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Possible mechanism of the synergistic effect of heparin and dihydroergotamine.

A combination of heparin and dihydroergotamine mesylate (Heparin-Dihydergot) has been shown to be more effective than either of these drugs alone in preventing postoperative venous thromboembolism. The possible mechanism for the synergistic effect of heparin and dihydroergotamine was assessed. Phlebograms obtained after administration of 0.5 mg of dihydroergotamine showed marked constriction of the tibial and soleal veins with a significant reduction in the mean diameter of the femoral vein. The effect on the coagulation mechanism was assessed in 28 patients. Blood samples were withdrawn from the femoral vein during varicose vein operations. A significant difference was observed in antithrombin III activity, kaolin-cephalin clotting time, beta-thromboglobulin, and fibrino-peptide levels between the control, dihydroergotamine, heparin, and the combination groups.

Antithrombin III↗

Phosphorus determination in phosphoglycerides from thin-layer chromatograms.

Phosphoglyceride phosphorus is readily determined directly on silica gel removed from thin-layer chromatograms, without elution, by a nondigestive procedure with a sulfuric-periodic acid reagent. The method is specific for hydrolyzable phosphoglyceride containing two acid-hydrolyzable groups. Cariolipin reacts only partially, while sphingomyelin, diether lecithin, and phosphonate cephalin fail completely to react.

Chromatography, Thin Layer↗

Factor VII Padua 2: another factor VII abnormality with defective ox brain thromboplastin activation and a complex hereditary pattern.

A new factor VII abnormality is presented. The propositus was a 9-yr-old child who presented a mild bleeding tendency characterized by epistaxis and easy bruising. The parents were not consanguineous, but they came from the same area. The laboratory features were mild prolongation of prothrombin time and P.P. test and normal partial thromboplastin and Stypven cephalin clotting times. The Thrombotest was moderately prolonged. Factor VII was 40%-50% of normal using rabbit or human brain thromboplastin, but only 13%-24% using ox brain thromboplastin. Factor VII cross-reacting material (CRM) was about 50% of normal. The father, a paternal aunt, and a paternal cousin showed similar clinical and laboratory findings. The brother of the propositus, the mother, and other members of her family showed about 50% factor VII activity and CRM and were considered to be heterozygotes for true factor VII deficiency. Similar findings were also present in the father and in the brother of the affected cousin. The defect in the propositus seems to consist of a double heterozygosity between abnormal factor VII and heterozygous factor VII true deficiency. The factor VII abnormality appears to consist of abnormal reactivity toward ox brain tissue thromboplastins and appears to be different from previously described factor VII abnormalities. The name factor VII Paudua2 is proposed for this condition.

Adolescent↗

Comparative studies of blood coagulation in hibernating and non-hibernating frogs (Rana tigrina).

1. During hibernation in frogs (Rana tigrina) there occurs prolongation of several clotting tests, viz, whole blood clotting time, plasma recalcification time, cephalin time and prothrombin time. 2. The ambient body temperature of the frog during winter hibernation is low and the retarded blood clotting at lower temperature may play an important protective role against intravascular thrombosis. 3. Shorter plasma recalcification time in low-spun plasma as compared to high-spun plasma indicated the presence of procoagulant activity in platelets/leucocytes of frogs.

Animals↗

A double-blind comparison of a new antidepressant, protryptiline, with imipramine and amitryptiline.

Protryptiline, a new antidepressant, was evaluated in a double-blind study. Results were compared with those obtained in similar groups of patients treated with imipramine and amitryptiline. After full psychiatric and medical assessment, patients were rated on a "target-symptom" scale, were assessed weekly and underwent a number of tests before and after treatment, including a hemogram and estimations of serum bilirubin, cephalin flocculation and serum protein values. Observations were made over four to six weeks. The starting dosage was 10 mg. protryptiline three times daily with a maximum of 60 mg. daily. Beneficial responses occurred in 13 of 20 patients (65%). Protryptiline-treated patients had the earliest response to drug treatment, 11 showing some improvement within the first week. Twelve patients (60%) had side effects, mainly minor, indicative of anticholinergic activity. One developed leukopenia which was reversible, and one showed increased excitement; in both, therapy was discontinued. Protryptiline gave clinical results that compared favourably with those of antidepressants of established value. While toxic effects should be carefully watched for, further trials are warranted to decide whether protryptiline possesses special or new advantages in psychopharmacotherapy.

