Common and uncommon imaging manifestations of hemophilia

Jessie T.H. Yeung, MBChB, Chiu Man Lee, MBBS, Adrian X.N. Lo, MBChB, Johnny K.F. Ma, MBBS, and Julian C.Y. Fong, MBBS, Princess Margaret Hospital, Lai Chi Kok, Hong Kong

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Abstract:  emophilia is a lifelong disease causing significant morbidity and mortality, and there is a wide spectrum of clinical manifestations and imaging findings associated with this disease. In this article, the authors illustrate common and rare imaging findings of hemophilia, focusing on hemophilic arthropathy, soft-tissue hematoma, infected soft-tissue pseudotumor eroding into the pleural cavity, intramural gastrointestinal hematoma, intracranial hemorrhage, and deep venous thrombosis.

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 Dr. Yeung, Dr. Lee, Dr. Lo, Dr. Ma, and Dr. Fong are from the Radiology Department, Princess Margaret Hospital, Lai Chi Kok, Hong Kong.

Hemophilia is a lifelong disease causing significant morbidity and mortality. A wide spectrum of clinical manifestations and imaging findings is associated with this disease. Hemophilias A and B are X-linked genetic disorders; hemophilia A is due to deficiency of clotting factor VIII, while hemophilia B is due to deficiency of clotting factor IX. The incidences of hemophilia A and B are 1:5000 male and 1:25000 male, respectively.1 The most common manifestation of hemophilia is hemophilic arthropathy.2,3 The authors illustrate common and rare imaging manifestations of hemophilia, focusing on hemophilic arthropathy, soft-tissue hematoma, infected soft-tissue pseudotumor eroding into the pleural cavity, intramural gastrointestinal hematoma, intracranial hemorrhage, and deep venous thrombosis.

Common manifestation

Hemophilic arthropathy

Hemophilic arthropathy is due to repeated episodes of bleeding into the synovial joints. Hemarthrosis causes a chemical reaction between blood and the synovium and cartilage, leading to pannus formation and cartilage erosion. Damage to the subchondral bone also occurs. Recurrent hyperemia of the growing joint will cause the epiphysis to enlarge and juxta-articular osteoporosis.4-6 Typical plain radiograph findings of hemophilic knee arthropathy include a widened intercondylar notch, squaring of the patella, joint space narrowing, subchondral cysts, osteoporosis, and accelerated degenerative changes.5

Magnetic resonance imaging (MRI) can be used to detect early erosions, subchondral cysts, bone marrow edema, joint effusion or hemorrhage, synovial hypertrophy, and concurrent ligament tears (Figures 1 and 3).

Hemophilic arthropathy most commonly affects the large joints. The frequency of joint involvement is, in descending order: the knee, elbow, ankle, hip, and shoulder.7, 8 Figures 4 through 8 provide examples of MRI and computed tomography (CT) images showing less commonly affected joints and include epiphyseal overgrowth, joint surface erosions, and osteonecrosis, another finding of hemophilic arthropathy that occurs secondarily to intra-articular bleeding.4

Less common manifestations

Soft-tissue hematoma

Intramuscular or soft-tissue hematomas account for 10% to 30% of musculoskeletal hemorrhages in hemophilia.9,10 Subcutaneous hemorrhagic nodules have also been reported by Davis et al as the presenting symptom in a 9-month-old boy with hemophilia (Figure 9).11

Infected soft-tissue pseudotumors

Hemophilic pseudotumors are chronic, organized, and encapsulated cystic masses that result from recurrent hemorrhage.10,12 It is estimated that 1% of severe hemophilic patients have pseudotumors.12,13 These can be osseous or soft-tissue lesions that are also able to cross anatomical boundaries.12 They are also known to cause bone erosion and pathological fractures.5 Pseudotumors may become calcified or ossified; infection is also a potential complication (Figure 10).10,14

Intramural gastrointestinal hematoma

Intramural gastrointestinal hematomas have been described in patients with bleeding diastheses and those being treated with anticoagulants. They can result from serious or minor injuries, such as those caused by traffic accidents and endoscopy.15 They are most commonly found along the small bowel.15 Intramural hematomas can be the first presentation of hemophilia, as Griffin et al have presented a case of intramural gastric hematoma in a patient with undiagnosed hemophilia (Figures 11 and 12).15

Intracranial hemorrhage

Intracranial hemorrhage is one of the most common causes of death in hemophiliacs; young patients are most often affected. It can be the initial manifestation of hemophilia. Seizures and neurological impairments are potential complications (Figures 13 and 14).16,17

Deep venous thrombosis

Venous thrombosis has been reported in hemophilia, resulting most often from indwelling catheters.18 Non-catheter-related deep vein thrombosis has also been reported by Girolami et al and Rao et al.18,19 Predisposing factors for thrombosis in hemophiliacs include the administration of coagulation factors, surgery, infection, and prothrombotic conditions, such as a Factor V Leiden mutation and Protein C or S deficiency (Figures 15 and 16).18

Conclusion

Hemophilia is a lifelong disease causing significant morbidity and mortality. A wide range of clinical manifestations and radiological findings can be seen in this disease. Bleeding diathesis and paradoxical thrombosis can occur.

