Clinical
study of low molecular weight Heparin(Jipailin®)As an anti-coagulant
during haemodialysis
Lin
Shantan,Qian Jiaqi, Mei Changlin --SHANGHAI HUASHAN HOSPITAL
Lu
Fumin -- SHANGHAI RENJI HOSPITAL
Ren
Qing, Zhang Yixiang --SHANGHAI CHANGZHENG HOSPITAL
[Abstract]
Objective:
To test and verify the efficacy and safety of Jipailin as
an anti-coagulant during haemodialysis.
Method:
119 cases were divided into two groups, a cross over self-controlled
method was used to compare them in two phases. Jipailin
group(119 cases) was compared respectively with Fragmin
group(39 cases) and unfractionated heparin (UFH) group (80
cases). The dosage for Jipailin and Fragmin was to single
inject each of them 5000IU, and UFH was administered according
to average individual dosage.
Result:
Compared between Jipailin group and Fragmin group, there
was no significant difference in completing haemodialysis
course, clotting of blood in dialyzator, coagulant deposition
in catheter and haemodialysis repeated application times
for single dialyzator (P>0.05). Time needed for pressure
at puncture site of Jipailin group was shorter than that
of Fragmin(P<0.05).Compared between Jipailin group and
UFH group, Jipailin group was superior than UFH group in
haemodialysis course completion, clotting of blood in dialyzator
and haemodialysis repeated application times for single
dialyzator. There were no significant difference of time
needed for pressure at puncture point (P>0.05).
Conclusion:
Jipailin is a safe and effective anti-coagulant as Fragmin
during haemodialysis, more effective, safer and convenient
than UFH.
[key
word] Low Molecular Weight Heparin(LMWH), Jipailin, haemodialysis
, clotting of blood in dialyzator and coagulant deposition
in catheter, Haemodialysis repeated application time for
single dialyzator , time needed for pressure at puncture
point.
[Background]
Anti-coagulation
in extracorpreal circulation is an important step in haemodialysis,
which not only relates to the conduction of haemodialysis
, but also affects haemodialysis efficacy. UFH is used as
a conventional anti-coagulant in haemodialysis , but it
can not be regarded as an ideal anti-coagulant, since its
use is associated with many side effects. With characteristics
such as high and long antithrombosis activity, lower bleeding
risk, high bioavailability, long half-life period and convenient
use, LMWH has gradually taken the place of UFH to be used
as an anticoagulant in haemodialysis in recent years .Jipailin
is a low molecular weight heparin sodium injection of Hangzhou
Jiuyuan Gene Engineering Co.,Ltd. To test and verify its
efficacy and safety as an anti-coagulant during haemodialysis,
we compared Jipailin with Fragmin and UFH, conducting randomizd,
self-controlled and multi-centered clinical observations.
Details are reported in the following.
Materials
and Methods
Patients
119
patients with maintaining haemodialysis having no obvious
tendency of hemorrhage, 60 males and 59 females, average
age 51.4±12.7 years old, average weight 52.8±8.8kg. Idiopathies for 119 patients with renal failure are desrcribed
respectively as follows: hypertension 9 cases, polycysticrenes
7 cases, diabetes 3 cases, pyelonephritis 3 cases, gout
2 cases, systematic erythem lupus 2 cases, rheumatoid arthritis,
calculi, abnormality, hydronphrosis, each 1 case , and
the others are all glomerulonphritis.
Haemodialysis
Dialysis
time: 2-3 times every week, 4-5 hours every time, blood
flow: 200-350ml/min (median: 250ml/Min); hollow fiberdialyzator,area:1.2-1.3m2;
bicarbonate dialysate.
Methods
3.1.Grouping
and course of treatment:
Among
119 patients, 39 patients were tested to compare between
Jipailin and Fragmin, and 80 patients Jipailin and UFH.
They were randomly divided into two groups and taken cross
controlled observations in two phases. As for one group,
Jipailin was used for anti-coagulant in the first course,
and Fragmin or UFH in the second course, and the other group
vice versa. New dialyzator was used in the beginning of
each course, dialysis 4 times as one course, the same dialyzator
used for 4 times, and the course terminated if the dialyzator
cannot be used again.
3.2
Drugs and Dosage
Jipailin:
Hangzhou Jiuyuan Gene Engineering Co., Ltd.
Specification:
5000 anti-Xa IU/2ml
5000IU
was single injected into artery end in the beginning of
haemodialysis.
