CLINICAL PROFILE AND LABORATORY CORRELATES OF DEEP VENOUS THROMBOSIS: THE PREDICTABILITY OF POINT OF CARE D- DIMER TESTING AMONG ADULTS IN AMINU KANO TEACHING HOSPITAL, KANO. A DISSERTATION SUBMITTED TO THE NATIONAL POST GRADUATE MEDICAL COLLEGE OF NIGERIA IN PARTIAL FULLFILMENT OF THE REQUIREMENTS FOR THE AWARD OF FELLOWSHIP OF THE COLLEGE IN INTERNAL MEDICINE. FACULTY OF INTERNAL MEDICINE (SUBSPECIALTY: CLINICAL HAEMATOLOGY) BY ABDULLAHI MUSBAHU DEPARTMENT OF INTERNAL MEDICINE AMINU KANO TEACHING HOSPITAL KANO MAY 2017 1 CERTIFICATION We certify that we supervised the project titled Clinical profile and laboratory correlates of Deep Venous thrombosis: The predictability of point of care D-dimer testing in adult patients in Aminu Kano Teaching Hospital, as part of the part II examination requirement of the National Postgraduate Medical College of Nigeria. First supervisor`s Name: DR. BAFFA ADAMU GWARAM Year of Fellowship…………….……………………………………………… Signature and Date………………..…………………………………………… Second supervisor`s Name: DR. ABDULHAMID ISA DUTSE Year of Fellowship………………………………...…………………………… Signature and Date……………………………………………………………… 2 DECLARATION The dissertation titled “Clinical profile and laboratory correlates of Deep Venous thrombosis: The predictability of point of care D-dimer testing in adult patients in Aminu Kano Teaching Hospital” was conducted in the department of Medicine, Aminu Kano Teaching Hospital by Dr Musbahu Abdullahi. Head of Department; Name: PROF. A.A. SAMA`ILA Signature and Date:..….……………………………………………………….. 3 Declaration/Attestation I declare that I conducted the above titled project according to the stated study protocol as part of the requirements for the award of Fellowship of the National Postgraduate Medical College of Nigeria. Candidate`s Name: MUSBAHU ABDULLAHI (AF/009/12/115/927) Signature………………………………………………………………………… 4 Dedication: This work is dedicated to my late father, Alh Abdullahi Aliyu Sumaila and my mother, Haj Saude A Aliyu whose support, guidance and encouragement have seen me through life. It is also dedicated to my siblings, Aliyu, Ahmed, Yusuf, Aminu, Rabi and late Abdullahi for being an indispensible pillar of support in my life. I also dedicate this work to my wife, Rabi for the patience, encouragement and support. 5 Acknowledgement: My appreciation goes to all my teachers in the department of medicine, especially Dr Abdulhamid Isa Dutse who provided immense academic, clinical and general guidance and training throughout my residency training, despite his tight schedule. I am particularly indebted to my teacher, Dr Baffa Adamu Gwaram, who saw to my training and provided invaluable academic, practical and social support at all times. He was ever present at times of need and patient with my shortcomings. I would like to appreciate Prof M.M.Borodo for his much needed fatherly guidance and inputs in completing my training and this work. I would also like to thank Prof K.M. Karaye for his contributions towards a successful training and this work. My appreciation also goes to my fellow resident doctors who provided me with an invaluable support during my residency training. I would like to appreciate my family members, especially my mother, siblings, and wife for the patience, encouragement and support. I also thank all the numerous people that contributed toward the success of this study which time and space may not permit me to mention. Finally, and above all, I thank the Almighty, Allah with whom all is achievable and without whom nothing is accomplished. 6 TABLE OF CONTENTS Title page i Certification ii Declaration iii-iv Dedication v Acknowledgement vi Table of contents vii-x List of tables xi List of figures and picture xii Abbreviations xiii Abstract xvi 1.0 Introduction 1 1.1 Aims 3 1.2 Objectives 3 1.3 Justification for the study 4 1.4 Ethical Consideration 4 1.5 Research question 5 1.6 Relevance of the project to the discipline 5 2.0 Literature review 6 7 Introduction 6 Epidemiology 6 Risk factors 6 Clinical features 7 Investigations 11 Treatment 13 3.0 Methodology 14 3.1 Study area 14 3.2 Study population 14 3.3 Sample size determination 15 3.4 Inclusion and exclusion criteria 16 3.5 Study design and procedure 17 3.5.2 Study period 19 3.5.3 Data collection tools 19 3.5.4 Blood sample collection 20 3.5.5 Sample transportation and storage 20 3.5.6 Laboratory tests 21 1 D-dimer 21 2 Plasma VWF antigen 22 8 3 Blood grouping 24 4 Full Blood count 25 3.5.7 Quality control 25 3.5.8 Biosafety standard 26 3.6 Data Analysis 26 3.7 Incentives/benefits to the study population 27 4.0 Chapter four 28 4.0 Results 28 4.1 Socio demographic characteristics of participants 28 4.2 Clinical risk factors of DVT in participants 31 4.3 Blood groups of the study population 40 4.4 D-dimer levels of the study population 41 4.5 vWF antigen levels of the study population 42 4.6 other laboratory results 45 4.7 Doppler ultrasound features of the study population 47 4.8 Reliability of D-dimer 48 4.9 Relationship between risk factors and DVT 49 5.0 Discussion 52 6.0 Conclusion and Recommendations. 