Prothrombin in normal human cerebrospinal fluid originates from the blood.

Abstract

In spite of the fact that prothrombin is produced by cells within the central nervous system, its presence in the cerebrospinal fluid (CSF) has not been investigated. We determined the concentration of prothrombin in CSF with reference to the concentration in plasma in paired samples from 18 "normal" control patients and 4 patients with relapsing-remitting type of multiple sclerosis (MS). The newly developed ELISA was very specific (no cross-reactivity with thrombin) and sensitive (detection limit--0.7 ng/ml) with an imprecision of CV = 8.3% (intraseries) and 7.0% (interassay). The mean prothrombin concentration in normal CSF was 0.55 mg/l (CV +/- 33%, range: 0.28-0.93 mg/l), in normal plasma 121.8 mg/l +/- 21%, resulting in a mean CSF/plasma concentration quotient (Q(Proth)--4.5 x 10(-3) (CV +/- 35%, range: 2.1-8.3 x 10(-3)) corresponding to a mean albumin quotient in this group of subjects of Q(Alb) = 5.8 x 10(-3). Due to the Q(Proth) and the molecular weight of prothrombin (72 kDa)--similar to that of albumin--we conclude that prothrombin in normal human CSF originates predominantly (>95%) from blood. The enzymatic activity in CSF is conserved. Comparable results obtained in MS patients with only few small MRI lesions suggest that local chronic inflammatory disease of the central nervous system does not influence prothrombin concentration in the CSF if the blood-CSF barrier function is normal.