Malignancy does not dictate the hypercoagulable state following liver resection

doi:10.1016/j.amjsurg.2014.12.022

The American Journal of Surgery

Volume 209, Issue 5, May 2015, Pages 870-874

https://doi.org/10.1016/j.amjsurg.2014.12.022 Get rights and content

Abstract

Background

A hypercoagulable state following intra-abdominal malignant resections has been reported. Whether this is because of the operation or the malignancy, a known cause of hypercoagulability, remains unclear. We determined if malignancy status affected the coagulation profile following liver resection by assessing perioperative thromboelastogram (TEG) values.

Methods

Retrospective review of prospectively collected TEG values in patients who received a liver resection was conducted. Values among patients with benign or malignant disease were compared.

Results

Fourteen and 63 patients were resected for benign and malignant disease, respectively. No significant differences in TEG values existed between the groups. Combining the groups, patients developed a relative hypercoagulable state postoperatively with decreased R-times (P < .05), although median values remained within the normal range.

Conclusion

Following liver resection, no differences in TEG values existed between patients with benign and malignant disease; the relative hypercoagulable state is more likely driven by postoperative coagulopathy rather than the malignancy status of the patient.

Section snippets

Methods

This study was a retrospective review of prospectively collected data for a noninterventional trial that was approved by the Institutional Review Board at Oregon Health & Science University. Methods for data collection of demographics, laboratory analysis, and perioperative management were conducted in an identical fashion as described in great detail in our previously published work.12, 13

The analysis comprised dividing patients into groups with benign or malignant disease. Later, the

Results

Between November 2010 and January 2013, 101 patients were enrolled in the study. Twenty-four patients were excluded because of nonanatomic wedge resections being conducted (19 patients), or unresectable disease (eg, carcinomatosis) being discovered during the operation (5 patients). The mean age was 57 years (standard deviation ±14 years). Men comprised 52% of the cohort.

A list of confirmed pathologic diagnoses for all the liver resections is depicted in Table 1. The majority of patients, 63/77

Comments

These data show that patients who received a liver resection have TEG values within the normal range suggesting that they are neither hypercoagulable nor hypocoagulable following resection. However, a relative hypercoagulable state occurs as the R-time decreased postoperatively compared with the baseline preoperative value. This effect persists to at least POD5, the last collection time point in the study. Furthermore, relative hypercoagulability is most likely because of the operation, rather

References (13)

C.M. Thorson et al.
Persistence of hypercoagulable state after resection of intra-abdominal malignancies
J Am Coll Surg
(2013)
J.S. Barton et al.
Coagulopathy after a liver resection: is it over diagnosed and over treated?
HPB (Oxford)
(2013)
S.G. Louis et al.
The international normalized ratio overestimates coagulopathy in patients after major hepatectomy
Am J Surg
(2014)
P.J. Dipasco et al.
Thrombophilic state in cancer, part I: biology, incidence, and risk factors
J Surg Oncol
(2011)
J.S. Lieberman et al.
Thrombophlebitis and cancer
JAMA
(1961)
E. Sproul
Carcinoma and venous thromboses: the frequency of association of carcinoma in the body or tail of the pancreas with multiple venous thrombosis
Am J Cancer
(1938)

There are more references available in the full text version of this article.

Cited by (11)

