Factor V deficiency is a rare coagulation disorder and can be either inherited or acquired. It presents clinically with bleeding from various body parts and the bleeding ranges in severity from minor bleeding to life-threatening hemorrhage. Coagulation studies form the mainstay of diagnosis.
Presentation
Factor V deficiency (FVD) is a rare bleeding disorder. It is either inherited as an autosomal recessive trait or acquired. Heterozygous individuals with this trait are asymptomatic [1] [2] while homozygous individuals can present as early as in the neonatal period with either minor bleeding from the nipple [3], the stump of the umbilical cord or epistaxis, and gum bleeding [4] or catastrophic subdural or intracerebral hemorrhage. In some cases, the bleeding disorder is first noticed post-surgery, typically circumcision [1] although epistaxis and oral bleeding are the most common forms of presentation [1]. Older individuals present with different patterns of bleeding such as hemarthrosis, menorrhagia and gastrointestinal bleeding. Studies have reported that there is no clear relationship between plasma factor V (FV) levels and the severity of bleeding [5] [2]. Several patients have severe bleeding although their factor V levels are greater than 5% while patients with less than 1% factor V levels can have mild to moderate bleeding [2].
Acquired FVD also has a varied clinical presentation ranging from asymptomatic to life-threatening hemorrhages [6] such as postoperative retroperitoneal bleeding and hemoperitoneum [7]. It occurs due to the formation of antibodies (inhibitors) to factor V. Earlier factor V inhibitors were reported to form after the intra-operative use of bovine thrombin [8] but now it is known that they can occur following transfusion of blood components, beta-lactam administration, surgical procedures, bacterial infections, malignancy, and autoimmune disorders [6] [9].
Entire Body System
- Asymptomatic
Heterozygous factor V deficiency was also found in one brother and one sister of the proposita, and they were both asymptomatic. [ncbi.nlm.nih.gov]
Heterozygous individuals with this trait are asymptomatic while homozygous individuals can present as early as in the neonatal period with either minor bleeding from the nipple, the stump of the umbilical cord or epistaxis, and gum bleeding or catastrophic [symptoma.com]
- Surgical Procedure
We report two patients with severe congenital factor V deficiency, one of whom also had a factor V inhibitor, who required correction of their coagulopathy prior to surgical procedures. [ncbi.nlm.nih.gov]
Earlier factor V inhibitors were reported to form after the intra-operative use of bovine thrombin but now it is known that they can occur following transfusion of blood components, beta-lactam administration, surgical procedures, bacterial infections [symptoma.com]
However, he had no history of significant coagulation disorders with prior surgical procedures or other family bleeding history. He had no documented history of medicines. [journals.lww.com]
procedure or with pregnancy/delivery Moderate (< 10% activity) : Patients may have mild spontaneous bleeding, or bleeding triggered by trauma, surgery, or pregnancy/delivery Severe (undetectable activity) : Patients may have spontaneous, severe, and [rarebleedingdisorders.com]
These cases are called acquired factor V deficiency and usually occur in individuals who have been treated with substances that stimulate the production of anti-factor V antibodies, such as bovine thrombin used during surgical procedures. [ghr.nlm.nih.gov]
- Anemia
Four new chapters cover anemias unique to the newborn period, pathology of LHC and other histiocytic disorders, tumors of the spleen, and pathology and classification of myeloproliferative disorders and mast cell disease. [books.google.com]
D64.81 Anemia due to antineoplastic chemotherapy D64.89 Other specified anemias D64.9 Anemia, unspecified D65 Disseminated intravascular coagulation [defibrination syndrome] D66 Hereditary factor VIII deficiency D67 Hereditary factor IX deficiency D68 [icd10data.com]
Sub Menu Disorders Bleeding Disorders Rare Bleeding Disorders Factor I Factor II Factor V Factor VII Factor VIII Factor X Factor XI Factor XIII Clotting Disorders Anemia (Also known as Owren's Disease, Labile Factor Deficiency, Proaccelerin Deficiency [ilbcdi.org]
