1481
for prenatal diagnosis-ie, for fetal karyotyping. All examined with transvaginal ultrasonography at patients between 10 and 15 weeks of gestation. A cystic hygroma, as we called the underlying lesion, was found in 36 fetuses.1 The hygroma was larger than 3 mm in diameter in all cases. An abnormal karyotype was found in 11 of the 36 fetuses (31 %): trisomy 21 in 7, trisomy 18 in 2, monosomy X in 1, and translocation Y,15in 1. Euploidy was found in 25 of 36 fetuses (69%). Associated anomalies were found in 8 of these euploid fetuses, and the other 17 euploid fetuses developed normally and had a normal neonatal outcome. Septate and non-septate hygroma were differentiated in this series. All 17 normally developing euploid fetuses demonstrated a non-septate hygroma. Of the 11aneuploid fetuses, 5 had nonseptate cystic hygroma and the other 6 had septate hygroma. Of the 8 fetuses with associated anomalies, 4 had non-septate hygroma and 4 septate hygroma. Detection of a cystic hygroma with a diameter more than 3 mm is not only a potential marker for an abnormally developing fetus, in particular trisomy 21, but also for other chromosomal and structural abnormalities. our centre
were
Division of Maternal-Fetal Medicine and Prenatal Diagnosis, Department of Obstetrics and Gynaecology, Free University Hospital, 1007 MB Amsterdam, Netherlands 1. Van Zalen MM,
hygroma,
van
course
Vugt JMG,
and outcome.
M. M. VAN ZALEN-SPROCK J. M. G. VAN VUGT H. P. VAN GEIJN
Geijn HP. First trimester diagnosis of cystic Am J Obstet Gynecol (in press). van
Protection against immune haemolytic disease of newborn infants by maternal monocyte-reactive IgG alloantibodies hypothesis1 and supportive data1,22 about HLA class I and II antibody-mediated protection from immunological materno-fetal incompatibility caused by alloantibodies against the blood group D (Rh) and other fetal antigens. We analysed these presumably protective HLA antibodies that inhibit the Fcy-receptor I (FcyRI) in the immune phagocytosis inhibition assay.3,4 As Dr Dooren and colleagues report (May 2, p 1067) (with an antibody-dependent cellular cytotoxicity inhibition assay for the comparison) we noted only allogenic, never autologous, reactions of these FcyRI-inhibiting antibodies and specificity to HLA class I and II, never specificity to FcyRI; furthermore we accounted for the inhibition by forming a three-molecular complex, consisting of class I or II antigen, corresponding antibody, and adjacent FcyRI with subsequent redistribution and intemalisation of the complex and intracellular degradation of the Fc7RI .3 ’ Fc7RI inhibition by class I antibodies in our analysis was always stronger than inhibition by class II antibodies.3,5 Although Dooren and colleagues do not find a protective effect of the FcyRI-inhibiting class I antibodies in vivo, we showed that the SIR,-We have published
a
function of monocytes from newborn babies whose mothers produce HLA antibodies with specificity to class I and II is significantly inhibited.2 Class I antibodies are certainly implicated because they are more common than class II antibodies in unselected pregnant women or patients. Mueller-Eckhardt and colleagues6 reported women with normal platelet counts who gave birth to thrombocytopenic infants presenting signs of neonatal alloimmune thrombocytopenia. The only selection criterion for this study was a clinical manifestation of NAT. According to our hypothesis, features of the disease are prevented in the presence of protective HLA antibodies, but the absence of protective HLA antibody can result in such features appearing. Thus, selecting by features of disease could be tantamount to selecting women who infrequently have HLA antibodies. Indeed, one of the intriguing findings of the study was that only 7-5% of these women who gave birth to infants with neonatal alloimmune thrombocytopenia have HLA antibodies, as opposed to between 25 and 30% of women who give birth to healthy infants. Dooren and colleagues maintain that if class I antibodies had a protective effect, unexpected mild haemolytic disease of the newborn would be much more common, since between 25 and 30% of all pregnant women produce such antibodies. This is hard to
FcyRI-dependent
understand because benign courses of this disease are found in as many as 40% of infants bom with a positive direct antiglobulin test due to maternal anti-D.1,7 We feel that it is too soon to exclude the protective effect by HLA class I antibodies. Institute of Transfusion Medicine, Christian Albrechts University Clinics, 2300 Kiel, 1, Germany
