Deep vein thrombosis outcome and the level of oral anticoagulation therapy.
(9/733)
OBJECTIVE: The purpose of this study was to assess the rate of deep vein thrombosis (DVT) resolution and DVT outcomes as functions of the level of oral anticoagulation therapy achieved with warfarin. METHODS: In 33 consecutive patients, a series of 35 limbs with acute symptomatic DVT was followed throughout 1 year of anticoagulation therapy. All the patients underwent 5 days of intravenous unfractionated sodium heparin therapy that was adjusted in dose to prolong the activated thromboplastin time to 2.0 to 2.5 times the control. In addition, warfarin was administered for a period of 6 months, with a target international normalized ratio (INR) between 2.0 and 3.0. All the patients underwent venous duplex scanning and physical examination at the time of diagnosis and at 1 week, 1 month, 3 months, 6 months, and 1 year. RESULTS: At the end of the 1-year study period, the rate of complete DVT resolution was 68%. The median INR values in patients with complete DVT resolution were significantly higher than those of patients with incomplete DVT resolution after 1, 3, and 6 months of treatment with warfarin. In addition, the proportion of patients with INR values below therapeutic range was significantly higher in patients with incomplete DVT resolution than in patients with complete DVT resolution after 1, 3, and 6 months of treatment with warfarin. The presence of occlusive thrombi was associated with incomplete DVT resolution. Of the patients with occlusive thrombi, 62% had chronic venous insufficiency symptoms develop, whereas only 11% of the patients with nonocclusive thrombi (P =.003) had these symptoms develop. CONCLUSION: Despite 6 months of oral anticoagulant therapy, almost one third of thrombi did not resolve completely. The INR values were significantly higher in those patients with complete DVT resolution. These results suggest that the maintenance of an INR level between 2.0 and 3.0 throughout oral anticoagulation therapy will minimize the rate of incomplete DVT resolution. (+info)
Laboratory evaluation of difenacoum as a rodenticide.
(10/733)
The efficacy of difenacoum as a new anticoagulant rodenticide was evaluated by blood coagulation studies and laboratory feeding tests using warfarin-resistant and non-resistant common rats (Rattus norvegicus), ship rats (R. rattus) and house mice (Mus musculus). Prothrombin assays indicated that the compound had as marked an activity with warfarin-resistant common rats as coumatetralyl had with non-resistant animals. Feeding tests confirmed that 0-005% would be a near-optimal concentration for field use, although there was some evidence of unpalatability. Results with ship rats and house mice were less favourable. Trials with enclosed colonies of warfarin-resistant mice confirmed the laboratory finding that although difenacoum was more effective than all other currently used anticoagulants, it was unlikely to give complete control. It is concluded that difenacoum is a valuable new rodenticide, especiaaly for controlling warfarin-resistant common rats. (+info)
Procoagulant effect of anti-beta2-glycoprotein I antibodies with lupus anticoagulant activity.
(11/733)
Prothrombin time (PT) is routinely used to monitor oral anticoagulant treatment in patients with the antiphospholipid antibody syndrome (APS). The fact that PT is a phospholipid (PL)-dependent coagulation test raises the possibility that lupus anticoagulant (LA) might interfere with this test, thus complicating the control of anticoagulant treatment. The effect of 6 affinity-purified preparations of anti- (a)beta2-glycoprotein I (GPI) antibodies with LA activity on the PT was tested. Instead of prolonging PT as expected, the abeta2-GPI antibodies reduced the PT of both normal plasma and anticoagulated plasma by a mean of 2.4 seconds and 5.6 seconds, respectively. This effect was also observed using other 5 commercially available preparations of thromboplastin. The abeta2-GPI-mediated reduction in PT was dose-dependent and was lost upon removal of beta2-GPI. The failure of abeta2-GPI antibodies to express LA activity in PT was found to depend on the fact that calcium ions were added together with PL at the beginning of the assay. In fact, modification of the standard diluted Russell viper venom time (dRVVT) test by adding calcium ions together with PL resulted in a loss of abeta2-GPI anticoagulant activity. The procoagulant effect was not as evident in an assay that used stimulated monocytes as a source of thromboplastin. These results show that abeta2-GPI antibodies exhibit an 'in vitro' procoagulant effect in PT and an anticoagulant effect in dRVVT only when the interaction with their antigen and PL occurs in the absence of calcium ions. (+info)
Interference of lupus anticoagulants in prothrombin time assays: implications for selection of adequate methods to optimize the management of thrombosis in the antiphospholipid-antibody syndrome.
