Haemophilia (2008), 14, 1164–1169
DOI: 10.1111/j.1365-2516.2008.01785.x
ORIGINAL ARTICLE
Factor V deficiency: a concise review
J. N. HUANG and M. A. KOERPER
UCSF ChildrenÕs Hospital, San Francisco, California
Summary. Factor V (FV; proaccelerin or labile
factor) is the plasma cofactor for the prothrombinase
complex that activates prothrombin to thrombin. FV
deficiency can be caused by mutations in the FV gene
or in genes encoding components of a putative cargo
receptor that transports FV (and factor VIII) from the
endoplasmic reticulum to the Golgi. Because FV is
present in platelet a-granules as well as in plasma,
low FV levels are also seen in disorders of platelet
granules. Additionally, acquired FV deficiencies can
occur in the setting of rheumatologic disorders,
malignancies, and antibiotic use and, most frequently, with the use of topical bovine thrombin.
FV levels have limited correlation with the risk of
bleeding, but overall, FV-deficient patients appear to
have a less severe phenotype than patients with
Introduction
Factor V (FV) was first identified by Owren in
Norway during World War II. His index patient,
Mary, presented at the age of 3 years with prolonged
epistaxis and a loss of vision. She subsequently had
symptoms of easy bruising, prolonged bleeding after
trauma, and menorrhagia. Owren determined that
Mary lacked a previously unrecognized procoagulant, which he designated FV. He named her disorder
parahemophilia [1]. Subsequently, FV was renamed
proaccelerin and was shown to be the same as the
labile factor independently identified by Quick [2,3].
FV is synthesized primarily by the liver, and levels
can decrease when liver synthetic function is
impaired. Plasma FV circulates as a 330-kDa single-chain polypeptide that is the inactive procoagulant. Although most FV is present in plasma,
Correspondence: Marion A. Koerper, MD, Department of Pediatrics, Box 0106, UCSF ChildrenÕs Hospital, San Francisco, CA
94143-0106, USA.
Tel.: 415-475-4901; fax: 415-476-3301;
e-mail: marionkoerper@sbcglobal.net
Accepted after revision 27 April 2008
1164
haemophilia A or B. The most commonly reported
symptoms are bleeding from mucosal surfaces and
postoperative haemorrhage. However, haemarthroses and intramuscular and intracranial haemorrhages
can also occur. Because no FV-specific concentrate is
available, fresh frozen plasma remains the mainstay
of treatment. Antifibrinolytics can also provide
benefit, especially for mucosal bleeding. In refractory
cases, or for patients with inhibitors, prothrombin
complex concentrates, recombinant activated FVIIa,
and platelet transfusions have been successfully used.
Some patients with inhibitors may also require
immunosuppression.
Keywords: bleeding disorder, factor V, inherited
disorder, mild bleeding, rare disorder, severe bleeding
approximately 20% of the circulating FV is found
within platelet a-granules. The source of platelet FV
has not been definitively established, but evidence
indicates that platelets or megakaryocytes can both
endocytose and synthesize FV. Platelet FV is partially
proteolysed and is stored bound to the protein
multimerin in a-granules [reviewed in 4,5].
Kingsley first described the autosomal recessive
inheritance pattern of congenital FV deficiency in
two South African families of Dutch ancestry [2].
More than 30 years passed, however, before the
cDNA was cloned and the amino acid sequence of
the protein was able to be determined [6]. The entire
genomic structure of the FV gene was characterized
in 1992 [7].
Aside from mutations in the FV gene, deficiencies
of FV can also arise because of acquired inhibitors to
FV and defects that affect the storage and processing
of FV. FV-specific inhibitors most often develop after
exposure to preparations of bovine thrombin but
have also been reported in patients who have
underlying rheumatologic conditions or malignancies
or who were being treated with antibiotics (for a
review of acquired FV inhibitors, see [8]). In FV
Quebec, the contents of platelet a-granules, including
2008 The Authors
Journal compilation 2008 Blackwell Publishing Ltd
FACTOR V DEFICIENCY
FV, are abnormally proteolysed [9]. Combined
deficiency of both FV and factor VIII (FVIII) can
result from mutations in either LMAN1 or MCFD2,
genes encoding proteins involved in the processing
and transport of FV and FVIII [10] (see the review of
combined deficiencies of FV + FVIII elsewhere in this
issue).
