Time course of immature platelet count and its relation to thrombocytopenia and mortality in patients with sepsis

<div><p>Introduction</p><p>The pathogenesis of thrombocytopenia in patients with sepsis is not fully understood. The aims of this study were to investigate changes in thrombopoietic activity over time by using absolute immature platelet counts (AIPC) and to examine the impact of platelet production on thrombocytopenia and mortality in patients with sepsis.</p><p>Methods</p><p>This retrospective observational study included adult patients with sepsis admitted to the intensive care unit at a university hospital. Two hundred five consecutive sepsis patients were stratified into four groups according to nadir platelet count: severe (nadir ≤40×10³/μL), moderate (41–80×10³/μL), or mild thrombocytopenia (81–120×10³/μL), or normal-increased platelet count (>120×10³/μL). The development of thrombocytopenia was assessed during the first week; mortality was assessed at day 28.</p><p>Result</p><p>Of the 205 patients included, 61 (29.8%) developed severe thrombocytopenia. On admission, AIPC did not differ among the four groups. In patients with severe thrombocytopenia, AIPC decreased significantly from days 2 to 7, but remained within or above the normal range in the other three groups (overall group comparison, <i>P</i><0.0001). Multivariate analysis including coagulation biomarkers revealed that AIPC was independently associated with the development of severe thrombocytopenia (day 3 AIPC, odds ratio 0.49 [95% confidence interval (CI) 0.35–0.66], <i>P</i><0.0001; day 5 AIPC, 0.59 [95% CI 0.45–0.75], <i>P</i><0.0001). AIPC was a significant predictor of 28-day mortality in Cox hazard models adjusted for Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores (day 3 AIPC, hazard ratio 0.70 [95% CI 0.52–0.89], <i>P</i> = 0.0029; day 5 AIPC, 0.68 [95% CI 0.49–0.87], <i>P</i> = 0.0012).</p><p>Conclusions</p><p>Thrombopoietic activity was generally maintained in the acute phase of sepsis. However, a decrease in AIPC after admission was independently associated with the development of severe thrombocytopenia and mortality, suggesting the importance of suppressed thrombopoiesis in the pathophysiology of sepsis-induced thrombocytopenia.</p></div

Baseline characteristics and outcomes of the 205 patients with sepsis.

<p>Baseline characteristics and outcomes of the 205 patients with sepsis.</p

Box plot showing (a) platelet and (b) absolute immature platelet count (AIPC).

<p>Platelet count and AIPC on the day of admission (day 1) and at the nadir during the 7 days are shown. Septic patients were classified into four groups according to nadir platelet count during the first 7 days of their ICU stay: severe thrombocytopenia (nadir platelet count ≤40×10³/μL); moderate thrombocytopenia (41–80×10³/μL); mild thrombocytopenia (81–120×10³/μL); and normal-increased platelet counts (>120×10³/μL). Multiple pairwise comparison used the Steel–Dwass test.</p

Time course of platelet count and absolute immature platelet count (AIPC).

<p>Platelet count and AIPC were measured from admission (day 1) to day 7 in patients with sepsis, classified into four groups according to nadir platelet count during the 7 days: severe thrombocytopenia (nadir platelet count ≤40×10³/μL); moderate thrombocytopenia (41–80×10³/μL); mild thrombocytopenia (81–120×10³/μL); and normal-increased platelet count (>120×10³/μL). Data are expressed as mean with the 95% confidence interval shown by the error bars. Multiple analysis of variance was among the four groups.</p

Time course of coagulation biomarkers from admission (day 1) to day 7 in patients with sepsis.

<p>Septic patients were classified into four groups according to nadir platelet count during the first 7 days of their ICU stay: severe thrombocytopenia (nadir platelet count ≤40×10³/μL); moderate thrombocytopenia (41–80×10³/μL); mild thrombocytopenia (81–120×10³/μL); and normal-increased platelet counts (>120×10³/μL). Data are expressed as mean with the 95% confidence interval shown by the error bars.</p

Univariate/multivariate logistic regression models for severe thrombocytopenia development (nadir platelet count <40×10³/μL).

<p>Univariate/multivariate logistic regression models for severe thrombocytopenia development (nadir platelet count <40×10³/μL).</p

Univariate and multivariate Cox regression models to predict 28-day mortality.

<p>Univariate and multivariate Cox regression models to predict 28-day mortality.</p