The Diagnostic Assessment of Inherited Platelet Function Defects - Part 1: An Overview of the Diagnostic Approach and Laboratory Methods

Gero Hoepner; Karina Althaus; Jens Müller; Barbara Zieger; Anna Pavlova; Doris Boeckelmann; Ralf Knöfler; Peter Bugert; Beate Kehrel; Werner Streif; Ingvild Birschmann; Heiko Rühl; Ulrich Sachs; Florian Prüller; Carlo Zaninetti; Harald Schulze; Nina Cooper; Kerstin Jurk; Tamam Bakchoul

doi:10.1055/a-2436-5318

Hämostaseologie, Inhaltsverzeichnis

Hamostaseologie 2025; 45(03): 229-242
DOI: 10.1055/a-2436-5318

Review Article

The Diagnostic Assessment of Inherited Platelet Function Defects - Part 1: An Overview of the Diagnostic Approach and Laboratory Methods

Gero Hoepner

¹Center for Clinical Transfusion Medicine Tuebingen, Tuebingen, Germany

²Department of Anaesthesiology and Intensive Care, University Hospital Tuebingen, Tuebingen, Germany

,

Karina Althaus

¹Center for Clinical Transfusion Medicine Tuebingen, Tuebingen, Germany

³Medical Faculty of Tuebingen, Institute for Clinical and Experimental Transfusion Medicine, Tuebingen, Germany

,

Jens Müller

⁴Institute of Experimental Haematology and Transfusion Medicine (IHT), University Hospital Bonn, Bonn, Germany

,

Barbara Zieger

⁵Department of Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Freiburg, Germany

,

Anna Pavlova

⁴Institute of Experimental Haematology and Transfusion Medicine (IHT), University Hospital Bonn, Bonn, Germany

,

Doris Boeckelmann

⁵Department of Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Freiburg, Germany

,

Ralf Knöfler

⁶Department of Paediatric Haemostaseology, Dresden University Hospital, Dresden, Germany

,

Peter Bugert

⁷Medical Faculty Mannheim, Institute of Transfusion Medicine and Immunology, Heidelberg University, Mannheim, Germany

,

Beate Kehrel

⁸Department of Anaesthesiology and Intensive Care, Experimental and Clinical Haemostasis, University-Hospital Munster, Münster, Germany

,

Werner Streif

⁹Kinder- und Jugendheilkunde, Innsbruck Medical University, Innsbruck, Austria

,

Ingvild Birschmann

¹⁰Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Institut für Laboratoriums- und Transfusionsmedizin, Bochum, Germany

,

Heiko Rühl

⁴Institute of Experimental Haematology and Transfusion Medicine (IHT), University Hospital Bonn, Bonn, Germany

,

Ulrich Sachs

¹¹Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany

¹²Center for Transfusion Medicine and Haemotherapy, Department of Thrombosis and Haemostasis, European Comprehensive Care Center for Haemophilia at Giessen and Marburg University Hospital, Giessen, Germany

,

Florian Prüller

¹³Medizinische Universität Graz, KIMCL, Graz, Austria

,

Carlo Zaninetti

¹⁴Institute of Immunology and Transfusion Medicine, Universitätsmedizin Greifswald, Greifswald, Germany

,

Harald Schulze

¹⁵Institute of Experimental Biomedicine, Universitätsklinikum Würzburg, Würzburg, Germany

,

Nina Cooper

¹¹Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany

¹²Center for Transfusion Medicine and Haemotherapy, Department of Thrombosis and Haemostasis, European Comprehensive Care Center for Haemophilia at Giessen and Marburg University Hospital, Giessen, Germany

,

Kerstin Jurk

¹⁶Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany

,

Tamam Bakchoul

¹Center for Clinical Transfusion Medicine Tuebingen, Tuebingen, Germany

³Medical Faculty of Tuebingen, Institute for Clinical and Experimental Transfusion Medicine, Tuebingen, Germany

› Institutsangaben

Abstract

In this article, our goal is to offer an introduction and overview of the diagnostic approach to inherited platelet function defects (iPFDs) for clinicians and laboratory personnel who are beginning to engage in the field. We describe the most commonly used laboratory methods and propose a diagnostic four-step approach, wherein each stage requires a higher level of expertise and more specialized methods. It should be noted that our proposed approach differs from the ISTH Guidance on this topic in some points. The first step in the diagnostic approach of iPFD should be a thorough medical history and clinical examination. We strongly advocate for the use of a validated bleeding score like the ISTH-BAT (International Society on Thrombosis and Haemostasis Bleeding Assessment Tool). External factors like diet and medication have to be considered. The second step should rule out plasmatic bleeding disorders and von Willebrand disease. Once this has been accomplished, the third step consists of a thorough platelet investigation of platelet phenotype and function. Established methods consist of blood smear analysis by light microscopy, light transmission aggregometry, and flow cytometry. Additional techniques such as lumiaggregometry, immune fluorescence microscopy, and platelet-dependent thrombin generation help confirm and specify the diagnosis of iPFD. In the fourth and last step, genetic testing can confirm a diagnosis, reveal novel mutations, and allow to compare unclear genetics with lab results. If diagnosis cannot be established through this process, experimental methods such as electron microscopy can give insight into the underlying disease.

Keywords

inherited/acquired platelet disorders - thrombocytopenia - diagnosis management - laboratory diagnostics - platelet pathology/inherited

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