Signs Of Hypersplenism Research Articles

Splenic hamartomas in children.

Splenic hamartomas (SHs) are uncommon, benign vascular lesions of unclear etiology and are mostly found incidentally on abdominal images, at surgery, or at autopsy. Since the first case description, in 1861, less than 50 pediatric SH cases have been reported in the literature. In this article, we have performed an analysis of all SH cases in children published in the literature to date and presented our case of an 8-year-old male with SH. These lesions in children were shown to cause symptoms more often than in the adult population. The observed SH sizes in children ranged from a few millimeters to 18 cm, and the symptomatic lesions were mostly larger or multiple. The most common clinical finding was splenomegaly. Signs of hypersplenism were present in children with a single SH larger than 4.5 cm (diameter range: 4.5-18.0 cm) and in those with multiple hamartomas, ranging from a few millimeters to 5 cm. Eighty percent of patients with available laboratory findings had hematological abnormalities such as anemia, thrombocytopenia, or pancytopenia. Other symptoms and signs included abdominal pain, recurrent infections, fever, night sweats, lethargy, growth retardation, and weight loss. The use of multiple imaging modalities may suggest the preoperative diagnosis of a splenic mass in children and determine the therapeutic approach. However, the final diagnosis of SH relies on histopathological evaluation. Surgery, including total or partial splenectomy (PS), is the mainstay of SH management. Although total splenectomy carries a greater risk of overwhelming post-splenectomy infection than PS it has remained the most performed surgical procedure in children with SH. In the majority of pediatric patients with symptomatic SH, resolution of symptoms and resolution or improvement of cytopenias occurred after surgical treatment.

Тирозинемія типу І у дитини: з досвіду гематолога

Tyrosinemia is a rare metabolic disease resulting from a metabolic disorder of amino acids, which can occur under the «masks» of various diseases, debut as a hemorrhagic syndrome in children of all age groups, hepatolienal syndrome, hypoglycemia, rickets-like disease, peripheral neuropathy. Clinical case. In our publication, we report on a girl at the age of 1 year 7 months who had recurrent nosebleeds, which led to a referral to a hematologist. Examination revealed hepatomegaly with impaired liver function (hypoproteinemia, long-term resistant hypoglycemia, coagulopathy) with the development of chronic liver failure, ascites and splenomegaly with signs of hypersplenism, ascites, and nephromegaly. Differential diagnostics was carried out between oncohematological process, myelodysplastic syndrome (MDS) and metabolic disease. Type 1 tyrosinemia (hereditary infantile tyrosinemia (HT-1)) was verified by a combination of clinical and biochemical, molecular genetic studies. Verification of the disease came from the spectrometry of amino acids, acylcarnitines, succinal acetates and molecular genetic studies. Molecular genetic studies in the INVITAE laboratory, USA revealed two pathogenic variants identified in the FAH gene c.1069G>T (p.Glu357*) and c.554-1G>T, which are associated with autosomal recessive tyrosinemia. The emphasis in the publication is on the differential diagnosis, the effectiveness of the treatment of this orphan disease. The method of pathogenetic therapy of HT-1 is described in detail, both with the use of the drug nitisinone (orphadin) registered in Ukraine, a special diet with a low content of phenylalanine / tyrosine, which have a pronounced positive clinical effect and prevent the formation of irreversible disabling disorders. We emphasize the need for early diagnosis of HT-1 and support the Ministry of Health of Ukraine in the initiative of routine neonatal screening for orphan diseases, which include HT-1, since timely treatment improves the quality of life in these patients. The research was carried out in accordance with the principles of the Helsinki declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors. Key words: hepatosplenomegaly, nephromegaly, tyrosinemia type 1, children.

Transfusion surgeries and infusion therapy in patients with malignant non-Hodgkin’s lymphoma after splenectomy

