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Factor 5 and Factor VIII, combined deficiency of, 2(F5F8D2)

MedGen UID:
462239
Concept ID:
C3150889
Disease or Syndrome
Synonym: Factor v and factor viii, combined deficiency of, 2
 
Gene (location): MCFD2 (2p21)
 
Monarch Initiative: MONDO:0013331
OMIM®: 613625

Definition

Combined deficiency of factor V and factor VIII type 2 (F5F8D2) is characterized by bleeding symptoms similar to those in hemophilia (306700) or parahemophilia (227400), caused by single deficiency of FV (612309) or FVIII (300841), respectively. The most common symptoms are epistaxis, menorrhagia, and excessive bleeding during or after trauma. Plasma FV and FVIII antigen and activity levels are in the range of 5 to 30%. Inheritance of F5F8D2 is autosomal recessive and distinct from the coinheritance of FV deficiency and FVIII deficiency (summary by Zhang and Ginsburg, 2004). For a general phenotypic description and a discussion of genetic heterogeneity of F5F8D, see 227300. [from OMIM]

Clinical features

From HPO
Epistaxis
MedGen UID:
4996
Concept ID:
C0014591
Pathologic Function
Epistaxis, or nosebleed, refers to a hemorrhage localized in the nose.
Menorrhagia
MedGen UID:
44358
Concept ID:
C0025323
Pathologic Function
Prolonged and excessive menses at regular intervals in excess of 80 mL or lasting longer than 7 days.
Persistent bleeding after trauma
MedGen UID:
375403
Concept ID:
C1844374
Finding
Reduced factor VIII activity
MedGen UID:
892907
Concept ID:
C4025649
Finding
Reduced activity of coagulation factor VIII. Factor VIII (fVIII) is a cofactor in the intrinsic clotting cascade that is activated to fVIIIa in the presence of minute quantities of thrombin. fVIIIa acts as a receptor, for factors IXa and X.
Factor V deficiency
MedGen UID:
1369551
Concept ID:
C4317320
Disease or Syndrome
Factor V Leiden thrombophilia is characterized by a poor anticoagulant response to activated protein C (APC) and an increased risk for venous thromboembolism (VTE). Deep vein thrombosis (DVT) is the most common VTE, with the legs being the most common site. Thrombosis in unusual locations is less common. Evidence suggests that heterozygosity for the Leiden variant has at most a modest effect on risk for recurrent thrombosis after initial treatment of a first VTE. It is unlikely that factor V Leiden thrombophilia (i.e., heterozygosity or homozygosity for the Leiden variant) is a major factor contributing to pregnancy loss and other adverse pregnancy outcomes (preeclampsia, fetal growth restriction, and placental abruption). The clinical expression of factor V Leiden thrombophilia is influenced by the following: The number of Leiden variants (heterozygotes have a slightly increased risk for venous thrombosis; homozygotes have a much greater thrombotic risk). Coexisting genetic thrombophilic disorders, which have a supra-additive effect on overall thrombotic risk. Acquired thrombophilic disorders: antiphospholipid antibody (APLA) syndrome, paroxysmal nocturnal hemoglobinuria, myeloproliferative disorders, and increased levels of clotting factors. Circumstantial risk factors including but not limited to pregnancy, central venous catheters, travel, combined oral contraceptive (COC) use and other combined contraceptives, oral hormone replacement therapy (HRT), selective estrogen receptor modulators (SERMs), obesity, leg injury, and advancing age.

Professional guidelines

PubMed

Peyvandi F, Menegatti M
Hematology Am Soc Hematol Educ Program 2016 Dec 2;2016(1):663-669. doi: 10.1182/asheducation-2016.1.663. PMID: 27913544Free PMC Article
Karimi M, Cairo A, Safarpour MM, Haghpanah S, Ekramzadeh M, Afrasiabi A, Shahriari M, Menegatti M
Blood Coagul Fibrinolysis 2014 Jun;25(4):360-3. doi: 10.1097/MBC.0000000000000046. PMID: 24389588
Zhang B, Spreafico M, Zheng C, Yang A, Platzer P, Callaghan MU, Avci Z, Ozbek N, Mahlangu J, Haw T, Kaufman RJ, Marchant K, Tuddenham EG, Seligsohn U, Peyvandi F, Ginsburg D
Blood 2008 Jun 15;111(12):5592-600. Epub 2008 Apr 7 doi: 10.1182/blood-2007-10-113951. PMID: 18391077Free PMC Article

Recent clinical studies

Etiology

Fogarty H, Doyle MM, Campbell R, Keenan C, White B, Ryan K, O'Donnell JS, Slevin J, O'Keeffe D, O'Connell NM, Lavin M
J Obstet Gynaecol 2019 Feb;39(2):271-272. Epub 2018 Apr 18 doi: 10.1080/01443615.2018.1448766. PMID: 29667457
Peyvandi F, Menegatti M
Hematology Am Soc Hematol Educ Program 2016 Dec 2;2016(1):663-669. doi: 10.1182/asheducation-2016.1.663. PMID: 27913544Free PMC Article
Hoffmann C, Falzone E, Mihai A, Gitz L, Itzhar-Baikian N, Martel-Jacob S, Mercier FJ
Ann Fr Anesth Reanim 2013 Nov;32(11):e163-5. Epub 2013 Oct 23 doi: 10.1016/j.annfar.2013.08.014. PMID: 24161289
Reitter-Pfoertner S, Waldhoer T, Mayerhofer M, Eigenbauer E, Ay C, Mannhalter C, Kyrle PA, Pabinger I
Thromb Haemost 2013 Jan;109(1):79-84. Epub 2012 Nov 22 doi: 10.1160/TH12-05-0361. PMID: 23178976
Nichols WC, Seligsohn U, Zivelin A, Terry VH, Arnold ND, Siemieniak DR, Kaufman RJ, Ginsburg D
J Clin Invest 1997 Feb 15;99(4):596-601. doi: 10.1172/JCI119201. PMID: 9045860Free PMC Article

