In elderly patients, hip fracture should be surgically treated within 48 hours from admission, since its deferral worsens the mortality. However, sometimes patients are affected by cardiovascular or cerebral comorbidities, deeming necessary the use of antiplatelets and/or anticoagulant therapies. Clopidogrel is a second-generation thienopyridine antiplatelet drug which exerts its effect by the inhibition of the platelet's purinergic receptor P2Y12 preventing adenosine diphosphate (ADP) from stimulating it. Guidelines recommend to withhold clopidogrel for 5 days before the possibility to perform neuraxial anesthesia, which is frequently the optimal perioperative management of a fragile patient. It should be mentioned however that around 30% of patients are resistant to clopidogrel and they show a normal platelet reactivity despite the antiplatelet therapy. Therefore, in principle, these patients do not require to defer surgery. We have therefore hypothesized that some patients taking clopidogrel might anticipate surgery before 5 days and within 48 hours, following a protocol based on the assessment of coagulation and platelet aggregation through thromboelastography (TEG) in combination with an ADP Platelet Mapping assay kit.

After hospital admission for femur fracture, eligible patients would be evaluated by the anesthesiologist and the orthopedic physicians for anesthesia and surgery. Immediately a sample of blood should be collected for TEG with ADP Platelet Mapping test. If both MA-ADP and platelets aggregation (%) will be within normal values, the patient could be considered as candidate for immediate surgery (within 48 hours) with neuraxial anesthesia and ultrasound-guided antalgic femoral nerve block. If MA-ADP and/or platelets aggregation (%) are lower, risk for mortality should be assessed. If the patient would be considered at high risk for mortality, he/she would undergo to general anesthesia and peripheral antalgic block to not postpone surgery. Otherwise, surgery would be postponed until the normalization of both MA-ADP and platelet aggregation.

Hip fracture is an established and recognized health problem associated with the age of the population. In the elderly, it is essential that surgery for hip fractures would be performed within 48 hours from admission. Whenever delayed beyond 48 hours, the probability of 30-day mortality increases by 41% and the odds of one-year mortality by 32%.

Neuraxial anesthesia and/or peripheral nerve block are generally preferred in elderlies. However, cardiovascular and/or cerebral comorbidities require antiplatelets therapies at home. This treatment precludes the possibility of an optimal anesthesiologic strategy (i.e., loco-regional anesthesia) within the recommended surgical timing. Therefore, an individual approach is required to balance the risk of drugs continuation/cessation on major cardiovascular events and on peri-operative bleeding.

Clopidogrel is a second-generation thienopyridine antiplatelet drug, that exerts its effect by the inhibition of the platelet's purinergic receptor P2Y12, preventing adenosine diphosphate (ADP) from stimulating it. In patients needing surgery, guidelines recommend withholding clopidogrel 5 days before. However, around 30% of patients are resistant to clopidogrel for several reasons. Patients resistant to clopidogrel may be identify through the thromboelastography (TEG). TEG is a resonance-frequency viscoelastic point-of-care diagnostic system that assesses hemostasis and response to antiplatelet therapy, in combination with the ADP Platelet Mapping assay kit.

It has been hypothesized that the assessment of platelet aggregation with TEG and ADP Platelet Mapping may identify patients resistant to clopidogrel, not requiring to wait for 5 days for hip replacement surgery. We have therefore designed this protocol to guide anesthesiologists in the management of elderlies receiving clopidogrel and requiring surgery for hip fracture. The aim of this pilot study is to evaluate if in a small population of patients, our protocol based on platelet function monitoring would anticipate surgery within 48 hours at least in 70% of elderly patients receiving clopidogrel.

Inclusion Criteria:

• all patients older than 65 years/old
• admission to the hospital for suspected traumatic femur fracture
• home therapy with clopidogrel 75 mg/die at home

Exclusion Criteria:

• pre-existing coagulopathies
• assumption of any anticoagulant oral therapy
• platelet count <100.000 mcL
• pre-existing liver disease
• known autoimmune diseases
• presence of hematological malignancies

All patients older than 65 years/old, admitted to the hospital for suspected traumatic femur fracture receiving clopidogrel 75 mg/die at home were consecutively included in the pilot study.

Patients with one or more of the following criteria were excluded: 1) pre-existing coagulopathies; 2) assumption of any anticoagulant oral therapy; 3) platelet count <100.000 mcL; 4) pre-existing liver disease; 5) known autoimmune diseases; 6) presence of hematological malignancies.

data will be shared on reasonable request to the corresponding author

After study publication