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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2015  |  Volume : 26  |  Issue : 1  |  Page : 1-5
Post-transplant venous thromboembolic events and their effect on graft survival


1 Section of Hepatopancreaticobiliary and Transplant Surgery, McGill University Health Center, Montreal, Canada
2 Department of Surgery, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
3 Department of Community Medicine, Faculty of Medicine, Kuwait University, Kuwait
4 Section of Hepatopancreaticobiliary and Transplant Surgery, McGill University Health Center, Montreal, Canada; Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia

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Date of Web Publication8-Jan-2015
 

   Abstract 

Venous thromboembolic events (VTEs) are a major cause of post-operative morbidity and mortality. Our objective is to establish the prevalence of VTEs in kidney transplant recipients and assess its impact on graft survival. Data regarding renal transplant patients with VTEs from 1985 to 2010 were identified and analyzed. After excluding recipients of combined grafts and late VTE development, 1596 recipients were included in this analysis. The prevalence of post-operative VTEs and graft survival were determined. Cox regression was used to analyze the survival data and data on prognostic (confounding) variables. The observed prevalence of VTEs in kidney transplant recipients was 1.6%. Of the 1596 kidney recipients, 25 recipients who developed VTEs had a mean graft survival of 12.3 years (compared with 20.5 years in patients without). The hazard ratio was 1.1 (95% confidence interval: 0.4-3.0, P = 0.447). The prevalence of VTEs post kidney transplantation is small. Although it did not reach statistical significance, it increased the risk of graft failure by 30%.

How to cite this article:
Abualhassan N, Aljiffry M, Thalib L, Coussa R, Metrakos P, Hassanain M. Post-transplant venous thromboembolic events and their effect on graft survival. Saudi J Kidney Dis Transpl 2015;26:1-5

How to cite this URL:
Abualhassan N, Aljiffry M, Thalib L, Coussa R, Metrakos P, Hassanain M. Post-transplant venous thromboembolic events and their effect on graft survival. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2020 Aug 9];26:1-5. Available from: http://www.sjkdt.org/text.asp?2015/26/1/1/148707

   Introduction Top


Venous thromboembolic events (VTEs), which include pulmonary embolism (PE) and deep vein thrombosis (DVT), are major causes of post-operative morbidity and mortality. Most deaths from PE can be prevented by providing adequate prophylaxis. [1] In general, the majority of VTEs occur due to failure to administer prophylaxis rather than a prophylaxis failure per se. [2] Approximately 10% of all patients with acute PE die during the first three months after their diagnosis. [3] Virchow's triad, [4] which consists of stasis, endothelial injury and hypercoagulable state, has long been identified as the documented underlying pathophysiology explaining VTEs. [4] Lankeit et al reported a 1% mortality rate due to PE in admitted patients. [3] Furthermore, the annual incidence of diagnosed DVT episodes is estimated to be 23-160 per 100,000 of the general population. [3],[5] The incidence of VTEs is well established in most surgical patients. This facilitates the selection of appropriate prophylaxis with a clear picture of associated risks and benefits. Similar data are not present when examining solid organ transplant recipients. We did not find many studies in the literature addressing this issue. From this limited evidence, the reported incidence of VTEs in kidney transplant patients is 4.5-8.3%. [6],[7]

Based on the current recommendation for post-operative prophylaxis, the risk of VTEs can be classified into three categories: Low, moderate and high. [8] The degree of prophylaxis is then determined based on the risk stratification. This may include either mechanical, pharmacological or both types of prophylaxis. Mechanical therapy consists of early ambulation, graduated compression stockings (GCS), intermittent pneumatic compression (IPC) and vena caval filter insertion. [9] Pharmacological therapy includes low-dose unfractionated heparin (LDUH), adjusted-dose heparin, low molecular weight heparin (LMWH), selective direct factor Xa inhibitors and oral anticoagulants. [10] VTE prophylaxis should be tailored to the patient's specific needs. In kidney transplant patients, renal dysfunction predisposes them to secondary platelet dysfunction and lower hematocrit levels, which could be a relative protective factor. [6]

