Testing strategies used in the diagnosis of rare inherited bleeding disorders

ABSTRACT

Introduction

Rare Bleeding Disorders have a low population prevalence and may not be recognized by most clinicians. In addition, knowledge gaps of the indicated laboratory tests and their availability add to the potential for delayed diagnosis or misdiagnosis. The lack of widely available commercial, regulatory body approved esoteric tests limits them to reference laboratories, thus limiting easy access for patients.

Areas covered

A literature search of PubMed, Medline, and Embase and a review of international society guidelines were performed. Additional references from published articles were reviewed. A patient-centered approach to recognition and evaluation of RBD is discussed.

Expert opinion

Recognition of RBD relies on obtaining a detailed patient's personal and family hemostatic history. Inquiry into a history of involvement of other organ systems is important and, if present, should lead to suspicion of an inherited platelet disorder or a variant of Ehlers-Danlos Syndrome. Multiple factors contribute to the complexity of developing efficient algorithms for diagnostic testing. Limitations in diagnostic sensitivity and specificity of screening tests, diagnostic tests, and esoteric tests further compound the complexity of establishing a diagnosis. Educational efforts focusing on clinician awareness of RBDs and available testing options are vital for optimal management of such patients.

KEYWORDS:

• Rare inherited bleeding disorders
• laboratory diagnosis
• esoteric testing
• inherited platelet disorders
• Ehlers-Danlos

Article highlights

• Rare bleeding disorders are not recognized because of their low prevalence.

• Through clinical evaluation is critical in the initial evaluation of the patient.

• Selected syndromic inherited platelet disorders and variants of Ehlers-Danlos have unique phenotypic features that help in initial recognition of the disorders.

• Gaps in knowledge of which tests to order and having access to these tests compound the problem.

• Screening tests of coagulation have limitations in sensitivity and specificity

• Platelet function tests cannot be shipped to remote testing sites, but selected platelet assays are validated for shipping.

Declaration of interest

RK Pruthi has received honoraria for attending advisory boards from CSL Behring, Genentech Inc, Bayer Healthcare AG, HEMA Biologics, Instrumentation Laboratory, BioMarin and consulting for Merck.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.