Point-of-care ultronography can help detect subclinical hemarthrosis in hemophilic patients undergoing regular optimal clotting factor prophylaxis to achieve zero bleeding

Joint bleeding (hemarthrosis) from childhood in one or more joints (elbows, knees, ankles) is the hallmark of hemophilia due to a deficiency of one of the coagulation factors: factor (F) VIII in hemophilia A, F IX in hemophilia B, and arthropathies are bleeding complications. Severe acute hemarthroses are very painful and therefore easy to diagnose even by clinical examination. Repeated hemarthroses may lead to synovitis, and then to a vicious circle of hemarthrosis-synovitis-hemarthrosis. This vicious circle eventually causes the destruction of the articular cartilage, which eventually leads to degeneration of the joint (hemophilic arthropathy), which ends up being deformed and painful, causing more or less severe disability to the patients [1,2]. However, not all hemarthroses lead to chronic synovitis. On the other hand, only a few bleeds may lead to chronic synovitis. On the other hand, not only can severe hemarthrosis trigger and lead to arthropathy, but small or mild bleeding can also have the same effects. Adult patients are very frequently conscious about the incoming bleeding (the so-called ‘aura’) and only early treatment or prophylaxis can avoid the trigger of arthropathy.

With primary prophylaxis from childhood and throughout the patient’s life, which is the gold standard of current hemophilia treatment, the aim is to ensure that no joint bleeding occurs in any of the aforementioned joints (0 joint bleeds) [3–6]. Unfortunately, this does not always occur, and some patients suffer a certain degree of hemophilic arthropathy that is considered to be due to one or several subclinical hemarthroses [7]. Therefore, it seems essential to be able to detect such subclinical hemarthroses in some way.

There is no doubt that magnetic resonance imaging (MRI) is the best technique to detect subclinical hemarthroses due to the higher resolution power, but some authors have published that ultrasonography (USG) can reliably detect hemarthroses. In 2012 Querol and Rodriguez-Merchan stated that USG was particularly important in acute hemarthrosis, as it could be used to objectively identify the presence of blood in the joints, measure its size, pinpoint its location, assess its evolution and confirm its complete disappearance [8]. In 2014 Sierra Aisa et al affirmed that USG was useful in detecting joint bleeds, synovial hyperplasia and joint erosions, with results comparable to those of MRI. A quick and affordable technique, USG may be useful for monitoring joint bleeds and structure normalization and maintenance in routine practice [9].

For the past 30 years, USG has been used to explore hemophilic joints to detect whether fluid (blood) and/or synovitis was present in them. USG diagnosis of hemarthrosis and hemophilic synovitis has come a long way, although the goal of zero hemarthrosis in all patients on primary prophylaxis has not yet been achieved [10–14]. The question that arises is therefore the following: could we use USG to detect the existence of subclinical hemarthrosis that do not cause pain to the patient and therefore do not go to the doctor? And this, especially during childhood, which is when these bleedings can occur and go unnoticed.

In short, I believe that periodic USG examination of the joints of hemophiliac children and adults can help to detect the presence of blood in a joint, and depending on this finding, act accordingly (adjust the prophylaxis).

According to Acharya et al, USG-Power Doppler Sonography (USG-PDS) is an inexpensive and easily implemented imaging tool for detecting hemophilic synovitis [15]. Contrast-enhanced ultrasound (CEUS) can more accurately assess the degree of synovial hypertrophy and vascularization and diagnose synovitis as compared to conventional ultrasound [16].

The current trend is that in centers specializing in the treatment of hemophilia, its members (hematologists, physiatrists, orthopedic surgeons and physical therapists) practice USG, with greater or lesser success and in greater or lesser proportion. Therefore, learning USG scanning should be generalized, so that all centers have experts in USG diagnosis of the joint complications of hemophilia (hemarthrosis, synovitis, and cartilage and bone damage). Ideally, it would be ideal to have radiologists dedicated to this topic, but unfortunately they do not seem to be very interested in the subject (something similar must have happened with USG in gynecology).

Another big problem is that hemophilia being a very rare disease, in general patients live far away from the specialized hemophilia center, which is why some centers are carrying out basic teaching courses on USG to the patients themselves, so that by means of telemedicine the specialized center can evaluate these images and decide on the guidelines to follow (especially in the detection of hemarthrosis, even if it is of low intensity) [17]. However, the economic cost of providing each patient with an ultrasound machine at home, and the evaluation of the images by telemedicine can become a serious charge of work for the specialized centers.

In short, I believe that all centers treating patients with hemophilia (children and adults) by primary prophylaxis should have point-of-care (POC)-USG equipment, operated by experts in the use of this diagnostic tool (ideally radiologists). Moreover, such POC-USG should be carried out periodically from infancy in these patients in order to detect (or not) any hemarthrosis however small (i.e. asymptomatic or subclinical), so that it can help hematologists to adjust treatment (if necessary) with the goal we all desire: 0 hemarthrosis, i.e. no hemophilic arthropathy in patients with hemophilia.

In this Editorial I have tried to underline the need of regular, noninvasive monitoring of joint health from early infancy in hemophilic patients to detect subclinical bleeding which could affect long-term joint health. However, I must remember that there are patients who are monitored in small centers that do not have USG. So the question arises as to what to do with these patients: are they being discriminated against compared to patients managed in major centers? The answer to this question is yes. Therefore, I believe that these patients should somehow be monitored in major centers.

Besides, I think that subclinical bleeding must also be monitored in patients with moderate or mild hemophilia because it is well known that arthropathy might develop also in these patients. This will involve a lot of work, but I believe that all hemophilic patients deserve to be treated equally by the doctors who are in charge of them.

The prevention of hemophilia arthropathy to achieve the goal of zero hemarthroses should be very difficult to realize by the implementation of periodic joint USG because only one bleeding does matter; when the USG is able to detect the bleeding it is too late.

It is complicated to define the interval of regular checks of the joint condition of hemophilia patients because it depends on many factors as the age of the patients, the availability of a POC-USG, the expertise of hematologists, and many other factors. Ideally, periodic evaluations should be performed every month.

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The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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