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Biomedical subjects

J Conard

Publications and source records attributed to J Conard.

At least 109 records · Page 6Linked to original sources
PubMed1988

Residual plasminogen activator inhibitor activity after venous stasis as a criterion for hypofibrinolysis: a study in 83 patients with confirmed deep vein thrombosis.

In eighty-three patients with confirmed deep vein thrombosis, the fibrinolytic system was studied before and after a 10-minute venous occlusion. Blood was collected at least 3 months after the last acute episode, and PAI-1 antigen and activity, as well as tissue-type plasminogen activator (t-PA) antigen, urokinase-type plasminogen activator (u-PA) antigen, and fibrinolytic activity were measured in these samples. During venous stasis, plasminogen activator inhibitor (PAI) activity decreased in almost all patients (81 of 83), from a median value of 8.2 to 2.9 U/mL (P less than .001, Wilcoxon signed-rank test). Because PAI-1 antigen augmented from a median value of 16 to 19.2 ng/mL (P less than .001), the decline in PAI activity was attributed to an increase in t-PA antigen from a median value of 10 to 21.7 ng/mL (P less than .001). Neutralization of PAI activity thus reflects the patient's capacity to overcome basal inhibitory potential through t-PA release. Based on residual PAI activity after 10-minute stasis, patients were classified as good or bad responders (PAI activity below detection limit, ie, less than or equal to 1.0 and greater than 1.0 U/ml, respectively). Good responders had a significantly higher fibrinolytic response after stasis than bad responders (median euglobulin clot lysis time 60 v 180 minutes; dilute whole blood clot lysis time 60 v 120 minutes; fibrinolytic activity on fibrin plates 7.7 v 0 U/mL). Furthermore, good responders, as compared with bad responders, had higher t-PA release (median 16.5 v 11.5 ng/mL), lower basal PAI activity (median 4.8 v 11.2 U/mL), and lower basal PAI-1 (median 11 v 21 ng/mL) and u-PA antigen (median 7.9 v 9.0 ng/mL, P less than .02). Hypofibrinolysis, as defined by the inability of released t-PA to overcome PAI-1 basal inhibitory potential, was observed in 45 of 83 patients (54%) and resulted either from an insufficient release of t-PA or from an increased basal PAI activity.

Adult↗
PubMed1988

[Actilyse: biological aspects].

Alterations of coagulation and fibrinolysis induced by administration of single or two chains rtPA are detailed from personal and published results. One should differentiate between the thrombolytic activity, responsible for the efficacy of the drug on thrombosis and the systemic fibrinolytic activity, inducing the decrease in fibrinogen and coagulation factors which probably contribute as to the risk of bleeding, mostly related to invasive explorations (arterial punctures, catheters...), but possibly spontaneous. Few assessments are made: a sufficient plasma level of rtPA should be present to obtain a good efficacy; the degree of fibrinogen decrease is variable between individuals, although it is moderate in most patients (80% of cases); results of the measurements of fibrin degradation products are disappointing and do not allow the laboratory diagnosis of thrombus dissolution. Concerning the risk of re-occlusion, a careful monitoring of heparin treatment may reduce this risk but further studies are needed.

Fibrinolysis↗
PubMed1988

[Hemorrhagic risk in intravenously administered thrombolytic treatment in acute myocardial infarction].

163 patients aged from 27 to 70 years (mean 52 +/- 10 years), including 152 men and 11 women, received a thrombolytic treatment within the first 6 hours (mean 192 +/- 73 mn) of a myocardial infarction. 61 patients received streptokinase (SK) intravenously (group 1), 64 patients, single-chain rt-PA (group 2), 11 patients, two-chain rt-PA (group 3), 11 patients, rt-PA followed by intracoronary streptokinase (group 4), and 16 patients, acyl enzyme (group 5). In addition, all patients had heparin and 86 (53%) had aspirin. Immediately after thrombolysis, coronary arteriography was performed in 95 patients (58%), and this was followed by transluminal angioplasty in 49 of them (30%). The infarction was either anterior (n = 81) or inferior (n = 78) or lateral (n = 4). No fatal or neurological bleeding occurred. 17 haemorrhagic complications were observed; 5 of these (3%) were severe, requiring blood transfusion and, in 1 case, surgery; 12 were significant (7.4%) and produced changes in haematocrit. Nine of the 17 haemorrhages were associated with catheterization and localized to the site of arterial puncture. Severe bleeding occurred in patients treated with intravenous SK (3/61) or with rt-PA followed by intracoronary SK (2/11). There was a significant difference in the incidence of spontaneous bleeding between the SK group (4/61) and the single-chain rt-PA group (0/64; p less than 0.05). In the latter group, the minimum fibrinogen level was lower in patients who had a haemorrhagic complication.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1988

