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

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 .

Exchange Between Intra- and Extravascularly Injected Radioiodinated Fibrinogen

10.1055/s-0039-1682436 ◽

1977 ◽

Author(s):

R. Rüegg ◽

P.W. Straub

Keyword(s):

Half Life ◽

Degradation Products ◽

Plasma Fibrinogen ◽

Lysis Time ◽

Euglobulin Lysis Time ◽

Cautious Interpretation ◽

Plasma Half Life

To test the hypothesis that in certain diseases plasma fibrinogen may be degraded extra-vascular ly and that circulating fibrin/-ogen degradation products (FDP) may stem from extra-vascular ly degraded fibrin/-ogen, 8 patients with pleural or peritoneal effusions (4 transudate, 4 exudate) were given 125I-fibrinogen i.v. and simultaneously 131I-fibrinogen intraca-vitarily. Measurements of plasma and effusion volumes allowed quantitation of the exchange of fibrinogen and its protein-bound derivatives. Plasma t/2 was shortened in 6/7 patients. At 48 hrs 7.6 ± 3.9% of i.v. injected radioactivity was found in the effusion (18% of it clottable, 24% protein-bound but unclottable), 4.8% ± 2.2% of intracavitarily injected radioactivity was found in plasma (29% clottable and 28% protein-bound unclottable). Iramunoreactive serum FDP were elevated in 7/8, plasma euglobulin lysis time normal in all 7/7 patients. Effusion fluids were fibrinolytically active, usually showing higher FDP concentrations than serum. It is concluded that 1) the shortened plasma half-life of fibrinogen is due in part to loss into the effusion, 2) fibrinogen is degraded in effusions and 3) plasma FDP in patients with ‘effusions may stem partly from extravascular fibrinogen proteolysis. The findings suggest cautious interpretation of FDP levels and fibrinogen turnover results in patients with suspected DIC and effusions.

The Amidolytic Activity of the SK-Plasminogen Complex Is Enhanced by a Potentiator which Is Generated in the Presence of Vascular Plasminogen Activator - Role of Fibrin Degradation Products

10.1055/s-0038-1657166 ◽

1982 ◽

Vol 47 (03) ◽

pp. 193-196 ◽

Cited By ~ 5

Author(s):

J Soria ◽

C Soria ◽

O Bertrand ◽

F Dunn ◽

M Samama ◽

...

Keyword(s):

Plasminogen Activator ◽

Degradation Products ◽

Venous Stasis ◽

Amidolytic Activity ◽

Fibrin Degradation Products ◽

Lysis Time ◽

Before And After ◽

Euglobulin Lysis Time ◽

High Responders

SummaryIn the presence of an excess of streptokinase (SK) the amidolytic activity of the plasminogen-SK complex on chromogenic substrates is 12% lower in serum than in the corresponding plasma. However, in subjects in whom venous stasis lead to a shortening of the euglobulin lysis time to less than 60 min (high responders), the amidolytic activity of the plasminogen-SK complex in serum was 60% higher than in the corresponding plasma. Attempts to find alterations of the plasminogen molecule itself which would account for the enhanced activity in high responder serum were negative. No free plasmin was present and the plasminogens isolated from plasma and serum before and after venous stasis had the same amidolytic activity as glu-plasminogen in the presence of an excess of SK. N-terminal analysis of these four plasminogens revealed in each instance glutamic acid.The enhancement of the amidolytic activity of the SK-plasminogen complex in serum of high responders (potentiator activity) could be reproduced by adding purified tissue plasminogen activator (TA) to native blood before clotting, but not if TA was added to plasma or to prestasis serum. Removal of fibrin degradation products from poststasis serum resulted in the disappearance of potentiator activity. These experiments suggest that fibrin degradation products, generated during clotting in the presence of vascular or tissular plasminogen activator act as a potentiator of the amidolytic activity of the plasminogen SK-complex.

