Background: Venous thromboembolism (VTE) is a common complication seen during or after hospitalization that manifests as deep venous thrombosis (DVT) and/or pulmonary embolism (PE). PE is considered the commonest preventable cause of death during and/or after hospitalization. Thus, pharmacological and mechanical methods are used to prevent VTE in hospitalized patients. Despite the availability of guidelines for VTE prophylaxis, it is crucial to assess the adherence and adaptation of the institution to these guidelines. Purpose: This study aimed to investigate adherence to the American College of Chest Physicians (ACCP) 2012 VTE prophylaxis guidelines in hospitalized medical patients in a tertiary care hospital in the United Arab Emirates. Methods: An observational prospective design was utilized in this study. To achieve the purpose, primary and secondary end points were identified to be the core of the investigation. The primary end points were: the incidence of bleeding, VTE, and cardiovascular events. While the secondary end points were: dose and indication validity for prophylaxis, VTE and bleeding risk assessments, adverse drug events (ADE) other than bleeding, appropriate monitoring when on low molecular weight heparin (LMWH) and the presence of contraindication at the time of prescribing LMWH. Results: 16 patients (20%) out of the total 80 met one or more of the primary end points. The vast majority of patients (81.25%) developed bleeding, while VTE was seen in one case only during hospitalization. 11 patients (13.75%) received LMWH while a contraindication was present. 15 patients (18.75%) who were prescribed LMWH had an International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) bleeding risk score of ≥7. However, 5 out of 13 patients (38.46%) who developed bleeding had a bleeding score of ≥7, and the relationship between bleeding score of ≥7 and the development of bleeding was statistically significant (p = 0.047). When investigating the doses that were utilized, 40% were prescribed an inappropriate dose. Conclusion: Various factors played a role in the inappropriateness of VTE prophylaxis such as; poor adherence to VTE guidelines, inappropriate dosing and monitoring, and not evaluating the bleeding risk. Hence, to be able to achieve effective VTE prophylaxis, these factors need to be addressed through adherence to and adaptation of the ACCP 2012 VTE prophylaxis guidelines.
VTE is a disease that might manifest as DVT and/or PE. DVT occurs by the formation of a blood clot (fibrin) in the veins of the lower extremities, often provoked by prolonged immobility and/or vascular injury. VTE can also occur with little or no provocation in patients who have an underlying hypercoagulable condition. DVT is further subdivided based on the involved vein into distal (calf) vein thrombosis and proximal vein thrombosis. The proximal vein thrombosis clinically is considered to be more important because of its close association with PE as per Thompson and Manninom (2003) [
Because VTE is one of the common complications seen during or after hospitalization, the importance of preventing such a complication was illustrated by several studies. Anderson et al. (2007) pointed out that 51% of total discharges in the United States (US) in 2003 were estimated as to be at risk of developing VTE [
Pharmacological and mechanical methods have been implemented to overcome this problem. However, in this research the focus will be on the pharmacological methods; specifically the use of LMWH for VTE prophylaxis. Enoxaparin, tinzaparin and dalteparin are the 3 most commonly used LMWH in clinical settings. LMWH are small heparin fragments obtained by chemical or enzymatic depolymerization of unfractionated heparin (UFH). These agents produce their anticoagulation effects by the binding of specific pentasaccharide sequence to antithrombin (AT), resulting in inhibition of factor xa and to a less extent factor IIa (thrombin). LMWHs have an improved pharmacokinetics and pharmacodynamics properties compared to unfractionated heparin (UFH). LMWH offers a longer half-life that enables once or twice daily administration and a subcutaneous administration providing more practicality, convenience and compliance to patients. Routine monitoring and frequent dose adjustments are other advantages that are not required for the majority of cases compared to UFH. If monitoring of anticoagulation is required while on LMWH for various reasons like pregnancy or renal disease, anti-xa activity laboratory test is utilized [
Despite the fact that guidelines to prevent VTE in hospitalized medical patients are readily available, a critical question remains, how much are we adherent to these guidelines?