Post-hepatectomy liver failure prediction and prevention: Development of a nomogram containing postoperative anticoagulants as a risk factor
2022, Annals of Hepatology
Citation Excerpt :
We found many of the PHLF patients had typical CT images of PHLF, including portal vein thrombosis and obstruction, as well as large infarcts in the liver (Fig. 6). Studies have shown that postoperative hypercoagulability is caused by liver coagulation dysfunction [25]. We speculate that liver failure may be the process of liver disseminated intravascular coagulation (DIC) leading to liver infarction.
Posthepatectomy liver failure (PHLF) is a serious complication after hepatectomy, and its effective methods for preoperative prediction are lacking. Here, we aim to identify predictive factors and build a nomogram to evaluate patients’ risk of developing PHLF.
A retrospective review of a training cohort, including 199 patients who underwent hepatectomy at the Shanghai Eastern Hepatobiliary Surgery Hospital, was conducted. Independent risk variables for PHLF were identified using multivariate analysis of perioperative variables, and a nomogram was used to build a predictive model. To test the predictive power, a prospective study in which a validation cohort of 71 patients was evaluated using the nomogram. The prognostic value of this nomogram was evaluated by the C-index.
Independent risk variables for PHLF were identified from perioperative variables. In multivariate analysis of the training cohort, tumor number, Pringle maneuver, blood loss, preoperative platelet count, postoperative ascites and use of anticoagulant medications were determined to be key risk factors for the development of PHLF, and they were selected for inclusion in our nomogram. The nomogram showed a 0.911 C-index for the training cohort. In the validation cohort, the nomogram also showed good prognostic value for predicting PHLF. The validation cohort was used with similarly successful results to evaluate risk in two previously published study models with calculated C-indexes of 0.718 and 0.711.
Our study establishes for the first time a novel nomogram that can be used to identify patients at risk of developing PHLF.
Utility of viscoelastic coagulation testing in liver surgery: a systematic review
2021, HPB
Citation Excerpt :
Similar findings were observed in the study by Tanner et al. with TEG demonstrating a hypercoagulable profile in 64%, 33%, 39% and 36% of patients following hepatectomy on POD0, POD1, POD3 and POD5, respectively.18 Gordon et al.31 recorded two cases of Internal Jugular Vein Thrombosis (IJVC) in the setting of a slight hypercoagulable status as indicated by TEG, although these were most likely related to central venous catheter trauma on site. Of note, De Pietri et al.32 reported that two patients (out of 38) developed pulmonary embolism after not receiving thromboprophylaxis following liver surgery.
The objective of the current study was to summarize and evaluate all published evidence regarding viscoelastic testing in the field of liver surgery.
A systematic search of the literature was performed using Medline/PubMed, Scopus, Cochrane Library Central, Google Scholar, and clinicaltrials.gov databases. The following keywords were used:“Thromboelastography”, “Thromboelastometry”, “Viscoelastic tests OR testing”, “Sonoclot Devices”, “Point-of-care tests OR testing”, “Coagulation OR Haemostasis OR Hemostasis”, “Liver OR Hepatic Surgery”, “Cirrhosis.”
A total of 12 studies analyzing 348 patients who underwent viscoelastic testing of coagulation during liver surgery for benign or malignant diseases were included; 7 (58.3%) studies reported on the use of thromboelastography (TEG), and 5 (41.7%) reported on rotational thromboelastometry (ROTEM). Viscoelastic testing (TEG and ROTEM) identified normo-, hyper- and hypo-coagulable status in 77% (n = 268/348), 18.4% (n = 64/348), and 4.6% (n = 16/348) of patients, respectively. In contrast, conventional coagulation tests indicated normo-coagulability in 111 patients (34.2% out of 325) and hypo-coagulability in 214 (65.8% out of 325) patients following liver resection. No patient (0% out of 291) experienced postoperative hemorrhage, whereas 5.8% (n = 17/291) experienced postoperative thromboembolic events.
Global viscoelastic testing may be a reasonable adjunct to conventional coagulation testing to provide a more robust assessment of the coagulation status of patients undergoing liver surgery.
Effect of Liver Disease Etiology on ROTEM Profiles in Patients Undergoing Liver Transplantation
2019, Transplantation Proceedings
Citation Excerpt :
Therefore, any explanations are conjectural and verification in further studies is recommended before this effect is accepted. Our results support previous studies that have found that patients with hepatocellular carcinoma demonstrate similar results on viscoelastic tests of coagulation to patients with non-biliary etiologies [24,25]. Our second hypothesis was that elevated baseline EXTEM A10 values may predict postoperative thrombotic complications.
Coagulation abnormalities in liver transplant patients are complex and may be related to the underlying liver disease. We evaluated the effects of disease etiology on whole-blood rotational thromboelastometry (ROTEM; Pentapharm GmbH, Munich, Germany) profile and association with thrombotic complications following liver transplantation.
Analysis of perioperative data from patients undergoing liver transplantation between January 1, 2012 and December 31, 2016. Patients were grouped based on the biology of their underlying liver disease: hepatocellular carcinoma (HCC), biliary etiology, and non-biliary etiology. The primary outcome was the EXTEM A10 value of the pre-incision ROTEM. Secondary outcomes included associations between EXTEM A10 value and incidence of postoperative thrombotic complications.
Three hundred fifty patients met the eligibility criteria: 60 had biliary etiologies, 203 had non-biliary etiologies, and 87 had HCC.
