PROTHROMBIN IN NORMAL HUMAN CEREBROSPINAL-FLUID ORIGINATES FROM THE BLOOD

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 prothromb in in CSF with reference to the concentration in plasma in paired samp les from 18 ''normal'' control patients and 4 patients with relapsing- remitting type of multiple sclerosis (MS). The newly developed ELISA w as very specific (no cross-reactivity with thrombin) and sensitive (de tection 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 plasm a 121.8 mg/l +/- 21%, resulting in a mean CSF/plasma concentration quo tient (Q(Proth))-4.5 . 10(-3) (CV +/- 35%, range: 2.1-8.3 . 10(-3)) co rresponding to a mean albumin quotient in this group of subjects of Q( Alb) = 5.8 . 10(-3). Due to the Q(Proth) and the molecular weight of p rothrombin (72 kDa)-similar to that of albumin-we conclude that prothr ombin in normal human CSF originates predominantly (>95%) from blood. The enzymatic activity in CSF is conserved. Comparable results obtaine d in MS patients with only few small MRI lesions suggest that local ch ronic inflammatory disease of the central nervous system does not infl uence prothrombin concentration in the CSF if the blood-CSF barrier fu nction is normal.