- Email: [email protected]
Deep vein thrombosis prophylaxis in a tertiary care center: An observational study
apollo medicine 13 (2016) 37–41
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/apme
Original Article
Deep vein thrombosis prophylaxis in a tertiary care center: An observational study Aparna Yerramilli a,*, Shilpa Katta b, Supriya Kidambi b, Naveen Kumar Kotari b, Santosh Devulapally b, Sanjeev Sharma c a
Associate Professor, Pharm. D Head of the Department, Sri Venkateshwara College of Pharmacy, Affiliated to Osmania University, Hyderabad 500081, Telangana, India b Pharm. D Interns, Sri Venkateshwara College of Pharmacy, Madhapur, Hyderabad, India c Clinical Pharmacologist, Apollo Hospitals, Jubilee Hills, Hyderabad, India
article info
abstract
Article history:
Background: Deep vein thrombosis (DVT) is a major health problem with substantial mor-
Received 15 February 2015
tality and morbidity in medically ill patients. Prevention of DVT by risk factor stratification
Accepted 24 August 2015
and subsequent antithrombotic prophylaxis in moderate- to severe-risk category patients is
Available online 20 October 2015
the most rational means of reducing morbidity and mortality. Objective: To study the management strategies for DVT prophylaxis in a tertiary care center
Keywords:
and evaluate the prophylactic dosing patterns for DVT prevention.
Deep vein thrombosis
Methods: A prospective, observational study was performed in the intensive care units and
Venous thromboembolism
medical wards of a tertiary care center. A structured proforma was designed for risk
DVT prophylaxis
assessment and stratification of DVT in critically ill patients with recommended thrombo-
Risk stratification
prophylaxis. The dosing patterns of all medications given for DVT prophylaxis were ana-
Enoxaparin
lyzed for their appropriateness according to 8th ACCP guidelines. Results: A total of 480 patient charts were reviewed. It was observed that 358 patients (74.6%) were on mixed prophylaxis, 38 patients (18.5%) were on pharmacological prophylaxis, and 33 patients (6.9%) were on mechanical prophylaxis only. Enoxaparin and graduated compression stockings were the most commonly used pharmacological and mechanical prophylaxes, respectively. The prophylaxis guidelines were followed in 77% of the study population. The reasons for inappropriate dosing patterns were found to be subtherapeutic dosing and overdosing. Conclusions: Our study revealed that a higher proportion of the patients who are at high risk are currently given thromboprophylaxis as per the standard prophylactic recommendations. There is still considerable scope for improvement in the management of DVT in all units of the institution. # 2015 Indraprastha Medical Corporation Ltd. Published by Elsevier B.V. All rights reserved.
* Corresponding author at: Sri Venkateshwara College of Pharmacy, 86, Hitech City Road, Madhapur, Hyderabad 500081, Andhra Pradesh, India. Tel.: +91 9704231971. E-mail address: [email protected] (A. Yerramilli). http://dx.doi.org/10.1016/j.apme.2015.08.002 0976-0016/# 2015 Indraprastha Medical Corporation Ltd. Published by Elsevier B.V. All rights reserved.
38
1.
apollo medicine 13 (2016) 37–41
Introduction
Venous thromboembolism (VTE), which includes deep venous thrombosis (DVT) and pulmonary embolism (PE), is a common and potentially life-threatening condition in critically ill patients. Anticoagulant drug therapy is aimed at preventing pathological clot formation in patients at risk and preventing clot extension and/or embolization in patients who have developed thrombosis.1,2 Majority of the studies have been conducted and published in western countries where DVT is more common, whereas, there is paucity of data from Indian subcontinent regarding the incidence of VTE. Some of the recent studies published from Asian countries have shown that DVT is not a rarity in Asian patients as was thought earlier.3 The prevailing belief that VTE in the ASIAN population is less than in the western population has been disproved by recent studies and there appears no reason to believe that it is any different in India.5 The incidence of DVT in India as reported is 1% of the adult population after the age of forty and 15–20% in hospitalized patients. The risk of DVT is 50% in patients undergoing orthopedic surgery, particularly involving the hip and knee, and it is 40% in patients undergoing abdominal or thoracic surgery. About 1 in 100 who developed DVT can develop PE, which can be fatal. As per India-specific ENDORSE study data presented at Geneva, 50% of hospitalized patients in India are at high risk of developing VTE at any point in time and the proportion of Indian patients considered at risk for VTE (53.6%) was similar to that of the global patients at risk for VTE (51.8%).3,4,6 In developing countries, such as India, a significant prevalence of etiological risk factors for DVT and prothrombotic factors has been shown amongst hospitalized patients.7 Studies have shown a need of DVT prophylaxis in 95% of intensive care unit (ICU) patients in India with significant underuse of prophylaxis in only 55% of the highrisk patients.8 Another study in the Indian population has shown an overall incidence of confirmed DVTs to be 17.46 per one lakh patients with 64% being nonsurgical nontrauma patients.9 Critically ill patients are at increased risk of VTE due to predisposing comorbid conditions, occurrence of sepsis, trauma, and postadmission events.10 Individual identification of suspected DVT cases could be a difficult task and many cases could be missed. However, blanket prophylaxis of all admitted patients may not be cost-effective, especially in a developing country, such as India.11 Thus primary prevention of VTE with risk assessment and stratification for DVT and subsequent antithrombotic prophylaxis in moderate- to severe-risk category patients is the most rational means of reducing mortality and morbidity. The need for DVT prophylaxis is usually underestimated. Only 10% of individuals who require DVT prophylaxis actually get it; the remaining 90% of individuals are deprived of DVT prophylaxis because of lack of awareness or skill.12 The 8th conference of American College of Chest Physicians (ACCP) developed guidelines for the use of low-molecular weight heparins (LMWHs) and unfractionated heparins (UFH) in the prevention of VTE in patients with acute illnesses.12
