SummaryThe process of fibrin formation using highly purified fibrinogen and thrombin was studied using laser fluctuation spectroscopy, a method that rapidly determines particle size in a solution. Two periods in fibrin clot formation were noted: an induction period during which no fibrin polymerization occurred and a period of rapid increase in particle size. Direct measurement of fibrin monomer polymerization and fibrinopeptide release showed no evidence of an induction period. These observations were best explained by a kinetic model for fibrin clot formation incorporating a reversible fibrinogen-fibrin monomer complex. In this model, the complex serves as a buffer system during the earliest phase of fibrin formation. This prevents the accumulation of free polymerizable fibrin monomer until an appreciable amount of fibrinogen has reacted with thrombin, at which point the fibrin monomer level rises rapidly and polymerization proceeds. Clinically, the complex may be a homeostatic mechanism preventing pathological clotting during periods of elevated fibrinogen.

INJURY to the spinal cord and the ensuing extensive paralysis of skeletal muscle is known to give rise to many metabolic changes (Cooper and Hoen, 1952; O'Connell and Gardner, 1953; Arieff et al., 1960). Some of these changes are generally reversible, such as the catabolic reaction resulting in marked loss of nitrogen, potassium and calcium (Cooper, et al., 1950), impairment of bromsulfalein clear ance (Cooper and Hoen, 1952) and development of gynecomastia in males. These abnormalities may disappear in the course of a few months, especially with modern treatment (Arieff et al., 1960). On the other hand, some changes seem to be essen tially permanent and these include disturbance of the distribution of serum proteins (Robinson, 1954; Arieff e t al., 1960), a tendency to creatinuria and decreased creatine tolerance (Pollock et at., 1954), a lowered excretion of creatinine and sub normal serum glutamic-oxalacetic transaminase levels (Arieff et al., 1960). The aim of the present work is to determine to what extent the gross body composition of spinal cord injured patients is altered as a result of such metabolic changes. The patients available in this hospital for the care and rehabilitation of the chronically ill were treated elsewhere during the acute post-injury phase. Consequently only the effects of relatively long-term metabolic changes would be apparent from these studies. In one approach, observations made on groups of paraplegic and quadriplegic patients were compared with those from groups of other chronically ill patients in this hospital in order to delineate differences specifically due to spinal cord injury. Comparison with data from the literature on healthy normal controls was also possible. In a second approach, in which the patient served as his own control, periodic observations were made on spinal cord injured subjects over a period of up to 51 months in order to follow changes in their body composition. Previous work on the variability in measurement of the selected parameters allowed assess ment of the statistical significance of the changes observed in the latter study (Greenway et al., 1965). METHODS Patient Selection. All patients were chronically ill, but in no acute distress. The spinal cord injured patients had no large decubitus ulcers and were all either 1 These studies have been supported in part by USPHS Grants A-1886, HD-00669 and VRA Grant RD-II44-M.

Pyridoxal can be oxidized by liver aldehyde oxidase. 2. The oxidation is competitively inhibited by antabuse. 3. The end product of the reaction has been isolated and identified as pyridoxic acid. The authors have pleasure in expressing their sincere thanks to Dr H. M. Kalckar, who made it possible for them to carry out this work, and whose unfailing help and suggestions were a constant source of encouragement. Their thanks are also due to the Carlsberg Fond, Nordisk Insulin Fond and Kong Christian Xendes Fond for financial support in this work.

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Using laser fluctuation spectroscopy, a technique that measures particle size change in solution, the kinetics of fibrin clot formation from fibrinogen can be studied. With this technique the effect of calcium on the three distinguishable phases of clot formation, (1) proteolysis of fibrinogen, (2) fibrinogen-fibrin monomer complex formation, and (3) fibrin monomer polymerization, were investigated. Only a small change in the length of the induction period that results from the fibrinogen-fibrin monomer interactions was observed. However, there was a marked increase in the rate of fibrin monomer polymerization in the presence of calcium ions. These data show that calcium decreases the time required for fibrin formation from fibrinogen by markedly accelerating the phase of fibrin monomer polymerization.