Antithrombotic prophylaxis is a critically important medical intervention to reduce VTE morbidity and mortality in patients during and after hospitalization for surgery or medical illness. Antithrombotic prophylaxis significantly reduces VTE risk but does not eliminate it completely. A recent study by the American College of Surgeons showed a 42% reduction in the odds of a 30-day postoperative VTE events in high-risk general surgery patients who received prophylaxis.⁸ Less favourable appear to be the results of prophylaxis in hospitalized medical patients. A systematic review of randomized trials supported by the National Institute for Health Research (NIHR), reported an approximately 30% reduction in symptomatic VTE with intermediate dose low-molecular weight heparin (LMWH) prophylaxis, but with an increased incidence of major bleeding. No difference was found in all-cause mortality.⁹

Risk stratification for VTE prevention is essential, and validated tools are available for physicians. Specific clinical variables and demographics, such as increasing age, BMI, family or personal history of VTE, type, and duration of surgery, and need for postoperative transfusion are included in the scores for stratification of VTE risk. Among the validated tools available, the Caprini score is widely used for assessing VTE risk in surgical patients,¹⁰ for hospitalized medical patients Padua Prediction¹¹ and IMPROVE¹² scores are commonly used.

Despite clear recommendations on the type, dose, and even duration, the prophylaxis remains underused, as shown by many studies. It has been reported that approximately 50% of at-risk patients receive no (or suboptimal) pharmacologic prophylaxis.¹³¹³ A recent study found that over one-third of high-risk patients (36%) received inappropriate or no prophylaxis.¹⁴¹⁴ An international survey in 2008 showed that only 39.5% of hospitalized high-risk patients received prophylaxis.¹⁵¹⁵ Over the years, efforts have been made to improve prophylaxis in hospitalized patients, including clinical decision support systems with electronic alerts. These electronic systems that automatically remind physicians of the need for VTE prophylaxis, along with continuing medical education on VTE prevention, have proven useful.¹⁶ These systems can help but may suffer from "alert fatigue" and do not guarantee a culture of prevention.¹⁷

It should be recognized that ordering appropriate therapy does not ensure its administration and missed doses are common. A study in hospitalized patients found that approximately 10% of ordered doses of pharmacologic VTE prophylaxis were not administered, 44% due to patients’ refusal.¹⁸ Several studies have shown that missed doses of inpatient chemoprophylaxis are common and associated with VTE occurrence.¹⁹²⁰²¹ Recently, a concept of "defect-free" VTE prophylaxis has been proposed,²² which includes several important aspects: clinicians must assess patients' risk for VTE and prescribe the appropriate therapy in relation to each patient's risk; patients must understand the role and importance of prophylaxis and accept the prescribed therapy; and nurses must administer the therapy as prescribed. However, these steps are not always well-coordinated. For example, the American College of Surgeons study showed that only 32% of over 4,200 high-risk surgical patients had a “perfect” in hospital VTE prophylaxis order, and missing orders were associated to higher VTE rates.⁸

A significant number of VTE events occur after hospital discharge, especially following major orthopedic surgeries like total hip arthroplasty, where 75% of VTEs occur post-hospitalization.²³²⁴

In turn, a short course of prophylaxis in hospitalized medical patients may be insufficient to prevent late symptomatic VTE events.²⁵ The transition from hospital to home care is certainly a vulnerable period for patients requiring careful coordination.²⁶ Discharge instructions are often incomplete or missing.²⁷ Clear and complete information should include the type, dose, and duration of any chemoprophylaxis to be continued at home, but they are frequently omitted. An analysis of thromboprophylaxis rates in a US medical centre showed that 66.1% of discharged patients received inadequate prophylaxis: 38.4% received no prophylaxis at all, 16.7% had an inappropriate duration of prophylaxis according to current guidelines, and 6.3% received an inappropriate dosage.²⁸

The problem of non-optimal patient compliance with post-discharge VTE prophylaxis is well known and has been studied especially in patients after high-risk orthopedic surgery.²⁹³⁰ The reasons include problems related to purchase, patient education, information on the importance of continuing prophylaxis at home, and patient training to self-administer LMWH injections, which is the most commonly used type of drug for VTE prophylaxis, at least in our country. A study published in 2010 showed a non-adherence rate ranging from 13% to 21% in outpatients receiving prophylaxis with LMWH after major orthopedic surgery.³¹ Nonadherent patients missed between 38% and 53% of LMWH injections, mainly due to forgetfulness, fear of self-administered LMWH injections, or occurrence of side effects (usually hematomas at the injection site).³²

To assess the problems that Italian patients and physicians may face with home prophylaxis with LMWH, a survey was launched among the readers of the "anticoagulazione.it" website, sponsored and funded by the "Arianna Anticoagulazione" Foundation, Bologna, Italy. There were two different surveys, one addressed to patients and the other to physicians (Supplementary Material).

