Combined FV and FVIII Deficiency

Clinical Manifestation

F5F8D is associated with a mild-to-moderate bleeding tendency, and the concomitant presence of two coagulation defects does not enhance the hemorrhagic tendency that is observed in each defect separately.14,18 Mild bleeding symptoms such as easy bruising, epistaxis, and gum bleeding are not uncommon in affected individuals. Other common types of bleeding include soft-tissue hematomas14,19,20 and bleeding after surgery, dental extraction, and trauma.19,20 Excessive bleeding after circumcision was also reported in a high number of male patients.18,21 More severe symptoms, such as gastrointestinal and central nervous system bleedings, have been reported in only a few patients.18,21 A case of cephalhematoma in a newborn has also been reported.22

Menorrhagia is a major bleeding symptom in women with F5F8D, regardless of factor level. In one of the largest studies on patients with F5F8D,18 more than 50% of affected women of reproductive age had menorrhagia. These data were recently confirmed by Spiliopoulos and Kadir in their review and analysis of 15 case reports and 10 case series, which identified a total of 86 women with F5F8D.23

To date, the amount of published data on bleeding during pregnancy or on management of pregnant women with F5F8D is insufficient. However, the fact that FVIII levels increase during pregnancy while FV levels do not must be emphasized; therefore, bleeding during labor and post-delivery are likely to be dependent on the FV level. In one study, three out of four women with F5F8D (who had pregnancies) experienced postpartum hemorrhage; however, no transfusions were necessary.18 Another study reported postpartum haemorrhage in six women (32% of deliveries), but no data on the amount of bleeding or prophylactic cover was provided.23

The occurrence of inhibitors after replacement therapy may not be uncommon (see Treatment section-Medication/Treatment).

Circulating levels of FV and FVIII in F5F8D patients are usually sufficient to prevent severe spontaneous bleeding episodes.18,24,25 The relationship between coagulation factor activity level and bleeding severity in patients with rare coagulation disorders has been recently evaluated by a cross-sectional study using data from 489 patients registered in the EN-RBD network.26 In this study, coagulation factor activities of 43 U/dL for both FVIII and FV were necessary for patients with F5F8D to remain completely asymptomatic. Moreover, a linear regression analysis showed a strong association between coagulant activity level and bleeding severity in the patients affected by F5F8D (n=20); however, the deficiency was mainly associated with minor bleeding.