Splenic non-infarction volume determines a clinically significant hepatic venous pressure gradient response to partial splenic embolization in patients with cirrhosis and hypersplenism.

BACKGROUND: This study aimed to investigate changes in the hepatic venous pressure gradient (HVPG) by partial splenic embolization (PSE) and to identify the determinants of a clinically meaningful postoperative HVPG reduction. METHODS: Sixty-eight patients with cirrhosis and hypersplenism who underwent PSE at our department between September 2007 and June 2020 were included. The HVPG was evaluated pre- and immediately post-PSE. The patients were divided into three groups according to their preprocedural HVPG: low-HVPG (< 10 mmHg, n = 22), intermediate-HVPG (10 mmHg ≤ HVPG < 16 mmHg, n = 33), and high-HVPG (≥ 16 mmHg, n = 13). RESULTS: Overall, PSE significantly reduced HVPG from 12.2 ± 4.0 to 9.4 ± 3.6 mmHg (p < 0.01) with a relative decrease of 22.2 ± 20.4%. In addition, HVPG reductions were 19.4 ± 28.7%, 24.0 ± 15.9%, and 22.5 ± 13.3% in the low-, intermediate-, and high-HVPG groups, respectively, indicating no significant difference in HVPG reduction between the groups. An HVPG decrease of ≥ 20% from the baseline, defined in this study as a clinically significant HVPG response to PSE, was achieved in 55.9% of all patients. Multivariate logistic regression and receiver operating characteristic curve analyses identified splenic non-infarction volume as an independent determinant of a 20% decrease in HVPG (p < 0.05), with a cut-off of 139.2 cm3 (sensitivity, 76.3%; specificity, 60.0%; p < 0.05). CONCLUSIONS: The splenic non-infarction volume, namely the residual functional spleen volume, independently determines a clinically significant HVPG response to PSE in patients with cirrhosis and hypersplenism.

Patterns of splenic arterial enhancement on computed tomography scan are related to portal venous hypertension.

OBJECTIVES: We have previously shown that patterns of splenic arterial enhancement on computed tomography scan change following liver transplantation. We suggested that this is related to changes in portal venous pressure. The aim of this study was to see if similar patterns occur in patients with and without portal hypertension and in patients before and after portal systemic shunts (transjugular portosystemic shunts). METHODS: We evaluated contrast enhanced computed tomography scans in patients being evaluated for liver disease and compared those from patients with and without portal hypertension. In addition we evaluated patients who had computed tomography scans before and after transjugular portosystemic shunts shunts. Splenic arterial enhancement was evaluated using Hounsfield units (pixel counts). RESULTS: Twenty-four patients with clinically significant portal hypertension were compared to 91 without. Mean splenic pixel count was significantly lower in patients with clinically significant portal hypertension (88.2 ± 17.7 vs. 115.2 ± 21.0; m ± SD, P < 0.01). Computed tomography scans were available in 18 patients pre- and post-transjugular portosystemic shunts. Pixel counts were significantly higher in the post-transjugular portosystemic shunts scans (99.7 ± 20.9 vs. 88.9 ± 26.3; P < 0.05). CONCLUSION: This study supports the hypothesis that changes in portal venous pressure are related to changes in splenic arterial enhancement. We suggest that this reflects changes in the splenic micro-circulation. This mechanism may be part of the innate immune response and may also be important in the pathogenesis of hypersplenism.

Thrombocytopenia in chronic liver disease.

Thrombocytopenia is a common haematological disorder in patients with chronic liver disease. It is multifactorial and severity of liver disease is the most influential factor. As a result of the increased risk of bleeding, thrombocytopenia may impact upon medical procedures, such as surgery or liver biopsy. The pathophysiology of thrombocytopenia in chronic liver disease has long been associated with the hypothesis of hypersplenism, where portal hypertension causes pooling and sequestration of all corpuscular elements of the blood, predominantly thrombocytes, in the enlarged and congested spleen. Other mechanisms of importance include bone marrow suppression by toxic substances, such as alcohol or viral infection, and immunological removal of platelets from the circulation. However, insufficient platelet recovery after relief of portal hypertension by shunt procedures or minor and transient recovery after splenic artery embolization have caused many to question the importance and relative contribution of this mechanism to thrombocytopenia. The discovery of the cytokine thrombopoietin has led to the elucidation of a central mechanism. Thrombopoietin is predominantly produced by the liver and is reduced when liver cell mass is severely damaged. This leads to reduced thrombopoiesis in the bone marrow and consequently to thrombocytopenia in the peripheral blood of patients with advanced-stage liver disease. Restoration of adequate thrombopoietin production post-liver transplantation leads to prompt restoration of platelet production. A number of new treatments that substitute thrombopoietin activity are available or in development.

