Subscribe to RSS
DOI: 10.1055/s-0040-1708841
Platelets in Advanced Chronic Kidney Disease: Two Sides of the Coin

Abstract
Rates of thrombosis and bleeding episodes are both increased in patients with advanced chronic kidney disease (CKD). The pathogenic mechanisms of thrombosis in these patients include platelet activation, increased formation of platelet-leukocyte conjugates, and platelet-derived microparticles, as well as effects of uremic toxins on platelets. On the other side of the coin, platelet hyporeactivity mediated by uremic toxins and anemia contributes to the increased bleeding risk in advanced CKD. Platelets also contribute to the inflammatory environment, thus increasing the risk of cardiovascular diseases in these patients. This review provides insights into the altered platelet function in advanced stages of CKD and their relationship with risks of thrombosis and bleeding. Particularly, the effect of dialysis on platelets will be discussed. Furthermore, therapeutic options with respect to thrombotic disorders as well as bleeding in patients with CKD are reviewed.
Publication History
Publication Date:
07 April 2020 (online)
© 2020. Thieme. All rights reserved.
Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA
-
References
- 1
Lutz J,
Menke J,
Sollinger D,
Schinzel H,
Thürmel K.
Haemostasis in chronic kidney disease. Nephrol Dial Transplant 2014; 29 (01) 29-40
MissingFormLabel
- 2
Boccardo P,
Remuzzi G,
Galbusera M.
Platelet dysfunction in renal failure. Semin Thromb Hemost 2004; 30 (05) 579-589
MissingFormLabel
- 3
Yang K,
Du C,
Wang X.
et al.
Indoxyl sulfate induces platelet hyperactivity and contributes to chronic kidney disease-associated
thrombosis in mice. Blood 2017; 129 (19) 2667-2679
MissingFormLabel
- 4
Melgaard L,
Overvad TF,
Skjøth F,
Christensen JH,
Larsen TB,
Lip GYH.
Risk of stroke and bleeding in patients with heart failure and chronic kidney disease:
a nationwide cohort study. ESC Heart Fail 2018; 5 (02) 319-326
MissingFormLabel
- 5
Molnar AO,
Bota SE,
McArthur E.
et al.
Risk and complications of venous thromboembolism in dialysis patients. Nephrol Dial
Transplant 2018; 33 (05) 874-880
MissingFormLabel
- 6
Ocak G,
Noordzij M,
Rookmaaker MB.
et al.
Mortality due to bleeding, myocardial infarction and stroke in dialysis patients.
J Thromb Haemost 2018; 16 (10) 1953-1963
MissingFormLabel
- 7
Ando M,
Iwata A,
Ozeki Y,
Tsuchiya K,
Akiba T,
Nihei H.
Circulating platelet-derived microparticles with procoagulant activity may be a potential
cause of thrombosis in uremic patients. Kidney Int 2002; 62 (05) 1757-1763
MissingFormLabel
- 8
Landray MJ,
Wheeler DC,
Lip GY.
et al.
Inflammation, endothelial dysfunction, and platelet activation in patients with chronic
kidney disease: the chronic renal impairment in Birmingham (CRIB) study. Am J Kidney
Dis 2004; 43 (02) 244-253
MissingFormLabel
- 9
Shlipak MG,
Fried LF,
Crump C.
et al.
Elevations of inflammatory and procoagulant biomarkers in elderly persons with renal
insufficiency. Circulation 2003; 107 (01) 87-92
MissingFormLabel
- 10
Stenvinkel P,
Alvestrand A.
Inflammation in end-stage renal disease: sources, consequences, and therapy. Semin
Dial 2002; 15 (05) 329-337
MissingFormLabel
- 11
Tripepi G,
Mallamaci F,
Zoccali C.
Inflammation markers, adhesion molecules, and all-cause and cardiovascular mortality
in patients with ESRD: searching for the best risk marker by multivariate modeling.
J Am Soc Nephrol 2005; 16 (Suppl. 01) S83-S88
MissingFormLabel
- 12
Glorieux G,
Cohen G,
Jankowski J,
Vanholder R.
Platelet/leukocyte activation, inflammation, and uremia. Semin Dial 2009; 22 (04)
423-427
MissingFormLabel
- 13
Ramezani A,
Massy ZA,
Meijers B,
Evenepoel P,
Vanholder R,
Raj DS.
Role of the gut microbiome in uremia: a potential therapeutic target. Am J Kidney
Dis 2016; 67 (03) 483-498
MissingFormLabel
- 14
Konopelski P,
Ufnal M.
Indoles - gut bacteria metabolites of tryptophan with pharmacotherapeutic potential.
Curr Drug Metab 2018; 19 (10) 883-890
MissingFormLabel
- 15
Jovanovich A,
Isakova T,
Stubbs J.
Microbiome and cardiovascular disease in CKD. Clin J Am Soc Nephrol 2018; 13 (10)
1598-1604
MissingFormLabel
- 16
Karbowska M,
Kaminski TW,
Marcinczyk N.
et al.
The uremic toxin indoxyl sulfate accelerates thrombotic response after vascular injury
in animal models. Toxins (Basel) 2017; 9 (07) E229
MissingFormLabel
- 17
Bär L,
Stournaras C,
Lang F,
Föller M.
Regulation of fibroblast growth factor 23 (FGF23) in health and disease. FEBS Lett
2019; 593 (15) 1879-1900
MissingFormLabel
- 18
Yang K,
Nie L,
Huang Y.
et al.
Amelioration of uremic toxin indoxyl sulfate-induced endothelial cell dysfunction
by Klotho protein. Toxicol Lett 2012; 215 (02) 77-83
MissingFormLabel
- 19
Karbowska M,
Kaminski TW,
Znorko B.
et al.
Indoxyl sulfate promotes arterial thrombosis in rat model via increased levels of
complex TF/VII, PAI-1, platelet activation as well as decreased contents of SIRT1
and SIRT3. Front Physiol 2018; 9: 1623
MissingFormLabel
- 20
Schoorl M,
Schoorl M,
Nubé MJ,
Bartels PC.
