SSR Inst. Int. J.
Life Sci., 10(1): 3606-3610, Jan 2024
Coagulation
Dynamics in Type 2 Diabetes Mellitus: Insights from PT and APTT Assessment
Sandhyarani Pati1,
Madhuchhanda Mohapatra2,
Sandeep Das3, Sangram Kishore Sabat4*
1Assistant Professor, Department of
General Medicine, MKCG Medical College & Hospital, Berhampur, Odisha, India
2Assistant Professor, Department of
Skin and VD, MKCG Medical College & Hospital, Berhampur, Odisha, India
3Assistant Professor, Department of
Anaesthesiology, Fakirmohan Medical College & Hospital, Balasore, Odisha,
India
4Assistant Professor, Department of
Orthopedics, MKCG Medical College & Hospital, Berhampur, Odisha, India
*Address for Correspondence: Dr.
Sangram Kishore Sabat, Assistant Professor, Department of Orthopedics, MKCG
Medical College & Hospital, Berhampur, Odisha, India
E-mail: sabatsangram@gmail.com
ABSTRACT- Background: Diabetes mellitus is a global health
concern associated with significant cardiovascular complications, particularly
coronary artery disease. The hyperglycemic environment in diabetes contributes
to increased thrombotic risks, affecting platelet reactivity, fibrinogen
levels, thrombin formation, and fibrinolysis. Coagulation parameter
assessments, such as prothrombin time (PT) and activated partial thromboplastin
time (APTT), offer insights into potential coagulation impairments, aiding in
preventing thromboembolic cardiovascular events.
Methods: A cross-sectional study involved 400 Type
2 diabetes mellitus patients above 35 with HbA1c levels >7 at SLN Medical
College and Hospital, Koraput, Odisha. Exclusion criteria encompassed patients
on anticoagulants, hepatic failure, coagulation disorders, malignancy, coronary
artery disease, or cerebrovascular accidents. Collected data included fasting
and postprandial blood sugars, HbA1c levels, PT, and APTT.
Results: Patients with diabetes for over 5 years
exhibited a distinct coagulation profile, indicating a significant correlation
between diabetes duration and coagulation dynamics. Poor glycemic control
(HbA1c >9) was associated with shortened PT and APTT values, highlighting a
link between hyperglycemia and altered coagulation parameters.
Conclusion: This study underscores the association
between diabetes mellitus and altered coagulation profiles, emphasizing the
importance of routine PT and APTT assessments. Effective glycemic control is
not only pivotal in managing diabetes but also plays a crucial role in
mitigating hypercoagulable states, preventing both micro and macrovascular
complications.
Keywords: Type 2 diabetes, mellitus, Coagulation impairment, Prothrombin,
Thromboplastin, Glycated Haemoglobin
INTRODUCTION-
Diabetes
mellitus is one frequent endocrine disorder that seriously jeopardises public
health throughout the world. One of the main macrovascular effects of diabetes
is cardiovascular disease, particularly coronary artery disease, for which
people with diabetes have a two- to four-fold increased risk.[1]
People with diabetes are more prone to thrombotic issues due to factors such
reduced fibrinolysis, hyperfibrinogenemia, increased thrombin generation, and
platelet hyperreactivity brought on by hyperglycemia. Persistent hyperglycemia
caused by diabetes glycates essential clotting proteins such haemoglobin,
fibrinogen, and prothrombin, leading to coagulopathies.[2-5] APTT
and prothrombin time (PT) can be used to identify the extrinsic and intrinsic
coagulation pathways. An observable hypercoagulable state, indicated by shorter
PT and APTT in diabetes mellitus, may contribute to the formation of occlusive
thrombi in coronary arteries.[6,7]
This
study aims to ascertain the significance of routinely measuring PT and APTT to
understand the coagulation anomalies linked to diabetes mellitus and maybe
prevent thromboembolic cardiovascular events. The goal of the research is to
evaluate the coagulation profile in individuals with Type 2 diabetes, with a
focus on prothrombin time (PT) and activated partial thromboplastin time
(APTT).[8-10] Additionally, it searches for connections between
glycated haemoglobin (HbA1c), coagulation indicators, and the duration of
diabetes. The findings of this study provide valuable insights into the
coagulation dynamics in diabetes, which may lead to the development of more
efficient preventive treatments against thromboembolic cardiovascular
illnesses. The major objective of this study is to determine the significance
of routinely measuring prothrombin time (PT) and activated partial
thromboplastin time (APTT) in individuals with Type 2 diabetes mellitus. The
aim is to understand the potential role that coagulation abnormalities
associated with diabetes may have in developing thromboembolic cardiovascular
issues.
