Over the last few decades, evidence has been mounting that VTE is as prevalent in non-Europeans as in Europeans; however, little is known about VTE in former populations [22]; this includes the risk factors associated with the development of VTE.
The present study is a retrospective study carried out in ICU patients with VTE, receiving guideline-anticoagulant thromboprophylaxis; VTE is known to be a very frequent complication in critically ill patients and quite often with negative impact on patients’ outcome [10, 18, 23–25]. These earlier studies agree that the use of anticoagulant thromboprophylaxis is associated with a significant reduction in the risk of VTE in these critically-ill patients. In the current study we aimed to identify the risk factors for VTE among ICU Saudi patients receiving prophylactic anticoagulants. It is already well established that ICU patients, other than the general risk factors associated with the development of VTE, such as age, obesity, sepsis, immobilization, malignancy, history of thrombotic disease, have their own risk factors, some of which may compound the general risk factors for VTE and these include, sepsis, immobilization (resulting from sedation), mechanical ventilation, cardio-respiratory failure and end stage renal failure [8, 9, 26–28].
There are wide disagreements among previous reports on the independent risk factors for VTE. The univariate and multivariate analysis of our data have shown that infection, longer stay in the ICU and mechanical ventilation were the most significant independent risk factors for VTE. Zhang et al [6] found that the use central venous catheter (P = .002, OR = 4.50), Caprini score (P = .012, OR = 1.20), and ICU length of stay (P = .006, OR = 1.08) were independent risk factors related to the development of VTE in patients admitted to the ICU. On the other hand, Kaplan et al [29] in their study of ICU patients with severe sepsis and septic shock identified the increased length of ICU stay as the only risk factor significantly associated with development of VTE. Shorr and Williams [30] in their earlier larger randomized controlled trial in critically ill patients with sepsis found that history of VTE was the only risk factor independently associated with the development of VTE (odds ratio, 3.66, 95% confidence interval 1.77–7.56, p = 0.005). Hong et al [31] in their survey among critically ill patients with DVT of the lower extremity identified age, gender and BMI as significant risk factors for deep vein thrombosis development (p < .05); ten of their patients (11%) developed deep vein thrombosis during their stay in the intensive care units.
These wide disagreements on the independent risk factors significantly associated with the development of VTE is not un-expected as different studies vary widely in the inclusion criteria of their critically ill patients, their co-morbidities, the clinical setting and last not least the ethnicity of their patients. Considerations should also take into account the disparity in the study design particularly sample size, whether the study is prospective or retrospective. It is no wonder; therefore, there are wide disagreements in the independent risk factors significantly associated with the development of VTE. These disagreements make it difficult to make meaningful comparisons between the findings of different published reports.
Nonetheless infection and/or sepsis seem to be the most frequent independent risk factor associated with, the development of VTE in these published reports. In the current study, CRE infection was found to be the most frequent trigger for the development of VTE and after unconditional multivariate adjustment, it has also resulted in an increased the risk of VTE by almost 3-fold after unconditional multivariate adjustment. Similarly, in the American Health and Retirement nationwide Study, aiming to identify the most common trigger to the development of VTE in hospitalized elderly patients (n = 399) infection was also shown to be the most common reason for hospitalization for venous thromboembolism and has also increased the risk for the development of VTE by 2.9-fold [32].
The important question that needs to be addressed in this respect is about the link between infection and the development of thrombosis. Recently emerging information on the pathophysiological mechanisms of infection-driven thrombosis and VTE has come from in the recent account of Iba et al, [9] who have proposed that microbial products trigger the production and release of inflammatory mediators called pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) during sepsis. Both products activate the coagulation system and trigger the formation of a thrombus. It was also suggested that the increased risk of PE, in particular, might be related to local inflammation in the infected area of the lung. This is compounded by the hypoxic lung environment leading to local vasoconstriction and activation of coagulation [33]. There is also the possibility that severe infection and the associated inflammatory process including the release of pro-inflammatory cytokines would result in activation of the coagulation system and localized thrombotic complications [34].
The other independent risk factor that was significantly associated with the development of VTE was the SOFA score, which was originally developed to give objective quantisation of the degree of the severity of the disease and organ failure of vital body systems including coagulation in patients with sepsis [20]. In patients with sepsis-induced disseminated intravascular coagulation (DIC), Iba et al [35] found that SOFA is a useful score in predicting outcomes including mortality. Additionally, The SOFA score has the added advantage of being relatively easy and is a routine component of patients admitted to ICU. In a recent study on the sepsis-induced hemostatic changes, positive correlation was demonstrated between D-dimer and SOFA score [36]. D-dimer is a fibrin degradation product (FDP) and is a small protein fragment resulting from the breakdown of a fibrin clot (or thrombus). The D-dimer test is now routinely used in the first-line assessment of patients suspected of suffering VTE [37].
One of the primary limitations of our study is its retrospective nature and limited sample size. A larger sample size could have validated better the various risk factors for the development of VTE. In addition, our study was conducted in a single centre and therefore the collected data are subject confounding that may influence our outcomes. A multicentre study with a larger sample size may be necessary to eliminate deviations in the results and to confirm the current findings.