RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1 / NAME OF THE CANDIDATE & ADDRESS / DR. SWETHA POST GRADUATE IN PHYSIOLOGY, KARNATAKA INSTITUTE OF MEDICAL SCIENCES (KIMS), HUBLI-580022.
2 / NAME OF THE INSTITUTION / KARNATAKA INSTITUTE OF MEDICAL SCIENCES, HUBLI-580022.
3 / COURSE OF STUDY AND SUBJECT / M.D. PHYSIOLOGY.
4 / DATE OF ADMISSION TO THE COURSE / 31st AUGUST, 2013
5 / TITLE OF TOPIC / “A COMPARATIVE STUDY ON COAGULATION PROFILE AND NEUTROPHIL-LYMPHOCYTE RATIO IN PREGNANCY INDUCED HYPERTENSION”
6 / BRIEF RESUME OF INTENDED WORK:
6.1Need for the study:
Pregnancy induced hypertension (PIH) is the most common medical disorder of pregnancy, that often results in multi-organ failure.1 Pregnancy induced hypertension is defined as hypertension that occurs in pregnancy for the first time after 20 weeks of gestation and disappears following delivery.1 It is defined by the triad of Hypertension, Proteinuria and Oedema.
Eclampsia is the occurrence of convulsions or coma unrelated to other cerebral conditions with signs and symptoms of preeclampsia.2
Women with pregnancy induced hypertension may develop a variety of haematological aberrations.3 Faulty coagulation of blood can be a cause of hemorrhages, was suggested by De Lee in 1901.6 Hemorrhage occupies an important position in the etiology of maternal mortality and therefore, remains a major problem.6 Out of all haematological changes that occur in preeclampsia and eclampsia, thrombocytopenia is the most common abnormality found.
Diagnosis of complications of PIH depends on many signs and symptoms as well as laboratory tests.
Neutrophil-Lymphocyte ratio(NLR) is a marker of Systemic inflammation and Endothelial dysfunction. In recent years,it has been reported that the individual components of differential white cell count, specifically the neutrophil and lymphocyte counts, may have clinical utility in prediciting disease. An elevated NLR has been shown to be a prognostic indicator in various malignancies. In the literature, many studies have been shown that NLR have predictive value in determining the prognosis of various diseases. However, little has been known about the predictive values of NLR in pregnancy complication.9
Thus, the present study will be undertaken to find out the changes that occur in the coagulation parameters and Neutrophil-Lymphocyte ratio in pregnancy induced hypertension as compared to that in normal pregnancy. The results of the present study may help in the better management of patients with pregnancy induced hypertension.
6.2Review of Literature
A Study was conducted by Mohapathra S et al., including 30 normal pregnant women and 90 pregnant women with varying degree of pregnancy induced hypertension. Blood platelets were estimated during the second or the third trimester.Platelet levels gradually decreased as the severity of the PIH increased.The study concluded that there was an inverse relationship between the severity of PIH and platelet numbers.1
UgurKazimonglu et al., conducted a study to evaluate the clinical utility of the laboratory studies, especially coagulation tests in the evaluation of the patients with preeclampsia. Coagulation profile, platelet count, serum levels of LDH and transaminases of 120 preeeclamptic patients were evaluated. Thrombocytopenia and elevated liver enzymes were observed in 32 patients. The coagulation profile was within normal limits in 68 patients. Their study recommended that the LDH with or without platelet count should be assessed in the evaluation of coagulation abnormalities in the preeclamptic patients. 2
A study was conducted by Line Leduce et al., on 100 women with severe pre-eclampsia. 50 women had platelet counts below 150,000/µl, of whom 13 had a prolonged prothrombin time or activated partial thromboplastin time. They concluded that thrombocytopenia was a strong indicator of severity of PIH.3
John G Kelton et al., conducted a prospective study on 26 preeclamptic patients and 17 pregnant control subjects. Blood samples were collected for the estimation of prothrombin time, activated partial thromboplastin time, thrombin clotting time and platelet count. The result of this study suggested that patients with preeclampsia can have a significant defect in platelet function as well as platelet number. The bleeding time may be important for the evaluation of preeclamptic patients and may provide information about the risk of certain procedures.4
