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Introduction In patients with lung adenocarcinoma (LA), metastasis (MTS), advanced stage and chemotherapy (CTx) are risk factors for thromboembolism (VTE). Routine thromboprophylaxis is not recommended but individualized risk assessment is encouraged. Aim The selection of the most relevant hypercoagulability biomarkers (HB) for incorporation into the risk assessment models (RAM) for VTE. Materials and Methods Patients with documented LA eligible for CTx at distance of at least 3 months from surgery or hospitalization were included. They were either CTx naive (NG) or had received CTx (OTG). Control group (CG) consisted of 30 healthy age & sex-matched individuals. We assessed them for thrombin generation (TG), P-Selectin, heparanase (HPA), procoagulant phospholipids (PPL), factor VIIa, D-Dimers (DDi) and Tissue Factor activity (TFa). Results Patients showed significantly shortened PPL and higher levels of TFa, DDi and HPA as compared to the CG. FVIIa levels were lower in patients compared to CG. The NG showed significantly shorter lag-time and lower ETP as compared to the OTG. It also showed significantly higher levels of HPA as compared to the OTG.The increase of TG and of HPA, P-Selectin, FVIIa was associated with the stage. Patients with MTS had higher levels of P-Selectin, TFa, DDi, FVIIa, TGT and HPA than those with localized or advanced disease.Patients with VTE had higher baseline levels of DDi, TGT, shorter PPL and lower levels of HPA as compared to those without. Patients who died within 3-months had higher baseline levels of DDi and lower HPA levels as compared to those who were alive. Conclusions Increased PPL, TF pathway up regulation, DDi and HPA increase is a universal phenomenon in LA. CTx has an impact on TGT and HPA levels. Baseline values of TGT, PPL, HPA, DDi were related with mortality and thrombosis. The incorporation of HB in VTE-RAMs might improve their predictive value. This concept is being studied on an ongoing trial.

Summary: The aim of this study was to correlate human seminal fructose determinations by enzymatic UV method with protein content, using three different methods (Biuret, Lowry, Meulemans). On one hand, the incidence on fructose levels of partial deproteinization after treatment by perchloric acid was tested: the fructose levels values increased after deproteinization 14.1 ± 3.7 versus 4.2 ± 1.7 mMol/l. On the other hand, physiologically, semen proteolysis occurs for many hours after collection and concerns mainly low molecular weight proteins. No modifications were found in protid levels and fructose concentrations during the first four hours, at 20° C. All these data seem to indicate a better linkage of fructose to the highest molecular weight proteins and might explain the absence of fructose rise during the first four hours. Zusammenfassung: Ziel dieser Studie war, die enzymatisch uber U.V. ermittelte Fruktose des menschlichen Spermaplasmas mit dem mittels drei verschiedener Methoden (Biuret, Lowry, Meulemans) bestimmten Proteinspiegel in Korrelation zu bringen. Einerseits wurde die Inzidenz der Deproteinisierung durch Perchlorsaure auf den Fruktose-Spiegel untersucht: dieser erhoht sich nach Deproteinisierung auf 14.1 ± 3.7 gegen 4.2 ±1.7 mMol/l und andererseits die physiologische Proteolyse, die mehrere Stunden nach Kollekte auftritt und die niedermolekularen Proteine betrifft: innerhalb der ersten vier Stunden wurde bei 20° C keinerlei Veranderung des Proteinspiegels oder der Fruktose angetroffen. Das Ganze scheint letztlich auf eine bessere Bindung der Fruktose an die hochmolekularen Proteine hinzuweisen und konnte das Fehlen einer Fruktose-Erhohung innerhalb dieser vier Stunden erklaren.

