Thromboplastic Activity of Split Products of Phosphatidyl Ethanolamine

1960 ◽  
Vol 04 (02) ◽  
pp. 283-288 ◽  
Author(s):  
Karl H. Slotta ◽  
Erwin Deutsch
Keyword(s):  
Phosphatidyl Ethanolamine ◽  
Stable Suspension ◽  
Thromboplastic Activity ◽  
Generation Test

SummaryPure synthetic L-α-(dioleoyl) PE is inactive as a platelet substitute in the thromboplastin generation test, even when in a stable suspension. Under humid conditions it is partly hydrolyzed. Among the split products lyso PE and phosphoryl ethanolamine were identified. The resulting mixture has thromboplastin generating activity. This thromboplastin is formed slowly, but it is stable over longer periods of time than thromboplastins formed from PS + PC or PS + PE mixtures, which are rapidly generated and lose activity faster.

The Separation of Thromboplastin Formed from Pig’s Plasma in the Thromboplastin Generation Test

1962 ◽  
Vol 08 (03) ◽  
pp. 485-501
Author(s):  
M. J Cross
Keyword(s):  
Original System ◽  
Factor V ◽  
Generation System ◽  
Thromboplastic Activity ◽  
Generation Test

Summary1. Plasma thromboplastin has been formed from a mixture of pigs’ plasma, serum and platelets using a modification of the thromboplastin generation system of Biggs and Douglas (1953). The thromboplastic activity in the modified system was more stable than in the original system.2. A sediment with considerable thromboplastic activity has been obtained by centrifugation. This sediment was free of platelets and contained very little thrombin.3. The sediment when resuspended in buffer was fully active only in the presence of calcium and between pH 6.6 and 7.0. The activity slowly decreased at 0—4° C and rapidly at 65° C.4. The sediment rapidly converted prothrombin to thrombin in the absence of factor V.5. The activity of the sediment was unaffected when it was incubated with thrombin.

PHOSPHOLIPIDS: II. A CORRELATION OF CHEMICAL STRUCTURE WITH THROMBOPLASTIC ACTIVITY

1965 ◽  
Vol 43 (9) ◽  
pp. 1465-1470 ◽  
Author(s):  
P. J. Grisdale ◽  
A. Okany
Keyword(s):  
Fatty Acid ◽  
Chain Length ◽  
Chemical Structure ◽  
Fatty Ester ◽  
Two Stage ◽  
Fatty Acid Chain Length ◽  
Fatty Acid Chain ◽  
Thromboplastic Activity ◽  
Generation Test

A series of synthetic phosphatidylserines containing saturated fatty ester residues (C6 to C18) has been synthesized. These compounds have been studied in combination with natural phosphatidylethanolamine in the two-stage thromboplastin-generation test. The observed activity of these mixtures depends on the fatty acid chain length of the phosphatidylserine. These variations are accounted for in terms of the micelle theory of thromboplastic activity.

scholarly journals Platelets and Platelet Phosphatides in Uremia

Blood ◽  
1960 ◽  
Vol 16 (4) ◽  
pp. 1439-1446 ◽  
Author(s):  
GERALD ALTSCHULER ◽  
AARON J. MARCUS ◽  
HARRIS L. ULLMAN
Keyword(s):  
Platelet Count ◽  
Prothrombin Time ◽  
Silicic Acid ◽  
Chromatographic Analysis ◽  
Normal Platelet ◽  
Chromatographic Pattern ◽  
Thromboplastic Activity ◽  
Phase Platelet ◽  
Generation Test ◽  
Column Chromatographic

Abstract 1. The platelets of 20 uremic subjects were studied, utilizing the following procedures; phase platelet count, serum prothrombin time, thromboplastin generation test with evaluation of plasma, serum, and platelet reagents. 2. Platelet phospholipids from these subjects were used as reagents in the thromboplastin generation test and examined by means of silicic acid paper and column chromatography. 3. Thrombocytopenia was the most common abnormality encountered and was associated with either normal or abnormal prothrombin consumption. Some patients demonstrated defective prothrombin utilization despite normal platelet counts, but their platelets had normal thromboplastic activity, as did those of all patients studied. 4. The paper chromatographic pattern of the phosphatides in all subjects was the same as that reported for normal platelets. Similar results were obtained on column chromatographic analysis of a pooled extract from nine of the uremic patients. 5. On the basis of these studies it was not possible to demonstrate a qualitative platelet defect in uremia.

