REPLY
Preventing Anticoagulant-Related Bleeding
C. Seth Landefeld and
Philip A. Anderson
15 January 1993 | Volume 118 Issue 2 | Pages 158-159
IN RESPONSE:
Dr. Davidson asks: What is the optimal range of the APT for an individual patient treated by continuous infusion of heparin? The question is important because low APT have been associated with bleeding [1, 2]. Unfortunately, available data do not provide a definitive answer.
Hirsh and colleagues [4] reported that 1) heparin levels of 0.2 to 0.4 U/mL by protamine titration achieved a full antithrombotic effect, as indicated by inhibition of fibrinogen accretion; 2) the APT value associated with a given heparin concentration varies directly with the patient's baseline APT; and 3) a heparin level of 0.3 U/mL correlated to an APT approximately twice the patient's baseline value. These observations led to the conclusion that "ideally, the patient's pretreatment blood sample should be used to calculate the ratio of the heparin effect" [4]—a recommendation that we think is reasonable, but that differs from usual practice [2, 3]. Also, before beginning our study[5], we obtained data from our hospital's clinical laboratory indicating that APT 1.5 to 2.5 times the patient's baseline value correlated with heparin levels of 0.2 to 0.5 U/mL.
We heartily agree with Dr. Davidson that "underdosing" is to be avoided in starting heparin therapy. We disagree, however, that the literature indicates that it is better to compare the APT with a mean laboratory control value than to the patient's baseline value, or vice versa. In the use of heparin, it is most important to recognize that the responsiveness of the reagents used in the APT test varies widely and that an APT equivalent to a heparin level of 0.2 to 0.4 U/mL should be attained quickly and should be maintained [2].
1. Hirsh J. Drug therapy: heparin. N Engl J Med. 1991; 324:1565-74.
2. Landefeld CS, McGuire E 3d, Rosenblatt MW. A bleeding risk index for estimating the probability of major bleeding in hospitalized patients starting anticoagulant therapy. Am J Med. 1990; 89:569-78.
3. Hull RD, Raskob GE, Hirsh J, Jay RM, Ledera JR, Geerts WH, et al. Continuous intravenous heparin compared with intermittent subcutaneous heparin in the initial treatment of proximal-vein thrombosis. N Engl J Med. 1986; 315:1109-14.
4. Hirsh J, Genton E, Hull R. Heparin. In: Venous Thromboembolism. New York: Grune and Stratton; 1981:166-7.
5. Landefeld CS, Anderson PA. Guideline-based consultation to prevent anticoagulant-related bleeding. Ann Intern Med. 1992; 116:829-37.
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