JURGEN NEPPERT KARIN KISSEL
-D incompatibility in the newborn without haemolytic disease: inhibition of immune phagocytosis? Vox Sang 1987; 53: 239. 2. Neppert J, Mueller-Eckhardt G, Heine O. Reduced immune phagocytosis of monocytes from neonates whose mothers produce HLA antibodies. Vox Sang 1988; 54: 177-80. 3. Neppert J, Marquard F, Mueller-Eckhardt C. Murine monoclonal antibodies and human alloantisera specific for HLA inhibit monocyte phagocytosis of anti-D sensitized human red blood cells. Eur J Immunol 1985; 15: 559-63. 4. Neppert J. Persistence and selectivity of the immune phagocytosis inhibition by major histocompatability complex antibodies. Scand J Immunol 1987; 26: 737-43. 5. Faust A, Neppert J. Detection of antibodies specific for HLA-A, B, C, DR, DQ and DP by the erythrocyte antibody rosette inhibition (EAI) and immune phagocytosis inhibition (IPI) tests. J Immunol Meth 1987; 102: 71-75. 6. Mueller-Eckhardt C, Kiefel V, Grubert A, et al. 348 cases of suspected neonatal alloimmune thrombocytopenia. Lancet 1989; i: 363-66. 7. Mollison PL. Some aspects of Rh hemolytic disease and its prevention. In: Garatty G, ed. Hemolytic disease of the newbom. Arlington: Americam Association of Blood Banks, 1984: 1-32. 1.
Neppert J. Rhesus-Du and
Alteplase for hepatic veno-occlusive disease after bone-marrow transplantation SIR,-Dr Laporte and colleagues (April 25, p 1057) report the effect of alteplase (recombinant tissue plasminogen activator, r-tPA) in the treatment of hepatic veno-occlusive disease (VOD) arising after bone-marrow transplantation (BMT). We also have a similar experience with this novel and so far promising agent. A 43-year-old woman with myeloma (IgA type, Salmon and Durie stage IIIA) resistant to conventional therapy underwent BMT after conditioning with busulphan (16 mg/kg) and cyclophosphamide (200 mg/kg). The donor was her identical twin and she received no prophylaxis for graft-versus-host disease. The early post-transplant course was uneventful, apart from grade II mucositis (World Health Organisation scale), which resolved by day 15. Engraftment was rapid, with 0-5 x 109/1 polymorphonuclear cells by day 14. On day 13 increases in aspartate aminotransferase (1178 U/1) and bilirubin (44 mmol/1) were noticed; the partial thromboplastin time also lengthened (44 s). Increasing refractoriness to platelet transfusions became evident. The next day body weight increased by more than 3 g and painful hepatomegaly developed. Echotomography revealed mild hepatomegaly, mild ascites, and normal blood flow in hepatic veins. Supportive treatment with dopamine (3 gjm1 per min), diuretics, fluid retention, plasma, and packed red cells was started. Repeat echotomography, five days later, showed pronounced hepatomegaly, abundant ascites, and a reduction of the diameter of the hepatic veins. Hepatic VOD was diagnosed. Over the next three weeks body weight increased by more than 10%, bilirubin further increased (237 mmol/1) whereas transaminases reverted to nearly normal values, and abdominal circumference increased from 65 to 94 cm because of massive ascites that required aspiration. Blood coagulation tests worsened strikingly: prothrombin time was 54%, PTT was 52 s, and AT III was 54%. On day 35 we started r-tPA (Actilyse), 50 mg/day, over a 3 h infusion, for 4 consecutive days. Tolerance to the treatment was good: despite severe thrombocytopenia, she had no bleeding apart from a subcutaneous haematoma of the abdominal wall from the site of the previous aspiration. Clinical and biochemical improvement was steady and dramatic: body weight returned to baseline 3 days after the end of therapy, abdominal circumference was normal within 7 days, and a repeat echotomography eighteen days after r-tPA showed a striking reduction of hepatomegaly, disappearance of abdominal fluid, and increased diameter of hepatic veins. AT III became normal within 36 h of the start of r-tPA and the other coagulation tests were normal within 10 days. By one month bilirubin and transaminases were normal. On day 45 the patient was about to be discharged from hospital, but sudden interstitial pneumonia developed, and she died within 48 h. Necropsy was not permitted. One of the main events in the pathophysiology of VOD might be the deposition of coagulation factors in the subendothelial areas of
