Anticoagulation monitoring part 1: warfarin and parenteral direct thrombin inhibitors

OBJECTIVE: To review the availability, mechanisms, limitations, and clinical application of point-of-care (POC) devices used in the management of warfarin and parenteral direct thrombin inhibitors. DATA SOURCES: Scientific articles were identified through a MEDLINE search (1966-August 2004), manufacturer Web sites, additional references listed in articles and Web sites, and abstracts from scientific meetings. STUDY SELECTION AND DATA EXTRACTION: English-language literature from clinical trials was reviewed to evaluate the accuracy, reliability, and clinical application of POC monitoring devices. DATA SYNTHESIS: The prothrombin time expressed as the international normalized ratio (PT-INR) is a well-established test for monitoring warfarin anticoagulation. Multiple devices are available for POC testing. Because there is no universally accepted standard, the performance of each device is typically tested against a standard test performed in a reference laboratory. Performance of currently available devices, as measured by correlations to a standard reference laboratory PT-INR, may be considered very good and acceptable for use in patient care. Utilization of patient self-testing and patient self-monitoring of warfarin anticoagulation using POC devices is increasing. Parenteral direct thrombin inhibitors are typically monitored using a standard laboratory activated partial thromboplastin time. Some research has shown that POC monitoring of direct thrombin inhibitors using the ecarin clotting time is helpful for patients undergoing cardiopulmonary bypass surgery, although that test is not readily available. CONCLUSIONS: POC testing for anticoagulation therapy has been available for >20 years. Multiple POC devices are available to monitor warfarin. There is some variability in results between devices and between reagents used in the same device. Despite these limitations, POC monitoring of warfarin via the PT-INR is an integral part of clinical practice. Additional research evaluating POC monitoring of direct thrombin inhibitors is necessary.     

The use of the activated clotting time for monitoring heparin therapy in critically ill patients

OBJECTIVE: To determine the correlation between activated clotting time (ACT) and activated partial thromboplastin time (aPTT) in patients receiving intravenous unfractionated heparin therapy, and the accuracy of the ACT in predicting the level of anticoagulation. DESIGN: Paired aPTT and ACT measurements were obtained from a convenience sample of critically ill patients requiring intravenous unfractionated heparin. The aPTT was determined in the hospital laboratory and ACT measurements were performed with a portable device. SETTING: The intensive care unit of Ghent University Hospital, a tertiary care facility with 54 beds. PATIENTS AND PARTICIPANTS: Twenty-eight patients were studied prospectively; a total of 105 paired samples were obtained. The indication for heparin therapy was cerebral ischemia in 8, various cardiac conditions in 10, pulmonary embolism in 3, continuous hemofiltration in 3, and peripheral arterial thrombosis in 4. RESULTS: There was a significant correlation between aPTT and ACT. Analysis of variance showed a significant difference in ACT between different levels of anticoagulation, aPTT shorter than 60 s (group 1), aPTT 60-90 s (group 2), and aPTT longer than 90 s (group 3): 142+/-16.7 s in group 1 vs. 155+/-29.6 and 192+/-39.1 in groups 2 and 3. CONCLUSIONS: The correlation between the aPTT and the ACT in this ICU setting is poor; ACT cannot differentiate between low and therapeutic levels of anticoagulation. The use of the ACT for monitoring low to moderate doses of heparin in ICU patients cannot be recommended.     

Monitoring of the heparin therapy during acute haemodialysis

Anticoagulation during renal replacement therapy is recommended to avoid thrombosis of the filter devices and to maintain the blood flow. However, in the case of multiorgan failure and sepsis, an imminent bleeding complication in patients with acute renal failure may cause the need for an extracorporeal circulation without anticoagulation. The most common drug used in renal replacement therapy is the unfractionated heparin (UFH). With low molecular weight heparin (LMWH) good experiences are reported, too. Based on the level of evidence from clinical studies plasma measurement of heparin is indispensable for patients with renal insufficiency. The activated whole blood clotting time (ACT), the activated partial thromboplastin time (aPTT), and the determination of the anti-factor Xa activity (anti Xa) with chromogenic substrates are available as routine as well as as point-of-care tests. To monitor plasma levels of LMWH the anti Xa assay serves exclusively as a suitable monitoring. The anti Xa assay using chromogenic substrates is the most specific and valid one for monitoring heparin therapy. In lack of large controlled studies for the anticoagulation therapy and its monitoring with the anti Xa test in acute renal failure, the current experiences are based on the results of chronic renal replacement therapy.     

