Use of EDTA samples for prothrombin time measurement in patients receiving oral anticoagulants

BACKGROUND AND OBJECTIVES: Oral anticoagulant therapy is commonly called for in health care. Hitherto sampling for prothrombin time (PT) has been measured on blood collected into a coagulation tube and diluted in citrate solution. Blood samples anticoagulated with EDTA are used for hematologic tests and the same sample could also be available for PT. DESIGN AND METHODS: We studied 107 patients on oral anticoagulant therapy. Samples were taken by from both coagulation tubes (citrate) and EDTA tubes. The PT from both samples was measured with an ACL 7000 analyzer and reported in seconds and as an international normalized ratio (INR). The regression equation between citrate and EDTA samples was calculated in both units. We studied the clinical significance of INR results from both sample types and compared the effect of different combined thromboplastin reagents on the correlation equation between citrate and EDTA samples. RESULTS: The regression equation for PT by Owren's PT reagent from citrate (y) and EDTA (x) plasma was y = 1.11 x -0.24 INR, R(2)= 0.99. We observed no clinically significant difference between INR results from citrate and EDTA samples using the regression equation for INR calculation from EDTA samples. ISI depends on sample type (dilution, anticoagulant) and the difference is 0.117, 10%. We calculated ISI for EDTA samples and no clinically significant difference was seen between citrate and EDTA INR results. INTERPRETATION AND CONCLUSIONS: A good correlation was observed between INR results with citrate and EDTA samples from patients receiving oral anticoagulants using Owren's PT reagent with the same citrate calibration. Using the regression equation (INR or sec) for analysis of INR results from EDTA samples is clinically acceptable and offers the possibility of using EDTA samples for PT measurement with citrate calibrators. Reagent international sensitivity index (ISI) values for citrate and EDTA samples differ from each other. ISI determination for EDTA samples requires mathematical calculation of EDTA ISI as in the present study or EDTA-based ISI calibrators. The regression equation for INR from citrate and EDTA samples depended on the reagent used, not only on sample dilution or anticoagulant.     

Impact of preemptive warfarin dose reduction on anticoagulation after initiation of trimethoprim-sulfamethoxazole or levofloxacin

BACKGROUND: Antibiotics can potentiate warfarin anticoagulation. While preemptive warfarin dose reduction (DR) upon initiation of antibiotics has been advocated by experts, there are no published data regarding the efficacy of this strategy vs. the conventional strategy of not changing warfarin dose and carefully following international normalized ratio (INR) results. METHODS AND RESULTS: We compared the efficacy of preemptive 10-20% DR vs. no change in warfarin dosing in 40 chronically anticoagulated patients initiating trimethoprim-sulfamethoxazole (TMP-SMX) or levofloxacin. Eighteen patients received preemptive warfarin DR and 22 control patients underwent no change in warfarin dosing. There was no difference between the DR and control groups in the mean INR before beginning antibiotic therapy (2.53 +/- 0.12 vs. 2.52 +/- 0.11; P > 0.9). Mean interval between initiation of antibiotic and next INR was 5.1 +/- 0.4 vs. 4.7 +/- 0.5 days for DR vs. control patients, respectively (P > 0.5). For both TMP-SMX and levofloxacin, patients managed with a preemptive warfarin DR strategy did not exhibit a statistically significant change in the INR after initiating antibiotic therapy. In contrast, for each antibiotic, control group patients exhibited a significant increase in mean post-antibiotic INR compared to mean pre-antibiotic INR, though the effect was more pronounced in patients treated with TMP-SMX than with levofloxacin. Of DR group patients who were treated with TMP-SMX, none (0/8) developed a subtherapeutic INR, while 40% (4/10) of levofloxacin-treated patients developed a sub-therapeutic INR. Supra-therapeutic INR results led to transient interruption of warfarin dosing in 2 patients (11%) in the DR group vs. 12 patients (55%) in the control group (P = 0.007). CONCLUSIONS: Prophylactic warfarin DR of 10-20% is effective in maintaining therapeutic anticoagulation in patients initiating TMP-SMX. An expectant strategy consisting of no change in warfarin dosing with short-term INR follow-up appears reasonable in patients treated with levofloxacin.     

