Splenic Pool Research Articles

Splenectomy in Anaemia

Splenectomy has been carried out for anaemia on 104 patients suffering from haematological disease. The mortality was 3 per cent. The indications for this operation are considered and the predictive value of estimations of splenic red cell destruction, splenic red cell pooling, and the plasma volume have been examined. None of these tests gives an unequivocal prediction but are of value in reaching a decision. Removal of a splenic site of red cell destruction and a reduction in plasma volume appear to be associated with post-operative haematological improvement. However, the changes in plasma volume seen after splenectomy are usually only temporary and revert slowly over several years.

Plasma volume and splenomegaly in polycythaemia vera.

SummaryBlood volume studies in 23 patients with polycythaemia vera showed the mean plasma volume to be normal when compared with control subjects, and variation in plasma volume for the group as a whole was no greater than in normal subjects. However, the polycythaemic subjects proved to be heterogeneous with respect to plasma volume: in one subgroup, showing splenomegaly with demonstrable intrasplenic red cell pooling, there was a moderate increase in mean plasma volume. In addition, the effect of intrasplenic red cell pooling on the whole body haematocrit/venous haematocrit ratio was found to differ in this condition from the effect in non‐polycythaemic subjects: the splenic pool failed to concentrate red cells significantly above the levels present in the extrasplenic circulation, and did not result in a rise in the Hb/Hv ratio.

Tropical splenomegaly syndrome in New Guinea. II. Long term results of splenectomy.

Between 1965 and 1967 splenectomy was performed on 21 Watuts and 5 other New Guineans to relieve persistent incapacitating symptoms of tropical splenomegaly syndrome. There were 3 operative deaths. Post-operatively abolition of the splenic red cell pool, correction of the shortened red cell survival time and reduction in plasma volume occurred, leading to a mean rise in haemoglobin concentration of 3·7 g./100 ml. Neutropenia and thrombocytopenia were also corrected. There was a rapid post-operative fall in serum IgG and IgM concentrations, and a prolonged reduction in intravascular pools of both immunoglobulin fractions. The 18 Watuts discharged from hospital and followed for from 41 to 74 months have had significant symptomatic relief, although 7 have died following short illnesses; this mortality rate (36%) is substantially less than that of a comparable group of Watuts not subjected to splenectomy.

Tropical splenomegaly syndrome in New Guinea. I. Natural history.

Abstract The course of the tropical splenomegaly syndrome has been observed for periods of up to 6 1 2 years in 75 adults living in the Upper Watut Valley of New Guinea. During this time there were 27 deaths, 2 from septicaemia and another 8 from similar fulminating febrile illnesses. The mortality rate in those with Grade V splenomegaly was 57%, almost 3 times that of the remainder. Serial hospital assessment of 26 subjects demonstrated progression of the disease, characterized by further enlargement of the spleen and a fall in haemoglobin concentration in 9; increases in splenic red cell pool, in plasma volume and in serum IgM concentration were sometimes, but not invariably, associated. In none of the total group of 75 subjects was a decrease in spleen size observed. Thus the natural history of the tropical splenomegaly syndrome is that of a progressive disease with a high mortality in the fully developed case. Periodic fluctuations in the clinical severity of the disorder are frequently seen and are largely related to the occurrence of episodes of acute haemolysis; however, spontaneous remission has not been observed.

Quantitation of the Cell-Mediated Immune Response

Abstract Quantitative aspects of the cell-mediated immune response of C57BL mice to a mouse DBA/2 mastocytoma cell have been studied by an in vitro assay involving the cytolytic activity of splenic lymphocytes towards 51Cr labeled target cells. Cytolysis of the DBA/2 mastocytoma cells by “sensitized” C57BL lymphocytes was shown to be a “one-hit” phenomenon, i.e., that lysis of a target cell resulted from single interaction with specifically sensitized “effector” cells. Kinetic studies showed that the rate of target cell destruction fell markedly with time following mixing with lymphocytes, and thus suggested that there is reciprocal death of the interacting cells at least from a functional standpoint, if not morphologically. These findings suggested a means of calculating the number of effector lymphocytes in the splenic pool of sensitized animals, by determining the maximal number of target cells that a given number of lymphocytes could lyse under specified conditions in gross target cell excess. Such determinations were used to compare the effect of mode and dose of antigenic stimulation on the cell-mediated immune response. Optimal antigenic stimulation of C57BL mice with alloantigenic mastocytoma cells was found to be by the intraperitoneal route. Maximal responses were elicited with 107 cells and occurred 11 days following antigenic stimulation. Under these conditions it was estimated that approximately 4% (4 × 104 out of 106) of the lymphocytes were effector cells. Incorporation of the mastocytoma cells into adjuvants (either complete or incomplete Freund's) resulted in a marked diminution of both humoral and cell mediated immune responses. Using complete Freund's adjuvant the maximal number of effector cells produced following antigenic stimulation with 3 × 107 mastocytoma cells was approximately 5 × 103/106 lymphocytes. The number of effector lymphocytes resulting from stimulation with 3 × 107 mastocytoma cells rose exponentially from day 4 (when the cytolytic activity was first demonstrable) and when there were calculated to be 50 effectors/106 lymphocytes to day 11 (4 × 104/106 lymphocytes) and fell therafter. The generation time of the cell population involved in cytolysis was estimated to be approximately 17 hr.

