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Alteration of blood coagulation in chronic kidney disease

patients undergoing dialysis

Project Report Submitted in Partial fulfilment of the requirement for the


award of Bachelor of Science in
DIALYSIS THERAPY TECHNOLOGY (DT)
Session 2020-2022
To

The ICFAI University Tripura, Kamalghat Tripura, 799010


By
Ananya Deb
Dialysis Therapy Technology (DT)
ID Number –18IUT0290004

Under the Supervision


Of
Mr. Waikhom Somraj Singh
The ICFAI University Tripura

August 2022
Abstract

Patients with Chronic kidney disease (CKD) are characterized by endothelial dysfunction and
increased coagulation. The abnormal haemostatic profiles may contribute to the elevated risk of
thrombotic events. CKD with its high prevalence, morbidity and mortality is an important public
health problem. Considering the nature of the haemodialysis process, it has a considerable impact
on the coagulation profile. Post dialysis values of platelet count were found to be decreased than
pre dialysis values.
This study of Coagulation profile and platelet count in pre and post haemodialysis patients with
chronic renal failure. In this study, there was significant reduction in platelet count from mean 2.29
cells/cu.mm in pre dialysis to 2.03 cell/cu.mm in post dialysis. There was a significant prolongation
in both Prothrombin time (PT) and Activated Partial Thromboplastin Time (aPTT) values in post
dialysis.
CKD patients to higher risk of bleeding disorders, which may have a role in increasing the rate of
patient mortality and morbidity. There is a need for nephrologist to monitor the coagulation profile
and platelet count of CKD patients on dialysis, and treat any derangements in the same, to improve
outcome for these patients.

i
The ICFAI University Tripura,
Faculty of Allied Health Sciences,
Kamalghat, Tripura-799010, INDIA.

CERTIFICATE BY GUIDE

Certified that this project report titled “Alteration of blood coagulation in chronic kidney disease
patients undergoing dialysis” is the bonafide work of “Ananya Deb” who carried out the project
work under my supervision in the partial fulfillment of the requirements for the award of the
Bachelor of Science in Dialysis Therapy Technology (DT).

Mr. Waikhom Somraj Singh


Assistant Professor
Department of Allied Health Sciences
ICFAI Tripura

ii
DECLARATION BY THE STUDENT

I, Ananya Deb bearing Reg. No: 18IUT0290004 hereby declare that this project report entitled
“Alteration of blood coagulation in chronic kidney disease patients undergoing dialysis” has
been prepared by me towards the partial fulfilment of the requirement for the award of Bachelor of
Science in Dialysis Therapy Technology (DT) under the guidance of Mr. Waikhom Somraj
Singh.

I also declare that this project report is my original work and has not been previously submitted for
the award of any Degree, Diploma, Fellowship, or other similar titles.

Ananya Deb
ID Number: 18IUT0290004

Place: Agartala
Date: 24th August, 2022
.

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Table of Contents

CHAPTER I – INTRODUCTION ......................................................................................... 1-2


1.1 Introduction .................................................................................................................. 1-2
CHAPTER 2 – SCOPE AND OBJECTIVE.............................................................................. 3
2.1 Scope of the study............................................................................................................ 3
CHAPTER 3 – LITERATURE REVIEW ............................................................................ 4-10
3.1 Introduction ................................................................................................................ 4-10
CHAPTER 4 –MATERIALS AND METHODS ............................................................... 11-13
4.1 Research approach ......................................................................................................... 11
4.2 Research design ............................................................................................................. 12
4.3 Data collection ............................................................................................................... 13
CHAPTER V – RESULTS AND DISCUSSION............................................................... 14-16
CHAPTER VI –CONCLUSIONS & RECOMMENDATIONS ............................................. 17
6.1 Conclusion ..................................................................................................................... 17
6.2 Suggestion ..................................................................................................................... 17
CHAPTER VII – LIMITATIONS AND SCOPE OF FUTURE RESEARCH ....................... 18
7.1 Limitation ...................................................................................................................... 18
7.2 Scope of Future Research .............................................................................................. 18
REFERENCES ................................................................................................................... 19-20

