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AUTHOR AND EDITOR INFORMATION
Section 1 of 11  
Author: Olga Kozyreva, MD, Fellow, Department of Hematology-Oncology, Tufts University School of Medicine
Coauthor(s):
Sarah K May, MD, Consulting Staff, Department of Hematology-Oncology, Caritas Carney Hospital, Commonwealth Hematology-Oncology PC;
Karl J D'Silva, MD, Fellow in Hematology/Oncology, Department of Internal Medicine, Breslin Cancer Center, Michigan State University
Editors: Paul Schick, MD, Emeritus Professor, Department of Internal Medicine, Thomas Jefferson University Medical College; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Ronald A Sacher, MD, Director of the Hoxworth Blood Center, Professor, Departments of Internal Medicine and Pathology, University of Cincinnati Medical Center; Rebecca J Schmidt, DO, FACP, FASN, Clinical Associate Professor of Medicine, West Virginia School of Osteopathic Medicine; Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine; Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Author and Editor Disclosure
Synonyms and related keywords:
factor V deficiency, FV, Owren disease, Owren's disease, accelerator globulin deficiency, hereditary factor V deficiency disease, proaccelerin deficiency, AC globulin deficiency, hereditary hypoproaccelerinemia, labile factor deficiency, hemophilia, parahemophilia, anticoagulation, coagulopathy anticoagulant, coagulation factors, hemostatic pathway, haemostatic pathway, coagulation pathway, acquired factor V inhibitor, von Willebrand factor, von Willebrand's factor, vWF, von Willebrand disease, von Willebrand's disease, vWD, coagulation factor V, thrombin, prothrombinase complex, platelet activation, platelet factor V, prothrombinase function, prothrombin time, PT, activated partial thromboplastin time, aPTT, partial thromboplastin time, PTT, factor IX, FIX, factor VIII, FVIII, bleeding disorder
Background
Isolated factor V deficiency is a rare inherited coagulopathy. Factor V deficiency is also known as Owren disease or parahemophilia. Dr Paul Owren identified this defect in Norway in 1943. Using relatively primitive technology, he was able to deduce the existence of a fifth component required for fibrin formation, which he named factor V, thus beginning the era of Roman numerology for coagulation factors. Dr Owren's work defined factor V as the activity in normal plasma that corrected the prothrombin time (PT) of the plasma in a patient with factor V deficiency. Factor V deficiency has been called parahemophilia since hemarthrosis can occur with severe deficiencies and with increased bleeding time.
Pathophysiology
Factor V is an essential component in the blood coagulation cascade. Factor V is synthesized in the liver and possibly in megakaryocytes. Factor V circulates in an inactive form. During coagulation, factor V is converted to the active cofactor, factor Va, via limited proteolysis by the serine protease a-thrombin. Factor Va and activated factor Xa form the prothrombinase complex. The prothrombinase complex is responsible for the rapid conversion of the zymogen prothrombin to the active serine protease a-thrombin. Factor V deficiency is a rare condition and is associated with an abnormal factor V plasma level. Acquired inhibitor against coagulation factor V is a rare clinical condition with hemorrhagic complications of varying severity. The addition of normal plasma cannot correct the prolonged PT and activated partial thromboplastin time (aPTT). Factor V inhibitors can occur after surgery, childbirth, autoimmune diseases, and with certain neoplasms. Thrombin cleaves fibrinogen to form fibrin, leading to the ultimate step in coagulation, the formation of a fibrin clot. Factor V Leiden is a completely different inherited disorder in which factor V is mutated in a specific gene, leading to hypercoagulable status. The mutation is very common, occurring in 5% of the US population. Factor V activity levels in patients with factor V Leiden are normal.
Frequency
International
Only 150 cases of congenital factor V deficiency have been reported worldwide since 1943. Homozygous factor V deficiency is rare, occurring in approximately 1 per million population.
Mortality/Morbidity
The severity of factor V deficiency varies from bruising to lethal hemorrhage.
Race
No apparent racial predilection for factor V deficiency exists.
Sex
Factor V deficiency affects males and females with equal frequency.
Age
Factor V deficiency affects all ages. The age at presentation indirectly varies with the severity of disease.
History
- Symptoms 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
- Intracerebral hemorrhages
- Pulmonary hemorrhage
- The severity of bleeding symptoms is only partially related to the degree of factor V deficiency in plasma from immeasurable plasma levels.
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. 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.
Platelet Disorders
von Willebrand Disease
Other Problems to be Considered
All other coagulation disorders
Lab Studies
- The presence of a mild prolongation of PT and aPTT may be the first indication of factor V deficiency. Use specific factor V activity and antigen assays for confirmation.
- Bleeding time can be prolonged in severe cases.
- aPTT - Prolonged
- PT - Prolonged
- Thrombin time - Normal
- Stypven time (Russell viper venom time [RVVT]) - Prolonged
- Mixing study - Correction of PT or partial thromboplastin time (PTT) with the mixing of equal amounts of normal and patient plasma
- Factor V inhibitor panel
- Factor V antigen - Quantifies factor V levels but does not test for functional factor V. Some patients have factor V deficiency caused by dysfunctional factor V while the level of factor V protein, estimated by factor V antigen levels, is normal. However, this test is not routinely ordered to diagnose factor V deficiency.
