Hematology Laboratory Tests

CBC & differential

See "How to interpret a CBC with differential" lecture for a detailed discussion.

Retic

• Reticulocytes are immature red blood cells that spend ~3 days maturing in the bone marrow, followed by 1–2 days in the peripheral blood before becoming mature RBCs.

• Retic count is a real-time indicator of bone marrow erythropoietic activity.

• Corrected reticulocyte count = % Retic × (Patient's Hct / Normal Hct)

• Reticulocyte production index (RPI) = Corrected retic count / Maturation factor

  • You do not need to calculate RPI yourself! Use Mdcalc.com.

  • Interpretation:

    • RPI >2 :

      • Appropriate BM response to anemia (hemolysis, acute blood loss)

    • RPI ≤2 :

      • Inadequate erythropoiesis (iron deficiency, BM suppression, chronic disease)

Peripheral Blood Smear (PBS)

*** SchistoSite will feature a separate lecture on peripheral blood smear (PBS) interpretation with a more detailed discussion and representative pathology images.

• Marked increase of mature-appearing lymphocytes:

  • Consider CLL (particularly in older adults; correlate with flow cytometry)

  • Other cause: Reactive lymphocytosis in viral infections

    • EBV, CMV, acute HIV infection

• Granulocytes at all stages of maturation + basophilia + eosinophilia

  • Consider CML (confirm with BCR-ABL1 testing)

• >20% blasts in blood or BM:

  • Acute leukemia:

    • Predominantly lymphoblasts → Consider ALL

    • Predominantly myeloblasts → Consider AML

• Smudge cells → Suggest CLL

• Auer rods → Suggest AML, particularly acute promyelocytic leukemia (APL)

  • Hematologic emergency until APL is excluded.

• Hairy cells → Hairy cell leukemia

• Sézary cells → Sézary syndrome

• Hypersegmented neutrophils → Vitamin B12/folate deficiency

  • Consider vitamin B12 deficiency before folate replacement.

• Schistocytes → Evaluate urgently for thrombotic microangiopathy (TTP/HUS, DIC), and mechanical valve

• Spherocytes → Autoimmune hemolytic anemia or hereditary spherocytosis.

• Platelet clumping → Exclude pseudothrombocytopenia before initiating a thrombocytopenia workup

  • Repeat the lab but collect the blood sample in a heparin or citrated tube (EDTA in the collecting tubes can cause platelet clumping)

• Rouleax formation → Consider plasma cell disorders

• Target cells → Consider liver disease and thalassemia

Mixing study

• When PT and/or aPTT is prolonged, mixing study can help to differentiate between factor deficiency or presence of an inhibitor.

• Technique:

  • Mix patient plasma 1:1 with normal pooled plasma (NPP)

    • NPP supplies ~50% of every factor and ~50% activity (sufficient to normalize the PT and aPTT)

  • Immediately repeat the prolonged lab test (PT and/or aPTT) on the mixture.

• Interpretation:

  • If the factor is deficient: Mixing study corrects PT and aPTT.

  • If an inhibitor presents: Inhibitor neutralizes the added normal factor in NPP as well as the patient's factor, so the clotting time stays long.

Iron Studies

Serum iron:

• Circulating iron bound to transferrin (the transport protein)

• Falsely elevates by recent oral iron or iron-containing food

Iron saturation (TSAT):

• The percentage of transferrin occupied by iron

• Reflects circulating bioavailable iron

Ferritin (storage iron):

• Iron deficiency is essentially the only cause of a low ferritin (high specificity).

  • Ferritin ≤30 has ~98% specificity and ~92% sensitivity for absent BM iron stores.

  • Ferritin is an acute-phase reactant and rises with inflammation, infection, liver disease, and malignancy, so a "normal" value never excludes deficiency in those settings.

• Diagnostic criteria for iron deficiency anemia:

  • Ferritin ≤30 in general population

  • Ferritin <100 AND Iron sat (TSAT) <20% in inflammatory states, elderly and heart failure

DIC Laboratory tests

• There is no single diagnostic lab test for DIC.

• Characteristic lab changes in DIC:

  • Low/ progressive downward trend platelet

    • Sensitive but nonspecific

  • Prolonged PT/aPTT:

    • Reflects consumption/depletion of clotting factors

    • Normal values do not exclude DIC (serial testing matters)

  • Elevated fibrin-related marker (D-dimer):

    • Highest diagnostic efficiency of the individual assays.

  • Low fibrinogen:

    • Insensitive because fibrinogen is an acute-phase reactant and can stay "normal" despite active consumption.

    • Hypofibrinogenemia appears only in severe DIC.

  • Schistocytes:

    • Add prognostic information but are not part of the formal ISTH score.

• ISTH score:

  • Only use if an underlying disorder known to cause DIC (e.g., sepsis, malignancy, or trauma) is present.

  • You can use Mdcalc.com

  • A score ≥5 is compatible with overt DIC

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