Experimental Studies on a Recombinant Hirudin, CGP 39393

1991 ◽  
Vol 65 (04) ◽  
pp. 355-359 ◽  
Author(s):  
E Gray ◽  
J Watton ◽  
S Cesmeli ◽  
T W Barrowcliffe ◽  
D P Thomas
Keyword(s):  
Thrombin Generation ◽  
Bleeding Time ◽  
Thrombus Formation ◽  
Experimental Studies ◽  
Venous Stasis ◽  
Antithrombotic Agent ◽  
Recombinant Hirudin ◽  
Excessive Bleeding ◽  
Generation Test

SummaryThe in vitro anticoagulant activities of recombinant desulphatohirudin (r-hirudin) were studied in the activated partial thromboplastin time (APTT) and the thrombin generation test : systems. In the APTT at concentrations below 5 μg/ml, r-hirudin showed a dose-response curye. At concentrations above 5 μg/ml, the plasma became unclottable, but in the thrombin generation test , at least 10 μg/ml of r-hirudin was required for full inhibition of thrombin generation. The antithrombotic effect was assessed using a rabbit venous stasis model; 150 μg/ml r-hirudin completely prevented thrombus formation at 10 and 20 min stasis. At antithrombotic dose, the mean bleeding time ratio measured in a rabbit ear template model, was not prolonged over control values. At higher doses, the bleeding time ratios were higher than those observed for the same dosage of heparin. These data indicate that while r-hirudin is an effective antithrombotic agent, antithrombotic doses have to be carefully titrated to avoid excessive bleeding.

The Effect of Adrenaline Infusions on Blood Coagulation in Normal and Haemophilia B Dogs

1966 ◽  
Vol 15 (03/04) ◽  
pp. 349-364 ◽  
Author(s):  
A.H Özge ◽  
H.C Rowsell ◽  
H.G Downie ◽  
J.F Mustard
Keyword(s):  
Body Weight ◽  
Factor Viii ◽  
Factor Ix ◽  
Clotting Factor ◽  
Blood Ph ◽  
Order Of Magnitude ◽  
Dose Dependent ◽  
Generation Test ◽  
Plasma Activity

SummaryThe addition of trace amounts of adrenaline to whole blood in plasma in vitro increased factor VIII, factor IX and whole plasma activity in the thromboplastin generation test. This was dose dependent.Adrenaline infusions less than 22 (μg/kg body weight in normal dogs accelerated clotting, increased factor IX, factor VIII and whole plasma activity in the thromboplastin generation test and caused a fall in blood pH. In a factor IX deficient dog, there was no increase in factor IX activity. After adrenaline infusions, however, the other changes occurred and were of the same order of magnitude as in the normal. Adrenaline in doses greater than 22 μg/kg body weight did not produce as great an effect on clotting in normal or factor IX deficient dogs. The platelet count in the peripheral blood was increased following the infusion of all doses of adrenaline. These observations suggest that the accelerating effect of adrenaline on clotting is not mediated through increase in activity of a specific clotting factor.

Evaluation of a New Preparation of Urokinase

1973 ◽  
Vol 30 (01) ◽  
pp. 114-122
Author(s):  
C.R.M Prentice ◽  
K.M Rogers ◽  
G.P McNicol
Keyword(s):  
Body Weight ◽  
Maintenance Therapy ◽  
Initial Dose ◽  
Fibrinolytic Activity ◽  
Pharmacological Effect ◽  
Whole Body ◽  
Fibrinolytic Agent ◽  
Thromboplastic Activity

SummaryThe pharmacological effect of a new preparation of urokinase (Leo) has been studied, both in vitro and in six patients suffering from thrombo-embolic disorders. It was a non-toxic, effective fibrinolytic agent if given in sufficient dosage. A regimen consisting of an initial dose of 7,200 ploug units per kg body weight, followed by hourly maintenance therapy with 3,600 ploug units per kg intravenously, gave satisfactory evidence of whole body fibrinolytic activity. The preparation had minor but insignificant thromboplastic activity both when assayed in the laboratory and when given to patients.

Spontaneous Haemophilia in a Female

1960 ◽  
Vol 04 (03) ◽  
pp. 369-375 ◽  
Author(s):  
E. H Braun ◽  
David B. Stollar
Keyword(s):  
Family History ◽  
Bleeding Time ◽  
Dental Extraction ◽  
White Girl ◽  
Complete Family ◽  
Normal Limits ◽  
Sex Chromatin ◽  
History Of ◽  
Generation Test

SummaryA case of haemophilia in a young white girl is described. There was a history of bleeding from birth. The thromboplastin generation test was grossly abnormal and A. H. G. levels were below 1%. Bleeding time and capillary morphology was within normal limits. Dental extraction after transfusion caused almost uncontrollable haemorrhage.A complete family history was obtained for four generations. There was no case of a “bleeder” amongst these.The girl’s apparent sex was confirmed by sex chromatin studies.

