Catalyzes the conversion of GDP-D-mannose to GDP-4-dehydro-6-deoxy-D-mannose. GDP-alpha-D-mannose = GDP-4-dehydro-alpha-D-rhamnose + H2O Nucleotide-sugar biosynthesis; GDP-L-fucose biosynthesis via de novo pathway; GDP-L-fucose from GDP-alpha-D-mannose: step 1/2. Belongs to the NAD(P)-dependent epimerase/dehydratase family. GDP-mannose 4,6-dehydratase subfamily.