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Characterization with a simple clotting assay of the tissue factor inhibiting activity in serum.

The serum inhibiting activity on tissue factor (TFI) was evaluated as follows: normal human serum was incubated at room temperature with highly diluted rabbit brain thromboplastin (TF) and calcium ions; after 30 min. rabbit brain cephalin, calcium and normal human plasma were added to a small aliquot of TF/serum mixture; the clotting time at 37 degrees C was then recorded. With this assay TFI activity is proportional to the serum level; it is low for incubation periods shorter than 30 min., is missing at TF concentrations higher than 8%, is strictly connected to the presence of F VII and F Xa in the serum sample, depends upon the presence of calcium ions and finally, is independent of antithrombin III. This inhibiting activity also seems to be saturable and reversible.

Animals↗

[Assessment of hemostasis in patients with myocardial infarction complicated by deep venous thrombosis].

The study was carried out of 53 patients with acute myocardial infarction receiving no anticoagulant treatment. Changes were traced in certain indices of the blood clotting system and fibrinolysis in plasma in the first 14 days of the disease, with particular attention given to patients in whom during the hospitalization signs of deep vein thrombosis in the lower extremities appeared or a positive result was obtained of the test with 125I-fibrinogen. In a group of 9 patients with deep vein thrombosis developing during the observation, on the first day of myocardial infarction shortening of the kaolin-cephalin clotting time and considerable rise of the level of fibrinogen-fibrin (FDP) degradation products were noted in serum, and on the 14th day raised fibrinogen level and reduced exogenous fibrinolytic activity of the plasma were noted. Increased level of fibrinogen and FDP and exogenous and endogenous plasma fibrinolytic activity observed on the 7th day of the disease were not related to the development of thrombotic complications. The thrombin clotting time, platelet count, factor X level, protein C concentration and antithrombin III activity in the plasma were not significantly changed during myocardial infarction. The obtained results suggest a limited usefulness of the basic tests of the clotting and fibrinolytic systems for early diagnosis of deep vein thrombosis in acute myocardial infarction.

Blood Coagulation↗

Functional activity of protein S determined with use of protein C activated by venom activator.

A new screening procedure, an easy and specific assay for determining functional Protein S activity, has been developed, with use of Protein C activated by venom activator (Protac). Purified Protein C (100% amidolytic activity) was activated by venom activator (6 units/mL). To a mixture of 100 microL of Protein S-deficient plasma, 20 microL of sample plasma, 100 microL of cephalin (Actin), and 20 microL of activated Protein C we added 100 microL of 25 mmol/L CaCl2 solution and measured the clotting time with a KC 10 coagulometer. The functional Protein S activity correlated well with the concentrations of Protein S antigen measured by enzyme immunoassay and the Laurell rocket technique (r = 0.810 and 0.850, respectively) in normal subjects, patients with myocardial infarction undergoing warfarin therapy, and patients with liver cirrhosis.

Glycoproteins↗

Serum and thyroid tissue lipids in patients with thyroid tumors in euthyroidism.

Plasma lipids of 24 euthyroid subjects with thyroid adenoma and non-toxic primary differentiated thyroid carcinoma (papillary and follicular types) were assessed and compared with a similar investigation conducted on 20 normal subjects. A parallel study with thyroid tumor tissues examined the lipid changes which occurred in the same group of patients. These were compared with the picture seen in 5 normal thyroids. The investigations examined the changes in total lipids; total, free and esterified cholesterol; total phospholipids; lecithin; cephalin and sphingomyelin; triglycerides and free fatty acids in both serum and thyroid tissue. Compared with normal subjects, the serum lipids were almost identical except for the concentration of free fatty acids which showed significantly lower values in the group with neoplastic changes. Tissue analysis of the cancerous thyroid however revealed a marked rise in virtually all lipid fractions but the cholesterol seemed to dominate the picture. The differential studies of total phospholipids for thyroid tissue membrane lipids further revealed a significant increase in the lecithin and sphingomyelin components of total phospholipids as well as the esterified cholesterol fraction in thyroid carcinoma. The changes in thyrophospholipids were more marked in females normal thyroids than males. An attempt has been made through evaluation of the results derived from differential lipid studies to elucidate the role of some of the various fractions determined and the possible effect of the changes described on thyroid hormone metabolism.