The Fractionation Properties of Human Factor VIII (Antihaemophilic Factor)

1960 ◽  
Vol 04 (02) ◽  
pp. 253-260 ◽  
Author(s):  
Franco Gobbi
Keyword(s):  
Factor Viii ◽  
Human Factor ◽  
Maximum Yield ◽  
Factor Vii ◽  
Precipitation Method ◽  
Salting Out ◽  
Human Factor Viii ◽  
Plasma Factor ◽  
Two Factors ◽  
Thromboplastic Activity

SummaryThe fractionation properties of human Factor VIII (antihaemophilic factor, AHF, antihaemophilic globulin) have been studied using a plasma of congenital afibrinogenaemia as a starting material.From a fibrinogen-free plasma, Factor VIII does not precipitate with ethanol at a final concentration of 8%; on the contrary the maximum yield is reached at an ethanol concentration of 25%.With a precipitation method carried out by a one to ten dilution of plasma with distilled water and acidification by N/10 hydrochloric acid to a pFI 5.2, Factor VIII does not precipitate with the euglobulin fraction; when normal plasma is used, such a precipitation is almost complete.With the salting-out fractionation method by ammonium sulphate, Factor VIII precipitates at a concentration between 25 and 33% of saturation either from fibrinogen-free and from normal human plasma.A non-specific thromboplastic activity appears in the fractions prepared by every method. This activity, which is probably due to the activation of seric accelerators, is easily removed by Al(OH)s adsorption. Thus, in order to insure the specificity of Factor VIII assays, the preliminary adsorption of the fractions is indispensable before testing their antihaemophilic activity.Fibrinogen and Factor VIII have different and definite precipitation patterns. When these two factors are associated the fractionation properties of AHF appear quite modified, showing a close similarity to those of fibrinogen. This fact can explain the technical difficulties encountered in the attempt to purify the antihaemophilic factor, and the lack of reproducible procedures for removing fibrinogen without affecting Factor VII.

Observations on the in vitro Effects of Chylomicra, Low-Density Lipoproteins and Phospholipids on Human Plasma Euglobulin Lysis

1963 ◽  
Vol 09 (01) ◽  
pp. 164-174 ◽  
Author(s):  
Albert R Pappenhagen ◽  
J. L Koppel ◽  
John H Olwin
Keyword(s):  
Human Plasma ◽  
Phosphatidyl Ethanolamine ◽  
Phosphatidyl Inositol ◽  
Plasma Lipoproteins ◽  
Low Density ◽  
Inhibitory Effects ◽  
Soybean Phospholipids ◽  
In Vitro Effects ◽  
Complete Precipitation

SummaryData have been presented on the in vitro effects of human chylomicra, low-density human plasma lipoproteins, and partially purified preparations of various phospholipids on human plasma euglobulin lysis. Euglobulin lysis was found to be accelerated by preparations of mixed soybean phospholipids (aso-lectin), cephalin, phosphatidyl inositol, phophatidyl serine and phosphatidyl ethanolamine. In contrast, it was found to be inhibited by preparations of human chylomicra, low-density human plasma liproproteins and lecithin. Inhibition of euglobulin lysis produced by any of these three agents could be diminished or completely overcome by the simultaneous presence of suitable levels of any one of the accelerating agents. In all cases studied, both inhibitory and accelerating effects were observed to be concentration-dependent. Evidence has been obtained to suggest that in the case of the accelerating agents the observed increased rate of euglobulin lysis is not a direct effect on lysis itself, but rather is due to more complete precipitation of plasminogen in the presence of these substances. On the other hand, it appears that the inhibitory effects observed are not related to the extent of plasminogen precipitation, but are actually true inhibitions of euglobulin lysis. The possible clinical significance of some of these observations has been briefly discussed.

The Spectrum of von Willebrand’s Disease

1967 ◽  
Vol 18 (01/02) ◽  
pp. 040-056 ◽  
Author(s):  
E. J Walter Bowie ◽  
P Didisheim ◽  
J. H Thompson ◽  
C. A Owen
Keyword(s):  
Factor Viii ◽  
Bleeding Time ◽  
Severe Bleeding ◽  
Platelet Adhesiveness ◽  
Platelet Activity ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
The Third ◽  
Generation Test

SummaryPatients (from 5 kindreds) with variants of von Willebrand’s disease are described. In one kindred the depression of factor VIII was moderate (20 to 40% of normal) and transfusion of 500 ml of normal plasma led to an increase higher than anticipated and to an almost normal level of factor VIII 17 to 24 hrs later. This represents the usual type of von Willebrand’s disease.In the second kindred the concentration of factor VIII was less than 2 % of normal in the son and daughter, who had severe bleeding and hemarthroses.The third kindred was characterized by reduction of factor VIII and a long bleeding time as well as by a serum defect in the thromboplastin-generation test comparable to that seen in patients with hemophilia B, yet with normal levels of factors IX, X, and VII. The severity of the serum defect, the positive result with the Rumpel-Leede test, and the reduced platelet activity in the thromboplastin-generation test are all compatible with the diagnosis of thrombopathy or ‘‘thrombopathic hemophilia.” In two other kindreds, one patient had a long bleeding time and normal levels of factor VIII and another had a normal bleeding time and decrease of factor VIII. The last patient had the type of response to transfusion usually seen in von Willebrand’s disease.In four kindreds, platelet adhesiveness in vivo was found to be strikingly abnormal (virtually absent).It would appear, therefore, that von Willebrand’s disease forms a spectrum, and whether the kindreds reported simply reflect variations of a single genetic disease state or represent separate entities will be answered only by clarification of the underlying etiology of that disease.

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