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ORIGINAL ARTICLE
Year : 2018  |  Volume : 7  |  Issue : 4  |  Page : 165-168

Thromboembolic disease - Etiological factors and diagnostic approach


1 Department of General Surgry, General Hospital, Konjic, Bosnia and Herzegovina
2 Department of Pharmacology, Faculty of Medicine, Sarajevo School of Science and Technology; Department of Cardiology, General Hospital “Prim.dr. Abdulah Nakas”, Sarajevo, Bosnia and Herzegovina

Date of Web Publication31-Dec-2018

Correspondence Address:
Dr. Edis Dzino
General Hospital, Konjic
Bosnia and Herzegovina
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/rcm.rcm_26_18

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  Abstract 


Background: The aim of the article was to define etiological factors for the occurrence of thromboembolism venous and arterial segments and preview of the sensitivity and specificity of diagnostic procedures in the treatment algorithm. Patients and Methods: The study included 60 patients during the 4-year period. The patients are classified into two groups according to the type of thromboembolism, in the group under the diagnosis of venous thromboembolism and group under the diagnosis of arterial thromboembolism. Results: Statistical analysis showed that arterial thromboembolisms occurred statistically significant later in comparison to venous (t = 4.0969; P = 0.0001). The mortality relationship with all analyzed parameters (age, erythrocytes, hemoglobin, platelets, gender, D-dimer, fibrinogen, immobility, veins surgery, pregnancy, smoking, orthopedic trauma, neoplasms, and pulmonary embolism) showed that statistically significant association was observed only in the case of pulmonary embolism. Conclusion: Biochemical parameters of the blood of patients; red blood cell count, hemoglobin concentration, and platelet counts in the study conducted showed a positive relationship with the occurrence of venous thromboembolism while D-dimer and fibrinogen present in increased values in most patients with venous and arterial thromboembolism. Pulmonary embolism directly affects the outcome of patients with thromboembolic diseases taking into account that in the study conducted in venous thrombosis complicated pulmonary embolism resulted in deaths.

Keywords: Algorithms, pulmonary embolism, thromboembolism


How to cite this article:
Dzino E, Begic E. Thromboembolic disease - Etiological factors and diagnostic approach. Res Cardiovasc Med 2018;7:165-8

How to cite this URL:
Dzino E, Begic E. Thromboembolic disease - Etiological factors and diagnostic approach. Res Cardiovasc Med [serial online] 2018 [cited 2019 Mar 22];7:165-8. Available from: http://www.rcvmonline.com/text.asp?2018/7/4/165/249050




  Introduction Top


Available data show that more than 95% of pulmonary embolisms are as a result of a thrombus located in the deep veins of the lower extremities.[1],[2] Larger veins in the legs (popliteal vein and the veins above it) are a very frequent source of lung embolisms, which are at the heart of clinical interest, and pulmonary embolisms should be considered the most serious complication of deep vein thrombosis (DVT).[2] Risk factors for DVT are inextricably linked to the causes of cardiovascular disease; hence, a high body mass index (obesity) and smoking increase the risk of DVT. The diagnosis is based on anamnestic data, clinical findings, coagulation parameters (nonspecific), and D-dimer (elevated values do not immediately mean thrombosis; however, normal values are probably excluded from the study).[3] Pulmonary embolism is the most serious DVT complication resulting in complete or partial obstruction of pulmonary arterial circulation of the distal part of the lung.[4],[5],[6]

Aim

The aim of the article was to define etiological factors for the occurrence of thromboembolism venous and arterial segments and preview of the sensitivity and specificity of diagnostic procedures in the treatment algorithm of thromboembolic disease.


