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DOI: 10.5482/HAMO-13-04-0024
Diagnose angeborener Störungen der Thrombozytenfunktion
Interdisziplinäre S2K-Leitlinie[*] der Ständigen Kommission Pädiatrie der Gesellschaft für Thrombose- und Hämostaseforschung e. V.Diagnosis of inherited diseases of platelet functionInterdisciplinary S2K guideline[*] of the Permanent Paediatric Committee of the Society of Thrombosis and Haemostasis Research (GTH e. V.)Publication History
received:
22 April 2013
accepted:
21 May 2014
Publication Date:
28 December 2017 (online)
Zusammenfassung
Angeborene Störungen der Thrombozytenfunktion sind eine heterogene Gruppe von Erkrankungen, die oft erst bei Auftreten von Blutungen erkannt werden. Im klinischen Bereich haben sich nur wenige Methoden zur Diagnose und Klassifizierung von angeborenen Thrombozytenfunktionsstörungen bewährt. Für eine rationelle Diagnostik ist ein stufenweises Vorgehen empfehlenswert. Anamnese und klinische Untersuchung sind Grundvoraussetzungen. Das von-Willebrand-Syndrom und andere plasmatische Gerinnungsstörungen sollten vor einer spezifischen Thrombozytenfunktionsdiagnostik immer ausgeschlossen werden. Die Bestimmung von Zahl, Größe, Volumen (MPV) und Morphologie der Thrombozyten erlauben Rückschlüsse auf die zu Grunde liegende Störung.
Die PFA-100®-Verschlusszeit eignet sich als Screening zum Ausschluss schwerer Thrombozytenfunktionsstörungen. Die Aggrego metrie ermöglicht die Untersuchung zahlreicher Aspekte der Thrombozytenfunktion. Die Durchflusszytometrie ist zur Diagnose von Thrombasthenie Glanzmann, Bernard-Soulier- Syndrom und Freisetzungsstörungen geeignet. Molekulargenetische Untersuchungen können die Verdachtsdiagnose bestätigen oder zum Nachweis nicht beschriebener Defekte verwendet werden. Hier wird die ungekürzte Version der inter -disziplinären Leitlinie* präsentiert.
Summary
Congenital disorders of platelet function are a heterogeneous group of disorders that are often not detected until bleeding occurs. In clinical settings only a few methods have proven to be useful for identification and classification of inherited platelet disorders. For a rational diagnostic approach, a step-wise algorithm is recommended. Patient history and clinical investigation are mandatory. Von Willebrand disease and other coagulation disorders should always be ruled out prior to specific platelet testing. Platelet count, size, volume (MPV) and morphology may guide further investigations.
The PFA-100® CT is suited for screening for severe platelet defects. Platelet aggregometry allows assessment of multiple aspects of platelet function. Flow cytometry enables diagnosis of thrombasthenia Glanzmann, Bernard-Soulier syndrome and storage pool defects. Molecular genetics may confirm a putative diagnosis or pave the way for identifying new defects.
We present an unabridged version of the interdisciplinary guideline.
* AWMF # 086–003; S2K
# Die Autoren RK, WE, HS haben zu gleichen Teilen bei getragen.
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Literatur
- 1 Cox K, Price V, Kahr WH. Inherited platelet disorders: a clinical approach to diagnosis and management. Expert Rev Hematol 2011; 04: 455-472.
- 2 Streif W, Olivieri M, Weickardt S. et al. Testing for inherited platelet defects in clinical laboratories in Germany, Austria and Switzerland. Platelets 2010; 21: 470-478.
- 3 Guidelines on platelet function testing. The British Society for Haematology BCSH Haemostasis and Thrombosis Task Force. J Clin Pathol 1988; 41: 1322-1330.
- 4 Christie JD, Avari T, Carrington RL. et al. H58-A – Platelet Function Testing by Aggregometry; Approved Guideline. Clinical And Laboratory Standards Institute (CLSI). 2008.