DVT can be prevented by regular physical activity, especially if an individual is immobilized for longer time. Mechanical DVT prophylaxis may be considered in all immobile patients and should be used for those who cannot receive anticoagulants, such as intermittent pneumatic compression (IPC) devices, graded compression stockings (GCS), and venous foot pumps. Pharmacological prophylaxis includes low-dose unfractionated heparin (LDUH), LMWH, vitamin K antagonists (most often warfarin), and fondaparinux. The guideline recommendations for thromboprophylaxis in patients at risk of VTE are given in Appendix.14 However, the use of DVT prophylaxis in hospitalized medical patients still remains suboptimal, around 15–16%.13 Hence, we sought to study the patient profiles for risk factors and evaluate the drug dosing patterns for DVT prophylaxis among medically ill and surgical patients treated at our institution. This study aims to evaluate the usage of prophylaxis in our institution.
2.
Methods
A single-center, prospective, and observational study was carried out for six months at Apollo Hospitals, Jubilee Hills, Hyderabad, which is a 630 bedded tertiary care hospital with 50 superspecialty services in India. Ethical clearance was obtained from the Institutional Ethics Committee (IEC) (Protocol No. SVCP/04/2013) before initiating the study. A structured proforma was designed for risk stratification of DVT in critically ill patients adapted from Caprini's risk stratification scorecard. The risk factors for DVT used in this protocol to stratify patients are similar to that published by ACCP and the International Union of Angiology (IUAS) consensus statement and have been used previously for DVT risk assessment alongside ACCP and IUAS risk score models in other studies done in developing countries. The risk assessment and stratification scorecard and data collection form used are given in Appendix. All the patient charts were reviewed in the medical and surgical units and the data of 480 patients who were on DVT prophylaxis were collected. Individual Risk factor screening was done to calculate risk factor score, thus categorizing patients into low, moderate, and high risk. Demographic data, including patient's age, sex, and body weight, were collected. Other baseline information like diagnosis, comorbidities, past medication history, past surgical history, family history, social history, allergies, any invasive instrumentation, such as ventilators, venous catheters, baseline laboratory data (hematological data, coagulation profile and renal parameters), etc. were also noted down. Renal data plays a crucial role because as per enoxaparin package insert dose adjustment is recommended in patients with severe renal impairment (creatinine clearance <30 mL/min). Patients were stratified to low-, moderate-, and high-risk categories. Any prophylaxis given and relevant investigations for DVT (D-dimer, Doppler ultrasound, high-resolution chest computed tomography, pulmonary angiography) that was done was also noted. Assessment of risk of bleeding and contraindications to thromboprophylaxis was performed. The current prescribed prophylaxis (mechanical and chemical)
apollo medicine 13 (2016) 37–41
[(Fig._1)TD$IG]
39
with dose, frequency, route of administration, date of drug initiation and stop date, and monitoring parameters were collected. Data were analyzed for the risk factor categorization and appropriateness of thromboprophylaxis compared to the 8th ACCP guidelines and reported. Descriptive statistical analysis was performed in calculation of categorical variables.
3.
Results
A total of 480 patient charts were reviewed and analyzed. It was observed that male patients were relatively higher than female patients. Of the total 480 patients, 58% were medical patients and 42% were surgical patients. Majority of the study population receiving thromboprophylaxis were in the age group of 61–80 years (40.1%) and least in the age group of 81– 100 years (4.6%), with a mean age of 56.7 years and mean BMI 25.3 kg/m2. The demographic characteristics are shown in Table 1. An average risk factor range of 3–4 per patient was observed with top three multiple risk factors being age (82.5%), obesity (48.1%), and surgery (42%) (Fig. 1). Orthopedic surgery (45%) was the most common type of surgery among the surgical patients. Risk factor screening was done and the patients were categorized into low (3%), moderate (24%), and high risk (73%) based on the risk factor scoring (Table 1). It was observed that 93.3% were on pharmacological prophylaxis and 6.7% were on only mechanical prophylaxis, of which 74.6% were on mixed prophylaxis, 18.5% were on only pharmacological prophylaxis, and 6.9% were on only mechanical prophylaxis. In our study, LMWH (92.7%), with enoxaparin 40 mg, was the preferred choice of anticoagulant in surgical as well as medical ward patients, followed by fondaparinux (1%). Among mechanical prophylaxis available, graduated compression
Fig. 1 – Patient risk factors for DVT. THR, total hip replacement; TKR, total knee replacement; COPD, chronic obstructive pulmonary disease; DVT, deep vein thrombosis; PE, pulmonary embolism.
