Elsevier

Seminars in Hematology

Volume 52, Issue 4, October 2015, Pages 287-303
Seminars in Hematology

Non-immune Hemolysis: Diagnostic Considerations☆

https://doi.org/10.1053/j.seminhematol.2015.07.005Get rights and content

Non-immune hemolytic anemia (NIHA) is characterized by positive routine hemolytic tests but negative anti-human immunoglobulin (Coombs) test. Hereditary non-immune hemolysis includes disorders of erythrocytic enzymes, membrane, hemoglobin (qualitative and quantitative disorders), as well as the rare hereditary forms of thrombotic microangiopathies. Acquired NIHA includes paroxysmal nocturnal hemolysis (PNH), infections, drug and metal intoxications with as a target red blood cells or endothelium of capillaries, the rare acquired forms of thalassemia or erythrocytic membrane disorders, and hemolysis secondary to a dysfunctioning artificial (prosthetic) cardiac valve. Identification of the specific cause of NIHA is sometimes difficult and requires not only a good knowledge of this entity but mainly a qualified specialized hematologic laboratory. An algorithm to be used in every new patient consulting for NIHA is proposed in the last part of this article.

Section snippets

Classification of Non-Immune Hemolysis: Acquired and Hereditary

NIHA can be classified using different bases. We preferred a first division into acquired and hereditary forms. Each form may primarily affect red blood cells (enzymopathies, membrane disorders, and pathologies of Hb) or may be the result of a toxic effect or insult to normal erythrocytes, or a pathology of the environment (drug and metal intoxication, micro- or macro-angiopathy, infections, intravascular coagulopathy, etc). Table 1 depicts this simplified classification, which has the great

NIHA Associated With Hereditary Enzymopathies

Because red blood cells have no nucleus and other organelles, they use the Embden-Meyerhof anaerobic glycolysis and its two shunts (Rapoport–Luebering and the pentose phosphate) to: (1) assure proper function of K+/Na+ pumps; (2) reduce oxidized Hb–both functions 1 and 2 are involved in maintaining the integrity of RBC membrane; (3) to regulate the affinity of oxygen to Hb; and (4) to provide protection against oxidative stress.1 Figure 1 is a schematic overview of the Embden-Meyerhof pathway

NIHA Secondary to Paroxysmal Nocturnal Hemoglobinuria

Some basic notions concerning complement: The term “complement” was introduced by Paul Ehrlich in 1890. Complement is part of our innate defense. Complement’s 35 proteins are produced in the liver.42 Complement needs activation to participate to our innate immune response. There is a network of plasma and cellular membrane proteins that regulate complement’s activation. Deficit of certain complement’s factors or its “hyperactivation” leads to diverse pathologic situations. In general, deficits

Conclusions and Proposed Diagnostic Algorithm

If it is easy to diagnose NIHA (association of hemolysis with negative anti-human immunoglobulin test), it may be difficult to identify the exact clinical entity. This is because causes of NIHA are extremely heterogeneous and sometimes two or more entities may have the same clinical and hematological presentation. Here, we propose a simplified classification where the basis is to distinguish hereditary from acquired forms of NIHA. For this reason, it is mandatory to begin with an exhaustive

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    Conflicts of interest: none.

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