MATERIALS
& METHODS- This research employs a cross-sectional
study design conducted among 400 patients diagnosed with Type 2 diabetes
mellitus. The study is conducted over one year at the General Medicine
Outpatient Department in SLN Medical College and Hospital, Koraput, Odisha,
India.
Data
Collection- Data is collected from 400 eligible
patients with Type 2 diabetes mellitus attending the General Medicine
Outpatient Department at SLN Medical College and Hospital, Koraput, Odisha. The
following investigations are conducted for each participant: Fasting blood
sugar levels- Postprandial blood sugar levels - Glycated Hemoglobin (HbA1c)
levels - Prothrombin time (PT) and activated partial thromboplastin time
(APTT).
Outcome
Measures- The tests are performed, and the results and outcomes are
meticulously documented and analyzed. The investigation outcomes aim to provide
insights into the coagulation profile of Type 2 diabetes mellitus patients,
specifically focusing on PT and APTT. The data collected will be subjected to
statistical analysis to identify any correlations between glycemic control
(HbA1c levels) and the coagulation parameters and assess the overall
coagulation status of the study population.
Inclusion
Criteria
· Individuals
diagnosed with Type 2 diabetes mellitus
· Age
above 35 years
· HbA1c
levels greater than 7
Exclusion
Criteria
· Patients
meeting any of the following criteria are excluded from the study:
· Individuals
on anticoagulants.
· Patients
with hepatic failure.
· History
of coagulation disorders.
· Presence
of malignancy, coronary artery disease, or cerebrovascular accidents.
· Clinical
evidence of macrovascular and microvascular complications associated with
diabetes mellitus.
Statistical
Analysis- Descriptive statistics were used to summarise the
characteristics of the research population, while inferential statistics may
employ correlation analysis to examine correlations between variables.
Ethical
Approval- The study adheres to ethical standards, ensuring
patient confidentiality, privacy, and informed consent. Approval from the
institutional ethics committee is obtained before commencing the study.
RESULTS- The
study involved 400 patients who met the inclusion and exclusion criteria. Most
of the participants were above 40 years of age. The duration of diabetes was
categorized into two groups, and the distribution among the study participants
is presented (Table 1).
Table
1: Distribution of patients based on duration of diabetes among study participants
Duration of
diabetes |
Number |
Percentage (%) |
1-5
years |
280 |
70 |
>
5 years |
120 |
30 |
Total |
400 |
100 |
The
HbA1c levels were assessed and categorized into two groups, and the
distribution is given (Table 2).
Table 2: Distribution
of patients based on HbA1c results among study participants
HBA1C |
Number of patients |
PER (%) |
7-9 |
160 |
40 |
>9 |
240 |
60 |
The
FBS levels were classified into three categories, and the distribution is
presented (Table 3).
Table 3: Distribution of
patients based on fasting blood sugar results among participants
FBS |
NUMBER |
PER (%) |
>180
mg/dl |
238 |
59.5 |
130-180mg/dl |
122 |
30.5 |
<130mg/dl |
40 |
10 |
TOTAL |
400 |
100 |
The
PPBS levels were categorized into two groups, and the distribution is given
(Table 4).
Table
4: Distribution of patients based on Post Prandial Blood Sugar results
PPBS |
Number |
PER (%) |
>200mg/dl |
338 |
84.5 |
<200mg/dl |
62 |
15.5 |
Total |
400 |
100 |
Table
5: Distribution of patients based on PT and APTT values
PT
and APTT |
Number |
PER
(%) |
Normal |
108 |
27 |
Low |
292 |
73 |
Total |
400 |
100 |
These
statistical analyses highlight significant correlations between coagulation
parameters (PT and APTT) and the duration of diabetes and HbA1c levels (Table 6
& 7). The study provides valuable insights into coagulation impairment in
Type 2 diabetes mellitus patients, emphasizing the importance of monitoring
these parameters for preventive measures against thromboembolic cardiovascular
events (Table 8 & 9).
