Multimodal Haematopoietic Intervention (IV Iron, Erythropoietin, Vitamin B12, Folic acid) for the prevention of postoperative anaemia in major orthopaedic tumour surgery: A Randomized Control Trial

Postoperative anaemia is a common and significant complication following major orthopaedic oncologic surgeries. The prevalence of postoperative anaemia in orthopaedic tumour surgeries is as high as 89.2%. Major reasons include high vascularity of the region, difficult-to-do preoperative blood control measures, including arterial embolization, extensive resection, difficulty in application of tourniquet during the intraoperative period due to the location of the surgery. As a part of  patient blood management protocol, blood transfusion is restricted to conditions when the haemoglobin falls below 8 grams per decilitres in orthopaedic surgery. Postoperative anaemia may lead to various other complications like increased surgical site infection, sepsis, increased in-hospital stay, delayed wound healing and even may need ICU admissions.

According to the WHO, postoperative anaemia could be classified

Mild (haemoglobin 11.0–11.9gm/dl in women and 11.0 – 12.9gm/dl in male)

Moderate (haemoglobin 8.0–10.9gm/dl) and

severe (haemoglobin < 8.0gm/dl)

Postoperative anaemia may be due to a restrictive intraoperative blood transfusion strategy, significant intraoperative blood loss, reduced erythropoiesis due to a generalized release of inflammatory mediators in the postoperative period, inadequate oral intake, and poor absorption of oral iron preparation. Iron is an essential component of erythropoiesis, and its absorption decreases significantly postoperatively from the gastrointestinal tract due to increased hepcidin secretion. Hepcidin is a positive acute-phase reactant that decreases iron absorption, transport, and release. These patients also have other nutritional deficiencies, such as vitamin B12 and folic acid, due to a generalized malnutrition state resulting from the malignancy and the chemotherapy.

The treatment of postoperative anaemia depends on either blood transfusions, oral use of haematinics (iron, folic acid, and vitamin B12), or parenteral iron, vitamin B12, and an erythropoietic stimulant in the form of subcutaneous erythropoietin. Blood transfusions increase haemoglobin (Hb) levels only transiently and come at the risk of blood transfusion-related reactions, infections, and cost.

In the perioperative period, patient blood management (PBM) strategies are developed for perioperative blood transfusion. Treatment or prevention of the preoperative anaemia is the mainstay of PBM. PBM mainly relies on three pillars: 1. Identifying and managing anaemia before surgery 2. Minimizing blood loss during the perioperative period 3. Supporting the patient’s individual ability to tolerate anaemia, like the use of more conservative transfusion thresholds. The first pillar of PBM is most effective but difficult to implement in malignancy surgery due to time sensitive nature of surgery. Also, the use of a lower Hb cut-off as a transfusion trigger implies that a certain degree of postoperative anaemia is accepted. Though blood transfusions are considered the mainstay treatment for the correction of perioperative anaemia, they are mainly considered for patients in the severe anaemia category( Hemoglobulin less than 8gm/dl). For the prevention of postoperative anaemia, the standard of care practised in our institution and most other institutions is oral iron and folic acid combination supplementation in the postoperative period once the patient takes it orally and their bowel habit normalizes. However, many patients may not comply with the oral formulation for several reasons. Common reasons include poor bioavailability of the drug due to inflammation and drug interaction with food; its metallic taste; constipation, and other side effects. Hence, parenteral iron will counteract the difficulties associated with oral tablets. Due to postoperative inflammation, the effect of erythropoietin also diminishes. This effect will be supplemented with one dose of erythropoietin on postoperative day one. A single erythropoietin dose also inhibits hepcidin synthesis and will help in the erythropoiesis process. Poor postoperative intake and preoperative clinical or subclinical deficiency of vitamin B12 and folic acid will be taken care of by postoperative vitamin B12 and folic acid supplementation.

So, we hypothesized that a single dose of multimodal bundle of hematinic (intravenous iron, intravenous vitamin B12, subcutaneous erythropoietin alpha) may help improve hemoglobin levels in patients with moderate postoperative anemia (hemoglobin concentration 8-11 g/dL) after major orthopedic tumor surgery with a significant intraoperative blood loss.