for prenatal diagnosis-ie, for fetal karyotyping. All examined with transvaginal ultrasonography at patients between 10 and 15 weeks of gestation. A cystic hygroma, as we called the underlying lesion, was found in 36 fetuses.1 The hygroma was larger than 3 mm in diameter in all cases. An abnormal karyotype was found in 11 of the 36 fetuses (31 %): trisomy 21 in 7, trisomy 18 in 2, monosomy X in 1, and translocation Y,15in 1. Euploidy was found in 25 of 36 fetuses (69%). Associated anomalies were found in 8 of these euploid fetuses, and the other 17 euploid fetuses developed normally and had a normal neonatal outcome. Septate and non-septate hygroma were differentiated in this series. All 17 normally developing euploid fetuses demonstrated a non-septate hygroma. Of the 11aneuploid fetuses, 5 had nonseptate cystic hygroma and the other 6 had septate hygroma. Of the 8 fetuses with associated anomalies, 4 had non-septate hygroma and 4 septate hygroma. Detection of a cystic hygroma with a diameter more than 3 mm is not only a potential marker for an abnormally developing fetus, in particular trisomy 21, but also for other chromosomal and structural abnormalities. our centre
were
Division of Maternal-Fetal Medicine and Prenatal Diagnosis, Department of Obstetrics and Gynaecology, Free University Hospital, 1007 MB Amsterdam, Netherlands 1. Van Zalen MM,
hygroma,
van
course
Vugt JMG,
and outcome.
M. M. VAN ZALEN-SPROCK J. M. G. VAN VUGT H. P. VAN GEIJN
Geijn HP. First trimester diagnosis of cystic Am J Obstet Gynecol (in press). van
Protection against immune haemolytic disease of newborn infants by maternal monocyte-reactive IgG alloantibodies hypothesis1 and supportive data1,22 about HLA class I and II antibody-mediated protection from immunological materno-fetal incompatibility caused by alloantibodies against the blood group D (Rh) and other fetal antigens. We analysed these presumably protective HLA antibodies that inhibit the Fcy-receptor I (FcyRI) in the immune phagocytosis inhibition assay.3,4 As Dr Dooren and colleagues report (May 2, p 1067) (with an antibody-dependent cellular cytotoxicity inhibition assay for the comparison) we noted only allogenic, never autologous, reactions of these FcyRI-inhibiting antibodies and specificity to HLA class I and II, never specificity to FcyRI; furthermore we accounted for the inhibition by forming a three-molecular complex, consisting of class I or II antigen, corresponding antibody, and adjacent FcyRI with subsequent redistribution and intemalisation of the complex and intracellular degradation of the Fc7RI .3 ’ Fc7RI inhibition by class I antibodies in our analysis was always stronger than inhibition by class II antibodies.3,5 Although Dooren and colleagues do not find a protective effect of the FcyRI-inhibiting class I antibodies in vivo, we showed that the SIR,-We have published
a
function of monocytes from newborn babies whose mothers produce HLA antibodies with specificity to class I and II is significantly inhibited.2 Class I antibodies are certainly implicated because they are more common than class II antibodies in unselected pregnant women or patients. Mueller-Eckhardt and colleagues6 reported women with normal platelet counts who gave birth to thrombocytopenic infants presenting signs of neonatal alloimmune thrombocytopenia. The only selection criterion for this study was a clinical manifestation of NAT. According to our hypothesis, features of the disease are prevented in the presence of protective HLA antibodies, but the absence of protective HLA antibody can result in such features appearing. Thus, selecting by features of disease could be tantamount to selecting women who infrequently have HLA antibodies. Indeed, one of the intriguing findings of the study was that only 7-5% of these women who gave birth to infants with neonatal alloimmune thrombocytopenia have HLA antibodies, as opposed to between 25 and 30% of women who give birth to healthy infants. Dooren and colleagues maintain that if class I antibodies had a protective effect, unexpected mild haemolytic disease of the newborn would be much more common, since between 25 and 30% of all pregnant women produce such antibodies. This is hard to
FcyRI-dependent
understand because benign courses of this disease are found in as many as 40% of infants bom with a positive direct antiglobulin test due to maternal anti-D.1,7 We feel that it is too soon to exclude the protective effect by HLA class I antibodies. Institute of Transfusion Medicine, Christian Albrechts University Clinics, 2300 Kiel, 1, Germany
