Improvement in the Haemostatic Defect of Uraemia After Treatment With Recombinant Human Erythropoietin

Moia, Marco; Vizzotto, Laura; Cattaneo, Marco; Mannucci, Pier Mannuccio; Casati, Stefano; Ponticelli, Claudio

doi:10.1016/s0140-6736(87)91849-6

Cited by 265 publications

(99 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It has been established that platelet count, 12 hematocrit, 12 and blood flow 13 -16 determine the amount of platelets available for adhesion. The low hematocrit in uremia was thus established as a major 17 - 19 but not the only 17 - 20 cause of uremic bleeding. Additionally, platelet adhesion to the subendothelium is inhibited by a factor in uremic plasma.…”

Section: Arteriosclerosis and Thrombosis Vol 11 No 3 May/june 1991mentioning

confidence: 99%

Defects in platelet adhesion and aggregate formation in uremic bleeding disorder can be attributed to factors in plasma.

Zwaginga¹,

Ijsseldijk²,

Groot³

et al. 1991

Arterioscler Thromb

View full text Add to dashboard Cite

Uremia is associated with bleeding diathesis. Platelet adhesion to the subendothelium is inhibited by a factor in uremic plasma that may play a role in the disturbed hemostasis of uremic patients. In the formation of the hemostatic plug, platelet adherence is followed by stimulus-induced platelet aggregation and reinforcement by thrombin-generated fibrin. To study these processes in uremic blood, a newly developed thrombosis model was used. Perfusates anticoagulated with low-molecular-weight heparin were circulated over a matrix of stimulated cultured endothelial cells. By stimulation of the endothelial cells, tissue factor was synthesized and deposited in the matrix. When this tissue factor rich-matrix was exposed to flowing blood, local thrombin was formed via activation of the extrinsic coagulation pathway. With this system, platelet adhesion, thrombin-dependent platelet activation, and fibrin formation can all be studied at the same surface. In addition to an adhesion defect, decreased aggregate formation was also found in uremic perfusates. Normal platelets in uremic plasma showed similar results, which indicates that a factor in uremic plasma caused this adhesion and aggregation defect. Platelet aggregation in the system was dependent on endogeneously formed thrombin. Fibrinopeptide A generation, however, was normal in uremic perfusates; therefore, uremic plasma has a normal capacity to form thrombin. Resuspension of washed uremic platelets in control plasma did not reverse the aggregation defect in perfusions. In contrast, aggregometer studies with isolated uremic platelets could not detect an abnormal response to threshold concentrations of exogenous thrombin. Thus, uremic toxin (s) cause defective aggregate formation in flow, but not necessarily in the aggregometer. This apparent discrepancy may be due to the higher shear forces in the flow system, which may prevent aggregate formation that is allowed in the aggregometer. Another explanation, that uremic platelets are less responsive to locally formed thrombin than they are to exogenously added thrombin, seems less likely. [Arteriosclerosis and Thrombosis 1991;ll:733-744)

show abstract

Section: Arteriosclerosis and Thrombosis Vol 11 No 3 May/june 1991mentioning

confidence: 99%

Defects in platelet adhesion and aggregate formation in uremic bleeding disorder can be attributed to factors in plasma.

Zwaginga¹,

Ijsseldijk²,

Groot³

et al. 1991

Arterioscler Thromb

View full text Add to dashboard Cite

show abstract

“…In addition, anemia associated with severe chronic renal failure is another factor influencing the uremic platelet defect because red cells can enhance platelet function by both biochemical and rheological mechanisms [4,5,17]. rHuEPO treatment corrects anemia in uremic patients and improves primary hemostasis through the hematocrit rise [6,7]. Although anemia is an important factor, it is not the sole determinant of uremic bleeding because rHuEPO can improve platelet function independently of the effect of rHuEPO on hematocrit [8][9][10][11].…”

Section: Discussionmentioning

confidence: 99%

“…The anemia frequently found in uremic patients has been associated also with the hemostatic defect in these patients [4,5]. Recombinant human erythropoietin (rHuEPO) effectively corrects the anemia of uremic patients and improves platelet function ''in vivo,'' mainly through increasing hematocrit and blood viscosity [6,7]. Furthermore, improvement of platelet aggregability has been reported during rHuEPO treatment [7][8][9][10] and amelioration of platelet function has also been observed in the early stages of treatment, when an effect on hematocrit is still not reached [10,11].…”

Section: Introductionmentioning

confidence: 99%

Untitled

1998

American J Hematol

View full text Add to dashboard Cite

Recombinant human erythropoietin improves platelet function in uremia through the correction of anemia, but this effect can be seen also before the hematocrit rise. We studied 12 hemodialyzed patients (seven men, five women) who received recombinant human erythropoietin (40 IU kg −1 i.v., three times weekly) and were evaluated before treatment and after three doses; 24 control subjects were used. Platelet aggregation induced by adenosine 5-diphosphate (ADP), epinephrine, collagen, arachidonic acid, and ristocetin, and reticulated platelets determined by flow cytometry after staining with thiazole orange were measured. Platelet aggregation induced by all the agonists were impaired in uremic patients (P < 0.01), but ADP and ristocetin-induced aggregations improved after treatment (P < 0.01). Hemodialyzed patients had less reticulated platelets than controls (P < 0.01). Reticulated platelets increased after three doses of treatment (P < 0.01). In conclusion, improvement of platelet function at early stages of recombinant human erythropoietin treatment may be attributed to the increase in young platelets detected as reticulated platelets. Am.

show abstract

“…Treatment with erythropoiesisstimulating agents was introduced in the mid1980s with a very favorable impact, not only in reducing the frequency of bleeding, but also in improving patients' overall quality of life. 2 The prothrombotic state in CKD may be related to an imbalance between coagulation factors and coagulation inhibitors, decreased fibrinolytic activity, platelet hyperactivity, and endothelial dysfunction. At present, although the incidence of bleeding is apparently decreasing, the thrombotic complications have become the main causes of mortality in this population.…”

Section: Indoxyl Sulfate a Uremic Trigger For Platelets ------------mentioning

confidence: 99%

Indoxyl sulfate, a uremic trigger for platelets

Díaz‐Ricart¹

2017

Blood

View full text Add to dashboard Cite

Improvement in the Haemostatic Defect of Uraemia After Treatment With Recombinant Human Erythropoietin

Cited by 265 publications

References 13 publications

Defects in platelet adhesion and aggregate formation in uremic bleeding disorder can be attributed to factors in plasma.

Defects in platelet adhesion and aggregate formation in uremic bleeding disorder can be attributed to factors in plasma.

Untitled

Indoxyl sulfate, a uremic trigger for platelets

Contact Info

Product

Resources

About