Coagulation activation, depletion of platelet granules and endothelial integrity in
case of uraemia and haemodialysis treatment. BMC Nephrol 2013; 14: 72
MissingFormLabel
- 21
Gawaz M,
Langer H,
May AE.
Platelets in inflammation and atherogenesis. J Clin Invest 2005; 115 (12) 3378-3384
MissingFormLabel
- 22
Sirolli V,
Strizzi L,
Di Stante S,
Robuffo I,
Procopio A,
Bonomini M.
Platelet activation and platelet-erythrocyte aggregates in end-stage renal disease
patients on hemodialysis. Thromb Haemost 2001; 86 (03) 834-839
MissingFormLabel
- 23
Furie B,
Furie BC,
Flaumenhaft R.
A journey with platelet P-selectin: the molecular basis of granule secretion, signalling
and cell adhesion. Thromb Haemost 2001; 86 (01) 214-221
MissingFormLabel
- 24
Wagner DD.
New links between inflammation and thrombosis. Arterioscler Thromb Vasc Biol 2005;
25 (07) 1321-1324
MissingFormLabel
- 25
Galbusera MRG,
Ondei P.
Hemostatic abnormalities in renal disease. In:
Marder VJ,
Aird WC,
Bennett JS,
Schulman S,
White II GC.
ed.
Hemostasis and Thrombosis: Basic Principles and Clinical Practice. Philadelphia, PA:
Lippincott Williams & Wilkins; 2012: 1491-1497
MissingFormLabel
- 26
Huang MJ,
Wei RB,
Wang Y.
et al.
Blood coagulation system in patients with chronic kidney disease: a prospective observational
study. BMJ Open 2017; 7 (05) e014294
MissingFormLabel
- 27
Bonomini M,
Sirolli V,
Dottori S,
Amoroso L,
Di Liberato L,
Arduini A.
L-carnitine inhibits a subset of platelet activation responses in chronic uraemia.
Nephrol Dial Transplant 2007; 22 (09) 2623-2629
MissingFormLabel
- 28
Bonomini M,
Dottori S,
Amoroso L,
Arduini A,
Sirolli V.
Increased platelet phosphatidylserine exposure and caspase activation in chronic uremia.
J Thromb Haemost 2004; 2 (08) 1275-1281
MissingFormLabel
- 29
Li M,
Wang Z,
Ma T.
et al.
Enhanced platelet apoptosis in chronic uremic patients. Ren Fail 2014; 36 (06) 847-853
MissingFormLabel
- 30
Owens III AP,
Mackman N.
Microparticles in hemostasis and thrombosis. Circ Res 2011; 108 (10) 1284-1297
MissingFormLabel
- 31
Milioli M,
Ibáñez-Vea M,
Sidoli S,
Palmisano G,
Careri M,
Larsen MR.
Quantitative proteomics analysis of platelet-derived microparticles reveals distinct
protein signatures when stimulated by different physiological agonists. J Proteomics
2015; 121: 56-66
MissingFormLabel
- 32
Sinauridze EI,
Kireev DA,
Popenko NY.
et al.
Platelet microparticle membranes have 50- to 100-fold higher specific procoagulant
activity than activated platelets. Thromb Haemost 2007; 97 (03) 425-434
MissingFormLabel
- 33
Goubran HA,
Burnouf T,
Stakiw J,
Seghatchian J.
Platelet microparticle: a sensitive physiological “fine tuning” balancing factor in
health and disease. Transfus Apheresis Sci 2015; 52 (01) 12-18
MissingFormLabel
- 34
Varon D,
Shai E.
Platelets and their microparticles as key players in pathophysiological responses.
J Thromb Haemost 2015; 13 (Suppl. 01) S40-S46
MissingFormLabel
- 35
Sims PJ,
Faioni EM,
Wiedmer T,
Shattil SJ.
Complement proteins C5b-9 cause release of membrane vesicles from the platelet surface
that are enriched in the membrane receptor for coagulation factor Va and express prothrombinase
activity. J Biol Chem 1988; 263 (34) 18205-18212
MissingFormLabel
- 36
Sims PJ,
Wiedmer T,
Esmon CT,
Weiss HJ,
Shattil SJ.
Assembly of the platelet prothrombinase complex is linked to vesiculation of the platelet
plasma membrane. Studies in Scott syndrome: an isolated defect in platelet procoagulant
activity. J Biol Chem 1989; 264 (29) 17049-17057
MissingFormLabel
- 37
Geiser T,
Sturzenegger M,
Genewein U,
Haeberli A,
Beer JH.
Mechanisms of cerebrovascular events as assessed by procoagulant activity, cerebral
microemboli, and platelet microparticles in patients with prosthetic heart valves.
Stroke 1998; 29 (09) 1770-1777
MissingFormLabel
- 38
Katopodis JN,
Kolodny L,
Jy W.
et al.
Platelet microparticles and calcium homeostasis in acute coronary ischemias. Am J
Hematol 1997; 54 (02) 95-101
MissingFormLabel
- 39
Cecchetti L,
Tolley ND,
Michetti N,
Bury L,
Weyrich AS,
Gresele P.
Megakaryocytes differentially sort mRNAs for matrix metalloproteinases and their inhibitors
into platelets: a mechanism for regulating synthetic events. Blood 2011; 118 (07)
1903-1911
MissingFormLabel
- 40
Plé H,
Maltais M,
Corduan A,
Rousseau G,
Madore F,
Provost P.
Alteration of the platelet transcriptome in chronic kidney disease. Thromb Haemost
2012; 108 (04) 605-615
MissingFormLabel
- 41
Schubert P,
Devine DV.
De novo protein synthesis in mature platelets: a consideration for transfusion medicine.
Vox Sang 2010; 99 (02) 112-122
MissingFormLabel
- 42
Schubert S,
Weyrich AS,
Rowley JW.
A tour through the transcriptional landscape of platelets. Blood 2014; 124 (04) 493-502
MissingFormLabel
- 43
Marques M,
Sacristán D,
Mateos-Cáceres PJ.
et al.
Different protein expression in normal and dysfunctional platelets from uremic patients.