stockings (68%) were commonly used followed by sequential compression devices (SCD) (13.3%) (Fig. 2). The most common contraindications to pharmacological prophylaxis were active bleeding (4.17%), clinically relevant renal impairment (1.04%), hepatic impairment (0.63%), and low platelets count (0.63%). ACCP recommended prophylaxis guidelines were followed in 77% of the study population, which was significantly higher compared to global ENDORSE data. The most common reasons attributed to the inappropriate thromboprophylaxis were subtherapeutic dosing (15.6%), overdosing (1.5%), and renal impairment (6%) (Table 2).
4.
This study explores the use of DVT prophylaxis in a tertiary care center. Out of 480 patient charts reviewed, majority of our study population were males, overweight, and above 50 years. Nearly two-thirds of the study population was in medical wards and the remaining in surgical units requiring acute care.
Table 1 – Demographic characteristics of the study population. Variables Gender Males Females Other characteristics Mean age (years) Mean BMI (kg/m2) Medical department Wards ICU Unit Medicine Surgery Comorbidities Cardiovascular Respiratory Others No comorbidities Level of risk Low (0–1) Moderate (2–4) High (≥5)
Total no of patients, n = 480 (%)
Discussion
[(Fig._2)TD$IG]
257 (54%) 223 (46%) 56.7 15.27 25.3 4.81 315 (66%) 165 (34%) 279 (58%) 201 (42%) 243 (51%) 35 (7%) 112 (23%) 90 (19%) 14 (3%) 117 (24%) 349 (73%)
Fig. 2 – Management strategies for DVT prophylaxis. GCS, graded compression stocking; SCD, sequential compression devices.
40
apollo medicine 13 (2016) 37–41
Table 2 – Reasons for inappropriate DVT prophylaxis. Reasons for inappropriate dosing Overdosing
Renal impairment Obesity Subtherapeutic dosing
Medical patients (n = 58)
Surgical patients (n = 53)
Total patients n = 480 (%)
20 6 32
9 1 43
29 (6%) 7 (1.5%) 75 (15.6%)
About half of the study population showed cardiovascular comorbidities followed by other comorbidities. Multiple system involvement was seen in many patients. Whereas in a study conducted by Pandey et al., at AIIMS, India, it was shown that respiratory system involvement was seen in 41.8% of the patients while cardiovascular system involvement was seen in only 17.1% of the patients.15 Nearly half of the study population was postsurgical, of which 75% are at highest risk for DVT. Orthopedic surgery runs a higher risk for DVT (45%). In addition to surgery, age, obesity, and immobility were among the most frequently documented risk factors. Patients at high risk (73% vs. 48.4%) were higher in our study when compared to TUNE-IN study conducted by Wessels and Riback.16 Overall prophylaxis in at-risk VTE patients was high (77%) in our study and as per ACCP recommendations, enoxaparin 40 mg once daily (54.3%) was the most common agent used. Whereas the Indian data from ENDORSE study revealed that despite a similar proportion of patients at risk in India and other participating countries, there was major underutilization of prophylaxis (17.4%) in India as compared to higher usage of prophylaxis globally (50.2%).4,17 Pharmacological prophylaxis in medical and surgical patients was evaluated for appropriateness. Pharmacological prophylaxis was commonly used type of prophylaxis (93.1%). Inappropriate thromboprophylaxis was observed in 111 patients (23%). The most common reasons attributed to the inappropriate thromboprophylaxis were overdosing due to overweight or obesity, renal impairment, and subtherapeutic dosing. The combination of enoxaparin 20 mg and mechanical prophylaxis is not appropriate according to the ACCP guidelines, hence considered as subtherapeutic dosing. This might be due to the misconception of some clinicians that the combination of enoxaparin 20 mg with mechanical prophylaxis would be sufficient to reduce the DVT incidence. The standard dose recommended is enoxaparin 40 mg OD and/or mechanical prophylaxis in moderate- to high-risk patients. Studies have not shown significant benefit of mechanical prophylaxis relative to anticoagulant therapy; however, according to CHEST guidelines, mechanical prophylaxis is an acceptable option in certain patient groups or in combination with anticoagulant therapy to improve efficacy.11,18 Documented contraindications (active bleeding, renal impairment, hepatic impairment, and low platelet counts) were noted in few patients, who were on only mechanical prophylaxis. Among mechanical prophylaxis available, graduated compression stockings were commonly used followed by SCD. A Point Prevalence study of DVT prophylaxis in the institution was conducted. Out of 226 patient charts reviewed, more than half of the study population (120 patients) had a very high risk for DVT. It was found that 25.6% were on DVT
prophylaxis, which was greater compared to that of Indian data from ENDORSE study (17.4%). The study showed that a significant percentage of admissions in medical wards and ICU were subject to very high risk of DVT. Early recognition of these risk factors and prompt prophylaxis in high-risk cases can be really effective in preventing these life-threatening complications. Though, ACCP has laid down clear guidelines on DVT prophylaxis in medically ill patients, several studies done in the Western countries have also shown the underuse of DVT prophylaxis in hospitalized medical patients.19,20 Overdosing may be due to lack of proper risk factor screening techniques, practical feasibility, lack of experience and awareness in healthcare personnel, and poor implementation of recommended guidelines. Reasons for underutilization or subtherapeutic dosing of prophylactic agents include: Concerns about an increased risk of bleeding from anticoagulants. Lack of clear indications and contraindications for anticoagulant prophylaxis. Lack of time to consider DVT prophylaxis in every patient. Physicians' belief that mixed prophylaxis would be sufficient to reduce DVT incidence. Lack of awareness and concerns for cost of DVT prophylaxis in all critically ill patients could also be an important factor, particularly in developing countries, such as India.
