Abstract
Background
Early recognition of venous thromboembolism (VTE) risk and intervention with appropriate thromboprophylaxis are effective for preventing adverse disease outcomes in hospitalized patients. However, there is a paucity of data to know the use of anticoagulant prophylaxis rate in the emergency department of Ethiopia. Therefore, this study aimed to assess the rate of prophylaxis use and associated factors in the emergency department of tertiary care hospitals in Addis Ababa city, Ethiopia.
Method
A multicentre hospital-based prospective study was conducted in patients admitted to the adult emergency department of three selected tertiary care hospitals. Multivariate logistic regression was performed to identify independent predictors for initiating anticoagulant prophylaxis. P < 0.05 was considered to indicate statistically significant.
Results
A total of 422 patients were enrolled. Nearly two-thirds (70.64%) of the participants had a Padua Risk Prediction Score of ≥ 4 points, indicating a high risk of developing venous thromboembolism. Among the 296 patients eligible for anticoagulant prophylaxis, only 33.4% received it. Patients who were bedridden ≥ 3 days were three times more likely to receive anticoagulant prophylaxis (adjusted odds ratio (AOR) = 3.129,95% CI = 1.310–7.474, P = 0.001). Similarly, patients aged ≥ 70 years were more likely to receive prophylaxis (AOR) = 1.880, 95% CI = 1.007–3.510, P = 0.047). However, patients with a length of stay (LOS) < 7 days (AOR) = 0.192, 95% CI = 0.095–0.385, P < 0.001) and those who presented with an acute infection (AOR) = 0.619, 95% (CI): 0.342–1.122, P < 0.014) were less likely to receive anticoagulant prophylaxis.
Conclusion
Thromboprophylaxis was underutilized in the emergency department, even among high-risk patients. Factors such as older age, prolonged immobility, prior VTE, active cancer, infection, and longer emergency department (ED) stay significantly influenced the likelihood of prophylaxis administration.
Clinical trial number
Not applicable.
Keywords: VTE risk, Thromboprophylaxis, Emergency department, Padua score
Background
Venous thromboembolism (VTE) is a condition in which a blood clot forms in a vein.VTE includes deep vein thrombosis (DVT) and pulmonary embolism (PE) [1]. This problem could occur as a result of different surgical or medical conditions and might result in significant morbidity and mortality unless appropriate measures are taken for its prevention. It is a major public issue in which approximately 20% of individuals who experience venous thromboembolism die within 1 year [2]. The likelihood of long term complications are also substantial, and include post thrombotic syndrome(PTS) where 50% of symptomatic DVTs develop and PE can complicate chronic pulmonary hypertension [3]. Treating VTE that has already occurred is more difficult than prevention strategies and results in a significant economic burden on the health care system [4]. Medical service fees are the largest contributor to total costs, and the length of hospital stay required for VTE treatment is a key factor associated with higher hospitalization costs [5].
Various factors increase the risk of VTE in acutely ill medical patients including advanced age, prolonged hospitalization, acute illness such as sepsis, cardiovascular complications and accidental trauma as these conditions enhance the hypercoagulability state [6]. The use of anticoagulant prophylaxis for at-risk individuals has been proposed as an effective strategy for preventing VT that is clinically and financially beneficial compared with treatment for individuals who have already experienced thrombosis [7]. The most popular worldwide VTE prevention guidelines including those of the American College of Chest Physicians (ACCP) and the American Society of Haematology (ASH) recommended low dose of unfractionated heparin(LDUFH) or low molecular weight heparin(LMWH) for patients stratified as having a high VTE risk unless contraindicated [8].
However, there are factors affecting the implementation of the recommendations in emergency departments (EDs). A cross-sectional survey conducted in China including 2079 medical staff working in emergency departments from different hospitals to assess the knowledge, attitudes, and practices regarding VTE prophylaxis among medical staff. The study found that more than half (58.2%) of the participants were concerned about increased workload, higher medical costs, prolonged hospital stays for prophylaxis completion, and the need to transfer high-risk patients to inpatient wards to initiate anticoagulant prophylaxis [9].
In resource-limited countries including the study area the trend of emergency care service has changed from stabilizing acute illness within an hour to admitting the patient for prolonged days to weeks due to service mismatch with increasing demand [10, 11]. This indicates that emergency physicians need to recognize VTE risk early at the time of ED admission and intervene with the occurrence of VTE through appropriate provision of anticoagulant prophylaxis to prevent potential complications resulting from the disease. Even though administering prophylactic medication to a patient who deserves it will significantly decrease VTE event, unnecessarily exposing patients who are not the appropriate candidate for receiving prophylactic medications will increase the risk of bleeding and other adverse outcomes of the drug [12]. As a result, pharmacological prophylaxis for VTE prevention should be initiated through the use of risk stratification tools [13]. However, the status of VTE prophylaxis utilization in the EDs in Ethiopian hospitals has not yet been studied. Hence, we aimed to assess the rate of thromboprophylaxis use in the EDs of tertiary care hospitals in Addis Ababa, Ethiopia.
Methods and materials
Study settings, design and period
A multicentre hospital-based prospective study design was employed at the ED of three selected hospitals from June 1 to September 15, 2023. The study included patients admitted to the adult emergency wards of three public hospitals in Addis Ababa city, Ethiopia. These hospitals are Tikur Anbesa Specialized Hospital (TASH), Addis Ababa Burn Emergency and Trauma Hospital, (AaBET), and St. Paulos Hospital Millennium Medical (SPHMMC). Out of these the 14 public hospitals in Addis Ababa city, these three are considered higher tertiary care and teaching hospitals in the country. They serve severe as referral centers for the communities of the capital city and all regions of the country providing emergency care and inpatient services.
Inclusion and exclusion criteria
Patients with complete documentation, who were admitted to the adult emergency wards of the selected hospitals during the study period, and who consented to participate were included. Patients admitted with established VTE and already on treatment were excluded from the study because they should not be taking prophylactic dose of anticoagulant medications.