  Patients and Methods Top


The study (retrospective, descriptive, and analytical) included 60 patients who were treated with the diagnosis of thromboembolic diseases of arterial and venous segments at the clinic for Angiology, UCC Sarajevo, in the period January 2012 - January 2016. Patients are classified into two groups according to the type of thromboembolism, in the group under the diagnosis of venous thromboembolism and group under the diagnosis of arterial thromboembolism. Criteria for involvement in the research of patients with the diagnosis of venous thromboembolism were as follows: the patients treated at the clinic under the diagnosis of vein thrombosis and pulmonary embolism, full data from the history of thrombosis localization, confirmed pulmonary embolism with ventilation scintigraphy, D-dimer test, and fibrinogen developed. Criteria for inclusion in the research of patients with a diagnosis of arterial thromboembolism were as follows: the patients treated at the clinic under the diagnosis of acute arterial occlusion, required consultation on treatment with a vascular surgeon. Exclusion criteria were as follows: incomplete parameter data in the history of the disease, occluded occlusive diseases, and the presence of already impaired thromboembolic disease. The analysis was carried out using Pearson's Chi-square test and Student's t-test for independent samples. The results of all the above analyzes were considered statistically significant with P < 0.05 or at a confidence level of 95%.


  Results Top


Analysis and comparison of common parameters for arterial and venous thromboembolism

Analysis of the average age of the patients in the group with venous thromboembolism shows that the same was 51 ± 18.5 years. Interquartile range indicates that half of the participants were aged from 33.25 to 68.75 years, which shows that age over 33 years represents a higher risk of venous thrombosis. The average age of the patients with arterial thromboembolism was 67.6 ± 12 years, with the youngest patient aged 38 years and the oldest at the age of 89 years. Interquartile range indicates that half of the patients were aged from 57.8 to 77.8 years, which indicates that the age above 55 can be considered as a risk. Statistical analysis showed that arterial thromboembolisms occurred statistically significant later in comparison to venous (t = 4.0969; P = 0.0001). There is no significant difference in sex distribution between arterial and venous thromboembolism (P > 0.05). In the group of patients with venous thromboembolism, elevated fibrinogen levels were recorded in 25 or 83.3% cases, with sensitivity and accuracy of 86.2%. In the group of patients with arterial thromboembolism, values above the reference ranges were recorded in 22 or 73.3% of cases with specificity and accuracy of 73.3%. In the total sample, n = 60 elevated values were recorded in 47 or 78.3% of cases, with specificity and accuracy of 79.7%. Statistical analysis of the value of fibrinogen in the group of venous and arterial thromboembolism showed that there is no significant difference in accuracy (P > 0.05). It can be noticed that venous (60%) as well as arterial (50.1%) thromboembolisms occurred more frequently in the proximal parts of the lower extremities. There was, however, a significant difference in the possible occurrence of arterial thromboembolism outside the lower extremities (P < 0.05). Smoking was also statistically significant (P < 0.05) more present in the group of patients with arterial thromboembolism – 63.3% compared to the group with venous thromboembolism – 23.3%.

Analysis of parameters in the venous thromboembolism group

The average erythrocyte values were 4.6 ± 0.5 × 1012/L and ranged from 3.55 × 1012/L to 5.94 × 1012/L. The interquartile range showed that half of the participants had erythrocyte values between 4.2 × 1012/L and 4.95 × 1012/ L with positive asymmetry indicating a higher number of participants with higher values. Lower erythrocyte values were recorded in 36.7% of cases, with specificity and accuracy of 36.7%. The mean hemoglobin value in a group of patients with venous thromboembolism was 130.6 ± 20.8 g/L and ranged from 91 to 177 g/L. The interquartile range showed that half of the participants had a value of 109–145.8 g/L, with positive asymmetry and a tendency to higher values. Lower hemoglobin values were recorded in 50% of the cases leading to specificity and accuracy of 50%.

The average platelet values in this group of participants were 257.3 ± 81.7 × 109/L and ranged from 87 to 411 × 109/L. The interquartile range showed that half of the participants had a value from 203 to 316.8 × 109/L and the highest number of patients had a value of about 300 × 109/L and a deviation from the expected distribution. Furthermore, platelets below the median as a cutoff value had a 50% reduced values below the reference ranges only for 2 or 6.47% of patients.

Analysis of predictors for the venous thromboembolism

The immobility analysis showed that only five patients or 16.7% were immobile, and regardless of the deviation from the expected distribution, the same cannot be considered as a predictor of venous thrombosis. Only three patients or 10% of the total sample had previous vein surgery and cannot be considered as a predictor of venous thrombosis. The same is for pregnancy as a predictor of venous thrombosis (in two patients or 6.7% of the total number of participants). Orthopedic trauma is also a predictor of low-grade venous thrombosis in the investigated sample (in three patients) and the presence of neoplasms was in three patients (χ2 = 9.200; P = 0.0001). Pulmonary embolism confirmed by perfusion scintigraphy was present in 25 or 83.3% of patients in our sample, and as such the specificity and accuracy was 83.3%. The value of D-dimer was elevated in 66.7% cases, while value in 10% of cases was within the reference ranges.

