Portal vein thrombosis associated with protein C deficiency and elevated Factor VIII in hepatosplenic schistosomiasis.

Portal vein thrombosis is considered a vaso-occlusive process that can appear during the course of hepatosplenic Schistosoma mansoni, but may result from impaired portal blood flow or be associated with acquired or inherited thrombophilic factors. Here, we report the case of a 67-year-old woman who developed thrombocytopenia as a result of hypersplenism. Following the diagnosis of hepatosplenic schistosomiasis, portal vein thrombosis was detected by ultrasound examination, while haematological tests revealed low levels of protein C (43.3%) and high levels of factor VIII (183.1%). The pathogenesis of portal vein thrombosis remains unclear in some patients with S. mansoni. We recommend, therefore, that early clinical and haemostatic investigations are done to evaluate risk of portal vein thrombosis and hence avoid further complications.

Splenectomy Improves Hemostatic and Liver Functions in Hepatosplenic Schistosomiasis Mansoni.

BACKGROUND: Schistosomiasis mansoni is a chronic liver disease, in which some patients (5-10%) progress to the most severe form, hepatosplenic schistosomiasis. This form is associated with portal hypertension and splenomegaly, and often episodes of gastrointestinal bleeding, even with liver function preserved. Splenectomy is a validated procedure to reduce portal hypertension following digestive bleeding. Here, we evaluate beneficial effects of splenectomy on blood coagulation factors and liver function tests in hepatosplenic schistosomiasis mansoni compared to non-operated patients. METHODOLOGY/PRINCIPAL FINDINGS: Forty-five patients who had undergone splenectomy surgery were assessed by laboratory analyses and ultrasound examination and compared to a non-operated group (n = 55). Blood samples were obtained for liver function tests, platelet count and prothrombin time. Coagulation factors (II, VII, VIII, IX and X), protein C and antithrombin IIa, plasminogen activator inhibitor-1 were measured by routine photometric, chromogenic or enzyme-linked immunosorbent assays, while hyperfibrinolysis was defined by plasminogen activator inhibitor-1 levels. Both groups had similar age, gender and pattern of periportal fibrosis. Splenectomized patients showed significant reductions in portal vein diameter, alkaline phosphatase and bilirubin levels compared to non-operated patients, while for coagulation factors there were significant improvement in prothrombin, partial thromboplastin times and higher levels of factor VII, VIII, IX, X, protein C and plasminogen activator inhibitor-1. CONCLUSION/SIGNIFICANCE: This study shows that the decrease of flow pressure in portal circulation after splenectomy restores the capacity of hepatocyte synthesis, especially on the factor VII and protein C levels, and these findings suggest that portal hypertension in patients with hepatosplenic schistosomiasis influences liver functioning and the blood coagulation status.

TGF beta and IL13 in Schistosomiasis mansoni associated pulmonary arterial hypertension; a descriptive study with comparative groups.

BACKGROUND: It is suggested that interleukin (IL)-13 and transforming growth factor (TGF)-beta play a role in the pulmonary vascular changes found in animal models of schistosomiasis. The aim of this study was to assess and compare the serum levels of total TGF-beta and IL-13 of patients with schistosomiasis with pulmonary arterial hypertension (PAH) and patients with schistosomiasis without PAH. METHODS: 34 patients from the schistosomiasis outpatient clinic of the Hospital das Clinicas, Recife, Pernambuco, Brazil, without PAH assessed by echocardiography and 34 patients from the Reference Centre of Pulmonary Hypertension of Pronto Socorro Cardiológico de Pernambuco, Recife, Brazil with PAH, confirmed by right heart catheterization, were enrolled on the study. Both groups presented with schistosomal periportal fibrosis after abdominal ultrasound. Serum levels of TGF-beta1 and IL-13 were determined by ELISA. Student t test to independent samples, Mann-Whitney test to nonparametric variables, Pearson correlation test for correlation analyses and Fisher Chi-squared test to compare categorical analyses were used. RESULTS: The median value of TGF-beta1 was significantly higher in patients with PAH (22496.9 pg/ml, interquartile range [IR] 15936.7 - 32087.8) than in patients without PAH (13629.9 pg/ml, IR: 10192.2- 22193.8) (p = 0.006). There was no difference in the median value of IL-13 in the group with Sch-PAH compared to patients without Sch-PAH (p > 0.05). CONCLUSION: Our results suggest that TGF-beta possibly plays a role in the pathogenesis of schistosomiasis-associated PAH.