Fragmin:
Kabivitrum Co. Switzerland
Specification:
5000IU/2ml
5000IU
was single injected into artery end in the beginning of
haemodialysis.
UFH
( Heparin sodium): Shanghai Biochemical Pharmaceutical Factory
Specification:12,500
IU/2ml
The
first and maintaining dosage was administered according
to normal individual dosage applied to patients.
3.3
Observation indexes
3.3.1
The state of blood clotting in dialyzator and coagulant
deposition in catheter are recorded after each dialysis.
Classification
for clotting of blood in dialyzator
Grade
0: no clotting of blood in a few fibers
Grade
Ⅰ:
some clotting of blood or clotting of blood in bundling
fibers
Grade
Ⅱ:severe
clotting of blood or clotting of blood in over half fibers
Grade
Ⅲ:
venous pressure arises obviously during dialysis, and dialyzator
has to be changed.
Classification
for coagulant deposition in catheter
Grade
0: no coagulant deposition
Grade
Ⅰ:a little coagulant deposition
Grade
Ⅱ:
severe coagulant deposition
Grade
Ⅲ:
a lot of coagulant deposition, venous pressure arises obviously
during dialysis, and dialyzator has to be changed.
3.3.2
Time needed for pressure at puncture site was recorded after
each dialysis.
3.3.3
Record time used of each dialyzator
3.3.4
Record bleeding and other concerned side effects during
the period of observation.
Result
1.Haemodialysis
courses accomplished
Table1. Comparison of haemodialysis courses completely
finished and not finished
|
Group
|
Case
|
Finished
|
%
|
|
Jipailin
|
119
|
117
|
98.3%
|
|
Fragmin
|
39
|
39
|
100%
|
|
UFH
|
80
|
74
|
92.5%*
|
X2-test
analysis, there was no significant difference between Jipailin
and Fragmin, when P>0.05;whereas there was significant
difference between Jipailin and UFH , when P<0.05.
119
patients finished haemodialysis totally 935 times, each
lasting 4-5 hours. 119 patients in Jipailin group received
470 times, of which 117 patients completely finished courses.
39 patients in Fragmin group received 156 times, all of
them finished haemodialysis . 80 patients in UFH group received
309 times, of which 74 patients completely finished courses.
According to X2-test analysis, there was no significant
difference between Jipailin and Fragmin groups, whereas
there was significant difference between Jipailin and UFH
groups.
2.Comparison
of clotting of blood in dialyzator and coagulant deposition
in catheter
2.1
Comparision of Jipailin and Fragmin
39
patients in Jipailin group received 156 times, both dialyzator
and catheter were all of 0 grade ; 39 patients in Fragmin
group received 156 times , except 2 times of dialyzator
is grade Ⅰ, all others were of 0 grade ; all of catheter were
grade 0. According to X2-test analysis, there
was no significant difference between them (see table 2).
Table
2 Comparison of Jipailin and Fragmin
|
Group
|
case
|
Clotting
of blood in dilalyzator
|
Coagulant
deposition in catheter
|
|
0
|
Ⅰ
|
Ⅱ
|
Ⅲ
|
0
|
Ⅰ
|
Ⅱ
|
Ⅲ
|
|
Jipailin
|
156
|
156
|
0
|
0
|
0
|
156
|
0
|
0
|
0
|
|
Fragmin
|
156
|
154
|
2
|
0
|
0
|
156
|
0
|
0
|
0
|
Under
X2-test analysis , there was not significant
difference between Jipailin and Fragmin groups , P>0.05
2.2
Comprarison of Jipailin and UFH
The clotting
of blood degree in dialyzator of Jipailin was less than
UFH. There was no significant difference in coagulant deposition
in catheter(see table 3)
Table
3 Comparision of Jipailin and UFH
|
Group
|
case
|
Clotting
of blood in dialyzator
|
Coagulation
deposition in catheter
|
|
0
|
Ⅰ
|
Ⅱ
|
Ⅲ
|
0
|
Ⅰ
|
Ⅱ
|
Ⅲ
|
|
Jipailin
|
314
|
72
22.9%
|
198
63.1%
|
41
13.1%
|
3
1.0%
|
124
39.5%
|
177
56.4%
|
12
3.8%
|
1
0.3%
|
|
UFH
|
309
|
50
16.2%
*
|
191
61.8%
|
65
21.0%**
|
3
1.0%
|
112
36.3%
|
183
59.2%
|
13
4.2%
|
1
0.3%
|
Under
X2-test analysis, *(p<0.05) means there was significant
difference between Jipailin and
UFH
in grade0 of clotting of blood in dialyzator.
