Venous Thromboembolism Risk and Prophylaxis in Hospitalized Patients in Iraq

Transcription

1 ORIGINAL ARTICLE Venous Thromboembolism Risk and Prophylaxis in Hospitalized Patients in Iraq ABSTRACT Venous thromboembolism (VTE) is a common unrecognized and underestimated preventable condition; there are no data estimating the prevalence of VTE risk factors among the Iraqi patients or information s about the Iraqi physician s practice for prophylaxis. Objective Assessing the prevalence of high-risk medical and surgical patients for developing VTE and to evaluate the utilization of appropriate prophylaxis in Iraq. Methods A prospective study conducted in eligible medical and surgical wards in ALYARMOUK teaching hospital in Baghdad-Iraq, we used Padua score and Caprini score as risk assessment models for medical and surgical patients, respectively, while the prophylaxis approaches were assessed according to the American College of Chest Physicians (ACCP) eighth edition. Results We enrolled 574 patients in this study (296 medical; 278 surgical) from April to June 2016, two hundred sixty-seven patients (46.5%) were at risk of VTE; 115 (38.9%) medical patients and 152 (54.7%) surgical patients. Among them, only 9 (7.8%) medical patients and 4 (2.6%) surgical patients received some form of prophylaxis. Only 25% of the prescribed prophylaxis was ordered according to the ACCP recommendations. Mechanical prophylaxis has never been ordered. Conclusion The prevalence of VTE risk is high in both medical and surgical patients with clear underutilization of prophylaxis for at-risk Iraqi hospitalized patients. The is a great need for implementing an educational program to improve both the quantity and quality of prophylaxis. KEYWORDS Iraq venous thromboembolism VTE prophylaxis VTE risk INTRODUCTION Venous thromboembolism (VTE) considered a global health concern; it includes deep vein thrombosis (DVT) and pulmonary embolism (PE), VTE affects medical and surgical hospitalized patients with a high rate of morbidity and mortality 1. The annual incidence of symptomatic VTE in the United States (US) estimated to be 100 per persons 2. Heit et al. documented that hospitalized patients are 100 times at higher risk for developing VTE than community residents 3. Studies reported that up to 10% of hospitalized deaths are attributed to fatal PE 4. Hospital-acquired VTEs are preventable if an effective prophylactic regimen adopted 1,5. Although surgery is a major risk factor for VTE, non-surgical patients account for more than two-thirds of fatal PE cases and up to 70% of symptomatic thrombotic events 4. The good knowledge of VTE pathophysiology and how each risk factor contributes to the development of the condition forms the basis for the optimum use of prophylaxis, many of VTE risk factors have been documented with the varying degree of effects. The most common individual risk factors are age above 70 years, history of VTE, immobility, cancer, congestive heart failure, obesity and many other medical conditions 6. Surgical patients are at risk for developing VTE depending on the type of the surgery and patient characteristics, hip or knee surgery carry the highest risk for developing VTE 4. VTE is often asymptomatic with more than half cases are silent, misdiagnosed and unidentified as the cause of death in many cases leading to underestimation of its incidence and risk 1, such underestimation suggesting the necessity for developing a strategy to identify patients at risk and providing an appropriate prophylaxis approaches. ISSN No CODEN NLM Title DOI JPBSCT Dhulfiqar Nidhal Alhilali 1, Haydar Fakhri Hadi Al Tukmagi 2, Hassan Mohammed Abass 2 * 1 Department of Clinical Pharmacy, College of Pharmacy, University of Baghdad, Baghdad, Iraq 2 Department of Clinical Pharmacy, Medical City, Baghdad, Iraq n Address reprint requests to: *Dr. Dhulfiqar Nidhal Alhilali, Department of Clinical Pharmacy, College of Pharmacy, University of Baghdad, Baghdad, Iraq dhulfiqar.nidhal@gmail.com n Article citation: Alhilali DN, Tukmagi HFHA, Abass HM. Venous thromboembolism risk and prophylaxis in hospitalized patients in Iraq. J Pharm Biomed Sci 2016; 06(11): Available at Statement of originality of work: The manuscript has