Weight-based heparin dosing nomograms for anticoagulation achieved therapeutic levels more rapidly then standard-practice nomograms
ACP J Club. 1994 Mar-April;120:35. doi:10.7326/ACPJC-1994-120-2-035
Raschke RA, Reilly BM, Guidry JR, Fontana JR, Srinivas S. The weight-based heparin dosing nomogram compared with a "standard care" nomogram. Ann Intern Med. 1993 Nov 1;119:874-81.
To compare the performance of a weight-based heparin dosing nomogram with that of a standard-practice nomogram in achieving anticoagulation in patients with thromboembolic disorders.
Randomized controlled trial.
2 community teaching hospitals.
115 patients (mean age 58 y,52% women) receiving intravenous therapy for pulmonary embolism or proximal deep vein thrombosis (n = 85), unstable angina (n = 26), or acute noncoronary arterial ischemia (n = 4). Exclusion criteria were recent anticoagulant or thrombolytic therapy, active hemorrhage, major cerebral vascular event, history of heparin-induced thrombocytopenia, or allergy to heparin.
62 patients were randomized to the weight-based nomogram group and initially received an intravenous bolus of heparin, 80 U/kg body weight, then an infusion dose, 18 U/kg per hour. The patients in the standard-treatment group (n = 53) initially received a 5000-U bolus of intravenous heparin and an infusion dose of 1000 U/h. Activated partial thromboplastin time (APTT) was measured every 6 hours and used to guide heparin dose adjustments.
Main outcome measures
Times from initial heparin administration to an APTT value exceeding 1.5 times the control APTT of 30 seconds (therapeutic threshold time) and an APTT within the range of 1.5 to 2.3 times the control APTT (therapeutic range time). Control APTT was based on the upper limit of the normal range for APTT.
Patients who were assigned to the weight-based nomogram exceeded the therapeutic threshold sooner than patients assigned to the standard-care nomogram (8.2 vs 20.2 h, P < 0.001). Patients in the weight-based group achieved an APTT within the therapeutic range faster than the standard-care group (14.1 vs 22.3 h, P = 0.003). During the first 24 hours 27% of APTT determinations in the weight-based group and 7% in the standard-care group were above the therapeutic range. 4 minor bleeding complications (2 in each group) and 1 major hemorrhage (retroperitoneal bleeding in a patient in the standard-care group) occurred during hospitalization.
An activated partial thromboplastin time above the therapeutic threshold and within the therapeutic range was achieved more rapidly using a weight-based heparin dosing nomogram than with a standard heparin therapy nomogram.
Source of funding: The Palms Clinic, Phoenix, Arizona.
For article reprint: Dr. R.A. Raschke, Department of Medicine, Good Samaritan Regional Medical Center, 1111 East McDowell Road, Phoenix, AZ 85006, USA. FAX 602-239-2084.
The results of the study by Raschke and colleagues as well as others (1) clearly indicate that common practices for adjusting heparin doses result in inadequate anticoagulation in most patients during the first 24 to 48 hours of therapy. In patients with venous thromboembolic disease, the failure to achieve a therapeutic range of heparin concentration, as defined by prolongation of the APTT, increases the risk for recurrent thromboembolism. In patients with arterial thrombosis, the relation between inadequate anticoagulation and recurrence of symptoms or progression of thrombosis is less clear; however, many believe that heparin requirements in patients with arterial thrombosis are greater than those in patients with venous thrombosis. The authors suggest that a heparin dosing regimen based on a weight-based nomogram should be adopted as the standard of practice. The primary advantage of the weight-based heparin dosing nomogram suggested in this study, compared with previous, widely cited nomograms not based on weight adjustment (1, 2), is the lower incidence of APTTs defined as above the therapeutic range (2.3 times the control). This proposed advantage, however, may not result in either a lower incidence of bleeding complications or greater efficacy. Further, recent data suggest that with some APTT reagents, a therapeutic heparin concentration may require prolongation of the APTT to greater than 2.3 times the control (3).
The value of the weight-based nomograms has been widely accepted (4). Issues that remain unresolved are the clinical significance of supratherapeutic prolongation of the APTT when heparin therapy is initiated with weight-based nomograms and variability in the relation between prolongation of the APTT and therapeutic heparin levels. Accordingly, it is of value for clinicians to participate in a multidisciplinary approach to managing heparin therapy.
Paul R. Eisenberg, MD, MPH
Washington University School of MedicineSt. Louis, Missouri, USA