The coagulation profile in hepatosplenic schistosomiasis.

The biological activity of blood coagulation factors II, V, VII, VIII, IX, X, XI and XII, fibrinogen and prekallikrein was assessed in 15 healthy subjects and 60 patients with endemic Egyptian hepatosplenomegaly. The degree of liver disease was graded according to the Child-Pugh classification, the intensity of S. mansoni infection was monitored by determination of circulating schistosome immune complexes (CSIC) level using a monoclonal antibody and hemostasis activation was detected by measurement of hemostatic markers D-dimer and prothrombin fragment 1 + 2 (F1+2). Functional activity of antithrombin III, alpha2-antiplasmin and protein C as well as quantitative determination of plasma concentrations of alpha1-antitrypsin, C1 activator inhibitor and alpha2-macroglobulin were also carried out. The progressive deterioration of liver function which matched the severity of the disease and the intensity of schistosomal infection led to a reduction in anticoagulant proteins (decreases in antithrombin III and protein C) resulting in hypercoagulability and thrombin generation (increased F1+2) subsequently followed by consumption (prolongation of coagulation screening tests, thrombocytopenia, hypofibrinogenemia and decreased factor VIII resulting in hypocoagulability and secondary fibrinolysis (increased D-dimer and decreased alpha2-antiplasmin). A significant decline in fibrinogen and factors VII, XII and prekallikrein was detected in bleeders compared with ascitic patients. The decline in factor XII was closely related to CSIC high titers in all disease groups, but was not correlated to D-dimer or F1+2 concentrations. This suggests that circulating schistosome immune complexes may exert an inhibitory effect on contact factor XII which should be taken into account when considering the reasons for schistosomal coagulopathy and bleeding in hepatosplenic schistosomiasis.

Hyperfibrinolysis in hepatosplenic schistosomiasis.

AIM: To evaluate the nature of accelerated fibrinolysis in hepatosplenic schistosomiasis. METHODS: The biological activity of plasminogen (Plg), plasminogen activators (PA), alpha 2-antiplasmin (alpha 2-AP) and plasminogen activator inhibitor-1 (PAI-1) was determined by photometric analysis in 15 compensated and 35 decompensated patients with endemic Egyptian hepatosplenomegaly. Quantitative measurement of plasma concentrations of tissue t-PA, t-PA-PAI-1 complex, alpha 2-antiplasmin-plasmin complex (alpha 2-APP), fibrinogen degradation products (FbDP), D-dimers (D-D), thrombin-antithrombin complex (TAT) and prothrombin fragment (F 1 + 2) complexes, using double antibody sandwich enzyme linked immunosorbent assays and grading of the degree of hepatic insufficiency according to the Child-Pugh classification, were also carried out. RESULTS: The progressive deterioration of liver function in schistosomal patients, which matched the severity of the disease, led to simultaneous defects in profibrinolytic (decreased Plg and increased PA and t-PA) and antifibrinolytic (decreased alpha 2-AP and PAI-1) factors-the latter defects being the most prominent-resulting in significant generation of plasmin (increased APP complexes) and therefore enhanced fibrinolysis (increased FbDP and D-dimer). The raised concentrations of FbDP, D-D, TAT and F 1 + 2 established its secondary nature. CONCLUSION: These findings suggest that the amount of PAI-1 available to bind and neutralise circulating t-PA may be a critical factor in the progress of hyperfibrinolysis observed in hepatosplenic schistosomiasis, and that the pronounced reduction in its plasma concentration may be regarded as a potential warning indicator of haemostatic imbalance in decompensated schistosomal patients at high risk of variceal bleeding.

Disseminated intravascular coagulation in endemic hepatosplenic schistosomiasis.

