Haemophilia (2008), 14, 1176–1182
DOI: 10.1111/j.1365-2516.2008.01856.x
ORIGINAL ARTICLE
Diagnosis and treatment of inherited factor X deficiency
D. L. BROWN* and P. A. KOUIDES *Department of Pediatrics, University of Texas Health Science Center in Houston, Houston, TX; and Mary M. Gooley
Hemophilia Treatment Center and the Rochester General Hospital, Rochester, NY, USA
Summary. Factor X is a vitamin K-dependent, liverproduced serine protease that serves a pivotal role in
coagulation as the first enzyme in the common
pathway to fibrin formation. Inherited factor X
deficiency is a rare autosomal recessive bleeding
disorder that is estimated to occur in 1:1 000 000
individuals up to 1:500 carriers. Several international
registries of FX-deficient patients have greatly
expanded the knowledge of clinical phenotype. A
proposed classification of severity is based on FX:C
activity measurements: an FX:C measurement <1%
is severe, an FX:C measurement of 1–5% is moderate
and an FX:C measurement of 6–10% is mild. Levels
above 20% are infrequently associated with bleeding
and heterozygotes are usually asymptomatic. Among
patients with FX:C levels <10%, unlike moderate or severe haemophilia A and B, mucocutaneous
Introduction
Morawitz may have been the first to isolate factor
(F)X in 1905 when he identified a factor named
ÔthromboplastinÕ that interacted with ÔthrombogenÕ
to form thrombin [1]. For many years, the terms
FVII, proconvertin and serum prothrombin conversion accelerator were used to describe a relatively
heat-stable factor adsorbable by barium sulphate and
reduced in dicoumarol plasma, which probably
included FX. In 1955, Duckert reported a factor
deficiency distinct from FVII and FIX in patients
receiving coumarins and named the new factor, FX
[2]. Inherited FX deficiency was subsequently identified by two independent groups. In 1956, Telfer
Correspondence: Deborah L. Brown, MD, University of Texas
Health Science Center in Houston, 6655 Travis St, Suite 400,
Houston, TX 77006, USA.
Tel.: +1 713 500 8360; fax: +1 713 500 8364;
e-mail: deborah.brown@uth.tmc.edu
Accepted after revision 21 July 2008
1176
bleeding symptoms such as epistaxis and menorrhagia occur in the majority. In addition, patients with
moderate–severe deficiency may have symptoms
similar to that of haemophilia A and B, including
haemarthrosis, intracranial haemorrhage, and gastrointestinal bleeding. Genotype characterization
may offer important clues about clinical prognosis.
More than 80 mutations of the F10 gene have been
identified, most of which are missense mutations.
There is no specific FX replacement product yet
readily available, but fresh frozen plasma and prothrombin complex concentrates can be used for
treatment of bleeding symptoms and preparation for
surgery.
Keywords: deficiency, diagnosis, factor X, gene,
haemophilia, treatment
et al. [3] described a 22-year-old woman named Miss
Prower with a bleeding diathesis who had an
abnormal thromboplastin generation test result and
a prolonged prothrombin time that was corrected
with the addition of plasma from two patients taking
coumarin analogues. In 1957, Hougie et al. [4]
described a 36-year-old man named Mr Stuart
thought to have FVII deficiency until it was found
that his plasma could correct the prolonged
prothrombin time of another FVII-deficient patient.
FX became known as the Stuart-Prower factor
until it was given its official nomenclature of FX in
1962.
Materials and methods
A MEDLINE search from 1965 to July 2007 was
performed using the search heading Ôfactor X deficiencyÕ. Only studies in English were selected. Eightytwo key publications were selected for review and an
additional 27 publications were identified through
citation cross-checking.