Diagnosis

Alsheikh S, Alghamdi R, Alqatari A, Alfareed A, AlSaleh M
Am J Case Rep 2022 Sep 18;23:e937312. doi: 10.12659/AJCR.937312. PMID: 36116005Free PMC Article
Link KG, Stobb MT, Sorrells MG, Bortot M, Ruegg K, Manco-Johnson MJ, Di Paola JA, Sindi SS, Fogelson AL, Leiderman K, Neeves KB
J Thromb Haemost 2020 Feb;18(2):306-317. Epub 2019 Nov 1 doi: 10.1111/jth.14653. PMID: 31562694Free PMC Article
Peyvandi F, Menegatti M
Hematology Am Soc Hematol Educ Program 2016 Dec 2;2016(1):663-669. doi: 10.1182/asheducation-2016.1.663. PMID: 27913544Free PMC Article
Mansouritorghabeh H, Shirdel A
J Thromb Haemost 2016 Feb;14(2):336-9. Epub 2016 Jan 30 doi: 10.1111/jth.13207. PMID: 26599105
Girolami A, Simioni P, Scarano L, Girolami B, Marchiori A
Blood Rev 1998 Mar;12(1):45-51. doi: 10.1016/s0268-960x(98)90029-7. PMID: 9597197

Therapy

Dobry AS, Ko LN, St John J, Sloan JM, Nigwekar S, Kroshinsky D
JAMA Dermatol 2018 Feb 1;154(2):182-187. doi: 10.1001/jamadermatol.2017.4920. PMID: 29238798Free PMC Article
Peyvandi F, Menegatti M
Hematology Am Soc Hematol Educ Program 2016 Dec 2;2016(1):663-669. doi: 10.1182/asheducation-2016.1.663. PMID: 27913544Free PMC Article
Mansouritorghabeh H, Shirdel A
J Thromb Haemost 2016 Feb;14(2):336-9. Epub 2016 Jan 30 doi: 10.1111/jth.13207. PMID: 26599105
Hoffmann C, Falzone E, Mihai A, Gitz L, Itzhar-Baikian N, Martel-Jacob S, Mercier FJ
Ann Fr Anesth Reanim 2013 Nov;32(11):e163-5. Epub 2013 Oct 23 doi: 10.1016/j.annfar.2013.08.014. PMID: 24161289
Devecioğlu O, Eryilmaz E, Celik D, Unüvar A, Karakaş Z, Anak S, Ağaoğlu L
Turk J Pediatr 2002 Apr-Jun;44(2):146-7. PMID: 12026204

Prognosis

Dobry AS, Ko LN, St John J, Sloan JM, Nigwekar S, Kroshinsky D
JAMA Dermatol 2018 Feb 1;154(2):182-187. doi: 10.1001/jamadermatol.2017.4920. PMID: 29238798Free PMC Article
Reitter-Pfoertner S, Waldhoer T, Mayerhofer M, Eigenbauer E, Ay C, Mannhalter C, Kyrle PA, Pabinger I
Thromb Haemost 2013 Jan;109(1):79-84. Epub 2012 Nov 22 doi: 10.1160/TH12-05-0361. PMID: 23178976
Karimi M, Haghpanah S, Amirhakimi A, Afrasiabi A, Dehbozorgian J, Nasirabady S
Blood Coagul Fibrinolysis 2009 Dec;20(8):642-5. doi: 10.1097/MBC.0b013e32832f4371. PMID: 19710607
Girolami A, Simioni P, Scarano L, Girolami B, Marchiori A
Blood Rev 1998 Mar;12(1):45-51. doi: 10.1016/s0268-960x(98)90029-7. PMID: 9597197
Burns ER, Goldberg SN, Wenz B
Am J Clin Pathol 1993 Aug;100(2):94-8. doi: 10.1093/ajcp/100.2.94. PMID: 8356955

Clinical prediction guides

Alsheikh S, Alghamdi R, Alqatari A, Alfareed A, AlSaleh M
Am J Case Rep 2022 Sep 18;23:e937312. doi: 10.12659/AJCR.937312. PMID: 36116005Free PMC Article
Hoffmann C, Falzone E, Mihai A, Gitz L, Itzhar-Baikian N, Martel-Jacob S, Mercier FJ
Ann Fr Anesth Reanim 2013 Nov;32(11):e163-5. Epub 2013 Oct 23 doi: 10.1016/j.annfar.2013.08.014. PMID: 24161289
Spreafico M, Peyvandi F
Semin Thromb Hemost 2009 Jun;35(4):390-9. Epub 2009 Jul 13 doi: 10.1055/s-0029-1225761. PMID: 19598067
Zhang B, Spreafico M, Zheng C, Yang A, Platzer P, Callaghan MU, Avci Z, Ozbek N, Mahlangu J, Haw T, Kaufman RJ, Marchant K, Tuddenham EG, Seligsohn U, Peyvandi F, Ginsburg D
Blood 2008 Jun 15;111(12):5592-600. Epub 2008 Apr 7 doi: 10.1182/blood-2007-10-113951. PMID: 18391077Free PMC Article
Ginsburg D, Nichols WC, Zivelin A, Kaufman RJ, Seligsohn U
Haemophilia 1998 Jul;4(4):677-82. doi: 10.1046/j.1365-2516.1998.440677.x. PMID: 9873813

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