Erythrokinetic Studies in Hairy-Cell Leukaemia

Erythrokinetics were studied in 29 patients with hairy-cell leukaemia. In all cases there was an increase in plasma volume, closely correlated to the size of the spleen, indicating that the true degree of anaemia can only be appreciated by red cell volume measurement. Moderately increased haemolysis was observed in most cases, which did not correlate with the spleen size. Simultaneous study of autologous and isologous red cell life-span suggested an extra-corpuscular mechanism for the haemolysis in most patients. A quantitative erythropoietic defect, either relative or absolute, was found in half the cases, without any qualitative defect. Only one case showed erythroid metaplasia of the spleen. Thus marrow failure appears to be largely responsible for the anaemia and granulocytopenia in hairy-cell leukaemia. A clear correlation was shown between the short-term prognosis after splenectomy and the degree of hypersplenism. However, long-term survival correlated chiefly with the degree of bone marrow failure, whether splenectomy had been carried out or not. The results indicate that isotope studies in hairy-cell leukaemia are useful both in determining the best form of treatment and predicting survival.     

The Anaemia of Chronic Disorders: Studies of Iron Reutilization in the Anaemia of Experimental Malignancy and Chronic Inflammation

The purpose of this study was to evaluate the contribution of defective reutilization of iron in the pathogenesis of the anaemia of chronic disease (ACD). Normal rats with or without splenectomy and rats with Walker 256 carcinosarcoma with or without splenectomy were studied. The reutilization of ⁵⁹Fe labelled heat-damaged red cells (⁵⁹Fe DRBC), the sequestration of ⁵⁹Fe DRBC in major organs, red cell mass, ⁵¹Cr red cell survival, serum iron, plasma erythropoietin and routine haematological parameters were measured.
Three weeks after tumour implantation in rats a moderate degree of anaemia was noted. The maximum ⁵⁹Fe reutilization in the tumour group and tumour with splenectomy group (63 ± 6% and 56 ± 9%, respectively) was not significantly different than observed in the normal group (64 ± 6%) or normal with splenectomy group (53 ± 7%). Excessive iron sequestration in liver and spleen was not observed in animals with cancer. Red cell survival in the tumour group was slightly decreased as compared to normal. Plasma erythropoietin levels were appropriately increased for the degree of anaemia in rats with cancer. This type of experiment was repeated in a second group of anaemic animals with turpentine induced abscesses. Reutilization of ⁵⁹Fe DRBC in rats with inflammation was normal.
These results indicate that adult rats with anaemia of malignancy or chronic inflammation do not have a decreased reutilization of red cell iron. Thus RE blockade of iron is not a major factor in anaemia of chronic disease in this experimental model. Furthermore, these experiments confirm the importance of decreased red cell production in the anaemia of malignancy.     

Littoral cell angioma of the spleen in a patient with severe aplastic anaemia

Littoral cell angioma (LCA) is a rare benign tumour of the spleen. We describe a patient with aplastic anaemia who, following multiple treatments with rabbit and horse Anti-Thymocyte Globulin and anabolic steroids developed marked splenomegaly and hypersplenism. LCA was diagnosed post splenectomy. This is the first case of LCA associated with aplastic anaemia and its treatment.     

Littoral cell angioma of the spleen in a patient with severe aplastic anaemia

Littoral cell angioma (LCA) is a rare benign tumour of the spleen. We describe a patient with aplastic anaemia who, following multiple treatments with rabbit and horse Anti-Thymocyte Globulin and anabolic steroids developed marked splenomegaly and hypersplenism. LCA was diagnosed post splenectomy. This is the first case of LCA associated with aplastic anaemia and its treatment.     

Splenectomy in patients with malignant non-Hodgkin's lymphoma

Splenectomy in patients with non-Hodgkin's lymphoma (NHL) is performed for either diagnostic or therapeutic reasons. We report on a series of 29 patients with NHL and splenomegaly who underwent splenectomy during the years 1979-1998 in our hospital. According to the indication for splenectomy our patients were categorized in three groups. Group A: In 20 patients splenectomy was performed for diagnostic reasons. Group B: Three patients were splenectomized for autoimmune haemolytic anaemia (AIHA). Group C: Six patients underwent splenectomy because of hypersplenism. A definitive histopathological diagnosis of NHL was obtained in all patients of group A. Hypersplenism and AIHA were resolved in all patients after splenectomy. One (3.5%) patient died postoperatively because of septicemia complicated by disseminated intravascular coagulation. Six postoperative complications were observed in 4 (14%) patients. Splenectomy, with an acceptable surgical risk, has the potential to establish the diagnosis of NHL in patients with splenomegaly without lymphadenopathy and negative bone marrow findings. Moreover, splenectomy has the capacity to modify the disease course in patients with NHL complicated by AIHA or hypersplenism.     

