Thrombosis risks of permanent vascular access

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Up to the moment, causes for complication of permanent vascular access (PDA) in patients with technically correct implementation of surgical intervention remain unclear [1]. The formed native arterio-venous fistula (AVF) works on average within 3-5 years, duration or this period reduces due to development of complications (thrombosis, stenosis, fistula vein aneurysm). With time the amount of patients with functional AVF declines [2]. The most common complication on the part of PVA which happens in 60% to 90% of cases is thrombosis of AVF. At present a number of rules are elaborated for use of PVA with the aim to prevent such complications as thrombosis, hemorrhage, infection of permanent vascular access, aneurysms of fistula vein. However, no methods have been developed permitting to detect changes in the fistula vein that impair the quality of hemodialysis to the extent of appearance of clinical manifestations requiring surgical, sometimes urgent, correction. Many works have been conducted to study factors that influence the risk of thrombus formation, such as low resistance of the vessel wall [3], prolongation of antiplatelet and anticoagulant therapy in dialysis patients [4, 5], stenosis of fistula vein [6], and to assess the influence of circulating complexes [7]. Nevertheless, there remain many causes and mechanisms of complications of PVA as well as factors influencing the frequency of complications, that are not yet completely studied.

Aim – to carry out a complex analysis of factors influencing initiation of thrombosis of permanent vascular access and to determine their significance.

Materials and Methods

The results of surgical treatment of 168 patients with terminal stage of chronic kidney disease were monitored. Of them 73 (43%) were women and 95 (57%) were men. The mean age was 56±14 years. The results of treatment of the diseases were traced within 1 year (from September 2016 to September 2017).

In all patients PVA was performed in the lower third of the forearm by a modified technique proposed by M.J. Brescia и J.E. Cimino (1966): under local anesthesia from transverse access in the lower third of forearm with formation of anastomose of the type ‘end of cephalic vein into the side of radial artery’ by microsurgery methods using general surgical and microvascular kits. In all patients in the postoperative period a distinct systolic-diastolic thrill of the anastomosed vein was noted.

According to the results of treatment patients were divided into 2 groups: the 1^st group – with no thrombosis of AVF within the first year of hemodialysis (n=126), the 2^nd group included patients with dysfunction of PVA within the first year due to thrombosis (n=42).

In all patients included into the study, the history of the main disease that led to the terminal stage of CKD and a related pathology were evaluated, and preoperative examination was conducted with the aim to determine localization of access depending on the condition of arterial and venous bed in the scope of US examination using the Philips Envisor C HD apparatus (the Netherland) before and after tourniquet test.

Parameters of the initial condition of the patient before surgical intervention were analyzed (gender, age, the main diagnosis, existence of essential hypertension, diabetes mellitus, hypotension, atherosclerosis,, ischemic heart disease, characteristics of the radial artery and of cephalic vein).

In pre- and postoperative period, parameters of CBC, of biochemical blood test, of formation of the aneurysm of the fistula vein during its use, speed characteristics of blood in the fistula, infections of vascular access were analyzed; in postoperative period – anticoagulant and antiplatelet therapy, antibiotic therapy.

Statistical processing was carried out using Statistica 12.0 (StatSoft Inc., USA), MedCalc® 18.2.1 (MedCalc Software, Belgium) programs. Basic descriptive characteristics, comparisons of differences between the groups, extended statistical methods including calculation of relative risk (RR) and odds ratio (OR), elements of multivariate statistics were used. The level of statistical significance was taken to be р<0.05.

Interpretation of the RR value was conducted in the following way. The relative risk parameter was compared to 1 (unity) to determine the character of relationship between the factor and outcome: if RR equaled 1, it was concluded that the studied factor did not influence the probability of outcome (absence of relationship between the factor and outcome); at the values >1 the factor increased the incidence of outcomes (feed-forward); the values <1 meant a reduction of the probability of outcome under influence of the factor (feedback).

Besides, the limits of 95% confidence interval (CI) were evaluated. If both values – of the lower and upper limits were located on the same side from 1, or, in other words, CI did not include 1, the conclusion was made about statistical significance of the identified link between the factor and outcome with the probability of error p≤0.05.

Results and Discussion

The analysis of the data obtained demonstrated an increase in the quantity of complications with the time of functioning of PVA, and in this context the patients’ data were analyzed in different periods of observation. In result, the patients were divided into groups depending on the time of development of thrombosis, and, accordingly, on the increase in the amount of these complications [8, 9] with the critical point 6 and 12 months (Tables 1, 2).

 

Table 1 Relative risk and odds ratio for initiation of thrombosis with critical point of 6 months of functioning

	Value	CI -95%	CI +95%	Significance Level, р
RR	4.75	2.06	10.93	0.0002
OR	5.77	2.35	14.17	0.0001

 

Table 2 Relative risk and odds ratio for initiation of thrombosis with critical point of 12 months of functioning

	Value	CI -95%	CI +95%	Significance Level, р
RR	1.20	0.24	5.89	0.0080
OR	1.63	1.22	2.17	0.0070

 

For evaluation of probable risk factors for thrombosis of PVA, relative risks were calculated in different critical intervals, namely before 6 months and after 6 months (Tables 3, 4).

