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ORIGINAL ARTICLE
Year : 2018  |  Volume : 31  |  Issue : 1  |  Page : 169-174

Risk factors for venous thromboembolism


Department of General Surgery, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission03-Dec-2016
Date of Acceptance11-Mar-2017
Date of Web Publication14-Jun-2018

Correspondence Address:
Ahmed E. H Abo Elhassan
Department of General Surgery, Faculty of Medicine, Menoufia University, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_659_16

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  Abstract 


Objective
The aim of this study was to describe the risk factors for venous thromboembolism(VTE) in hospitalized patients.
Background
VTE is a major health issue worldwide. To improve survival, avoid recurrence, and prevent complications, the occurrence of VTE must be reduced. To reduce VTE incidence, persons at risk for VTE must first be identified. Independent risk factors for VTE include patient age, surgery, trauma, hospital or nursing home confinement, active malignant neoplasm with or without concurrent chemotherapy, central vein catheterization or transvenous pacemaker implantation, previous superficial vein thrombosis, varicose veins, and neurological disease with extremity paresis.
Materials and methods
This hospital-based prospective study included 400patients with VTE. Patients aged above 18years of both sexes were included. The only exclusion criterion was patients younger than 18years.
Results
There were 400patients diagnosed with VTE. Of all patients, 44% were unprovoked and 56% were provoked. Provoked risk factors included major surgery(4.5%), obesity(12%), hip, femur, and knee surgery(12.5%), history of malignancy(16%), and history of long-term immobility(18%).
Conclusion
Several risk factors were identified in patients with VTE, and their comprehension may improve appropriateness and efficiency of the different methods available for thromboprophylaxis.

Keywords: deep venous thrombosis, pulmonary embolism, risk factors


How to cite this article:
Abu Gruidah HS, Eldsouky MS, Omran WM, Abo Elhassan AE. Risk factors for venous thromboembolism. Menoufia Med J 2018;31:169-74

How to cite this URL:
Abu Gruidah HS, Eldsouky MS, Omran WM, Abo Elhassan AE. Risk factors for venous thromboembolism. Menoufia Med J [serial online] 2018 [cited 2018 Nov 17];31:169-74. Available from: http://www.mmj.eg.net/text.asp?2018/31/1/169/234244




  Introduction Top


Venous thromboembolism(VTE) is a single disease affecting venous circulation. It has two distinct presentations–deep vein thrombosis(DVT) and pulmonary embolism(PE) [1].

To improve survival, avoid recurrence, prevent complications, and reduce healthcare costs, the occurrence of VTE must be reduced. To reduce VTE incidence, persons at risk for VTE must first be identified. Independent risk factors for VTE include patient age, surgery, trauma, hospital or nursing home confinement, active malignant neoplasms with or without concurrent chemotherapy, central vein catheterization or transvenous pacemaker implantation, previous superficial vein thrombosis, varicose veins, and neurological disease with extremity paresis [2].

The risk among surgery patients can be further stratified on the basis of patient age, type of surgery, and the presence of active cancer [3]

High-risk surgical procedures include neurosurgery, major orthopedic surgery of the leg, thoracic, abdominal, or pelvic surgery for malignancy, renal transplantation, cardiovascular surgery, and obesity [4].

Risk factors for VTE among patients hospitalized for acute medical illness may include infection, age more than 75years, cancer, and previous VTE [5].

Active cancer accounts for almost 20% of incident VTE events occurring in the community. Cancer patients receiving immunosuppressive or cytotoxic chemotherapy are at even higher risk for VTE. Previous superficial vein thrombosis is an independent risk factor for subsequent DVT or PE isolated from the episode of superficial thrombophlebitis. BMI, current or past tobacco smoking, chronic obstructive pulmonary disease, and renal failure are not independent risk factors for VTE. The risk associated with congestive heart failure independent of hospitalization is low[2].

Among women, additional risk factors for VTE include oral contraceptive(OC) use and hormone therapy [6].

Risks are higher during pregnancy and in the postpartum period[7], as well as with the use of selective estrogen receptor modulators increase risk. First-generation and third-generation OCs convey higher risk than second-generation OCs [6].

According to the guidelines of the American College of Chest Physicians, risk factors for DVT are classified as provoked or unprovoked [8].

Provoked DVT occurs following surgery or by a nonsurgical transient risk factor such as history of VTE, venous insufficiency, chronic heart failure, thrombophilia, obesity, immobility(such as prolonged travel, acute medical illness, or hospitalization), cancer, use of estrogens(pregnancy, use of OCs, or hormone-replacement therapy), and trauma [9].