Relationship between splenomegaly and hematologic findings in patients with hepatosplenic schistosomiasis.

BACKGROUND: Schistosomiasis is a tropical disease. Patients who develop hepatosplenic schistosomiasis have clinical findings including periportal fibrosis, portal hypertension, cytopenia, splenomegaly and gastrointestinal hemorrhage. OBJECTIVE: The aim of this study was to analyze the hemostatic and hematologic findings of patients with schistosomiasis and correlate these to the size of the spleen. METHODS: Fifty-five adults with hepatosplenic schistosomiasis and 30 healthy subjects were selected through a history of contact with contaminated water, physical examination and ultrasound characteristics such as periportal fibrosis and splenomegaly in the Gastroenterology Service of the Universidade Federal de Pernambuco. Blood samples were collected to determine liver function, blood counts, prothrombin (international normalized ratio), partial thromboplastin time and fibrinogen and D-Dimer levels using the Pentra 120 hematological analyzer (HORIBA/ABX), Density Plus (test photo-optical Trinity Biotech, Ireland) and COBAS analyzer 6000 (Roche). Furthermore, the longitudinal size of the spleen was measured by ultrasound (Acuson X analyzer 150, Siemens). The Student t-test, the Fisher test and Pearson's correlation were used to analyze the results with statistical significance being set for a p-value < 0.05. RESULTS: The mean age was higher for the Study Group than for the Control Group (54 ± 13.9 vs. 38 ± 12.7 years). The average longitudinal diameter of the spleen was 16.9 cm (Range: 12.3-26.3 cm). Anemia is a common finding in patients with schistosomiasis (36.3%). The mean platelet and leukocyte counts of patients were lower than for the Control Group (p-value < 0.001). Moreover, the international normalized ratio (1.42 vs. 1.04), partial thromboplastin time (37.9 vs. 30.5 seconds) and D-Dimer concentration (393 vs. 86.5 ng/mL) were higher for the Study Group compared to the Control Group. CONCLUSION: This study suggests that hematological and hemostatic abnormalities are associated with splenomegaly, hypersplenism and portal hypertension.

Hemostatic dysfunction is increased in patients with hepatosplenic schistosomiasis mansoni and advanced periportal fibrosis.

BACKGROUND: Schistosomiasis mansoni is an endemic parasitic disease and a public health problem in Northeast Brazil. In some patients, hepatic abnormalities lead to periportal fibrosis and result in the most severe clinical form, hepatosplenic schistosomiasis. This study aimed to evaluate whether abnormal blood coagulation and liver function tests in patients with hepatosplenic schistosomiasis (n = 55) correlate with the severity of their periportal fibrosis. METHODOLOGY/PRINCIPAL FINDINGS: Blood samples were used for liver function tests, hemogram and prothrombin time (International Normalized Ratio, INR). The blood coagulation factors (II, VII, VIII, IX and X), protein C and antithrombin IIa (ATIIa), plasminogen activator inhibitor 1 (PAI-1) and D-dimer were measured by photometry or enzyme linked immunosorbent assay. Hyperfibrinolysis was defined on the basis of PAI-1 levels and a D-dimer concentration greater than a standard cut-off of 483 ng/mL. Standard liver function tests were all abnormal in the patient group compared to healthy controls (n = 29), including raised serum transaminases (p<0.001) and lower levels of albumin (p = 0.0156). Platelet counts were 50% lower in patients, while for coagulation factors there was a 40% increase in the INR (p<0.001) and reduced levels of Factor VII and protein C in patients compared to the controls (both p<0.001). Additionally, patients with more advanced fibrosis (n = 38) had lower levels of protein C compared to those with only central fibrosis (p = 0.0124). The concentration of plasma PAI-1 in patients was one-third that of the control group (p<0.001), and D-dimer levels 2.2 times higher (p<0.001) with 13 of the 55 patients having levels above the cut-off. CONCLUSION/SIGNIFICANCE: This study confirms that hemostatic abnormalities are associated with reduced liver function and increased liver fibrosis. Of note was the finding that a quarter of patients with hepatosplenic schistosomiasis and advanced periportal fibrosis have hyperfibrinolysis, as judged by excessive levels of D-dimer, which may predispose them to gastrointestinal bleeding.