Prevalence and quality of warfarin use for patients with atrial fibrillation in the long-term care setting.

BACKGROUND: Evidence-based clinical practice guidelines recommend the use of warfarin sodium for stroke prevention in most patients with atrial fibrillation (AF) who do not have risk factors for hemorrhagic complications, irrespective of age. METHODS: The medical records of all residents of a convenience sample of long-term care facilities in Connecticut (n = 21) were reviewed. The percentages of all patients with AF (AF patients) and ideal candidates for warfarin therapy (ie, AF patients with no risk factors for hemorrhage) who received warfarin were determined; for patients receiving warfarin, the percentage of days spent in the therapeutic range of international normalized ratio (INR) values (2.0-3.0) was also assessed. The relationship between receipt of warfarin and the presence of stroke and bleeding risk factors was assessed in multivariate models. RESULTS: Atrial fibrillation was present in 429 (17%) of the 2587 long-term care residents. Overall, 42% of AF patients were receiving warfarin. However, only 44 (53%) of 83 ideal candidates were receiving this therapy. In residents who received warfarin therapy, the therapeutic range of INR values was maintained only 51% of the time. The odds of receiving warfarin in the study sample decreased with increasing number of risk factors for bleeding and increased (nonsignificant trend) with increasing number of stroke risk factors present. CONCLUSIONS: Atrial fibrillation is very common among residents of long-term care facilities. Even among apparently ideal candidates, warfarin therapy is underused for stroke prevention in patients with AF. Prescribing decisions and monitoring related to warfarin therapy in the long-term care setting warrant improvement.     

Improvements in balloon aortic valvuloplasty: Closure devices for large artery access

Objectives : To prospectively compare the efficacy and procedural safety of the radial versus femoral route for cardiac catheterization during uninterrupted warfarin therapy. Background : The optimal treatment strategy for cardiac catheterization in patients receiving long‐term oral anticoagulation has not been defined. Increasing evidence suggests the feasibility and safety of catheterization without warfarin interruption. However, the relative safety and efficacy of the radial and femoral access in fully anticoagulated patients are unknown. Methods : Fifty‐six consecutive patients on chronic warfarin treatment with international normalized ratio (INR) between 1.8 and 3.5 were randomized to undergo coronary angiography, alone, or followed by percutaneous coronary intervention (PCI), via the femoral (n = 29) or radial route (n = 27). Procedural success, in‐hospital major adverse cardiac and cerebrovascular events, access‐site, and bleeding complications were recorded. Results : The two groups were well balanced with similar clinical characteristics at baseline. There were no significant differences in preprocedural antiplatelet therapy or in INR levels between the radial and femoral group (2.62 ± 0.7 vs. 2.48 ± 0.6, respectively, P = 0.63). Procedural success was achieved in all femoral patients, whereas one patient in the radial group (3.7%) required crossover to femoral access. Eight patients from the femoral and 10 patients from the radial group successfully underwent PCI. Access‐site complications occurred only in patients who underwent PCI: three (37.5%) in the femoral versus none in the radial group (P = 0.034). Conclusion : The radial access is as efficacious and safe as the femoral route for coronary angiography in fully anticoagulated patients, but is likely to result in fewer access‐site complications in patients who also undergo PCI. © 2010 Wiley‐Liss, Inc.     