Currently, the recommended VTE prophylaxis for low-risk patients is early ambulation and GCS. [8] In the moderate risk group, the use of LMWH or LDUH is recommended. [8] The recommended prophylaxis for the high-risk group is LDUH 5000 U three times a day or LMWH >3400 U daily combined with the use of GCS and/or IPC for at least seven to 10 days. [8] In selected high-risk patients, such as patients undergoing total hip replacement, extended prophylaxis with LMWH for 28-45 days is advised. [11],[12]

There are no available guidelines regarding the appropriate mode of prophylaxis in renal transplant recipients. In our cohort, all transplant recipients received either LDUH or LMWH daily combined with GCS. We did not find sufficient data evaluating the effect of VTEs on graft survival in the literature. Thus, in this study, we attempted to determine the prevalence of VTEs in kidney transplant recipients and to assess its impact on graft survival.


   Methods Top


Using the collected data stored at the McGill University Multi-Organ Transplant Database, kidney transplant recipients who were diagnosed with VTEs from 1985 till 2010 were identified. All transplant patients were given LDUH 5000 U three times a day or enoxaparin 40 mg daily combined with pneumatic compression stockings. Kidney transplants were performed according to the standard technique in which the graft was implanted in the iliac fossa. Vascular clamps were applied to the external iliac artery and vein for vascular anastomosis with intravenous heparinization.

The diagnosis of DVT was made based on clinical suspicion and confirmed radiologically using Doppler ultrasound. [13],[14],[15] Findings confirming DVT were abnormal compressibility and/or persistent filling defect or thrombus in the color column of the lumen. [14] PE was diagnosed using either the ventilation/perfusion scanning with high probability, [16] segmental perfusion deficits with normal ventilation or computed tomography angiography with the PE protocol [17],[18] with single or multiple filling defects in conjunction with clinical presentation and positive result for d-dimer.

Our aim was to analyze perioperative VTE events in renal transplant recipients. Hence, we excluded VTEs more than 90 days post-transplantation and recipients of combined grafts. One thousand five hundred and ninety-six recipients were included in the analysis. Prevalence of post-operative VTEs and graft survival were determined. Other prognostic confounders were also collected and accounted for. These included age, gender and cold ischemia time. Summary statistics for categorical variables (e.g., gender) were expressed as frequency (percentage) while continuous variables (e.g., age) were expressed as median, range or mean and standard deviation (SD). Mean survival time along with standard error (SE) of these estimates was also presented as summary measures. The relative risk of developing a VTE was estimated using Cox regression and Hazard ratio (HR) along with the 95% confidence interval were reported. Further multiple Cox regression models were used to obtain adjusted HR for the effect of VTE on graft survival. A P-value of < 0.05 was considered significant and all data analyses were carried out using SPSS (Version 19).


   Results Top


A total of 1596 kidney transplant recipients were analyzed. [Table 1] summarizes the demographics of kidney transplant recipients in this study. One thousand and fourteen (64%) of these recipients were men with a median age of 47 years and 582 (36%) were women with a median age of 45 years. The overall age ranged between 18 and 74 years. Twenty-five recipients (1.6%) developed VTEs. Of these, three patients were diagnosed with PE (there were no women with reported PE) and 22 with DVT only. The mean graft survival in patients without a VTE was 20.5 years while that in patients with VTEs was 12.3 years. The over-all fiveyear graft survival of the whole group was 78.3%.
Table 1: Demographics of patients and incidence of VTEs, PE and DVT and graft survival in kidney transplant recipients.

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The transplant patient population ratio (HR) was 1.1 [95% confidence interval (CI): 0.4-3.0]. This effect was not statistically significant (P = 0.447). [Table 2] summarizes the results of the statistical analysis conducted to estimate the HR with respect to the effect of VTEs on graft survival. When the confounders were adjusted for, there was again no statistical significance of the effect of VTEs on graft survival.
Table 2: Effect of VTEs (crude and adjusted HR) on graft loss in kidney transplant recipients.

