From www.bloodjournal.org by guest on February 10, 2018. For personal use only.
Factor
13
Deficiency
By
A
SHARON
FISHER,
HEMORRHAGIC
Five The
and
as
of
one
clots.
stabilizing the
linkage
bonds
only,
and
consequently
case
of Factor
hydrogen
exhibited
various
bleeding
interrupted
by
spontaneous
By
the
clotting
treating
any
bleeding,
and
B.
S.,
gave
a 29-year-old
the
hematologic
birth
of
hemorrhagic
in
to
abortions. hemorrhage
The
the
with
bleeding
by
the
started of the
after
cuts,
transient
for
6 months,
neurologic
hematuria. The
During
these
patient’s
were bleedings.
No
repeated
abortions.
were
stages
gynecologic
or
The
physical
in
concen-
female
who
were
all
hemorrhage.’2
normally
was
without
disorders
and
gvnecologic
childless,
was
of
hospital.
our
been Dr.
on
because
hematoma
to
because
admitted
Naor)
and prolonged childhood she
and
referred
several of
these
umbilical vein had repeatedly
into
the
skin
after
of wounds. In the last 10 years. the patient because of Douglas hematoma with severe urinary disorders. In 1957 she had been diagnosed In
as 1960
a large she
umsumally treated Bumt, most
development
other
had
a severe Since
extractions
normal.
and
She
with cord.
finally
of fetal
adult
decidual
Rikover,
compression.
the patient
periods
at various
was to
in an
departmiient
(Dr.
at birth, umbilical
what
vitro,
proceeded
married
abortions.
or dental
due
episodes
menstrual
interrupted
Family
with
disorders
in
blood
aggregated
pregnancies
severe
gynecologic
minimal trauma. She also exhibited slow healing had been admitted 4 times to various hospitals abdominal and perineal pains and at times hospitalized
the
are
child.
Morocco,
department
history ligation
to
1963 enzy-
of
molecules
whose
in
REPORT
in
repeated
gynecological
bleeding after the
severe
1963
al.1
Loewy),
determines
soluble,
pregnancy
to a normal
born
June
diathesis
occasions
suffered
woman
clinic
are
due
fibrin et
of
monomers
its
13 deficiency
last
of
Duckert
accepted
factor
fibrin
and
CASE R.
the
abortions
her
was
This
is weak,
manifestations
defect,
she
13.
between polymer
by
fibrinase
20 years,7-11
Factor
fibrin
trated solutions of urea. Here we report the first
factor,
almost
the
1960
cOuntries.2’6
( Lorand-Laki
absence,
deficiency
in
in different
for
NAOR
a congenital
described
since,
Diathesis
AND SHIrstox
to
first
factors-i.e.
stable
Hemorrhagic
RIK0vER
due
was
in vitro
clotting
a strong In its
)
factor
investigated
maticalby
MOSHE
factor (f.s.f. were discovered
fibrin
known
Severe
DIATHESIS
stabilizing other cases
by
with
could
pelvic
had
an
with
blood
important,
all
by
spontaneous
be
found
examinations
hematoma
episode
of
transfusions. her
12
pregnancies
abortions as
were
an
with painless
with
explanation
severe to
the
of
the
negative.
Studies
The
patient
mother.
The
From
was
a child
patient’s
the
of
a
parents
Departments
of
consanguineoums and
her
Hematology
marriage: 5
the
siblings
and
did
Obstetrics,
not
Jaffa
father
was
exhibit
an any
Government
umncle
hemorrhagic
Hospital,
Jaffa,
Israel. First
submitted
SHARON
MOSHE Hospital. Jaffa
FISHER, RIKOVER,
SHIIsION Government
July
19,
M.D.: M.D.: NAOR,
1965; Head,
Head, M.D.:
accepted Department Department Assistant
for publication Nov. 13, 1965. of Hematology, Jaffa Governnment Hospital. of Obstetrics and Gynecology, Jaffa Government Head,
Department
of
Obstetrics
and
Gynecology,
Hospital. 34
BLOOD,
VOL.
28,
No.
1
(JuLY),
1966
From www.bloodjournal.org by guest on February 10, 2018. For personal use only.
FACTOR
DEFICIENCY
1 3
manifestations.
The
WITH
clotting
SEVERE
HEMORRHAGIC
mechanism
was
DIATHESIS
investigated
in
35
3 siblings
without
any
abnormal
findimigs.
