Hemoglobin E is the most common hemoglobin (Hb) variant in Southeast Asia and the second most prevalent worldwide. However, in India, it is prevalent in Bengal and the north-eastern region, but relatively rare in the rest of the country.(1) It is important to distinguish Hb E disorders diagnostically because there is marked difference in clinical course among different genotypes. Screening tests, including hemoglobin electrophoresis and high-pressure liquid chromatography (HPLC).(2) Microcytosis and, frequently, mild erythrocytosis are characteristic of HbE trait. These features must be recognized in order that persons with this innocuous condition not be subjected to unnecessary medical examinations and inappropriate treatment. Because it is a rare clinical entity, literature about open heart surgery in the presence of HbE trait is limited to either case reports or small series. With advances in diagnostic and surgical techniques and improvements in anesthetic management skills, the number of patients with HbE trait who require cardiac surgery is increasing considerably. Nevertheless, literature on the evaluation and specific management of these patients remains limited, and further studies are strongly recommended.(3) AIMS AND OBJECTIVES: To study the perioperative results in patients with HbE Trait undergoing open heart surgery

A prospective non-randomised controlled study was conducted from January 2024 to January 2025 in 26 patients with HbE Trait who underwent valvular heart surgery at our institution. The patient’s demographic characteristics, Pre-operative haemoglobin, Pre-operative Liver Function Test, Pre-operative blood transfusion requirements, Intra-operative blood requirements, Post-operative haemoglobin on immediate Post-operative period and 1st, 2nd and 3rd post-operative days, post-operative Liver Function Test, Duration of hospital stay, complications developed post-operatively were observed in these patients. Place of study: CN Center, Gauhati Medical College and Hospital, Assam Duration of study: January 2024 to January 2025 Study Design: Prospective non-randomized controlled study Sample size: 26 patients with HbE Trait who underwent Valvular heart surgery Inclusion Criteria: All patients with HbE trait who requires surgical management for valvular heart disease. Exclusion criteria: • Patients with Thalessemia • Patients with Chronic Kidney Disease, Chronic Liver Disease • Patients unfit for surgery Statistical Analysis: All the data were expressed as means ±SDs. Fisher’s exact tests were used for statistical analysis, and p<0.05 was accepted as a significant statistical value. Anaesthesia Care: All invasive procedures were performed while the patients were under deep anesthesia. After endotracheal intubation, arterial, and central venous lines were inserted. Further incremental doses of fentanyl were administered during the operation. Tranexamic acid was used routinely to prevent bleeding complications.Arterial blood pressure, central venous pressure, electrocardiogram, saturation with pulse oximetry, and nasopharyngeal temperature were routinely monitored during and after surgery. Anesthesia was maintained with an infusion of propofol. The patients were transferred to the intensive care unit while still under sedation. Tracheal extubation was performed once optimal cognitive, hemodynamic, and respiratory functions were achieved. For postoperative pain management, Fentanyl, and Paracetamol were administered. Cardiopulmonary Bypass: CPB was performed in a routine manner. The bypass circuit volume was adjusted according to the age, weight, and body surface area of each individual patient to reach a hematocrit value of average 30% during CPB. Additional crystalloid, colloid, or red blood cells were added to the CPB circuit as needed according to the desired hematocrit levels. Throughout the bypass, venous oxygen saturation was kept at >80%. Temperature was maintained >34°C, pH was maintained between 7.35 and 7.45 by correction of acidosis with sodium bicarbonate. The flow was adjusted as a body surface area times cardiac index (2.2–2.4). Myocardial protection was performed using a 20 ml/kg of anterograde cold crystalloid cardioplegia. A second or a third shot of crystalloid cardioplegia was given every 20 min with half of initial dose (10 ml/kg).

