Paroxysmal nocturnal haemoglobinuria. A clinicopathological study of 26 cases.

26 patients, 13 male and 13 female, with paroxysmal nocturnal haemoglobinuria (PNH) are described. The diagnosis was based on the finding of a positive Ham's test. PNH developed in 4 patients with aplastic anaemia, and 3 patients with established PNH developed marrow hypoplasia during the course of the disease. In 2 cases autoimmune haemolysis was also present; this association has not been described previously. The majority of patients presented with anaemia and dark urine, or with evidence of thrombosis. A high index of suspicion was needed to avoid missing the diagnosis. Haemolytic crises were usually precipitated by infection, and renal failure requiring dialysis sometimes resulted; a positive direct antiglobulin test was often found at times of increased haemolysis. Thromboses were the most frequent complication, and when intra-abdominal vessels were affected, pain was particularly troublesome. The disease had a widely variable course; 4 patients made a complete recovery and 10 died, 8 from thrombotic complications and 2 from infections associated with marrow hypoplasia. Survival ranged from 1 year to 30 years and the median survival in those who died was 3.5 years.

Autoimmune haemolysis in childhood and adolescence.

The clinico-pathological features of 42 children with autoimmune haemolysis are described. Over 65% of cases were seen before their 5th birthday. In this group males predominated by the ratio of 2.5:1, but in the older children both sexes were equally affected. The incidence decreased from 1 in 188 X 10(3) in young males to 1 in 1,780 X 10(3) in children over 10. Cases were classified serologically. Of particular note was the frequency of Donath-Landsteiner haemolysis which equalled that due to warm autoantibodies; together these groups made up 79% of the total cases. Most haemolytic episodes followed an acute infection. This was frequently mild and often involved the upper respiratory tract; in only 2 patients was haemolysis associated with underlying collagenosis. Typically there was a sudden onset of pallor and malaise; jaundice, splenomegaly and hepatomegaly were found in about half the subjects. Haemoglobinuria was characteristic of Donath-Landsteiner haemolysis. The illness was severe, with Hb levels falling below 6.0 g/dl in 28 patients. Prednisolone, blood transfusion and, where indicated, antibiotics were usually effective in treating the illness, with splenectomy reserved for cases where this treatment was unsatisfactory. In several individuals no treatment was required. Recovery was rapid, and complete recovery occurred in 83% of patients, usually within 6 months. Although 2 patients died, a generally optimistic prognosis can be given, particularly in the absence of an underlying chronic disorder.

Autoimmune hemolysis: mixed warm and cold antibody type.

25 patients with mixed autoimmune haemolysis are described; in these cases the combined criteria for warm antibody autoimmune haemolysis and also the cold agglutinin syndrome were present. The direct antiglobulin tests were positive with IgG and complement coating of the red cells. The IgM and IgG components could be separated. The cold autoantibodies were active at 30 degrees C or above and often showed blood group specificity within the Ii system; specificity was not usually evident in the warm component. Haemolysins were found in 18 patients. Serologically, the condition maintained its mixed nature throughout; only 2 cases later changed to a warm type picture. Mixed autoimmune haemolysis was found in all age groups but was more frequent in later life; the male:female ratio was 1:15. The cases were either idiopathic (44%) or secondary; in the latter, systemic lupus erythematosus or lymphoma were the most frequently associated disorders. The patients tended to have severe haemolysis which, although usually responding well to treatment, ran a chronic course with intermittent exacerbations, thus making overall management difficult; plasma exchange may be a useful adjunct to chemotherapy.

Autoimmune haemolysis associated with Donath-Landsteiner antibodies.

The clinical pattern of haemolysis associated with Donath-Landsteiner antibodies has undergone a change over the years. In the current study 13 patients developed the acute form of the disease whilst only 1 presented with the classical picture of chronic paroxysmal cold haemoglobinuria. The acute illness typically occurred in young children with a male predominance of about 2.5:1; 10 patients were less than 5 years old. There was often a history of a preceding infection, the onset was sudden, prostration, haemoglobinuria and pallor were prominent. The patients were very ill but rapid and complete recovery usually occurred within a few days; however, 1 patient died. Treatment consisted of rest and warmth; in addition blood transfusion was needed in 7 patients. The chronic disease (which was non-syphilitic in origin) followed a benign course, warmth and avoidance of cold being all that were necessary to maintain the patient's well-being. It is felt that the general term for this disorder should be Donath-Landsteiner haemolysis rather than the traditional paroxysmal cold haemoglobinuria.

Erythrocyte autoantibodies, autoimmune haemolysis and pregnancy.

The clinical and serological records of 20 pregnant patients with erythrocyte autoantibodies were critically reviewed and analysed. This series, the largest reported, confirmed an association between erythrocyte autosensitization and pregnancy, and suggested that this occurred on an average of 1 in 50,000 pregnancies. The clinical presentation varied from severe haemolytic anaemia to serological abnormalities discovered during the routine testing of well patients; overt haemolysis was present in 7 cases. Treatment was only necessary in 3 patients where the haemolysis was severe. 3 infants were mildly affected with haemolytic disease due to the maternal autoantibodies crossing the placenta but no treatment was needed. The risks to the infant were increased when other active autoimmune conditions (e.g., systemic lupus erythematosus) were present. With early diagnosis and appropriate treatment, outlook for mother and child is good.

Autoimmune haemolysis: an 18-year study of 865 cases referred to a regional transfusion centre.

Clinical and serological records of 865 patients with confirmed autoimmune haemolysis (AIH)--a much larger series than any previously reported--were critically reviewed nd analysed. A proposed new classification for AIH based on serological findings differs from traditional classifications in that a new category of "mixed" AIH has been defined in which both "warm" and "cold" autoantibodies are present, and both are capable of causing haemolysis. Patients in this mixed group tend to have severe disease that may run a chronic intermittent course. The presentation of cold agglutinin disease is much more variable than has been seen in previous studies, haemolysis due to low titre autoantibodies being common. The AIH associated with pregnancy, usually considered as being of bad prognosis, is often mild and self limiting in the absence of other associated disorders.