References

  1. 1. Agaliotis DP, Zaiden RA, Ozturk S. Hemophilia in: Hematology. eMedicine. http://emedicine.medscape.com/article/210104-overview. Updated Nov. 22, 2010.
  2. Soreff J. Joint debridement in the treatment of advanced hemophilic knee arthropathy. Clin Orthop Relat Res. 1984;191:179-184.
  3. Yu W, Lin Q, Guermazi A, et al. Comparison of radiography, CT and MR imaging in detection of arthropathies in patients with hemophilia. Haemophilia. 2009;15:1090-1096.
  4. Kilcoyne RF. Imaging in musculoskeletal complications of hemophilia. eMedicine. http://emedicine.medscape.com/article/401842-overview. Updated Mar 21, 2008.
  5. Dahnert W. Radiology review manual, 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2007:101-102.
  6. Maclachlan J, Gough-Palmer A, Hargunani R, et al. Hemophilia imaging: A review, Skeletal Radiol. 2009;38:949-957.
  7. Weissleder R, Wittenberg J, Harisinghani MG. Primer of diagnostic imaging. 3rd ed. St. Louis, MO: Mosby; 2003.
  8. Blickman JG, Vanderschueren G. Skeletal System. In: Blickman J, Parker B, Barnes P. Pediatric Radiology: The Requisites, 3rd ed. Philadelphia, PA: Mosby/ Elsevier; 2009:157-204.
  9. Beeton K, Alltree J, Cornwall J. Rehabilitation of muscle dysfunction in hemophilia. Haemophilia. 1990;4:532-537.
  10. D’Young A I. Conservative physiotherapeutic management of chronic haematomata and haemophilic pseudotumours: Case study and comparison to historical management. Haemophilia. 2009:15;253-260.
  11. Davis G, Butler DF, Greene J Jr. Hemorrhagic subcutaneous nodules: An initial clinical sign of hemophilia A. Pediatr Dermatol. 2007;24: 121-124.
  12. Park J S, Ryu K N. Hemophilic pseudotumor involving the musculoskeletal system: Spectrum of radiologic findings. AJR Am J Roentgenol. 2004;183:55-61.
  13. Ahlberg AK. On the natural history of hemophilic pseudotumor. J Bone Joint Surg Am. 1975; 57:1133-1136.
  14. Auger MJ, Critchley M, McVerry BA. Unusual presentation of a large infected hemophiliac pseudotumor in an autologous indium-111 WBC scan. Clin Nucl Med. 1986;11:568-569.
  15. Griffin PH, Schnure FW, Chopra S, et al. Intramural gastrointestinal hemorrhage. J Clin Gastroenterol. 1986;8:389-394.
  16. Rodriguez V, Schmidt KA, Slaby JA, Pruthi PK. Intracranial haemorrhage as initial presentation of severe haemophilia B: Case report and review of Mayo Clinic Comprehensive Hemophilia Center experience. Haemophilia. 2005; 11:73-77.
  17. Nelson MD Jr, Maeder MA, Usner D, et al. The Hemophilia Growth and Development Study-Prevalence and incidence of intracranial haemorrhage in a population of children with haemophilia. Haemophilia. 1999;5:306-312.
  18. Rao AN, Kumar R, Arteaga GM, et al. Non-catheter-related internal jugular vein thrombosis in a patient with severe haemophilia A. Haemophilia. 2009;15:1339-1340.
  19. 1Girolami A, Scandellari R, Zanon E, et al. Non-catheter-associated venous thrombosis in hemophilia A and B. A critical review of all reported cases. J Thromb Thrombolysis. 2006; 21:279-284.

