Reference Intervals and Percentiles for Hematologic and Serum Biochemical Values in Captive Bred Rhesus (Macaca mulatta) and Cynomolgus Macaques (Macaca fascicularis)

Abstract

Several physiological characteristics and housing conditions are known to affect hematologic and serum biochemical values in macaques. However, the studies that have been conducted either report values calculated based on a small number of animals, were designed specifically to document the effect of a particular condition on the normal range of hematologic and serum biochemical values, or used parametric assumptions to calculate hematologic and serum biochemical reference intervals. We conducted a retrospective longitudinal cohort study to estimate reference intervals for hematologic and serum biochemical values in clinically healthy macaques based on observed percentiles without parametric assumptions. Data were obtained as part of the Biomedical Primate Research Centre (Rijswijk, The Netherlands) health monitoring program between 2018 and 2021. In total, 4009 blood samples from 1475 macaques were analyzed with a maximum of one repeat per year per animal. Data were established by species, gender, age, weight-for-height indices, pregnancy, sedation protocol, and housing conditions. Most of the parameters profoundly affected just some hematologic and serum biochemical values. A significant glucose difference was observed between the ketamine and ketamine-medetomidine sedation protocols. The results emphasize the importance of establishing uniform experimental groups with validated animal husbandry and housing conditions to improve the reproducibility of the experiments.

Hematological and Serum Biochemical Reference Intervals for Alphaxalone Sedated Common Marmosets (Callithrix jacchus)

“…In marmosets, higher levels of Fe in adult males compared to juvenile males have been previously described [ 6 ]. In rhesus and cynomolgus macaques, a similar effect has also been observed [ 15 ]. Other research groups have also reported higher levels of cholesterol, creatinine, red blood cells, HGB, HCT [ 2 , 7 ] in males compared to females and higher levels of MCV, MCH [ 7 ], and PLT [ 5 ], which we did not conclude in this article.…”

“…However, in order to present the reader with a usable set of reference intervals, the decision was made to focus only on parameters that were judged clinically relevant. Delta values > 5% [ 15 ] and with a p -value ≤ 0.001 were regarded to be clinically relevant. Figures show all delta values calculated for the comparisons for each variable with the differences > 5% in bold.…”

“…For both sexes, increased levels of ALP, phosphate, WBC, lymphocyte count, and basophil count were observed for juveniles compared to adults. Increased levels of ALP in juvenile animals compared to adults have been described across species, including marmosets [ 2 , 6 ] and other nonhuman primates [ 15 ], and is the result of increased bone iso-enzyme activity associated with growth [ 20 , 21 , 22 ]. ALP and phosphate are markers of bone metabolism.…”

“…The reason for this difference cannot be explained and is most likely attributed to a difference in facilities and housing. In rhesus macaques, a similar effect of lymphocyte count and ALT, as well as a similar basophil count, monocyte count, and neutrophil count effect in cynomolgus macaques [ 15 ].…”

“…Muscle damage indicators (CK, AST, and LDH) for repeated sedations with alphaxalone were increased the least compared to repeated sedation with ketamine or ketamine–medetomidine in marmosets [ 12 ]. In rhesus macaques, the addition of medetomidine to ketamine causes an increase in glucose levels compared to sedation with only ketamine [ 15 ]. This effect has not been described for alphaxalone.…”