Adenocarcinoma↗

Hemostatic changes in neonates with anoxia and sepsis.

Hemostatic profile (prothrombin time (PT), thrombin time (TT), kaolin cephalin clotting time (KCCT), plasma fibrinogen, serum fibrin/fibrinogen degradation products (FDP) and platelet counts) was examined in 153 neonates with birth anoxia and 86 with sepsis. Remarkable hemostatic alterations occurred in neonates with severe anoxia and sepsis, while those with moderate anoxia exhibited minimal or no change. Vitamin K administration to anoxic babies showed no improvement in the hemostatic profile after 48-72 hours. The hemostatic alterations were presumably due to incipient disseminated intravascular coagulation (DIC). In spite of the marked coagulation changes, only 3 neonates with sepsis and none of the anoxic newborns presented with clinical bleeding indicating a well balanced hemostatic mechanism.

Bacterial Infections↗

[Comparison of platelet activity, fibrinolysis and environmental factors in 50 Africans and 50 Europeans. Role of fish consumption].

The authors have studied 50 Ivorians and 50 Europeans people, all living in Abidjan for at least 10 years. Platelet aggregability with increasing ADP concentration (0.6, 1.2, 2.4 mumoles/l), collagen (0.4 mg/l), or ristocetin (1 g/l) was examined. Fibrinolysis and the euglobulin test were also studied before and after anoxia. Other blood parameters measured were: hematocrit, hemoglobin level, platelet count, bleeding time, Howell coagulation test, cephalin tests, prothrombin activity ratio, fibrinogen level. Metabolic tests included: glycemia, cholesterolemia, triglyceridemia, uricemia, A1 and B apoproteins, protidemia, gamma globulinemia. Environmental factors such as physical activity, alcohol and smoking habits, fish consumption, chloroquine prophylaxis were evaluated. The most evident result was lower platelet aggregability in Ivorian people as compared to Europeans. A more precocious and important fibrinolysis activity, either spontaneous or after anoxia was noted in the Ivorian group. Lower platelet number, fibrinogen level, and prothrombin activity were present in the Ivorian group as compared to the European people. The authors eliminated the influence of age, and considered environmental factors as predominant in the genesis of such difference, i.e., hypocholesterolemia, lower smoking and drinking levels. They emphasized the higher fish consumption in Ivorian people.

Adult↗

[Preliminary results of a randomized trial comparing the efficacy of standard heparin with that of fragmine, a low molecular weight heparin, in the prevention of postoperative thrombosis in cancer surgery].

Low molecular weight heparins have stimulated much interest because of their supposedly more selective action on Xa factor. A randomized study in 50 patients compared efficacy of low doses of a standard heparin, calciparin (5,000 IU/8 h) with that of a low molecular weight heparin, fragmine (Kabi 2165) (5,000 anti-Xa U/24 h), in the prophylaxis of postoperative thrombosis after oncologic surgery. Three of 25 patients receiving calciparin developed pulmonary embolism, as against one of 25 treated with fragmine who developed a periphlebitis. Hemorrhagic complications were comparable in the two groups. Anti-Xa activity was significantly higher in the fragmine group, whereas platelet counts, cephalin times with activator and anti-IIa activity were similar. These findings indicate equal efficacy of fragmine and calciparin in the prophylaxis of post-oncology surgery venous thrombosis.

Adult↗

[Comparison of the efficacy and tolerance of Kabi 2165 and standard heparin in the prevention of deep venous thrombosis in total hip prosthesis].

A series of 80 patients operated for total hip prosthesis under epidural anesthesia was randomly allocated to treatment with Kabi 2165 (n = 40): 2,500 U anti-Xa preoperatively and evening of operation and 2,500 U anti-Xa morning and evening daily up to the 9th or 10th day postoperatively, or standard heparin (n = 40): 3,750 U preoperatively and then 8 hourly, at a dose adjusted with thrombin time and cephalin + activator time, daily up to the 9th or 10th day. Phlebography was performed routinely on the 9th or 10th day. Venous thrombosis occurred in 7 patients (17.5%) in the Kabi 2165 group, including two high, potentially emboligenic, localizations (5%), and in 4 patients (10%) in the standard heparin group, including 2 potentially emboligenic clots (5%). The difference is not statistically significant (total number: p = 0.5; potentially emboligenic: p = 0.33). Pulmonary embolism did not occur. Overall tolerance, evaluated from hemoglobin and hematocrit values, intra- and post-operative bleeding and operation wound hematoma and at injection site was comparable in the two groups.

