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Correspondence

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^a Department of Pathology and Molecular Medicine, McMaster University, 120 Main St West, Hamilton, Ontario, LBN 3Z5 Canada
^b Department of Medicine, McMaster University, 120 Main St West, Hamilton, Ontario, LBN 3Z5 Canada
^c Department of Anesthesia, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, Berlin, D-13353 Germany

(Email: twarken{at}mcmaster.ca; crowthrm{at}mcmaster.ca; koster{at}dhzb.dc).

To the Editor:

Dr Warkentin discloses that he has a financial relationship with The Medicines Company.

 

We thank Barzaghi and colleagues [1], for responding to the article of Koster and colleagues [2] reporting on an observational study of patients with immune heparin-induced thrombocytopenia (HIT) in association with use of a ventricular assist device (VAD), and to the accompanying editorial [3] addressing the difficulties of accurate laboratory diagnosis of HIT in this patient population. Barzaghi and colleagues [1] point out that the more diagnostically specific platelet activation assays (eg, serotonin-release assay) are not widely available; therefore, "in [the] presence of a thrombocytopenia that could be suggestive for HIT, and [while] waiting for a laboratory confirmation, ... alternative anticoagulant strategies, not causing HIT, could be considered [1]." Then they discuss the advantages and disadvantages of several nonheparin alternatives, concluding that the direct thrombin inhibitor (ie, bivalirudin) is most promising for this clinical situation.

We appreciate these comments, as they outline the very pragmatic problems associated with HIT diagnosis, depending particularly on the hospital laboratory infrastructure. In view of this dilemma, we suggest going a step further. Why not pursue a nonheparin agent as the standard post-VAD insertion anticoagulant for all patients, whether they are thrombocytopenic or not?

It is well-known that heparin has important drawbacks in VAD patients besides the high risk of HIT (and the diagnostic conundrum posed by non-HIT thrombocytopenia in even more patients) [2, 3]. These include its inability to block well surface (fibrin)-bound thrombin [4], its indirect (antithrombin-dependent) inhibition of hemostasis that is compromised by the low antithrombin levels commonly found in post-cardiac surgery [5], and the risk of heparin "resistance," all of which contribute to poor outcomes. It could well emerge that a carefully-selected nonheparin anticoagulant for postoperative VAD anticoagulation, besides minimizing HIT risk, would achieve a much more effective prevention of VAD thrombosis and its serious consequences, such as embolic strokes.

Bivalirudin is a promising agent for VAD anticoagulation for the reasons given by Barzaghi and colleagues [1] (ie, short half-life, predominant nonhepatic and renal elimination) [6]. Moreover, unlike heparin, bivalirudin inhibits well any thrombin that is bound to fibrin coating the device surface [6]. However, there are two considerations that warrant caution. One is that because bivalirudin is degraded enzymically, it loses anticoagulant effect in areas of blood stasis [7]; it will be important to show that sluggish blood flow compromising anticoagulant efficacy does not arise in certain areas within the device. The second consideration is that one can not assume that routine anticoagulant monitoring with standard global assays (eg, activated partial thromboplastin time) will necessarily provide safe and effective monitoring in this clinical setting. This too will need to be established through careful clinical study. The "law of unintended consequences" infers that the potential for avoiding HIT could be offset by new problems of stagnation-related clotting or monitoring challenges with resulting under-anticoagulation or over-anticoagulation. Thus, despite its very promising pharmacologic profile, careful study of bivalirudin is needed in this high-risk indication of VAD anticoagulation in which there is a delicate balance between hemorrhage and thrombosis.

	References

Top References

 

1. Barzaghi N, Locatelli A, Ranucci M. Ventricular assist device implantation and the risk for heparin-induced thrombocytopenia(letter) Ann Thorac Surg 2008;85:360-361.[Free Full Text]
2. Koster A, Huebler S, Potapov E, et al. Impact of heparin-induced thrombocytopenia on outcome in patients with ventricular assist device support: single institution experience in 358 consecutive patients Ann Thorac Surg 2007;83:72-76.[Abstract/Free Full Text]
3. Warkentin TE, Crowther MA. When is HIT really HIT? Ann Thorac Surg 2007;83:21-23.[Free Full Text]
4. Weitz JI, Hudoba M, Massel D, Maraganore J, Hirsh J. Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors J Clin Invest 1990;86:385-391.[Medline]
5. Ranucci M, Frigiola A, Menicanti L, Ditta A, Boncilli A, Brozzi S. Postoperative antithrombin levels and outcome in cardiac surgery Crit Care Med 2005;33:355-360.[Medline]
6. Bartholomew JR. Bivalirudin for the treatment of heparin-induced thrombocytopeniaIn: Warkentin TE, Greinacher A, editors. Heparin-induced thrombocytopenia. 4th ed.. New York: Informa Healthcare USA, Inc; 2007. pp. 409-439.
7. Koster A, Pötzsch B, Madlener K. Management of intraoperative anticoagulation in patients with heparin-induced thrombocytopenia undergoing cardiovascular surgeryIn: Warkentin TE, Greinacher A, editors. Heparin-induced thrombocytopenia. 4th ed.. New York: Informa Healthcare USA, Inc; 2007. pp. 487-502.

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