Register Login

Snakebite and D-dimer.

I am trying to discontinue the fibrin (ogen) degradation products (FDP) assay in favor of the D-dimer.  I have read and used several of the posts here as references and reasons for this decision.  A recent question from an ER physician has me doing some further research and I need your help.  What about snake bites?  Many text recommend the FDP along with the routine PT, PTT and Fibrinogen.  Will the D-dimer serve the same purpose in this situation? Joe Lamb

Thank you for your question, Joe. The short answer is yes, but there is some disagreement on this issue, so I’ll go into more detail.

Some venoms, particularly the one injected by the western diamondback rattlesnake, Crotalus atrox may cause a “primary fibrinogenolytic state” as discussed in Budzynski AZ, Pandyz DV, Rubin RN, et al. Fibrinogenolytic afibrinogenemia after envenomation by western diamondback rattlesnake. Blood 1984;63:1-14. This particular venom activates tissue plasminogen activator (TPA) which in turn activates plasminogen to digest circulating fibrinogen. This produces des-fibrinopeptide A fibrin monomers and FDPs D, E, X and Y, but theoretically no D-dimers. Others envenomate with serine proteases or metalloproteinases that digest fibrinogen or activate plasminogen. See Lu Q, Clemetson JM, Clemetson KJ. Snake venoms and hemostasis. J Thromb Haemostas 2005;3:1791-9.

Experts have dubbed the condition systemic or primary fibrinogenolysis, and because there is theoretically no thrombin activation of factor XIII and thus no fibrin crosslinking, there can be no D-dimer formation. Following this reasoning, I wrote in the second edition of Rodak BR. Hematology: Clinical Principles and Applications back in 2002 that one can use the combination of FDP and D-dimer tests to distinguish primary fibrinogenolysis from disseminated intravascular coagulation in which the D-dimer markedly elevates, and that this condition may be triggered by snakebite.

But, when put to the laboratory test, it just ain’t true, and so much for conventional wisdom. In the case of that 1984 Blood reference, we didn’t have the D-dimer assay in those days. Here’s a current reference. Demplfe CE, Argirlou S, kucher K, et al. Analysis of fibrin formation and proteolysis during intravenous administration of ancrod. Blood 2008;95:2793-2802. Ancrod is purified Malayan pit viper Calloselasma rhodostoma venom containing a serine protease that cleaves fibrinopeptide A but not fibrinopeptide B from fibrinogen. The venom does not activate factor XIII, Nevertheless, the D-dimer level rises markedly within one hour of ancrod therapy for ischemic stroke.

My favorite reference for this is a case study, Molk B. Acute myocardial infarction in an unsuspecting male. Cllnical Hemostasis Review 1997;11(2): 14. The unsuspecting male is my friend and colleague, Gordon Ens, who was president of Colorado Coagulation Consultants in Denver when he experienced the sympoms of a heart attack in 1997. He arranged to have his blood collected periodically during the initial phase of therapy, which included aspirin, TPA, and unfractionated heparin. His D-dimer became markedly elevated after ten minutes of TPA and remained elevated four hours post-infusion. He also measured fibrin monomer in the form of thrombus precursor protein (TPP, no longer available), which was elevated in parallel with the D-dimer.

The truth is that despite what we deduce from our understanding of fibrinolysis, D-dimer has been shown to be elevated in nearly all acute inflammatory and thrombotic conditions, and can be reliable used to monitor the course of a thrombotic event, whatever its source. Mr. Ens’ experience is the illustrative as the primary fibrinolytic action of TPA is well characterized. By the way, Gordon is fine.

Having said this, I know there are a number of institutions that keep, at some expense, a fresh Thrombo-Wellcotest kit around just because there may be a doc or two who insist on it. Maybe it makes economic, if not clinical, sense. Geo.

Comments (0)

No comments here.

Leave a Reply