Tables & Figures

  • Figure 1. Knee radiographs of a 23-year-old male patient with hemophilia A and recurrent hemarthrosis of right knee. (A and B) Bilateral tibiofemoral joint space narrowing, osteophytes and subchondral cystic changes, together with intercondylar notch widening and squaring of patella are compatible with hemophilic arthropathy.
    Figure 1.
  • Figure 2A. MRI right knee of the same patient as in Figure 1. Images demonstrate a T2*WI (A*) sagittal view, T1WI (B*) with contrast and fat saturation, and (C) a T1WI, coronal view. There is small amount of joint effusion with hemosiderin deposition, which are hypointense on all sequences. Synovial enhancement is compatible with synovial hypertrophy (arrows), associated cartilage loss and articular erosions of the joint surfaces are seen. There is also evidence of subchondral cysts, squaring of patella, enlargement of intercondylar notch, and epiphyseal hypertrophy on MRI. *These images were presented at the AOSPR Congress in 2011 as a poster.
    Figure 2A.
  • Figure 2B.
    Figure 2B.
  • Figure 2C.
    Figure 2C.
  • Figure 3A. Right elbow radiograph of a 15-year-old boy with hemophilia A and spontaneous onset of right elbow swelling. There is high-density soft tissue swelling with elevation of anterior and posterior fat pads, indicative of hemarthrosis (A). Epiphyseal hypertrophy, enlargement of the olecranon fossa and premature degenerative changes are in keeping with hemophilic arthropathy (B).
    Figure 3A.
  • Figure 3B.
    Figure 3B.
  • Figure 4A. Coronal MRI of the left elbow of a 16-year-old boy with severe hemophilia. Images featured include STIR (A) and T1WI (B*) with contrast and fat saturation. Olecranon fossa is enlarged. Small amount of joint effusion and small subchondral cysts are seen. There is mild joint space narrowing over the ulnar aspect, suggestive of cartilage loss. Linear contrast enhancement over the capitulum is compatible with mild synovial hypertrophy (arrows). *This image was presented at the AOSPR Congress in 2011 as a poster.
    Figure 4A.
  • Figure 4B.
    Figure 4B.
  • Figure 5.  Right ankle radiograph of a 25-year-old man with known hemophilia B. There is marked joint space narrowing. A mild tibiotalar slant is also present. Sclerosis and flattening of talus are suggestive of osteonecrosis.
    Figure 5.
  • Figure 6. A left hip radiograph of a 24-year-old patient. There is marked erosion of the femoral head and juxta-articular osteoporosis.
    Figure 6.
  • Figure 7. Left shin USG with Doppler. Ultrasound of shin of a 2-year-old boy with hemophilia B who developed spontaneous onset of left shin swelling and bruising. Ultrasound was performed around 5 days after onset of swelling. A collection of mixed echogenicity, mainly hypoechoic at the centre, is seen over the left shin, compatible with subcutaneous hematoma. *This image was presented at the AOSPR Congress in 2011 as a poster.
    Figure 7.
  • Figure 8A. CT thorax (A and B*) of a 50-year-old male patient with hemophilia B. A large organized, septated and encapsulated collection is seen over the back. Findings are compatible with a pseudotumor. Calcifications are seen within the pseudotumor. The pseudotumor extends from the lower posterior cervical region to the lumbar level. Gas pockets within the pseudotumor are due to active infection. Another pseudotumor is present over the right lateral chest wall (C). It has eroded the underlying rib and extended into the pleural cavity. Rim enhancement and gas pockets are also due to infection. *These images were presented at the AOSPR Congress in 2011 as a poster.
    Figure 8A.
  • Figure 8B.
    Figure 8B.
  • Figure 8C.
    Figure 8C.
  • Figure 9A. A CT abdomen performed for a 25-year-old man with known hemophilia B, who developed generalized abdominal pain. Images featured include precontrast CT abdomen (A*), postcontrast CT abdomen (B*), and postcontrast coronal reformat (C). There is hyperdense wall thickening along segments of small bowel loops, compatible with intramural hematoma. *These images were presented at the AOSPR Congress in 2011 as a poster.
    Figure 9A.
  • Figure 9B.
    Figure 9B.
  • Figure 9C.
    Figure 9C.
  • Figure 10. CT brain scan of a 50-year-old man with hemophilia A admitted because of headache. Acute subdural hematoma is seen over the left cerebral hemisphere, extending to the falx cerebri. Patient also developed facial twitching. He was treated conservatively with factor VIII and anticonvulsants.
    Figure 10.
  • Figure 11A. CT right lower limb of the same patient as Figure 9. (A) Thin strands of filling defects with calcification are seen within the contracted lumen of superficial femoral vein, suggestive of chronic thrombosis with recanalization. Large superficial venous varices are seen within the Quadriceps femoris muscle. Muscle atrophy with fatty infiltration is also evident. (B) Round collection with faint peripheral calcifications is seen in the Bicep femoris muscle, compatible with chronic collection  pseudotumor. (C) Marked muscle atrophy is seen over the lower calf, where skin thickening due to chronic venous ulcer is also seen. There is also cortical thickening of the underlying tibia and fibula due to periosteal reaction.
    Figure 11A.
  • Figure 11B.
    Figure 11B.
  • Figure 11C.
    Figure 11C.
  • Figure 12. Lower-limb radiograph of patient in Figure 11. Solid periosteal reaction due to chronic venous insufficiency is better demonstrated on radiograph. There is also widening of the intercondylar notch of the knee, and fusion of the knee and ankle, due to hemophilic arthropathy.
    Figure 12.