HYPERTENSION AND DIABETES MELLITUS ARE ASSOCIATED WITH DEEP VENOUS THROMBOEMBOLISM: A CASE CONTROL STUDY

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S.P Ogundeji, F.A Fasola, T.R Kotila

Department of Haematology, College of Medicine, University of Ibadan, Ibadan, Nigeria.

Abstract

Introduction: Identifying risk factors for venous thromboembolism (VTE) is useful in deciding thromboprophylaxis for VTE. A retrospective study had shown an association between hypertension and diabetes mellitus with VTE in our population. The objective of this study was to confirm these findings and to determine if the complete blood count and coagulation tests can also be useful parameters in stratifying VTE patients for prophylaxis.

Methods: This is a gender and age matched prospective case-control study of 45 Doppler’s confirmed DVT and 43 apparently healthy controls.

Results: Identified risk factors included history of hypertension, diabetes mellitus, previous DVT, recent surgery, recent trauma, malignancy, sepsis, and immobility. The cases had a significantly lower mean haematocrit (33±7.4% vs 38±4.6%, p<0.001). Though no differences were observed in leucocyte and platelet counts between cases and controls but stratification as leucocytosis vs leucopaenia (P=0.003) and thrombocytosis vs thrombocytopaenia (P=0.045) differed between both groups. Also, the International normalized ratio (INR) was higher in cases (1.1±0.2 vs 1.0±0.1; P=0.001), hypercoagulable state (INR<0.9) and hypocoagulable state (INR>1.2) were observed in 4.4% and 28.9% of cases respectively but not in controls (P<0.001). Also, aPTT>40 seconds was seen in 4.4% vs 4.7% of cases and controls respectively and aPTT< 30 seconds in 22% of cases but not in controls (P=0.004).

Conclusion: Hypertension and diabetes mellitus are identified risk factors not traditionally associated with DVT. These in addition to a complete blood count and coagulation tests can be useful in stratifying patients for prophylaxis in our population and other similar communities.

Keywords: Anaemia, Diabetes mellitus, Hypercoagulable, Hypocoagulable, Hypertension, Race, Thromboprophylaxis

Introduction

Venous thromboembolism (VTE) affects 1-3 patients per 1000 years.^1,2 One percent of all hospitalized patients die of acute pulmonary embolism (PE) and 10% of all in-patient deaths are PE related.³ The pathogenesis of VTE is complex and includes both hereditary and environmental factors.⁴ Though anaemia was found to be independently associated with the risk of VTE in acutely ill medical patients⁵ there appears to be no demonstrable relationship between it and PE.⁶ However, there is a relationship between platelet counts and the rate of major and fatal bleeding in patients with VTE.⁷ Reactive thrombocytosis is also found to be a risk for venous thromboembolism during the recovery phase of an acute illness.⁸ Recently, it was observed that comorbidities like hypertension and diabetes mellitus appear to be associated with VTE in our population of patients in a retrospective study.⁹ We therefore sought to identify comorbidities and laboratory parameters that are associated with VTE in our community. This can be useful in deciding the requirements for thromboprophylaxis in hospitalized patients in our population and similar communities.

MATERIALS AND METHODS
Study Design: This was a gender and age matched (±3 years of index case) prospective case-control study of consecutive patients with deep venous thromboembolism. Setting: The study was carried out in a 964 bedded tertiary health facility in a cosmopolitan city in Nigeria.

Study Population: The cases were in-patients confirmed to have deep venous thrombosis by ultrasonography. Patients with established renal failure and inheritable risk factors like deficiency of Protein C, Protein S, antithrombin, resistance to activated protein C as documented in the case notes were excluded from the study. Also, excluded were pregnant women or women with a history of recent childbirth. The body mass index was calculated from the weight and height of the participants (weight (kg)/height (m), a BMI of 25-30kg/m2 was considered overweight while a BMI of >30kg/m2 was considered obese.The controls were apparently healthy individuals who work in and around the hospital and consented to participate.

Variables: The outcome variable is deep venous thrombosis which was confirmed by Doppler ultrasonography. The risk factors were obtained using an interviewer administered questionnaires and laboratory blood samples which were processed by automation.

Sample size: The estimated sample size of 45 was based on a significance threshold of 0.05, a statistical power of 80%, prevalence of 20%10 and attrition rate of 5%. Prevalence from our community was 2.9%11 giving a sample size of 37.

Sample Collection: After an informed consent, a questionnaire detailing the risk factors was administered to all participants. Blood samples were collected and dispensed into bottles containing EDTA for complete blood count and trisodium citrate for prothrombin time (PT) and activated partial thromboplastin time (aPTT). Platelet poor plasma was obtained from the sample collected into trisodium citrate bottle after centrifugation at 3000g for 15 minutes. The PT and aPTT were run manually immediately after separation. The complete blood count was determined by automation using a five- part particle counter by Sysmex 1000i.

Anaemia was classified as haematocrit (PCV) of less than 36% while a count of greater than 51% was classified as polycythaemia, other readings were considered normal. Leucopaenia was a leucocyte count of less than 4.0 x 109/ L, while counts greater than 10.0 X 109/L were considered as leucocytosis and values between 4.0 x 109/ L and 10.0 X 109/L were considered normal. Platelet count of between 100 X 109/L and 300.0 X 109/L was considered normal, values below were classified as thrombocytopaenia and values above as thrombocytosis. The international normalized ratio was calculated by dividing the PT of the patient by that of the control plasma multiplied by the international sensitivity index (ISI) of the thromboplastin used. INR within the range of 0.9 and 1.2 was considered normal, values above were classified as hypocoagulable and values below as hypercoagulable. The reference ranges used for the complete blood count parameters and the coagulation profile were based on that of our laboratory.

Statistical consideration and Data analysis: Data were entered and analyzed using Statistical Package for the Social Sciences (SPSS) version 16. Descriptive variables were summarized as mean and SD for continuous variables and as numbers and percentages for categorical variables. Frequency distribution tables were generated for the different variables while crosstabulations and test statistics for bivariate analysis were carried out as applicable; independent t test was used to compare continuous variables and Chi square test for categorical variables. Level of significance was set at a P-value of less than 0.05.

Ethical Consideration: Ethical approval for the study was obtained from the UI/UCH institutional review board (UI/EC/10/0203). An informed consent was obtained from all participants before the commencement of the study. Privacy and confidentiality of the participants were ascertained by the coding of the data to ensure anonymity

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