Factor II and Factor V Deficiencies: Current Management, Care Gaps and Call to Action for Therapeutic Advances

Among rare inherited coagulation disorders (RICDs), prothrombin (factor II) and factor V (FV) deficiency are still orphans of treatments, lacking availability of single-factor replacement products. This clinical care gap is hampering the implementation of prophylactic and episodic treatment regimens in patients.

We chose to produce a narrative review to evaluate to which degree bleeding prophylaxis, that is the standard of care for inherited coagulation disorders, has been implemented in these RICDs with the currently available therapeutics, that is fresh frozen plasma and prothrombin complex concentrates. The outcome of the episodic treatment of acute bleeding episodes and invasive procedures was also reviewed.

Perusal of the published case reports shows a paucity of prophylaxis implementation even after life-threatening bleeding episodes such as intracerebral hemorrhage and ovulation-associated hemoperitoneum: only seven cases for prothrombin and three for FV deficiency. By the same token, there are relatively few reports on the acute treatment of bleeding episodes (particularly for prothrombin deficiency), as well as on the episodic treatment at the time of surgery or invasive procedures.

Our review indicates that currently available therapeutics are largely suboptimal and justify a call to action in order to streamline regulatory pathways for single-factor concentrate development, as well as for the potential evaluation of prophylaxis of coagulation-rebalancing, non-replacement products.