Pancreatic fistula after laparoscopic splenectomy in patients with hypersplenism due to liver cirrhosis: effect of fibrin glue and polyglycolic acid felt on prophylaxis of postoperative complications.

BACKGROUND: This study aimed to determine the effect of fibrin glue and polyglycolic acid (PGA) felt on prevention of pancreatic fistula (PF) after laparoscopic splenectomy in patients with hypersplenism due to liver cirrhosis. METHODS: Fifty consecutive patients were enrolled in this prospective study. Twenty-three patients underwent laparoscopic splenectomy with a fibrin sheet (fibrin sheet group). The sealing ability of each treatment was evaluated by an ex vivo pressure test model. Based on the results from ex vivo experiments, 27 patients received prophylaxis using fibrin glue and PGA felt (PGA with fibrin group). The primary endpoint was the incidence of PF. RESULTS: Significantly more (5, 22%) patients developed PF in the fibrin sheet group than in the PGA with fibrin group (0%, P = .037). CONCLUSIONS: Our new application of fibrin glue and PGA felt is an effective prophylactic procedure for preventing development of PF after laparoscopic splenectomy.

Portal and splanchnic hemodynamics after partial splenic embolization in cirrhotic patients with hypersplenism.

To assess the acute effects of partial splenic embolization (PSE) on portal and splanchnic hemodynamics in patients with cirrhosis. Ninety-five patients with hypersplenism were included in the study. Duplex examinations were performed before and 3 and 7 days after PSE. Portal and splanchnic hemodynamics including vessel cross-sectional area (CSA), mean flow velocities (cm/s), blood flows (mL/min), Doppler indices as portal congestion index (CI), liver vascular index, hepatic artery and superior mesenteric artery (SMA) pulsatility and resistive indices (PI and RI), were performed before and after PSE. In our study, 69 of 95 patients were males (72.6%) and 26 females (27.3%). Chronic hepatitis C virus infection was the main cause of cirrhosis (81.1%). PSE failed technically in six patients (6.3%). After PSE, both CSA and CI significantly decreased (p < 0.05 and <0.01). The portal vein velocity significantly increased (p < 0.01). The portal flow volume (892.4 ± 151 mL/min) did not show significant changes. The hepatic artery RI and PI showed a steady increase that became significant 7 days post-PSE (p < 0.05). The RI and PI of SMA increased significantly after 7 days of PSE (p < 0.05). PSE has an immediate portal decompression effect in patients with portal hypertension without reduction in portal flow. This effect on portal pressure should be investigated in future studies as a potential tool for management of acute variceal bleeding when other medical procedures fail.

Laparoscopic splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension.

Since the first laparoscopic splenectomy (LS) was reported in 1991, LS has become the gold standard for the removal of normal to moderately enlarged spleens in benign conditions. Compared with open splenectomy, fewer postsurgical complications and better postoperative recovery have been observed, but LS is contraindicated for hypersplenism secondary to liver cirrhosis in many institutions owing to technical difficulties associated with splenomegaly, well-developed collateral circulation, and increased risk of bleeding. With the improvements of laparoscopic technique, the concept is changing. This article aims to give an overview of the latest development in laparoscopic splenectomy for hypersplenism secondary to liver cirrhosis and portal hypertension. Despite a lack of randomized controlled trial, the publications obtained have shown that with meticulous surgical techniques and advanced instruments, LS is a technically feasible, safe, and effective procedure for hypersplenism secondary to cirrhosis and portal hypertension and contributes to decreased blood loss, shorter hospital stay, and less impairment of liver function. It is recommended that the dilated short gastric vessels and other enlarged collateral circulation surrounding the spleen be divided with the LigaSure vessel sealing equipment, and the splenic artery and vein be transected en bloc with the application of the endovascular stapler. To support the clinical evidence, further randomized controlled trials about this topic are necessary.

[Splenic embolization combined with double-mirror method in treatment of cirrhosis with hypersplenism of advanced schistosomiasis patients: a report of 38 cases].