Therapeutic equivalency of low-molecular-weight heparins

OBJECTIVE: To review the recent literature on the approved uses of enoxaparin, dalteparin, ardeparin, and tinzaparin and the evidence for therapeutic equivalence. DATA SOURCES: A MEDLINE search (1993-January 2001) was conducted to identify English-language literature available on enoxaparin, dalteparin, ardeparin, and tinzaparin. STUDY SELECTION: All controlled trials evaluating low-molecular-weight heparins (LMWHs) versus standard therapy powered to detect a significant difference were reviewed. DATA EXTRACTION: Agents were reviewed with regard to safety and efficacy. DATA SYNTHESIS: As a class, LMWHs have chemical, physical, and clinical similarities. LMWHs have greater bioavailability, longer half-lives, a more predictable pharmacologic response, possible improved safety, and similar or greater efficacy compared with unfractionated heparin (UFH). Because of this, enoxaparin, dalteparin, ardeparin, and tinzaparin are being considered as alternatives to UFH or warfarin, and there is potential for therapeutic interchange. Evaluation of clinical trials is limited because of differing diagnostic methods, drug administration times, dose equivalencies, and outcome measurements. CONCLUSIONS: Only 1 trial has evaluated 2 LMWHs in a direct comparison in the same study. There is insufficient evidence for determining the therapeutic equivalence of LMWHs.     

Correlation between activated clotting time and activated partial thromboplastin times

OBJECTIVE: To evaluate the correlation between clotting time tests and heparin concentration, the correlation between activated clotting time (ACT) and activated partial thromboplastin time (aPTT) results, and to compare the clinical decisions based on ACT results with those based on aPTT results. METHODS: Retrospective evaluation of a large database containing heparin concentrations, ACT results (1 device), and aPTT results (3 different instruments: 2 bedside, 1 laboratory-based). Correlations between heparin concentrations and clotting time tests and between ACT results and aPTT results were determined. Clinical decisions regarding heparin dosage adjustments based on ACT results were compared with those based on aPTT results. RESULTS: Correlations between clotting time tests and heparin concentrations were r = 0.72 for ACT and r = 0.74-0.86 for the aPTT instruments. The laboratory-based aPTT had the highest correlation to heparin concentrations. The correlation between ACT and aPTT results ranged from r = 0.64-0.67. Heparin dosage adjustment decisions based on ACT results agreed with decisions based on aPTT results 59-63% of the time. CONCLUSIONS: The laboratory-based aPTT has a stronger correlation to heparin concentration than the bedside-based aPTT and ACT. The correlation between ACT and aPTT was similar among 3 different aPTT instruments. Decisions to adjust heparin therapy based on ACT results differed from decisions based on aPTT results more than one-third of the time.     

Safety and efficacy of combined use of low molecular weight heparin (enoxaparin,lovenox) and glycoprotein IIb/IIIa receptor antagonist (eptifibatide,integrelin) during nonemergent coronary and peripheral vascular intervention

Coronary and peripheral intervention requires intraprocedural anticoagulation to prevent intraluminal thrombosis. Traditionally, unfractionated heparin (UFH) is administered during the procedure to achieve activated clotting time (ACT) of 300 to 400 seconds. When the intravenous IIb/IIIa antagonists are also used, the recommended ACT is 250 to 300 seconds because higher anticoagulation (ACT, 300-400 seconds) is accompanied by an unacceptable bleeding complication rate without added benefits. Because low molecular weight heparin has a more predictable anticoagulant effect and a higher anti-factor Xa/anti-factor IIa ratio, allows better bioavailability, is resistant to inhibition by activated platelets, and does not require routine monitoring using ACT, its use for intraprocedural anticoagulation (instead of UFH) has been an area of increasing interest. The safety and efficacy of coadministration of low molecular weight heparin with IIb/IIIa antagonists have not been adequately evaluated. We report a study of prospective evaluation of the safety and efficacy of combined use of intravenous enoxaparin and intravenous eptifibatide during nonemergent coronary and peripheral vascular intervention in 93 consecutive procedures performed on 56 patients. The procedural success rate was 99% (92/93 procedures), the acute clinical success rate was 98% (54/55 patients), the major bleeding complication rate was 2% (1/56 patients), and the vascular complication rate was 0.0%. In conclusion, the use of intravenous enoxaparin in conjunction with intravenous eptifibatide during nonemergent coronary and peripheral vascular intervention is safe and effective and eliminates the need for routine measurement of ACT during the procedure.     