Sample size and sampling method
The sample size of this study was determined by a single population formula. Since the proportion of VTE prophylaxis rate in the emergency setting in Ethiopia has not yet been determined, considering the assumptions of a 50% proportion and 95% confidence interval (CI), and a precision of 5% with the addition of a 10% nonresponse rate, the sample size calculated was 422. Theproportional allocation method was employed to obtain the sample proportion from each hospital. Accordingly, an average of 2080 patients were assumed to visit EDs every month 800,760 and 522 patients from TASH, AaBET and SPHMMC respectively were considered to determine sample proportion. Overall, 800/2080, 760/2080, and522/2080 yielded 162 patients, 154 patients and 106 patients from TASH, AaBET and SPHMMC respectively for a total of 422 sample patients.
Data collection, management, quality assurance, and analysis
The data collection tool was designed to assess Sociodemographic data such as age and sex. The Padua risk assessment model (RAM) was used to assess VTE risk. Eligibility for anticoagulant prophylaxis was determined if the Padua risk prediction score was ≥ 4 points and there was no contraindication according to ACCP guidelines including recent bleeding from trauma, gastrointestinal tract bleeding within 3 months, severe thrombocytopenia and intracranial haemorrhagic. Inappropriate thromboprophylaxis was considered if anticoagulants are given to patients with Padua risk prediction score of < 4 points or given in the presence of contraindications. The data was collected by three nurses and the principal investigator after one day training was given. A pre-test was conducted at ED of Yekatit 12 hospital medical college on 5% of the study population for checking data collection; instrument clarity, simplicity, and necessary modifications were made to it before actual data collection.
Statistical analysis
Statistical Package for the Social Sciences (SPSS) version 25 was used for analyzing the data. Descriptive statistics were used to analyze relevant socio-demographic and clinical characteristics, and logistic regression analysis was performed to assess the associations between thromboprophylaxis initiation and independent variables. The adjusted odds ratio was used to measure the strength of association. P < 0.05 was considered to indicate statistically significant.
Results
Sociodemographic and baseline characteristics
Of the 422 participants included in the study, nearly half (51.7%) were male. The ages of the participants ranged from 19 to 97 years. Approximately 61 (14.5%) were alcohol drinkers, 9 (2.1%) were cigarette smokers, and 11 (2.6%) reported using both alcohol and cigarettes. About one-third of the participants (130, 30.8%) had spent the entire week in a sitting or lying position prior to ED admission due to chronic illness (Table 1).
Table 1.
Sociodemographic characteristics of the study participants at emergency departments of AaBET, TASH, SPHMMC from June to September 2023 (n = 422)
| Characteristics | Category | Frequency (%) | |||
|---|---|---|---|---|---|
| AaBET | SPHMMC | TASH | Total | ||
| Age | 18–29 | 32(7.6%) | 7(1.7%) | 11(2.6%) | 50(11.8%) |
| 30–49 | 47(11.1%) | 43(10.2%) | 74(17.5%) | 164(38.9%) | |
| 50–69 | 50(11.8%) | 28(6.6%) | 44(10.4%) | 122(28.9%) | |
| >=70 | 25(5.9%) | 28(6.6%) | 33(7.8%) | 86(20.4%) | |
| Sex | Male | 97(23%) | 48(11.4%) | 73(17.3%) | 218(51.7%) |
| Female | 57(13.5%) | 58(13.7%) | 89(21.1%) | 204(48.3%) | |
| Physical activity | Active | 121(28.7%) | 65(15.4%) | 106(25.1%) | 292(69.2%) |
| Inactive | 33(7.8%) | 41(9.7%) | 56(13.3%) | 130(30.8%) | |
| Social habit | Alcohol drinker | 26(6.2%) | 16(3.8%) | 19(4.5%) | 61(14.5%) |
| Cigarette smoker | 6(1.4%) | 1(0.2%) | 2(0.5%) | 9(2.1%) | |
| Both | 3(0.7%) | 3(0.7%) | 5(1.2%) | 11(2.6%) | |
| None | 119(28.2%) | 86(20.4%) | 136(32.2%) | 341(80.8%) | |
Nearly two-thirds (76.3%) of the patients had comorbid illnesses. The most common comorbidity was hypertension (49.5%), followed by malignancies (26.3%), heart disease (24.4%), and diabetes mellitus (20.3%). The most frequent admission diagnoses were trauma (23.7%), infectious diseases (19.2%), sepsis (14.7%), stroke (9.7%), and acute kidney injury (5.9%). The average length of stay in the emergency department was 8 days (SD ± 6.06), ranging from 1 to 32 days. Among the participants followed in the ED during the study period, 47.4% were discharged, 34.6% were transferred to the internal medicine ward, 7.8% to the intensive care unit (ICU), 3.1% to the surgical ward, 4% to the oncology ward, and 3.1% died (Table 2).
Table 2.
Baseline clinical characteristics of study participants at emergency departments of AaBET, TASH, SPHMMC from June to September 2023 (n = 422)
| Characteristics | Category | Setting N(%) | ||||
|---|---|---|---|---|---|---|
| AaBET | SPHMMC | TASH | Total | |||
| Co- morbidity | Yes | 78(18.5%) | 93(22%) | 151(35.8%) | 322(76.3%) | |
| No | 76(18%) | 13(3.1%) | 11(2.6%) | 100(23.7%) | ||
| Co-morbidity types | Hypertension | 67(21.3%) | 43(13.7%) | 46(14.6%) | 156(49.5%) | |
| Heart disease | 10(3.2%) | 27(8.6%) | 40(12.7%) | 77(24.4%) | ||
| DM | 18(5.7%) | 16(5.1%) | 30(9.5%) | 64(20.3%) | ||
| Cancer | 0(0%) | 15(4.8%) | 68(21.6%) | 83(26.3%) | ||
| Asthma | 6(1.9%) | 6(1.9%) | 9(2.9%) | 21(6.7%) | ||
| HIV | 4(1.3%) | 10(3.2%) | 17(5.4%) | 31(9.8%) | ||
| CKD | 2(0.6%) | 9(2.9%) | 10(3.2%) | 21(6.7%) | ||
| COPD | 1(0.3%) | 6(1.9%) | 0(0%) | 7(2.2%) | ||
| Other | 29(6.9%) | 31(7.3%) | 24(5.7%) | 84(19.9%) | ||
| Admission Diagnosis | Sepsis | 11(2.6%) | 13(3.1%) | 38(9%) | 62(14.7%) | |
| Infectious disease | 6(1.4%) | 18(4.3%) | 57(13.5%) | 81(19.2) | ||
| AKI | 0(0)%) | 15(3.6%) | 10(2.4%) | 25(5.9%) | ||
| Acute heart failure | 1(0.2%) | 11(2.6%) | 13(3.1%) | 25(5.9%) | ||
| Acute asthma | 3(0.7%) | 6(1.4%) | 2(0.5%) | 11(2.6%) | ||
| Malignancy | 1(0.2%) | 2(0.5%) | 4(0.9%) | 7(1.7%) | ||
| Acute COPD | 2(0.5%) | 4(0.9%) | 3(0.7%) | 9(2.1%) | ||
| Trauma | 100(23.7%) | 0(0%) | 0(0%) | 100(23.7%) | ||
| Stroke | 22(5.2%) | 14(3.3%) | 5(1.2%) | 41(9.7%) | ||
| Severe Anaemia | 2(0.5%) | 4(0.9%) | 9(2.1%) | 15(3.6%) | ||
| Electrolyte abnormality | 1(0.2%) | 4(0.9%) | 5(1.2%) | 10(2.4%) | ||
| Others | 5(1.2%) | 15(3.6%) | 16(3.8%) | 36(8.5%) | ||
| Length of ED stay | 1–7 days | 75(17.8%) | 87(20.6%) | 96(22.7%) | 258(61.1%) | |
| 8-14days | 40(9.5%) | 19(4.5%) | 45(10.7%) | 104(24.6%) | ||
| ≥ 15 days | 39(9.2%) | 0(0%) | 21(5%) | 60(14.2%) | ||
Abbreviations: DM diabetes mellitus, HIV human immune-virus, CKD chronic kidney disease, COPD chronic obstructive pulmonary disease
Levels of VTE risk and identified Padua prediction scores among the study participants
The Padua scores ranged from 1 to 9 points, with a median score of 4. According to the Padua risk prediction score, nearly two-thirds of patients (70.6%) had a score ≥ 4, indicating a high risk of developing VTE. Reduced mobility was the most common risk factor (63.5%), followed by acute infection (47.4%), trauma (29.1%), and active cancer (20.6%) (Table 3).
Table 3.
VTE risk factors among patients admitted to the emergency departments of AaBET, TASH, SPHMMC from June to September 2023, based on the Padua risk prediction score (n = 422)
| Padua VTE risk factors | Score | N(%) | |||
|---|---|---|---|---|---|
| ABET | SPHMMC | TASH | Total | ||
| Active Cancer | 3 | 1(0.2%) | 16(3.8%) | 70(16.6%) | 87(20.6%) |
| Previous VTE | 3 | 1(0.2%) | 5(1.2%) | 1(0.2%) | 7(1.7%) |
| Reduced mobility | 3 | 112(26.5%) | 74(17.5%) | 82(19.4%) | 268(63.5%) |
| Known thrombophilia | 3 | 0(%) | 0(0%) | 2(0%) | 2(0.5%) |
| Trauma and/or Surgery | 2 | 110(26.1%) | 4(0.9%) | 9(2.1%) | 123(29.1%) |
| Age > = 70 years | 1 | 24(5.7%) | 27(6.4%) | 33(7.8%) | 84(19.9%) |
| Heart/Respiratory Failure | 1 | 8(1.9%) | 18(4.3%) | 27(6.4%) | 53(12.6%) |
| Acute MI/Ischemic Stroke | 1 | 17(4%) | 12(2.8%) | 18(4.3%) | 47(11.1%) |
| Infection/Rheumatoid | 1 | 30(7.1%) | 57(13.5%) | 115(27.3%) | 202(47.9%) |
| Obesity | 1 | 1(0.2%) | 3(0.7%) | 3(0.7%) | 7(1.7%) |
| Hormonal Therapy | 1 | 4(0.9%) | 10(2.4%) | 10(2.4%) | 24(5.7%) |
Abbreviations: MI myocardial infarction
Thromboprophylaxis utilization pattern and contraindication conditions among study participants
Of the 296 eligible patients, only 99 (33.4%) received pharmacological prophylaxis. The only prophylaxis used was unfractionated heparin (UFH): 86 (78%) patients received UFH 7,500 IU SC twice daily, 13 (12%) received UFH 5,000 IU SC twice daily, and 11 (10%) received UFH 17,500 IU SC twice daily. UFH prophylaxis was initiated within 24–48 h of emergency admission for 70 (63%) patients, within 72 h for 14 (13%) patients, and after more than 72 h for approximately 26 (24%) patients. Of the total study participants, 78 (18.5%) had contraindications to pharmacological prophylaxis at baseline. Among these, 10 (12.8%) patients received anticoagulants despite contraindications. The most common reason for contraindication was intracranial hemorrhage (27, 34.6%), followed by bleeding from current trauma (22, 28.3%), gastrointestinal bleeding within the past 3 months (20, 25.6%), and severe thrombocytopenia (platelet count < 50,000/µL) (9, 11.5%) (Table 4).
Table 4.