A total of 38 patients with schistosomiasis cirrhosis complicated with hypersplenism were cured by endoscopic variceal ligation (EVL), partial splenic embolization (PSE) and laparoscopic splenectomy (LS). After the surgery, the hemogram and liver function of all the patients recovered within two weeks. The average hospitalization time was shorter, the average hospitalization expense was less, and the complications were also less compared with those of the patients who received the routine therapy. In conclusion, the combination therapy of EVL and PSE combined with LS is effective and safe in the treatment of schistosomiasis cirrhosis complicated with hypersplenism.

Bone marrow biopsy findings in brucellosis patients with hematologic abnormalities.

BACKGROUND: Brucellosis can mimic various multisytem diseases, showing wide clinical polymorphism that frequently leads to misdiagnosis and treatment delay, further increasing the complication rates. In this study, we aimed to examine bone marrow biopsy findings in brucellosis cases presenting with hematologic abnormalities. METHODS: Forty-eight brucellosis cases were prospectively investigated. Complaints and physical examination findings of patients were recorded. Patients' complete blood count, routine biochemical tests, erythrocyte sedimentation rate, C-reactive protein and serological screenings were performed. Bone marrow biopsy and aspiration was performed in patients with cytopenia, for bone marrow examination and brucella culture, in accordance with the standard procedures from spina iliaca posterior superior region of pelvic bone. RESULTS: Of the 48 patients, 35 (73%) were female and 13 (27%) were male. Mean age was (34.8 ± 15.4) years (age range: 15 - 70 years). Anemia, leukopenia, thrombocytopenia and pancytopenia were found in 39 (81%), 28 (58%), 22 (46%) and 10 patients (21%), respectively. In the examination of bone marrow, hypercellularity was found in 35 (73%) patients. Increased megacariocytic, erythroid and granulocytic series were found in 28 (58%), 15 (31%) and 5 (10%) patients, respectively. In addition, hemophagocytosis was observed in 15 (31%) patients, granuloma observed in 12 (25%) and increased eosinophil and plasma cells observed in 9 (19%) patients. CONCLUSION: According to the results of our series, hemophagocytosis, microgranuloma formation and hypersplenism may be responsible for hematologic complications of brucellosis.

The effect of splenic arterial blood flow (SBF) on severity of hypersplenism and analysis of factors associated with SBF.

BACKGROUND: This study aims to explore the relationship between spleen arterial blood flow (SBF) with platelet count, spleen index (SPI) and the serum nitric oxide (NO) level of patients with liver cirrhosis and to investigate the role of SBF in the development of hypersplenism. METHODOLOGY: Platelet count, SPI, SBF and serum NO levels were evaluated in 100 patients with liver cirrhosis caused by hepatitis B with hypersplenism (cirrhosis group) and 30 healthy persons without hypersplenism (control group). RESULTS: Platelet count in cirrhosis group and control group was 57.0 +/- 25.6 x 109/L and 205.8 +/- 47.4 x 109/L (p = 0.000), SBF was 535.7 +/- 263.7 milmin and 172.2 +/- 66.9 ml/min (p = 0.000), and serum NO level was 98.51 +/- 23.06 micromol/L and 48.43 +/- 19.47 micromol/L (p = 0.000). Linear correlations were made between SBF and platelet count in cirrhosis group (r = -0.573, p = 0.000), SBF and SPI (r = 0.607, p = 0.01), SBF and serum NO level (r = 0.754, p = 0.000). Moreover, serum NO level increased as liver disease aggravated (82.50 +/- 15.04 pmol/L in Child grade A, 94.61 +/- 21.00 micromol/L in grade B and 116.83 +/- 18.03 micromol/L in grade C; grade A versus grade C, p = 0.003). CONCLUSION: The elevation of SBF may play an important role in the development of hypersplenism and disorders in vasoactive factors such as the serum NO caused by liver cirrhosis may play an important role in the elevation of SBF.

Spectrum of anemia associated with chronic liver disease.

Anemia of diverse etiology is a common complication of chronic liver diseases. The causes of anemia include acute or chronic gastrointestinal hemorrhage, and hypersplenism secondary to portal hypertension. Severe hepatocellular disease predisposes to hemorrhage because of impaired blood coagulation caused by deficiency of blood coagulation factors synthesized by hepatocytes, and/or thrombocytopenia. Aplastic anemia, which is characterized by pancytopenia and hypocellular bone marrow, may follow the development of hepatitis. Its presentation includes progressive anemia and hemorrhagic manifestations. Hematological complications of combination therapy for chronic viral hepatitis include clinically significant anemia, secondary to treatment with ribavirin and/or interferon. Ribavirin-induced hemolysis can be reversed by reducing the dose of the drug or discontinuing it altogether. Interferons may contribute to anemia by inducing bone marrow suppression. Alcohol ingestion is implicated in the pathogenesis of chronic liver disease and may contribute to associated anemia. In patients with chronic liver disease, anemia may be exacerbated by deficiency of folic acid and/or vitamin B12 that can occur secondary to inadequate dietary intake or malabsorption.