been read and approved by all the authors, the requirements for authorship have been met, and that each author believes that the manuscript represents honest and original work. Source of funding: None. J Pharm Biomed Sci Competing interest / Conflict of interest: The author(s) have no competing interests for financial support, publication of this research, patents, and royalties through this collaborative research. All authors were equally involved in discussed research work. There is no financial conflict with the subject matter discussed in the manuscript. Disclaimer: Any views expressed in this paper are those of the authors and do not reflect the official policy or position of the Department of Defense. Copyright 2016 Received Date: 16 August 2016 Accepted Date: 08 November 2016 Published Online: 18 November 2016

2 Venous thromboembolism risk 603 Many evidence-based guidelines evolved to help in patients risk assessment and recommend an appropriate prophylaxis according to the risk category. Despite the publication of such guidelines for more than 25 years, adherence to these guidelines still low with underutilization of prophylaxis worldwide 7. Guidelines uses different methods to assess patients risk factors, some using individual patient risk assessment score (for example Caprini et al. develop a risk assessment model for both surgical and medical patients and his score has been validated for surgical patients in ,9. Padua risk assessment model also developed to assess medical patients 10. Many clinicians prefer to rely on the American college of chest physician (ACCP) which classifies the patients into groups with low, moderate and high risk. The ACCP recommend prophylaxis for moderate and high-risk groups, using either mechanical prophylaxis and/or pharmacological agents which include unfractionated heparin (UFH), Low molecular weight heparin (LMWH) and fondaparinux 4. Cohen et al. reported that 52% of hospitalized patients worldwide are at risk of VTE, only 58.5% of at-risk surgical patients received appropriate ACCP recommended prophylaxis compares to 39.5% of at-risk medical patients 7. Specific studies demonstrating the prevalence of VTE risk in Iraq and the rate of using prophylaxis are lacking, countries near Iraq like Gulf states (Kuwait, Kingdom of Saudi Arabia, and United Arab Emirates) reported that 62% of total hospitalized patient where at-risk for VTE with only 40.2% of at-risk patients received appropriate ACCP recommended prophylaxis (40.7% for medical patients and 39.8% for surgical patient) 11. We conduct this study to determine the prevalence of high-risk medical and surgical patients for developing VTE and to evaluate the utilization of appropriate prophylaxis in Iraq. METHODS Study design We planned a prospective study with blinded assessment of study outcomes; our goal was to evaluate VTE risk among surgical and medical patients and assess the current clinical practice of VTE prophylaxis in a major Iraqi hospital and whether this practice is compatible with the guideline-recommended VTE care. We conduct the Study in the period between April 2016 to June 2016 at ALYARMOUK teaching hospital, which is a major hospital with 992 beds in Baghdad Iraq. At the hospital, we consider medicine ward and three units from the surgical ward which are a general surgery unit, orthopedic unit, and urological surgery unit are eligible to include its patients to the study. We didn t include patients from the following wards in our study: Maternity and Obstetric: neonatal: burns; psychiatric; ear, nose and throat, dental and emergency. Patients excluded from the study are; patient age under 18 years, patients already on anticoagulant therapy before admission or require Anticoagulation for any indication during hospitalization, Pregnant woman, admission less than 24 hours and patients admitted after cardiac surgery or neurosurgical procedure. Other than the mentioned excluded criteria all patients admitted to the eligible medical and surgical wards are included in the study. Risk assessment model Despite the easiness of group risk assessment for medical patients that recommended by the ACCP we prefer to adopt the individual risk assessment model (RAM). The RAM that we