Imaging Studies
- Early and aggressive imaging studies are indicated, even with low suspicion for hemorrhage, after coagulation therapy is initiated.
- Head CT scan (noncontrast): Assess spontaneous or traumatic hemorrhage.
- Body CT scan
- Perform with or without intravenous contrast, oral contrast, or both.
- Perform as indicated by clinical suspicion and anatomical location.
- Assess spontaneous or traumatic hemorrhage.
- Head and spinal column MRI: Further assess spontaneous or traumatic hemorrhage.
- Radiograph for joint assessment: This is of limited value in an acute setting of hemarthrosis. Chronic degenerative joint disease is often present.
- Special studies: Perform angiography and nucleotide bleeding scan as clinically indicated.
Medical Care
No concentrates of factor V are commercially available, so fresh plasma or fresh frozen plasma (FFP) infusions are used to correct the deficiency temporarily and should be given daily during a bleeding episode. The loading dose of FFP is 15-20 mL/kg and then 3-6 mL/kg daily. Subsequent dosages depend on monitoring the factor V level by obtaining peak and trough factor V level assays. The half-life ranges from 24-36 hours, with the aim being a factor V level of 25%. Fluid overload and viral transmission may be a complication of plasma therapy.
- Preoperative and postoperative care when patients with factor V deficiency require surgery include the following:
- In pregnant women, considerable bleeding can occur at the time of delivery; however, the administration of FFP can properly control bleeding, with excellent fetal outcome.
- The safe level of factor V for adequate surgical hemostasis is 25% of the activity of factor V in normal control plasma.
- Postoperatively, FFP should be administered for 3-10 days, with careful observation of wound bleeding.
- Tooth extraction in a patient with factor V hereditary deficiency is safely performed with both supplementation of FFP and application of local hemostasis.
- Patients with factor V deficiency can be given oral contraceptives to decrease menometrorrhagias, thereby improving anemia and decreasing transfusion needs.
- The optimal treatment of patients with factor V inhibitors is uncertain. Fu et al were successful in using a combination of factor replacement, chemotherapy, and plasmapheresis in a patient with spontaneous, life-threatening intracranial bleeding caused by a factor V inhibitor. The patient deteriorated after initial treatment with FFP and platelet transfusions. He was subsequently treated with a combination of plasma exchange and chemotherapy, and he completely recovered.1 The experience of Fu et al shows that combinations of therapies may be needed in patients with serious hemorrhage caused by acquired factor V deficiency.
Consultations
Consultations may include hematologists, blood bank specialists, pathologists, and others as indicated based on hemorrhagic complications.
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Drug Category: Blood products
Plasma is the fluid compartment of blood that contains the soluble clotting factors.
| Drug Name | Fresh frozen plasma |
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| Description | For use in patients with blood product deficiencies. |
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| Adult Dose | Dose depends on severity of coagulopathy
Initially, 2 U are administered IV , then more is administered as needed to control bleeding; monitor at peak and trough using a factor V assay to fine-tune the administration of FFP |
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| Pediatric Dose | Administer as in adults; administer 2 U IV initially; further administration depends on severity of coagulopathy |
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| Contraindications | Documented hypersensitivity |
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| Interactions | None reported |
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| Pregnancy | A - Fetal risk not revealed in controlled studies in humans
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| Precautions | Viral contamination and infection are possible but unlikely because of prescreening; ineffective in patients with factor V inhibitors; may induce an anamnestic response; fluid overload can occur with multiple infusion and should be borne in mind |
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Further Outpatient Care
Ideally, a hematologist who has experience in the diagnosis and management of inherited bleeding disorders should monitor individuals with severe factor V deficiency.
Deterrence/Prevention
- Factor V deficiency is an inherited disorder; no known means of prevention exists.
- Immunize patients who may require plasma-derived coagulation factor concentrates with hepatitis B vaccines.
Complications
Complications of factor V deficiency are directly related to the site of bleeding (eg, hemarthrosis, intracranial hemorrhage, uncontrolled postoperative bleeding).
Prognosis
The prognosis of factor V deficiency is good with diagnosis and proper treatment.
Patient Education
- Give patients and families instruction and educational materials to enable them to understand factor V deficiency.
- For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center. Also, see eMedicine's patient education article Hemophilia.
Medical/Legal Pitfalls
- Because factor V deficiency is treatable, albeit rare, consider it in the differential diagnosis when confronted with a bleeding patient. As always, when confronted with a potential coagulopathy, physicians must respond quickly with their evaluation and management to avoid catastrophic hemorrhage.
- Child abuse and congenital coagulation disorders may present with similar neurologic symptoms and radiologic findings. In these patients, coagulation tests are mandatory. If the results of the tests are abnormal, enable early deficit substitution and prevent inappropriate suspicion or accusation of caretakers.
Special Concerns
- Factor V deficiency must be differentiated from combined deficiency of factors V and VIII, which is an entirely separate disorder observed in a number of populations around the world. Family history and a very abnormal aPTT may suggest factor V-VIII disorder; factor VIII and factor V assay results will range from 15-20%, which would help in the diagnosis of this complication.
| Media file 2:
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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Media type: Graph
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Factor V excerpt Article Last Updated: Dec 18, 2007
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