Aged↗

[Absence of transplacental passage of Fraxiparin (low molecular weight heparin) during the 3d trimester of pregnancy].

Using low molecular weight fractions of heparin (HBPM) can be at least potentially useful in pregnant women for certain indications. After animal studies had been carried out for toxic effects, one HBPM, CY216, which has been put on the market under the name of Fraxiparin, was studied to see whether it crosses the placenta in pregnant women by analysing fetal blood directly. Seven women who had fetal indications for terminating their pregnancies in the third trimester received a subcutaneous injection of 17,500 Choay units of Fraxiparin (0.7 ml). The haemostatic state was assessed in the mothers before the injection and three hours after it, and in the fetus approximately three hours after the injection into the mother. The fetal blood was taken in the uterus by direct aspiration using ultrasound guidance techniques. Anti Xa, anti IIa, and cephalin-kaolin time (TCK) were estimated. The anti Xa, anti IIa and the TCK were not changed in the 7 fetuses that were studied, 3 hours after the subcutaneous injection of a large dose of CY 216 although marked changes were noted in the mothers.

Blood Coagulation↗

[Acquired deficiencies in antithrombin III and C protein during treatment with L-asparaginase].

Fourteen children treated by L-Asparaginase for acute lymphoblastic leukemia had sequential coagulation studies performed including cephalin-kaolin time, Quick time, fibrinogen, factors II, VII + X and V, as well as antithrombin III and protein C, the major coagulation inhibitors. A severe antithrombin III and protein C deficiency was observed during therapy, with a coexisting hypocoagulability. This equilibrium partially explains the lack of thrombo-embolic phenomena in these children, despite the risk factors present. Although no substitutive therapy was instituted in these cases, their use in high-risk cases is discussed.

Adolescent↗

[The new heparins].

The new, so-called molecular weight heparins (mean MW : about 5,000 daltons) are less heterogeneous than the old, fractionated heparins (mean MW: about 15,000 daltons). Both types of preparations contain molecules with affinity for antithrombin III (AT III) and anticoagulant activity, as well as other molecules without affinity for AT III but which are thought to contribute to the antithrombotic activity of heparin. The anticoagulant effect of low molecular weight heparins (defined as their ability to prolong the activated cephalin time) in 3 to 4 times lower than that of standard heparin, but their activity against the activated factor X (Xa) is approximately the same. The half-life of the anti-Xa activity of low molecular weight heparins is twice that of standard heparin. The bioavailability of low molecular weight heparins administered subcutaneously is greater than 90%, as against less than 30% with standard heparin. Clinical trails have shown that one single subcutaneous injection of low molecular weight heparin 2 hours before an operation, then every 24 hours reduces the incidence of isotopic venous thrombosis in general surgery at least as much as 2 daily injections of calcium heparinate 5000 I.U. Low molecular weight heparins are virtually devoid of the pro-platelet aggregation activity exhibited by standard heparin.

Blood Coagulation↗

[Lupus-type anticoagulants and thromboses].

The presence of a lupus circulating anticoagulant factor is recognised by prolongation of the coagulation time of certain tests such as the activated cephalin time and Quick's test: this abnormality is not corrected by adding plasma and is not associated with a deficit of any of the factors of coagulation. This is a common abnormality not only in patients with disseminated lupus erythematosis but also in other conditions, and it may also be observed in healthy subjects. This abnormality is often associated with thromboembolic complications although it is not possible to demonstrate a cause and effect relationship.

Blood Coagulation Factors↗

Monoclonal hybridoma anti-cardiolipin antibodies from SLE mice.

To determine whether the anti-cardiolipin antibodies are identical with the lupus anticoagulant and other antibodies to phospholipids and DNA, we prepared monoclonal hybridoma autoantibodies to cardiolipin from SLE-prone MRL/lpr mice and characterized their specificity. Using a somatic cell hybridization technique, we established three hybridoma clones which produce antibodies to cardiolipin (CAL-1: IgG2b, k, CAL-2: IgM, k and CAL-3: IgM, k). These hybridoma antibodies preferentially reacted with cardiolipin and phosphatidylserine, weakly reacted with phosphatidylinositol, but not with other phospholipids such as phosphatidylcholine, sphingomyelin, phosphatidylethanolamine and VDRL antigen. Two hybridoma anti-cardiolipin antibodies bound to ssDNA and were found to act as the lupus anticoagulant when mixing activated partial thromboplastin time with cephalin. These autoantibodies may prove to be good tools for elucidating mechanisms of thrombosis, thrombocytopenia, fetal loss and other related manifestations found in patients with systemic lupus erythematosus.