The aim of this study was to describe VTE risk factors in hospitalized patients.


  Materials and Methods Top


After obtaining approval from Menoufia Ethics Committee for the study proposal, between December 2015 and November 2016, this prospective observational study was conducted at Menoufia University Hospitals.

We include 400patients who presented with VTE for this study.

Inclusion criteria

Patients aged 18years or older of both sexes with serious medical or surgical conditions admitted to Menoufia University Hospitals were included.

Exclusion criteria

The only exclusion criterion was patients younger than 18years.

As a first step, in this study, a report sheet was filled out on a predefined date by an independent observer for identification of wards, patient demographics, reasons for admission or type of surgical procedure, and risk factors for VTE.

During the screening phase, eligible medical services and patients were identified in Menoufia University Hospitals. This was followed by the data collection phase, which was undertaken by paper chart reviews, recording patient characteristics, medical history, VTE risk status, VTE prophylaxis strategies, and its delivery. Each patient was subjected to full history taking, thorough clinical examination, laboratory investigations including D-dimer testing, and radiological investigations in the form of systematic color-coded Duplex ultrasonography of the symptomatic limb. Multislice computed tomography(CT) scan of the pulmonary vessels was carried out selectively in patients with suspected PE as well as abdominal ultrasound. Classification of patients into risk categories was adopted according to the clinically validated Caprini Risk Assessment Model[Table1]. In this model, the patient fills out a health history; this is given to a nurse or admitting physician who completes and scores the risk assessment form. Approximately 40 risk factors are listed with weights of 1–5 points each. The total risk factor score then is used to group patients into one of four categories(low, moderate, high, and highest risk), each with a recommended prophylactic regimen: score 0–1, low risk of VTE; score 2, moderate risk of VTE; score 3–4, high risk of VTE; and score more than or equal to 5, highest risk for VTE. Patients classified into the moderate-risk category should receive VTE drug prophylaxis(whether unfractionated heparin, low-molecular weight heparin(LMWH), or other approved substances), and patients belonging to the high-risk or very high-risk categories should receive both drug and mechanical prophylaxis. In case of a contraindication to drug prophylaxis, only mechanical prophylaxis should theoretically be considered.
Table 1: Clinically validated Caprini Risk Assessment Model

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We used different treatment options for DVT according to the patient's medical condition and availability of drugs.

  1. The standard anticoagulation treatment for the acute phase of VTE involved the use of LMWH, e.g.,enoxaparin 1mg/kg twice daily
  2. Intravenous unfractionated heparin 5000IU every 2h was used with routine monitoring of activated partial thromboplastin time for dose adjustment followed by long-term administration of warfarin
  3. Vitamin K antagonists were used to prevent recurrent VTE, such as warfarin therapy after parenteral anticoagulant therapy. The recommended target prothrombin time–international normalized ratio (INR) for VTE is 2.0 (range: 1.5–2.5)
  4. Novel oral anticoagulants such as rivaroxaban at an initial dose of 15mg orally twice daily with food for the first 21days were given. Amaintenance dose of 20mg orally once daily in patients with a creatinine clearance of 30–50ml/min and body weight of less than 60kg was given.


Statistical analysis

Results were collected, tabulated, and statistically analyzed by an IBM-compatible personal computer with statistical package for the social sciences(SPSS, version20; SPSS Inc., Chicago, Illinois, USA) software, statistical package version16.

Data are presented as mean, ranges or values, 95% confidence intervals, and frequencies and percentages.

Two types of statistics were performed:

  1. Descriptive statistics, e.g.,number, percentage, mean, and SD
  2. Analytic statistics such as the following:


    1. Student's t-test is a test of significance used for comparing quantitative variables between two groups
    2. The X2 was used to study associations between qualitative variables. Whenever any of the expected cells were less than five, Fischer's exact test was used.



      Results Top


    This study was carried out at Menoufia University Hospital from the period between December 2015 and November 2016. It included 400patients of both sexes with VTE. All of them underwent assessment for the presence of risk factors of VTE.

    There were 122(30.5%) surgical patients and 278(69.5%) medical patients. Patients' age ranged from 23 to 78years, with a mean of 44.20. There were 232(58%) male patients and 168(42%) female patients. Atotal of 400patients presented with DVT, and 27patients out of them presented with PE.

