MRI can detect subclinical joint bleeding in severe hemophilia A

Subclinical bleeds usually cannot be detected by standard tests

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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An illustration of a patient entering an MRI scanner.

MRI screening can identify subclinical joint bleeding in some patients with severe hemophilia A on preventive treatment, according to a study in the Netherlands.

Subclinical bleeds occur without symptoms and usually cannot be detected by standard physical and ultrasound examinations.

“These MRI findings support the hypothesis that subclinical bleeding may occur despite [preventive treatment],” researchers wrote, adding that MRI might be particularly useful to assess the effect of new therapies on joint bleeding due to its ability to detect subclinical bleeds.

The study, “MRI evidence for subclinical joint bleeding in a Dutch population of people with severe hemophilia on prophylaxis,” was published in the Journal of Thrombosis and Haemostasis.

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Subclinical bleeding and inflammation can contribute to joint deterioration

Hemophilia is a bleeding disorder caused by deficiencies in certain blood clotting factors — proteins that help the blood to form clots to control bleeding — usually due to genetic mutations. This results in excessive bleeding, with patients with severe forms of hemophilia experiencing spontaneous and traumatic joint bleeds, mainly in the ankles, knees, and elbows.

Hemophilia A is caused by a deficiency in a clotting protein called factor VIII (FVIII).

Treatments mainly aim to prevent bleeds, including those occurring in the joints. With the introduction of preventive clotting factor replacement therapies (prophylaxis) — a type of treatment in which patients are given a version of the clotting protein they are missing — the number of clinically relevant joint bleeds has decreased.

However, subclinical bleeding and inflammation can contribute to joint deterioration, even in the absence of clinically evident joint bleeds. Currently, standard methods are unable to detect subclinical joint damage.

These MRI findings support the hypothesis that subclinical bleeding may occur despite [preventive treatment].

In the study, researchers in the Netherlands used MRI scans to detect possible signs of previous subclinical bleeding in patients with severe hemophilia A who were on long-term prophylaxis and had no previous history of joint bleeds.

They analyzed data from 43 adults and adolescents, with a median age of 23.5 years. Most were on prophylactic treatment with FVIII (40 patients; 93%). Three were on prophylactic treatment with Hemlibra (emicizumab): one for one year, and two for a few months before entering the study after being on FVIII prophylaxis.

Joint bleeds were rare, with patients having a median of 0.4 joints bleeds per year. The status of the joints was good, according to ultrasound, radiologic, and physical symptom scales that evaluate joint health, with no signs of abnormalities.

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MRI scans used to evaluate 43 joints without previous bleeding history

The researchers used MRI scans to evaluate a total of 43 joints (16 elbows, 13 knees, and 14 ankles) without a previous history of bleeds. Signs of previous subclinical bleeding on MRI were observed in seven of them (16%), with ankles being the most frequently affected (43%), followed by elbows (6%). The knees showed no signs of previous subclinical bleeding.

From the joints showing signs of previous subclinical bleeding on MRI, abnormalities on physical and ultrasound examinations were detected only in one ankle.

Although MRI can detect subclinical bleeding, its use for screening these bleeds in daily clinical practice is difficult due to its high cost, limited availability, and technical requirements, the researchers noted.

“Nevertheless, detecting (previous) subclinical bleeding with MRI is important with the currently emerging novel therapies (emicizumab, gene therapy) and the clinically overt bleeds becoming increasingly rare,” the team wrote.

Assessing the effectiveness of new hemophilia therapies based on clinical bleeding rates, physical, and ultrasound examination is insufficient since these methods are unable to detect subclinical bleeds, the team noted.

“MRI-based outcome measures should therefore be considered in the outcome assessment of novel nonfactor replacement therapies,” the researchers wrote.