Safety of inferior vena cava filter retrieval in anticoagulated patients

PURPOSES: To evaluate the safety of inferior vena cava (IVC) filter retrieval in therapeutically anticoagulated patients in comparison to prophylactically or not therapeutically anticoagulated patients with respect to retrieval-related hemorrhagic complications. MATERIALS AND METHODS: This was a retrospective study of 115 consecutive attempted IVC filter retrievals in 110 patients. Filter retrievals were stratified as performed in patients who were therapeutically anticoagulated (group 1), prophylactically anticoagulated (group 2), or not therapeutically anticoagulated (group 3). The collected data included anticoagulant and antiplatelet medications (type, form and duration of administration, dosage) at the time of retrieval. Phone interviews and chart review was performed for the international normalized ratio (INR), activated partial thromboplastin time, platelet count, infusion of blood products, and retrieval-related hemorrhagic complications. RESULTS: Group 1 included 65 attempted filter retrievals in 61 therapeutically anticoagulated patients by measured INR or dosing when receiving low-molecular-weight heparin (LMWH). Four retrievals were not successful. In patients receiving oral anticoagulation, the median INR was 2.35 (range, 2 to 8). Group 2 comprised 23 successful filter retrievals in 22 patients receiving a prophylactic dose of LMWH. Group 3 included 27 attempted filter retrievals in 27 patients not receiving therapeutic anticoagulation. Six retrievals were not successful. Five patients were receiving oral anticoagulation with a subtherapeutic INR (median, 1.49; range, 1.16 to 1.69). No anticoagulation medication was administered in 22 patients. In none of the groups were hemorrhagic complications related to the retrieval procedures identified. CONCLUSIONS: These results suggest that retrieval of vena cava filters in anticoagulated patients is safe. Interruption or reversal of anticoagulation for the retrieval of vena cava filters is not indicated.     

Monitoring age-dependent effect of anticoagulation treatment in patients with atrial fibrillation

Oral anticoagulation treatment with dicumarol preparations (warfarin sodium) is the standard in patients with atrial fibrillation. The effect of treatment depends on many factors, especially in elderly patients. In the study, we assessed the effect of treatment in patients with atrial fibrillation hospitalized in our cardiology ward from 2004 to 2005, in the form of a telephone survey (who controlled the treatment--general practitioner or internist?, the last 2 INR results, complications). INR 2.0-3.5 is considered an efficient therapeutic range. The proportion of permanently correctly anticoagulated patients is approximately 47% across the whole age range, the hypothesis of lower efficiency of treatment in elderly patients does not apply (48% of efficiently anticoagulated patients younger than 75 years vs. 46% of older patients--however, the study does not include polymorbid patients who could not take warfarin at all!) The fact whether a patient is monitored by a general practitioner or an outpatient specialist does not make any difference (49% of anticoagulated patients monitored by a general practitioner vs. 52% of patients monitored by an internist). The percentage of severe complications is relatively low (3.4%).     

Analysis of warfarin therapy in pediatric patients: A prospective cohort study of 319 patients.

This study details warfarin use in a large pediatric population followed in a central anticoagulation clinic. A prospective, consecutive cohort of nonselected children were studied. Patients were divided into groups by age, target international normalized ratio (INR) range, disease, medications, and vitamin K supplemented enteral nutrition use. Groups were analyzed on multiple aspects of warfarin therapy using multivariate methods. A total of 319 patients received 352 warfarin courses representing 391 treatment years. Age independently influenced all aspects of therapy. When compared with all older children, the 相似文献   

Warfarin dose reduction vs watchful waiting for mild elevations in the international normalized ratio

BACKGROUND: Whether clinicians should decrease the warfarin dose in response to a mild, asymptomatic elevation in the international normalized ratio (INR) is unknown. OBJECTIVES: The study objectives were as follows: (1) to evaluate the safety of an anticoagulation service (ACS) policy advocating that the warfarin dose not be changed for isolated, asymptomatic INRs of < or = 3.4; (2) to compare the dosing strategies of an ACS and primary care providers (PCPs); and (3) to quantify the relationship between reduction of the warfarin dose and the subsequent fall in the INR. DESIGN AND SETTING: Randomized controlled study of health maintenance organization outpatients who were receiving warfarin. PATIENTS: We identified 231 patients with a target INR of 2.5 and an isolated, asymptomatic INR between 3.2 and 3.4. Our ACS monitored 103 of the patients; PCPs monitored the remaining 128 patients. MEASUREMENTS: From all 231 patients, we obtained INRs and warfarin dosing history. From the 103 ACS enrollees, we also recorded adverse events. RESULTS: One ACS patient had epistaxis in the 30 days after the elevated INR. Twenty-three percent of ACS enrollees and 47% of PCP patients reduced their warfarin dose (p < 0.001). The median follow-up INRs were similar in both cohorts: 2.7 in the ACS enrollees and 2.6 in the PCP patients. However, in a subgroup analysis of 190 patients who presented with an INR of 3.2 or 3.3, ACS enrollees were more likely to have a follow-up INR in the range of 2 to 3 (p = 0.03). The median follow-up INR was 2.7 in 148 patients who maintained their warfarin dose, 2.5 in 77 patients who decreased their dose by 1 to 20%, and 1.7 in 6 patients who decreased their dose by 21 to 43% (p < 0.001). CONCLUSIONS: These findings support maintaining the same warfarin dose in asymptomatic patients with an INR of < or = 3.3, and reducing the dose for patients who have a greater INR or an increased risk of hemorrhage. Warfarin dose reductions > 20% should be avoided for mildly elevated INRs.     