The average age of the 14 male and 12 female patients was 33 years. Patient outcomes were analysed through the use of the institutional database. The average pre-operative haemoglobin was 8.2mg/dl. All patients were having unconjugated hyperbilirubinaemia pre-operatively. 6 patients require haemoglobin optimization. The average immediate post-operative haemoglobin was 9.6mg/dl. On first three post-operative days, haemoglobin was maintained above 9mg/dl. All patients Bilirubin level was raised post-operatively which comes down to baseline level on subsequent follow-up. 3 patients had haematuria post-operatively which subsides by 2nd post operative day. 2 patients had intra-thoracic collection.

Patients suffering from HbE disease are potentially at high risk of perioperative complications as a result of hemolysis. There are currently two approaches to patient treatment: strict control of hemolysis triggers, intending to lower the risk of hemolytic breakthrough, and a liberal approach, with no deviation from the standard of care for patients undergoing cardiac surgery. There is still no study comparing these different strategies, and evaluating these approaches is further hindered by the disorder’s rarity and the variety of symptoms among patients. When red blood cells are destroyed, the hemoglobin is released into the bloodstream. This can lead to several different outcomes. Free hemoglobin binds to haptoglobin, a protein that limits hemoglobin loss through the urine and facilitates hemoglobin uptake in the reticuloendothelial system. The breakdown of hemoglobin in the reticuloendothelial system releases the heme moiety, which is then converted into biliverdin and bilirubin. The accumulation of bilirubin can result in hyperbilirubinemia and jaundice. Moreover, if the hemolysis rate is high, the haptoglobin may be depleted, and free hemoglobin can accumulate in the bloodstream, resulting in severe cellular and organ damage.(4) Of the different types of cardiac surgery, the most common are those involving CPB, which, due to their construction, are potentially the main source of hemolysis. Red blood cells are irreversibly damaged during CPB, but hemolysis is usually minimal in patients without RBC disorders when CPB is properly managed.(5) In a cannula, the shear stress depends on the radius, length, and the pressure gradient across the cannula or oxygenator. As blood flows at high speed through a small cannula, shear stresses act on red blood cells, resulting in a change in their shape. In addition, small cannulas can cause turbulence in blood flow contributing to hemolysis. Heparin-coated polyvinyl chloride PVC tubing can cause some hemolysis.(6) Priming is often debated regarding hemodilution and thus hemolysis. While numerous publications highlight the possible decrease in hemoglobin concentration and thus potential reduction in global oxygen delivery (DO2) during massive transfusions of crystalloids and colloids, the essence of the problem of hemodilution anemia is the decrease in Hb concentration rather than the absolute value. Potentially, a decrease in the concentration of other plasma constituents including proteins and electrolytes can induce abnormal oncotic pressure resulting in hemolysis. Cardiotomy suction is one of the main causes of hemolysis, also contributing to the systemic inflammatory response by activating leukocytes, platelets, and the complement system. The critical pressure for blood morphotic element damage ranges from − 120 to − 600 mmHg. When the suction tip is obstructed, the inlet pressure can exceed − 600 mmHg, resulting in cavitation, turbulent flow, and significant shear stress.(7) Cold cardioplegia can induce hemolysis, while RBC membranes become more rigid in cold temperatures, limiting the cell’s capacity to adapt and pass through narrow blood capillaries. RBCs are also more vulnerable to mechanical and shear stress, while cold temperatures can alter the membrane and cytoskeleton of RBCs. Blood product transfusions to compensate for oxygen carrier loss, administration of vasoactive drugs, or end-organ damage protection are crucial for patients with intravascular hemolysis. Patients with heart failure and coronary disease may not tolerate anemia due to their reduced ability to improve cardiac output. This leads to a decrease in DO2 and organ hypoxia, which in the case of the heart cannot be fully compensated by increased oxygen extraction, leading further to myocardial ischemia. Therefore, the recommended hemoglobin transfusion threshold is 7 g/dl for stable critically ill patients (including patients with moderate ischemic heart disease), with a target value of 7–9 g/dl. In patients with acute coronary syndrome, higher threshold values of 8.5–9.5 g/dl may be appropriate improving long‐term cardiovascular outcomes.(8) In addition to the free hemoglobin, bilirubin, LDH, and reticulocyte count, haptoglobin is a parameter that may indicate the presence of intravascular hemolysis. Haptoglobin is an acute-phase protein that binds irreversibly to fHb preventing its glomerular filtration, and the complex is phagocytized in the mononuclear phagocyte system. The half-life of free haptoglobin is approximately 5 days whereas the hemoglobin-haptoglobin complexes just few minutes.(7)

