PubMed Health⌕ Search

Biomedical subjects

E A Loeliger

Publications and source records attributed to E A Loeliger.

At least 19 recordsLinked to original sources
PubMed1992

Therapeutic target values in oral anticoagulation--justification of Dutch policy and a warning against the so-called moderate-intensity regimens.

Careful scrutiny of relevant thrombosis prevention studies in the light of recent knowledge on the responsiveness to the anticoagulant defect of the various prothrombin time assays used in these studies casts serious doubts on the adequacy of the so-called moderate-intensity warfarin regimens, currently recommended by British and North American experts, in the majority of clinical situations. As long as there is strict laboratory monitoring, more intensive anticoagulation provides satisfactory prevention of thromboembolic events. The Federation of Dutch Thrombosis Centers recommends a target of 3.0 International Normalized Ratio (INR) for the primary and secondary prevention of venous thrombosis and thromboembolism, 3.5 INR in case of recurrence under the former regimen and for patients at risk for a cardiogenic embolism from any source (including tissue heart valve replacement) and those with atherothrombotic disease, and 4.0 INR for patients with a mechanical heart valve prosthesis. The risk of hemorrhage at such levels of anticoagulation remains acceptable.

Administration, Oral↗
PubMed1979

The optimal therapeutic range in oral anticoagulation. History and proposal.

For patients on oral anticoagulation controlled with Quick's prothrombin time test using rabbit brain thromboplastin American clinicians proposed in the early 1940s that the lower limit of prolongation be taken at 1.5 and the upper limit at 3, corresponding to 10-30% prothrombin activity on a saline dilution curve. Thromboplastins derived from other tissues and species were later introduced, methods were modified, and adsorbed plasma was used instead of saline in the construction of the dilution curve to obtain percentage prothrombin activity; ratios and percentages lost their initial significance, but too often without the clinicians' awareness. With the detection of PIVKAs, finally, it became clear that transformation of prothrombin times into percentage activity, as obtained from dilution curves, could never be a valid means of standardization. It also became evident that only direct comparison of thromboplastins with (fresh) plasma from patients on stabilized oral anticoagulants could be used to determine equivalent therapeutic ranges for different types of thromboplastins. Reference thromboplastins were established and calibration procedures developed. A series of well-controlled clinical trials has provided sufficient information to define, in terms of these reference thromboplastins, therapeutic ranges for the prophylaxis and treatment of venous as well as arterial thrombosis. Definition of the ranges in terms of the biochemical defect induced by coumarin congeners remains, however, to be established.

Administration, Oral↗
PubMed1979

Results of calibration by the Dutch National Reference Laboratory of the thromboplastins included in the ICTH/ICSH collaborative study of prothrombin time standardization.

Results obtained with the original calibration procedure of Biggs and Denson obtained by one expert laboratory compare well with those obtained from the ICTH/ICSH collaborative study. The simplified calibration procedure described in 1975 should only be used for the assessment of inter-batch variability of a given brand of thromboplastin; for the calibration of unlike thromboplastins, the simplified procedure should be revised by using more than two abnormal plasmas, e.g. different plasmas representing seven levels of anticoagulation between international calibrated ratios (ICRs) from 1.5 to 4.5. The formula for the calculation for the proposed ICRs based on the calibration constant should be modified to allow for instances where the calibration line for dissimilar thromboplastins, fitted in the therapeutic range, does not pass through the origin of ratio 1,1.

Blood Preservation↗
PubMed1979

Spectrophotometric assays of prothrombin in plasma of patients using oral anticoagulants.

