|Year : 2018 | Volume
| Issue : 2 | Page : 142-147
Utilization of antithrombotic medicines in primary prevention and risk assessment of deep vein thrombosis at a tertiary care teaching hospital
Chandresh B Dumatar, Sandip S Jadav, Aashutosh J Patel
Department of Pharmacology, B. J. Medical College, Ahmedabad, Gujarat, India
|Date of Web Publication||14-Sep-2018|
Dr. Sandip S Jadav
Department of Pharmacology, B. J. Medical College, Ahmedabad, Gujarat
Source of Support: None, Conflict of Interest: None
Background: Deep vein thrombosis (DVT) and pulmonary embolism (PE) are common preventable conditions often associated with high morbidity if not treated promptly. Evaluation of antithrombotic drugs is essential in considering the spectrum of use and the risks associated with their therapy in patients with DVT. Therefore, this study was undertaken to evaluate the usage pattern of antithrombotics and assessment of DVT risk in primary prevention of DVT at a tertiary care teaching hospital. Materials and Methods: It was an observational, prospective and single-center study carried out over a period of 18 months. Out of 26,687 hospitalized patients assessed for eligibility as per Wells' score. Only 186 patients met inclusion criteria, but 164 patients were analyzed for primary prevention and risk assessment of DVT. Results: Out of 164 patients of primary prevention of DVT, 54 (32.92%) patients were given thromboprophylaxis for DVT. Out of 54 patients, 23 patients were given warfarin either alone or in combination with other drugs, whereas aspirin was given as a single drug in two patients only. No modification in the treatment of either anticoagulant or antiplatelet drugs was observed in patients for primary prevention of DVT (n = 54). As per Wells' score, 87 patients were considered to be “high” risk of DVT, but only six patients developed DVT versus, whereas 31 patients were considered to be of “moderate” risk, only two patients developed DVT. Conclusion: Few patients of primary prevention of DVT received adequate antithrombotic thromboprophylaxis. Heparin and warfarin were mainly used for thromboprophylaxis of DVT. DVT prophylaxis is very important and thromboprophylaxis is the mainstay of treatment among patients of primary prevention of DVT.
Keywords: Antithrombotic, deep vein thrombosis, Wells' score
|How to cite this article:|
Dumatar CB, Jadav SS, Patel AJ. Utilization of antithrombotic medicines in primary prevention and risk assessment of deep vein thrombosis at a tertiary care teaching hospital. Niger J Basic Clin Sci 2018;15:142-7
|How to cite this URL:|
Dumatar CB, Jadav SS, Patel AJ. Utilization of antithrombotic medicines in primary prevention and risk assessment of deep vein thrombosis at a tertiary care teaching hospital. Niger J Basic Clin Sci [serial online] 2018 [cited 2019 Jun 17];15:142-7. Available from: http://www.njbcs.net/text.asp?2018/15/2/142/241161
| Introduction|| |
Deep vein thrombosis (DVT) and pulmonary embolism (PE) or better defined as venous thromboembolic (VTE) disorders are the most common preventable causes of undiagnosed and frequently unrecognized acute medical conditions that could result in sentinel event or morbidity if not treated promptly. It is reported that one out of every four cases newly diagnosed VTE is associated with hospitalization and has been reported as a significant cause of illness and death worldwide irrespective of etiology. According to the American College of Chest Physicians criteria, hospitalized medical patients have moderate or high risk of VTE. Another study has reported that approximately 20% of hospitalized medical patients are at a risk of developing VTE secondary to hospitalization. Several factors have been deemed responsible for inadequate thromboprophylaxis particularly in medical wards. This is often due to complex and multiple comorbidities  which create a perception of significantly higher bleeding risks and result in grossly inadequate measures and hesitation to prescribe VTE prophylaxis. Autopsy data suggest that VTE contributes to more than 10% of unexplained and sudden deaths among hospitalized medical patients. PE is thought to be associated with 5%–10% of deaths in hospitalized patients, but this diagnosis is not suspected clinically in a majority of cases. Multiple clinical guidelines, protocols, and risk assessment models are available to support decision-making, and evidence suggests that their adoption significantly increases the use of VTE prophylaxis and decreases VTE events, due to double-edged sword nature of using anticoagulation or not to give treatment to high-risk patients. In this study, we evaluated utilization and DVT risk assessment for primary prevention of DVT at a tertiary care teaching hospital.
