Treatment of AVN in Patients with Sickle Cell Disease

Avascular Necrosis in Patients with Sickle Cell DiseaseMegan Gaugler Im sure everyone here knows what sickle cell disease is and the genetic mutations etc so Im not going to go into that since this is supposed to be a quick mini-presentation.

Im going to try and stay focused on orthopedic complications caused by sickle cell disease, and more specifically, talk about avascular necrosis.

1Vasoocclusive Pain Episodes - PathophysiologyDeoxygenation of RBCs causes the Hb to polymerize into a long triple-helical chainDisrupts cell integrityIon fluxes leading to cell dehydrationAlteration of cell membrane compositionIncreased RBC fragility which leads to sickling Chronic hemolytic anemiaSticky cells leading to adhesions to other blood cells and vascular endothelium which causes occlusion

We all have heard of sickle cell patients having sickle cells crises or vasoocclusive pain episodes. While these episodes can occur anywhere in the body, they can, as we all know, occur to bone. As a quick review of the pathophysiology of these episodes, when the hemoglobin of sickle cell patients becomes deoxygenated, it has an increased tendency to polymerize into long triple-helical chain. This polymerization the causes many changed in the RBC including disruption of the cell integrity, ion fluxes across the cell membrane that can result in cell dehydration, and alterations in the composition to the cell membrane. These changes then cause a increased fragility of the RBC and causes them to sickle. These sickled RBC becomes more fragile leading to a chronic hemolytic anemia as the body tries to eliminate them, and the RBCs also become more sticky which causes then to adhere to other blood cells and vascular endothelium causing vasoocclusion.

2Vasoocclusion of Musculoskeletal SystemVasoocclusion can occur almost anywhereMost common places in musculoskeletal system include:Bone marrowPeriosteumDeep musclesSlow movement of RBC through sinusoids and capillaries + relative hypoxia increased likelihood of sickling

Vasoocclusion to the musculoskeletal system can occur almost anywhere but are more common in the bone marrow, periosteum, and deep muscles. The slow movement of RBCs through the marrow sinusoids and capillary beds along with the relative hypoxic tissue environment increase the likelihood of sickling. 3Vasoocclusion Pain Episode Clinical Presentation Acute deep-seated painMild erythema and warmthLocal tenderness to palpationPossible low-grade feverAcutely, plain radiographs do not show abnormalitiesNecrosis and remodeling can be seen 1-2 weeks after an eventThese patients will present with acute onset of deep-seated pain, mild erythema, warmth, local tenderness to palpation, and possible a low grade fever. In the acute setting, plain radiographs do not show any abnormalities, but one to two weeks down the line, you can see necrosis and remodeling of bone. 4Vasoocclusion Pain Episodes - TreatmentHydration 1.5-2L/m2/dayWarm packsPain and anti-inflammatory medicationsContinued pain monitoringOxygenation monitoringAs with other sickle cell pain episodes, treatment includes hydration, warm packs, pain and anti-inflammatory medications with continued pain monitoring, and oxygenation monitoring.5Avascular NecrosisCommon complication of SCDMost common in head of humerus and head of femur

It is easy to see how sickle cell disease can lead to the complication of avascular necrosis. AVN is a common complication of SCD and is most common in the head of the humerus and femur. 6AVN of Humeral Head5% of people with SCD have radiographic evidence of osteonecrosis of one or both shouldersHigh likelihood of progressing to collapseAs high as 86% of patients have humeral head collapse 20 years after AVN diagnosis with the median interval between onset of pain and collapse being 8 years.

It is estimated that 5% of sickle cell patients have radiographic evidence of osteonecrosis in one or both shoulders. Unfortunately this condition has a high likelihood of progressing to humeral head collapse. One study showed that of 82 adults with SCD and symptomatic osteonecrosis of the humeral head, 86 percent had humeral head collapse at a 20 year follow up, with a median interval between onset of pain and collapse of eight years (range = 6mo to 17 years).7AVN of Femoral HeadOccurs at any agePrevalence increases with ageFirst symptoms of pain occur around 12 years oldProgresses from childhood into adulthood80% of femoral heads with AVN showed to have both pain and some sort of permanent damage (decreased mobility, abnormal gait, limb-length discrepancy) 19 years after the diagnosisAVN of the hip occurs at any age and prevalence increases with age. The first symptom of pain has been noted at an average of 12 years old. Its also been shown that progression occurs from childhood into adult life. 80% of effected hips diagnosed with AVN were shown to be bone painful and have some sort of permanent damage (such as decreased mobility, abnormal gait, and limb-length discrepancies) 19 years after the dx of AVN. 8AVN of Femoral HeadSome have no pain at diagnosisLook at the other hip, even with no symptoms