**(p<0.01)
means there was significant difference between Jipailin
and UFH in grade Ⅱ of clotting of blood in dialyzator.
3.Time
needed for pressure at puncture site
Expressed
in average, Jipailin group was 7 minutes, Fragmin group
10 minutes, and UFH 6 minutes. The time needed in Jipailin
group was shorter than that of Fragmin (P<0.05), there
was no significant between Jipailin and UFH group (P>0.05).
4.
Comparison of haemodialysis repeated application times for
single dialyzator
Table
4 Comparison of haemodialysis repeated application times
for single dialyzator in each group
|
Group
|
case
|
Haemodialysis
times
|
Average
haemodialysis repeated application times using single
dialyzator
|
|
Jipailin
|
119
|
470
|
3.95
|
|
Fragmin
|
39
|
156
|
4
|
|
UFH
|
80
|
309
|
3.86*
|
Under X2-test
analysis, there was no significant difference between Jipailin
and Fragmin groups when P>0.05, whereas there was significant
difference between Jipailin and UFH groups when P<0.05.
The
119 patients of Jipailin group received haemodialysis for
470 times; the 39patients of Fragmin group received haemodialysis
156 times; the 80 patients of UFH group received haemodialysis
309 times. There was no significant difference between Jipailin
and Fragmin groups in the average haemodialysis repeated
application times using single dialyzator( P>0.05). Whereas
there was significant difference between Jipailin and UFH
group (P<0.05). see Table 4
5. The relation
of time needed for pressure at puncture site and body weight
The
relation co-efficient number of the body weight of Jipailin,
Fragmin and UFH groups and time needed for pressure at puncture
site and weight were 0.10, 0.42,0.04 respectively, indicating
body weight is not related to pressure time under fixed
dosage of heparin.
6.
Adverse reaction
No
hypersusceptibility, severe bleeding, gastrointestinal-tract
reactions, pyrogen reaction or other adverse reactions were
found for 119 patients during the period of observation
in two courses.
Discussion
LMWH
is produced through nitrous acid depolymerization of UFH
or other methods followed by separation and collection of
the low molecular weight parts. It acts by inhibiting factor
Xa activity whereas has only weak effects on Ⅱa. Therefore,
compared with UFH, LMWH doesn't significantly increase the
bleeding tendency of patients whereas showing sufficient
efficacy under anti-coagulant extracorporeal circulation.
In this study, dialysis lasting 4-5 hours has been accomplished
both in Jipailin group and Fragmin group. Not only the ratios
of accomplishing the total course were higher than that
of UFH group, but also without obvious bleeding tendency
or other side effects. The results show Jipailin can be
used as an effective and safe anti-coagulant during haemodialysis
as Fragmin.
Through
the observations on clotting of blood in dialyzator and
coagulant deposition in catheter ,anti-coagulant effects
of Jipailin were similar to Fragmin and stronger than UFH,
the same applied in the repeated application times used
for single dialyzator. We noticed that anticoagulant effects
depended on the type of dialyzator , therefore dosage should
be adjusted according to the quality of dialyzator in clinical
use later.
Time
needed for pressure at puncture site was affected by many
factors, for example, basal blood clotting state of patient,
the skin state at puncture site, whether repeatedly puncture
the original eyelet or not, the method of pressing to stop
bleeding and so on, which might lead to different results
for different study and observation methods.
In
this study Jipailin and Fragmin used were of the same dosage,
5000IU single injection was applied. UFH was applied according
to normal individual dosage of patient, total dosage including
the first and maintaining was 52.2±11.8mg by average.LMWH was superior or
identical to UFH in all indexes, indicating Jipailin has
wide range of safe dosage and convenient to use as Fragmin.
It should be mentioned that although the same dosage was
applicable for most of patients, blood clotting in exceptional
cases was relatively high or time needed for pressure at
puncture site was prolonged. So in order to further improve
anticoagulant effects and the quality of dialysis ,we suggest
that the dosage should be adjusted according to the difference
of individuals. The dosage adjusting is not related to body
weight.
In
conclusion, domestic LMWH Jipailin is similar to imported
LMWH Fragmin in anti-coagulant efficacy during haemodialysis,
and more effective, safer and more convenient than UFH.
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