Patients with factor V deficiency can be given oral contraceptives to decrease menorrhagias, thereby improving anemia and decreasing transfusion needs. [rnpedia.com]
- Ecchymosis
The hemorrhage of nasal and oral cavity and ecchymosis are common but intracranial hemorrhage is very rare. We experienced a 53 year old male patient with intracranial hemorrhage due to factor V deficiency. [ncbi.nlm.nih.gov]
Our patient had no ecchymosis, epistaxis, oral bleeding and other bleeding manifestations. He developed only spontaneous intracranial hemorrhage. [kjim.org]
[…] hospitalized patients -Sepsis/severe infection (most common cause) -Cancer -Trauma -Burns -Obstetrical complications: amniotic fluid emboli, HELLP syndrome Other Bleeding from multiple sites -IV insertion sites or incisions; may be widespread -Petechiae, ecchymosis [quizlet.com]
- Inguinal Hernia
Patient was diagnosed with a non-obstructed left inguinal hernia and was scheduled for elective surgical repair. [sci.amegroups.com]
Hematological
- Hemophilia A
Abstract Abstract Hemophilia A (MIM 206700; classic hemophilia) is an X-linked bleeding disorder characterized by a deficiency in the activity of factor VIII, a key component of the coagulation cascade. [ommbid.mhmedical.com]
B: commoness 90% of hemophilia patient have hemophilia A Hemophilia A frequency: Hemophilia B frequency: -1/5000 live male births -1/25,0000 live male births Inherited condition: -X-linked recessive: males are affected, females are usually carriers Hemophilia [quizlet.com]
Factor V deficiency (National Hemophilia Foundation, USA) Source: What are rare clotting factor deficiencies? World Federation of Hemophilia, Montreal, Canada, 2009. NB We provide these links as a service to the haemophilia community. [haemophilia.org.au]
The object of the present paper was to report the bleeding control for extraction of 4 wisdom teeth with congenital factor V deficiency hemophilia and review the literature. [ncbi.nlm.nih.gov]
- Easy Bruising
Isolated factor V deficiency due to mutations in the F5 gene is a rare inherited coagulopathy typically associated with a broad spectrum of bleeding symptoms, ranging from easy bruising, delayed bleeding after haemostatic challenges such as trauma or [ncbi.nlm.nih.gov]
Common symptoms Nosebleeds (epistaxis) Easy bruising Heavy or prolonged menstrual bleeding (menorrhagia) Bleeding in the mouth, particularly after dental surgery or tooth extraction Other reported symptoms Bleeding in the gut (gastrointestinal haemorrhage [haemophilia.ie]
See Bleeding Symptoms of Rare Clotting Factor Deficiencies Common symptoms nosebleeds (epistaxis) easy bruising heavy or prolonged menstrual bleeding (menorrhagia) bleeding in the mouth, particularly after dental surgery or tooth extraction Other reported [wfh.org]
Affected individuals suffer joint and muscle hemorrhage, easy bruising, and prolonged bleeding from wounds. Because platelet function is not affected, blood loss from minor cuts and abrasions is not excessive. [ommbid.mhmedical.com]
- Prolonged Bleeding
He complained of easy bruisability, prolonged bleeding from the mouth after minor trauma and hemarthrosis and flexion contracture of the right knee. His parents are heterozygous (maternal Factor V concentration 52%, paternal 40%). [ncbi.nlm.nih.gov]
Diagnostic methods Diagnosis is based on prolonged prothrombin and activated partial thromboplastin times (PT, aPTT) and on low FV levels measured using a PT based assay. The bleeding time (BT) may be prolonged. [orpha.net]
Affected individuals suffer joint and muscle hemorrhage, easy bruising, and prolonged bleeding from wounds. Because platelet function is not affected, blood loss from minor cuts and abrasions is not excessive. [ommbid.mhmedical.com]
Skin
- Skin Bleeding
Other symptoms can include: Bleeding into the skin Bleeding of the gums Excessive bruising Nosebleeds Prolonged or excessive loss of blood with surgery or trauma Umbilical stump bleeding You will be given fresh blood plasma or fresh frozen plasma infusions [medlineplus.gov]
Other symptoms can include: Bleeding into the skin Bleeding of the gums Excessive bruising Nosebleeds Prolonged or excessive loss of blood with surgery or trauma Umbilical stump bleeding Exams and Tests Tests to detect factor V deficiency include: Factor [mclaren.org]
Factor V deficiency commonly causes nosebleeds; easy bruising; bleeding under the skin; bleeding of the gums; and prolonged or excessive bleeding following surgery, trauma, or childbirth. [ghr.nlm.nih.gov]
