This study was carried out in two university hospitals that are part of the same institution, located in the city of Buenos Aires (Argentina).

Both hospitals share the same personnel. Paper based prescriptions are usually issued by first-year residents and supervised by the senior residents and the attending physicians. The team on call daily assess patient's risk factors and prophylaxis contraindications listed in the CPG and prescribe VTE prophylactic measures according with the institutional recommendations.

Both centers share the same VTE prophylaxis CPG. An institutional multidisciplinary group composed of medical members from the departments of emergency, hematology, and internal medicine developed and updated the VTE prophylaxis CPG based on accepted scientific standards and guidelines [^10-13]. Distribution of these recommendations were done annually using pocket size booklets and educational talks. Reminders were placed in areas where the prescriptions are usually filled out and in pre-designed paper-based prescriptions. Also audit and feedback about the appropriateness of VTE-prophylaxis practice were performed.

The local CPG define 5 risk groups according to each patient's risk for VTE and any contraindications. Prescription recommendations of a specific mechanical and/or pharmacologic prophylaxis measures are as follows:

-Group A (patients with any major risk factor for VTE): low molecular weight heparin (LMWH) 4000 IU (international units) Anti Xa/day.

-Group B (patients with four or more risk factors for VTE): unfractionated heparin (UFH) 5000 IU/8 hours or UFH 7500 IU/12 hours.

-Group C (patients with 2 or 3 risk factors for VTE): UFH 5000 IU/12 hours.

-Group D (patients with any major risk factor for VTE, who recently underwent surgery and were anesthetized for more than 2 hours): LMWH 4000 UI Anti Xa/day plus a mechanical prophylactic measure.

-Group E (patients with no or only one risk factor for VTE): no prophylaxis is recommended.

In the case of patients belonging to groups A to D who have contraindications for pharmacologic prophylaxis, the use of mechanical prophylaxis is recommended instead. The institutional CPG define the following conditions as major risk factors: cancer, prior VTE, severe limb paresis or paralysis, thrombophilia, major trauma, severe inferior limb trauma, knee or hip surgery. In addition, they define the following as (non-major) risk factors: immobility (perception of treating physician that the patient will be confined to bed for more than 48 hours, excepting mobilization to toilet), age over 40 years, heart failure, body mass index > 30, respiratory failure, acute myocardial infarction, sepsis, estrogen therapy, travel by car or plane for more than 4 hours in the previous week, delivery during the last month, family history of VTE, surgery, central lines, chemotherapy, burns, stroke, inflammatory bowel disease, mild trauma, and myeloproliferative syndromes.

Contraindications for pharmacological prophylaxis included: platelet count < 100,000/μL, heparin-induced thrombocytopenia, active bleeding, severe coagulophaty, malignant hypertension, trauma with high risk for bleeding, hemorrhagic stroke in the last 15 days and hemispheric ischemic stroke in the last 72 hours. Contraindications for mechanical prophylaxis included: cellulitis, gangrene or recent skin grafting on inferior limb, severe peripheral vascular disease and heel decubitus ulcer.

This cross-sectional study was conducted between September 2007 and January 2008.

Prescriptions of medical general-ward admitted patients issued by the internal medicine physicians of both centers were included. Prescriptions were excluded in the case of (1) patients under 16 years old, (2) pregnant women, (3) patients who had received recent fibrinolytic therapy or (4) were currently treated with anticoagulant therapy, (5) patients hospitalized for less than 24 hours, (6) patients who had undergone neurosurgery, (7) those who were under palliative care, (8) patients already included in the study during the ongoing hospitalization and (9) patients hospitalized in other areas (e.g. critical care units, transplant unit, surgery, obstetrician and paediatrician wards).

Data was collected using medical records, filled-out prescriptions and interviews with the head attending physician, if necessary (see below). Information was gathered at different times during 16 days randomly selected over the 4-month study period.

Medical prescriptions were considered "appropriate" when VTE prophylaxis was prescribed according to the institutional CPG recommendations at the time of recruitment. Otherwise, prescriptions were considered "inappropriate". Inappropriate prescriptions were classified into the following exclusive categories:

a) Excessive prescription: use of a VTE prophylactic measure that was unnecessarily more effective, complex or redundant than those recommended by the institutional guidelines.

b) Insufficient prescription: use of a VTE prophylactic measure that was less effective, complex or complete than those recommended by the institutional guidelines. Those prescriptions lacking prophylactic measures were excluded from this category.

c) Absent prescription: No prophylaxis measure was prescribed when recommended.

We also evaluated if prescription error was due to inappropriate drug, dose or dose interval, disregarded contraindications, lack of pharmacologic or mechanical prophylaxis, unnecessary mechanical or pharmacologic prophylaxis and others causes.

Furthermore, in case of inappropriate prophylaxis, the error was analyzed by consulting the medical records and an immediate interview with the head attending physician. The purpose of this interview was to determine whether the inappropriate prescription was based on any clinical grounds that went unreported in the medical record or prescription.

Apart from the type of prophylaxis prescribed and recommended by the institutional CPG, other variables were registered: (1) socio-demographic data, (2) presence of major or non-major risk factors for VTE (3) presence of contraindication for the use of heparins, graduated compression stockings (GCS) or intermittent pneumatic compression devices (IPC), (4) date, time, center and diagnosis at admission, (5) weight under 40 kg, (6) renal failure with glomerular filtration rate < 30 ml/min -- Cockcroft-Gault formula [¹⁹], (7) data of the physician who prescribed the prophylaxis, (8) discontinuation of prophylaxis at any time during hospitalization, (9) prophylaxis prescription within 24 hours of admission, (10) changes in prophylactic regimen during hospitalization, and (11) stay at the intensive care units (ICU) during the ongoing hospitalization.