Table 6: Difference in PT values between in duration of Diabetes
Duration of DM |
Mean |
S.D |
1-5 years |
10.4 |
1.3 |
>5 years |
9.4 |
1.4 |
p-value–0.002, therefore
study shows significant correlation between PT and duration of diabetes.
Table
7: Difference in PT values between HbA1c categories
HBA1C |
Mean |
S.D. |
7-9 |
10.4 |
1.3 |
>9 |
9.3 |
0.8 |
p-value–0.001, therefore
study shows significant correlation between PT andHBA1C
Table
8: Difference in APTT values between Duration of Diabetes
Duration of DM |
Mean |
S.D. |
1-5 years |
31.2 |
5.8 |
>5 years |
20.7 |
4.4 |
p-value–0.003, therefore
study shows significant correlation between APTT and duration of diabetes
Table 9: Difference in APTT values between HbA1c categories
HBA1C |
Mean |
S.D |
7-9 |
27.1 |
7.3 |
>9 |
19.4 |
1.6 |
p-value
0.001, therefore study shows significant correlation between APTT and HBA1C
levels
DISCUSSION-
Atherothrombotic
disease emerges as a leading cause of morbidity and mortality in individuals
with diabetes, marked by the synergy of metabolic and vascular abnormalities.
Diabetes, recognized as an independent risk factor, significantly contributes
to the development of atherosclerosis—a primary culprit for macrovascular
complications, escalating platelet activation, coagulation factor activation,
and hypo-fibrinolysis, thereby heightening the risk of cardiovascular disease.[11-14]
In
this instance, coagulation equilibrium is largely maintained by naturally occurring
anticoagulants like protein C and antithrombin III. However, non-enzymatic
glycation of antithrombin III due to hyperglycemia in diabetes lowers its
biological activity and, as a result, the concentration of protein C in the
blood. When natural anticoagulants are not working effectively, clotting
factors are activated, leading to hypercoagulability in Type 2 diabetes. [15,16]
The
study, which included 400 patients with diabetes, looked at the impact of the
length of diabetes on the coagulation profile and found a significant
correlation. Specifically, patients with diabetes for over 5 years exhibited
distinct coagulation profile alterations, emphasizing the importance of disease
duration in influencing coagulation dynamics. Furthermore, the study
investigated the impact of glycemic control, as reflected in HbA1c levels, on
the coagulation profile.[17-20] Notably, patients with poor glycemic
control, represented by HbA1c >9, exhibited shortened PT and APTT values,
indicating a potential link between hyperglycemia and altered coagulation
parameters. This observation aligns with similar studies emphasising the
association between glycemic control and coagulation profiles.
CONCLUSIONS-
This
study highlights the association between altered coagulation patterns and
diabetes mellitus, particularly in individuals with HbA1c values ≥7. This
suggests a greater chance of thrombosis, as demonstrated by decreased PT and
APTT. Routine PT and APTT tests are crucial for assessing coagulation
impairment in diabetes mellitus and ultimately preventing thromboembolic
cardiovascular diseases.
The
findings underscore the importance of effective glucose regulation in the
management of diabetes mellitus and in lowering the risk of hypercoagulable
states, which subsequently averts the micro- and macrovascular complications
associated with the disease.
CONTRIBUTION
OF AUTHORS
Research
concept-
Sandhyarani Pati, Sandeep Das, Sangram Kishore Sabat
Research design- Sandhyarani Pati, Sangram
Kishore Sabat
Supervision- Sangram Kishore Sabat
Materials- Sandhyarani Pati, Sangram Kishore Sabat
Data collection- Sandhyarani Pati, Madhuchhanda Mohapatra,
Sandeep Das, Sangram Kishore Sabat
Data analysis and Interpretation- Sandhyarani Pati,
Madhuchhanda Mohapatra
Literature search- Sandeep Das, Sangram
Kishore Sabat
Writing article- Sandhyarani Pati, Sandeep Das
Critical review- Sandhyarani Pati, Madhuchhanda Mohapatra,
Sandeep Das
Article editing- Sangram Kishore Sabat
Final approval- Sangram Kishore Sabat
REFERENCES
1.
