Hypersplenism and splenectomy in lymphoproliferative and myeloproliferative disorders

Splenic pooling of red cells and an expanded plasma volume are considered to be among the major mechanisms responsible for the anaemia in hypersplenism. In those conditions in which massive splenomegaly is associated with various degrees of marrow failure, diagnosis of the cause of anaemia may be difficult. A simple technique was used to estimate the degree of hypersplenism, from red cell mass data, in 94 patients with unequivocal lymphoproliferative or myeloproliferative disorders. The splenic effect was found to correlate well with both the size of the spleen (r = 0.75-0.90) and the actual red cell mass (0.79), and was abolished by splenectomy. Clinical data is also presented on 43 of these patients who underwent splenectomy. The incidence and type of complications, survival figures, and possible criteria for patient selection are discussed.     

Erythrocyte Pooling and Sequestration in Enlarged Spleens: Estimations of Splenic Erythrocyte and Fiasma Volume in Splenomegalic Patients

Erythrocyte pooling and sequestration in the spleen were studied in 73 patients with splenomegaly due to various haematological disorders using ⁵¹Cr-labelled autologous erythrocytes and surface counting. Arbitrary values for the accumulation of activity in spleens of different sizes were obtained by correcting measured splenic surface activities (correction factors have been experimentally estimated). Absolute values for the splenic content of ⁵¹Cr and ¹²⁵I were obtained by comparative surface activity measurements over the enlarged spleen and a model of the spleen charged with a known amount of activity. In this way the splenic erythrocyte and plasma volume may be estimated. In cases of pronounced splenomegaly without complicating immunohaemolysis the splenic erythrocyte pool (splenic erythrocyte volume/total erythrocyte volume) increases with increasing splenic weight, apparently independently of the underlying haematological disorder, the splenic erythrocyte content varying only with body haematocrit. Hyperhaemolysis is a regular finding in enlarged spleens. The splenic erythrocyte sequestration rate increases with increasing splenic erythrocyte pool and is much higher in myeloproliferative than in lymphoproliferative disorders. The total plasma volume is expanded in splenomegalic patients, but the splenic plasma volume constitutes only a minor part of this increment. The anaemia of splenomegalic patients is a consequence of splenic erythrocyte concentration and hypersequestration combined with expansion of the plasma volume. Frequently the total erythropoietic capacity is reduced. Splenectomy is regularly followed by an increased venous haemoglobin concentration.     

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.     

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.     

Th1/Th2 balance alteration in the clinical course of a patient with pure red cell aplasia and thymoma

Peripheral T helper subsets in a patient with acquired pure red cell aplasia (PRCA) and thymoma were analysed by flow cytometry. Thymectomy resulted in a transient but definite improvement in anaemia. A continuous remission was attained by cyclosporin A (CsA) therapy. The changes in Th1/Th2 ratios corresponded with the haematological changes. Specifically, Th2 type lymphocytes were dominant during a haemopoietic suppression and elevation of the Th1/Th2 ratio was concomitant with haematological improvement. These observations suggest that polarization of Th subsets to Th2, induced by clonally expanded (γδ-type) T cells in thymoma, are involved in the pathogenesis of PRCA.     

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 Pseudocyst Associated with Hypersplenism

A patient with hypersplenism, who was found to have a splenic pseudocyst containing an organized hematoma, is described. There are only two patients with splenic pseudocyst and hypersplenism and an additional two patients with splenic cysts and hypersplenism reported in the world literature. The hypersplenism associated with splenic cysts and pseudocysts is explained on the basis of an expansion of the plasma volume and the total blood volume, an increased destruction of red blood cells and a pooling of blood in the enlarged spleen. The combined use of ultrasonography and computerized tomography has increased the accuracy of noninvasive diagnosis and made more invasive examinations unnecessary. When the ultrasound is technically unsuccessful or when it shows a mixed echo pattern, one should resort to computerized tomography with which it is possible, almost invariably, to differentiate between cysts and neoplasms.     

The Haematology of Anorexia Nervosa

S ummary . The haematological features of six patients with anorexia nervosa have been studied in a prospective fashion. Hypocellularity and the presence of large amounts of gelatinous acid mucopolysaccharide in the bone marrow has been confirmed and appears to be a common feature of this disorder. Rapid reversal occurred with clinical improvement in one patient. It is suggested that this represents a physiological response to starvation and evidence is presented that these changes are of minimal functional significance in most patients. Although mild subclinical deficiency of iron and folic acid, a slightly reduced red-cell lifespan and a relative increase in plasma volume may also occur, anaemia is not universal and is usually mild. Plasma volume changes are probably the major mechanism. Neutropenia was common and is probably due to redistribution of granulocytes within the various granulocyte compartments. Lymphopenia and thrombocytopenia were also found. Morphological abnormalities of the red cells were a frequent finding, particularly the presence of spur cells. These were not associated with abetalipoproteinaemia nor with biochemical evidence of liver disease and did not appear to be subject to significant haemolysis. These haematological changes are also reversible with improvement in nutritional status. Blue-green granules, probably representing ceroid, were observed in marrow histiocytes. The various abnormalities are discussed in relation to current concepts of the role of nutrition in haematopoiesis in man and haematopoietic roles for dietary factors other than protein are tentatively proposed.     