Warfarin anticoagulation and outcomes in patients with atrial fibrillation: a systematic review and metaanalysis

OBJECTIVE: To examine the relationship between international normalized ratio (INR) and outcomes (major bleeding events and strokes) in patients with atrial fibrillation (AF) receiving anticoagulation with warfarin. METHODS: A systematic review and metaanalysis of studies published in the English language between January 1, 1985, and October 30, 2002, was performed. MEDLINE (PubMed), Current Contents, and relevant reference lists were searched. Studies enrolling patients with nonvalvular AF receiving warfarin anticoagulation were eligible for inclusion if they reported stroke and/or major bleeding events in relation to INR, or time spent in therapeutic range. The risk of bleeds in overanticoagulated patients (INR > 3) and the risk of strokes in underanticoagulated patients (INR < 2) were assessed. RESULTS: Twenty-one studies (6,248 patients) met all inclusion criteria. Of the 21 studies, a target conventional INR of 2 to 3 was used in 9 studies. An INR < 2, compared with an INR > or = 2, was associated with an odds ratio (OR) for ischemic events of 5.07 (95% confidence interval [CI], 2.92 to 8.80). An INR > 3, compared with an INR < or = 3, was associated with an OR for bleeding events of 3.21 (95% CI, 1.24 to 8.28). On average, in the four studies with a target INR range of 2 to 3, patients with AF receiving warfarin spent 61% of time within, 13% of time above, and 26% below the therapeutic range. CONCLUSION: Available evidence indicates that in patients with nonvalvular AF, the risk of ischemic stroke with insufficient warfarin anticoagulation (INR < 2), and the risk of bleeding events with overanticoagulation (INR > 3) are significantly higher relative to patients with AF maintained within the recommended INR of 2 to 3. However, the published data are sparse, heterogeneous, and primarily reported from clinical trials. More studies evaluating clinical outcomes in relation to INR are needed, especially in a real-world setting.     

Evaluation of the phospholipid-rich dilute Russell's viper venom assay to monitor oral anticoagulation in patients with lupus anticoagulant.

The International Normalized Ratio (INR) is generally recommended to monitor anticoagulant therapy in patients treated with warfarin. However, there has been concern about the validity of the INR to monitor warfarin therapy in patients with lupus anticoagulant, particularly when there is prolongation of the baseline INR. An alternative approach is to use a chromogenic factor X assay that is not sensitive to lupus anticoagulant. However, this assay is expensive, not widely available, and does not have an established therapeutic range. We hypothesized that the phospholipid-rich dilute Russell viper venom time (prdRVVT), a simple, rapid and inexpensive assay, might be suitable to monitor warfarin therapy in this situation since Russell's viper venom directly activates coagulation factor X while the phospholipid in the reagent reduces or negates any effect of lupus anticoagulant on the assay. We measured the INR, chromogenic factor X, and prdRVVT in 50 patients stabilized on warfarin for at least 6 weeks, 12 of whom had lupus anticoagulant, and 37 patients not taking warfarin, 17 of whom had lupus anticoagulant. Factor X was negatively correlated with INR in anticoagulated patients both in the absence (r = -0.45, P = 0.01) and presence (r = -0.43, P = 0.17) of lupus anticoagulant. The prdRVVT was also strongly correlated with INR in anticoagulated patients without lupus anticoagulant (r = 0.60, P < 0.0001) but there was no correlation in the presence of lupus anticoagulant (r = -0.13, P = 0.68). Our results suggest that the prdRVVT is not suitable for monitoring warfarin therapy in patients with lupus anticoagulant.     

