AHEPA
University Hospital A’ Propedeutic Medical Clinic
|
Haemostasis and Thrombosis
Unit |
rFVIIa
treatment
of an
haemophiliac with a very high responder inhibitor
PE
Makris, G Gerotziafas,
E
Pithara, Th Papageorgiu,
F
Athanasiadu, D Katriu.
Haemostasis
& Thrombosis Unit,
AHEPA
University Hospital,
Thessaloniki-Greece.
case
report
*
A boy 2,5 years old, (haemophiliac A, FVIII:C <1%)
had received 2000 units of Monoclate-P for a gastrointestinal
bleeding.
*
40 days later he had had an hemarthrosis in the left knee
and was treated with 1000 units Kogenate. In the same time we
decided to implant a infuse-a- port.
On
the day of operation (6 days later) he received 1000 units of
Kogenate without any haemorragic problem. After 2h, the child
started to bleed and another administration of 1000 units
didn’t give any result. There was no apparent surgical reason
of bleeding.
The
general situation of the boy had been aggravated and he received
two units of red blood cells and another 2.000 units of Kogenate.
On the 2nd day an overdose of 3000 units of Kogenate was without
any real haemostatic effect.
The
laboratory control revealed a strong inhibitor of FVIII:C
(256 Bethesda units). Waiting for Novo Seven (kindly offered from
Novo Nordisk), we treated with cyclophosphamide and Kogenate,
but the results were poor.
Furthermore,
the surgical field had been infected by Pseydomonas and
Timentin was administered.
Treatment
(22/11) with NovoSeven at 1,2 mg every 4 h had poor results. The
child was re-operated (25/11) for the removal of the
infuse-a-port for it was considered as the possible cause of
infection
During
this operation the patient was covered with 2,4 mg every 3h and
only after this dosage the bleeding definitively stopped.
table
I. Laboratory findings.
date
FI Inhib A2-APL TAT F1+2
PAP Di-D Hct
g/l B/u % ìg/l nm/l
ìg/l ìg/l %
19/10
3.9 - - 10
1.2 300 0.5 33
22/11
6.9 256 122 17 2.2 1200 1.0 -
25/11
4.4 256 `99 70 2.3 950 4.0 30
4/12
2.3 256 108 5.5 1.7 470 1.0 36
comments
In
this table we present some laboratory parametrs indicating the
activation of haemostasis after the Novo-Seven
administration, like fI, A2-APL, TAT, F1+2,,
PAP, Di-D-
It
is obvious that the increased dose of rFVIIa (2,4 mg/kgr)
on 25/11 activated transiently the coagulation and the
fibrinolysis.
conclusion
The
administration of rFVIIa was effective for the treatment of this
inhibitor in a very high titer.
Hematuria
and
renal
colics
in
haemophilic patients.
GT Gerotziafas, K. Konstantinidis, G. Kaiafa,
E.Pithara, PE Makris.
Haem.
& Throm. Unit,
AHEPA
Univ. Hospital Thessaloniki Greece.
In
the past, hematuria in haemophilic patients used to be treated by
replacement therapy or by å-aminocaproic acid -EAKA
As
a result, patients could develop transient anuria, calculi
formation and gradual deterioration of renal function,
complications associated with the formation of haemoglobin
crystalls inside the kidney.
Later,
conservative management of these episodes, which included
fluid replacement
and administration of soda, was recommended.
These
measures not only shortened, but they prolonged the duration of
hematuria for 25-30 days, a fact that leads to excessive blood
loss and provokes anxiety to the patient.
Furthermore,
hematuria is often accompanied. by renal colics (1 patient in
3), even after the administration of EAKA, replacement
therapy with concetrated factors or without any treatment.
In
addition, because of the often infection of haemophiliacs with
HIV virus, it is imperative that the duration of hematuria be
short, for the safety of the persons related to the patient.
