Hamostaseologie 2011; 31(01): 28-40
DOI: 10.5482/ha-1145
Review
Schattauer GmbH

The impact and management of acquired platelet dysfunction

Bedeutung und Behandlung erworbener Plättchen funktionsstörungen
R. E. Scharf
1   Department of Experimental and Clinical Haemostasis, Haemotherapy and Transfusion Medicine, and Haemophilia Comprehensive Care Center, Heinrich Heine University Medical Center, Düsseldorf, Germany
,
M. M. Rahman
1   Department of Experimental and Clinical Haemostasis, Haemotherapy and Transfusion Medicine, and Haemophilia Comprehensive Care Center, Heinrich Heine University Medical Center, Düsseldorf, Germany
2   Division of Haematology, Dhaka Medical College Hospital, Dhaka, Bangladesh
,
H. Seidel
1   Department of Experimental and Clinical Haemostasis, Haemotherapy and Transfusion Medicine, and Haemophilia Comprehensive Care Center, Heinrich Heine University Medical Center, Düsseldorf, Germany
› Author Affiliations
Acknowledgements: This work was supported in part by grants of the Deutsche Forschungsgemeinschaft (Scha 358/3–1 and Sonderforschungsbereich 612 „Molecular analysis of cardiovascular functions and dysfunctions“, TPB2 „Modulation of platelet thrombogenicity through genetically determined variants of platelet integrins“). Additional support was provided by the Biological Medical Research Center, Heinrich Heine University, Düsseldorf. We thank Prof. Zaverio M. Ruggeri, The Scripps Research Institute, La Jolla, CA, USA, for providing monoclonal antibodies (LJ-P4, LJ-CP8, and LJ-Ibα) and purified human fibrinogen; Prof. Sanford J. Shattil and Prof. Mark H. Ginsberg, Department of Medicine, University of California San Diego, La Jolla, CA, USA, for PAC1 and anti-LIBS1, respectively. Dr. M. Mizanur Rahman is recipient of a fellowship (“Reach the World Education Program”) from the International Society on Thrombosis and Haemostasis.
Further Information

Publication History

Publication Date:
27 December 2017 (online)

Summary

Platelet function can be abnormally increased, as in association with acute vascular events, or defective, as in a variety of clinical settings. Acquired platelet dysfunction may occur at any age and range in severity from mild to life-threatening haemorrhages. Diagnostic work-up of platelet disorders requires meticulous evaluation of medical history, specifically of any drugs interfering with platelet function, careful clinical examination and a staged laboratory protocol to assess the underlying platelet defect(s). To identify hyperactive platelets ex vivo, costly procedures may be required using flow cytometry and distict epitope-specific monoclonal antibodies. Currently, this approach can be recommended for research purposes only. Drugs represent the most common cause of platelet dysfunction in our overmedicated society. While aspirin, clopigogrel (more recently also prasugrel) and integrin αIIbβ3 (GPIIb-IIIa) receptor antagonists (ab-ciximab, eptifibatide and tirofiban) are well-known prototypes of antiplatelet drugs, other widely used agents (e.g. nonsteroidal anti-inflammatory drugs, antibiotics, serotonin reup-take inhibitors and volume expanders) can also impair platelet function and thus cause or aggravate hemorrhages. Identification of individual patients with pre-existing hemostatic defects remains crucial (i) to prevent bleeding complications, (ii) to manage symptoms adequately, (iii) to minimize the risk from invasive procedures, and (iv) to avoid unnecassary exposure to blood products. Screening for platelet dysfunction can be performed by point-of-care testing followed by platelet aggregometry in response to various agonists. While mild bleeding episodes due to antiplatelet therapy can be managed by withdrawal of the drug(s), severe hemorrhages may require immediate platelet transfusions. Apart from that, the prohemostatic armamentarium is limited to desmopressin, antifi-brinolytic agents, and recombinant factor VIIa.

Zusammenfassung

Thrombozytäre Funktionen können abnorm gesteigert sein, etwa bei akuten vaskulären Ereignissen, oder – im Gefolge einer Vielzahl von Krankheitsbildern – Defekte aufweisen (Thrombozytopathien). Defizitäre Plättchenstörungen treten in jedem Lebensalter auf und können leichte bis lebensbedrohliche Blutungen hervorrufen. Die exakte Zuordnung thrombozytärer Störungen erfordert eine genaue Erhebung der Vorgeschichte einschließlich einer akribischen Medikamentenanamnese, besonders von Substanzen, die mit Plättchenfunktionen interferieren können, ebenso eine sorgfältige klinische Untersuchung und laboranalytische Stufen-diagnostik. Zum Nachweis hyperaktiver Plättchen ex vivo können aufwändige, kosteninten-sive Verfahren wie durchflusszytometrische Un-tersuchungen unter Einsatz epitopspezifischer monoklonaler Antikörper erforderlich werden. Allerdings sollten solche Techniken zurzeit auf Forschungsvorhaben beschränkt bleiben. Bei dem hohen Medikamentenkonsum überrascht es nicht, dass Pharmaka die Hauptursache er-worbener Plättchenfunktionsstörungen dar-stellen. Typische antithrombozytäre Substanzen sind Azetylsalizylsäure, Clopidogrel (neuerdings Prasugrel) und Integrin αIIbβ3 (GPIIb-IIIa)-Re-zeptorantagonisten (Abciximab, Eptifibatid und Tirofiban). Daneben können andere häufig ein-gesetzte Medikamente wie nichtsteroidale entzündungshemmende Substanzen, Antibiotika, Serotonin-Wiederaufnahme-Inhibitoren und Volumenexpander die Plättchenfunktion beein-trächtigen und eine Blutungsneigung bedingen oder verstärken. Die Identifizierung einezelner Patienten mit vorbestehenden Hämostasede-fekten ist entscheidend, um (i) Blutungskomplikationen vorzubeugen, (ii) Symptome adäquat zu behandeln, (iii) Risken invasiver Verfahren zu minimieren und (iv) eine unnötige Exposition gegenüber Blutprodukten zu vermeiden. Als Screening-Verfahren einer gestörten Plättchen-funktion werden zunächst Point-of-Care-Techniken, anschließend die Thrombozytenaggrego-metrie nach Plättchenstimulation mit verschie-denen Agonisten eingesetzt. Bei geringer Blutung infolge antithrombozytärer Therapie ge-nügt in der Regel das Absetzen des Medikaments. Schwerwiegende Blutungen können hingegen die sofortige Transfusion von Throm-bozytenkonzentraten erfordern. Das übrige Behandlungsspektrum zur Blutstillung beschränkt sich auf den Einsatz von Desmopressin, Antifi-brinolytika und rekombinanten Faktor VIIa.

 
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