JURGEN NEPPERT KARIN KISSEL
-D incompatibility in the newborn without haemolytic disease: inhibition of immune phagocytosis? Vox Sang 1987; 53: 239. 2. Neppert J, Mueller-Eckhardt G, Heine O. Reduced immune phagocytosis of monocytes from neonates whose mothers produce HLA antibodies. Vox Sang 1988; 54: 177-80. 3. Neppert J, Marquard F, Mueller-Eckhardt C. Murine monoclonal antibodies and human alloantisera specific for HLA inhibit monocyte phagocytosis of anti-D sensitized human red blood cells. Eur J Immunol 1985; 15: 559-63. 4. Neppert J. Persistence and selectivity of the immune phagocytosis inhibition by major histocompatability complex antibodies. Scand J Immunol 1987; 26: 737-43. 5. Faust A, Neppert J. Detection of antibodies specific for HLA-A, B, C, DR, DQ and DP by the erythrocyte antibody rosette inhibition (EAI) and immune phagocytosis inhibition (IPI) tests. J Immunol Meth 1987; 102: 71-75. 6. Mueller-Eckhardt C, Kiefel V, Grubert A, et al. 348 cases of suspected neonatal alloimmune thrombocytopenia. Lancet 1989; i: 363-66. 7. Mollison PL. Some aspects of Rh hemolytic disease and its prevention. In: Garatty G, ed. Hemolytic disease of the newbom. Arlington: Americam Association of Blood Banks, 1984: 1-32. 1.
Neppert J. Rhesus-Du and
Alteplase for hepatic veno-occlusive disease after bone-marrow transplantation SIR,-Dr Laporte and colleagues (April 25, p 1057) report the effect of alteplase (recombinant tissue plasminogen activator, r-tPA) in the treatment of hepatic veno-occlusive disease (VOD) arising after bone-marrow transplantation (BMT). We also have a similar experience with this novel and so far promising agent. A 43-year-old woman with myeloma (IgA type, Salmon and Durie stage IIIA) resistant to conventional therapy underwent BMT after conditioning with busulphan (16 mg/kg) and cyclophosphamide (200 mg/kg). The donor was her identical twin and she received no prophylaxis for graft-versus-host disease. The early post-transplant course was uneventful, apart from grade II mucositis (World Health Organisation scale), which resolved by day 15. Engraftment was rapid, with 0-5 x 109/1 polymorphonuclear cells by day 14. On day 13 increases in aspartate aminotransferase (1178 U/1) and bilirubin (44 mmol/1) were noticed; the partial thromboplastin time also lengthened (44 s). Increasing refractoriness to platelet transfusions became evident. The next day body weight increased by more than 3 g and painful hepatomegaly developed. Echotomography revealed mild hepatomegaly, mild ascites, and normal blood flow in hepatic veins. Supportive treatment with dopamine (3 gjm1 per min), diuretics, fluid retention, plasma, and packed red cells was started. Repeat echotomography, five days later, showed pronounced hepatomegaly, abundant ascites, and a reduction of the diameter of the hepatic veins. Hepatic VOD was diagnosed. Over the next three weeks body weight increased by more than 10%, bilirubin further increased (237 mmol/1) whereas transaminases reverted to nearly normal values, and abdominal circumference increased from 65 to 94 cm because of massive ascites that required aspiration. Blood coagulation tests worsened strikingly: prothrombin time was 54%, PTT was 52 s, and AT III was 54%. On day 35 we started r-tPA (Actilyse), 50 mg/day, over a 3 h infusion, for 4 consecutive days. Tolerance to the treatment was good: despite severe thrombocytopenia, she had no bleeding apart from a subcutaneous haematoma of the abdominal wall from the site of the previous aspiration. Clinical and biochemical improvement was steady and dramatic: body weight returned to baseline 3 days after the end of therapy, abdominal circumference was normal within 7 days, and a repeat echotomography eighteen days after r-tPA showed a striking reduction of hepatomegaly, disappearance of abdominal fluid, and increased diameter of hepatic veins. AT III became normal within 36 h of the start of r-tPA and the other coagulation tests were normal within 10 days. By one month bilirubin and transaminases were normal. On day 45 the patient was about to be discharged from hospital, but sudden interstitial pneumonia developed, and she died within 48 h. Necropsy was not permitted. One of the main events in the pathophysiology of VOD might be the deposition of coagulation factors in the subendothelial areas of