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Chapter 1
Introduction

1.1 Introduction

The introduction of new anticoagulants into clinical practice has again shed light on the
problem of coagulation disorders in patients with chronic renal failure as these patients can
experience severe bleeding disorders during a therapy with microparticles and microRNAs
compounds. A major problem is the prolonged half-life of some new substances due to
pharmacokinetic changes accumulation of the compounds during renal failure. Little is known so
far about the reasons why one patient develops bleeding problems, while another tends to head
towards excessive thrombus formation. However, both problems are of significant clinical
relevance as some patients can be endangered by fatal bleeding episodes such as prolonged
bleeding from the dialysis fistula, gastrointestinal bleeding, or cerebral hemorrhage, while other
patients experience a prothrombotic status associated with an increased number of cardiovascular
events or recurrent thrombosis of the dialysis access with insufficient dialysis quality. The reasons
for these disorders are complex and involve the coagulation cascade, the fibrinolytic system, the
platelets, the endothelium, or the vessel wall with its extracellular matrix. The relationship between
these components is influenced by uraemic toxins and metabolic compounds accumulating during
renal insufficiency [12].
Chronic kidney disease (CKD) is a global health problem, with a very high cost of care and
a great burden particularly in developing countries like India. The Kidney Disease Outcomes
Quality Initiative describes 5 stages of CKD, with the Stage 5 being End Stage Renal Disease
(ESRD) which is characterized by progressive, irreversible deterioration in the renal function and
the body failing to maintain fluid and electrolyte balance resulting in uraemia [6]. In CKD both
bleeding and thrombotic complications are observed mainly because of disturbed balance between
pro and anti-haemostatic factors, leading to high morbidity and mortality [16]. Due to the high cost
and difficulty in finding a compatible organ donor associated with transplantation, dialysis remains
as one of the most common modalities of RRT worldwide [5]. Haemodialysis (HD) results in
alterations of platelet function and changes in both coagulation and fibrinolytic systems. Platelets
have been well-known to interact with dialysis membranes since the 1970’s; dialysis membranes
have been shown to cause platelet adhesion, aggregation, and activation [7]. Thrombotic events

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result from variations in vessel wall integrity, platelet activation and reduced blood flow into the
fistula used to access the vessel. Hypercoagulability states are associated with cerebral spill, cardiac
disease, and pulmonary embolism. Both PT (Prothrombin time) and aPTT (activated Partial
Thromboplastin time) tend to increase post dialysis. In cases where fistulas of
polytetrafluorethylene (PTFE) are used, increased coagulation has a risk for thrombus formation in
vascular access for dialysis [9]. The aim of the study is to find out the variations in platelet count,
PT, International Normalized Ratio (INR) and aPTT before and after HD. The present study might
help the clinicians to initiate proper precautions before and after the dialysis procedures.

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Chapter 2
Scope and Objective

2.1 Scope and objective of the study

With studying the literature and looking after the diagnosis of the patients, it has been
discovered that Thromboembolic events are the major factor affecting the prognosis of patients
with chronic kidney disease. Haemostatic alterations are possible causes of these complications, but
their roles remain poorly characterized.
In the prospective observational study, our main objectives are-

➢ To investigate the entire coagulation process in dialysis patients.


➢ To investigate the dialysis patients with chronic kidney disease to elucidate the mechanisms
of their high thromboembolic risk.
➢ To understand the complete phenomenon behind the alteration of blood coagulation in
dialysis patients.

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Chapter 3
Literature Review

3.1 Introduction

In the recent years, early demises of dialysis patients due to the alteration of blood
coagulation, force us to identify and discover many new methods for remediation of such incidents.
It has been obvious that after going through literature and past record, we might be knowing the
remediation method and discover new methods for mitigation of alteration of blood coagulation in
chronic kidney disease patients undergoing dialysis treatment.