Animals↗

[Blood coagulation indices of turkey poults experimentally infected with Eimeria adenoeides].

Studied were the changes, taking place in the thrombocytes, the cephalin-kaolin time, the fibrinogen, the prothrombin time, the presence and the quantity of the soluble fibrin monomer complexes. Used were 70 3-week-old turkey poults, divided into two groups--experimental and control. It was established that up to the 24th hour after the invasion no serious changes were observed. Changes take place on the 48th, 72nd, 96th and 120th hour, after the invasion, characterizing the disseminated intravascular coagulation. Most typical are the changes on the 96th and 120th hour after the invasion, which express in decreasing the number of thrombocytes and the quantity of fibrinogen and in increasing the content of the soluble fibrin monomer complexes.

Animals↗

[Effect of the C1q complement subcomponent on blood coagulability and fibrinolysis].

The in vitro experiments on human plasma have shown that C1q addition in a concentration of 120 micrograms/ml led to a substantial shortening of coagulation time of test-plasma, as well as kaolin- and cephalin time. The effect is preserved in plasma deficient in factors V, X and VII. It is assumed that C1q has properties similar to those of thromboplastin.

Blood Coagulation↗

[Low-molecular weight heparins. Prospects in 1985].

Interaction of low molecular weight heparin (LMW-Hep) along with coagulation system is characterized through an increase of the proportion between activity anti-Xa and anticoagulation activity. In animals, their antithrombotic role can be compared with the heparin one. Longer life of the biological effect (close to 100 p. 100) enables to act subcutaneously as well as to reduce posology: only one injection is then required so as to prevent from post-operative thrombosis. There are neither method nor international standard to control preparations efficacy. At the moment, posologies are better to be expressed in mg. Trials are assessed in the treatments of thrombosis with results increasing therapeutic efficacy. Too high posologies did supply hemorrhagic syndromes in surgical patients. A biological survey is thus required. As usual tests, such as "time" of cephalin are slightly sensible to LMW-Hep, only anti-Xa activity can be used. LMW-Hep with a low anticoagulant action thus demonstrate a new concept of antithrombotic therapy.

Animals↗

Hemostatic parameters in newborn--II. Sequential study during the first four weeks of life.

A sequential study of kaolin cephalin clotting time (KCCT), prothrombin time (PT), thrombin time (TT), plasma fibrinogen and serum FDP was conducted during the first four weeks of life on term and preterm babies. A "physiological dip" of PT and TT was noted inappropriate for gestational age (AGA) babies both term and preterm; in case of KCCT, the dip was significant in term AGA babies only. At the end of four weeks, PT and TT had moderately improved in term babies but showed little improvement in preterm ones; KCCT reached almost an adult value in all babies except in preterm AGA and term LGA (large for gestational age) ones. Plasma fibrinogen showed no "physiological dip" and reached adult level in two to four weeks. Serum FDP levels were appreciably raised in preterm AGA babies only at birth and there too normalised by 72 h.

Age Factors↗

[Thrombophlebitis and pulmonary embolism in congenital factor XII deficiency].

The case of a young man hospitalised for bilateral lower limb deep vein thrombosis is reported. None of the usual causes were found after systematic wide-ranging investigation. The only abnormality on admission was a spontaneous increase in the cephalin-kaolin time to 65 seconds compared to a control time of 40 seconds. Measurements of the clotting factors showed a moderate and isolated deficiency in factor XII (30 p. 100), also present in a brother (50 p. 100) and a sister (42.5 p. 100). Fibrinolytic therapy was administered : an initial course of Streptokinase was followed by extension of a left femoral vein thrombosis and pulmonary embolism. Two courses of Urokinase were given with an eight day interval without significantly improving the venous circulation. This case is an example of thrombogenic disease due to a deficiency of a clotting factor resulting in non-activation of physiological fibrinolysis.

Adult↗