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Measuring circulating histones may help physicians predict the onset of thrombocytopenia or allow them to monitor the condition in patients who are critically ill, according to researchers.
They noted that histones induce profound thrombocytopenia in mice and are associated with organ injury when released after extensive cell damage in patients who are critically ill.
So the team decided to examine the association between circulating histones and thrombocytopenia in patients in the intensive care unit (ICU).
Cheng-Hock Toh, MD, of the University of Liverpool in the UK, and his colleagues conducted this research and reported the results in a letter to JAMA.
The researchers analyzed 56 patients with thrombocytopenia and 56 controls with normal platelet counts who were admitted to the ICU at Royal Liverpool University Hospital between June 2013 and January 2014.
Thrombocytopenia was defined as a platelet count less than 150 × 103/µL, a 25% or greater decrease in platelet count, or both within the first 96 hours of ICU admission.
The researchers noted that, at approximately 30 µg/mL, histones bind platelets and cause platelet aggregation, which results in profound thrombocytopenia in mice.
So the team used this as a cutoff to stratify thrombocytopenic patients. A “high” level of histones was 30 µg/mL or greater, and a “low” level was below 30 µg/mL.
The researchers detected circulating histones in 51 of the thrombocytopenic patients and 31 controls—91% and 55%, respectively (P<0.001). Histone levels were 2.5- to 5.5-fold higher in thrombocytopenic patients than in controls.
Thrombocytopenic patients with high histone levels at ICU admission had significantly lower platelet counts and a significantly higher percentage of decrease in platelet counts at 24 hours (P=0.02 and P=0.04, respectively) and 48 hours (P=0.003 and P=0.005, respectively) after admission.
High admission histone levels were associated with moderate to severe thrombocytopenia and the development of clinically important thrombocytopenia (P<0.001).
A 30 µg/mL histone concentration was able to predict thrombocytopenia with 76% sensitivity and 91% specificity. The positive predictive value was 79.4%, and the negative predictive value was 89.2%.
