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Combined deficiency of factor V and factor VIII, 1(F5F8D1)

MedGen UID:
384006
Concept ID:
C1856883
Disease or Syndrome
Synonyms: F5F8D1; FAMILIAL MULTIPLE COAGULATION FACTOR DEFICIENCY I; FMFD I; MULTIPLE COAGULATION FACTOR DEFICIENCY I
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: HPO
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): LMAN1 (18q21.32)
OMIM®: 227300

Definition

Combined deficiency of factor V (612309) and factor VIII (300841) is characterized by bleeding symptoms similar to those in hemophilia (306700) or parahemophilia (227400), caused by single deficiency of FV or FVIII, 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 F5F8D is autosomal recessive and distinct from the coinheritance of FV deficiency and FVIII deficiency (summary by Zhang and Ginsburg, 2004). Genetic Heterogeneity of Combined Deficiency of Factor V and Factor VIII Another form of combined deficiency of factor V and factor VII (F5F8D2; 613625) is caused by mutation in the MCFD2 gene (607788) on chromosome 2. [from OMIM]

Clinical features

Factor V deficiency
MedGen UID:
4633
Concept ID:
C0015499
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 venous 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 a heterozygous factor V Leiden mutation has at most a modest effect on recurrence risk after initial treatment of a first VTE. Heterozygosity for factor V Leiden is associated with a two- to threefold increase in relative risk for pregnancy loss, and possibly other pregnancy complications such as preeclampsia, fetal growth retardation, and placental abruption. The clinical expression of factor V Leiden thrombophilia is influenced by: The number of factor V Leiden alleles (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 antibodies, hyperhomocysteinemia, high factor VIII levels, malignancy; and Circumstantial risk factors: travel, central venous catheters, pregnancy, oral contraceptive use, hormone replacement therapy (HRT), selective estrogen receptor modulators (SERMs), organ transplantation, advancing age, and surgery.
Tendency to bleed
MedGen UID:
264316
Concept ID:
C1458140
Pathologic Function
Normally, if you get hurt, your body forms a blood clot to stop the bleeding. For blood to clot, your body needs cells called platelets and proteins known as clotting factors. If you have a bleeding disorder, you either do not have enough platelets or clotting factors or they don't work the way they should. . Bleeding disorders can be the result of other diseases, such as severe liver disease. They can also be inherited. Hemophilia is an inherited bleeding disorder. Bleeding disorders can also be a side effect of medicines.
Factor VIII deficiency
MedGen UID:
488140
Concept ID:
C3494187
Disease or Syndrome
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.

Recent clinical studies

Etiology

de Haan HG, Bezemer ID, Vossen CY, van Hylckama Vlieg A, Böehringer S, Hasstedt SJ, Levy S, Rosendaal FR, Bovill EG
Thromb Res 2014 Dec;134(6):1186-92. Epub 2014 Sep 23 doi: 10.1016/j.thromres.2014.09.018. [Epub ahead of print] PMID: 25306186Free 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. [Epub ahead of print] PMID: 24161289
Neerman-Arbez M, Johnson KM, Morris MA, McVey JH, Peyvandi F, Nichols WC, Ginsburg D, Rossier C, Antonarakis SE, Tuddenham EG
Blood 1999 Apr 1;93(7):2253-60. PMID: 10090934
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
Garcia VV, Silva IA, Borrasca AL
Thromb Haemost 1982 Aug 24;48(1):91-3. PMID: 6813999