1165
No precise epidemiologic data exist for congenital
FV deficiency, but its prevalence has been estimated
to be 1 in 1 000 000 persons, and no clear ethnic
predisposition is apparent [4]. In Iran, where a
registry of rare bleeding disorders has been kept since
the early 1970s, 35 FV-deficient patients have been
identified in a population of 65 million as of 1998
[11]. A similar Italian registry (overall population of
55 million) that has been enrolling patients since
1980 lists 35 FV-deficient patients [12]. As ascertainment is almost certainly incomplete, the prevalence is likely higher than what is suggested by the
number of patients in these registries [12].
enhances prothrombin activation by five orders of
magnitude when compared with FXa alone.
FVa is functionally and structurally similar to
FVIIIa. Like FVIII, FV is composed of six domains:
A1, A2, B, A3, C1, and C2. The A and C domains of
the two proteins are approximately 40% homologous, but the B domains are not conserved. As is the
case with FVIII, FV activity is tightly regulated via
site-specific proteolysis. Thrombin, and to a lesser
extent FXa, are primarily responsible for FV activation via proteolytic cleavages at arginine residues in
positions 709, 1018, and 1545. These cleavages
release the B domain and create a dimeric molecule
composed of a 105-kDa heavy chain that contains
the A1 and A2 domains and a 71- to 74-kDa light
chain that contains the A3, C1, and C2 domains.
These two chains are held together by calcium and
hydrophobic interactions. The heavy chain provides
the contacts for both FXa and prothrombin, whereas
the two C domains in the light chain are needed for
the interaction of FVa with the phospholipid surface.
The A3 domain in the light chain is involved in both
FXa and phospholipid interactions. Taken together,
these two FVa chains link FXa to the phospholipid
surface formed by the platelet plug at the site of
injury and enable FXa to efficiently bind and cleave
prothrombin to generate thrombin.
Inactivation of FVa is mediated by activated
protein C (APC), which cleaves FVa at arginine
residues in positions 506, 306, and 679 and at lysine
994. The cleavage at Arg 506 reduces both the
cofactor activity and its affinity for FXa, and the
cleavage at Arg 306 completes the inactivation. Once
cleaved at Arg 506, FVa is converted to FVac (FV
anticoagulant), which interacts with APC and protein S to inactivate FVIIIa. Thus, APC not only turns
off the FVa procoagulant activity but also converts it
to an anticoagulant.
Pathophysiology
Levels associated with severity of bleeding
Materials and methods
The PUBMED (http://www.ncbi.nlm.nih.gov/sites/
entrez) database was searched using the term Ôfactor
V deficiencyÕ. A total of 602 abstracts were read to
determine whether the article referred to FV deficiency, not FV Leiden, or the combined deficiencies
of FV and FVIII; 168 references were saved and read.
The Online Mendelian Inheritance in Man database
entry for Ôfactor V deficiencyÕ (MIM *227400; http://
www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=
227400) was examined. In addition, the FV Mutation Database (http://www.lumc.nl/4010/research/
factor_V_gene.html) was reviewed.
Incidence, racial/ethnic predilection
Role of the clotting factor in coagulation
Activated FV (FVa) is the cofactor in the prothrombinase complex that cleaves and activates prothrombin to thrombin (reviewed in [4,5]; see references
therein). This multicomponent enzyme complex
consists of FVa, calcium, phospholipids, and activated factor X (FXa). FVa increases the concentration of FXa at the membrane surface by acting as a
receptor for FXa and allosterically alters the active
site of FXa to optimize its ability to cleave prothrombin. By stabilizing the complex and increasing
the rate at which FXa cleaves prothrombin, FVa
2008 The Authors
Journal compilation 2008 Blackwell Publishing Ltd
The FV activity level has limited correlation with the
severity of bleeding. Overall, patients with lower
levels are more likely to have bleeding episodes than
those with higher levels. Patients who come to
medical attention are typically symptomatic homozygotes or compound heterozygotes with FV activity
levels less than 5%, although one patient in the FV
mutation database who is thought to be a compound
heterozygote had 26% activity [13,14]. In contrast,
Kingsley found that the heterozygotes in the two
families he studied had levels that ranged from 24%
to 68%, and none had bleeding symptoms [2].