Evaluation of a new point of care heparin test for cardiopulmonary bypass: the TAS heparin management test

Patients undergoing cardiopulmonary bypass (CPB) require anticoagulation with heparin to avoid thrombosis within the bypass circuit. The common method used to monitor the degree of anticoagulation is the activated clotting time (ACT). We evaluated a novel point of care device, the TAS (Pharmanetics, Raleigh, NC, USA) heparin management test (HMT), for its suitability in monitoring anticoagulation during CPB. In vitro analysis showed a dose-response (r2=0.988) of the HMT from 0.078-10.0 U/ml heparin, covering the range of heparin used during cardiac surgery (2-5 U/ml). Fifty randomly selected patients undergoing CPB were studied. Preheparin clotting times for these patients were 143+/-32 s for the HMT and 146+/-18 s for the ACT; 435+/-60 s HMT and 438+/-39 s ACT during CPB; 145+/-50 s HMT and 128+/-14 s ACT post-protamine (r2=0.797). epsilon-Aminocaproic acid treatment for inhibition of fibrinolysis did not affect the HMT. We conclude that the HMT correlates well with the ACT and may be useful for monitoring heparin during CPB. Advantages of the HMT are small sample volume and good sensitivity to heparin.     

Changing systems for measuring activated clotting times: impact on the clinical practice of heparin anticoagulation during cardiac surgery

BACKGROUND: The activated clotting time (ACT) is a standard monitor for heparin anticoagulation during cardiopulmonary bypass (CPB). This study determines the effect of upgrading our ACT system on our clinical practice with regards to the conduct and safety of heparin anticoagulation during cardiopulmonary bypass. METHODS: We compared the intraoperative heparin doses required for all adult cardiac surgery patients (n=1240) and postoperative bleeding for a subset of primary aortocoronary bypass (CABG) surgery procedures (n=285) from cohorts before and after the change in ACT systems. RESULTS: The heparin dose needed to exceed our target ACT of 480 sec for the duration of CPB was higher (45000 vs. 40000 units; p<0.0001), and the mean ACT during CPB was lower (557 vs. 618 sec; p<0.05) using the new ACT system. Furthermore, this coincided with decreased postoperative bleeding in the CABG subset (median value of 417 vs. 575 ml over 12 h; p<0.0005). CONCLUSIONS: We demonstrated that the introduction of the Actalyke ACT system significantly altered our clinical practice by increasing the heparin dose required to exceed our target ACT during CPB. Prospective study to determine the effect of Actalyke ACT system monitoring on hemostasis after cardiac surgery is merited.     

Comparing methods of establishing the aPTT therapeutic range of heparin

BACKGROUND: The American College of Chest Physicians (ACCP) recommends that the activated partial thromboplastin time (aPTT) therapeutic range for unfractionated heparin be defined as the aPTT corresponding to a heparin concentration of 0.3-0.7 micro/mL by heparin anti-factor Xa assay. This recommendation suggests that a therapeutic range defined in this manner should be superior to traditional empiric therapeutic ranges of 1.5-2.5 times the control. A pilot study was conducted to evaluate the ACCP recommendation for heparin monitoring. OBJECTIVE: To compare heparin dosage adjustments guided by a heparin concentration-derived therapeutic range (HCDTR) with those influenced by traditional empiric therapeutic ranges for the aPTT. METHODS: This study was conducted in 2 phases. In phase 1, the various aPTT therapeutic ranges were established and/or defined. The first empiric therapeutic range (E1) was established by performing an aPTT test on healthy volunteers. This E1 was defined as 1.5-2.5 times the mean normal aPTT. A second empiric therapeutic range (E2) was defined as 1.5-2.5 times the patient's baseline aPTT. The aPTT HCDTR had been defined in a previous study as 48-61 seconds. In phase 2, heparin dosage adjustment decisions guided by each empiric range and the HCDTR for the aPTT were compared with heparin dosage adjustment decisions guided by actual heparin concentrations. Decisions were in agreement when both the aPTT result and plasma heparin concentration indicated the same dosage change. Forty patients had a bedside aPTT determined prior to receiving continuous infusion heparin and again within 48 hours of heparin initiation. Plasma heparin concentration by anti-factor Xa assay was performed on the blood samples obtained after heparin initiation. Heparin dosage adjustment decisions were evaluated by determining the agreement of each aPTT test result with the corresponding plasma heparin concentration. An overall level of agreement (defined as the % of decisions that were in agreement) for each aPTT therapeutic range was determined. RESULTS: The level of agreement in dosage adjustment decisions between heparin concentration and E1, E2, and HCDTR was 28/40 (70%), 28/39 (72%), and 23/40 (58%), respectively (p = 0.34). Heparin dosage adjustment decisions based on an aPTT HCDTR did not significantly differ from heparin dosage adjustment decisions guided by traditional empiric therapeutic ranges for a bedside aPTT. CONCLUSIONS: This pilot study showed similar heparin dosage adjustment decisions using an empiric aPTT therapeutic range versus a heparin concentration-derived aPTT therapeutic range.     