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Journal compilation 2008 Blackwell Publishing Ltd
FACTOR X DEFICIENCY
Incidence, racial/ethnic predilection
Severe FX deficiency (homozygous) is a rare bleeding
disorder that is estimated to have a worldwide
incidence of 1:500 000–1 000 000 [5], although it
is more common in populations in which consanguineous marriage is common, such as Iran, where
the frequency is reported to be 1:200 000 [6]. FX
deficiency accounts for 1.3% of patients with inherited coagulation deficiencies in Iran, 0.4% in Italy
and 0.5% in the UK [5]. The prevalence of heterozygous FX deficiency (carrier state) may be as high as
1:500 [7].
Pathophysiology
Role of the clotting factor in coagulation. Factor X
synthesis occurs in the liver and similar to other
vitamin K-dependent proteins requires post-translational carboxylation of 11 glutamic acid (Gla) residues. The Gla residues allow Ca++-dependent binding
of FX to negatively charged phospholipid membranes.
Glycosylation of 2 Asn residues and B-hydroxylation
must occur before FX can be activated. The mature 2chain form of FX consists of a light chain of 139 amino
acids and heavy chain linked by a disulphide bond.
The light chain contains the Gla domain and two
epidermal growth factor domains; the heavy chain
contains the catalytic serine protease domain. The 59kDa 2-chain protein circulates in the plasma at a
concentration of 10 lg mL)1.
The active form (FXa) is a catalytic serine protease
that is produced when the zymogen is cleaved in the
heavy chain, releasing the 52-residue activation
peptide that contains the His236, Asp228 and
Ser379 catalytic site. Activation can occur through
the extrinsic or intrinsic pathway and is considered
to be the first step in the Ôcommon pathwayÕ to fibrin
conversion. Activation occurs through the extrinsic
pathway via tissue factor:FVIIa complex with calcium ions on a phospholipid surface. Intrinsic pathway activation occurs most efficiently in the ÔtenaseÕ
complex, which contains the serine protease FIXa
and its cofactor FVIIIa in the presence of calcium
ions on a phospholipid surface.
Factor Xa is the most important activator of
prothrombin, cleaving prothrombin to generate
thrombin in complex with FVa, Ca++ and phospholipids. FXa can also activate FV and FVIII and
hydrolyses FVII to FVIIa, completing a FVII–FX
feedback loop. FXa is inactivated by antithrombin,
which forms a complex that is rapidly cleared from
the circulation. FXa also binds to tissue factor
pathway inhibitor to form a quaternary complex
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with tissue factor: FVIIa, blocking the extrinsic
pathway to thrombin generation. FXa is also inactivated by protein Z-dependent protease inhibitor, a
serine protease inhibitor (serpin). The affinity of this
protein for factor Xa is increased 1000-fold by the
presence of protein Z [8]. Defects in protein Z lead to
increased FXa activity and a possible increased risk
of thrombosis [9] .
Levels associated with severity of bleeding. Factor X
deficiency produces a variable bleeding tendency, but
patients with severe FX deficiency tend to have the
most severe symptoms of the rare coagulation disorders, similar to those of FVIII and FIX deficiency. On
the basis of the plasma levels of FX coagulant activity
(FX:C) measured with a prothrombin time-based
assay using rabbit thromboplastin and FX-deficient
plasma, patients have been classified into three
groups: severe (FX:C, <1%), moderate (FX:C, 1%–
5%) and mild (FX:C, 6%–10%) [10]. Severe clinical
symptoms, such as intracranial haemorrhage (ICH),
gastrointestinal bleeding and haemarthrosis, are
uncommon in patients with FX:C levels >2%. In the
Greifswald Factor X Deficiency Registry, the median
level of FX:C in symptomatic patients was 13.3%.
Patients genetically proven to be heterozygotes are
usually asymptomatic but may have minor mucocutaneous bleeding symptoms.
Types of disorder if more than one. The classification
of FX deficiency is based on the results of both
immunological and functional laboratory assays. In
type I deficiency, both functional activity and antigen
level are proportionally decreased, as proved to be
the case in the original patient (Mr Stuart). In type II
deficiency, represented by Miss Prower, a dysfunctional FX protein results in a near-normal antigenic
level, whereas the FX activity is reduced.