Analysis of parameters observed in arterial thromboembolism

Sinus rhythm was observed in 21 or 70% of cases, with 8 or 26.7% of patients with arrhythmia and one patient with built-in pacemaker. Statistical analysis indicated a deviation from expected distribution in favor of greater sinus rhythm representation (P < 0.05). Hypertension was present in 26.7. Diabetes mellitus was present in 13 or 43.3% of cases and corresponds to the expected distribution of the half of the patients with diabetes mellitus. Hyperlipoproteinemia is present in half of the patients 15 or 50%. The mortality relationship with all of the mentioned parameters showed that statistically significant association was observed only in the case of pulmonary embolism [Table 1].
Table 1: Analysis of examined variables in relation to mortality

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  Discussion Top


Thromboembolic disease or thromboembolism is the third most frequent cardiovascular disease presently occurring immediately after acute myocardial infarction and cerebrovascular injury.[6],[7],[8] Thromboembolism occurs rarely in children. In addition, Abbott et al. in a study that included 7589 participants concluded that the incidence of thromboembolism increases proportionally with the years or the risk of cardiac or stroke in venous thromboembolism increases after 45 years of age.[9] Anderson et al. reported that the incidence of thromboembolism increases exponentially with the years, with a negligible rate of <5/100,000 annually in children, from 450 to 600 cases/100,000 in persons over the age of 80, and the incidence is drastically increasing after 60 years of age. Hansson et al. recorded an incidence of 132–100,000, in the population aged 50–59 years, while in persons aged 70–79, there were 316 cases/100,000.[10],[11] Silverstein et al. recorded an incidence of 147/100,000 in women and 122/100,000 in men. Although this difference is not significant, it is widely assumed that the increased incidence of women occurs due to the use of oral contraceptives, hormonal therapy, or pregnancy.[12],[13] On the other hand, Cushman et al. found a similar incidence in women and men; however, Kniffin et al. noted that women had a slightly higher risk of thromboembolism.[14],[15] Payne et al. investigated the effect of elevated fibrinogen levels as a risk factor in the development of thromboembolism. Increased levels of fibrinogen observed in research were associated with the risk of venous thromboembolism.[16] On the other hand, Folsom et al. examined γ-fibrinogen concentrations and total fibrinogen concentrations in 16,234 participants, both black and white, both sexes older than 50 years. However, after two decades of follow-up, only 521 respondents showed a positive correlation.[17] Pulmonary embolism occurs in 6%–10% of cases when thromboembolism is present in the upper extremities, while as much as 15%–32% of cases with thromboembolism in the lower extremities.[18] Smoking cigarettes is a very important risk factor for thromboembolism. Smoking also increases the mortality rate in people with thromboembolism. Our research has shown that smoking habits and statistically significant (P < 0.05) were more represented in the group of patients with arterial thromboembolism – 63.3% compared to the group with venous thromboembolism – 23.3%. A cohort study involving 57,053 participants, of which 27,178 males and 29,876 women, 50–64 years of age, conducted by Albertsen et al. investigated the effect of smoking on arterial thromboembolism.[19],[20] The mortality rate in patients with thromboembolism was 3.13 for persons consuming >25 cigarettes/day. In addition, the risk of thromboembolism was 3.64, and this study found that smoking significantly increased the risk of thromboembolism and also the mortality due to the already present thromboembolism. In the observation study carried out by Simanek et al., 665 patients were examined, of which 314 were women and 351 males. These patients also had a tumor.[21] Back in 1957, Gibbs in his study showed that in 15% of patients who were lying a week before death, their autopsy revealed the presence of venous thrombosis. In the present study, only five patients or 16.7% were immobile, and statistically immobility is not to be considered a predictor of venous thrombosis but if we consider that our study had a much smaller number of respondents, we are thus be able to ignore statistical indicators and to 16.7% of immobile patients were much more serious information. The incidence is increased to 80% in patients who lie longer period.[22] Multiple traumas in addition to fractures are also a risk factor for the occurrence of thromboembolism. However, they are difficult to interpret because of the different nature of injuries. Geerts et al. in their study show that the deep venous thrombosis occurs in 47% of patients, including proximal DVT in 12%. Deep venous thrombosis, which can further progress to venous thromboembolism, was present in 56% of patients with lower extremity injury and in 40% of patients with head injury, chest, and abdomen.[23] The risk of developing thromboembolism during pregnancy and postpartum is small. Carter and Gent note that the incidence of DVT is similar in women who are pregnant and who are not but are the same age; however, the incidence is 20 times higher in the postpartum period.[24] Ventilation-perfusion lung scans the appearance of computerized tomography was the most commonly used method in the diagnosis of pulmonary embolism. Prospective Investigation of Pulmonary Embolism Diagnosis, wherein ventilation-perfusion imaging compared with the gold standard, angiography of the pulmonary artery. The diagnostic value of the method was the best when the ventilation-perfusion scan was combined with a clinical assessment of the disease. The patients with high clinical suspicion and the high probability of pulmonary embolism in a ventilation-perfusion lung scans had a 95% probability of pulmonary embolism. Le Gal et al. examined 1721 patients with suspected pulmonary embolism. In addition, the majority of these patients already had been present venous thromboembolism. The results confirmed that the D-dimer was negative with 32.7% of patients who have not previously had diagnosed venous thromboembolism whereas in patients with previously diagnosed venous thromboembolism it amounted to 15.9%. Twice less chance for negative D-dimer test depends on the age of the patient, presence of malignancy, or recent surgery. D-dimer test is, therefore, shown to be very important for the diagnosis of venous thromboembolism.[25] Correlation of mortality in relation to all of these parameters in our study showed that there was a statistically significant correlation observed only in the case of pulmonary embolism.


