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Fibrinogen chapel hill: Hypodysfibrinogenemia with a tertiary polymerization defect
Author(s) -
McDonagh R. P.,
Carrell N. A.,
Roberts H. R.,
Blatt P. M.,
McDonagh Jan
Publication year - 1980
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.2830090104
Subject(s) - fibrinogen , fibrin , plasmin , chemistry , proteolysis , medicine , biochemistry , immunology , enzyme
A patient with a functionally defective fibrinogen (fibrinogen Chapel Hill) has been investigated. Fibrinogen Chapel Hill is characterized by hypofibrinogenemia, with a plasma concentration about one third of normal, as measured both functionally and immunochemically. Fibronogen survival is normal; so also is fibrinopeptide release. A polymerization defect in this fibrinogen results in the delay of fibrin fibrils in solution to form a normal three‐dimensional gel. This defect is not associated with end‐to‐end aggregation or with lateral associations in solution. Delayed gelation results from an abnormality in a tertiary contact site involved in network branching, which is associated with the hydrophilic, carboxy‐terminal segment of the α chain. Fibrinogen Chapel Hill exhibits two additional abnormal responses, which are also associated with the same region. The early plasmin cleavages of fibrinogen and fragment X are delayed, and there is a concomitant delay in the appearance of fragments Y, D, and E. This fibrinogen also has an unusual sensitivity to Ancrod proteolysis, whereby Ancrod cleaves a large carboxy‐terminal segment of the α chain more rapidly than in normal fibrinogen. The abnormalities in fibrinogen Chapel Hill can be explained by a structural abnormality which is functionally related to an α chain associated polymerization domain.