Search

Purpose: To evaluate the safety and efficacy of intravitreal injection of autologous plasmin enzyme (APE) in inducing a posterior vitreous detachment (PVD). APE was obtained by a modified method 1 hour before surgery., Methods: APE was obtained by centrifugation of autologous whole blood from the patients 1 hour before surgery and by incubation with streptokinase. APE was injected in the vitreous cavity 20 minutes before surgery. This procedure was applied for 20 patients who underwent vitrectomy for macular pucker, macular hole, and macular edema due to vitreoretinal traction. The status of PVD was graded intraoperatively. The plasmin concentration obtained by this method and the plasminogen titer of the plasma from each patient were compared. Activated partial thromboplastin time was controlled before surgery and 1, 6, 12, and 24 hours after surgery to evaluate alteration of the coagulation due to systemic absorption of the plasmin., Results: Preparation of APE was easy and took on average 45 minutes for all patients. A PVD with an evident Weiss ring was observed during surgery in 17 eyes (85%). The average plasmin activity was 0.26 IU/0.2 mL activated plasma. The partial thromboplastin time did not show any alteration in any of the patients with respect to preoperative values., Conclusion: APE obtained by this method can lead to a PVD and facilitate the complete remotion of vitreous cortex. The intravitreal injection does not lead to alteration of systemic blood coagulation.

Background/aims: A non-enveloped single-stranded DNA virus (TTV) was detected in Japanese patients with fulminant hepatitis (47%) and chronic liver disease of unknown etiology (46%) more frequently than in blood donors (12%). Subsequent studies, however, questioned the association of TTV with liver disease. We further investigated the role of this novel virus in liver diseases., Methods: We tested 106 patients and 102 blood donors for TTV by polymerase chain reaction using conserved region primers., Results: TTV DNA was found in 19 of 102 volunteer blood donors (18.6%) and in 27 of 106 patients with liver disease (25.5%): 10 of 28 chronic hepatitis B (35.7%), 9 of 28 chronic hepatitis C (32.1%) and 8 of 50 (16%) cryptogenic liver disease patients. Previous interferon treatment was not associated with a significantly lower prevalence of TTV infection. TTV prevalence was higher in patients with blood exposure (42.8%, 6/14) than in patients without risk factors (21.4%, 18/84). Four of five patients (80%) with HBV familial infection and without blood exposure were also TTV positive. Partial nucleotide sequences from 3 Italian isolates diverged more than 30% from the 2 prototype genotypes G1 and G2 and were 88% homologous to the recently described genotype G4., Conclusions: G1 and G2 TTV are common in Italy and in the USA in liver disease patients and in blood donors. The prevalence is high in patients with blood exposure but also in subjects without risk factors; other routes of transmission should therefore be considered.

D-dimer (DD) plasma levels are significantly higher in patients with ovarian cancer than in those with benign ovarian masses. The aim of this paper is to assess whether preoperative DD plasma assay has a prognostic relevance for 35 patients with advanced ovarian cancer receiving platinum-based chemotherapy. Preoperative DD levels ranged from 162 to 3720 ng/ml. The 25, 50, and 75% quartiles of DD levels were 1600, 1894, and 2069 ng/ml, respectively. Preoperative DD levels correlated neither with the common clinicopathological prognostic variables nor with the disease status at the end of first-line chemotherapy. Survival was related to residual disease after initial surgery (> or =2 cm vs <2 cm, P = 0.003), but not to preoperative DD levels. In conclusion, the present data seem to show that preoperative DD plasma assay is not a predictor of clinical outcome for patients with advanced ovarian cancer.

The pretreatment plasma levels of prothrombin fragment F1+2 and thrombin-antithrombin III complex (TAT) were measured in 56 consecutive patients with gynecological cancer and in 33 apparently healthy volunteer nonpregnant women as control. Prothrombin fragment F1+2 concentrations were significantly elevated in the 18 patients with ovarian cancer (median, 3.2 nmol/ liter; range, 0.9-17.0 nmol/liter, P < 0.0001), in the 24 patients with cervical cancer (median, 1.7 nmol/liter; range, 0.6-15.0 nmol/ liters, P < 0.0001), and in the 14 patients with endometrial cancer (median, 1.5 nmol/liter; range, 0.6-3.0 nmol/liter, P = 0.036) when compared to controls (median, 1.0 nmol/liter; range, 0. 1 -2.1 nmol/ liter). Similarly, TAT levels were significantly higher in patients with ovarian cancer (median, 5.3 microgram /ml; range, 1.3-65.0 microgram/ml , P < 0.0001), cervical cancer (median, 3.8 microgram/ml; range, 2.1 - 11.0 microgram / ml, P < 0.0001), and endometrial cancer (median, 2.7 microgram/ml; range, 1.9-19.0 microgram /ml, P = 0.008) when compared to controls (median, 2.2 microgram/ml; range, 1.0-5.0 microgram/ml). Prothrombin fragment F1+2 levels correlated with TAT levels (r = 0.659, P < 0.0001). Among ovarian cancer patients, prothrombin fragment F1+2 and TAT concentrations correlated with FIGO stage (III-IV versus 1, P = 0.01 and P = 0.003, respectively) and CA 125 levels (P 0.02 and P < 0.0001, respectively). The present data confirmed the occurrence of hemostasis activation in patients with gynecological cancer, and in particular in those with ovarian cancer.

