Assessment of Clinical Hypercoagulability Tendency

1979 ◽  
Author(s):  
E. von Kaulla ◽  
K.N. von Kaulla
Keyword(s):  
Platelet Aggregation ◽  
Thrombin Generation ◽  
Antithrombin Iii ◽  
Clotting Factors ◽  
Lysis Time ◽  
Euglobulin Lysis Time ◽  
Blood Specimens ◽  
The Many ◽  
Generation Test ◽  
Natural Relation

Optimal assessment of hypercoagulability which may result in various types of intravascular clotting requires the following procedures. No storage of blood specimens, analyzation right after withdrawal of blood (with few persons involved in work), blood obtained with siliconized, not plastic syringes. Use of citrate Na as anticoagulant by only 20 % dilution, further dilution increases but does not decrease coagulability. Hypercoagulability can be correctly assessed with the thrombin generation test resulting in a curve leaving clotting factors in their natural relation and platelets in suspension. Synthetic substrates can be misleading. Some patients with a prothrombin time in therapeutic range have a normal thrombin generation showing that they are not protected. Short antithrombin III times reflect reduction of another protection against intravascular clotting. They must become prolonged by prothrombin-depressing agents, if not these agents are ineffective. Platelet aggregation induced by stirring only reveals another type of hypercoagulability tendency which cannot be treated with anticoagulants. Prolonged euglobulin lysis time reflects loss of yet another type of protection again, an intravascular clotting potential. Fast test for fibrin monomeres should be added. The tests mentioned revealed various types of hypercoagulability in most of the many patients who were referred to us for assessment of this tendency.

Warfarin Induced Fibrinolysis: The Effect Of Recovery With And Without Vitamin K

1981 ◽  
Author(s):  
N A Marsh
Keyword(s):  
Prothrombin Time ◽  
Plasminogen Activator ◽  
Vitamin K ◽  
Dynamic Equilibrium ◽  
Degradation Products ◽  
Direct Action ◽  
Plasma Fibrinogen ◽  
Clotting Factors ◽  
Lysis Time ◽  
Euglobulin Lysis Time

We have previously shown that fibrinolysis in the rat is enhanced by levels of warfarin administration sufficient to produce moderate anticoagulation. This effect is mediated largely by an increase in plasma plasminogen activator. Plasminogen levels are decreased and fibrin(ogen) degradation products raised confirming the presence of a systemic hyperfibrinolytic state. In order to investigate this phenomenon further we have measured fibrinolytic components in rats recovering from warfarin administration. Groups of male Hooded rats received 14 yg warfarin/100 g body weight /day by mouth for one to two weeks. The animals were then allowed to recover without further treatment or following a single 50 μg dose of vitamin K1. Euglobulin lysis time, one stage prothrombin time, plasma plasminogen activator (fibrin plate method), plasma plasminogen (caseinolytic method), plasma fibrinogen (clot weight method) and plasma fibrinolytic inhibitors were measured at intervals after the end of the warfarin treatment. In animals recovering without vitamin K prothrombin time returned to normal within one week. However fibrinolysis remained elevated with plasma plasminogen activator concentrations of more than twice the control value. Plasma inhibitor levels were depressed and fibrinogen levels elevated. After two weeks all fibrinolytic components had returned to normal. Following vitamin Kj administration a different pattern emerged; prothrombin time returned to normal within 24 hours but fibrinolysis was diminished. The latter effect was due to a marked increase in plasma fibrinogen and moderate fall in plasma plasminogen activator both of which contributed to a prolonged euglobulin lysis time. These results indicate that fibrinolysis and coagulation in the rat are not linked in a 'dynamic equilibrium' like that proposed for man. The enhanced fibrinolysis rather than being a result of the fall in vitamin K dependant clotting factors may be due to the direct action of warfarin. The 'fibrinolytic shutdown' following vitamin K remains unexplained .