An Examination of the Association Between Therapeutic Anticoagulation Control and Glycemic Control for Patients with Diabetes on Oral Anticoagulation Therapy

Background: Observations by pharmacists monitoring anticoagulated patients suggested that patients with diabetes often require more frequent international normalized ratio (INR) monitoring than patients without diabetes. The purpose of this investigation was to examine the association between glycemic control and therapeutic anticoagulation control.Methods: Patients with diabetes who were receiving warfarin therapy monitored by the Kaiser Permanente of Colorado Clinical Pharmacy Anticoagulation Service were eligible for inclusion. Patients were included if they had a diagnosis of diabetes mellitus type 1 or 2, aged ≥18 years, and had initiated anticoagulant therapy ≥120 days before their most recent hemoglobin A1C measurement. The primary outcome was the correlation between hemoglobin A1C value and percent of time in the patient-specific INR range. Multivariate analysis was undertaken to regress percent of time in INR range on an A1C value ≥8.0 while adjusting for other possible explanatory variables.Results: A total of 911 patients with diabetes were included in the study. Subjects with an A1C value ≥8.0 had similar characteristics as those subjects with an A1C value < 8.0. Correlation analysis revealed no relationship between percent of time spent in INR range and A1C value (Spearman Correlation Coefficient = 0.012, p = 0.805). Multivariate analysis revealed no relationship between percent of time spent in INR range and A1C value ≥8.0 (Odds Ratio = 1.00; 95% Confidence Interval = 0.99, 1.01) when adjusting for possible explanatory variables.Conclusions: For patients with diabetes on warfarin anticoagulation therapy, there is no association between glycemic control and therapeutic anticoagulation control. However, anticoagulation therapy providers should manage these patients with the same diligence and care as patients without diabetes.     

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

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. J. Hematol. 57:193–199, 1998. © 1998 Wiley-Liss, Inc.     

Inpatient warfarin management: pharmacist management using a detailed dosing protocol

Hospitalized patients receiving anticoagulants such as warfarin are at increased risk for adverse events because of difficulties maintaining a therapeutic international normalized ratio (INR). We sought to determine whether a detailed warfarin dosing protocol administered by pharmacists with minimal physician oversight significantly reduced the proportion of hospitalized patients with a supratherapeutic INR. We conducted a prospective, nonrandomized trial with patients on cardiology, internal medicine, and family medicine inpatient services who received at least 1 dose of warfarin while hospitalized. The baseline group included 293 patients, and the intervention group comprised 217 patients. Baseline characteristics were similar in each group, except that more patients received antibiotics in the intervention group. The defect rate (INR > 5 after receiving warfarin) in the baseline group was significantly higher than in the intervention group (7.85 vs. 1.85%). Conversely, the percentage of patients with an INR less than 1.7 after 4 warfarin doses was lower in the intervention patients, indicating overall improvement in therapeutic levels. Dosing discussions were required between the pharmacist and a physician for only 6% of intervention patients. The protocol effectively reduced overanticoagulation without increasing under anticoagulation during hospitalization and reduced the need for close physician oversight.     

Effectiveness of Warfarin among Patients with Cancer

BACKGROUND

Among patients treated with warfarin for venous thromboembolism (VTE), cancer patients have more thrombotic and hemorrhagic events than patients without cancer. Is this also the case when cancer patients are anticoagulated for other indications?

OBJECTIVE

The objective of the study is to evaluate the effectiveness of warfarin, given for any indication, among patients with cancer in a community setting.

METHODS

We identified patients with cancer from a larger prospective cohort of 6,761 patients from 101 clinical sites in the United States, matched to controls without cancer. The proportion of time spent in the therapeutic range, international normalized ration (INR) variability, and the rate of thromboembolic and major hemorrhagic events were compared between the two groups.