Amitriptyline↗

Reactions of activated factor X-phosphatide mixtures in vitro and in vivo.

The composition, surface properties, and capacity of lipid particles to bind activated factor X can be correlated both with the influence of various phosphatide combinations on activated factor X activity in vitro and on the intensity and duration of the thrombogenic stimulus as measured by a standard bioassay for thrombus formation. The measurable activity of activated factor X in vitro increased as a linear function of lipid concentration from 0 to 40 micro moles/liter. The effectiveness of the lipids examined was in the following decreasing order: phosphatidyl serine-phosphatidylcholine mixture, "cephalin", and phosphatidyl serine alone. An increase in the duration of hypercoagulability with increasing lipid concentration was also observed, but, with regard to the three lipid fractions tested, the in vivo system appeared to be more discriminatory than in vitro assays. Lipid mixtures containing phosphatidyl serine with either phosphatidylcholine, phosphatidyl ethanolamine, or cetyltrimethylammonium bromide markedly enhanced the in vitro activity of activated factor X. Phosphatidic acid-phosphatidylcholine mixtures had a similar but smaller effect, and phosphatidyl ethanolamine-phosphatidylcholine mixtures were inert. The duration of the hypercoagulability was similarly related to the composition of the phosphatide infused. In mixtures containing phosphatidyl serine, the surface charge density of the lipid particles and the binding of the activated factor X activity to lipid showed some correlations with the in vitro activated factor X assay and with the intensity and duration of the thrombogenic stimulus. These data suggest that the catalytic effect of phosphatides on prothrombin activation and their role in the retardation of in vivo compensatory mechanisms directed against circulating activated factor X, are dependent on the affinity of activated factor X for the lipid surface.

Animals↗

[Studies on the lipid composition in serum and lymphocytes in chronic leukemia].

In 33 patients with chronic lymphatic leukaemia (CLL) the lipids were examined quantitatively and qualitatively in the serum and in the lymphocytes. Besides the 5 main categories of lipids, lysolecithin, sphingomyelin, lecithin and cephalin as well as cholesterol ester subfractions were determined according to their degree of saturation of their fatty acids. Patients suffering from CLL were found to have a moderately raise of serum triglycerides and an increase of cholesterol esters with simple unsaturated fatty acids. Simultaneously the fraction of ester with poly-unsaturated fatty acids is lowered. Leukaemic lymphocytes reveal in general a lowered total lipid content. It mainly consists of phosphatides and free cholesterol. Moreover, the leukaemic lymphocytes contrary to normal ones reveal a lowered content of cholesterol esters, diglycerides and triglycerides.

Aged↗

Blood coagulation and fibrinolysis in haemorrhagic stroke.

Studies of 11 patients with haemorrhagic stroke revealed no significant change in kaolin cephalin clotting time, prothrombin time, thrombin time, PF 3 availability, platelet count and factor V and VIII during the first week. Plasma fibrinogen was significantly increased while factors VII + X were decreased (borderline significance). Prolongation of plasma recalcification time and decrease in heparin tolerance reached borderline significance. There was moderate, but significant, increase in serum antithrombin activity and plasma (euglobulin fraction) fibrinolytic activity.

Blood Coagulation↗

Chromogenic substrate (S-2222) factor X assays in the follow-up of coumarin treated patients. No advantage over prothrombin time and/or thrombotest.

Factor X was assayed in 30 patients on long-term anticoagulation by means of a chromogenic substrate (S-2222) for a total of 120 determinations. The average level found was 25.38 +/- 9.38% of normal. A satisfactory correlation was found between the factor X chromogenic level and the prothrombin time or Thrombotest percental values. However, factor X levels as determined by the chromogenic assay were usually higher than the global tests percental figures. The factor X chromogenic level was also slightly higher than the RVV-cephalin factor X assay. Since the chromogenic assay does not allow any new information to be made on the coumarin induced defect and since the costs of the assay are about 20-30 times higher than those of a simple prothrombin time, the test seems to play no part in the follow-up of coumarin therapy.