The uncalibrated prothrombinase-induced clotting time test. Equally convenient but more precise than the aPTT for monitoring of unfractionated heparin

The activated partial thromboplastin time test (aPTT) represents one of the most commonly used diagnostic tools in order to monitor patients undergoing heparin therapy. Expression of aPTT coagulation time in seconds represents common practice in order to evaluate the integrity of the coagulation cascade. The prolongation of the aPTT thus can indicate whether or not the heparin level is likely to be within therapeutic range. Unfortunately aPTT results are highly variable depending on patient properties, manufacturer, different reagents and instruments among others but most importantly aPTT's dose response curve to heparin often lacks linearity. Furthermore, aPTT assays are insensitive to drugs such as, for example, low molecular weight heparin (LMWH) and direct factor Xa (FXa) inhibitors among others. On the other hand, the protrombinase-induced clotting time assay (PiCT?) has been show to be a reliable functional assay sensitive to all heparinoids as well as direct thrombin inhibitors (DTIs). So far, the commercially available PiCT assay (Pefakit?PiCT?, DSM Nutritional Products Ltd. Branch Pentapharm, Basel, Switzerland) is designed to express results in terms of units with the help of specific calibrators, while aPTT results are most commonly expressed as coagulation time in seconds. In this report, we describe the results of a pilot study indicating that the Pefakit PiCT UC assay is superior to the aPTT for the efficient monitoring of patients undergoing UFH therapy; it is also suitable to determine and quantitate the effect of LMWH therapy. This indicates a distinct benefit when using this new approach over the use of aPPT for heparin monitoring.     

两种低分子肝素和肝素钙在血液透析中抗凝效果对比研究

目的观察速避凝和法安明两种低分子肝素在血液透析中抗凝效果。方法选择39例常规血液透析患者,随机分3组,分别使用肝素钙、法安明和速避凝抗凝进行血液透析2次。观察透析结束后出血、透析器凝血情况,测量透析器容量及KT/V值,同时检测透析前,透析后30分钟、2和4小时部分凝血酶原时间（APTT）、凝血酶原活动度（PA）、凝血酶原时间（PT）、凝血酶凝固时间（TT）及纤维蛋白原（FIB）含量。结果透析后齿龈出血肝素钙组明显多于法安明组和速避凝组;两种低分子肝素组压迫止血时间明显短于肝素钙组（P均<0.05）;速避凝组体外循环系统血栓形成率最高,与肝素钙组比较P<0.05;但3种肝素使透析器容量下降率及对KT/V值的影响无显著差异。在血液透析过程中,法安明组及速避凝组PT无变化,PA增加,APTT、TT延长,FIB升高;肝素组透析30分钟即出现PT、APTT、TT显著延长,PA降低及FIB升高,并延续至透析结束。结论低分子肝素作为血液透析抗凝剂可起到与肝素钙同样的抗凝效果,同时减少出血倾向。使用速避凝抗凝时,至少应用0.4ml,才可达到理想抗凝效果。     

Lack of clinically significant pharmacological interactions between ticagrelor and enoxaparin or unfractionated heparin in healthy subjects