Relationship between splenomegaly and hematologic findings in patients with hepatosplenic schistosomiasis

BACKGROUND Schistosomiasis is a tropical disease. Patients who develop hepatosplenic schistosomiasis have clinical findings including periportal fibrosis, portal hypertension, cytopenia, splenomegaly and gastrointestinal hemorrhage. OBJECTIVE The aim of this study was to analyze the hemostatic and hematologic findings of patients with schistosomiasis and correlate these to the size of the spleen. METHODS Fifty-five adults with hepatosplenic schistosomiasis and 30 healthy subjects were selected through a history of contact with contaminated water, physical examination and ultrasound characteristics such as periportal fibrosis and splenomegaly in the Gastroenterology Service of the Universidade Federal de Pernambuco. Blood samples were collected to determine liver function, blood counts, prothrombin (international normalized ratio), partial thromboplastin time and fibrinogen and D-Dimer levels using the Pentra 120 hematological analyzer (HORIBA/ABX), Density Plus (test photo-optical Trinity Biotech, Ireland) and COBAS analyzer 6000 (Roche). Furthermore, the longitudinal size of the spleen was measured by ultrasound (Acuson X analyzer 150, Siemens). The Student t-test, the Fisher test and Pearson's correlation were used to analyze the results with statistical significance being set for a p-value < 0.05. RESULTS The mean age was higher for the Study Group than for the Control Group (54 ± 13.9 vs. 38 ± 12.7 years). The average longitudinal diameter of the spleen was 16.9 cm (Range: 12.3-26.3 cm). Anemia is a common finding in patients with schistosomiasis (36.3%). The mean platelet and leukocyte counts of patients were lower than for the Control Group (p-value < 0.001). Moreover, the international normalized ratio (1.42 vs. 1.04), partial thromboplastin time (37.9 vs. 30.5 seconds) and D-Dimer concentration (393 vs. 86.5 ng/mL) were higher for the Study Group compared to the Control Group...

Hepatopulmonary syndrome in patients with Schistosoma mansoni periportal fibrosis.

UNLABELLED: Hepatopulmonary syndrome (HPS) is characterized by the presence of liver disease, arterial hypoxemia and intrapulmonary vascular dilatation (IPVD). IPVD includes diffused or localized dilated pulmonary capillaries and, less commonly, pleural and pulmonary arteriovenous communications. The aim of the present study was to investigate the occurrence of HPS in patients with Schistosoma mansoni periportal fibrosis in treatment at a university hospital in northeastern Brazil. PATIENTS AND METHODS: Eighty-four patients were enrolled in the study between April and July 2007 and underwent arterial blood gas analysis. Patients with an alveolar-arterial oxygen gradient (DA-aO(2)) > or = 15 mmHg were submitted to contrast-enhanced transthoracic echocardiogram (CE-TTE) with saline microbubbles. The diagnostic criterion for HPS was DA-aO(2) > or = 15 mmHg associated to IPVD, as identified through CE-TTE. Patients with HPS underwent contrast-enhanced 16-channel multidetector-row computed tomography (MDCT) of the thorax. RESULTS: Twenty-two patients (26.19%) had DA-aO(2) > or = 15 mmHg (mean value=20.86+/-7.91). CE-TTE was positive for IPVD in five of the 22 patients with DA-aO(2) > or = 15 mmHg and all these patients had hepatosplenic disease, revealing a 6% prevalence of HPS (CI: 1.96-13.35) in the overall population of 84 patients, with a 10.2% prevalence in the group with hepatosplenic disease. The following were the 16-channel MDCT findings in these five patients: dilated peripheral pulmonary vasculature (100%); ratio of segmental arterial diameter to adjacent bronchial diameter equal to or greater than 2:1 (100%); higher number of visible terminal vessel branches in lung dependent regions (40%); and micronodules associated with subpleural surface centrilobular vessels (40%). No patient had evidence of arteriovenous fistula. These findings reveal that HPS occurs (usually in a mild form) in patients with Schistosoma mansoni periportal fibrosis and portal hypertension seems to be an important factor related to the occurrence of HPS in such cases.