Objective. To present the immediate results of the splenectomy and preferable variants of transfusion therapy performance in patients with malignant non-Hodgkin’s lymphoma (MNHL).
 Materials and methods. 109 splenectomies were performed in patients with MNHL at the Department of General and Hematological Surgery of the institute from 1987 to 2020. The surgery was conducted by upper middle laparotomy under general anesthesia with intubation and, in particular cases, under spinal anesthesia.
 Results and discussion. The indications for splenectomy in patients with MNHL were as follows: massive splenomegaly, abdominal syndrome, associated hemocytopenia, inefficacy of cytostatic therapy, absence of diagnosis. All patients underwent vaccination against capsular bacteria for prevention of post-splenectomy infection in 10-14 days prior to the surgery. In case of anemia, which has been observed in 55 % of patients, the RBC concentrate was applied. All the patients, who received corticosteroid hormones prior to splenectomy, were administered prednisolone and hydrocortisone in the amount of 3 mg/kg of body mass at similar doses in an hour before the surgery for prevention of adrenal insufficiency during the surgery. The patients, who did not receive those medications, were also intramuscularly administered prednisolone at a dose of 0.5 mg/kg of body mass in an hour before the surgery for the same aim. The patients with PLT value <150.0×109/L were administered 1-2 doses of PLT concentrate immediately before the laparotomy. M-gradient was found in blood serum of 3 patients prior to the surgery. They underwent courses of therapeutic plasmapheresis due to the risk of intraoperative hemorrhage. 2 patients with hyperleukocytosis (WBC >80.0×109/L) underwent two courses of leukapheresis. The patients with concomitant regional portal hypertension and in case of manipulations close to the pancreatic tail were administered somatostatin drugs in the course of the splenectomy. The splenectomy proved to be effective in 100 (92 %) of patients with MNHL: the great tumor mass was removed, the abdominal syndrome and concomitant hemocytopenia were neutralized, the signs of hypersplenism ceased, the hemolysis ceased, the cytostatic therapy became less necessary or unnecessary, the final diagnosis was established. The most serious postsurgical complications were acute adrenal failure (n=3), postsurgical intra-abdominal hemorrhage (n=2), pancreonecrosis (n=6). The postsurgical lethality was 2.7 %.
 Conclusions. The splenectomy proved to be effective in 92 % of patients with MNHL. The infusion therapy is individual for each patient and may include transfusion surgeries if indicated. The main objective of the infusion therapy in patients with MNHL is prevention and elimination of intra- and postsurgical complications.

Profile of Anemia in pediatric liver transplant recipients

Objection: To investigate the frequency, etiology and clinical significance of anemia in pediatric liver transplant recipients according to the pre-transplant and post-transplant file records. Material and Method: The study included 81 of 97 children with complete file records who underwent liver transplantation between May 2000 and February 2011 at the Istanbul University Istanbul School of Medicine Departments of Hepatobiliary Surgery and Pediatric Hepatology. We recorded hemoglobin values before and at 1st day, 1st week and 1st month after transplantation. Results: Majority of the transplanted children were males 67.9% and transplant recipients from living donors 76.5% . The median age of the patients was 54 months and most common indications of transplantation were cholestatic liver diseases 37% , metabolic liver disease 19.7% and cryptogenic cirrhosis 13.5% mostly with signs of hypersplenism. Anemia was detected before transplantation n=50, 61.7% , first day n=63, 77.8% , first week n=51, 63.0% and first month n=41, 50.6% of transplantation. The mean Hb values before 10.0±1.4 g/dL , and first day 9.42±1.32 g/dL , first week 9.75±1.20 g/dL , and first month 10.2±1.56 g/dL of transplantation. The Hb change between pre- and post-transplant periods was significant. Splenomegaly was detected in 36 of 50 cases with anemia before transplantation. A significant difference was detected between splenomegaly and anemia before transplantation. Splenomegaly was detected in 19 of 41 cases with anemia in the first month of post-transplant. Conclusion: The frequency of anemia has increased during early period of transplantation 77.8% in first day while its incidence significantly decreased by 50.6% in the first month of transplantation due to ameliorating hypersplenism. In addition, splenomegaly that has determinant role in frequency of anemia during pre-transplant period had lost its significance after transplantation.

Iliac-mesenteric-caval shunting in patients under two years of age. Case reports and review of the literature

Introduction: in treating portal hypertension in pediatric patients, some form of portosystemic shunting is indicated, a surgical procedure rarely used in patients under two years of age due to the infrequency of the condition in that age group and the increase in complications.1 Objective: discuss the experience and results of this procedure in patients under two years of age attended at the Hepatobiliopancreatic Surgery clinic of the General Surgery Service at Instituto Nacional de Pediatria. Discussion: the causes of portal hypertension at pediatric age are varied. Of extrahepatic manifestations, the most common is portal cavernomatous degeneration. Children under two years of age with portal hypertension have severe symptoms such as recurrent or anemia-causing digestive bleeding; others have signs of hypersplenism. In many cases medical treatment has no usefulness and surgical intervention, such as portosystemic shunting, is required to reduce the size of varices and prevent life-threatening bleeding. Conclusion: iliac-mesenteric-caval shunting in patients under two years of age is a feasible alternative which improves the patient’s clinical status, reducing the risk of bleeding; however, long-term studies are needed to observe such patients’ evolution.

