JMH-bearing protein

Red blood cells

Some B and T lymphocytes


Lymphocytes All blood cells"

All blood cells6 All blood cellsc All blood cells

Neutrophils, NK cells,d Macrophages,d some T lymphocytesd Monocytes, macrophages, granulocytes Monocytes, granulocytes

Red blood cells

Red blood cells

Red blood cells

Red blood cells, lymphocytes

Red blood cells

Neutrophils Neutrophils

All blood cells B lymphocytes, neutrophils, eosinophils

"On lymphocytes expressed in GPI-linked and transmembrane form. •"Level of expression on T lymphocytes varies.

'Expression of C8bp on human blood cells is controversial (personal communication. Taroh Kinoshita) ^Expressed in a transmembrane form.

From Young NS, Bressler M, Casper JT, Liu J. Biology and therapy of aplastic anemia. In: Schacter GP, McArthur TR, editors. Hematology 1996. American Society of Hematology, 1996; with permission; and Ware RE. Autoimmune hemolytic anemia. In: Nathan DG, Orkin SH, Ginsburg D, Look TA, editors. Nathan and Oski's Hematology of Infancy and Childhood. 6th ed. Philadelphia: WB Saunders, 2003, with permission.

Mechanism of Hemolysis and Hemoglobinuria in Paroxysmal Nocturnal Hemoglobinuria

The absence of surface complement-regulatory proteins, namely, CD55 and CD59, allows deposition of complement factors and C3 convertase complexes, which leads to chronic complement-mediated intravascular hemolysis, resulting in hemoglobinuria.

Mechanism of Hypercoagulable State

The mechanism of a hypercoagulable state in PNH is not well understood. Complement deposition on platelets results in vesiculations of their plasma membranes, which leads to increased procoagulant activity of the platelets. The mono-cytes and granulocytes of PNH cells lack the receptor for the GPI-linked urokinase plasminogen activator and this deficiency may lead to impaired fibrinolysis.

The antithrombin (AT), protein C, and protein S levels are normal in PNH patients.

Mechanism of Defective Hematopoiesis

The mechanism of defective hematopoiesis (macrocytosis with bone marrow eryth-roid dysplasia) evolving to severe aplastic anemia in some patients is not well understood. However, the following explanations have been considered:

• The initial step is the development of the PIG-A mutation. This is followed by a bone marrow insult.

• Resistance of PNH clones to injury by the insulting agents compared with susceptibility of normal hematopoietic stem cells.

• The intrinsic proliferation advantage of PNH stem cells compared with normal hematopoietic stem cells results in selection of abnormal stem cells followed by clonal expansion.

• Suppression of normal hematopoietic stem cells by PNH cells and evolution to MDS or AML

In the preceding list, it is assumed that two populations of stem cells normally reside in bone marrow: (1) a large population of normal stem cells and (2) a minor population of PNH stem cells.

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