Hypersplenism in Wilson''s disease

Thirteen patients with Wilson's disease were compared with seven cirrhotic and 13 normal controls to define better the haematological abnormalities in this condition. Hypersplenism (anaemia, leukopenia, thrombocytopenia, and reduced red cell survival) commonly occurred in patients with both Wilson's disease and cirrhosis. These abnormalities correlated with splenic enlargement. Despite reduced haematocrits, red cell mass was greater in these two groups than in normal controls. Plasma volume and the body haematocrit/peripheral haematocrit ratios were also greater in patients with Wilson's disease and cirrhosis. Increased splenic sequestration of ⁵¹Cr-tagged red blood cells was not demonstrated in any subjects. The hypersplenism in patients with Wilson's disease is similar to that found in patients with cirrhosis from other causes.     

Haematological Effects of the Idiopathic Splenomegaly Seen in Uganda

The haematological effects of idiopathic splenomegaly have been studied in a group of 15 Ugandan patients. The results of the main investigations were compared with those obtained in five patients with miscellaneous diseases and without palpable splenomegaly.
The splenic enlargement was mainly due to reticuloendothelial hyperplasia and not to sinusoidal congestion.
A normochromic anaemia was present in almost all the patients and a proportion had leucopenia and thrombocytopenia. One patient presented with a crisis of anaemia; she was later shown to have red cell G6PD deficiency which was believed to be coincidental.
Three aetiological factors were found in relation to the anaemia; reduction of red cell survival time, present in all the patients, haemodilution from expansion of the plasma volume, and the exclusion of a proportion of the red cell mass from the general circulation by the spleen. Six to 39 per cent of the red cell volume, the amount varying with spleen size, was sequestered in a slow mixing compartment, believed to be the extrasinusoidal spaces (the spleen pool) in the patients with splenomegaly. No spleen pool could be shown in any of the patients without splenomegaly.
Intrasplenic red cell destruction was not conspicuous and it has been suggested that the red cells, after damage from repeated stagnation in the spleen pool, are destroyed widely throughout the body.
The reasons for expansion of the plasma volume is not known. It relates to spleen size but cannot wholly be explained by plasma in the spleen pool.
A good result from splenectomy was obtained in six out of seven patients in whom this was undertaken. Two months after operation the red cell survival time was corrected in the patients in whom this was measured. The rise in the PCV could be explained only by substantial reduction in plasma volume.     

Splenic Red Cell Pooling in Hairy Cell Leukaemia

The splenic red cell volume has been measured directly by an isotope method with quantitative scanning in 10 patients with leukaemic reticuloendotheliosis (hairy cell leukaemia). The volume ranged between 211 and 726 ml (mean 410 ml, SD 158) and this constituted 15–48% (mean 28.1%, SD 9.5) of the total circulating red cell volume. This is an exceptionally large pool when compared with that found in myeloproliferative and lymphoproliferative disorders with the same degree of splenomegaly. It is consistent with the histological features which show marked red cell accumulation in the splenic cord areas. The red cell pooling in the spleen thus appears to be a significant factor in the anaemia and there was fairly good correlation between the percentage of improvement in the anaemia and the percentage of red cell volume contained in the spleen. By direct measurement of the splenic red cell pool, it is possible to predict the extent to which splenectomy will benefit the anaemia and this may also provide an indirect measure of the extent of bone marrow dysfunction in the causation of the anaemia.     

Blood Volume Changes in Splenomegaly

S ummary . 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.     

