Journal of Indira Gandhi Institute Of Medical Sciences

ORIGINAL ARTICLE
Year
: 2019  |  Volume : 5  |  Issue : 1  |  Page : 31--34

To Evaluate the Levels of PT, APTT & Fibrinogen Values in Patients With Type 2 Diabetes Mellitus


Priyanka Prasad1, RP Gupta2, Rakesh Kumar3,  
1 Senior Resident, Dept of Biochemistry, NMCH, Patna, India
2 Professor & HOD, Dept of Biochemistry, NMCH, Patna, India
3 Assistant Professor, Dept of Pediatrics, NMCH, Patna, India

Correspondence Address:
Rakesh Kumar
Assistant Professor, Department of Pediatrics, Nalanda Medical College & Hospital, Patna-7
India

Abstract

Introduction: Complication of diabetes mellitus (DM) includes coagulation impairment. Hypercoagulable state in patient with DM may accelerate thromboembolic risk for cardiovascular diseases (CVD). Hyperglycemia in diabetes contributes to hyperfibrinogenemia and activates the coagulation cascade thereby producing atherothrombotic events. Objective: This study was designed to evaluate the coagulation profile (Activated partial thromboplastin time, Prothrombin time and Fibrinogen) in Type 2 diabetes Mellitus. Methods: This study included 100 type 2 diabetics and 50 controls. Fasting blood glucose, coagulation parameters such as prothrombin time, activated partial thromboplastin time and fibrinogen along with other biochemical parameters were investigated. Results: In this study fibrinogen was found to be significantly higher (p-value = 0.000) in diabetic patients as compared to the control group. Prothrombin time in Diabetes Mellitus type 2 is shortened as compared to Non- Diabetic Population whereas APTT is slightly prolonged in DM Type 2. Conclusion: From this study, it may be concluded that diabetic patients are prone to develop coagulation impairment.



How to cite this article:
Prasad P, Gupta R P, Kumar R. To Evaluate the Levels of PT, APTT & Fibrinogen Values in Patients With Type 2 Diabetes Mellitus.J Indira Gandhi Inst Med Sci 2019;5:31-34


How to cite this URL:
Prasad P, Gupta R P, Kumar R. To Evaluate the Levels of PT, APTT & Fibrinogen Values in Patients With Type 2 Diabetes Mellitus. J Indira Gandhi Inst Med Sci [serial online] 2019 [cited 2021 Feb 25 ];5:31-34
Available from: http://www.jigims.co.in/text.asp?2019/5/1/31/301073


Full Text



 Introduction:



Diabetes mellitus (DM) is a metabolic disorder which exhibits prolonged hyperglycemia and altered coagulation hemostasis. Diabetes Mellitus is the major risk factor for micro and macrovascular complications by inducing hypercoagulable state leading to thrombotic events[1]. Diabetes is an iceberg disease. Worldwide prevalence and incidence of Type 2 Diabetes Mellitus has increased dramatically because of urbanization and changes in life style. Many studies have shown high risk of atherothrombotic events in patients with Diabetes Mellitus. Persistent hyperglycemia in diabetics exposes red blood cells to elevated glucose concentration, resulting in glycation of clotting factors[2],[3]. Glycation of proteins in clotting cascade affect the hematological status.

Although modern coagulation test are becoming more sophisticated, coagulation screening tests such as, Prothrombin test, Activated Partial Thromboplastin Time and Fibrinogen level are still important basic examinations in clinical laboratories. These haematological indices are used as screening test in patients with suspected coagulopathy[4]. Prothrombin Time is used to assess activity of extrinsic and common pathways. APTT measures activities of intrinsic and common pathways. Fibrinogen play critical role in blood viscosity. Hyperfibrinogenemia in Type 2 Diabetes Mellitus is implicated in vascular damage induction[5],[6],[7]. The current study focuses on the importance of routine determination of PT and APTT along with Fibrinogen level in order to assess the impairment of the coagulation cascade in Diabetes Mellitus to evaluate the association in DM patients with complications and hypercoagulability.

