The hyperfibrinolytic state of liver cirrhosis: possible pathogenetic role of ascites.

We evaluated coagulation and fibrinolytic parameters in both plasma and ascitic fluid of 39 patients with ascites secondary to liver cirrhosis and in 14 cirrhotic patients without ascites, in order to verify if the peritoneal compartment could be involved in the pathogenesis of the hyperfibrinolytic state of the disease. An activation of fibrinolysis, as suggested by increased levels of FDP, D-dimer and tissue plasminogen activator (t-PA) was demonstrated in both ascitic fluid and to a lesser extent in plasma. A positive correlation was also observed between plasma and ascitic fluid plasminogen, anti-plasmin and fibrinogen, while a negative correlation was found between plasma and ascitic fluid plasminogen activator inhibitor-1 (PAI-1). Moreover, plasma PAI-1 was significantly lower in patients with ascites than in those without ascites and among ascitic patients in those who had bleeding into soft tissues when compared to those who did not present haemorrhagic events. Finally, a significant association was also shown between positivity for plasma D-dimer (> 200 ng/ml) and the presence of ascites. Taken together, our data suggest an exchange of some coagulation and fibrinolytic proteins between plasma and ascitic fluid and point out the key role of PAI-1 in regulating plasma fibrinolytic potential and in bleeding complications in cirrhotic patients.

Structural and functional characterization of plasma fibronectin in patients with essential mixed cryoglobulinaemia.

Experimental studies suggest that plasma fibronectin may be involved in the cryoprecipitation of cryoglobulins in essential mixed cryoglobulinaemia; reduced plasma concentrations of the glycoprotein have been shown in the disease. The present work was undertaken in order to verify this latter finding and to detect a possible structural alteration of plasma fibronectin as result of enzymatic digestion of the molecule in vivo. This could, in turn, induce a decreased reactivity of the protein in immunometric assays and a reduced opsonic activity, which is normally due to the affinity of fibronectin to the C1q component of complement. Moreover, since a polymorphic variant of fibronectin has been described in plasma during experimental vascular injury and in patients with autoimmune vascular diseases, the aim of this study was also to verify the presence of a polymorphism of the glycoprotein in cryoglobulinaemic vasculitis. Twenty seven patients with essential mixed cryoglobulinaemia and 26 normal subjects were included in the study. Significantly reduced concentrations of plasma fibronectin, as assessed by ELISA, were found in patients when compared with controls (231.7 +/- 15.3 vs 316.1 +/- 16.6 mg/l, P less than 0.0002). In contrast, when affinity-purified plasma fibronectin from 10 patients with essential mixed cryoglobulinaemia and 8 healthy subjects were analysed by western blotting, employing a panel of five monoclonal antibodies to different regions of the molecule, no differences were observed between patients and controls, suggesting integrity of the glycoprotein in the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical significance of endothelial damage markers in essential mixed cryoglobulinemia.

Essential mixed cryoglobulinemia (EMC) is a rheumatic disorder characterized by widespread vasculitis. To better define the nature of the vasculitic process and to possibly outline assessment methods reliable for using in a clinical context, we studied plasma levels of three endothelial related peptides: fibronectin (FN), von Willebrand factor (vWF) and tissue plasminogen activator (t-PA), and those of thrombin-antithrombin III complexes (TAT) as markers of activation of the coagulation in 21 patients and in 16 controls. In EMC we found a picture consisting of reduced FN and increased vWF, t-PA, and TAT levels, suggesting a condition of endothelial cell damage with thrombin formation in vivo. Since we previously demonstrated the presence of chronic disseminated intravascular coagulation in these patients, we may assume that endothelial cells stressed by cryoprecipitation or stimulated by soluble mediators may be actively involved in the vasculitic process and possibly express procoagulant properties. This is a good example of the complex interplay existing between autoimmunity and coagulation mechanisms. We also suggest that FN, vWF, t-PA and TAT should be considered as additional clinical parameters when evaluating patients with EMC.

Persistent Epstein-Barr virus infection in patients with type II essential mixed cryoglobulinemia.

The pattern of response to Epstein-Barr virus (EBV) has been investigated in 17 patients with essential mixed cryoglobulinemia (EMC) and in 17 control subjects. All subjects in both groups had IgG to the viral capsid antigen at comparable titers. In the absence of signs of recent infection, 13 patients had IgM to viral capsid antigen and 5 had also IgA, while all the controls were negative. EBV genome was present in bone marrow lymphocytes obtained from 4 patients with type II EMC, but not in those of one patient with type III disease; the latter patient's lymphocytes also failed to produce detectable levels of rheumatoid factor in culture, while the other four patients' lymphocytes released high amounts in culture supernatants. These data support the evidence of an association between type II EMC and persistent EBV infection.