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   Discussion Top


VTE is a well-known complication that may occur after any type of surgery. In a study by Gangireddy et al, VTEs were associated with a significant increase in post-operative 30-day mortality. [19] He included in his study nine common general, vascular and orthopedic procedures. Pre-operative factors associated with symptomatic VTEs were old age, male gender, corticosteroid use, chronic obstructive pulmonary disease, recent weight loss, disseminated cancer, low albumin and low hematocrit (P < 0.01 for all). [19] Post-operative factors associated with symptomatic VTEs were urinary tract infection, acute renal insufficiency, postoperative transfusion (>4 units), myocardial infarction and pneumonia (P < 0.01 for all). [19]

He found in his evaluation that hemodialysis, diabetes and higher pre-operative albumin levels were found to be protective from symptomatic VTEs (odds ratio 0.3, 0.75 and 0.8, respectively, with 95% CIs of 0.07-0.71, 0.61-0.93 and 0.74-0.96, respectively). [19] These risk factors can have a cumulative effect on the probability of VTEs.

The transplant patient population is considered a high-risk group for developing VTEs given the fact that most of these patients have multiple identifiable risk factors. However, the exact risk of developing VTEs in these patients and its implication on graft survival are not clearly defined in the literature. In addition, there are no clear guidelines regarding the appropriate use of thromboprophylaxis in transplant recipients.

Studies have shown that the incidence of asymptomatic VTEs in patients undergoing general surgery without thromboprophylaxis varies between 15% and 30%, while the rates of fatal PE range between 0.2% and 0.9%. [8]

The reported incidence of VTEs in kidney transplant recipients ranges from 4.5% to 8.3%. [6],[7] In a study by Yegen et al, the incidence of VTEs in lung transplant patients was reported to be 22% despite thromboprophylaxis. [20] The authors identified that pre-transplant diagnosis of pulmonary fibrosis as a risk factor and immunosuppression were linked to VTEs in recipients of solid organ transplantation. [20]

In kidney transplant recipients, VTEs are more commonly localized to the same side of the grafted tissue. [6] Possible etiologies that might favor the occurrence of VTEs in kidney transplant recipients include pelvic dissection and venous anastomosis with clamping of the external iliac vein as well as compression of the pelvic veins by the graft and post-operative hematomas. [6] However, in theory, uremic patients suffer from secondary platelet dysfunction and lower hematocrit levels, which may serve as protective factors against VTEs. Allen et al recorded two peaks of VTE post kidney transplantation. The first peak is in the first month while the second peak is in the fourth month, which likely represent the resolution of the effects of uremia on erythropoiesis and platelet dysfunction. [7] In our study, a total of 1596 kidney transplant recipients were analyzed. Twenty-five recipients (1.6%) developed VTEs. We report a 1.6% risk of developing VTE in kidney transplant recipients, slightly lower than what is reported in the literature (4.5-8.3%). The effect of this complication on graft failure was not statistically significant (P = 0.45), with an HR of 1.1 (95% CI: 0.4-3.0). The mean graft survival in patients with VTEs was 12.3 years compared with 20.5 years without VTEs. The overall five-year graft survival of the whole group was 78.3%.

To the best of our knowledge, this is the largest analysis of VTEs post kidney transplantation in the literature. This retrospective analysis showed that VTEs increased the risk of graft failure by about 30%, but this effect was not statistically significant. Adjusting for confounding variables did not alter this finding. These included age, gender and cold ischemia time. The lack of statistical significance could be due to the study being underpowered. In addition to being a single-center experience, this study is also limited by its retrospective nature, which made it impossible to account for silent venous thromboembolic attacks. These might have potentially biased the findings of this study.


   Conclusion Top


VTEs increase the risk of graft failure in recipients of kidney transplants. However, in our study, these effects were not statistically significant. Till the impact of VTEs on graft and patient survival is proven in further largerscale studies, we feel that thromboprophylaxis in these transplant recipients may be useful as they are a high-risk group.

