Effects of Epoetin Alfa on Hemostasis in Chronic Renal Failure

Tang, Winson W.; Stead, Richard A.; Goodkin, David A.

doi:10.1159/000013349

Cited by 32 publications

(19 citation statements)

References 35 publications

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“…In the present study there was no difference between the groups in the aggregation response to ADP, probably explained by an improvement of platelet function by EPO treatment in uremic patients [20]. Since the objective of the present study was to compare NO-mediated inhibition of ADP-induced platelet aggregation, a high concentration of ADP (10 ÌM) was used and thus subtle differences of activator-dependent responses may be missed.…”

Section: Discussionmentioning

confidence: 50%

Adenosine 5’-Diphosphate-Induced Platelet Aggregation in Uremia Shows Resistance to Inhibition by the Novel Nitric Oxide Donor GEA 3175 but Not by S-Nitroso-N-Acetylpenicillamine

Whiss¹,

Larsson

1998

Pathophysiol Haemos Thromb

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Both bleeding and thrombosis are complications of uremia in patients on regular hemodialysis. An excessive endogenous formation of the vasodilator and platelet inhibitor nitric oxide (NO) has been proposed to contribute to the bleeding defect. Since exposure to pharmacological donors of NO, nitrovasodilators, can cause tolerance to NO, we investigated whether platelets from uremic patients on regular hemodialysis are influenced differently by NO donors than platelets from healthy subjects. A frequently used S-nitrosothiol, S-nitroso-N-acetylpenicillamine (SNAP), was compared to a recently synthezised mesoionic oxatriazole derivate, GEA 3175, regarding its capacity to inhibit adenosine 5′-diphosphate (ADP)-induced platelet aggregation in vitro. The final products of NO production, nitrite + nitrate, were found to be significantly increased in uremic patients. The capacity to inhibit platelet aggregation by SNAP was only slightly different between the groups. However, GEA 3175 showed a significantly marked and reduced capacity to inhibit aggregation of uremic platelets compared to controls. Interactions of erythropoietin (EPO) with NO have earlier been reported. Addition of EPO to platelets from healthy donors in vitro did not significantly influence the NO donor capacity to inhibit platelet aggregation, but showed a tendency to enhance the effect of SNAP while the effect of GEA 3175 was inhibited. These results suggest compound-specific resistance to NO donors in uremic platelet activation.

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Section: Discussionmentioning

confidence: 50%

Adenosine 5’-Diphosphate-Induced Platelet Aggregation in Uremia Shows Resistance to Inhibition by the Novel Nitric Oxide Donor GEA 3175 but Not by S-Nitroso-N-Acetylpenicillamine

Whiss¹,

Larsson

1998

Pathophysiol Haemos Thromb

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“…KBH'lı hastalarda sık olarak uygulanan ve megakaryopoezde rolü olan eritropoetinin de tromboz oluşumuna yatkınlık oluşturduğu bilinmektedir [2,3,4]. Megakaryositlerde EPO reseptörlerinin olduğu ve EPO'nun bir büyüme faktörü olarak görev yaptığı, megakaryositlerin büyümesinde ve farklı-laşmasında rolü olduğu gösterilmiştir [19,20,21].…”

Section: Discussionunclassified

“…Eritropoezde temel rol oynayan ve kronik böbrek hastalığı (KBH) olan hastalardaki aneminin tedavisinde yaygın kullanılan eritropoetin (EPO)'in önemli bir yan etki olarak trombotik olayları artırdığı bilinmektedir [2,3,4]. EPO'nun pro-trombotik etki mekanizmasının; eritrosit kütle artışı, genç ve büyük trombositlerin kemik iliğinden salınımının artması, endotelial hücre aktivasyonu, tirozin kinaz bağımlı sinyal iletim yolağının aktivasyonu ve trombositlerdeki uyarılmış sitozolik ve bazal kalsiyum seviyelerinin artması ile tetiklendiği düşünülmektedir [5,6,7].…”

Section: Introductionunclassified

“…EPO'nun pro-trombotik etki mekanizmasının; eritrosit kütle artışı, genç ve büyük trombositlerin kemik iliğinden salınımının artması, endotelial hücre aktivasyonu, tirozin kinaz bağımlı sinyal iletim yolağının aktivasyonu ve trombositlerdeki uyarılmış sitozolik ve bazal kalsiyum seviyelerinin artması ile tetiklendiği düşünülmektedir [5,6,7]. EPO'yla birlikte artan protrombotik etkiler ile kronik hemodiyaliz (HD) hastalarında yüksek oranda greft trombozu gelişmekte ve mortalite artışına katkıda bulunmaktadır [2,3,4]. Bu nedenle üremik hastalarda tromboz oluşum riskinin erken dönemde belirlenebileceği göstergelere ihtiyaç vardır.…”