adopt for medical patients is Pauda prediction score (Table 1) that generated by adding items and modifying Kucher s Model in a way that permits identification of all conditions that require prophylaxis according to the international guidelines 12. For surgical patients, we adopt Caprini risk assessment model Fig. 1, which is accredited by the ACCP 4,14. Recommended pharmacological VTE prophylaxis regimens We classify all recruited patients according to the chosen risk assessment model as being at high (Padua score 4) or low risk for the medical patient. Surgical patients classified as very low (Caprini score 0), low (Caprini score 1 2), moderate (Caprini score 3 4) and High (caprine score 5). Patients considered at risk for VTE were patients who classified as moderate or high risk according to the scores. Table 1 Baseline features Risk assessment model (high risk of VTE: 4). Score Active cancer* 3 Previous VTE (with the exclusion of superficial vein thrombosis) Reduced mobility** 3 Already known thrombophilic condition*** 3 Recent (<1 month) trauma and/or surgery 2 Elderly age ( 70 years) 1 Heart and/or respiratory failure 1 Acute myocardial infarction or ischemic stroke 1 Acute infection and/or rheumatologic disorder 1 Obesity (BMI 30) 1 Ongoing hormonal treatment 1 *Patients with local or distant metastases and/or in whom che motherapy or radiotherapy had been performed in the previous 6 months. **Bedrest with bathroom privileges (either due to patient s limitations or on physicians order) for at least 3 days. ***Carriage of defects of antithrombin, protein C or S, factor V Leiden, G20210A prothrombin mutation, antiphospholipid syndrome. 3

3 604 Dhulfiqar Nidhal Alhilali 691 patients in eligible wards 574 enrolled patients 117 Excluded patients 49 patients admitted with indications for anticoagulants therapy 24 patients stayed less than 1 day in the hospital 23 patients age <18 years 20 patients using anticoagulants before admission 1 pregnant patient 296 in medical ward 278 in surgical ward Fig. 2 Selection of study population and exclusion reasons. The recommended prophylaxis was assessed according to the eighth edition ACCP guidelines. Prophylaxis methods including administration of pharmacological agents (UFH and LMWH) and/or graduated compression stocking (GCS) as a mechanical agent. Patients with contraindication for pharmacological prophylaxis were: patients with active bleeding, known cases of hepatic induced thrombocytopenia and medical patients with International Medical Prevention Registry on Venous thromboembolism (IMPROVE) Bleeding Risk Score Statistical analysis Data collected were checked several times to reduce the chance of error. Quantitative data were summarized using the mean. Categorical data were summarized using number and percentage. The CI we calculate was 95%. We calculate the fraction of patients at-risk as the number of patients at moderate and high risk of VTE divided over the total number of patients included. The fraction of patients received prophylaxis was calculated as the number of patients who received prophylaxis divided over the total number of patients at risk of VTE. RESULTS Fig. 1 Caprini risk assessment model. Between April 2016 and June 2016, we screened 601 patients, of them 574 were enrolled for VTE assessment in our study; 296 patients were admitted to the medicine ward while 278 patients were admitted to surgical care units. The number of patients assessed and the reasons for exclusion are shown in Fig. 2, Patient s demographic data and the reasons for admission are shown in Table 2. Table 2 Characteristics Patients characteristics and reasons for admission. Medical patients (n = 296 ) Surgical patient (n = 278 ) Age (Mean ± SD) 54.3 ± ± 17.2 Range Men 153 (51.7%) 107 (38.5%) Cause of admission to medical ward Infection or parasitic disease 52 (17.6%) Malignant neoplasms 13 (4.4%) blood 6 (2 %) Endocrine, nutrition and metabolic diseases nervous system circulatory system respiratory system digestive system genitourinary system Miscellaneous conditions Surgical care 20 (6.8%) 2 (0.7%) 77 (26%) 19 (6.4%) 52 (17.6%) 47 (15.9%) 8 (2.7%) General 192 (69%) Urological 43 (15.5%) Orthopedic 43 (15.5%) Data are expressed as number (%).