| Materials and Methods|| |
The study was observational, prospective, and single center conducted to assess usage pattern of antithrombotic medicines and risk assessment for primary prevention of DVT among the hospitalized patients in Departments of Surgery, Orthopaedics, and Neurosurgery at Civil Hospital, a tertiary care government teaching hospital over a period of 18 months from November 2013 to April 2015. Patient above 25 years of age of either gender who were bedridden for more than 3 days in the ward with presence of at least one major risk factor based on Wells' score were included in the study. Patients less than 25 years of age, operated for emergency/minor surgical procedures, ambulatory hospitalized patients for more than 3 days in wards, and not willing to participate in study were excluded. Study protocol was approved by Institutional Ethics Committee. During the study period, the investigator visited the wards of Surgery, Orthopaedics, and Neurosurgery. For every patient, general characteristics [demographic details, relevant history, Doppler ultrasound, international normalized ratio (INR) at baseline and during follow-up, risk factors for development of DVT] and usage pattern of antithrombotic drugs were recorded in a predesigned case record form. Patients were assessed for risk of DVT and stratified based on Wells' score into low, moderate, or high risk of DVT. During the study, patients were monitored for modification in antithrombotic therapy.
The data collected were compiled, entered, and analyzed in Microsoft Excel spreadsheet 2007 and GraphPad version 4. The results are expressed in terms of numbers and percentage. The association between two variables' correlation of presence of risk factor and thromboprophylaxis with occurrence of DVT was analyzed using contingency table. Absolute risk rate, relative risk rate, and risk ratio (RR) were estimated with 95% confidence interval. All reported P values were two-sided, and P values ≤0.05 were considered statistically significant. Number needed to treat (NNT) was used to know an expression of the number of patients who must be treated to prevent one adverse event (DVT).
| Results|| |
During the study period, 26,687 patients were assessed but only 186 patients met inclusion criteria as per Wells' score. Data of 164 patients were analyzed [8 patients were lost to follow-up and 14 patients were transferred to other hospital wards (data could not be collected)] [Figure 1]. General characteristics and reasons for hospitalization of patients are given in [Table 1]. The majority of patients (n = 58) were admitted for orthopaedic procedure (hip fracture and hip replacement). Risk factors for development of DVT in patients of primary prevention of DVT are given in [Table 2]. In 164 patients of primary prevention of DVT, INR was measured in only 69 patients, and it was within the normal range (1.5–2.0) in 60 (86.96%) patients, but in 9 (13.04%) patients it was above normal range (average 2.2). The use of anticoagulant and antiplatelet drugs is mentioned in [Table 4]. Out of 136 drugs prescribed in 86 patients, 65 drugs were prescribed by brand name and 71 drugs were prescribed by generic name. All antithrombotic drugs (warfarin, heparin, enoxaparin, and aspirin) were included in Essential Drug List of India (2011), Essential Drug List of Gujarat (2015), and Essential Drug List of WHO (2013).
|Table 4: Usage pattern of anticoagulant and antiplatelet drugs in patients of primary prevention of DVT (n=164)|
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Establishment of DVT risk and antithrombotic treatment in different DVT risk categories in patients of primary prevention of DVT based on Wells' score is given in [Figure 2]. Of 164 patients of primary prevention of DVT, 19 (11.58%) patients in high-risk category had contraindication [history of previous bleeding (n = 7)] to anticoagulation therapy. Among this high-risk group, six patients developed DVT, whereas two patients in moderate-risk group developed DVT. Major contraindication was history of previous bleeding (n = 7).
|Figure 2: Stratification for risk of DVT and antithrombotic treatment in patients of primary prevention of DVT based on Wells” score (n = 164)|
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Monitoring and outcome
The mean INR value changes from baseline to end of study in patients of primary prevention of DVT are shown in [Figure 3]. Among patients receiving antithrombotic treatment for primary prevention of DVT (n = 54), no modification (increase or decrease in dose) in the treatment of either anticoagulant or antiplatelet drugs was observed in any patient during the study period. None of the patients developed stroke, systemic embolism, PE, or death during follow-up. No major bleeding event was observed.