5.
Limitations
All the patients who are at risk of DVT were not considered. Only those patients on any thromboprophylaxis were studied. This was a single-center study and the results cannot be generalized to other medical centers. There was no follow-up to evaluate the duration of prophylaxis. Another limitation of the study was that pediatric patients, who were excluded, also might have been at risk for VTE.
6.
Conclusion
The findings of our study showed that a relatively larger proportion of the patients were currently on prophylaxis as per standard prophylactic recommendations. The overall rate of inappropriate thromboprophylaxis was 23%, the most common reasons being: overdosing and subtherapeutic dosing. A high rate of appropriateness and increased use of LMWH was seen in our study population due to frequent awareness campaigns in hospital. Risk assessment forms are being used
apollo medicine 13 (2016) 37–41
in some units but need to be followed in more units and patients. This study data may be useful to implement DVT risk stratification strategy in hospitalized patients and improve the prescribing patterns of prophylaxis where indicated. Successful programs like incorporation of risk assessment and stratification tools in routine patient work-up and interventions to increase awareness of DVT prophylaxis in health care professionals need to be implemented in our heath care system to improve VTE prophylaxis and decrease rates of VTE and its complications.
Conflicts of interest The authors have none to declare.
Acknowledgements We are immensely thankful to Dr Rajib Paul, Internal Medicine for his guidance and support during the Point Prevalence study; Apollo Hospitals, Osmania University, Principal Prof. Prathima Srinivas; and Management of Sri Venkateshwara College of Pharmacy, for the encouragement and support provided.
Appendix. Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.apme.2015.08.002.
references
1. Koda Kimble MA, Young LY, Alldredge BK, et al. Applied therapeutics: the clinical use of drugs. 9th ed. United States of America: Lippincott Williams & Wilkins; 2009. 2. Sukhendu SB, Swapan B, Mohit K, Tapan KC, Subhangkar N. Utilization of DVT prophylaxis in non ICU hospitalized patients. Asian Pac J Trop Dis. 2012;2:S707–S711. 3. Angral R, Islam MS, Kundan S. Incidence of deep vein thrombosis and justification of chemoprophylaxis in Indian patients: a prospective study. Bangladesh Med Res Counc Bull. 2012;38(2):67–71.