 Materials & Methods:



This study was done in the Department of Biochemistry in Nalanda Medical College, Patna in July 2012 to June 2013. Protocol of this study was approved by Ethical committee of Nalanda Medical College, Patna. For this study 100 type 2 diabetic patients, aged (45-70 years) were selected. 50 healthy age matched individuals were considered as control. Control group comprised of 34 males & 16 females. They were normal healthy individuals, free from any disease especially stroke consist of ward attendants and medical professionals. The study group comprised of 45 males and 55 females and were clinically established cases of Diabetes Mellitus Type 2 taken from medicine ward of Nalanda Medical College and Hospital, Patna. Blood was collected after confirmation of diagnosis both clinically and pathologically in cases of Diabetes Mellitus type 2. The exclusion criteria were considered patients with a history of venous thromboembolism, hypercoagulability, known inherited coagulation disorders, malignancy, pregnancy, hyperthyroid and patients who were receiving anticoagulant therapy.

Specimen Collection and Preparation:

Nine parts of freshly collected patient venous blood was mixed with one part 3.2% sodium citrate (customary blood collection systems). The blood specimen was centrifuged for a minimum of 10 minutes at 1500 x g as soon as possible after collection. If immediate testing is to be done, the plasma may remain on the packed cells or be separated. To separate the plasma, we use a plastic transfer pipette; the plasma was removed to a plastic tube and keep refrigerated until ready to test. Plasma should be tested within four hours of blood collection.

 Specific Test for Study:



  1. Blood Sugar- Enzymatic method (glucose oxidase - peroxidase method)
  2. Estimation of Prothrombin Time (PT) by Thromboplastin reagent (quick one stage method)
  3. Estimation of Activated Partial Thromboplastin Time (APTT) by cephaloplastin reagent using ellagic acid as an activator.
  4. Estimation of fibrinogen by Dade Fibrinogen Determination reagent.


 Statistical Analysis:



Means, SDs and CVs of analytes was calculated for numerical variable. Percentage changes in concentration of analytes was calculated for categorial variable. All p value <0.05 was considered statistically significant. All statistical analysis was achieved using the Statistical Package for Social Sciences (SPSS) version 17 software.

 Results:



This study examined the coagulation profile of diabetic patients. For the study 50 controls and 100 diabetics aged 45-70 years were investigated. Blood samples were collected from known diabetic patients who were undergoing treatment for Diabetes in indoor ward of dept of medicine of NMCH, Patna and Prothrombin time, Activated partial thromboplastin time and fibrinogen level were estimated. Among the diabetic, male were 45% and female were 55% and among the Non-diabetic male were 68% and female were 32%. The mean age of diabetic was 54.27±7.32 (range :45-70 years) with most of the patients in the 45 to 65years of age.

Activated Partial Thromboplastin Time APTT is slightly prolonged in Diabetes Mellitus Type 2 though it is within normal range and fibrinogen was found to be significantly higher (p-value = 0.000) in diabetic patients compared to the control group. Prothrombin time in Diabetes Mellitus type 2 is shortened as compared to Non- Diabetic Population. However, PT did not show any significant difference between the groups.

 Discussion:



Measurement of coagulation profile are the most commonly employed laboratory tests in patients with a suspected coagulopathy (Furlanello et al, 2006). To assess hemostatic profile, Prothrombin time is used to detect disorders of the extrinsic and common pathways (Hinchcliff et al, 2004). Activated partial thromboplastin time is used to screen for abnormalities of the intrinsic and common pathways (Iazbik et al, 2001). Dunn and Grant (2005) studied on ‘Type 2 Diabetes: An atherothrombotic syndrome’ and suggested that changes in plasma levels of clotting factors favor the development of hypercoagulable and pro-thrombotic state , which may in turn enhance cardiovascular risk by increasing the likelihood of developing an occlusive thrombus within a coronary/cerebral artery contributing to the development of atherosclerotic lesion[8].