RESULTS

Ninety-five patients undergoing treatment for cancer were matched to 283 patients without cancer. The cancer group spent less time in the target INR range (54 vs 66%, P?P?P?

CONCLUSIONS

Compared to matched controls, cancer patients receiving warfarin spend less time in the target INR range, have more variable INR values, and have more thrombotic events. These effects are not dependent on whether the patient is anticoagulated for VTE or another indication.

     

Improving the outcomes of anticoagulation: an evaluation of home follow-up of warfarin initiation

OBJECTIVES: A number of studies have reported that the risk of bleeding associated with warfarin is highest early in the course of therapy. This study examined the effect of a programme focused on the transition of newly anticoagulated patients from hospital to the community. DESIGN: Open-label randomized controlled trial. SETTING: Home-based follow-up of patients discharged from acute care hospital in southern Tasmania, Australia. SUBJECTS: A total of 128 patients initiated on warfarin in hospital and subsequently discharged to general practitioner (GP) care were enrolled in the study. Sixty were randomized to home monitoring (HM) and 68 received usual care (UC). INTERVENTIONS: HM patients received a home-visit by the project pharmacist and point-of-care international normalized ratio (INR) testing on alternate days on 4 occasions, with the initial visit two days after discharge. The UC group was solely managed by the GP and only received a visit 8 days after discharge to determine anticoagulant control. RESULTS: At discharge, 42% of the HM group and 45% of the UC group had a therapeutic INR. At day 8, 67% of the HM patients had a therapeutic INR, compared with 42% of UC patients (P < 0.002). In addition, 26% of UC patients had a high INR, compared with only 4% of HM patients. Bleeding events were assessed 3 months after discharge and occurred in 15% of HM patients, compared with 36% of the UC group (P < 0.01). CONCLUSIONS: This programme improved the initiation of warfarin therapy and resulted in a significant decrease in haemorrhagic complications in the first 3 months of therapy.     

Interaction between capecitabine and gemcitabine with warfarin in a patient with pancreatic cancer

Gemcitabine is the only chemotherapeutic agent approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced pancreatic cancer. 5-fluorouracil or its oral pro-drug, capecitabine is the second most commonly used agent in this malignancy. Capecitabine or 5-fluorouracil is the second most common agent used either in second-line or as a radiosensitizer. Thromboembolism requiring anticoagulation is a common paraneoplastic complication in these patients. We report a patient with pancreatic cancer, challenged with maintaining the international normalized ratio (INR) with gemcitabine-capecitabine combination, and later with gemcitabine monotherapy with concomitant warfarin, as well as, a brief review of the literature. Patients with pancreatic cancer who receive warfarin and gemcitabine should be monitored for any potential drug interactions. Frequent prothrombin time and INR evaluations are suggested for anticoagulated patients receiving gemcitabine, especially when combined with capecitabine.     

不同抗凝强度华法林抗凝治疗对老年阵发性心房颤动患者预后的影响

目的探讨应用拜阿司匹林及不同抗凝强度的华法林抗栓对老年阵发性心房颤动(paroxysmal atrial fibrillation,PAF)患者预后的影响。方法选择老年PAF患者663例,并随机单盲分为4组:A组154例(拜阿司匹林150 mg/d),B组132例[华法林抗凝,国际标准化比值(INR)控制在1.2～1.6],C组197例(华法林抗凝,INR控制在1.7～2.5),D组180例(华法林抗凝,INR控制在2.6～3.0),随访近5年,记录4组终点事件及出血事件。结果与A组、B组比较,C组患者主要终点事件、次要终点事件、总主要事件、总事件所占的比例均明显下降(P<0.05,P<0.01);D组患者主要出血事件增加,总主要事件有所下降,但差异均无统计学意义(P>0.05)。结论老年PAF患者的抗凝治疗,华法林抗凝强度INR在1.7～2.5安全有效,而再增加抗凝强度并不增加获益,反而增加出血及其他事件发生率。     

Prevention of central venous catheter associated thrombosis using minidose warfarin in patients with haematological malignancies