Tapson et al. (2007) mentioned that 6 of every 10 acutely ill patients who fulfill the criteria of the CHEST 2012 guidelines to receive VTE prophylaxis actually received it as referred in
Risk group | Recommended prophylaxis |
---|---|
Low VTE risk (Padua < 4) | Recommend against the use of pharmacologic or mechanical prophylaxis (Grade 1B) |
Low VTE risk (Paudua < 4) with high bleed risk | Recommend against anticoagulant thromboprophylaxis (Grade 1B) |
High VTE risk (Padua ≥ 4) | Thromboprophylaxis with LMWH (Grade 1B), LDUH BID or TID (Grade 1B), or fondaparinux (Grade 1B). |
High VTE risk (Padua ≥ 4) with high bleed risk | Mechanical thromboprophylaxis with graduated compression stockings (GCS) (Grade 2C) or intermittent pneumatic compression (IPC) (Grade 2C). When bleeding risk decreases suggest pharmacologic thromboprophylaxis is substituted for mechanical thromboprophylaxis (Grade 2B). |
Extended duration of thromboprophylaxis | Recommend against extending the duration of thromboprophylaxis beyond the period of patient immobilization or acute hospital stay. |
(p < 0.001) [
The aim of this study was to conduct a medication use evaluation (MUE) by assessing the adherence of VTE prophylaxis management in adult medical patients to the American College of CHEST Physicians (ACCP) 2012 guideline for VTE prophylaxis in medical patients [
1) Primary end points; incidence of bleeding, VTE, and cardiovascular events.
2) Secondary end points; dose validity, indication validity for VTE prophylaxis, bleeding risk assessment, adverse drug events (ADE) other than bleeding, appropriate monitoring when on LMWH and presence of contraindication (C/I) at the time of prescribing LMWH.
An observational prospective study design was utilized to investigate the primary and secondary end points. The study was conducted at Tawam Hospital in Affiliation with John Hopkins; a 468-bed tertiary care facility located in Al Ain district, Abu Dhabi city, United Arab Emirates.
Data collection period started from January 1, 2014 until May 23, 2014. During this period the lists of patients hospitalized in the adult medical wards were accessed 3 days per week via the Cerner Millennium® Computerized Provider Order Entry (CPOE) to filter the patients that were prescribed LMWH for VTE prophylaxis purposes [
Inclusion criteria: patients ≥18 of any gender and ethnic group who were hospitalized in one of the adult medical wards for a reason other than surgery, and were given LMWH for VTE prophylaxis during the period of hospitalization. Oncology patients and pregnant females were included as well. All patients included in this study were on enoxaparin which was not intentional, but because enoxaparin is the most commonly used LMWH in Tawam hospital.
Exclusion criteria: surgical patients, patients given LMWH for VTE treatment and patients who have been hospitalized more than once during the period of data collection.
The instrument that was used to gather all the information was Excel spread sheet (Microsoft office 2013). The sheet included as well the Padua and the IMPROVE scoring systems.
The guideline used in this study to evaluate the adherence of the medical units to for VTE prophylaxis was the ACCP CHEST 2012 VTE prophylaxis guideline for medical patients [
Continuous variables were presented by actual numbers (N) and/or means ± SD, while the discrete variables were presented as percentages. In addition, the Chi-square test was used to establish the relationship between a
Padua risk assessment model | Point |
---|---|
Risk factor | 3 |
Active Cancer* | 3 |
Previous VTE | 3 |
Reduced mobility○ | 3 |
Thrombophilic condition | 2 |
Recent (< 1 month) trauma/surgery | 1 |
Age ≥ 70 years | 1 |
Heart or Respiratory Failure | 1 |
Acute Myocardial Infarction or Ischemic Stroke | 1 |
BMI ≥ 30 | 1 |
Ongoing Hormonal Treatment | 3 |
Scores interpretation: Score < 4: Low VTE risk; Score ≥ 4: High VTE risk |
*Active cancer is defined as local or distant metastases and with chemotherapy or radiation in the previous 6 months. ○Reduced mobility is defined as anticipated bed rest with bathroom privileges for at least 3 days.
