DÄ internationalArchive18/2008Treatment of Deep Vein Thrombosis in the Pelvis and Leg: Variability of the Intravascular Space

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Treatment of Deep Vein Thrombosis in the Pelvis and Leg: Variability of the Intravascular Space

Dtsch Arztebl Int 2008; 105(18): 344. DOI: 10.3238/arztebl.2008.0344a

Spannagel, U

LNSLNS I would like to point out a number of errors and make a few comments. In table 1, the approved low-molecular-weight heparins (LMWH) are listed; in the adjacent column, it is stated that LMWH should be given in doses adapted to the patient's body weight. This is not true of all LMWH, however: certoparin is approved for the treatment of deep vein thrombosis in a dosage of 8000 IU anti-Xa b.i.d., independently of body weight. In general, it seems to me that the authors fail to address the issue of body-weight-adjusted administration of LMWH in a critical manner. This type of administration is often inappropriate from the pharmacological point of view. The authors do, indeed, write that an abnormal body weight should be taken into account, among other factors, but they do not explain why. The reason can be stated simply enough: LMWH are strongly hydrophilic substances that are distributed exclusively in the intravascular space once they are absorbed after subcutaneous injection. The size of the intravascular space, which is the smallest distributive space in the body, depends only in part on body weight. It indeed increases with increasing muscle and organ mass, but not with an increase in body weight due to fatty tissue. Thus, two patients of identical weight, but different heights, can have intravascular spaces of very different sizes. It follows that, despite the relatively wide therapeutic window of LMWH, dosing them exclusively on the basis of the patient's body weight would lead to overdosing of short but markedly overweight patients, which would then be likely to produce hemorrhagic complications. This risk of overdose can be avoided by basing the LMWH dose not on the patient's body weight per se, but rather on his or her normal weight – or else by using an LMWH preparation that can be given in a dose that is independent of body weight. This is not a new idea, by the way; I read it for the first time in 1983, in my pharmacology textbook (1). DOI: 10.3238/arztebl.2008:0344a
1.
Forth W, Henschler D, Rummel W: Allgemeine und Spezielle Pharmakologie und Toxikologie. Mannheim, Wien, Zürich: Bibliographisches Institut 1983; 17 ff.
1. Forth W, Henschler D, Rummel W: Allgemeine und Spezielle Pharmakologie und Toxikologie. Mannheim, Wien, Zürich: Bibliographisches Institut 1983; 17 ff.