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HLA class II alleles in Japanese patients with immune thrombocytopenic purpura. Associations with anti-platelet glycoprotein autoantibodies and responses to splenectomy.

HLA class II alleles and immunoglobulin allotypes were determined in 83 Japanese patients with immune thrombocytopenic purpura (ITP) and 114 race-matched healthy controls. Distribution of DRB and DQB1 alleles as well as G1M(f, z), G2M(n+, n-), and KM(1, (1,2), 3) were not different between ITP patients and healthy controls, while DPB1*0201 was marginally increased in ITP patients vs. healthy controls (51% vs. 28%, Pc= 0.04, OR=2.6 [1.4-4.8]). In contrast, strong associations between anti-glycoprotein autoantibodies and HLA class II genes were found as follows: antiGPIIb-IIIa antibody with DRB1*0405 and DQB1*0401; and anti-GPIb-IX antibody with DRB1*0803 and DQB1*0601. When factors influencing therapeutic responses to splenectomy were examined, a poor response was correlated with the presence of DRB1*0405, DQB1*0401 and anti-GPIIb-IIIa antibody (P=0.01, 0.002, and 0.03, respectively). Our results indicate that HLA class II genes influence the production of anti-glycoprotein antibody specificities rather than the development of ITP. In addition, HLA class II genotyping could be useful in predicting therapeutic responses to splenectomy in Japanese patients with ITP.

Adult↗

Refractory chronic GVHD emerging after splenectomy in a marrow transplant recipient with accelerated phase CML.

We report a 39-year-old female patient who underwent HLA-identical sibling allogeneic BMT for CML in accelerated phase. Severe pancytopenia refractory to G-CSF associated with progressive splenomegaly and RBC/platelet transfusion dependency were present from day +60 after BMT. MRD assessed by FISH and RT-PCR multiplex for BCR-ABL rearrangement was negative, and complete chimerism was documented by VNTR on days +100, +180, +360 and 2 years after BMT. Splenectomy was performed on day +225 and pancytopenia resolved but chronic extensive graft-versus-host disease developed, with hepatic cholestasis, diffuse scleroderma and sicca-like syndrome. She was sequentially and progressively treated with different immunosuppressive therapy combinations with no clear benefit. On day +940, she presented with infection over the previously present ulcers on both limbs, which culminated in septic shock and death on day +1041. We conclude that, although splenectomy may reverse poor graft function after allogeneic BMT, hyposplenism may trigger or worsen chronic extensive GVHD leading to increased morbidity and mortality.

Adult↗

2-Chlorodeoxyadenosine treatment after splenectomy in patients who have myelofibrosis with myeloid metaplasia.

2-Chlorodeoxyadenosine (2-CdA) is a purine nucleoside analogue with therapeutic activity in low-grade lymphoproliferative disorders. In addition, 2-CdA has a potent myelosuppressive effect, and it has been shown to be toxic to malignant myeloid cells both in vitro and in vivo. In this pilot study we treated nine patients who had advanced myelofibrosis with myeloid metaplasia (MMM) and progressive hepatomegaly or symptomatic thrombocytosis after therapeutic splenectomy. 2-CdA was administered at 0.05-0.1 mg/kg/d for 7 d for one to five treatment cycles. A reduction in liver size associated with marked improvement in fatigue and control of thrombocytosis and leucocytosis was achieved in seven of the nine patients (78% response rate). In four of the seven responding patients the reduction in liver size was durable (4-28 months) and was associated with a decrease in serum alkaline phosphatase levels. However, no patient had improvement in anaemia, and two of the seven initially responding patients have since died of acute leukaemia or progressive disease. Improvement in bone marrow fibrosis was noted in two of five available post-treatment marrow examinations. Toxicity was mainly myelosuppression, which was severe in two patients. 2-CdA may be considered a palliative therapeutic agent after splenectomy in noncytopenic patients with MMM who have progressive hepatomegaly or extreme thrombocytosis.

Anemia↗

Laparoscopic splenectomy: single-centre experience of a district general hospital.