J Nephrol 2010; 23 (01) 90-101
MissingFormLabel
- 44
Walkowiak B,
Kaminska M,
Okrój W.
et al.
The blood platelet proteome is changed in UREMIC patients. Platelets 2007; 18 (05)
386-388
MissingFormLabel
- 45
Weyrich AS,
Denis MM,
Schwertz H.
et al.
mTOR-dependent synthesis of Bcl-3 controls the retraction of fibrin clots by activated
human platelets. Blood 2007; 109 (05) 1975-1983
MissingFormLabel
- 46
Zhu P,
Tang XF,
Xu JJ.
et al.
Platelet reactivity in patients with chronic kidney disease undergoing percutaneous
coronary intervention. Platelets 2019; 30 (07) 901-907
MissingFormLabel
- 47
Golebiewska EM,
Poole AW.
Platelet secretion: from haemostasis to wound healing and beyond. Blood Rev 2015;
29 (03) 153-162
MissingFormLabel
- 48
Pintucci G,
Froum S,
Pinnell J,
Mignatti P,
Rafii S,
Green D.
Trophic effects of platelets on cultured endothelial cells are mediated by platelet-associated
fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF).
Thromb Haemost 2002; 88 (05) 834-842
MissingFormLabel
- 49
Sheu JR,
Fong TH,
Liu CM.
et al.
Expression of matrix metalloproteinase-9 in human platelets: regulation of platelet
activation in in vitro and in vivo studies. Br J Pharmacol 2004; 143 (01) 193-201
MissingFormLabel
- 50
Battinelli EM,
Markens BA,
Italiano Jr JE.
Release of angiogenesis regulatory proteins from platelet alpha granules: modulation
of physiologic and pathologic angiogenesis. Blood 2011; 118 (05) 1359-1369
MissingFormLabel
- 51
Radziwon-Balicka A,
Moncada de la Rosa C,
Jurasz P.
Platelet-associated angiogenesis regulating factors: a pharmacological perspective.
Can J Physiol Pharmacol 2012; 90 (06) 679-688
MissingFormLabel
- 52
Horowitz HI.
Uremic toxins and platelet function. Arch Intern Med 1970; 126 (05) 823-826
MissingFormLabel
- 53
Horowitz HI,
Stein IM,
Cohen BD,
White JG.
Further studies on the platelet-inhibitory effect of guanidinosuccinic acid and its
role in uremic bleeding. Am J Med 1970; 49 (03) 336-345
MissingFormLabel
- 54
Rabiner SF,
Molinas F.
The role of phenol and phenolic acids on the thrombocytopathy and defective platelet
aggregation of patients with renal failure. Am J Med 1970; 49 (03) 346-351
MissingFormLabel
- 55
Remuzzi G,
Livio M,
Marchiaro G,
Mecca G,
de Gaetano G.
Bleeding in renal failure: altered platelet function in chronic uraemia only partially
corrected by haemodialysis. Nephron 1978; 22 (4-6): 347-353
MissingFormLabel
- 56
Benigni A,
Boccardo P,
Galbusera M.
et al.
Reversible activation defect of the platelet glycoprotein IIb-IIIa complex in patients
with uremia. Am J Kidney Dis 1993; 22 (05) 668-676
MissingFormLabel
- 57
Di Minno G,
Martinez J,
McKean ML,
De La Rosa J,
Burke JF,
Murphy S.
Platelet dysfunction in uremia. Multifaceted defect partially corrected by dialysis.
Am J Med 1985; 79 (05) 552-559
MissingFormLabel
- 58
Gawaz MP,
Dobos G,
Späth M,
Schollmeyer P,
Gurland HJ,
Mujais SK.
Impaired function of platelet membrane glycoprotein IIb-IIIa in end-stage renal disease.
J Am Soc Nephrol 1994; 5 (01) 36-46
MissingFormLabel
- 59
Sreedhara R,
Itagaki I,
Lynn B,
Hakim RM.
Defective platelet aggregation in uremia is transiently worsened by hemodialysis.
Am J Kidney Dis 1995; 25 (04) 555-563
MissingFormLabel
- 60
Remuzzi G,
Marchesi D,
Livio M.
et al.
Altered platelet and vascular prostaglandin-generation in patients with renal failure
and prolonged bleeding times. Thromb Res 1978; 13 (06) 1007-1015
MissingFormLabel
- 61
Mekawy MA,
Habashy DM,
Abd El-Mohsen WA.
Effect of hemodialysis on platelet function in end-stage renal disease Egyptian patients
using in vitro closure time test (PFA-100 analyzer). Platelets 2015; 26 (05) 443-447
MissingFormLabel
- 62
Linthorst GE,
Avis HJ,
Levi M.
Uremic thrombocytopathy is not about urea. J Am Soc Nephrol 2010; 21 (05) 753-755
MissingFormLabel
- 63
Eknoyan G,
Brown III CH.
Biochemical abnormalities of platelets in renal failure. Evidence for decreased platelet
serotonin, adenosine diphosphate and Mg-dependent adenosine triphosphatase. Am J Nephrol
1981; 1 (01) 17-23
MissingFormLabel
- 64
Elshamaa MF,
Elghoroury EA,
Helmy A.
Intradialytic and postdialytic platelet activation, increased platelet phosphatidylserine
exposure and ultrastructural changes in platelets in children with chronic uremia.
Blood Coagul Fibrinolysis 2009; 20 (04) 230-239
MissingFormLabel
- 65
Ware JA,
Clark BA,
Smith M,
Salzman EW.
Abnormalities of cytoplasmic Ca2+ in platelets from patients with uremia. Blood 1989;
73 (01) 172-176
MissingFormLabel
- 66
Schiffl H.
Correlation of blood pressure in end-stage renal disease with platelet cytosolic free-calcium
concentration. Klin Wochenschr 1990; 68 (14) 718-722
MissingFormLabel
- 67
Zhou XJ,
Vaziri ND.
Defective calcium signalling in uraemic platelets and its amelioration with long-term
erythropoietin therapy. Nephrol Dial Transplant 2002; 17 (06) 992-997
MissingFormLabel
- 68
Smith MC,
Dunn MJ.