41
4. Ramakrishna P. Venous thromboembolism risk & prophylaxis in the acute hospital care setting (ENDORSE), a multinational cross-sectional study: results from the Indian subset data. Indian J Med Res. 2012;136:60–67. 5. Gandharba R, Manoranjan B. Venous thromboembolism – Indian perspective. Med Update. 2010;20:329–334. 6. Kanaan AO, Silva MA, Donovan JL, Roy T, Al-homsi AS. Meta analysis of venous thromboembolism prophylaxis in medically ill patients. Clin Ther. 2007;29(11):2395–2405. 7. Garewal G, Das R, Ahluwalia S, Mittal N, Varma S. Prevalence of risk factors for VTE: a study from north India. J Thromb Haemost. 2005;3(1):1270. 8. Ansari K, Dalal K, Patel M. Risk stratification and utilisation of thrombo-embolism prophylaxis in a medical – surgical ICU: a hospital based study. J Indian Med Assoc. 2007;105:536–540. 9. Lee AD, Stephen E, Agarwal S, Premkumar P. Venous thromboembolism in India. Eur J Vasc Endovasc Surg. 2009;37 (4):482–485. 10. Attia J, Ray JG, Cook DJ, Douketis J, Ginsberg JS, Geerts W. Prophylaxis of venous thromboembolism in the critically ill. Arch Intern Med. 2001;161:1268–1279. 11. Nuijten MJ, Berto P, Kosa J. Cost-effectiveness of enoxaparin as thromboprophylaxis in acutely ill medical patients from the Italian NHS perspective. Recenti Prog Med. 2002;93:80–91. 12. Geerts WH, Pineo GF, Heit JA, et al. Prevention of venous thromboembolism: the seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest. 2004;126 (3):338S–400S. 13. Kahn SR, Panju A, Geerts W, et al. Multicenter evaluation of the use of venous thromboembolism prophylaxis in acutely ill medical patients in Canada. Thromb Res. 2007;119:145–155. 14. Caprini JA. Thrombosis risk assessment as a guide to quality patient care. Dis Mon. 2005;7:3–74. 15. Ambarish P, Nivedita P, Mansher S, Randeep G. Assessment of risk and prophylaxis for deep vein thrombosis and pulmonary embolism in medically ill patients during their early days of hospital stay at a tertiary care center in a developing country. Vasc Health Risk Manag. 2009;5:643–648. 16. Wessels P, Riback WJ. DVT prophylaxis in relation to patient risk profiling – the tune-in study. S Afr Med J. 2012;102(2):85–89. 17. Cohen AT, Tapson VF, Bergmann JF, et al. Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): a multinational cross-sectional study. Lancet. 2008;371:387–394. 18. Kalodki EP, Hoppensteadt DA, Nicolaides AN. Deep venous thrombosis prophylaxis with low molecular weight heparin and elastic compression in patients having total hip replacement. A randomised controlled trial. Int Angiol. 1996;15:162–168. 19. Geerts W, Selby R. Prevention of venous thromboembolism in the ICU. Chest. 2003;124(6S):357S–363S. 20. Kakkar AK, Davidson BL, Haas SK. Compliance with recommended prophylaxis for venous thromboembolism: improving the use and rate of uptake of clinical practice guidelines. J Thromb Haemost. 2004;2:221–227.
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/apme
Original Article
Deep vein thrombosis prophylaxis in a tertiary care center: An observational study Aparna Yerramilli a,*, Shilpa Katta b, Supriya Kidambi b, Naveen Kumar Kotari b, Santosh Devulapally b, Sanjeev Sharma c a
Associate Professor, Pharm. D Head of the Department, Sri Venkateshwara College of Pharmacy, Affiliated to Osmania University, Hyderabad 500081, Telangana, India b Pharm. D Interns, Sri Venkateshwara College of Pharmacy, Madhapur, Hyderabad, India c Clinical Pharmacologist, Apollo Hospitals, Jubilee Hills, Hyderabad, India
article info
abstract
Article history:
Background: Deep vein thrombosis (DVT) is a major health problem with substantial mor-
Received 15 February 2015
tality and morbidity in medically ill patients. Prevention of DVT by risk factor stratification
Accepted 24 August 2015
and subsequent antithrombotic prophylaxis in moderate- to severe-risk category patients is
Available online 20 October 2015
the most rational means of reducing morbidity and mortality. Objective: To study the management strategies for DVT prophylaxis in a tertiary care center
Keywords:
and evaluate the prophylactic dosing patterns for DVT prevention.
Deep vein thrombosis
Methods: A prospective, observational study was performed in the intensive care units and
Venous thromboembolism
medical wards of a tertiary care center. A structured proforma was designed for risk
DVT prophylaxis
assessment and stratification of DVT in critically ill patients with recommended thrombo-
Risk stratification
prophylaxis. The dosing patterns of all medications given for DVT prophylaxis were ana-
Enoxaparin
lyzed for their appropriateness according to 8th ACCP guidelines. Results: A total of 480 patient charts were reviewed. It was observed that 358 patients (74.6%) were on mixed prophylaxis, 38 patients (18.5%) were on pharmacological prophylaxis, and 33 patients (6.9%) were on mechanical prophylaxis only. Enoxaparin and graduated compression stockings were the most commonly used pharmacological and mechanical prophylaxes, respectively. The prophylaxis guidelines were followed in 77% of the study population. The reasons for inappropriate dosing patterns were found to be subtherapeutic dosing and overdosing. Conclusions: Our study revealed that a higher proportion of the patients who are at high risk are currently given thromboprophylaxis as per the standard prophylactic recommendations. There is still considerable scope for improvement in the management of DVT in all units of the institution. # 2015 Indraprastha Medical Corporation Ltd. Published by Elsevier B.V. All rights reserved.
* Corresponding author at: Sri Venkateshwara College of Pharmacy, 86, Hitech City Road, Madhapur, Hyderabad 500081, Andhra Pradesh, India. Tel.: +91 9704231971. E-mail address: [email protected] (A. Yerramilli). http://dx.doi.org/10.1016/j.apme.2015.08.002 0976-0016/# 2015 Indraprastha Medical Corporation Ltd. Published by Elsevier B.V. All rights reserved.
