Both FV and FVIII replacement therapies are needed for the management of individuals with F5F8D.
Factor V
No virally inactivated, specific plasma-derived FV concentrates are currently available to treat patients that are affected with FV deficiency. FV is also not present in cryoprecipitate or prothrombin complex concentrates. Therefore, replacement of FV can be currently achieved only through the use of fresh frozen plasma (FFP), preferably virally-inactivated.
Factor VIII
A large number of FVIII replacement products are available, including FFP, plasma-derived concentrates, and recombinant FVIII (rFVIII) (different generations). Information on the features of these products can be retrieved at https://www.euhass.org/cfpd.html and at https://www.cdc.gov/ncbddd/hemophilia/index.html, the EUHASS (EUropean HAemophilia Safety Surveillance) and CDC (Centers for Disease Control and Prevention) websites, respectively.
Bleeding episodes are usually treated on demand for F5F8D patients and do not require regular prophylaxis.27 Treatment of bleeding episodes is generally chosen according to the nature of the bleed and the FV and FVIII levels of affected individuals. The half-lives of both FV (36 h) and FVIII (10-14 h) have to be taken into consideration.
Factor V replacement
FV levels should be raised to at least 25 IU/dL by using 15-20 mL/kg FFP.25,26 The initial dose should be 15-20 mL/kg followed by smaller amounts, such as 5 mL/kg every 12 h, adjusting the dosage based on FV levels. Studies of FV recovery recommend maintaining a level of 20-25% of FV activity for surgery or in cases of severe bleeding.27
Development of alloantibodies to FV in FFP is a potential complication of hereditary FV deficiency.27 After FFP replacement therapy, the occurrence of inhibitors, especially transient ones of low titer, may occur and can be neutralized using large amounts of FFP.27 However, as in the treatment of surgical cases, fluid overload is of concern in this situation, and close cardiovascular monitoring is advised. Intravenous immunoglobulin also may be effective in eradicating the FV inhibitor.28
Factor VIII replacement
FVIII levels should be raised to at least 30-50 IU/dL for the treatment of minor bleeding episodes, and to at least 50-70 IU/dL for more severe bleeds. The synthetic hormone desmopressin,29 as well as antifibrinolytic agents or combined hormonal contraceptives, can be successfully used for minor bleeding episodes.27 For severe bleeding episodes, rFVIII concentrates are the treatment of choice. Surgical procedures should be addressed by administering FVIII replacement 30 minutes before surgery and then every 12 h to maintain FVIII levels above 50 IU/dL.30
Other treatment options
The use of recombinant activated factor VII (rFVIIa) in combination with FFP and platelets in the management of 13 invasive procedures in 3 children with severe FV deficiency has been reported.30 However, more data are required to further consider such a therapeutic option.
Consideration of platelet transfusions if FFP replacement does not control the bleeding or in individuals with inhibitor development has been suggested: a case of severe FV deficiency associated with multiple episodes of intracranial bleeding at birth and inhibitor development after FFP infusion was resolved by additional administration of platelets.31
Treatment of menorrhagia and pregnancy
Menorrhagia is a common bleeding symptom in women with F5F8D. Management of this symptom usually includes treatment with antifibrinolytic agents, desmopressin, oral contraceptives, levonorgestrel intrauterine device, and surgical treatments, such as endometrial ablation and hysterectomy.32
Available data regarding pregnancy in women with F5F8D are too limited to draw a conclusion. A recent review of the literature by Spiliopoulos and Kadir identified 19 pregnancies in women with F5F8D among various case reports and case series. Different prophylactic treatment schemes were used to cover labor and delivery in 7 of these pregnancies; 2 others were not treated with prophylactic therapy; and for the remaining 10, prophylactic treatment information was not available.23 Recommendations of 2C level (weak recommendation of low-quality evidence) are reported in the UK Centre Doctors’ Organization guidelines.25
Perioperative and post-surgery treatment
The rarity of combined F5F8D also poses a challenge to anesthesiologists and surgeons at the time of surgery. Recently, daily therapeutic plasma exchange with FFP was suggested to reach surgical hemostatic levels for Factor V in a patient with the F5F8D requiring cardiac surgery.33 A few additional cases are reported in the literature,34,35 and the general conclusion is that a multidisciplinary approach to such patients with a careful coordination between outpatient physicians and inpatient consultants to create a timely and individualized successful treatment scheme is needed.
Rare Coagulation Disorders Resource Room, an extension of the RBDD Registry (eu.rbdd.org), was developed in collaboration with the Indiana Hemophilia & Thrombosis Center (www.innovativehematology.org).
The Resource Room serves as a platform to promote international collaboration to increase knowledge of these very rare disorders and to improve the care of affected individuals. The international RBDD mission, under the leadership of Dr. Peyvandi, will continue to be expanded over time.
The Resource Room thanks all contributing authors of the website articles that have made this valuable information available to the global community of both individuals affected with rare coagulation disorders and their healthcare providers.