|Figure 3: Mean INR value changes in primary prevention of DVT patients not given antithrombotics (n = 110) and given antithrombotics (n = 54). Data expressed as mean value; FU, follow-up|
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Occurrence of DVT in relation to the presence of risk factors in primary prevention of DVT is given in [Table 3]. If major risk factors were present, then risk of DVT was 7%; if major risk factors were absent, then risk of DVT was 2%. If major risk factors were absent, absolute risk reduction (ARR) was 4%, whereas relative risk reduction (RRR) was 34%. RR was 2.6, [95% confidence interval (CI) 0.55–12.77, P = 0.28]. Prevalence of DVT in hospitalized patients was 149 per 100,000 admissions. Patients receiving/not receiving antithrombotic drugs and occurrence of DVT in high-risk patients of primary prevention of DVT are shown in [Table 5]. Risk of DVT was 12% versus 2% for those DVT patients receiving antithrombotic prophylaxis and not receiving, respectively. If patient was given antithrombotics, ARR was 8%, whereas RRR was 80%. RR was 2.2. (95% CI, 0.03–1.84, P = 0.2). NNT was 13 which shows that 13 patients needed to be treated with antithrombotics to prevent one case of DVT.
|Table 3: Correlation of presence of risk factor and occurrence of DVT in patients of primary prevention of DVT (n=164)|
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|Table 5: Association of use of antithrombotic and occurrence of DVT in high-risk patients of primary prevention of DVT (n=87)|
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| Discussion|| |
The incidence of VTE is presumed to be low in India and in other Asian countries when compared with Western countries due to less awareness. It may also be that Asians are less prone to thrombosis as traditionally believed. DVT is the most common condition of lower limbs, responsible for high incidence of mortality and morbidity from PE and systemic thrombosis. This study included patients of varying ages (25–70 years) with mean age of 46.2 ± 12.6 years and the maximum number of patients belonged to age group 40–70 years. According to one more study, the mean age of DVT patients was 70 years with the range from 58 to 79 years. All these studies showed that occurrence of DVT was more in patients aged 50 years or more. The reason may be that we enrolled patients from 25 to 70 years of age, whereas in other studies it was above 40 years. Patients from the surgery department were more in this study. The reason could be longer duration of hospitalization and immobilization in surgery department compared with other departments. The presence of risk factor during hospitalization was a major concern in development of DVT. In this study, we found that presence of risk factors such as central venous catheter (13%) and cancer therapy (1.2%) was similar to an international study (11% and 2%, respectively). In this study, complete immobilization was present in 11%, whereas in another study it was 33%.
In this study, patients of primary prevention of DVT were given both anticoagulants and antiplatelets. Here, use of low-molecular-weight heparin (enoxaparin) was low and use of warfarin or unfractionated heparin (UFH) was high. This may be because UFH or warfarin was easily available and cheaper when compared with lower molecular weight heparin (LMWH). Antiplatelets were prescribed in 11.1% (n = 6) patients in primary prevention of DVT in our study. In a study conducted in London, only 1.5% patients were prescribed antiplatelet which is in contrast to our study. The reason could be that aspirin was cheaper and easily available in India. However, anticoagulants are most commonly used drugs in patients of DVT for prophylaxis when compared with antiplatelet. Also, warfarin was the only oral anticoagulant used in our study.
In this study, 54 (32.9%) patients were prescribed antiplatelet and anticoagulant drugs and 110 (67.1%) patients were not prescribed antithrombotic drugs. However, another study showed that 50% patients received anticoagulants and 1.4% patients received antiplatelet agent, while 48.6% patients received no anti-thrombotic therapy. This was in contrast to another study conducted in India  where 98% patients were prescribed anticoagulants. However, one study showed that the extent of use of anticoagulant was 91%. Many eligible patients were not receiving adequate warfarin therapy. The reasons could be delayed therapeutic response (4–5 days), dose of warfarin varying from patient to patient (need for trial and error), need for frequent INR monitoring (every 2–4 weeks), and narrow therapeutic range of INR (1.5–2.0).
