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Biomedical subjects

E A Loeliger

Publications and source records attributed to E A Loeliger.

At least 37 records · Page 2Linked to original sources
PubMed1986

The calibration of rabbit tissue thromboplastins: experience of the Dutch Reference Laboratory for anticoagulant control.

A number of commercial rabbit tissue thromboplastins used in oral anticoagulant control have been calibrated against the first International Reference Preparation for thromboplastins. This was done in a three-stage procedure by one laboratory, each stage representing a different level of thromboplastin comparability. The calibration model recently recommended by ICTH and ICSH was tested. This model proved to be suitable, although a statistically significant aberration was observed for some of the thromboplastins. The bias introduced by using the model in these non-ideal cases was small compared to the overall variation of the International Normalized Ratio, being the universal scale for reporting the prothrombin time during oral anticoagulant control. Batch-to-batch calibration using lyophilized pooled plasmas could be reliably performed for several commercial thromboplastins.

Administration, Oral↗
PubMed1986

Recurrent coumarin-induced skin necrosis in a patient with an acquired functional protein C deficiency.

An elderly woman who had been receiving long-term oral anticoagulant therapy developed skin and subcutaneous fat necrosis on five repeated occasions of extreme hypocoagulability, associated with coinciding periods of congestive cardiac failure. In each episode, the skin necrosis developed within days after the prothrombin time (as determined with Thrombotest) exceeded 200 s (International Normalized Ratio greater than 5.4). Widespread thrombosis in the subcutaneous vasculature and interstitial bleeding, as observed in a skin biopsy specimen, were consistent with a diagnosis of coumarin necrosis. On two occasions, an acquired functional protein C deficiency was present. It is hypothesized that an imbalance between anticoagulant and procoagulant vitamin K-dependent factors contributed to the pathogenesis of coumarin-induced skin necrosis. This imbalance was related to repeated periods of congestive heart failure.

Biopsy↗
PubMed1985

[What can be expected today from long-term anticoagulation for cardiac and arterial thrombosis?].

Appropriate long-term oral anticoagulation prevents cardiogenic thromboembolism to a large extent in patients with artificial heart valves, rheumatic heart disease, myocardiopathy, atrial fibrillation of non-rheumatic origin, sick sinus syndrome, cardiac aneurysm, and in the exceptional cases of mitral valve prolapse with thromboembolic complications. In arterial thrombosis, oral anticoagulation remains a controverted, probably because a much higher intensity would be needed to achieve the same degree of effectiveness. With target prothrombin times between 3.5 and 4 International Normalized Ratios (INRs) and a compliance of the INRs with the range of 2.5-5 INRs for greater than or equal to 80%, cardiogenic thromboemboli can be prevented in approximately 95% whereas only about two thirds of the cases of recurrent coronary thrombosis can be avoided. The intensity and stability of treatment needed in cardiovascular thrombosis involve a considerable risk of bleeding, but--as shown by the results of the Dutch Sixty Plus Reinfarction Study--intracranial haemorrhages are more than compensated for by the prevention of cerebrovascular thromboembolic events. Appropriate administration of oral anticoagulation requires painstaking laboratory and therapeutic control, the former being based on continuous quality assessment and strict standardization of the prothrombin time. Therapeutic control consists of continuous patient education and adequate dosage regulation. Similar to the situation prevailing for hemophilia patients, an organization must be available to which long-term anticoagulated patients can apply for expert advice. In The Netherlands, an organization has been built up on a voluntary basis, called Federation of Thrombosis Centres, meeting this requirement and covering more than 90% of the country.

Anticoagulants↗
PubMed1985

Questions and answers on prothrombin time standardisation in oral anticoagulant control.

One of the reasons why oral anticoagulants fell into disrepute is the absence of internationally accepted standardised procedures for controlling the level of anticoagulation. This deplorable situation resulted in over- and under-coagulation and uncertainty in the therapeutic range. International conformity can now be obtained by using an International Normalised Ratio (INR) which is derived from the individual result obtained in a given plasma sample and the International Sensitivity Index (ISI) of the tissue thromboplastin reagent used. Any thromboplastin reagent can be calibrated against an international primary or secondary W. H. O. reference preparation, so as to obtain its International Sensitivity Index. The new system of reporting the level of anticoagulation was designed and can only safely be applied in patients taking oral anticoagulants.

Administration, Oral↗
PubMed1985

Reliability and clinical impact of the normalization of the prothrombin times in oral anticoagulant control.

In 1983, the World Health Organization (WHO) published recommendations for normalization, in oral anticoagulant control, of the prothrombin time (PT). The common denominator is the International Sensitivity Index (ISI) of a thromboplastin, obtained by means of thromboplastin calibration. The common scale is that of the International Normalized Ratio (INR). The INR is the PT ratio (Formula: see text) which would have been found with the WHO primary international reference preparation (IRP) 67/40. The reliability of the INR depends on the extent of calibration precision, patient-specific influences, as well as inter-laboratory variation in the PT determination. Under well-controlled conditions the overall coefficient of variation (CV) of the INR is 11-13.5%, if thromboplastins of ISI congruent to 1 are used. For so-called low-sensitivity thromboplastins (ISI congruent to 2-2.5), the overall variation is larger due to a large between-laboratory variation of the measured PT-ratios. The user of thromboplastin will be provided with a chart or graph enabling him to convert the conventional terms used for expressing PTs into INRs. For quality assurance, and to prepare his own calibration chart if necessary, he should check normalization by means of control plasmas to which INRs have been assigned. There is sufficient clinical evidence to express optimal therapeutic ranges in terms of INR. Manufacturers should revise and adapt their inserts where necessary in order to conform to these requirements.

Administration, Oral↗
PubMed1985

Optimal therapeutic anticoagulation.

The relevant literature on the intensity of anticoagulation needed to prevent the development or growth of thrombi in patients at risk is reviewed. In case of elective surgery, prevention of venous thrombosis is easily attained with heparin or with coumarin alone, at levels of anticoagulation involving only a minor risk of bleeding complications. For posttraumatic prophylaxis, more intensive oral anticoagulation is required, similar to that for the management of active venous thrombosis, for which a combined heparin/coumarin regimen is proposed. A 90% reduction of the incidence of systemic emboli in patients with a high risk of developing intracardiac thrombosis requires high-intensity treatment with a target INR of 4. More intensive anticoagulation would be needed to obtain the same 90% protection in case of arterial (coronary) thrombosis. This is prohibited, however, by the rapidly increasing bleeding risk in cases with INR values greater than 5. With a target INR of 3.5 (sixty-Plus patients), the reinfarction rate will not be lowered by more than two thirds. Antiplatelet drugs given alone or in combination with anticoagulants have not been convincingly successful thus far in the prevention and treatment of thrombosis.

Anticoagulants↗