Hemarthrosis

Etiology

Many diseases and disorders can present with hemarthrosis. However, categorization is generally divided into traumatic, non-traumatic, and postoperative. Traumatic injury is the most common cause of hemarthrosis.

Non-traumatic hemarthrosis can be caused by a variety of bleeding disorders that are either hereditary or acquired. Hereditary bleeding disorders include hemophilia and other inherited coagulation factor deficiency disorders. Examples of acquired bleeding disorders include advanced liver or renal disease, vitamin K deficiency, disseminated intravascular coagulation, or anticoagulation medication use. Other more rare causes of non-traumatic hemarthrosis include the following:

• Neurologic: Reflex sympathetic dystrophy, diabetic neuropathic arthropathy 
• Infectious: Septic bacterial arthritis
• Vascular: Vitamin C deficiency, ruptured peripheral artery aneurysms, osteoarthritis (degenerative tears of peripheral arteries associated with a posterior horn of the lateral meniscus)
• Neoplasms: Benign synovial hemangiomas, pigmented villonodular synovitis, or any malignant tumor arising near a joint cavity or metastatic[1][2]

Post-operative recurrent hemarthrosis is frequently associated with total knee arthroplasty and has also been described as an uncommon complication following arthroscopy.[3]

Epidemiology

The exact prevalence of hemarthrosis in the hemophiliac population is unknown; however, there have been reports that approximately 50% will develop hemarthrosis at some time during their life. Joint trauma increases the chance of developing hemarthrosis in this population.[4] Based on a cohort study of 1145 consecutive patients who developed a traumatic hemarthrosis of the knee, approximately half had an anterior cruciate ligament (ACL) injury, and the annual incidence of ACL injury was 77 per 100,000 inhabitants with a significant difference between men (91 per 100,000) versus women (63 per 100,000). In those 16 years of age or younger, lateral patellar dislocation was the most frequent structural injury associated with traumatic hemarthrosis of the knee both in boys (39%) and girls (43%); in this age group, the annual incidence of lateral patellar dislocation was 88 per 100,000 and higher in boys (113 per 100,000) than girls (62 per 100,000).[5]

Pathophysiology

Traumatic hemarthrosis typically occurs in the setting of intra-articular injury with ligamentous, osseous, and/or cartilage damage leading to a bloody synovial fluid collection. Post-operative hemarthrosis from total knee arthroplasty has been attributed to the development of intra-capsular vascular tissue which subsequently causes bleeding into the joint after joint replacement surgery. The development of a lipohemarthrosis stems from marrowfat leakage into the synovial fluid; this is usually the result of intra-capsular fractures or extensive intra-articular soft tissue injury.[6]

Histopathology

The histopathology of hemophilic arthropathy can be divided into early and late disease characteristics. In early disease, there is synovial hypertrophy and fibrosis which displays changes similar to rheumatoid arthritis. Progression of the disease shows disruption of cartilage and subchondral cyst formation from interosseous bleeding. The intra-articular bleeding has direct toxic effects leading to the destruction of cartilage and bone. Iron in the form of ferric citrate stimulates human fibroblast cells to proliferate. Studies involving mice imply hemarthrosis leads to blood vessel hyperplasia which may explain the predisposition for hemophiliacs to experience recurrent intra-articular bleeding.[7][8]

Toxicokinetics

Rodenticides are superwarfarins that, upon ingestion, can cause spontaneous bleeding including acute hemarthrosis. Patients can be asymptomatic up to 72 hours after ingestion. Gastrointestinal symptoms can be present early in the course of poisoning, and spontaneous bleeding can present as early as 8 hours after exposure.

History and Physical

In most patients, especially those without pre-existing neurologic sensation dysfunction or bleeding disorders, a traumatic incident is known to the patient, and the cause of the hemarthrosis is suggestive from history. Following an injury with intra-articular damage, the swelling from bloody synovial fluid accumulation is typically rapid within a few hours. Pain is a significant component, however, may take time to develop, or may be minimal or absent in patients with pre-existing impaired sensation. The range of motion of the affected joint is typically significantly reduced.