Thromboprophylaxis utilization status among study participants at emergency departments of AaBET, TASH, SPHMMC from June to September 2023 (n = 110)
| Prophylaxis eligibility status | AaBET N(%) |
SPHMMC N(%) | TASH N(%) |
Total N(%) |
|---|---|---|---|---|
| Eligible for Pharmacologic thromboprophylaxis and received it | 59(19.9%) | 21(7.1%) | 19(6.4%) | 99(33.4%) |
| Eligible for Pharmacologic thromboprophylaxis but not received | 52(17.6%) | 45(15.2%) | 100(33.8%) | 197(66.6%) |
| Not eligible for Pharmacologic thromboprophylaxis and not received | 41(32.5%) | 35(27.8%) | 39(31%) | 115(91.3%) |
| Not eligible for Pharmacologic thromboprophylaxis and received | 2(1.6%) | 5(4%) | 4(3.1%) | 11(8.7%) |
| Prophylaxis order status | ||||
| UFH 7500 IU SC twice a day | 56(50.5%) | 17(15.5%) | 13(12%) | 86(78%) |
| UFH 5000 IU twice a day | 5(4.5%) | 3(3%) | 5(4.5%) | 13(12%) |
| UFH 17,500 IU twice a day | 0(0%) | 6(5.5%) | 5(4.5%) | 11(10%) |
| Initiated within 24–48 h | 45(41%) | 19(17.2%) | 6(4.8%) | 70(63%) |
| Initiated within 72 h | 7(6.3%) | 3(3%) | 4(3.7%) | 14(13%) |
| Initiated within > 72 h | 9(8.3%) | 4(3.7%) | 13(12%) | 26(24%) |
| Early ambulation advised | 74(17.5%) | 1(0.2%) | 111(26.3%) | 186(44%) |
| Earl ambulation not advised | 80(19%) | 105(24.9%) | 51(12.1%) | 236(56%) |
Abbreviations: UFH unfractionated heparin, IU international unit, SC subcutaneous
Reasons for omission of thromboprophylaxis among study participants
Among the study participants, 73.9% did not receive pharmacological prophylaxis. Of these, 36.7% were not considered candidates due to a Padua risk prediction score < 4. Despite being at high risk of developing VTE, 19.9% of patients did not receive pharmacological prophylaxis because physicians were concerned about bleeding. Additionally, 8% were skipped without any documented reason, and 14.1% were not given anticoagulant prophylaxis because physicians planned to transfer them immediately, even though they were at risk. A small proportion (0.6%) of patients refused to purchase the medication despite support from the facility’s social worker, and 20.7% received only advice on physical prophylaxis, such as early ambulation, leg elevation, and flexion.
Factors associated with the initiation of pharmacological prophylaxis
Logistic regression analysis was employed to identify determinants of receiving pharmacological prophylaxis during ED follow-up. According to bivariate logistic regression analysis, older age (> 70 years), trauma, length of emergency stay, immobility for ≥ 3 days, previous history of VTE, level of VTE risk, cancer, and infection were significantly associated with receiving pharmacological prophylaxis during an emergency stay. All these variables were included in multivariable logistic regression to control for covariates simultaneously. In the multivariable analysis, length of hospital stay, immobility, age > 70 years, history of previous VTE, active cancer, and infection remained significantly associated with receiving pharmacological prophylaxis. Patients who were bedridden for ≥ 3 days were three times more likely to receive VTE pharmacological prophylaxis than their counterparts (AOR = 3.129; 95% CI: 1.310–7.474), whereas patients with an emergency stay of less than one week were less likely to receive anticoagulant prophylaxis (AOR = 0.192; 95% CI: 0.095–0.385; P < 0.001) (Table 5).
Table 5.
Factors associated with the use of pharmacological prophylaxis among study participants at emergency departments of AaBET, TASH, SPHMMC from June to September 2023 (n = 422)
| Variables | Category | ppx given N(%) | COR(95%CI) | P-value | AOR(95%CI) | P-value | |
|---|---|---|---|---|---|---|---|
| Yes | No | ||||||
| VTE Risk |
High Low |
99(90%) 11(10%) |
199(63.8%) 113(36.2%) |
5.111(2.640–9.915) | 0.001 | 2.180(0.860–5.524) | 0.101 |
| Previous VTE |
Yes No |
6(5.5%) 104(94.5%) |
1(0.3%) 311(99.7%) |
17.92(2.13,150.77) | 0.008 | 47.561(4.072–555.51) | 0.002 |
| Immobility |
Yes No |
99(90%) 11(10%) |
166(53.4) 146(46.6%) |
7.916(4.085–15.37) | < 0.001 | 3.129(1.310–7.474) | 0.001 |
| Cancer |
Yes No |
10(9.9%) 100(90.1%) |
76(24.4%) 236(75.6%) |
0.311(0.153–0.567) | 0.001 | 0.365(0.156–0.844) | 0.018 |
| Infection |
Yes No |
37(33.6%) 73(66.4%) |
162(51.9%) 150(48.1%) |
0.468(0.298–0.766) | 0.001 | 0.619(0.342–1.122) | 0.014 |
| LOS in emergency |
≤ 7 days > 7days |
41(37.3%) 69(62.7%) |
217(69.6%) 95(30.4%) |
0.388(0.202–0.732) | < 0.001 | 0.192(0.095–0.385) | < 0.001 |
| Age ≥ 70 year |
Yes No |
35(31.8%) 75(68.2%) |
49(15.7%) 263(84.3%) |
2.505(1.513–4.146) | < 0.001 | 1.880(1.007–3.510) | 0.047 |
| Trauma |
Yes No |
46(41.8%) 64(58.2%) |
77(24.7%) 236(75.3%) |
2.102(1.388–3.458) | 0.001 | 1.102(0.568–2.136) | 0.774 |
Abbreviations: ppx pharmacologic prophylaxis, LOS length of stay
Discussion
In this study we found that nearly two-thirds (70.4%) of patients were at high risk of developing VTE and needed prophylaxis according to the Padua risk prediction score. Indeed, providing prophylaxis in these high-risk individuals is a lifesaving process and can also reduce the extra cost for the treatment of already occurred VTE. It prevents the occurrence of post thrombotic syndrome which is estimated to occur in 15–40% of patients with a history of DVT and PE which contributes to a mortality rate of 30% [14, 15].
Despite the above potential benefit of VTE prophylaxis, a global report from a multinational study conducted in 32 countries showed that only 39% of pharmacological prophylaxis was utilized among identified VTE-risk groups [16]. However, according to the Padua risk prediction score RAM, patients who have a total risk score of 4 or above should receive pharmacological VTE prophylaxis unless contraindicated for the risk of bleeding [17]. In this regard, only 33.4% of eligible patients were given pharmacological prophylaxis in our study. Although this rate was comparable to the results reported from elsewhere Senegal 35.2% [18], Cameron 32.5% [19], and Gonder Ethiopia.(31.6%) [20]. This could be due to similarities in standards of health care services. In contrary, the rate was lower than those reported from Lebanon, the USA, and Italy showed that 58.5%, 47.5% and 39%, respectively [21–23], the use of VTE prevention techniques and adherence to VTE prophylaxis guidelines in the study setting remain poor as per guidelines [24].
The underutilization of VTE prophylaxis in the area of the study might be because of the failure to recognize VTE risk in the ED while emergency care providers place more emphasis on multiple admission diagnoses [17]. The other possible reason could be a lack of awareness among clinicians regarding VTE risk stratification practices and the trend of implementing VTE prevention guidelines in the ED is also poor. In addition, majority of clinicians (71.8%) were using their own clinical judgment to determine a patient’s risk as they are unfamiliar with standardized guidelines and risk assessment models [25]. The other possible explanation for the lower rate of anticoagulant prophylaxis use in high VTE risk emergency attending patients could be fear of bleeding from the clinician’s perspective as 19.9% of patients were not given pharmacological prophylaxis although this rate was much lower than that reported in Canada where 52.1% patients skipped thromboprophylaxis due to fear of bleeding [12, 25].
The immediate plan of transferring patients from the emergency to respective ward before initiating anticoagulants for high VTE risk patients could be the other reason identified in this study as 14.1% of patients skipped anticoagulant prophylaxis due to immediate plan of physicians to transfer even though patients were at risk starting from the baseline of their admission. A similar problem was reported in a previous study showing that approximately 84.3% of clinicians did not reassess the need for VTE prophylaxis at transition of emergency care during transfer or home discharge [26].
With regard to the optimal utilization of anticoagulant prophylaxis, the observed inadequacy could also be improved by involving clinical pharmacists in all settings of EDs, while they may play a key role in improving appropriate use of pharmacological prophylaxis by implementing VTE prophylaxis guidelines, policies and reminding physicians that helps in reducing the occurrence of VTE, bleeding complications and overall preventing under or extreme utilization of anticoagulants which leads to adverse outcomes and increases in overall cost among acutely ill patients in EDs [27]. Given that a better outcome could be achieved based on the findings from previous studies suggesting that interdisciplinary collaboration between pharmacists and physicians within the hospital setting can significantly increase the rate of appropriate prophylaxis and significantly decrease the rate of VTE occurrence by 74% [28], inappropriate utilization of anticoagulant in hospitalized patients remains problematic as reported 27.3%, 36.7%, 31.6% from Saud Arabia, Iran and Ethiopia, respectively [20, 29, 30] have been reported possibly because of the small contribution of clinical pharmacists in this study areas.
In this study,11(8.7%) patients who were not eligible for pharmacological prophylaxis were exposed unnecessarily to anticoagulant prophylaxis, and approximately 11(10%) patients were given a therapeutic dose of UFH 17,500 IU SC twice a day which is an inappropriate dose for prophylaxis according to the ACCP guidelines [31]. This proportion was lower than the study conducted by Abdullah Daminet al.,2022 in which39.7% of patients were given anticoagulants beyond the prophylactic dose [32]. This difference might be due to the use of more types of anticoagulants other than UFH, such as low molecular weight heparin.
The study revealed that approximately 70 (63%) of patients received anticoagulant prophylaxis early, within 24 to 48 h of emergency admission. However, 24% of patients who initiated pharmacological prophylaxis experienced delays of more than 72 h after emergency admission despite being at baseline risk. Previous studies have shown that a delay in initiating thromboembolic prophylaxis can potentially lead to increased thromboembolic complications. A delay of more than three days in initiating VTE prophylaxis for high risk patients is associated with a three-fold increase in the occurrence of VTE. Initiating prophylaxis earlier than 48 h following hospitalization < 72 h of admission decreased the incidence of VTE by 42% compared to initiating prophylaxis after 72 h of admission [33, 34].
In multivariable logistic regression analysis revealed that individual patients having history of previous venous thromboembolism were associated with up to 47-fold increase the odds of receiving anticoagulant prophylaxis which was consistent with the other study conducted by Drake G. et al. 2022 [35]. This could be associated with the fact that history of previous VTE is a strong risk factor for developing VTE as recurrence. Older patients aged ≥ 70 years were approximately 1.8 times more likely received anticoagulant prophylaxis might be because of the assumption that chronic venous insufficiency is a common condition in older patients and is associated with 3 times more likely to have risk of venous thrombosis [36, 37]. However, an age greater than 70 years is also related to an increased risk of bleeding as well and need to calculate the bleeding risk score using standard risk stratification tool before exposing patients to the adverse effect [38].
Our study also demonstrated that patients with bedridden for ≥ 3days were three times more likely received anticoagulant prophylaxis than their comparators. On the other hand, patients stayed in ED for less than one week were less likely receiving the prophylaxis. This could be due to the fact that the hypercoagulability state described by Rudolf Virchow might be considered to be high in patients with prolonged hospital stay [39]. However, adherence of standard guideline is recommended to avoid overestimation of the risk in specific group of patients by physicians own decision and underestimation of VTE risk in other vulnerable individuals [40] such as cancer patients where these patients in our study were less likely receiving anticoagulant prophylaxis as compared to those without active cancer. The finding was inconsistent with the studies elsewhere [41, 42]. The reason for the variation in the results could be an indication of a lack of clinician adherence to standard VTE prevention guidelines and perception of emergency physicians for their own decision [43] and our result may also reflect the misperception of emergency-care providers considering ambulating patients and those shorter duration of hospital stay to have lower risk of blood stasis and less risk of developing venous thromboembolism. But even ambulating cancer patients having at least one additional risk factor can increase the possibility of VTE event because of the pathogenesis nature of cancer cells [44, 45]. Previous study assessed the mortality rate among cancer patients reported that the one- year mortality of PE was 73% [46]. Moreover managing already occurred VTE in cancer patients is more challenging as compared to noncancerous patients because of the frail balance between the increased risk of recurrent VTE and the increased risk of major bleeding due to the anticoagulant treatment [47] which indicating that implementing the guidelines and early prevention strategies are more beneficial in these group of patients. Similarly, patients with acute infection such as sepsis in our study were less likely be received the prophylaxis than their comparators. In contrary to our finding, the use of thromboprophylaxis in acutely ill patients with sepsis after VTE risk assessment is highly encouraged by recent studies because systemic inflammation and the pro-coagulatory shift as host responses during sepsis leads the patients to be at an increased risk for developing thrombosis [48].
Strength and limitation of the study
The study was conducted as a multicentre prospective study in the largest tertiary care hospitals in the country and targeted a relatively a larger sample size, which can enhance the generalizability of the findings a strength of the study. However, this study has several limitations. First, we did not assess the duration of thromboprophylaxis after transfer to other wards or discharge, nor did we evaluate clinical outcomes such as venous thromboembolism (VTE) occurrence or bleeding events. This restricts our ability to draw conclusions regarding the effectiveness or safety of thromboprophylaxis decisions. Second, our sample size calculation relied on an assumed prevalence of 50% due to the absence of prior data, which may have affected the precision of our estimates. Third, with only 99 patients receiving prophylaxis, the limited number of events per variable raises concerns about potential statistical overfitting in the multivariate analysis. Finally, although the Padua score was used to assess VTE risk, our study did not compare its performance against other validated risk prediction models, such as IMPROVE or the Caprini score, which may be more suitable for mixed medical-surgical populations. Future studies comparing these models in Ethiopian emergency settings could optimize risk stratification practices.
Conclusion
Despite many patients being at high risk for VTE, pharmacological prophylaxis in the emergency department was underutilized. Older age, immobility, prior VTE, active cancer, infection, and longer ED stay were significant determinants of prophylaxis use, highlighting the need for systematic risk assessment and targeted strategies to ensure guideline-recommended care.
Acknowledgements
We would like to express our heartfelt gratitude to the St. Paul Millennium Medical College, Addis Ababa Burn and Emergency Trauma Hospital and Tikur Anbessa Specialized Hospital, College of Health Science, Addis Ababa University for their cooperation and permission during patient enrolment and data collection. Our acknowledgment extends to all the data collectors and health care professionals at the three tertiary hospitals for their friendly work.
Clinical trial number
Not applicable.
Abbreviations
- AaBET
Addis Ababa Burn Emergency and Trauma
- DVT
Deep vein thrombosis
- ED
Emergency department
- PE
Pulmonary embolism
- SC
subcutaneous
- SPHMMC
St Paulos Hospital Millennium Medical College
- TASH
Tikur Anbesa Specialized Hospital
- UFH
Unfractionated heparin
- VTE
Venous thromboembolism
Authors’ contributions
W.D designed and conducted the study, analysed and interpreted the results and prepared the draft of the manuscript. M.A.W and D.M were involved in the study’s design and overseeing the research activities. A.B.B contributed to the design and analysis of the study, supervised the work, prepared the draft and final manuscript and critically reviewed it. All authors have read and approved the final manuscript for publication.
Funding
The study was supported by Addis Ababa University.
Data availability
All relevant data are included in the article and uploaded as supporting information files.
Declarations
Ethical approval and consent to participate
