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MEAS URM EN T O F FIBR IN DEG RDATI ON PR ODU CTS I N CH RONIC R EN AL

FAI LU RE PATI EN TS USIN G D-DI MER TEST


Submitted by: Mohammed Jomaa Ali Al-haj Faraj
B.Sc. In Medical Laboratory Sciences
UNIVERSITY OF SCIENCE AND TECHNOLOGY
YEMEN ( 2001 )
A Thesis
Submitted for Fulfillment of Master Degree
IN
Medical Laboratory Sciences ( Hematology )
Faculty of Medical Laboratory Sciences
UNIVERSITY OF GEZIRA
Main Supervisor: Prof. Ahmed Abdalla Mohamedani
MBBS,D.C.P,F.R.C. Path. U.K.
Co Supervisor: Dr. Mohammed Al-sabq
MD, Medicine
( September 2006 )
It is disseminated intravascular
coagulation with widespread deposition
of fibrin and platelets within the
microcirculation and consumption of
.coagulation factors and platelets
Cont.
Systemic
activation of
coagulation

Intravascular Depletion of
deposition of platelets and
fibrin coagulation
factors

Thrombosis of
small and Bleeding
midsize vessels
and organ failure

The mechanism of disseminated intravascular coagulation


Cont.

The clinical and laboratory features of


acute disseminated intravascular
coagulation differ from those of
chronic disseminated intravascular
.coagulation
Con.

:Laboratory findings *
Prolonged prothrombin time, activated partial -
. thromboplastin time and thrombin time
- Decreased fibrinogen levels.
- Increased levels of fibrin degradation products
and D-dimer tests.
- Relative or absolute decrease of Platelet count.
- Presence of schistocytes in peripheral smear.
Cont.

*Laboratory findings:
- Modestly increased prothrombin time
in some patients
- Shortened or lengthened partial
thromboplastin time.
- Normal thrombin time in most patients.
- High, normal or low platelet count.
- Increased levels of fibrin degradation products
and D-dimer.
Cont.

 The association of altered hemostasis and


uraemia has long been recognized, as well as the
fairly high morbidity associated with such
events.
 The pathogenesis of bleeding disorders is
multifactorial and no single explanation.
 The platelet count in ureamia is usually
normal, but platelet function is impaired.
Cont.

 There was a previous belief that some dialyzable


substances, found in increased concentration in the
plasma of uremic patients, could play a role in the
abnormal platelet function seen in chronic renal
failure.
Thrombotic and severe haemorrhagic
complications are common in patients with end stage
renal disease and contribute substantially to the
morbidity and mortality in this populations.
Cont.

Disseminated intravascular coagulation


(DIC) remains a clinical diagnosis
supported by laboratory data.
Cont.

What is D-dimer ?

D-dimer is a protein that is released


into the circulation during the process
of fibrin blood clot break down.
Cont.

 D- dimer tests are ordered, a long with other


laboratory tests and imaging scan to help
rule out, diagnosis and monitor disease and
conditions that cause hypercoagulability.
 One of the most common of these conditions
is DVT and pulmonary embolism.
Cont.

 Measurements of D-dimer may also be


ordered, along with other tests, to help
diagnosing DIC (Disseminated intravascular
coagulation).
 D-dimer levels may be used to monitor
the effectiveness of disseminated
intravascular coagulation treatment.
Cont.

 There are many different D-dimer


assays currently available on the market.

 All of these assays rely on monoclonal


antibodies.
 The original assay is semi-quantitative and
utilizes visual macroscopic latex agglutination
(used in disseminated intravascular
coagulation diagnosis).
Cont.

 The most sensitive quantitative D-dimer


assay is based on the ELISA format.

 The most practical quantitative assays are


the latex-enhanced photometric assays that
are turbidimetric or colorimetric.
Cont.

What are FDPs?

Fibrin degradation products (FDPs), also known as


fibrin spilt products, are present in blood when the
thrombolytic enzyme plasmin cleaves fibrin or
fibrinogen.
This is a test that measures fibrin degradation
products (which are produced when clots
dissolve) in blood.
Cont.

 The measurement of FDPs provides a


direct indication of the activity of the
fibrinolytic (clot dissolving) system.

 When they are present in large amounts,


they indicate increased fibrinolysis, or clot
breakdown.
To determine the level of D-dimer in
chronic renal failure patients using a
latex agglutination method.
Cont.

1. To evaluate the association between chronic


renal failure and disseminated intravascular
coagulation.
2. To evaluate the effect of dialysis on the
level of D-dimer test, FDPs and
others .
3. To evaluate performance of FDPs
screening test.
4. To compare the performance of FDPs
compared to D-dimer test.
Study area:
This is study was conducted at Gezira hospital for
renal diseases and surgery.

Study population:
Patients diagnosed as chronic renal failure (CRF).
Study location:
The study conducted in central laboratory at Gezira hospital
for renal diseases and surgery.
Cont.