Histological and immunological features of primary Kaposi's sarcoma: evaluation before and after chemotherapy.

Forty-one patients with primary Kaposi's sarcoma (KS) have been evaluated clinically, histologically and immunologically at the time of diagnosis. There was no correlation between histological and immunological features. Moreover, the disease did not appear to be related to particular HLA phenotypes. The T4/T8 ratio was augmented. Leu 7+ cells were also significantly increased. The last 15 patients who received chemotherapy were recently reevaluated after treatment and an increase in B lymphocytes was observed. We also observed that spindle-shaped cells (SSC), which appear later in the histopathological course of the disease, disappear first during chemotherapy, concomitantly with the increase in B cells. We conclude that the course of the disease appears to be controlled by the host's immune response, though there is no clear correlation between histological and immunological evolution. Several immunological features differentiating it from AIDS associated KS have been found.

Plasma fibronectin and microvascular damage in essential mixed cryoglobulinaemia.

Plasma fibronectin (FN) was measured in 17 patients with essential mixed cryoglobulinaemia (EMC) and in 17 normal subjects by single radial immunodiffusion (RID) and enzyme-linked immunosorbent assay (ELISA). In 9 patients the presence of FN in the cryoprecipitates was also assessed by immunoblotting. In the EMC group, plasma FN levels were significantly lower than in control subjects, using both methods, and FN was constantly demonstrated in EMC cryoprecipitates. Capillaroscopic observation of the capillary bed in skin and bulbar conjunctiva, performed in all cases, showed severe alterations of microcirculation in EMC patients. A negative correlation between plasma FN and capillaroscopic abnormalities of skin capillaries was observed. These data support the hypothesis that plasma fibronectin plays a role in the pathogenesis of systemic vasculitis in EMC.

Acquired factor VIII inhibitor in a non-haemophilic patient: successful treatment with plasma exchange associated with factor VIII concentrate and immunosuppressors.

We report the successful treatment of a 55-year-old man with an acquired factor VIII inhibitor, the appearance of which followed surgery for a carcinoma of the biliary tract. The patient, who had recurrent life-threatening bleeding episodes, was treated with intensive plasmapheresis, factor VIII concentrates, azathioprine and methylprednisolone. Disappearance of the inhibitor was observed after the second series of plasma exchanges. Controls 2 and 3 months after treatment confirmed the complete absence of the inhibitor and normal levels of factor VIII. The crucial role of plasma exchange is considered and discussed.

Peripheral blood lymphocyte subpopulations in polycythaemia and thrombocythaemia.

Lymphocyte subpopulations from peripheral blood of normal subjects and patients with primary proliferative polycythaemia (PPP), idiopathic erythrocytosis (IE) and essential thrombocythaemia (ET) were separated using antihuman immunoglobulin antiserum for B lymphocytes and the following monoclonal antibodies: OKT3, directed against the general T-lymphocyte subpopulation, OKT4 and OKT8, detecting respectively T-helper and T-suppressor lymphocyte subpopulations, OKM1 reacting mainly with monocytes. A decrease in the number of OKT3+ cells was observed both in PPP and IE, with a particular fall of the OKT8+ (suppressor) cells, so that the T4/T8 ratio was significantly increased (P less than 0.03 in PPP and P less than 0.0005 in IE). The ratio remained normal in samples from ET. OKM1+ cells were significantly increased in PPP (P less than 0.04), but not in IE, while in ET there was a rise in a few cases only. The present data point out some definite changes in the circulating lymphomonocytic cell subsets, which may be of interest in the study of this group of myeloproliferative disorders.

[Rehabilitation in myocardial infarct. Study of various coagulation parameters and platelet function]. / La riabilitazione nell'infarto miocardico. Studio di alcuni parametri coagulativi e di funzionalità piastrinica.

In order to evaluate coagulation and platelet function modifications in patients undergoing a rehabilitation trial after myocardial infarction, we have studied 26 patients (24 males and 2 females) of age comprised between 37 and 62 years. The effectiveness of the trial was assessed on the basis of an increased mechanical work (expressed in Kgm) at the end of the period. Modifications in platelet number, AT III and plasminogen levels were noticed at the same time, while platelet aggregation and the levels of platelet 5 HT, plasma alfa2 macroglobulin and alfa1 antitrypsin remained unchanged. The possible effects of the trial on coagulation and platelet function are discussed.

Expression of thymidine kinase activity in hybrids between human leukemic cells and a TK-mouse cell line.

A series of actively proliferating clones have been isolated after PEG-induced fusion of a thymidine kinase deficient murine line and white blood cells from two leukemic patients. Their hybrid nature was proved both cytologically and biochemically. All the hybrids tested showed levels of TK activity significantly higher than the TK- mouse parental cell line and comparable to those exhibited by replicating TK+ cells.