Pseudothrombocytosis in a patient with severe burn injuries: A case report highlighting the pitfalls of automated platelet counting

INTRODUCTION

Pseudothrombocytosis, a spurious elevation in platelet (PLT) counts due to interference from red blood cell (RBC) fragments, is a well-documented artifact of automated hematology analyzers in hemolytic conditions, including microangiopathic hemolytic anemia.^[1,2] However, its association with severe burn injuries remains underreported, despite the high prevalence of burn-induced hemolysis and RBC fragmentation.^[3]

Severe burns trigger oxidative RBC injury, generating microcytic fragments and spherocytes that may be misclassified as PLTs by impedance-based analyzers (e.g., Coulter DxH series).^[4] This error risks masking true thrombocytopenia, delaying interventions, or prompting unnecessary testing.^[5] While recent guidelines emphasize smear review for schistocyte-rich samples,^[6] burn-specific thresholds for fragment-induced pseudothrombocytosis are few.

This case underscores the critical role of manual verification in burn patients with discordant PLT counts and proposes a diagnostic algorithm to mitigate analyzer pitfalls.

CASE REPORT

Investigations

A 39-year-old Caucasian male was admitted to the emergency department with severe burn injuries after a workplace accident. The patient had second- and third-degree burns over approximately 45% of his total body surface area, comprising injuries to his chest, abdomen, and upper and lower extremities. On admission, the patient was hemodynamically stable with severe pain. Initial management included intravenous (IV) fluid resuscitation, aggressive analgesia, and wound care.

Laboratory evaluation revealed marked hemoconcentration (hemoglobin 18.3 g/dL, hematocrit 54.1%), leukocytosis (20.8 × 10³/μL), and apparent thrombocytosis (PLT count 1630 × 10³/μL). The peripheral smear examination identified spherocytes, abundant RBC fragments (16-18 per oil immersion field [OIF]), and rare schistocytes [Figure 1, Smear A], prompting suspicion of pseudothrombocytosis due to hemolysis.

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Figure 1:

Peripheral smears in a burn patient showing red blood cell fragments (red arrows), platelets (blue arrows), and spherocyte aggregates (green arrows) before (Smear A) and after fluid resuscitation (Smear B); May-Grünwald Giemsa stain, ×1000 magnification, image acquired through CellaVision.

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DISCUSSION

In this case, a 39-year-old male with 45% total body surface area burns presented with an apparent thrombocytosis of 1630 × 10³/μL, as measured by the Coulter DxH 850 analyzer. However, peripheral smear evaluation and manual PLT counts revealed true thrombocytopenia (150 × 10³/μL at admission; 60 × 10³/μL post-resuscitation), confirming that the overestimation was due to RBC fragment interference.^[5]

This diagnostic discrepancy underscores the limitations of impedance-based technologies in fragment-rich samples. The Coulter DxH 850, which utilizes both platelet impedance count (impedance-based platelet counting method) (PLT-I) and Volume-Conductivity-Scatter (VCS) optical analysis, significantly overcounted PLTs due to misclassification of RBC fragments as PLTs.^[3,5] On the contrary, fluorescence-based platforms such as Sysmex XN-series Platelet Fluorescence count (fluorescence-based platelet counting method) (PLT-F) may offer superior accuracy in burn-related hemolysis. PLT-F utilizes PLT-specific RNA staining, reducing interference from fragments. Although spherocyte aggregates increased post-resuscitation, RBC fragments remained the primary cause of analyzer error.^[6]

RBC fragments were the dominant cause of pseudothrombocytosis in this case, and the analyzer’s overestimation closely correlated with fragment density.^[5] Manual smear review played a critical role in confirming true thrombocytopenia and preventing inappropriate clinical decisions.^[7]

Burn-induced hemolysis leads to the generation of both RBC fragments and spherocytes. The latter results from membrane loss and oxidative injury, creating rigid, spherical cells prone to aggregation.^[8] Although not directly misclassified as PLTs, large spherocyte clusters may mimic PLT clumps or inclusions on smear, potentially misleading interpretation. Therefore, recognizing these distinct morphologies is crucial for accurate assessment.

Pseudothrombocytosis in burn patients should be suspected when the automated PLT count exceeds 1000 × 10³/μL and there are at least five RBC fragments per OIF, or when spherocyte aggregates are greater than five per field-findings that reflect burn-induced hemolysis and oxidative RBC injury^[1,5,8] [Box 1]. These criteria are particularly relevant in the setting of extensive thermal injury, where analyzer overestimation of PLTs may obscure true thrombocytopenia.

Confirmation of pseudothrombocytosis requires a manual PLT count performed using the ICSH reference method^[7] or fluorescence-based PLT enumeration (PLT-F) if available, which uses RNA-specific staining to reduce interference from fragments.^[3] This diagnostic approach is consistent with international smear review protocols and accommodates burn-specific thresholds, where fragment densities greater than five per OIF have been shown to strongly correlate with spurious PLT elevations.^[1,5]

CONCLUSIONS

This case underscores the essential role of clinical judgment and manual verification when interpreting automated laboratory results. Although pseudothrombocytosis is a laboratory artifact, its misinterpretation can lead to serious clinical consequences. In patients with severe burns or other hemolytic conditions, a high index of suspicion for pseudothrombocytosis must be maintained. Manual PLT counts should be performed whenever automated results appear inconsistent with the clinical scenario. This approach ensures diagnostic accuracy and supports appropriate patient management.