Genetics/molecular basis of disorder
The FX gene (F10) is 22 kb long and is located at
13q34-ter, 2.8 kb downstream of the F7 gene. The
coding sequence is homologous to the other vitamin
K-dependent proteins and is divided into eight exons,
each of which encodes a specific domain within the
protein: exon 1 encodes the signal peptide, exon 2
encodes the propeptide and Gla domain, exon 3
encodes the aromatic amino acid stack domain, exons
4 and 5 each code for the epidermal growth factor-like
regions, exon 6 encodes the activation domain, and
exons 7 and 8 encode the catalytic domain. The F10
cDNA consists of 1474 bp coding for the pre-proleader sequence, the 488 amino acid mature protein, a
Haemophilia (2008), 14, 1176–1182
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D. L. BROWN and P. A. KOUIDES
short 3¢ untranslated region and the poly (A) tail. No
TATA box has been identified in the 5¢ region,
allowing for multiple transcription initiation sites.
Severe (homozygous) FX deficiency is inherited as
an autosomal recessive disorder and is more prevalent in populations in which consanguineous
marriage is common. The earliest reported molecular
abnormality affecting the F10 gene was reported by
Scambler and Williamson in 1985, who described a
female who was monosomic for 13q34 and was
deficient in both FVII and FX [11]. Her brother was
trisomic for 13q34 and had increased levels of both
FVII and FX.
The FX knockout mouse with an 18-kb deletion of
the F10 gene died of bleeding complications in utero
or within the first 30 days of life [12], suggesting that
a complete absence of FX is incompatible with life,
perhaps explaining why severe FX deficiency is one of
the rarest of the known bleeding disorders. Most of
the F10 gene mutations responsible for human
disease are single base pair substitutions [5]. To
date, more than 80 different mutations of the F10
gene have been identified among individuals with FX
deficiency [4,5,13,14]. Most of these mutations are
private (i.e., unique to a particular patient or family).
Among 102 patients with confirmed F10 gene mutations in the Greifswald Factor X Deficiency Registry,
29 different mutations from 45 families were identified. Twenty-six of these were missense mutations,
two were microdeletions and one was a splice site
mutation. The most common sites of mutations have
been localized to the Gla domain (exon 2) and the
catalytic site (exons 7 and 8) [15] (Fig. 1).
Clinical manifestations
Related to level of deficiency
Clinical information about FX deficiency has improved as several important registries have been
developed, including the Greifswald Registry of Factor X Deficiency in Europe and Latin America [14],
the Rare Bleeding Disorder Registry in North America
[16] and population registries of inherited bleeding
disorders from the UK Hemophilia Centre Directors
Organization [17] and the Hemophilia Surveillance
System in Iran [6]. The bleeding symptoms reported
from these registries are summarized in Table 1.
In contrast to FVIII and FIX deficiency, the most
frequent bleeding symptoms are mucocutaneous:
easy bruising, epistaxis and gum bleeding. Menorrhagia has been reported in 10–75% of women with
severe FX deficiency [9,14,18]. FX levels increase
in pregnancy of non-affected women [19], but FXdeficient women have been described to have uterine
bleeding, foetal loss and postpartum haemorrhage.
Among 14 reported pregnancies in women with
homozygous FX, there were two instances of miscarriage and two of postpartum haemorrhage [20].
Haemarthrosis occurred in 69% of Iranian patients
with FX levels <10% [10]. Several patients with
moderate to severe FX deficiency have been described
to have recurrent haemarthrosis with development of
haemophiliac arthropathy. Intracranial haemorrhage
is reported in 9–26% patients and is most common
during the neonatal period. One in utero subdural
haemorrhage occurring at 35 weeks of gestation in an
affected foetus has been reported. Umbilical cord
bleeding is also a common bleeding symptom in the
neonatal period, having been reported in 28%
patients with FX levels <10% [10].
