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T C Bithell

Publications and source records attributed to T C Bithell.

12 recordsLinked to original sources

Fibrin glue from stored human plasma. An inexpensive and efficient method for local blood bank preparation.

European surgeons have used fibrin glue extensively during thoracic, cardiovascular, and general surgical operations. Until now, however, it has been available only as a commercial preparation made from pooled human plasma, and it has not been approved by the U.S. Food and Drug Administration for use in the United States because of a high associated risk of hepatitis and acquired immune deficiency syndrome. Methods of obtaining fibrinogen, an essential component of fibrin glue, from cryoprecipitate or fresh frozen plasma have been published recently. However, the cryoprecipitate method results in relatively low concentrations of fibrinogen, which can reduce glue effectiveness. The fresh frozen plasma method is more expensive and does not meet the standards of the American Association of Blood Banks for the "closed" system required for safe handling and management of blood component products. Both the cryoprecipitate and the fresh frozen plasma methods result in waste of unstable clotting factors. These factors are necessary to replace human plasma clotting deficiencies but are not necessary for the production of fibrin glue. The authors have developed an efficient, high-concentration blood bank method for producing and maintaining a local supply of a safer and less expensive but equally effective material derived from stored human plasma. This material is produced using approved blood bank techniques for a "closed" system in blood component production, thus reducing the risks of contamination and infection, and its fibrinogen concentration is higher than that of standard cryoprecipitate. The cost of 1 unit of this fibrin glue is comparable to that for 1 unit of cryoprecipitate and less than that for 1 unit of fresh frozen plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Aprotinin↗

Hereditary dysfibrinogenemia.

Inherited qualitative abnormalities of fibrinogen have been documented in more than 100 families. These dysfibrinogenemias usually are clinically silent, but in some cases are associated with bleeding, thrombosis, or defective wound healing. Abnormalities of the fibrinogen molecule may impair any of the major steps involved in the conversion of fibrinogen into stabilized fibrin; i.e., cleavage of the fibrinopeptides by thrombin, polymerization, and cross-linking of fibrin. Biochemical studies of several abnormal fibrinogens have demonstrated that the functional defects are the result of single amino acid substitutions. The hereditary dysfibrinogenemias are the first coagulation disorder in which the pathophysiology has been elucidated on a molecular level. Studies of these "experiments of nature" have important implications in such diverse processes as wound healing and thrombosis.

Biopolymers↗

Hereditary dysfibrinogenemia characterized by slow fibrinopeptide release and competitive inhibition of thrombin.

A qualitative abnormality of fibrinogen was identified in a 40-year-old woman with recurrent thrombophlebitis. Fibrinogen levels were normal when determined by immunologic, gravimetric, or nephelometric methods (200-390 mg/dl), but were diminished when tested by techniques based on the thrombin time (13 mg/dl). Asymptomatic family members, including both parents of the proposita, were less severely affected (mean fibrinogen level 100 mg/dl). The rate of fibrinopeptide release from purified fibrinogen was abnormally slow, whereas purified fibrin monomers polymerized at a normal rate. The abnormal fibrinogen was found to act as a competitive inhibitor of thrombin with an inhibitor constant (Ki) of 0.2 microM. This value was the same as the Michaelis constant (Km) of the normal thrombin-fibrinogen reaction, an observation consistent with an abnormality that retards fibrinopeptide release without affecting enzyme-substrate affinity.

Adult↗