  Conclusion Top


The incidence of thromboembolism either arterial or venous increases with age and is frequently occur in people older than 45 years. Biochemical parameters of the blood of patients; red blood cell count, hemoglobin concentration, and platelet counts in the study conducted showed a positive relationship with the occurrence of venous thromboembolism while D-dimer and fibrinogen present in increased values in most patients with venous and arterial thromboembolism; hence, we can talk about the positive relationship of elevated D-dimer fibrinogen to thromboembolism. Antineoplastic changes, orthopedic trauma, immobility, surgery, and pregnancy were not significant preconditions for the occurrence of thromboembolism in this study since they were present in a very small number of patients. Pulmonary embolism directly affects the outcome of patients with thromboembolic diseases taking into account that in the study conducted in venous thrombosis complicated pulmonary embolism resulted in deaths.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Dilić M, Žutić H, Dizdarević Z, Bukša M. Guideline for deep vein thrombosis and pulmonary thromboembolism, Sarajevo: Ministry of Health Canton Sarajevo; 2006. p. 7-19.  Back to cited text no. 1
    
2.
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Piazza G, Hohlfelder B, Goldhaber Z.S. Handbook for Venous Thromboembolism. USA: Springer; 2015.  Back to cited text no. 5
    
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Dilic M. Clinical angiology, diagnostic and therapy of blood vessel pathology. Faculty of Medicine, University of Sarajevo, Sarajevo; 2011. p.178-83.  Back to cited text no. 6
    
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Griffin P.B. Manual of Cardiovascular Medicine. 4th ed. Philadelphia: Wolters Kluwer, Lipincott Williams and Williams; 2012. p. 451-7.  Back to cited text no. 7
    
8.
Stein PD, Hull RD, Kayali F, Ghali WA, Alshab AK, Olson RE, et al. Venous thromboembolism according to age: The impact of an aging population. Arch Intern Med 2004;164:2260-5.  Back to cited text no. 8
    
9.
Abbott RD, Curb JD, Rodriguez BL, Masaki KH, Popper JS, Ross GW, et al. Age-related changes in risk factor effects on the incidence of thromboembolic and hemorrhagic stroke. J Clin Epidemiol 2003;56:479-86.  Back to cited text no. 9
    