Phenotypic–genotypic relationships have been
described in several of the registries. Several homozygous mutations [Leu()32)Pro, Glu102Lys,Gly114Arg] are associated with higher levels of
FX:C, and these patients describe mild or no bleeding
symptoms [14]. Twenty-six of 28 homozygous individuals from the Greifswald Factor X Deficiency
Registry [15] were symptomatic for spontaneous
bleeding symptoms. Of the 42 symptomatic patients,
26 were found to be homozygous, whereas seven
were compound heterozygotes and nine had a
mutation identified in one allele only. The seven
compound-heterozygous patients had FX:C activities
of <1–3% and all had a severe bleeding phenotype.
Severe bleeding complications in the homozygous
and compound heterozygous patients were similar to
those of severe FVIII and FIX deficiencies, including
haemarthrosis, ICH and gastrointestinal bleeding.
Haemarthrosis appears to be particularly common
among patients with the Gly()20)Arg and Gly94Arg
mutations. Five of the seven patients with ICH in the
Fig. 1. Location of factor X mutations
projected on functional protein domains.
Haemophilia (2008), 14, 1176–1182
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Journal compilation 2008 Blackwell Publishing Ltd
FACTOR X DEFICIENCY
Table 1. Frequency of bleeding symptoms in patients with factor
X deficiency.
Symptoms
Herrmann
et al [13]
(n = 35)*
Easy bruising
18 (51%)
Epistaxis
12 (34%)
Gum bleeding
12 (34%)
Menorrhagia
9/12 (75%)
GI bleeding
4 (14%)
Haematuria
3 (9%)
Haematomas
16 (46%)
Haemarthrosis
14 (40%)
ICH
9 (26%)
Umbilical cord
NR
Circumcision
NR
Acharya
et al [15]
(n = 19) (45%)
(4–9)%
(27%)
15%
NR
NR
Peyvandi
et al [5]
(n = 32)à
Anwar
et al [17]
(n = 20)§
NR
9 (45%)
23 (72%)
7 (35%)
NR
7 (35%)
4/8 (50%) 1/10 (10%)
12 (38%)
2 (10%)
8 (25%)
1 (5%)
21 (66%)
NR
22 (69%)
1 (5%)
3 (9%)
NR
9 (28%)
3 (15%)
NR 3/10 (30%)
GI, gastrointestinal; ICH, intracranial haemorrhage; NR, not
reported.
*Includes 28 homozygous and seven compound heterozygous
patients.
Includes homozygous patients with factor X levels of 0–13%.
à
All patients have factor X levels <10%.
§
Factor X levels were not reported.
Greifswald Factor X Deficiency Registry were
homozygous for the Gly380Arg mutation, found
only in subjects enrolled from Costa Rica.
Several kindreds have been described in which
heterozygotes (carriers) have mucocutaneous bleeding symptoms, including gastrointestinal bleeding.
The Stuart kindred included several family members
who were obligate carriers who had prolonged
prothrombin times and a mild bleeding tendency
[7]. Registry data suggest that most heterozygotes are
asymptomatic, however. In the Greifswald Factor X
Deficiency Registry, 9 of 67 heterozygotes (13%)
described mucocutaneous bleeding symptoms, such
as epistaxis, easy bruising and menorrhagia. One
female had postpartum bleeding. The nine symptomatic heterozygotes had FX:C levels similar to the
asymptomatic heterozygotes (50.7% vs. 52%).
Symptomatic carriers may have F10 gene mutations,
which result in a mutant protein that exerts an
inhibitory effect on the normal protein [21], or there
may be other extragenic modifiers in heterozygotes
with bleeding manifestations.
Timing of presentation
Patients with severe FX deficiency may present in the
neonatal period with bleeding with circumcision,
umbilical stump bleeding (usually when the stump
falls off at 7–14 days), ICH or gastrointestinal
haemorrhage. Moderately affected patients may be
recognized only after haemostatic challenge, such as
surgery, trauma or menses. Mild FX deficiency may
2008 The Authors
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be diagnosed during routine screening or because of
a positive family history.