Long-term effect of splenectomy on transfusion requirements in thalassemia major

Splenectomy reduces transfusion requirements in the first year after surgery in patients with thalassemia major and hypersplenism. To determine whether this response is maintained, we have studied transfusion requirements in 16 patients with thalassemia major for 2-17 years after splenectomy. Transfusion requirements remained stable (mean yearly change -0.1%) after the predictable fall in the first year after surgery. The mean change between the first postoperative year and the most recent year was -7 ml/kg. Transfusion requirements and the magnitude of change from year to year were unrelated to the time since splenectomy. These studies indicate that the effect of splenectomy on transfusion requirements is long-lasting and that large variations in annual transfusion requirements after splenectomy should prompt a search for accessory spleens or other causes of red cell destruction.     

Splenectomy before hepatectomy for patients with hepatocellular carcinoma and hypersplenism: A retrospective study

The spleen plays an important role in tumor progression and the curative effects of splenectomy before hepatectomy for hypersplenism and hepatocellular carcinoma (HCC) are not clear. We investigated whether splenectomy before hepatectomy increases survival rate among patients with HCC and hypersplenism compared with that of patients who underwent synchronous hepatectomy and splenectomy or hepatectomy alone.Between January 2011 and December 2016, 266 patients who underwent hepatectomy as a result of HCC and portal hypertension secondary to hepatitis were retrospectively analyzed. Their perioperative complications and survival outcome were evaluated.Patients underwent synchronous hepatectomy and splenectomy (H-S group) and underwent splenectomy before hepatectomy (H-preS group) exhibited significantly higher disease-free survival (DFS) rates than those of patients underwent hepatectomy alone (H-O group). The DFS rates for patients in the H-S group, H-preS group, and H-O group were 74.6%, 48.4%, 39.8%, and 80.1%, 54.2%, 40.1%, and 60.5%, 30.3%, 13.3%, at 1, 3, and 5 years after surgery, respectively. Tumor size, tumors number, and levels of alpha fetoprotein (AFP) were independent risk factors for DFS. Gender and tumor size were independent prognostic factor for overall survival (OS). The preoperative white blood cell (WBC) and platelet (PLT) counts were significantly higher in the H-preS group than in those of the H-S group and the H-O group. After operation, the WBC and PLT counts in the H-S group and H-preS groups were significantly higher compared to those of the H-O group.No matter splenectomy before hepatectomy or synchronous hepatectomy and splenectomy, hepatectomy with splenectomy may improve DFS rates in patients with HCC and hypersplenism, and splenectomy before hepatectomy alleviates hypersplenism without an increased surgical risk.     

Red cell deformability, splenic function and anaemia in thalassaemia

Red cell deformability (RCD) was measured in 38 patients with alpha-thalassaemia and 48 patients with beta-thalassaemia, of whom 13 had undergone splenectomy. All splenectomized patients, but none of those with intact spleens, had very rigid erythrocytes with an elongation index <0.45 at a high shear stress of 30 Pa suggesting a splenic recognition threshold for removal of rigid red cells. At this shear stress RCD correlated strongly with the degree of anaemia in both the splenectomized (r = 0.81, P < 0.001) and non-splenectomized beta-thalassaemic patients (all patients r = 0.81, P < 0.001; homozygous beta-thalassaemic patients r = 0.51, P = 0. 01). These data suggest that reduced RCD is a major determinant of anaemia in thalassaemia.     

Haemorheology in Gaucher disease

In Gaucher disease, a deficiency of glucocerebrosidase results in the accumulation of glucocerebroside within the lysosomes of the monocyte-macrophage system. Prior to the availability of enzyme replacement therapy (ERT), splenectomy was often indicated for hypersplenism. Haemorheological abnormalities could be expected in view of the anaemia and abnormal lipid metabolism in these patients and the role of the spleen in controlling erythrocyte quality. OBJECTIVES: To investigate the effect of Gaucher disease on blood and plasma viscosity, erythrocyte aggregation and erythrocyte deformability, and to determine whether observed rheological differences could be attributed to splenectomy. METHODS: Haematological and haemorheological measurements were made on blood collected from 26 spleen-intact patients with Gaucher disease, 16 splenectomised patients with Gaucher disease, 6 otherwise healthy asplenic non-Gaucher disease subjects and 15 healthy controls. RESULTS: No haemorheological differences could be demonstrated between spleen-intact patients with Gaucher disease and the control group. Compared to controls, both asplenic Gaucher disease and asplenic non-Gaucher disease study groups had a reduced MCHC (P = 0.003 and 0.005, respectively) and increased whole blood viscosity at 45% haematocrit (Hct), relative viscosity and red cell aggregation index - all measured at low shear (P < 0.05 for all). Additionally, asplenic patients with Gaucher disease alone showed an increased MCV (P = 0.006), an increased whole blood viscosity at 45% Hct measured at high shear (P = 0.019), and a reduced relative filtration rate (P = 0.0001), compared to controls. CONCLUSION: These observations demonstrate a direct and measurable haemorheological abnormality in Gaucher disease only revealed when there is no functioning spleen to control erythrocyte quality.     