Alghythan and Alsaeed (2012) have studied and found that most of the hematological
parameters measured in HD patients, pre- or post-HD were either elevated or lowered compared to
the control groups. Furthermore, it was noticed that there were changes in these parameters between
post-HD and pre-HD levels. More significantly, PT, APTT and fibrinogen were found to increase
post-HD compared to pre-HD procedures while there was a concurrent decrease of platelet counts.
A significant positive correlation was noticed between the period the patients have been on dialysis
and each of fibrinogen, APTT and PT levels. However, there was a significant negative correlation
between the time periods the patients have been on dialysis and platelets count. Thus, the longer the
time period the patients are on dialysis, the more the coagulation profile is affected, that is,
fibrinogen, APTT and PT levels increase with longer duration of HD whereas the platelet count
decreases with longer duration of HD. Therefore, it is recommended that all patients be screened
appropriately before and after dialysis to avoid complications. The present investigation might help
clinicians to initiate precautions before and after dialysis procedures. Thus, it is recommended that
all patients be screened appropriately before and after dialysis to avoid complications [1].

Chakravarti et al. (2017) have studied and found that anemia was prevalent 96.8% cases
and the cause of anemia is understood to low erythropoietin levels but the data of that is not
available in this study. Hb less than 9 gm% was statistically significant in CKD patients.
Normocytic normochromic morphology was seen in majority of anemias. Neutrophilic
Leucocytosis was seen in 27.3% cases and suggests underlying infective etiology in these patients.
Platelet count was on the lower side in 43.7% cases and thus further platelet function and
coagulation studies should be carried out to know the underlying cause. MCV was within the
normal limits. RDW was raised and statistically significant suggesting further workup to know the
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underlying pathophysiology. With this study you come to know how the various hematological
parameters varies in hemodialysis patients and how these parameters can affect the prognosis and
further management in these patients [2].

Dasaprakash et al. (2019). have studied and indicate that Hb and Red cell indices in pre or
post HD were either elevated or lowered. The most frequent finding is the moderate degree of
anemia in both pre and post dialysis patients, and there is increase in severity of anemia after
hemodialysis in many patients. However, in both pre and post dialysis, the anemia is normocytic
normochromic. These findings expose CKD patients to higher risk of anemia related complications,
which may have a role in increasing the rate of patient mortality and morbidity. In the light of this
study, there is a need for nephrologist to monitor the hematological profile of CKD patients on
dialysis, and treat any derangements in the same, to improve outcome for these patients [3].

Gautam and Patil (2018) have studied and found that-


i. Most of the hematological parameters like Hb, WBC, MCH, MCHC and HCT increased
after HD as compared to predialysis cases. Platelet count was found to be decreased after
dialysis as compared to predialysis cases.
ii. So, to evaluate the effectiveness of hemodialysis, it is necessary to test the complete
hemogram before and after HD [4].

Habib et al. (2017) have studied and found that thrombocytopenia is regarded because of
hemodialysis. Platelet count tends to be decreased in both pre-dialysis and hemodialysis patients.
However, its occurrence is rare in patients undergoing hemodialysis using biocompatible
membranes. Many studies found a statistically significant decrease in platelet count of CKD
patients. Chronic renal failure is associated with different degrees of abnormality in hematological
parameters that needs careful evaluation and management [5].
Hakim et al. (2016) have studied and found that-

i. 99,5% of patients have reduced platelets count after hemodialysis, while 0.5% have stable
count of platelets.
ii. 98,5% of patient have reduced hemoglobin concentration after hemodialysis.
iii. 83,9% show increase in total white blood cells count after hemodialysis.
iv. 14,1% have stable white blood cells count and only 2% their count decrease from pre-
dialysis count [6].

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Huang et al. (2017) have found that Patients with chronic kidney disease commonly have
blood coagulation disorders. Thromboembolic events are the major factor affecting the prognosis of
complications, but their roles remain poorly characterized. Patients with chronic kidney disease are
characterized by endothelial dysfunction and increased coagulation, especially FVIII activity. The
abnormal haemostatic profiles may contribute to the elevated risk of thrombotic events but further
longer-term study with large samples is still required to determine the relationship more precisely
between the elevation of procoagulant factors and clinical outcomes [7].