The Reaction of Thiol Compounds with the Vitamin-K Dependent Clotting Factors

10.1055/s-0038-1653570 ◽

1969 ◽

Vol 21 (03) ◽

pp. 573-579 ◽

Author(s):

P Fantl

Keyword(s):

Prothrombin Time ◽

Vitamin K ◽

Anaerobic Conditions ◽

Clotting Factors ◽

Thiol Compounds ◽

Aerobic Conditions ◽

One Stage ◽

Factor Ii ◽

Ph Dependent ◽

The One

SummaryTreatment of human and dog oxalated plasma with 0.2 to 1.0 × 10−1 M 2.3-dithiopropanol (BAL) or dithiothreitol (DTT) at 2–4° C for 30 min results in the reduction of the vitamin-K dependent clotting factors II, VII, IX and X to the respective-SH derivatives. The reaction is pH dependent. Under aerobic conditions the delayed one stage prothrombin time can be partly reversed. Under anaerobic conditions a gradual prolongation of the one stage prothrombin time occurs without reversal.In very diluted plasma treated with the dithiols, prothrombin can be converted into thrombin if serum as source of active factors VII and X is added. In contrast SH factors VII, IX and X are inactive in the specific tests. Reoxidation to active factors II, VII, IX and X takes place during adsorption and elution of the SH derivatives. The experiments have indicated that not only factor II but also factors VII, IX and X have active-S-S-centres.

FIBRINOLYTIC ACTIVITY IN MALIGNANCY

10.1055/s-0038-1643186 ◽

1987 ◽

Author(s):

A Aranda ◽

J A Páramo ◽

B Cuesta ◽

J Fernández ◽

M J Paloma ◽

...

Keyword(s):

Plasminogen Activator ◽

Fibrinolytic Activity ◽

Degradation Products ◽

Plasminogen Activator Inhibitor ◽

Tissue Type ◽

Clinical Complications ◽

Significant Prolongation ◽

Type Plasminogen Activator ◽

Lung Malignancies ◽

Euglobulin lysis time (ELT), euglobulin fibrinolytic activity on fibrin plate (EFA), plasminogen, tissue-type plasminogen activator (t-PA) activity and antigen, ;2-antiplasmin (α2-AP), plasminogen activator inhibitor (PAI) and fibrinogen degradation products (FDP) were determined in a group of 149 patients (mean age 57 ± 13 years, 93 male), with different malignancies (digestive 61, lung 18, urological 24, ginaecological 16, others 30). Findings were compared with those of 44 age-sex matched healthy subjects. There was a significant prolongation of ELT (p <0.003), a decrease of plasminogen (p < 0.004) and an increase of PAI (p < 0.0001) in patients as compared to controls, being similar EFA, t-PA, α2AP and FDP. No differences in any ot these parameters were found in patients with metastatic disease (n= 65) as compared with those with local disease (n= 84). As regards to tumour localization, plasminogen and t-PA decrease were more pronounced in lung malignancies and PAI increase in lung and digestive malignancies. We conclude that there is an impairment in blood fibrinolytic activity in malignancy. Reduced fibrinolysis seems to be related to localization but not to degree of tumoral activity. That might have clinical complications.

MODIFICATION OF COAGULATION AND FIBRINOLYSIS DURING TRANSLUMINAL ANGIOPLASTY IN PATIENTS RECEIVING HEPARIN OR PENTOSAN POLYSULFATE (HEMOCLAR)

10.1055/s-0038-1643247 ◽

1987 ◽

Author(s):

N Bel Lakhal ◽

J M Pernes ◽

D Lichtenstein ◽

M Roncato ◽

J C Gaux ◽

...

Keyword(s):

