Skip to main content
PLOS One logoLink to PLOS One
. 2020 Jul 15;15(7):e0235495. doi: 10.1371/journal.pone.0235495

The rational use of thromboprophylaxis therapy in hospitalized patients and the perspectives of health care providers in Northern Cyprus

Syed Sikandar Shah 1,*, Abdikarim Abdi 1, Barçin Özcem 2, Bilgen Basgut 1
Editor: Joel Msafiri Francis3
PMCID: PMC7363080  PMID: 32667938

Abstract

Background

Despite the presence of effective strategies and standard guidelines for the prevention of deep vein thrombosis (DVT), a considerable proportion of patients at risk of developing thromboembolism did not receive prophylaxis during hospitalization, while others received it irrationally, thus led to unwanted side effects.

Aim

This study aimed to evaluate the current thromboprophylaxis practice and management of hospitalized patients at risk of developing DVT, along with the assessment of health care providers (HCPs) knowledge, and attitudes regarding DVT prevention.

Methods

An observational study was conducted in the general wards of two leading tertiary university hospitals in Northern Cyprus in which patients from multiple clinics were enrolled to investigate the rational use of DVT prophylaxis using the Caprini risk assessment tool. Patients were also followed for possible complications two weeks post-hospitalization. A cross-sectional study followed to assess the knowledge and attitude of HCPs regarding DVT risks and prophylaxis.

Results

Of the 180 patients enrolled, 47.7% were identified as irrationally managed, 52.3% were identified as rationally managed, 77.8% of patients were identified as having a high level of risk. Notably, Four of thirteen patients who received more thromboprophylaxis developed minor complications. Additionally, 73.3% of nurses had not received DVT education. Furthermore, more than 50% of physicians and nurses achieved a low knowledge score for DVT risks and prophylaxis.

Conclusions

A high degree of irrationality in the administration of thromboprophylaxis therapy to hospitalized patients was observed. The overall scores for HCPs indicated insufficient knowledge of DVT risk assessments and prophylaxis.

Introduction

Deep venous thrombosis (DVT) is still a life-threatening condition with significant mortality and morbidity [1]. It typically affects the deep veins of the leg or pelvis [2]. Venous thromboembolism (DVT and pulmonary embolism) is the most frequent preventable cause of death among hospitalized surgical patients [3]. Every year, approximately 2 million people experience deep venous thrombosis, and approximately 0.6 million of these patients experience a pulmonary embolism (PE). PE causes the death of approximately 0.2 million patients annually [4].

The American College of Chest Physicians (ACCP) indicates that all hospitalized patients have a minimum of one risk factor for venous thromboembolism and approximately 40% show 3 risk factors or more [5], thus requiring adequate thromboprophylaxis to decrease mortality and morbidity [6]. Primary prophylaxis is the most common method and uses medications and mechanical methods to prevent DVT. Meanwhile, secondary prophylaxis is less commonly used and includes screening methods and the treatment of subclinical DVT [7]. Factors influencing the determination of appropriate prophylaxis include patient factors, setting, drug therapy, and knowledge of these aids in the accurate control of DVT. Evidence-based risk assessment tools (RAT) have been adopted to accurately evaluate these risk factors [8]. After a risk assessment, pharmacological prophylaxis regimens should be prescribed for moderate- to high-risk patients, while pharmacological prophylaxis may not be necessary for low-risk patients after a risk-benefit evaluation [9]. Irrational use of medications may lead to adverse drug reactions, waste of rare health resources, and increased treatment costs [10]. Many observers reported that healthcare providers may under or overestimate thrombosis risk factors in hospitalized patients, leading to either DVT or overmedication, which may result in bleeding and unwanted side effects [11].

The determination of competence of health care providers in deep venous thrombosis risk assessments and preventive measures may be valuable in improving their education and awareness and attenuating this significant public health issue. Multidisciplinary teams including clinical pharmacists, nurses, and physicians are needed to ensure rational drug use and adherence to evidence-based guidelines [12]. However, no study has assessed the rational use of DVT prophylaxis in tertiary care hospitals in North Cyprus.

This study aims to evaluate the current thromboprophylaxis practice and management of hospitalized patients having risks of developing DVT, along with the assessment of health care providers (HCPs) knowledge, and attitudes regarding DVT prophylaxis.

Materials and methods

Study setting and subjects

The study was conducted in the general wards of two tertiary university hospitals, NEU hospital in Nicosia and KUH in Kyrenia of Northern Cyprus. In the first phase, an observational prospective study was performed. All (n = 310) patients admitted between 01 April 2018 and 01 July 2018 who met the inclusion criteria were invited to participate in the analysis. The inclusion criteria were acute and chronically ill hospitalized patients for whom complete medical records were available and who were hospitalized for at least 7 days in a certain ward. Patients having age <18 years, superficial vein thrombosis, or any contraindications for DVT prophylaxis and patients who had deep venous thrombosis prophylaxis within the last month were excluded from the analysis.

Information was collected from eligible patients, who were assessed for risk factors and the rational use of prophylaxis for DVT using an evidence based DVT risk assessment tool.

Demographic information of patients willing to participate in the study were recorded including age, sex, height, weight, primary diagnosis, chief complaints. Also the presence of risk factors of DVT, a drug used for DVT, sign, and symptoms of DVT, laboratory results, other comorbidities, any prophylaxis treatment administered for VTE, and a history of signs and symptoms of PE or DVT or anticoagulant complications documented in the patient files during hospitalization were collected. Patients were also assessed for possible complications by the research team during their follow-up visit two weeks after hospitalization to record any deep venous thrombosis signs and symptoms, pulmonary embolism, or adverse effects of medications.

In the second phase performed between 5th September 2018 and 5th November 2018, a cross-sectional questionnaire was distributed to health care providers at the two health care settings in a face to face meeting to assess the knowledge, practices, and attitudes of health care providers towards DVT risks and prophylaxis.

Study tools

Risk assessment tool

The Caprini tool is a validated DVT risk assessment tool [13] that has been used in many healthcare settings worldwide to analyse hospitalized patients [14] and includes 20 variables [15].

The Caprini risk score for the assessment of thrombosis risk in adult hospitalized patients was used to categorize patient risk and accordingly identify the required thromboprophylaxis mode. Patients’ risk factors are classified into four categories: “very low risk” (0 points), “low risk” (1–2 points), “moderate risk” (3–4 points), and “highest risk” (≥5 points).