However, the severity of the clinical phenotype
Haemophilia (2008), 14, 1164–1169
1166
J. N. HUANG and M. A. KOERPER
cannot be easily predicted by the activity level.
Patients with identical mutations or activity levels,
including related patients with identical genotypes
and equally low (<1%) FV activities, can vary greatly
in their bleeding symptoms [4,15].
The North American Rare Bleeding Disorders
Registry classified all patients with FV levels less
than 0.2 U mL–1 (<20%) as homozygotes and those
with levels greater than or equal to 0.2 U mL–1
(‡20%) as heterozygotes. The 18 presumed homozygous patients had a median FV activity of <1%
(range, <0.01–0.05 U mL–1). All 18 experienced
spontaneous bleeding events, even those who first
came to attention through preoperative screening or
family history. Furthermore, only patients in the
more severely affected group had complications
(anaemia, target joint development or muscular
contractures, or central nervous system [CNS]
events) from the bleeding episodes. In contrast, only
half of the 19 presumed heterozygous patients
(median FV activity of 35%; range, 21–55 U mL–1)
bled excessively. Unfortunately, the report did not
further subdivide the mild patients to correlate their
bleeding episodes with FV activity [16].
The Iranian registry divided its 35 FV-deficient
patients into three groups: severe (FV £ 1%, n = 16),
moderate (FV 2–5%, n = 13), and mild (FV 6–10%,
n = 6). They found the prevalence of epistaxis (10/16
vs. 5/13 vs. 5/6), haemarthrosis (5/16 vs. 2/13 vs. 2/
6), postprocedural bleeding (7/16 vs. 4/13 vs. 4/6),
and oral mucosal bleeding (9/16 vs. 7/13 vs. 4/6) to
be similar in all three groups. Menorrhagia was
common in both the severe and moderate groups (3/4
vs. 2/6) but could not be evaluated in the mild group
because there were no women of child-bearing age in
that group. Of note, the two cases of CNS haemorrhage and the one case of umbilical stump bleeding
occurred in severely affected individuals. Although
the small number of patients precludes firm conclusions, these data suggest that all three groups are
similarly likely to bleed at common sites such as
mucosal surfaces but that only the more severely
affected patients are at risk for bleeding in less
commonly affected areas such as the CNS [11].
the FV gene itself can result in either a quantitative
(type I) or qualitative (type II) defect. Thus far, the
only qualitative defect that has been described is FV
New Brunswick [4,14].
Types of disorder
Relation to level of deficiency
FV deficiency can be categorized as either congenital
or acquired. The congenital deficiencies arise from
either mutations in the FV gene itself or in genes that
affect the processing or storage of FV. Examples of
the latter are mutations in LMAN1 or MCFD2,
which lead to combined FV and FVIII deficiency, and
FV Quebec, a platelet a-granule defect. Mutations in
In the more severely affected subgroup of the North
American registry, 44% of the bleeding episodes
were in skin and mucosa, 23% in joint and muscle,
19% in the genitourinary tract, 6% in the gastrointestinal tract, and 8% in the CNS. Bleeding
episodes in the mild group consisted of 62% skin
and mucous membrane bleeding and 19% each of
Haemophilia (2008), 14, 1164–1169
Genetics/molecular basis of disorder
The FV gene (GenBank accession no. NM_000130)
is located on the long arm of chromosome 1 at 1q23.
The entire gene spans approximately 80 kb, contains
25 exons, and is transcribed into a nearly 7-kb long
mRNA encoding a 2224-amino acid protein that
contains a 28-amino acid residue signal peptide.
