Pre-analytical Phase

The pre-analytical phase covers everything that happens before the specimen reaches the bench: test ordering, patient identification, collection, labeling, transport, and accessioning. It is the single largest source of laboratory error (often cited as 60-70% of all errors) and the only phase where errors can usually be prevented but not corrected after the fact. For genetic testing the stakes are higher because many assays cannot be repeated without recollection, and the wrong tube can silently invalidate a result rather than fail outright.

• Patient identification: minimum of two identifiers (typically full name plus date of birth or MRN) verified at collection. Labels must be applied at the bedside, in the patient's presence, before the sample leaves the room. Pre-labeled tubes and post-collection labeling are common root causes of wrong-patient errors.
• Requisition completeness: clinical indication, ICD code, ordering provider, family history when relevant, ethnicity (for carrier screening), and gestational age (for prenatal samples). Incomplete requisitions delay accessioning and can lead to the wrong test being run.
• Tube and anticoagulant selection by assay:
  • Karyotype requires viable, dividing cells. Use sodium heparin (green top); EDTA chelates calcium needed for cell culture and is unacceptable.
  • Molecular DNA testing (PCR, NGS, MLPA, Sanger) uses EDTA (lavender top). Heparin inhibits Taq polymerase.
  • Cell-free DNA (NIPS, liquid biopsy) uses Streck cfDNA BCT or equivalent stabilized tubes. Streck tubes contain a fixative that stabilizes nucleated cells and prevents genomic DNA contamination of the cfDNA fraction; standard EDTA allows leukocyte lysis and dilutes fetal/tumor fraction within hours.
  • RNA / expression testing uses PAXgene or Tempus tubes that stabilize RNA at room temperature.
  • Biochemical genetics assays (acylcarnitines, organic acids, amino acids) often have specific tubes, dried blood spot cards, or 24-hour urine requirements.
• Specimen integrity: hemolysis can interfere with spectrophotometric and PCR assays; clotted EDTA samples cannot be processed for DNA reliably; light-sensitive analytes (bilirubin, some metabolites) require foil wrapping; temperature-sensitive samples (cfDNA, RNA, viable cells for karyotype) require defined cold-chain or ambient handling.
• Transport and time-to-receipt: karyotype samples should reach the lab within 24-48 hours at room temperature (not frozen, which kills cells); cfDNA in Streck is stable up to 7 days at ambient; PAXgene RNA tubes have defined incubation times before freezing. Frozen blood for karyotype is non-viable.
• Specimen rejection criteria: wrong tube, unlabeled or mislabeled tube, insufficient volume (QNS), clotted EDTA, hemolysis (assay-dependent), exceeded stability window, leaking container, and any specimen-requisition mismatch. Rejection is documented, the ordering provider is notified, and recollection is requested.

• A "failed" karyotype on a sample drawn into a lavender (EDTA) tube is a classic preanalytic error - the test cannot be salvaged and the patient must be redrawn into sodium heparin.
• Low fetal fraction on NIPS sometimes reflects a preanalytic problem (wrong tube, delayed shipping) rather than true biological low fetal fraction.
• Two-identifier verification is the single most effective intervention to prevent wrong-patient results, particularly in busy obstetric and oncology workflows.
• For cascade testing of a known familial variant, the requisition must specify the exact variant (gene, transcript, HGVS nomenclature) so the lab runs the correct targeted assay rather than a full panel.