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].

• Gangrene

  Notably, only six patients on factor V inhibitors have presented with thrombotic manifestations that include limb gangrene [5], multiple cerebral infarctions [6], deep vein thromboli [7–9], and upper extremity thrombi [10]. [journals.lww.com]

• Turkish

  Aim of this study was the identification and the molecular characterization of genetic defects underlying severe FV deficiency in a 7-month-old Turkish patient. [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]

  Thrombin cleaves fibrinogen to form fibrin, leading to the ultimate step in coagulation, the formation of a fibrin clot. image by : leememorial.org Signs and Symptoms Nosebleeds Bleeding of the gums Easy bruising Excessive menstrual bleeding (menorrhagia [rnpedia.com]

  Signs and Symptoms Nosebleeds Bleeding of the gums Easy bruising Excessive menstrual bleeding (menorrhagia) Umbilical stump bleeding Excessive bleeding following injury Excessive bleeding following surgery Excessive bleeding after giving birth Prolonged [nursingcrib.com]

  Signs and symptoms, from most to least common, include: Nosebleeds Easy bruising Heavy or prolonged menstrual bleeding (menorrhagia) Bleeding in the mouth, particularly after dental surgery or tooth extraction Inability to straighten or bend a joint normally [rarebleedingdisorders.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]

  Umbilical stump bleeding Excessive bleeding following injury Excessive bleeding following surgery Excessive bleeding after giving birth Prolonged bleeding time Diagnosis factor V assay (showing decreased activity) activated partial thromboplastin time [rnpedia.com]

• Exertional Dyspnea

  A 73-year-old woman presented with chest discomfort and exertional dyspnea. Coronary stenting was performed successfully using DES stents. [ncbi.nlm.nih.gov]

• Hepatosplenomegaly

  Autopsy revealed hepatosplenomegaly and massive deposits of AL amyloid in the liver, spleen, heart and other parenchymal organs. [ncbi.nlm.nih.gov]

• Flexion Contracture

  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]

• Bleeding from the Nipple

  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]

• Nipple Discharge

  Sigalas J, Roilides E, Tsanakas J, Karpouzas J: Bloody nipple discharge in infants. J Pediatr 1985;107:484. [karger.com]

• Bloody Nipple Discharge

  Sigalas J, Roilides E, Tsanakas J, Karpouzas J: Bloody nipple discharge in infants. J Pediatr 1985;107:484. [karger.com]

• Polyneuropathy

  A 57 year-old woman presented with spontaneous right knee haemarthrosis in association with bilateral symmetrical polyneuropathy and proteinuria. [ncbi.nlm.nih.gov]

• Hemospermia

  A 50-year-old man who had no previous hemorrhagic diathesis was referred to our hospital because of recurrent epistaxis, gingival bleeding and hemospermia. [ncbi.nlm.nih.gov]

• 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]

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.

• 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]

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]

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]

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]

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]

[…] 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]

Factor V Deficiency: pathophysiology. Medscape.com. Retrieved from [ [1] ]. [biology-online.org]

[…] 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]

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]

[…] 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]

Response was good and she was then placed on oral contraceptives (OC) which prevented any recurrence. [ncbi.nlm.nih.gov]

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