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PubMed1983

The transfer test: a new screening procedure for thrombotic diseases.

The transfer test (TT) measures by means of thromboelastography the capacity of a plasma to shorten the coagulation time of a control plasma. The value of the TT was compared to that of fibrin(ogen), degradation products (FDP), and ethanol gelatin test (EGT) in various diseases (group I), in confirmed deep venous thrombosis (group II), and in confirmed pulmonary embolism (group III). In 211 consecutive patients admitted for various diseases the results of the TT, FDP, and EGT were abnormal in 12.3, 11.3, and 66.6%, respectively, of the cases. In 59 consecutive patients with deep venous thrombosis confirmed by radiological phlebography the results of TT, FDP, and EGT were abnormal at admission time in 96.6, 89.8, and 44%, respectively, of the cases. In 45 consecutive patients with pulmonary embolism confirmed by lung scintigraphy the results of TT, FDP, and EGT were abnormal at admission time in 97.7, 97.6, and 88%, respectively, of the cases. Among the three parameters which were evaluated, the TT seems to be the most sensitive screening procedure for thrombotic diseases. A normal result of TT is a strong argument against a recent thrombotic venous phenomenon.

Acute Disease↗
PubMed1987

Hemostatic evaluation of patients undergoing liver transplantation.

A detailed coagulation and thromboelastographic study was done on the first 50 liver transplantation procedures performed at the Mayo Clinic between March 1985 and June 1986. Most of the patients suffered from primary sclerosing cholangitis, primary biliary cirrhosis, or chronic active hepatitis. Seven patients required a second liver transplantation, and six patients died, none intraoperatively. Most of the patients had distorted hemostatic mechanisms preoperatively, as would be expected because the liver generates most of the clotting factors. The outstanding exception was factor VIII, which was usually in the high-normal range or even more elevated. Substantial deterioration of coagulation factors occurred regularly during reperfusion of the donor liver. In some instances, this trend was corrected within 1 hour, but platelet counts continued to decrease, and some coagulation factors rebounded only partially. Because thromboelastographic tracings are quickly available to the liver transplant team and because they tend to forewarn of impending hemostatic problems, we believe that thromboelastography is a reasonably effective procedure for monitoring coagulation during liver transplantation.

Blood Coagulation Factors↗
PubMed1989

Hemodynamic and metabolic changes in hepatic transplantation.

In this study, we retrospectively analyzed the intraoperative hemodynamic, laboratory, and coagulation data on the first 83 patients who underwent an initial liver transplantation procedure at our institution. The major hemodynamic changes at the time of reperfusion of the donor liver were significant decreases in arterial blood pressure, systemic vascular resistance, and pulmonary artery temperature and significant increases in cardiac output and pulmonary capillary wedge pressure. The alterations in laboratory values reflected intraoperative therapeutic manipulations. Citrate toxicity is a concern, and the amount of calcium chloride administered reflected the volume of blood transfused. On reperfusion, the fibrinogen concentration decreased and both the prothrombin time and the activated partial thromboplastin time increased. This coagulopathy was also evident in the thromboelastographic values. Aggressive monitoring and prompt intervention are necessary to maintain hemodynamic and metabolic homeostasis in these patients.

Blood Chemical Analysis↗
PubMedDate not supplied

The role of thromboelastography in the management of children with snake-bite in southern Africa.

In the absence of a direct laboratory test of envenomation, there is a need for an alternative mechanism for the early recognition of envenomation following snake-bite in children. A severe clinical diathesis may result either from envenomation or from the release of an inappropriate tourniquet applied as 'first-aid' often several hours before presentation to hospital. Abnormalities of clotting are associated with both events. A normal thromboelastogram (TEG) provides early recognition of patients in whom the clinical course is likely to be benign (sensitivity = 94%). An abnormal TEG identifies patients of whom 50% will develop a severe clinical diathesis. A TEG is a more accurate predictor of disease severity than International Normalized Ratio alone. The TEG does not supplant clinical observation in the management of snake-bite in children but allows stratification into high- and low-risk categories.

Child↗
PubMed2001

Comparison of the effect of different platelet GPIIb/IIa antagonists on the dynamics of platelet/fibrin-mediated clot strength induced using thromboelastography.

