Platelet-type von Willebrand Disease: Diagnostic Challenges. Flaws and Pitfalls Experienced in the THROMKID Quality Project

Abstract

Background: Primary haemostasis defects comprise von Willebrand disease (VWD) and platelet disorders (PD). Although presenting with mild to moderate bleeding tendency in most cases, severe bleeding and blood loss may occur unexpectedly in trauma and surgery. Diagnosis of VWD and PD often remains difficult owing to the wide spectrum of clinical and laboratory manifestations. Platelet-type von Willebrand disease (PT-VWD) is frequently misdiagnosed as type 2B VWD. Discrimination between type 2B VWD and PT-VWD is crucial as treatment differs.

Methods and results: A literature review revealed difficulties in diagnostic work-up and choice of optimal treatment of PT-VWD. Guidelines favour the therapeutic use of platelet concentrates. A telephone survey of diagnostic practice with regard to type 2B VWD/PT-VWD was conducted. The prevalence and incidence of type 2B and PT-VWD remained unclear, but PT-VWD may be underestimated.

Discussion: An international study estimated that PT-VWD constitutes up to 15% of the total number of patients diagnosed with type 2B VWD. Our survey confirmed difficulties with diagnosis and showed that some centres did not exclude PT-VWD in type 2B patients. Some authors emphasize that genetic testing is the gold standard for diagnosis, but functional testing allows immediate diagnosis. Due to the important therapeutic implications we suggest that type 2B VWD be confirmed by genetic testing and that in case of a negative result PT-VWD should be excluded.

Conclusion: PT-VWD should be excluded in all suspected cases of type 2B. PT-VWD should be treated with platelet concentrates.

Zusammenfassung

Hintergrund: Das von Willebrand Syndrom (VWS) und die angeborenen Thrombozytenfunktionsstörungen gehören zu den Störungen der primären Hämostase. Trotz der zumeist moderaten Blutungsneigung, können schwere Blutungen und großer Blutverlust bei Verletzungen oder chirurgischen Eingriffen unerwartet eintreten. Die Vielfalt der klinischen und laborchemischen Eigenheiten erschwert die Diagnose des VWS und der Thrombozytenfunktionsstörungen. Das PT-VWS wird häufig als Typ 2B VWS fehldiagnostiziert. Die Unterscheidung zwischen Typ 2B und PT-VWS ist wichtig, da sich die Therapie wesentlich unterscheidet.

Methoden und Ergebnisse: Die Durchsicht der Literatur zeigte Schwierigkeiten bei der Diagnose und der Auswahl der optimalen Therapie. Aktuelle Leitlinien empfehlen die Gabe von Thrombozytenkonzentraten beim PT-VWS. Zur klinischen Praxis der Diagnose des Typ 2B VWS und PT-VWS führten wir eine Umfrage durch. Die Prävalenz und Inzidenz von Typ 2B- und PT-VWS bleiben unklar, PT-VWS wird aber wahrscheinlich unterschätzt.

Diskussion: Eine internationale Studie zeigte, dass bis zu 15% der Patienten bei denen ein Typ 2B VWS diagnostiziert wurde tatsächlich am PT-VWS leiden. Unsere Umfrage bestätigte diagnostische Schwierigkeiten und zeigte, dass nicht alle Zentren ein PT-VWS bei Typ 2B VWS ausschließen. Einige Autoren empfehlen die genetische Untersuchung als Goldstandard; die funktionelle Untersuchung erlaubt jedoch eine raschere Diagnose. Wegen der therapeutischen Konsequenzen empfehlen wir bei Verdacht auf Typ 2B VWS die genetische Bestätigung, im Falle eines negativen Ergebnisses, den genetischen Ausschluss eines PT-VWS.

Schlussfolgerung: In allen Typ 2B VWS Verdachtsfällen soll ein PT-VWS ausgeschlossen werden. Das PT-VWS sollte mit Thrombozytenkonzentraten behandelt werden.

Key words

blood platelet disorders - von Willebrand disease - platelet-type or pseudo von Willebrand disease - von Willebrand disease/diagnosis

Schlüsselwörter

Thrombozytopathien - von Willebrand Syndrom - Platelet-Typ oder pseudo von Willebrand Syndrom - von Willebrand Syndrom/Diagnose

^* http://www.awmf.org/leitlinien/detail/ll/086-003.html last visited 28.12.2014

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