Health care providers questionnaire

Two different questionnaires were used to assess the knowledge, practice, and attitudes towards DVT. Questionnaires comprising 53 items for nurses [16] and 21 items for physicians [17] were adapted based on a literature review. The adapted questionnaire was reviewed by a committee of experts comprising a clinical pharmacist, pharmacologist, and cardiologist practicing in Northern Cyprus.

The first part of the questionnaire designed for nurses collects information about demographic characteristics using 12 questions. The second part comprises 20 questions assessing the nurses’ knowledge of deep venous thrombosis risks with 3 choices (false, true and do not know), and the third part examines knowledge of the prevention of deep venous thrombosis using 8 questions with 3 choices (false, true and do not know). Both false and do not know responses were considered negative in the analysis. The fourth section examining the practices of nurses in deep venous thrombosis prevention consisted of 13 questions with a 3-point Likert scale (always, sometimes, and never).

A short questionnaire lacking demographic characteristics was distributed to physicians to increase the response rate. The adopted questionnaire consisted of two sections. The first section contained 15 questions, of which 11 questions assessed knowledge of DVT with 4 multiple choice responses while the other 4 questions had 2 choices (true and false). The second section examining the attitudes of physicians towards DVT prevention consisted of 6 questions with 5 choices (Strongly disagree, Disagree, Neutral, Agree, and Strongly Agree).Physicians’ knowledge and attitudes were assessed using a questionnaire that included 15 knowledge-related questions scored from 0–15 points and 6 attitude-related questions scored from 6–30 points with a Likert scale. For the present study, favourable knowledge and attitudes were defined as a score greater than 70% [18]. Two native Turkish speakers with experience in translating health questionnaires independently translated the questionnaire. The two translators then compared their translations and a third questionnaire was produced jointly.

Pilot study

A pilot study was performed that targeted 10 to 15% of the study population, i.e. patients (n = 35), nurses (n = 40) and physicians (n = 15) [19]. The internal consistency was measured for different scales using Cronbach’s alpha and Kuder-Richardson (KR-21), which reflect good internal consistency (0.8) for both nurses’ and physicians’ knowledge and (0.7) for the attitudes of physicians.

Ethical consideration

The study protocol was approved on 29th March 2018 by the Institutional Review Board (IRB) of Near East University (YDU/2018/56-530) and assigned as an observational study. A written consent form was signed by healthcare providers upon their participation in the study. Verbal consent was obtained from patients and recorded on data collection form upon their follow-up interview.

Statistical analysis

Statistical Package for Social Sciences (SPSS) software, version 22.0, IBM corp., New York, USA was used to analyse the data. Descriptive statistics for qualitative and quantitative variables were used to analyse the results of the study. Categorical data are reported as frequencies and percentages (%), while continuous data are reported as the means (± standard deviations) or medians (ranges).

Raosoft software version 2.3 (Raosoft. Inc., Seattle, USA) was used to calculate the minimum sample size required for the study. Assuming a 95% confidence level, a 5% margin of error, and a 50% response distribution, at least 172 patients were needed to participate in the study out of 310 admitted to the hospital during the study duration. While 98 physicians and 169 nurses were required as a minimum required sample out of 130 physicians and 300 nurses providing care at the two hospitals involved in the study.

Following the testing of normality, non-parametric hypothesis tests were performed throughout the whole data analysis phase. The Mann-Whitney U test and the Kruskal-Wallis test were performed to compare data between multiple groups. The associations between categorical variables were analysed using Fisher’s exact test and Pearson’s Chi-square test. The level of significance was set to P < 0.05.

Observational results

Patient demographics and characteristics

One hundred eighty patients with multiple pathologies from the general wards were enrolled to investigate their risk of thrombosis. The mean age ± SD of the patients was 65.47± 16.39 years, and 59.4% were male and 40.6% were females. The median length of hospitalization stay was 15 with 29.75–7.00 IQR. The minimum number of risk factors for patients was 0 and the maximum number of risk factors was 14 (median of 6/patient). The most common drug used for thromboprophylaxis in patients was enoxaparin (58.8%). Notably, 4.4% of patients died during follow-up but the cause of death was not related to DVT. Table 1 presents the main demographic and clinical characteristics of the patients included in the present study.

Table 1. Main demographic and clinical characteristics of the 180 patients N (%).

Clinics Cardiology Pulmonary GIT
Number 83 (46.1%) 11 (6.1%) 18 (10%)
DM Orthopaedics Neurology
3 (1.7%) 16(8.9%) 22(12.2%)
Respiratory Allergy and chest disease Infectious disease
5 (2.8%) 2(1.1%) 5 (2.8%)
Geriatrics Oncology Surgery
7 (3.9%) 7(3.9%) 1 (6%)
Average age 65.47 ± 16.39 (mean ± SD)
The average number of drugs 9.41 ± 4.7 (mean ± SD)
Males 107 (59.4%)
Females 73 (40.6%)
High level of risk 140 (77.8%)
Moderate level of risk 27 (15%)
Low level of risk 10 (5.6%)
Very low level of risk 3 (1.7%)
Rationally managed cases 94 (52.3%)
İrrationally managed cases 86 (47.7%)
Patients with no need for prophylaxis (total) 3 (1.7%)

The most common risk factors identified in the sampled patients included age of 41–60 years (26.1%), obesity (BMI>25) (21.1%), patients who were confined to bed for more than 3 days (100%), an age of 61–74 years (37.8%), and an age ≥75 years (28.3%). The distribution of risk assessment items and risk factors among sampled patients is shown in Table 2.

Table 2. Distribution of the most common risk factors among sampled patients.