Blood Coagulation Tests↗

Inhibition of human factor Xa by various plasma protease inhibitors.

The inhibitory effects of the plasma protease inhibitors antithrombin III, alpha 2-macroglobulin and alpha 1-antitrypsin on the activity of human factor Xa have been studied using purified proteins. The rate of inhibition was determined by measuring the residual factor Xa activity at timed intervals utilizing the synthetic peptide susbtrate Bz-Ile-Glu(piperidyl)-Gly-Arg-pNA. Kinetic analysis with varying molar concentrations of inhibitors demonstrated that the inhibition of factor Xa by antithromin III, alpha 2-macroglobulin and alpha 1-antitrypsin followed second-order kinetics. Calculated values of the rate constants for the inhibition of factor Xa by antithrombin III, alpha 2-macroglobulin and alpha 1-antitrypsin were 5.8 . 10(4), 4.00 . 10(4) and 1.36 . 10(4) M -1 . min -1, respectively. The plasma concentrations of the inhibitors can be used to assess their potential relative effectiveness against factor Xa. In plasma this was found as alpha 1-antitrypsin greater than antithrombin III greater than alpha 2-macroglobulin in the ratio 4.64: 2.08: 1.0. Cephalin was shown to inhibit the rate of reaction between factor Xa and antithrombin III.

Antithrombin III↗

Anti-phospholipid antibodies and biological false positive serological test for syphilis in patients with systemic lupus erythematosus.

Utilizing a newly developed solid phase enzyme immunoassay for the detection of anti-phospholipid antibodies, we found that 41.7% of sera from patients with active systemic lupus erythematosus (SLE) had the anti-cardiolipin antibody and 22.7% of sera were positive for the anti-phosphatidylinositol (PI) antibody. But antibodies to lecithin, cephalin and sphingomyelin were rarely found in this assay. We also examined antibodies to the VDRL (Venereal Disease Research Laboratory) antigen which consists of cardiolipin-cholesterol-lecithin mixtures. The incidence of the anti-VDRL antibody in the IgG class was 29.2% and 25% in the IgM class, and the magnitude of these antibodies correlated well with the incidence of biological false positive serological test for syphilis (BFP-STS), but no association between the anti-VDRL antibody titre and the anti-cardiolipin antibody titre was observed. Furthermore, the cardiolipin binding activity of sera from patients with SLE was inhibited by DNA and poly(I), both of which have polynucleotide backbones structurally similar to the phosphodiester groups of cardiolipin. On the contrary, these polynucleotides failed to inhibit the PI and the VDRL binding of SLE sera. These observations may support the concept that the anti-cardiolipin antibody in sera from patients with SLE might be a part of the anti-DNA antibodies, which are serologically polymorphic in that they can react with a variety of polynucleotides, but differ from the BFP reactors.

Antibodies↗

[Importance of disorders of primary hemostasis in the occurrence of upper digestive hemorrhage in cirrhosis].

In order to assess the true incidence of haemostatic disorders in cirrhotic gastro-intestinal haemorrhage, a comparative prospective study of primary haemostasis, coagulation and fibrinolysis was carried out in 37 patients distributed into two groups: cirrhotics with gastro-oesophageal varices that had never bled (Group A = 22), and cirrhotics who had had an intestinal bleed from "ruptured" gastro-oesophageal varices (Group B = 15). Combination of thrombocytopenia (less than 100 10(9)/l) and a bleeding time greater than 8 mn was more frequent in Group B (80%) than in Group A (45%) (p = less than 0.05). On the other hand, no significant difference between the two groups was found in the activated cephalin time, thrombin time, prothrombin complex factors (II, V, VII-X), fibrinogen, antithrombin III, Factor VIII complex factors, FDP levels or plasminogen. In conclusion, these results suggest that disorders of primary haemostasis may be involved in bleeding from gastro-intestinal varices in cirrhosis. However, coagulation disorders and anomalies of fibrinolysis would not seem to play a determining role.

Bleeding Time↗

Influence of long-term plasmapheresis on blood coagulation.

