Persevere-II: redefining the pediatric sepsis biomarker risk model with septic shock phenotype
The methods disclosed herein relate to an improved tool incorporating platelet count into a multi-biomarker based outcome risk stratification model for evaluating mortality risk in pediatric patients having sepsis. The methods described here are useful for treating sepsis, for point of care clinical decision support, for stratifying septic shock patients based on baseline mortality risk, and for clinical trial design, among other uses.
1. A method of treating septic shock in a pediatric patient presenting with multiple organ failure (MOF) in the absence of new onset thrombocytopenia, the method comprising
obtaining at least one biological sample from the patient presenting with multiple organ failure (MOF) in the absence of new onset thrombocytopenia;
determining a blood platelet count and the amount of each of the following protein biomarkers in the at least one biological sample: C-C chemokine ligand 3 (CCL3), heat shock protein 70 kDa 1B (HSPA1B), interleukin-8 (IL8), granzyme B (GZMB), and matrix metalloproteinase 8 (MMP8);
classifying the patient as intermediate or high risk of mortality based on the blood platelet count and the amount of each of the protein biomarkers in the sample; and
treating the intermediate or high risk patient with a treatment selected from the group consisting of extracorporeal membrane oxygenation/life support, plasmapheresis, plasma exchange, pulmonary artery catheterization, high volume continuous hemofiltration, and combinations thereof.
2. A method of classifying risk of mortality and treating a pediatric patient with septic shock presenting with multiple organ failure (MOF) in the absence of new onset thrombocytopenia the method comprising:
obtaining a biological sample from the patient;
determining a blood platelet count and the amount of each of the following protein biomarkers in the at least one biological sample: platelets, C-C chemokine ligand 3 (CCL3), heat shock protein 70 kDa 1B (HSPA1B), interleukin-8 (IL8), granzyme B (GZMB), and matrix metalloproteinase 8 (MMP8); and
classifying the patient as intermediate risk if any of the following are true:
a) an amount of CCL3 protein less than or equal to 150 pg/ml, an amount of HSPA1B greater than 90,000 pg/ml, an amount of IL8 protein greater than 200 pg/ml, a platelet count greater than 38/mm 3 , an amount of IL8 protein less than or equal to 830 pg/ml, and an amount of MMP8 protein less than or equal to 27,400 pg/ml, or
b) an amount of CCL3 protein less than or equal to 150 pg/ml, a amount of HSPA1B protein greater than 90,000 pg/ml, an amount of IL8 protein greater than 200 pg/ml, a platelet count greater than 38/mm 3 , and an amount of IL8 protein greater than 830 pg/ml, or
c) an amount of CCL3 protein greater than 150 pg/ml, and a platelet count less than or equal to 90/mm 3 , or
d) an amount of CCL3 protein greater than 150 pg/ml, a platelet count greater than 90/mm 3 , an amount of GZMB protein greater than 32 pg/ml, an amount of HSPA1B protein less than or equal to 1.6×10 6 pg/ml, and an amount of IL8protein greater than 3,350 pg/ml;
and
classifying the patient as high risk if any of the following are true:
e) an amount of CCL3 protein less than or equal to 150 pg/ml, an amount of HSPA1B protein greater than 90,000 pg/ml, an amount of IL8 protein greater than 200 pg/ml, and a platelet count less than or equal to 38/mm 3 , or
f) an amount of CCL3 protein greater than 150 pg/ml, a platelet count greater than 90/mm 3 , an amount of GZMB protein greater than 32 pg/ml, and an amount of HSPA1B protein greater than 1.6×10 6 pg/ml; and
treating the intermediate or high risk patient with a treatment selected from the group consisting of extracorporeal membrane oxygenation/life support, plasmapheresis, plasma exchange, pulmonary artery catheterization, high volume continuous hemofiltration, and combinations thereof.
3. The method of claim 1 , wherein the classifying is performed using a classification and regression tree methodology.
4. The method of claim 1 , wherein the sample is obtained within the first hour of presentation with septic shock.
5. The method of claim 1 , wherein the sample is obtained within the first 48 hours of presentation with septic shock.
6. The method of claim 1 , wherein the protein biomarkers are blood proteins and the biological sample is whole blood or plasma, or a combination thereof.