Impaired platelet thromboxane production in renal failure. Nephron 1981; 29 (3-4):
133-137
MissingFormLabel
- 69
Bloom A,
Greaves M,
Preston FE,
Brown CB.
Evidence against a platelet cyclooxygenase defect in uraemic subjects on chronic haemodialysis.
Br J Haematol 1986; 62 (01) 143-149
MissingFormLabel
- 70
Frenette PS,
Johnson RC,
Hynes RO,
Wagner DD.
Platelets roll on stimulated endothelium in vivo: an interaction mediated by endothelial
P-selectin. Proc Natl Acad Sci U S A 1995; 92 (16) 7450-7454
MissingFormLabel
- 71
André P,
Denis CV,
Ware J.
et al.
Platelets adhere to and translocate on von Willebrand factor presented by endothelium
in stimulated veins. Blood 2000; 96 (10) 3322-3328
MissingFormLabel
- 72
Bombeli T,
Schwartz BR,
Harlan JM.
Adhesion of activated platelets to endothelial cells: evidence for a GPIIbIIIa-dependent
bridging mechanism and novel roles for endothelial intercellular adhesion molecule
1 (ICAM-1), alphavbeta3 integrin, and GPIbalpha. J Exp Med 1998; 187 (03) 329-339
MissingFormLabel
- 73
Mezzano D,
Tagle R,
Panes O.
et al.
Hemostatic disorder of uremia: the platelet defect, main determinant of the prolonged
bleeding time, is correlated with indices of activation of coagulation and fibrinolysis.
Thromb Haemost 1996; 76 (03) 312-321
MissingFormLabel
- 74
Salvati F,
Liani M.
Role of platelet surface receptor abnormalities in the bleeding and thrombotic diathesis
of uremic patients on hemodialysis and peritoneal dialysis. Int J Artif Organs 2001;
24 (03) 131-135
MissingFormLabel
- 75
Sloand EM,
Sloand JA,
Prodouz K.
et al.
Reduction of platelet glycoprotein Ib in uraemia. Br J Haematol 1991; 77 (03) 375-381
MissingFormLabel
- 76
Himmelfarb J,
Nelson S,
McMonagle E.
et al.
Elevated plasma glycocalicin levels and decreased ristocetin-induced platelet agglutination
in hemodialysis patients. Am J Kidney Dis 1998; 32 (01) 132-138
MissingFormLabel
- 77
Díaz-Ricart M,
Estebanell E,
Cases A.
et al.
Abnormal platelet cytoskeletal assembly in hemodialyzed patients results in deficient
tyrosine phosphorylation signaling. Kidney Int 2000; 57 (05) 1905-1914
MissingFormLabel
- 78
Janson PA,
Jubelirer SJ,
Weinstein MJ,
Deykin D.
Treatment of the bleeding tendency in uremia with cryoprecipitate. N Engl J Med 1980;
303 (23) 1318-1322
MissingFormLabel
- 79
Kaw D,
Malhotra D.
Platelet dysfunction and end-stage renal disease. Semin Dial 2006; 19 (04) 317-322
MissingFormLabel
- 80
Lee HK,
Kim YJ,
Jeong JU,
Park JS,
Chi HS,
Kim SB.
Desmopressin improves platelet dysfunction measured by in vitro closure time in uremic
patients. Nephron Clin Pract 2010; 114 (04) c248-c252
MissingFormLabel
- 81
Moal V,
Brunet P,
Dou L,
Morange S,
Sampol J,
Berland Y.
Impaired expression of glycoproteins on resting and stimulated platelets in uraemic
patients. Nephrol Dial Transplant 2003; 18 (09) 1834-1841
MissingFormLabel
- 82
Jurk K,
Kehrel BE.
Platelets: physiology and biochemistry. Semin Thromb Hemost 2005; 31 (04) 381-392
MissingFormLabel
- 83
Wratten ML,
Tetta C,
De Smet R.
et al.
Uremic ultrafiltrate inhibits platelet-activating factor synthesis. Blood Purif 1999;
17 (2-3): 134-141
MissingFormLabel
- 84
Sreedhara R,
Itagaki I,
Hakim RM.
Uremic patients have decreased shear-induced platelet aggregation mediated by decreased
availability of glycoprotein IIb-IIIa receptors. Am J Kidney Dis 1996; 27 (03) 355-364
MissingFormLabel
- 85
Sohal AS,
Gangji AS,
Crowther MA,
Treleaven D.
Uremic bleeding: pathophysiology and clinical risk factors. Thromb Res 2006; 118 (03)
417-422
MissingFormLabel
- 86
Noris M,
Benigni A,
Boccardo P.
et al.
Enhanced nitric oxide synthesis in uremia: implications for platelet dysfunction and
dialysis hypotension. Kidney Int 1993; 44 (02) 445-450
MissingFormLabel
- 87
Kyrle PA,
Stockenhuber F,
Brenner B.
et al.
Evidence for an increased generation of prostacyclin in the microvasculature and an
impairment of the platelet alpha-granule release in chronic renal failure. Thromb
Haemost 1988; 60 (02) 205-208
MissingFormLabel
- 88
Defreyn G,
Dauden MV,
Machin SJ,
Vermylen J.
A plasma factor in uraemia which stimulates prostacyclin release from cultured endothelial
cells. Thromb Res 1980; 19 (4-5): 695-699
MissingFormLabel
- 89
Radomski MW,
Palmer RM,
Moncada S.
An L-arginine/nitric oxide pathway present in human platelets regulates aggregation.
Proc Natl Acad Sci U S A 1990; 87 (13) 5193-5197
MissingFormLabel
- 90
Yokokawa K,
Mankus R,
Saklayen MG.
et al.
Increased nitric oxide production in patients with hypotension during hemodialysis.
Ann Intern Med 1995; 123 (01) 35-37
MissingFormLabel
- 91
Remuzzi G,
Perico N,
Zoja C,
Corna D,
Macconi D,
Viganò G.
