Thrombophilic risk factors in hemodialysis: Association with early vascular access occlusion and patient survival in long-term follow-up

English version

Autoři: Clemens Grupp ^aff001; Ilka Troche-Polzien ^aff001; Johanna Stock ^aff001; Carsten Bramlage ^aff001; Gerhard A. Müller ^aff001; Michael Koziolek ^aff001
Působiště autorů: Department of Nephrology and Rheumatology, Georg-August University, Goettingen, Germany ^aff001
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0222102

Souhrn

Objective

Thrombophilic risk factors (TRFs) occur rather frequently in hemodialysis (HD) patients. However, little is known about their significance in HD patients, besides their potential impact on arteriovenous (AV) access failure, with varying results. We examined the effects of a wide variety of TRFs on both early AV fistula occlusion and survival among HD patients in long-term follow-up.

Methods

In this single-center, observational study, 70 consecutive HD patients from our dialysis center were examined with respect to shunt occlusion within the first 2 years after fistula creation and patient survival in a long-term follow-up (at least 16 years). We examined the presence of factor V, prothrombin, and MTHFR mutations using real-time fluorescence polymerase chain reaction. Furthermore, antithrombin (AT), protein C, protein S, and antiphospholipid antibodies (APL-Abs) were assessed.

Results

Among the 70 patients, 32 had MTHFR mutations, 10 had heterozygous factor V Leiden mutations, 4 had prothrombin mutations, 4 had protein S deficiency, 2 had protein C deficiency, 9 had AT deficiency, and 14 had APL-Abs. 40 patients had shunt occlusion. TRFs were associated with a significantly increased risk for shunt thrombosis (P<0.02). Kaplan–Meier analysis with a log-rank test revealed significantly shorter survival in HD patients with TRFs (P<0.02). Cox regression analysis showed that the presence of TRFs (P<0.05; hazard ratio, 1.94; 95% CI: 1.07–3.56), but not early shunt occlusion, was associated with short patient survival.

Conclusions

TRFs in hemodialysis patients have a strong impact on patient survival and early AV fistula failure; however, patient survival is not significantly affected by early shunt occlusion.

Klíčová slova:

Biology and life sciences – Biochemistry – Enzymology – Enzymes – Proteins – Medicine and health sciences – Pathology and laboratory medicine – Diagnostic medicine – Signs and symptoms – Hematology – Surgical and invasive medical procedures – Proteases – Cardiovascular medicine – Epidemiology – Medical risk factors – Transplantation – Organ transplantation – Renal transplantation – Urinary system procedures – Nephrology – Medical dialysis – Serine proteases – Cardiovascular diseases – Fistulas – Blood coagulation – Coagulation disorders – Protein C deficiency – Factor V Leiden

Zdroje

1. Osinbowale O, Ali L, Chi YW. Venous thromboembolism: a clinical review. Postgrad Med. 2010; 122: 54–65 doi: 10.3810/pgm.2010.03.2122 20203456

2. Khan S, Dickerman JD. Hereditary thrombophilia. Thromb J. 2006; 4: 15 doi: 10.1186/1477-9560-4-15 16968541

3. Reitsma PH. Genetics in thrombophilia. An update. Hamostaseologie. 2015; 35: 47–51

4. Salmela B, Hartman J, Peltonen S, Albäck A, Lassila R. Thrombophilia and arteriovenous fistula survival in ESRD. Clin J Am Soc Nephrol. 2013; 8: 962–968 doi: 10.2215/CJN.03860412 23411429

5. Klamroth R, Orlovic M, Fritsche I, Seibt S, Seibt F, Wegscheider K, et al. The influence of thrombophilic risk factors on vascular access survival in chronic dialysis patients in a retrospective evaluation. Vasa. 2013; 42: 32–39 doi: 10.1024/0301-1526/a000245 23385224

6. Knoll GA, Wells PS, Young D, Perkins SL, Pilkey RM, Clich JJ, et al. Thrombophilia and the risk for hemodialysis vascular access thrombosis. J Am Soc Nephrol. 2005; 16: 1108–1114 doi: 10.1681/ASN.2004110999 15728780

7. Ghisdal L, Broeders N, Wissing KM, Mena JM, Wijns W, Pradier O, et al. Thrombophilic factors in Stage V chronic kidney disease patients are largely corrected by renal transplantation. Nephrol Dial Transplant. 2011; 26: 2700–2705 doi: 10.1093/ndt/gfq791 21285127

