Immunoglobulin-induced hemolysis,splenomegaly and inflammation in patients with antibody deficiencies

IgG replacement for primary antibody deficiencies is a safe treatment administered to prevent recurrent infections and reduce mortality. Recently, several reports described acute hemolytic episodes following IgG administration due to a passive transfer of blood group alloantibodies, including anti-A, anti-B, as well as anti-Rh antibodies. Here, we reviewed and discussed the consequences of passively transferred RBCs antibodies. The chronic passive transfer of alloantibodies might also cause a subclinical condition due to a compensated extravascular chronic hemolysis with poorly understood consequences. This phenomenon might possibly represent an unrecognized cause of splenomegaly and might contribute to inflammation in patients with primary antibody deficiencies.     

Splenomegaly—an insensitive sign of portal hypertension

The prevalence of splenomegaly associated with portal hypertension was examined in a consecutive population of III patients who had portal hypertension diagnosed using specific endoscopie, sonographic, and Doppler signs. Splenic size was measured objectively via its cranio-caudal length on coronal section using ultrasound and by clinical examination. Sonographically, 52% of patients had a definitely large spleen and 35% a spleen less than one standard deviation from the normal mean, while a further 13% had equivocal splenomegaly. Only 52% of patients had splenomegaly on clinical assessment. Splenomegaly was less common in patients with alcoholic (41% definite, 15% equivocal) than in those with non-alcoholic liver disease (66% definite, 17% equivocal, p= 0.02) and splenic length was significantly smaller in alcoholic patients (12.7±0.5cm) compared to patients with either non-alcoholic liver disease (15.0±0.6cm, p= 0.003) or portal hypertension due to vascular occlusive diseases (16.5 ± 2.0 cm, p= 0.006). Splenomegaly, whether assessed sonographically or clinically, is an insensitive sign of portal hypertension and its absence cannot be used as a negative predictor of the presence of portal hypertension in patients with chronic liver disease.     

Splenic respiratory gas exchange and glucose uptake in patients with splenomegaly in hypersplenism and hodgkin's disease

Summary Blood samples are taken from the splenic artery, vein and pulp of patients suffering from Hodgkin's disease (n=10) or hypersplenism (n=7) and undergoing splenectomy. In these samples, the relevant parameters of the respiratory gas exchange as well as glucose and lactate concentrations are determined. In hypersplenism (mean splenic wet weight: 543 g) the mean oxygen consumption of the splenic tissue amounts to 0.9 ml O₂/100 g/min taking into account a mean splenic blood flow of 80 ml/100 g/min. The glucose uptake and the lactate release are 9 mg/100 g/min and 5.5 mg/100 g/min, respectively. These values are in close agreement with the results obtained in the normal and undisturbed spleen in situ. In Hodgkin's disease (mean splenic wet weight: 484 g) an increase is occurring in oxygen consumption ( =1.3 ml O₂/100 g/min) and in glucose uptake ( =13 mg/100 g/min). The corresponding lactate release by the splenic tissue into the venous blood is calculated to be 9.6 mg/100 g/min.Despite high glucose uptake rates and pronounced glycolytic activities there is no evidence for the existence of low pH-values, a glucose depletion or hypoxia within the enlarged spleen in hypersplenism and Hodgkin's disease. Within the enlarged spleens investigated here, the intrasplenic conditioning of red blood cells during splenomegaly is nearly the same as in the normal and undisturbed spleen in situ. It cannot be demonstrated that the slight changes in red cells caused by the metabolic peculiarities of their intrasplenic environment in hypersplenism account for the intensified intrasplenic sequestration of red blood cells in hypersplenism.Dedicated to Professor Dr. med. F. Kümmerle to his 60th birthday     

诊断性脾切除术对不明原因发热伴脾肿大的临床意义

目的探讨不明原因发热伴脾肿大行诊断性脾切除术的临床意义及可能的危险因素。方法回顾分析了我院20年来因不明原因发热、脾肿大行剖腹探查加诊断性脾切除术的54例患者的临床资料及病理检查结果,并对可能的危险因素进行分析。结果54例患者手术后经病理确诊39例,病理诊断率为72．2％（39／54）,其中恶性淋巴瘤32例（59．3％,32／54）。25．9％的（14／54）患者出现手术并发症,并发症发生依次主要为：术后感染、出血、心功能衰竭、肝功能衰竭及膈下积液。9例（16．7％）患者围手术期死亡,死亡原因主要为：严重感染、术后出血、本身疾病恶化、心功能衰竭、肝功能衰竭及猝死。在相关危险因素中,有、无浆膜腔积液组死亡率分别为46．2％和7．5％（P=0．011）;脾脏重量≤500g,500—1500g及≥1500g组围手术期死亡率分别为0％、11．8％、50．0％（后2组比较,P=0．01）;有无黄疸、血三系减少、转氨酶升高及乳酸脱氢酶升高及病程长短与围手术期死亡率无明显相关（P〉0．1）。浆膜腔积液和巨脾是相对独立的影响死亡的因素（P值分别为0．011和0．01;／bY分别为20．4和18．6）。结论不明原因发热伴肝脾肿大患者,在高度怀疑恶性血液病但又不能明确诊断时,剖腹探查及诊断性脾切除术是有意义的方法。合并浆膜腔积液及巨脾者围手术期死亡率增高。     

Influence of aggression on erythropoiesis--the hypersympathetic syndrome

Male CF₁ mice were isolated for 3 weeks at weaning. Pairs were then selected for similarity in weight and placed together for two 30 min periods per day for 21 days. A dominant-subordinate relationship was established by fighting. The subordinate animals developed a marked splenomegaly, decreased hematocrit and increased reticulocyte count while dominant and control mice showed no change in these parameters. The experiment was repeated using splenectomized individuals. Again the subordinates showed decreased hematocrits and increased reticulocyte counts with no change observed in dominants and controls. An hypothesis is advanced which suggests that the behaviorally induced stimulus to erythropoiesis results from a series of events which we have termed a hypersympathetic syndrome.     

