History

Clinical manifestations of factor V deficiency include the following:

Bleeding into the skin
Excessive bruising with minor injuries
Nosebleeds
Bleeding gums
Excessive menstrual bleeding and prolonged or excessive loss of blood with surgery or trauma
Bleeding in mucosal tracts (gastrointestinal, urinary)
Hemarthrosis and flexion contracture
Bleeding during delivery and postpartum^[17]
Intracerebral hemorrhages^{[18, 19]}
Pulmonary hemorrhage^[20]

The severity of bleeding symptoms is only partly related to the degree of factor V deficiency in plasma. Some patients with undetectable plasma levels of factor V experience only relatively mild bleeding.^[1]

Physical

The most common physical findings of factor V deficiency are ecchymoses, bleeding from mucosal surfaces, and pallor secondary to blood loss. Petechiae are uncommon because platelet numbers and function are not affected.

Causes

Factor V deficiency is caused by a large number of genetic abnormalities. The deficiency is a rare bleeding disorder whose genetic bases have been characterized in only a limited number of cases.^[9]The inheritance of factor V deficiency is autosomal recessive, with varying expressivity in the heterozygote; however, other modes of inheritance have been described. Heterozygotes have lowered levels of factor V but probably never bleed abnormally.

Consanguinity has been observed in families with factor V deficiency, related to its autosomal recessive inheritance. Heterozygous deficiency states are generally unrecognized because of a lack of significant clotting time prolongation or bleeding risk.

Differential Diagnoses

Thalji N, Camire RM. Parahemophilia: new insights into factor v deficiency. Semin Thromb Hemost. 2013 Sep. 39(6):607-12. [QxMD MEDLINE Link].
Quek JKS, Wong WH, Tan CW, Tha MH, Nagarajan C, Lee LH, et al. Acquired factor V deficiency in a patient with myeloma and amyloidosis. Thromb Res. 2018 Apr. 164:1-3. [QxMD MEDLINE Link].
Owren P. Parahaemophilia: haemorrhagic diathesis due to absence of a previously unknown clotting factor. Lancet. 1947. Vol I:446-8.
Duckers C, Simioni P, Rosing J, Castoldi E. Advances in understanding the bleeding diathesis in factor V deficiency. Br J Haematol. 2009 Jun. 146(1):17-26. [QxMD MEDLINE Link].
Asselta R, Peyvandi F. Factor V deficiency. Semin Thromb Hemost. 2009 Jun. 35(4):382-9. [QxMD MEDLINE Link].
Cramer TJ, Gale AJ. The anticoagulant function of coagulation factor V. Thromb Haemost. 2011 Nov 24. 107(1):[QxMD MEDLINE Link].
Ni Ainle F, Preston RJ, Jenkins PV, et al. Protamine sulfate down-regulates thrombin generation by inhibiting factor V activation. Blood. 2009 Aug 20. 114(8):1658-65. [QxMD MEDLINE Link].
Delev D, Pavlova A, Heinz S, Seifried E, Oldenburg J. Factor 5 mutation profile in German patients with homozygous and heterozygous factor V deficiency. Haemophilia. 2009 Sep. 15(5):1143-53. [QxMD MEDLINE Link].
Liu HC, Shen MC, Eng HL, Wang CH, Lin TM. Asp68His mutation in the A1 domain of human factor V causes impaired secretion and ineffective translocation. Haemophilia. 2014 Jul. 20(4):e318-26. [QxMD MEDLINE Link].
Mitterstieler G, Muller W, Geir W. Congenital factor V deficiency. A family study. Scand J Haematol. 1978 Jul. 21(1):9-13. [QxMD MEDLINE Link].
Zehnder JL, Hiraki DD, Jones CD, Gross N, Grumet FC. Familial coagulation factor V deficiency caused by a novel 4 base pair insertion in the factor V gene: factor V Stanford. Thromb Haemost. 1999 Sep. 82(3):1097-9. [QxMD MEDLINE Link].
Liu S, Luo S, Yang L, Jin Y, Xie H, Xie Y, et al. A novel homozygous mutation (Gly1715Ser) causing hereditary factor V deficiency in a Chinese patient. Blood Coagul Fibrinolysis. 2019 Nov 26. [QxMD MEDLINE Link].
Zheng C, Zhang B. Combined deficiency of coagulation factors V and VIII: an update. Semin Thromb Hemost. 2013 Sep. 39 (6):613-20. [QxMD MEDLINE Link]. [Full Text].
Van den Berg SA, Verwer PE, Idema RN, Van Guldener C. Transient cefuroxime/metronidazole treatment induced factor V antibodies. BMJ Case Rep. 2014 Aug 19. 2014:[QxMD MEDLINE Link].
Wang X, Qin X, Yu Y, Wang R, Liu X, Ji M, et al. Acquired factor V deficiency in a patient with a urinary tract infection presenting with haematuria followed by multiple haemorrhages with an extremely low level of factor V inhibitor: a case report and review of the literature. Blood Coagul Fibrinolysis. 2017 Jun. 28 (4):334-341. [QxMD MEDLINE Link]. [Full Text].
Hamedani AG, Cole JW, Cheng Y, Sparks MJ, O'Connell JR, Stine OC, et al. Factor V Leiden and Ischemic Stroke Risk: The Genetics of Early Onset Stroke (GEOS) Study. J Stroke Cerebrovasc Dis. 2011 Nov 17. [QxMD MEDLINE Link].
Girolami A, Scandellari R, Lombardi AM, Girolami B, Bortoletto E, Zanon E. Pregnancy and oral contraceptives in factor V deficiency: a study of 22 patients (five homozygotes and 17 heterozygotes) and review of the literature. Haemophilia. 2005 Jan. 11(1):26-30. [QxMD MEDLINE Link].
Totan M, Albayrak D. Intracranial haemorrhage due to factor V deficiency. Acta Paediatr. 1999 Mar. 88(3):342-3. [QxMD MEDLINE Link].
Sacco S, Dragani A, Davi G, Carolei A. Four recurrent intracerebral haemorrhages. Cerebrovasc Dis. 2003. 16(4):435-6. [QxMD MEDLINE Link].
Satoh H, Yamashita YT, Ohtsuka M, Sekizawa K, Hasegawa Y. Pulmonary hemorrhage in factor V deficiency. Can Respir J. 1999 Jul-Aug. 6(4):320. [QxMD MEDLINE Link].
Paraboschi EM, Menegatti M, Rimoldi V, Borhany M, Abdelwahab M, Gemmati D, et al. Profiling the mutational landscape of coagulation factor V deficiency. Haematologica. 2020 Apr. 105 (4):e180-e185. [QxMD MEDLINE Link]. [Full Text].
Bulato C, Novembrino C, Anzoletti MB, Spiezia L, Gavasso S, Berbenni C, et al. "In vitro" correction of the severe factor V deficiency-related coagulopathy by a novel plasma-derived factor V concentrate. Haemophilia. 2018 Jul. 24 (4):648-656. [QxMD MEDLINE Link].
Gavva C, Yates SG, Rambally S, Sarode R. Transfusion management of factor V deficiency: three case reports and review of the literature. Transfusion. 2016 Jul. 56 (7):1745-9. [QxMD MEDLINE Link].
Bello A, Salazar E, Heyne K, Varon J. Aortic Valve Replacement in Severe Factor V Deficiency and Inhibitor: Diagnostic and Management Challenges. Cureus. 2019 Oct 15. 11 (10):e5918. [QxMD MEDLINE Link].
Passarelli PC, De Angelis P, Pasquantonio G, Manicone PF, Verdugo F, D'Addona A. Management of Single Uncomplicated Dental Extractions and Postoperative Bleeding Evaluation in Patients With Factor V Deficiency: A Local Antihemorrhagic Approach. J Oral Maxillofac Surg. 2018 Jun 21. 3(3):196-8. [QxMD MEDLINE Link].
Yanagiya R, Kanouchi K, Toubai T, Yamada A, Aizawa K, Shiono Y, et al. Plasma Exchange as an Initial Treatment for Severe Bleeding Induced by Acquired Factor V Deficiency: A Case Report and Mini Literature Review. Acta Haematol. 2020 Aug 12. 12 (8):1-5. [QxMD MEDLINE Link].
Fu YX, Kaufman R, Rudolph AE, Collum SE, Blinder MA. Multimodality therapy of an acquired factor V inhibitor. Am J Hematol. 1996 Apr. 51(4):315-8. [QxMD MEDLINE Link].
Wu AH, Manje Gowda A, Peng S, Kaur S, Maroules M. Successful Management of Life-threatening Pelvic Hemorrhage From Acquired Factor V Deficiency With immunosuppressive Therapy. Cureus. 2020 Aug 23. 12 (8):e9972. [QxMD MEDLINE Link]. [Full Text].
Nakamura T, Morishige S, Ozawa H, Kuboyama K, Yamasaki Y, Oya S, et al. Successful correction of factor V deficiency of patient-derived iPSCs by CRISPR/Cas9-mediated gene editing. Haemophilia. 2020 Sep. 26 (5):826-833. [QxMD MEDLINE Link].

