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A B S T R A C T The red cells of patients with hereditary erythroblastic multinuclearity with a positive acidified serum test (HEMPAS), a form of congenital dyserythropoietic anemia, and the cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) are lysed more readily than normal cells by certain antibodies, notably cold agglutinins (anti-I) and complement. With some but not other examples of anti-I, HEMPAS and PNH cells adsorbed more antibody than normal cells. Equal quantities of adsorbed antibody bound equal quantities of the first component of complement (Cl) to normal, PNH, and HEMPAS cells. However, for a given quantity of bound antibody and C1, much more of the fourth component of complement (C4) was bound to HEMPAS cells than to normal cells. This resulted in the binding of proportionately larger quantities of the third component of complement (C3) to these cells. The same amount of bound C3 was found on the membranes of normal and HEMPAS cells for a given degree of lysis. Hence, the marked increase in lysis of HEMPAS cells is due to the increased adsorption of antibody and/or increased binding of C4.PNH cells bound the same amount of C4 per bound C1 as normal cells but bound more C3 than normal cells. However, the mean concentration of C3 on the membrane of PNH cells was one-third to one-fifth that on normal cells for a given degree of lysis. Hence, the increased lysis of PNH cells is due to the increased binding of C3 and increased hemolytic effectiveness of the bound C3.

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This report addresses the difficult situation in which a patient or surrogate decision maker wishes cardiopulmonary resuscitation to be attempted even though the physician believes that resuscitation efforts would be futile. It also reviews current controversies surrounding the subject of do-not-resuscitate (DNR) orders and medical futility, discusses the complex medical, legal, and ethical considerations involved, and then offers recommendations as a guide to clinicians and ethics committees in resolving these difficult issues. Conflicts over DNR orders and medical futility should not be resolved through a policy that attempts to define futility in the abstract, but rather through a predefined and fair process that addresses specific cases and includes multiple safeguards. As it examines these issues, the report focuses on the Veterans Health Administration (VHA). Current national VHA policy constrains physicians from entering a DNR order over the objection of a patient or surrogate even if the physician believes cardiopulmonary resuscitation to be futile. The VHA National Ethics Committee recommends that VHA policy be changed to reflect the opinions expressed in this report. The National Ethics Committee, which is composed of VHA clinicians and leaders, as well as veterans advocates, creates reports that analyze ethical issues affecting the health and care of veterans treated in the VHA, the largest integrated health care system in the United States. This report does not change or modify VHA policy.

Three patients are described who either died suddenly or had severe, lifethreatening arrhythmias during or immediately after doxorubicin administration. Since doxorubicin and daunorubicin administration is known to be associated with acute EKG abnormalities, the acute decompensation in these patients appeared to be caused by the administration of these agents. The importance of careful observation of patients receiving doxorubicin, because of the possibility of acute cardiac arrhythmias, is stressed.

Patients with heterozygous C4A null phenotype have increased complement activation by heparin-protamine complexes during cardiac operations, possibly because of their defective clearance. The classic pathway complement activation by heparin-protamine interaction correlates with postoperative pulmonary shunt fractions.