Introduction

Combined factor V and factor VIII deficiency (F5F8D, OMIM 227300) is a rare autosomal recessive bleeding disorder first described in 1954 by Oreri and colleagues [1]. Since then, more than 200 cases were reported all over the world. Noticeable number of these patients belonged to Mediterranean and Asian countries in particular the Middle East. Regarding autosomal recessive inherited pattern of this disorder, parents of these patients are obligatory heterozygotes. So, the prevalence of this rare mutation increases in regions with higher rate of consanguineous marriages like afibrinogenemia [2-4]. Simultaneous decrease of plasma factor V and factor VIII as the underlying F5F8D characteristic leads to mild-to-moderate bleeding symptoms including: epistaxis, postsurgical bleeding, menorrhagia, hemarthrosis and muscular hematomas [5-7]. We report a patient suffering from F5F8D with no evidence of common symptoms before diagnosis.

Case Presentation

A 5-year-old girl born out of consanguineous marriage referred to our pediatric hematology clinic of Baqiyatallah hospital, Tehran, Iran for clarifying the reason of her extraordinary bleeding after dental extraction procedure. She did not have a history of spontaneous bleeding like epistaxis and gum bleeding or prolonged bleeding after skin rupture. But her history revealed the bruising after falls.Admission examination did not show ecchymosis or any joint swelling, and review of systems was remarkable. She did not have a history of spontaneous bleeding like epistaxis and gum bleeding or prolonged bleeding after skin rupture; although, her past history revealed the bruising after falls. The patient was hemodynamically normal with a temperature of 36.8°C, blood pressure of 110/ 58 mmHg, heart rate of 95 beats/min, and respiratory rate of 22 breaths/min. Laboratory investigations demonstrated an activated partial prothrombin time (aPTT) of 86.9s (control 35.5s), a prothrombin time (PT) of 21s (control 13.2s) and a bleeding time (BT) of 3 minutes. Because of prolonged PT and PTT, we doubted a common pathway factor deficiency including factor V and factor X, congenital Vitamin K deficiency and vitamin K related factor deficiency including factor II, factor VII, factor IX and factor X as differential diagnoses. The patient’s hemostatic assessment showed the level of factor II at 67%, factor V 10%, factor VIIIc 9%, factor IX 64%, factor X 45%, vWF activity (RCo) 48%, vWF antigen 55%, and fibrinogen 249 mg/dl.Our patient belonged to a 4-member family comprising of an older brother and consanguinity parents. There were no positive history and symptoms in favor of hematologic disorders. Even though, her mother had a PT of 14.7s (control 13.6s) simultaneously with factor VII 39% in her coagulation assessment (Table1).

After definitive diagnosis of combined factor V and factor VIII deficiency, the patient was asked on regular visits. The patient was also recommended to receive factor injection before any surgery procedure.

Discussion

Combined factor V and factor VIII deficiency is known as the most prevalent combined plasma coagulation factor deficiency [8]. The affected person was a case of F5F8D without classic manifestation described for this disorder. We reported this case because Iran is located in the most prevalent area for this disorder based on our literature review [8, 9]. So, each physician might be faced with patients suffering from this disorder. In the United Kingdom, Haemophilia Centre Doctors’ Organization guideline has been recommended to use fresh frozen plasma (FFP) as a part of treatment regimen which can provide FV and FVIII concentrate. Some previous reports have demonstrated that FFP containing regimen could successfully control bleeding during dental extraction, male circumcision and preparation for labor [10].

So, in patients with coagulation defect symptoms along with a history of parents with kindred marriage, inherited deficiency of factor V and VIII should be considered due to autosomal recessive inherited pattern of F5F8D. More investigations are needed to establish valuable guidelines for hemorrhage management in individuals with combined factor V and VIII deficiency.

Conclusion

Combined factor V and VIII deficiency seems more common among Iranians particularly in frequent consanguineous marriage regions. So, inherited deficiency of factor V and VIII should be considered in patients with coagulation defect symptoms. Finally, we recommend the evaluation of factor VIII level in patients with prolonged PT and PTT and factor V deficiency.

Conflict of Interest

The authors report that there is no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

 Correspondence to: Hassan Abolghasemi, Department of Pediatrics, Baqiyatallah University of Medical Sciences, Tehran, Iran Telephone Number: +982188620826 Email Address: h.abolghasemi.ha@gmail.com

GMJ. 2016;5(1):42-44

www.gmj.ir

References

1. Oeri J, Matter M, Isenschmid H, Hauser F, Koller F. Angeborener mangel an faktor V (parahaemophilie) verbunden mit echter haemophilie A bein zwei brudern. Med Probl Paediatr. 1954;1:575-88.
2. Farah RA, De Moerloose P, Bouchardy I, Morris MA, Barakat W, Sayad AE et al. Combined factor V-factor VIII deficiency (F5F8D): compound heterozygosity for two novel truncating mutations in LMAN1 in a consanguineous patient. THROMBOSIS AND HAEMOSTASIS-STUTTGART-. 2006;95(5):893.
3. Zheng C, Zhang B, editors. Combined deficiency of coagulation factors V and VIII: an update. Seminars in thrombosis and hemostasis; 2013: NIH Public Access.
4. Abolghasemi H, Shahverdi E. Umbilical bleeding: a presenting feature for congenital afibrinogenemia. Blood Coagulation & Fibrinolysis. 2015;26(7):834-5.
5. Viswabandya A, Baidya S, Nair SC, Lakshmi KM, Mathews V, George B, et al. Clinical manifestations of combined factor V and VIII deficiency: a series of 37 cases from a single center in India. American journal of hematology. 2010;85(7):538-9.
6. Zhang B. Recent developments in the understanding of the combined deficiency of FV and FVIII. British journal of haematology. 2009;145(1):15-23.
7. Zhang B, Cunningham MA, Nichols WC, Bernat JA, Seligsohn U, Pipe SW, et al. Bleeding due to disruption of a cargo-specific ER-to-Golgi transport complex. Nature genetics. 2003;34(2):220-5.
8. Peyvandi F, Tuddenham E, Akhtari A, Lak M, Mannucci P. Bleeding symptoms in 27 Iranian patients with the combined deficiency of factor V and factor VIII. British journal of haematology. 1998;100(4):773-6.
9. Mansouritorgabeh H, Rezaieyazdi Z, Pourfathollah A, Rezai J, Esamaili H. Haemorrhagic symptoms in patients with combined factors V and VIII deficiency in north-eastern Iran. Haemophilia. 2004;10(3):271-5.
10. Bolton-Maggs P, Perry D, Chalmers E, Parapia L, Wilde J, Williams M, et al. The rare coagulation disorders–review with guidelines for management from the United Kingdom Haemophilia Centre Doctors’ Organisation. Haemophilia. 2004;10(5):593-628.