(12/733)
BACKGROUND AND OBJECTIVE: Prolonged anticoagulation aiming at International Normalized Ratio (INR) values > 3.0 has been recommended for patients with thrombosis and the antiphospholipid-antibody syndrome. We evaluated the influence of anticoagulant antibodies in two different prothrombin time (PT) assays carried out on plasma from lupus anticoagulant patients on oral anticoagulation. DESIGN AND METHODS: INR values obtained with a combined (final test plasma dilution 1:20) and a recombinant (final test plasma dilution 1:3) thromboplastin were compared in 17 patients with persistent lupus anticoagulants (LA) receiving oral anticoagulant treatment and monitored for 69.8 patient-years. Doses of anticoagulant drugs were always assigned based on the results obtained with the combined thromboplastin, aiming at a target INR of 2.5 or 3.0 for patients with venous or arterial thromboembolic disease. Paired determinations with both reagents were also obtained throughout the study period in 150 patients on stable oral anticoagulation but free of antiphospholipid antibodies. Total IgG fractions were purified from selected patients to evaluate effect in the two PT assay systems. RESULTS: No patient experienced recurrence of thrombosis or major bleeding complications (95% confidence interval: 0.1-6.5 per 100 patient-years). INR values with the recombinant reagent were significantly higher than with the combined reagent in 8 LA patients (mean DINR ranging from 0.17 to 0.54) of the degree of anticoagulation was overestimated in all but one LA patients with the recombinant reagent when compared to the DINR observed in non-LA patients (-0.64 +/- 0.42). The anti-cardiolipin IgG titer (r(2) = 0.43, p = 0.004) and the anti-b(2)GPI IgG titer (r(2) = 0.30, p = 0.023) were positively associated with the mean deltaINR observed in LA patients. When added to plasmas with different levels of vitamin K-dependent factors, total IgG fractions from 6 LA patients with significant overestimation of the INR with the recombinant reagent (mean DINR ranging from 0.17 to 0.54, group 1) and from 7 LA patients with mean deltaINR < or = 0.0 (ranging from -0.25 to 0.04, group 2) reproduced the effects observed ex vivo in the two assay systems. However, when total IgG fractions were tested at the same final concentration in the two PT assay systems, there was no difference in the clotting times determined with total IgG fractions from group 1 and group 2 LA patients. Addition of negatively charged liposomes (0.4 and 0.8 mg/mL final concentrations) to platelet free plasma from LA-free patients on stable oral anticoagulation caused a 20% to 48% prolongation of the prothrombin time determined with the recombinant reagent. In contrast, no significant prolongation of the prothrombin time determined with the recombinant reagent was observed upon addition of negatively charged liposomes to plasma from group 1 LA patients. INTERPRETATION AND CONCLUSIONS: These results confirm previous suggestions of assay-dependency of INR values in LA patients on oral anticoagulation. For these patients, accurate INR values may be obtained using combined thromboplastin reagents that permit testing at high plasma dilution. (+info)
The effects of freeze drying and freeze drying additives on the prothrombin time and the international sensitivity index.
(13/733)
AIM: To determine whether freezing, freeze drying protective additives, or freeze drying of plasma samples from patients on coumarin treatment and from normal individuals affects prothrombin times or the international sensitivity index (ISI) calibration. METHODS: The effect of the addition of the protective additives singly and combined on the prothrombin time of coumarin samples and normal samples before and after freeze drying was observed using high and low ISI reference thromboplastins. ISI values were also determined. RESULTS: Freezing caused a prolongation of prothrombin time in the normal plasma samples with both reagents, which was significant with the low ISI human. Prolongation (non-significant) of the prothrombin time in coumarin plasma samples occurred with the human reagent only. Significant prolongation of normal prothrombin time by some of the protective additives before and after freeze drying was observed with both thromboplastins but to a greater extent with the human. Significant prolongation of prothrombin time in coumarin plasma samples was observed, but again was more marked with human thromboplastin. An approximate ISI was determined on the 20 coumarin samples. The only marked ISI change was with the WHO human thromboplastin after freeze drying of plasma, where a decrease from 0.95 to 0.90 was observed, corresponding to a marked prothrombin ratio increase. CONCLUSIONS: Freeze drying additives and the freeze drying procedure prolong normal and coumarin prothrombin times, with low ISI thromboplastin. Less marked prolongations occurred with a high ISI rabbit reagent, coumarin samples showing more significant prolongations. Marked ISI change in freeze dried plasma was only recorded with the low ISI ECAA human reagent. Frozen normal plasma samples cannot be used with confidence for ISI calibrations. (+info)
Anticoagulative effect of pepsin.
