ASH Clinical News May 2016 | Page 35

CLINICAL NEWS “Thrombocytopenic sepsis patients have a different and more disturbed host response.” —THEODORA A.M. CLAUSHUIS, MD Using the lowest platelet count within the first 24 hours of ICU admission, patients were also stratified into groups according to: • Very-low platelet counts: <50 x 109/L (n=61; 6.6%) • Intermediate-low platelet counts: 50-99 x 109/L (n=121; 13%) • Low platelet counts: 100-149 x 109/L (n=167; 17.9%) • Normal platelet counts: 150-399 x 109/L (n=580; 62.3%) To account for baseline differences other than platelet counts (demographics, chronic comorbidity, concomitant drugs, medical admission type, and primary source of infection) the authors used propensity score matching. Results were also compared to normal values generated from plasma from 27 age- and gender-matched healthy volunteers. “Platelet counts remained relatively stable across all groups in the first four to six days after ICU admission,” Dr. Claushuis and coauthors noted. “Thereafter, platelet counts [tended to] increase, although patients with very-low platelet counts remained thrombocytopenic for prolonged periods of time while in the ICU.” Patients with very-low platelet counts were more likely to be younger than those with low or normal platelet counts, had fewer comorbidities, and were more often admitted for medical reasons. Among all platelet count groups, the primary source of infection was similar, though patients with normal platelet counts were more often admitted with pulmonary sepsis and less often with urinary sepsis. Patients with low or intermediate-low platelet counts were more severely ill at admission (as indicated by higher Acute Physiology and Chronic Health Evaluation IV and Sequential Organ Failure Assessment scores). Patients in the very-low and intermediate-low platelet groups had a higher risk of mortality in the ICU, as well as a higher risk of mortality at day 30 and up to one year after ICU admission (TABLE 2), compared with patients with normal platelet counts (hazard ratios [HR] = 2.00 [1.32-3.05] and 1.72 [1.22-2.44], respectively; p values not reported). Full outcomes of sepsis stratified by platelet counts at admission to the ICU are presented in TABLE 2. “[Evaluation of the genomic response of blood leukocytes showed that] thrombocytopenia was associated with a more disturbed host response, independent of disease severity,” Dr. Claushuis added. “Sepsis patients with thrombocytopenia had more impaired vascular integrity, increased cytokine levels, and had leukocytes with reduced (RNA) signaling in adhesion and diapedesis, compared with patients with normal platelet counts.” The researchers also observed a distinct whole-blood leukocyte transcriptome pattern, revealing decreased leukocyte adhesion, diapedesis, and extravasation signaling. “The association between increased mortality and thrombocytopenia is generally regarded as a reflection of disease severity,” Dr. Claushuis concluded. “Our study shows that apart from this, thrombocytopenic sepsis patients also have a different and more disturbed host response.” The study results are limited in generalizability due to the location at two sites in the Netherlands. Additionally, though the researchers used propensity-matching to correct for baseline differences, they noted, “a bias may have remained after propensity matching due to unmeasured confounders.” REFERENCE Claushuis TAM, van Vught LA, Scicluna BP, et al. Thrombocytopenia is associated with a dysregulated host response in critically ill sepsis patients. Blood. 2016 March 8. [Epub ahead of print] Outcomes of Sepsis Patients Stratified by Platelet Counts at ICU Admission TABLE 2. Patients Very low (<50x109/L) Intermediate-low (50-99x109/L) Low (100-149x109/L) Normal (150-399x109/L) 61 (6.6%) 121 (13%) 167 (17.9%) 580 (62.3%) p value Median length of stay, in days