Colorado Care Network

4. One odd lab value

Clinicians with complex patients Planned episode, outlier patients in primary care. One objective finding that points somewhere: a low alkaline phosphatase, a ferritin that won't settle, an unexplained cytopenia.

Listener title: One odd lab value: when to repeat, act or ask about genetics

Listener description: A biochemical geneticist talks through the single objective finding that points somewhere: a low alkaline phosphatase, a ferritin that won't settle, an unexplained cytopenia. The conversation covers which values to repeat and which to act on once, when a lab result becomes a genetic question, and how to avoid a cascade of tests that answers nothing. For primary care clinicians who find the odd value and have to decide what it means.

Run of show (about 40 minutes)

Time Segment What happens
0:00 to 2:00 Opening The host introduces the topic and the guest's role. The guest states any industry relationships, including any with laboratories. The host notes that no patient information is discussed and that the guest speaks for themselves, not for the network.
2:00 to 6:00 The guest's work The guest describes biochemical genetics practice and the lab results that reach them from primary care, and what makes such a referral useful.
6:00 to 15:00 Repeat or act once Which values do you always repeat, and which do you act on once? The guest explains how they confirm that a value is persistent and how they read it against a properly defined reference range. The host uses low alkaline phosphatase as the worked example, reading the finding the CCN specific signs page cites from Larid 2024: 70.8% of adults with persistently low ALP who were given a bisphosphonate never had an ALP measured before it started. The guest explains what that means for checking prior values, and what the persistence data in Tornero 2020 add.
15:00 to 24:00 When a lab result becomes a genetic question When does a lab result become a genetic question? For low ALP, the guest explains how they use the biochemical algorithm in Tornero 2022 and the proposed diagnostic criteria in Khan 2024, and what a PLP level adds. For ferritin, the guest explains when iron studies lead to HFE genotyping and when they lead elsewhere, with reference to the ACG hemochromatosis guideline (Kowdley 2019). For cytopenias, the guest explains which unexplained cytopenias make them think of an inherited cause and what they want primary care to send.
24:00 to 32:00 Avoiding the cascade How do you avoid a cascade of tests that answers nothing? The guest explains how they sequence testing: one question per test, whether to confirm before broadening, targeted gene testing for a specific sign versus exome or genome for a broader picture. The host asks how they handle incidental findings from broad panels, and how they explain the cost of each step to a cash-pay patient, as method only.
32:00 to 37:00 Composite scenario, not a real patient A patient sent in to start a bisphosphonate after a bone density result has an ALP flagged low on two earlier panels in the chart, never commented on. The guest walks through the next orders and the order they go in, and what they would tell the patient about why the bisphosphonate waits.
37:00 to 40:00 Closing Takeaway: before acting on an odd value, pull every prior value in the chart to see whether it is persistent. The specific signs care map is at coloradocarenetwork.com/cohorts/specific-signs/, and members discuss it in #cohort-specific-signs. Listeners reach the network at coloradocarenetwork.com/join/ or hello@coloradocarenetwork.com.

Guest prep questions (sent to the guest a week ahead)

  1. Which lab values do you always want repeated before anyone acts, and which single values are enough on their own?
  2. For a persistently low alkaline phosphatase, what workup do you want done before referral, and when do you send ALPL testing?
  3. For a ferritin that stays high, how do you separate iron overload from other causes, and when does it become a genetic question?
  4. Which unexplained cytopenias make you think of an inherited metabolic or storage disorder, and what should primary care send with the referral?
  5. How do you keep testing from cascading, including incidental findings on broad panels? Please send the sources you plan to cite (PubMed, DOI, GeneReviews or guideline) before recording, especially for the cytopenia discussion.

Show notes

A biochemical geneticist discusses what to do with a single odd lab value in primary care, using a low alkaline phosphatase, a persistently high ferritin and an unexplained cytopenia as examples. The conversation covers which values to repeat before acting, when a lab result becomes a genetic question, and how to sequence testing so that each test answers a question. A composite scenario, not a real patient, walks through a low ALP found before a planned bisphosphonate. The episode draws on the CCN specific signs care map.

  • Sources:
  • Larid G, Vix J, Preuss P, et al. Detection of hypophosphatasia in hospitalised adults in rheumatology and internal medicine departments: a multicentre study over 10 years. RMD Open. 2024;10(2):e004316. doi:10.1136/rmdopen-2024-004316
  • Tornero C, Navarro-Compán V, Tenorio JA, et al. Can we identify individuals with an ALPL variant in adults with persistent hypophosphatasaemia? Orphanet J Rare Dis. 2020;15(1):51. doi:10.1186/s13023-020-1315-y
  • Tornero C, Navarro-Compán V, Buño A, et al. Biochemical algorithm to identify individuals with ALPL variants among subjects with persistent hypophosphatasaemia. Orphanet J Rare Dis. 2022;17(1):98. doi:10.1186/s13023-022-02253-5
  • Khan AA, Brandi ML, Rush ET, et al. Hypophosphatasia diagnosis: current state of the art and proposed diagnostic criteria for children and adults. Osteoporos Int. 2024;35(3):431-438. doi:10.1007/s00198-023-06844-1
  • Kowdley KV, Brown KE, Ahn J, Sundaram V. ACG clinical guideline: hereditary hemochromatosis. Am J Gastroenterol. 2019;114(8):1202-1218. doi:10.14309/ajg.0000000000000315
  • For the cytopenia discussion: the guest supplies them before recording (PubMed, DOI, GeneReviews or guideline sources only).
  • No patient information is discussed on this episode.

All planned episodes. To be the guest for this episode, email hello@coloradocarenetwork.com with the episode number.

Colorado Care Network. 4. One odd lab value. Version 2026-10-30.