Prothrombin is cleaved by factor Xa (activated factor ten ) in combination with the protein, factor Va (activated factor five).
Factor Xa is produced by pathways that will be explored later in the curriculum (the extrinsic and intrinsic clotting pathways). Factor Va is produced when factor V is cleaved by thrombin.

One cause of an increased likelihood of blood clots is a common variant of the gene that encodes prothrombin.
People with this variant, prothrombin 20210, make more than the normal amount of prothrombin. You will see why this variant produces more than the normal amount of prothrombin in the lectures on gene expression.
About 2% of the U.S. population, primarily Caucasians, are heterozygotes for the prothrombin 20210 variant.
Being a heterozygote for the 20210 allele increases the risk of thrombophlebitis about two to three fold.