Skip to main content
Log in

Anti-platelet factor 4/heparin antibody is associated with progression of peripheral arterial disease in hemodialysis patients

  • Nephrology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Background

Heparin therapy may induce anti-platelet factor 4/heparin antibody (PF4-H Ab). Hemodialysis patients receive scheduled heparin and are at a risk of developing PF4-H Ab. Hemodialysis patients are also at a high risk of peripheral arterial disease (PAD). This study examines whether chronic PF4-H Ab exposure contributes to the progression of PAD measured by ankle brachial index (ABI) in hemodialysis patients.

Materials and methods

A total of 71 hemodialysis patients were enrolled, and the association between clinical, biochemical parameters and ABI after 3 years was studied. PF4-H Ab was evaluated by ELISA, and patients with titer ≥0.4 were taken as having PF4-H Ab.

Results

Mean ABI was 1.04 ± 0.18 at baseline and 1.01 ± 0.17 after 3 years. Mean ΔABI (change in ABI after 3 years) was −0.04 ± 0.13. PF4-H Ab was positive in 26 patients. PF4-H Ab was not related to hemodialysis duration, DM history, smoking and age. Platelet count showed no correlation with PF4-H Ab. However, there was significance in ΔABI between PF4-H Ab-positive and PF4-H Ab-negative patients (p = 0.002). ΔABI was negatively correlated with PF4-H Ab and 3-year averaged serum Ca × P only (β = −0.378, p = 0.001; β = −0.263, p = 0.018, respectively). However, in PF4-H Ab-positive patients, the extent of ΔABI did not correlate with PF4-H Ab titers (r = −0.021, p = 0.921).

Conclusions

PF4-H Ab positivity, along with high levels of serum Ca × P, played a potential role in the progression of PAD over time.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Haase M, Bellomo R, Rocktaeschel J et al (2005) Use of fondaparinux (arixtra) in a dialysis patient with symptomatic heparin-induced thrombocytopaenia type ii. Nephrol Dial Transplant 20:444–446

    Article  PubMed  Google Scholar 

  2. Kelton JG, Warkentin TE (2008) Heparin-induced thrombocytopenia: a historical perspective. Blood 112:2607–2616

    Article  CAS  PubMed  Google Scholar 

  3. Blank M, Shoenfeld Y, Tavor S et al (2002) Anti-platelet factor 4/heparin antibodies from patients with heparin-induced thrombocytopenia provoke direct activation of microvascular endothelial cells. Int Immunol 14:121–129

    Article  CAS  PubMed  Google Scholar 

  4. Carrier M, Rodger MA, Fergusson D et al (2008) Increased mortality in hemodialysis patients having specific antibodies to the platelet factor 4-heparin complex. Kidney Int 73:213–219

    Article  CAS  PubMed  Google Scholar 

  5. Krane V, Berger M, Lilienthal J, Winkler K, Schambeck C, Wanner C (2010) Antibodies to platelet factor 4-heparin complex and outcome in hemodialysis patients with diabetes. Clin J Am Soc Nephrol 5:874–881

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Pena de la Vega L, Miller RS, Benda MM et al (2005) Association of heparin-dependent antibodies and adverse outcomes in hemodialysis patients: a population-based study. Mayo Clin Proc 80:995–1000

    Article  PubMed  Google Scholar 

  7. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY (2004) Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 351:1296–1305

    Article  CAS  PubMed  Google Scholar 

  8. Golomb BA, Dang TT, Criqui MH (2006) Peripheral arterial disease: morbidity and mortality implications. Circulation 114:688–699

    Article  PubMed  Google Scholar 

  9. O’Hare AM, Katz R, Shlipak MG, Cushman M, Newman AB (2006) Mortality and cardiovascular risk across the ankle-arm index spectrum: results from the cardiovascular health study. Circulation 113:388–393

    Article  PubMed  Google Scholar 

  10. Halperin JL (2002) Evaluation of patients with peripheral vascular disease. Thromb Res 106:V303–V311

    Article  CAS  PubMed  Google Scholar 

  11. Tanaka M, Ishii H, Aoyama T et al (2011) Ankle brachial pressure index but not brachial-ankle pulse wave velocity is a strong predictor of systemic atherosclerotic morbidity and mortality in patients on maintenance hemodialysis. Atherosclerosis 219:643–647

    Article  CAS  PubMed  Google Scholar 

  12. Kitahara T, Ono K, Tsuchida A et al (2005) Impact of brachial-ankle pulse wave velocity and ankle-brachial blood pressure index on mortality in hemodialysis patients. Am J Kidney Dis 46:688–696

    Article  PubMed  Google Scholar 

  13. Matsuo T, Kobayashi H, Matsuo M et al (2006) Frequency of anti-heparin-PF4 complex antibodies (hit antibodies) in uremic patients on chronic intermittent hemodialysis. Pathophysiol Haemost Thromb 35:445–450