Summary Abnormal response to venous stasis is a frequent finding in patients with previous venous thrombosis. The factors studied to explain the response of the fibrinolytic system to venous occlusion (VO) have included tissue plasminogen activator (t-PA), PAI antigen and activity measurements as additional tests to the conventional euglobulin fibrinolytic activity. However, there is no consensus on the definition of an abnormal response. In order to further investigate the clinical relevance and the definition of good and bad responders (GR, BR), we have used a 10 min VO test in 109 patients with well documented venous thromboembolic events. Hematocrit, euglobulin clot lysis time (ECLT), diluted whole blood lysis time (DWBLT), tissue plasminogen activator (t-PA ag), fibrinolytic activity of euglobulins on fibrin plates (EFA), activity of the t-PA inhibitor (PAI act), a complete study of haemostasis, and a platelet count were performed before and after VO. Clinical characteristics did not reveal a significant difference between GR and BR. Among these 109 patients, 46 patients had a GR according to our previous definition (residual PAI≤2 U/ml). In this subgroup, results are homogeneous in the various fibrinolytic tests used. In the 63 remaining patients, results are heterogeneous: in 28 patients a BR was observed whatever the test used and could be attributed to a high basal PAI act in 17 cases, or a poor t-PA release in 11 cases. In the remaining 35 cases, interpretation of results is difficult: in 16 patients the anomaly of the t-PA-PAI balance coexists with a satisfactory response of global fibrinolytic activity judged on the ECLT after VO (≤90 min) or on the EFA after VO (t-PA>2 U/l). This discordance may be linked to a compensating activity of another pathway of the fibrinolytic system. In 19 cases the discordances remain unexplained. In these subgroups of BR, clinical characteristics were not clearly different. However, the subgroup ‘concordant BR’ seems to be more frequently associated with recurrences or familial thrombotic tendency. This work underlines the difficulties of clinical interpretation of hypofibrinolysis testing. Global tests (ECLT, DWBLT) and EFA are not only dependent on the t-PA-PAI balance but also on the contact phase and u-PA course. Combinations of tests and a better understanding of the multiple pathways involved will be necessary if we wish to prospectively identify patients at significant risk of thrombosis.

SummaryWe describe a 57-year-old woman with homozygous protein C deficiency and mild thrombotic manifestations consisting of three spontaneous distal deep vein thromboses occurring after the age of 45. Previous surgery and pregnancies had been uneventful. Low but detectable protein C antigen and activity levels (both 20%) were discovered on the occasion of skin necrosis induced by oral anticoagulation. This therapy was interrupted because of skin necrosis and several episodes of disseminated intravascular coagulation (DIC) at the initiation of treatment despite a cautious protocol. No recurrent thromboembolic event has occurred in our patient using prophylactic doses of low molecular weight heparin for 24 months. New therapeutic approaches might be the administration of low molecular weight heparin or oral anticoagulation associated with protein C replacement in the induction period. This case reflects the variability of expression of protein C deficiency as well as the potential hazards of antivitamin K anticoagulation in this disorder.

Activated protein C (APC) resistance is related to a single point mutation in the factor V gene (FV:Q506) and appears to be the most common inherited risk factor for venous thromboembolism. A reliable screening test is therefore useful. We aimed to evaluate a new APC resistance test, on the basis of the procoagulant activity present in one snake venom of a crotalidae family: STA Staclot APC-R. We studied 36 consecutive patients with an acute deep venous thrombosis (DVT) confirmed by compression ultrasonography and carrying the FV:Q506 allele, assessed by DNA analysis, 103 of their family members and 35 consecutive patients with a proven DVT but who did not carry the FV:Q506 allele. Blood samples were collected within 24 h of admission for the DVT cases and on the day of medical registration for the family members. Tests were performed blind. The STA Staclot APC-R test, using a cut-off value of 0.80, had an overall sensitivity of 100% (95% CI, 95–100) and a specificity of 98.8% (95% CI, 92.0–99.6). An acute thrombosis process did not influence the performance of the test. We conclude that this test is easy and rapid to perform in every day practice and fulfills the criteria for a screening test. Blood Coag Fibrinol 9:355–359 × 1998 Lippincott-Raven Publishers.

We describe a 57-year-old woman with homozygous protein C deficiency and mild thrombotic manifestations consisting of three spontaneous distal deep vein thromboses occurring after the age of 45. Previous surgery and pregnancies had been uneventful. Low but detectable protein C antigen and activity levels (both 20%) were discovered on the occasion of skin necrosis induced by oral anticoagulation. This therapy was interrupted because of skin necrosis and several episodes of disseminated intravascular coagulation (DIC) at the initiation of treatment despite a cautious protocol. No recurrent thromboembolic event has occurred in our patient using prophylactic doses of low molecular weight heparin for 24 months. New therapeutic approaches might be the administration of low molecular weight heparin or oral anticoagulation associated with protein C replacement in the induction period. This case reflects the variability of expression of protein C deficiency as well as the potential hazards of antivitamin K anticoagulation in this disorder.

Summary. The determination of total fibrinolytic activity of ejaculates was realized by fibrin plate method. For the same seminal samples, tissue plasminogen activator (t-PA), urinary plasminogen activator (uPA) antigens and uPA activity were specifically quantified. The seminal values were fifty times higher than in the blood for t-PA and fifteen times for uPA. There was no correlation between the both levels but from split ejaculates measurements a higher concentration was observed in all first fractions. By zymography assays, it was shown that seminal plasminogen activators are under active forms. The lack of proUrokinase in semen was also demonstrated.

In patients with congenital deficiency in AT III, PC or PS, the risk of venous thromboembolism is increased and the first episode of thrombosis is frequently observed before the age of 40: pregnancy is often the precipitating condition