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Vitamin K-dependent clotting factors, combined deficiency of, type 2(VKCFD2)

MedGen UID:
334505
Concept ID:
C1843832
Disease or Syndrome
Synonyms: Vitamin K-Dependent Clotting Factors, Combined Deficiency Of, Type 2; VKCFD2
 
Gene (location): VKORC1 (16p11.2)
 
Monarch Initiative: MONDO:0011837
OMIM®: 607473

Definition

Deficiency of all vitamin K-dependent clotting factors leads to a bleeding tendency that is usually reversed by oral administration of vitamin K. Familial multiple coagulation factor deficiency is rare. Clinical symptoms of the disease include episodes of intracranial hemorrhage in the first weeks of life, sometimes leading to a fatal outcome (Fregin et al., 2002). For a general phenotypic description and a discussion of genetic heterogeneity of combined deficiency of vitamin K-dependent clotting factors, see VKCFD1 (277450). [from OMIM]

Clinical features

From HPO
Abnormal bleeding
MedGen UID:
264316
Concept ID:
C1458140
Pathologic Function
An abnormal susceptibility to bleeding, often referred to as a bleeding diathesis. A bleeding diathesis may be related to vascular, platelet and coagulation defects.
Reduced factor IX activity
MedGen UID:
868754
Concept ID:
C4023159
Finding
Decreased activity of coagulation factor IX. Factor IX, which itself is activated by factor Xa or factor VIIa to form factor IXa, activates factor X into factor Xa.
Reduced factor X activity
MedGen UID:
892449
Concept ID:
C4024702
Finding
Reduced activity of coagulation factor X. The extrinsic and intrinsic pathways converge at factor X (fX). The extrinsic pathway activates fX by means of d factor VII with its cofactor, tissue factor. The intrinsic pathway activates fX by means of the tenase complex (Ca2+ and factors VIIIa, IXa and X) on the surface of activated platelets. Factor Xa in turn activates prothrombin (factor II) to thrombin (factor IIa).
Reduced factor VII activity
MedGen UID:
892851
Concept ID:
C4024722
Finding
Reduced activity of coagulation factor VII. Factor VII is part of the extrinsic coagulation pathway, which is initiated at the site of injury in response to the release of tissue factor (fIII). Tissue factor and activated factor VII catalyze the activation of factor X.
Reduced prothrombin antigen
MedGen UID:
901989
Concept ID:
C4280698
Finding
Reduced prothrombin antigen as measured by ELISA assay. Prothrombin is a vitamin K-dependent coagulation factor that is proteolytically cleaved to form thrombin.

Recent clinical studies

Etiology

Wypasek E, Undas A
Adv Clin Exp Med 2013 Jul-Aug;22(4):459-67. PMID: 23986205

Diagnosis

Ghosh S, Oldenburg J, Czogalla-Nitsche KJ
Int J Mol Sci 2022 Jan 12;23(2) doi: 10.3390/ijms23020798. PMID: 35054981Free PMC Article
Rishavy MA, Hallgren KW, Zhang H, Runge KW, Berkner KL
J Thromb Haemost 2019 Jul;17(7):1053-1063. Epub 2019 Jun 7 doi: 10.1111/jth.14456. PMID: 31009158Free PMC Article
Naz A, Jamal MY, Amanat S, Din Ujjan I, Najmuddin A, Patel H, Raziq F, Ahmed N, Imran A, Shamsi TS
Orphanet J Rare Dis 2017 Apr 7;12(1):66. doi: 10.1186/s13023-017-0620-6. PMID: 28388959Free PMC Article
Wypasek E, Undas A
Adv Clin Exp Med 2013 Jul-Aug;22(4):459-67. PMID: 23986205
Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Hörtnagel K, Pelz HJ, Lappegard K, Seifried E, Scharrer I, Tuddenham EG, Müller CR, Strom TM, Oldenburg J
Nature 2004 Feb 5;427(6974):537-41. doi: 10.1038/nature02214. PMID: 14765194

Therapy

Wypasek E, Undas A
Adv Clin Exp Med 2013 Jul-Aug;22(4):459-67. PMID: 23986205
Rost S, Geisen C, Fregin A, Seifried E, Müller CR, Oldenburg J
Blood Coagul Fibrinolysis 2006 Sep;17(6):503-7. doi: 10.1097/01.mbc.0000240927.88177.d1. PMID: 16905958

Prognosis

Wypasek E, Undas A
Adv Clin Exp Med 2013 Jul-Aug;22(4):459-67. PMID: 23986205

Clinical prediction guides

Barg AA, Brutman-Barazani T, Avishai E, Budnik I, Cohen O, Dardik R, Levy-Mendelovich S, Livnat T, Kenet G
Blood Cells Mol Dis 2022 Jul;95:102663. Epub 2022 Apr 12 doi: 10.1016/j.bcmd.2022.102663. PMID: 35525014
Rishavy MA, Hallgren KW, Zhang H, Runge KW, Berkner KL
J Thromb Haemost 2019 Jul;17(7):1053-1063. Epub 2019 Jun 7 doi: 10.1111/jth.14456. PMID: 31009158Free PMC Article
Czogalla KJ, Biswas A, Rost S, Watzka M, Oldenburg J
Blood 2014 Aug 21;124(8):1354-62. Epub 2014 Jun 24 doi: 10.1182/blood-2013-12-545988. PMID: 24963046
Wypasek E, Undas A
Adv Clin Exp Med 2013 Jul-Aug;22(4):459-67. PMID: 23986205
Furutani H
Medinfo 1995;8 Pt 2:909. PMID: 8591581

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