Plasma levels of D-dimer (DD) and CA 125 were measured preoperatively in 121 patients with ovarian masses submitted to laparotomy. DD and CA 125 levels were higher in the 56 patients with epithelial ovarian cancer than in the 65 patients with benign ovarian disease (P < 0.0001). The logistic regression procedure showed that both DD assay (cutoff 416 ng/ml) and CA 125 assay (cutoff 65 U/ml) were significant predictive variables for malignancy (P = 0.0001). The concordance between predicted probabilities and observed responses was 75.7% for DD, 72.1% for CA 125, and 90.8% for Dd and CA 125. It is worth noting that DD was increased ( > 416 ng/ml) in 73% of FIGO stage I patients, whereas CA 125 was above 65 U/ml in only 33.3%. Sensitivity, specificity, positive predictive value, and negative predictive value of the tests in differentiating benign from malignant ovarian masses were as follows: 76.8, 93.8, 91.5, and 82.4%, respectively, for CA 125; 94.6, 76.9, 77.9, and 94.3%, respectively, for the combination CA 125 or DD; and 73.2, 100.0, 100.0, and 81.3%, respectively, for the combination CA 125 and DD. The combination CA 125 and DD seems to be a useful diagnostic tool to differentiate benign from malignant ovarian masses. Elevated preoperative levels of both antigens are invariably associated with a postsurgical diagnosis of epithelial ovarian cancer.

Peripheral blood samples for the measurement of DD and CA 125 were drawn from 39 patients with ovarian cancer at different times from first surgery. Both median DD and CA 125 levels were significantly higher in the 20 samples drawn from patients with clinically evident disease than in the 37 samples from patients without clinical evidence of disease (477 vs 300 ng/ml p = 0.006, and 66 vs 11 U/ml, p < 0.0001, respectively). DD levels did not correlate with CA 125 levels. The sensitivity, specificity and diagnostic accuracy of the tests in the assessment of clinical disease status were as follows: 65%, 62% and 63% for DD (cut-off = 416 ng/ml); 70%, 92% and 84% for CA 125 (cut-off = 35 U/ml); 90%, 59% and 70% for DD "or" CA 125; and 45%, 95% and 77% for DD "and" CA 125. DD levels correlated with the clinical course of disease in ovarian cancer patients. However, the concomitant determination of DD and CA 125 did not improve the reliability of CA 125 assay alone in the follow-up of these patients.

Activated partial thromboplastin time (aPTT) during heparin infusion in 10 patients on regular dialytic treatment was evaluated. At end-dialysis (3 hours) plasma heparinization ranged between 2000-4000 IU and from the clinical point of view dialytic performance was good. At end-dialysis aPTT was 53 +/- 14 seconds: this value is under the prescribed aPTT prolongation (1.5-2 times baseline values) to achieve a therapeutic heparin plasma level. Physiopathological implications of this aPTT "resistance" to heparin infusion are studied.

The preoperative plasma levels of fibrinopeptide-A (FPA), D-dimer (DD), and von Willebrand Factor (vWF) were measured in 125 patients with ovarian masses undergoing laparotomy and in 88 healthy nonpregnant women as controls. FPA, DD, and vWF levels were significantly higher in the 58 patients with ovarian carcinoma than in the 67 patients with benign ovarian disease or controls. FPA and DD values were significantly higher in advanced (FIGO stage III-IV) than in early ovarian carcinoma. Among patients with advanced disease, FPA and DD levels correlated with none of the common clinicopathological prognostic variables; conversely, vWF values were related to FIGO stage (IV versus III, P < 0.02) and size of residual disease after initial surgery (> 2 cm versus < or = 2 cm, P < 0.05). In conclusion, increased fibrin production and degradation occur in patients with ovarian carcinoma.

