A Tale of Two Lines

This week in Morning Report, we discussed two different patients who presented with CBC abnormalities — elevated hemoglobin, and elevated platelets. We used this as a jumping-off point to discuss an approach to erythrocytosis, thrombocytosis, and hematological malignancies.

Let’s summarize the main learning points from this case!

1. If you understand hematopoiesis, you can understand almost any hematological malignancy

Heme malignancies are often an area of confusion, partially due to the complex nomenclature involved. To make sense of the acronym soup (AML, CML, ALL, CLL, MDS, MPN…), it’s really useful to go back to basics and remind ourselves of the pluripotent hematopoietic stem cell.

The hematopoeitic stem cell, which can differentiate into myeloid vs. lymphoid lineages (Image from Wikimedia Commons, used with attribution)

The hematopoeitic stem cell can differentiate into myeloid or lymphoid progenitors:

  • Myeloid lineage: RBCs, Platelets, and Granulocytes (Neutrophils, Eosinophils, Basophils)
  • Lymphoid lineage: T-lymphocytes, B-lymphocytes

Once we understand the two lineages, we can understand all the ways in which a cell can go wrong on its pathway to self-actualization (i.e., end-differentiation):

  • Precursor, or immature cells (blasts) can start to overproliferate:
    • In the myeloid lineage, this is Acute Myelogenous Leukemia (AML)
    • In the lymphoid lineage, this is Acute Lymphocytic Leukemia (ALL)
  • Mature, or end-differentiated cells can start to overproliferate:
    • Myeloid Lineage:
      • Too many RBCs: Polycythemia Vera (PV)
      • Too many Platelets: Essential Thrombocythemia (ET)
      • Too many Granulocytes (Eos, Basos, Neuts): Chronic Myelogenous Leukemia (CML)
    • Lymphoid Lineage:
      • Too many Lymphocytes: Lymphoma (in nodes/spleen) or Chronic Lymphocytic Leukemia (CLL) (in blood)
      • Too many Plasma Cells: Myeloma spectrum disorders (e.g., MGUS, Smoldering Myeloma, Multiple Myeloma), Amyloidosis, Waldenstrom’s/Lymphoplasmocytic Lymphoma
  • Cells can fail to mature properly, causing them to look abnormal, or dysplastic. This leads to fewer numbers of mature, well-functioning myeloid cells.
    • This is Myelodysplastic Syndrome (MDS)

I’ve listed all of these in the annotated diagram below:

A means of understanding heme malignancies. Note, this is a very simplified explanation (e.g., there is often disease overlap and many stages of progenitor cells), but this is a useful scaffolding to build in, nonetheless!

2. A tale of two lines

We discussed two cases: one of a previously healthy patient with incidentally noted erythrocytosis (Hb 175), and another of a patient with profound longstanding thrombocytosis (Plt 1450) and numerous arterial/venous thrombotic complications.

We discussed the importance of terminology: erythrocytosis vs. polycythemia vera, thrombocytosis vs. essential thrombocythemia. Remember that -cytosis generally simply names the condition of RBC or Plt excess, whereas polycythemia vera and essential thrombocythemia specifically refer to the myeloproliferative neoplasms that cause this excess.

3. Approach to Erythrocytosis

We went through a few visual quizzes and then discussed an approach to Erythrocytosis, summarized in the table below. There is also an excellent (and very recent!) review of Investigation and Management of Erythrocytosis in the August 2020 CMAJ that is worth perusing (especially their diagnostic approach flowchart).

4. Approach to Thrombocytosis

Here is a summary of the approach to Thrombocytosis that we discussed. I also recommend this ASCO post on ‘How I Work Up the Patient with Thrombocytosis’ for a useful step-by-step diagnostic approach.

Don’t forget that referral to your hematology colleagues is a key step in management of erythrocytosis or thrombocytosis with suspicious features concerning for myeloproliferative disease.

I hope you found this Morning Report useful! As always, please direct any questions or comments to the CMR.

Note: These recaps are based on real-life cases presented during weekly Morning Report; however, no real patient findings/investigations/images/identifying details are used. Any clinical information presented has been modified and completely de-identified for privacy.

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