4 Venous thromboembolism risk 605 Most hospitalized patients (86.8% of medical patients and 91% of surgical patients) had at least one risk factor for VTE. Table 3 shows the distribution of risk factors for medical patients, the most prevalent risk factor in medical patients was reduced mobility (29.7%) followed by heart and/or respiratory failure (27.4%). From the other side, the most prevalent risk factor in surgical patients (without considering major surgery) was bed rest (26.3%) as shown in Table 4. Of the 574 enrolled patients, 267 (46.5%) were assessed to be at risk for VTE, from which 115 (38.9%) medical patients were at risk according to Padua score criteria while 152 (54.7%) surgical patients were at risk for VTE according to the ACCP guidelines. Moderate risk was identified in 65 (23.4%) surgical patients and 87 (31.3%) surgical patients were at high risk of VTE, as shown in Figs. 3 and 4. The fraction of at-risk patients that receive prophylaxis in medical ward was very low, nine patients (7.8%) received some form of prophylaxis from them only two patients received appropriate ACCP recommended prophylaxis. For surgical patients the number of patients who received prophylaxis was much lower, only four patients (2.6%) received some form of prophylaxis, three of them were in the orthopedic unit and one patient were in the general surgical unit while none of the patients in the urological unit received prophylaxis. Unfractionated heparin was the preferred choice for medical ward physicians in all cases of prophylaxis with 5000 International Units (IU) twice daily regimen. Three times daily regimen has never been ordered. In the surgical ward, surgeons prescribe enoxaparin 4000 IU once daily in three of the four cases of Table 3 Risk factors VTE risk factors for hospitalized medical patients. Medical patients (n = 296) Active cancer 21 (7.1%) Previous VTE 9 (3%) Reduced mobility >3 Days 85 (28.7%) Already known thrombophilic condition 3 (1%) Recent (<1 month ) trauma and/or surgery 17 (5.7%) Elderly age (>70 years ) 72 (24.3%) Heart and/or respiratory failure 81 (27.4%) Acute myocardial infarction or ischemic stroke Acute infection and/or rheumatologic disorder 58 (19.6%) 73 (24.7%) Obesity (BMI > 30 ) 48 (16.2%) Ongoing hormonal treatment 37 (12.5%) ordered prophylaxis while the last case prescribed UFH 5000 IU twice daily. Contraindications to pharmacological prophylaxis recorded in 14 at-risk medical patients (12.2%) while nine patients (6%) of at-risk surgical patients show a contraindication reason. Table 4 VTE risk factors for hospitalized surgical patients. Risk factors Surgical patients (n = 278) Age years 103 (37.1%) Swollen legs 5 (1.8%) Varicose veins 2 (0.7%) Obesity 12 (4.3%) Minor surgery planned 19 (6.8%) Sepsis 10 (3.6%) Oral contraceptives 4 (1.4%) Pregnancy or postpartum 1 (0.4%) History of unexplained 2 (0.7%) stillborn infants Congestive heart failure 3 (1.1%) Medical patients currently at bed rest 41 (14.7%) History of inflammatory bowel disease 1 (0.4%) History of prior major surgery <1 month 12 (4.3%) Abnormal pulmonary function (COPD) 3 (1.1%) Age years 28 (10.1%) Malignancy 14 (5%) Patients confined to bed >72 hours 32 (11.5%) Central venous access 1 (0.4%) Major surgery >45 minutes 141 (50.7%) Age 75 years or older 10 (3.6%) History of DVT/PE 1 (0.4%) Elevated anticardiolipin antibodies 1 (0.4%) Multiple trauma 2 (0.8%) Elective major lower extremity arthroplasty 8 (2.9%) Hip, Pelvis or leg fracture <1 month 24 (8.6%) Low risk High risk Fig. 3 Medical patients at risk of VTE.