We report the results of 20 consecutive laparoscopic splenectomies performed on haematology patients for a number of indications. Our series includes patients up to 77 years of age at the time of surgery and removal of spleens weighing up to 3530 g. The most significant benefit is the early rate of discharge post-operatively (median 2 d); however, there is a risk of conversion to open laparotomy (in this series 3/20, 15%). We show that laparoscopic splenectomy can be offered as a therapeutic option to patients unfit for conventional laparotomy and that even large and bulky spleens can be removed safely using this approach.

Adolescent↗

Long-term decrease of CD4+CD45RA+ T cells and impaired primary immune response after post-traumatic splenectomy.

Congenital or acquired absence of the spleen and functional hyposplenism are associated with abnormalities of host defence such as an increased susceptibility to infection with encapsulated bacteria. The effects of the lack of the spleen on cell-mediated immunity are largely unknown. In the present study we have investigated peripheral blood lymphocyte subpopulations in healthy adults who had undergone splenectomy because of severe abdominal trauma > 4 years before the study. The results show a significant reduction in the percentage of CD4+ T cells due to a selective and long-term decrease in the percentage of CD4+CD45RA+ lymphocytes, the CD4+ T-cell subset mainly involved in primary immune responses to newly encountered antigens. Levels of the reciprocal CD45RO+CD4+ T-cell subset were comparable between splenectomized and control individuals, as were lymphoproliferative responses and IFN-gamma production to recall antigens. Decreased levels of CD4+CD45RA+ cells were accompanied by an impairment in primary immune responsiveness, as assessed by investigating T-cell proliferation to stimulation with keyhole limpet haemocyanin and by measuring antibody responses following primary immunization with a clinically relevant T-dependent antigen, hepatitis A vaccine, in vivo. These findings suggest a possible role of the spleen in the generation, maintenance and/or differentiation of naive, unprimed T cells or their precursors, which might have a possible functional relevance for primary immune responses following splenectomy.

Abdominal Injuries↗

On the mechanism of post-splenectomy leukocytosis in mice.

BACKGROUND: Increased number of peripheral white blood cells (PWBCs) has been noted after removal of the spleen. DESIGN: To clarify the possible mechanisms by which splenectomy affects the PWBC number, the percentage of apoptotic PWBCs, the number and migration rate of peritoneal cells, as well as the 3H-TdR incorporation into PWBCs, were examined in splenectomized, sham-operated and control mice. In addition, the effect of control plasma injected to splenectomized animals on the number of PWBCs was examined. RESULTS: One and two months after splenectomy the PWBC counts significantly increased, whereas the percentage of apoptotic PWBCs and the number of cells in the peritoneal cavity decreased in comparison with that of the control and sham-operated mice. Seventeen days after injection of carboxy-fluorescein diacetate succinimidyl ester (CFSE)-labelled peritoneal cells into the peritoneal cavity of the animals, their number was significantly higher in the peripheral blood and lower in the peritoneal cavity of the splenectomized animals in comparison with that of the control and sham-operated mice. Injection of control plasma into the splenectomized mice prevented the development of postsplenectomy leukocytosis. Finally, 3H-TdR incorporation into nonstimulated and Con A stimulated PBMCs from the splenectomized mice was higher as compared with cells from the control and sham-operated mice. CONCLUSIONS: The results of the study present several mechanisms that may clarify the cause of postsplenectomy leukocytosis.

Animals↗

ABO-incompatible liver transplantation with no immunological graft losses using total plasma exchange, splenectomy, and quadruple immunosuppression: evidence for accommodation.