Section: Introductionunclassified

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Effect of erythropoietin use on mean platelet volume in children undergoing chronic dialysis

Özdemir

Kara²,

Dinçel³

et al. 2014

J Clin Exp Invest

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Objective: In this study, it was aimed to determine the relationship between erythropoietin (EPO) use and mean platelet volume (MPV) in the children undergoing dialysis. Methods:MPV values before and after EPO use in 36 patients (16 hemodialysis -HD, 20 peritoneal dialysis -PD) were retrospectively evaluated. Patients were divided into two groups according to weekly EPO need as; given less than 150 U/kg defined as low EPO and more than 150 U/kg as high EPO groups. The age, weight, primary cause of chronic renal failure, dialysis methods and EPO dosages of patients were recorded. Blood samples were taken before and 4 weeks after EPO usage and MPV values were noted from complete blood counts.Results: While significant increase was seen in the MPV values after EPO in comparison to MPV values before EPO in the HD group (8.18±1.52 fL vs. 9.20±1.46 fL; p=0.046); near significant difference was found in the MPV levels after EPO (8.28±1.80 fL vs. 9.39±1.50 fL; p=0,051) in PD group. In HD patients when high dose of EPO was given, MPV levels were found to be significantly elevated (7.81 ± 1.04 vs 9.61 ± 1.05; p=0.06) after EPO. However, no difference was seen with the lowe dose EPO subgroup (8.64 ± 1.97 ve 8.67 ± 1.81; p>0,05). No effect of EPO dose was found on MPV values in PD patients (9.57 ± 1.58 ve 9.1 ± 1.42; p>0.05). Conclusion:It was observed that EPO influenced MPV values in children undergoing HD, while no effect of erythropoietin was found on MPV values of PD patients. Physicians should be careful while using high dose erythropoietin in children with high thrombosis risk. J Clin Exp Invest 2014; 5 (3): 415-419 Key words: Mean platelet volume, erythropoietin, hemodialysis, child ÖZET Amaç: Bu çalışmada diyaliz uygulanan çocuklarda ortalama trombosit hacmi (OTH) ve eritropoetin (EPO) kullanımı arasındaki ilişkinin incelenmesi amaçlanmıştır.Yöntemler: Çalışmada 16 hemodiyaliz (HD), 20 periton diyalizi (PD) olmak üzere 36 hastanın eritropoetin önce-si ve sonrası OTH değerleri retrospektif olarak incelendi. Hastalar haftalık eritropoetin alımı 150 Ü/kg'ın altında (düşük EPO) ve 150 Ü/kg üzerinde (yüksek EPO) olmak üzere 2 gruba ayrıldı. Hastaların yaşları, vücut ağırlıkları, kronik böbrek yetmezliğine neden olan primer hastalıkla-rı, uygulanan diyaliz tedavi yöntemleri, EPO dozları kaydedildi. EPO başlanmadan önce ve başlandıktan 4 hafta sonra alınan kan örneklerinde tam kan sayımı (hemogram) yapılarak OTH değerleri kaydedildi.. Bulgular:Hemodiyaliz grubunun EPO sonrası OTH değerlerinde EPO öncesi OTH değerlerine göre anlamlı yük-selme (8,18±1,52 fL ve 9,20±1,46 fL, p=0,046) saptanır-ken, PD grubunda ise EPO sonrası değerlerde yükselme olmasına rağmen, fark istatistiksel anlamlılık sınırına çok yakın bulundu (8,28±1,80 fL ve 9,39±1,50 fL, p=0,051).Yüksek dozda EPO alan HD hastalarında EPO sonrası OTH değerleri artmış olarak bulundu (7,81 ± 1,04 ve 9,61 ± 1,05 fL; p=0,06). Düşük doz EPO kullananlarda ise farklılık görülmedi (8,64 ± 1,97 ve 8,67 ± 1,81 fL; p>0,05). PD hastalarında ise EPO dozu OTH değerler...