Role of endothelium-derived nitric oxide in the bleeding tendency of uremia. J Clin
Invest 1990; 86 (05) 1768-1771
MissingFormLabel
- 92
Simon DI,
Stamler JS,
Loh E,
Loscalzo J,
Francis SA,
Creager MA.
Effect of nitric oxide synthase inhibition on bleeding time in humans. J Cardiovasc
Pharmacol 1995; 26 (02) 339-342
MissingFormLabel
- 93
Jankowski J,
van der Giet M,
Jankowski V.
et al.
Increased plasma phenylacetic acid in patients with end-stage renal failure inhibits
iNOS expression. J Clin Invest 2003; 112 (02) 256-264
MissingFormLabel
- 94
Makhoul S,
Walter E,
Pagel O.
et al.
Effects of the NO/soluble guanylate cyclase/cGMP system on the functions of human
platelets. Nitric Oxide 2018; 76: 71-80
MissingFormLabel
- 95
Fernandez F,
Goudable C,
Sie P.
et al.
Low haematocrit and prolonged bleeding time in uraemic patients: effect of red cell
transfusions. Br J Haematol 1985; 59 (01) 139-148
MissingFormLabel
- 96
Galbusera M,
Remuzzi G,
Boccardo P.
Treatment of bleeding in dialysis patients. Semin Dial 2009; 22 (03) 279-286
MissingFormLabel
- 97
Howard AD,
Moore Jr J,
Welch PG,
Gouge SF.
Analysis of the quantitative relationship between anemia and chronic renal failure.
Am J Med Sci 1989; 297 (05) 309-313
MissingFormLabel
- 98
Martin W,
Villani GM,
Jothianandan D,
Furchgott RF.
Blockade of endothelium-dependent and glyceryl trinitrate-induced relaxation of rabbit
aorta by certain ferrous hemoproteins. J Pharmacol Exp Ther 1985; 233 (03) 679-685
MissingFormLabel
- 99
Fass RJ,
Copelan EA,
Brandt JT,
Moeschberger ML,
Ashton JJ.
Platelet-mediated bleeding caused by broad-spectrum penicillins. J Infect Dis 1987;
155 (06) 1242-1248
MissingFormLabel
- 100
Shattil SJ,
Bennett JS,
McDonough M,
Turnbull J.
Carbenicillin and penicillin G inhibit platelet function in vitro by impairing the
interaction of agonists with the platelet surface. J Clin Invest 1980; 65 (02) 329-337
MissingFormLabel
- 101
Jurk K.
Analysis of platelet function and dysfunction. Hamostaseologie 2015; 35 (01) 60-72
MissingFormLabel
- 102
Lassila R.
Platelet function tests in bleeding disorders. Semin Thromb Hemost 2016; 42 (03) 185-190
MissingFormLabel
- 103
Soyoral YU,
Demir C,
Begenik H.
et al.
Skin bleeding time for the evaluation of uremic platelet dysfunction and effect of
dialysis. Clin Appl Thromb Hemost 2012; 18 (02) 185-188
MissingFormLabel
- 104
Bilgin AU,
Karadogan I,
Artac M,
Kizilors A,
Bligin R,
Undar L.
Hemodialysis shortens long in vitro closure times as measured by the PFA-100. Med
Sci Monit 2007; 13 (03) CR141-CR145
MissingFormLabel
- 105
Zupan IP,
Sabovic M,
Salobir B,
Ponikvar JB,
Cernelc P.
Utility of in vitro closure time test for evaluating platelet-related primary hemostasis
in dialysis patients. Am J Kidney Dis 2003; 42 (04) 746-751
MissingFormLabel
- 106
Gäckler A,
Rohn H,
Lisman T.
et al.
Evaluation of hemostasis in patients with end-stage renal disease. PLoS One 2019;
14 (02) e0212237
MissingFormLabel
- 107
Waki K,
Hayashi A,
Ikeda S.
et al.
Measuring platelet aggregation in dialysis patients with a whole blood aggregometer
by the screen filtration pressure method. Ther Apher Dial 2011; 15 (02) 203-206
MissingFormLabel
- 108
Tanios BY,
Itani HS,
Zimmerman DL.
Clopidogrel use in end-stage kidney disease. Semin Dial 2015; 28 (03) 276-281
MissingFormLabel
- 109
Polzin A,
Dannenberg L,
Sansone R.
et al.
Antiplatelet effects of aspirin in chronic kidney disease patients. J Thromb Haemost
2016; 14 (02) 375-380
MissingFormLabel
- 110
Cattaneo M.
P2Y12 receptors: structure and function. J Thromb Haemost 2015; 13 (Suppl. 01) S10-S16
MissingFormLabel
- 111
Best PJ,
Steinhubl SR,
Berger PB.
et al;
CREDO Investigators.
The efficacy and safety of short- and long-term dual antiplatelet therapy in patients
with mild or moderate chronic kidney disease: results from the Clopidogrel for the
Reduction of Events During Observation (CREDO) trial. Am Heart J 2008; 155 (04) 687-693
MissingFormLabel
- 112
Morel O,
El Ghannudi S,
Jesel L.
et al.
Cardiovascular mortality in chronic kidney disease patients undergoing percutaneous
coronary intervention is mainly related to impaired P2Y12 inhibition by clopidogrel.
J Am Coll Cardiol 2011; 57 (04) 399-408
MissingFormLabel
- 113
Park SH,
Kim W,
Park CS,
Kang WY,
Hwang SH,
Kim W.
A comparison of clopidogrel responsiveness in patients with versus without chronic
renal failure. Am J Cardiol 2009; 104 (09) 1292-1295
MissingFormLabel
- 114
Edfors R,
Sahlén A,
Szummer K.
et al.
Outcomes in patients treated with ticagrelor versus clopidogrel after acute myocardial
infarction stratified by renal function. Heart 2018; 104 (19) 1575-1582
MissingFormLabel
- 115
James S,
Budaj A,
Aylward P.
et al.
Ticagrelor versus clopidogrel in acute coronary syndromes in relation to renal function:
results from the Platelet Inhibition and Patient Outcomes (PLATO) trial. Circulation
2010; 122 (11) 1056-1067
MissingFormLabel
- 116
Gremmel T,
Müller M,
Steiner S.
et al.