Sample selection and size :


Blood samples obtained
from adult males and females (aged between 10 to 70 years).
During the period from March 2005 to November 2005 as
follows:

-Control persons 60 samples with no clinical or Biochemical


evidence of renal failure.
-Patients with chronic renal failure 120 samples.
-60 samples pre-dialysis.
-60 samples post-dialysis.
-The total numbers of samples was 180 samples.
Cont.

Study design:
It was an observational prospective comparative
case control study.

:Data collection
A questionnaire was designed to collect
demographical and clinical data.
Using latex agglutination slide test for
qualitative and semi-quantitative assay.
Cont.

Using qualitative and semi-quantitative


determination of FDPs in plasma by
latex agglutination method.
Cont.

Note:
In addition to D-dimer & FDPS tests, we
performed both PT & APTT tests.
Age Distribution
: 30

27
25

20

17
15
13

10
Percent

3
0
10-20 21-30 31-40 41-50 51-60 61-70

age group
Cont.

Sex
distribution :

Male 71.7%
(I n (43
Female
28.3%
In (17)
Cont.

:Table (1): Types and frequency of dialysis

Type of
No of patients Percent %
dialysis
Peritoneal
Dialysis 20 33.3

Haemodialysis 40 66.7

Total 60 100.0
Cont.

Table (2): Duration of Haemodialysis:

Duration /
No. of patients Patient %
months
1-6 20 50.0
7-12 10 25.0
13-18 3 7.5
19-24 2 5.0
25-30 1 2.5
31-36 1 2.5
37-42 1 2.5
43-48 2 5.0
Total 40 100.0
Cont.

Table (3): Duration of Peritoneal dialysis:

No. of dialysis No. of patients Patient %

1 6 30.0
2 8 40.0
3 4 20.0
4 1 5.0
6 1 5.0
Total 20 100.0
Cont.

Table (4): Result of D-dimer test pre peritoneal and haemodialysi

Type of dialysis Level of D-dimer Frequency Patient %


< 0.5 6 30.0
<0.5 > 1.0 6 30.0
Peritoneal <1.0 < 2.0 3 15.0
Dialysis <2.0 <4.0 3 15.0
> 4.0 <8.0 2 10.0
Total 20 100.0
< 0.5 12 30.0
> 0.5 < 1.0 23 57.5
Haemodialysis > 1.0 < 2.0 3 7.5
> 2 < 4.0 2 5.0
Total 40 100.0
Cont.

Table (5): Result of D-dimer test post peritoneal & haemodialysis

Type of Level of D- Frequency Patient %


dialysis dimer
< 0.5 6 30.0
> 0.5 < 1.0 6 30.0
Peritoneal > 1.0 < 2.0 3 15.0
Dialysis > 2.0 < 4.0 3 15.0
> 4.0 < 8.0 2 10.0
Total 20 100.0

< 0.5 26 65.0


> 0.5 < 1.0 13 32.0
Haemodialysis <1.0 < 2.0 1 2.5
Total 40 100.0
Cont.

Table (6): Result of FDPS test pre peritoneal and haemodialysis:

Level of
Type of dialysis Frequency Patient %
FDPS
< 5.0 5 25.0
Peritoneal > 5.0 < 20 4 15.0
Dialysis > 20 11 60.0
Total 20 100.0

< 5.0 17 42.5


<5.0 <20 14 35.0
Haemodialysis > 20 9 22.5
Total 40 100.0
Cont.

Table (7): Result of FDPS test post peritoneal and haemodialysis:

Type of dialysis Level of FDPS Frequency Patient %

< 5.0 5 25.0


Peritoneal > 5.0 < 20 3 15.0
Dialysis > 20 12 60.0
Total 20 100.0

< 5.0 26 65.0


> 5.0 < 20 11 27.5
Haemodialysis
> 20 3 7.5
Total 40 100.0
Cont.
Table (8) T-test between pre PT and post PT
in the types of dialysis:

Type of Dialysis N Mean Correlation P value

Pre PT
Peritoneal 20 16.6
& post 0.98 0.189
Dialysis 20 16.2
PT

Pre PT& 40 14.6


Haemodialysis 0.968 0.000
Post PT 40 18.6

P value < 0.05 is*


.significant
Cont.
Table (9) Test of significant between pre APTT and post APT
according to type of dialysis :

Type of Dialysis N Mean Correlation P value

Peritoneal Pre PTT 20 31.05 0.963 0.016


Dialysis Post PTT 20 29.5 0.963

Pre PTT 40 36.3 0.915 0.000


Haemodialysis &
Post PTT 40 42.9

P value < 0.05 is*


.significant
Cont.