Risk factor N (%)
Age of 41–60 years 47 (26.1%)
Swollen legs 16 (8.9%)
Obesity (BMI >25) 38 (21.1%)
Serious lung disease, including pneumonia 12 (6.7%)
Acute myocardial infarction 8 (4.4%)
Congestive heart failure 8 (4.4%)
Abnormal pulmonary functions (COPD) 11 (6.1%)
Age of 61–74 years 68 (37.8%)
Patient confined to bed for > 72 hours 180 (100%)
Major surgery > 45 minutes 11 (6.1%)
Minor surgery 13 (7.2%)
Aged 75 or older 51 (28.3%)

Thromboprophylaxis and rationality

Of the 180 patients, thromboprophylaxis was appropriately provided to only 94 patients who received rational thromboprophylaxis. Of the 86 irrationally managed patients, 65 patients did not take any form of thromboprophylaxis and 3 patients received inadequate prophylaxis (e.g., insufficient doses of enoxaparin or compression stockings alone). Thirteen patients received more thromboprophylaxis than was indicated (either taking an increased dose or taking medicine when only compression stockings were indicated). The only four of these 13 patients developed minor complications while anticoagulation therapy was stopped in 2 patients. The most common minor complications were wound haematoma, injection site bruising and haematuria. These minor complications developed mostly in elderly patients (>70). However, a statistically significant difference in complications was not observed between genders. No major complications (e.g. gastrointestinal or retroperitoneal bleeding, thrombocytopenia, or fatal pulmonary emboli) were recorded during hospitalization and post-hospitalization follow-up visits.

Fifty-eight patients out of 140 high-risk patients (41.4%) were not treated with thromboprophylaxis requiring both compression devices and an antithrombotic agent. Eight of these patients developed signs and symptoms of DVT (e.g. Warm feelings of legs in 4 patients, Leg swelling in 3 patients, etc.) Fig 1 shows the proposed management of the sampled patients based on the Caprini score.

Fig 1. Proposed management of the sampled patients based on the Caprini score.

Fig 1

SCD, Sequential Compression Device.

Based on the data, 80.7% (n = 113) of the female patients and 75.7% (n = 106) of the male patients had high-risk factors, but no statistically significant associations were observed between gender and the categories of risk factors. Of the 104 patients aged greater than 65 years, 2.8% (n = 3) displayed a low level of risk, 7.6% (n = 8) of these patients belonged to the moderate risk group, and the other 89.4% (n = 93) were assigned the high-risk group. The presence of stroke, multiple trauma or acute spinal cord injury less than one month prior to DVT, hip or leg fracture, a family or personal history of VTE, hospitalization or treatment for cancer in the last year, and current immobility were among the minor risk factors and were the strongest independent predictors of VTE among sampled patients.

Responses and characteristics of the nurses

Two hundred sixty-five questionnaires were dispensed to nurses, and 237 were returned, corresponding to a response rate of approximately 89.4%. 232 questionnaires were evaluated, while 5 were improperly filled and discarded. Most of the respondents had a bachelor’s degree (58.6%), were females (69%) and (53.4%) had <5 years of experience. Most of the respondents were working in internal medicine (16.8%), and emergency units (15.9%). The most common age group was <25 years (53.4%). Nurses’ responses to the question “Did you receive previous education on deep venous thrombosis?” indicated that 73.3% of the respondents had not received DVT training. Those nurses (n = 62) who received DVT training reported 5 resources. Most of the nurses (n = 42) and (n = 9) had received this training at their congress/conferences and vocational high school, respectively. Other training resources were internet resources (n = 4), courses (n = 2) and workplace training (n = 5). Approximately (n = 206) of the nurses expressed that they needed education on DVT. Participants rated the quality of previous deep venous thrombosis education as excellent (n = 4), very good (n = 15), good (n = 31) and poor (n = 12).

Nurses’ knowledge of and practice in thromboprophylaxis

Most of the respondents recorded correct answers for most of the questions (6 of 6 questions) examining their general knowledge of DVT. They recorded correct answers for the statements “DVT occurs as a result of injury to a vessel wall, altered blood coagulation, and stasis of blood” (84.5%), and “DVT typically occurs in the lower extremities (deep leg veins)” (53.4%).

Most of the nurses had a low percentage of correct answers to most of the questions (5 of 8 items) examining their general knowledge of the prevention of deep venous thrombosis. They also recorded correct answers for the question “Exercise of the leg and foot (lower extremities) may prevent deep venous thrombosis” (77.2%). Furthermore, most of the nurses had a high percentage of incorrect answers to the question “Development of deep venous thrombosis may be prevented by elastic compression stockings.”

The analysis of respondents’ knowledge of deep venous thrombosis risk factors revealed a low percentage of correct answers to most of the questions (12 of 20 questions). The most common correct answers were recorded for the question “Prolonged immobilization may cause deep venous thrombosis in hospitalized patients” (78.4%), and the most common incorrect answers were recorded for the question “Inflammation or infections may predispose a patient to deep venous thrombosis” (71.6%).

Regarding the practice of nurses in preventing DVT, the investigation revealed that most of the participants responded with the option “always” to all questions compared with the choices “sometimes” and “never”. The most common answers receiving a rating of “always” were recorded for the question “Educating the patients to avoid injury” (72.8%). The nurses more frequently responded with the choice “sometimes” to the question “Educating the patients about the appropriate utilization of graduated compression stockings” (29.3%) and frequently responded, “never” to the question “Educating the patients about adequate or sufficient fluid intake” (23.3%).

No statistically significant differences were observed in the four different scores between genders (p>0.05), as shown in Table 3. The median for practice on DVT prevention for nurses >31 years old was significantly lower than the median of nurses aged from 26–30 years and <25 years, (17), (18) and (21) (p<0.05), respectively. Meanwhile, the median for the general knowledge of DVT attained by nurses >31 years old was significantly higher than the median of nurses aged from 26–30 years and < 25 years old, (5), (4) and (4) (p<0.05), respectively. The median for knowledge of risk factors for DVT attained by nurses >31 years old was significantly higher than the median of nurses aged 26–30 years and <25 years old, (15), (12) and (12) (p<0.05), respectively. The median for knowledge of the prevention of DVT attained by nurses >31 years old was significantly higher than the median of nurses <25 years old, (6) and (5) (p<0.05), respectively.

Table 3. Nurses knowledge of DVT in groups stratified by demographic characteristics.