Conflict of interest: None

 
   References Top

1.
Anderson FA Jr, Wheeler HB. Venous thromboembolism. Risk factors and prophylaxis. Clin Chest Med 1995;16:235-51.  Back to cited text no. 1
    
2.
Abdel-Razeq H. Venous thromboembolism prophylaxis for hospitalized medical patients, current status and strategies to improve. Ann Thorac Med 2010;5:195-200.  Back to cited text no. 2
[PUBMED]  Medknow Journal  
3.
Lankeit M, Konstantinides S. Mortality risk assessment and the role of thrombolysis in pulmonary embolism. Clin Chest Med 2010;31: 759-69.  Back to cited text no. 3
    
4.
Bagot CN, Arya R. Virchow and his triad: A question of attribution. Br J Haematol 2008;143:180-90.  Back to cited text no. 4
    
5.
Anderson FA Jr, Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hos-pital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study. Arch Intern Med 1991;151:933-8.  Back to cited text no. 5
    
6.
Humar A, Johnson EM, Gillingham KJ, et al. Venous thromboembolic complications after kidney and kidney-pancreas transplantation: A multivariate analysis. Transplantation 1998;65:229-34.  Back to cited text no. 6
    
7.
Allen RD, Michie CA, Murie JA, Morris PJ. Deep venous thrombosis after renal transplantation. Surg Gynecol Obstet 1987;164:137-42.  Back to cited text no. 7
[PUBMED]    
8.
Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians EvidenceBased Clinical Practice Guidelines (8th Edition). Chest 2008;133(6 Suppl):381-453S.  Back to cited text no. 8
    
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Roberts A, Young WF. Prophylactic retrievable inferior vena cava filters in spinal cord injured patients. Surg Neurol Int 2010;1:68.  Back to cited text no. 9
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Ageno W. Recent advances in the management of venous thromboembolism. Korean J Hematol 2010;45:8-13.  Back to cited text no. 10
    
11.
Huo MH, Muntz J. Extended thromboprophylaxis with low-molecular-weight heparins after hospital discharge in high-risk surgical and medical patients: A review. Clin Ther 2009;31:1129-41.  Back to cited text no. 11
    
12.
Hull RD, Pineo GF, Stein PD, et al. Extended out-of-hospital low-molecular-weight heparin prophylaxis against deep venous thrombosis in patients after elective hip arthroplasty: A systematic review. Ann Intern Med 2001;135:858-69.  Back to cited text no. 12
    
13.
Lensing AW, Prandoni P, Brandjes D, et al. Detection of deep-vein thrombosis by real-time B-mode ultrasonography. N Engl J Med 1989;320:342-5.  Back to cited text no. 13
    
14.
Mattos MA, Londrey GL, Leutz DW, et al. Color-flow duplex scanning for the surveillance and diagnosis of acute deep venous thrombosis. J Vasc Surg 1992;15:366-75.  Back to cited text no. 14
    
15.
Monreal M, Montserrat E, Salvador R, et al. Real-time ultrasound for diagnosis of symptomatic venous thrombosis and for screening of patients at risk: Correlation with ascending conventional venography. Angiology 1989;40:527-33.  Back to cited text no. 15
    
16.
PIOPED Investigators. Value of the ventilation/ perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA 1990;263:2753-9.  Back to cited text no. 16
    
17.
Schoepf UJ, Goldhaber SZ, Costello P. Spiral computed tomography for acute pulmonary embolism. Circulation 2004;109:2160-7.  Back to cited text no. 17
    
18.
Trowbridge RL, Araoz PA, Gotway MB, Bailey RA, Auerbach AD. The effect of helical computed tomography on diagnostic and treatment strategies in patients with suspected pulmonary embolism. Am J Med 2004;116:84-90.  Back to cited text no. 18
    
19.
Gangireddy C, Rectenwald JR, Upchurch GR, et al. Risk factors and clinical impact of postoperative symptomatic venous thromboembolism. J Vasc Surg 2007;45:335-41.  Back to cited text no. 19
    
20.
Yegen HA, Lederer DJ, Barr RG, et al. Risk factors for venous thromboembolism after lung transplantation. Chest 2007;132:547-53.  Back to cited text no. 20
    

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Correspondence Address:
Dr. Mazen Hassanain
Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia

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DOI: 10.4103/1319-2442.148707

PMID: 25579708

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