In response to Sharma's comment that subtherapy may be a confounder in the intravenous heparin arm of our study, we administered heparin by a protocol that achieved high rates of successful therapy, and most patients receiving warfarin sodium achieved therapeutic international normalized ratios (INRs). There was a similar low frequency of subtherapeutic INRs during long-term therapy in both treatment groups. The only difference between the 2 treatment groups with regard to subtherapeutic monitoring and recurrent venous thromboembolism occurred in one patient with subtherapeutic activated partial thromboplastin times in the unfractionated heparin group. The necessity for anticoagulant monitoring to achieve therapeutic levels is a practical limitation of unfractionated heparin therapy. The advantage of low-molecular-weight heparin (LMWH) is that the required dosage is predicted by body weight, and anticoagulant monitoring is not required. Our findings demonstrate that the regimen of LMWH used was superior to protocol-driven unfractionated intravenous heparin. In the absence of a heparin protocol, many more patients receiving intravenous unfractionated heparin would have had subtherapeutic levels.
Hull RD, Raskob GE, Brant RF, Pineo GF, Stein PD, Mah AF. Is There Enough Evidence That Low-Molecular-Weight Heparin Is Superior to Unfractionated Heparin in Pulmonary Embolism?—Reply. Arch Intern Med. 2000;160(13):2061-2067. doi: