Journal of Applied Hematology

ORIGINAL ARTICLE
Year
: 2020  |  Volume : 11  |  Issue : 3  |  Page : 126--131

Anatomical sites and clinical characteristics of venous thromboembolism in a tertiary hospital


Saeed Alshahrani1, Abdulrahman Alfawzan1, Ahmad Alswaidan1, Ala Alkharaan1, Mohammed Alabduljabar1, Altaf Khan2, Mohsen Alzahrani3,  
1 Department of Medical Education, College of Medicine, King Saud bin Abdulaziz for Health and Science, Riyadh, Saudi Arabia
2 King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
3 Department of Medical Education, College of Medicine, King Saud bin Abdulaziz for Health and Science; King Abdullah International Medical Research Center; Department of Oncology, King Abdulaziz Medical City - National Guard Health Affairs, Riyadh, Saudi Arabia

Correspondence Address:
Dr. Saeed Alshahrani
College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, National Guard Health Affairs Ar Rimayah, Riyadh 14611, SA 11426
Saudi Arabia

Abstract

BACKGROUND: Thrombosis is simply the inappropriate activation of clotting factors that occurs in veins. Venous thromboembolism (VTE) is a common medical problem in hospitalized patients that might progress into serious lethal complications. Provoked VTE is associated with well-known risk factors, while unprovoked VTE remains idiopathic. OBJECTIVES: The aim of this study is to describe the anatomical sites, clinical characteristics, and factors associated with recurrence of the thrombotic event within 5 years. METHODS: This retrospective cross-sectional study was conducted in King Abdulaziz Medical City (KAMC), which included 351 hospitalized patients consecutively. We included all Saudi adults diagnosed with initial VTE in 2006–2017 at KAMC. Patients with incomplete medical charts were excluded. The data collected from electronic charts were analyzed using SAS-9.4. RESULTS: Among the 351 participants, 52% were female and two-thirds (62.4%) exceeded the normal body mass index. Provoked VTE (53.5%) was slightly more prevalent than unprovoked VTE (46.4%), but unprovoked VTE was more frequent in populations with recurrent VTE at 19.1%. The most common VTE sites were the left lower limb (38.5%) followed by right lower limb (20.5%) then bilateral lower limbs (12.2%). Only pulmonary embolisms (<0.01) and unprovoked VTE (0.01) were associated with a higher risk of recurrence. However, unprovoked VTE (P = 0.0305) was the only one associated with a higher risk of recurrence after multivariant analysis. CONCLUSION: Venous thrombosis presents mostly with multiple clinical comorbidities in hospitalized patients. Unprovoked VTE was the only risk factor associated with recurrence after multivariant analysis.



How to cite this article:
Alshahrani S, Alfawzan A, Alswaidan A, Alkharaan A, Alabduljabar M, Khan A, Alzahrani M. Anatomical sites and clinical characteristics of venous thromboembolism in a tertiary hospital.J Appl Hematol 2020;11:126-131


How to cite this URL:
Alshahrani S, Alfawzan A, Alswaidan A, Alkharaan A, Alabduljabar M, Khan A, Alzahrani M. Anatomical sites and clinical characteristics of venous thromboembolism in a tertiary hospital. J Appl Hematol [serial online] 2020 [cited 2020 Oct 20 ];11:126-131
Available from: https://www.jahjournal.org/text.asp?2020/11/3/126/295120


Full Text

 Introduction



Thrombosis results from any disturbance to Virchow's triad, which involves endothelial injury, venous stasis, and hypercoagulability. Several etiological factors have been linked to venous thrombosis, including aging, immobilization, obesity, pregnancy, trauma or surgery, vasculitis, and other thrombophilic disorders.[1],[2] According to recent studies conducted in Japanese and Thailand, malignancy was documented in 25.% of Japanese and 62.4% of Thai hospitalized venous thrombosis patients.[2],[3] Furthermore, a case–controlled Sudanese study showed that deep-venous thrombosis was highly prevalent in patients ages >40 years (46.7%), especially among women.[4],[5] Drug-induced thrombosis was diagnosed in 33% of Sudanese and 20.5% of Thai patients.[2],[4] According to the Japanese study, both postoperative status and prolonged immobilization equally constitute 27% of the presented pulmonary embolism (PE) cases.[3]

It is a well-known documented fact that the deep-venous thrombosis of lower limbs were the most common site of thrombosis, with a certain predilection to occur in the left side.[2],[3],[6],[7] In fact, the most common sites for nonextremities-related thrombosis were portal venous thrombosis (29.7%), followed by cerebral venous sinus thrombosis (17%), and pulmonary venous embolism (13.3%).[2] A local study conducted in Jeddah reported that both right lower limb and left lower limb deep vein thrombosis (DVT) were almost equal with (48.4%).[5] However, the results of a Sudanese study showed that DVT in the left side was the most common site with 93.3%.[4] Moreover, DVT in the Sudanese patients was more common in the proximal veins of the lower limb in 84% of cases, especially in pregnant and postpartum women.[4] Previous past medial history of venous thromboembolism (VTE) can increase the risk of another venous thrombotic event, especially in the first 6–12 months after the diagnosis.[8] Furthermore, around one-third of VTE patients will have a recurrence within 10 years.[6]

The most common cancer in Thai patients who were diagnosed with VTE was solid cancers, particularly hepatocellular carcinoma and adenocarcinoma,[3] while cancer in the digestive organs was the most common among Swedish patients with first primary VTE.[9] Locally, the most common cancer among Saudi DVT patients was breast cancer, followed by non-Hodgkin's lymphoma.[10] A Swedish retrospective study showed that around 10% of patients diagnosed with unprovoked and recurrent VTE developed cancer in the 1st year, whereas 2.7%–2.5% developed cancer in the 2nd year.[9]

Many studies have addressed various aspects of DVT in hospitalized patients. However, there is a need to describe the pattern of venous thrombosis with respect to their anatomical sites. In addition, few studies have described the clinical characteristics and comorbidities associated with venous thrombosis in Saudi Arabia.[5],[10],[11],[12] Therefore, we conducted this study to describe the sites and clinical characteristics associated with venous thrombosis.

 Methods



We conducted a retrospective cross-sectional hospital-based study to address the clinical characteristics of patients who presented with venous thrombosis from 2006 until 2017 at King Abdulaziz Medical City in Riyadh, which has a capacity of 1500 beds. With consecutive sampling, we included 351 Saudi adults (age >18-year-old) with venous thrombosis who had their first episode between 2006 and 2017 and then followed up for at least 5 years from the date of their first thrombotic event. We screened 402 patients for inclusion criteria, but we excluded 51 patients for incomplete data or unproven diagnosis of venous thrombosis.

The data collected included patient age, gender, and body mass index (BMI). Furthermore, the site and date of venous thrombosis beside the recurrence times and the presence of concurrent PE were also collected. The diagnosis of venous thrombosis was confirmed by clinical and radiological evaluation. We classified thrombotic events into provoked and unprovoked VTE based on the guidelines of the International Society on Thrombosis and Hemostasis.[13] We assessed multiple comorbidities during the first episode of thrombosis included the presence of documented diabetes mellitus, hypertension (HTN), and chronic kidney disease. We also considered a previous history of myocardial infarction, cardiac arrhythmias, congestive heart failure, and unstable angina as significant cardiac comorbidities. We then assessed inherited and acquired causes of thrombophilia, such as Factor V Leiden, Factor II mutation, antithrombin, proteins C, S deficiencies, anti-phospholipid antibody syndrome, and paroxysmal nocturnal hemoglobinuria. We assessed the history of trauma and/or major surgery, which required general anesthesia for longer than 30 min. In addition, we assessed the presence and type of cancer, chemotherapy used, medications with a high risk to induce thrombosis, oral contraceptives, pregnancy status during the first thrombosis episode, clinical hypothyroidism, and peripheral vascular disorder.

We used Microsoft Excel for data entry and SAS 9.4 for both data entry and analysis. We presented categorical data in frequencies and percentages. We used a Chi-square test to analyze categorical variables and multivariate logistic regression to address the independent risk factors of thrombosis recurrence. We considered a value of P < 0.05 statistically significant.

 Results



According to [Table 1], patient gender distribution was almost equal, with a slight increase in female patients at 54.4%. Furthermore, two-thirds (62.4%) of patients had their BMI scores >25. Provoked venous thrombosis with 53.6% was slightly more prevalent than unprovoked VTE.{Table 1}

Sites of venous thrombosis

According to [Table 2], around 80% of 351 participants had extremity related venous thrombosis, especially the lower limbs compared to upper limbs. The left lower limb was the most common site (115, 32.8%) followed by the lower right lower limb (92, 26.2%) then bilateral lower limbs (43, 12.2%). On the other hand, the left upper limb was almost equal with the right upper limb with 4.3%, 4.6%, respectively. The chest veins, including the superior and inferior vena cava, were reported in 24 patients (6.8%) as the most common site for axial VTE followed by jugular VTE in 15 patients (4.3%). Furthermore, visceral veins, including the portal veins, renal veins, and mesenteric veins, were the lower prevalence in the study population with 3.4%, 2.8%, and 0.8%, respectively.{Table 2}

Clinical manifestations of venous thrombosis

Among 351 patients who had venous thrombosis, around 51.8% of them were considered elderly, as shown in [Table 3]. The most common comorbid condition was HTN at 47.6% (n = 167), followed by diabetes at 37.9% (n = 133), heart failure at 37.9% (n = 133), and chronic kidney disease at 25.6% (n = 90). Cancer accounted for 19.6% (n = 69) of all VTE cases. In addition, 6.8% (n = 24) had paraplegia related to spinal cord disease, while cerebrovascular accidents alone accounted for 14.2% (n = 50) of cases. We found that around 18.5% of our patients had exposed to either of the following: motor vehicle accident trauma, major surgery, or prolonged procedures exceeded 30 min under general anesthesia within 3 months of the provoking venous event. At least one episode of PE was reported in 11.1% (n = 39) of patients. Meanwhile, 19.6% (n = 69) of patients took certain medications that enhances coagulopathy which was distributed as 14% (n = 49) of patients underwent chemotherapy alone, 1.1% (n = 16) took erythropoietin, and 4.6% (n = 4) took oral contraceptive pills. Furthermore, only 4.3% of patients were pregnant during the first detection of thrombosis (n = 15).{Table 3}

Regarding the recurrent VTE, around 120 participants (34.1%) had recurrent VTE within a 5-year interval from their first VTE episode. Only PE (P < 0.01) and unprovoked VTE (P = 0.01) showed a significant risk of recurrence in a univariant analysis. After multivariate analysis, only unprovoked VTE (P = 0.0305) was associated with a higher risk of recurrence. The left lower limb was the most common site for recurrence at 13.1%, followed by the right lower limb at 3.9% and bilateral lower limbs at 2.4%. Within a 5-year interval from the first episode, 23.5% of patients had single episode of venous thrombosis, while 8.2% had two episodes and 2.1% of patients had three episodes.

Cancer-associated thrombosis

Of the 351 patients presented with VTE, around 19.7% (n = 69) were associated with cancer. The most common cancer was lymphoma, with a proportion of 20.3% (n = 14), followed by both breast and colorectal cancer at 8.7% (n = 6), then pancreatic (7.25%, n = 5) and hepatocellular (7.25%, n = 5) cancers. These five types of cancer represented 52% (n = 36) of all cancers in this study. Among those who had VTE, 7.1% (n = 25) had unprovoked venous thrombosis with subsequent cancer diagnoses. We divided cancer-associated thrombosis in terms of cancer diagnosis date into unprovoked preceding thrombosis, concurrent thrombosis, and provoked or postcancer thrombosis. Unprovoked preceding thrombosis, which was detected within a year of cancer diagnosis, was found in 4% of patients (n = 14). Meanwhile, 3.1% (n = 11) of patients presented with unprovoked venous thrombosis concurrently within a month of cancer diagnosis after a simple or routine evaluation. We considered the other 12.5% (n = 44) of cancer-associated thrombosis detected after the diagnosis of cancer or initiation of chemotherapeutic agents to be provoked thrombotic events. Among the cancer patients, 26% had a recurrence of a venous thrombotic event, which accounted for 5% of all patients presented with thrombotic events.

 Discussion



Baseline characteristics

Around half of the patients enrolled in this study were the elderly (above 60 years old). This shift toward older age is typical in studies addressing the incidence and factors associated with VTE in hospitalized patients, as it might not be possible to detect VTE in the general population. In addition, the risk of thrombosis significantly increases after the age of 60 years, as aging is associated with the presence of multiple risk factors.[14] There is a strong association between elevated BMI and the risk of thrombosis, as obesity enhances the prothrombotic state through increased expression of plasminogen activator inhibitor-1.[15] More than 60% of our patients had a BMI >25. The mean BMI score was found to be 28 in a similar study done in Germany.[16] This might be explained by the higher prevalence of obesity in Saudi Arabia, which was estimated to be 35%.[17] There is no clear common epidemiology regarding the distribution of provoked and unprovoked VTE. The prevalence of unprovoked VTE in this study, which was 46.4% was low compared to one study reported that 58.1% of thrombosis cases to be unprovoked.[16]

Sites of venous thrombosis

There are few local studies that have addressed the possible different locations of venous thrombosis.[5],[11] We have reported all possible VTE sites and not restricted such sites only to the lower limbs. First, we found DVT in extremities (including upper and lower) present in 80.1% of our patients, where the upper limbs comprised 8.8% and lower limbs 71.2%. The left lower limb was the most frequent site for VTE. According to this study, there is a slight tendency to have left-side thrombosis (37%) compared to the right (30.8%), which is in accordance with other global studies.[2],[3],[7],[8] Axial thrombosis, including superior vena cava, inferior vena cava, and jugular veins, was reported at 11.1%. Visceral thrombosis was less frequently reported in the literature,[17] though we found it to account for 6.6% out of all VTE events. We found portal vein thrombosis to be the most common site among visceral venous thrombosis at a proportion of 3.4%. In fact, visceral venous thrombosis could be associated with relevant organ diseases. For example, people with hepatic thrombosis tend to have hepatic risk factors such as hepatocellular carcinoma, people with renal thrombosis tend to have kidney transplants or other kidney risk factors, and so on.[18] It is noted from previous studies that certain sites of thrombosis might dominate in certain ethnicities.[4]

