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Long-term study of 21 PNH patients revealed an unexpectedly high incidence of functional and anatomic renal abnormalities. Most patients demonstrated varying degrees of hematuria and proteinuria distinct from hemoglobinuria. Evaluation of renal function revealed hyposthenuria, abnormal tubular function, and declining creatinine clearance. Radiologically these patients had enlarged kidneys, cortical infarcts, cortical thinning, and papillary necrosis which were confirmed by autopsy studies. Hypertension developed in eight patients. Urinary tract infection was uncommon. The renal findings bear striking similarity to those of sickle cell anemia. Contrary to the usual opinion, out studies clearly showed evidence of widespread renal pathology in PNH most likely due to repeated microvascular thrombosis similar to the venous thrombosis involving other organs in this disorder.

1. Clonal theories of disease, particularly progressive clonal growth and selection in tumorogenesis, were briefly cited. 2. Evidence for the clonal nature of PNH was presented. Correlation of red cell hemolysis with (a) G-6-PD type in two female G-6-PD mosaics with PNH and with (b) erythrocyte acetylcholinesterase deficiency, provides strong evidence for the clonal theory of PNH. 3. Possible pitfalls in defining "hidden PNH clones" in other diseases by the use of PNH hemolytic tests were discussed. 4. The potential of PNH as a study model for clonal evolution in human disease was emphasized.

We have reported a case of coronary artery thrombosis in a 36-year-old man with paroxysmal nocturnal hemoglobinuria (PNH), a potentially lethal thrombotic complication not previously documented in this unique patient population. Although the etiology of PNH remains unknown, the pathogenesis appears to be related to the deficiency of a specific membrane complement-regulatory protein, decay accelerating factor. Coronary artery thrombosis must now be added to the list of potential life-threatening thrombotic complications.

A long-term study of 17 patients with paroxysmal nocturnal hemoglobinuria revealed an unexpectedly high incidence of functional and anatomic renal abormalities. All patients demonstrated varying degrees of hematuria and proteinuria distinct from hemoglobinuria. All patients also had granular casts in multiple urinalyses. Evaluation of renal function revealed hyposthenuria, abnormal tubular function and declining creatinine clearance. Radiologically, one or more of these demonstrated enlarged kidneys, renal cortical infarcts and thinning, papillary necrosis, acute renal atrophy, retroperitoneal hematoma and ureteral infarction, which were confirmed by autopsy studies. Hypertension developed in 7 patients. Urinary tract infection was uncommon and no patient had a clinical history compatible with chronic or acute pyelonephritis. Contrary to usual opinion our compatible clearly showed evidence of frequent and widespread renal pathology in paroxysmal nocturnal hemoglobinuria most likely due to repeated microvascular thromboses similar to the venous trombosis involving other organs in this disorder. Since most of these patients present initially to urologists knowledge of this entity is mandatory.

Hepatic venous thrombosis (HVT) should be recognized as a distinct and highly lethal thrombotic complication of paroxysmal nocturnal hemoglobinuria. In a patient with fulminant onset prompt recognition of a triad of clinical, laboratory and liver scan findings facilitated early, aggressive and prolonged heparinization followed by coumadin maintenance, all with good results. Additionally a case of asymptomatic, smoldering HVT was unearthed by liver scan survey and confirmed by hepatic venogram; the patient was started on a regimen of Coumadin (crystalline sodium warfarin, Endo).

During the past two decades, we have had the opportunity to study a large number of patients with the rare hemolytic anemia, paroxysmal nocturnal hemoglobinuria. Sixteen surgical procedures have been performed upon ten patients with paroxysmal nocturnal hemoglobinuria. From this experience, we have developed certain recommendations for preoperative evaluation and preparation, intraoperative management and post-operative care. Any proposed surgical procedure for a patient with paroxysmal nocturnal hemoglobinuria should be closely managed by a team consisting of a surgeon, hematologist and anesthesiologist. In the preoperative evaluation, particular attention should be paid to the hematologic, renal and hepatic status. Transfusion requirements, whether precipitated by hemolytic episodes or surgical blood loss, should be met with either washed or perviously frozen erythrocytes, with consideration of the use of dextran for volume replacement. Dextran is the treatment of choice for thrombotic epidsodes. Close attention should be given to avoiding hypoxia and dehydration. Anesthetic agents which may activate complement or may be hepatotoxic are to be avoided.

Complement coating and hemolysis were observed when erythrocytes from patients with paroxysmal nocturnal hemoglobinuria (PNH) were incubated in isotonic sucrose solution in the presence of small amounts of serum. Normal cells were likewise coated with complement components but did not hemolyze. Both normal and PNH erythrocytes reduced the hemolytic complement activity of the serum used in this reaction. Experience with other simple saccharides and related compounds suggests that the low ionic strength of the sucrose solution is the feature that permitted complement coating of red cells and hemolysis of PNH erythrocytes. Isotonic solutions of other sugars or sugar alcohols that do not readily enter human erythrocytes could be substituted for sucrose. The mechanism for these reactions may possibly relate to the agglutination observed with erythrocytes tested in the serum-sucrose system. Even though PNH hemolytic activity could be removed by prior heating of serum or barium sulfate treatment of plasma, the agglutination phenomenon still persisted. The in vitro conditions necessary for optimal sucrose hemolysis of PNH erythrocytes were described and compared with those of the classical acid hemolysis test. The requirement for less serum in the sucrose hemolysis system than needed in the standard acid hemolysis reaction makes certain experiments, especially those using large amounts of autologous PNH serum, much more feasible. Additional advantages of the sucrose hemolysis test are that it can be carried out at room temperature in the presence of oxalate and citrate and that critical pH control is not essential. To date, the sucrose hemolysis test has been a sensitive and specific one for PNH. A modified test used for screening purposes, the "sugar water" test, is very easy to perform.