More than 60 mutations associated with FV deficiency (defined as DNA changes that reduce FV
activity or antigen levels by >50%) and more than
700 polymorphisms that do not have a clinical
phenotype have now been identified [17]. At present,
no clear correlation between genotypes and the
clinical phenotypes have been identified [4]. Clinically important nonsense, frameshift, missense, and
splice-site mutations in the FV gene have all been
described. Recently a patient has been described with
a FV level of 9% who has a complete deletion of one
FV allele in association with a 1q deletion on one
chromosome combined with a point mutation in the
other FV allele [18]. In light of the severe phenotype
of the FV knockout mice, which die either in utero at
embryonic day 9–10 or within a few hours of birth
from massive haemorrhage [19], the lack of patients
with complete gene deletions has led to the hypothesis that complete FV deficiency is incompatible
with life [4].
Clinical manifestations
Approximately 200 patients with FV deficiency have
now been described in the literature. Although most
are case reports or small patient series, data are also
available from registries from Iran, Italy, and North
America [11,12,16]. Data from the registries indicate
that, unlike patients with haemophilia A and B, FVdeficient patients are more likely to have skin and
mucocutaneous bleeding rather than haemarthroses.
2008 The Authors
Journal compilation 2008 Blackwell Publishing Ltd
FACTOR V DEFICIENCY
musculoskeletal and genitourinary bleeding events
[16]. In the Iranian cohort, 57% of patients had
epistaxis and oral mucosa bleeding, 50% of the
women had menorrhagia, 43% had postprocedural
or postpartum bleeding, 29% had muscle haematomas, and 26% had haemarthroses. Gastrointestinal,
genitourinary, and CNS bleeding episodes were each
present in 6% of the patients [11].
Timing of presentation
Patients with FV deficiency are thought to present at
an early age. Most patients in the Iranian registry
had bleeding symptoms before the age of 6 years.
Perinatal presentation, though, was not common in
that cohort; there was only one patient with
umbilical stump bleeding and none with cephalohaematoma [11]. Although intracranial haemorrhage
is relatively less common in the patient registry
cohorts, at least seven reports are available in the
English literature of such episodes during the perinatal period [20–26]. However, at the other
extreme, there is also one case report of a patient
with <5% activity who presented at the age of
62 years with an intracranial haemorrhage [27]. The
North American registry did not detail the timing of
presentation, but three-quarters of the more severely
affected (presumed homozygous) group presented
with bleeding episodes, whereas one-fifth were
diagnosed because of family history. In contrast,
most of the patients with mild disease (presumed
heterozygous) in that registry came to attention
because of either family history (44%) or preoperative screening (39%), and only 17% presented with
haemorrhage [16].
Diagnosis
Laboratory diagnosis
Typically, FV deficiency is first suspected in a patient
with bleeding symptoms who has a prolongation of
both the prothrombin time and partial thromboplastin time. If a low FV activity is discovered, then
FV deficiency must be distinguished from consumptive coagulopathy, liver disease, combined FV and
FVIII deficiencies, and an acquired FV inhibitor. The
clinical setting is often sufficient to differentiate FV
deficiency from disseminated intravascular coagulation or liver disease, but testing for d-dimers,
fibrinogen levels, and liver dysfunction or damage
may be useful. A FVIII level is necessary to distinguish isolated FV deficiency from the combined
deficiency of FV and FVIII and may help in distin 2008 The Authors
Journal compilation 2008 Blackwell Publishing Ltd
1167
guishing congenital FV deficiency from that owing to
liver failure, as FVIII levels are often elevated in liver
dysfunction. Importantly, the clinical history is also
useful for distinguishing between congenital FV
deficiency and an acquired inhibitor to FV. Inhibitors
are most often associated with surgical procedures in
which topical bovine thrombin has been used. If an
inhibitor is suspected, its presence should be confirmed with a mixing study and the inhibitor titre
determined with a Bethesda assay.
Molecular diagnosis
Almost all FV mutations identified to date are private
mutations specific to each family. Hence, the entire
gene must be screened for the molecular diagnosis of
FV deficiency to be made. Currently, FV sequencing
is not available as a clinical test. However, sequencing may be available in interested research laboratories (see next).