Factor X deficiency commonly causes nosebleeds, easy bruising, bleeding under the skin, bleeding of the gums, blood in the urine (hematuria), and prolonged or excessive bleeding following surgery or trauma. [icdlist.com]
Musculoskeletal
- Long Arm
Hemophilia A arises from a variety of mutations within the factor VIII gene, which is located near the telomere of the long arm of the X chromosome. The gene comprises 26 exons and spans 186 kb. [ommbid.mhmedical.com]
Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 5q33” refers to band 33 on the long arm of chromosome 5. [rarediseases.org]
The most common genetic defect is mutation of the F5 gene on the long arm of chromosome 1q23 ( 5 ). FV belongs to the family of multicopper oxidases, and is homologous to coagulation factor VIII. [sci.amegroups.com]
The gene for factor VIII maps at the end of the long arm of chromosome X. There may be various types of mutations: deletions, insertions, missense mutations and nonsense mutations. [flipper.diff.org]
NM_000130 ) is located on the long arm of chromosome 1 at 1q23. [onlinelibrary.wiley.com]
Face, Head & Neck
- Epistaxis
Epistaxis and blood-tinged sputum occurred on day 3. [ncbi.nlm.nih.gov]
In some cases, the bleeding disorder is first noticed post-surgery, typically circumcision although epistaxis and oral bleeding are the most common forms of presentation. [symptoma.com]
Urogenital
- Hematuria
Factor X deficiency commonly causes nosebleeds, easy bruising, bleeding under the skin, bleeding of the gums, blood in the urine (hematuria), and prolonged or excessive bleeding following surgery or trauma. [icdlist.com]
Case report A 36-year-old black male patient was hospitalized in March 2013 after a four-day period of low back pain, bruised hips, macroscopic hematuria, and gingival bleeding. [scielo.br]
[…] platelets. 6 A syndrome of combined factor V and VIII deficiencies has been described in over 60 families in and around the Mediterranean basin. 8 Symptoms (homozygotes) can include hematoma formation, postsurgical and postpartum hemorrhage, menorrhagia, hematuria [labcorp.com]
Hematuria, gastrointestinal bleeding or hemarthrosis occurred in approximately 15 to 20 percent 3 ). Our patient had no ecchymosis, epistaxis, oral bleeding and other bleeding manifestations. He developed only spontaneous intracranial hemorrhage. [kjim.org]
The manifestations classify hemophilia into three types depending on the more or less marked absence of the factor in question: - Moderate: bleeding joints (hemarthrosis) or early muscle bleeding, severe epistaxis, persistent gengivorragia, persistent hematuria [flipper.diff.org]
- Scrotal Pain
Case presentation A 59-year-old gentleman from Pakistan with no significant past medical history presented with sudden onset of severe scrotal pain and enlargement. The patient presented to local emergency room. [sci.amegroups.com]
Workup
In all cases presenting with bleeding a detailed family history inquiring about bleeding disorders and consanguinity is important. FVD should be considered in a full term neonate who presents with subdural or intracerebral bleeding, especially if the baby is born of a consanguineous marriage [10]. Signs of bleeding such as hemarthrosis, epistaxis, oral bleeding as well as pallor should be looked for during physical examination. Coagulation studies must be promptly initiated by the physician or surgeon on noticing the first signs of bleeding. Bleeding time is prolonged in severe cases of FVD and thrombin time is usually normal. Prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) with a normal platelet count are the first indicators of a coagulation disorder and clotting factor assay showing low levels of factor V activity confirms the diagnosis [11]. If acquired FVD is suspected then factor V inhibitor panel is ordered. A mixing test is helpful to differentiate between the inherited and acquired forms of FVD. In this test, a sample of the patient's plasma is mixed with normal plasma and the coagulations study (PT, aPTT, FV) is repeated. The presence of factor V inhibitor is confirmed if the coagulation study does not reveal correction of the abnormalities [12]. Other supportive laboratory tests like complete blood count and hematocrit are also performed to manage the patient.
