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[Natural plasma inhibitors of factors activated by coagulation. Their behavior under various clinical conditions].

Levels of anti-Xa and anti-thrombin III activity have been determined in a series of patients clinically definable as "thrombophiliac" and of women undergoing oestroprogestinic contraceptive treatment. The levels of plasma Co-Ep activity for potentiating anti-Xa activity on the part of differing in vitro added doses of Ep have also been determined. The fact that anti-Xa fell in more marked a fashion than the corresponding anti-thrombin III may be the humoral equivalent of a condition of plasma hypercoagulability. Treatment with coumarin derivatives may bring about an appreciable increase anti-Xa plasma levels. The significance of these variations is discussed and the sensitivity of the anti-Xa method for monitoring small dose heparin therapy, i.e. based on antithrombotic rather than anti-coagulant effect, is confirmed.

Adult

Anticoagulant activities of high and low molecular weight heparin fractions.

The anticoagulant activities of high and low molecular weight heparin fractions were measured by three assay methods, both in vitro, and after intravenous injection in volunteers. The low molecular weight (LMW) fraction had similar anti-Xa activity in vitro to the high molecular weight (HMW) fraction, but in APTT assays the HMW fraction was about twice as potent. After intravenous injection, the two fractions gave equal heparin levels by anti-Xa assays, but in APTT assays using synthetic substrate S-2222 gave about 20% lower levels than anti-Xa clotting assays for both heparins. Complete protamine neutralization of the post-injection heparin activity was found in APTT and synthetic substrate assays, but about 20% of the clotting anti-Xa effect could not be neutralized. Complete neutralization of the fractions by protamine was shown by all three assays in vitro. This non-neutralizable activity probably accounts for the difference between the anti-Xa clotting and synthetic substrate assays. Studies by crossed immunoelectrophoresis and affinity chromatography indicated that the antithrombin III binding properties of the two fractions were similar.

Adult

Surgery, venous thrombosis and anti-Xa.

Deep venous thrombosis is a common and unpredictable complication of surgery. In this study it is proposed that patients who develop this complication may be predicted by a low preoperative level of a naturally occurring inhibitor of coagulation, anti-Xa. Two groups of patients were investigated. Women taking the oral contraceptive pill had lower preoperative anti-Xa levels than their non-pill controls (P less than 0.01) and in addition had a significantly higher incidence of deep venous thrombosis (DVT) following emergency surgery (P less than 0.05). In 90 patients undergoing total hip replacement, the mean preoperative anti-Xa level of those patients who developed DVT was significantly lower than those who did not (P less than 0.001). Ninety-four per cent of patients with a preoperative anti-Xa level of less than 80 per cent developed DVT. The effect of low dose heparin on anti-Xa was studied. The results suggest a mechanism for the cause of postoperative thrombosis which also permits selection of individual patients who will develop this complication.

Adolescent

Direct Oral Anticoagulant Transition Strategies Using Anti-Xa Concentrations Upon Intensive Care Unit Admission.

Background: The increased utilization of oral factor Xa inhibitors (FXaI) has led to a growing interest in the clinical utility of FXaI-specific anti-Xa concentrations. Critically ill populations are at risk of bleeding secondary to FXaI accumulation in the setting of end-organ dysfunction. To mitigate this risk, an FXaI anti-Xa concentration-guided approach to transitioning between oral and parenteral anticoagulation has been explored. Objective: To compare the incidence of bleeding upon intensive care unit (ICU) admission between 2 different FXaI transition strategies: concentration versus non-concentration-guided. Methods: We performed a retrospective chart review of patients admitted between January 2019 and May 2022 with objective evidence of FXaI exposure within 48 hours preceding ICU admission. Patients were excluded if they were admitted to the ICU with a primary diagnosis related to a bleeding event, received a non-FXaI anticoagulant 48 hours preceding ICU admission, remained off anticoagulation during their ICU admission, or underwent surgical procedures. The primary outcome was the incidence of major bleeding within 5 days of ICU admission. Thromboembolic events were evaluated as a secondary endpoint. Results: A total of 433 patients (184 concentration-guided vs 249 non-concentration-guided) were included. There was no difference in major bleeding between groups (2.7% in concentration-guided vs 3.6% in non-concentration-guided; P = 0.79). Thromboembolic complications were similar between groups (1.6% in concentration-guided vs 2.0% in non-concentration-guided; P = 1.00) despite a longer time from last FXaI dose to anticoagulant transition in the concentration-guided group (29.9 hours vs 19.4 hours; P < 0.01). Conclusion and relevance: Use of FXaI concentrations to guide anticoagulation transition in the ICU had no impact on major bleeding events or thromboembolic complications. Further analyses are needed to validate FXaI concentration-guided strategies and solidify anti-Xa cutoffs to create a standardized approach to FXaI transitions in the critically ill patient population.

