|Year : 2020 | Volume
| Issue : 1 | Page : 63-67
Radiological aspects of musculoskeletal complications in three hemophilic patients with long-term follow-up
Ousmane Aminata Bah1, Jawad Mesrar2, Alpha Abdoulaye Balde3, Abarchi Habibou Boube4, Mamadou Oury Bah3, Lantam Sonhaye4, Douraied Ben Salem5, Mar Garetier6
1 Department of Radiology, Cavale Blanche Hospital, CHRU Brest, University of Western Brittany, Brest, France; Department of Radiology, Donka National Hospital, Conakry University Hospital, University of Conakry, Guinea
2 Department of Radiology, Cavale Blanche Hospital, CHRU Brest, University of Western Brittany, Brest, France
3 Department of Radiology, Donka National Hospital, Conakry University Hospital, University of Conakry, Guinea
4 Department of Radiology, University of Lome, University Campus Lome, Lome, Togo
5 Department of Radiology, Cavale Blanche Hospital, CHRU Brest, University of Western Brittany; LaTIM, INSERM, UMR 1101, Univ Brest, Brest, France
6 LaTIM, INSERM, UMR 1101, Univ Brest; Department of Radiology, HIA Clermont Tonnerre, Brest, France
|Date of Submission||05-Jul-2018|
|Date of Acceptance||28-May-2019|
|Date of Web Publication||13-Mar-2020|
Dr. Ousmane Aminata Bah
Department of Radiology, Cavale Blanche Hospital, University of Western Britany, Brest; Department of Radiology, Donka National Hospital, Conakry University Hospital, University of Conakry
Source of Support: None, Conflict of Interest: None
Objective: The objective of the study is to describe the radiological aspects of musculoskeletal complications of hemophilia found in three patients.
Patients and Methods: It is a retrospective review of clinical and radiological records of three known and followed hemophilic patients, whose radiological examinations were carried out and archived on the Picture Archiving and Communication System of the University Hospital.
Results: The three patients were male with severe hemophilia A, using recombinant factor VIII replacement therapy on demand, followed during 10 years. Joint bleeding was the most frequent complication. We found hemarthrosis at ultrasound in two patients (one after a minor trauma of the knee and one after repeated traumas of the ankle) and at magnetic resonance imaging (MRI) in the three patients (three in the knee and two in the ankle) and chronic arthropathy in two patients (two in the knee and one in ankle. The muscular lesions detected at ultrasound were hematomas of the left soleus muscle, right vastus medialis muscle, and right rectus abdominis muscle.
Conclusion: Bleeding in hemophilic patients affects both muscles and joints, with long-term consequences for the joints. Medical imaging was very useful for the detection and follow-up of joint and muscle lesions in these three patients, based on ultrasound and MRI with T2* sequence.
Keywords: Hemophilia, imaging, musculoskeletal complications
|How to cite this article:|
Bah OA, Mesrar J, Balde AA, Boube AH, Bah MO, Sonhaye L, Salem DB, Garetier M. Radiological aspects of musculoskeletal complications in three hemophilic patients with long-term follow-up. West Afr J Radiol 2020;27:63-7
|How to cite this URL:|
Bah OA, Mesrar J, Balde AA, Boube AH, Bah MO, Sonhaye L, Salem DB, Garetier M. Radiological aspects of musculoskeletal complications in three hemophilic patients with long-term follow-up. West Afr J Radiol [serial online] 2020 [cited 2022 May 24];27:63-7. Available from: https://www.wajradiology.org/text.asp?2020/27/1/63/280604
| Introduction|| |
Hemophilia is a congenital disorder of the hemostasis that is linked to X chromosome. This chromosome is responsible for the deficiency in factor VIII in hemophilia A and factor IX in the B subtype., It is a rare pathology with a global incidence ranging from 1/5000 to 1/10,000 for hemophilia A and from 1/20,000 to 1/25,000 for hemophilia B., Hemophilia biological examination is marked by lengthening of the activated partial thromboplastin time (APTT) compared to that of control plasma. The rate of missing factor determines the severity of this disease that can be rough when it is 30% greater than the normal value (normal hemostasis), minor between 5% and 30%, moderate between 1% and 5%, and severe if <1%., The most common complications of hemophilia are the occurrence of joint and muscular hemorrhages. Imaging is useful for the detection and surveillance of these complications.