Splenic blood flow and intrasplenic flow distribution in rats

Summary In 75 rats, anesthetized with pentobarbital and breathing spontaneously, regional splenic blood flow (rSBF) was measured by means of the⁸⁵Kr(β)-clearance technique after an intraaortic slug injection of the dissolved indicator. In the normal and undisturbed spleen in situ rSBF is linearly related to the mean arterial blood pressure (MABP) within the range of 30–140 mm Hg. Mean rSBF is 0.71 ml/g/min, the mean arterial blood pressure being 105 mm Hg. In normal rats rSBF decreases significantly with increasing body weight or age. After total obstruction of the open circulation by application of rigid spherocytes, mean rSBF is reduced to 0.26 ml/g/min and is independent of the mean arterial blood pressure within the same range. In splenomegaly, due to enhanced reticuloendothelial activity and intensified immunological responses after tumor implantation, an increase in total splenic blood flow is found. However, related to 1 g of splenic wet weight, rSBF is diminished. In splenomegaly, rSBF also linearly depends on MABP within a wide range. Mean rSBF is 0.51 ml/g/min, the mean arterial blood pressure being 91 mm Hg. The distribution of intrasplenic blood flow between open and closed circulation depends on the size of the mean arterial blood pressure. The perfusion rate of the open circulation, compared with rSBF amounts to 72–93% (MABP=80–130 mm Hg).     

Practical Measures of Clinical Benefit With Ruxolitinib Therapy: An Exploratory Analysis of COMFORT-I

BackgroundThe phase III COMFORT (Controlled Myelofibrosis Study With Oral JAK inhibitor Treatment)-I and COMFORT-II trials in patients with intermediate-2 or high-risk myelofibrosis (MF) showed that ruxolitinib was superior to placebo and best available therapy, respectively, for improvements in spleen volume, MF-related symptoms, and overall survival (OS). However, patients managed in community settings might not have access to the methods used in the COMFORT trials. In this exploratory analysis we summarize efficacy findings of COMFORT-I using practical, community-oriented measures of patient outcomes.Patients and MethodsIn this post hoc analysis of data from COMFORT-I we evaluated changes from baseline to week 12 in spleen size (palpable length and volume), patient-reported outcomes (Patient Global Impression of Change; Myelofibrosis Symptom Assessment Form; Patient-Reported Outcomes Measurement System Fatigue Scale), body weight, and serum albumin levels in 5 subgroups of ruxolitinib-treated patients on the basis of week 12 spleen length changes from baseline: (1-4) ≥ 50%, 25% to < 50%, 10% to < 25%, or < 10% reduction; and (5) worsening. OS was evaluated in ruxolitinib-treated patients with week 12 spleen length reductions from baseline ≥ 50%, 25% to < 50%, or < 25% (including worsening).ResultsIn all spleen length subgroups, including patients with worsening spleen length at week 12, ruxolitinib (n = 150) was associated with improvements in spleen volume, patient-reported symptom burden, body weight, and serum albumin levels. Greater reductions in spleen length were associated with prolonged OS.ConclusionA variety of assessment methods beyond palpable spleen length that are easily accessible in the community setting might be useful in evaluating the clinical benefit of ruxolitinib over time in patients with MF.     

门静脉高压症合并脾肿大外周血细胞的变化

目的 探讨门静脉高压症合并脾肿大患者外周血细胞变化情况,以及外周血细胞改变的原因.方法 同顾性分析1991年1月至2006年12月收治309例门静脉高压症合并脾肿大患者的临床资料.按外周血细胞是否减少,分为减少组(278例)和非减少组(31例).结果 减少组278例中177例为多种血细胞减少,包括全血细胞减少71例,WBC+PLT减少48例,RBC+PLT减少25例,WBC+RBC减少33例;101例为单种血细胞减少,其中PLT减少28例,WBC减少26例,RBC减少47例.手术切除脾脏后,减少组患者的血细胞均明显升高(t=6.53,P<0.01);非减少组31例,全血细胞均在正常范围.结论 门静脉高压症合并脾肿大患者不一定均有外周血细胞减少.外周血细胞减少是脾肿大的并发症,但不是必然表现.对于部分患者外周血细胞没有减少,其原因可能与脾脏病理改变轻和骨髓极度增生有关.     

A Case Report of Early Idiopathic Portal Hypertension

We report herein a case (46 years, female) of very early idiopathic portal hypertension. During an examination for in situ uterine cervical cancer, splenomegaly and hypersplenism were incidentally found. CT and MRI showed a nonatrophic liver with dilated portal veins and marked splenomegaly. The portal venous blood flow was increased, while portal venous blood pressure was not high. The spleen (1,220 g) showed hyperplasia of white pulp and congestion. The lobular architecture of the liver was well-preserved, and the subcapsular regions were not atrophic or dropped out. The portal tracts were not fibrotic, and portal veins were neither stenotic nor sclerotic. Instead, lymphoid cell infiltrations were found in about half the portal tracts, and there was subendothelial mononuclear cell infiltration of small portal vein branches. The hepatic lobules showed non-specific reactive change. This case suggests that early hepatic changes recognizable histologically in this disease are lymphoid cell infiltration of the portal tract and of subendothelial regions of portal vein branches, and nonspecific lobular hepatitis. These hepatic changes, as well as marked splenomegaly, may represent an altered immunophenomenon of this disease.