    The included risk factors and their incidence are discussed in [Table2].
    Table 2: Risk factors of venous thromboembolism

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    The main risk factors for VTE development were malignancy, history of long-term immobility, obesity, and orthopedic operations(16, 18, 12, and 12.5%, respectively).

    By using a duplex study to locate the site of DVT, two patients with inferior vena cava thrombosis, 21patients with common iliac vein thrombosis, 30patients with external iliac vein thrombosis, 246patients with common and superficial vein thrombosis, and 101patients with popliteal and calf vein thrombosis were identified[Table3].
    Table 3: Location of deep venous thrombosis depending on the duplex study

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    According to the Caprini Risk Assessment Model, the VTE risk factors stratified into low, moderate, high, and very high were found in 184(46%), 24(6%), 56(14%), and 136(34%) patients, respectively[Table4].
    Table 4: Risk factor stratification

    Click here to view


    Therefore, there is need for prophylaxis in the moderate-risk, high-risk, and the very high-risk groups. In this study, there were 346(86.5%) patients at risk of VTE eligible for chemical prophylaxis, whereas 47(11.75%) patients were not eligible for chemoprophylaxis; therefore, those patients received mechanical prophylaxis. The remaining patients were not eligible for either chemo or mechanical prophylaxis.

    Regarding D-dimer testing, we found 378patients with positive results and 22patients with negative results despite existence of VTE[Table5].
    Table 5: D-dimer testing

    Click here to view


    In this study, the majority of patients(304) were treated with LMWH followed by warfarin, 84patients received UFH followed by warfarin, and 12patients received new oral anticoagulants[Table6].
    Table 6: Lines of treatment

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      Discussion Top


    In this prospective, hospital-based study, patient demographics, risk assessment, and VTE prophylaxis practices were studied. There were 400patients who developed DVT diagnosed using clinical data, duplex study, and D-dimer testing. Twenty seven of them developed PE diagnosed using clinical data, multislice CT scanning, and D-dimer testing. Patients' age ranged from 23 to 78years, and the mean age was 44.20, as aging leads to aging of veins and valves with decreased muscle pump power. There were 232(58%) male patients and 168(42%) female patients with no well-established data to declare the cause of increased incidence in males.

    Using clinical data and the duplex study on admission, we identified the location of the DVT; there were two patients with inferior vena cava thrombosis, 21patients with common iliac vein thrombosis, 30patients with external iliac vein thrombosis, 246patients with common and superficial femoral vein thrombosis, and 101patients with popliteal and calf vein thrombosis.

    The number of medical patients was higher than surgical patients. Patients at low and very high risk for VTE development formed the main bulk of our patients.

    In this study, there were 48(12%) obese patients (BMI>25), whereas the rest o them were nonobese (88%). Eichinger etal.[10] demonstrated that among 1107patients the probability of DVT was 16.7% among overweight patients(BMI 25–29kg/m 2) and 17.5% among obese patients(BMI≥30kg/m 2).

    In this study, 6% of women who received OC pills had associated VTE. The official reports of 2012 show that OCs are being used by 11 million women(17%) in the USA and 100 million women worldwide [11].

    In this study, 64(16%) patients with malignant diseases or receiving chemotherapy presented with VTE. Medical records of residents from the Worcester metropolitan area were obtained, including a total of 1399 individuals with a confirmed episode of venous thrombosis. Of these patients, 29% had a recent or active malignant neoplasm [12].

    In this study, 16/400(4%) patients who underwent major surgery suffered from VTE. Studies from the USA indicate a perioperative incidence of 2–3% [13].

    In this study, 48/400(12%) patients with knee or hip surgery developed DVT, and 40/400(10%) patients with leg and other lower-extremity fractures who underwent surgery or not developed VTE.

    The risk of DVT appears to increase with the proximity of the fracture to the knee; tibia plateau fractures have the highest risk(43%), followed by fractures of the tibia shaft(22%), and the distal tibia [14].

    In this study, 72/400(18%) patients suffered from VTE due to long-term immobility caused by bed rest, fever, gastroenteritis, or paraplegia. Gibbs found that 15% of patients on bed rest for 1week before death had venous thrombosis at autopsy, whereas the incidence rose to 80% in patients in bed for a longer period [15].

    In this study, 8/400(2%) patients who had a past history of VTE developed DVT.

    A cohort study of 673patients found that 3.0% of patients suffered recurrence despite anticoagulation and that most(79%) recurrences were fatal. Risk factors for recurrence despite anticoagulation included immobilization, cancer, or chronic obstructive pulmonary disease [16].

    In this study, about 8/400(2%) patients who had a family history of VTE developed DVT.