Diagnosis
Laboratory
The diagnosis of FX is usually suspected when both
the prothrombin time (PT) and activated partial
thromboplastin time (APTT) are abnormal and
correct with a 1:1 mix with normal plasma. FX
functional activity (FX:C) is quantified by performing serial dilutions with FX-deficient plasma. PT
reagents may vary in sensitivity to FX deficiency and
congenital variants have been identified in which
both the PT and PTT are normal [21]. Additional
assays which are available for protein characterization include the russell viper venom (RVV) time.
RVV is a metalloproteinase that will activate FX (as
well as FV, prothrombin and fibrinogen) directly and
will detect deficiency of FX if FX-deficient plasma is
used as substrate. Immunological assays, such as
enzyme-linked immunosorbent assay, measure FX
antigen. Chromogenic assays use a FXa-sensitive
chromophoric substrate that can be detected spectrophotometrically. Immunological and chromogenic
assays may miss cases of dysfunctional FX and
therefore should not be used as screening tests for FX
deficiency.
Factor X levels are low at birth and should be
compared with age- and gestational age-matched
normal ranges before a deficiency is diagnosed in the
neonate. FX levels in healthy full-term infants
average 0.40 (SD, 0.14) IU mL)1 and do not
approximate adult values until after 6 months of
age [22]. Because FX is synthesized in the liver, liver
disease will result in low levels of FX, along with the
other liver-produced factors prothrombin, FV, FVII
and FIX. Vitamin K deficiency and warfarin use also
result in low levels of FX, FVII and FIX.
Acquired FX deficiency occurs in up to 5% of
patients with amyloidosis as a result of adsorption
into amyloid fibrils in the spleen [23]. There have
been reports of acquired FX deficiency with cancer,
myeloma, infection and use of sodium valproate.
Acquired inhibitors to FX have been identified in
burns, respiratory infections and exposure to topical
thrombin [24].
Molecular – where can it be done?
Currently, no clinical laboratory in the US offers
genetic mutation analysis or prenatal diagnosis for
FX deficiency.
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D. L. BROWN and P. A. KOUIDES
Management
Treatments currently available
Because of the rarity of FX deficiency, evidencebased management guidelines are lacking. Guidelines
for management of FX deficiency and other rare
coagulation disorders based on literature and extensive clinical experience have been published by the
United Kingdom Haemophilia Centre DoctorsÕ Organisation [17]. For minor bleeding symptoms, topical
therapies and antifibrinolytic agents may be sufficient
treatment. Nosebleeds Quick Release powder,
which is a hydrophilic polymer (Biolife; LLC, Sarasota, FL, USA), may be helpful in the treatment of
nosebleeds and fibrin glue preparations can be used
at surgical sites to achieve local haemostasis. Aminocaproic acid (Amicar; Xanodyne Pharmaceuticals
Inc, Newport, KY, USA) can be used as a mouthwash
(15 mL every 6 h) or taken orally (50–100 mg kg)1,
maximum of 3 g every 6 h) for mouth bleeding or
recurrent nosebleeds. Aminocaproic acid is also
reported to be effective in the treatment of idiopathic
menorrhagia and is used with generally good results
in women with bleeding disorders. Tranexamic acid
is a better-tolerated and more potent antifibrinolytic
agent [25] (oral dose is 15 mg kg)1 or 1 g every
6–8 h). Although an oral preparation is not currently
available in the US, there are on-going trials in the US
studying a sustained release formulation of tranexamic acid (XP12B; Xanodyne Pharmaceuticals Inc) in
healthy women with menorrhagia [http://ClinicalTrials.gov; Efficacy and Safety Study of XP12B in
Women With Menorrhagia, 2007 (http://clinicaltrials.gov/ct/show/NCT00386308)].
Factor X replacement therapy can be accomplished
with fresh frozen plasma (FFP) or plasma-derived
FIX concentrates [prothrombin complex concentrates (PCC)]. No purified FX concentrate is available in the US. FFP has been associated with allergic
reactions and transfusion-associated lung injury.