EXTEM A10 values were significantly higher in patients with biliary etiologies than those with non-biliary etiologies (mean difference, 13.8; 95% CI: 10.1 to 17.5; P = .001) and those with HCC (mean difference, 10.4; 95% CI: 6.2 to 14.7; P = .001). Patients with non-biliary etiologies had slightly higher values than those with HCC (mean difference, −3.3; 95% CI: -6.6 to -0.1; P = .04). Higher values for biliary etiologies remained after adjusting for liver disease severity, platelet count, and fibrinogen level. There was no significant difference in EXTEM A10 values between patients who suffered thrombotic complications and those who did not (mean difference: 4.3, 95% CI: −1.3 to 9.9, P = .13).
Patients with biliary diseases demonstrated higher EXTEM A10 values compared to those with non-biliary diseases or HCC. This was not fully explained by differences in disease severity, platelet count, or fibrinogen level. Pre-incision EXTEM A10 values do not predict incidence of postoperative thrombotic complications.
Coagulation profile following liver resection: Does liver cirrhosis affect thromboelastography?
2018, American Journal of Surgery
Citation Excerpt :
In our patient population, despite a statistically significant increase in prothrombin time/international normalized ratio, there was not a concordant hypocoagulable state in any of the different measurements in the thromboelastogram or the overall coagulation index. This is consistent with other groups that have shown similar findings.2,8,11 Utilizing the coagulation index we found that up to 64% of patients were in fact hypercoagulable at some point following liver resection and therefore are at increased risk for venous thromboembolism.
Thromboelastography has called into question the coagulopathy seen following partial hepatectomy. However the coagulation profile in cirrhotic livers has not been studied. Our objective was to determine the coagulation profile following partial hepatectomy in normal and cirrhotic livers.
Patients undergoing liver resection were prospectively enrolled in the study. The prothrombin time and international normalized ratio, as well as the thromboelastogram, were obtained preoperatively, post-operatively, and on post-operative days 1, 3, and 5.
22 noncirrhotic and 11 cirrhotic patients undergoing liver resection were enrolled. Postoperatively the thromboelastogram demonstrated a hypercoagulable profile in 64%, 33%, 39% and 36% of patients on post-operative days 0, 1, 3 and 5 respectively. There was no difference between patients with cirrhosis and those without underlying liver disease.
Patients appear to have a similar coagulation profile after liver resection regardless of underlying cirrhosis with many having a hypercoagulable profile.
Thromboelastography demonstrates perioperative hypercoagulability in hepato-pancreato-biliary patients and supports routine administration of preoperative and early postoperative venous thromboembolism chemoprophylaxis
2017, HPB
Citation Excerpt :
This could be due to low pancreatectomy sample size in both our cohorts (18 in theirs and 37 in ours). In one of the Portland group's studies, they evaluated 77 patients who had undergone liver resection and found that the median time to clot formation was higher in the immediate postoperative period and on postoperative days 1 and 5.29 The authors stated they administered VTE chemoprophylaxis to the “majority” of their patients early postoperatively, but had patients who received it much later (postoperative day 9–11) or not at all.
We hypothesized hepato-pancreato-biliary (HPB) surgery patients are more likely to be hypercoagulable than hypocoagulable, and that bleeding risks from VTE chemoprophylaxis are low. This study sought to use thromboelastography (TEG) to compare coagulation profiles with bleeding/thrombotic events in HPB patients receiving standardized perioperative chemoprophylaxis.
Consecutive patients undergoing HPB resections by three surgeons at one institution (January 2014–December 2015) received preoperative and early postoperative VTE chemoprophylaxis and were evaluated with TEGs. Coagulation profiles were compared to bleeding/thrombotic events.
Of 87 total patients, 83 (95.4%) received preoperative chemoprophylaxis and 100% received it postoperatively. Median estimated blood loss was 190 ml. Only 2 (2.3%) patients received intraoperative transfusions. None required transfusions at 72-hours. Only 2 were transfused within 30 days. There was 1 (1.1%) 30-day VTE event. Of 83 preoperative TEGs, 29 (34.9%) were hypercoagulable and only 8 (9.6%) were hypocoagulable/fibrinolytic. Of 73 postoperative TEGs, 34 (46.6%) were hypercoagulable and just 8 (11.0%) were hypocoagulable/fibrinolytic. .
With routine perioperative chemoprophylaxis, both VTE and bleeding events were negligible. Perioperative TEG revealed a considerable proportion (46.6%) of HPB patients were hypercoagulable. HPB patients can receive standardized preoperative/early postoperative VTE chemoprophylaxis with effective results and minimal concern for perioperative hemorrhage.
Thromboelastograhpy of hemostasis in hepatocellular carcinoma with underlying cirrhosis and massive intraoperative blood loss in liver resection
2023, Research Square

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: A part of this work was funded by the Medical Research Foundation of Oregon Health & Science University. This foundation provided financial support to obtain laboratory samples and analysis as well as administrative support for patient recruitment. The funding did not affect data analysis or manuscript preparation.

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North Pacific Surgical AssociationMalignancy does not dictate the hypercoagulable state following liver resection

Abstract

Background

Methods

Results

Conclusion

Section snippets

Methods

Results

Comments

J Am Coll Surg

HPB (Oxford)

Am J Surg

Thrombophilic state in cancer, part I: biology, incidence, and risk factors

J Surg Oncol

Thrombophlebitis and cancer

JAMA

Carcinoma and venous thromboses: the frequency of association of carcinoma in the body or tail of the pancreas with multiple venous thrombosis

Am J Cancer

North Pacific Surgical Association
Malignancy does not dictate the hypercoagulable state following liver resection