A deficiency of free protein S, known to increase the risk of peripheral venous thrombosis, has not been well described in patients with cerebrovascular disease. In a pilot study of 35 patients with symptomatic cerebrovascular disease, using a qualitative crossed immunoelectrophoresis assay we found eight patients with a free protein S deficiency. A Laurell immunoelectrophoresis assay was used to quantify the percentage of free protein S after removal of the inactive protein S C4b-binding protein complex by precipitation with polyethylene glycol 8000. In a quantitative study of 103 patients with cerebrovascular disease, 21 had a free protein S that was <20% of the average normal total protein S concentration (normal range 20-40%); 19 had suffered cerebral infarction and the other two had suffered intracranial hemorrhage. The frequency of free protein S deficiency in this group of stroke patients was far higher than the expected prevalence in the general population. (Stroke 1989;20:1657-1661

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We have determined the extent of fragment X formation during thrombolytic therapy by integration over time of the plasma fibrinopeptide B#1-42 concentration. This peptide is quantitatively released when fragment X is formed by plasmin action on fibrinogen or fibrin I. In response to streptokinase (SK) and rt-PA, 264±54 and 95±12 mg/dl respectively of fibrinogen was converted to fragment X. By immunoblotting, fragment X was demonstrated as early as 5 min after SK and 30 min after rt-PA, and was still evident 24 h after treatment. Patients treated with SK showed extensive further plasmin degradation of fragment X to fragments Y and D. Thus fragment X concentrations tend to be more similar in the two groups than would be expected from the extent of fibrinogen breakdown. Fragment X forms clots, but these have lower tensile strength and are more susceptible to further plasmin lysis than clots of fibrin. Thus the similar bleeding observed in the two treatment groups might be a reflection of their similar plasma fragment X concentrations.