Chronic kidney disease is associated with increased platelet activation and poor response
to antiplatelet therapy. Nephrol Dial Transplant 2013; 28 (08) 2116-2122
MissingFormLabel
- 117
Collette C,
Clerc-Urmès I,
Laborde-Castérot H.
et al.
Antiplatelet and oral anticoagulant therapies in chronic hemodialysis patients: prescribing
practices and bleeding risk. Pharmacoepidemiol Drug Saf 2016; 25 (08) 935-943
MissingFormLabel
- 118
Johansen KB,
Balchen T.
Tinzaparin and other low-molecular-weight heparins: what is the evidence for differential
dependence on renal clearance?. Exp Hematol Oncol 2013; 2: 21
MissingFormLabel
- 119
Weitz DS,
Weitz JI.
Update on heparin: what do we need to know?. J Thromb Thrombolysis 2010; 29 (02) 199-207
MissingFormLabel
- 120
Clark NP.
Low-molecular-weight heparin use in the obese, elderly, and in renal insufficiency.
Thromb Res 2008; 123 (Suppl. 01) S58-S61
MissingFormLabel
- 121
Crowther M,
Lim W.
Low molecular weight heparin and bleeding in patients with chronic renal failure.
Curr Opin Pulm Med 2007; 13 (05) 409-413
MissingFormLabel
- 122
Lim W.
Low-molecular-weight heparin in patients with chronic renal insufficiency. Intern
Emerg Med 2008; 3 (04) 319-323
MissingFormLabel
- 123
Wilke T,
Wehling M,
Amann S,
Bauersachs RM,
Böttger B.
Renal impairment in patients with thromboembolic event: prevalence and clinical implications.
A systematic review of the literature [in German]. Dtsch Med Wochenschr 2015; 140
(17) e166-e174
MissingFormLabel
- 124
Murray PT,
Reddy BV,
Grossman EJ.
et al.
A prospective comparison of three argatroban treatment regimens during hemodialysis
in end-stage renal disease. Kidney Int 2004; 66 (06) 2446-2453
MissingFormLabel
- 125
Poterucha TJ,
Goldhaber SZ.
Warfarin and vascular calcification. Am J Med 2016; 129 (06) 635.e1-635.e4
MissingFormLabel
- 126
Chan KE,
Lazarus JM,
Thadhani R,
Hakim RM.
Warfarin use associates with increased risk for stroke in hemodialysis patients with
atrial fibrillation. J Am Soc Nephrol 2009; 20 (10) 2223-2233
MissingFormLabel
- 127
Olesen JB,
Lip GY,
Kamper AL.
et al.
Stroke and bleeding in atrial fibrillation with chronic kidney disease. N Engl J Med
2012; 367 (07) 625-635
MissingFormLabel
- 128
Friberg L,
Benson L,
Lip GY.
Balancing stroke and bleeding risks in patients with atrial fibrillation and renal
failure: the Swedish Atrial Fibrillation Cohort study. Eur Heart J 2015; 36 (05) 297-306
MissingFormLabel
- 129
Carrero JJ,
Evans M,
Szummer K.
et al.
Warfarin, kidney dysfunction, and outcomes following acute myocardial infarction in
patients with atrial fibrillation. JAMA 2014; 311 (09) 919-928
MissingFormLabel
- 130
Knoll F,
Sturm G,
Lamina C.
et al.
Coumarins and survival in incident dialysis patients. Nephrol Dial Transplant 2012;
27 (01) 332-337
MissingFormLabel
- 131
van Leeuwen Y,
Rombouts EK,
Kruithof CJ,
van der Meer FJ,
Rosendaal FR.
Improved control of oral anticoagulant dosing: a randomized controlled trial comparing
two computer algorithms. J Thromb Haemost 2007; 5 (08) 1644-1649
MissingFormLabel
- 132
Harel Z,
Sood MM,
Perl J.
Comparison of novel oral anticoagulants versus vitamin K antagonists in patients with
chronic kidney disease. Curr Opin Nephrol Hypertens 2015; 24 (02) 183-192
MissingFormLabel
- 133
Diener HC,
Aisenberg J,
Ansell J.
et al.
Choosing a particular oral anticoagulant and dose for stroke prevention in individual
patients with non-valvular atrial fibrillation: part 2. Eur Heart J 2017; 38 (12)
860-868
MissingFormLabel
- 134
Harel Z,
Sholzberg M,
Shah PS.
et al.
Comparisons between novel oral anticoagulants and vitamin K antagonists in patients
with CKD. J Am Soc Nephrol 2014; 25 (03) 431-442
MissingFormLabel
- 135
Hohnloser SH,
Hijazi Z,
Thomas L.
et al.
Efficacy of apixaban when compared with warfarin in relation to renal function in
patients with atrial fibrillation: insights from the ARISTOTLE trial. Eur Heart J
2012; 33 (22) 2821-2830
MissingFormLabel
- 136
Agnelli G,
Buller HR,
Cohen A.
et al;
AMPLIFY Investigators.
Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med 2013;
369 (09) 799-808
MissingFormLabel
- 137
Chan KE,
Giugliano RP,
Patel MR.
et al.
Nonvitamin K anticoagulant agents in patients with advanced chronic kidney disease
or on dialysis with AF. J Am Coll Cardiol 2016; 67 (24) 2888-2899
MissingFormLabel
- 138
Wang X,
Tirucherai G,
Marbury TC.
et al.
Pharmacokinetics, pharmacodynamics, and safety of apixaban in subjects with end-stage
renal disease on hemodialysis. J Clin Pharmacol 2016; 56 (05) 628-636
MissingFormLabel
- 139
Fox KA,
Piccini JP,
Wojdyla D.
et al.
Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin
in patients with non-valvular atrial fibrillation and moderate renal impairment. Eur
Heart J 2011; 32 (19) 2387-2394
MissingFormLabel
- 140
Mannucci PM,
Remuzzi G,
Pusineri F.
et al.