[Is Behçet's disease associated with characteristic abnormalities of coagulation and fibrinolysis? Apropos of 70 case reports].

The frequency of thrombotic episodes in patients with Behçet's disease prompted us to study their hemostasis. Seventy patients were investigated and 27 of them (38%) had history of venous thrombosis; they were compared to 27 healthy subjects and to 16 hospitalized patients in whom the diagnosis of Behçet disease was ruled out. Fibrinolytic activity after a 10 minute venous occlusion was significantly decreased while fibrinogen, factor VIII and von Willebrand factor was increased as well as the tPA inhibitor (PAI-I): the last 3 proteins are synthetized by the endothelial cell. No significant difference was observed between patients with or without history of thrombosis. Coagulation and fibrinolysis changes observed are not specific of Behçet disease since they were also found in a population of patients without Behçet disease and without history of thrombosis.

Adolescent↗
PubMed1987

[Hereditary protein S deficiency and recurrent venous thrombosis. Study of a family].

Hereditary protein S deficiency was detected in three subjects belonging to three generations of one single family. The deficiency was heterozygous and was associated with recurrent venous thromboembolism in two of the subjects affected. Plasma analysis by two-dimensional immunoelectrophoresis showed that the protein S fraction bound to C4b-binding protein was quantitatively normal, whereas the free protein S fraction was much reduced. Since it has been well established that only free protein S intervenes in the regulation of blood coagulation, any quantitative deficiency, even moderate, in protein S resulting in redistribution of its free and bound fractions will have major functional repercussions.

Adult↗
PubMed1987

Multicenter evaluation of a chromogenic substrate method for photometric determination of prothrombin time.

A multicenter study of a chromogenic substrate method for photometric determination of prothrombin time was conducted in order to evaluate its clinical application. Seven laboratories participated in the study using a total of 742 plasma samples from 417 patients on oral anticoagulant therapy, 261 healthy subjects and 64 patients with different diseases especially of the liver as well as 30 patients with hereditary deficiency of coagulation factors II, V, VII, X. The chromogenic PT method was compared to a standardized coagulometric PT assay which uses the same sensitive human placenta thromboplastin calibrated against international reference preparations. A high correlation of the prothrombin ratio values of the chromogenic and the coagulometric assay was obtained in 402 plasma samples (r = 0.940; y = 1.02x - 0.1). The study showed that the chromogenic PT reagent is sensitive to deficiency of the coagulation factors of the extrinsic pathway but not affected by heparin up to 1 IU/ml because of the heparin antagonist added. The precision (coefficient of variation) of the photometric method ranged between 0.6 and 3% (intraassay CV) and between 1.4 and 5.8 (interassay CV). The International Sensitivity Index (ISI) obtained for the used lot was 1.09. The therapeutical range in percentage activity for patients in a stable phase of an anticoagulant therapy was found to be from 15 to 27 percent of normal. The results of the clinical evaluation proved the good comparability of the new chromogenic PT test with coagulometric methods, its high factor sensitivity, good reproducibility and easy performance.

Anticoagulants↗
PubMed1987

[Deep venous thrombosis in Behçet's disease. 106 localizations in a series of 177 patients].

