1,721,033 research outputs found
The accuracy of the International Normalized Ratio and the American College of Chest Physicians recommendations on the use of vitamin K to reverse over-anticoagulation
New oral anticoagulants in thrombotic antiphospholipid syndrome
A main goal in clinical management of patients with antiphospholipid syndrome (APS) is to prevent thrombotic recurrences and/or miscarriages. For many decades, the only available oral anticoagulant drugs have been vitamin K antagonists (VKA), which are still the cornerstone of long-term treatment of thromboembolism. However, the limits of VKA treatment are well known: narrow therapeutic window and high patient-to-patient variability of response. Moreover, in some patients with APS a higher international normalized ratio (INR) therapeutic target was suggested, and INR inaccuracy due to antiphospholipid antibodies was reported. Therefore, VKA management in APS patients is frequently cumbersome, requires close INR monitoring and may affect patient's quality of life. A new class of oral anticoagulant agents has been developed, the Direct Oral Anticoagulants (DOA), which directly inhibit a single enzyme of the coagulation cascade. Compared with VKA, they have more stable pharmacokinetic and pharmacodynamic profiles, little interaction with food or drugs with a predictable anticoagulation effect, they can thus be prescribed in a fixed dose, without requiring frequent laboratory monitoring. The efficacy and safety of DOA has been shown in large phase III clinical trials. Unfortunately, translating these good results to APS patients is not straightforward: currently, at least three randomized controlled clinical trials are ongoing
Catheter-related thrombosis in hematologic patients
For many years central venous catheters (CVC) have been utilized to monitor hemodynamics and to deliver parenteral nutrition, blood products, pharmacological therapies or infusion fluids. Recently, CVC use has greatly increased with significant impact on the administration of chemotherapy, stem cell transplantation and other treatments to cancer patients. However, CVC use may be accompanied by a variety of side-effects, which increase with the duration of implantation. The most common catheter-related complications are thrombotic events and blood-stream infections. The true incidence of these complications is still uncertain and has changed over time due to CVC device improvement. More data are available in solid tumor than in oncohematologic patients. Recently, much attention has been paid to the issues of prevention and treatment of these complications. Some strategies have been proposed: fixed dose warfarin or low molecular weight heparins have been evaluated in some clinical trials of thromboprophylaxis in this condition. However, more studies are still needed to address this issue. This review will focus on CVC use and complications in oncohematologic patients
False-negative or false-positive: laboratory diagnosis of lupus anticoagulant at the time of commencement of anticoagulant: a rebuttal
CYP2C9 genotypes and dose requirements during the induction phase of oral anticoagulant therapy
Objective: Variant alleles of the CYP2C9 gene encoding the cytochrome P450 (CYP) enzyme (2C9*2 [Arg144Cys] and 2C9*3 [Ile359Leu]) are known to increase the anticoagulant effect of warfarin and decrease the mean daily dose required to maintain the international normalized ratio (INR) of the prothrombin time within the target therapeutic range. However, little information is available on the effect of CYP2C9 polymorphisms; on dose requirements during the most critical step of anticoagulant therapy, the induction phase.
Methods. This retrospective study evaluated the dosages given to 125 patients who started therapy with warfarin in a clinical center where physicians used the same approach for dosing and frequency of monitoring. CYP2C9 allelic variants were evaluated by polymerase chain reaction followed by restriction enzyme analysis.
Results. From the time of the first INR estimate (day 4) until the end of the induction phase (arbitrarily established at day 24), patients with 2C9*2 or 2C9*3 variant alleles required lower mean daily doses than patients carrying only wild-type alleles 2C9*1 (-17% and -40%, P < .0001). They also more frequently had INR values above the upper limit of the target range (3.0) (65% for 2C9*2/- and 66% for 2C9*3/- versus 33% for 2C9*1/*1; P = .006 and .012, respectively).
Conclusions: The requirement of smaller doses of warfarin in relation to CYP2C9 polymorphisms is already manifest on the fourth day of treatment, at the time of the first INR estimate. CYP2C9 genotyping is as yet not warranted, but frequent INR monitoring with appropriate dose adjustments is recommended during the first 3 weeks of treatment to avoid overanticoagulation and the inherent risk of bleeding in carriers of variant alleles
Evaluation of a new PT-INR monitoring system in patients with the antiphospholipid syndrome
IntroductionPatients on anticoagulant therapy with vitamin K antagonists (VKA) need frequent INR monitoring. Reliability of point-of-care (POC) devices for measuring INR needs rigorous evaluation, particularly in patient with the antiphospholipid syndrome (APS). The aim of this study was to evaluate the accuracy of the ProTime InRhythm System (here called device) for INR measurement in patients with APS on VKA.
MethodsWe compared the device INR vs. the laboratory INR measurement for blood samples from 29 APS-positive and 31 APS-negative patients consecutively enrolled. APS was confirmed by positive serological and/or phospholipid-dependent coagulation tests. Chromogenic factor X assay was used to evaluate anticoagulation. Bland-Altman difference plot for paired INR (POC vs. laboratory) was used to evaluate agreement between the device and the laboratory. The device INR relationship with factor X chromogenic assay was evaluated by orthogonal regression analysis.
ResultsOverall, 97% of the device INR measurements were similar to laboratory INR values with an absolute difference less than 0.4 units. Correlation coefficient for the device INR vs. factor X was -0.69 (P < 0.0001, CI 95% -0.80 to -0.52).
ConclusionsThe ProTime InRhythm System is an accurate point-of-care device for measuring INR also in patients with and without APS
A multicentre randomised clinical end-point study of PARMA 5 computer-assisted oral anticoagulant dosage
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