N (%) Nurses practice on prevention score Nurses general knowledge score Nurses knowledge of risk factor score Nurses knowledge of prevention score
Median (IQR) P Median (IQR) p Median (IQR) P Median (IQR) p
Gender
Males    72 (31) 18 (9.75) >0.05 4 (2) >0.05 12 (3) >0.05 5 (2) >0.05
Females   160 (69) 19 (10) 4 (2) 12 (4) 5 (2)
Age
<25   124 (53.4) 21 (10) <0.05 4 (2) <0.05 12 (4) <0.05 5 (2) <0.05
26–30   73 (31.5) 18 (10) 4 (2) 12 (4) 5 (2)
> 31*   35 (15.1) 17 (6) 5 (2) 15 (5) 6 (2)
Experience
1–5   153 (65.9) 18 (11) <0.05 4 (2) <0.05 12 (4) >0.05 5 (2) >0.05
6–10   50 (21.6) 19 (9.5) 4 (1.2) 11 (4) 5 (2)
> 11   29 (12.5) 17 (7.5) 5 (3) 14 (5.5) 6 (2.5)
Education
Diploma   65 (28) 18 (9.5) >0.05 4 (2) >0.05 12 (3) >0.05 5 (2) >0.05
Bachelor   136 (58.6) 19 (10.7) 4 (2) 12 (4.7) 5 (2)
Master   31 (13.4) 18 (11) 4 (2) 14 (4) 5 (2)
Working Unit
Emerg   37 (15.9) 18 (6) <0.05 4 (2) <0.05 13(3.5) <0.05 6 (2.5) >0.05
ICU   36 (15.5) 22 (11) 3 (1.7) 11 (3) 5 (2.7)
Internal  39 (16.8) 18 (11) 4 (2) 13 (5) 5 (4)
Gynae   21 (9.1) 16 (5.5) 5 (2.5) 14 (6) 6 (2)
Onco   16 (6.9) 27 (6.7) 3 (1.7) 12 (3) 5 (1.7)
Sugery   29 (12.5) 18 (11.5) 4 (2) 12 (4.5) 5 (2)
Polycli   15 (6.5) 15 (7) 4 (3) 14 (5) 5 (2)
Orthopaed  29 (12.5) 20 (8.5) 6 (2) 11 (3) 6 (2)

^ Kruskal-Wallis test and Mann-Whitney U tests were used for the statistical analyses, when applicable. IQR (Interquartile range).

Regarding the number of years of experience, nurses with >11 years of experience had a median for general practice that was significantly lower than the median of the nurses with 6–10 years of experience (17) and (19*) (p<0.05), respectively. Also, no statistically significant differences were observed in the four different scores between education subgroups (p>0.05).

Regarding the work units, nurses who worked in an ICU had a median for practice that was significantly higher than the median of the nurses who worked in gynaecology, (22) and (16) (p<0.05), respectively. The nurses who worked in gynaecology unit attained a median for general knowledge that was significantly higher than the median of the nurses who worked in both polyclinic and an oncology unit, (5) (4) and (3.5) (p<0.05), respectively. The nurses who worked in an ICU had median for risk factor knowledge that was significantly lower than the median of the nurses who worked in polyclinic units, (11) and (14) (p<0.05), respectively.

Physicians’ demographics, knowledge, and attitudes towards thromboprophylaxis

One hundred seventeen questionnaires were dispersed to physicians, and 109 were returned, corresponding to a response rate of approximately 93%. One hundred three questionnaires were evaluated, while 6 that were improperly filled were discarded. Physicians who responded to questionnaires were professors (n = 29), associate professors (n = 15), assistant professors (n = 18) and specialists (n = 41) working in different clinics. Table 4 presents the descriptive statistics of knowledge and attitude scores for physicians. Regarding the knowledge of physicians who completely responded to the questionnaire, a high percentage of incorrect answers were observed for most of the questions (10 of 15 questions). More than 50% of physicians did not know that VTE is a fatal combination of DVT. Similarly, 77.7% of physicians did not know that the administration of general anaesthesia for <30 minutes does not increase the risk of deep venous thrombosis. However, the most common correct knowledge answers were recorded for the question “Patients undergoing surgery are more susceptible to deep venous thrombosis/venous thromboembolism than medical patients” (76.7%).

Table 4. Descriptive statistics of knowledge and attitude scores of physicians.

Variables Mean Standard deviation Minimum Maximum
Knowledge 6.58 2.37 0.00 11
Attitude 20.12 4.86 9.00 30

In response to attitude questions, the majority of the respondent (38.8%) stated that they “Strongly Agree” that prevention/prophylaxis of DVT is necessary prior to surgery, and only (16.5%) stated that they “Strongly Disagree” that educating patients regarding preventive measures of DVT is necessary. Furthermore, they indicated a requirement for routine ultrasound screening in asymptomatic patients at discharge or during outpatient follow-up, as shown in Table 5.

Table 5. Responses of physicians to questions examining attitudes towards DVT (N = 103).

Attitude statements Strongly Disagree N (%) Disagree N (%) Neutral N (%) Agree N (%) Strongly Agree N (%) Mean ± SD Total attitude score
1. I believe that Doppler sonography (sensitive and objective tests) is necessary to screen for post-surgical DVT in patients. 12 (11.7) 20 (19.4) 26 (25.2) 30 (29.1) 15 (14.6) 3.16 ± 1.2 20.12 ± 4.9
2. I believe that an assessment of DVT risk factors is necessary prior to surgery. 13 (12.6) 14 (13.6) 17 (16.5) 26 (25.2) 33 (32) 3.50 ± 1.39
3. I believe that the prevention/prophylaxis of DVT is necessary prior to surgery. 7 (6.8) 19(18.4) 17 (16.5) 20 (19.4) 40 (38.8) 3.65 ± 1.34
4. I believe that educating patients regarding preventive measures of DVT is necessary. 17 (16.5) 16 (15.5) 22 (21.4) 34 (33) 14 (13.6) 3.12 ± 1.30
5. I believe that nurses require training in methods to prevent DVT. 13 (2.6) 17 (16.5) 27 (26.2) 19 (18.4) 27 (26.2) 3.29 ± 1.33
6. I believe that the prevention of DVT with low dose heparin is irrational before surgery. 15 (14.6) 8 (7.8) 26 (25.2) 28 (27.2) 26 (25.2) 3.41 ± 1.33

Discussion

Indeed, after assessing 180 patients using the Caprini risk assessment tool, finding of the current study show that thromboprophylaxis regimens were appropriately provided to only approximately 52.3% of patients, consistent with the studies by White RH et al. [20], Nekoonam B et al. [21] and Kingue et al. [22], where 50%, 32.6% and 58.5% of the subjects received correct prophylaxis, respectively. In contrast, 20.3% of patients examined in the study by Cristiano et al. [23] received rational prophylaxis and venous thromboembolism is still the major cause of their sudden death. The results are also consistent with the findings reported by Sharif-Kashani et al. showing that rational prophylaxis was provided to less than half of the patients included in the study [24]. In our study, 3.4% of patients received inadequate prophylaxis (e.g., insufficient doses of enoxaparin or compression stockings alone), in contrast to the results by Zeitoun et al. [25] and Nekoonam B et al., where inadequate VTE prophylaxis was administered to 35% and 17.3% of the subjects, respectively. In our study, 15.1% of patients received a higher dose, but 6.52% of patients analysed in the study by Nekoonam B et al. received higher doses for thromboprophylaxis. Compared to risk scores in the study by Nekoonam B et al., 73.08% of all patients had a high risk with a risk score of 3 or more points, 11.5% had a moderate risk with a risk score of 2 points, and 15.3% had a low risk with a risk score of 1 or fewer points. Our study obtained similar results, where 77.8% of patients had a high level of risk, 15% of patients displayed a moderate level of risk, and only 5.6% and 1.7% displayed a low and very low level of risk, respectively.

