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Cryofibrinogenemia was found in 10 of 24 plasma samples (42%) from subjects with FMF. This precipitate was found during active disease as well as during intervals between crises. We found a higher incidence of cryofibrinogenemia in subjects with mild to moderately severe disease not being treated with colchicine (six of eight) as compared with colchicine-treated subjects who were in partial or complete clinical remission (four or 16; p less than 0.02). All cryofibrinogen precipitates contained fibrin, as assessed by electrophoretic analyses showing the presence of multimeric crosslinked forms of fibrin(ogen) linked by gamma-dimers. This finding in clinical specimens supports the hypothesis that fibrin in an obligatory component of cryofibrinogen. Fibrin was also found in HPF (two of six specimens) prepared from cryofibrinogen-negative FMF plasmas, thus showing that soluble forms of fibrin are even more prevalent in this disorder than is indicated by the frequent finding of cryofibrinogenemia.

Plasma fibronectin binds in a specific and saturable manner to thrombin-stimulated platelets. gamma-Thrombin stimulated 80% as much fibronectin binding to platelets as alpha-thrombin with conversion of less than or equal to 1% of platelet fibrinogen to fibrin. Afibrinogenemic and normal platelets bound similar quantities of fibronectin in the presence of calcium or magnesium-ethylene glycol tetra-acetic acid (EGTA). These observations indicate that fibronectin can interact with platelets without involvement of fibrin or fibrinogen. Nevertheless, two different effects of fibrin(ogen) on fibronectin binding were observed. First, exogenous fibrinogen inhibited fibronectin binding to thrombin-stimulated platelets. This inhibition was unidirectional, as fibronectin did not inhibit fibrinogen binding to ADP or thrombin-stimulated cells. Second, formaldehyde-fixed cells with surface-associated fibrin bound significant quantities of fibronectin. This interaction required calcium and did not occur on fixed cells with or without surface-bound fibrinogen. A portion of the ligand bound to fixed cells with surface-associated fibrin was modified to form a derivative with a molecular weight identical to that of the fibronectin subunit cross-linked to the alpha-chain of fibrin. This high mol wt derivative was also observed to a variable extent with living cells in the presence of magnesium or calcium but not in the presence of magnesium-EGTA. Thus, fibronectin binds to platelets by at least two mechanisms: (1) a fibrin(ogen)-independent pathway that requires divalent ions and is inhibited by exogenous fibrinogen; and (2) a fibrin-dependent pathway with an absolute calcium requirement. With nonaggregated, thrombin-stimulated platelets, the former pathway appears to predominate.