Dialysis Technique Anti-coagulant, Something You Should Know Assoc. Prof. Bancha Satirapoj, MD Division of Nephrology Department of Medicine Phramongkutklao Hospital and College of Medicine
Low molecular weight heparin ❖ More specific binding action >UFH ❖ Easier to dose by weight ❖ Single prefilled syringe injection ❖ Prefer IV > SC
LMWH for Anticoagulation During Long-term Hemodialysis LMWH MW Anti-Xa: HF Dose Dose for high risk of (kDa) anti-IIa (hr) bleeding Enoxaparin ratio Nadroparin Tinzaparin 4,200 3.8 13.9 0.7 mg/kg 0.5 mg/kg Dalteparin 4,200 3.6 2.5-3.5 70 IU/kg 35 IU/kg 4,500 1.9 2.3 1,500-3,500 IU 2,000 IU 6,000 2.7 2.2 5,000 IU 2,500 IU บัญชา สถิระพจน์, Manual of Dialysis. กรุงเทพ: นำอักษรการพิมพ์; 2561.
LMWH for Anticoagulation During Long-term Hemodialysis LMWH MW Anti-Xa: HF Dose Dose for high risk of (kDa) anti-IIa (hr) bleeding Enoxaparin ratio Nadroparin Tinzaparin 4,200 3.8 13.9 0.7 mg/kg 0.5 mg/kg Dalteparin 4,200 3.6 2.5-3.5 70 IU/kg 35 IU/kg 4,500 1.9 2.3 1,500-3,500 IU 2,000 IU 6,000 2.7 2.2 5,000 IU 2,500 IU บัญชา สถิระพจน์, Manual of Dialysis. กรุงเทพ: นำอักษรการพิมพ์; 2561.
Monitor anticoagulations ❖ No routinely measure anticoagulation parameters ❖ Dialyzer clotting ❖ Prolonged bleeding following dialysis ❖ Monitoring with the activated partial thromboplastin time (aPTT) is not accurate ❖ Measurement of anti-factor Xa levels keep 0.4-0.6 IU/mL or high risk bleeding 0.2-0.4 IU/mL
❖ 36 chronic HD patients: randomly assigned to enoxaparin (1 MKD) or standard heparin, followed for 12 wks Frequency of clot formation (%) in dialyser, graded on a 10-point scale Saltissi D, et al. Nephrol Dial Transplant 1999;14:2698-703.
❖ 3 6Sicnhgrloen-idcoHsDeppartoietonctso:lroafndeonmoxlyapaasrsingnisedan etoffencotixvaepanridn v(1erMyKcDo)novresntaienndtaardltehrenpaatriivne, to followed for 12swodkisum heparin Frequency of clot formation (%) in blood line, graded on a 10-point scale Saltissi D, et al. Nephrol Dial Transplant 1999;14:2698-703.
Efficacy and Safety of Enoxaparin during Hemodialysis: Results from the HENOX Study A❖sinCglilnei-cdaol seeffirceagcimy eandofseanfeotxyaopfareinosxoadpiaurmin0s.7odmiugm/kgfoirstahneeafnfeticctoivaeg,uwlaetlilo-ntoelfeferactted, during HD in 99 calinndiccaollnyvsetnaibenlet EaSlteRrDnaptaivtieentotss.odium heparin Vareesangthip K et al. J Med Assoc Thai 2011; 94 (1): 21-6.
Meta-analysis: LMWH vs. Heparin Extracorporeal circuit thrombosis LMWH and unfractionated heparin are similarly effective in preventing extracorporeal circuit thrombosis Lim W, et al. J Am Soc Nephrol 2004;15:3192-206.
Systematic review and meta-analysis: LMWH vs. Heparin From a total of 971, we identified 17 studies (total 15 studies, bleeding 9 studies and lipid 11 studies) Lazrak et al. BMC Nephrology. 2017: 18:187
Systematic review and meta-analysis: LMWH vs. Heparin Total bleeding LMWH showed to be at least as safe as UFH for ECC anticoagulation in chronic hemodialysis Lazrak et al. BMC Nephrology. 2017: 18:187
Kessler M et al. Seminars in Dialysis. 2015: 28: 474-89.
Adverse effects: LMWH vs. Heparin ❖ Hyperlipidemia ❖ Osteoporosis ❖ Hyperkalemia ❖ Thrombocytopenia UFH releases and depletes endothelium-bound lipoprotein lipase causing hypertriglyceridemia
Reduced TG concentrations during four years of dialysis with LMWH TG levels were decreased when patients switched to LMWH and rebounded when they reverted to UFH Deuber HJ, Schulz W. Kidney Int 1991;40:496-500.
Reduced TG concentrations during four years of dialysis with LMWH Cholesterol levels were decreased when patients switched to LMWH and rebounded when they reverted to UFH Deuber HJ, Schulz W. Kidney Int 1991;40:496-500.
Systematic review and meta-analysis: LMWH vs. Heparin Triglyceride level The WMD calculated for triglycerides of −55.57 mg/dl (95% CI -94.49 to −16.66) Lazrak et al. BMC Nephrology. 2017: 18:187
Systematic review and meta-analysis: LMWH vs. Heparin Cholesterol level The WMD calculated for total cholesterol was −28.70 mg/dl (95% CI -51.43 to −5.98), Lazrak et al. BMC Nephrology. 2017: 18:187
Adverse effects: LMWH vs. Heparin ❖ Hyperlipidemia ❖ Osteoporosis ❖ Hyperkalemia ❖ Thrombocytopenia UFH is known to increase the risk of osteoporosis
Following LMWH treatment, TRACP was reduced by 13% (p<0.05) Tartrate-resistant acid phosphatase (TRACP) and i-PTH Bone-specific alkaline phosphatase (BALP) and intact osteocalcin (OSC) ❖ Tartrate-resistant acid phosphatase (TRACP) reflecting osteoclastic activity was elevated in 35% of patients. Lai KN, et al. Int J Artif Organs 2001;24:447-55.
Heparin and LMWH with bone mineral disease ❖ UFH is known to increase the risk of osteoporosis in pregnancy ❖ LMWH may partially alleviate osteoporosis associated with UFH administration in patients on maintenance hemodialysis.
Systematic review and meta-analysis: LMWH vs. Heparin LMWH showed to be at least as safe as UFH for ECC anticoagulation in chronic hemodialysis The limited number of studies reporting on osteoporosis and HIT does not allow any conclusion for these outcomes. Lazrak et al. BMC Nephrology. 2017: 18:187
Adverse effects: LMWH vs. Heparin ❖ Hyperlipidemia ❖ Osteoporosis ❖ Hyperkalemia ❖ Thrombocytopenia Aldosterone suppression and subsequent hyperkalemia are well described reversible side effects of prolonged treatment with heparin
Heparin-induced hyperkalemia in chronic hemodialysis patients: comparison of LMWH and unfractionated heparin Predialysis potassium levels decreased from 5.66 mEq/L to 5.15 mEq/L when patients were given LMWH instead of UFH Hottelart C, et al. Artif Organs. 1998;22(7):614-617.
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