A study was conducted by Kulkarni RD et al., on a total of 84 pregnant females, out of which 20 were normal pregnant women, 55 were cases of pregnancy with toxaemia and 9 cases of pregnant women in whom roll over test was positive. Platelet count in the normal pregnant women were found to be in the normal range. In mild and severe toxaemia, there was fall in platelet count. The study concluded that lowering of platelet count was a feature of toxaemia of pregnancy.5
A study was conducted by Agarwal S et al., on 100 subjects out of whom 10 were normal non pregnant women, 20 normal pregnant women, 40 cases of mild preeclampsia, 20 of severe preeclampsia and 10 of eclampsia. In eclampsia, platelet count and plasma fibrinogen levels decreased, and platelet adhesiveness and fibrinolytic activity markedly increased.Their study suggested that there was a slow process of disseminated intravascular coagulation in toxaemias of pregnancy, and this process occurs to a greater extent in eclampsia.6
A study was conducted by Jack A Prichard et al., oneclamptic patients. In their study, they identified thrombocytopenia in 29% of patients, a prolonged bleeding time in 50%, abnormally elevated serum fibrinogen–fibrin degradationproducts in 3%, and circulating fibrin monomer in 5% of patients.It was concluded that the coagulation changes when present in eclampsia,were effect rather than cause.7
A study was conducted by DubeB et al., on 12 Indian patients with pre-eclampsia, 15 with eclampsia and 15 with normal pregnancy in their third trimester. Coagulation studies showed significant prolongation of thrombin time, elevation of serum fibrinogen degradation products and hypo fibrinogenemia in patients with pre-eclampsia as well as eclampsia. In patients with eclampsia, significant thrombocytopenia was also observed. With the above laboratory findings, they suggested that there was occurrence of intravascular coagulation in patients wiyh preeclampsia and eclampsia.8
A study was done by ZekaiTahirBurak on the effect of neutrophil to lymphocyte ratio in preeclampsia- eclampsia. In this study it was concluded that NLR is a marker of systemic inflammation and endothelial dysfunction. An elevated NLR has been shown to be a prognostic indicator in various malignancies.s
6.3Objectives of study:
  1. To study the platelet count, bleeding time, clotting time, prothrombin time, activated partial thromboplastin time and Neutrophil-Lymphocyte ratio in pregnancy induced hypertensive subjects.
  2. To study the above coagulation parameters and NLR in normal pregnant women (>20 weeks of gestation).
  3. To compare the above parameters between the normal pregnant women and pregnancy induced hypertensive subjects.
  4. To correlate the above parameters in relation to the severity of pregnancy induced hypertension.

7 / MATERIALS AND METHODS:
7.1 Source of data:
Pregnancy induced hypertensive subjects admitted in OBG Dept KIMS Hubli. Study group consists of 90 subjects and control group consists of 90 normal pregnant women.
INCLUSION CRITERIA :
  1. Pregnancy induced hypertensive subjects( >20 weeks of gestation) of age group 20 to 30 years.
Study group divided into 3 sub-groups-
Group A: Patients with BP ≥ 140/90 mm Hg
Group B: Patients with BP ≥ 140/90 mm Hg with urine albumin
≥ 1 + dipstick.
GroupC: Patients with BP ≥ 140/90 mm Hg with urine albumin ≥ 1 + dipstick + Convulsions/coma.
  1. Ninty normal pregnant women ( >20 weeks of gestation) of age group 20 to 30 years are taken as controls.
EXCLUSION CRITERIA:
  1. Age < 20 years and > 30 years
  2. Previous history of Diabetes mellitus
  3. Previous history of Renal disease
  4. Previous history of Thyroid disorder
  5. Previous history of Hypertension
  6. Haemoglobin <10gm%
  7. On medications ( except multi vitamins, iron, calcium) which affect the present study.
Statistical Analysis will be done by “ANOVA” test.