Locoregional intrasplenic chemotherapy for hypersplenism in myelofibrosis

A 79-year-old patient with post-polycythaemic myelofibrosis presented with severe hypersplenism. After splenic artery catheterization, cytosine arabinoside was given intrasplenically from November 1999 to March 2000 for 5 d/month at 10 mg/m2 and increased each month by 10 mg/m2. It was then administered by continuous infusion until June 2000, starting at 20 mg/m2/d and tapering by 5 mg/m2 every 2 weeks to a final daily dose of 5 mg/m2/d. The drug was then stopped. The spleen had decreased to one third of the initial volume. Clinical conditions and haematological indices improved substantially. Intrasplenic therapy could be a new therapeutic tool for hypersplenism in chronic idiopathic and post-myeloproliferative myelofibrosis.     

Splenic regrowth in sickle cell anaemia following hypertransfusion

We describe five adult patients with sickle cell anaemia (SS) who developed clinical, radiological and histological evidence of splenic regrowth while receiving regular blood transfusions. Five patients, all homozygous SS, range 23–34 years, were commenced on hypertransfusion therapy. Three patients were transfused because of severe recurrent vaso-occlusive crises, one for chronic sickle lung and one in an attempt to prevent deterioration of renal function. The mean duration of hypertransfusion prior to documentation of splenic regrowth was 52 months (range 12–97 months). Two patients developed significant hypersplenism. One patient had clinically-apparent splenomegaly and four patients had splenomegaly documented on ultrasound. Splenic regrowth in hypertransfused adults with sickle cell anaemia is not infrequent and may have important clinical implications.     

Erythrokinetic Studies as a Guide to the Value of Splenectomy in Primary Myeloid Metaplasia

S ummary . Red cell survival, plasma volume and erythrokinetic studies were carried out in 13 patients with progressive myeloid metaplasia. The patterns obtained were extremely variable. The majority had a haemodilutional anaemia, due to expansion of the plasma volume, which showed a rough correlation with splenic size. Although most patients showed evidence of haemolysis, only two had a severe haemolytic anaemia. Eight cases were selected for splenectomy; the best results were obtained in those in whom medullary erythropoiesis was still demonstrable by ferrokinetic studies pre-operatively. In another two cases the spleen appeared to be the principal organ of erythropoiesis. Patients who had a haemodilutional anaemia pre-operatively showed a substantial contraction in the plasma volume after splenectomy and, although this may not occur immediately after operation, it appears to be of long duration. It is suggested that the possibility of splenectomy be considered at an earlier stage in the evolution of the disease than has previously been customary.     

Radiofrequency ablation for treatment of hypersplenism: A feasible therapeutic option

We present a case of a patient with hypersplenism secondary to portal hypertension due to hepato-splenic schistosomiasis, which was accompanied by severe and refractory thrombocytopenia. We performed spleen ablation and measured the total spleen and ablated volumes with contrast-enhanced computed tomography and volumetry. No major complications occurred, thrombocytopenia was resolved, and platelet levels remained stable, which allowed for early treatment of the patient’s underlying disease. Previous work has shown that splenic radiofrequency ablation is an attractive alternative treatment for hypersplenism induced by liver cirrhosis. We aimed to contribute to the currently sparse literature evaluating the role of radiofrequency ablation (RFA) in the management of hypersplenism. We conclude that splenic RFA appears to be a viable and promising option for the treatment of hypersplenism.     

Partial splenic embolization as pretreatment for antiviral therapy in hepatitis C virus infection

Chronic hepatitis C virus infection is frequently complicated by cirrhosis and hypersplenism, which together with several other factors, such as reduced thrombopoietin synthesis in the liver, cause cytopenia. The antiviral combination therapy with pegylated interferon and ribavirin itself is impaired by haematological toxicity. Partial splenic embolization (PSE) by the injection of microspheres via a catheter comprising approximately 30-70% of the splenic parenchyma is now a safe method, which significantly reduces the cytopenia induced by hypersplenism, especially thrombocytopenia. The effect is long lasting up to 20 years and has been documented in a variety of disorders. PSE is now carefully described in a combination modality as a pretreatment to reduce cytopenia in hepatitis C virus-induced cirrhosis patients with hypersplenism, making antiviral therapy possible per se at higher dosages with a sustained duration.     

