Evaluation of Point-of-Care Testing for C-Reactive Protein in Forensic Medicine

C-reactive protein (CRP) is an acute-phase protein that is secreted from the liver in response to tissue injury, infection, or other inflammation.1 It is used as a marker for inflammation in clinical and forensic medicine.2 Although postmortem CRP level is lower than the corresponding antemortem level, it remains stable for a postmortem interval (PMI) of 31 days. CRP testing is used in routine autopsy practice to detect inflammatory disease.2, 3 Recent technological advances have facilitated point-of-care (POC) testing,4 which provides an immediate result at the bedside, and in addition, it is considered to be useful for postmortem examination, facilitating decision-making during an autopsy and diagnosis of serious inflammation. According to the POC CRP test results, the forensic pathologist can change the autopsy technique and conduct additional postmortem tests such as histologic examination and bacterial culture. However, laboratory testing of postmortem blood samples is difficult due to hemolysis and postmortem clotting. Therefore, the present study aimed to confirm the possibility of POC testing for CRP and evaluate the forensic application of POC CRP tests.

According to the POC tests, CRP was elevated in 20 cases, with a mean level of 5.8 mg/dL. The putative causes for elevated CRP levels include pneumonia, liver abscess, etc. These elevated CRP results correlated with antemortem clinical data and postmortem examination results including an autopsy and histologic examination. Moreover, the present study indicated that POC CRP testing had a high positive predictive value and specificity between the antemortem and postmortem CRP results. In the 3 cases with a disagreement between antemortem and postmortem CRP results, the antemortem CRP levels were 1.2–1.6 mg/dL and the postmortem CRP results were < 1.0 mg/dL. In these cases, both POC and laboratory instruments provided negative CRP values (< 1.0 mg/dL), which indicated that these results were not performance errors of the portable POC testing instrument. Therefore, it was suggested this disagreement was due to postmortem changes. A previous study reported that postmortem CRP levels decreased by approximately 35%, compared to the antemortem CRP levels.5

The CRP results from the portable POC instrument were highly correlated with the CRP results from the laboratory instruments (r = 0.971 and r = 0.911). However, false negative results should be considered during interpretation.

The portable POC instrument showed testing errors in 13 of the 85 cases, which were mainly related to low blood sample quality or high/low hematocrit levels. These problems are an inevitable limitation of a postmortem blood sample and are most likely caused by postmortem hemolysis and hemoconcentration. Among the 15 cases with error results, 13 cases had errors from the portable POC instrument, with detectable CRP levels from the laboratory instrument in 9 cases. Thus, failure of the POC testing should be addressed using laboratory testing of pre-treated samples. Interestingly, POC testing of whole blood samples provided testing errors in all 4 cases of carbon monoxide intoxication, which indicates that laboratory testing after sample preparation is necessary in carbon monoxide intoxication cases. Further, these error results might be due to change of hemoglobin into carboxyhemoglobin.

A previous study has described POC CRP testing in the autopsy setting using the NycoCard^®.6 However, this study used serum samples to correct the CRP values for hematocrit levels. In contrast, the POC instrument from the present study evaluated whole blood samples, and it automatically corrected for the hematocrit levels. Thus, it is a simpler and faster method for POC testing than the instrument described in the previous study. Moreover, immediate POC CRP testing without sample preparation may facilitate decision-making regarding the autopsy procedure and may increase the frequency of usage at the death scene investigation. In this study, whole blood was collected from the IVC assuming it was right heart blood. However, in the previous report, the postmortem CRP levels were similar in the heart and peripheral blood samples.3

Laboratory testing of postmortem blood samples is difficult due to hemolysis and postmortem blood clotting which could induce laboratory device failure by blocking the capillary. In this study, the POC testing device uses a cartridge, and thus, postmortem clotted blood does not enter into the POC testing device and does not induce a POC testing device failure. Therefore, POC testing overcomes the disadvantages of laboratory testing to some degree. We conclude that immediate POC CRP testing is reliable in forensic settings such as during autopsy and the postmortem inspection.