Effect of Indobufen (K 3920) A New Antiplatelet Agent After Oral Administration in Patients with Vascular Diseases

1979 ◽  
Author(s):  
S. Coccheri ◽  
G.C. Fortunato
Keyword(s):  
Platelet Aggregation ◽  
Antiplatelet Agent ◽  
Vascular Diseases ◽  
Maximal Amplitude ◽  
Marked Inhibition ◽  
Lysis Time ◽  
Euglobulin Lysis Time ◽  
Circulating Platelet Aggregates ◽  
Platelet Aggregates ◽  
Induced Aggregation

The antiaggregating effect of a new butyric acid derivative, indobufen (K 3920), was investigated in 30 patients with vascular diseases. A between-patient study was performed by administering 50 mg b.i.d. or 100 mg b.i.d. for 14 days to 2 groups of patients. A series of platelet function and clotting parameters were recorded at the end of the treatment period, both 2 and 24 h after the last administration.A marked inhibition of platelet aggregation was observed in both groups, as shown from the significant changes in maximal amplitude, reaction time and slope of ADP- and collagen-induced aggregation wave.Similar results were observed at the Breddin test in both groups of patients and at all experimental times.Platelet adhesiveness was also reduced and circulating platelet aggregates were normalized in all patients who had abnormal basal values.A shortening of euglobulin lysis time was observed 2 h but not 24 h after administration of both doses.Tolerability was excellent.Indobufen appears to be a promising drug for treatment of vascular diseases where platelet aggregation is involved.

scholarly journals Marathon Run: Effects on Blood Coagulation, Fibrinolysis and Platelet Aggregation

1977 ◽  
Author(s):  
T. Mandalaki ◽  
A. Dessypris ◽  
C. Louizou ◽  
C. Dimitriadou ◽  
C. Panayotopoulou
Keyword(s):  
Platelet Aggregation ◽  
Blood Coagulation ◽  
Significant Rise ◽  
Marathon Runners ◽  
Protamine Sulphate ◽  
Mean Values ◽  
Lysis Time ◽  
Euglobulin Lysis Time ◽  
The Mean ◽  
The Difference

Blood coagulation, fibrinolysis and platelet aggregation were assessed in Finnishamateur Marathon runners, aged 30 to 57 in 1975 and 1976. After the run the mean valuesof aPTT showed a very significant shortening, prothrombin time and fibrinogen were not altered, euglobulin lysis time were significantly shorter, F.D.P. increased highly significantly. Protamine sulphate precipitation test became strongly positive, whereas ethanol gelation test and cryofibrinogen remained negative. Identical changes of the above parameters wereobtained both in 1975 and 1976. The mean values of platelet count showed a very significant rise in 1975 but not in 1976. A highly significant increase was noted for both the intensity and velocity of platelet aggregation induced by ADP and collagen in 1975. However in 1976this increase was not observed in all runners. The difference in response could be attributed to the environmental temperature factor (1975 :25°c-sunny, 1976 :18°C-cloudy). Also in 1976 the running time of the group was shorter than in 1975. Data on Cortisol levels are also given.

scholarly journals Evaluation of thrombin generating capacity in plasma from patients with haemophilia A and B

2005 ◽  
Vol 93 (03) ◽  
pp. 475-480 ◽  
Author(s):  
Suzette Béguin ◽  
Anne Lienhart ◽  
Raed Al Dieri ◽  
Christine Trzeciak ◽  
Jean Bordet ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Ex Vivo ◽  
Factor Ix ◽  
Haemophilia A ◽  
Clotting Factors ◽  
Time To Peak ◽  
Promising Tool ◽  
Generating Capacity ◽  
Generation Capacity ◽  
Generation Test

