Principles of Clinical Pathology
Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard in Toxicologic Pathology, 2018
Hemolytic conditions are categorized as intravascular or extravascular. Intravascular hemolysis occurs when red cells lyse directly within circulation. Extravascular hemolysis occurs when red cells, usually damaged in some manner, are phagocytized prematurely by macrophages. Extravascular hemolysis is more common and is associated with increased spleen weight, bone marrow hypercellularity, and extramedullary hematopoiesis (especially in rodents). Pigment from breakdown of hemoglobin may be present, especially in splenic macrophages. Relatively extensive hemolysis may result in increased serum and urine bilirubin concentrations. Extensive intravascular hemolysis is characterized by free hemoglobin in plasma or urine. Most hemolytic conditions result in a mild inflammatory response with increased absolute neutrophil or monocyte counts.
Immunohematology
Gabriel Virella in Medical Immunology, 2019
Immune Complex Mechanism (Drug Dependent Antibody Mechanism). Traditionally this mechanism has been thought to be due to the formation of soluble immune complexes between the drug and the corresponding antibodies that is followed by non-specific adsorption to red cells and complement activation. Alternatively the neoantigen concept proposes that the drug binds transiently with the red cell forming a “non-self” epitope that stimulates antibody formation. The distinction between this mechanism and the drug adsorption mechanism, where a stable bond is formed between the drug and the cell membrane, may be more apparent than real. When IgM antibodies are predominantly involved, intravascular hemolysis is frequent and the direct Coombs’ test is usually positive. IgG antibodies can also form immune complexes with different types of antigens and be adsorbed onto red cells and platelets. In vitro, such adsorption is not followed by hemolysis or by phagocytosis of red cells, but in vivo it has been reported to be associated with intravascular hemolysis.
Disseminated Intravascular Coagulation
Rodger L. Bick in Disseminated Intravascular Coagulation and Related Syndromes, 2019
Intravascular hemolysis of any etiology is also a common triggering event for disseminated intravascular coagulation. Classically it has been taught that a frank hemolytic transfusion reaction is a triggering event for DIC; however, hemolysis of any etiology and even of low grade may, in fact, provide a trigger for disseminated intravascular coagulation. In instances of hemolysis, the release of red cell ADP or red cell membrane phospholipoprotein may activate the clotting sequence and in clinical practice either/or a combination of these may account for episodes of disseminated intravascular coagulation.21–25 A particular trigger in this instance may be the use of multiple transfusions with banked whole blood over a short period of time. For example, the use of 5 to 10 units of banked whole blood within a 24-hr period provides a significant trigger for DIC via the aforementioned mechanisms. Thus, any type of hemolysis spanning from a frank hemolytic transfusion reaction to a minor hemolytic reaction with the release of red cell ADP or red cell membrane phospholipoprotein may provide a trigger for activation of the coagulation system and an episode of acute disseminated intravascular coagulation.
Renal involvement in paroxysmal nocturnal hemoglobinuria: an update on clinical features, pathophysiology and treatment
Published in Hematology, 2018
Styliani I Kokoris, Eleni Gavriilaki, Aggeliki Miari, Αnthi Travlou, Elias Kyriakou, Achilles Anagnostopoulos, Elissavet Grouzi
In classical PNH, red cell intravascular hemolysis is continuous and appears in various degrees. When hemoglobin is free in the plasma, it exists mostly as alpha/beta dimers that rapidly complex to haptoglobin (Hp), a liver-produced plasma protein. This is the first mechanism of hemoglobin iron salvage. By binding to Hp, hemoglobin avoids filtration at the glomerulus and the release of its heme moiety is prevented [33]. More specifically, the haptoglobin–hemoglobin complexes are too large to be filtered by the glomerulus, so they are carried to the liver, where they are recognized by the CD163 receptors (these are membrane proteins expressed on monocyte/macrophage surfaces and hepatocytes) [34–36]. The binding of the hemoglobin molecules to CD163 receptors results in the neutralization of free hemoglobin’s toxic actions. Hemoglobin, also, has the ability to up-regulate CD163’s expression. The uptake of hemoglobin by CD163 receptors not only attenuates the toxic effects of cell-free hemoglobin, but it also induces several anti-inflammatory responses, including interleukin-10 release and heme oxygenase-1 synthesis (HO-1) [15]. In cases where hemolysis is accelerated, Hp molecules are depleted, due to the liver’s inability to increase Hp’s production as a response to the increased hemolysis: Hp molecules are typically adequate to salvage only a normal amount of plasma hemoglobin.
Hemolysis during short-term mechanical circulatory support: from pathophysiology to diagnosis and treatment
Published in Expert Review of Medical Devices, 2022
Tim Balthazar, Johan Bennett, Tom Adriaenssens
Hemolysis is the consequence of degradation of the RBCs. The normal life span of a RBC is around 120 days. Older erythrocytes become less elastic and are more easily destroyed by mechanical stress. This occurs at a rate of around 1% of RBCs daily. The hemoglobin (Hb) content of these cells is released into the blood plasma and further degraded in the liver, where the iron atoms are recycled. In a healthy person, this normal process of destruction of older RBCs (natural hemolysis) is balanced by a compensatory release of newly formed RBCs by the bone marrow, via increased erythropoietin (EPO) secretion by the kidney. In case of intravascular hemolysis, these compensatory mechanisms are overwhelmed and a decrease of the Hb level below the normal range can ensue, termed hemolytic anemia. Furthermore, other laboratory and clinical findings (such as jaundice and dark-colored urine) can be observed [23].
Complement-directed therapy for cold agglutinin disease: sutimlimab
Published in Expert Review of Hematology, 2023
Catherine M. Broome
Cold agglutinin–antigen complexes on red blood cells bind complement protein C1q generating the C1 complex, resulting in classical complement pathway activation and production of C3a and C3b [3,14]. C3b is deposited on the red blood cells and acts as a powerful opsonin causing predominantly extravascular hemolysis in the liver. It also causes, to a lesser extent, intravascular hemolysis via the terminal complement cascade and formation of the membrane attack complex. Both C3a, from proximal complement activation and C5a from terminal complement activation contribute to a systemic inflammatory state in CAD (Figure 1) [4,11,14,18]. Complement-mediated symptoms include hemolysis, anemia, fatigue, dyspnea, jaundice, hemoglobinuria, and an increased risk of thromboembolic events [4,9,10,17,22,23]. Beyond activating the classical complement system, IgM bound to the surface of red blood cells can cause agglutination of red blood cells, leading to agglutination-mediated circulatory symptoms in 40–90% of patients with CAD [10,14]. Circulatory symptoms in CAD are often first observed in the exposed, peripheral vasculature [16].
Related Knowledge Centers
- Babesia
- Haptoglobin
- Hemoglobinemia
- Proximal Tubule
- Bilirubin
- Circulatory System
- Hemolysis
- Methemoglobin
- Hemopexin
- Methemalbumin