Laboratory No
Tests
abnorniality
and
no
was
performed
was
by
coagulation, system
Investigation The
in Table
show
any
only
defect
cent
Na
1. No
not
only
show
circulating (Table
Protein
found
electrophoresis after
was
bleedings.
abnormalities
anticoagumlant
in
was
present.
hours.
Loewy
was
and
oxalate),
Only
tests
any
stages
The
fibrinolytic
of
1).
in
clot
Edsall.9
0.2
ml.,
stal)ilitV.
The
Oxalated
was
study
plasma
clotted
with
of
(blood
0.1
clot
drawn
ml.
calcium
stability
was
on
volume
of
solumtion
0.05
1/10
chloride
The clots were incumbated at 37 C. for 30 minumtes and suspended in 2 ml. NI urea or 1 p cent muonochloracetic acid. The clots were examined after 24
normal,
Clotting
Stability
detected
by
tests.
was did
abnormality
of Clot
as described!
laboratory
anemia
niethods13”6
shown
not
in various
found;
standard
as did
per
foumnd
cryoglobulin
clots
which
disappeared
completely
after
24
hours
performed 1.34 NI.
of a solution 1 hour and
were
of 5 after
considleredi
as
soluble. Normal addeel
plasma, in
This than
somiie
assay
gave
1 hour
of
addition
of
patient’s
clots
to
the
concentration
to we
days.
With
section
was
as
intervention The days,
an
well
no
condition,
as
developed
to
the
days
less
Table
2. the
1/4. of
the
patient’s
aminoacid,
of 300
18
in
rendered
stability
ml.
after
soluble
view
up
bank the
to
plasma,
a
her
transfusion,
the
in umrea.
the
intervention,
ml.
fresh
and
blood
of
blood
dumring was
showed
an
the of
infant
no
plasma,
without plasma
repeated 300
any
were 8
ml.
bleeding
elective
operation;
he
could
cesarian
administered days
after
the
administered.
cicatrization newborn
bank
pregnancy
ml.
of
which
normally, 600
plasnia
the The
month
history
past defect
human
developed
before
normal,
her
clotting
with
ninth
ml.
of
the
the
occured.
normally,
in Factor
In
pregnancy
of 300
was
patient
were
after
shown
system
the of
were
to
treatment of
1000
coumrse
the and
and
the
amoumnt
complications
on
NI
chloride.
completely As
clotting
addition
pregnant.
beginning
additional
postoperative and
deficiency
treatment day
the
0.1
calcium
Pregnancy
hemorrhages
One
of of
solutions.
effect
Fifteen
abnormal
became
the
performed.
prophylactically
into
solutions.
addition
omily imp to a dilution no
transfusion urea
concentration
disappeared
to
but had after
a prophylactic
this At
1/50
serumm.
become
a the
acid
soluble
during
severe
clots
of
system
to
before
plasma
dilution
normal
in
patient
started
disorders.
The
still
again
imp
mixture,
mnonochloracetic
clotting
insoluble
the
1964
demonstrated, 10
a
were
had
clots
due
other
ump to so did
Treatment
May
abortions
or
or
the
clots
became
plasma
Prophylactic
each
urea
of 0.1 NI, bumt after
clots
In
plasma
solution
clotting
results: in
and
cysteine
the
conclusive
cysteine
clots:
plasma
to
insolumble of
patient’s
serummii,
incubation
normal
Addition plasma
normal experimiients
the
wound
3000
was
Gm.
coagulation
at
disorder
comiipleted
birth,
was
and
no
at in
8
good
detectable
13.
DIswsSIorc
The
severe
ciency
of
disorder
hemorrhagic
Factor
13,
already
Biggs
calcium
cules,
with
insoluble
and ions,
the in vitro
for
formation
of
cases and
present
promotion of a clot
in concentrated
case
In
have in
capable solutions.
was
addition
recently
Tsevrenis
due
to been
to the cases
defiof
this
discovered
by
in Greece.’7
plasma
of strong urea
described
factor.
further factor
the
the
stabilizing
by Mandalaki
13 is a clotting
with
fibrin
published,2’”
in England
Factor
disorder
the
bonds
of normal
and
responsible,
between hemostatic
the
together fibrin function
moleand
From www.bloodjournal.org by guest on February 10, 2018. For personal use only.
FISHER,
36 Table
1.-Clotting
Clot
Patient
(direct)
retraction
(after
Bleeding
150.000-350.000
3+
2-4+
3 hours)
negative
( Duke)
time
Clotting
Normal
220.000
Rumnipel-Leede time
< 4 ruin.