Thrombin and plasmin generation were assessed in patients with endemic hepatosplenic schistomiasis (15 hepatosplenomegalic, 15 splenomegalic, 15 with advanced hepatic fibrosis and ascites and 15 hepatosplenic patients with hematemesis). Prolongation of prothrombin time, partial thromboplastin time and thrombin time, thrombocytopenia, hypofibrinogenemia, a decrease in antithrombin III and protein C and S levels and elevation in fibrinopeptide A, D-dimer and thrombin-antithrombin complex levels were detected in all groups. The deficit in hemostatic parameters was more pronounced with the advancement of the disease and was maximal in the hematemesis group. Our data demonstrate an increase in both thrombin and plasmin generation and indicate that low grade disseminated intravascular coagulation may occur in association with endemic Egyptian hepatosplenic schistosomiasis even in the steady state without overt bleeding.

Vitamin K dependent coagulation proteins in endemic hepatosplenomegaly in Egypt.

AIMS: To evaluate the role of bilharzial hepatic fibrosis--whether pure or combined with chronic hepatitis B virus infection--on the functional activity of vitamin K dependent coagulation proteins. METHODS: Coagulation screening using prothrombin time (PT), partial thromboplastin time (PTT), and thrombin time (TT) was carried out on 31 patients with endemic Egyptian hepatosplenomegaly and on 14 healthy controls. The functional activities of factors II, VII, IX and X and protein C were measured. Patients were classified as pure hepatosplenic schistosomiasis (n = 17) and schistosomiasis with concomitant chronic hepatitis B virus infection (n = 14). RESULTS: Prolongation of the PT and PTT were noticed in bilharzial patients compared with the controls. The increase in the TT remained within the upper range of normal. Factors II, VII, IX and X and protein C functional activities were significantly reduced in all groups studied. CONCLUSION: The decreased activity of vitamin K dependent coagulation factors might be partially offset by the reduced activity of circulating protein C which tends to establish a haemostatic balance at a lower level in endemic Egyptian hepatosplenomegaly. No significant difference could be shown between the pure and mixed cases. Schistosomal coagulopathy is therefore not necessarily aggravated by chronic hepatitis B virus infection.

Assessment of factors II, VII, IX, X, and protein C in hepatosplenic schistosomiasis.

Forty-four patients with schistosomiasis mansoni were divided into two groups: a group of 31 patients with hepatosplenomegaly and a group of 13 patients with advanced hepatic fibrosis and ascites. Both groups were compared to a control group of 14 healthy subjects. Screening of the extrinsic and intrinsic coagulation pathways was performed by PT (%) and aPTT. Functional assays of vitamin-K-dependent coagulation proteins: factors II, VII, IX, X, and protein C were conducted by using standard methods. A progressive reduction in PT (%) and prolongation in aPTT were detected in the diseased groups. Furthermore, all studied coagulation proteins showed a progressive reduction in their activities, which became more pronounced in the group with advanced ascites. We conclude that the significant reduction in vitamin-K-dependent coagulation proteins might add to the coagulopathy and bleeding diathesis noted in patients infected with Schistosoma mansoni.

Fibrinolytic parameters during acute haematemesis in endemic hepatosplenomegaly.

Fibrinogen (Fg), plasminogen (Plg), alpha 2-antiplasmin (alpha 2-AP), plasminogen activator (PA), tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI), D-dimer (DD) and fibrin(ogen) degradation products (FDP) were studied in 60 subjects: 40 patients with endemic hepatosplenomegaly (20 during acute haematemesis from ruptured oesophageal varices, 20 with endemic hepatosplenomegaly assigned to the same grade of oesophageal varices but with no history of haematemesis) and 20 normal controls. All parameters were markedly altered in the disease groups. Reduced levels of Fg, Plg, alpha 2-AP and PAI were associated with increasing levels of PA, t-PA, DD and FDP. Alterations were most marked in the group complicated by acute bleeding. It was concluded that these patients have an enhanced fibrinolytic state. This was probably aggravated in the haematemesis group by an acute haemostatic imbalance that superimposed the low grade chronic DIC reported in cases of hepatosplenic schistosomiasis.

The pathogenesis of accelerated fibrinolysis in hepatosplenic schistosomiasis.

