Effects of human antithrombin III (at III) and heparin on endotoxin-induced disseminated intravascular coagulation (DIC) in rabbits

SummaryFive patients with chronic liver disease and acquired antithrombin III (AT III) deficiency undergoing peritoneovenous (LeVeen) shunting for ascites, resistant to medical therapy, were studied prospectively for the development of disseminated intravascular coagulation (D.I.C.) after selective correction of the plasma AT III activity. This was accomplished by continuous infusion of purified human AT III concentrate beginning one day prior to surgery and continuing five to seven days post-operatively. This rigorous transfusion scheme of AT III concentrate could not prevent D.I.C. and bleeding.

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Antithrombin-III as a Diagnostic AID in Disseminated Intravascular Coagulation

10.1055/s-0039-1682431 ◽

1977 ◽

Author(s):

R.L. Bick ◽

M.L. Dukes ◽

W.L. Wilson ◽

L.F. Fekete

Keyword(s):

Disseminated Intravascular Coagulation ◽

Serine Proteases ◽

Antithrombin Iii ◽

Degradation Products ◽

Clinical Manifestations ◽

Heparin Therapy ◽

Diagnostic Aid ◽

Intravascular Coagulation ◽

At Iii ◽

Initiation Of Therapy

Antithrombin-III (AT-III )/heparin cofactor is now recognized as a major inhibitor of thrombin and other serine proteases in coagulation. Since the reaction between AT-III and serine proteases is irreversable.AT-III consumption should be expected in pathological intravascular coagulation and attendent generation of thrombin and other serine proteases. Using a new AT-III assay system, unaffected by heparin or fibrino(geno)lytic degradation products, AT-III was monitored in 17 patients with DIC, It was found that early and significant decreases occured in all pts. It was further noted that monitoring of AT-III during therapy for DIC reflected a cessation of AT-III consumption and, thus, appeared to reflect efficacy of therapy in stopping the clotting process. Only 1 of 17 patients failed to show an increase in AT-III with initiation of therapy. In this group of patients, mini-heparin therapy appeared to be as efficacious as large doses of heparin in correcting AT-III consumption and other laboratory abnormalities of acute DIC, and in controlling hemorrhage of acute DIC. Four patients had chronic DIC with malignancy; the use of ASA and dipyridamole corrected AT-III consumption and clinical manifestations in these patients, although the response required more time than with heparin or mini-heparin. These findings suggest that the monitoring of DIC with AT-III levels may be useful in both confirming the diagnosis and, more importantly, in monitoring efficacy of therapy. Significant rises in AT-III were noted in all but 1 patient after initiating therapy, presumably reflecting cessation of consumption. In addition, mini-heparin appeared to be as efficacious as large heparin doses in stopping acute DIC and antiplatelet therapy appeared to stop AT-III consumption and clinical manifestations in patients with chronic DIC associated with malignancy.

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ANTITHROMBIN-III SUPPLEMENTATION ATTENUATES DISSEMINATED INTRAVASCULAR COAGULATION IN THEE.COLI ENDOTOXEMIC DOG MODEL

10.1055/s-0038-1644890 ◽

1987 ◽

Author(s):

J G Hauptman ◽

H I Hassouna ◽

J A Penner ◽

T G Bell ◽

T E Emerson

Keyword(s):

Disseminated Intravascular Coagulation ◽

Antithrombin Iii ◽

Degradation Products ◽

Treated Group ◽

Control Group ◽

Sodium Pentobarbital ◽

E Coli ◽

Intravascular Coagulation ◽

Fibrin Degradation Products ◽

At Iii

We reported previously that disseminated intravascular coagulation (DIC) occurs early during E. coli endotoxemia in the rat, before the development of serious cardiovascular, metabolic or biochemical abnormalities, and that pretreatment with large doses of purified human antithrombin-III (AT-III; 250 U/kg) markedly attenuates DIC and increases survival (PC0.05). The present study was an extension ofan earlier one in which pretreatment of dogs with a low dose ofhuman AT-III (50 U/kg) provided borderline protection against DIC during endotoxemia. In the present study, mongrel dogs were anesthetized with sodium pentobarbital, continuously monitored over a 21 hour protocol and given full fluid support. Twenty-three dogs were given iv infusions of E. coli endotoxin (0.5mg/kg) at times zero and 15 hours. Of these, seven received iv infusions of purified human AT-III (250 U/kg) 30 minutes prior to endotoxin; 16 received no AT-III and served as controls. Comparing the AT-III treated with the control group, there was significantimprovement in the activated partial thromboplastin time and prothrombin time (P<0.05). Also, fibrinogenand fibrin degradation products were improved significantly in the AT-III treated group (P<0.05). Platelet counts decreased in both groups and there was no between group difference (P>0.05). There was no s i gni fi cant between group differences in other parameters (e.g. hemodynamic, acid-base, metabolic). These data are in agreement with earlier studies in the endotoxemic rat which show that ore occurs early in endotoxemia, that DIC occurs before the development of serious abnormalities in other systems and that AT-III supplementation significantly attenuates OIC. This study supports the hypothes1s that AT-III supplementation is efficacious in conditions of impending OIC such as gram-negative endotoxemia/septicemia.