8. Palomo I, Pereira J, Alarcon M, Vasquez M, Pierangeli S. Vascular access thrombosis is not related to presence of antiphospholipid antibodies in patients on chronic hemodialysis. Nephron. 2002; 92: 957–958 doi: 10.1159/000065580 12399653

9. Hojs R, Gorenjak M, Ekart R, Dvoršak B, Pečovnik-Balon B. Homocysteine and vascular access thrombosis in hemodialysis patients. Ren Fail. 2002; 24: 215–222 doi: 10.1081/jdi-120004098 12071595

10. Adler S, Szczech L, Qureshi A, Bollu R, Thomas-John R. IgM anticardiolipin antibodies are associated with stenosis of vascular access in hemodialysis patients but do not predict thrombosis. Clin Nephrol. 2001; 56: 428–434 11770794

11. Fodinger M, Mannhalter C, Pabinger I, Koizar D, Rintelen C, Horl WH et al. Resistance to activated protein C (APC): mutation at Arg506 of coagulation factor V and vascular access thrombosis in haemodialysis patients. Nephrol Dial Transplant. 1996; 11: 668–672. 8671856

12. LeSar CJ, Merrick HW, Smith MR. Thrombotic complications resulting from hypercoagulable states in chronic hemodialysis vascular access. J Am Coll Surg. 1999; 189: 73–79 10401743

13. Fukasawa M, Matsushita K, Kamiyama M, Mikami Y, Araki I, Yamagata Z et al. The methylentetrahydrofolate reductase C677T point mutation is a risk factor for vascular access thrombosis in hemodialysis patients. Am J Kidney Dis. 2003; 41: 637–642 doi: 10.1053/ajkd.2003.50125 12612987

14. Feldman HI, Kobrin S, Wasserstein A. Hemodialysis vascular access morbidity. J Am Soc Nephrol. 1996; 7: 523–535 8724885

15. Almasri J, Alsawas M, Mainou M, Mustafa RA, Wang Z, Woo K et al. Outcomes of vascular access for hemodialysis: A systematic review and meta-analysis. J Vasc Surg. 2016; 64: 236–243 doi: 10.1016/j.jvs.2016.01.053 27345510

16. Biuckians A, Scott EC, Meier GH, Panneton JM, Glickman MH. The natural history of autologous fistulas as first-time dialysis access in the KDOQI era. J Vasc Surg. 2008; 47: 415–421; discussion 420–421 doi: 10.1016/j.jvs.2007.10.041 18241764

17. Dixon BS, Novak L, Fangman J. Hemodialysis vascular access survival: upper-arm native arteriovenous fistula. Am J Kidney Dis. 2002; 39: 92–101 doi: 10.1053/ajkd.2002.29886 11774107

18. Puskar D, Pasini J, Savic I, Bedalov G, Sonicki Z. Survival of primary arteriovenous fistula in 463 patients on chronic hemodialysis. Croat Med J. 2002; 43: 306–311 12035137

19. Allon M, Robbin ML. Increasing arteriovenous fistulas in hemodialysis patients: problems and solutions. Kidney Int. 2002; 62: 1109–1124 doi: 10.1111/j.1523-1755.2002.kid551.x 12234281

20. von Ahsen N, Schutz E, Armstrong VW, Oellerich M. Rapid detection of prothrombotic mutations of prothrombin (G20210A), factor V (G1691A), and methylenetetrahydrofolate reductase (C677T) by real-time fluorescence PCR with the LightCycler. Clin Chem. 1999; 45: 694–696 10222362

21. von Ahsen N, Oellerich M, Schutz E. A method for homogeneous color-compensated genotyping of factor V (G1691A) and methylenetetrahydrofolate reductase (C677T) mutations using real-time multiplex fluorescence PCR. Clin Biochem. 2000; 33: 535–539 doi: 10.1016/s0009-9120(00)00161-2 11124338

22. Huisman MV, Rosendaal F. Thrombophilia. Curr Opin Hematol. 1999; 6: 291–297 10468143

23. Middeldorp S, Levi M. Thrombophilia: an update. Semin Thromb Hemost. 2007; 33: 563–572 doi: 10.1055/s-2007-985752 17768688

24. Seligsohn U, Lubetsky A. Genetic susceptibility to venous thrombosis. N Engl J Med. 2001; 344: 1222–1231 doi: 10.1056/NEJM200104193441607 11309638

25. Ambuhl PM, Wuthrich RP, Korte W, Schmid L, Krapf R. Plasma hypercoagulability in haemodialysis patients: impact of dialysis and anticoagulation. Nephrol Dial Transplant.1997;12(11): 2355–2364 doi: 10.1093/ndt/12.11.2355 9394323