Jalal et al. (2010) have studied and found that CKD patients exhibit many abnormalities in
their hemostatic response that may account for their increased risk of both atherothrombotic events
and bleeding. The early stages of CKD are mainly dominated by derangements that likely result in
increased risk of major cardiovascular events disease, a major source of morbidity and mortality in
these individuals. In patients with advanced CKD, the procoagulant state persists, and in addition
uremia is strongly associated with platelet dysfunction that gives these patients an increased risk of
hemorrhagic events. Much of these pathways remain poorly characterized in patients with CKD.
Although the current belief is that hemostatic abnormalities such as increased circulating TF and
PAI-1 may contribute to the increased risk of cardiovascular disease, the exact role that any one
abnormality may play is unknown. Therefore, identifying potential therapeutic targets is difficult.
Furthermore, it is still unclear how these procoagulant tendencies in patients with CKD interact
with other traditional and nontraditional cardiovascular risk factors. The current treatment
recommendations in patients with CKD are based on clinical trials conducted in the general
population, and these trials have generally excluded individuals with CKD. Thus, further research is
required to better understand the procoagulant state in patients with CKD, to explore the role it
plays in increasing cardiovascular morbidity and mortality in this patient population, and to identify
potential therapeutic interventions that could translate into improved cardiovascular and potentially
renal outcomes in these patients [8].

Khalid and Zafar (2015) have studied and found that coagulation parameters; prothrombin
and activated partial thromboplastin time are prolonged after hemodialysis in patients with end
stage renal disease. Therefore, monitoring of coagulation (prothrombin and activated partial
thromboplastin time) parameters may help in determining the risk of development of bleeding
complications and the consequent increasing morbidity rate and therefore may be used as a guide
for further management of their patients [9].

Kovesdy et al. (2016) have studied and found that in veterans with incident CKD, SBP

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showed different associations in older versus younger patients. The association of higher SBP with
adverse outcomes was present but markedly reduced in older individuals, especially in those aged
≥80 years. Elevated DBP showed no consistent association with vascular outcomes in patients with
incident CKD [10].

Lutz et al. (2013) have studied the coagulation system has gained much interest again as
new anticoagulatory substances have been introduced into clinical practice. Especially patients with
renal failure are likely candidates for such a therapy as they often experience significant
comorbidity including cardiovascular diseases that require anticoagulation. Patients with renal
failure on new anticoagulants have experienced excessive bleeding which can be related to a
changed pharmacokinetic profile of the compounds. However, the coagulation system itself, even
without any interference with coagulation modifying drugs, is already profoundly changed during
renal failure. Coagulation disorders with either episodes of severe bleeding or thrombosis represent
an important cause for the morbidity and mortality of such patients. The underlying reasons for
these coagulation disorders involve the changed interaction of different components of the
coagulation system such as the coagulation cascade, the platelets, and the vessel wall in the
metabolic conditions of renal failure. Recent work provides evidence that new factors such as
microparticles (MPs) can influence the coagulation system in patients with renal insufficiency
through their potent procoagulant effects. Interestingly, MPs may also contain microRNAs thus
inhibiting the function of platelets, resulting in bleeding episodes. This review comprises the
findings on the complex pathophysiology of coagulation disorders including new factors such as
MPs and microRNAs in patients with renal insufficiency [11].

Mandi et al. (2016) have found that –

a. In the pre-dialysis group, all the studied parameters were affected more than in the group of
patients who were stable with conservative management. So, the coagulation parameters are
progressively affected as the renal disease progresses.
b. In the group that was studied after dialysis, all the coagulation factors improved to a certain
extent. So, dialysis has an important impact on coagulopathy in CKD.
c. In all the groups studied, the coagulation parameters have no statistically significant correlation
with the degree of uremia, i.e., GFR. This may be because each of the three patient groups was
different, and each case was not studied as the disease progressed [12].