ABO-incompatible liver transplants (LTX) have been associated with a high risk of antibody-mediated rejection, poor patient and graft survival, and a high risk of vascular thrombosis and ischemic bile duct complications. We used pretransplantation and posttransplantation double-volume total plasma exchange (TPE), splenectomy, and quadruple immunosuppression (cyclophosphamide or mycophenolate mofetil, prednisone, cyclosporine or tacrolimus, and OKT3 induction) in 14 patients receiving ABO-incompatible LTX between June 1992 and February 2001: A(1) to O (seven), B to O (two), B to A (two), A to B (one), AB to A (one), and AB to O (one). Actuarial 1- and 5-year patient and graft survival rates are 71.4% and 61.2 % and 71.4% and 61.2%, respectively, with a mean follow-up of 62.9 +/- 39.4 months. Ten acute cellular rejections occurred, and the mean time to the first episode was 62 +/- 33 days. All were steroid sensitive. No antibody-mediated rejection or vascular thromboses occurred. Pretransplantation pre-TPE immunoglobulin (Ig) G mean isohemagglutinin titers were 262 +/- 326, compared with pretransplantation post-TPE titers of 65 +/- 103 (P =.04). Eight of nine patients with measurable titers before and after TPE achieved a reduction in titers. The mean number of posttransplantation TPE was 5.5 +/- 4.1 (range, 0 to 12), and the last TPE was on postoperative day 9.4 +/- 5.3. IgG isohemagglutinin titers 2 weeks posttransplantation had increased to 153 +/- 309 (P =.03 compared with pretransplantation pre-TPE IgG). ABO-incompatible liver transplantations can be performed with acceptable patient and graft survival rates with a low risk of antibody-mediated rejection with a combination of TPE, splenectomy, and quadruple immunosuppression. Recovery of isohemagglutinin antibody levels without humoral rejection suggests that accommodation may be the protective mechanism preventing late antibody-mediated rejection.

ABO Blood-Group System↗

Portal vein thrombosis after laparoscopy-assisted splenectomy and cholecystectomy.

A 12-year-old girl underwent laparoscopy-assisted splenectomy and cholecystectomy with removal of her spleen through a small Pfannenstiel incision. She had an unremarkable postoperative course but returned 16 days later because of increasing right-sided abdominal pain. The pain was constant, sharp, and stabbing without radiation. Abdominal examination showed diffuse right upper quadrant and epigastric tenderness without peritoneal irritation. Laboratory test results included white blood cell count, 14.4 x 10(9)/mm3; hemoglobin, 8.5 g/dL; platelets, 1,483,000; and normal values for lipase, amylase, aspartate transaminase, and alanine transaminase. Evaluation with ultrasonography and vessel Doppler studies showed an occlusive thrombus throughout the portal and splenic veins. The patient underwent intravenous heparin anticoagulation therapy. Her symptoms resolved completely over the next 2 days. The patient is currently receiving warfarin and anagrelide as an outpatient (international normalized ratio, 2). There were no long-term complications caused by portal vein thrombosis. This is the first reported case of portal vein thrombosis after laparoscopic splenectomy in the pediatric population.

Anemia, Hemolytic, Autoimmune↗

Pharmacoeconomics of therapy for ITP: steroids, i.v.Ig, anti-D, and splenectomy.

Factors that influence the choice of therapeutic option in treating idiopathic thrombocytopenic purpura (ITP) include cost, toxicity, and efficacy of the agent. Today the most commonly used agents for treating ITP include glucocorticoids, intravenous immunoglobulin (i.v.Ig), anti-D, and splenectomy. Splenectomy cannot be avoided in some instances, but i.v.Ig, and anti-D offer viable treatment alternatives in many cases. i.v.Ig and anti-D are both equally efficacious; however, anti-D therapy may come with lower cost to the patient and the healthcare system. Thus, in treating patients with ITP, clinical and economic considerations should be considered when choosing among the various treatment options.

Adult↗

Postoperative recurrence of splenic epithelial cyst; treatment with subtotal splenectomy.