SummaryIn haemophilia patients, a relationship is usually observed between the clinical expression of the disease and plasmatic factor VIII/factor IX (FVIII/FIX) activity. However, it is known from clinical experience, that some haemophilia patients, despite similar FVIII/FIX plasma levels, could exhibit different bleeding phenotype. After determining preanalytical test conditions, we evaluated the thrombin generation capacity from haemophilia plasma samples in various conditions and the potential usefulness of thrombin generation test (TGT) in haemophilia patients. In a series of 46 haemophilia patients (34 haemophilia A and 12 haemophilia B patients), we found a significant correlation between plasmatic FVIII/FIX levels and endogenous thrombin potential (ETP), peak and time to peak obtained by thrombin generation measurement. In addition, a correlation was found between severe clinical bleeding phenotype and ETP. Our results suggest that TGT could be a promising tool to evaluate haemostasis capacity in patients with haemophilia. Our ex vivo results, obtained 24 hours after FVIII concentrate administration, showed that in patients presenting similar plasmatic FVIIII levels, thrombin generation capacity may be significantly different. These results suggest that in patients with haemophilia, TGT could be useful for individually tailoring prophylactic regimens as well as for adapting clotting factors infusions in surgical situations, in addition to FVIII/FIX plasma clotting activities.

scholarly journals Antithrombin III and Hypercoagulability in Smokers

1977 ◽  
Author(s):  
R. Losito ◽  
D. Nathan ◽  
H. Gattiker ◽  
B. Longpré
Keyword(s):  
Factor Viii ◽  
Thrombin Generation ◽  
Antithrombin Iii ◽  
Intravascular Coagulation ◽  
Coagulation Tests ◽  
At Iii ◽  
History Of ◽  
Generation Test

It is known that various coagulation tests such as the thromboplastin generation test (TGT), thrombin generation (TG), levels of factor VIII or antithrombin III have been found to be abnormal in individuals with intravascular coagulation or having an increased tendancy to thrombosis. The aim of this study was to evaluate the role of the TGT, TG, factor VIII and antithrombin III assays in the diagnosis of possible mild intravascular coagulation in patients undergoing cardiac catheterization who had a history of smoking. In addition to these four tests, a routine coagulogram was performed for a total of 13 tests. It appeared that smokers had more abnormal tests (7.3/patient) than the controls (3.3/patient). The greatest association was between TGT and TG (29.6%) and TG and AT-III (25.9%). If by definition, hypercoagulability is present where 3 or more of these 4 mentioned tests were abnormal, then five patients were found to be in this category; all, except one, formed clots. In the patients (50) with a history of smoking, a third were found to have the TGT and the TG abnormal; however, the most striking observation in this group was in the antithrombin III where it was noted to be low in forty-five percent of the patients compared to the controls (patients having catheterization and were non-smokers) whose antithrombin III was found to be decreased in only five percent of the individuals. It is concluded that determination of antithrombin III may be of more importance in assisting the detection of hypercoagulability, especially in the smoking population, than the TGT, TG, or factor VIII.

Hemostatic Variables In A Group Of Traffic Police Men

1981 ◽  
Author(s):  
T Mandalaki ◽  
A Hatzakis ◽  
C Louizou ◽  
A Antonopoulou ◽  
M Vergi ◽  
...  
Keyword(s):  
Antithrombin Iii ◽  
Degradation Products ◽  
Heavy Traffic ◽  
Normal Subjects ◽  
Coagulation Factors ◽  
Fibrin Degradation Products ◽  
Lysis Time ◽  
Traffic Policemen ◽  
At Iii ◽  
Euglobulin Lysis Time

A study of various haemostasis parameters in a group of twenty-two traffic policemen working under special conditions, i.e. in locations of heavy traffic (5 hours shifts in the centre of Athens) is presented. These normal subjects (aged 22-39) are subjected to physical and psychological stress and to the effect of increased air pollution. Pretests were conducted before the beginning of the shift (6 a.m.) and postests were conducted at the end of the shift (12 noon).The following tests were performed: 1. Prothrombin Time (P.T.), 2. Activated Partial Thromboplastin Time (A.P.T.T.), 3. Fibrinogen, 4. Euglobulin Lysis Time (E.L.T.), 5. Fibrin Degradation Products (F.D.P.), 6. Platelets, 7. Platelet Aggregation by A.D.P., 8. PF4 9. F VIII:C, F VIII:Ag, F VIII:Rcof, 10. Antithrombin III (AT III).Results: Significant decrease of Fibrinogen, ELT and AT III, significant increase in APTT, FDP. Increase in PF4 levels. The results are indicative of the occurence of an activation of the fibrinolytic mechanism after the shift with signs of consumption of certain coagulation factors. There is an adverse effect on the hemostatic balance of traffic policemen during their service.