Two spectrophotometric assays for prothrombin have been developed and compared with a one stage coagulant and an immunological assay. One of these assays (called the XAPC assay) uses a combination of factor Xa, phospholipid, Ca2+ and factor V as activator of prothrombin, and measures only normal prothrombin. The second (the ECAR assay) uses Echis carinatus venom as activator. This assay measures both normal prothrombin and PIVKA II (protein induced by vitamin K antagonists/absence). Combination of the results obtained by the XAPC and ECAR assays provides rapid and reliable information on the degree of "subcarboxylation" of prothrombin (oral anticoagulation, vitamin K deficiency). For patients on long term anticoagulant treatment the prothrombin time (Thrombotest) shows better correlation with the ratio prothrombin/prothrombin plus PIVKA II (XAPC/ECAR) than with the factor II concentration. For patients starting the anticoagulant treatment there is no correlation between the Thrombotest time and the XAPC/ECAR ratio. It seems doubtful that (a) spectrophotometric factor II assay(s) will be as useful as the prothrombin time in the control of oral anticoagulation.

Administration, Oral↗
PubMed1978

Thromboplastin calibration. Experience of the Dutch reference laboratory for anticoagulant control.

Standardization of the thromboplastin most commonly used for anticoagulant control in The Netherlands has been achieved by the Dutch Reference Laboratory for Anticoagulant Control. The system established for control indicates the performance characteristics of each batch of thromboplastin in patients relative to a national calibration batch. Calibration constants were assessed according to an ICTH/ICSH proposal and with a reproducibility of approximately 2% (CV). With the use of a given calibration constant of the International Reference Preparation of Thromboplastin (1.0) and after assessment of the calibration constant of the National Reference Preparation in international terms (0.93), the accuracy of calibration with the various modifications of the calibration procedure is of the order of magnitude of 3% (CV). On the basis of the calibration protocol, physicians will be provided with correlation tables containing, for their convenience, prothrombin (thromboplastin) times in terms of the reference thromboplastin (uniform, i.e., batch-independent, prothrombin times), conventional prothrombin activity (percentages), and in due course with International Calibrated Ratios. With this approach current practice in the prescription of oral anticoagulants will be maintained. Opportunity is given, however, to aim at internationally proposed therapeutically optimal target values.

Blood Coagulation Tests↗
PubMed1978

Successful prevention of coumarin-induced hemorrhagic skin necrosis by timely administration of vitamin k1.

Successful prevention of the progression of incipient hemorrhagic skin necrosis by timely administration of vitamin K1 in a woman treated with phenprocoumon is presented. From a critical review of the literature strong evidence emerges that coumarin necrosis does only occur in cases with severe initial drug induced hypocoagulability. Non- recognition thusfar of its importance is due to insufficient knowledge of the biological activities of thromboplastin preparations presently used in the laboratory control of oral anticoagulation. All well documented cases with apparently adequate Quick values were monitored with Faktor VIII insensitive thromboplastin. Therefore, such preparations should no longer be used in anticoagulant control.

4-Hydroxycoumarins↗
PubMed1977

Interlaboratory oral anticoagulant quality assessment by the Netherlands Federation of Thrombosis Services.

The 50 laboratories of the Netherlands Federation of Thrombosis Services, covering a population of 9 million and responsible for the laboratory control of approximately 150,000 patients under oral anticoagulation, have participated since 1974 in a voluntary external and internal quality control program. The external program comprises a monthly distribution to the member laboratories of a series of artificially prepared control blood samples, two of which are identical. The overall variation of the coagulation times found were 10% (CV) in 1974 and 8% (CV) in 1975. Performance improved rather abruptly at the beginning of 1975, after the application of a tight methodological standardization and improvement by the manufacturer of the thromboplastin preparation (Thrombotest) used by the great majority of the laboratories involved. The main source of variation was found to be random error in the Thrombotest determination, approximately 6%. Interbatch variation of Thrombotest and inter-aliquot variation of control blood samples both do amount to approximately 3%(CV). In terms of rabbit tissue thromboplastins, which have a lower sensitivity than Thrombotest (i.e., a flatter slope of the correlation between the PT and the anticoagulant effect), the total variation in the performance of the Dutch laboratories is 2.2--5.6% (CV), which is unusually low. The main reason for this is the fact that the laboratories can rely not only on the services of the manufacturer but also on a central information office and a reference laboratory responsible for the preparation of the control blood as well as the standardization (calibration) of thromboplastin.

Anticoagulants↗