Clinical manifestations of venous thrombosis

Similar to our findings, many studies have shown that HTN is the most common chronic disease among VTE patients.[19] Although diabetes mellitus was highly prevalent in our study (34.9%), diabetes is unlikely to contribute to the venous thrombosis risk.[20] Such a high prevalence of diabetes in our sample could be explained by the higher proportion of diabetes among the Saudi population.[21] Moreover, around half of our patients were elderly and hence more likely to have comorbid conditions like diabetes. We detected cardiac diseases, including heart failure, myocardial infarction, and unstable angina, in 33% of our patients. Previous estimates of 17.5%, 9.9%, and 2.7% correspondingly represent the clinical history of heart failure, myocardial infarction, and unstable angina.[22] Chronic kidney disease was present in 25.6% of our patients. The risk of thrombosis increased 1.3–2 folds with mild-to-moderate kidney disease and 2.3-fold in end-stage renal disease. Studies have discussed hemostatic abnormalities in chronic kidney disease, but the pathogenesis is still unclear.[23] Surgery also increases the risk of VTE, especially with general anesthesia.[24] One study reported the incidence of untreated postoperative venous thrombosis was 71% after total knee replacement, 51% after total hip replacement, 41% after urologic surgery, 23%–34% after vascular surgery, and around 20% after general abdominal surgery.[25] Trauma is also a significant risk factor of thrombosis, as it increases the risk of extremity fracture.[25] We found that the prevalence of VTE following major trauma or surgery was 18.5%. In our data, concurrent PE with DVT measured at 11.1% (n = 39). In a systematic review, the rate of PE in concurrent DVT ranged between 5.1%–43.4%, with a median of 12.8%.[26] In another review, PE was prevalent in 24 of 183 patients (13.1%) (95% confidence interval, 8.9%–18.8%).[27] Although PE has a high mortality rate, it also has a wide range of incidence, and diagnosis is most likely to be missed. Cancer-associated thrombosis was estimated worldwide to comprise 20% of all VTE events.[28] There has been no previous study in Saudi Arabia investigated the incident. Our results were 19.7%, which are similar to the global findings.[28] Moreover, our findings showed that 14.2% of patients had a stroke, and according to previous studies, the incidence of DVT after the stroke occurs in 3%–8.7% of patients.[29],[30] It is well-known that HTN is the most modifiable stroke risk factor. In one study, a quarter of stroke patients had HTN (24.9%).[1] In this analysis, approximately half of the patients had HTN, and many were older and obese, which may explain the increased incidence of stroke. In this analysis, 8% of the patients had hypothyroidism, and two studies that are consistent with ours discussed the incidence of DVT among hypothyroidism, giving percentages of 0.9% and 1.4%.[31],[32] We found 6.8% of our patients had thrombophilia, either congenital or acquired. One paper studied the most common genetic type, Factor V Leiden, and found it in 20%–25% of patients with VTE.[33]

Factors associated with recurrence of the thrombotic event

Perhaps, the most important finding in this analysis is that half of the patients who experienced unprovoked VTE had a recurrent event. Among the 121 recurrent VTE patients, 67 had unprovoked initial VTE episodes. In this analysis, unprovoked VTE (P = 0.0305) was the only significant finding for VTE recurrence. These findings match with global results.[6],[8] Recommendations for thromboprophylaxis treatment consider indefinite thromboprophylaxis after balancing the benefits and risks for patients with unprovoked initial VTE.[34],[35] In a univariant analysis, PE (P < 0.01) is also considered a risk for recurrence. However, this was not after multivariant analysis. As per two global studies, 10% and 5.6% of patients who experienced PE had recurrent VTE episodes.[36],[37] In addition, 24% of patients after the discontinuation of thromboprophylaxis had recurrent episodes.[37] In a meta-analysis, PE patients had a threefold increased risk of recurrence than distal DVT patients.[38] As PE has a higher mortality rate than distal DVT and a higher risk of recurrence than other provoked VTE factors, the dose or duration of thromboprophylaxis should be reviewed, as well as the cost of bleeding. All in all, more evidence is needed to determine the proper thromboprophylaxis. On the other hand, provoked VTE was shown to not be a risk for recurrence. In our data, 59 males and 61 females had recurrent venous thrombosis. Therefore, gender is unlikely a risk factor for recurrent venous thrombosis within 5 years. The female patients' risk of thrombosis recurrence appears to be similar to that of males, although global evidence studies identified that males have a 1.5–2-fold increased risk of recurrent venous thrombosis.[39]

This retrospective study answered many questions about sites, clinical features of hospitalized patients with venous thrombosis, but many other important risk factors were unavailable in the chart reviews such as smoking, family history, travel history, mortality, etc. Furthermore, the level of significance in terms of the recurrence was also affected by the higher proportion of elderly patients (52%) in our study, where patients presented multiple comorbidities.

 Conclusion



Recurrence and clinical comorbidities of the thrombotic event are common in our hospitalized patients. Unprovoked VTE was the only risk factor associated with recurrence after multivariant analysis. Our results need to be confirmed in a prospective study or a national registry-based study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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