Risk factors | Point |
---|---|
Moderate renal failure (CrCl 30 - 50 ml/min.) | 1 |
Male Sex | 1 |
Age 40 - 84 years | 1.5 |
Active Cancer | 2 |
Rheumatic disease | 2 |
Central venous catheters | 2 |
Admissions in Intensive Care | 2.5 |
Severe Renal Failure (CrCl < 30 ml/min.) | 2.5 |
Liver insufficiency (INR > 1.5) | 2.5 |
Age ≥ 85 | 3.5 |
Thrombocytopenia (<50 × 109 cell/L) | 4 |
Recent (3 months) bleeding | 4 |
Active gastro-intestinal ulcer | |
High bleeding risk when total score ≥ 7 |
If the score ≥ 7, the overall rate of major bleedings is 7.9% and clinically relevant non-major bleedings is 4.1%; If the score < 7, the overall rate of major bleedings is 1.5% and clinically relevant non-major bleedings is 0.4%.
score of ≥7 in the IMPROVE bleeding risk assessment score and the actual development of a bleeding incidence. Also, the Chi- square test was utilized to test the existence of a relationship between increased age and sensitivity to develop bleeding. Furthermore, the statistical analysis was carried out using Microsoft office excel 2013 and IBM SPSS Statistics V.21.
This study was approved by Al Ain District Research Ethics Committee.
A total number of 80 patients were eligible to be included in this study, and the baseline characteristics are presented in
Characteristics | Sub-Characteristic | Number of Patients/values | Percentage | |
---|---|---|---|---|
Age | <40 years old | 70 | 8.75% | |
40 - 59 | 15 | 18.75% | ||
60 - 69 | 18 | 22.5% | ||
≥70 | 40 | 50% | ||
Gender | Male | 38 | 47.5% | |
Female | 42 | 52.5% | ||
Height | Mean of height (±SD) | 155.4 cm (±18.94) | - | |
Height was not documented | 6 | 7.5% | ||
Weight | Mean of weight (±SD) | 71.4 kg (±25.42) | - | |
Weight was not documented | 3 | 3.75% | ||
BMIa | BMI ≤ 18 | 10 | 12.5% | |
BMI 18.5 - 25 | 22 | 27.5% | ||
BMI 26 - 29 | 16 | 20% | ||
BMI ≥ 30 | 19 | 23.75% | ||
BMI > 40 | 8 | 10% | ||
BMI not documented | 5 | 6.25% | ||
Renal function Creatinine clearance (CrCl) | CrCl > 30 ml/ minute | 67 | 83.75% | |
CrCl < 30 ml/ minutes | 7 | 8.75% | ||
Dialysis | 4 | 5% | ||
CrCl was not possible to calculate | 2 | 2.5% | ||
Hepatic function (acute/ chronic) | Presence of hepatic dysfunction | 3 | 3.75% | |
Absence of hepatic dysfunction | 77 | 96.25% | ||
Thrombophilic condition | Cancer | 8 | 10% | |
Hormonal Therapy | 1 | 1.25% | ||
Obesity | 16 | 20% | ||
Ulcerative colitis | 1 | 1.25% | ||
Inflammatory bowel disease | 1 | 1.25% | ||
Pregnancy | 1 | 1.25% | ||
Medications that increase bleeding risk | Aspirin only | 27 | 33.75% | |
Clopidogrel only | 6 | 7.5% | ||
Aspirin and clopidogrel | 10 | 12.5% | ||
None | 37 | 46.25% |
BMI (kg/m2) interpretations: 18.5―underweight; 18.5 to 24.9 - Normal range; 25.0 - 30.0―Obese; >30―Morbidly obese.