ADENOCARClNOMPrOF COLON AND THROMBOSIS: INCREASED THROMBIN,PLASMIN OR NEUTRAL PROTEASES ACTIVITY

1987 ◽  
Author(s):  
B Grand ◽  
A Blanco ◽  
A Kempfer ◽  
G Elgue ◽  
D Riveros ◽  
...  
Keyword(s):  
Clotting Factors ◽  
Laboratory Findings ◽  
Lysis Time ◽  
Acti Vity ◽  
Euglobulin Lysis Time ◽  
Von Willebrand ◽  
Deep Vein ◽  
Willebrand Factor ◽  
Tumoral Cells ◽  
Ristocetin Cofactor

Thrombotic and hemorrhagic complications are common in cancer patients and are an important cause of morbidity andmortality in these subjects.Hemostatic abnormalities, with or without these complications are found in nearly 95% of these patients .These abnormalities havebeen atributed to the presence of intravascular coagulation produced by an increased fibrin gene rat ion. We report apatient with adenocarcinoma of colon and multiple venous thrombosis, whose laboratory findings were consistent with anincreased proteolytic activity different from thrombin or plasmin.A 36 year old man with deep vein throrribosis and adenocarcinoma of colon was admitted^He started anti coagulationwith heparin and continued with acenocoimarine.In spite of a correct range of anticoagulation he developed a pulmonarthromboembolism and an axilar vein thrombosis.Coagulation studies on admissionwere as follows: Platelet count;250xl03/μl ,APTT;33 sec.,Prothrombin time;80%,FII; 150%,FV;110%,FVII-X;90%,FVIII;220%,FIX;210%,FDP;156pμ/ml.Thrombin time was shortened and clot solubility in urea 5 M was normal. Euglobulin lysis time and plasminogen(S-2251) were normal.The antithrombin 111 (AT III) concentration measured with specific antiserum (107%) and chromogenic substrates (95%) were normal.The ATIII crossed immunolectrophoresis(CIE) did not show the presence of thrombin-ATI 11 complexes .Studies on von Willebrand factor (vWF) revealed:elevation of vWF:Ag(511%) and normal ristocetin cofactor acti vity(vWF:RCof)(110%); the CIEshowed an increased mo-bi 1 ity( 1.46).Immunological levels of FXIII subunits A and S were decreased(30% and 41%) .Spontaneous proteolytic acti vity(SPA) measured with S-2288 was elevated.Though coagulation findings were consistent with consumption coagulopathy, classicaly related to thrombin gene rati on, thenormal levels of ATI 11 and the abscence of thrombin-ATIII complexes speaks against thrombin intervention.In addition, no evidence of primary fibrinolysis was observed.The increased SPA,the low levels of FXIII subunits A and S, and a faster mobility of vWF:Ag with an increased vWF:Ag/vWF:RCof ratio, suggest that hemostatic abnormalities in this patient could be due to proteolytic degradationof clotting factors by enzymes released from tumoral cells or granulocytes.

Marathon Run III: Effects on Coagulation, Fibrinolysis, Platelet Aggregation and Serum Cortisol Levels

1980 ◽  
Vol 43 (01) ◽  
pp. 049-052 ◽  
Author(s):  
T Mandalaki ◽  
A Dessypris ◽  
C Louizou ◽  
C Panayotopoulou ◽  
C Dimitriadou
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Physical Fitness ◽  
Prothrombin Time ◽  
Blood Coagulation ◽  
Serum Cortisol ◽  
Lysis Time ◽  
Euglobulin Lysis Time ◽  
Cortisol Levels ◽  
Gelation Test

