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01.02.2014 | 2013 SSAT Plenary Presentation | Ausgabe 2/2014

Journal of Gastrointestinal Surgery 2/2014

Pharmacologic Prophylaxis, Postoperative INR, and Risk of Venous Thromboembolism after Hepatectomy

Journal of Gastrointestinal Surgery > Ausgabe 2/2014
Hari Nathan, Matthew J. Weiss, Gerald A. Soff, Michelle Stempel, Ronald P. DeMatteo, Peter J. Allen, T. Peter Kingham, Yuman Fong, William R. Jarnagin, Michael I. D’Angelica
Wichtige Hinweise


Dr. Thomas Aloia (Houston, TX): In this manuscript, the authors describe a retrospective, large volume, single-institution analysis of VTE after liver surgery. The study population had considerable variability regarding the utilization of VTE prophylaxis and the timing of VTE prophylaxis. This variability gives the opportunity to comment on the influence of VTE prophylaxis on VTE events, however, it also introduces significant opportunity for bias to affect the results. The study describes the following important findings:
VTE events occurred at a rate of 3 %, placing liver surgery in a middle range risk among general surgery procedures.
Extent of hepatectomy and an associated increase in INR correlated with VTE risk, confirming our new understanding of rebalanced coagulation after hepatectomy and further refuting the past belief that transient postoperative liver insufficiency protects the patient from VTE.
In their patients VTE prophylaxis did not correlate with VTE outcomes.
Globally, there is a consensus that perioperative VTE prophylaxis in liver surgery does not hurt patients and may help them. The results of this study suggest that preoperative VTE prophylaxis does not hurt patients, but also does not help them. Although we, as liver surgeons, believe that the postoperative rheology of liver patients is “different”, we are learning more and more that our patients are similar to other patients undergoing major surgery, with the paradigm that “bigger surgery” equals “bigger VTE risk”. Therefore, the idea that VTE prophylaxis does not impact posthepatectomy VTE rates goes against considerable data in other types of surgery including GI surgical oncology.
The questions I have are as follows:
The authors group patients who received prophylaxis on “POD 0–1.” What exactly does this mean? Did these patients receive a preop dose? In this early dosing group, was the post op dosing routinely started in the post op recovery room or on day 1? Was it regimented or triggered by an “acceptable” INR value?
The best data on this issue requires risk adjustment. As a NSQIP member institution, do you know your risk-adjusted VTE rate for general surgery? Liver surgery?
Our previous analysis of VTE in liver surgery identified postoperative bile leak and/or abscess as the predominant covariate with VTE after liver surgery. Your VTE patients had a median length of stay of 15 days, suggesting that other complications occurred along with VTE. Do you have any data on this aspect?
How has this study changed your practice? The assumption would be that without a benefit, you have abandoned VTE prophylaxis in all liver patients to reduce patient discomfort and cost.
36 % of VTE patients had concomitant extrahepatic resections, most likely bowel resection. Would you now consider giving VTE prophylaxis in this patient population?

Closing Discussant

Dr. Hari Nathan: Dr. Aloia, thank you for your insightful comments and questions, and if I may take this opportunity I would also like to complement you on the work that you and your group have also done on this topic.
With respect to your question regarding our categorization of prophylaxis, approximately half of the patients who received heparin in the group we categorized as “immediate prophylaxis” received it on POD 0, and half on POD 1. The timing of prophylaxis at our institution is really dictated by individualized clinical judgment and is not regimented. Our categorization is just an effort to simplify these choices for presentation in the paper, but it was reassuring to us that our conclusions were robust to several different approaches to categorizing prophylaxis. During the time period of this study, it was not standard practice for patients to receive a preoperative dose of heparin.
With respect to our own NSQIP data, unfortunately I do not have our specific institutional NSQIP VTE incidence after liver resection. However, I find it reassuring that the 2.6 % incidence at 30 days that we found in this study is comparable to the 2.9 % incidence that your group published based on NSQIP data and that other groups, such as Duke and Pittsburgh, have published based on their own institutional data. I think that collectively we have established what the incidence of VTE after hepatectomy is. The question, of course, is whether and how pharmacologic prophylaxis can decrease it.
Regarding your question about bile leaks, the rate of biloma was 1.8 %, compared to the nearly 6 % incidence in the NSQIP data, and there was no significant relationship between bile leaks and VTE in our data. Incidence of intra-abdominal infection, meaning biloma or abscess, was 7.5 % and was associated with VTE (7.1 % in patients with no VTE, 20 % in patients with VTE). This paralleled the data on major complications.
With respect to your last two questions: regarding the impact of this study on our institutional practice, I really think it's too early to tell. We do not interpret these data to mean that VTE prophylaxis is ineffective. Quite the contrary. You mentioned those who had other organ resections such as colon resections—as the data show, we actually tend to prophylax these patients more aggressively. I want to be clear: we recognize the limitations of all the retrospective studies on this issue, whether they are based on our own institutional data, other institutional data, or NSQIP data. We also recognize the limitations of the evidence in favor of routine pharmacologic prophylaxis, much of which is based on routine surveillance for VTE rather than detection of clinically significant VTE. AACP guidelines assume a risk reduction of fatal PE from 6 to 2 per 1,000. We had only two deaths attributable to PE in our study, out of over 2,000 patients. It is clear that patients undergoing major hepatectomy have a moderate risk of VTE. According to the AACP, the evidence supporting pharmacologic prophylaxis in general surgical patients is of moderate quality—hardly a slam dunk. So I hope that the impact of our work on our institutional practice and perhaps more broadly is that perceived coagulopathy due to elevated INR but without evidence of bleeding does not preclude pharmacologic prophylaxis against VTE. I would not broaden that conclusion, however, to make any sweeping recommendations based on very limited data regarding routine use of pharmacologic prophylaxis after hepatectomy.
Thank you again for reviewing the paper and for your questions.



Pharmacologic prophylaxis (PP) is recommended for patients undergoing general surgical procedures with at least moderate risk of venous thromboembolism (VTE). The role of PP in patients undergoing hepatectomy is controversial, however, due to concerns regarding postoperative liver dysfunction and bleeding.


We conducted a retrospective analysis of a prospectively maintained institutional database in order to clarify the relationship between PP, postoperative INR, and risk of VTE.


Postoperative VTE occurred in 55 of 2,147 patients (2.6 %) and was independently associated with advanced age, higher BMI, longer procedure time, and development of a major complication, as well as higher postoperative INR (≥1.5 versus <1.5: OR 2.50, P = 0.006). Patients undergoing more extensive liver resection with higher postoperative INR were less likely to receive PP, but receipt of PP demonstrated no relationship with either VTE incidence or hemorrhagic complications.


In this large single-institution study, incidence of VTE was not associated with PP but was associated with higher postoperative INR, contrary to the notion that postoperative liver dysfunction is protective against VTE. The interplay between prothrombotic and antithrombotic mechanisms in posthepatectomy patients must be more completely characterized before broad recommendations can be made regarding PP use in these patients.

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