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Thrombozytopathie und Blutungskomplikationen bei Urämie

Platelet dysfunction in Uremia

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Summary

Bleeding diathesis and thrombotic tendencies are characteristic findings in patients with end-stage renal disease. The pathogenesis of uremic bleeding tendency is related to multiple dysfunctions of the platelets. The platelet numbers may be reduced slightly, while platelet turnover is increased. The reduced adhesion of pltelets to the vascular subendothelial wall is due to reduction of GPIb and altered conformational changes of GPIIb/IIIa receptors. Alterations of platelet adhesion and aggregation are caused by uremic toxins, increased platelet production of NO, PGI2, calcium and cAMP as well as renal anemia. Correction of uremic bleeding is caused by treatment of renal anemia with recombinant human erythropoietin or darbepoetin α, adequate dialysis, desmopressin, cryoprecipitate, tranexamic acid, or conjugated estrogens. Thrombotic complications in uremia are caused by increased platelet aggregation and hypercoagulability. Erythrocyte-platelet-aggregates, leukocyte-platelet-aggregates and platelet microparticles are found in higher percentage in uremic patients as compared to healthy individuals. The increased expression of platelet phosphatidylserine initiates phagocytosis and coagulation. Therapy with antiplatelet drugs does not reduce vascular access thrombosis but increases bleeding complications in endstage renal disease patients. Heparin-induced thrombocytopenia (HIT type II) may develop in 0–12 % of hemodialysis patients. HIT antibody positive uremic patients mostly develop only mild thrombocytopenia and only very few thrombotic complications. Substitution of heparin by hirudin, danaparoid or regional citrate anticoagulation should be decided based on each single case.

Zusammenfassung

Hämorrhagische Diathese und Thromboseneigung sind charakteristische Befunde bei Patienten mit terminaler Niereninsuffizienz. Die Pathogenese der Blutungsneigung bei Urämie beruht auf multiplen Funktionsstörungen der Thrombozyten. Die Zahl der Thrombozyten kann bei Urämie leicht erniedrigt sein, der Thrombozytenturnover ist erhöht. Die verminderte Adhärenz von Thrombozyten an das Subendothel der Gefäße beruht auf einer Reduktion bzw. veränderten Konformation der GPIb- und GPIIb/IIIa-Rezeptoren. Störungen der Adhärenz und Aggregation der Thrombozyten sind bedingt durch Urämietoxine, die vermehrte thrombozytäre Produktion von NO, PGI2, Calcium und cAMP sowiedurch die renale Anämie. Eine Korrektur der urämischen Blutung lässt sich durch die Therapie der renalen Anämie mit rekombinantem humanen Erythropoietin oder Darbepoetin α, eine adäquate Dialysedosis sowie durch die Gabe von Desmopressin, Kryopräzipitat, Tranexaminsäure oder konjugierte Östrogenen erzielen. Die Thromboseneigung bei Urämie beruht auf einer gesteigerten Plättchenaggregation und Hyperkoagulabilität. Erythrozyten-Thrombozyten-Aggregate, Leukozyten-Thrombozyten-Aggregate und Plättchenmikropartikel zirkulieren bei Urämie in höherem Prozentsatz als beim Nierengesunden. Die vermehrte thrombozytäre Expression von Phosphatidylserin initiiert Phagozytose und Gerinnung. Eine Therapie mit Thrombozytenaggregationshemmern führt bei Patienten mit terminaler Niereninsuffizienz zu keiner Reduktion von Shuntthrombosen, vermehrt jedoch zu Blutungskomplikationen. Hämodialysepatienten können in 0–12 % der Fälle eine Heparin-induzierte Thrombozytopenie (HIT-II) entwickeln, wobei HIT-Antikörper-positive urämische Patienten meist nur milde Thrombozytopenien und nur selten thrombotische Komplikationen erleiden. Ein Ersatz von Heparin durch Hirudin, Danaparoid oder regionale Zitratantikoagulation muss anhand des Einzelfalls entschieden werden.

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  1. Klinische Abteilung für Nephrologie und Dialyse, Medizinische Universitätsklinik III, Medizinische Universität Wien, Austria

    Walter H. Hörl

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  1. Walter H. Hörl
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Hörl, W. Thrombozytopathie und Blutungskomplikationen bei Urämie. Wien Klin Wochenschr 118, 134–150 (2006). https://doi.org/10.1007/s00508-006-0574-5

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  • DOI: https://doi.org/10.1007/s00508-006-0574-5

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