38
1.
apollo medicine 13 (2016) 37–41
Introduction
Venous thromboembolism (VTE), which includes deep venous thrombosis (DVT) and pulmonary embolism (PE), is a common and potentially life-threatening condition in critically ill patients. Anticoagulant drug therapy is aimed at preventing pathological clot formation in patients at risk and preventing clot extension and/or embolization in patients who have developed thrombosis.1,2 Majority of the studies have been conducted and published in western countries where DVT is more common, whereas, there is paucity of data from Indian subcontinent regarding the incidence of VTE. Some of the recent studies published from Asian countries have shown that DVT is not a rarity in Asian patients as was thought earlier.3 The prevailing belief that VTE in the ASIAN population is less than in the western population has been disproved by recent studies and there appears no reason to believe that it is any different in India.5 The incidence of DVT in India as reported is 1% of the adult population after the age of forty and 15–20% in hospitalized patients. The risk of DVT is 50% in patients undergoing orthopedic surgery, particularly involving the hip and knee, and it is 40% in patients undergoing abdominal or thoracic surgery. About 1 in 100 who developed DVT can develop PE, which can be fatal. As per India-specific ENDORSE study data presented at Geneva, 50% of hospitalized patients in India are at high risk of developing VTE at any point in time and the proportion of Indian patients considered at risk for VTE (53.6%) was similar to that of the global patients at risk for VTE (51.8%).3,4,6 In developing countries, such as India, a significant prevalence of etiological risk factors for DVT and prothrombotic factors has been shown amongst hospitalized patients.7 Studies have shown a need of DVT prophylaxis in 95% of intensive care unit (ICU) patients in India with significant underuse of prophylaxis in only 55% of the highrisk patients.8 Another study in the Indian population has shown an overall incidence of confirmed DVTs to be 17.46 per one lakh patients with 64% being nonsurgical nontrauma patients.9 Critically ill patients are at increased risk of VTE due to predisposing comorbid conditions, occurrence of sepsis, trauma, and postadmission events.10 Individual identification of suspected DVT cases could be a difficult task and many cases could be missed. However, blanket prophylaxis of all admitted patients may not be cost-effective, especially in a developing country, such as India.11 Thus primary prevention of VTE with risk assessment and stratification for DVT and subsequent antithrombotic prophylaxis in moderate- to severe-risk category patients is the most rational means of reducing mortality and morbidity. The need for DVT prophylaxis is usually underestimated. Only 10% of individuals who require DVT prophylaxis actually get it; the remaining 90% of individuals are deprived of DVT prophylaxis because of lack of awareness or skill.12 The 8th conference of American College of Chest Physicians (ACCP) developed guidelines for the use of low-molecular weight heparins (LMWHs) and unfractionated heparins (UFH) in the prevention of VTE in patients with acute illnesses.12
DVT can be prevented by regular physical activity, especially if an individual is immobilized for longer time. Mechanical DVT prophylaxis may be considered in all immobile patients and should be used for those who cannot receive anticoagulants, such as intermittent pneumatic compression (IPC) devices, graded compression stockings (GCS), and venous foot pumps. Pharmacological prophylaxis includes low-dose unfractionated heparin (LDUH), LMWH, vitamin K antagonists (most often warfarin), and fondaparinux. The guideline recommendations for thromboprophylaxis in patients at risk of VTE are given in Appendix.14 However, the use of DVT prophylaxis in hospitalized medical patients still remains suboptimal, around 15–16%.13 Hence, we sought to study the patient profiles for risk factors and evaluate the drug dosing patterns for DVT prophylaxis among medically ill and surgical patients treated at our institution. This study aims to evaluate the usage of prophylaxis in our institution.
2.
Methods
A single-center, prospective, and observational study was carried out for six months at Apollo Hospitals, Jubilee Hills, Hyderabad, which is a 630 bedded tertiary care hospital with 50 superspecialty services in India. Ethical clearance was obtained from the Institutional Ethics Committee (IEC) (Protocol No. SVCP/04/2013) before initiating the study. A structured proforma was designed for risk stratification of DVT in critically ill patients adapted from Caprini's risk stratification scorecard. The risk factors for DVT used in this protocol to stratify patients are similar to that published by ACCP and the International Union of Angiology (IUAS) consensus statement and have been used previously for DVT risk assessment alongside ACCP and IUAS risk score models in other studies done in developing countries. The risk assessment and stratification scorecard and data collection form used are given in Appendix. All the patient charts were reviewed in the medical and surgical units and the data of 480 patients who were on DVT prophylaxis were collected. Individual Risk factor screening was done to calculate risk factor score, thus categorizing patients into low, moderate, and high risk. Demographic data, including patient's age, sex, and body weight, were collected. Other baseline information like diagnosis, comorbidities, past medication history, past surgical history, family history, social history, allergies, any invasive instrumentation, such as ventilators, venous catheters, baseline laboratory data (hematological data, coagulation profile and renal parameters), etc. were also noted down. Renal data plays a crucial role because as per enoxaparin package insert dose adjustment is recommended in patients with severe renal impairment (creatinine clearance <30 mL/min). Patients were stratified to low-, moderate-, and high-risk categories. Any prophylaxis given and relevant investigations for DVT (D-dimer, Doppler ultrasound, high-resolution chest computed tomography, pulmonary angiography) that was done was also noted. Assessment of risk of bleeding and contraindications to thromboprophylaxis was performed. The current prescribed prophylaxis (mechanical and chemical)
apollo medicine 13 (2016) 37–41
[(Fig._1)TD$IG]
39
with dose, frequency, route of administration, date of drug initiation and stop date, and monitoring parameters were collected. Data were analyzed for the risk factor categorization and appropriateness of thromboprophylaxis compared to the 8th ACCP guidelines and reported. Descriptive statistical analysis was performed in calculation of categorical variables.