DOAC

Anti-Xa factor as a predictor of postoperative deep vein thrombosis in general surgery.

This study was stimulated by a recent report linking a low preoperative level of an endogenous coagulation inhibitor (anti-Xa factor) with an increased incidence of postoperative deep venous thrombosis (DVT) (Stamatakis et al., 1977). Preoperative and postoperative levels of anti-Xa were measured and correlated with the postoperative incidence of deep venous thrombosis assessed by the 125I fibrinogen uptake test to determine whether a high risk group could be isolated and a suitable regimen of prophylaxis introduced. In this study of 22 surgical patients the postoperative DVT rate was 41 per cent. However, preoperative measurements of anti-Xa activity failed to show any statistically significant difference between those patients with DVT and the non-DVT groups. The findings do not support the use of anti-Xa levels as a preoperative predictor of postoperative DVT in the individual.

Adult

The determination of antithrombin III by radioimmunoassay and its clinical application.

A radioimmunoassay (RIA) had been developed for the determination of antithrombin III (AT III) in man. The detection limit was 25 microgram/dl. AT III-RIA level and biological activity (anti-Xa) was significantly correlated (r = 0.737, P less than 0.001). Plasma levels in 36 healthy males (mean +/- SD, 19.9 +/- 2.5 mg/dl) and 21 healthy females (19.1 +/- 2.4 mg/dl) were similar. Serial AT III measurements in normal menstruating females showed lower levels during midcycle and higher concentrations during menstruation. In carcinomas, the AT III levels were lower than normal, particularly in hepatocellular carcinoma. In cirrhosis of liver, the levels were markedly decreased and in some patients were below that found in congenital AT III deficiency. Patients with deep vein thrombosis and patients with heart valve replacement had lower levels than normal, while patients with cerebral vascular occlusion had normal levels. The possible use of AT III as a diagnostic tool of post-operative deep vein thrombosis was demonstrated in one patient after hysterectomy. The increased sensitivity, specificity and precision of this type of assay offer distinct advantages over existing methods of AT III estimation.

Adult

Four heparin preparations: anti-Xa potentiating effect of heparin after subcutaneous injection.

Four different heparin preparations--sodium and calcium salts of the same batch of heparin (mean molecular weight 15,000), low molecular weight sodium heparin (mean m.w. 9,000) and high molecular weight sodium heparin (mean m.w. 22,000) were injected subcutaneously on different days each into 6 healthy young volunteers in a randomized trial. Plasma heparin levels were measured using the anti-Xa assay at 1 hour, 3-4 hours and 6-7 hours after the injection. The highest anti-Xa potentiating effect was obtained after the injection of the low molecular weight sodium heparin (mean 0.381 i.u./ml) at 3-4 hours after the injection. With sodium heparin (m.w. 15,000) the highest values (0.135 i.u./ml) were found at 1 hour. Significantly lower anti-Xa potentiating effect was obtained 1 hour after the injection of calcium heparin and in particular after the injection of high molecular weight heparin (mean values 0.072 i. u./ml and 0.043 i. u./ml respectively). Both these preparations showed an increase from 1 hour after injection to 3-4 hours after injection (mean values 0.082 i. u./ml and 0.057 i. u./ml at 3-4 hours after injection). These results indicate that the salt and the molecular weight of the preparation may strongly influence the degree of anticoagulation achieved after subcutaneous injection.

Calcium

[Antithrombin III deficiency and tendency to thrombosis (author's transl)].

Antithrombin III (AT III) was determined in 290 patients with deep venous thrombosis and/or pulmonary embolism by immunological methods (radial immunodiffusion, Laurell technique) and by biological activity (heparin cofactor activity and anti-Xa activity). Patients with venous thrombosis had a significantly lower AT III concentration, as determined by the immunological methods or biological method (heparin cofactor activity), than normal persons without any history of venous thrombosis. A decreased level of AT III was found in 27 patients. In these patients the immunoreactive antithrombin III was decreased to the same degree as biological activity (heparin cofactor activity or anti-Xa activity). Thirteen out of these 27 patients belonged to 9 families and, hence, congenital AT III deficiency can be assumed in these cases. The aetiology was unknown in the other half. Patients with AT III deficiency are prone to spontaneous and/or recurrent venous thrombosis. A high incidence of pulmonary embolism and particularly, of fatal pulmonary embolism is remarkable. In more than half of the patients the first thrombotic event occurred before the age of 35. The treatment of choice in such patients is with oral anticoagulants of the coumarin group.

Adult