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Effect of Anabolic Steroids on Plasma Antithrombin III

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651450 ◽

1975 ◽

Vol 34 (01) ◽

pp. 106-114 ◽

Cited By ~ 3

Author(s):

I. D Walker ◽

J. F Davidson ◽

P Young ◽

J. A Conkie

Keyword(s):

Heart Disease ◽

Ischaemic Heart Disease ◽

Oral Contraceptives ◽

Disseminated Intravascular Coagulation ◽

Fibrinolytic Activity ◽

Antithrombin Iii ◽

Anabolic Steroids ◽

Intravascular Coagulation ◽

Clear Cut ◽

Α2 Macroglobulin

SummaryThe effect of seven different anabolic steroids (Ethyloestrenol, Methenolone acetate, Norethandrolone, Methylandrostenediol, Oxymetholone, Methandienone, and Stanozolol) on three α-globulin antiprotease inhibitors of thrombin and plasmin was studied in men with ischaemic heart disease. In distinct contrast to the oral contraceptives, five of the six 17-α-alkylated anabolic steroids studied produced increased plasma Antithrombin III levels and five produced decreased levels of plasma α2-macroglobulin. The effect on plasma α1antitrypsin levels was less clear-cut but three of the steroids examined produced significantly elevated levels. The increased plasma fibrinolytic activity which the 17-α-alkylated anabolic steroids induce is therefore unlikely to be secondary to disseminated intravascular coagulation.

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Immunologic measurement of antithrombin III-heparin cofactor and α2macroglobulin in disseminated intravascular coagulation and hepatic failure coagulopathy

Thrombosis Research ◽

10.1016/0049-3848(75)90148-6 ◽

1975 ◽

Vol 6 (1) ◽

pp. 27-38 ◽

Cited By ~ 45

Author(s):

Paul S. Damus ◽

Garn A. Wallace

Keyword(s):

Disseminated Intravascular Coagulation ◽

Hepatic Failure ◽

Antithrombin Iii ◽

Intravascular Coagulation

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Disseminated Intravascular Coagulation: A Clinical/Laboratory Correlation In 48 Patients

10.1055/s-0038-1653198 ◽

1981 ◽

Author(s):

R L Bick

Keyword(s):

Platelet Count ◽

Disseminated Intravascular Coagulation ◽

Clinical Laboratory ◽

Fibrinogen Level ◽

Degradation Products ◽

Severe Bleeding ◽

Thrombin Time ◽

Intravascular Coagulation ◽

At Iii ◽

Pre Treatment

Disseminated intravascular coagulation (DIC) is a frequent clinical entity spanning from a moderately severe bleeding disorder to a catastrophic, fulminant, and often fatal form usually associated with hemorrhage or, less commonly,as diffuse thromboses. The clinical and laboratory features of DIC remain confusing and controversial. To critically evaluate the usefulness of coagulation tests in aiding in the diagnosis and monitoring of therapy in DIC the clinical and laboratory findings were summarized in 48 patients with DIC. All patients were subjected to a prothrombin time (PT), activated partial thromboplastin time (PTT), reptilase time (RT), thrombin time (TT), fibrin(ogen) degradation products (FDP), platelet count, protamine sulfate test (PSO4), fibrinogen determination, and biological antithrombin-III (AT-III) level at the time of diagnosis. In addition, these same laboratory modalities were used to monitor patients during and after therapy. In this series of 48 patients, 38 patients had acute DIC and 10 patients had chronic DIC. In those patients with acute DIC, 100% of patients presented with hemorrhage and 53% of patients had thrombosis; 26% of patients died of their DIC type syndrome. In those patients with chronic DIC, 100% presented with hemorrhage, 80% presented with thrombosis, and none died of their intravascular clotting process. The probability of a pre-treatment abnormality in acute DIC was: FDP > AT-III = platelet count PS04 > TT > PT > fibrinogen level > PTT > RT. The probability of pre-treatment abnormalties in chronic DIC was: FDP > PSO4 = PT > AT-III = RT platelet count fibrinogen level = TT. These studies suggest the FDP level, the AT-III level, PSO4, and fibrinogen level to be reliable for aiding in the diagnosis of acute DIC. In chronic DIC the fibrinogen level, PS04, PTT, and AT-III level appear to be the most reliable indicies.

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