3.
Results
A total of 480 patient charts were reviewed and analyzed. It was observed that male patients were relatively higher than female patients. Of the total 480 patients, 58% were medical patients and 42% were surgical patients. Majority of the study population receiving thromboprophylaxis were in the age group of 61–80 years (40.1%) and least in the age group of 81– 100 years (4.6%), with a mean age of 56.7 years and mean BMI 25.3 kg/m2. The demographic characteristics are shown in Table 1. An average risk factor range of 3–4 per patient was observed with top three multiple risk factors being age (82.5%), obesity (48.1%), and surgery (42%) (Fig. 1). Orthopedic surgery (45%) was the most common type of surgery among the surgical patients. Risk factor screening was done and the patients were categorized into low (3%), moderate (24%), and high risk (73%) based on the risk factor scoring (Table 1). It was observed that 93.3% were on pharmacological prophylaxis and 6.7% were on only mechanical prophylaxis, of which 74.6% were on mixed prophylaxis, 18.5% were on only pharmacological prophylaxis, and 6.9% were on only mechanical prophylaxis. In our study, LMWH (92.7%), with enoxaparin 40 mg, was the preferred choice of anticoagulant in surgical as well as medical ward patients, followed by fondaparinux (1%). Among mechanical prophylaxis available, graduated compression
Fig. 1 – Patient risk factors for DVT. THR, total hip replacement; TKR, total knee replacement; COPD, chronic obstructive pulmonary disease; DVT, deep vein thrombosis; PE, pulmonary embolism.
stockings (68%) were commonly used followed by sequential compression devices (SCD) (13.3%) (Fig. 2). The most common contraindications to pharmacological prophylaxis were active bleeding (4.17%), clinically relevant renal impairment (1.04%), hepatic impairment (0.63%), and low platelets count (0.63%). ACCP recommended prophylaxis guidelines were followed in 77% of the study population, which was significantly higher compared to global ENDORSE data. The most common reasons attributed to the inappropriate thromboprophylaxis were subtherapeutic dosing (15.6%), overdosing (1.5%), and renal impairment (6%) (Table 2).
4.
This study explores the use of DVT prophylaxis in a tertiary care center. Out of 480 patient charts reviewed, majority of our study population were males, overweight, and above 50 years. Nearly two-thirds of the study population was in medical wards and the remaining in surgical units requiring acute care.
Table 1 – Demographic characteristics of the study population. Variables Gender Males Females Other characteristics Mean age (years) Mean BMI (kg/m2) Medical department Wards ICU Unit Medicine Surgery Comorbidities Cardiovascular Respiratory Others No comorbidities Level of risk Low (0–1) Moderate (2–4) High (≥5)
Total no of patients, n = 480 (%)
Discussion
[(Fig._2)TD$IG]
257 (54%) 223 (46%) 56.7 15.27 25.3 4.81 315 (66%) 165 (34%) 279 (58%) 201 (42%) 243 (51%) 35 (7%) 112 (23%) 90 (19%) 14 (3%) 117 (24%) 349 (73%)
Fig. 2 – Management strategies for DVT prophylaxis. GCS, graded compression stocking; SCD, sequential compression devices.