26. Hessner MJ, Luhm RA, Pearson SL, Endean DJ, Friedman KD, Montgomery RR. Prevalence of prothrombin G20210A, factor V G1691A (Leiden), and methylenetetrahydrofolate reductase (MTHFR) C677T in seven different populations determined by multiplex allele-specific PCR. Thromb Haemost. 1999; 81: 733–738 10365746

27. Lee HA, Choi JS, Ha KS, Yang DH, Chang SK, Hong SY. Influence of 5,10- methylenetetrahydrofolate reductase gene polymorphism on plasma homocysteine concentration in patients with end-stage renal disease. Am J Kidney Dis. 1999; 34: 259–263 doi: 10.1016/s0272-6386(99)70353-7 10430972

28. Rodriguez JA, Ferrer E, Olmos A, Codina S, Borrellas J, Piera L. [Analysis of the survival of permanent vascular access ports]. Nefrologia 2001; 21: 260–273 [Article in Spanish] 11471307

29. Fodinger M, Horl WH, Sunder-Plassmann G. Molecular biology of 5,10- methylenetetrahydrofolate reductase. J Nephrol. 2000; 13: 20–33 10720211

30. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ. 2002; 325: 1202 doi: 10.1136/bmj.325.7374.1202 12446535

31. Bremer C, Schaefer RM. Heterozygosity for factor V Leiden in a haemodialysis patient with recurrent shunt thrombosis. Nephrol Dial Transplant. 1997; 12: 1775–1776 doi: 10.1093/ndt/12.8.1775 9269682

32. Valeri A, Joseph R, Radhakrishnan J. A large prospective survey of anti-cardiolipin antibodies in chronic hemodialysis patients. Clin Nephrol. 1999; 51(2): 116–121 10069647

33. Tonelli M, Wiebe N, Knoll G, Bello A, Browne S, Jadhav D, et al. Systematic review: kidney transplantation compared with dialysis in clinically relevant outcomes. Am J Transplant. 2011; 11: 2093–2109 doi: 10.1111/j.1600-6143.2011.03686.x 21883901

34. Nakashima MO, Rogers HJ. Hypercoagulable states: an algorithmic approach to laboratory testing and update on monitoring of direct oral anticoagulants. Blood Res. 2014;49(2): 85–94 doi: 10.5045/br.2014.49.2.85 25025009

35. Brunet P, Aillaud MF, San Marco M, Philip-Joet C, Dussol B, Bernard D, et al. Antiphospholipids in hemodialysis patients: relationship between lupus anticoagulant and thrombosis. Kidney Int. 1995;48(3): 794–800 doi: 10.1038/ki.1995.352 7474666

36. Prakash R, Miller CC 3rd, Suki WN. Anticardiolipin antibody in patients on maintenance hemodialysis and its association with recurrent arteriovenous graft thrombosis. Am J Kidney Dis. 1995;26(2): 347–352 doi: 10.1016/0272-6386(95)90656-8 7645540

37. Chuang FR, Chen TC, Yang CC, Cheng YF, Hsu KT, Lee CH, et al. IgM-anticardiolipin antibody and vascular access thrombosis in chronic hemodialysis patients. Ren Fail 2005;27(1): 25–30 15717631

38. Chen TY, Lin L, Hsieh MY, Chen YF, Hsu KT, Lee CH. Thrombophilia Associated with Early Post-angioplasty Thrombosis of Dialysis Vascular Access. Cardiovasc Intervent Radiol 2018;41(11): 1683–1690 doi: 10.1007/s00270-018-2046-5 30066093

39. Palmer SC, Di Micco L, Razavian M, Craig JC, Perkovic V, Pellegrini F et al. Effects of antiplatelet therapy on mortality and cardiovascular and bleeding outcomes in persons with chronic kidney disease: a systematic review and meta-analysis. Ann Intern Med. 2012; 156: 445–459 doi: 10.7326/0003-4819-156-6-201203200-00007 22431677

40. Palmer SC, Di Micco L, Razavian M, Craig JC, Ravani P, Perkovic V, et al. Effects of antiplatelet therapy on mortality and cardiovascular and bleeding outcomes in persons with chronic kidney disease: a systematic review and meta-analysis. Ann Intern Med 2012;156(6):445–459 doi: 10.7326/0003-4819-156-6-201203200-00007 22431677

41. Tanner NC, Da Silva A. Medical adjuvant treatment to increase patency of arteriovenous fistulae and grafts. Cochrane Database Syst Rev 2015(7): Cd002786 doi: 10.1002/14651858.CD002786.pub3 26184395