Prenatal diagnosis
Prenatally obtained FV levels need to be interpreted
with caution, as FV levels appear to be developmentally regulated. At 19–23 weeksÕ gestation, the mean
FV level is 32.1%, whereas it is 48.9% at 30–38
weeks and 89.9% at term [28]. However, prenatal
molecular diagnosis is in theory possible if the
mutations in both parents are known and facilities
are available for sequencing the foetal DNA.
Management
Treatments currently available
Fresh frozen plasma (FFP) is the primary therapeutic
option because no FV-specific concentrate is available. For less severe mucosal bleeding, antifibrinolytic agents such as aminocaproic acid may be
sufficient [16]. Patients with menorrhagia may also
benefit from hormonal therapy.
Most patients are only treated episodically for
bleeding and before invasive procedures [16]. However, case reports are available of severely affected
patients presenting early in life who require routine
prophylactic FFP infusions [21,24,29]. For procedures
and acute haemorrhage, the goal of therapy is
to maintain FV levels above 20%. The half-life of
FV is 12–36 h, and, typically, daily infusions
of 15–20 mL kg–1 of FFP are sufficient [11,12].
However, the frequency and dosing should be adjusted
empirically to achieve haemostasis. Aside from concerns with potential allergic reactions and infection,
Haemophilia (2008), 14, 1164–1169
1168
J. N. HUANG and M. A. KOERPER
treatment with FFP has the additional risk of volume
overload. Plasma exchange has been successfully used
to circumvent this complication [30].
A possible alternative to FFP is recombinant FVIIa
[31], which is currently only approved for use in
patients with FVII deficiency and patients with
inhibitors (see next). However, this product is being
used off-label to treat bleeding as a result of liver
disease and overdoses of warfarin. The mechanism of
action in these settings is unknown but is thought to
be related to the massive infusion of activated FVII.
Thus, it is theoretically possible that this product
may stop bleeding in patients with FV deficiency. The
advantages are the lower volume of infusion and the
lack of risk of viral infections from this recombinant
product. However, the disadvantages are the
unknown mechanism of action and the unknown
dose; overdose might put the patient at risk for
excessive clotting. FEIBA, another FVIII-inhibitor
bypassing agent, is less likely to be of benefit and has
a greater risk of thrombosis than rFVIIa because of
the presence of multiple species of activated clotting
factors. The volume is less than FFP but greater than
rFVIIa, and the viral risk is also less than with FFP
but greater than with rFVIIa, as FEIBA is a plasmaderived product.
Rarely, FV-deficient patients have developed inhibitors to FV after receiving FFP [4,16,23]. For such
patients, activated prothrombin complex concentrate
(FEIBA) and rFVIIa concentrate are options. The
latter has been reported to be effective in patients with
severe FV deficiency [31,32]. Platelet transfusions
may provide a source of FV that is more resistant to
inhibition by the circulating antibodies [33].
At present we are not aware of any individuals
holding treatment IND for FV.
Individuals doing research in pathophysiology,
molecular basis, registries
1. Rodney Camire, PhD, ChildrenÕs Hospital of
Philadelphia, web page: http://www.med.upenn.
edu/apps/faculty/index.php/g5165284/p32208.
2. Donna DiMichele, MD, Weill Cornell School of
Medicine, web page: http://www.cornellphysicians.com/ddimichele/index.html.
3. David Ginsburg, MD, University of Michigan and
Howard Hughes Medical Institute, web page: http:/
www.hg.med.umich.edu/faculty_bio.php?f=11.
4. Kenneth Mann, PhD, University of Vermont, web
page: http://www.uvm.edu/cmb/faculty_details.php?
people_id=74.
5. Flora Peyvandi, MD, University of Milan
Hemophilia Center, e-mail: flora.peyvandi@
unimi.it.
6. Amy Shapiro, MD, Indiana Hemophilia and
Thrombosis Center, e-mail: ashapiro@ihtc.org.