The Utilization of a New Strength Citrate Anticoagulant during Centrifugal Plateletpheresis: I. ASSESSMENT OF DONOR EFFECTS

It has been suggested that the megaloblastic anaemia in pernicious anaemia is due to inadequate intracellular concentration of monoglutamyl folates other than methyltetrahydrofolate caused by diminished conversion of methyltetrahydrofolate to tetrahydrofolate (methylfolate trap). To test this, we have increased the concentration of methyltetrahydrofolate in the plasma of six patients with pernicious anaemia by feeding DL-5-formyltetrahydrofolate. The effect of therapy on bone marrow morphology and routine haematologic parameters was measured. Of two patients receiving 800 mug/d of DL-5-formyltetrahydrofolate, one had a significant response; of four receiving 6 mg/d, one converted erythroid maturation to normoblastic, and in two others some improvement was noted in levels of neutrophils, platelets or reticulocytes although marrow morphology remained megaloblastic. Response did not correlate with the degree of elevation of plasma folate. In patients receiving this therapy, slight increase of methylcobalamin in plasma may have occurred (P less than 0.05). These observations support ineffective utilization of methyltetrahydrofolate as the major cause of megaloblastic anaemia in pernicious anaemia, but indicate that the degree and location of block varied in different patients, and in different precursor cells of a single patient.     

脾动脉阻断技术在射频消融治疗门脉高压性脾功能亢进症中的应用

目的探讨脾动脉阻断技术联合脾脏射频消融（RFA）治疗门静脉高压性脾功能亢进症（脾亢）的有效性和临床应用前景。方法对阻断或未阻断脾动脉主干的接受脾脏RFA治疗的肝硬化性门静脉高压合并重症脾亢患者,分析随访6个月的临床疗效;并评估脾动脉阻断对肝硬化合并脾动脉盗血综合征的治疗效果。结果阻断或未阻断脾动脉主干的接受脾脏RFA治疗的门脉高压性脾亢患者各15例,术后未发生严重并发症。阻断脾动脉后实施脾脏RFA组消融（56±35）%脾脏体积,较未阻断脾动脉组消融体积（38±21）%显著增加（P〈0.01）;且阻断脾动脉组治疗后血小板计数、Child-Pugh评分和分级改善明显优于未阻断脾动脉组。合并巨脾的脾动脉阻断组15例患者经影像学诊断都符合脾动脉盗血综合征诊断,经脾动脉栓塞（13例）和脾动脉结扎（2例）后肝动脉内径显著增粗,肝动脉供血明显改善。结论脾动脉阻断联合脾脏射频消融术是治疗门静脉高压性脾亢,可以显著提高脾亢治疗的安全性和有效性,同时纠正脾动脉盗血综合征和有效改善肝功能。     

Studies of Splenic Function in the Myeloproliferative Disorders and Generalized Malignant Lymphomas

The relative importance of splenic red-cell pooling, sequestration and cell destruction in the causation of anaemia has been studied in 29 patients—16 with generalized lymphoproliferative disease, 12 with myeloproliferative disease and one with idiopathic autoimmune haemolytic anaemia.
A scanning method with [¹¹C]carbon monoxide was used for direct in vivo measurement of splenic red-cell volume, and the spleen was delineated by-a scan after injection of ⁸¹Rb-labelled red cells, damaged with non-radioactive 1-mercuri-2-hydroxypropane (MHP). The clearance time of the damaged cells from the circulation was used as an index of splenic function. The fraction of red cells in the spleen varied from 2.9% to 32% and the splenic red-cell volume ranged from 38 to 1000 ml. In patients with lymphoproliferative disorders their spleens contained a smaller proportion of red cells, relative to splenic size, than patients with myeloproliferative disease. Clearance of cells damaged with 1-mercuri-2-hydroxypropane (MHP) was 30–60 min in normal subjects. Slow clearances were found in some patients with lymphosarcoma; fastest clearances occurred in patients with obvious haemolytic anaemia. No clear relationship was noted between the rate of clearance and splenic size or splenic red-cell volume.     