According to a study conducted in London [26], 16% and 20% [21] of patients treated with enoxaparin required dose adjustments upon administration, while in our study, only 13.9% of patients administered enoxaparin required a dose adjustment. The enoxaparin prescription pattern identified in the present study was inappropriate, similar to the studies by Fahimi et al. and Nekoonam B et al. As shown in the study by Fahimi et al. [27], the improper dosing, administration, and prescription of enoxaparin occur frequently, and health care providers require training programs and the implementation of evidence-based protocols to control prescription patterns. Regarding complications, a study by Novo-Veleiro et al. [28] reported wound haematoma (7.3%) and major bleeding (0.5%) as the main complications, while wound haematoma occurred in 16.6% of patients and no major bleeding was noted during and after hospitalization in our study.

Regarding the knowledge of the prevention of DVT, most of the nurses had a low score of knowledge, similar to the results of a quantitative study conducted by Abin et al., which concluded that 42% of the nurses attained a low score for knowledge of deep venous thrombosis prevention in hospitalized patients [29]. In the present study, most respondents (88.8%) require DVT education, and this issue should be taken into account to improve the awareness and willingness of nurses to attend training programs, workshops and congresses on the prevention of DVT.

Regarding the evaluation of the knowledge and attitudes of physicians, more than 50% of physicians did not know that VTE is a fatal combination of deep venous thrombosis. Similarly, 77.7% of physicians did not know that the administration of general anaesthesia for <30 minutes does not increase the deep venous thrombosis risk, consistent with the result reported by Mehdi et al. showing that more than 50% of the study population recorded a similar answer. In addition, more than half of physicians did not know that surgery posed a higher risk for patients with cancer to develop deep venous thrombosis than in obese or aged patients [17]. The American College of Chest Physicians (ACCP) recommend that patients must be classified as having very high, high, moderate, and low risks of developing VTE, and a prophylaxis method must be used according to this risk stratification score and every health care setting must develop a formal and effective strategy for the prevention and complication of venous thromboembolism [30]. Thromboprophylaxis was underutilized in tertiary care hospitals in Northern Cyprus which denote a gap between evidence-based guidelines and practice. By giving proper training to (HCPs) about DVT prevention and establishing a hospital-wide clinical Pharmacist based DVT prevention program will decrease the morbidity and mortality associated with this disease process and will assure rational practices in North Cyprus.

Strength and limitations of the study

The present study assesses the rational use of thromboprophylaxis therapy in hospitalized patients and perceptions of health care providers in two tertiary care hospitals in North Cyprus. However, this study also has some limitations that might decrease the generalizability of the results. As only 2 hospitals were chosen as study setting, we may not be able to generalize the study findings overall hospitals in North Cyprus. Both studied hospitals were teaching hospitals, in which healthcare professionals provide beside complex care; clinical education and training to current and future health professionals through educational and mentoring activities [31]. Teaching hospitals tend to be early adopters of new evidence and technologies which leads to better outcomes and less mortality compared to non-teaching hospitals [32]. Healthcare providers in teaching hospitals are more exposed to learning and teaching activities besides their preceptorship which encourages them to be theoretically and practically prepared for the role, adheres more closely to clinical policies, best practices and deliver high-quality care and services as role models [33]. This may further suggest inferior knowledge and practice of DVT prophylaxis in other settings with less teaching and mentorship, which necessitate further research and comparison to reach such a conclusion.

The demographic data of the physicians were not collected to increase the response rate. we were unable to document pulmonary embolism as the cause of death of the patients who died during hospitalization because it was not documented properly.

An interventional program that incorporates both education and a daily individual assessment of DVT risk factors is needed with an enclosed prophylaxis policy. The establishment of an effective deep venous thrombosis prophylaxis strategy in health care settings with evidence-based recommendations may be useful to improve patient safety, quality of life, and best practices. Clinical pharmacists can utilize the Caprini risk assessment tool and assist health care providers in the rational implementation of the rational use of medications and antithrombotic prophylaxis in hospitals. Investments in training health care providers about deep venous thrombosis prophylaxis are needed to achieve the proper utilization of antithrombotic medications, this public health issue and regular medication errors related to inappropriate anticoagulant use deserve further consideration to decrease morbidity and mortality.

Conclusions

Based on the findings of the present study and international reports, adherence to VTE prophylaxis is still low in practice, a high level of irrationality in thromboprophylaxis therapy of hospitalized patients, and inappropriate administration of anticoagulants was observed. Furthermore, a low degree of knowledge of risk factors for deep venous thrombosis, preventive measures, bad practices in preventing deep venous thrombosis among nurses and, a lack of knowledge of health care providers and standard guidelines was also noted in assessed hospitals.

Supporting information

S1 Appendix

(DOCX)

S2 Appendix

(DOCX)

S3 Appendix

(DOCX)

S4 Appendix

(DOCX)

Acknowledgments

The authors have gratefully acknowledged the Near East University hospital, for the supply and guidance on the subject, Department of Clinical Pharmacy, Faculty of Pharmacy, Near East University, Nicosia, North Cyprus, for providing necessary facilities. The authors would like to give special thanks to Dr. Wahab Ali Shah, Dr. Louai M Saloumi and Sibel Severler to provide help and statements that greatly improved the manuscript preparation.

Data Availability

All relevant data are within the paper and its Supporting Information files.

Funding Statement

The author(s) received no specific funding for this work.