included in the study, with 1 pregnant female among them. With regards to the body mass index (BMI), 27 patients (33.75%) were morbidly obese, while 5 (6.25%) did not have a documented BMI, and manual calculation of BMI was not possible because height and/or weight were not documented as well. While assessing the renal function of the study population using Cockroft-Gault equation, data illustrated that 67 of the study population (83.75 %) had a creatinine clearance (CrCl) > 30 ml/min at the time of prescribing the medication. However, calculating CrCl was not possible in 2 patients due to the missing data on weight. Moreover, when investigating the hepatic function of the study population the results showed that the majority (77 out of 80) of the population had no existing hepatic dysfunctional condition (acute or chronic). Furthermore, the patients were evaluated for the presence of thrombophilic conditions which are summarized in
As mentioned previously, to prevent VTE effectively and appropriately the Padua and IMPROVE scores need to be utilized. After calculating the Padua and IMPROVE scores for each patient, the results indicated that 15 patients (18.75%) who were prescribed LMWH had a bleeding risk score of ≥7. Five (38.46%) of who developed bleeding during hospitalization had a bleeding risk score of ≥7. Another major issue is dose appropriateness that requires the availability of 3 important parameters; CrCl, BMI and weight in Kilogram (kg). Forty-five patients (56.25%) were given a correct VTE prophylaxis dose, while 32 (40%) were given an inappropriate dose, which is defined as under dose or over dose. Additionally, only 2 patients were suspected to have developed heparin induced thrombocytopenia (HIT).
Congenital | Acquired |
---|---|
Type II: ・ Factor V Leiden (a mutation in the F5 gene at position 1691) ・ Prothrombin G20210A, a mutation in Prothrombin (at position 20210 in the 3’ untranslated region of the gene) Type I: ・ Antithrombin III deficiency ・ Protein C deficiency ・ Protein S deficiency ・ Factor XIII mutation ・ Familial dysfibrinogenemia | ・ Antiphospholipid syndrome ・ Paroxysmal nocturnal hemoglobinuria (PNH) ・ Heparin-induced thrombocytopenia (HIT) ・ Sickle cell anemia ・ Myeloproliferative disorders ・ Cancer, particularly when metastatic ・ Nephrotic syndrome ・ Inflammatory bowel disease (ulcerative colitis and Crohn's disease) ・ Pregnancy ・ Hormone replacement therapy ・ Morbid obese |
Parameter investigate | Number of patients | Percentage |
---|---|---|
Bleeding (possible & definite) | 13 | 16.25% |
VTE | 1 | 1.25% |
Cardiovascular events | 2 | 2.5% |
Parameter investigate | Sub-title | Number of patient | Percentage |
---|---|---|---|
Contraindications (C/I) for the use of LMWH at the time of prescribing | Present | 11 | 13.75% |
Absent | 67 | 83.75% | |
History and initial investigation were not sufficient to detect C/I | 2 | 2.5% | |
Type of C/I¥ (N = 11) | Uncontrolled hypertension at the time of prescribing | 10 | 90.9% |
Active major bleeding | 1 | 9.1% | |
Indication validity‡ | Valid | 57 | 71.25% |
Not valid | 23 | 28.75% | |
Bleeding risk◊ | IMPROVE bleeding score < 7 | 65 | 81.25% |
IMPROVE bleeding score ≥ 7 | 15 | 18.75% | |
Dose appropriateness | Appropriate | 56.25% | |
Not appropriate | 40% | ||
Not applicable | 1.25% | ||
Not able to verify the appropriateness of the dose | 2.5% | ||
Measuring platelets at baseline | Yes | 75 | 93.75% |
No | 5 | 6.25% | |
Appropriate monitoring of plateletsᶲ | Yes | 31 | 38.75% |
No | 49 | 61.25% | |
Adverse drug events other than bleeding | Osteoporosis | 0 | 0% |
Heparin induced thrombocytopenia | 0 | 0% | |
Possible heparin induced thrombocytopenia (HIT) | 2 | 2.5% | |
Hyperkalemia | 0 | 0% | |
Hypersensitivity | 0 | 0% |
‡Indication validity to prevent against VTE based on padua score (≥4 is valid); ◊Bleeding risk is assessed by the IMPROVE Bleeding risk Score; ¥C/I [
Medication use evaluation and adherence to guidelines are criticle parameters to optimize patient care, effective use of medications and avoiding undesirable effects. The importance of VTE prophylaxis was demonstrated by Samama et al. (1999) and Leizorovicz et al. (2004), where VTE prophylaxis resulted in reducing the risk of developing VTE by 50% [
The relationship between an IMPROVE score of ≥7 and bleeding was examined in our study as well via a chi-square test, showing the existence of a statistically significant relationship between the 2 parameters (p = 0.047) as seen in