Degradation Products ◽

Transluminal Angioplasty ◽

Thrombin Time ◽

Pentosan Polysulfate ◽

Heparin Group ◽

Lysis Time ◽

Before And After ◽

Euglobulin Lysis Time ◽

Thrombotic Complications ◽

To Receive

Twenty patients with high stenosis of iliac or femoral artery were randomely allocated to receive by intra arterial route (IA) either 5,000 IU heparin or 50 mg Hemoclar immediately before starting the angioplasty. Those receiving Hemoclar were given a second IA 50 mg bolus at the end of the dilatation.Two blood samples were obtained by venous punction 1) after an initial 30 min resting (V1), 2) at the end of the procedure (V2)- Arterial punction by the dilatation catheter was also performed immediately before and after the dilatation leading to two other samples A1 and A2 The coagulation studies include activated partial thromboplastin time (APTT), thrombin time (TT), hep test (Hemachem, St-Louis, USA), anti Xa activity (Stachrom heparin, Diagnostica-Stago Asnieres, France). There was a significant increase in APTT, TT, and hep test between A1 and A2 as well as V1 and V2 in both groups of patients. However, the prolongation was significantly higher for heparin. Anti Xa activity significantly increased only in heparin group.Fibrinolysis was studied by measuring tPA by the SOFIA assay described by Angles-Cano (Anal. Biochem. 1985, 153, 201), euglobulin lysis time (ELT) and a new plasma ELISA assay specific for fibrinogen degradation products (FDPs) using monoclonal antibody described at the Gaubius Institute (Blood 1985, 66, 503). A significant increase in tPA was observed during the dilatation (A2/A1) and V2/V1) only in the patients receiving Hemoclar. The slight increase of the fibrinolytic activity was further corroborated by a significant increase in FDPs (A2/A1). In both groups, but only in the venous samples (V2/V1), ELT was shortened (p<0.05) and fibrinogen was decreased (p<0.05)No thrombotic complications were observed during the procedure in both groupsConclusion: This study confirms that Hemoclar has an inhibiting effect on coagulation by inhibiting thrombin and thrombin generation, but no anti Xa activity. However, the anticoagulant potency is much reduced when compared to heparin. The profibrinolytic effect seems to be related to the release of free tPA.

Blood Coagulation, Fibrinolytic Activity, Platelet Function and Immunoglobulins in Frostbite

10.1055/s-0039-1680749 ◽

1977 ◽

Author(s):

I.S. Chohan ◽

I. Singh

Keyword(s):

Blood Coagulation ◽

Fibrinolytic Activity ◽

Degradation Products ◽

Western Himalayas ◽

Platelet Adhesiveness ◽

Intravascular Thrombosis ◽

Lysis Time ◽

Coagulation Defects ◽

Fifteen males, 19-45 years old, stationed between altitudes 3690 and 5540 m in the Western Himalayas who were frostbitten were studied within 24 hours of the injury and then 4 weeks and 1 year after for blood coagulation defects. The following disturbances were found: fibrinogen degradation products and factor VIII-related antigen were increased; fibrinogen, platelet counts and haematocrit were decreased; platelet adhesiveness was increased; euglobulin lysis time was prolonged; antithrombin III,α-1 antitrypsin and α-2 macroglobulin were markedly decreased; IgG and IgA immunoglobulins and cryoglobulins were increased; serum albumin was decreased and IgM immunoglobulin consumption was increased.These abnormalities increase platelet adhesiveness and diminish fibrinolytic activity and promote intravascular thrombosis.Furosemide increases fibrinolytic activity and suppresses platelet adhesiveness in vivo (I. Singh and I.S. Chohan, Int. J. Biometeor. 17, 73, 1973). Its use in the prevention of frostbite is under investigation.

Lack of fibrin formation in exercise-induced activation of coagulation

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1979.236.4.h577 ◽

1979 ◽

Vol 236 (4) ◽

pp. H577-H579 ◽

Author(s):

A. Vogt ◽

V. Hofmann ◽

P. W. Straub

Keyword(s):

Physical Exercise ◽

Degradation Products ◽

Bicycle Ergometer ◽

Strenuous Exercise ◽

Thrombin Time ◽

Fibrinopeptide A ◽

Lysis Time ◽

Exercise Period ◽

Euglobulin Lysis Time ◽

Exercise Induced

Strenuous physical exercise leads to a significant shortening of blood clotting in various test systems. Such short times are also characteristic of those observed in sedentary patients with thrombosis or disseminated intravascular coagulation, and of those observed in experimental animals after thrombin infusion. The patients exhibit an increase in circulating fibrinopeptide A, which is attributed to thrombin action on circulating fibrinogen, and to an increase of fibrinogen degradation products, which is thought to indicate reactive fibrinolysis. To check whether physical exercise leads to fibrinemia, 10 healthy male volunteers were subjected to strenuous exercise on a bicycle ergometer. Blood samples were taken immediately before and on completion of the exercise period. Despite a significant shortening of the activated partial thromboplastin time, the thrombin time, and the Reptilase time, no increase of fibrinopeptide A could be demonstrated and the ethanol gelation test remained consistently negative. Simultaneously, the euglobulin lysis time was significantly shortened, whereas the fibrin(ogen) degradation products did not increase. The results indicate that the shortening of the coagulation times associated with physical exercise must be explained by mechanisms other than thrombin-mediated conversion of fibrinogen to fibrin.

