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Patterns that point to an interference

Cold-reactive IgM can agglutinate red cells below body temperature. On a method-specific histogram this can produce an irregular, broadened, high-volume aggregate pattern rather than a reliable cell-volume distribution. Aggregates may be counted as fewer, larger particles: RBC count and hematocrit fall while MCV, MCH, and especially MCHC rise; lysed-sample hemoglobin is comparatively reliable. Confirm with visible RBC agglutination on the original smear and apply a locally validated warmed rerun or warm recollection pathway.

Lipemic plasma is a turbidity-related photometric hemoglobin bias: inspect for lipemia, review the hemoglobin channel and internal relationships, and use a validated alternate hemoglobin approach or hold/escalate if it remains unresolved. Cell-free hemoglobin can also raise the photometric hemoglobin result, but requires separate evidence of free hemoglobin and a specimen/context review; a plasma observation alone does not establish its source. RBC destruction can occur in vitro or in vivo and is a separate process that can reduce intact RBC count and hematocrit; inspect specimen appearance, smear, collection history, and clinical context, then recollect or escalate when the destruction pathway cannot be resolved.

EDTA-dependent clumping makes the platelet count unreliable but does not exclude true thrombocytopenia. Confirm clumps on the original smear. Giant platelets can be undercounted above an impedance gate, while fragments or microcytes can be overcounted inside it; use direct morphology and an available validated alternate method to determine the reportable result.

For a short-filled K2EDTA tube, first confirm fill and specimen integrity, then review for relative anticoagulant excess (including reduced MCV, increased MCHC, and distorted morphology), inspect the original smear, and obtain a suitable recollection when the locally validated reportability limit is not met. For extreme leukocytosis, review analyzer linearity, flags, platelet separation, specimen, and original smear; use the validated dilution or alternate method, determine whether the analyzer or laboratory information system has already corrected the diluted rerun, compare evidence, then release only a verified result or suppress, recollect, consult, or escalate.

Illustrative drawing — this picture was drawn rather than captured.

Comparison matrix for cold agglutination, photometric interference, platelet clumps, and fragments or giant platelets with verification actions.
Figure 1Common patterns, affected signals, and next evidence for spurious CBC results.
Method-linked patterns to compare before release.
InterferenceLikely distorted resultUseful evidenceBounded action
Cold agglutinationRBC and Hct low; MCV, MCH, MCHC highIrregular/broad high-volume aggregate pattern and RBC clumps on original smearValidated warming/rerun; if unresolved, warm recollection or consultation
Lipemic photometric biasHgb, MCH, MCHC highTurbid plasma and channel/consistency reviewValidated alternate Hgb approach; compare relationships before release
Cell-free hemoglobinPhotometric Hgb, MCH, MCHC may be highFree-hemoglobin evidence plus specimen and clinical-context reviewIdentify source where possible; hold, recollect, or escalate if unresolved
RBC destructionIntact RBC/Hct may be low; photometric Hgb interpretation may be affectedSpecimen appearance, original smear, collection history, and clinical contextDistinguish in vitro from clinical context; recollect or escalate when unresolved
EDTA platelet clumpsPlatelets unreliable, often lowClump flag and clump-positive original smearHold; use valid alternate-anticoagulant path only after clump-free citrate smear
Giant platelets / fragments / microcytesPlatelets low with giants, high with fragments or microcytesHistogram/gate review and labeled morphologyValidated optical/fluorescent method or manual review; escalate unresolved discordance
Short-filled K2EDTAMCV may be low and MCHC high; morphology may be distortedFill assessment, analyzer relationships, and original smearUse local reportability limit; recollect a suitable specimen or suppress/escalate
Extreme leukocytosisWBC may exceed linearity; platelet separation may be compromisedLinearity/flag review, specimen, original smear, and platelet consistencyValidated dilution or alternate method; check for prior system correction, verify, then release or suppress/escalate

Knowledge checks

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Knowledge check 1

Which evidence/action pair is defensible for a cold-agglutination pattern?

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Knowledge check 2

Which findings support investigation of a spurious platelet count? Select all that apply.

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