DISCUSSION

Erythrocyte sequestration was studied in 24 patients with chronic lymphocytic leukaemia (CLL) by infusion of autologous 51Cr‐labelled erythrocytes followed by surface measurements at regular intervals over the spleen, liver, and heart.To obtain a comparable expression of the accumulation of activity in spleens of different sizes, the splenic surface activities were corrected. The correction factors were determined using fluid‐filled balloons (simulating spleens) with the same amount of activity.In 19 patients with CLL the splenic erythrocyte pool increased with increasing spleen weight (500–4, 300 g). Moreover, the erythrocyte sequestration in the spleen increased with increasing pool. The maintenance of a large erythrocyte pool makes increased demands upon the erythropoiesis, which is perhaps already insufficient, and an increased splenic erythrocyte sequestration contributes to reducing the number of circulating erythrocytes. Splenectomy is invariably followed by increasing haemoglobin level and an average 30% increase of erythrocyte survival (22–48%).In cases of CLL plus splenomegaly the indications for splenectomy appear to be fairly simple, but may be supported by the demonstration of a large splenic erythrocyte pool and a large splenic erythrocyte destruction.The studies support the likelihood of lymphocytic infiltration in the liver (increased accumulation of activity), a finding which seems of prognostic significance.

Blood volume changes in splenomegaly.

Summary. Blood volume changes have been measured in 65 patients with splenomegaly due to a miscellany of causes. The red‐cell mass is often normal despite the fact that anaemia is present, and the anaemia is in part due to sequestration of red cells in a splenic pool and haemodilution of the red cells in an expanded plasma volume. Both factors may be relieved by splenectomy although the ultimate prognosis is dependent on the primary disease present.

Thrombokinetics in man.

Platelet production, distribution, and destruction have been quantitated in normal man and in selected patients with platelet disorders. In most instances, total production as calculated from the megakaryocyte mass agreed with production estimated from platelet turnover. In patients with megaloblastosis, a discrepancy between these two measurements indicated the presence of ineffective thrombopoiesis. Thrombopoiesis was regulated by (a) alterations in megakaryocyte number, and (b) changes in megakaryocyte volume (produced by changes in endomitosis). The volume-endomitosis changes were closely related to the peripheral platelet count and were a useful indicator of thrombopoietic stimulus. Thrombocytopenic disorders have been classified on the basis of the disturbed physiology into disorders of (a) production (hypoproliferative or ineffective), (b) distribution (splenic pooling), or (c) destruction (immune or consumptive). Less than a twofold increase in platelet production in the presence of significant thrombocytopenia was taken to represent impaired proliferation. Thrombocytosis was classified as reactive or autonomous. Reactive thrombocytosis was consistently associated with a mean megakaryocyte volume and endomitosis less than normal but appropriate for the elevated circulating platelet count. In contrast, the average megakaryocyte volume and nuclear number were always greater than normal in thrombocythemia findings indicating autonomy.

Thrombocytopenia and alcoholism.

Eight patients with acute and chronic alcoholism and liver disease, who suffered one or more episodes of acute thrombocytopenic purpura after heavy alcoholic intake, are described. Recovery was rapid after withdrawal from alcohol, and the use of corticosteroids did not appear to alter their course. Folic acid deficiency, splenic pooling of platelets, and massive hemorrhage do not appear to be causal factors. The possible role of excessive coagulation and a direct effect of alcohol on the bone marrow or circulating platelet are discussed.

Blood: Studies of Leukocyte Kinetics in Chronic Lymphocytic Leukemia

Abstract Intravenously administered H3TdR was used to study peripheral blood leukocyte kinetics of ten patients with CLL in relapse and one in partial remission. Two distinct patterns were found. The first pattern indicates the presence of a small, proliferating population of lymphocytes which is present in the blood for a relatively brief time. This pattern was found in patients with no organomegaly and with relatively lower peripheral lymphocyte counts. In the second pattern almost all of the cells present were non-proliferating and long-lived. The patients with the latter pattern had organomegaly. These studies support the concept that there is a progressive widespread accumulation of long-lived lymphocytes in CLL often leading to splenic pooling and, in some cases, hypersplenism.

Increased splenic pooling and the pathogenesis of hypersplenism.

Increased splenic pooling and the pathogenesis of hypersplenism.

Gaucher's disease with portal hypertension: Case report

Summary A case of Gaucher's disease with marked portal hypertension is described. The portal vein was patent and hepatic cirrhosis was minimal. All evidence of portal hypertension disappeared following splenectomy. It is inferred that forward flow from the splenic venous pool was a significant factor in the causation of the increased pressure in the portal system.