5 606 Dhulfiqar Nidhal Alhilali Very low risk Low risk Moderate risk High risk Mechanical prophylaxis approach has never utilized in both wards for all risk group patients even for patients with contraindications to pharmacological prophylaxis. DISCUSSION Fig. 4 Surgical patients at risk of VTE. This research is the first institutional study that screens the prevalence of VTE risks among Iraqi patients and evaluates the Iraqi physician practice in ordering appropriate prophylaxis for at-risk medical and surgical patients. We found that most hospitalized patients have at least one risk factor for VTE and around 40% of medical patients were at high risk for developing VTE. Although these findings are consistent with many global studies, other researchers documented that the risk in medical patients is higher than 50% and it reached levels of more than 75% in other studies 11,15. These differences in results may be due to each study uses a different model for screening the patients at risk, many studies depend on group assessment as recommended by the ACCP while we depend on the individual patient risk assessment Padua score which require higher criteria to address the high risk patients. For surgical patients our finding estimated the patients at moderate or high risk by 55%, Similar to medical patients there is a huge variation in estimating the prevalence of VTE risk among countries 11. This variation may be due to the difference in the surgical care unit where that study conducted, the type of the risk assessment model used for each study and the percent of patients who undergo a major surgery. Unfractionated heparin was the only agent that available for VTE prophylaxis in the hospital where we conducted our study, LMWH and any form of mechanical prophylaxis were not available. Despite the huge number of evidence-based guidelines for the need of VTE prophylaxis, the usage of prophylaxis underutilized worldwide with variation between countries from 4% to 80% for medical patients and from 0.4% to 94% for surgical patients 11. Our findings are consistent with most studies that refer to the low rate of prophylaxis usage, Surprisingly, the percent of patients received prophylaxis was much lower than our expectations it was 7.8% for medical patients and much lower for at-risk surgical patients (2.6%), countries near Iraq and countries of similar health care system showed a much higher prophylaxis usage (Egypt prophylaxis rate was 35.2% for at-risk surgical patients and 37.5% for at-risk medical patients 16, Arabian gulf states which include neighbors countries to Iraq reported 40.7% usage of prophylaxis for at-risk surgical patients and 39.8% for at-risk medical patients 7. Using prophylaxis was higher in the orthopedic unit (6.9%) compared to the general surgical unit (0.6%) and Urological unit (0%), suggesting that orthopedists awareness about the VTE risk and the necessity for prophylaxis higher than other surgeons. The main reasons for underutilization of prophylaxis were the lack of awareness about the risk and the true prevalence of VTE complications, overestimation of bleeding risk for pharmacological prophylaxis regimen, the relative complexity of the guidelines and financial constraints. The unavailability of enoxaparin in the hospital may be the main reason for apparent lower prophylaxis rate of surgical ward when compared to the medical ward; most surgeons we met believe that enoxaparin is safer and ensure a higher patient compliance when used for extended duration of prophylaxis after discharge from the hospital, as most surgeries require extended duration of prophylaxis along with the fact that UFH and LMWH are not interchangeable obligate the surgeons to initiate enoxaparin as a prophylactic agent for the high risk patients during their admission to the hospital. From other side many surgeons refuse prescribing enoxaparin even though they are convinced with its superiority over UFH in the safety and patients compliance because the Iraqi hospital policy prevent any doctor from prescribing a medication that is not available in the hospital when an alternative to that medication is available, so considering UFH as alternative to enoxaparin was a part of this problem. We recorded there is no use of any kind of mechanical prophylaxis for both medical and surgical patients, this may be due to its unavailability in the hospital and the only available type of mechanical prophylaxis outside the hospital is the graduated compression stocking (GCS), and many physicians categorize GCS as adjuvant therapy for varicose veins with no role in the prophylaxis from VTE. Surprisingly, all patients with scores equal to or above 8 according to caprini who needed a combination of pharmacological and mechanical approaches, didn t receive any form of prophylaxis; the possible explanation is the misconception of the surgeons that very high risk patients may be more liable for bleeding than the lower risk ones. Our results show the quality of prophylaxis was very low also. When prophylaxis ordered, guidelines recommendations are not followed, in our study more than 75% of medical patients received inappropriate prophylaxis either due to not enough duration, delayed