Certain locations and types of injury following a traumatic incident are more likely to develop a hemarthrosis. Intra-articular elbow fractures including those of the radial head are universally associated with hemarthrosis. The knee is a frequent site of hemarthrosis with the most common mechanism being forced twisting of the loaded joint. The majority of these post-traumatic hemarthroses are from ligamentous and meniscal damage. Anterior cruciate ligament (ACL) tears are the most common, representing 70% of post-traumatic hemarthrosis of the knee, followed by 10% to 15% patellar subluxation/dislocation injuries, 10% from meniscal tear, 2% to 5% from osteochondral fracture fragments, and 5% represented from other injuries including posterior cruciate ligament (PCL) or capsule tears. Depending on the site and kind of injury, tenderness to palpation of the joint lines or patella will be present and clinical tests for joint laxity may be positive.[9]

Lipohemarthrosis indicates either a fracture with intra-articular extension or significant intra-articular soft tissue injury (ligamentous or meniscal). If a lipohemarthrosis of the knee is identified, suspect in order of likelihood: tibial plateau fracture (lateral plateau fractures often associated with ACL and MCL injuries), tibial spine avulsion (anterior attachment point of ACL and more common in pediatric patients who have tougher ligaments than bones), and femoral condyle fracture (uncommon, however, associated with popliteal artery and fibular nerve injury).

If hemarthrosis occurs spontaneously or after minimal trauma, bleeding disorders such as hemophilia should be suspected. Hemarthrosis is the most common musculoskeletal manifestation of hemophilia. Severe hemophilia (less than 1% of normal factor activity) causes hemarthrosis in 75% to 90% of patients with the first attack typically occurring between ages 2 to 3. Any joint can be affected; however, the knee is the most common site. Patient history regarding family history, extensive or prolonged bleeding during or after surgery, use of anticoagulant medications, and diet habits should be elicited to help determine whether the presence of a bleeding diathesis exists.[10]

Clinical presentation of hemophilia with hemarthrosis can vary by age. In adults and older children, there is typically a prodromal stiffness or tingling which precedes pain and swelling. In infants, signs of hemarthrosis may include irritability and decreased use of the affected limb. Bleeding into the hip joint is concerning due to the greater risk of increased intra-articular pressure and osteonecrosis of the femoral head. In hemophilic hemarthrosis, one joint is typically affected at a time; however, bilateral joint involvement is possible.[11][10]

Evaluation

A suspected hemarthrosis can be evaluated by plain radiographs, computed tomography (CT) scan, or magnetic resonance imaging (MRI). The preferred initial imaging modality is plain film radiology of the involved joint and surrounding bones. If a fracture is not seen but strongly suspected, further evaluation with a CT scan is warranted. MRI may be able to diagnose ligamentous or other soft tissue injuries as the cause of hemarthrosis. Ultrasound (US) in the right clinical setting can help identify and characterize intra-articular fluid collections.[12]

Arthrocentesis and joint aspirate fluid analysis may be required for definitive diagnosis. The synovial fluid from a hemarthrosis may appear red, pink, or brown depending on the cause of bleeding. Aspiration of the joint and subsequent analysis can differentiate simple effusion, hemarthrosis, lipohemarthrosis, and septic arthritis. Arthrocentesis can also provide significant relief of pain for the patient. The presence of lipid globules in the aspirate represents a lipohemarthrosis. If the initial synovial fluid aspirate is non-bloody but bright red blood soon appears after withdrawing fluid, then this is indicative of a traumatic hemarthrosis. A true hemarthrosis typically does not clot due to fibrinolysis compared to a bloody aspirate from traumatic aspiration that does coagulate. Centrifugation of the synovial fluid aspirate and examination of the supernatant may also be helpful to discern the difference between true hemarthrosis and traumatic aspiration; a true hemarthrosis will display a serous appearance of the synovial fluid supernatant with xanthochromia.[13]

Lipohemarthrosis can be detected by arthrocentesis, plain radiographs, CT scan, MRI, and in a minority of patients by US. The presence of a linear interface between 2 different densities with an effusion suggests lipohemarthrosis. This feature results from the entry of marrow fat into the joint cavity and is highly suggestive of an intra-articular fracture. One series demonstrated that 65% of patients with intra-articular fracture did not have fat-fluid levels on plain radiographs; however, all patients with lipohemarthrosis visible on plain radiographs were found to have intra-articular fractures. On plain radiographs the finding of a single fluid-fluid level (layering of fat and blood) on a cross-table view is suggestive of a lipohemarthrosis; however, it can occur without the presence of fat globules. The finding of a double fluid-fluid level (layering fat, blood, and serum) is specific for lipohemarthrosis and can be seen on either US or CT or MRI scans. The sonographic finding of lipohemarthrosis may be used as a sensitive surrogate marker for intra-articular fracture. When used alone for evaluation of acute knee trauma, plain radiographs can miss up to 21% of fractures. If a lipohemarthrosis is identified on either plain film or US, there should be a high suspicion for an occult fracture which should prompt further evaluation with CT scan.[14][15]

See Figure 1, a horizontal, cross-table lateral view plain radiograph of the knee with a fat fluid level in the supra-patellar recess compatible with a lipohemarthrosis.