Matsuo and wanaka (2011) have studied and found that the principal of heparin re-exposure is
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based on a characteristic immune response in T-cell-independent B-cell activation because of the
lack of a memory response, perhaps explaining transience and a lack of anamnesis of the anti-
PF4/heparin immune response. The reexposure can be effectively performed due to a lack of
immune memory for the PF4/heparin complex antigen in patients with previous episodes of HIT
when their HIT antibodies are ablated in circulation. However, there is no clinical consensus
regarding re-exposure to heparin for acute HIT. The re-exposure is necessary at least 100 days after
no detection of HIT antibodies by ELISA. Reductions in the optical density of ELISA are quite
variable after the cessation of heparin. While a positive ELISA continues long-term over years, a
short span type is also recognizable. Since the various half-lives of HIT antibodies may reveal the
presence of different properties of HIT antibodies, each patient should be followed by ELISA until
there is no longer a detection of HIT antibodies. Reexposure to heparin should be introduced under
negative ELISA where adequate emergent measures are adopted, including platelet- counting tests.
Most heparin-re-exposure patients show no recurrence of HIT unless they undergo cardiovascular
surgery, catheter intervention, and, rarely, receive platelet-stimulating drugs. Re-exposure to
heparin in HD patients showing a stable titer with an optical density over 0.4 may not be allowed
because the risk of HITrecurrence is likely to rise on heparin reuse [13].

Nunns et al. (2017) have found that chronic kidney disease generates a distinct haemostatic
potential as compared to normal controls. CKD patients manifest a coagulopathy consisting of
delayed clot formation with increased final clot strength and decreased clot breakdown when
compared to healthy patients. The increased clot strength (maximal amplitude) that is seen in this
population is mediated by supra-normal fibrinogen levels. The increased clot strength and
decreased clot breakdown is attenuated in patients receiving haemodialysis. This increased clot
strength is mediated by increasing levels of fibrinogen. Given the known platelet dysfunction in
CKD, increased fibrinogen appears to be responsible for the observed hypercoagulability as a
compensatory mechanism to normalize haemostasis in the presence of platelet dysfunction.
Elevated fibrinogen levels have been shown to correlate with myocardial complications in patients
with Stage 5 CKD. This supports the theory that hyperfibrinogenemia and associated increased clot
strength as assessed by increased maximal amplitude, is mechanistic in the physiologic
coagulopathy and the complications with thrombosis in CKD patients clinically [14].

Pahim and Megalamane (2017) have studied and found that poor glycaemic control shows
significant changes in MPV and PDW, thus platelet indices play a very crucial role in diabetic CKD
patients. Hence, it aids as an important prognostic marker in assessing the complications. Basic
coagulation profile like PT and APTT can predict long term complications of diabetic platelets in

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these patients. Haemodialysis preferred treatment of choice having more advantageous effect with
few preventable causes which can be overcome with monitoring PDW and MPV values [15].

Pandian et al. (2017) have studied and found that many hematological parameters
measured in post dialysis patients were either increased or decreased when compared with those in
predialytic patients. The most frequent finding is the moderate degree of anemia in both pre- and
post dialysis patients, and, there is increase in severity of anemia after hemodialysis in many
patients. However, in both pre- and post dialysis, the anemia is normocytic normochromic.
Furthermore, there is a significant decrease in total leukocyte count and slight decrease in platelet
count. In this study, variations also noted in differential count with decrease in neutrophil along
with monocyte count and increase in lymphocyte as well as eosinophil count. Probably, many
factors were responsible for the observed changes in complete hemogram in patients on
hemodialysis. The present study might help clinicians to initiate precautions before and after
dialysis procedures and thereby reduce anemia, thrombosis, hemorrhage, and related complications
[16].

Raja et al. (2021) have found that hypertensive nephrosclerosis is the most common
cause of CKD. This may be an indicator of lack of blood pressure control in hypertensive
patients. Post dialysis values of platelet count were found to be decreased than pre dialysis
values. Coagulation studies like prothrombin time and activated partial thromboplastin time
were prolonged after hemodialysis. These findings expose CKD patients to higher risk of
bleeding disorders, which may have a role in increasing the rate of patient mortality and
morbidity. Therefore, monitoring of coagulation parameters (prothrombin and activated partial
thromboplastin time) may help the clinicians to determine the risk of development of bleeding
complications [17].