In order to preserve patients' safety, the head attending physician was notified of the errors encountered and asked to make the necessary changes according to his/her clinical judgment. Confidentiality of both, the patients and the physicians, was ensured. This study was approved by the Institutional Review Board.

Categorical variables were compared using Chi-squared test or Fisher exact test.

Normally distributed continuous variables were compared using t-Test, otherwise Mann-Whitney test was used. All of them were two tailed-tests. Predictors of inappropriate prescribing were assessed using a multiple logistic regression analysis. Independent variables considered to be clinically relevant or statistically significant (p < 0.1) in the univariate analysis were included in the model. Patients categorized as risk Group D were not included. We accepted a statistical significance of 95%. SPSS 13.0.2004 software was used (SPSS, Inc., Chicago, IL, USA).

A total of 584 medical prescriptions were evaluated, and 274 were excluded (194 [70,8%] were from patients already included in the study during the ongoing hospitalization, 65 [23,7%] were currently treated with anticoagulant therapy and 15 [5,5%] had others exclusion criteria). Thus, 310 medical prescriptions were included in this study.

The patient characteristics of the included prescriptions are summarized in Table 1. One hundred twenty four patients (40%) were hospitalized due to infectious diseases (40 patientes had pneumonia and 22 urinary tract infection). Seventy patients (23%) required hospitalization in ICU. One third of the population had at least one major risk factor for VTE, seventy four (72%) of these patients presented cancer and fifteen (15%) had severe limb paresis or paralysis. Non-major risk factors included immobility 268 (86%) patients, age over 40 years 260 (84%), sepsis 117 (38%), surgery 38 (12.6%) and heart failure 28 (9%). Other risk factors were observed in less than 5% of the patients. Twenty nine patients (9.4%) had less than 2 risk factors and thus did not require thromboprophylaxis (Risk group E). Only six patients required both pharmacologic and mechanical prophylaxis (1.9%) Risk group D.

According to the institutional guidelines, VTE prophylaxis was appropriately prescribed to 188 patients (60.6%). Inappropriate prescribing was due to excessive (14.2%), insufficient (15.8%), and absent (9.4%) prescription. Rates and reasons of inappropriateness differed among risk groups (Figure 1).

Group A had 76 (77.6%) appropriate prescriptions. In this group, 50% of inappropriate prescriptions had insufficient prophylaxis, while 40% lacked all prophylactic measures. Of the 9 patients without prophylaxis, 7 had contraindications for pharmacologic prophylaxis (6 due to thrombocytopenia and 1 due to active bleeding) and no mechanical prophylaxis prescribed. Thirty eight patients in Group B (44.7%) had appropriate prescriptions. In this group, two thirds of the inappropriate prescriptions had insufficient prophylaxis prescribed. Although Group C had 59 (64%) appropriate prescriptions, it had the highest rate of absent prescriptions (40% of inappropriate prescriptions).

In Group D (n = 6), none of the prescriptions were appropriate. In 5 cases (83%) mechanical measures were not prescribed. Finally, Group E showed 15 (51.7%) appropriate prescriptions. Inappropriate prescriptions were all due to excessive mechanical or pharmacologic prophylaxis.

Thirty nine (72%) patients with contraindications for pharmacologic prophylaxis had an appropriate VTE-prescription. In these patients, the absence of mechanical prophylaxis was the most frequent error observed (73% of inappropriate prescriptions). The interviews with the head attending physician revealed that only 11 (3.5%) of inappropriate prescriptions were based on clinical judgment, aware that recommendations were not being followed. We found that 256 (82.6%) prescriptions were appropriate according to the ACCP recommendations.

Two hundred and sixty five patients (85.5%) received thromboprophylaxis. Drugs and doses prescribed included UFH 5000 IU every 12 hours (31.3%), UFH 5000 IU every 8 hours in (8.1%), UFH 7500 IU every 12 hours in (6.5%), LMWH 4000 UI anti Xa every 24 hours in (25.2%), and others not mentioned in the guidelines in (1%). Moreover, GCS were used on 41 patients (13.2%) and IPC in one case.

Figure 2 shows the prophylaxis recommended by guidelines and that actually prescribed during the study. The prescription of UFH 5000 IU every 8 hours or UFH 7500 IU every 12 hours was lower than that recommended. (p < 0,001)

Table 2 shows that several variables were associated with the appropriateness of VTE-prophylaxis prescription: surgery, VTE prescription at admission, risk group, the fact of being enrolled during the second half of the study, obesity, prophylaxis discontinuation during hospitalization, the presence of contraindications for pharmacologic prophylaxis, and discharge diagnosis (p < 0.10). When adjusted for the above variables, patients who received prophylaxis since the admission and those admitted for gastrointestinal diseases (compared with patients admitted for infectious conditions) were more likely to have an appropriate VTE prescription. On the contrary, the odds of inappropriateness in patients who underwent surgery tripled that of patients who did not require a surgical procedure. Patients in Groups C, E and B had an increasingly higher risk of inappropriate prescription compared with patients in Group A (Table 3).

SD = Standard Deviation

GCS = Graduated compression stockings

IPC = Intermittent pneumatic compression devices

RF = Risk factor

SD = Standard Deviation

ICU = Intensive care unit

OR: Odds ratio

CI: Confidence interval

# Reference category: Infection

* Reference category: Group A