Three children were operated upon for congenital epithelial cysts of the spleen in the five-year period 1983-1987. Their mean age was 9.8 +/- 2.3 years. Two of them were boys. They comprise 1.6% of the surgical pathology of the spleen in our hospital, which is a Reference Centre for congenital haemolytic diseases. Two of the children had been suffering from intermittent colic pain in the left hypochondrium with a tender palpable mass for a short while to the present day. The third patient was asymptomatic; a splenic cyst with calcification of its wall was accidentally revealed by a plain x-ray of the abdomen. Contrast gastrointestinal studies and intravenous pyelography helped us with the diagnosis; they indicated a splenic mass that caused visceral displacement adjacent to the spleen. Ultrasonography proved the cystic nature of the enlargement of the spleen in all the cases. Marsupialization was performed in one patient and removal of the cysts in the other two. All three patients were followed up and re-checked 1-5 years postoperatively (May-June 1988). In one boy who underwent removal of the cyst four years ago, recurrence of the splenic cyst was revealed by ultrasonography, CT scan and radionuclide scan. Subtotal splenectomy was performed. The remaining upper pole is supplied with blood by the short gastric arteries. The recurrence was attributed to coexistence of invisible tiny cysts that had remained in the splenic tissue after the dissection of the major cyst during the previous operation. Subtotal splenectomy is an acceptable alternative procedure for splenic cysts.

Adolescent↗

Partial splenectomy in the treatment of thalassaemia major.

From 1981-1982 we performed partial splenectomy in 6 children with beta-thalassaemia major as an alternative to splenectomy to reduce transfusion and to preserve some splenic immune function. In two of our young patients with transfusion requirements of 150 ml/kg/year, where more than 2/3 of the spleen was removed, the number of transfusions was significantly reduced with prolonged intervals, haemoglobin rose with a marked improvement in the general condition, nutrition and growth. There were no major post-operative complications. 2 years' follow-up revealed no infection without sepsis prophylaxis.

Blood Transfusion↗

[Post-splenectomy infections and Pneumococcus vaccination in paediatric surgery (author's transl)].

Morbidity and lethality rates in pneumococal infections are higher among children with underlying diseases associated with restricted or absent splenic function. Vaccination with polyvalent vaccine is indicated in all children who are more than 2 years old and who have been splenectomized or have a congenital asplenia. Since protection by vaccination is 80% only, we combine the vaccination with penicillin prophylaxis for at present at least three to five years after splenectomy and draw the express attention of parents and family physicians to the limited nature of protection afforded by vaccination. An increase in the immunogenicity of polysaccharid antigen vaccine might lead to successful vaccination of children below 2 years of age who are notable for a particularly high risk of infection. First reports have been published in literature on the possibility of re-implantation of splenic tissue after post-traumatic rupture (17, 27, 28) so that it may become possible to employ this method additionally to pneumococcus vaccination. In case of haematological indication for splenectomy this should be postponed as far as possible until the child has completed his fifth year of life.

Antibodies, Bacterial↗

Two unusual cases of wandering spleen requiring splenectomy.

The occurrence of wandering spleen is rarely referred to in the pediatric surgical literature. We treated two unusual cases with this anomaly. The first case had an acute abdominal problem associated to a wandering spleen and a diaphragmatic eventration. Splenectomy was performed because of splenic infarction. In the second case the wandering spleen was associated with gastric bleeding due to left-sided portal hypertension, and splenectomy was inevitable.

Abdomen, Acute↗

[Remission of cold agglutinin disease following splenectomy].

An anaemia (haemoglobin content 8.3 g/dl) of undetermined cause, accompanied by mild jaundice and nocturnal leg oedema, developed in a 68-year-old woman who also had an increased erythrocyte sedimentation rate (128/135 mm). Primary cold-agglutinin anaemia was established as the cause. After administration of prednisone (2 mg/kg body-weight daily), cyclophosphamide (up to 150 mg daily) and plasmapheresis (twice weekly) had failed to bring about improvement, splenectomy achieved a clear reduction of haemolysis. At last examination the haemoglobin content had risen to 12 g/dl. This report demonstrates that in individual cases splenectomy may be useful, but it needs to be determined first by radioisotope study whether the spleen is in fact the main site of erythrocyte sequestration.

Aged↗

[Balloon catheter arterial occlusion before high-risk splenectomy and nephrectomy].