66 9 References 68 Appendix one: Proforma/Questionnaire 78 Appendix two; Consent form 83 Appendix three: Ethical clearance 87 10 LIST OF TABLES Page No: Table 4.1: Socio demographic characteristics of study participants 41 Table 4.2: Clinical profile of the study participants: risk factors 44 Table 4.3: Causes of immobility among participants 45 Table 4.4: Clinical findings of the affected limb 48 Table 4.5: Wells’ score of the subjects 49 Table 4.6: Blood group distribution among participants 50 Table 4.7: D-dimer in the various Wells score risk category 51 Table 4.8: Positive D-dimer levels in the various blood groups. 52 Table 4.9: Plasma vWF antigen levels in the various blood groups 54 Table 4.10 Plasma vWF antigen levels according to D-dimer levels of the study participants 54 Table 4.11 Doppler ultrasound findings in study subjects 55 Table 4.12: True positives and negatives, and False positives and negatives of D-dimer test 56 Table 4.13: positive D-dimer values among subjects 58 Table 4.14: Positive D-dimer values among study participants 59 11 LIST OF FIGURES Page No. Figure 3.1: COBAS® Roche cardiac D-dimer portable reader and D-dimer testing Kit 22 Figure 4.1: Age distribution of study participants 40 Figure 4.2: BMI of study participants 47 Figure 4.3: Distribution of VWF antigen levels in study cases and controls 53 12 ABBREVIATIONS AKTH: Aminu Kano Teaching Hospital APS: Antiphospholipid syndrome APPT: Activated Partial Thromboplastin Time BMI: Body Mass Index. CAD: Coronary Artery Disease CLD: Chronic Liver Disease CD4: Cluster of differentiation 4 CTPH: Chronic Thromboembolic Pulmonary Hypertension CMV: Cytomegalovirus CV: Contrast Venography CVD: Cerebro Vascular disease DIC: Disseminated Intravascular Coagulopathy DM: Diabetes mellitus DVT: Deep Venous Thrombosis ELISA: Enzyme-linked immunosorbent assay HDL: High Density Lipoprotein HIV: Human Immunodeficiency Virus HRT: Hormone Replacement Therapy 13 IBD: Inflammatory Bowel Disease ICU: Intensive Care Unit INR: International Normalised Ratio LDL: Low Density Lipoprotein MRI: Magnetic Resonance Imaging. NCEP-ATP III:National Cholesterol Education Program-Adult Treatment Panel III NPV: Negative predictive value OCP: Oral Contraceptive Pills PTB: Pulmonary Tuberculosis P.E: Pulmonary Embolism PPV: Positive Predictive Value SVD: Superficial Venous Dilation TAFI: Thrombin Activatable Fibrinolysis Inhibitor TB: Tuberculosis TGs: Triglycerides USS: Ultrasound scan vWF: von Willebrands factor VTE: Venous thromboembolism 14 SUMMARY Deep vein thrombosis (DVT) is a major cause of morbidity and mortality especially in hospitalized patients. This study examines the clinical profile and some laboratory correlates of DVT in the study environment. It also explores the possibility of using the Roche point-of- care D-dimer test as an alternative to Doppler USS in the diagnosis of DVT, which is cheaper and easier to use, with less technical expertise and faster turnaround time. This descriptive, cross-sectional study of consenting adult patients with clinical risk factors suggestive of DVT was carried out at the out-patient clinics and various wards and emergency units of AKTH, Kano. Diagnosis of DVT was established or ruled out using the gold standard, Doppler ultrasound scan. Forty patients with DVT and forty age- and sex- matched controls without DVT were recruited following informed consent. The socio- demographic and clinical characteristics of the patients and the risk factors associated with DVT were obtained using a structured questionnaire. Weight (Kg) and height (m) were obtained to calculate the BMI, and both limbs circumference were measured. Venous blood (9ml) was obtained to determine the D-dimer levels using the Roche cardiac D-dimer portable reader, blood group type, and plasma vWF antigen levels. Data was analysed statistically using SPSS version 20.0 to check for true associations. The sensitivity, specificity, Negative Predictive Value (NPV), Positive Predictive Value (PPV) of D-dimer in the diagnosis of DVT was determined. P-values ≤0.05 was used to define statistical significance. Forty subjects and 39 age and sex-matched controls were recruited for the study. Their mean age was 47.8 ±11.8 years for the subjects and 48.3±9.8 years for the controls (p = 0.8384). There were 16 males (40%) and 24 females (60%) amongst the subjects and 16 males and 23 females amongst the controls, with a male to female was 1: 1.5 in each arm. The sensitivity and NPV of the D-dimer test was determined to be 87.5% and 85.29% respectively, while the specificity and PPV were 72.50% and 85.29% respectively. History of surgery was obtained 15 among 17 (42.5%) subjects and 6 (15%) controls (p = 0.0135), 14 (35%) subjects had a history of HIV compared to 5 (12.5%) controls (p = 0.0355), while history of immobility was obtained in 21 (52.5%) subjects compared to 11 (28.2%) controls (p = 0.0399).