Haptoglobin in pregnancy: Trimester-specific reference intervals

Pregnancy induces physiologic changes that can affect serologic and immunologic markers, potentially resulting in lower haptoglobin values than nonpregnant counterparts. Such variations may lead to concern for hemolysis in pregnancy. This study aims to analyze reference intervals (RIs) for haptoglobin in each trimester of pregnancy.

We employed a quality improvement project to analyze a total of 401 remnant serum samples (BD Vacutainer SST) collected from routine outpatient pregnancy patients. Roche Cobas 8000 (c 502) systems were used to examine at least 80 samples per trimester: first trimester (86 samples), second trimester (230 samples), and third trimester (80 samples). Haptoglobin between trimesters was compared using the Mann-Whitney test.

Nonparametric RIs were calculated to be 27 to 196 mg/dL for the first trimester, 27 to 178 mg/dL for the second trimester, 34 to 191 mg/dL for the third trimester, and 30 to 185 mg/dL for the entire sample population. The distribution of second-trimester haptoglobin (median, 98 mg/dL) was significantly different compared to the first trimester (median, 113.5 mg/dL; P < .05) and the third trimester (median, 112.5 mg/dL; P < .05).

Although overall haptoglobin RI during pregnancy aligned with the nonpregnant population, our study revealed a significant shift during the second trimester. This finding suggests that pregnant individuals in the second trimester may have lower haptoglobin values and potentially be misdiagnosed with intravascular hemolysis when consequent added factors further decrease haptoglobin below the level of detection without hemolysis.