 

Table 3 Relative risks for development of thrombosis of permanent vascular access before 6 months

Factor	RR	CI -95%	CI +95%	Significance Level, р
Atherosclerosis	2.18	0.85	5.60	0.1000
Urea level before operation	0.90	0.51	1.60	0.7200
Blood flow velocity through fistula	0.62	0.27	1.41	0.2500
Stenosis of fistula vain	3.75	0.59	23.66	0.1600
Sepsis	10.50	0.44	252.56	0.1500
Repeated operations	2.57	1.77	3.72	<0.0001
Quantity of repeated operations	0.24	0.09	0.66	0.0050
Reason for repeated operation	0.18	0.03	1.23	0.0800
Duration of anticoagulant therapy	8.79	3.68	20.95	<0.0001
Correction of anticoagulant therapy	5.06	2.56	10.02	<0.0001
Antibiotic treatment	2.51	1.74	3.63	<0.0001
Urea level after operation	1.47	0.60	3.57	0.4000

 

Table 4 Relative risks for development of thrombosis of permanent vascular access in period from 6 to 12 months

Factor	RR	CI -95%	CI +95%	Significance Level, р
Hypotension	9.00	0.96	84.21	0.0541
Atherosclerosis	3.07	1.23	7.67	0.0161
Fistula vein diameter	1.50	1.02	2.22	0.0418
Urea level before operation	0.85	0.48	1.48	0.5583
Repeated operations	2.87	1.97	4.18	<0.0001
Quantity of repeated operations	4.61	1.37	15.54	0.0137
Reason for repeated operation	0.25	0.08	0.77	0.0155
Antiplatelet therapy	1.39	0.57	3.387	0.4713
Anticoagulant therapy	2.95	0.19	46.037	0.4405
Duration of anticoagulant therapy	10.37	4.10	26.28	<0.0001
Correction of anticoagulant therapy	5.90	2.86	12.19	<0.0001
Antibiotic therapy	0.44	0.29	0.69	0.0003
Urea level after operation	1.39	0.57	3.39	0.4644

 

On the basis of the obtained data, risk factor for thrombosis of PVA in 6-month period included: repeated operations, duration of anticoagulant therapy, correction of anticoagulant therapy, antibiotic therapy. Risk factor for thrombosis of PVA in the period from 6 to 12 months included: atherosclerosis, fistula vein diameter, repeated operations, quantity of repeated operations, reason for a repeated operation, duration of anticoagulant therapy, correction of anticoagulant therapy, antibiotic therapy.

Thus, calculation of risk factors in two critical periods permitted to determine a set of parameters that influence development of thrombosis of the permanent vascular access with a high chance of realization that should be taken into consideration.

In the world literature much attention is given to search for dependence of thrombosis on mutations of thrombophilic genes [10, 11], to analysis of blood flow types for development of stenosis [6], and also to monitoring of intraluminal pressure during hemodialysis procedure. All these goals are resource-consuming from the point of view of both labor and money. In the given study for the first time a search for interrelations of thrombosis of permanent vascular access was undertaken using routine diagnostic methods.

Conclusion

The main risk factors promoting thrombosis of permanent access within the first year irrespective of the analyzed period (before 6 months and after 6 months) are atherosclerosis, duration of anticoagulant therapy, correction of anticoagulant therapy, antibiotic therapy, fistula vein diameter, multiple operations, reasons for a repeated operation.

Realization of the stated risk factors is probably not the only reason for development of complications. To consider the probability for development of thrombosis of vascular access in different periods of time it would be reasonable to continue the work with use of multidimensional mathematical modeling.

About the authors

Ilya N. Staroverov

Yaroslavl State Medical University; Regional Clinical Hospital

Email: vestnik@rzgmu.ru
ORCID iD: 0000-0001-9855-9467
SPIN-code: 8011-7176
ResearcherId: М-8174-2014

MD, PhD, Associate Professor, , Head of the Surgery Department of Postgraduate Education Institute, Head of the Department of Vascular Surgery

Russian Federation, Yaroslavl; Yaroslavl

Nikita S. Noshchenko

Yaroslavl State Medical University; Regional Clinical Hospital

Author for correspondence.
Email: noschenko.ns@gmail.com
ORCID iD: 0000-0001-7770-4370
SPIN-code: 4755-6307
ResearcherId: A-7229-2019

PhD-Student of the Surgery Department of Postgraduate Education Institute, Cardiovascular surgeon of the Department of Vascular Surgery

Russian Federation, Yaroslavl; Yaroslavl

Leonid B. Shubin

Yaroslavl State Medical University

Email: vestnik@rzgmu.ru
ORCID iD: 0000-0003-4562-7731
SPIN-code: 8021-7289
ResearcherId: A-9339-2019

MD, PhD, Associate Professor of the Department of Pathological Anatomy

Russian Federation, Yaroslavl

References

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