The influence of serial, double plasmapheresis on blood coagulation was evaluated in two groups of plasma donors that had undergone from 3 to 306 plasmapheresis sessions. Averages of 375 and 660 ml of plasma, respectively, were harvested weekly from the donors. No statistically significant changes were observed in platelet count, activities of factor V and factor VIII, fibrinogen, plasminogen, alpha 2-macroglobulin, antithrombin III and prothrombin time, irrespectively of the frequency and the number of the plasmapheresis sessions. The concentration of alpha 1-antitrypsin was already increased after seven plasmapheresis sessions in both groups of donors. The kaolin-cephalin clotting time was progressively shortened with the increasing volume of harvested plasma (p less than 0.05) and the thrombin time was prolonged (p less than 0.05).

Adult↗

[Inducing effects of bis-hydroxyethylthio-1,10-decane (tiadenol) on hepatic microsomal enzymes of the rat].

1. Male Wistar rats were treated with tiadenol, 200 mg/kg/ p.o. daily for 7 days. 2. The administration of tiadenol markedly increased the activity of bilirubin glucuronosyl transferase in hepatic microsomes. Cytochrome P 450 levels and ethoxycoumarin deethylase activity were more slightly increased. 3. Electrophoresis of microsomal proteins showed the induction of a protein with a molecular weight of about 72,000. 4. Tiadenol alone only slightly affected the fatty acid composition of microsomal lecithins and cephalins. When given with phenobarbital, however, tiadenol modified the phenobarbital-induced changes in the fatty acid composition of microsomal lipids.

7-Alkoxycoumarin O-Dealkylase↗

[Clinico-biochemical parallels in neurotoxicoses in children].

The authors present the results of examining the plasma lipids in 62 children with an infectious neurotoxic syndrome. The children were suffering from acute respiratory viral infections, lobular pneumonia, or intestinal infections. Hyperlipidemia and dysphospholipidemia were revealed: the former was due primarily to a rise of the content of non-saturated fatty acids and triglycerides, and the latter to a drop of the lecithin and cephaline levels. These changes correlated with the disease gravity. No substantial differences in the plasma lipid spectrum were revealed in the children with the neurotoxicoses due to the acute respiratory infections, pneumonias, and intestinal infections, however, in the latter cases a more marked rise of the triglyceride content was noted.

Child, Preschool↗

[Evaluation of Owren's thrombotest in the monitoring of treatment with antivitamin K].

The need to standardize the monitoring of oral anticoagulant treatments has led some countries to adopt, generally, Owren's Thrombotest. Apart from needing only one reagent and being perfectly adapted to this type of monitoring, the thrombotest has the advantage of being able to be used on capillary blood and venous blood and of not being influenced by the storage of the blood samples. Its disadvantages are that it is slow to perform, difficult to automate and that it has a therapeutic range which is narrow and close to the limits of precision of the technique. The results of the Thrombotest correlate well with those of the Quick test, the activated cephalin time and the X level measured by the amidolytic technique. Until the chromogenic assays are developed, the Owren's Thrombotest provides a better homogeneity and standardization of the results coming from different laboratories.

Anticoagulants↗

[Distribution of the fatty acids of the oyster C. gigas in different lipid fractions].

Extraction of oyster lipids were carried out on total wet organic tissues with a mixture of chloroform-methanol. The different fractions of polar and not polar lipids were separated by thin layer chromatography (TLC) and the methyl esters of the constituant fatty acids has been prepared by transmethylation a cold for use in subsequent gas-liquid chromatography (open tubular gas chromatography). The oyster contained considerable proportions of C16:0 and heiglhly unsaturated acids (specially in lecithin and cephalin) of C20, C22 series which are characteristic of the lipids of most acquatic plants and animals. Studies were made of the seasonal variations.

Animals↗

Blood coagulation profile in patients with acute diffuse peritonitis.

Coagulation studies conducted on 42 patients with acute peritonitis of varying etiology revealed statistically significant prolongation of kaolin cephalin clotting time, decrease of platelets and elevation of plasma fibrinogen and serum fibrinogen degradation products. The relationship of the coagulopathy to bacterial invasion of peritoneal cavity was indicated by the absence of significant change in KCCT, prothrombin time, and bleeding time in patients with sterile peritoneal fluid. The results suggest a process of insidious defibrination intricately superimposed on the hypercoagulable state in these patients.

Acute Disease↗