International Diabetes Federation.
Diabetes Atlas. Sixth edition.2013
2.
Carr ME. Diabetes mellitus: A
hypercoagulable state. J Diabetes Complicat., 2001; 15(11): 44–54.
3.
Madan R et al. Coagulation profile in
diabetes and its association with diabetic microvascular complications. J Assoc
Phycian India. 2010; 58: 481-89.
4.
Arpaci D, Saglam F, et al. Does glycemic regulation affect
hypercoagulable states in diabetic patients? Int J Diabetes Developing
Countries, 2015; 35(3): 512-15.
5.
American Diabetes Association. Glycemic
targets: Standards of medical care in Diabetes. Diabetes Care, 2018; 41:
S55-S64.
6.
Richard IG, Clive S, et al. Textbook of
Diabetes. 5th edition. New Jersey: Wiley Blackwell, 2017.
7.
Sobczak AIS. Coagulatory defects in Type-1
and Type-2 Diabetes. Int J Mol Sci., 2019; 20: 6345.
8.
Debele GJ, Fita FU, Tibebu M. Prevalence
of ABO and Rh Blood Group Among Volunteer Blood Donors at the Blood and Tissue
Bank Service in Addis Ababa, Ethiopia. J Blood Med., 2023; 14: 19-24.
9.
Belali TM. Distribution of ABO and Rhesus
Types in the Northern Asir Region in Saudi Arabia. J Blood Med., 2022; 13:
643-48.
10.
Khattak ID, et al. Frequency of ABO and
rhesus blood groups in District Swat, Pakistan. J Ayub Medical College
Abbottabad, 2008; 20: 127–29.
11.
Allawati M, Kalbani L. ABO and Rh (D)
phenotypes, allele frequencies and estimated genotypes in Omanis: A
retrospective study from Armed Forces Hospital. J Med Sci Clin Res., 2009;
9(4): 1-7.
12.
Adrian CR, Abraham CR, et al. Blood groups
distribution and gene diversity of the ABO and Rh (D) loci in the Mexican
population. Biomed Res Int., 2018; pp. 1-11.
13.
Das PK, Nair SC, Harris VK, Rose D, Mammen
JJ, et al. Distribution of ABO and Rh-D blood groups among blood donors in a
tertiary care centre in South India. Tropical Doctor, 2001; 31: 47–48.
14.
Puri PL, Kochhar, AK. Distribution of ABO
Blood Groups and RH (D) factor in Haryana. Int J Med Res Rev., 2016; 4(6):
982-86.
15.
Behra R, Joshi YR. Distribution of ABO
blood group and RH (D) factor in Western Rajasthan. National J Med Res., 2013;
3: 73–75.
16.
Bala SS, Handoo S, Jalloo AS. Gender
Differences in Blood Donation among Donors of Kashmir Valley. IOSR J Dental Med
Sc., 2015; 14(2): 116-19. doi:
10.9790/0853-14214116119.
17.
Tyagi M, Singh S, Bajpai M, Dhot PS.
Distribution and occurrence of ABO and rhesus blood groups in blood donors of
Ghaziabad: A hospital-based study. Int J Sci Res., 2020; 9(9), 23-25.
18.
Periyavan S, Sangeetha SK, Marimuthu P,
Manjunath BK, Seema DM. Distribution of ABO and Rhesus-D blood groups in and
around Bangalore. Asian J Transfus Sci., 2010; 4(1): 41. doi:
10.4103/0973-6247.59391.
19.
Swamy C et al. Prevalence of ABO and
Rhesus blood group among blood donors. Indian J Public Health Res Dev., 2012;
3: 10609.
20.
Nag I, Das SS. ABO and rhesus blood groups
in potential blood donors at Durgapur Steel city of the district of Burdwan,
West Bengal. Asian J Transfus Sci., 2012; 6: 54–55.