Sabry et al. (2009) have found that haemodialysis requires anticoagulation to avoid clotting
of the dialyser and extracorporeal circuit. Hitherto, the anticoagulation regimen has consisted of an
intravenous bolus dose of unfractionated heparin (UFH) followed either by continuous infusion or a
new bolus dose during dialysis. However, low-molecular-weight heparins (LMWHs) are being
frequently used as they were reported to have several potential advantages over UFHs. The risk of
bleeding is lower with LMWHs than with UFHs as LMWHs interact less with platelets and the
vessel wall. The risk of heparin-induced thrombocytopaenia is also less. In addition, the
administration is practical, and the effect on the blood lipids may be more favorable. LMWHs act
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longer than UFHs and can be given as a single-bolus injection at the start of the dialysis session.
LMWHs are as effective as UFHs in preventing thrombosis in animal models and cause less blood
loss than UFHs. However, these findings have not been confirmed in clinical studies.
Tinzaparin sodium should be considered as effective and well tolerated and may be a superior
alternative to conventional heparin anticoagulation in haemodialysis. However, at least – on the
short term – tinzaparin sodium therapy did not improve lipid profile in haemodialysis patients.
Currently, the direct cost in Saudi Arabia is a little more than standard heparin by about 23%.
However, with more widespread usage, the price of tinzaparin sodium is likely to reduce and the
small extra cost is counterbalanced by the convenience of administration [18].

Zoya et al. (2019) have studied and found that dialysis causes a visible and significant
change in various hematological and biochemical parameters, and to the coagulation profile as well,
so it is important for a clinician/nephrologist to keep these factors in mind while dealing with such
patients, to know the efficacy and adverse effects of hemodialysis and further planning the
necessary treatment [19].

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Chapter 4
Materials and Methods

4.1 Research approach

This study of coagulation profile and platelet count in pre and post haemodialysis patients with
chronic renal failure was conducted in the Department of Dialysis unit, Indra Gandhi Memorial
Hospital. A total of 150 patients diagnosed as CKD and subjected for haemodialysis were
included in this study. An informed consent was obtained from all the subjects. Haematological
changes were assessed before and after dialysis, by considering the parameters such as platelet
count, PT, INR and aPTT. Patients of all age group and gender diagnosed as chronic kidney disease
in the Department of Nephrology and initiated for renal replacement therapy in the form of
haemodialysis were included in this study. Patients suffering from muscular atrophy, malignancy,
inherited or acquired blood diseases, hepatitis or other liver diseases, infection, acute or chronic
inflammation, connective tissues diseases, dehydration, or recent haemorrhagic episode
were excluded from this study. Clinical history of Age, Gender, Cause of the disease, Duration of
haemodialysis and associated co-morbid illness (diabetes, hypertension) were recorded. The
parameters assessed for each case included:

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4.2 Research design

CKD related Anaemia Reduction in platelet activity


Exacerbated impaired platelet ➢ Disturbance in the composition of α
vessel wall interaction due to granules.
decreased ADP released and ➢ Alteration in arachidonic acid and
increased activation of prostaglandin metabolism and thromboxane
Prostaglandin I2 A2 synthesis/release.
➢ Decreased platelet adhesion and
aggregation.

Factors contributing to a
prohemorrhagic state in
patients with kidney failure

Therapies
Platelet vessel wall interaction
➢ Used in patients undergoing
surgical procedures. ➢ Insufficient binding of vWF and fibrinogen
➢ Β-Lactam antibiotics interfere to activated platelets.
with ADP receptors. ➢ Increased proteolysis of the platelet GPlb
➢ Aspirin or nonsteroidal anti- receptors.
inflammatory drugs. ➢ Decreased function of the GPllb-GPllla
complex.
➢ Increased levels of nitric oxide, which
inhibits platelet aggregation.