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apollo medicine 13 (2016) 37–41
Table 2 – Reasons for inappropriate DVT prophylaxis. Reasons for inappropriate dosing Overdosing
Renal impairment Obesity Subtherapeutic dosing
Medical patients (n = 58)
Surgical patients (n = 53)
Total patients n = 480 (%)
20 6 32
9 1 43
29 (6%) 7 (1.5%) 75 (15.6%)
About half of the study population showed cardiovascular comorbidities followed by other comorbidities. Multiple system involvement was seen in many patients. Whereas in a study conducted by Pandey et al., at AIIMS, India, it was shown that respiratory system involvement was seen in 41.8% of the patients while cardiovascular system involvement was seen in only 17.1% of the patients.15 Nearly half of the study population was postsurgical, of which 75% are at highest risk for DVT. Orthopedic surgery runs a higher risk for DVT (45%). In addition to surgery, age, obesity, and immobility were among the most frequently documented risk factors. Patients at high risk (73% vs. 48.4%) were higher in our study when compared to TUNE-IN study conducted by Wessels and Riback.16 Overall prophylaxis in at-risk VTE patients was high (77%) in our study and as per ACCP recommendations, enoxaparin 40 mg once daily (54.3%) was the most common agent used. Whereas the Indian data from ENDORSE study revealed that despite a similar proportion of patients at risk in India and other participating countries, there was major underutilization of prophylaxis (17.4%) in India as compared to higher usage of prophylaxis globally (50.2%).4,17 Pharmacological prophylaxis in medical and surgical patients was evaluated for appropriateness. Pharmacological prophylaxis was commonly used type of prophylaxis (93.1%). Inappropriate thromboprophylaxis was observed in 111 patients (23%). The most common reasons attributed to the inappropriate thromboprophylaxis were overdosing due to overweight or obesity, renal impairment, and subtherapeutic dosing. The combination of enoxaparin 20 mg and mechanical prophylaxis is not appropriate according to the ACCP guidelines, hence considered as subtherapeutic dosing. This might be due to the misconception of some clinicians that the combination of enoxaparin 20 mg with mechanical prophylaxis would be sufficient to reduce the DVT incidence. The standard dose recommended is enoxaparin 40 mg OD and/or mechanical prophylaxis in moderate- to high-risk patients. Studies have not shown significant benefit of mechanical prophylaxis relative to anticoagulant therapy; however, according to CHEST guidelines, mechanical prophylaxis is an acceptable option in certain patient groups or in combination with anticoagulant therapy to improve efficacy.11,18 Documented contraindications (active bleeding, renal impairment, hepatic impairment, and low platelet counts) were noted in few patients, who were on only mechanical prophylaxis. Among mechanical prophylaxis available, graduated compression stockings were commonly used followed by SCD. A Point Prevalence study of DVT prophylaxis in the institution was conducted. Out of 226 patient charts reviewed, more than half of the study population (120 patients) had a very high risk for DVT. It was found that 25.6% were on DVT
prophylaxis, which was greater compared to that of Indian data from ENDORSE study (17.4%). The study showed that a significant percentage of admissions in medical wards and ICU were subject to very high risk of DVT. Early recognition of these risk factors and prompt prophylaxis in high-risk cases can be really effective in preventing these life-threatening complications. Though, ACCP has laid down clear guidelines on DVT prophylaxis in medically ill patients, several studies done in the Western countries have also shown the underuse of DVT prophylaxis in hospitalized medical patients.19,20 Overdosing may be due to lack of proper risk factor screening techniques, practical feasibility, lack of experience and awareness in healthcare personnel, and poor implementation of recommended guidelines. Reasons for underutilization or subtherapeutic dosing of prophylactic agents include: Concerns about an increased risk of bleeding from anticoagulants. Lack of clear indications and contraindications for anticoagulant prophylaxis. Lack of time to consider DVT prophylaxis in every patient. Physicians' belief that mixed prophylaxis would be sufficient to reduce DVT incidence. Lack of awareness and concerns for cost of DVT prophylaxis in all critically ill patients could also be an important factor, particularly in developing countries, such as India.
5.
Limitations
All the patients who are at risk of DVT were not considered. Only those patients on any thromboprophylaxis were studied. This was a single-center study and the results cannot be generalized to other medical centers. There was no follow-up to evaluate the duration of prophylaxis. Another limitation of the study was that pediatric patients, who were excluded, also might have been at risk for VTE.
6.
Conclusion
The findings of our study showed that a relatively larger proportion of the patients were currently on prophylaxis as per standard prophylactic recommendations. The overall rate of inappropriate thromboprophylaxis was 23%, the most common reasons being: overdosing and subtherapeutic dosing. A high rate of appropriateness and increased use of LMWH was seen in our study population due to frequent awareness campaigns in hospital. Risk assessment forms are being used
apollo medicine 13 (2016) 37–41
in some units but need to be followed in more units and patients. This study data may be useful to implement DVT risk stratification strategy in hospitalized patients and improve the prescribing patterns of prophylaxis where indicated. Successful programs like incorporation of risk assessment and stratification tools in routine patient work-up and interventions to increase awareness of DVT prophylaxis in health care professionals need to be implemented in our heath care system to improve VTE prophylaxis and decrease rates of VTE and its complications.
Conflicts of interest The authors have none to declare.
Acknowledgements We are immensely thankful to Dr Rajib Paul, Internal Medicine for his guidance and support during the Point Prevalence study; Apollo Hospitals, Osmania University, Principal Prof. Prathima Srinivas; and Management of Sri Venkateshwara College of Pharmacy, for the encouragement and support provided.
Appendix. Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.apme.2015.08.002.
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