PCC is a plasma-derived concentrate which has
undergone viral inactivation procedures to lessen
the risk of viral transmission. The use of PCC in high
doses has been associated with thrombosis in haemophilia patients, but the precise frequency is unknown.
There have been no reported cases of inhibitory
antibodies to FX in patients with congenital FX
deficiency in patients treated with FFP or PCC.
The biological half-life of infused FX is 20–40 h,
but varies among individuals and with repeated
dosing [1]. A loading dose of 10–20 mL kg)1 of FFP,
followed by 3–6 mL kg)1 twice daily, will usually
achieve trough levels above 10–20% [18]. PCC or
highly purified FIX concentrates may contain therapeutic amounts of FX as well (Table 2). PCC
products with a FX: FIX ratio of 1:1 will increase
plasma levels approximately 1.5% for every
1 IU kg)1 BW given. Because of the long half-life,
daily treatment may result in increasing levels and is
not usually required [16]. Monitoring FX and FIX
levels is required during long-term treatment or in
the postoperative period to avoid overtreatment and
risk of thrombosis. Adjuvant use of antifibrinolytic
therapy should be avoided during treatment with
PCCs because of an increased risk of thrombosis.
Targeted levels for treatment and surgery are not
well established. Patients with FIX levels >10% and
no significant bleeding history may not require
treatment [16]. In a single case report from 1985,
FX levels of 9–17% achieved with FFP were
sufficient to control minor bleeding [26] . Emergency
surgery for haemoperitoneum was safely performed
with the use of PCC to achieve a level of 35%,
followed by FFP to maintain levels of 10–20% for
6 days in the postoperative period [26]. A subdural
haematoma was evacuated in an infant after treatment with 10 mL kg)1 of plasma every 8 h for
10 days [27]. A central venous catheter was
placed without bleeding complications using PCC
Table 2. Commercial clotting factor products that contain factor X*.
Factor units/100 U of factor IX
Manufacturer
II
CSL Behring, King of Prussia, PA, USA
CSL Behring, King of Prussia, PA, USA
Grifols USA, Biocience Division, Los Angeles, CA, USA
Baxter Pharmaceuticals, Deerfield, IL, USA
Baxter Pharmaceuticals, Deerfield, IL, USA
Baxter Pharmaceuticals, Deerfield, IL, USA
0
100
148
50
120
Product name
Factor X P
Factor IX HS
Profilnine SD
Proplex T
Bebulin VH
FEIBA
VII
IX
X
0
100
100–200à
20
100
140
11
100
64
400
100
50
13
100
140
Variable amounts of activated factors
*Modified from Roberts and Bingham [1].
Licensed in Switzerland.
à
Actual factor X content is included on the product label.
Haemophilia (2008), 14, 1176–1182
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FACTOR X DEFICIENCY
40–80 IU kg)1 given on alternate days, maintaining
a FX level >50% [17].
Thirteen pregnancies among women homozygous
for FX deficiency have been reported in the literature,
and all of these women have been treated with FFP,
PCC or plasmapheresis prior to delivery and some
have received additional dosing postdelivery [20]. In
spite of this treatment, the complication rate was
relatively high, including two cases of postpartum
haemorrhage. None of the women were reported to
have had thrombosis.
Although prophylactic replacement therapy has
been used by FVIII- and FIX-deficient patients to
prevent recurrent haemarthrosis and ICH, these
strategies have only recently been attempted for
FX-deficient patients. Kouides and Kulzer report on
a patient with recurrent haemarthrosis treated with
Profilnine-SD (Grifols USA, Bioscience Division, Los
Angeles, CA, USA; FX: FIX ratio of 0.5–1.0), 30 FIX
U kg)1 twice weekly, who had only a single traumainduced bleeding episode during the 23-month
follow-up period [28]. A trough FX level drawn
48 h after infusion was 30% and the patient had no
thrombotic complications. Seven patients in the
Greifswald Factor X Deficiency Registry have been
initiated with prophylaxis for joint disease and were
treated with 15–20 FX U kg)1 (FIX HS; CSL
Behring, King of Prussia, PA, USA) once weekly
[29]. Dosing was increased to 2–3 times weekly to
prevent breakthrough bleeding and two patients have
required every other day treatment.