Media Gallery

Antithrombin sites of action.
Cell surface-directed hemostasis. Initially, a small amount of thrombin is generated on the surface of the tissue factor (TF)–bearing cell. Following amplification, the second burst generates a larger amount of thrombin, leading to fibrin (clot) formation. Adapted from Hoffman and Monroe, Thromb Haemost 2001, 85(6): 958-65.

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Author

Olga Kozyreva, MD Attending Physician, Division of Hematology-Oncology, St Elizabeth's Medical Center; Assistant Professor, Tufts University School of Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Sarah K May, MD Consulting Staff, Department of Hematology-Oncology, Caritas Carney Hospital, Commonwealth Hematology-Oncology PC

Disclosure: Nothing to disclose.

Karl J D'Silva, MD Assistant Clinical Professor of Medicine, Department of Hematology/Oncology, Lahey Clinic, Sophia Gordon Cancer Center

Karl J D'Silva, MD is a member of the following medical societies: Massachusetts Medical Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ronald A Sacher, MD, FRCPC, DTM&H Professor Emeritus of Internal Medicine and Hematology/Oncology, Emeritus Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center

Ronald A Sacher, MD, FRCPC, DTM&H is a member of the following medical societies: American Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Perumal Thiagarajan, MD Professor, Department of Pathology and Medicine, Baylor College of Medicine; Director, Transfusion Medicine and Hematology Laboratory, Michael E DeBakey Veterans Affairs Medical Center

Perumal Thiagarajan, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society for Biochemistry and Molecular Biology, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Royal College of Physicians

Disclosure: Nothing to disclose.

Additional Contributors

Paul Schick, MD † Emeritus Professor, Department of Internal Medicine, Jefferson Medical College of Thomas Jefferson University; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital

Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology

Disclosure: Nothing to disclose.

Sections Factor V Deficiency
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Factor V Deficiency Clinical Presentation

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