Aggressive Systemic Mastocytosis Is Associated with a High Kit D816V Allele Burden in Peripheral Blood.

Abstract 2899Poster Board II-875According to 2008 WHO definitions, diagnosis of systemic mastocytosis (SM) is based on the presence of one major criteria (multifocal dense infiltrates of mast cells in bone marrow or organ biopsies) and at least one of the following minor criteria (i) >25% are atypical cells on bone marrow smears or are spindle-shaped in mast cell infiltrates of visceral organs, ii) KIT point mutation at codon 816 in the bone marrow or other extracutaneous organs, iii) mast cells express CD2 and/or CD25, iv) baseline serum tryptase concentration >20 ng/mL) or the presence of at least three minor criteria. Patients with aggressive SM (ASM) have to present with one or more C-findings (i) neutrophils <1,000/μL, Hb <10g/dL, or platelets <100,000/μL, ii) hepatomegaly with impaired liver function – elevated transaminases and/or bilirubin levels and/or hypoalbuminemia, iii) palpable splenomegaly with signs of hypersplenism, iv) malabsorption with significant hypoalbuminemia and/or significant loss. ASM and MCL are clearly associated with an inferior survival. The activating KIT D816V point mutation is thought to be pivotal for pathogenesis and potential targeted therapy with novel tyrosine kinase inhibitors. However, conventional sequencing (CS) of RNA/DNA extracted from bone marrow (BM) samples of SM patients reveals the mutation in less than 50-60% of patients while peripheral blood (PB) samples are frequently negative as consequence of low numbers of malignant cells and poor assay sensitivity. For better qualitative and additional quantitative assessment of the KIT D816V allele burden (expressed as ratio KIT D816V vs. KIT wildtype), we sought to establish (i) a D-HPLC (denaturing-high performance liquid chromatography) assay combined with direct sequencing in case of a positive D-HPLC signal and (ii) a LightCyclerTM based quantitative PCR (RQ-PCR). The assay sensitivities were calculated through serial cell (KIT D816V positive HMC-1 cells in NB4 cells) and RNA dilutions. The detection limit was estimated between 0.1 and 0.5% for both assays which was thus significantly improved in comparison to the detection limit of CS which was at 10–15%. Patient material was available from BM (n=134) and PB (n=93) from 173 patients (88 m, 85 f, median age 54 years) with diagnosis of SM including 10 patients with confirmed ASM (n=9) or aleukemic variant of MCL (n=1) according to WHO definitions. At diagnosis, D-HPLC, RQ-PCR and CS were positive in 78% (104/134), 84% (112/134) and 60% (80/134) of BM samples, respectively. Two patients had a KIT D816H and one patient had a KIT D816L mutation. In 54 cases with contemporaneously collected BM and PB samples, the KIT D816V mutation was found in PB of BM positive patients by D-HPLC, RQ-PCR and CS in 47% (22/46), 55% (27/49) and 38% (14/37) of cases, respectively. This information allowed the detection of the KIT D816V mutation in an additional 27 of 39 (69%) patients without available bone marrow biopsies. All ASM patients were KIT D816V positive in PB with a median KIT D816V allele burden of 36% (range 26–98%) vs. 7.8% (range 0.1–61%) in other stages of SM (p=0.0021). Eleven of 124 (8.9%) SM patients with a KIT D816V allele burden >20% are currently explored for the potential diagnosis of ASM or MCL. In conclusion, D-HPLC is a reliable and sensitive method for the screening of variable KIT mutations in BM and PB of SM patients and is clearly superior to CS. Application of RQ-PCR assays for the most common D816V mutation may overlook rare mutations but allows quantification of the KIT D816V allele burden which may be useful for diagnosis of ASM and monitoring of residual disease during treatment with novel tyrosine kinase inhibitors, e.g. midostaurin or dasatinib. Disclosures:No relevant conflicts of interest to declare.

