Strengths and limitations of high-throughput sequencing for the diagnosis of inherited bleeding and platelet disorders

J Thromb Haemost. 2020 Aug;18(8):1839-1845. doi: 10.1111/jth.14945.

Abstract

Inherited bleeding and platelet disorders (BPD) are highly heterogeneous and their diagnosis involves a combination of clinical investigations, laboratory tests, and genetic screening. This review will outline some of the challenges that geneticists and experts in clinical hemostasis face when implementing high-throughput sequencing (HTS) for patient care. We will provide an overview of the strengths and limitations of the different HTS techniques that can be used to diagnose BPD. An HTS test is cost-efficient and expected to increase the diagnostic rate with a possibility to detect unexpected diagnoses and decrease the turnaround time to diagnose patients. On the other hand, technical shortcomings, variant interpretation difficulties, and ethical issues related to HTS for BPD will also be documented. Delivering a genetic diagnosis to patients is highly desirable to improve clinical management and allow family counseling, but making incorrect assumptions about variants and providing insufficient information to patients before initiating the test could be harmful. Data-sharing and improved HTS guidelines are essential to limit these major drawbacks of HTS.

Keywords: blood platelets; high-throughput nucleotide sequencing; inherited blood coagulation disorders; molecular diagnostic techniques; thrombosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Blood Coagulation Disorders, Inherited* / diagnosis
  • Blood Coagulation Disorders, Inherited* / genetics
  • Blood Platelet Disorders* / diagnosis
  • Blood Platelet Disorders* / genetics
  • Blood Platelets
  • Genetic Testing
  • High-Throughput Nucleotide Sequencing
  • Humans