Thrombosis is a well-recognized complication following insertion of central venous catheters and is associated with significant morbidity. In an attempt to reduce line-associated thrombosis, 108 consecutive patients with haematological malignancies were commenced on prophylactic 'minidose' warfarin, 1 mg/d, at the time of line insertion. This group of patients were compared with a historic group of 115 consecutive patients who had not received warfarin. Clinically-suspected venous thrombosis was confirmed by Doppler ultrasound or venography. Patients taking prophylactic warfarin had their prothrombin time measured three times per week with the aim of maintaining an INR < 1.6. Five (5%) of the 108 patients who received minidose warfarin developed a thrombosis, at a median of 72 d (range 5–166) from the time of catheter insertion. In the 115 patients who were not anticoagulated 15 (13%) developed a catheter-associated thrombosis at a median of 16 d (range 1–35). There was a significant reduction in line-associated thrombosis in patients receiving warfarin ( P  = 0.03). These data suggest that minidose warfarin reduces the incidence of central venous catheter related thrombosis in patients with haematological malignancies.     

Improving the safety profile of warfarin

Since warfarin remains the predominate drug administered for long-term anticoagulation, optimizing therapy for maximum antithrombotic effect with minimal bleeding risk continues to challenge clinicians. Genetic differences exist that affect an individual's response to warfarin. The clinician can use genetic information in the future, along with current approaches to improved monitoring and dose schedules, to maintain even more successfully the appropriate therapeutic range for anticoagulation. The international normalized ratio (INR) is a good indicator of warfarin effect and addressing a high INR result often prevents bleeding complications. However, even with a therapeutic INR, patients are still at risk for bleeding. This review will discuss optimizing warfarin dosing, reducing an elevated INR, and managing the anticoagulated patient who has a bleeding event.     

Oral anticoagulation and hemorrhagic complications in an elderly population with atrial fibrillation

BACKGROUND: Warfarin sodium therapy in patients with atrial fibrillation markedly reduces the incidence of embolic stroke. However, in elderly patients warfarin therapy is often underused owing to the perceived higher risk of hemorrhagic complications. OBJECTIVES: To assess the quality of anticoagulant control and the incidence of hemorrhagic complications and stroke in an elderly population (>75 years old) compared with a younger control group (between 60 and 69 years) and to assess the quality of anticoagulant control and incidence of hemorrhagic complications in those patients who recently commenced receiving warfarin therapy (first year of therapy). PATIENTS AND METHODS: In this retrospective follow-up study, anticoagulant control and the incidence of hemorrhagic complications and stroke were assessed in an elderly population (>75 years old) compared with a younger control group (between 60 and 69 years), all with atrial fibrillation(target international normalized ratio [INR] 2.5) and attending a hospital outpatient anticoagulant clinic. RESULTS: A total of 328 patients were studied over a 21-month period. There were 204 patients in the control group providing 288 patient-years of follow-up and 124 patients in the elderly group providing 170 patient-years of follow-up. The percentage of INR results in the target range was not statistically significantly different between the elderly and control groups (71.5% vs 66.1%) and the occurrences of incidences of INR greater than 7 were 4.2% in the control group and 4.7% in the elderly group (P =.96). The incidences of major hemorrhage were 2.8% per year in the elderly group and 2.9% per year in the control group (P =.96); overall incidence was 2.8% (95% confidence interval, 1.3%-4.4%). One hundred one of the 328 patients studied commenced warfarin therapy during or within 3 months of the start of the study. In this induction group, 62.1% of INRs were within the target range compared with 70.9% of INRs in patients who had been receiving warfarin therapy for more than 3 months at the start of the study (P =.002). The incidences of INR greater than 7 and major hemorrhage were 7.9% per year and 6.9% per year, respectively, in the cohort who recently began warfarin therapy compared with 3.4% per year and 1.7% per year in the group who were receiving warfarin therapy for more than 3 months. CONCLUSION: While it was impossible to consider any selection bias at the level of referral to the clinic, these findings suggest that the elderly population attending our anticoagulant clinic did not have poorer anticoagulant control or an increased incidence of hemorrhage while receiving warfarin therapy.