Atipical immunophenotype in a littoral cell angioma

Littoral-cell angioma (LCA) is a recently described benign vascular tumor of the spleen, whose imaging and pathologic characteristics have been discussed only by a few authors. The tumor is characterized by a mixture of papillary and cystic areas lined by neoplastic cells deriving from normal splenic lining--littoral cells. The neoplastic LCA cells express both endothelial and histiocytic antigens associated with CD8 negativity, compared with the normal endothelium of the venous sinuses of the spleen red pulp that only expresses endothelial antigens and CD8 positivity. Therefore, the typical and characteristic immunohistochemical pattern of the LCA is as follows: CD31, CD68, CD163, CD21, FVIII antigen positive; CD34, CD8 negative. We reported a 60-year-old male with moderate nodular splenomegaly with one large hypoechogenic solid lesion and mild thrombocytopenia in whom the diagnosis of LCA was made after the elective splenectomy. Namely, histopathological and immunohistochemical data allowed a final diagnosis of classical LCA in spite of CD21 negativity. As far as we know this is the first reporeted CD21-negative LCA patient. Histological specimens were presented and differential diagnoses discussed. Littoral-cell angioma is a very rare benign splenic neoplasm that should be considered in the differential diagnosis of multinodular splenomegaly, particularly if the patient has the signs of hypersplenism.

Late Results of a Modified New Surgical Procedure for the Treatment of Portal Hypertension

The aim of this study is to report on the late results of the modified surgical procedure "subtotal splenectomy with omentopexy and partial splenic attachment to the parietal peritoneum" for the treatment of portal hypertension in children. Over a period of twenty years (1984 - 2004), two modifications have been performed of the procedure of "partial splenectomy and partial splenic attachment for the treatment of portal hypertension", which were reported in the Zeitschrift für Kinderchirurgie [ ], in 1990. The modifications were due to the recurrence of splenomegaly in five cases, with signs of hypersplenism in three of them after ten years. The follow-up ranges between one and fourteen years. All the patients are in good health, with good growth and development, except for one case with liver failure due to liver cirrhosis. No mortality occurred in this group of patients. Severe bleeding occurred in only one case after four years. Treatment consisted of sclerotherapy and ligation of the splenic artery. Splenomegaly was found in five cases, with hypersplenism in three of them. Splenic artery embolisation in two cases and ligation in one case produced good results. Howell-Jolly bodies were negative in all cases and radionuclide scan showed satisfactory to good results in most cases. Good results were also obtained in the studies of immunoglobulins and complements in most cases, with two exceptions of reduced IGM in one case and C4 in the other. Subtotal splenectomy with omentopexy and partial splenic attachment is a good alternative to other operative procedures for the treatment of portal hypertension. With this method, the precipitation and increase in collateral circulation leads to rapid improvement.

Extrahepatic portal vein thrombosis in children: etiology and long-term follow-up.

Mortality of extrahepatic portal vein thrombosis depends on underlying causes other than gastrointestinal bleeding. The aim of this study was to evaluate the etiology, treatment, and prognosis of patients with extrahepatic portal vein thrombosis. The records of 12 patients (age range: 1-9 years) diagnosed with extrahepatic portal vein thrombosis with a minimum follow-up of 2 years were analyzed retrospectively. Their diagnostic evaluations, treatment modalities, complications and long-term follow-ups were noted. Mean follow-up period was 7.4 +/- 3.9 years (2-14 years). Hemorrhage from esophageal varices was the prevalent symptom in 6 patients (50%). Six patients had signs of hypersplenism, 5 were found to have thrombophilia: 2 protein C, 1 protein S, 1 combined protein S, C, and antithrombin III deficiency, and 1 homozygous factor V Leiden mutation. Two patients had congenital cardiovascular abnormalities, and 1 patient developed portal thrombosis after splenectomy operation. None of the patients who started propranolol prophylaxis before first bleeding episode bled during their follow-up periods. Endoscopic sclerotherapy succeed in 66.6% variceal hemorrhages. Shunt surgery was performed in 1 patient. The patients neither faced a life-threatening variceal bleeding nor died during follow-up period. Prognosis of extrahepatic portal vein thrombosis is good in childhood. Thrombophilic states are the most frequent precipitating causes. Propranolol for prophylaxis of variceal bleeding and sclerotherapy might be the preferred modalities.

