Platelet activation in clinical haemodialysis: LMWH as a major contributor to bio-incompatibility?

Gritters, Mareille; Borgdorff, Piet; Grooteman, Muriël P.C.; Schoorl, Marianne; Schoorl, Margreet; Bartels, P. C. M.; Tangelder, G. J.; Nubé, Menso J.

doi:10.1093/ndt/gfn137

Cited by 44 publications

(39 citation statements)

References 17 publications

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“…This hypothesis fits with the study of Gritters et al, who previously demonstrated an effect of heparin during HD on proteoglycan-bound PF4 possibly due to LMWH-induced endothelial detachment [16]. VanTeeffelen et al showed in mice that a heparin challenge is associated with increased vascular leakage of dextrans and impaired arteriolar vasodilation during reactive hyperemia, suggesting that competitive binding of heparin to glycocalyx-associated proteins may affect glycocalyx barrier properties [29].…”

Section: Discussionsupporting

confidence: 86%

“…Given the effects of hemodialysis (HD) on platelet activation, and due to the highly dynamic blood-ESL interaction, it can be hypothesized that HD may also have acute effects on the ESL [14,15,16]. However, it is unknown whether ESL damage is exacerbated even during the HD treatment in patients with end-stage renal disease (ESRD).…”

Section: Introductionmentioning

confidence: 99%

“…Another potentially important mediator in ESL alterations could be the use of low molecular weight heparin (LMWH) in HD patients. A recent study showed increased levels of platelet factor 4 (PF-4), released by activated platelets but also after endothelial activation, during HD following LMWH administration [16]. …”

Section: Introductionmentioning

confidence: 99%

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Effects of Ultrapure Hemodialysis and Low Molecular Weight Heparin on the Endothelial Surface Layer

et al. 2014

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Background: Chronic kidney disease patients show changes in the endothelial surface layer (ESL). Whether hemodialysis (HD) itself or low molecular weight heparins (LMWH) induce ESL alterations is unknown. Methods: We studied the ESL in 20 HD patients with Sidestream Dark Field Imaging [measuring perfused boundary region (PBR)] and measurement of ESL constituents in plasma during HD in 2 studies. LMWH was administered at the start of HD in study A, and 120 min after the start of HD in study B. Mean platelet volume (MPV) and platelet large cell ratio (P-LCR) were also measured. Results: Syndecan-1 increased significantly 30 min after LMWH administration. sP-Selectin increased 120 min after HD start, and MPV and P-LCR decreased significantly during HD. No significant changes of PBR, sE-Selectin, sICAM-1, or sVCAM-1 were perceived. Conclusions: HD caused a significant increase in Syndecan-1 without a change in PBR. The administration of LMWH appeared to precede the rise in Syndecan-1.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

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Effects of Ultrapure Hemodialysis and Low Molecular Weight Heparin on the Endothelial Surface Layer

et al. 2014

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“…Leitienne et al [19] showed that the proinflammatory mediator release during hemodialysis depends on heparin dose. In addition, Gritters et al [20] found that myeloperoxidase and platelet factor 4 were released into the systemic circulation directly after the infusion of heparin before connection of the extracorporeal circuit. These and other studies suggest that inflammatory mediators may not only arise from neutrophils and platelets, but also from endothelial cells [21] .…”

Section: Patient and Kidney Survivalmentioning

confidence: 99%

Citrate Anticoagulation for Continuous Renal Replacement Therapy in the Critically Ill

Straaten

2010

Blood Purif

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Background: Heparins are used for circuit anticoagulation during continuous renal replacement therapy (CRRT). Because heparins cause systemic anticoagulation, they increase the risk of bleeding. Citrate provides regional anticoagulation. Since citrate is a buffer as well, its use has metabolic consequences. The preferential use of citrate therefore remains controversial. Methods: A synthesis was performed of published studies comparing citrate to heparin for anticoagulation in CRRT with specific regard to feasibility, efficacy and safety. Search of the literature was made to explain the reported superiority of citrate. Results: Citrate provides good metabolic control if and when a well-designed protocol is strictly followed. Randomized studies report similar or longer circuit survival with citrate compared to heparin and less bleeding. The largest randomized trial up to now found that citrate was better tolerated than heparin and improved patient and kidney survival, especially in patients after surgery, with sepsis, a high degree of organ failure or younger age. Both citrate and heparin interfere with inflammation. Conclusion: During critical illness, regional anticoagulation with citrate for CRRT seems superior to heparin anticoagulation concerning tolerance and safety, mainly due to less bleeding. Whether circuit survival is better depends on the modality. In addition, citrate seems to improve patient and kidney survival. This finding needs to be confirmed. Citrate seems to confer a specific benefit in severe organ failure and sepsis. To what extent citrate protects or heparin does harm in the setting of multiple organ failure needs to be unraveled.

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“…With respect to platelets (PLTs), during HD both an increase in the expression of cell surface molecules and the release of intragranular substances has been well documented. Recently, we showed that the upregulation of the PLT surface marker P-selectin (CD62p) is an early process, occurring over the entire length of the extracorporeal circuit (ECC) [2] . Of the many PLT granule products that may increase during the course of HD, Gritters-van platelet factor 4 (PF4) and ␤ -thromboglobulin (BTG) are well documented [3] .…”

Section: Introductionmentioning

confidence: 99%

The Role of the Extracorporeal Circuit in the Trapping and Degranulation of Platelets

Oever¹,

Schoorl

et al. 2009

Blood Purif

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Background: Although platelet (PLT) activation and degranulation are well-known phenomena during hemodialysis (HD), controversies still exist about their nature and origin. Methods: PLT characteristics [PLT numbers, mean PLT volume (MPV), PLT distribution width (PDW), PLT large cell ratio (p-LCR), immature PLT fraction] and activation status [CD62p expression, platelet factor 4 (PF4) and β-thromboglobulin (BTG) plasma levels] were estimated in 19 patients before and during HD. Blood was sampled from both the afferent and efferent lines. Additionally, the influence of low-molecular-weight heparin (LMWH) on PF4 and BTG concentrations was analyzed. Results: CD62p expression increased in the extracorporeal circuit (ECC) in the first 30 min. Simultaneously, PLT numbers dropped markedly within the ECC. MPV, PDW and p-LCR decreased over time. Like CD62p expression, BTG reached peak values at t30, was exclusively released within the ECC and was not influenced by the application of LMWH. In contrast, PF4 was significantly released outside the ECC in response to LMWH. Conclusions: PLTs are predominantly activated within the ECC and not on a remote distance. PLTs stick to the ECC, particularly after first passage. BTG is an appropriate marker for HD-induced PLT degranulation, whereas PF4 originates from both activated PLTs and LMWH-induced detachment from the endothelium. PLTs are not exhausted due to the repetitive stimulation of clinical HD. Hence, dialysis modalities with longer duration or greater frequency may be associated with a less beneficial PLT activation profile, which may counteract their clinical benefits.

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Platelet activation in clinical haemodialysis: LMWH as a major contributor to bio-incompatibility?

Cited by 44 publications

References 17 publications

Effects of Ultrapure Hemodialysis and Low Molecular Weight Heparin on the Endothelial Surface Layer

Effects of Ultrapure Hemodialysis and Low Molecular Weight Heparin on the Endothelial Surface Layer

Citrate Anticoagulation for Continuous Renal Replacement Therapy in the Critically Ill

The Role of the Extracorporeal Circuit in the Trapping and Degranulation of Platelets

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