Ethical approval was obtained from the Ethical Review Board (ERB) of the School of Pharmacy, Addis Ababa University (Ref. No. ERB/SOP/524/15/2023), and from the Institutional Review Board (IRB) of St. Paul’s Hospital Millennium Medical College (Ref. No. Pm23/60). The study was conducted in compliance with the principles of the Declaration of Helsinki. Informed consent was obtained from all study participants and/or their caregivers. To maintain anonymity, participants’ names and medical record numbers were not recorded during data collection, and all other personal information was kept strictly confidential throughout the study period.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.Baglin T. What happens after venous thromboembolism? J Thromb Haemost. 2009;7:287–90. [DOI] [PubMed] [Google Scholar]
- 2.Lutsey PL, Zakai NA. Epidemiology and prevention of venous thromboembolism. Nat Rev Cardiol. 2023;20(4):248–62. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Winter MP, Schernthaner GH, Lang IM. Chronic complications of venous thromboembolism. J Thromb Haemost. 2017;15(8):1531–40. [DOI] [PubMed] [Google Scholar]
- 4.Gadó K, Kicsi D, Markovics D, Domján G. Importance of thromboprophylaxis in hospitalized non-surgical patients. Orv Hetil. 2019;160(17):654–61. [DOI] [PubMed] [Google Scholar]
- 5.Fernandez MM, Hogue S, Preblick R, Kwong WJ. Review of the cost of venous thromboembolism. Clinicoecon Outcomes Res. 2015;7:451–62. 10.2147/CEOR.S85635. [DOI] [PMC free article] [PubMed]
- 6.Kumar A, Mehta Y, Ali T, Gupta MK, George JV. Deep vein thrombosis in medical and surgical intensive care unit patients in a tertiary care centre in North India: incidence and risk factors. J Anaesthesiol Clin Pharmacol. 2017;33(2):181–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Zeidan AM, Streiff MB, Lau BD, Ahmed SR, Kraus PS, Hobson DB, et al. Impact of a venous thromboembolism prophylaxis smart order set: improved compliance, fewer events. Am J Hematol. 2013;88(7):545–9. [DOI] [PubMed] [Google Scholar]
- 8.Abukhalil AD, Nasser A, Khader H, Albandak M, Madia R, Al-Shami N, Naseef HA. VTE Prophylaxis Therapy: Clinical Practice vs Clinical Guidelines. Vasc Health Risk Manag. 2022;18:701-710. 10.2147/VHRM.S382050. [DOI] [PMC free article] [PubMed]
- 9.Feng S, Li M, Wang K, Hang C, Xu D, Jiang Y, et al. Knowledge, attitudes, and practices regarding venous thromboembolism prophylaxis: a survey of medical staff at a tertiary hospital in China. Medicine (Baltimore). 2021;100(49):e28016. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Tefera GM, Feyisa BB, Umeta GT, Kebede TM. Predictors of prolonged length of hospital stay and in-hospital mortality among adult patients admitted at the surgical ward of Jimma university medical center, Ethiopia: prospective observational study. J Pharm Policy Pract. 2020;13(1):24. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Fekadu G, Lamessa A, Mussa I, Beyene Bayissa B, Dessie Y. Length of stay and its associated factors among adult patients who visit emergency department of university hospital, Eastern Ethiopia. SAGE Open Med. 2022;10:20503121221116867. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Leonardi MJ, McGory ML, Ko CY. The rate of bleeding complications after pharmacologic deep venous thrombosis prophylaxis: a systematic review of 33 randomized controlled trials. Arch Surg. 2006;141(8):790–9. [DOI] [PubMed] [Google Scholar]
- 13.Farfan M, Bautista M, Bonilla G, Rojas J, Llinás A, Navas J. Worldwide adherence to ACCP guidelines for thromboprophylaxis after major orthopedic surgery: a systematic review of the literature and meta-analysis. Thromb Res. 2016;141:163–70. [DOI] [PubMed] [Google Scholar]
- 14.Ahmad HA, Geissler A, MacLellan DG. Deep venous thrombosis prophylaxis: are guidelines being followed? ANZ J Surg. 2002;72(5):331–4. [DOI] [PubMed] [Google Scholar]
- 15.Robinson GV. Pulmonary embolism in hospital practice. BMJ. 2006;332(7534):156–60. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Bergmann J-F, Cohen AT, Tapson VF, Goldhaber SZ, Kakkar AK, Deslandes B, Huang W, Anderson FA, Investigators E. Venous thromboembolism risk and prophylaxis in hospitalised medically ill patients. Thromb Haemost. 2010;103(04):736–48. [DOI] [PubMed] [Google Scholar]
- 17.Barbar S, Noventa F, Rossetto V, Ferrari A, Brandolin B, Perlati M, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua prediction score. J Thromb Haemost. 2010;8(11):2450–7. [DOI] [PubMed] [Google Scholar]
- 18.Affangla DA, Adomayakpor KSL, Akanni S, Dione J-MA, Ngwa HEE, Ba DM, Leye M, Da Veiga JA, Diop BM. Evaluation of thromboprophylaxis practice in hospitalized patients in the medical department of saint Jean de dieu hospital of Thies, Senegal. World J Cardiovasc Dis. 2020;10(5):313–8. [Google Scholar]
- 19.Nkoke C, Tchinde Ngueping MJ, Atemkeng F, Teuwafeu D, Boombhi J, Menanga A. Incidence of venous thromboembolism, risk factors and prophylaxis in hospitalized patients in the South West region of Cameroon. Vasc Health Risk Manag. 2020. 10.2147/VHRM.S205935. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Ayalew MB, Horsa BA, Zeleke MT. Appropriateness of pharmacologic prophylaxis against deep vein thrombosis in medical wards of an Ethiopian referral hospital. Int J Vasc Med. 2018. 10.1155/2018/8176898. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Barbar S, Rossetto V, Prandoni P. Thromboprophylaxis in medical inpatients with cancer. Am J Med. 2014;127(10):e11. [DOI] [PubMed] [Google Scholar]
- 22.Hajj I, Al-Masri M, Bashaireh K, Hani MB, Hamouri S, Khouzami J, et al. A cross-sectional, multicenter, observational study to assess the prophylaxis of venous thromboembolism in Lebanese and Jordanian hospitals. Thromb J. 2021;19:1–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Huang W, Anderson FA, Rushton-Smith SK, Cohen AT. Impact of thromboprophylaxis across the US acute care setting. PLoS ONE. 2015;10(3):e0121429. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Queensland So: Guideline for the Prevention of Venous Thromboembolism (VTE) in Adult Hospitalised Patients. 2018. https://www.health.qld.gov.au/__data/assets/pdf_file/0031/812938/vte-prevention-guideline.pd
- 25.Golemi I, Adum JPS, Tafur A, Caprini J. Venous thromboembolism prophylaxis using the Caprini score. Dis Mon. 2019;65(8):249–98. [DOI] [PubMed] [Google Scholar]