References

  • 1.Stone J, Hangge P, Albadawi H, Wallace A, Shamoun F, Knuttien MG, et al. Deep vein thrombosis: pathogenesis, diagnosis, and medical management. Cardiovasc Diagn Ther. 2017; 3: S276–S284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Kesieme E, Kesieme C, Jebbin N, Irekpita E, Dongo A. Deep vein thrombosis: a clinical review. J Blood Med. 2011; 2:59–69. 10.2147/JBM.S19009 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.O'Donnell M, Weitz JI. Thromboprophylaxis in surgical patients. Can J Surg. 2003; 46(2):129–135. [PMC free article] [PubMed] [Google Scholar]
  • 4.Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005; 51(2–3):70–78. 10.1016/j.disamonth.2005.02.003 [DOI] [PubMed] [Google Scholar]
  • 5.Geerts WH, Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR, et al. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2008; 133(6): 381S–453S. [DOI] [PubMed] [Google Scholar]
  • 6.Alikhan R, Forster R, Cohen AT. Heparin for the prevention of venous thromboembolism in acutely ill medical patients (excluding stroke and myocardial infarction). Cochrane Database Syst Rev. 2014; 5:1–52. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Badireddy M, Mudipalli VR. Deep Venous Thrombosis (DVT) Prophylaxis. 2018. [PubMed] [Google Scholar]
  • 8.Polish Working Group. A scoring system for thromboembolic risk assessment in surgery, developed by the Polish Working Group, on the basis of the scoring system developed by Joseph Caprini. Acta Angiol. 2011; 17(1):49–76. [Google Scholar]
  • 9.Motykie GD, Zebala LP, Caprini JA, Lee CE, Arcelus JI, Reyna JJ, et al. A guide to venous thromboembolism risk factor assessment. J Thromb Thrombolysis. 2000; 9(3):253–262. 10.1023/a:1018770712660 [DOI] [PubMed] [Google Scholar]
  • 10.Ofori-Asenso R, Agyeman AA. Irrational use of medicines-a summary of key concepts. Pharmacy. 2016; 4(4):35. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Deng J, Thomas L, Li H, Varughesekutty E, Shi Q, Sambharia M, et al. Overuse of DVT Prophylaxis in Medical Inpatients. Am Soc Hematology. 2015. [Google Scholar]
  • 12.Imberti D, Becattini C, Bernardi E, Camporese G, Cuccia C, Dentali F, et al. Multidisciplinary approach to the management of patients with pulmonary embolism and deep vein thrombosis: a consensus on diagnosis, traditional therapy and therapy with rivaroxaban. Intern Emerg Med. 2018; 13(7):1037–1049. 10.1007/s11739-018-1802-5 [DOI] [PubMed] [Google Scholar]
  • 13.Obi AT, Pannucci CJ, Nackashi A, Abdullah N, Alvarez R, Bahl V, et al. Validation of the Caprini venous thromboembolism risk assessment model in critically ill surgical patients. JAMA surg. 2015; 150(10):941–948. 10.1001/jamasurg.2015.1841 [DOI] [PubMed] [Google Scholar]
  • 14.Liu X, Liu C, Chen X, Wu W, Lu G. Comparison between Caprini and Padua risk assessment models for hospitalized medical patients at risk for venous thromboembolism: a retrospective study. Interact Cardiovasc Thorac Surg. 2016; 23(4):538–543. 10.1093/icvts/ivw158 [DOI] [PubMed] [Google Scholar]
  • 15.Caprini JA. Risk assessment as a guide for the prevention of the many faces of venous thromboembolism. Am J Surg. 2010; 199(1):S3–S10. [DOI] [PubMed] [Google Scholar]
  • 16.Al-Mugheed KA, Bayraktar N. Knowledge and practices of nurses on deep vein thrombosis risks and prophylaxis: A descriptive cross sectional study. J Vasc Nurs. 2018; 36(2):71–80. 10.1016/j.jvn.2018.02.001 [DOI] [PubMed] [Google Scholar]
  • 17.Zobeiri M, Najafi F. Prophylaxis for deep venous thrombosis: Knowledge and practice of surgeons. 2011. [Google Scholar]
  • 18.Mariam MG, Bedaso A, Ayano G, Ebrahim J. Knowledge, attitude and factors associated with mental illness among nurses working in public hospitals, Addis Ababa, Ethiopia. J Ment Disord Treat. 2016; 2(108):2. [Google Scholar]
  • 19.Connelly LM. Pilot studies. Medsurg Nurs. 2008; 17(6):411 [PubMed] [Google Scholar]
  • 20.White RH. The epidemiology of venous thromboembolism. Circulation. 2003; 107(23):I-4-I-8. [DOI] [PubMed] [Google Scholar]
  • 21.Nekoonam B, Eshraghi A, Hajiesmaeili M, Sahraei Z. Deep vein thrombosis prophylaxis evaluation in intensive care unit. Arch Crit Care Med. 2016; 1(4): e8497. [Google Scholar]
  • 22.Kingue S, Bakilo L, Mvuala R, Minkande JZ, Fifen I, Gureja YP, et al. Epidemiological African day for evaluation of patients at risk of venous thrombosis in acute hospital care settings. Cardiovasc J Afr. 2014; 25(4):159 10.5830/CVJA-2014-025 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Pereira CA, Brito SS, Martins AS, Almeida CM. Deep venous thrombosis prophylaxis: practical application and theoretical knowledge in a general hospital. J Vasc Bras, 2008; 7(1):18–27. [Google Scholar]
  • 24.Sharif-Kashani B, Mohebi-Nejad A, Abooturabi SM. Estimated prevalence of venous thromboembolism in Iran: Prophylaxis still an unmet challenge. Tanaffos. 2015; 14(1):27 [PMC free article] [PubMed] [Google Scholar]
  • 25.Zeitoun AA, Dimassi HI, El Kary DY, Akel MG. An evaluation of practice pattern for venous thromboembolism prevention in Lebanese hospitals. J Thromb Thrombolysis. 2009; 28(2):192 10.1007/s11239-008-0298-7 [DOI] [PubMed] [Google Scholar]
  • 26.Jetha L. A drug usage review of therapeutic doses of enoxaparin at Barnet and Chase Farm Hospitals: London Pharmacy Education and Training Pzifer Project Awards. 2007. [Google Scholar]
  • 27.Fahimi F, Bani AS, Behzad NN, Ghazi TL. Enoxaparin utilization evaluation: An observational prospective study in medical inpatients. 2008. [Google Scholar]
  • 28.Novo-Veleiro I, Alvela-Suárez L, Costa-Grille A, Suárez-Dono J, Ferrón-Vidan F, et al. Compliance with current VTE prophylaxis guidelines and risk factors linked to complications of VTE prophylaxis in medical inpatients: a prospective cohort study in a Spanish internal medicine department. BMJ open, 2018; 8(5): e021288 10.1136/bmjopen-2017-021288 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Antony AM, Moly KT, Dharan DR. Assessment of knowledge and self reported clinical practice on prevention of Deep Vein Thrombosis (DVT) among staff nurses. IOSR Nurs Health Sci 2016; 5(1):18–24. [Google Scholar]
  • 30.Geerts WH, Pineo GF, Heit JA, Bergqvist D, Lassen MR, Colwell CW, et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004; 126(3):338S–400S. [DOI] [PubMed] [Google Scholar]
  • 31.Shahian DM, Nordberg P, Meyer GS, Blanchfield BB, Mort EA, Torchiana DF, et al. Contemporary performance of US teaching and nonteaching hospitals. Acad Med. 2012; 87 (6):701–708. 10.1097/ACM.0b013e318253676a [DOI] [PubMed] [Google Scholar]
  • 32.Burke LG, Frakt AB, Khullar D, Orav EJ, Jha AK. Association between teaching status and mortality in US hospitals. Jama. 2017; 317(20):2105–2113 10.1001/jama.2017.5702 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Bukhari Elham, and Rogers Margaret. Nature of preceptorship and its impact on clinical nursing care from the perspectives of relevant nursing staff. University of Manchester. 2012. [Google Scholar]