Intraglomerular fibrin deposition has been implicated as an important pathogenetic mechanism in patients with glomerular diseases and the nephrotic syndrome. To investigate fibrin formation and degradation in nephrosis, we measured fibrinopeptide A by radioimmunoassay and D-dimer by enzyme-linked immunosorbent assay in the plasma of 30 consecutive adult patients with the nephrotic syndrome; in 10 the serum creatinine was more than 2 mg/dl. Both fibrinopeptide A and D-dimer were abnormally elevated in the majority of nephrotics (P < 0.001 vs. healthy controls), providing evidence of increased fibrin generation and lysis "in vivo." A positive correlation was found between fibrinopeptide A and D-dimer (correlation coefficient 0.64, P < 0.001), suggesting a close relationship between fibrin formation and degradation. Calcium heparin, administered to 12 nephrotics, caused a marked decrease in plasma fibrinopeptide A, due to a reduction of in vivo thrombin activity. As enhanced thrombin activity can favor fibrin deposition within the renal parenchyma, as well as vascular complications, it is reasonable to assume that an antithrombotic treatment aimed at controlling thrombin generation may ameliorate the natural history of nephrosis.

The preoperative plasma levels of fibrinopeptide A (FPA), D-dimer (DD), and von Willebrand Factor (vWF) were measured in 38 patients with cervical cancer undergoing radical hysterectomy with pelvic lymphadenectomy. The surgical-pathological stage of disease was Ib in 17 patients, IIa in 9 patients, and IIb in 12 patients. The tumor size was < or = 4 cm in 20 patients and > 4 cm in 18 patients. The histologic type was squamous cell carcinoma in 32 patients and adenocarcinoma in 6 patients. Positive pelvic lymph nodes were found in 10 patients. When compared to controls, FPA, DD, and vWF levels were significantly raised in patients with surgical-pathological stage IIb disease but not in patients with stage Ib or IIa disease. The values of FPA, DD, and vWF were related to surgical-pathological stage (stage IIb vs stage Ib-IIa: P < 0.005, P < 0.001, and P < 0.001, respectively) and tumor size (> 4 cm vs < or = 4 cm: P < 0.05, P < 0.005, and P < 0.02, respectively), but not to histologic type. vWF values were also related to lymph node status (positive vs negative lymph nodes: P < 0.02). FPA and DD levels were higher in patients with positive lymph nodes than in patients with negative lymph nodes, but the difference did not reach the statistical significance even due to the small number of patients involved. In conclusion, increased fibrin production and degradation seem to occur in patients with stage IIb cervical cancer. The biological meaning of this hemostasis activation deserves further investigation.

IgA nephropathy (Berger's disease) is one of the commonest forms of glomerular disease, not rarely progressing to renal failure. Hemostatic system activation may play a role in the development of glomerular injury. In a series of 12 adult patients affected with IgA nephropathy we have observed increased plasma levels of D-dimer, a stable end-product of cross-linked fibrin degradation that is considered a reliable index of blood clotting activation, as well as "in vitro" raised generation of thromboxane, the main platelet product of arachidonic acid metabolism that seems to play an important role in glomerulosclerosis. Picotamide, a novel antiplatelet drug acting as thromboxane synthase inhibitor as well as thromboxane receptor antagonist, administered for 8-12 weeks, was effective in reducing thromboxane generation. We conclude that picotamide may be useful in the management of glomerular nephropathy.

Plasma concentration of fibrinopeptide A (FpA) and D-dimer (DD), sensitive indicators of coagulation and fibrinolysis activation, were measured in 21 patients thyroidectomized for differentiated cancer (4 had distant metastases) and in 27 control subjects. Only two patients (one with distant metastases) presented elevated FpA values. All the four patients with distant metastases showed elevated DD levels. In three patients who developed distant metastases the time course of the circulating levels of plasma DD and serum thyroglobulin (Tg) was monitored. Monitoring of plasma DD concentration correctly indicated the time course of all the 3 metastatic patients while serum Tg levels failed to adequately describe the outcome of one metastatic patient. These data suggest that fibrinolysis is enhanced in thyroid cancer patients with distant metastases and that plasma DD levels are useful in the monitoring of this condition.