7 ruin.
< 10 nuimi.
3 nun.
< 3 nun.
time
Tliromuiboplastin
generation
NAOR
Range
-
2 mm.
(Lee-\Vhite)
Recalcification
AND
Tests
Test
Platelets
RIKOVER
normal
-
( Biggs-Douiglas) Serum
protlurombin
Plasmuua Thrombin
clotting
Fibrinogen
fibrin
shows
an
urea
250
that
the those
)
13, fibrin
fibrin
per
cent
200-400
chains
3-4
formation it has
is neither
per
c’mut
can
aggregated
u/nil.
delayed
an insufficient and
are
mg.
> 5 Ii.
4 u./ml.
in quality:
biochemical
The
is a
of
role
nor
hemostatic
be
by
reduced, capability,
reversibly
only
cuts,
with
by Duckert
gated An
dispersed
weak
in
intermolecular
and
the
12
patient’s
child.
normal
rhages
feature
last This
with
connected
usually
of
f.s.f.
in
of
of
Loewytm9
of
function
is controversial.uu
similar
in
late
to 30 hours
24
f.s.f.
strong
suggested
the
is quite
hemastasis
al.’8
studies has
hematomas,
reported
and prevents
of our
successive
was
deficiency
had
course
a normal
suggests
that
all
bleed-
(Table
and
stretching
concentric
the
continuation
and
growth
rupture
of the
of the
severe
investi-
she
13
gave
gives
of the placenta. to decidual of
veins,
of
and
birth
to
protection
It is known microhemor-
their
Prompt
bleeding
bleeding
transfusions
and
placenta.
decidual
uterine
regular
Factor
normal development there is a tendency
the
the By
observation
the
case
pregnancies.
pregnancy
bleeding during the during normal pregnancy
trophoblasts,
the
at birth,
normal
been
the
et
13 deficiency
bleedings of
has
dramatic
interrupted
plasma,
interval
wounds
to
activation
Factor
promoting
Lorand
Laki,2#{176}f.s.f.
in the
of
in
according
and
umbilical
13
clarified.
et al.”7
unusual
which
an
of
Factor
been
but
of thrombin
severe
healing
yet
Osbahr
syndrome
cases:2’6
of
not
transpeptidase,
hemorrhagic after
has
Chandrasekhar, The
Slow
function
monomers
factor
described
that
mg. 5 hours
thrombelastogram,”17
Its
transamidase.
against
)
( Milstone
abnormal
of fibrin
and
a
sec.
of Factor
precise
linkage
3).
1()-12
> 20 sec.
bonds.8”#{176}”T
The
ings
sec.
11 sec.
is defective
solutions.
hydrogen
12-14
timuue ( Fletcher)
( Remniert-Cohn
absence
the
13 sec.
tinue
Plasmuuinogen
In the
35 sec.
timuue (Quick)
(Ratnoff)
Eumglobumlinlysis
but
timiue (Quick)
protluromuul)in
invasion
by
clot
formation
any
complica-
tions.2’
The
beneficial
effect
deficiency has been A concentration sufficient case,
the
of plasma
observed of Factor
for
stabilizing
effect
of
transfusion
the
transfusions
in
the
treatment
by most investigators. 13 of less than 10 per
cent
clot
normal
of
and
for
300
ml.
assuring
plasma,
10 per
of its
of normal
hemostasis.
cent
of the
Factor
13
value
In
is
our
patient’s
From www.bloodjournal.org by guest on February 10, 2018. For personal use only.
FACTOR
1:; DEFICIENCY
WITH
SEVERE
Table Tube
Patiemit’s
1
plasma
HEMORRHAGIC
2.-Urea 2
0.2
37
DIATHESIS
Solubility
Tests
:3
4
5
6
0.2
0.2
0.2
0.2
7
0.2
8
9
10
0.2
0.2
0.2
(miil.) Normiial
plasma
0.2
(ml.) Normal
plasmiia
1/10
0.1
(miil.) Normal
plasmiia
1/50
0.1
Normal (ml.)
plasmiia
1/100
Normal
scrumrn
(ml.) 0.1
0.1
(nil.) Normal
serum
1/2
0.1
serummn
1/4
(mimI.) Normal
0.1
(nil.) Normal
serummii 1/10
0.1
(nil.) Cysteine
solution
0.1
0.1
NI (ml.)
