincingly demonstrated involve the modification of the red cell during its passage through the organ, where the specific vascular organisation of the spleen imposes critical stresses on the cells. Susceptibility to the adverse effects of splenic passage is conditioned by abnormalities of cell shape, the viscosity of the intracellular contents and the intrinsic properties of the membrane, any of which may lead to delay and retention in a metabolically disadvantageous environment. Biological properties, such as the presence of membrane-bound antibody are also significant, but their relative importance is incompletely defined. Within the spleen the red cell may undergo loss of membrane surface area, with progression towards a sphered shape, as the result of (1) an incubation lesion predisposing to fragmentation, (2) partial phagocytosis, and (3) membrane loss during the extraction of intracellular inclusion bodies. Ultimately the membrane loss becomes incompatible with further circulation, but destruction does not necessarily occur within the spleen itself, many of the affected (‘conditioned’) cells being destroyed at other sites. In general, the spleen is a sensitive monitor of red-cell abnormality and splenectomy may permit the survival of abnormal cells which would otherwise be destroyed by the organ. Other processes, such as antibody production by the spleen, are also probably relevant to haemolytic disease but are less well understood and are more difficult to quantitate. Anaemia in the presence of splenomegaly is not solely dependent on accelerated red-cell destruction: other factors which may be contributory include (1) the diversion of red cells to a nonfunctional role by splenic pooling, (2) the dilutional effect of blood volume expansion, in which the plasma volume may expand greatly in excess of any increase in red-cell mass, and (3) the reduction in erythropoiesis and in responsiveness of the bone marrow which is present in many conditions characterised by splenic enlargement. The prediction of spleen-dependence is important therapeutically, but is possible only within broad limits: with the recognition that several mechanisms are involved a more categorical approach may become practicable.