(14/733)
Anticoagulative effect of pepsin is observed in vitro when its concentration is 36 microM and higher. This effect is due to inhibition of fibrin monomer polymerization. Protamine abolishes anticoagulative effect of pepsin. Pepsin does not influence platelet aggregation induced by ADP and collagen. (+info)
Clinical outcomes of point-of-care testing in the interventional radiology and invasive cardiology setting.
(15/733)
BACKGROUND: Point-of-care testing (POCT) can provide rapid test results, but its impact on patient care is not well documented. We investigated the ability of POCT to decrease inpatient and outpatient waiting times for cardiovascular procedures. METHODS: We prospectively studied, over a 7-month period, 216 patients requiring diagnostic laboratory testing for coagulation (prothrombin time/activated partial thromboplastin time) and/or renal function (urea nitrogen, creatinine, sodium, and potassium) before elective invasive cardiac and radiologic procedures. Overall patient management and workflow were examined in the initial phase. In phase 2, we implemented POCT but utilized central laboratory results for patient management. In phase 3, therapeutic decisions were based on POCT results. The final phase, phase 4, sought to optimize workflow around the availability of POCT. Patient wait and timing of phlebotomy, availability of laboratory results, and therapeutic action were monitored. Split sampling allowed comparability of POCT and central laboratory results throughout the study. RESULTS: In phase 1, 44% of central laboratory results were not available before the scheduled time for procedure (n = 135). Mean waiting times (arrival to procedure) were 188 +/- 54 min for patients who needed renal testing (phase 2; n = 14) and 171 +/- 76 min for those needing coagulation testing (n = 24). For patients needing renal testing, POCT decreased patient wait times (phases 3 and 4 combined, 141 +/- 52 min; n = 18; P = 0.02). For patients needing coagulation testing, wait times improved only when systematic changes were made in workflow (phase 4, 109 +/- 41 min; n = 12; P = 0.01). CONCLUSIONS: Although POCT has the potential to provide beneficial patient outcomes, merely moving testing from a central laboratory to the medical unit does not guarantee improved outcomes. Systematic changes in patient management may be required. (+info)
Effects of unfractionated heparin, low-molecular-weight heparin, and heparinoid on thromboelastographic assay of blood coagulation.
(16/733)
Thromboelastography (TEG) has been used increasingly as an intraoperative hemostasis monitoring device. Low-molecular-weight heparins are given increasingly to reduce the development of antibodies against the heparin-platelet factor 4 complex, and heparinoids are given to patients who have developed the antibody. We studied the effect of unfractionated heparin, a low-molecular-weight heparin (enoxaparin sodium [Lovenox]), and a heparinoid (danaparoid sodium [Orgaran]) on blood clotting assayed with TEG (TEG clotting) in vitro and the efficacy of protamine sulfate and heparinase for reversing the effect. Heparin, enoxaparin, and danaparoid all caused a dose-dependent inhibition of TEG clotting of normal blood. Concentrations of enoxaparin and danaparoid that totally inhibited TEG clotting only minimally prolonged the activated partial thromboplastin time. While inhibition of TEG clotting by heparin and enoxaparin was reversed by protamine sulfate and heparinase, inhibition by danaparoid was reversed only by heparinase. Abnormal TEG clotting was observed in patients receiving enoxaparin whose plasma level of the drug was more than 0.1 antiXa U/mL. However, the degree of TEG abnormality did not always coincide with plasma levels of the drug. (+info)