Diagnosis

de Haan HG, Bezemer ID, Vossen CY, van Hylckama Vlieg A, Böehringer S, Hasstedt SJ, Levy S, Rosendaal FR, Bovill EG
Thromb Res 2014 Dec;134(6):1186-92. Epub 2014 Sep 23 doi: 10.1016/j.thromres.2014.09.018. [Epub ahead of print] PMID: 25306186Free PMC Article
Zheng C, Page RC, Das V, Nix JC, Wigren E, Misra S, Zhang B
J Biol Chem 2013 Jul 12;288(28):20499-509. Epub 2013 May 24 doi: 10.1074/jbc.M113.461434. [Epub ahead of print] PMID: 23709226Free PMC Article
Sirachainan N, Zhang B, Chuansumrit A, Pipe S, Sasanakul W, Ginsburg D
Haemophilia 2005 May;11(3):280-4. doi: 10.1111/j.1365-2516.2005.01092.x. PMID: 15876275
Segal A, Zivelin A, Rosenberg N, Ginsburg D, Shpilberg O, Seligsohn U
Blood Coagul Fibrinolysis 2004 Jan;15(1):99-102. PMID: 15166951
Girolami A, Simioni P, Scarano L, Girolami B, Marchiori A
Blood Rev 1998 Mar;12(1):45-51. PMID: 9597197

Therapy

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. [Epub ahead of print] PMID: 24161289
Einhäupl K, Stam J, Bousser MG, De Bruijn SF, Ferro JM, Martinelli I, Masuhr F; European Federation of Neurological Societies
Eur J Neurol 2010 Oct;17(10):1229-35. doi: 10.1111/j.1468-1331.2010.03011.x. PMID: 20402748
Spreafico M, Peyvandi F
Haemophilia 2008 Nov;14(6):1201-8. doi: 10.1111/j.1365-2516.2008.01845.x. PMID: 19141160
Chuansumrit A, Mahaphan W, Pintadit P, Chaichareon P, Hathirat P, Ayuthaya PI
Southeast Asian J Trop Med Public Health 1994 Mar;25(1):217-20. PMID: 7825020
Garcia VV, Silva IA, Borrasca AL
Thromb Haemost 1982 Aug 24;48(1):91-3. PMID: 6813999

Prognosis

de Haan HG, Bezemer ID, Vossen CY, van Hylckama Vlieg A, Böehringer S, Hasstedt SJ, Levy S, Rosendaal FR, Bovill EG
Thromb Res 2014 Dec;134(6):1186-92. Epub 2014 Sep 23 doi: 10.1016/j.thromres.2014.09.018. [Epub ahead of print] PMID: 25306186Free PMC Article
Segal A, Zivelin A, Rosenberg N, Ginsburg D, Shpilberg O, Seligsohn U
Blood Coagul Fibrinolysis 2004 Jan;15(1):99-102. PMID: 15166951
Ghosh K, Shetty S, Mohanty D
Haemophilia 2001 Jan;7(1):9-12. PMID: 11136374
Neerman-Arbez M, Johnson KM, Morris MA, McVey JH, Peyvandi F, Nichols WC, Ginsburg D, Rossier C, Antonarakis SE, Tuddenham EG
Blood 1999 Apr 1;93(7):2253-60. PMID: 10090934
Girolami A, Simioni P, Scarano L, Girolami B, Marchiori A
Blood Rev 1998 Mar;12(1):45-51. PMID: 9597197

Clinical prediction guides

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. [Epub ahead of print] PMID: 24161289
Zhang B, Zheng C, Zhu M, Tao J, Vasievich MP, Baines A, Kim J, Schekman R, Kaufman RJ, Ginsburg D
Blood 2011 Sep 22;118(12):3384-91. Epub 2011 Jul 27 doi: 10.1182/blood-2011-05-352815. [Epub ahead of print] PMID: 21795745Free PMC Article
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
Segal A, Zivelin A, Rosenberg N, Ginsburg D, Shpilberg O, Seligsohn U
Blood Coagul Fibrinolysis 2004 Jan;15(1):99-102. PMID: 15166951
Suzuki K, Nishioka J, Hashimoto S, Kamiya T, Saito H
Blood 1983 Dec;62(6):1266-70. PMID: 6315113

Recent systematic reviews

Einhäupl K, Stam J, Bousser MG, De Bruijn SF, Ferro JM, Martinelli I, Masuhr F; European Federation of Neurological Societies
Eur J Neurol 2010 Oct;17(10):1229-35. doi: 10.1111/j.1468-1331.2010.03011.x. PMID: 20402748

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