Valvular Heart surgery can be performed safely in patients with HbE Disease with acceptable outcome and survival rate as those in patients without HbE Disease. No excessive blood loss was observed in our study comparing to the normal population. Adequate oxygenation, avoidance of acidosis and dehydration during surgery are important. Blood Transfusion during cardiopulmonary bypass is recommended based on haemoglobin level. Pre-operative transfusion and blood priming is non recommended.(4) Clinical Significance: HbE Disease is an inherited blood disorder that leads to abnormal form of haemoglobin that may cause Anaemia and Jaundice. This trait has high prevalence in Southeast Asia and is very common in North-east India. In this study, it was observed that these patients did not developed any major haemolytic crisis or excessive post-operative bleeding. The blood requirement intra-operatively was similar to the normal population. Hence, patients should not be denied the needed cardiac surgical treatment.

1. Kishore B, Khare P, Gupta RJ, Bisht S, Majumdar K. Hemoglobin E disease in North Indian population: A report of 11 cases. Hematology [Internet]. 2007 Aug [cited 2025 Jun 7];12(4):343–7. Available from: https://www.tandfonline.com/doi/pdf/10.1080/10245330701255247 2. Vichinsky E. Hemoglobin E Syndromes. Hematology [Internet]. 2007 Dec 7 [cited 2025 Jun 7];2007(1):79–83. Available from: https://dx.doi.org/10.1182/asheducation-2007.1.79 3. Yousafzai SM, Ugurlucan M, Al Radhwan OA, Al Otaibi AL, Canver CC. Open Heart Surgery in Patients With Sickle Cell Hemoglobinopathy. Circulation [Internet]. 2010 Jan 5 [cited 2025 Jun 8];121(1):14–9. Available from: /doi/pdf/10.1161/CIRCULATIONAHA.109.882464?download=true 4. Métras D, Coulibaly AO, Ouattara K, Longechaud A, Millet P, Chauvet J. Open-heart surgery in sickle-cell haemoglobinopathies: report of 15 cases. Thorax [Internet]. 1982 Jul 1 [cited 2025 Aug 15];37(7):486–91. Available from: https://thorax.bmj.com/content/37/7/486 5. Vercaemst L. Hemolysis in Cardiac Surgery Patients Undergoing Cardiopulmonary Bypass: A Review in Search of a Treatment Algorithm. J Extra Corpor Technol [Internet]. 2008 Dec 1 [cited 2025 Aug 15];40(4):257–67. Available from: https://ject.edpsciences.org/articles/ject/abs/2008/04/ject-40-257/ject-40-257.html 6. Wright G. Haemolysis during cardiopulmonary bypass: Update. Perfusion [Internet]. 2001 [cited 2025 Aug 15];16(5):345–51. Available from: /doi/pdf/10.1177/026765910101600504?download=true 7. Shin H, Yozu R, Maehara T, Matayoshi T, Morita M, Kawai Y, et al. Vacuum Assisted Cardiopulmonary Bypass in Minimally Invasive Cardiac Surgery: Its Feasibility and Effects on Hemolysis. Artif Organs [Internet]. 2000 Jun 1 [cited 2025 Aug 15];24(6):450–3. Available from: /doi/pdf/10.1046/j.1525-1594.2000.06587.x 8. Martinez G, Whitbread J. Cardiopulmonary bypass. Anaesthesia & Intensive Care Medicine [Internet]. 2012 Oct 1 [cited 2025 Aug 15];13(10):482–7. Available from: https://www.sciencedirect.com/science/article/abs/pii/S1472029912001816