A retrospective study of 177 patients (137 male, 40 female) with a disease that fulfilled the criteria of complete or incomplete Behçet's disease showed 106 thrombotic lesions of a venous trunk in 62 (35%) of these patients, superficial phlebitis and retinal vein thrombosis excluded. The incidence of thrombosis was unrelated to race and sex. The venous lesions were single in 38 cases and multiple in 24 cases, including 4 with more than 4 territories involved. Arterial lesions were also present in 7 cases. The lesions were located in the sural (n = 63), iliofemoral (n = 14), inferior vena cava (n = 13), superior vena cava (n = 3), axillary (n = 2) and cerebral (n = 13) veins or territories. Thrombosis developed during the first 4 years of Behçet's disease in one half of the patients. It preceded the aphthosis by 1 to 10 years in 11 cases, was concomitant with it in 15 cases and appeared more than 10 years after the diagnosis in 8 cases. Pulmonary embolism occurred in 11 patients, requiring clipping of the vena cava in 2, but it was never lethal. However, 2 of the 5 patients who died had venous thrombosis (Hughes Stovin syndrome). Thirty-eight patients could be followed up for 12 to 192 months (mean 43) under anticoagulant or antiplatelet therapy. Five vascular recurrences (13%) were observed, 2 of them (1 arterial graft thrombosis, 1 cerebral thrombosis) under anti-vitamin K agents. Cerebral thrombosis (9 men, 4 women) accounted for 27% of the neurological lesions; its prognosis was favourable in the 7 patients successfully treated with anticoagulants. Thrombosis could not be explained. Haemostasis studies showed a decrease of fibrinolytic activity compared to a group of normal subjects and an increase in fibrinogen, factor VIII and Willebrand's factor levels; these abnormalities did not seem to be specific. Thus, phlebitis truly is an element of Behçet's disease. Until its mechanism is better understood, effective anticoagulant therapy in cases with proven thrombosis and preventive antiplatelet therapy in the other cases seem to be rational measures.

Adult↗
PubMed1987

Treatment of hereditary protein C deficiency with stanozolol.

Five type I protein C deficient male patients received 5 mg stanozolol b.i.d. during 4 weeks. After four weeks of treatment plasma protein C activity increased from 0.42 to 0.74 U/ml and protein C antigen from 0.49 to 0.75 U/ml. This approximately 1.6 fold increase in plasma protein C was accompanied by an increase in factor II antigen (1.5 fold), factor V activity (1.6 fold), factor X antigen (1.1 fold), antithrombin III antigen (1.3 fold) and heparin cofactor II antigen (1.5 fold), while the concentration of factor VII, factor VIII, and factor IX activity, and of protein S antigen remained unchanged. Prothrombin fragment F1+2, measured in two patients, increased 1.3 fold. In addition to its effect on procoagulant and anticoagulant factors stanozolol had profibrinolytic effects, reflected in an increase in tPA activity and in the concentration of plasminogen. These data indicate that in type I protein C deficient patients stanozolol increases the concentrations of both procoagulant and anticoagulant factors and favours fibrinolysis. The efficacy of stanozolol in preventing thrombotic disease in type I protein C deficient patients, however, remains to be established. During the four weeks of stanozolol treatment no thrombotic manifestations were observed in the protein C deficient patients.

Administration, Oral↗
PubMed1987

Laboratory monitoring of a low molecular weight heparin (enoxaparin) with a new clotting test (Heptest).

A new simple clotting test (Heptest) for low molecular weight heparins was compared to anti-Xa determination by an amidolytic assay in volunteers and in patients receiving standard calcium heparin or low molecular weight (LMW) heparin (Enoxaparin) by subcutaneous administration. The results obtained with both methods are in very good agreement. It seems that the Heptest, although influenced by various other clotting parameters, is nevertheless relatively specific for anti-Xa activity. Despite our positive first impression, we object to expressing the results in micrograms of heparin per milliliter or anti-Xa units. Until rigorous standardization is possible, we prefer to express the results as clotting times. Preliminary results warrant a more extensive study in order to assess the clinical relevance of Heptest in patients receiving unfractionated or LMW heparins.

Blood Coagulation Tests↗
PubMed1987

Biological study of intravenous anisoylated plasminogen streptokinase activator complex in acute myocardial infarction.