7.2 Methods of collection of data:
1. Informed consent taken.
2. BP measurement in lying down or sitting position.
3. Urine albumin detection by dipstick method.
4. Bleeding time and Clotting time estimation.
5. Platelet count estimation by Automated haematology analyzer.
6. Prothrombin time and Activated partial thromboplastin time estimation by Semi automated analyzer.
7. NLR calaulated by Absolute neutrophil count divided by Absolute lymphocyte count.
7.3. Does the study require any investigation to be conducted on patients or animals, specify.
Yes, This study requires following investigations to be conducted on patients.
a) Platelet count
b) Bleeding time
c) Clotting time
d) Prothrombin time
e) Activated partial thromboplastin time
f) Neutrophil-Lymphocyte ratio
No animal experiment is required.
7.4 Has the ethical clearance been obtained from ethical committee of your Institution?
“Yes”. The ethical clearance has been obtained from ethical committee of KIMS, HUBLI.
LIST OF REFERENCES
  1. Mohapatra S, Pradhan BB, Satpathy UK, ArathiMohanthy, PattnaikJR.Platelet Estimation: Its prognostic value in pregnancy induced hypertension. Indian Journal of Physiology and Pharmacology 2007;51(2):160-164.
  2. UgarKazimolgu, SeukiCelen , Mehmet SA Ozkul, Bekir S Unlu, HazanAytan, SenolKalyonku, GorkemTuncay, Murat Ozel. Necessity of Coagulation profile in Preeclampsia. Artemis 2004;5(3):217-219.
  3. Line Leduce, James M Wheeler , Brain Kirshon, Patricia Mitchell, David B Cotton. Coagulation profile in Severe Preeclampsia. Journal of Obstetrics and Gynaecology 1992;79(1):14-18.
  4. John G Kelton, David JS Hunter, Peter B Naeme. A platelet function defect in Preeclampsia. Journal of Obstetrics and Gynaecology 1985;65(1):107-109.
  5. Kulkarni RD, Sutaria UD. Platelet counts in toxaemias of pregnancy. Journal of Obstetrics and Gynaecology of India 1983;33:321-325.
  6. Agarwal S, AshaBuradkar.Coagulation studies in toxaemias of pregnancy. Journal of Obstetrics and Gynaecology of India 1978; 992-996.
  7. Jack A Prichard, Gary Cunningham F, Ruble A Mason. Coagulation changes in Preeclampsia: Their frequency and pathogenesis. American Journal of Obstetrics and Gynaecology 1976;124:855-864.
  8. Dube B, Sulekha Bhattacharya, Rama KantaDube. Blood coagulation profile in Indian patients with Preeclampsia and Eclampsia. British Journal of Obstetrics and Gynaecology 1975;82:35-39.
  9. ZekaiTahirBurak. The effect of Neutrophil to lymphocyte ratio in preeclampsia – eclampsia. Article in 01856387.

9 / SIGNATURE OF CANDIDATE
10 / REMARKS OF THE GUIDE
11 / NAME & DESIGNATION
11.1 GUIDE / DR.NAGARAJA PURANIK M Sc., Ph D.
ASSOCIATE PROFESSOR,
DEPARTMENT OF PHYSIOLOGY,
KIMS, HUBLI.
11.2 SIGNATURE
11.3 CO-GUIDE
11.4 SIGNATURE
11.5 HEAD OF THE DEPARTMENT / DR.K. F. KAMMAR MD.
PROFESSOR & HEAD, DEPARTMENT OF PHYSIOLOGY, KIMS, HUBLI.
11.6 SIGNATURE
12 / 12.1 REMARKS OF CHAIRMAN AND PRINCIPAL
12.2 SIGNATURE