What is known and Objective: Patients with acute coronary syndromes (ACS) receive several pharmacological therapies concomitantly, including antiplatelet and anticoagulant agents. As unfractionated heparin (UFH) activates platelets in vitro and in vivo, co‐administration with an antiplatelet agent may lead to decreased clinical effectiveness of the latter. The aim was therefore to determine any potential drug–drug interactions between the new oral antiplatelet agent ticagrelor, and UFH or enoxaparin. Methods: In two open‐label, three‐period, crossover trials, healthy subjects were randomized to receive ticagrelor alone or with enoxaparin (study 1) or UFH (study 2), or enoxaparin or UFH alone. Ticagrelor plasma concentrations, inhibition of platelet aggregation (IPA), anti‐factor Xa levels, activated partial thromboplastin time (aPTT) and activated coagulation time (ACT) were measured. Results: Thirty and 28 subjects completed studies 1 and 2, respectively. Study drugs were generally well tolerated, with no significant bleeding or serious adverse events. Co‐administration with enoxaparin or UFH had no significant effect on ticagrelor pharmacokinetics. The effect of ticagrelor on IPA was unimpaired by co‐administration of enoxaparin, except for a marginal (?2·9%; 908·7%.h, 881·9%.h) reduction in final extent area under the effect curve (AUEC)_2–12 (95% CI: ?51·6%.h, ?2·0%.h). Co‐administering UFH with ticagrelor caused small decreases in IPA_max (?3·8%; 94·6%, 91·0%) and AUEC_2–12 (?6·8%; 888·6%.h, 828·3%.h) vs. ticagrelor alone (95% CI: final extent IPA_max?5·7%, ?1·6%; AUEC_2–12?109·8%.h, ?10·8%.h). Ticagrelor had no clinically significant effects on enoxaparin as assessed by anti‐factor Xa (study 1), or UFH as assessed by aPTT or ACT (study 2). What is new and conclusions: Enoxaparin and UFH had no effect on the pharmacokinetics and no clinically significant effect on the pharmacodynamics of ticagrelor. Ticagrelor had no clinically significant effects on the pharmacodynamics of enoxaparin or UFH.     

LMWH for perioperative anticoagulation in patients on chronic warfarin therapy

OBJECTIVE: To review current data regarding low-molecular-weight heparin (LMWH) use for perioperative anticoagulation in patients receiving chronic warfarin therapy. DATA SOURCES: Data were obtained from the Sixth American College of Chest Physicians Consensus Conference on Antithrombotic Therapy guidelines and a MEDLINE search (1996-January 2003). Search terms included heparin, low-molecular-weight heparin, warfarin, perioperative care, and anticoagulants. DATA SYNTHESIS: Heparin is the most common agent used as bridge therapy for perioperative anticoagulation in patients on chronic warfarin therapy; LMWHs are also used. Studies that evaluated enoxaparin and/or dalteparin were reviewed. CONCLUSIONS: Although published studies demonstrate efficacy and safety of LMWHs, more data are needed to support their use as bridge therapy.     

Interlaboratory agreement in the monitoring of unfractionated heparin using the anti-factor Xa-correlated activated partial thromboplastin time

Summary.  Background:  In an effort to improve interlaboratory agreement in the monitoring of unfractionated heparin (UFH), the College of American Pathologists (CAP) recommends that the therapeutic range of the activated partial thromboplastin time (APTT) be defined in each laboratory through correlation with a direct measure of heparin activity such as the factor Xa inhibition assay. Whether and to what extent this approach enhances the interlaboratory agreement of UFH monitoring has not been reported. Objectives:  We conducted a cross-validation study among four CAP-accredited coagulation laboratories to compare the interlaboratory agreement of the anti-FXa-correlated APTT with that of the traditional 1.5–2.5 times the midpoint of normal (1.5–2.5:control) method for defining the therapeutic APTT range. Patients and methods:  APTT and FXa inhibition assays were performed in each laboratory on plasma samples from 44 inpatients receiving UFH. Results:  Using the anti-FXa-correlation method, there was agreement among all four laboratories as to whether a sample was subtherapeutic, therapeutic or supratherapeutic in seven (16%) patient samples. In contrast, consensus was achieved in 23 (52%) samples when the 1.5–2.5:control method was employed. Conclusions:  The anti-FXa-correlation method does not appear to enhance interlaboratory agreement in UFH monitoring as compared with the traditional 1.5–2.5:control method. Adoption of the anti-FXa-correlation method produces considerable disparity in UFH dosing decisions among different centers, although the clinical impact of this disparity is not known.     