The presence of C/I at the time of prescribing LMWH is an end point that was explored in our study. If a C/I(s) for the use of pharmacological VTE prophylaxis is/are present, the CHEST guidelines recommends utilizing mechanical prophylaxis instead. Use of pharmacological agents in such situations should be exercised with an extreme caution if clinically relevant. Bateman et al. (2013) mentioned that despite the improvement in VTE risk assessment documentation, the percentage of patients who received LMWH when a contraindication is present did not change, 14% in 2009 versus 15% in 2010 (95% CI: −16.5% to 17.2%; p = 0.97) [
IMPROVE score | Bleed | Total | P value | |
---|---|---|---|---|
Yes | No | |||
≥7 | 5 | 10 | 15 | 0.047 |
<7 | 8 | 57 | 65 |
The possibility of the existence of a relationship between increased age and risk of bleeding was explored via chi square test. Because the majority of patients admitted to the medical wards in Tawam hospital are geriatrics (≥60 years old), and in the IMPROVE scoring system an age of ≥85 is assigned to a higher scoring power; such an analysis thought to be prominent. Also, as it is shown
Appropriate dosing is essential to provide optimal protection when pharmacological methods are chosen. Weight in kilograms, BMI and kidneys function should be taken into consideration when deciding on the dose of LMWH. The appropriate doses for VTE prophylaxis are available in
The optimal duration for the use of pharmacological VTE prophylactic agents is still considered to be an area of controversy. Yu et al. (2007) conducted a retrospective study to evaluate the compliance to the 6th ACCP consensus conference on antithrombotic therapy guidelines for the prevention of VTE in hospitals [
As per guidelines, LMWH needs to be monitored appropriately to prevent bleeding and the development of rare but potentially life threatening adverse event which is heparin induced thrombocytopenia (HIT). Although HIT is less common with the use of LMWH compared to UFH, it is a life threatening condition that occurs in up to 5% of patients. HIT occurs because of the production of autoantibody against the endogenous platelet factor 4% (PF4), that complexes with heparin. This will activate platelets, resulting in catastrophic arterial and venous thrombosis [
Of note, in the study site VTE risk is assessed via a calculator that is similar to the Padua score which is available in the CPOE system―Cerner Millennium®. However, a tool to assess the bleeding risk is not yet available in the CPOE, which is essential for safe and effective VTE prophylaxis.
Recommendations based on the results of this study were as follows; adopting institutional guidelines based on the CHEST recommendations for the use of LMWH to prevent against VTE, to enhance initial assessment, optimize drug dosing (inappropriate in 40%) and monitoring while on LMWH (inappropriate in 49%). In addition, optimizing the use of risk assessments tools and adding a bleeding risk assessment tool (IMPROVE) to the electronic VTE assessment tool in the health information system. Furthermore, the IMPROVE score had a
Points | Probability |
---|---|
0 to 3 points | Low probability |
4 to 5 points | Intermediate probability |
6 to 8 points | High probability |
limitation of not assigning a score to anti-platelets. Hence, if the score will be adapted, it would be reasonable to assign a score to the use of apirin and/or clopidogrel.
In conclusion, various factors have been found to play a significant role in the ineffectiveness and lack of safety while on VTE prophylaxis. These factors include: poor adherence to VTE guidelines, inappropriate dosing and monitoring, and not utilizing risk assessment tools. Despite the fact that Padua VTE risk assessment tool is available in the health information system, reluctance to use it and/or poor documentation is not uncommon. The IMPROVE score is another important tool that needs to be incorporated in the health information system. Not assigning a score to the anti-platelets in the IMPROVE score is a limitation which was identified during this study; as 61.45% of the bleeding cases were on at least one anti-platelet agent. On the other hand, this study was not without limitations; the small sample size (N = 80) and the inability to evaluate the appropriateness of the duration of VTE prophylaxis were the most evident ones.
The authors thank “Tawam Hospital in Affiliation with John Hopkins” for supporting carrying this study.
LamiaAlHajri,NicoleGebran, (2015) The Use of Low Molecular Weight Heparin for Venous Thromboembolism Prophylaxis in Medical Patients: How Much Are We Adherent to the Guidelines?. Open Journal of Internal Medicine,05,81-91. doi: 10.4236/ojim.2015.54012