Safety of synchronous hepatectomy and splenectomy for patients with hepatocellular carcinoma and hypersplenism

Background/Aims: To assess the surgical safety of synchronous hepatic resection and splenectomy for patients with hepatocellular carcinoma (HCC) and hypersplenism. Methodology: Patients with HCC and hypersplenism who underwent surgical treatment were included in this study. According to the difference of operations, patients were divided into two groups (group A, patients who underwent hepatic resection; group B, patients who underwent synchronous hepatic resection and hypersplenism). Pre- and intra-operative parameters were statistically analyzed. Postoperative outcomes including white blood cell and platelet count changes, surgical complications and long-term survival rates were compared. Results: The pre- and intra-operative parameters of two groups were comparable except for preoperative white blood cell and platelet counts. The incidences of postoperative surgical complication were 53.33% for group A and 35.48% for group B (p=0.161). The 1- and 3-year survival rates of the two groups were 83%, 42% and 82%, 54%, respectively (p=0.313). Conclusions: Synchronous hepatic resection and splenectomy could increase the postoperative WBC and platelet level for patients with hepatocellular carcinoma and hypersplenism without increasing surgical risks.     

Laparoscopic and open splenectomy and azygoportal disconnection for portal hypertension

AIM： To compare the outcomes of laparoscopic and open splenectomy and azygoportal devascularization for portal hypertension.
METHODS： From June 2006 to March 2009, laparoscopic splenectomy and azygoportal disconnection （LSD） were performed on 28 patients with cirrhosis, bleeding due to portal hypertension, and secondary hypersplenism. Success was achieved in 26 patients. Demographic, intraoperative, and postoperative variables of the patients were compared.
RESULTS： Success of laparoscopic splenectomy and azygoportal disconnection was achieved in all but two patients （7.14%） who required open splenectomy and azygoportal devascularization （OSD）. The operation time was significantly longer in patients undergoing LSD than in those undergoing OSD （235 ± 36 min vs 178 ± 47 rain, P 〈 0.05）. The estimated intraoperative blood loss was much more in patients receiving OSD than in those receiving LSD （420 ± 50 mL vs 200 ± 30 mL, P 〈 0.01）. The proportion of patients undergoing laparoscopic and open splenectomy and azygoportal disconnection who received transfusion of packed red blood cells during or after the operation was 23.08% and 38.46%, respectively （P 〈 0.05）. The time of first oral intake was faster in patients after LSD than in those after OSD （1.5 ± 0.7 d vs 3.5 ± 1.6 d, P 〈 0.05）. The hospital stay of patients after LSD was shorter than that of patients after OSD （6.5 ± 2.3 d vs 11.7 ± 4.5 d, P 〈 0.05）. The pain requiring medication was less severe in patients after LSD than in those after OSD （7.69% vs 73.08%, P 〈 0.001）. The overall complication rate was lower in patients after LSD than in those after OSD （19.23% vs 42.31%, P 〈 0.05）.
CONCLUSION： Laparoscopic splenectomy and azygoportal disconnection are the feasible, effective, and safe surgical procedure, and are advantageous over minimally invasive surgery for bleeding portal hypertension and hypersplenism.     

Homozygosity for dominant form of hereditary spherocytosis

A 6-month-old male infant with hereditary spherocytosis (HS) who was the first child of a cousin marriage is presented. The patient had splenomegaly and severe anaemia. Examination of the peripheral blood smear revealed spherocytes and the osmotic fragility of red blood cells was greatly increased. Physical examination of the parents revealed that both parents had mild anaemia, jaundice and splenomegaly. Their peripheral blood smears showed spherocytes and a few acanthocytes. Osmotic fragility of red blood cells of both parents were increased. Red cell membrane electrophoresis indicated a deficiency of ankyrin in the propositus; mild deficiency was also detected in both parents. Electrophoretic patterns of red cell membrane proteins suggested that the child was homozygous for the dominant form of HS associated with ankyrin deficiency, while both parents had the simple dominant form of the disease. Red blood cell transfusions were given to the patient starting at the age of 1 month until splenectomy was performed at the age of 1 year that resulted in complete haematological response. This observation indicates that homozygosity for dominant type of HS associated with ankyrin deficiency is life compatible and splenectomy may cure the anaemia.     