The objective of this work is to review the radiological aspects of musculoskeletal complications of hemophilia in three patients followed during long term.
| Patients and Methods|| |
We analyzed the clinical and radiological records of three known and followed hemophiliac patients whose radiological examinations (X-rays, ultrasounds, and magnetic resonance imaging [MRI]) were performed and archived on the Picture Archiving and Communication System of our University Hospital.
| Results|| |
The three male patients had a severe form of type A hemophilia, initially diagnosed in their 1st year of life. None of these patients used replacement therapy by recombinant factor VIII concentrates during their first 10 years of life.
He was 24 years old in 2017, with a weight of 55 kg.
In 2009, an urothelial hematoma of the left ureter was diagnosed by computed tomography (CT) and treated with factor VIII (Advate®) 2000 units at the dose of two injections per day for 3 days.
In 2012, he presented an acute pain of the left calf. Ultrasonography showed a spontaneous hematoma of the left soleus muscle treated with factor VIII Advate® 2000 units at the dose of two injections per day for 4 days. He then started after a prophylaxis with Advate® 2000 units at a dose of three injections per week and a steroid therapy by cortencyl at a dose of 50 mg per day in the morning for a month.
The patient was noncompliant, with nonregular prophylaxis until 2014, when he consulted for a hematoma of the right vastus medialis muscle diagnosed on ultrasound and also treated with Advate® 2000 units at a dose of two injections per day for 3 days. Prophylaxis with Advate® 2000 units at a dose of three injections per week had been proposed. He had a factor VIII <1%, a fibrinogen elevation of 7.69 g/l, a prothrombin time (PT) at 13.8 s (normal reference level at 13 s), and increased cephalin kaolin time (CKT) and APTT, respectively, at 2.83 and 3.26.
In 2015, he consulted for an increased volume of the right knee with limited flexion, following several episodes of trauma. Hemoglobin levels were normal at 13.4 g/dl with mean corpuscular volume (MCV) of 80 μg, normal platelet count of 329 μg/l, factor VIII level <1%, and anti-factor VIII level being normal below 0.4 Unit Bethesda (UB). MRI found hemarthrosis and arthropathy of the right knee, with synovial hypertrophy of the suprapatellar recess, which appeared in high signal on proton-density weighted sequence with fat saturation, enhanced after gadolinium injection, associated with a deposit of hemosiderin in low signal on T2* sequence. He received joint and muscular rehabilitation and continued regular prophylaxis three times a week.
The hypertrophy of the right knee persisted, with a slight limitation of the flexion without pain, which did not seem to interfere with daily life. Prophylaxis was well followed. In 2017, a radiography of the knee showed joint effusion. MRI confirmed hemophilic synovitis of both knees predominantly on the right [Figure 1] and also confirmed osteochondral involvement of the left femorotibial joint. Prophylaxis was always well followed. Hemoglobin and platelet levels were normal, APTT was elevated at 2.52, and factor VIII was <1%.
|Figure 1: Hemophilic arthropathy of the right knee with synovitis (Patient 1). The profile radiography of the right knee showed a joint effusion inside suprapatellar recess (a). This was linked to a synovial hypertrophy of the suprapatellar recess which appeared in high signal in proton density sequence with fat saturation (b), associated with a deposit of hemosiderin in low signal in T2* sequence (c) and contrast enhancement in T1-weighted sequence after fat saturation and gadolinium injection (d)|
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He has 33 years old in 2017, with a weight of 78 kg, under self-treatment with factor VIII (Helixate®) 3000 units per injection on demand.
He had a history of hemarthrosis of the left ankle without significant trauma, confirmed by an MRI in 2009 which showed an effusion inside the talocrural joint in low T1 signal and high T2 signal with fluid–fluid levels. The hemoglobin level was normal at 15.7 g/dl with MCV of 87 ug, platelets of 214 g/l, leukocytes of 5.2 g/l, PT at 13.5 s (normal reference level at 13.1 s), increased APTT and CKT at 2.41 and 2.69, respectively, normal fi brinogen at 2.45 g, factor VIII <1%, normal anti-factor VIII level <0.5 UB, and ferritinemia at 376 g/l.
In 2010, a splenectomy was performed after abdominal trauma.