A modified canine model of portal hypertension with hypersplenism.

OBJECTIVE: The aim of this study was to develop and describe an experimental canine model of portal hypertension with hypersplenism. MATERIAL AND METHODS: Twenty-five dogs were used randomly divided into three groups: group I (control group, n = 5), group II (PVS, n = 10) and group III (PVS + SVS, n = 10). Portal vein stenosis (PVS) was performed in dogs of group II; in group III dogs the model was first prepared by PVS and additional splenic vein stenosis 3 weeks later (PVS + SVS). Portal vein pressure (PVP), length of spleen and fluctuation of hematocyte counts were measured and recorded at the appointed times. Surgery permitted visual verification of portosystemic collateral circulation. Histopathological variation of the spleen and condition of the bone marrow hyperplasia were examined to confirm the development of hypersplenism. RESULT: Both group II and group III developed prehepatic portal hypertension; group III also presented satisfactory hypersplenism compared to the control group and group II, as documented at surgery and by hematologic and pathologic examination. CONCLUSIONS: Based on this study, the modified model of portal hypertension (by PVS + SVS) appears appropriate when studying the relationship between hypersplenism and hemodynamics in portal hypertension. It is also likely to be useful in studying the influence of diseased spleen in the treatment of portal hypertension.

Splenectomy improves liver function in patients with liver cirrhosis.

BACKGROUND/AIMS: Partial splenic embolization or splenectomy has been reported to improve liver function as well as hypersplenism. The aim of this study was to evaluate the effects of splenectomy in patients with liver cirrhosis (LC) on liver function. METHODOLOGY: Twelve consecutive patients with LC were followed for more than 6 months using laboratory examinations, ultrasonography (US) and computed tomography. Portal blood flow was measured using color Doppler US before and after splenectomy in 6 cases. RESULTS: Hypersplenism was improved in all patients. Protein synthesis in the liver was improved, which significantly correlated with these patients' increased liver volume. Having a large spleen and a low serum alanine aminotransferase (ALT) levels are predictive factors for favorable improvement of liver function after splenectomy. Splenectomy was safely carried out in all patients without major complications except for portal thrombus occurred in 4 patients, but did not affect liver function if it was well treated. CONCLUSIONS: Splenectomy improved liver function in patients with LC, and could be a supportive and bridging therapy for patients waiting for liver transplantation, especially with large spleen and lower ALT levels.

Splenic changes in sickle cell anaemia.

BACKGROUND: The spleen is one of the most frequently affected organ in Sickle cell anaemia (SCA). This has been attributed to its complex anatomy and prominent reticuloendothelial functions which include clearance of unwanted particulate matter in blood ( culling), defense against infection and reservoir for blood cells. This paper aims to highlight the current information on the changes that occur in the spleen of Sickle Cell Disease patients in this environment. METHOD: A review of relevant literature on the subject of splenic changes in Sickle Cell Disease sourced by manual library and medline search. RESULTS: The essential splenic change in SCA is splenomegaly and subsequent shrinkage in size (autosplenectomy), which maybe due to several factors. These include: high levels of irreversible sickle cells, decreased HbF associated with increased intravascular sickling and chronic Malaria infection secondary to hyperplasia of the reticulo-endothelial system and increased antibody production especially IgG and IgM. Finally, the clinical complications of these splenic changes such as increased susceptibility to infection, acute splenic sequestration and hypersplenism are also reviewed in this paper. CONCLUSION: In view of the above changes, it is important to ensure regular monitoring and follow-up in order to prevent complications, recurrent crisis and death.

Fatal relapse of hyperreactive malarial splenomegaly (HMS) in a 10-year old Nigerian female--a case report.

