APCR reflects resistance to proteolysis of activated factor V by activated protein C (APC). Ninety-five percent of APCR cases are due to factor V Leiden, a genetic mutation in factor V that predisposes to venous thromboembolism (5–10 times greater risk in heterozygotes and 50–100 times greater risk in homozygote carriers). The remaining 5% are found in pregnancy, malignancy, and the antiphospholipid antibody syndrome. Ratios are generated either from a modified PTT or, more recently, by activating protein C with southern copperhead venom, using dilute Russell viper venom as the clotting reagent. The test is performed in the presence of added APC, where in normal individuals, there is an elongation due to delayed generation of fibrin when factor V is lysed; in the absence of APC, where factor V remains intact, there is no elongation. Patients with APCR have a lesser prolongation of clotting in the presence of APC than controls.
Normal value:
>1.8.
Use
APCR is one of the assays recommended to investigate the etiology of venous thrombophilia. The congenital form, factor V Leiden, is present in 5% of individuals of European descent and in a high proportion of patients with unprovoked venous thromboembolism. It is virtually absent in patients of pure African ancestry.
Limitations
Protein C levels <50% and initial anticoagulation with vitamin K antagonists may give falsely low ratios. In these situations, the genetic test for factor V Leiden is recommended. The APCR assay is valid in patients stabilized on vitamin K antagonists or heparin.
The assay is invalid in clotted specimens, as well as in lipemic, hemolyzed, or icteric samples. The assay is also invalid if blood is drawn with the wrong anticoagulant or the tubes are not filled appropriately.
ADIPONECTIN
Definition
Adiponectin, a hormone secreted exclusively by adipose tissue, has an important role in the regulation of tissue inflammation and insulin sensitivity. Perturbations in adiponectin concentration have been associated with obesity and the metabolic syndrome. Levels of the hormone are inversely correlated with body fat percentage in adults, whereas the association in infants and young children is more unclear.
Normal range:
see Table 16.3.
TABLE 16–3. Normal Range of Adiponectin
Use