Table (10) D-dimer and FDPs of Controls:

Test N Frequency percent


D-dimer
60 60 100
<0.5
FDPs <5.0 60 60 100

All controls (n=60 ) were normal for both D-dimer (<0.5µg/ml) &
FDPs (<5.0µg/ml).
 D-dimer is a blood test performed in the medical
laboratory to diagnose I.V. thrombosis. When clots
are formed at the wrong time and place as a result of
underlying disease, D-dimer becomes available
marker because its presence indicates the
occurrence of unwanted thrombotic events.
 In this study the majority of the cases (38.3%)
were 50 years and above. At this age we expect
co-morbid conditions, which warrant a timely
multidisciplinary approach towards the management
of chronic renal failure.
Cont.

 There are gross clinical problems regarding those


patients with high D-dimer and/or FDPs. There might
be also some subclinical problems. This may have an
effect on the morbidity and mortality of these patients.
We observed that those with high D-dimer and/or
FDPs bled more at the site of veinipuncture.

 Elevated baseline levels of D-dimer and FDPs


test in chronic renal failure.
Cont.

 Plasma level of D-dimer and FDPs were


significantly elevated in patients before peritoneal
dialysis and haemodialysis but both (D-dimer and
FDPs) showed normal or decreased level after
haemodialysis (may be due to heparin intake because
the heparin can decrease D-dimer and possibly
generate a falsely low value), and no changes
occurred after peritoneal dialysis because the
.patients usually are not given heparin
Cont.

 Matsui E. and etal. results on fibrinolaysis in End


Stage Renal Disease have shown decreased fibrinolytic
activity in uraemia. Tomura S. and etal. have
documented hyperfibrinolaysis of coagulation activation,
which seems to be secondary to fibrin deposition.
Our results show activation of the fibrinolytic system,
as evidenced by raised levels of D-dimer.
 Comparing the levels of D-dimer with FDPs
different results were obtained.
Cont.

 The D-dimer test is more accurate and sensitive


compared to FDPs test. It is important to remember
that high concentration of FDPs are not specific for
disseminated intravascular coagulation, as they may
occur after surgery, in patients with haematomas and
liver or renal failure`. So, when in doubt, a D-dimr
test is useful, as it is specific for fibrin degradation
and thus indicates that thrombosis has occurred
before fibrinolysis, thereby distinguishing
disseminated intravascular coagulation from primary
fibrinolysis.
Cont.

 Looking at the prothrombin time (PT) and activated


partial thromboplastin time (APTT) of our study
patients, they showed increased PT and APTT in 7 out
of 40 haemodialysis cases and 6 out of 20 peritoneal
dialysis cases.
 Most studies found that PT and APTT were normal
before haemodialysis and peritoneal dialysis, but both
showed significant prolongation after haemodialysis and
no changes occurred after peritoneal dialysis. This
prolongation may be due to heparin therapy because
heparin can contribute to an increase in PT and APTT.
Cont.

 The results of PT & APTT are agreement with Enaam


Hussein results (In Khartoum), who studied a group of 30
patients (20 patients on haemodialysis and 10 on
peritoneal dialysis) she found that PT and APTT were
normal before haemodialysis and peritoneal dialysis, but
both showed significant prolongation after haemodialysis
and no changes after peritoneal dialysis .
 Seven of out 60 patients (haemodialysis and
peritoneal dialysis patients) had classical laboratory
findings of DIC i.e. elevation of D-dimer, FDPs, PT
and APTT.
Cont.

 Whether these results may contribute to and add


more complications to renal failure patients needs to
be investigated further as they may be suffering from
some degree of disseminated intravascular
coagulation.
 In this study the levels of D-dimer and FDPS
tests were increased in chronic renal failure
patients (peritoneal dialysis and haemodialysis
patients).

 Both D-dimer and FDPS tests showed normal


and decreased level after haemodialysis (may be
due to heparin therapy), and no changes occurred
after peritoneal dialysis.
Cont.

 The D-dimer test is more accurate and sensitive


compared to FDPS test .The D-dimer test is a confirmatory
test for diagnosis disseminated intravascular coagulation.

 PT and APTT tests were normal before


haemodialysis and peritoneal dialysis, but both
showed prolongation after haemodialysis (may be due
to heparin therapy) and no changes occurred after
peritoneal dislysis, but some patients had abnormal
PT and APTT before and after dialysis.
1. Further studies are suggested to explain more the
relationship between chronic renal failure and
disseminated intravascular coagulation.
2. The use of D-dimer test is recommended to
confirm diagnosis of disseminated intravascular
coagulation.
3. Periodical coagulation profile test in chronic renal
failure patients are advisable.
My deep and sincere gratitude to my
supervisor prof. Ahmed Abdalla Mohamedani,
professor of pathology, Dean Faculty of
Medical Laboratory Science, University of
Gezira, and to my Co-Supervisor Dr.
Mohammad Al-Sabq, Director General of
Gezira Hospital for Renal Diseases and
surgery. My thanks are due to all the staff of
the central laboratory in the Gezira Hospital
for Renal Diseases and surgery for their help
and cooperation.
My thanks are also due to Dr. Ameer Hasabo,
T