Na Cl solution 0.15
CaCL,
0.05
State 1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
-
+
+
+
+
+
+
+
-
-
-
+
+
+
-
+
+
+
-
-
NI (nil.)
NI (ml.)
of clot:
-
0.1
h.
Aftcr:24h. +
0.1
= =
Clot
still
present.
Dissolumtion
of
Table Type
Unibilical
3.-Bleeding
bleedling
Our
(at
1)irtli)
13
Deficiency Nine Cases in the Literature
Case
+
9
9
Ecchymosis
+
7
bleedings
after
cuts
+
occurred
lasted after
13 deficiency
for
16-18
days.
intravenous
No
defect family
affected
her
parents,
of this
defect.
of
affecting members
who
-
or
intraoperative
administration
is a congenital
patient, no similarly should be emphasised that (heterozygotes)
6
+
bleeding
our
carriers
in Factor
of Bleeding
volume,
Factor
Manifestations
+
I)ecidual
plasma
clot.
Hematoma Late
bleeding
the
are
600 ml. both could
blood-related,
postoperative
of plasma. sexes
he
In
equally.’7
detected,
may
but
possibly
it
he
SUMMARY
This Her
report presemits the first hemorrhagic manifestations
case
of Factor 13 deficiency imi an adult were repeated and severe: umbilical
female. vein
From www.bloodjournal.org by guest on February 10, 2018. For personal use only.
FLS}IER,
38 bleeding most
at birth,
hematomas
important,
severe
on
uterine
all interrupted by spontaneous Plasma infusions, assuring of its normal
level,
course; a cesarian birth to a normal
the
hemostatic
Iste
section child.
communication
was
Le
del
vena
sanguination
prolongate
post
umterin
12
spontanee. Infusiones 10
Iue
static
de
pro
del
solutiones
Gratias
a
patiente
regular
e
de
esseva in
esseva un
had
a normal
and
she
Factor
gave
e
sitos,
sever:
sanguination
sanguinationes
omnes
interrumpite de
per
Factor
aborto
13 de
minus
Ic functiones
normalisava
patiente
13 in un
repetite
vane
concentration
normal,
del
cent
plasma
importantemente-sever
producente
10 per
e rendeva
los
hemo-
insolubile
in
con-
de urea. de
transfusiones
sequeva
incidentia,
plus
concentration plasmatic
and, were
patient’s
incident,
carentia
hematomas
he quales
plasma,
de
caso
a nato,
e-le
than
urea solutions. last pregnancy
hemorrhagic
umbilical
cuts
INTERLINGUA
Ic prime
pregnantias
cento coagumlos
del
centrate
IN
NAOR
which
of the
any
AND
after
of less
without
mamiifestationes
secaturas,
durante
bleeding
12 pregnancies,
functions
performed
presente
adumlte.
late
insoluble in concentrated of plasma the patient’s
SuIi.LAmo
feminina
sites, during
abortions. a Factor 13 concentration
normalized
clots and rendered them By regular transfusions
various
bleedings
RIKOVER
un
curso
le patiente
plasma,
normal.
parturiva
he plus
Section
un
inf ante
recente
cesaree
pregnantia
del
executate
sin
Department Shapiro for
of her
esseva
normal.
ACKNOWLEDGMENT We
are
grateful to Hematology for performuing skillful technical assistance.
Dr.
NI. the
Schwartz
and
transfumsions
of
Dr.
0.
plasma,
Speizer and
to
of Mrs.
the Sarah
REFERENCES 1. Duckert, D.
F.,
H.:
ital
haemorrhagic
dime
to
Sper.
congen-
diathesis
fibrin
5.
factor
Diath.
defi-
Haemorrh.
Nevanhinna,
deficiency
factor.
of
Thromb.
7:567,
H.
R.:
fibrin
Proum-Wartelle, Soulier, J. P.:
F.,
and
Con-
Haemorrh.
genital
en
fibrine
facteumr
(facteumr Nouv.
Rev.
0., Le
Alagille,
deficit
con-
stahilisant
die
XIII).
Etumde
Franc.
Hemnat.
de
6.
Soumlier,
8.
Laki,
Ia
deux
un de
la
deficit en Fibrine.
1963.
bility
4:267,
142:581,
K..
and
of fibrin
1944.
Lonard,
clots.
L.:
On
Science
the
solum-
108:208,
1948.
Nlandelli.
F.:
Difetto ico
3:119,
congenitalde
a
J. P.,
Physiol.
1964. 4.