Balloon catheter occlusion of the splenic or renal artery was undertaken in 10 patients (7 men and 3 women, aged 20-76 years) 30 to 120 min before a splenectomy (n = 8) or nephrectomy (n = 2), for the purpose of preventing a high intra- and post-operative blood loss and facilitating the technical procedure of removing an often markedly enlarged spleen. The operation time after balloon catheter occlusion was only 60-140 min; intra- and post-operative complications did not occur, other than one instance of pneumonia and one of subcutaneous haematoma. This method would seem to be suitable for reducing the operative risk of splenectomy or nephrectomy in the presence of a giant spleen or reduced tolerance of operation.

Adult↗

Opsonic requirements for intravascular clearance after splenectomy.

We investigated the opsonic requirements for intravascular clearance of pneumococci in guinea pigs and of sensitized erythrocytes in human beings after splenectomy. The impaired clearance of injected pneumococci in splenectomized guinea pigs was corrected by immunization. This improvement in clearance was due to increased hepatic sequestration of organisms. There was a significant delay in antibody-mediated clearance of autologous erythrocytes sensitized with IgG (P < 0.001), although the rate of complement-mediated clearance in splenectomized patients was normal. A fourfold increase in sensitizing antibody resulted in a significant improvement in clearance that was due to increased hepatic sequestration (P < 0.005). One patient who had an intact spleen and who had previously received Thorotrast (thorium oxide) had impaired antibody-mediated clearance despite increased sensitization. These observations suggest that, after splenectomy the remaining macrophages of the reticuloendothelial system require increased amounts of antibody to mediate efficient intravascular clearance of opsonized particles.

Animals↗

Laparoscopic splenectomy: outcomes and lessons learned from over 200 cases.

BACKGROUND: In this study of laparoscopic splenectomy (LS), we evaluate prospectively gathered perioperative patient data and review lessons learned in the evolution of this procedure. METHODS: At 2 university medical centers between November 1993 and March 2000, there were 203 patients (122 female patients and 81 male patients) who underwent LS after preoperative evaluation. RESULTS: LS was successfully completed in 197 patients (97%). The mean operative time was 145.5 minutes and the length of stay averaged 2.7 days with 143 (70.4%) staying less than 48 hours. The most common indication was idiopathic thrombocytopenic purpura (ITP). Six patients required conversion to open splenectomy (OS), with only 2 conversions in the last 163 cases. No deaths were attributed to the procedure. Complications occurred in 19 patients (9.3%). Thirty accessory spleens were identified in 25 patients (12.3%). Seventeen patients (8.4%) underwent concomitant procedures, most commonly cholecystectomy. CONCLUSIONS: LS by the lateral approach is both safe and feasible in patients of all ages.

Adolescent↗

Hand-assisted laparoscopic splenectomy in patients with splenomegaly or prior upper abdominal operation.

BACKGROUND: Laparoscopic splenectomy (LS) in patients with significant splenomegaly or prior upper abdominal operation is technically challenging with a high conversion rate to open operation. We hypothesized that hand-assisted laparoscopic splenectomy (HLS) in this setting would improve operative (OR) outcomes without impacting post-OR ileus, length of stay, morbidity, or mortality, compared with LS. METHODS: All patients with splenomegaly (spleen weight > or = 500 g) or prior upper abdominal operation undergoing LS or HLS between March 1996 and June 2001 were reviewed. Nonparametric continuous variables were expressed as median and intraquartile range with statistical significance determined by Wilcoxon rank sum test. RESULTS: Of 41 patients reviewed, 22 underwent HLS, whereas 19 underwent LS. Median OR time for HLS was significantly less than for LS (161 minutes vs 212 minutes, P =.004). HLS was associated with a lower conversion rate (13.6% vs 36.8%, P =.08) and blood loss (325 mL vs 550 mL, P =.18) than LS, which approached statistical significance. HLS did not increase post-OR ileus, length of stay, morbidity, or mortality. CONCLUSIONS: HLS in patients with significant splenomegaly or prior upper abdominal operation significantly shortens OR time compared with LS without adversely impacting post-OR ileus, length of stay, morbidity, or mortality. In addition, HLS may be associated with a lower conversion rate and decreased blood loss.

Female↗