6 Venous thromboembolism risk 607 initiation or inappropriate dosing. The picture was similar in Surgical ward, of the four patients who received prophylaxis, three of them received enoxaparin as a prophylactic agent for inadequate duration with lag for more than 24 hours after surgery. Increase physicians awareness about the importance of VTE prophylaxis and the availability of safe and effective approaches is crucial, implementing VTE risk assessment tools to identify the at-risk admitted patients to the surgical and medical wards. We should also adopt a local guideline for prophylaxis taking into the considerations the socioeconomic situation of the Iraqi patient and the current financial situation of the health care system in Iraq. It is important to refer that our data extracted from a large teaching hospital in the center of Baghdad, which is ALYARMOUK teaching hospital, hospitals in the rural areas may show a much lower prophylaxis rate. CONCLUSION Our study shows that high prevalence of the risk of VTE among hospitalized Iraqi patients with an underestimation of the problem and terrifying underutilization of effective prophylaxis for at-risk patients. These findings confirm the necessity for increasing the awareness about the substantial morbidity and mortality of the problem along with adopting a risk stratification tools to change both the quantity and the quality of prophylaxis. REFERENCES 1. Cohen AT, Agnelli G, Anderson FA, Arcelus JI, Bergqvist D, Brecht JG, et al. VTE Impact Assessment Group in Europe (VITAE). Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost. 2007;98: White R. The Epidemiology of venous thromboembolism. Circulation. 2003;107:I Heit JA, Melton LJ, Lohse CM, Petterson TM, Silverstein MD, Mohr DN, et al. Incidence of venous thromboembolism in hospitalized patients vs community residents. Mayo Clin Proc. 2001;76: 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 (8th Edition). Chest. 2008;133:381S 453S. 5. Leizorovicz A, Cohen AT, Turpie AG, Olsson CG, Vaitkus PT, Goldhaber SZ. PREVENT Medical Thromboprophylaxis Study Group. Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients. Circulation 2004;110: Turpie AG. Thrombosis prophylaxis in the acutely ill medical patient: insights from the prophylaxis in MEDical patients with ENOXaparin (MEDENOX) trial. Am J Cardiol. 2000;86: 48M 52M. 7. Alsayegh F, Kamaliddin H, Sheshah E, Bukhamseen N, Alkhuwaitir T, Elhoufi A. Assessment of venous thromboembolism risk and adequacy of prophylaxis in selected acute care medical centres in Arabian gulf states: results from the ENDORSE Study. Med Princ Pract. 2012;21: Lutz L, Haas S, Hach-Wunderle V, et al. Venous thromboembolism in internal medicine: risk assessment and pharmaceutical prophylaxis: publication for the specialist forum. Med Welt. 2002;53: Bahl V, Hu HM, Henke PK, Wakefield TW, Campbell DA, Caprini JA. A validation study of a retrospective venous thromboembolism risk scoring method. Ann Surg. 2010;251: 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: Cohen AT, Tapson VF, Bergmann JF, Goldhaber SZ, Kakkar AK, Deslandes B, et al. Endorse Investigators. Venous thromboembolism risk and prophylaxis in the acute hospital care setting (Endorse study): a multinational cross-sectional study. Lancet. 2008;371: 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;212: Pannucci CJ, Bailey SH, Dreszer G, Fisher C, Zumsteg JW, Jaber RM, et al. Validation of the Caprini risk assessment model in plastic and reconstructive surgery patients. J Am Coll Surg. 2010;51: Hostler D, Marx E, Moores LK, Petteys SK, Hostler JM, Mitchell JD, et al. Validation of the International Medical Prevention Registry on venous thromboembolism bleeding risk score. Chest. 2016;149: Stinnett J, Pendleton R, Skordos L, Wheeler M, Rodgers GM. Venous thromboembolism prophylaxis in medically ill patients and the development of strategies to improve prophylaxis rates. Am J Hematol. 2005;78: Goubran HA, Sholkamy S, El-Haddad A, Mahmoud A, Rizkallah MA, Sobhy G. Venous thromboembolism risk and prophylaxis in the acute hospital care setting: report from the ENDORSE study in Egypt. Thromb J. 2012;10:20.