An anisoylated plasminogen streptokinase activator complex (APSAC) has been administered as a bolus intravenous injection of 30U to 14 patients with acute myocardial infarction. Systemic effects on coagulation and fibrinolysis were studied. In 1 patient, the treatment produced no biological modification, which could be explained by an increased streptokinase resistance in this patient, apparent from the sample collected before treatment. In the other patients, as expected, fibrinogen, plasminogen, alpha 2-antiplasmin and factors V and VIIIc fell dramatically, while there was an increase in serum fibrinogen degradation product concentrations. In addition, plasma fibrin derivatives increased during APSAC therapy, both in patients who had occluded or patent coronary arteries. Discrepancies were found between methods used to measure fibrinogen: with the Ellis and Stransky method, concentrations were higher than with the Clauss method; and for plasminogen, automated methods using different analysers may give higher results in some patients.

Adult↗
PubMed1987

[Platelet aggregation tests in 26 cases of heparin-induced thrombopenia. Methodological, diagnostic problems and therapeutic aspects].

A diagnosis of heparin induced thrombocytopenia (HIT) in the 26 patients was based on: 1. normal platelet count prior to heparin administration; 2. its fall to less than 100 Giga/l (m = 46 +/- 23) at time of first sample collection for test to detect a platelet aggregation factor (PAF); 3. restoration of normal values after discontinuation of heparin treatment during which the thrombocytopenia had appeared. The result of the first PAF test in these 26 patients was positive in 22 cases, negative in 2; twice the plasma provoked platelet control aggregation without in vitro addition of heparin. The origin, dose and mode of administration of the heparin did not appear determinant in the production of the thrombocytopenia: 16 of the patients were later treated with a low molecular weight heparin (LMWH). An in vitro "compatibility" test was able to be performed 8 times previously and was negative in 7 cases in the 16 patients. Samples were collected during LMWH treatment and were negative in 13 cases, and this in agreement with the increased platelet count after 7 +/- 3 days and the clinical improvement. In 3 patients the test was positive: in one case the count did not return to normal, in the second case this did occur, but slowly (21 days); the PAF test in the last patient was positive prior to LMWH treatment and remained so while the count became normal. Concordance exists therefore between negativity of the test practiced with LMWH and the increase in count when this heparin is administered; inversely, the positivity of the test does not exclude normalization of the platelet count.

Adult↗
PubMed1987

[Biological modifications induced by 3 low molecular weight heparins, PK 10169, Kabi 2165 and CY 216, compared to unfractionated heparin injected subcutaneously in healthy subjects in general surgery and in aged subjects in internal medicine].

Activities of anti-Xaam, anti-IIaam, Heptest and calcium thrombin time (Ca TT) were compared in: 12 male healthy volunteers after increasing doses of 20, 40, 60 and 80 mg/day of Enoxaparine; 76 patients after gynecological surgery treated with 20 mg (12 cases), 40 mg (15 cases) or 60 mg (10 cases) per day of Enoxaparine versus calcium heparin as 5,000 IU x 3/day (39 cases); 68 patients after general surgery treated with 2,500 units Fragmine/day (34 cases) versus calcium heparin 5,000 IU x 2/day (34 cases); 27 patients in a medical ward treated with either 7,500 Choay Institute units/day of Fraxiparine (14 cases) or Cutheparine (magnesium heparinate) (13 cases). In this latter case results of Heptest only are reported. In healthy volunteers and patients after gynecological operations, the Ca TT and anti-IIaam activity were significantly modified after doses greater than or equal to 40 mg. Values for anti-Xaam and anti-IIaam were dose-related but higher in healthy volunteers. The anti-Xa/anti-IIa ratio was 3-4. Correlation between Heptest, a simple test, and anti-Xa activity--both very good markers of low molecular weight heparins (LMWH)--was very good (r = 0.93, p less than 0.02 in healthy volunteers; r = 0.87, p less than 0.01 in operated patients). Peak activity was at about 3 to 4 hours after injection, the half-life of anti-Xa and anti-IIa activities being 4 and 2 hours respectively. After heparin injection, the anti-Xa/anti-IIa ratio was 1 but activities were weak (5,000 IU x 2 = 0.02 +/- 0.02), a little higher with 5,000 IU x 3 (0.05 +/- 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