A descriptive analysis was performed, categorical variables are expressed as frequencies and percentages and were compared using the Chi-square test or Fisher exact test, as appropriate. The data were analyzed with the use of SPSS software for Windows, V.26 (IBM, Armonk, NY, USA).

The patients (n=154) and caregivers (n=23) who participated in the survey lived in different geographical areas of Italy, but more frequently in the north (north 115, central 28, south and islands 34). The most common indication for home prophylaxis was the continuation of treatment started in hospital after surgery (74/177; 42%; 95% CI 34-49%),), followed by medical problems occurring at home (without hospitalization) (52/177; 29%; 95%CI 23-36%), continuation of treatment started in hospital for medical illness (33/177; 19%; 95%CI 13-25%), and home prophylaxis for orthopedic problems (trauma, bandages, etc.) (18/177; 10%; 95% CI 6-15%). In most cases (154/177; 87-95% CI 0.8114 to 0.9158), chemoprophylaxis was prescribed by a hospital physician (even without hospitalization), in 7% of cases (13/177; 95%CI 4-12% ) it was prescribed in an outpatient clinic, and in only 6% of cases (10/177; 95%CI 3-10%) it was a decision of the family physician. In the majority of cases (170/177; 96%; 95%CI 92-98%), participants reported that they had adhered to the prescription, including for the duration of treatment. Only 7 patients (4%) admitted that they had stopped the prophylaxis before it was prescribed. Tree out of seven declared it was mainly due to difficulties in obtaining drug prescription by general practitioners (GP)and drug dispensing by the Italian National Health Service. This is likely due to strict regional rules on heparin prescriptions by GP which vary from one region to the other in Italy. Two of the three patients were from southern Italy and on from central Italy. Only two patients cited difficulties with injections or the occurrence of side effects (pain) as a reason for discontinuation (Table 1). However, these problems (pain and/or bruising at the injection site) were reported by eleven more patients who continued the treatment. Six people complained about the lack of proper instructions on the injection technique. In a few cases, patients were unable to self-administer the drug and needed the help of a nurse.

One hundred fifty-three health system professionals took part in the survey, living in 17 out of the 20 Italian regions. In most cases, they were hospital doctors (<5% were surgeons), and only 10% of cases were family doctors (15/153; 95%CI 6-16%). Differently from what was reported by patients, about 40% of doctors (58/153; 95%CI 30-46%) declared to have observed frequent arbitrary discontinuation of chemoprophylaxis by patients, which was ascribed to an insufficient perception of the seriousness of thromboembolic complications , as well as to a deficit in doctor-to-patient communication, by 74% of responders (43/58; 95%CI 61-85%). Seventeen percent of physicians (10/58; 95%CI 9-29%) attributed to fear of, or problems in self-administered injections the reason for discontinuation of treatment, while 9% of them (5/58; 95%CI 3-19%) believe that patients fear the risk of bleeding (Table 2). The difference between the percentages of arbitrary suspension of treatment reported by patients\caregivers or doctors was highly significant (4% vs 38%; p<0.0001).

Most clinicians (72%) confirmed to prescribe prophylaxis in line with the relevant international guidelines, while 20% declared to follow primarily the hospital indications or guidelines, and only 8% admitted prescribing prophylaxis according to personal experience. However, many of them reported some doubts which still represent “gray areas” in the field of chemoprophylaxis, especially regarding the need for prophylaxis, its dose, and optimal duration, in particular settings of patients (e.g. chronic patients at home, after high-risk surgery, after minor orthopedic or arthroscopy surgery, patients with renal insufficiency, and patients with extreme body weight).

As expected, the majority of clinicians (105/153, 69%; 95%CI 61-76%) usually prescribed LMWH prophylaxis for up to 14 days, in line with the fact that a high proportion of respondents were internal medicine specialists (38%) and hematologists or angiologist (24%). Nonetheless, 31% of clinicians (48/153; 95%CI 24-39%) usually prescribe chemoprophylaxis for 4 or more weeks.

The most common indications for antithrombotic prophylaxis were acute medical illness, major orthopedic surgery, and abdominal-pelvic surgery but a remarkably high proportion of clinicians (42/153; 27%; 95%CI 20-53%) declared that the most frequent reason for prescribing LMWH prophylaxis was “chronic patients and\or reduced motility”. The survey revealed considerable doubts about the proper management of chronic patients. In fact, more than half of the physicians (83/149; 53%; 95%CI 51-68%)) reported that the main “gray area” in thromboprophylaxis was the “chronic patient”. One-third (45/149; 30%; 95%CI 23-38%) of clinicians responded that the most important “gray area” was the need and duration of “home prophylaxis for acute patients with medical illness.”