Effects of therapeutic plasma exchange on anticoagulants in patients receiving therapeutic anticoagulation: a systematic review

Therapeutic plasma exchange (TPE) removes coagulation proteins, but its impact on therapeutic anticoagulation is unknown. We performed a systematic review of the literature to determine the coagulation effects of TPE in patients receiving systemic anticoagulation. We searched MEDLINE, CINAHL, EMBASE, and Web of Science until June 2018 for studies combining controlled vocabulary and keywords related to therapeutic plasma exchange, plasmapheresis, anticoagulants, and therapy. The primary outcome was the effect of TPE on anti‐Xa activity, activated partial thromboplastin time (aPTT), or international normalized ratio (INR). The secondary outcome was reports of post‐TPE bleeding or thrombosis. A total of 1830 references were screened and eight studies identified. Our selected studies (five case reports and three case series) involved 23 patients and evaluated the effects of seven anticoagulants. Six studies of unfractionated heparin, low‐molecular‐weight heparins, and direct oral anticoagulants demonstrated an anti‐Xa level decline. Two studies of unfractionated heparin and low‐molecular‐weight heparins showed an aPTT increase. One study of warfarin showed a post‐TPE INR increase. Reports of post‐TPE bleeding occurred in two patients and thrombosis in one. In patients receiving therapeutic anticoagulation, TPE is associated with anti‐Xa activity decline and aPTT and INR increase. These coagulation changes do not appear to significantly increase bleeding or thrombotic risk. Our data suggest the need for prospective studies to investigate the true clinical impact of TPE on therapeutic anticoagulation.     

Role of low-molecular-weight heparin in invasive management of non-ST-elevation acute coronary syndromes

OBJECTIVE: To review the available literature addressing the role of low-molecular-weight heparin (LMWH) as an alternative to unfractionated heparin (UFH) in percutaneous coronary intervention (PCI) for treatment of non-ST-elevation acute coronary syndromes (NSTEACS). DATA SOURCES: A MEDLINE search (1966-March 2004) identified pertinent articles using the key words acute coronary syndromes, unstable angina, non-ST-elevation myocardial infarction, low-molecular-weight heparin, enoxaparin, dalteparin, glycoprotein IIb/IIIa receptor antagonists, abciximab, tirofiban, eptifibatide, percutaneous transluminal coronary angioplasty, and percutaneous coronary intervention. The references of these articles were reviewed for additional pertinent references. STUDY SELECTION AND DATA EXTRACTION: All human trials of LMWH in PCI for treatment of NSTEACS were evaluated. All pertinent studies were included in the review. DATA SYNTHESIS: Administration of LMWH with or without a glycoprotein IIb/IIIa inhibitor during PCI appears to be similar to UFH in terms of efficacy. LMWH, especially in combination with a glycoprotein IIb/IIIa inhibitor, may increase risk of bleeding compared with UFH. CONCLUSIONS: Available clinical trials do not provide definitive evidence to suggest superiority of LMWH over UFH when managing NSTEACS during PCI; however, dosing strategies are available if an LMWH is to be used in this setting.     

Cost-minimization analysis of low-molecular-weight heparin (dalteparin) compared to unfractionated heparin for inpatient treatment of cancer patients with deep venous thrombosis

Goals Low-molecular-weight heparin (LMWH) has shown to be as effective as unfractionated heparin (UFH) in the treatment of deep venous thrombosis (DVT). Although the acquisition cost of LMWH is significantly greater than that of UFH, we hypothesized that once-daily dalteparin, a LMWH, could reduce treatment costs of cancer patients with DVT by eliminating anticoagulation monitoring and shortening hospitalization.Patients and methods We developed a cost-minimization model by using outcomes and resource utilization data from two retrospective matched cohorts of cancer patients who, between 1994 and 1999, were hospitalized at our comprehensive cancer center for treatment of DVT with either LMWH (n=21) or UFH (n=168). We assumed all LMWHs and UFH to be equally effective. The total costs for the dalteparin strategy and the UFH strategy were calculated in year 2003 U.S. dollars, from the providers perspective, by multiplying the number of resources used for inpatient treatment of DVT by their unit costs.Results The mean total cost for inpatient care was $3,383 (95% CI= $2,683– $4,083) for dalteparin and $4,952 (95% CI=$4,718–$5,185) for UFH. Substantial savings resulted from shorter hospitalization among the dalteparin-treated patients (mean 3.19 versus 5.22 days). Sensitivity analysis did not change the conclusion that dalteparin is less expensive than UFH.Conclusions Savings realized from less anticoagulant monitoring and shorter hospitalization offset the higher acquisition cost of dalteparin. The dalteparin strategy is less expensive than the UFH strategy for the inpatient treatment of DVT among cancer patients.Presented in part at the 3rd Annual Houston Area Health Services & Outcomes Research Conference, Houston, TX, USA, November 25, 2002     