多层螺旋CT全肝灌注成像对不同程度脾功能亢进患者肝脾血流状态的评估

目的应用多层螺旋CT全肝灌注模式,探讨不同程度脾功能亢进患者脾脏体积、肝总动脉、脾动静脉、门静脉内径差异及肝脏血流状态变化情况。方法收集慢性乙型肝炎肝硬化脾功能亢进患者42例,无肝脾疾病患者15例作为对照,所有患者均行多层螺旋CT全肝灌注成像:(1)测量比较不同程度脾功能亢进组与对照组脾脏体积、肝总动脉、脾动静脉、门静脉内径之间的差异;(2)分析比较脾脏体积与各相关血管内径之间的相关性;(3)测量比较基于Couinaud分段肝脏五叶相关灌注参数值:肝动脉灌注量(HAP)、门静脉灌注量(PVP)、总肝灌注量(TLP)和肝动脉灌注指数(HPI)。计量资料采用单因素方差分析,采用Pearson相关分析对脾脏体积与各血管内径进行相关性分析。结果(1)肝硬化脾功能亢进组脾脏体积及脾动脉、脾静脉、门静脉内径均大于对照组,差异有统计学意义(F值分别为37.108、17.484、23.124、13.636,P值均<0.05)。(2)中、重度脾功能亢进组脾脏体积及脾动脉、脾静脉、门静脉内径明显大于轻度脾功能亢进组,差异有统计学意义(F值分别为25.418、13.293、15.136、7.093,P值均<0.05),但中、重度脾功能亢进组间差异无统计学意义(P>0.05)。(3)脾静脉、门静脉、脾动脉内径与脾脏体积呈正相关(r值分别为0.680、0.548、0.726)。(4)脾功能亢进组全肝叶PVP、TLP均低于对照组,差异有统计学意义(P<0.05);不同程度脾功能亢进组HPI均高于对照组,中、重度脾功能亢进组肝右后叶HPI高于轻度脾功能亢进组,差异有统计学意义(F值为3.555、4.570,P值均<0.05);各组间全肝叶HAP差异无统计学意义(P>0.05),但重度脾功能亢进组全肝叶HAP均低于对照组、轻及中度脾功能亢进组。结论不同程度脾功能亢进患者脾动静脉内径均有不同程度的增宽,与脾脏体积增大一致,且中、重度为著;不同程度脾功能亢进患者门静脉灌注量及总肝灌注量均减少,肝动脉灌注量以重度脾功能亢进患者减少显著。     

Interrelationship between splenic and superior mesenteric venous circulation manifested by transient splenic arterial occlusion using a balloon catheter

We examined the hemodynamic changes induced by transient splenic arterial occlusion using a balloon catheter to investigate the hemodynamic effect of transcatheter splenic arterial embolization--a procedure that has been used since its introduction in 1973 as therapy for hypersplenism and more recently for portal hypertension. The blood flow volume was measured in 20 patients with liver disease using an ultrasonic duplex system (Toshiba SAL50A/SDL-01A). The portal venous pressure was also measured via a 3F catheter using a transducer. The catheter was placed in position by substituting it for a 25-gauge needle that had been inserted into the portal vein under ultrasonic guidance percutaneously and transhepatically. Splenic arterial occlusion caused a drop in splenic venous blood flow from 708 +/- 487 to 241 +/- 155 ml per min, in portal venous blood flow from 993 +/- 439 to 807 +/- 419 ml per min and in portal venous pressure from 17.4 +/- 7.2 to 14.4 +/- 6.1 mm Hg. The latter two reductions were less than expected from the decrease in the splenic venous blood flow volume. This phenomenon was caused by an increase in the mesenteric venous blood flow from 475 +/- 126 to 630 +/- 270 mm per min. This increase may be due to a compensatory mechanism under the control of a regulatory loop in the liver or portal vein, and there seems to be a relationship between splenic and intestinal circulation in portal hypertension that maintains hepatic circulation.     

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.     

Bleeding portal-hypertensive gastropathy managed successfully by partial splenic embolization

The use of partial splenic embolization to decrease portal pressure and reduce gastric bleeding from portal-hypertensive gastropathy, a complication of liver cirrhosis, is described. A 62-year-old man with hepatic cirrhosis secondary to hepatitis C and documented portal hypertension was admitted with hypersplenism and bleeding esophageal varices. Endoscopic ligation successfully controlled acute bleeding, but blood loss continued over the next 45 days. Bleeding secondary to portal-hypertensive gastropathy was diagnosed endoscopically. The patient's poor surgical status precluded a portosystemic shunt procedure, so partial splenic embolization was performed radiologically by the injection of Gelfoam squares. Splenic volume decreased 50% following partial embolization. Over 3 weeks, the hemoglobin concentration increased from 8.5 g/dL to 9.8 g/dL, and the platelet count increased from 41,000 to 90,000/microL. Repeat endoscopy found no gastric bleeding 18 days post-procedure. Partial splenic embolization is a radiologic procedure which can be performed safely in patients too ill to undergo portosystemic shunt. This report documents its successful use to manage hypersplenism and reduce portal pressure in a cirrhotic patient with portal-hypertensive gastropathy and hypersplenism.