Treatment / Management

Treatment of hemarthrosis includes interventions that are helpful for any patient who develops acute hemarthrosis for any reason along with specific treatments that target the underlying cause of the hemarthrosis. Initial treatment of any acute hemarthrosis includes immobilization, ice, and compression. Analgesia for pain control may be required in the acute period, especially to obtain a radiographic evaluation. Arthrocentesis with aspiration from a joint can be both diagnostic and therapeutic by reducing pressure from the effusion.[16]

In patients receiving therapeutic anticoagulation, clinically significant hemarthrosis is rare. These patients typically tolerate arthrocentesis. In the rare event, these patients develop persistent or recurrent hemarthrosis, repletion of clotting factors with fresh frozen plasma or reversal of anticoagulation with the appropriate pharmacologic agent could be considered. In patients with recurrent postoperative hemarthrosis, revision angioplasty may be necessary. For the cases of ruptured aneurysms, vascular surgery intervention or arterial embolization may be warranted. For benign tumors, arthroscopic or surgical synovectomy is the treatment of choice to prevent recurrent episodes of hemarthrosis.

Special treatment considerations should be given for hemophiliacs presenting with acute hemarthrosis. Coagulation factor specific to hemophilia should be infused promptly at the first sign of joint bleeding (including the prodromal stiffness or tingling phase prior to pain and swelling) ideally within 2 hours of bleed identification. For bleeding into the hip, a target joint, or bleeding associated with trauma, higher factor activity levels of 80% to 100% are targeted; for hemophilia A give 50 units/kg of factor VIII and for hemophilia B given 100 to 120 units/kg of factor IX. For hemarthrosis in peripheral joints such as knees, elbows, or ankles, the factor activity level should be raised to at least 40% to 50%; for hemophilia A give 25 units/kg of factor VIII and for hemophilia B give 50 to 60 units/kg of factor IX. Medications with anti-platelet activity such as non-steroidal anti-inflammatory agents (NSAIDs) should be avoided. Arthrocentesis is not necessary to diagnose joint bleeding in patients with known hemophilia; however, if arthrocentesis is deemed necessary to rule out a septic joint or reduce pressure from accumulated blood, it should only be performed after the factor has been infused to raise the specific factor levels. In hemophiliacs with target joints who undergo repeated hemorrhage, a short course of glucocorticoids has been found beneficial to reduce pain and swelling associated with synovial inflammation, as long as no signs of septic arthritis exist. Joint surgery for chronic synovitis or arthropathy may be indicated including synovectomy for recurrent bleeding or joint replacement for extensive joint damage.[17][18](A1)

Differential Diagnosis

The differential diagnosis of an acute joint effusion includes other notable disease processes. Conditions which can be mistaken for an acute hemarthrosis include:

• Septic arthritis
• Lyme disease
• Tuberculosis
• Gout (monosodium urate crystals)
• Pseudogout (calcium pyrophosphate crystals)
• Rheumatoid arthritis
• Systemic lupus erythematosus
• Leukemia
• Seronegative spondyloarthropathies (psoriatic arthritis, reactive arthritis, inflammatory bowel disease arthritis)
• Osteoarthritis

This may be especially true if associated with trauma is remote, unclear, or unknown. Arthrocentesis with synovial fluid analysis, diagnostic imaging, and further laboratory workup specific to these other disease processes may be required to differentiate between the causes of an acute joint effusion.

Prognosis

The acute swelling and pain of a hemarthrosis with proper treatment, including arthrocentesis when indicated, can be significantly reduced over the course of days; however, it may take several weeks to resolve completely. In the event the hemarthrosis was caused by an intra-articular fracture or significant soft tissue injury, orthopedic surgery may be warranted for these individuals. Following the resolution of a hemarthrosis, a rehabilitation program to increase the range of motion, weight-bearing, and joint strength is indicated. A physical therapist with expertise in hemophilia is ideal for this specific patient population.[11]

Complications

Severe or recurrent hemarthrosis can lead to the destruction of intra-articular cartilage and degenerative arthritis. The toxic effects of blood cause intra-articular damage leading to synovial hypertrophy and fibrosis. In hemophiliacs, these joints which undergo chronic inflammatory changes from repetitive attacks of hemarthrosis are called “target joints.” Repeated or prolonged attacks can lead to chronic disabling arthropathy due to internal joint derangement and impaired joint movement. Chronic arthropathy affects approximately 20% of hemophiliacs. Recurrent hemarthrosis in hemophiliacs can be prevented with the administration of prophylactic coagulation factors.[6][11]