He consulted in 2017 for episodes of left ankle hemarthrosis. This ankle was stiffed, with preserved mobility at clinical examination. MRI found left talocrural hemophilic arthropathy, with bone defect of the tibia, synovial hypertrophy, and hemosiderin deposits on the periphery of the joint appearing as low signal in T2* sequence [Figure 2]. He was treated subsequently regularly with Elocta® 3000 units twice a week in self-injection.
|Figure 2: Hemophilic arthropathy of the left ankle with osteochondral involvement (Patient 2). Magnetic resonance imaging showing in sagittal T2 STIR sequence (a) and in coronal T1 (b) and fat-saturated proton density sequences; (c) a narrowing of the talocrural joint with cartilaginous ulcerations, bone edema and subchondral cysts.|
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A treatment by Elocta® 3000 units two times per week in auto-injection was proposed and well followed, without need for surgery. The blood test found an international normalized ratio at 1, an increased APTT at 2.3, and a factor VIII level below 1%.
He has 22 years old in 2017, with a weight of 64 kg, treated with factor VIII Advate® 2000 units by injection on command.
In 2007, a spontaneous renal hematoma was diagnosed by CT and treated with Advate® 2000 units at the dose of two injections per day during 5 days and then at the prophylactic dose of three injections per week.
Prophylaxis was not regular. In 2013, he developed a spontaneous hematoma of the right rectus abdominis muscle diagnosed by ultrasound [Figure 3] and a synovitis of the right knee diagnosed on MRI. Factor VIII was <1%. He was treated with Advate® 2000 units at a dose of two injections per day for 3 days and subsequently with prophylactic Advate® 2000 units at a dose of three injections per week.
|Figure 3: Hematoma of the right rectus abdominis muscle (Patient 3). Ultrasonography showing an hyperechoic intramuscular hematoma inside the right rectus abdominis muscle|
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Until 2017, he did not have any complaint or recent clinical or radiological bleeding event. The hemoglobin level and prothrombin ratio were normal, with a slight elevated APTT ranging between 1.30 and 1.50, a factor VIII gradually increasing to 6% at last controls.
| Discussion|| |
Hemophilia A was present in three patients of our case series. This type of hemophilia is the most common form, with estimated prevalence between 68% and 85% according to the literature. The severe form is the most common in Western countries, unlike in Africa where Benajiba et al. and Diop et al. in Senegal reported a predominance of the minor and the moderate forms. The complications of hemophilia are mostly joint bleeding (hemarthrosis) in the acute period and hemophilic arthropathy in the chronic period. The hemophilic arthropathy starts first with synovitis and secondarily osteochondral impairment takes place. However, hemophilia complications can also be muscular in the form of a hematoma.
Joint damages are the leading cause of morbidity in severe hemophiliac patients., These lesions are the result of spontaneous recurrent hemarthrosis, usually starting before 2 years of life (walking–learning period). It is not completely preventable under primary prophylaxis. Progression of joint lesions can be slowed by secondary prophylaxis as well as primary.
We had two cases of hemarthrosis in our patients. One case followed a minor trauma of the right thigh (Patient 1) and the other one repeatedly occurring in the left ankle (Patient 2).
Standard radiography is of little interest in the acute phase. It can show a displacement of the fatty edgings around the joint. Nevertheless, standard radiography remains unspecific because it is unable to differentiate between synovitis and intra-articular fluid effusion, unlike ultrasound or MRI. However, it mainly visualizes bone lesions appearing late in the process of hemophilic arthropathy. Hemarthrosis is visualized in ultrasound in the form of an intra-articular echogenic effusion. It can be drained under ultrasound guidance with the aim to relieve the pain depending on its abundance.,
According to some authors, Doppler energy study could be used to determine whether bleeding is active or not., The MRI signal of hemarthrosis depends on the age of the blood and is variable under time. It is usually heterogeneous, from high T1 signal and low T2 signal during acute phase, and then high signal in T1- and T2-weighted sequences in subacute phase due to the presence of methemoglobin. Sometimes, we can observe fluid–fluid levels which are better visible in T2-weighted sequences. Finally, hemarthrosis can be seen as a nonspecific fluid effusion in low T1 signal and high T2 signal in the late stage.,
Synovitis-Type joint damage was observed in the three patients of our series. Two of them suffered from chronic hemophilic arthropathy (Patients 1 and 3). Hisaya et al. reported 105 cases of synovial hypertrophy alone or associated with hemosiderin deposition out of 116 cases (90.5%), which was the major joint lesion detected by MRI in the annual assessment of hemophilic arthropathies during 7 years. None of our patients were on primary prophylaxis. Oldenburg et al. reported less injury in prophylaxis patients, especially those who started prophylaxis at a younger age compared to patients on-demand treatment. Synovial hypertrophy usually appears as intermediate signal in T1- and T2-weighted sequences, unlike articular fluid appearing in low T1 signal and in marked high T2 signal sometimes sloping., However, when the synovial hypertrophy is active, it can adopt a signal close to the liquid. The injection of gadolinium can help to distinguish between active synovitis, fibrous synovitis, and joint liquid that is usually associated. However, fibrosis and hemosiderin within the synovial proliferation limit the visibility of contrast taking., Synovial deposits of hemosiderin, in combination or not with synovial hypertrophy, can be unique, multiple, or diffuse. These deposits appear in a black signal due to the magnetic susceptibility artifacts that they generate. The synovial deposits detection is optimized by the use of T2 gradient echo sequences (T2*).