10.
Anderson FA Jr., Wheeler HB, Goldberg RJ, Hosmer DW, Patwardhan NA, Jovanovic B, et al. Apopulation-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT study. Arch Intern Med 1991;151:933-8.  Back to cited text no. 10
    
11.
Hansson PO, Welin L, Tibblin G, Eriksson H. Deep vein thrombosis and pulmonary embolism in the general population. ‘The study of men born in 1913’. Arch Intern Med 1997;157:1665-70.  Back to cited text no. 11
    
12.
Silverstein MD, Heit JA, Mohr DN, Petterson TM, O'Fallon WM, Melton LJ 3rd, et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism: A 25-year population-based study. Arch Intern Med 1998;158:585-93.  Back to cited text no. 12
    
13.
Moores L, Bilello KL, Murin S. Sex and gender issues and venous thromboembolism. Clin Chest Med 2004;25:281-97.  Back to cited text no. 13
    
14.
Cushman M, Tsai AW, White RH, Heckbert SR, Rosamond WD, Enright P, et al. Deep vein thrombosis and pulmonary embolism in two cohorts: the Longitudinal Investigation of Thromboembolism Etiology. Am J Med 2004;117:19-25.  Back to cited text no. 14
    
15.
Kniffin WD Jr., Baron JA, Barrett J, Birkmeyer JD, Anderson FA Jr. The epidemiology of diagnosed pulmonary embolism and deep venous thrombosis in the elderly. Arch Intern Med 1994;154:861-6.  Back to cited text no. 15
    
16.
Payne AB, Miller CH, Hooper WC, Lally C, Austin HD. High factor VIII, von willebrand factor, and fibrinogen levels and risk of venous thromboembolism in blacks and whites. Ethn Dis 2014;24:169-74.  Back to cited text no. 16
    
17.
Folsom AR, Tang W, George KM, Heckbert SR, MacLehose RF, Cushman M, et al. Prospective study of γ' fibrinogen and incident venous thromboembolism: The longitudinal investigation of thromboembolism etiology (LITE). Thromb Res 2016;139:44-9.  Back to cited text no. 17
    
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Kucher N. Clinical practice. Deep-vein thrombosis of the upper extremities. N Engl J Med 2011;364:861-9.  Back to cited text no. 18
    
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Albertsen IE, Rasmussen LH, Lane DA, Overvad TF, Skjøth F, Overvad K, et al. The impact of smoking on thromboembolism and mortality in patients with incident atrial fibrillation: Insights from the Danish Diet, cancer, and health study. Chest 2014;145:559-66.  Back to cited text no. 19
    
20.
Cheng YJ, Liu ZH, Yao FJ, Zeng WT, Zheng DD, Dong YG, et al. Current and former smoking and risk for venous thromboembolism: A systematic review and meta-analysis. PLoS Med 2013;10:e1001515.  Back to cited text no. 20
    
21.
Simanek R, Vormittag R, Ay C, Alguel G, Dunkler D, Schwarzinger I, et al. High platelet count associated with venous thromboembolism in cancer patients: Results from the Vienna cancer and thrombosis study (CATS). J Thromb Haemost 2010;8:114-20.  Back to cited text no. 21
    
22.
Gibbs NM. Venous thrombosis of the lower limbs with particular reference to bed-rest. Br J Surg 1957;45:209-36.  Back to cited text no. 22
    
23.
Geerts WH, Code KI, Jay RM, Chen E, Szalai JP. A prospective study of venous thromboembolism after major trauma. N Engl J Med 1994;331:1601-6.  Back to cited text no. 23
    
24.
Carter C, Gent M. The epidemiology of venous thrombosis, in hemostasis and thrombosis. In: Coleman RW, Hirsh J, Marder VJ, Clowes AW, George JN, editors. Basic Principles and Clinical Practice. Philadelphia, PA: JB Lippincott Co.; 2000. p. 805-19.  Back to cited text no. 24
    
25.
Le Gal G, Righini M, Roy PM, Sanchez O, Aujesky D, Perrier A, et al. Value of D-dimer testing for the exclusion of pulmonary embolism in patients with previous venous thromboembolism. Arch Intern Med 2006;166:176-80.  Back to cited text no. 25
    



 
 
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