The aim of this work was to evaluate the phytohaemagglutinin-induced aggregation of circulating neutrophils isolated from 25 patients affected by chronic myeloproliferative syndromes (polycythaemia vera, chronic myeloid leukaemia in chronic phase, and essential thrombocythaemia). The results showed a lesser aggregating capacity in chronic myeloid leukaemia (CML) and an opposite behaviour in polycythaemia vera and essential thrombocythaemia. Patients with polycythaemia vera whose neutrophils showed a greater aggregating capacity were shown to have had various vascular complications.

It is well known that cancer induces changes in hemostasis. Plasma levels of Fibrinopeptide A (FPA), D-Dimer (DD), von Willebrand Factor (FvW) and fibrinogen were-assayed at diagnosis in 66 patients with cervical carcinoma and in 67 healthy women as controls. FPA, DD and fibrinogen levels were significantly higher in patients with FIGO stage I b-IIa cervical carcinoma than in controls (2.25 +/- 0.25 vs 1.19 +/- 0.15 p less than 0.001; 307 +/- 35 vs 112 +/- 8 p less than 0.001; 375 +/- 23 vs 280 +/- 17 p less than 0.001 respectively). A further increase of DD, FPA but not of fibrinogen concentrations was observed in advanced stages of disease (3.52 +/- 0.81 vs 2.25 +/- 0.25 p less than 0.1; 943 +/- 98 vs 307 +/- 35 p less than 0.001; 407 +/- 26 vs 375 +/- 23 p = NS respectively). FvW levels in patients with early stage cervical carcinoma were in the normal range, while in patients with advanced cancer, they were significantly higher (175 +/- 8 vs 104 +/- 2 p less than 0.001). A significant correlation was found between plasmatic levels of FPA and DD, FPA and FvW, DD and FvW (r = 0.57 p less than 0.01; r = 0.76 p less than 0.01; r = 0.54 p less than 0.01 respectively). Our data seem to indicate that in patients with cervical carcinoma, and in particular in those with advanced cancer, there is an activation of blood coagulation and fibrinolysis.

Prophylaxis replacement therapy has been assessed for a period of 12 months in 10 patients with severe haemophilia B showing a high incidence of spontaneous bleeding episodes. Two different schedules of administration of a freeze-dried factor IX concentrate were randomly evaluated: according to scheme A, 7.5 U/kg were administrated biweekly, whereas scheme B was based on the weekly infusion of 15 U/kg. On prophylaxis the frequency of bleeding episodes was significantly reduced (P less than 0.005) when compared with that observed in one-year period preceding the trial. Biweekly infusions were superior to weekly infusion (P less than 0.01), and the benefit appeared to be related to the higher number of days in which measurable levels of factor IX were attained in plasma. Range of motion, which was redeced at the start of the trial in 26 joints, was found to have improved in 23. Favourable changes of the joint radiological picture were observed in 6 cases. Hepatitis and factor IX inhibitors did not develop during the trial period. Side effects were rare and mild.

The present paper describes the case of a patient who developed a B-cell chronic lymphocytic leukemia (B-CLL) 15 months after the diagnosis of polycythemia vera, which had been treated only with phlebotomies. In spite of lymphocytosis and the clinical signs and symptoms of leukemia, the patient exhibited at the same time presumptive elements of polycythemia (high LAP index levels, a high number of neutrophils). Cytogenetic investigations, carried out after the appearance of B-CLL, revealed the presence of an unusual abnormality (18 p+) both in bone marrow not stimulated by mitogens and in PWM-stimulated circulating lymphocytes. This case, which is the ninth of its kind described in the literature, offers some interesting observations about the association between myeloproliferative and lymphoproliferative syndromes.

The Authors measured Factor VIII Related Antigen (FVIIIR:Ag), Factor VIII Coagulant Activity (FVIII:C) and fibrinogen plasma levels in 21 patients with cervical carcinoma and in 14 ones with ovarian carcinoma. In the women with cervical cancer, FVIIIR:Ag was significantly higher than controls only in advanced stages. No significant variation of fibrinogen according to stage and no correlation between FVIIIR:Ag and fibrinogen plasma levels were observed. In the patients with ovarian cancer FVIIIR:Ag was significantly increased in stage III-IV and not significantly in stage I. In these subjects too there was a lack of correlation between FVIIIR:Ag and fibrinogen plasma levels. These results seem to indicate that FVIIIR:Ag increase in advanced stages is due to its major release in circulation resulting from invasion of vascular endothelium and not to an aspecific reactivity. These data could suggest a role of FVIIIR:Ag as an aspecific marker of vascular involvement by cervical and ovarian neoplasms.