BACKGROUND: The Hyperreactive Malarial Splenomegaly Syndrome (HMS) originally called the tropical splenomegaly syndrome (TSS) or Big spleen disease refers to cases of splenomegaly in the tropics for which no cause was found despite thorough investigation. It is restricted to the malarial belt, yet there are few reports on HMS in Nigeria, probably due to a low index of suspicion and non-availability of laboratory facilities to determine titres of malarial antibodies. The objective of this paper is to highlight the features, management, risk of relapse and prognosis of HMS. METHOD/RESULT: We present a 10-year old female with recurrent massive splenomegaly with previous clinical response to antimalarials and evidence of hypersplenism. CONCLUSION: HMS should be suspected in any child with moderate to massive splenomegaly with evidence of hypersplenism and clinical response to antimalarials.

Survey of hematological aspects of Gaucher disease.

Hematologists have classically been the treating physicians of patients with Gaucher disease, and today, despite both specific and symptomatic therapeutic advances, they remain at the forefront of specialists to whom patients with Gaucher disease present. It is therefore appropriate to review that has changed and what has remained the same in hematological signs and symptoms of the disease in the decade and a half since therapy has become available.

Value of portal hemodynamics and hypersplenism in cirrhosis staging.

AIM: To determine the correlation between portal hemodynamics and spleen function among different grades of cirrhosis and verify its significance in cirrhosis staging. METHODS: The portal and splenic vein hemodynamics and spleen size were investigated by ultrasonography in consecutive 38 cirrhotic patients with cirrhosis (Child's grades A to C) and 20 normal controls. The differences were compared in portal vein diameter and flow velocity between patients with and without ascites and between patients with mild and severe esophageal varices. The correlation between peripheral blood cell counts and Child's grades was also determined. RESULTS: The portal flow velocity and volume were significantly lower in patients with Child's C (12.25+/-1.67 cm/s vs 788.59+/-234 mm/min, respectively) cirrhosis compared to controls (19.55+/-3.28 cm/s vs 1254.03+/-410 mm/min, respectively) and those with Child's A (18.5+/-3.02 cm/s vs 1358.48+/-384 mm/min, respectively) and Child's B (16.0+/-3.89 cm/s vs 1142.23+/-390 mm/min, respectively) cirrhosis. Patients with ascites had much lower portal flow velocity and volume (13.0+/-1.72 cm/s vs 1078+/-533 mm/min) than those without ascites (18.6+/-2.60 cm/s vs 1394+/-354 mm/min). There was no statistical difference between patients with mild and severe esophageal varices. The portal vein diameter was not significantly different among the above groups. There were significant differences in splenic vein diameter, flow velocity and white blood cell count, but not in spleen size, red blood cell and platelet counts among the various grades of cirrhosis. The spleen size was negatively correlated with red blood cell and platelet counts (r = -0.620 and r = -0.8.34, respectively). CONCLUSION: An optimal system that includes parameters representing the portal hemodynamics and spleen function should be proposed for cirrhosis staging.

[Effect of portosystemic anastomosis on the degree of splenic inhibition]. / Vliv portosystemické spojky na míru splenického útlumu.

UNLABELLED: Secondary hypersplenism is a well-known complication of portal hypertension. Reduced platelet count is a more alarming sign for the physician than risk for the patient. Improvement of thrombocytopenia is urgent, when portal hypertension with splenomegaly and thrombocytopenia presents with life-threatening haemorrhage from gastroesophageal varices. In this case, treatment aimed at stopping the bleeding may be more beneficial than any intervention on the spleen. In this study, we evaluated long-term effects of an elective distal splenorenal shunt or small diameter H-shunt on splenomegaly and thrombocytopenia in 26 patients with portal hypertension operated for repeated bleeding from oesophageal varices. 25 patients had splenomegaly and 16 patients had thrombocytopenia before shunting. Surgery corrected splenomegaly in 16 patients (64%), platelet counts increased in 13 of 16 patients with thrombocytopenia (81.2%). CONCLUSION: Selective or partial portal decompression is sufficient to alleviate thrombocytopenia and splenomegaly associated with portal hypertension.

Hypersplenism.

Cytopenias in liver disease are a common finding. In the past they have mostly been attributed to pooling and/or destruction of blood cells in the enlarged spleen, leading to the term 'hypersplenism'. With recent advances in the understanding of the physiology of blood formation, in particular with the discovery of several haematopoietic growth factors, new insight into the pathophysiology of blood cell derangements in liver disease has been obtained. Recombinant haematopoietic growth factors present new opportunities for support of the haematopoietic system, which is required because of toxic antiviral therapies or surgical interventions in these patients.