- 5 Schambeck CM. Blutungsneigung: Diagnostische Strategie zur Abklärung einer Thrombozytendysfunktion. Consensus-Papier der DGKL-Arbeitsgruppe “Hämostaseologische Labordiagnostik”. J Lab Med 2004; 28: 453-462.
- 6 Cattaneo M, Hayward CP, Moffat KA. et al. Results of a worldwide survey on the assessment of platelet function by light transmission aggregometry: a report from the platelet physiology subcommittee of the SSC of the ISTH. J Thromb Haemost 2009; 07: 1029.
- 7 Duncan EM, Bonar R, Rodgers SE. et al. Methodology and outcomes of platelet aggregation testing in Australia, New Zealand and the Asia-Pacific region. Int J Lab Hematol 2009; 31: 398-406.
- 8 Harrison P, Mackie I, Mumford A. et al. Guidelines for the laboratory investigation of heritable disorders of platelet function. Br J Haematol 2011; 155: 30-44.
- 9 Hayward CP, Moffat KA, Plumhoff E, Van Cott EM. Approaches to investigating common bleeding disorders: an evaluation of North American coagulation laboratory practices. Am J Hematol 2012; 87 (Suppl. 01) S45-S50.
- 10 Rodgers RP. Bleeding time tables. A tabular summary of pertinent literature. Semin Thromb Hemost 1990; 16: 21-138.
- 11 Hayward CP, Harrison P, Cattaneo M. et al. Platelet function analyzer (PFA)-100 closure time in the evaluation of platelet disorders and platelet function. J Thromb Haemost 2006; 04: 312-319.
- 12 Halimeh S, Angelis G, Sander A. et al. Multiplate whole blood impedance point of care aggregometry: preliminary reference values in healthy infants, children and adolescents. Klin Pädiatr 2010; 222: 158-163.
- 13 Favaloro EJ. Clinical utility of the PFA-100. Semin Thromb Hemost 2008; 34: 709-733.
- 14 Born GV. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 1962; 194: 927-929.
- 15 Cardinal DC, Flower RJ. The electronic aggregometer: a novel device for assessing platelet behavior in blood. J Pharmacol Methods 1980; 03: 135-158.
- 16 Bonduel M, Frontroth JP, Hepner M. et al. Platelet aggregation and adenosine triphosphate release values in children and adults. J Thromb Haemost 2007; 05: 1782-1783.
- 17 Knöfler R, Weissbach G, Kuhlisch E. Platelet function tests in childhood. Measuring aggregation and release reaction in whole blood. Semin Thromb Hemost 1998; 24: 513-521.
- 18 Lundin A, Richardsson A, Thore A. Continuous monitoring of ATP-converting reactions by purified firefly luciferase. Anal Biochem 1976; 75: 611-620.
- 19 George JN, Shattil SJ. The clinical importance of acquired abnormalities of platelet function. N Engl J Med 1991; 324: 27-39.
- 20 Schmitz G, Rothe G, Ruf A. et al. European Working Group on Clinical Cell Analysis: Consensus protocol for the flow cytometric characterisation of platelet function. Thromb Haemost 1998; 79: 885-896.
- 21 Michelson AD. Evaluation of platelet function by flow cytometry. Pathophysiol Haemost Thromb 2006; 35: 67-82.
- 22 Wall JE, Buijs-Wilts M, Arnold JT. et al. A flow cytometric assay using mepacrine for study of uptake and release of platelet dense granule contents. Br J Haematol 1995; 89: 380-385.
- 23 Israels SJ, Kahr WH, Blanchette VS. et al. Platelet disorders in children: A diagnostic approach. Pediatr Blood Cancer 2011; 56: 975-983.
- 24 Balduini CL, Cattaneo M, Fabris F. et al. Inherited thrombocytopenias: a proposed diagnostic algorithm from the Italian Gruppo di Studio delle Piastrine. Haematologica 2003; 88: 582-592.
- 25 Nurden A, Nurden P. Advances in our understanding of the molecular basis of disorders of platelet function. J Thromb Haemost 2011; 09 (Suppl. 01) 76-91.