PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA AND PREGNANCY
1
1099 POST-TRANSFUSION GRAFT-VERSUS-HOST DISEASE AFTER OPEN HEART SURGERY StR,—Graft-versus-host disease (GVHD) can develop after transfusions in patients with deficient cell-mediated immunityl that is congenital (eg, severe combined immunodeficiency disease) or acquired (eg, leukaemia or advanced carcinoma). However, we know of no report in the English language or post-transfusion GVHD after open heart surgery. In Japan, there have been several reports of "postoperative erythroderma (POE)", a condition characterised by fever, rashes, agranulocytosis, and aplastic marrow, with rapid deterioration resulting in death; most cases have followed open heart surgery 2 At first, drug allergy was suspected.3 In a typical case of POE the patient, about 10 days after a seemingly uneventful recovery from open heart surgery, has a fever and rash; transaminase levels rise; diarrhoea often develops; and then there is rapidly progressive pancytopenia, aplastic marrow, and erythroderma, and the patient dies from- septicaemia. These findings resemble post-transfusion GVHD, except that there seems to be no cause for the immuno- deficiency.4 Ino et al2 suggested that POE be called "GVHD like syndrome". The incidence is 1 in every 300-400 cases of open heart surgery in Japan. The pancytopenia in POE progresses so rapidly that it is very difficult to get enough lymphocytes for HLA typing. However, we have succeeded in two cases, both men with only one child. One patient was 68 years old and the other 44. Both received unirradiated fresh blood from random donors. No parents were available for testing but HLA typing of the patients and their wives and children revealed that the patients’ HLA phenotypes were not those deduced from the child’s HLA findings (see figure). The wives confirmed repeatedly that there was no chance that the husband was not the father of the child. We strongly suspect that the patient’s lymphocytes had been replaced by those of the donors. This is consistent with post-transfusion GVHD. HLA types in two families in which the father had postoperative B erythroderma. Disparate haplotypes are circled. Although more open heart surgery is done in the United States there have been no reports of POE in that country. We suspect that fresh blood--especially when used immediately after collection, which is the common practice in Japan-increases the risk of this disease. Sakakibara Heart Institute, 2-5-4 Yoyogi Shibuya-ku, Tokyo 151, Japan University of Tokyo TAKAYUKI SAKAKIBARA TAKEO JUJI 1. Holland PV. Transfusion-associated graft-versus-host disease: Prevention using irradiated blood products. In: Garratty G, ed. Current concepts in transfusion therapy. Arlington: American Association of Blood Banks, 1985: 259-315. 2. Ino T, Matsuura A, Takahashi R, et al. GVHD like syndrome following transfusion at the time of surgery. Geka 1986; 48: 706-12 (Japanese). 3. Shimoda T. On postoperative erythroderma. Geka 1985; 17: 487-92 (Japanese). 4. Aoki Y, Nakamura H, Sakakibara Y. Probable graft-versus-host reaction following massive blood transfusion in an aged patient with postoperative aortic aneurysm: a case report. Nippon Naika Gakkai Zasshi 1984; 73: 99-106 (Japanese). PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA AND PREGNANCY SIR,-Paroxysmal nocturnal haemoglobinuria (PNH) is a chronic haemolytic disorder the manifestations of which include a predisposition to thromboembolism and Budd-Chiari syndrome ;2 the latter may be precipitated by stress, including pregnancy.3-5 Experience of pregnancy in PNH is limited but awareness of the risks involved has prompted the suggestion that conception should be avoided if possible. 6We report experience with a patient who has had two healthy babies at full term, showing that, at least in the more benign forms of PNH, uncomplicated pregnancy is possible despite severe thrombocytopenia. The patient was first seen in 1978 at the age of 22 with palpitations, easy fatigue, and shortness of breath. Laboratory findings were: haemoglobin 4-6 g/dl, total white cell count 2-5 x 109/1 (41 % neutrophils, 1 % eosinophils, 51 % lymphocytes, 7% monocytes), and platelet count 127 x 109/1. The diagnosis was established by strongly positive Ham’s acid lysis and sucrose water test. Bone-marrow aspiration and trephine biopsy showed well marked erythroid hyperplasia with megaloblastic haematopojesis and absent iron stores. Coagulation screens and platelet function studies were normal. Haemoglobin was maintained at 10 g/dl with washed packed red cells and supplementary iron and folate. Treatment did not aggravate the haemolysis. She remained well for 5 years until, in April, 1979, she was admitted to hospital with an acute haemolytic episode associated with pelvic sepsis. , In 1981 the patient presented 2 months pregnant. There was no progression