Decision Letter 0

Joel Msafiri Francis

19 Mar 2020

PONE-D-20-04896

The rational use of thromboprophylaxis therapy in hospitalized patients and the perspectives of health care providers in Northern Cyprus

PLOS ONE

Dear MR SHAH,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

We would appreciate receiving your revised manuscript by May 03 2020 11:59PM. When you are ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Joel Msafiri Francis, MD, MS, PhD

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please provide additional details regarding participant consent. In the ethics statement in the Methods and online submission information, please ensure that you have specified (a) whether consent was informed and (b) what type you obtained (for instance, written or verbal, and if verbal, how it was documented and witnessed). If your study included minors, state whether you obtained consent from parents or guardians. If the need for consent was waived by the ethics committee, please include this information.”

3. Please address the following:

a) Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, if you developed a questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy, in both the original language and English, as Supporting Information. Please also include the exact number of individuals involved in the pilot testing of the questionnaire.

b) Please refer to any sample size calculations performed prior to participant recruitment. If these were not performed please justify the reasons. Please refer to our statistical reporting guidelines for assistance (https://journals.plos.org/plosone/s/submission-guidelines.#loc-statistical-reporting).

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Reviewer’s comments

1. What is the aim of the study? There more than one version

a. This study aims to evaluate the current thromboprophylaxis practice and management of patients with risks of developing DVT in different clinics, to determine the adherence to thromboprophylaxis guidelines and to assess healthcare providers’ (HCPs) knowledge, practice and attitudes towards deep vein thrombosis risks and prophylaxis with the goal of optimizing care and ensuring rational practices.

b. An observational study was conducted in which patients from multiple clinics were enrolled to investigate the rational use of DVT prophylaxis using the Caprini risk assessment tool

c. This study aims to investigate current thromboprophylaxis practice at two university hospitals in North Cyprus by evaluating the management of patients with a low, medium, and high risk of developing DVT who are treated in different clinics to determine the adherence to thromboprophylaxis guidelines and to assess healthcare providers’ knowledge, practices and attitudes towards deep vein thrombosis risks and prophylaxis

Please harmonize the statements in different sections

2. Where was the study done?

a. An observational study was conducted in which patients from multiple clinics were enrolled to investigate the rational use……..

b. The study was conducted in the general wards of two leading tertiary university hospitals, namely, Near East University Hospital (NEUH) and Dr. Suat Günsel Kyrenia University Hospital (SGKUH) in

c. Study settings are not described

3. The inclusion criteria were acute and chronically ill medical patients…. But table 1 shows patients from diverse wards – including orthopaedic and surgery? This needs to be described.

4. Although the authors reported having followed up participants to asses for possible complications, the development of post-discharge complications (deep venous thrombosis signs and symptoms, pulmonary embolism or adverse effects of medications) was not obvious in the manuscript.

5. The statement “The average length of hospitalization was 12.48 days (median of 11 days)” is unclear. Did the authors report the mean (average – 12.48) and median (11) at the same time? Why were the two measures reported together?

6. Table 2 describes "major" risk factors. Why are these risk factors called major? I am not sure if the term major is used in the Caprin score.

7. In some areas, absolute numbers and percentages are given without reference to what is the denominator. A reader would struggle to identify the denominator. One of these sentences includes "Four of these patients (30.76%) developed 6 minor complications. Anticoagulation therapy was stopped in 2 patients (50%)”

8. The importance of table 3 is unclear. What does table 3 answer? It looks redundant if there is nothing exclusive that it adds to the study.

9. There are several areas where authors used the word "female" to refer to "females."

Reviewer #2: Reviewer Comments

Manuscript Title: The rational use of thromboprophylaxis in hospitalized patients and the perspectives of health care providers in Northern Cyprus

General Impression: The paper describes an important area of thromboprophylaxis. However, some clarifications to the manuscript are required.

1. Materials and Methods:

a) Study Setting and Subjects: “All inpatients admitted between 01 April 2018 and 01 July 2018 who met the inclusion criteria were included in the analysis”. The authors need to clarify and edit the exclusion criteria stated. (lines 87 to 89) as the language is unclear

b) Did the authors have a predetermined minimum required sample size for their analysis plan?

c) The authors also need to clarify at what point data was initially collected-did this happen while patient was still on the ward or after they had been discharged. Also, it’s not clear what data was collected from the patient’s chart/record

d) Ethical consideration: The authors clearly state that they received IRB ethics approval. However, it is also essential to state whether study participants provided written or verbal informed consent prior to participation and if not, state justification for waiver of this requirement

2. Observational Results:

a) Patient demographics and characteristics:

The authors need to mention the number of patients admitted during the 3-month study period from which they selected participants as stated in the methods section.