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“…[5][6][7] Initially used in hemodialysis patients, the restoration of a normal hemoglobin level was shown to decrease anemia-related complications such as left ventricular hypertrophy and congestive heart failure as well as to attenuate the uremia-related bleeding diathesis seen in chronic renal failure patients. 8,9 The preoperative use of recombinant human erythropoietin is a more recent strategy, having received HPB approval for this use in Canada in 1996. Healthy patients can expect a rapid return to baseline hemoglobin levels after the donation autologous blood for retransfusion during elective surgery.…”

Section: Discussionmentioning

confidence: 99%

Liver transplantation in a Jehovah’s Witness with ankylosing spondylitis

Baldry

Backman

Metrakos

et al. 2000

Can J Anesth/J Can Anesth

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Purpose: Orthotopic liver transplantation is typically associated with large volume blood loss. Technological and pharmacological advances permit liver transplantation in patients who formerly were not candidates for this surgery because of strict limitations on blood product administration. We describe a liver transplant in a Jehovah's Witness with ankylosing spondylitis.Clinical features: A 49-yr-old Jehovah's Witness with ankylosing spondylitis and end stage liver disease secondary to sclerosing cholangitis underwent orthotopic liver transplantation. Recombinant human erythropoietin (4,000 IU sc every two days for four weeks, then 4,000 IU sc every week) established a normal hemoglobin concentration preoperatively (>140 g·L -1 compared with 120 g·L -1 baseline). Intraoperatively, strategies for reducing risk of blood product transfusion included avoidance of hypothermia (T>35°C), minimal blood sampling (four 1 ml samples), normovolemic hemodilution (two units), administration of Aprotinin (2 million units bolus dose followed by infusion of 500,000 u·hr -1 ), and return of blood (1,500 ml) scavenged from the operative field. Estimated blood loss was 2,200 ml. The preoperative and postoperative hemoglobin concentration was 147 g·L -1 (hematocrit 0.45) and 123 g·L -1 (hematocrit 0.37), respectively. No blood products were required and he was discharged three weeks postoperatively without complication.Conclusion: Technological and pharmacological advances allow patients to undergo surgery traditionally associated with large volume blood loss with reduced risk of blood product administration.Objectif : La transplantation du foie orthotopique est typiquement associée à une perte de sang importante. Les progrès technologiques et pharmacologiques permettent de réaliser une transplantation hépatique chez des patients qui n'auraient pu subir cette opération auparavant à cause de limitations rigoureuses d'administration des produits sanguins. Nous décrivons une greffe hépatique chez un témoin de Jéhovah qui présente une spondylarthrite ankylosante.Éléments cliniques : Un témoin de Jéhovah de 49 ans souffrant de spondylarthrite ankylosante et d'une maladie hépatique terminale secondaire à une cholangite sclérosante a subi une greffe hépatique. L'administration d'érythropoïétine recombinante humaine (4 000 UI sc aux deux jours pendant quatre semaines, puis 4 000 UI sc chaque semaine) a établi une concentration d'hémoglobine préopératoire normale (>140 g·L -1 comparée à 120 g·L -1 au départ). Les stratégies peropératoires adoptées pour réduire le risque lié à la transfusion de produit sanguin comprenaient l'absence d'hypothermie (T >35 o C), le prélèvement minimal de sang (quatre échantillons de 1 ml), l'hémodilution normovolémique (deux unités), l'administration d'aprotinine (des bolus de deux millions d'unités suivis de perfusion de 500 000 u·h -1 ) et le retour du sang épuré (1 500 ml) provenant du champ opéra-toire. La perte sanguine a été de 2 200 ml. La concentration préopératoire et postopératoire d'hémoglobine a ét...

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Effects of Epoetin Alfa on Hemostasis in Chronic Renal Failure

Cited by 32 publications

References 35 publications

Adenosine 5’-Diphosphate-Induced Platelet Aggregation in Uremia Shows Resistance to Inhibition by the Novel Nitric Oxide Donor GEA 3175 but Not by S-Nitroso-N-Acetylpenicillamine

Adenosine 5’-Diphosphate-Induced Platelet Aggregation in Uremia Shows Resistance to Inhibition by the Novel Nitric Oxide Donor GEA 3175 but Not by S-Nitroso-N-Acetylpenicillamine

Effect of erythropoietin use on mean platelet volume in children undergoing chronic dialysis

Liver transplantation in a Jehovah’s Witness with ankylosing spondylitis

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