SummaryBlood coagulation, fibrinolysis, platelet count-aggregation and Cortisol were assessed in 35 Finnish amateur runners aged 27 to 56 years (mean 40) and three aged 65, 67, and 82 who had run a non-competitive Marathon in 1975, 1976 and 1977 over the classical itinerary. After the run, in all 3 years, APTT showed shortening (p < 0.001); prothrombin time and plasma fibrinogen were not significantly altered; euglobulin lysis time was shorter (p < 0.001) and FDP increased (p < 0.001); PSPT became positive in all subjects, whereas the ethanol gelation test remained negative; no cryofibrinogen was detected. Platelet count and aggregation showed increase (p < 0.001) in 1975 (extreme heat, 25° C) but remained unaltered in 1976, 1977 (15–18° C). Cortisol levels were always significantly increased – more markedly in 1975. Women’s responses were similar to those of men. A possible correlation between physical fitness and the responses of haemostatic balance is suggested and the influence of weather is discussed.

Effects of Bradykinin on Coagulation and Fibrinolysis Study in Vitro and in Vivo

1965 ◽  
Vol 14 (03/04) ◽  
pp. 508-518 ◽  
Author(s):  
G. G Neri Serneri ◽  
P. L Rossi Ferrini ◽  
P Paoletti ◽  
A Panti ◽  
G D’Ayala Valva
Keyword(s):  
Thrombin Generation ◽  
Thrombin Time ◽  
Lysis Time ◽  
Time Determination ◽  
Recalcification Time ◽  
Generation Test ◽  
Coagulation And Fibrinolysis

SummaryThe effects of bradykinin on coagulation and fibrinolysis have been studied both “in vitro” and “in vivo” in man. “In vitro” bradykinin employed at different concentrations does not affect the coagulation and fibrinolysis processes in any appreciable way. Bradykinin, intraarterially injected in man in the dose of 10 y, does not modify coagulation studied both with global investigations (thrombelastogram, recalcification time) and with analytical researches (Quick’s time, activation test of intrinsic thromboplastin, thrombin generation test and thromboplastin test, thrombin time, determination of antithrombin II and III). Bradykinin instead produces an activation of fibrinolysis both in the thrombelastographic investigation and in the lysis time of euglobulins. The decrease in the activity of the proactivator and of plasminogen supports our view that bradykinin produces an activation of the fibrinolytic system by liberating tissue kinases which act on the proactivator. The authors have discussed the physiological and physiopathological significance of the observed findings.

Endogenously Increased Fibrinolytic Activity Induced by Liver-Bypass in Pigs and its in Vitro Synergism with Synthetic Fibrinolytic Compounds

1975 ◽  
Author(s):  
P. Ostendorf ◽  
K. N. von Kaulla
Keyword(s):  
Fibrinolytic Activity ◽  
Point Of View ◽  
Flufenamic Acid ◽  
Synthetic Compounds ◽  
Clear Cut ◽  
Lysis Time ◽  
Euglobulin Lysis Time ◽  
Blood Specimens ◽  
Fibrinolytic Compounds

The marked increase of fibrinolytic activity during the unhepatic phase during liver transplantation in animals and man is well known. Based on these observations the liver-bypass in the pig was used for producing endogenous increase of fibrinolytic activity of several hours duration thus providing fibrinolytic blood specimens suitable for in vitro studies of the synergism of endogenously induced fibrinolytic activity with the fibrinolytic activity induced by synthetic compounds. Liver-bypass in the pig results within a few minutes in a marked drop of the euglobulin lysis time from an average of 16 hrs. to one hour or less. Whereas the antiplasmin activity does not show any clear-cut change during the bypass, the antiactivator activity had dropped after about 2 hrs. to half of the original values. The fibrinolytic activity of the lover-bypass plasma is markedly enhanced by synthetic fibrinolytic compounds such as flufenamic acid applied at concentrations which themselves do not induce fibrinolytic activity. This can be demonstrated in various ways such as the use of thrombelastograms or lysis of clots formed by the bypass plasma. Also, as the bypass goes on, the clots start to dissolve spontaneously and the lysis time is considerably shortened by addition of synthetic compounds. Seen from the point of view of a potential clinical use, the most pertinent observation is that plasma obtained during an early bypass phase which does not dissolve preformed human clots, does so after addition of synthetic compounds.

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