810 Proc. roy. Soc. Med. Volume 69 November 1976

Meeting 12 March 1976

Cases Paroxysmal Nocturnal Hsemoglobinuria C Pollick BSC MRCP (for J G Lewis MD FRCP) (Edgware General Hospital, Edgware, Middlesex, HA8 OAD) Mrs C R, aged 64 History: In June 1971, after being a blood donor for ten years, she was refused by the Transfusion Service when her Hb was 11.7 g/dl. Her doctor prescribed Ferrograd-C without further tests and she took it daily until February 1976. In October 1975 her urine became dark mahogany throughout the 24 hours of the day. She was jaundiced and nauseated but had no abdominal pain; the ftces remained normal. Jaundice lasted six weeks and relapsed two weeks later for a further six weeks. There was no significant weight loss. She was referred to hospital in January 1976 when she appeared well but was mildly icteric and anemic without lymphadenopathy or hepatosplenomegaly. Investigations: Hb 9.0 g/dl, MCV 15 fl, reticulocytes 12.7%, ESR 47 mm in first hour (Westergren). WBC 4.6 x 109/1 (neutros. 60 %, lymphos. 30%, monos. 8%, eosinos. 2 %). Platelets 100 x 109/1. Serum B12 and folate normal. Iron 98, total iron-binding capacity 248 ,g/dl. Direct Coombs test negative. ANF negative. Sternal marrow aspirate showed normoblastic erythroid hyperplasia, normal leukopoiesis and thrombopoiesis. Plasma: hamoglobin not detected but methkmalbumin present and haptoglobin reduced. Urine: himoglobin not detected but h2emosiderin present in large quantities. Ham's test showed 18 % lysis in presence of acid and complement. Leukocyte alkaline phosphatase score 10 (normal range 40-100). Bilirubin 3.0 mg/dl (conjugated 1.0 mg/dl), alkaline phosphatase 6.6 K-A units. SGOT 280 SF units. Albumin 4.0, globulin 2.2 g/dl. Urine: bilirubin negative) urobilinogen normal. Liver scan normal.

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Comment Comprehensive reviews of paroxysmal nocturnal hiemoglobinuria (PNH) have been published by Dacie & Lewis (1972) and, more recently, by Sirchia & Lewis (1975). Several features of this patient's history are relevant for discussion. She appears to have been anmmic for four years before the episodes of severe hiemolysis that were apparent clinically. This accords with Dacie's experience that 38% of patients present solely as anmmia without clinical signs or symptoms of haemolysis. The red cell is not the only abnormality found in PNH. For instance, this patient's platelet count is reduced and the neutrophils are low normal (2500 x I08/1); in addition her leukocyte alkaline phosphatase score is low. Dacie found that 80% of his patients had fewer than 150 x 109/1 platelets and 55% fewer than 1500 x 109/l neutrophils. Iron therapy is not generally given in PNH even though the majority will become iron deficient, as it may produce exacerbations of htmolysis, possibly by stimulating marrow output of new cells sensitive to hemolysis (Hartmann & Kolhouse 1972) or perhaps by rendering the cell more sensitive to complement. The patient's long-term iron therapy may therefore have contributed to the hemolysis. She has not yet required any treatment. The last relevant point in this patient is her raised SGOT. This may be elevated two to ten times above-normal in severe hkmolysis and does not indicate hepatic venous thrombosis which is the cause of death in 30% of patients (Dacie & Lewis 1972). This is best diagnosed by a liver scan examined serially every six months (Peytreman et al. 1972). Her liver scan was normal and in a period of remission from severe hkmolysis her SGOT has decreased from 280 to 98 SF units (normal limit 40 SF units).

Acknowledgment: I am grateful to Dr S Ardeman for his help with this case. REFERENCESj Dacie J V & Lewis S M (1972) Series H!znatologica 5, pt. 3, 3-23 Hartmann R C & Kolhouse J F (1972) Series Hrmatologica 5, pt. 3, 42-60 Peytreman R, Rhodes R S & Hartman R C (1972) Series Ha-niatologica 5, pt. 3, 115-136 Sirchia G & Lewis S M (1975) Clinics in He'niatology 4, 199-229

(Meeting to be continued)