Use of a modified dosing weight for heparin therapy in a morbidly obese patient

OBJECTIVE: To report a case of successful anticoagulation using a modified dosing weight (DW) for unfractionated heparin (UFH) therapy in a morbidly obese female. CASE SUMMARY: A 54-year-old morbidly obese (182.4 kg, 155 cm) white female presented to the emergency department with tachycardia, shortness of breath, and chest pain, and was diagnosed with a pulmonary embolism. Anticoagulation with UFH was initiated. A modified DW of 120 kg was obtained from the average of the actual body weight (ABW) and ideal body weight ( approximately 50 kg). We selected this modified DW to account for heparin's altered volume of distribution in an obese patient and avoid potentially supratherapeutic activated partial thromboplastin times (aPTTs) using ABW and subtherapeutic aPTTs using DW. Therapy was initiated with a bolus dose of 9600 units (80 units/kg x 120 kg) and continuous infusion rate of 2160 units/h (18 units/kg/h x 120 kg). This infusion rate was maintained throughout the course of heparin therapy and was successful in maintaining therapeutic aPTTs. DISCUSSION: Proper diagnosis and rapid initiation of therapy prevent mortality in patients with PE. Although weight-based heparin nomograms provide standardization through initial bolus and continuous infusion recommendations, many do not address dosing in morbidly obese patients. Several retrospective studies have evaluated actual, dosing, and ideal body weights for heparin therapy in obese patients; however, none has evaluated modified DW. In our patient, successful anticoagulation was objectively confirmed. CONCLUSIONS: Further investigation is necessary to determine the optimal DW for UFH in morbidly obese patients presenting with acute thrombosis.     

低分子量肝素在血液透析应用中的评价

目的：比较低分子量肝素与普通肝素在常规血液透析抗凝中的有效性和安全性。方法：40例血液透析患分别用低分子量肝素和普通肝素抗凝进行自身对照，并作低分子肝素组与普通肝素组的组间对照。观察透析器及透析管道的凝血状态，内瘘穿刺点的压迫止血时间，抗因子Xa活性(AFXa)、凝血酶时间(TT)和活化部分凝血活酶时间(APTT)。结果：两组患均能顺利完成5小时透析，透析器及透析管道凝血程度及穿刺点压迫止血时间两组均无显差异(P＞0．05)。两组患使用低分子肝素抗凝透析结束时AFXa较血液透析前有显性差异(P＜0．001)，且透析开始后30分钟及透析结束时均明显高于普通肝素组，而APTT、TT在LMWH抗凝过程中无显延长，而普通肝素组则明显延长。结论：低分子量肝素在血液透析抗凝过程中较之普通肝素更有效，安全，方便，可替代普通肝素。     

Osteoporosis: point-of-care testing

OBJECTIVE: To review the literature concerning the utility of point-of-care (POC) testing devices for the diagnosis and management of osteoporosis. DATA SOURCES: Articles were identified from a MEDLINE search (1993-June 2003). Additional references were obtained from cross-referencing the bibliographies of selected articles. STUDY SELECTION AND DATA EXTRACTION: After evaluation of clinical trials and select review articles, articles comparing peripheral dual-energy absorptiometry (pDXA) or quantitative ultrasound (QUS) with central DXA (cDXA) measurements were emphasized in this analysis. DATA SYNTHESIS: Sensitivity for detecting osteoporosis by QUS or pDXA varies widely (range 35-75%). Using adjusted T-score cutoffs increases sensitivity to 85-95%, at the price of reducing device specificity to 23-49%. Many states require a radiology technician to perform pDXA tests. CONCLUSIONS: POC testing with peripheral devices should only be considered in areas with limited access to cDXA or for women who initially refuse cDXA testing. T scores of-1.0 or less with POC testing typically require further evaluation via cDXA. Many states require pDXAs to be performed by certified radiology technologists, making QUS use more feasible for pharmacists. POC testing should not be used for assessing response to osteoporosis therapy.