Trouble
associe Stabilisant
Proum-Wartelle, 0., and Josse, F.: Turnover of clotting factors. Gleneagles Conference, 1963: Fibrinogen and Fibrin. Stuttgart, F. K. Schattauer, 1964. p. 123. 7. Robbins, K. C.: A study of the conversion of fibrinogen to fibrin. Amer. J.
1962.
Josso.
1963.
R.:
Hemostase
stabilizing
Diath.
13:175,
Masuire,
l’hemostase Facteur
probably
stabilizing
and
E.,
genital
cas.
Shmerling,
1960.
Ikkala,
D.,
and
undescribed
Thromb.
5:179.
3.
E.,
A hitherto
ciency. 2.
Jung,
del di
Laki
Sindrome
Fattore e
Emorragica
Stabilizante Lorand.
da
FibrinMed.
Clin.
9.
Loewy,
on fibrin.
and Edsall. J. T.: Studies formuation of urea-insolumble J. Biol. Chem. 211:289, 1954.
A.
the
G.,
From www.bloodjournal.org by guest on February 10, 2018. For personal use only.
FACTOR
10.
13
Loewy,
A.
K.,
Kriel.
L.,
J.
brinase. 11.
12.
13.
Luischer,
E.
Dahlberg, A., Dunathan, and Wolfingen, H.: Fi-
Biol. F.:
Chem. Em
Biggs,
pp.
211,
R.,
and
throniboplastin 15.
Path.
6:28,
1953.
Ratnoff,
0.,
and
method
16.
HEMORRHAGIC
236:262,
for
214,
218.
Douglas,
A. test.
Menzie, the
C.:
determination
fibrinogen in small samples J. Lab. Clin. Med. 37:316, Fletcher, A. P., Alkjaersig, Sherry, S.: The maintenance tained thrombolytic state
38:1096,
F.:
The
Congr.
A.:
S.:
Clin.
A
new
A.
wart,
W.
K.,
and
Jacobsen,
mechanism
Jr.,
J. Weber,
A transamidase fibrin
Biophys.
Res.
in
194:1148,
Dahlberg,
V.,
insoluble
facHaemat.,
press).
Nature G.,
J.:
chem.
1962.
E.,
Dor-
N.,
and
mechanism formation.
Commun.
Bio15:177,
1964. 20.
Chandrasekhar, Laki,
of
of plasma. 1951. N., and of a susin man. J.
(in
Konishi,
clotting.
Loewy,
for
stabilizing Sec.
Transpeptidation
Eisele,
The
J.
L.,
l)lOOd 19.
1964
Lorand,
1959.
fibrin Intern.
Stockholm, 18.
247.
generation
Invest.
Duckert, tor.
fibrinstabilisierender
39
DIATHESIS
Clin. 17.
1961.
Factor aims Thrombocyten. Schweiz. Med. Wschr. 87:1220, 1957. Fisher, Sharon: Fibrimiase Deficiency. Congress of the Asian and Pacific Society of Hematology, Jerumsalemu. 1964. Dacie. J. V., and Lewis, S. NI.: Practical Haemotology. London, Chtmrchill, 1963,
14.
C.,
SEVERE
WITH
DEFICIENCY
21.
K.:
N., The
Osbahr,
mode
Laki-Lorand
Factor
fibrinogen.
Biochemn.
Commumn. Javert, C.:
15:182, New
pp.
in
78,
285.
A., action
the
and of
the
clotting
Biophys.
of Res.
1964.
Spontaneous
Abortions. 1957,
of
York,
and
Habitual
McGraw-Hill,
From www.bloodjournal.org by guest on February 10, 2018. For personal use only.
1966 28: 34-39
Factor 13 Deficiency with Severe Hemorrhagic Diathesis SHARON FISHER, MOSHE RIKOVER and SHIMON NAOR
Updated information and services can be found at: http://www.bloodjournal.org/content/28/1/34.full.html Articles on similar topics can be found in the following Blood collections Information about reproducing this article in parts or in its entirety may be found online at: http://www.bloodjournal.org/site/misc/rights.xhtml#repub_requests Information about ordering reprints may be found online at: http://www.bloodjournal.org/site/misc/rights.xhtml#reprints Information about subscriptions and ASH membership may be found online at: http://www.bloodjournal.org/site/subscriptions/index.xhtml
Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly by the American Society of Hematology, 2021 L St, NW, Suite 900, Washington DC 20036. Copyright 2011 by The American Society of Hematology; all rights reserved.