Deamino-8-D-arginine vasopressin shortens the bleeding time in uremia. N Engl J Med
1983; 308 (01) 8-12
MissingFormLabel
- 141
Kim JH,
Baek CH,
Min JY,
Kim JS,
Kim SB,
Kim H.
Desmopressin improves platelet function in uremic patients taking antiplatelet agents
who require emergent invasive procedures. Ann Hematol 2015; 94 (09) 1457-1461
MissingFormLabel
- 142
Viganò GL,
Mannucci PM,
Lattuada A,
Harris A,
Remuzzi G.
Subcutaneous desmopressin (DDAVP) shortens the bleeding time in uremia. Am J Hematol
1989; 31 (01) 32-35
MissingFormLabel
- 143
Schulz-Stübner S,
Zielske D,
Rossaint R.
Comparison between nasal and intravenous desmopressin for the treatment of aminosalicylic
acid-induced platelet dysfunction. Eur J Anaesthesiol 2002; 19 (09) 647-651
MissingFormLabel
- 144
Hedges SJ,
Dehoney SB,
Hooper JS,
Amanzadeh J,
Busti AJ.
Evidence-based treatment recommendations for uremic bleeding. Nat Clin Pract Nephrol
2007; 3 (03) 138-153
MissingFormLabel
- 145
Franchini M.
The use of desmopressin as a hemostatic agent: a concise review. Am J Hematol 2007;
82 (08) 731-735
MissingFormLabel
- 146
Hörl WH.
Thrombocytopathy and blood complications in uremia [in German]. Wien Klin Wochenschr
2006; 118 (5-6): 134-150
MissingFormLabel
- 147
Pavord S,
Myers B.
Bleeding and thrombotic complications of kidney disease. Blood Rev 2011; 25 (06) 271-278
MissingFormLabel
- 148
Zeigler ZR,
Megaludis A,
Fraley DS.
Desmopressin (d-DAVP) effects on platelet rheology and von Willebrand factor activities
in uremia. Am J Hematol 1992; 39 (02) 90-95
MissingFormLabel
- 149
Köhler M,
Hellstern P,
Tarrach H,
Bambauer R,
Wenzel E,
Jutzler GA.
Subcutaneous injection of desmopressin (DDAVP): evaluation of a new, more concentrated
preparation. Haemostasis 1989; 19 (01) 38-44
MissingFormLabel
- 150
Watson AJ,
Keogh JA.
Effect of 1-deamino-8-D-arginine vasopressin on the prolonged bleeding time in chronic
renal failure. Nephron 1982; 32 (01) 49-52
MissingFormLabel
- 151
Heunisch C,
Resnick DJ,
Vitello JM,
Martin SJ.
Conjugated estrogens for the management of gastrointestinal bleeding secondary to
uremia of acute renal failure. Pharmacotherapy 1998; 18 (01) 210-217
MissingFormLabel
- 152
Liu YK,
Kosfeld RE,
Marcum SG.
Treatment of uraemic bleeding with conjugated oestrogen. Lancet 1984; 2 (8408): 887-890
MissingFormLabel
- 153
Livio M,
Mannucci PM,
Viganò G.
et al.
Conjugated estrogens for the management of bleeding associated with renal failure.
N Engl J Med 1986; 315 (12) 731-735
MissingFormLabel
- 154
Viganò G,
Gaspari F,
Locatelli M,
Pusineri F,
Bonati M,
Remuzzi G.
Dose-effect and pharmacokinetics of estrogens given to correct bleeding time in uremia.
Kidney Int 1988; 34 (06) 853-858
MissingFormLabel
- 155
Zoja C,
Viganò G,
Bergamelli A,
Benigni A,
de Gaetano G,
Remuzzi G.
Prolonged bleeding time and increased vascular prostacyclin in rats with chronic renal
failure: effects of conjugated estrogens. J Lab Clin Med 1988; 112 (03) 380-386
MissingFormLabel
- 156
Noris M,
Todeschini M,
Zappella S.
et al.
17beta-estradiol corrects hemostasis in uremic rats by limiting vascular expression
of nitric oxide synthases. Am J Physiol Renal Physiol 2000; 279 (04) F626-F635
MissingFormLabel
- 157
Heistinger M,
Stockenhuber F,
Schneider B.
et al.
Effect of conjugated estrogens on platelet function and prostacyclin generation in
CRF. Kidney Int 1990; 38 (06) 1181-1186
MissingFormLabel
- 158
Shemin D,
Elnour M,
Amarantes B,
Abuelo JG,
Chazan JA.
Oral estrogens decrease bleeding time and improve clinical bleeding in patients with
renal failure. Am J Med 1990; 89 (04) 436-440
MissingFormLabel
- 159
Sloand JA,
Schiff MJ.
Beneficial effect of low-dose transdermal estrogen on bleeding time and clinical bleeding
in uremia. Am J Kidney Dis 1995; 26 (01) 22-26
MissingFormLabel
- 160
Gonzalez J,
Bryant S,
Hermes-DeSantis ER.
Transdermal estradiol for the management of refractory uremic bleeding. Am J Health
Syst Pharm 2018; 75 (09) e177-e183
MissingFormLabel
- 161
Ross CS,
Pruthi RK,
Schmidt KA,
Eckerman AL,
Rodriguez V.
Intranasal oestrogen cream for the prevention of epistaxis in patients with bleeding
disorders. Haemophilia 2011; 17 (01) 164
MissingFormLabel
- 162
Moia M,
Mannucci PM,
Vizzotto L,
Casati S,
Cattaneo M,
Ponticelli C.
Improvement in the haemostatic defect of uraemia after treatment with recombinant
human erythropoietin. Lancet 1987; 2 (8570): 1227-1229
MissingFormLabel
- 163
Viganò G,
Benigni A,
Mendogni D,
Mingardi G,
Mecca G,
Remuzzi G.
Recombinant human erythropoietin to correct uremic bleeding. Am J Kidney Dis 1991;
18 (01) 44-49
MissingFormLabel
- 164
Livio M,
Gotti E,
Marchesi D,
Mecca G,
Remuzzi G,
de Gaetano G.
Uraemic bleeding: role of anaemia and beneficial effect of red cell transfusions.