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4.3 Data collection
a) Platelet count: Under aseptic precautions, two milliliters of venous blood were obtained
by routine phlebotomy procedure from renal failure patients before and after
haemodialysis within 2 hours. The samples were collected in an Ethylene Diamine Tetra
Acetic Acid (EDTA) vacutainer and analyzed within 2 hours for platelet count using Sysmex
XT 1800i (automated haematology analyzer).

b) PT & aPTT: 2.7ml venous blood before dialysis and after dialysis within 2 hours was
collected in vacutainer containing anticoagulant of 3.2% trisodium citrate (0.3ml). The
international sensitivity index (ISI) of the reagent used was 0.95, where the PT of the control
sample was calculated to be 13 seconds & aPTT of the sample was calculated to be 31 seconds
using semiautomated analyzer (Stago START 4). The International Normalized Ratio (INR)
was calculated according to the chart provided by the reagent supplier (Hemosil)

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Chapter 5
Results and Discussion

In present study, out of 150 CKD patients, 104 (69.3%) were males and 46 (30.7%) were
females. The total number of cases were compared between males and females and was not
statistically significant (Table 1).

Table 1: Age and gender distribution of CKD patients.

Chi square
Age Group Female (n =46) Male (n =104) & P value
N % N %
21-30 3 6.5 4 3.8
31-40 7 15.3 12 11.5 𝑥 2 = 3.382
41-50 11 23.9 17 16.4 p= 0.496
51-60 14 30.4 33 31.8
>60 11 23.9 38 36.5

Table 2: Causes of ESRD leading to dialysis.

Causes of CKD No. of cases(n=150) Percentage of patients


Hypertensive nephrosclerosis 69 46
Diabetic nephropathy 46 30.7
Chronic glomerulonephritis 13 8.7
APCKD 2 1.3
Renal calculi 5 3.3
Drug induced 3 2
Ig A nephropathy 3 2
Lupus nephritis 3 2
Sea food allergy 1 0.7
Chronic Tubulointerstitial diseases 5 3.3

Table 3: Platelet count in pre and post dialysis values of CKD patients.

Platelet count (/ 𝑚𝑚3 ) Paired T test p value


Period Mean Standard error of
mean 14.352 0.0001
Pre dialysis 229260.00 8439.37
Post dialysis 203760.00 7653.97

Table 4: Grading of platelet count in pre and post dialysis values of CKD patients.

Grading of Pre dialysis Post dialysis Chi square


platelet count & p value
Class % Class %

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Normal platelet 128 85.3 105 70 𝑥 2 = 10.17
count &
Mild 16 10.7 33 22 P = 0.006
thrombocytopenia
Moderate 6 4 12 8
thrombocytopenia

Table 5: Mean PT, INR & aPTT in pre and post dialysis values of CKD patients.

Parameters Pre dialysis (n=150) Post dialysis (n=150) Paired T test P value
PT 15.99 ± 0.43 22.01 ± 0.47 -35.208 0.0001
INR 1.21 ± 0.03 1.65 ± 0.03 -35.109 0.0001
aPTT 40.31 ± 1.91 47.73 ± 1.91 -49.483 0.0001

Table 6: Platelet, PT and aPTT in post dialysis compared to pre dialysis with previous studies.

Study Year Cases Platelet PT aPTT


Pahim et al 2017 160 Increased No change Increased
Mandi et al 2016 30 Increased Decreased Decreased
Alghythan et al 2012 100 Decreased Increased Increased
Khan et al 2015 100 Decreased Increased Increased
Present study 2022 150 Decreased Increased Increased

