Osteonecrosis is a pathological condition that could lead to a debilitating physical disease and impede daily activities

Osteonecrosis is a pathological condition that could lead to a debilitating physical disease and impede daily activities. in primary osteonecrosis due to thrombophilia or hypofibrinolysis. We report a case of primary osteonecrosis associated with hypofibrinolysis and successful control with lifelong direct oral anticoagulation therapy. strong class=”kwd-title” Keywords: Haematology, orthopaedics, rehabilitation, occupational therapy, anticoagulation, direct oral anticoagulants, osteonecrosis Introduction Osteonecrosis is generally categorised into its aetiological development C primary (idiopathic) or secondary causes. Secondary osteonecrosis occurs when direct damage to the bone vasculature or direct injury of the bone marrow is related to an identifiable cause such as traumatic injuries, steroid or bisphosphonate use, increased alcohol intake, sickle cell disease, autoimmune diseases, chemotherapy or malignancy.1 On the other hand, osteonecrosis is categorised while idiopathic or major when the introduction of the osteonecrosis isn’t fully understood. With this category, inherited hypofibrinolysis and thrombophilia are reported in medical literatures as potential causes.2 The abnormalities and gene mutations from the protein in the coagulation and fibrinolytic pathways are well described in the pathogenesis of osteonecrosis. Research and retrospective reviews suggest an elevated prevalence from the Element V Leiden mutation in individuals with hip or leg osteonecrosis weighed against healthy settings.3C6 Within an observational research of individuals with osteonecrosis, 82% of osteonecrosis individuals were found to have at least one coagulopathy weighed against 30% of settings, and 47% of individuals with osteonecrosis had several coagulopathies, weighed against 3% of settings.7 Many reports have already been completed on thrombophilia and hypofibrinolysis connected with osteonecrosis recently. They are mainly linked to complications inside the coagulation cascade. Two separate studies found that 12 of 32 patients diagnosed with primary osteonecrosis of the knee and 10 of 35 patients diagnosed with primary osteonecrosis of the femoral head had Factor V Leiden or mutations on the prothrombin 20210A gene.5,6 Both studies suggested that coagulation abnormalities may play a role in osteonecrosis of the knee and C646 the femoral head. Another problem that leads to thrombophilia is the resistance to activated protein C or low levels of protein C.8 These have been found in patients with primary or secondary osteonecrosis of the femoral head. High levels of Factor VIII is another heritable thrombophilic condition that increases the risk for both primary and secondary osteonecrosis of the femoral head.9,10 It has also been suggested that hypofibrinolysis (i.e. increased levels of lipoprotein(a), high levels of plasminogen activator inhibitor and subsequently low levels of stimulated tissue plasminogen activator (tPA)) leads to inadequate lysis of venous thrombi in bone, compromised C646 bone venous circulation, venous hypertension of the bone and, ultimately, hypoxia within the bone leading to osteonecrosis.8 In our search of the literature, we found several reports wherein anticoagulation, including direct oral anticoagulants (DOACs), was used in primary osteonecrosis. Currently, the main treatment of osteonecrosis due to hypofibrinolysis is with a low-molecular-weight heparin (LMWH), enoxaparin. One study showed that patients with primary osteonecrosis of the hip treated with LMWH had lower rates of progression from the pre-collapsed to the collapsed stage of the hip.11 Studies also C646 reported that long-term use of anticoagulation prevents the progression of idiopathic osteonecrosis, helps with pain and improves functionality.12,13 In one study, patients with Factor V Leiden or resistance to activated protein C who developed osteonecrosis of the hip and were started on long-term (4C16?years) anticoagulation therapy did not show signs of radiological progression and remained at low Ficat (I and II) stages.13 Most of the samples in the same study were treated with warfarin (Coumadin). DOACs were utilised in mere two individuals C one individual was treated with dabigatran (Pradaxa) 150?mg daily following completion of 90 double?days treatment with enoxaparin (Lovenox), as C646 KDR the other individual was on warfarin, then switched to rivaroxaban (Xarelto) 20?mg. In another full case, apixaban (Eliquis) 5?mg double daily was used to take care of major osteonecrosis connected with thrombophiliaChypofibrinolysis rather than warfarin.14 Several research backed that despite becoming asymptomatic also, untreated osteonecrosis advances to symptomatic disease. One research found that, generally, regardless of root trigger (major or supplementary), asymptomatic osteonecrosis includes a high prevalence of development to symptomatic disease.15 In another scholarly study, a subgroup of individuals with asymptomatic idiopathic osteonecrosis, 46.2% progressed to symptomatic osteonecrosis.16 Similarly, in a report previously mentioned, 50% to 80% of individuals hips, ficat stage II initially, progressed to Ficat phases III to IV within 2?years without anticoagulation treatment.13 Our record focuses on an instance of major osteonecrosis connected with hypofibrinolysis and effective control with lifelong direct oral anticoagulation therapy of low-dose apixaban. Case presentation A 40-year-old Caucasian female with no significant medical morbidities presented in 2013 with persistent left leg pain after she twisted her left ankle. An evaluation with plain X-ray and magnetic resonance imaging (MRI) of her left lower extremity revealed abnormal densities, suggesting osteonecrosis, in the distal femur (see Figures.