    Sørensen etal. [17] recently published a large, Danish, nationwide study including 30179 siblings of 19599 VTE cases, and showed that siblings of the index patient were found to have a two-fold to three-fold higher risk of VTE compared with the general population.

    In this study, among patients who had VTE, 3/400(0.7%) patients had congenital or acquired thrombophilia either due to protein C or due to protein S deficiency, antithrombin III deficiency, lupus anticoagulants, or any other cause of thrombophilia.

    Inherited thrombophilic states probably also contribute to childhood thrombosis, although their importance has not been determined, and the incidence of inherited prothrombotic states in childhood thrombosis is unclear, with recent reports suggesting incidences between 3.9 and 83% [18].

    In this study, 16(4%) patients who were pregnant or in the postpartum period developed VTE.

    In the USA, nationwide, inpatient sample, the VTE rate was 17.2% for deliveries. During pregnancy, the risk of VTE begins in the first trimester [19].

    In a Mayo Clinic study, the highest risk period seemed to be the postpartum period [20].

    In this study, the incidence of unprovoked VTE was 42%.

    In the study by Cushman etal. [21], 47% of 304cases had idiopathic VTE, defined as no associated cancer, antecedent trauma, or recent surgery or immobilization.

    In this study, we also discussed the use of abdominal ultrasound to detect whether there is hidden malignancy; this is performed selectively in patients with suspected malignancy, as there are no provoked risk factors of VTE. We found that two patients with DVT at the common femoral vein had developed cancer of the pancreas, and this diagnosis was confirmed by CT scanning with oral and intravenous contrast and the tumor marker CA19.9 and CEA; therefore, ultrasound is very important to exclude the presence or absence of hidden malignancy for earlier management and intervention.

    Cornuz etal. [22] reported 10% malignancy-detection rate in patients with VTE using abdominal ultrasonography.

    In this study, D-dimer testing was used to complete our diagnosis. Atotal of and 378patients who developed VTE had positive D-dimer test results, whereas 22patients with VTE had negative D-dimer test results; thus, this test is important for the diagnosis of VTE.

    In the emergency department, apart from clinical assessment, testing for D-dimer levels is performed to rule out a diagnosis of VTE in low-risk patients. In a meta-analysis performed by Stein etal. [23], which included 31 studies to determine the accuracy of D-dimer testing in patients with suspected VTE, the prevalence of VTE ranged from 20 to 78%(average, 36%).

    According to the Carpini risk factor assessment model, patients are classifieds into low-risk, moderate-risk, high-risk, and very high-risk groups. Accordingly the patient received prophylactic regimen as follow : First grade : early ambulation and mechanical prophylaxis, grade 2: chemical prophylaxis (LMWH ) with or without mechanical prophylaxis and finally grade 3: chemical with mechanical prophylaxis, respectively.

    The current standard for initial treatment is to administer once daily, weight-adjusted LMWH (1mg/kg) until the INR from the concomitant VKA therapy is achieved. This is generally 5–10days. As LMWH is predominantly excreted by the kidneys, in patients with significant renal dysfunction, unfractionated heparin is the parenteral anticoagulant of choice [24].

    In this study, we started to give the patients of VTE anticoagulant therapy including: LMWH (304 patients ) and unfractionated heparin and vitamin K antagonist (84 patients). We started anticoagulants from the second day and on the fourth day we stopped the parenteral heparin and completing our regimen using vitamin K antagonist until the patient's INR within 1.5–2.5. So patients who had INR (<1.5) were 27 patients (6.8%), patients who had INR (1.5–2.5) were 339 (84.9%) patients, patients with INR (>2.5) were 21 (5.1%) patients and patients who are not available with no available INR were 13(3.1%) patients and this regimen is continued for 6months if the patient had VTE for the first time and for 1year if second time for VTE and for life if the patient had recurrent VTE.

    There were 12patients who received novel oral anticoagulants from the start with an initial dose of 15mg orally twice daily with food for the first 21days. The maintenance dose was 20mg orally once daily for 6months.


      Conclusion Top


    An improved understanding of the epidemiology and risk factors for first and recurrent venous thrombosis can translate to improved clinical outcomes in practice. Consideration of risk factors can allow optimal use of prophylactic strategies against venous thrombosis.

    Financial support and sponsorship

    Nil.

    Conflicts of interest

    There are no conflicts of interest.



     
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        Tables

      [Table1], [Table2], [Table3], [Table4], [Table5], [Table6]



     

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