Radiological investigations are recommended immediately after initiation of coagulation therapy in patients suspected to have CNS hemorrhage or hemarthrosis. Depending on the suspected anatomical location of the bleeding computed tomographic scan, magnetic resonance imaging, angiography or nucleotide bleeding scan can be performed.
Serum
- Partial Thromboplastin Time Prolonged
The D-dimer, prothrombin time, and partial thromboplastin time prolongation persisted from admission until 24 hours after coronary stenting. Epistaxis and blood-tinged sputum occurred on day 3. [ncbi.nlm.nih.gov]
Prothrombin time Normal Normal Activated partial thromboplastin time Prolonged Normal or prolonged Test Haemophilia VWD Platelet count Normal Normal or reduced Bleeding time Normal Normal or prolonged Prothrombin time Normal Normal Activated partial [academic.oup.com]
Biopsy
- Hepatocellular Carcinoma
Keywords Acquired factor V deficiency Transcatheter arterial chemoembolization Hepatocellular carcinoma This is a preview of subscription content, log in to check access. [link.springer.com]
Biosynthesis of coagulation factor V by a human hepatocellular carcinoma cell line. J Clin Invest 1984;73:654–658. 7. Gewirtz AM, Keefer M, Doshi K, Annamalai AE, Chiu HC, Colman RW. Biology of human megakaryocyte factor V. [kjim.org]
Treatment
We describe a case of 2 siblings with Factor V deficiency and menorrhagia who achieved control of bleeding with differing treatments. [ncbi.nlm.nih.gov]
Management and treatment Fresh frozen plasma (FFP) is the only treatment as FV concentrates are not available. In acute cases of severe bleeding, the addition of platelet concentrates may be helpful. [orpha.net]
Treatment Treatment for factor V deficiency is usually only needed for severe bleeds or before surgery. Fresh frozen plasma (FFP) is the usual treatment because there is no concentrate containing only factor V. [wfh.org]
Prognosis
Prognosis Prognosis is good with early diagnosis and adequate treatment. The documents contained in this web site are presented for information purposes only. [orpha.net]
[…] treatment include the development of factor V alloantibodies (inhibitors) Laboratory Prolonged PT / PTT with correction after mixing study with normal pooled plasma Normal thrombin time Specific clot-based factor V assay for diagnosis Prognostic factors Prognosis [pathologyoutlines.com]
[…] on factor V deficiency: National Hemophilia Foundation -- www.hemophilia.org/Bleeding-Disorders/Types-of-Bleeding-Disorders/Other-Factor-Deficiencies/Factor-V NIH/NLM Genetics Home Reference -- ghr.nlm.nih.gov/condition/factor-v-deficiency Outlook (Prognosis [mclaren.org]
Etiology
Etiology Congenital FV deficiency is caused by mutations in the F5 gene (1q23) controlling the production of plasma FV. [orpha.net]
This practical text covers disorders of thrombosis and hemostasis in a logical and sequential manner: etiology, pathophysiology, clinical and laboratory diagnosis, and management. [books.google.ro]
These varices can also be secondary to procedures such as pacemaker insertion or hemodialysis access. 3,4 Hypercoagulability disorders are another etiology, with one case reported in the literature. 2 We describe herein a case of “Downhill” esophageal [revistagastroenterologiamexico.org]
Epidemiology
Summary Epidemiology Prevalence of homozygous forms is estimated at 1/1,000,000. Both sexes are equally affected. Clinical description Congenital FV deficiency can manifest at any age, with the most severe forms manifesting early in life. [orpha.net]
