Blood, 1950, Vol. 5, No. 9, pp. 822-842.
© 1950 American Society of Hematology, Inc.
PAROXYSMAL NOCTURNAL HEMOGLOBINURIA
THE MECHANISM OF HEMOLYSIS AND ITS RELATION TO THE
COAGULATION MECHANISM
WILLIAM H. CROSBY MAJOR, MC, AUS1 and
WILLIAM DAMESHEK M.D.1
1 Ziskind Research Laboratories (Hematology) of the J. H. Pratt and New England Center
Hospitals, and the Department of Medicine, Tufts College Medical School, Boston, Mass.
1. Paroxysmal nocturnal hemoglobinuria is a hemolytic anemia of obscure origin, characterized by a defect of the erythrocytes which makes them susceptible to
hemolysis by a normal plasma or serum factor.
2. The hemolytic reaction does not involve a complement-antibody reaction
but is rather an enzyme-like reaction which is related to the coagulation mechanism of the blood.
3. Evidence suggests that the heat-labile hemolytic factor in PNH, if not
identical with the serum coagulation accelerator, resembles it in many aspects.
The hemolytic factor is present in plasma as an inert precursor which is activated
by thrombin.
4. The action of this enzyme in vivo is discussed. Its possible relationship to
various other manifestations of the disease is mentioned.
5. Dicumarol was able to inhibit hemolysis in a patient with PNH. Therapeutically, the drug was disappointing. It did not reduce the hemolytic precursor
and did not prevent hemolytic crises. However, its use was not dangerous, suggesting that it may be of value during crises of this disease when thrombosis is a threat.
It is possible that as yet undiscovered dicumarol-like drugs which would inhibit
the production of serum Ac-globulin factor and of the hemolytic factor might offer
a means of treatment for patients with paroxysmal nocturnal hemoglobinuria.
6. Dilute heparin facilitates the activation of the hemolytic enzyme by thrombin. The use of heparin in paroxysmal nocturnal hemoglobinuria may be dangerous.
7. Lysis of PNH cells by a substance related to clotting mechanism offers a new
approach to the study of the coagulation problem.
Note:
ACKNOWLEDGMENT
We are indebted to Dr. Thomas Hale Ham and Dr. Walter H. Seegers for their suggestions during
the course of this work and for their helpful criticism of the manuscript.
