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].

• 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]

• 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]

• Inguinal Hernia

  Patient was diagnosed with a non-obstructed left inguinal hernia and was scheduled for elective surgical repair. [sci.amegroups.com]

• 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]

  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]

• 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]

  Excessive and prolonged bleeding during or following surgery, delivery or trauma are frequent. Women may present with menorrhagia. In severe forms of the disease, there can be a risk of intracranial, pulmonary or gastrointestinal bleedings. [orpha.net]

  bleeding time Diagnosis factor V assay (showing decreased activity) activated partial thromboplastin time (aPTT) test (prolonged) prothrombin time (PT) test (prolonged) thrombin clotting time (TCT) test Treatment Fresh frozen plasma infusions (FFP). [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]

• 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.

1. 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.
2. 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
3. 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
4. Kashyap R, Saxena R, Choudhury V. Rare inherited coagulation disorders in India. Haematologia. 1996;28:13–19.
5. Camire RM. A new look at blood coagulation factor V. Curr Opin Hematol. 2011;18:338–342.
6. 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
7. Streiff MB, Ness PM. Acquired FV inhibitors: a needless iatrogenic complication of bovine thrombin exposure. Transfusion. 2002;42(1):18–26.
8. 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
9. Ang AL, Kuperan P, Ng CH, Ng HJ. Acquired factor V inhibitor. A problem-based systematic review. Thromb Haemost. 2009;101:852–859.
10. 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.
11. 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.
12. 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.