DESIGN AND METHODS: Inconsistencies in results of the epidemiological studies may stem from a failure to identify other variables in factor V which might contribute to an increased risk of thrombosis in selected HR2 carriers. [ncbi.nlm.nih.gov]
[…] factor deficiency or parahemophilia (severe deficiency) Deficiency classified as either: Type I: both reduced antigen level and activity (quantitative defect) Type II: normal or mildly reduced antigen level and reduced activity (qualitative defect) Epidemiology [pathologyoutlines.com]
Pathophysiology
Factor V Deficiency: pathophysiology. Medscape.com. Retrieved from [ [1] ]. [biology-online.org]
This practical text covers disorders of thrombosis and hemostasis in a logical and sequential manner: etiology, pathophysiology, clinical and laboratory diagnosis, and management. [books.google.ro]
[…] described including insertion/deletion, missense, splice site and nonsense mutations (in order of decreasing frequency) Parental consanguinity is often present, especially in countries (Muslim or southern India) where consanguineous marriages are common Pathophysiology [pathologyoutlines.com]
[…] associated with liver disease, factor V inhibitors, myeloproliferative disorders, and intravascular coagulation and fibrinolysis Investigation of prolonged prothrombin time or activated partial thromboplastin time Clinical Information Discusses physiology, pathophysiology [mayomedicallaboratories.com]
Prevention
Response was good and she was then placed on oral contraceptives (OC) which prevented any recurrence. [ncbi.nlm.nih.gov]
References
- Lak M, Sharifian R, Peyvandi F, Mannucci PM. Symptoms of inherited factor V deficiency in 35 Iranian patients. Br J Haematol. 1998;103:1067–1069.
- Duckers C, Simioni P, Rosing J, Castoldi E. Advances in understanding the bleeding diathesis in factor V deficiency. Br J Haematol. 2009;146(1):17–26
- Chingale A, Eisenhut M, Gadiraju A, et al. A neonatal presentation of factor V deficiency: a case report. BMC Pediatr. 2007 Feb 21; 7:8
- Kashyap R, Saxena R, Choudhury V. Rare inherited coagulation disorders in India. Haematologia. 1996;28:13–19.
- Camire RM. A new look at blood coagulation factor V. Curr Opin Hematol. 2011;18:338–342.
- Park YH, Lim JH, Yi HG, et. al. Factor V Deficiency in Korean patients: clinical and laboratory features, treatment and outcome. J Korean Med Sci. 2016 Feb; 31(2): 208-213
- Streiff MB, Ness PM. Acquired FV inhibitors: a needless iatrogenic complication of bovine thrombin exposure. Transfusion. 2002;42(1):18–26.
- Bayani N, Rugina M, Haddad-Vergnes L, Lelong F. High-titer acquired factor V inhibitor responsive to corticosteroids and cyclophosphamide in a patient with two malignant tumors. Am J Hematol. 2002;71(1):33–36
- Ang AL, Kuperan P, Ng CH, Ng HJ. Acquired factor V inhibitor. A problem-based systematic review. Thromb Haemost. 2009;101:852–859.
- Ehrenforth S, Klarmann D, Zabel B, Scharrer I, Kreuz W. Severe factor V deficiency presenting as subdural haematoma in the newborn. Eur J Pediatr. 1998;157:1032–1038.
- Salooja N, Martin P, Khair K, Liesner R, Hann I. Severe factor V deficiency and neonatal intracranial hemorrhage: a case report. Haemophilia. 2000;6:44–46.
- Kamal AH, Tefferi A, Pruthi RK. How to interpret and pursue an abnormal prothrombin time, activated partial thromboplastin time, and bleeding time in adults. Mayo Clin Proc. 2007;82(7):864–873.