Fibrinogen Stony Brook, a heterozygous Aα16Arg → Cys dysfibrinogenemia. Evaluation of diminished platelet aggregation support and of enhanced inhibition of fibrin assembly

Assessed by high performance liquid chromatographic and amino acid sequence determinations, approximately one half (n = 4) of A peptide in fibrinogen Stony Brook (φ SB) contained the Aα16Arg → Cys substitution. To examine its functional behavior, mutant molecule-rich soluble subfractions that partly or fully lacked their normal A peptide were obtained from cryoprecipitates or from incoagulable material, respectively. Such subfractions consistently induced a more pronounced decrease (n = 3) in the turbidity of normal polymerizing fibrin than that induced by normal fibrinogen, by whole φ SB (n = 4) or by fibrinogen from an unrelated homozygous proband. These subfractions also exhibited decreased (12-50% of normal controls, fibrinogen 30-590 nM, n = 5) ADP-induced aggregation support of gel-sieved platelets, a decrease not demonstrable by whole φ SB, by fibrinogen from the homozygous proband, or by enrichment of the latter with normal soluble fibrin. A single isolate displaying diminished platelet aggregation support was ¹²⁵I-labeled and examined further. It exhibited decreased binding to platelets, and Scatchard analysis indicated decreased binding affinity but normal maximum binding. We infer that φ SB contained heterodimers that exhibited these distinct functional properties when their normal A peptide had been cleaved.