7. Hans Vos, PhD, Leiden University Medical Center, e-mail: H.L.Vos@lumc.nl.
8. James Zehnder, MD, Stanford University Medical
Center, web page: http://med.stanford.edu/profiles/James_Zehnder/.
Disclosures
M. A. Koerper has acted as a paid consultant to
Baxter and Novo Nordisk pharmaceutical companies. J. N. Huang has received funding from Baxter
for research unrelated to the present review and has
acted as a paid consultant to Novo Nordisk.
Prognosis
Overall, the prognosis for most FV-deficient patients is good. None of the patients in the North
American Registry, including those with FV activity
<1%, required prophylaxis [16], and the Iranian
cohort appeared to have a more benign course than
patients with haemophilia A and B with comparable
factor activity levels [11]. The most severe cases
appear to be patients who present in the perinatal
period with intracranial haemorrhage [21,23,24].
OwrenÕs index case, Mary, died in 2002 at the age
of 88 years [3].
Individuals with interest in area
Individuals holding Investigational New Drug (IND)
for treatment
Haemophilia (2008), 14, 1164–1169
References
1 Owren PA. Parahaemophilia: haemorrhagic diathesis
due to absence of a previously unknown clotting factor.
Lancet 1947; 249: 446–8.
2 Kingsley CS. Familial factor V deficiency: the pattern of
heredity. Q J Med 1954; 23: 323–9.
3 Stormorken H. The discovery of factor V: a tricky
clotting factor. J Thromb Haemost 2003; 1: 206–13.
4 Kalafatis M. Coagulation factor V: a plethora of anticoagulant molecules. Curr Opin Hematol 2005; 12:
141–8.
5 Asselta R, Tenchini ML, Duga S. Inherited defects of
coagulation factor V: the hemorrhagic side. J Thromb
Haemost 2006; 4: 26–34.
6 Jenny RJ, Pittman DD, Toole JJ et al. Complete cDNA
and derived amino acid sequence of human factor V.
Proc Natl Acad Sci USA 1987; 84: 4846–50.
2008 The Authors
Journal compilation 2008 Blackwell Publishing Ltd
FACTOR V DEFICIENCY
7 Cripe LD, Moore KD, Kane WH. Structure of the gene
for human coagulation factor V. Biochemistry 1992;
31: 3777–85.
8 Streiff MB, Ness PM. Acquired FV inhibitors: a needless iatrogenic complication of bovine thrombin exposure. Transfusion 2002; 42: 18–26.
9 Janeway CM, Rivard GE, Tracy PB, Mann KG. Factor
V Quebec revisited. Blood 1996; 87: 3571–8.
10 Zhang B, McGee B, Yamaoka JS et al. Combined
deficiency of factor V and factor VIII is due to mutations in either LMAN1 or MCFD2. Blood 2006; 107:
1903–7.
11 Lak M, Sharifian R, Peyvandi F, Mannucci PM.
Symptoms of inherited factor V deficiency in 35 Iranian
patients. Br J Haematol 1998; 103: 1067–9.
12 Mannucci PM, Duga S, Peyvandi F. Recessively
inherited coagulation disorders. Blood 2004; 104:
1243–52.
13 FactorV-gene-mutations-table-27sept2006. DOC: http://
www.lumc.nl/4010/research/factor_V_gene.html.
14 Murray JM, Rand MD, Egan JO, Murphy S, Kim HC,
Mann KG. Factor V New Brunswick: Ala221-to-Val
substitution results in reduced cofactor activity. Blood
1995; 86: 1820–7.
15 Castoldi E, Lunghi B, Mingozzi F et al. A missense
mutation (Y1702C) in the coagulation factor V gene is
a frequent cause of factor V deficiency in the Italian
population. Haematologica 2001; 86: 629–33.
16 Acharya SS, Coughlin A, DiMichele DM. Rare Bleeding Disorder Registry: deficiencies of factors II, V, VII,
X, XIII, fibrinogen and dysfibrinogenemias. J Thromb
Haemost 2004; 2: 248–56.
17 Vos HL. An online database of mutations and polymorphisms in and around the coagulation factor V
gene. J Thromb Haemost 2007; 5: 185–8.