Chronic hemophilic arthropathy would be due to the direct effects of blood on the articular cartilage, reinforced by persistent chronic synovitis and recurrent hemarthrosis., The progressive deterioration of the cartilage is generally observed from the second decade onward, but in some cases, it may occur earlier, depending on the number and the severity of the bleedings. Standard radiography detects osteochondral alterations only at the late stage, in the form of diffuse tight joints, osteophytes, erosions, and marginal or central large size cavities, contrasting with a little-marked pinch. Standard radiography also undervalues the importance of joint damage., Ultrasound can help to diagnose and objectify cartilage anomalies (irregularities, erosions, and hyperechogenic areas), marginal bony erosions (defects of bony contours), and osteophytes. An ultrasound score based on the rating of the hemarthrosis, synovial hypertrophy, hemosiderin deposition, erosion and bone remodeling, and cartilage modification was proposed by Melchiorre et al. in 2011. Compared to the radiography, MRI remains the first choice examination in the exploration of hemophilic arthropathy,, particularly for the early detection of the subchondral bone damage.,, Subchondral edema is seen in low signal in T1-weighted sequence and high signal in T2-weighted sequence after suppression of the fat signal. Hemophilic arthropathy usually has a very variable signal according to the joint alterations: low T1 signal and high T2 signal for the liquid component and synovial hypertrophy, low signal in T1- and T2-weighted sequences for the fibrous component and hemosiderin deposits, and high signal in T1- and T2-weighted sequence for the hemorrhagic component.
Knee and ankle were the main joints affected in our cases. This is due to the frequency of falls in childhood as well as the number of restricted mobility scope of these joints, for which any movement outside the conventional mobility range leads to capsular-synovial elongation that can be a source of hemorrhage. Elbow is also a joint often affected but not observed in our case series.
The hematomas of the soft tissue were described in two patients with or without minor trauma (hematoma of the right soleus muscle and the right vastus medialis for Patient 1 and hematoma of the right rectus abdominis muscle for Patient 3). The diagnosis was brought by ultrasound to specify the exact size and topography of the hematomas (subcutaneous, inter-, or intra-muscular location). The hematoma was seen in the form of an intra-muscular collection responsible for a mass effect on the injured muscle. Its appearance is variable in time. It could pass in a few hours from a hyperechogenic stage to a hypo- or non-echogenic aspect.
Ultrasound or MRI can also be used to study the relationship and the potential impact on the surrounding neurovascular structures. The absence of a full regression of these hematomas under treatment may favor iterative bleedings and consequently the development of pseudotumors.
None of the three patients presented hemophilic pseudotumor, osteoporosis, fractures, or osteonecrosis during the study period.
The clinical history of hemophilia is often evident and the question of differential diagnosis with other juvenile arthropathies rarely arises. The main differential diagnosis is established between hemophilic arthropathy and pigmented villonodular synovitis on MRI. In contrast to hemophilia, pigmented villonodular synovitis affects only one joint with a more intense postgadolinium enhancement of the synovial hypertrophy.,
| Conclusion|| |
Hemophilia is a rare pathology that can be responsible for musculoskeletal complications. Bleeding in hemophilic patients affects both muscles and joints, with long-term consequences for the joints. Medical imaging was very useful for the detection and follow-up of joint and muscle lesions in these three patients, based on ultrasound and MRI with T2* sequence.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]