Partial dearterialization of the spleen in thalassemia major

Methods: Nine patients with thalassemia major (8 boys, 1 girl; age 3 to 8 years) who had signs of hypersplenism and required more than one blood transfusion per month (1 to 2 weeks) underwent partial dearterialization of the spleen (PDAS) from April through December 1992. All were on a low transfusion regimen (Hb < 10 g%). Hematologic profile, IgM and splenic dimensions (SD) by sonography were determined preoperatively and postoperatively during follow-up periods. Isotopic scan was also performed a few months and 2 to 4 years after operation. The patients did not receive pneumovax or long-term prophylactic antibiotics. The procedure consists of division of the splenic arterial branches, except the one that supplies the superior pole, along with preservation of all the veins. Results: Seven patients with SD less than 11 cm (6.9 to 10.8 cm; four with less than 9.5 cm) had uneventful recovery. Two others with SD greater than 13 cm (13.2 to 13.5 cm) required total splenectomy a few days after PDAS because of splenic enlargement associated with high fever. One patient was lost to follow-up after 18 months. The remaining six patients underwent follow-up for 4 to 4.5 years. The hematologic profile (Hb, RBC, platelet counts) showed significant improvement during follow-up period. The blood transfusion requirement in all patients was once every 25 to 32 days except one in which transfusion was increased to every 2 to 3 weeks during the fourth postoperative year. The ultimate magnitude of the hematologic response compared with 15 matched splenectomized patients studied retrospectively in a 4-year period was almost the same in the majority after the first postsplenectomy year. There was no significant change in SD by sonography in four patients compared with preoperative state, but a 30% decrease was seen in the other two during the follow-up period. Isotope scan showed a functional residual spleen in all six, with no remarkable difference in size 4 years after operation, except in the one who relapsed. The IgM level did not fall significantly after operation, nor did signs of infection develop in any patient. Conclusion: PDAS is a safe and effective mode of therapy in thalassemia major, provided the disease is not advanced and SD does not exceed 11 cm in its greatest diameter.

Pregnancy in Liver Cirrhosis

Eleven patients with liver cirrhosis who had a pregnancy between 1974 and 1992 are reported. Prior to pregnancy 2 patients were splenectomized, 1 of them also had an unsuccessful mesocaval shunt and therefore underwent sclerotherapy. Furthermore, 3 patients were managed by injection sclerotherapy, 6 patients had episodes of hepatocellular failure and 5 had signs of hypersplenism. Gastrointestinal hemorrhage associated with pregnancy was noted in 6 patients. Jaundice was encountered in 2 patients, a raised bilirubin level in 3, ascites in 3, impairment of the synthetic liver function in 5, thrombocytopenia in 8, hemorrhagic diathesis in 5, and infectious puerperal complication in 5 patients. Esophageal sclerotherapy was used in 5 and transfusion in 6 patients. Of 12 births, 6 newborns were small-for-date and 1 of them died. Three neonates were preterm. Fetal wastage did not occur. The present data suggest that gastrointestinal hemorrhage in liver cirrhosis contributes to developing fetal growth retardation; cirrhotic patients can be prepared for pregnancy and the hematemesis during pregnancy can successfully be managed by esophageal sclerotherapy.

Splenectomy in hematologic disorders.

DURING the past sixty years splenectomy (Sx) has become a common procedure for the treatment of hypersplenism. Hypersplenism is a hematologic term describing premature destruction of blood cells by the spleen, usually with consequent anemia or leukocytopenia or thrombocytopenia — or all three. Dameshek established four signs of hypersplenism, the tetralogy consisting of cytopenia of the blood, corresponding hyperplasia of the precursor tissue in the bone marrow (e.g., thrombocytopenia with increased megakaryocytes), splenomegaly and — the clincher — cure of the cytopenia after Sx. There are exceptions to the first three rules. For example, in hereditary spherocytosis (HS) the red-cell . . .

Early splenectomy in the management of thalassemic children in Djakarta.

A comparison was made between the results of splenectomy performed on 19 children with thalassemia major, who were operated on after the signs of hypersplenism and hemosiderosis appeared, and on 25 children (11 with thalassemia Hb E disease and 14 with thalassemia major), who splenectomized indication of increased blood requirement only, before signs of hypersplenism or hemosiderosis appeared.From the results, it can be concluded that splenectomy should be performed as soon as increased transfusion requirement appears, before hypersplenism Or hemosiderosis becomes apparent. Due to high frequency of postsplenectomy infections, it is still preferable to operate the child after 2 years of age.