Laboratory diagnosis of clinically relevant platelet function disorders

Area of Science:

• Hematology
• Clinical Pathology
• Molecular Diagnostics

Background:

• Inherited platelet function disorders (IPFDs) are a major cause of congenital bleeding disorders, often presenting with severe bleeding.
• Accurate diagnosis of IPFDs is challenging and necessitates thorough clinical assessment and bleeding history evaluation.
• Current diagnostic strategies require a systematic laboratory approach to identify these conditions effectively.

Purpose of the Study:

• To outline a rational diagnostic algorithm for inherited platelet function disorders (IPFDs).
• To discuss the role of various laboratory tests in the diagnosis of IPFDs.
• To highlight recent advancements and considerations in IPFD diagnosis, including point-of-care testing and genotyping.

Main Methods:

• Initial clinical examination and bleeding history assessment.
• A tiered laboratory investigation including platelet count, peripheral blood smear, light transmission aggregometry, platelet granule analysis, and flow cytometry for glycoprotein expression.
• Consideration of point-of-care testing and genotyping (including next-generation sequencing) with critical evaluation of phenotype-genotype correlations.

Main Results:

• A structured algorithm employing a panel of laboratory tests is crucial for IPFD diagnosis.
• Established tests like aggregometry and flow cytometry are key, with ongoing development in point-of-care diagnostics.
• Genotyping, particularly via next-generation sequencing, offers value but requires careful interpretation alongside clinical and laboratory findings.

Conclusions:

• A systematic, algorithm-based laboratory approach is essential for diagnosing inherited platelet function disorders (IPFDs).
• Validated screening and confirmatory tests form the cornerstone of diagnosis, with emerging technologies like point-of-care tests and NGS offering future potential.
• Integrating clinical, laboratory, and genotypic data is critical for accurate IPFD diagnosis and management.