Table 1: Table shows that the patients included some from the Orthopedics and Surgery clinics- The authors need to clarify their patient sample description in the Methods Section (line 85)-Are these ‘medical’ patients?

To improve readability, authors should consider making the percentage proportions reported consistent by using uniform number of decimal values throughout the manuscript.

3. Discussion:

a) The authors have made many comparisons of their findings to those from similar studies elsewhere. However, I expected the authors to also expound the implications of their findings on the knowledge gaps in relation to those on rationality of thromboprophylaxis in this study

b) Limitations: Was the sampling method ideal and was the sample size for the different phases adequate to draw conclusions? This needs to be considered.

Both study sites are university (teaching) hospitals. Could this have affected the findings on knowledge levels of physicians/nurses?

Also, whilst the authors assessed nurse and physicians’ knowledge on DVT, it is not clear if the HCWs are aware of the Caprini’s RAM and if this is actually standard of practice. Is it possible that the low utilization/rationalization of thromboprophylaxis could have been due to lack of awareness?

Finally,the authors need to check the language and revise text where necessary throughout the manuscript to improve readability.Ensure the references are correctly written

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2020 Jul 15;15(7):e0235495. doi: 10.1371/journal.pone.0235495.r002

Author response to Decision Letter 0


3 May 2020

Dear reviewers and academic editor,

Thanks much for your time and fruitful comments on the article “The rational use of thromboprophylaxis therapy in hospitalized patients and the perspectives of health care providers in Northern Cyprus” Your review and comments would further help enhance the readability and the delivering of the message this article carries.

In response to reviewers section, we reviewed and corrected all the questions raised by the academic editor and reviewers and described the enhancement made on the article following your comments and recommendations which further improved the readability of the manuscript.

Thanks much for your effort and thus contribution to our work.

Attachment

Submitted filename: Response to Reviewers.docx

Decision Letter 1

Joel Msafiri Francis

21 May 2020

PONE-D-20-04896R1

The rational use of thromboprophylaxis therapy in hospitalized patients and the perspectives of health care providers in Northern Cyprus

PLOS ONE

Dear Dr. SHAH,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Jul 05 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Joel Msafiri Francis, MD, MS, PhD

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: No

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: 1.The sample size calculation is stil not clear. Authors reported using 50% response distribution as one of the parameters in the sample size calculation. What was this response referring to? Is this a justifiable way of sample size calculation?

2.Mean and median still appear in table 3. Is there a need for continous variables to be described/ summarised in both ways?

3. In table 3: How were the comparisons made? were mean or median used for the comparisons of continous variables?

4. The Mann-Whitney U test and the Kruskal-Wallis tests were reported as the methods used to compare diffrences accross groups. One would then assume that the data were deemd as being assymetrical . Yet, mean(and SD) were compared as seen in the texts (line 264, 267, 270, 272. etc)

Reviewer #2: The authors have addressed all my previous comments satisfactorily.

The authors should have a second look at the wording and punctuation and correct any typos in the manuscript

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Julius Mwita

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2020 Jul 15;15(7):e0235495. doi: 10.1371/journal.pone.0235495.r004

Author response to Decision Letter 1


4 Jun 2020

Dear reviewers and academic editor, thanks much for your time and fruitful comments on the article “The rational use of thromboprophylaxis therapy in hospitalized patients and the perspectives of health care providers in Northern Cyprus” Your review and comments would further help enhance the readability and the delivering of the message this article carries.

Attachment

Submitted filename: Response to Reviewers.docx

Decision Letter 2

Joel Msafiri Francis

12 Jun 2020

PONE-D-20-04896R2

The rational use of thromboprophylaxis therapy in hospitalized patients and the perspectives of health care providers in Northern Cyprus

PLOS ONE

Dear Dr. SHAH,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Jul 27 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Joel Msafiri Francis, MD, MS, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

Please kindly address the few additional comments from the reviewers.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: All the comments have been addressed. No more comments from my side. The manuscript can be accepted for publication

Reviewer #2: Abstract: Ensure you use a uniform tense throughout the abstract.The 'Aims' section is stated in present tense.

Ensure that the proportions mentioned here match those in the results and discussion sections

Discussion:

Line 313

"Indeed, after assessing 180 patients using the Caprini risk assessment tool, finding of the current study show that thromboprophylaxis regimens were appropriately provided to only approximately 52.2% of patients, consistent with the studies by White RH et al..."

The percentage proportion stated here does not add up with that stated in the abstract (47.7%).The authors should consider correcting this statement to reduce its ambiguity .

Conclusion:

There is some repetition in the authors conclusion.It needs to be made more succinct and focused on their study

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Julius Mwita

Reviewer #2: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2020 Jul 15;15(7):e0235495. doi: 10.1371/journal.pone.0235495.r006

Author response to Decision Letter 2


14 Jun 2020

Dear reviewers and academic editor, thanks much for your time and fruitful comments on the article “The rational use of thromboprophylaxis therapy in hospitalized patients and the perspectives of health care providers in Northern Cyprus” Your review and comments would further help enhance the readability and the delivering of the message this article carries.

Attachment

Submitted filename: Response to Reviewers.docx

Decision Letter 3

Joel Msafiri Francis

17 Jun 2020

The rational use of thromboprophylaxis therapy in hospitalized patients and the perspectives of health care providers in Northern Cyprus

PONE-D-20-04896R3

Dear Dr. SHAH,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Joel Msafiri Francis, MD, MS, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The authors have addressed all the comments in the 'Response to reviewer comments' and just need to double check that these changes are included in the main text.For example the proportion of rationally managed patients is 52.3% according to figure 1 but is stated as 52.2% in the abstract and discussion sections.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: No

Acceptance letter

Joel Msafiri Francis

22 Jun 2020

PONE-D-20-04896R3

The rational use of thromboprophylaxis therapy in hospitalized patients and the perspectives of health care providers in Northern Cyprus

Dear Dr. Shah:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Joel Msafiri Francis

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Appendix

    (DOCX)

    S2 Appendix

    (DOCX)

    S3 Appendix

    (DOCX)

    S4 Appendix

    (DOCX)

    Attachment

    Submitted filename: Response to Reviewers.docx

    Attachment

    Submitted filename: Response to Reviewers.docx

    Attachment

    Submitted filename: Response to Reviewers.docx

    Data Availability Statement

    All relevant data are within the paper and its Supporting Information files.


    Articles from PLoS ONE are provided here courtesy of PLOS

    RESOURCES