In this study, as per Wells's criteria in patients of primary prevention of DVT, 87 patients are at “high” risk, whereas 31 patients were at “moderate,” and 46 patients were at “low” risk. Of 87 patients at “high” risk, 6 (6.9%) patients developed DVT, whereas of 31 patients at “moderate” risk, 2 (2.6%) patients developed DVT. This shows some correlation between development of DVT and presence of risk factor. The reason could be shift from low or moderate risk to high risk during the period of hospitalization. In another study, the American College of Chest Physician (ACCP) 2004 guidelines were used to define the “at-risk” population and effective types of prophylaxis. Other standards could have been applied such as International Consensus Statement.
In this study, 40.3% of patients at “high” risk were given antithrombotic therapy. In another study, 50.2% patients at “high” risk received antithrombotic therapy. This shows underuse of antithrombotic therapy even in patients at “high” risk because patients receiving antithrombotic therapy require intense monitoring and adverse effects associated with use of antithrombotic is higher. Moreover, availability of guidelines and national healthcare resources play an important role. Various studies showed use of antithrombotics in “high”-risk patients around 32%–37%.,,, The benefit of prophylaxis is expected to be smaller among lower risk patients. The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) study observed that 60% of patients judged to be at risk of DVT received prophylaxis. This rate is somewhat higher than recorded in this study, possibly because IMPROVE had a broader definition of prophylaxis. This variability is largely due to individual studies limiting their assessment to predefined population and the substantial differences that can exist between institutions within a country, as shown by Otero et al., who reported prophylaxis rates of 27%–70% across different hospitals in Spain. Among patients of primary prevention of DVT (n = 164), no modification (increase or decrease in dose) in the treatment of either anticoagulant or antiplatelet drugs was observed in any patient during the study period.
This study had some limitations. One of the limitations was short duration of study. The sample size was small and therefore we were not able to determine effectiveness of antithrombotic therapy in prevention of recurrence of DVT. It would be worthwhile to follow these patients for at least 5 years. Another potential limitation of this study was that although we defined and collected information on standard risks, some physicians could have applied broader interpretations and withheld DVT prophylaxis accordingly. Furthermore, the data still show a large gap between ideal and real-world practices, despite the theoretical possibility that physician awareness might have led to increased use of DVT prophylaxis.
Despite these limitations, some important clinical implications can be drawn from our results like prevalence of DVT was similar to developed countries published literature. More than 75% of drugs were supplied from hospital store. Therefore, if newer anticoagulants drugs would be available in hospital store, their usefulness could be evaluated. Patients contraindicated for anticoagulation did not receive percutaneous transcatheter treatment or intermittent pneumatic compression devices for treatment of DVT. More than 50% of patients were monitored with INR for risk of DVT and monitoring of anticoagulant therapy. This shows greater awareness regarding DVT in our institution. At our hospital, antithrombotic medicines were used to treat all patients of DVT, but use in primary prevention of DVT was less than 40% of hospitalized surgical patients. Our data reinforce the rational for use of Wells' score to assess patients' DVT risk and to implement measures that ensures that “at-risk” patients receive appropriate prophylaxis. This information may be useful in planning surveillance trial to determine the incidence of DVT among all indoor patients having such risk factors and in verifying whether a primary prevention of DVT might be indicated in these patients.
| Conclusion|| |
DVT prophylaxis is very important and antithrombotic medicines are used for primary prevention of DVT. Heparin and warfarin are mainly used for prophylaxis and for treatment in primary prevention of DVT. Wells' scoring system can be used to guide the assessment for DVT and appropriate prophylaxis. Antithrombotic therapy use mainly depends on patient characteristics, concomitant therapy, and clinician's own experience. Repeated monitoring, cost-effective therapy, and reducing complications associated with their use are essential in DVT. Therefore, considering this fact, further studies are required to redesign and validate Wells' score before it can be used as a guideline in India.
The authors would like to acknowledge the patients, clinicians, and staff of Civil Hospital.
Ethical approval: The study was approved by Institutional Ethics committee.
Financial support and sponsorship
Conflicts of Interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]