18 Caudill JS, Sood R, Zehnder JL, Pruthi PK, Steensma
DP. Severe coagulation factor V deficiency associated
with an interstitial deletion of chromosome 1q.
J Thromb Haemost 2007; 5: 626–8.
19 Cui J, OÕShea KS, Purkayastha A, Saunders TL, Ginsburg D. Fatal haemorrhage and incomplete block to
embryogenesis in mice lacking coagulation factor V.
Nature 1996; 384: 66–8.
20 Ajzner EE, Balogh I, Szabó T, Marosi A, Haramura G,
Muszbek L. Severe coagulation factor V deficiency
caused by 2 novel frameshift mutations: 2952delT in
exon 13 and 5493insG in exon 16 of factor 5 gene.
Blood 2002; 99: 702–5.
21 Chingale A, Eisenhut M, Gadiraju A, Liesner R.
A neonatal presentation of factor V deficiency: a case
report. BMC Pediatr 2007; 7: 8.
22 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.
23 Lee WS, Chong LA, Begum S, Abdullah WA, Koh MT,
Lim EJ. Factor V inhibitor in neonatal intracranial
2008 The Authors
Journal compilation 2008 Blackwell Publishing Ltd
24
25
26
27
28
29
30
31
32
33
1169
hemorrhage secondary to severe congenital factor V
deficiency. J Pediatr Hematol Oncol 2001; 23: 244–6.
Salooja N, Martin P, Khair K, Liesner R, Hann I.
Severe factor V deficiency and neonatal intracranial
haemorrhage: a case report. Haemophilia 2000; 6:
44–6.
Totan M, Albayrak D. Intracranial haemorrhage
due to factor V deficiency. Acta Paediatr 1999; 88:
342–3.
Whitelaw A, Haines ME, Bolsover W, Harris E. Factor
V deficiency and antenatal intraventricular haemorrhage. Arch Dis Child 1984; 59: 997–9.
Yoneoka Y, Ozawa T, Saitoh A, Arai H. Emergency
evacuation of expanding intracerebral haemorrhage in
parahaemophilia (coagulation factor V deficiency).
Acta Neurochir 1999; 141: 667–8.
Reverdiau-Moalic P, Delahousse B, Body G, Bardos P,
Leroy J, Gruel Y. Evolution of blood coagulation
activators and inhibitors in the healthy human fetus.
Blood 1996; 88: 900–6.
Schrijver I, Koerper MA, Jones CD, Zehnder JL.
Homozygous factor V splice site mutation associated with severe factor V deficiency. Blood 2002; 99:
3063–5.
Baron BW, Mittendorf R, Baron JM. Presurgical plasma exchange for severe factor V deficiency. J Clin
Apheresis 2001; 16: 29–30.
González-Boullosa R, Ocampo-Martı́nez R, AlárconMartin MJ, Suarez-Rodrı́guez M, Domı́nguez-Viguera
L, González-Fajo G. The use of activated recombinant
coagulation factor VII during haemarthroses and
synovectomy in a patient with congenital severe
factor V deficiency. Haemophilia 2005; 11: 167–
70.
Petros S, Fischer J, Mössner J, Schiefke I, Teich N.
Treatment of massive cecal bleeding in a 28-year-old
patient with homozygous factor V deficiency with
activated factor VII. Z Gastroenterol 2008; 46:
271–3.
Chediak J, Ashenhurst JB, Garlick I, Desser RK.
Successful management of bleeding in a patient with
factor V inhibitor by platelet transfusions. Blood 1980;
56: 835–41.
Links to organizations – professional, lay
1. National Hemophilia Foundation, http://www.
hemophilia.org.
2. International Society for Thrombosis and Hemostasis, http://www.med.unc.edu/isth/welcome.html.
3. World Federation of Hemophilia, http://www.
wfh.org/index.asp?lang=EN.
4. Rare Bleeding Disorder Database, http://www.
rbdd.org/.
5. National Organization of Rare Disorders, http://
www.rarediseases.org.
Haemophilia (2008), 14, 1164–1169