Efficacy of splenectomy for hypersplenic patients with advanced hepatocellular carcinoma

Aim: Chemotherapy for advanced hepatocellular carcinoma (HCC) patients with hypersplenism is generally unsatisfactory, as a lower-dose therapy is usually administered. Splenectomy may represent a better approach to overcoming the complication due to hypersplenism in patients with advanced HCC. This retrospective study was conducted to evaluate whether HCC patients who undergo splenectomy show improved prognosis. Methods: We examined 34 HCC patients. Twenty-two had thrombocytopenia and/or leucopenia and underwent laparoscopic splenectomy. The completion rate of full-dose drug regimens, the response rate, the toxicity of chemotherapy and the cumulative survival rate were compared between the splenectomy and non-splenectomy groups. Results: The response rate and the cumulative survival rate in the splenectomy group were significantly better than that in the non-splenectomy group. Conclusions: Splenectomy is an efficient method for advanced HCC patients with hypersplenism treated by chemotherapy.     

Spleen irradiation in chronic lymphocytic leukemia (CLL): palliation in patients unfit for splenectomy

In 22 patients with CLL given 30 courses of spleen irradiation, 23 responses were observed (77%, 95% confidence limits, 58-90%). Response was defined as reduction in palpable spleen size accompanied by relief of symptoms (pain, abdominal discomfort, and sweating) or improvement in hypersequestration or hemolytic anemia. Reduction in leukocyte count alone was not regarded as response. All responses were partial. The median response duration was 1 year. Subsequently, three patients underwent splenectomy. The median survival from the beginning of spleen irradiation was 2.5 years (range: 1 month-greater than 5 years). Only six patients had minor side effects from the gastrointestinal tract. The hematologic effect was most pronounced on the white blood cell count, but also the platelet count was affected. It is concluded that spleen irradiation is a gentle and effective alternative in CLL patients suffering from splenomegaly (pain and hypersplenism), refractory to chemotherapy and glucocorticosteroids and unfit for splenectomy. Splenic irradiation may also be used with benefit preoperatively before splenectomy in patients with excessive splenomegaly and hypersplenism.     

Unclassified type of congenital dyserythropoietic anaemia (CDA) with prominent peripheral erythroblastosis

Two unrelated cases of congenital dyserythropoietic anaemia (CDA) are described. They show striking similarities which could not be attributed to one of the well-known types of CDA or any other congenital disease of the erythroid system. Both patients were followed for many years before and after splenectomy. There was a long-lasting, prominent post-splenectomy erythroblastosis, suggesting impairment of red cell denucleation. The type of heredity is unknown, and the enzymatic or molecular basis of the changes observed is not understood.     

A Genetically Determined Disorder with Features both of Thalassaemia and Congenital Dyserythropoietic Anaemia

S ummary . What appears to be a hitherto unreported type of congenital anaemia has been found in six members of an Irish family. It is inherited in an autosomal dominant manner and is characterized by moderate anaemia, lifelong jaundice, cholelithiasis and splenomegaly, marked morphological abnormalities of the red cells (which are, however, well haemoglobinized), erythroid hyperplasia of the bone marrow with increased numbers of multinucleate red cell precursors, and the presence of large inclusion bodies in the normoblasts, both in the marrow, and in the peripheral blood after splenectomy. Potassium flux across the red cell membranes is increased and there is imbalanced globin chain synthesis with α-chain production exceeding that of β-chains by a factor of 2/1. Excess α-chains in the bone marrow form a pool of similar magnitude to that observed in β-thalassaemia heterozygotcs but the latter do not have red cell precursor inclusion bodies or the degree of ineffective erythropoiesis seen in the present cases. The most likely molecular mechanisms for this disorder are either an 'overproduction abnormality' of α-chain synthesis, or a defect in cell division leading to increased amounts of genetic material per cell, a mechanism postulated recently as a basis for the unusual distribution of red cell enzyme levels in congenital dyserythropoietic anaemia.