Seventy patients with different stages of hepatosplenic schistosomiasis and 18 non-bilharzial normal controls were studied. Plasminogen, plasminogen activators (PA), tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), alpha 2-antiplasmin (alpha 2-AP), plasminogen activator inhibitor (PAI), fibrinogen/fibrin degradation products (FDP) and D-dimer were determined to elucidate the role of plasminogen activators and inhibitors in the pathogenesis of accelerated fibrinolysis in schistosomiasis. There was a progressive increase in the levels of PA, t-PA, u-PA, FDP and D-dimer indicating enhanced fibrinolytic activity with advancing disease. In addition, there was progressive decrease of plasminogen, alpha 2-AP and PAI levels which might be due to decreased hepatic synthesis and/or increased peripheral consumption. These findings suggest that the pathogenesis of accelerated fibrinolysis in schistosomiasis is multifactorial, but may be due to the progressive increase in the levels of plasminogen activators. In addition, the increase of FDP and D-dimer levels are evidence of secondary fibrinolysis following thrombin generation.

Study of contact activation in endemic hepatosplenomegaly.

Factors of the contact activation complex--FXII, FXI, high-molecular-weight kininogen (HMWK) and prekallikrein (PK) as well as D-dimer were measured in 68 schistosomal patients with and without co-existing chronic hepatitis B virus infection (HBV). Fifty-four cases had mixed hepatosplenic schistosomiasis and HBV infection whereas 14 were suffering from hepatosplenic (HS) schistosomiasis alone. A group of twelve age-matched, healthy individuals served as controls. All coagulation parameters were significantly reduced in both disease groups compared to the healthy controls. The decreased activity of the contact proteins could be attributed to decreased hepatic synthesis, consumption due to disseminated intravascular coagulation (DIC) and to the effect of endotoxins. In mixed schistosomiasis and HBV infections, however, the levels of the contact activation factors were not significantly different from those obtained in patients with HS alone. This apparently paradoxical finding does not, however, exclude a role for co-existing HBV infection in speeding up complications in hepatosplenic schistosomiasis.

Fibrinolysis and the bleeding tendency in patients with hepatosplenic schistosomiasis.

Fifty seven patients with schistosomiasis of the liver and spleen in both the compensated and decompensated states and 15 non-bilharzial subjects were studied. Fibrinogen, plasminogen, fibrinogen/fibrin degradation products, alpha 2-macroglobulin, antithrombin III and Cl-activator concentrations were evaluated in an attempt to assess abnormalities at various stages of the disease. The results showed a progressive decrease in fibrinogen and plasminogen concentrations; fibrin degradation products showed a progressive increase as the disease progressed. Together with a falling platelet count, these data indicate the possible occurrence of disseminated intravascular coagulation with enhanced fibrinolysis which was most pronounced in those who vomited blood. Antithrombin III concentration showed a progressive decrease in parallel with the progress of the disease, possibly due to decreased synthesis or increased consumption, or both. Cl-activator concentration showed no significant change from that in normal controls at any stage of the disease. These findings provide further evidence that disseminated intravascular coagulation and enhanced fibrinolysis in the late stages of schistosomiasis may contribute to the haemorrhagic diathesis seen in the liver and spleen.

Iron deficiency and dyserythropoiesis in bilharzial and non-bilharzial patients.

The degree of dyserythropoiesis was studied in bilharzial patients with iron deficiency anaemia. It provides a reliable indication of the severity of iron deficiency as measured by the serum iron and total iron binding capacity. A positive correlation has been found between the percentage incidence of dyserythropoiesis in the bone marrow and both the serum iron and percentage of iron saturation.

Effect of schistosomal infection on some functional activities of blood platelets.

The present study deals with the quantitative and the qualitative platelet functions and their relation to the different stages of hepatosplenic schistosomiasis. The work has been carried on 40 subjects as non-bilharzial control, and 54 patients with schistosomiasis in the different stages of the disease. The statistical analysis of the results obtained, showed no difference in both the quantitative and the qualitative platelet functions in the early active intestinal bilharziasis, when compared to the non-bilharzial control group. The impairment in the platelet functions started to be evident in the group of hepatosplenomegalic bilharziasis and became most obvious in the splenomegalic and ascitic stages. This denotes that there was a correlation between the impairment of both the quantitative and the qualitative platelet functions and the progress of the disease.