In the current study, it was observed that that 63.4% diabetic patients had prothrombin time within the reference range of 10-15 seconds and only 4% were having prothrombin time more than 20 seconds whereas 90% of the non-diabetic persons had prothrombin time in between 10-15 seconds and only 4% were having prothrombin time more than 20 seconds. This study showed that mean prothrombin time in Diabetes Mellitus type 2 is shortened as compared to non diabetic population. The mean prothrombin time in Diabetes Mellitus type 2 was 12.34 seconds whereas in non diabetic population it was 12.43 seconds. All the values were in the normal limits. This is in agreement with the findings of Ying Zhao et al (2011)[9]. In the current study, an elevation of APTT when compared with non diabetic individuals. These findings agreed with the study of Hassan et al (2009) and Maysam et al (2011)[10]. Among diabetic subjects, the maximum no. of patients (39%) were having APTT in between 20-25 seconds and only 18% were having APTT >30 seconds.

Mean Activated Partial Thromboplastin Time (26.06 seconds) is slightly prolonged in diabetic population although within normal limits whereas in non diabetic individuals mean APTT is 25.76 seconds. It is noteworthy that this study found the APTT to be slightly prolonged among diabetics when compared with the controls.

While noting that values were still within normal limits, the slight prolongations of these parameters raise a number of issues. First, it is known that the general notion about diabetes is that of a hypercoagulable tendency resulting from a shift of thrombo-haemorrhagic balance in favor of thrombosis and one would have expected a relative shortening of these parameters. Hence, the slightly prolonged APTT found in the diabetic group in this study may appear to be at variance with this submission.

The exact patho-physiological reasons for these observations may not be immediately evident for now. Could there possibly be other in-vivo pathways that may occasionally tilt this thrombo-haemorrhagic balance in favor of haemorrhage in some diabetics! The prolongation of these parameters in the diabetic group may also be due to in-vitro interference of fibrin clot formation by inhibitors such as fibrinogen fragments 1& 2 and D-Dimers as reported in several studies (Laffan MA, 1995)[11]. Whatever may be the plausible reasons, these findings suggest that haemorrhagic tendencies and complications should not be entirely ruled out among diabetics, and should be born in mind during the management of these patients. It would also be helpful to incorporate coagulation screening as routine tests for better management of diabetic patients. Various studies have demonstrated that induction and progression of vascular damage leads to inflammation and is concomitant with increased fibrinogen level(Merlo et al,2002; Weiss et al, 2000; Bots et al, 2002)[12],[13],[14]. Hyperfibrinogenemia is a strong and independent cardiovascular risk factor. In hyperglycemia fibrinogen gets hyperglycosylated. When clotting occurs in abnormal fibrinogen they become markedly resistant to degradation by plasmin[15],[16].

In the present study mean fibrinogen level in diabetics was 370.05 mg/dl and in non diabetic individuals it was 233.52 mg/dl. Fibrinogen levels have been shown to be significantly increased in diabetic patients which was in accordance with Lippi et al[17]. The exact biological mechanisms of thrombosis in diabetics are likely to be multifactorial and incompletely understood18. Based on present findings and previous studies, since thrombotic complications and hypercoagulable state in diabetic populations are introduction to vascular and cardiovascular complications, as a prognostic clue the measurement of PT, APTT and fibrinogen level show critical and more specific alterations in Diabetes Mellitus and gives bad prognosis coagulation disturbance leading to vascular complications. Therefore, the present seemed to reveal that hypercoagulable state management may have preventive value in subsequent vascular complication in this patients.