    Article  CAS  PubMed  Google Scholar 

  14. Palomo I, Pereira J, Alarcon M et al (2005) Prevalence of heparin-induced antibodies in patients with chronic renal failure undergoing hemodialysis. J Clin Lab Anal 19:189–195

    Article  CAS  PubMed  Google Scholar 

  15. Sitter T, Spannagl M, Banas B, Schiffl H (1998) Prevalence of heparin-induced PF4-heparin antibodies in hemodialysis patients. Nephron 79:245–246

    Article  CAS  PubMed  Google Scholar 

  16. O’Hare AM, Hsu CY, Bacchetti P, Johansen KL (2002) Peripheral vascular disease risk factors among patients undergoing hemodialysis. J Am Soc Nephrol 13:497–503

    PubMed  Google Scholar 

  17. Cheung AK, Sarnak MJ, Yan G et al (2000) Atherosclerotic cardiovascular disease risks in chronic hemodialysis patients. Kidney Int 58:353–362

    Article  CAS  PubMed  Google Scholar 

  18. Tsai YF, Chen CA, Kuo C, Lin KC (2012) Anti-PF4/heparin antibodies are associated with arteriovenous fistula thrombosis in non-diabetic hemodialysis patients. Clin Exp Nephrol 16:300–305

    Article  CAS  PubMed  Google Scholar 

  19. DeLoach SS, Mohler ER 3rd (2007) Peripheral arterial disease: a guide for nephrologists. Clin J Am Soc Nephrol 2:839–846

    Article  PubMed  Google Scholar 

  20. Asmis LM, Segal JB, Plantinga LC et al (2008) Heparin-induced antibodies and cardiovascular risk in patients on dialysis. Thromb Haemost 100:498–504

    CAS  PubMed  Google Scholar 

  21. Whitlatch NL, Perry SL, Ortel TL (2008) Anti-heparin/platelet factor 4 antibody optical density values and the confirmatory procedure in the diagnosis of heparin-induced thrombocytopenia. Thromb Haemost 100:678–684

    PubMed Central  CAS  PubMed  Google Scholar 

  22. Morel O, Toti F, Hugel B et al (2006) Procoagulant microparticles: disrupting the vascular homeostasis equation? Arterioscler Thromb Vasc Biol 26:2594–2604

    Article  CAS  PubMed  Google Scholar 

  23. Neven E, De Schutter TM, Behets GJ, Gupta A, D’Haese PC (2011) Iron and vascular calcification. Is there a link? Nephrol Dial Transplant 26:1137–1145

    Article  CAS  PubMed  Google Scholar 

  24. Ohtake T, Oka M, Ikee R et al (2011) Impact of lower limbs’ arterial calcification on the prevalence and severity of pad in patients on hemodialysis. J Vasc Surg 53:676–683

    Article  PubMed  Google Scholar 

  25. Schoppet M, Shroff RC, Hofbauer LC, Shanahan CM (2008) Exploring the biology of vascular calcification in chronic kidney disease: what’s circulating? Kidney Int 73:384–390

    Article  CAS  PubMed  Google Scholar 

  26. Rajagopalan S, Dellegrottaglie S, Furniss AL et al (2006) Peripheral arterial disease in patients with end-stage renal disease: observations from the dialysis outcomes and practice patterns study (DOPPS). Circulation 114:1914–1922

    Article  PubMed  Google Scholar 

  27. Libby P, Ridker PM, Maseri A (2002) Inflammation and atherosclerosis. Circulation 105:1135–1143

    Article  CAS  PubMed  Google Scholar 

  28. Takemoto M, Liao JK (2001) Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors. Arterioscler Thromb Vasc Biol 21:1712–1719

    Article  CAS  PubMed  Google Scholar 

  29. McDermott MM, Guralnik JM, Greenland P et al (2003) Statin use and leg functioning in patients with and without lower-extremity peripheral arterial disease. Circulation 107:757–761

    Article  CAS  PubMed  Google Scholar 

  30. Kumbhani DJ, Steg PG, Cannon CP et al (2014) Statin therapy and long-term adverse limb outcomes in patients with peripheral artery disease: insights from the reach registry. Eur Heart J 35:2864–2872

    Article  PubMed  Google Scholar 

  31. Schillinger M, Exner M, Mlekusch W et al (2004) Statin therapy improves cardiovascular outcome of patients with peripheral artery disease. Eur Heart J 25:742–748

    Article  CAS  PubMed  Google Scholar 

  32. Wanner C, Krane V, Marz W et al (2005) Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 353:238–248

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Chien-An Chen.

Ethics declarations

Funding sources

This study was not funded.

Conflict of interest

All authors declare no conflict of interest.

Additional information

Yen-Hsun Chen and Kao-Chang Lin contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, YH., Lin, KC., Tsai, YF. et al. Anti-platelet factor 4/heparin antibody is associated with progression of peripheral arterial disease in hemodialysis patients. Int Urol Nephrol 47, 1565–1570 (2015). https://doi.org/10.1007/s11255-015-1056-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-015-1056-3

Keywords

Navigation