It is also important to note that even though AVN is associated with pain, almost half of those diagnosed with AVN in a surveillance study, had no pain at diagnosis. It is also known that some patients that present with symptomatic osteonecrosis of one hip, also have asymptomatic osteonecrosis of the contralateral hip. It is therefore suggested to get an image of the contralateral hip in patients dx with AVN. 9AVN ImagingAn immature epiphysis can undergo remodeling despite initial necrosis and result in flattening of the femoral headAVN of mature femoral heads leads to collapse, degenerative changes, and painMRI will show increased signal within the femoral head

Radiographic images may show flattening of the femoral head and MRI can show an abnormal bright signal. An immature epiphysis can undergo remodeling despite initial necrosis and result in flattening of the femoral head, but AVN of the mature femoral head leads to collapse which results in persistent degenerative changes and pain. 10AVN ManagementNo general consensusStart with conservative managementPain management (especially in acute phase)Reduced or non-weight bearingBed restMobilization with crutches or wheelchairSustained PT to maintain range of motion, strengthen muscles, gait trainingTry for 4-6 months before surgical interventionIn terms of management of AVN of the hip, there is no general consensus on whether to treat with conservative management or surgery. For the most part, it is often advocated to try conservative measures first which include pain management (typically in the acute phase), reduced or non-weight bearing, bedrest, mobilization with crutches or a wheelchair, and sustained PT to maintain ROM in the hip, strengthen hip muscles, and provide gait training. Unfortunately, success rate is low. Although there is no good evidence or consensus for how long conservative measures should be tried before surgery, it is recommended 4-6 months. 11AVN TreatmentCore decompressionRemoves necrotic tissue +/- filling cored area with bone graftUnknown if this slows progression of joint damagePT alone shown to be as effective as core decompression + PTNo evidence that adding core decompression to PT resulted in clinical improvementWhen looked at for all etiologies, surgery showed benefits in early cases of AVNPathophysiology of ANV in SCD vs non-SCD could differ, therefore use conservative management firstCore decompression would be the next step which would remove the necrotic tissue with or without filling the cored area with a bone graft. However, it is controversial whether this slows the progression of joint damage. One small randomized study of individuals with SCD, PT alone was as effective as hip core decompression followed by PT in improving hip function and postponing the need for additional surgical intervention at a mean of 3 years after treatment. Another systematic review showed no evidence that adding surgical decompression of PT resulted in clinical improvement. However when core decompression was looked at for AVN from all etiologies (not just sickle cell), surgery showed benefits in early cases of AVN. This could possibly indicate a difference in pathophysiology of ANV in patients with SCD vs those without and therefore favors the use of conservative management 12AVN TreatmentArthroplastyReserved for those not helped by conservative and core decompression managementMany cases do not provide better or prolonged mobilityCan have high post-operative morbidity, but improvingFailure rate around 19% at 15 years, but improvingIf using cementless prosthetic components, outcomes are comparable to those outcomes in patients without SCDAlthough treatments are improving, it is still recommended to start with conservative therapyArthroplasty should be reserved for those not helped by both PT and core decompression. Success is limited as many cases are not allowing for better or prolonged mobility and even associated with high post-op morbidity although this is improving with better pre-op care.. Failure rates used to be as high as 30% by 5 years in 1991 but are currently around 19% by 15 years. One report even showed THA outcomes comparable to those in individuals without SCD with the use of cementless prosthetic components. So although surgical treatments are still improving with time, it is still recommended to try conservative management first before moving on to surgical approaches.

13ReferencesGeorge, A., & DeBaun, M. R. (2014, 11 13). Bone and Joint Complications in Sickle Cell Disease. Retrieved from UpToDate: http://www.uptodate.com/contents/bone-and-joint-complications-in-sickle-cell-disease?source=search_result&search=sickle+cell+bone+disease&selectedTitle=1%7E150#H993585Lee E. Rubin, Scott A. Ritterman and Timothy McTighe (2013). Neck-Sparing Total Hip Arthroplasty, Arthroplasty - Update, Prof. Plamen Kinov (Ed.), ISBN: 978-953-51-0995-2, InTech, DOI: 10.5772/54830. Available from: http://www.intechopen.com/books/arthroplasty-update/-neck-sparing-total-hip-arthroplastyLuijkx, T., & Gaillard, F. (2014, 11 13). Avascular Necrosis. Retrieved from Radiopaedia: http://radiopaedia.org/articles/avascular-necrosisShetty, A., & Gaillard, F. (2014, 11 13). Avascular Necrosis of the Hip Classification. Retrieved from Radiopaedia: http://radiopaedia.org/articles/avascular-necrosis-of-the-hip-classification