The most common primary etiology for ESRD leading to dialysis was patient suffering from
hypertension 46% followed by diabetes 30.7%. The other causes included chronic
glomerulonephritis (8.7%), Adult Polycystic Kidney Disease (APCKD, 1.3%), renal calculi (3.3%),
drug induced (2%), Ig A nephropathy (2%), lupus nephritis (2%), sea food allergy (0.7%) and
Chronic tubulointerstitial disease (3.3%, Table 2).
The platelet count ranges from 69,000-7,05,000/mm 3 and 56,000 – 6,50,000/mm 3 in pre
dialysis and post dialysis respectively. There was significant reduction in platelet count from mean
2.29/mm 3 to 2.03/mm 3 in post dialysis when compared to pre dialysis value. This value was
statistically significant with a p value of 0.0001 (Table 3).
In this study, among pre dialysis a normal platelet count was noted in 85.3%, mild
thrombocytopenia in 10.7% and moderate thrombocytopenia in 4%. Normal platelet count was
present in 70%, cases with mild thrombocytopenia was increased to 22% in post dialysis when
compared with pre dialysis and cases with moderate thrombocytopenia was increased to 8% when
compared with pre dialysis values which was statistically significant (Table 4).
There was significant prolongation of prothrombin time from mean 15.99 sec and mean INR
1.21 to a mean value of 22.01 sec and mean INR 1.65 in post dialysis when compared to pre
dialysis. There was statistically significant prolongation of aPTT in post dialysis with mean of
47.73 sec when compared to pre dialysis value with mean of 40.31sec (Table 5).

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HD is the most common modality for renal replacement treatment in India where near
normal kidney function is attained in CKD patients with the use of HD machine. There is an averse
improvement in the life expectancy of CKD patients on HD over a long period of time and thus the
need to interpret haematological comorbidity associated with CKD. Among 150 patients
undergoing HD and enrolled for the study, 104(69.3%) were males with the maximum age of
>60years and 46(30.7%) were females, the maximum number of patients were from the age group
51-60 years. This could be explained due to the cause that most of the patients were identified with
hypertensive nephrosclerosis followed by diabetic nephropathy which is prevalent above 50years.
Similar findings were reported in studies conducted by and Hakim et al where CKD patients were
above 50years of age.
From the present study we found that there was a marked significant change in the
coagulation profile among CKD population. Platelet count decreased among the post dialysis when
compared with the pre dialysis value. In this study, there was significant reduction in platelet count
from mean 2.29 cells/cu.mm in pre dialysis to 2.03 cell/ cu.mm in post dialysis. The percentage of
cases towards thrombocytopenia increased after dialysis when compared to pre dialysis. Normal
platelet count was present only in 70%, cases with mild thrombocytopenia was increased to 22% in
post dialysis when compared with pre dialysis and cases with moderate thrombocytopenia was
increased to 8% when compared with pre dialysis.

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Chapter 6
Conclusions and Recommendations

6.1 Conclusion

Hypertensive nephrosclerosis is the most common cause of CKD. This may be an indicator of lack
of blood pressure control in hypertensive patients. Post dialysis values of platelet count were found
to be decreased than pre dialysis values. Coagulation studies like prothrombin time and activated
partial thromboplastin time were prolonged after hemodialysis. These findings expose CKD
patients to higher risk of bleeding disorders, which may have a role in increasing the rate of patient
mortality and morbidity. Therefore, monitoring of coagulation parameters (prothrombin and
activated partial thromboplastin time) may help the clinicians to determine the risk of development
of bleeding complications.

6.2 Suggestion
It has been observed that patients with irregular visit to the dialysis treatment hospital are facing a
lot of issues in their health. They are seeing lacking improvement in their health. In most of
irregular patients had fallen early demises. Their blood coagulation alters during treatment in
dialysis. The main recommendations to them are to consult with nephrologist regularly to monitor
their health issues. Patients should take care of their food consumptions.

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Chapter 7
Limitations and Scope of Future Research

7.1 Limitation

Follow up of patients more than one dialysis visit could not be done due to the irregular visit
of the patients for the dialysis procedure. The state of morbidity and mortality of the patients could
not be assessed as most of the patients were discharged after dialysis procedure.

7.2 Scope of Future Research

Future research should be directed towards the identification of the factors and their specific
site of interaction within the haemostatic system to specifically treat the related clinical problems.
Furthermore, research is needed to better understand under which conditions patients with renal
failure develop bleeding disorders or are more prone to thrombotic complications while others
experience bleeding disorders and thrombotic complications during a short period of time.
Moreover, the role of micro RNAs and microparticles for the development of disorders of the
coagulation cascade in renal failure warrants further research.

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