Lancet 1982; 2 (8306): 1013-1015
MissingFormLabel
- 165
Cases A,
Escolar G,
Reverter JC.
et al.
Recombinant human erythropoietin treatment improves platelet function in uremic patients.
Kidney Int 1992; 42 (03) 668-672
MissingFormLabel
- 166
Zwaginga JJ,
IJsseldijk MJ,
de Groot PG.
et al.
Treatment of uremic anemia with recombinant erythropoietin also reduces the defects
in platelet adhesion and aggregation caused by uremic plasma. Thromb Haemost 1991;
66 (06) 638-647
MissingFormLabel
- 167
Peng J,
Friese P,
Heilmann E,
George JN,
Burstein SA,
Dale GL.
Aged platelets have an impaired response to thrombin as quantitated by P-selectin
expression. Blood 1994; 83 (01) 161-166
MissingFormLabel
- 168
Tàssies D,
Reverter JC,
Cases A,
Calls J,
Escolar G,
Ordinas A.
Effect of recombinant human erythropoietin treatment on circulating reticulated platelets
in uremic patients: association with early improvement in platelet function. Am J
Hematol 1998; 59 (02) 105-109
MissingFormLabel
- 169
Diaz-Ricart M,
Etebanell E,
Cases A.
et al.
Erythropoietin improves signaling through tyrosine phosphorylation in platelets from
uremic patients. Thromb Haemost 1999; 82 (04) 1312-1317
MissingFormLabel
- 170
Farag YM,
Keithy-Reddy SR,
Mittal BV,
Bansal V,
Fareed J,
Singh AK.
Modulation of platelet activation in chronic kidney disease patients on erythropoiesis-stimulating
agents. Clin Appl Thromb Hemost 2012; 18 (05) 453-461
MissingFormLabel
- 171
Besarab A,
Bolton WK,
Browne JK.
et al.
The effects of normal as compared with low hematocrit values in patients with cardiac
disease who are receiving hemodialysis and epoetin. N Engl J Med 1998; 339 (09) 584-590
MissingFormLabel
- 172
Cardigan RA,
McGloin H,
Mackie IJ,
Machin SJ,
Singer M.
Activation of the tissue factor pathway occurs during continuous venovenous hemofiltration.
Kidney Int 1999; 55 (04) 1568-1574
MissingFormLabel
- 173
Pawlak K,
Pawlak D,
Mysliwiec M.
Association between tissue factor, its pathway inhibitor and oxidative stress in peritoneal
dialysis patients. Blood Coagul Fibrinolysis 2007; 18 (05) 467-471
MissingFormLabel
- 174
Davenport A.
What are the anticoagulation options for intermittent hemodialysis?. Nat Rev Nephrol
2011; 7 (09) 499-508
MissingFormLabel
- 175
Gritters M,
Borgdorff P,
Grooteman MP.
et al.
Platelet activation in clinical haemodialysis: LMWH as a major contributor to bio-incompatibility?.
Nephrol Dial Transplant 2008; 23 (09) 2911-2917
MissingFormLabel
- 176
Schoorl M,
Grooteman MP,
Bartels PC,
Nubé MJ.
Aspects of platelet disturbances in haemodialysis patients. Clin Kidney J 2013; 6
(03) 266-271
MissingFormLabel
- 177
Hoenich NA.
Platelet and leucocyte behavior during haemodialysis. In:
Ronco C.
ed.
Polymethylmethacrylate: A Flexible Membrane for a Tailored Dialysis. Basel, Switzerland:
Karger; 1998: 120-132
MissingFormLabel
- 178
Bonomini M,
Sirolli V,
Stuard S,
Settefrati N.
Interactions between platelets and leukocytes during hemodialysis. Artif Organs 1999;
23 (01) 23-28
MissingFormLabel
- 179
Gawaz MP,
Mujais SK,
Schmidt B,
Gurland HJ.
Platelet-leukocyte aggregation during hemodialysis. Kidney Int 1994; 46 (02) 489-495
MissingFormLabel
- 180
Daniel L,
Fakhouri F,
Joly D.
et al.
Increase of circulating neutrophil and platelet microparticles during acute vasculitis
and hemodialysis. Kidney Int 2006; 69 (08) 1416-1423
MissingFormLabel
- 181
Aggarwal A,
Kabbani SS,
Rimmer JM.
et al.
Biphasic effects of hemodialysis on platelet reactivity in patients with end-stage
renal disease: a potential contributor to cardiovascular risk. Am J Kidney Dis 2002;
40 (02) 315-322
MissingFormLabel
- 182
Kabbani SS,
Watkins MW,
Ashikaga T.
et al.
Platelet reactivity characterized prospectively: a determinant of outcome 90 days
after percutaneous coronary intervention. Circulation 2001; 104 (02) 181-186
MissingFormLabel
- 183
Thaulow E,
Erikssen J,
Sandvik L,
Stormorken H,
Cohn PF.
Blood platelet count and function are related to total and cardiovascular death in
apparently healthy men. Circulation 1991; 84 (02) 613-617
MissingFormLabel
- 184
Trip MD,
Cats VM,
van Capelle FJ,
Vreeken J.
Platelet hyperreactivity and prognosis in survivors of myocardial infarction. N Engl
J Med 1990; 322 (22) 1549-1554
MissingFormLabel
- 185
Remuzzi G,
Benigni A,
Dodesini P.
et al.
Platelet function in patients on maintenance hemodialysis: depressed or enhanced?.
Clin Nephrol 1982; 17 (02) 60-63
MissingFormLabel
- 186
Sirolli V,
Ballone E,
Di Stante S,
Amoroso L,
Bonomini M.
Cell activation and cellular-cellular interactions during hemodialysis: effect of
dialyzer membrane. Int J Artif Organs 2002; 25 (06) 529-537
MissingFormLabel
- 187
Lindsay RM,
Friesen M,
Koens F,
Linton AL,
Oreopoulos D,
de Veber G.
Platelet function in patients on long term peritoneal dialysis. Clin Nephrol 1976;
6 (02) 335-339
MissingFormLabel