Joint Damage Seen in Hem A Patients With Milder Disease, Few Bleeds
People whose hemophilia A is mild or moderate can show marked alterations to their joints on MRI scans, particularly in the ankles, despite having few joint bleeds, a study reported.
These findings highlight the need for closer monitoring of joint health and a likely need for preventive treatment approaches in patients with non-severe disease, its researchers said.
The study, “Joint status of patients with non-severe hemophilia A,” was published in the Journal of Thrombosis and Haemostasis.
Hemophilia A is caused by the lack of a blood-clotting protein called factor VIII (FVIII). Patients with severe disease — characterized by extremely low levels of FVIII — can experience spontaneous bleeds, often affecting the joints. In people with moderate and mild hemophilia, bleeds are sporadic and usually triggered by trauma.
MRI scans of people with severe hemophilia have shown that even in those without a history of noticeable joint bleeding, minor (subclinical) bleeds can still cause damage to joints, the researchers noted.
This suggests that people with non-severe disease may also be at risk of developing joint damage, “calling for more intensive monitoring or treatment to halt further progression,” they wrote.
As most studies have focused on patients with severe disease, a team led by researchers at the Emma Children’s Hospital in Amsterdam looked specifically at joint health in people with non-severe hemophilia A.
In total, 51 male hemophilia A patients, with a median age of 43, were randomly recruited from the DYNAMO study (NCT03623295), a large and observational study assessing bleeds in hemophilia A and B patients with non-severe disease.
Of the enrolled patients, 19 (37%) had moderate and 32 (63%) had mild hemophilia A. Over half of them had experienced a bleed in a knee (53%) and ankle (57%), while 20% had an elbow bleed. The group’s median annual joint bleeding rate (AJBR) was zero.
Bleeds were more common in moderate than mild hemophilia patients in the elbow (47% vs. 3%), knee (74% vs. 41%), and ankle (74% vs. 47%) joints.
Causes were known for almost half of the reported joint bleeds (45%). In 66% of the cases, bleeds were caused by trauma, 24% occurred spontaneously, and 10% were related to an activity.
Elbow, knee, and ankle joints were evaluated using MRI scans and scored according to the International Prophylaxis Study Group (IPSG), with alterations in joints and soft tissues recognized by sub-scores greater than zero. Higher IPSG scores are indicative of greater joint abnormalities, and the maximum score is 17 points per joint.
The median IPSG score of the entire group was four. Patients with moderate hemophilia had a median IPSG score of seven, and those with mild disease a score of four.
Soft tissue changes in the elbows were detected in 19% of patients, and such changes in the knees and ankles were seen in 71% of patients for both these joints.
Osteochondral changes — those affecting both the cartilage and the underlying bone — were detected in the knees of 20% of patients, and in the ankles of 35%. No such changes were seen in the elbows.
Researchers noted that osteochondral changes affecting the knees were detected in those over the age of 40. Osteochondral changes in the ankles were seen in 47% of patients with moderate hemophilia, and in 28% of those with mild disease.
Joint function was evaluated using the Hemophilia Joint Health Score (HJHS), whose higher scores (maximum of 20 points per joint) also indicate poorer joint health.
Patients with moderate hemophilia had significantly worse joint health (median HJHS of seven) compared with those with mild disease (median HJHS of two).
In the knees and ankles, the most common impairment was crepitus on motion, or an abnormal popping or crackling sensation upon movement (67% in knees and 14% in ankles). This was followed by flexion loss (15% in knees and 11% in ankles) and extension loss (8% in knees and 13% in ankles).
Statistical analyses revealed that age and joint bleeding rates significantly associated with poorer joint health. For ankle joints, FVIII activity was also a contributing factor.
“The results of our study show that a substantial proportion of patients with non-severe hemophilia A exhibits joint changes on MRI despite low joint bleed rates,” the researchers wrote, with “the ankles being most affected.”
These findings carry important clinical implications, the researchers added, noting that “more intensive monitoring of joint health and preventive treatment strategies are warranted, particularly for patients with moderate hemophilia.”