Material
and methods
We studied
65
episodes of hematuria in 50 patients
* 46 suffering from haemophilia A and
·
4 from haemophilia B.
Table.
Comparison
among the different treatment procedures.
treatment |
hematuria |
colics |
duration
|
no
treatment |
15 |
6 |
8-10
days |
FVIII/FIX |
12 |
4 |
4-8
days |
Transamin |
25 |
8 |
5-10
days |
All
of them |
13 |
0 |
1-2
days |
conclusion
1.
Conservative measures.
2.
administration of 5-20 iu/Kgr of high purity concentrated
factors.
3.
tranexamic acid, 500 mg 3 times a day. In this way the duration
of hematuria is only 1-2 days.
Coronary
artery by-pass
surgery
in an
haemophiliac
patient :
continuous
infusion
of
factor VIII:C concentrate.
Makris
PE, Oikonomidis A, Diarmisakis E, Pithara E, Papadopulos K,
GT
Gerotziafas, Z Foka, Spirou P.
Haemostasis
& Thrombosis Unit
AHEPA
University Hospital,
Cardio-Surgery
Clinic
“G
Papanikolaou” Hospital
Thessaloniki
Greece.
Elevated
factor VIII levels are related with coronary artery disease.
Furthermore,
bolus administration of concentrated factor is associated with
athe-rogenic effect due to its high peak levels.
Continuous
infusion is a method which can minimise these side-effects.
Material
and methods:
Man
62 years old, weighing 104 kg, had suffered from severe
haemophilia A, mitroid valve stenosis with atrial fibrillation
and developed atheromatic coronary disease.
As
a consequence, he underwent surgical opening of the valve and
coronary artery "by-pass" surgery of one vesicle.
We
administered highly purified FVIII (Monoclate -P) according to
the following protocol:
a)
6000 iu bolus in the beginning of the operation,
b)
12000 iu continuous infusion using a pump, during the operation
(which had lasted for 4 h),
c)
during the first 24 h 48000 iu. Rate of administration: 2000
iu FVIII:C plus 20 iu of heparin (5 ml/h).
Every
4h we were renewing the solution.
On
the second day the dosage was reduced to 18000 iu,
on
the third day to 6000 iu, from
the
fourth till the tenth day to 3000 iu and
on
the tenth till the fourteenth day to 500 iu/24h.
Results
-comments:
Levels
of FVIII:C varied between 95-31%, TAT increased the third day (90ìg/ml),
while F1+2 remained less than 4 nmol/l.
The
patient was successfully treated with this alternative method
without any clinical or laboratory complications
Stability
of concentrated factors of coagulation
E
Pithara, G Gerotziafas,
K
Konstantinidis, PE Makris
Haemostasis
and Thrombosis Unit,
AHEPA
University Hospital,
Thessaloniki,
Greece.
In
order
to
start using the continuous infusion of concentrated factors of
coagulation in the clinical praxis for the replacement therapy
of haemophilic syndromes,
we
checked the stability of these compounds after their
reconstitution.
We
took 500 ìl of each compound, which had already been ready for
administration, and
we
checked its activity at the beginning, and after 30 min 4h and 24
h respectively.
We
checked the following commercial preparations: Monoclate-P,
Mononine, Coate-H and Kogenate.
Results:
preparation |
0
min |
30
min |
4h |
24h |
Koate-H |
88% |
79% |
53% |
27% |
Monoclate-P |
162% |
140% |
128% |
59% |
Kogenate |
100% |
79% |
54% |
54% |
Mononine |
105% |
89% |
79% |
70% |
The
changes in factor activity observed during the above four time
periods didn’t establish the stability of these compounds.
Therefore,
we decided to use a new solution every 4 h for the case of
replacement therapy by continuous infusion.
The
experiment took place in very high external temperature (in
July).
In
September we repeated the experiment and realised that all the
preparations had remained stable for 24 h.
Nevertheless,
for security reasons, we recommend to change the dilution every
4 h in the case of continuous infusion.