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Immunohematology
Published in Gabriel Virella, Medical Immunology, 2019
Gabriel Virella, Armand Glassman
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.
Hemolytic Anemias: General Considerations
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
The rapid decline in hemoglobin/hematocrit, lack of evidence of bleeding, and indirect hyperbilirubinemia makes the diagnosis of hemolysis apparent, even in the absence of significant reticulocytosis. The limited reticulocyte response undoubtedly reflects functional marrow compromise by acute leukemia. The presence of hemoglobinuria (blood detected on urine dipstick out of proportion to red cells) confirms that this is intravascular hemolysis.
Disseminated Intravascular Coagulation
Published in Rodger L. Bick, 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.
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].
Sickle cell disease in the era of precision medicine: looking to the future
Published in Expert Review of Precision Medicine and Drug Development, 2019
Martin H Steinberg, Sara Kumar, George J. Murphy, Kim Vanuytsel
Intravascular hemolysis can be assessed using a principal component analysis that includes reticulocyte count, LDH, AST and bilirubin levels that computes a hemolytic component. When this estimate was used as a phenotype in a GWAS, hemolysis was associated with rs7203560 in NPRL3. The HBA2/HBA1 regulatory elements, termed HS-48 [R1], HS-40 [R2] and HS-33 [R3], are located in introns of NPRL3. They act independently and additively to regulate α-globin gene expression. It was hypothesized that α-globin gene regulatory loci tagged by rs7203560 downregulated the expression of the α-globin genes [52]. Two variants, rs11865131 and rs11248850, upregulate α-globin gene expression [53]. Unlike rs7203560, these variants were not associated with hemolysis. Adjusting for the effects of these SNPs did not change the association of rs7203560 with hemolysis. However, in patients with sickle cell anemia and concurrent gene deletion α thalassemia, rs11248850 and rs11865131 nullified the hemolysis-reducing effect of α thalassemia [54]. Regulatory elements of the α-globin gene cluster can up- or down-regulate gene expression; variants of these elements might account for some of the phenotypic heterogeneity of sickle cell anemia.
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.