A 21-month-old child with recurrent intracranial
haemorrhage was given 40 FIX U kg)1 of PCC twice
weekly and had a preinfusion level of 7% and a
postinfusion of 85% with no further bleeding while
following this regimen [27]. However, in two other
young children with ICH, PCC given weekly or twice
weekly was insufficient to prevent recurrent ICH [30].
Four Irish children with severe FX deficiency and
history of bleeding symptoms who were treated with
PCC (Bpl 9A; Bio Products Laboratory, Elstree, Herts,
UK and Prothromplex; Baxter, Vienna, Austria), 70–
70 FIX U kg)1 1–2 times per week, had no breakthrough bleeding when FX levels were maintained
over 5% [31]. Survival studies on two of the children
found a half-life of 16.7–27 h and the authors suggest
that dosing could be based on pharmacokinetics.
Activated recombinant factor VII (rVIIa) has been
reported to be effective in treating persistent skin and
muscle bleeding in a patient with acquired FX
deficiency as a result of amyloidosis [23]. Because
FX is a substrate for rVIIa, it has been suggested that
it may prove to be ineffective in cases of severe FX
deficiency [17].
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Research/investigational new drug treatment
protocols (IND)
The Centers for Disease Control Universal Data Collection study of patients with haemophilia that involves
longitudinal study, including serial range of motion
assessment and infectious disease testing, is an on-going
protocol available for US FX-deficient patients.
A parallel study compiling obstetrical and gynaecological data points for women with inherited coagulation
disorders, including FX deficiency, is also planned.
Prognosis
With early recognition and diagnosis of severe FX
deficiency, bleeding symptoms can be effectively
treated and managed. Home treatment with FX-containing concentrates allows for prompt resolution of
bleeding symptoms and patients with severe bleeding
tendencies may benefit from prophylactic therapy.
Certain genotypes appear to be associated with a high
rate of haemarthrosis and ICH, and this information
could influence the decision to start prophylactic
therapy. Women with mild FX deficiency who have
menorrhagia may benefit from visiting a comprehensive
haemophilia treatment centre with coordinated services to manage menses and pregnancy issues. Heterozygotes of FX deficiency are most likely to be identified
by abnormal coagulation screening tests or family
history and may benefit from genetic counselling and
haematology consultation during surgical procedures.
Individuals with interest in area
Individuals holding INDs for treatment
Currently, no individuals in the US are holding INDs
for treatment of inherited FX deficiency. FX
P Behring by CSL Behring is available in Switzerland.
Individuals doing research in pathophysiology,
molecular basis, etc.
Currently, Dr Flora Peyvandi, Milan, Italy and
Dr Karin Wulff, Greifswald, Germany, are performing epidemiological, clinical presentation and genetic
studies on FX deficiency. Dr James Uprichard and
David Perry, Cambridge, England, are researching
the pathophysiology of FX deficiency.
Disclosures
D. L. Brown has acted as a paid consultant and has
received funds for research. P. A. Kouides has stated
Haemophilia (2008), 14, 1176–1182
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D. L. BROWN and P. A. KOUIDES
that he has no interests that might be perceived as
posing a conflict or bias.
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Links to organizations – professional, lay
National Hemophilia Foundation: http://www.hemo
philia.org/NHFWeb/MainPgs/MainNHF.aspx?menu
id=188&contentid=52&rptname=bleeding
Canadian Hemophilia Society: http://www.hemophilia.ca/en/2.3.6.php
National Library of Medicine and National Institutes of Health Medline Plus: http://www.nlm.nih.
gov/medlineplus/ency/article/000553.htm
2008 The Authors
Journal compilation 2008 Blackwell Publishing Ltd