The effect of various platelet glycoprotein IIb/IIIa (GPIIb/IIIa) antagonists on the dynamics of platelet-fibrin clot formation and strength induced by various stimuli was measured by thromboelastography (TEG). GPIIb/IIIa antagonists with high affinity for resting and activated platelets and with slow rates of dissociation from GPIIb/IIIa (Class I antagonists) demonstrated potent and comparable inhibition of platelet aggregation and tissue factor (TF), lipopolysaccharide (LPS), Factor Xa, and thrombin-induced clot strength, in contrast to antagonists that dissociate rapidly from GPIIb/IIIa (Class II antagonists). For example, the Class I antagonist XV459 (the free acid form of roxifiban) inhibited TF, endotoxin, Factor Xa, and thrombin-induced maximal clot strength and platelet aggregation with an IC(50)=30-70 nM, whereas the IC(50) of the Class II antagonist YZ211 (the free acid form of sibrafiban) for altering clot formation and strength was 0.3-4.7 microM. Moreover, the IC(50)'s of sibrafiban, and another Class II antagonist, orbofiban, for inhibiting platelet-fibrin clot formation and strength were substantially greater than their clinically achievable concentrations. Further, although aspirin treatment improved the efficacy of all GPIIb/IIIa antagonists, it did not alter the differences between Classes I and II antagonists. Thus, these data indicate that there are differences in the efficacy of various GPIIb/IIIa antagonists in inhibiting platelet-fibrin clot formation and strength. They also suggest that inhibiting platelet aggregation may not be the sole determinant for the in vivo efficacy of various GPIIb/IIIa antagonists.

Biomechanical Phenomena↗
PubMed1998

Species specificity of the anticoagulant activity of human urinary soluble thrombomodulin.

The anticoagulant activities of human urinary soluble thrombomodulin (UTM) in blood taken from various species using several anticoagulant assay systems were compared; it was examined which coagulant assay system is appropriate for evaluation of the antithrombotic effects of UTM and how the species specificity of UTM is involved in the mechanisms of action of UTM. When anticoagulant activities were compared using activated partial thromboplastin time (APTT), thromboelastography (TEG), and thrombin generation test (TGT), the effect of UTM was found to be the strongest in humans among various species tested. Among the anticoagulant assays tested, TGT reflecting protein C (PC) activation by UTM, appeared to be more sensitive than APTT and TEG in detection of thrombomodulin activity. In the study of the mechanisms of action of UTM, UTM exhibited nearly the same antithrombin activity against human and rat thrombin; the rate of activation of human PC by thrombin/UTM complex was much higher than that of rat PC. Therefore, the species specificity of the anticoagulant activity of UTM may be attributable to thrombin/UTM-PC interaction, but not to UTM-thrombin interaction. From these results, we concluded that TGT reflecting PC activation by UTM will be a more useful assay than APTT and TEG for estimating the antithrombotic effects of UTM in humans. Furthermore, our findings suggest that UTM will exhibit more potent antithrombotic effects in humans than those in rats by strongly enhancing thrombin-catalyzed PC activation.

Animals↗
PubMedDate not supplied

Thrombophilia and pregnancy loss.

Thrombophilia is defined as a tendency to thrombosis. The association between specific thrombophilic defects--both inherited and acquired--and pregnancy loss is a rapidly developing field. However, apart from antiphospholipid antibodies (aPL), an acquired thrombophilic defect, the role of other defects in the haemostatic pathways remains to be established. In this invited review we discuss the recent advances in our understanding of aPL related pregnancy loss, the association between genetic thrombophilic mutations and pregnancy outcome and the role of whole blood haemostasis testing in the investigation of women with recurrent miscarriage.

Abortion, Habitual↗
PubMed1997

In vitro paraoxon (E 600) exposure: no activating effect on human blood coagulation.

The in vitro effects of the organophosphorus compound (OPC) paraoxon (POX) on human blood coagulation were assessed by fibrin monomer (FM) concentration measurements and thrombelastographic (TEG) determinations. Increasing doses of POX dissolved in alcohol (POX + ALO) or alcohol (ALO) only in corresponding quantities were added to blood drawn from six human volunteers. In both series (POX + ALO and ALO-only) FM concentrations increased in comparison to the baseline levels. No statistically significant differences exist, however, between FM measurements performed on blood with POX + ALO and those performed on blood with ALO-only. No coagulation-activating effect of POX in vitro was demonstrable; the changes seen in vitro are due to the ALO used as a vehicle. The thrombelastographic parameters showed several changes in the POX + ALO series as dosage increased. At high POX levels, reaction time r and clot formation time k became longer than in the baseline measurements, the clot formation rate alpha and the maximum amplitude MA were reduced. The TEG changes indicate a hypocoagulable state, probably due to the POX effect on platelet function and/or inhibition of clotting factors (serine proteases).

Blood Coagulation↗
PubMed1999

A novel high molecular weight fibrinogenase from the venom of Bitis arietans.

A fibrinogenase (Ba100) with an apparent molecular mass of 100 kDa under non-reducing conditions and a pI of 5.4 was purified from the venom of the African puff adder (Bitis arietans) by fibrinogen affinity chromatography. Under reducing conditions the protease dissociates into subunits of 21 kDa and 16 kDa. N-Terminal amino acid sequencing showed these two chains to have 66.7% homology and homology to C-type lectins. The fibrinogenase activity of Ba100 cleaves the Aalpha and Bbeta chain of fibrinogen rendering the molecule unable to polymerise into fibrin clots. Ba100 inhibited platelet aggregation in platelet rich plasma, and clot formation in whole blood, in a concentration dependent manner.

Amino Acid Sequence↗