to bone-marrow hypoplasia or evidence for leukaemic transformation. She was vaginally delivered of a full-term normal child. Her platelet count fluctuated between 30 and 50 x 109/1. In October, 1984, she again presented 2 months pregnant and was delivered of a full-term normal child; on this occasion allogeneic platelet cover was needed to control bleeding from the thrombo- cytopenia. Evaluation post partum showed that she had progressed to severe bone-marrow hypoplasia. Despite the apparently benign nature of this patient’s clinical and haematological syndrome, her illness is now following the well- recognised course in which normal bone marrow becomes increas- ingly hypoplastic and ultimately aplastic. Reversion to fetal type haematopoiesis with rising HbF levels and expression of i antigen provides further evidence for the expression of this acquired defect in haematopoiesis, and bone-marrow transplantation may yet be required. Nevertheless, despite the usual view that pregnancy is too hazardous in patients with PNH, a poor outlook may not be inevitable. Leukaemia Centre, University of Cape Town and Department of Haematology, Groote Schuur Hospital, Observatory, Cape, South Africa PETER JACOBS LUCILLE WOOD 1. Dacie JV, Lewis SM. Paroxysmal nocturnal haemoglobinuria clinical manifestations, haematology, and nature of the disease. Ser Haematol 1972; 5: 3-23. 2. Liebowitz AI, Hartmann RC. The Budd-Chiari syndrome and paroxysmal nocturnal haemoglobinuria. Br J Haematol 1981; 48: 1-6. 3. Payne PR, Holt JM, Neame PB. Paroxysmal nocturnal haemoglobinuria parturition complicated by presumed hepatic vein thrombosis. J Obstet Gynaecol Br Commonw 1968; 75: 1066-68. 4. Frakes JT, Burmeister RE, Giliberti JJ. Pregnancy in a patient with paroxysmal nocturnal hemoglobinuria. Obstet Gynec 1976; 47 (suppl): 22s. 5. Spencer JAD. Paroxysmal nocturnal haemoglobinuria in pregnancy. Br J Obstet Gynaecol 1980; 87: 246. 6. Wosniak AJ, Kitchen CS. Prospective hemostatis studies in a patient having paroxysmal nocturnal hemoglobinuria, pregnancy , and cerebral venous thrombo- sis. Am J Obstet Gynecol 1982; 142: 591-93.
Transcript of PAROXYSMAL NOCTURNAL HAEMOGLOBINURIA AND PREGNANCY
1099
POST-TRANSFUSION GRAFT-VERSUS-HOSTDISEASE AFTER OPEN HEART SURGERY
StR,—Graft-versus-host disease (GVHD) can develop aftertransfusions in patients with deficient cell-mediated immunityl thatis congenital (eg, severe combined immunodeficiency disease) oracquired (eg, leukaemia or advanced carcinoma). However, weknow of no report in the English language or post-transfusionGVHD after open heart surgery.
In Japan, there have been several reports of "postoperativeerythroderma (POE)", a condition characterised by fever, rashes,agranulocytosis, and aplastic marrow, with rapid deteriorationresulting in death; most cases have followed open heart surgery 2 Atfirst, drug allergy was suspected.3 In a typical case of POE thepatient, about 10 days after a seemingly uneventful recovery fromopen heart surgery, has a fever and rash; transaminase levels rise;diarrhoea often develops; and then there is rapidly progressivepancytopenia, aplastic marrow, and erythroderma, and the patientdies from- septicaemia. These findings resemble post-transfusionGVHD, except that there seems to be no cause for the immuno-deficiency.4 Ino et al2 suggested that POE be called "GVHD likesyndrome". The incidence is 1 in every 300-400 cases of open heartsurgery in Japan.The pancytopenia in POE progresses so rapidly that it is very
difficult to get enough lymphocytes for HLA typing. However, wehave succeeded in two cases, both men with only one child. Onepatient was 68 years old and the other 44. Both receivedunirradiated fresh blood from random donors. No parents wereavailable for testing but HLA typing of the patients and their wivesand children revealed that the patients’ HLA phenotypes were notthose deduced from the child’s HLA findings (see figure). Thewives confirmed repeatedly that there was no chance that thehusband was not the father of the child. We strongly suspect that thepatient’s lymphocytes had been replaced by those of the donors.This is consistent with post-transfusion GVHD.
HLA types in two families in which the father had postoperative B
erythroderma.Disparate haplotypes are circled.
Although more open heart surgery is done in the United Statesthere have been no reports of POE in that country. We suspect thatfresh blood--especially when used immediately after collection,which is the common practice in Japan-increases the risk of thisdisease.
Sakakibara Heart Institute,2-5-4 Yoyogi Shibuya-ku,Tokyo 151, Japan
University of Tokyo
TAKAYUKI SAKAKIBARA
TAKEO JUJI
1. Holland PV. Transfusion-associated graft-versus-host disease: Prevention usingirradiated blood products. In: Garratty G, ed. Current concepts in transfusiontherapy. Arlington: American Association of Blood Banks, 1985: 259-315.
