The Optimal Therapeutic Range in Oral Anticoagulation
History and Proposal

Ea, Loeliger

doi:10.1055/s-0038-1657009

Cited by 81 publications

(22 citation statements)

References 6 publications

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“…Despite concerted efforts over the span of decades to standardize the prothrombin time, oral anticoagulation exists in the absence of definitive clinical trials demonstrating the most efficacious regimen for induction, maintenance, and monitoring of therapy [24,25]. Accepted practice in the in-patient setting begins with 5 days of combined heparin and warfarin therapy.…”

Section: Discussionmentioning

confidence: 99%

Comparison of plasma prothrombin and factor VII and urine prothrombin F1 concentrations in patients on long‐term warfarin therapy and those in the initial phase

et al. 1998

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Control of warfarin anticoagulation during the initial phase of therapy is difficult and empirically based. Plasma and urine samples were obtained from normal controls, patients under stable anticoagulation, and patients in the initial phase of anticoagulation. Total plasma prothrombin, des-carboxy (non-adsorbable with barium chloride) prothrombin, and native (total minus non-adsorbable) prothrombin were quantitated using Echis carinatus venom activation. Functional plasma factor VII (VII) was measured using a one-stage clotting assay. Total and des-carboxy urine prothrombin F1 (F1) were measured by ELISA. All urine F1 in normals and both anticoagulated groups was adsorbed by barium chloride. Plasma des-carboxy prothrombin concentration was similar for the two anticoagulated groups and did not correlate with 1/INR. Native prothrombin correlated with 1/INR in both the stable (r = 0.76) and initial phase (r = 0.74) groups. For any given INR, the subjects on stable anticoagulation had lower native prothrombin concentrations than the initial phase patients. Functional factor VII concentration also correlated significantly with 1/INR in both the stable (r = 0.64) and initial phase (r = 0.76) patients. Unlike native prothrombin, VII concentrations did not vary between the two cohorts for any given INR. Previous studies indicate that native prothrombin is a superior predictor of both hemorrhagic and thromboembolic complications during warfarin therapy. Our findings indicate that VII, and not prothrombin, may be the predominant factor monitored by the INR. This further supports the need to reevaluate the usefulness of the INR in the monitoring of warfarin therapy during the initial phase. Am.

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Section: Discussionmentioning

confidence: 99%

Comparison of plasma prothrombin and factor VII and urine prothrombin F1 concentrations in patients on long‐term warfarin therapy and those in the initial phase

et al. 1998

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“…Thromboplastins can vary markedly in their responsiveness to the defects induced by vitamin K antagonist therapy. As a result, the poor agreement between PT in different laboratories whatever the methods of reporting results 4 has led to important differences in oral anticoagulant dosing. 5,6 Standardization of PT reporting in patients on oral anticoagulation has been improved by the calibration model for thromboplastins proposed by the World Health Organization (WHO).…”

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confidence: 99%

A modified international normalized ratio as an effective way of prothrombin time standardization in hepatology†

et al. 2007

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International Normalized Ratio (INR), which standardizes prothrombin time (PT) during oral anticoagulation, has been extended to standardize PT in liver diseases and is included in prognostic models such as the Model for End stage Liver Disease (MELD). However, mechanisms of PT prolongation in liver diseases differ from those involved in oral anticoagulation, and the thromboplastin reagents differ in their sensitivities to these 2 mechanisms. Our aim was to determine whether, in the calibration model for thromboplastins proposed by the World Health Organization, the use of plasmas from patients with liver diseases instead of plasmas from patients on oral anticoagulation could lead to a new INR specific for liver diseases (INR "LD"), achieving a real standardization of PT. First, 5 thromboplastins were calibrated against an international reference using 60 plasmas of patients with liver failure and, in a second step, the variation of PT reported as seconds, the ratio of patient PT to normal PT, See Editorial on Page 295 P rothrombin time (PT) is the usual test for monitoring oral anticoagulation by vitamin K antagonists 1 and is widely adopted to assess the severity of acute and chronic liver injury. 2 PT is the recalcification time of citrated plasma in the presence of a thromboplastin reagent. 3 The term thromboplastin refers to a complex mixture of tissue factor and phospholipids prepared from tissue extracts of animal or human origin. Recent thromboplastins contain recombinant tissue factor. PT is influenced by the levels of the following coagulation factors: I (fibrinogen), II, V, VII, and X, all factors being synthesized by the liver and, among them, 3 (II, VII, and X) being vitamin K dependent. Thromboplastins can vary markedly in their responsiveness to the defects induced by vitamin K antagonist therapy. As a result, the poor agreement between PT in different laboratories whatever the methods of reporting results 4 has led to important differences in oral anticoagulant dosing. 5,6 Standardization of PT reporting in patients on oral anticoagulation has been improved by the calibration model for thromboplastins proposed by the World Health Organization (WHO). 7 This system defines, for a specific thromboplastin reagent, the International Sensitivity Index (ISI) obtained by a calibration using plasmas of patients on stable oral anticoagulant doses, against a WHO international reference thromboplastin. 7 The ISI is a numerical value that reflects the responsiveness of a given thromboplastin to reduction of the vitamin K-dependent coagulation factors; the lower the ISI value, the greater the sensitivity of the reagent. The recommended scale of reporting PT results is

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“…In 1979, a first proposal was made for optimal therapeutic anticoagulation [5]. [ 10], the group of Poller [11], and Francis et al [12], Detailed information about the postoperative course is given only by Francis et al; Van der Linde is less explicit and the group of Poller gives no data.…”

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confidence: 99%

Optimal Therapeutic Anticoagulation

Loeliger¹

1985

Pathophysiol Haemos Thromb

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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 > 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.

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The Optimal Therapeutic Range in Oral Anticoagulation History and Proposal

Cited by 81 publications

References 6 publications

Comparison of plasma prothrombin and factor VII and urine prothrombin F1 concentrations in patients on long‐term warfarin therapy and those in the initial phase

Comparison of plasma prothrombin and factor VII and urine prothrombin F1 concentrations in patients on long‐term warfarin therapy and those in the initial phase

A modified international normalized ratio as an effective way of prothrombin time standardization in hepatology†

Optimal Therapeutic Anticoagulation

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