- 26.Lam BD, Dodge LE, Datta S, Rosovsky RP, Robertson W, Lake L, et al. Venous thromboembolism prophylaxis for hospitalized adult patients: a survey of US health care providers on attitudes and practices. Res Pract Thromb Haemost. 2023;7(6):102168. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Gharaibeh L, Younes N, Albsoul-Younes A. Role of the clinical pharmacist in improving the appropriateness of venous thromboembolism prophylaxis in hospitalised patients in Jordan. J Pharm Pract Res. 2017;47(1):57–62. [Google Scholar]
- 28.Dobesh PP, Trujillo TC, Finks SW. Role of the pharmacist in achieving performance measures to improve the prevention and treatment of venous thromboembolism. Pharmacotherapy. 2013;33(6):650–64. [DOI] [PubMed] [Google Scholar]
- 29.Alabdulkarim DA, Almohammed OA, Al AMA, Almaklafi NS, Alkathiri MA, Aljohani MA. Venous thromboembolism prophylaxis-prescribing patterns among elderly medical patients in a Saudi tertiary care center: success or failure? J Geriatric Cardiology: JGC. 2020;17(12):775. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Khalili H, Dashti-Khavidaki S, Talasaz AH, Mahmoudi L, Eslami K, Tabeefar H. Is deep vein thrombosis prophylaxis appropriate in the medical wards? A clinical pharmacists’ intervention study. Pharm World Sci. 2010;32:594–600. [DOI] [PubMed] [Google Scholar]
- 31.Comerota AJ, Prandoni P, Bounameaux H, Dentali F. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis. Chest. 2012;141(2):eS419–94. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Abukhalil AD, Nasser A, Khader H, Albandak M, Madia R, Al-Shami, Nm. Naseef HA: VTE prophylaxis therapy: clinical practice vs clinical guidelines. Vasc Health Risk Manag. 2022;18(null):701–10. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Ho KM, Litton E. Venous thromboembolism prophylaxis in hospitalized elderly patients: time to consider a ‘MUST’strategy. J Geriatric Cardiology: JGC. 2011;8(2):114. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Hecht JP, Han EJ, Cain-Nielsen AH, Scott JW, Hemmila MR, Wahl WL. Association of timing of initiation of pharmacologic venous thromboembolism prophylaxis with outcomes in trauma patients. J Trauma Acute Care Surg. 2021;90(1):54–63. [DOI] [PubMed] [Google Scholar]
- 35.LeBrun DG, Salvati EA, Gonzalez Della Valle A. Multimodal thromboprophylaxis in patients with a history of venous thromboembolism undergoing primary and revision knee arthroplasty. HSS Journal®: The Musculoskeletal Journal of Hospital for Special Surgery. 2022;18(2):212–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Sellier E, Labarere J, Bosson J-L, Auvray M, Barrellier M-T, Le Hello C, et al. Hospitalière aplpdla: effectiveness of a guideline for venous thromboembolism prophylaxis in elderly Post–Acute care patients: A multicenter study with systematic ultrasonographic examination. Arch Intern Med. 2006;166(19):2065–71. [DOI] [PubMed] [Google Scholar]
- 37.Prandoni P, Lensing AW, Piccioli A, Bernardi E, Simioni P, Girolami B, et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood. 2002;100(10):3484–8. [DOI] [PubMed] [Google Scholar]
- 38.Birhane S, Beyene MG, Tadesse F, Baye AM. Outcomes of deep venous thrombosis management and associated factors among patients in tertiary hospitals in Addis Ababa, Ethiopia: a multicenter retrospective cohort study. Thromb J. 2024;22(1):62. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Kumar DR, Hanlin E, Glurich I, Mazza JJ, Yale SH. Virchow’s contribution to the understanding of thrombosis and cellular biology. Clin Med Res. 2010;8(3–4):168–72. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 40.Almodaimegh H, Alfehaid L, Alsuhebany N, Bustami R, Alharbi S, Alkatheri A, et al. Awareness of venous thromboembolism and thromboprophylaxis among hospitalized patients: a cross-sectional study. Thromb J. 2017;15(1):19. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 41.South A, Iveson E, Allgar V, Harbison J. The under use of thromboprophylaxis in older medical in-patients: a regional audit. QJM. 2007;100(11):685–9. [DOI] [PubMed] [Google Scholar]
- 42.Ruiz-Artacho HERNÁNDEZSJ, LORANCA PC, BACH MM, GARCÍA MMC, SANTALIESTRA AA, SORIANO AA, VENOSA GDET. Appropriateness of thromboprophylaxis in patients with medical conditions admitted from the emergency department: the PROTESU study. Emergencias. 2014;26:281–91. [Google Scholar]
- 43.Schleyer AM, Schreuder AB, Jarman KM, LoGerfo JP, Goss JR. Adherence to guideline-directed venous thromboembolism prophylaxis among medical and surgical inpatients at 33 academic medical centers in the United States. Am J Med Qual. 2011;26(3):174–80. [DOI] [PubMed] [Google Scholar]
- 44.Falanga A, Schieppati F, Russo L. Pathophysiology 1. Mechanisms of thrombosis in cancer patients. Cancer Treat Res. 2019;179:11–36. [DOI] [PubMed] [Google Scholar]
- 45.Poenou G, Dumitru Dumitru T, Lafaie L, Mismetti V, Ayoub E, Duvillard C, Accassat S, Mismetti P, Heestermans M, Bertoletti L. Pulmonary embolism in the cancer associated thrombosis landscape. J Clin Med. 2022;11(19):5650. 10.3390/jcm11195650. [DOI] [PMC free article] [PubMed]
- 46.Sørensen H, Pedersen L, Van Es N, Büller H, Horváth-Puhó E. Impact of venous thromboembolism on the mortality in patients with cancer: a population-based cohort study. Lancet Reg Health. 2023;34:100739. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 47.Aggarwal A, Fullam L, Brownstein AP, Maynard GA, Ansell J, Varga EA, et al. Deep vein thrombosis (DVT) and pulmonary embolism (PE): awareness and prophylaxis practices reported by patients with cancer. Cancer Invest. 2015;33(9):405–10. [DOI] [PubMed] [Google Scholar]
- 48.Hanify JM, Dupree LH, Johnson DW, Ferreira JA. Failure of chemical thromboprophylaxis in critically ill medical and surgical patients with sepsis. J Crit Care. 2017;37:206–10. 10.1016/j.jcrc.2016.10.002. [DOI] [PubMed]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
All relevant data are included in the article and uploaded as supporting information files.