Is hemolytic crisis in Sickle Cell Anemia (SCA) intravascular or extravascular?

From the Guidelines

Hemolytic crisis in SCA is primarily characterized by both intra vascular and extra vascular hemolysis, with the latter being the predominant mechanism in steady state, while the former becomes more significant during acute crises. The pathophysiology of hemolytic crisis in SCA involves the destruction of red blood cells, which can occur both within and outside the blood vessels. According to the american society of hematology 2020 guidelines for sickle cell disease: transfusion support 1, hyperhemolysis, a severe form of hemolysis, can occur in patients with SCD, suggesting clearance of the patient’s own red cells in addition to transfused cells. This process can be accompanied by both intra vascular and extra vascular hemolysis, as evidenced by laboratory findings such as elevated indirect bilirubin and lactate dehydrogenase (LDH), reduced haptoglobin, and sometimes hemoglobinuria. Some key points to consider in the management of hemolytic crisis in SCA include:

• The use of extended matched red cells that also lack the offending antigen for patients experiencing life-threatening anemia 1
• The potential use of IVIg, high-dose steroids, eculizumab, and/or rituximab to treat hyperhemolysis in patients with SCD, although the optimal management remains unclear 1
• The importance of recognizing hyperhemolysis, as additional transfusions should be avoided if possible, to prevent worsening of hemolysis and potential induction of multiorgan failure and death 1

From the Research

Hemolytic Crisis in SCA

• Hemolytic crisis in Sickle Cell Anemia (SCA) can be either intra vascular or extra vascular, depending on the context and underlying mechanisms.
• According to 2, complement plays a crucial role in hemolytic transfusion reactions, particularly in cases of intravascular hemolysis, where free heme and hemoglobin are released and interact with complement, causing tissue damage.
• Intra vascular hemolysis is characterized by the destruction of red blood cells within the blood vessels, leading to the release of hemoglobin and other cellular contents into the circulation.
• Extra vascular hemolysis, on the other hand, occurs when red blood cells are removed from the circulation and destroyed in the spleen or other organs.

Pathophysiology of Hemolytic Crisis

• The pathophysiology of hemolytic crisis in SCA is complex and involves multiple factors, including alloimmunization, abnormal complement activation, and the underlying condition of chronic hemolysis 2.
• Hyperhemolysis syndrome, a rare complication of repeat blood transfusions in SCA, can occur acutely or have a delayed presentation and often goes unrecognized due to its rapid progression and similarity to acute chest syndrome and other common complications of SCA 3.
• The syndrome is characterized by a rapid drop in hemoglobin levels, hyperkalemia, hyperbilirubinemia, and uncontrolled pain, and can lead to severe complications, including acute liver failure, bone marrow necrosis, and fever of unknown origin 3.

Clinical Implications

• The diagnosis of hemolytic crisis in SCA requires a high index of suspicion, particularly in patients who have received recent blood transfusions 3, 4.
• Early recognition and treatment of hyperhemolysis syndrome are critical to preventing severe outcomes, and may involve the use of steroids, intravenous immunoglobulin, and exchange transfusion 3, 5.
• Transfusion support in patients with SCA should be individualized and based on the specific needs of each patient, taking into account the risks of alloimmunization, transfusional hemosiderosis, and other complications 5.