There are limitations concerning the present study. Firstly, this study was limited to a single hospital only. Secondly, the sample size might not be the exact representative of the whole case so as to generalize the findings of the study. The low ratio of non diabetic to diabetic population was due to the fact that less number of study population came to the study site during the study period.{Figure 1}{Figure 2}{Figure 3}{Table 1}

 Conclusion:



The patients suffering from Type 2 Diabetes Mellitus were found to have an increased level of Fibrinogen, relatively shortened Prothrombin Time and prolonged Activated Partial Thromboplastin Time as compared to the non- diabetic individuals. Therefore, it is indicated that shortened PT and increased Fibrinogen levels might be useful hemostatic markers in diabetic patients, especially in those at high risk for thrombotic complications. Further investigations of these markers could potentially be used as screening test for hypercoagulable states that are applicable to diabetes and other clinical conditions.

References

1Maysam MS et al. Coagulation Factors Evaluation in NIDDM Patients. Am. J. Biochem. Mol. Biol. 2011; 1(3):244-254.
2Abdulrahaman Y. Evaluation of Prothrombin Time and Activated Partial Thromboplastin in Patients with Diabetes Mellitus.NJBAS. 2012;20(1):60-63.
3Alao O et al. Haemostatic Profile of Patients withType 2 Diabetes Mellitus in Northern Nigeria. Internet Journal of Endocrinology.2010;6:122-132.
4Furlanello, T., Caldin, M. and Stocco, A. (2006). Stability of stored canine plasma for hemostasis testing. Veterinary Clinical Pathology, 35:204-207.
5Hinchcliff KW et al. Equine sports medicine and surgery. Basic and clinical science of the equine athlete.2004;1295-1302.
6Iazbik C et al. Effect of storage conditions on hemostatic parameters of canine plasma obtained for transfusion. American Journal of Veterinary Research.2001;62:734-735.
7Zachary T and Bloomgarden MD. Diabetes and cardiovascular disease. Diabetes Care.2011;34:24-30.
8Dunn, E.J. and Grant, P.J. (2005). Type 2 diabetes: an atherothrombotic syndrome. Current Molecular Medicine, 5(3): 323-322.
9Zhao Y et al. Diabetes Mellitus is Associated with Shortened Activated Partial Thromboplastin Time Increased Fibrinogen Value. Plos ONE2011;6(1).
10Hassan FM. Prothrombin time activated thromboplastin among type II non insulin dependant diabetes mellitus. Recent Research Science Technology.2009; 1(3):131-133.
11Laffan MA, Brandshow AE, (1995) Investigation of haemostasis. In: practical haematology, Dacie JV, Lewis SM (eds), 8th edition. Edinburgh, Churchill Livingstone: 297-310.
12Merlo, C., Wuillemin, W.A., Redondo, M., Furlan, M. and Sulzer, I. (2002). Elevated levels of plasma prekallikrein, high molecular weight kininogen and factor XI in coronary heart disease. Atherosclerosis. 161: 261-267.
13Behnam, R.M., Ghayour, M.B. and Ghayour, N. (2010). Microvascular complications of diabetes. Journal of Biological Science, 10: 411-423.
14Berliner, J.I., Rybicki, A.C., Kaplan, R.C., Monrad, E.S., Freeman, R. and Billett, H.H. (2002). Elevated levels of Factor XI are associated with cardiovascular disease in women. Thrombosis Research, 107: 55-60.
15Carr, M.E. (2001). Diabetes mellitus: A hypercoagulable state. Journal of Diabetics Complication, 15: 44-54
16Cooke, D.W. and Plotnick, L. (2008). Type 1 diabetes mellitus in pediatrics. Pediatric Revision, 29 (11): 374-84
17Lippi, G., Franchini, M., Targher, G., Montagnana, M. and Salvagno, G.L. (2009) Epidemiological association between fasting plasma glucose and shortened APT. Clinical Biochemistry, 42:118-120
18Binaya Sapkota, Saroj Kumar Shrestha and Sunil Poudel. Association of activated partial thromboplastin time and fibrinogen level in patients with type II diabetes mellitus BMC Research Notes 2013, 6:485 doi:10.1186/1756-0500-6-485.