Need For Laboratory Monitoring Research Articles

Low Molecular Weight Heparin Therapy: Is Monitoring Needed?

Recent meta-analyses indicate that low molecular weight heparins (LMWH) are more effective than unfractionated heparin (UH) in preventing and treating deep vein thrombosis. This article presents the arguments for and against the need for laboratory monitoring. At the present time, the only tests currently available for monitoring LMWH therapy are those which measure the anti Xa activity in the plasma. Due to lower binding to plasma proteins and to cell surfaces, the plasma anti Xa activity generated by a given dose of LMWH is more predictable than for UH. Some clinical trials suggest that LMWH delivered at the recommended dose expose the patient to less bleeding risk than UH. Several meta-analyses indicate comparable risk while any overdose unacceptably increases the haemorrhagic risk. The lowest dose of LMWH still effective in treating established DVT is presently unknown; some reports indicate that inadequate doses of LMWH are associated with a lack of efficacy for prevention. An overview of the published clinical trials indicates that the LMWH dose has never been monitored for prevention of DVT. In the treatment of established DVT, several trials have been performed without any monitoring, while in others the dose was adapted to target a given anti Xa activity. These considerations suggest that in prevention of DVT, monitoring the dose is not required.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term oral anticoagulant therapy for coronary artery disease.

The findings of recent clinical trials have led to renewed interest in the role of oral anticoagulant therapy in patients with coronary artery disease. However, there are currently two major limitations to the routine use of oral anticoagulant therapy. The first is the need for laboratory monitoring and dose adjustment. This limitation may be overcome if fixed low doses of warfarin (e.g. 1 mg/day), which have antithrombotic effects, are shown by clinical trials to be effective and safe. A second limitation to oral anticoagulant therapy is uncertainty about its effectiveness and safety compared to aspirin, or in combination with aspirin. The current pathophysiologic knowledge and recent clinical trial data provide support for further clinical trials evaluating combined warfarin and aspirin treatment in the long-term care of patients with coronary artery disease, and in the primary prevention of myocardial infarction.

Comparison of subcutaneous low-molecular-weight heparin with intravenous standard heparin in proximal deep-vein thrombosis

In view of the potential of low-molecular-weight heparins (LMWH) to simplify initial therapy and allow outpatient treatment of proximal deep-vein thrombosis, we undertook a randomised comparison of fixed-dose subcutaneous LMWH with adjusted-dose intravenous standard heparin in the initial treatment of this disorder. Our main objectives were to compare the efficacy of these regimens for 6 months of follow-up and to assess the risk of clinically important bleeding. Of 170 consecutive symptomatic patients with venographically proven proximal deep-venous thrombosis, 85 received standard heparin (to achieve an activated partial thromboplastin time of 1·5 to 2·0 times the pretreatment value) and 85 LMWH (adjusted only for body weight) for 10 days. Oral coumarin was started on day 7 and continued for at least 3 months. The frequency of recurrent venous thromboembolism diagnosed objectively did not differ significantly between the standard-heparin and LMWH groups (12 [14%] vs 6 [7%]; difference 7% [95% confidence interval -3% to 15%]; p=0·13). Clinically important bleeding was infrequent in both groups (3·5% for standard heparin vs 1·1% for LMWH; p>0·2). We conclude that fixed-dose subcutaneous LMWH is at least as effective and safe as intravenous adjusted-dose heparin in the initial treatment of symptomatic proximal-vein thrombosis. Since there is no need for laboratory monitoring with the LMWH regimen, patients with venous thrombosis can be treated at home.

Application of the Syva EMIT and Abbott TDx Amphetamine Immunoassays to the Detection of 3,4-Methylenedioxymethamphetamine (MDMA) and 3,4-Methylenedioxyethamphetamine (MDEA) in Urine

MDMA and MDEA are hallucinogenic analogs of amphetamine. The need for laboratory monitoring of these substances has developed as a result of their increased recreational use. Since the Abbott TDx and Syva EMIT-d.a.u. immunoassays are commonly used tests for urine monitoring of drugs-of-abuse, the amphetamine assay of each manufacturer was assessed to determine the degree of cross-reactivity with MDMA and MDEA. Cross-reactivity was evaluated using a series of MDMA- and MDEA-spiked urine samples. Testing was performed over a two-day period with 3 runs/day and each sample run in duplicate. The Syva EMIT d.a.u. amphetamine assay was positive only at the highest concentration standard (10.0 micrograms/mL) for both MDMA and MDEA. Consequently, no further testing was performed with this assay. Calibration curves were generated for the TDx runs and percent cross-reactivity determinations were made. Precision for the TDx data was evaluated based on within-day and between-day coefficients of variation (CV). CVs for MDMA runs were below 6% for within-day and below 5% for between-day runs. Values of CV for MDEA were below 16% for both within-day and between runs; CVs were less than 2.5% for positive values. Cross-reactivity for MDMA ranged from 18% (10.00 micrograms/mL) to 118% (0.15 microgram/mL). Cross-reactivity for the MDEA standards ranged from 12% (10.00 micrograms/mL) to 47% (0.15 micrograms/mL). The presence of MDMA and/or MDEA in samples resulting in a negative EMIT-d.a.u. test and a positive TDx test was confirmed by GC/MS analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Thrombolytic therapy

The accepted role for thrombolytic therapy has until recently been limited because of its complexity and side-effects. It has generally been reserved for use systemically in a limited number of patients with acute, major pulmonary embolism or iliofemoral venous thrombosis, and locally in some patients with acute, peripheral arterial occlusion. Its indications have now been greatly expanded by the confirmation from large, multicentre trials completed within the last year that it is also effective in acute myocardial infarction, with a reduction in acute mortality of 20–25%. Moreover, administration has become greatly simplified as dosage regimens have been standardised and the need for laboratory monitoring eliminated. The standard thrombolytic agent used for nearly 3 decades has been streptokinase but within the last year recombinant, human, tissue-type plasminogen activator (the first ‘third generation’ thrombolytic agent) has become clinically available. This protein is the body's own chief plasminogen activator and has been produced by recombinant DNA technology. Compared with streptokinase, it appears to be both somewhat more effective and also safer (less bleeding and probably no allergic reactions). Other new thrombolytic agents are also being developed but the cost-effectiveness of the newer agents in relation to streptokinase will be for many the main practical issue.