Prothrombin time prolongation in paracetamol poisoning: a relevant marker of hepatic failure?

Human & Experimental Toxicology ◽

10.1191/0960327103ht398oa ◽

2003 ◽

Vol 22 (11) ◽

pp. 617-621 ◽

Cited By ~ 14

Author(s):

C Payen ◽

A Dachraoui ◽

C Pulce ◽

J Descotes

Keyword(s):

Liver Failure ◽

Prothrombin Time ◽

Vitamin K ◽

Hepatic Failure ◽

Paracetamol Overdose ◽

Paracetamol Poisoning ◽

Clotting Factors ◽

Prolonged Prothrombin Time ◽

Few Data

The association between paracetamol overdose and prolonged prothrombin time due to hepatic failure is well recognized. However, little is known of the possibility that paracetamol overdose can prolong the prothrombin time without overt hepatic failure. The few data from the literature suggest this is either due to a reduction in the functional levels of the vitamin K-dependent clotting factors by elevated doses of paracetamol, or a consequence of the administration of the antidote N-acetylcystein. The three reported cases provide further evidence that paracetamol overdose can be associated with a prolongation in the prothrombin time without overt hepatic failure. Even though the prothrombin time provides useful prognosis information, decisions regarding the management of these patients should not solely be based on this endpoint to avoid misinterpretation of the accuracy and the severity of liver failure.

Platelet Adhesiveness and Euglobulin Lysis Time in Dogs Given Repeated Infusion of Sodium Palmitate

10.1055/s-0038-1651337 ◽

1969 ◽

Vol 22 (01) ◽

pp. 164-173 ◽

Author(s):

M Cucuianu ◽

V. V Papilian ◽

N Bareliuc ◽

I Crisnic

Keyword(s):

Fatty Acids ◽

Initial Level ◽

Progressive Increase ◽

Plasma Fibrinogen ◽

Sodium Palmitate ◽

Platelet Adhesiveness ◽

Cortical Necrosis ◽

Lipid Mobilization ◽

Lysis Time ◽

SummaryThe effect of infusions with sodium palmitate 3.5 m Mol/1 on platelet adhesiveness and euglobulin lysis time was studied in 16 dogs. A decrease of platelet adhesiveness was noted 15 min after infusion. Decreased platelet adhesiveness persisted 3 and 24 hrs later, although platelet counts that were diminished 15 min after the infusion, returned to the initial level. Fibrinogen levels were not found to decrease during infusions of fatty acids. A progressive increase of plasma fibrinogen was even noted in animals that survived more than 7 days after the first infusion. Following a transient acceleration of euglobulin lysis time, a delayed fibrinolysis was noted, probably as a result of the exhaustion of blood activator.Fibrin depositions were emphasized in histological sections. In some animals aspects of obliterative thromboangiitis were noted. However bilateral cortical necrosis was found in only 1 dog.It seems that correlations between increased lipid mobilization and changes of coagulability and fibrinolysis in atherosclerosis are much more complex.

The Effects of Infusing Thrombin and Its Acetylated Derivative

10.1055/s-0038-1651259 ◽

1968 ◽

Vol 20 (01/02) ◽

pp. 190-201 ◽

Author(s):

L Pechet ◽

A. M Engel ◽

C Goldstein ◽

B Glaser

Keyword(s):

Degradation Products ◽

Hypercoagulable State ◽

Factor Vii ◽

Fibrinogen Degradation Products ◽

Fibrin Monomer ◽

Lysis Time ◽

Factor Ii ◽

Euglobulin Lysis Time ◽

Fibrin Monomers

Summary and ConclusionsDogs and rabbits were infused with acetylated thrombin (thrombin E) and clotting thrombin (thrombin C). Similar effects were noted in both animal series. Very large amounts of thrombin E could be tolerated, but resulted in defibrination. Following a transient hypercoagulable state, the blood became unclottable. The platelets and factors I, V, and VIII were markedly decreased. Factor II was moderately affected and factor VII-X showed no significant changes in most experiments. The presence of fibrinogen degradation products was indicated by a delay in the polymerization of fibrin monomers.Based on the shortening of the euglobulin lysis time, a decrease in the proactivator, and the appearance of inhibitors of fibrin monomer polymerization, it is concluded that transient fibrinolysis is induced by the infusion of thrombin. Its immediate mechanism could not be determined.