Deep vein thrombosis (DVT) and pulmonary embolism (PE) are severe but often unrecognised complications in critically ill hospitalised patients.1,2 In adult patients admitted to the ICU, the prevalence of DVT or PE with evident clinical manifestations exceeds 20 cases per 1000 patients, with an incidence higher than 14.5 cases per 1000 patients despite the use of pharmacological thromboprophylaxis (PTP),3 so its use is justified unless there is a recognised contraindication for anticoagulation.4

Using the scarce data available for children admitted to paediatric intensive care units (PICUs), the prevalence of DVT or PE with clinical manifestations is estimated at 9 cases per 1000 patients and their incidence at 7 cases per 1000 patients,5 and there are no specific recommendations for the use of PTP in these patients.6

A survey of paediatric intensivists in the United States showed that they were more likely to prescribe PTP to adolescents receiving mechanical ventilation, with a hypercoagulable state, a prior history of DVT or a cavopulmonary anastomosis.7

The PROTRACT prospective multicentre study concluded that the low frequency and great variability in the use of thromboprophylaxis in PICUs call for well-designed research that can set the foundation for establishing the indication of PTP in children.1 In the secondary analysis of the PROTRACT data performed in our study,1 we evaluated the frequency of thromboprophylaxis in critically ill children in Spain and Portugal in an attempt to determine the patient and PICU characteristics associated with its use.

Venous thromboembolism is a significant cause of morbidity and mortality in hospitalised adults, with reported incidence rates ranging from 10% to 40%.2,16 The incidence in children seems to be much lower at about 0.5% of the total number of hospitalisations.2,17–19 When children are critically ill, the risk factors for DVT increase in number, so it is likely that its incidence also increases, although no reliable data are available on this particular.1

In light of this, the use of a thromboprophylaxis regimen in children admitted to the PICU may be justified, although this remains a matter of contention. On one hand, its indiscriminate use could unnecessarily expose low-risk children to an increased risk of bleeding or complications such as heparin-induced thrombocytopaenia.2 On the other hand, failure to use of thromboprophylaxis in high-risk children could result in episodes of DVT or PE that could have been prevented.2 In addition to pharmacological measures, mechanical thromboprophylaxis (which is usually indicated starting at 8 years of age) is a preventive measure available to the patient that poses no risks.

Intensivists acknowledged that the criterion they use for prescribing thromboprophylaxis in actual practise is the presence of one or more risk factors, such as the patient having a CVC, mechanical ventilation, heart disease, or hypergoagulability.1,7,20

The PROTRACT multicentre study, which included a considerable number of PICUs and patients from various developed countries and of which our study made a secondary analysis, demonstrated the great variability that exists in the use of thromboprophylaxis in critically ill children.1 It identified a series of characteristics associated to the use of PTP, such as congenital heart disease, immobility, obesity, a previous history of thrombosis or cavopulmonary anastomosis, the presence of one or more CVCs, and adolescence.1

However, given the aforementioned variability, we had to compare the results obtained in the PICUs in our region (the Iberian Peninsula) to gain a more accurate perspective on what occurs in our units. Our results show that the characteristics of Iberian PICUs and their patients differ significantly from the rest of the sample, with Iberian PICUs having fewer beds, a lower percentage of patients in the extreme age groups (younger than 1 year and older than 13 years) and a small percentage of non-white patients. Still, the risk factors for DVT found in patients in the Iberian Peninsula were similar to those found in patients of PICUs in other countries, although we found a significantly higher frequency for factors such as CVCs (femoral and jugular), cancer and sepsis. While our study was not designed to establish or rule out causality, we believe that the number of beds in the PICUs or the age of the patients should probably not be considered relevant factors.

While the percentage of patients who received PTP was similar in Iberian and international PICUs, the regimens applied diverged, with low molecular weight heparin being the most frequently used drug in Iberian PICUs and aspirin in international PICUs, which shows greater compliance of Iberian PICUs with current recommendations.1,6

Many of the patients admitted to the PICU have complex clinical conditions, and may have more than one risk factor for DVT. In our series, the median number of risk factors was 3, while in the multinational PICU study the median was 2. The median number in patients that did receive PTP was higher in countries other than Spain and Portugal (5 vs. 4).

Despite their simplicity (as in using graduated compression stockings) and their safety (since they do not carry a risk of bleeding), mechanical thromboprophylaxis measures were used rarely in Iberian PICUs, while they were used in one-fourth of candidate patients in the international PICUs. Although there is no conclusive evidence on their efficacy,1 we believe that they offer an opportunity to improve the prevention of DVT that should be taken into consideration by intensivists in children aged more than 8 years that have any risk factors.

Why is thromboprophylaxis used so rarely in critically ill children? Several factors are probably at play, such as the lack of evidence for the paediatric age group, underestimation of the risk of DVT by paediatricians, current protocols being based on expert opinions (and therefore less binding) and the varying compliance with some recommendations found in clinical practise,1,6 as well as the concern of bleeding following administration of heparin or other antiaggregant or anticoagulant drugs.7,17 Having a formal protocol for thromboprophylaxis would contribute to the homogeneous implementation of these measures. Such protocols, which are in place in over half of the PICUs in Portugal, Spain, and the remaining countries, have the drawback of being necessarily based on the extrapolation of adult data and protocols and the opinions and personal preferences of the professionals in each unit.1

There are limitations to our results that need to be taken into account. As happened in the multinational PROTRACT study, we did not gather data on the clinical outcome of patients as it relates to DVT, PE or bleeding, as the study was designed solely to determine the presence of risk factors and the thromboprophylactic measures applied. Thus, it would be interesting to conduct another study with a large enough sample of PICUs with a methodology that would make it possible to establish the clinical significance of the risk factors for DVT and PE as well as the risks and benefits (individual and comparative) of different thromboprophylactic measures.1 Such a study could provide the foundation to develop an evidence-based thromboprophylaxis protocol for the PICU.

Participation of the PICUs was voluntary, which may have led to a bias in patient characteristics. In any case, based on the characteristics of the participating Portuguese and Spanish PICUs we believe that they provide an accurate reflection of intensive care in their countries. As for the potential heterogeneity of PICUs in other countries, we consider that while their structure and work may be organised differently, since they all are in developed countries they may be comparable in terms of human and material resources, the type of admitted patients, and the procedures performed. The fact that due to administrative reasons the Portuguese and Spanish PICUs are smaller (have fewer beds) than those of other countries may have biased the results slightly, so this should be taken into account.

Although many critically ill children have more than one risk factor for DVT, thromboprophylactic measures are used infrequently in this set of patients, both in Spain and Portugal and at the international level. The use of low molecular weight heparin in Spanish and Portuguese PICUs is more frequent and widespread and mechanical thromboprophylaxis is rarely used, while the latter is used more frequently in PICUs from other countries. An effort should be made to reach a consensus on the indications and regimens of thromboprophylaxis in critically ill children.

Dr. E.V. Faustino has received support from the National Center for Advancing Translational Sciences under award numbers UL1TR000142 and KL2TR000140.

The authors have no conflicts of interest to declare.