2. Ino T, Matsuura A, Takahashi R, et al. GVHD like syndrome following transfusion atthe time of surgery. Geka 1986; 48: 706-12 (Japanese).
3. Shimoda T. On postoperative erythroderma. Geka 1985; 17: 487-92 (Japanese).4. Aoki Y, Nakamura H, Sakakibara Y. Probable graft-versus-host reaction following
massive blood transfusion in an aged patient with postoperative aortic aneurysm: acase report. Nippon Naika Gakkai Zasshi 1984; 73: 99-106 (Japanese).
PAROXYSMAL NOCTURNAL HAEMOGLOBINURIAAND PREGNANCY
SIR,-Paroxysmal nocturnal haemoglobinuria (PNH) is a
chronic haemolytic disorder the manifestations of which include apredisposition to thromboembolism and Budd-Chiari syndrome ;2the latter may be precipitated by stress, including pregnancy.3-5Experience of pregnancy in PNH is limited but awareness of therisks involved has prompted the suggestion that conception shouldbe avoided if possible. 6We report experience with a patient who hashad two healthy babies at full term, showing that, at least in the morebenign forms of PNH, uncomplicated pregnancy is possible despitesevere thrombocytopenia.The patient was first seen in 1978 at the age of 22 with
palpitations, easy fatigue, and shortness of breath. Laboratoryfindings were: haemoglobin 4-6 g/dl, total white cell count
2-5 x 109/1 (41 % neutrophils, 1 % eosinophils, 51 % lymphocytes,7% monocytes), and platelet count 127 x 109/1. The diagnosis wasestablished by strongly positive Ham’s acid lysis and sucrose watertest. Bone-marrow aspiration and trephine biopsy showed wellmarked erythroid hyperplasia with megaloblastic haematopojesisand absent iron stores.
Coagulation screens and platelet function studies were normal.Haemoglobin was maintained at 10 g/dl with washed packed redcells and supplementary iron and folate. Treatment did not
aggravate the haemolysis.She remained well for 5 years until, in April, 1979, she was
admitted to hospital with an acute haemolytic episode associatedwith pelvic sepsis. ,
In 1981 the patient presented 2 months pregnant. There was noprogression to bone-marrow hypoplasia or evidence for leukaemictransformation. She was vaginally delivered of a full-term normalchild. Her platelet count fluctuated between 30 and 50 x 109/1.
In October, 1984, she again presented 2 months pregnant andwas delivered of a full-term normal child; on this occasion allogeneicplatelet cover was needed to control bleeding from the thrombo-cytopenia. Evaluation post partum showed that she had progressedto severe bone-marrow hypoplasia.
Despite the apparently benign nature of this patient’s clinical andhaematological syndrome, her illness is now following the well-recognised course in which normal bone marrow becomes increas-ingly hypoplastic and ultimately aplastic. Reversion to fetal typehaematopoiesis with rising HbF levels and expression of i antigenprovides further evidence for the expression of this acquired defectin haematopoiesis, and bone-marrow transplantation may yet berequired. Nevertheless, despite the usual view that pregnancy is toohazardous in patients with PNH, a poor outlook may not beinevitable.
Leukaemia Centre,University of Cape Townand Department of Haematology,
Groote Schuur Hospital,Observatory, Cape, South Africa
PETER JACOBSLUCILLE WOOD
1. Dacie JV, Lewis SM. Paroxysmal nocturnal haemoglobinuria clinical manifestations,haematology, and nature of the disease. Ser Haematol 1972; 5: 3-23.
2. Liebowitz AI, Hartmann RC. The Budd-Chiari syndrome and paroxysmal nocturnalhaemoglobinuria. Br J Haematol 1981; 48: 1-6.
3. Payne PR, Holt JM, Neame PB. Paroxysmal nocturnal haemoglobinuria parturitioncomplicated by presumed hepatic vein thrombosis. J Obstet Gynaecol Br Commonw1968; 75: 1066-68.
4. Frakes JT, Burmeister RE, Giliberti JJ. Pregnancy in a patient with paroxysmalnocturnal hemoglobinuria. Obstet Gynec 1976; 47 (suppl): 22s.
5. Spencer JAD. Paroxysmal nocturnal haemoglobinuria in pregnancy. Br J ObstetGynaecol 1980; 87: 246.
6. Wosniak AJ, Kitchen CS. Prospective hemostatis studies in a patient havingparoxysmal nocturnal hemoglobinuria, pregnancy , and cerebral venous thrombo-sis. Am J Obstet Gynecol 1982; 142: 591-93.
