A Rare Presentation of Extramedullary Hematopoiesis in Post-polycythemic Myelofibrosis

Intravenous Immunoglobulin G (IVIG) therapy has been used as a component of the treatment of hemolytic disease of the newborn. There is still no consensus on its use in ABO hemolytic disease of the newborn routinely. The aim of this study is to determine whether administration of IVIG to newborns with ABO incompatibility is necessary. One hundred and seventeen patients with ABO hemolytic disease and positive Coombs test were enrolled into the study. The subjects were healthy except jaundice. Infants were divided into two groups: Group I (n = 71) received one dose of IVIG (1 g/kg) and LED phototherapy whereas Group II (n = 46) received only LED phototherapy. One patient received erythrocyte transfusion in Group I, no exchange transfusion was performed in both groups. Mean duration of phototherapy was 3.1 ± 1.3 days in Group I and 2.27 ± 0.7 days in Group II (p < 0.05). Mean duration of hospital stay was 5.34 ± 2.2 days in Group I and 3.53 ± 1.3 days in Group II (p < 0.05). Mean duration of phototherapy was 4.0 ± 1.5 days and 2.73 ± 1.1 days in double and single doses of IVIG respectively, and this was statistically significant (p < 0.05). IVIG therapy didn’t decrease neither phototherapy nor hospitalization duration in infants with ABO hemolytic disease. Meticulus follow-up of infants with ABO hemolytic disease and LED phototherapy decreases morbidity. IVIG failed to show preventing hemolysis in ABO hemolytic disease.     

ABO hemolytic disease of the newborn, without hyperbilirubinemia.

ABO hemolytic disease of the newborn without hyperbilirubinemia is described in 17 full-term infants. The erythrocyte characteristics, such as reticulocytosis, microspherocytosis, and positive indirect antiglobulin (Coomb's) test, resembled those in ABO disease with hyperbilirubinemia. Erythrocyte acetylcholinesterase activity was reduced in this group to the same degree as in the more severely affected infants. Negro infants predominated over white, in a 2.5:1 ratio in this mild ABO group.     

IgG亚型与新生儿ABO溶血病的关系

目的：探讨IgG亚型与新生儿ABO溶血病高胆红素血症的发生及危重程度的关系。方法：对实验室诊断为新生儿ABO溶血病的患儿，用德国欧盟公司的亚型试剂盒测定其血清IgG亚型。结果：153例实验室诊断为新生儿ABO溶血病的患儿中检测出IgG1和IgG3亚型的27例，其中24例发生高胆红素血症，检出IgG3亚型的全部发生高胆红素血症且胆红素增高明显。结论：测定新生儿IgG亚型抗体，可有助于诊断新生儿ABO溶血病高胆红素血症的发生并预测其严重程度。     

2013年南京及周边地区新生儿溶血病统计分析

目的:了解2013年南京市区、郊区及周边地区新生儿溶血病发病情况。方法:对2013年南京市区、郊区及周边地区14家医院送检的1 430例疑似新生儿溶血病的血液标本检测结果进行分析。结果:1 430例标本主要来源于南京市区3家医院,其次为郊区及周边地区。新生儿溶血病总的阳性率为33.3%,市区医院阳性率低于郊区及周边地区。新生儿溶血病主要以ABO血型系统溶血为主,南京市区3家医院溶血血型系统种类较多;ABO血型系统溶血阳性标本中,母亲血清抗体效价1∶64的占29.4%,其中周边地区的比例最高。另有检出13例C3d阳性标本。结论:新生儿溶血病是一种免疫性溶血性疾病,当新生儿出现黄疸症状或母子血型不合但未出现黄疸时,应及时送检,及早确定是否是新生儿溶血病,达到早发现早治疗的目的,对于新生儿生存以及生长发育有益无害。     

Low glucose-6-phosphate dehydrogenase enzyme activity level at the time of hemolysis in a male neonate with the African type of deficiency.

Glucose-6-phosphate dehydrogenase (G6PD) levels are not usually drawn in the evaluation of black neonates with hyperbilirubinemia because of the oft-stated opinion that the levels may be normal at the time of hemolysis and thus will be misleading. In fact, this opinion is not applicable to newborns as many studies have shown that deficiency in the conjugating ability of the liver, not hemolysis, is the main cause of neonatal jaundice associated with G6PD deficiency. We present a case report of a neonate with brisk hemolysis and hyperbilirubinemia in whom the G6PD level was abnormally low at the time of the hemolytic episode. DNA analysis showed him to have the A-(202A,376G) variant and, as well, the UGT1A1 promoter repeat polymorphism associated with Gilbert's disease. This case, as well as a review of the literature, indicates that enzyme levels are not normal in patients with G6PD A- who are undergoing hemolysis.     

Single versus multiple dose intravenous immunoglobulin in combination with LED phototherapy in the treatment of ABO hemolytic disease in neonates

Intravenous immunoglobulin (IVIG) has been found to decrease hemolysis in neonatal jaundice due to blood group incompatibility, but a consensus on its usage has not been reached. We conducted a study to compare single versus multiple dose of IVIG in combination with light emitting diode (LED) phototherapy in patients with neonatal jaundice secondary to ABO blood incompatibility, and compared the efficacy of these treatments with that in a group of patients who received LED phototherapy solely. Thirty-nine term neonates with ABO blood group incompatibility were enrolled in the study. Group I received one dose of IVIG (1 g/kg) and LED phototherapy, and group II two doses of IVIG (1 g/kg) and LED phototherapy, whereas group III received LED phototherapy only. In group I, exchange transfusion was performed in one patient (6%) and in group II in one patient (10%). In the control group, none of the patients required exchange transfusion. Duration of LED phototherapy was 4.3 ± 0.7 days in group I + II (IVIG group), 3.9 ± 0.6 days in group III (P = 0.06). Lowest hematocrit level in group I + II was 35.0 ± 7.8 and group III was 38.9 ± 4.2, this was statistically significant (P = 0.034). IVIG therapy, single or multiple, did not affect exchange transfusion, need of erythrocyte transfusion and hospitalization time when used in combination with LED phototherapy in the treatment of ABO hemolytic jaundice in neonates.     

Primary biliary cirrhosis and hemolytic anemia confusing serum bilirubin levels.

Hemolysis is observed in more than 50% of patients with cirrhosis. However, there has been little documentation of the association of primary biliary cirrhosis with autoimmune hemolytic anemia. Two cases, found within a single practice, of primary biliary cirrhosis coexisting with autoimmune hemolysis and a third case coexisting with hereditary spherocytosis are presented. Anemia in such patients is commonly attributed to chronic disease, and hyperbilirubinemia is attributed to primary biliary cirrhosis. These patients were considered for liver transplantation until the diagnosis of a comorbid hemolytic process was established. This association may be more prevalent than previously recognized. A diagnosis of comorbid hemolysis must always be considered in context with anemia and serum bilirubin levels that rise out of proportion to the severity of the primary biliary cirrhosis.     

Mercaptoethanol-Stable Antibody Test Predicting Hemolytic Disease of the Newborn Due to ABO Incompatibility

Abstract. Maternal sera were titrated after 2-mercaptoethanol treatment for anti-A and anti-B agglutinations by the saline and the anti-globulin methods; the results were expressed in titration scores. Each case was graded into mercaptoethanol-stable antibody (MESA) grade 1: A and B mothers with compatible infants; 2: mothers with unaffected incompatible infants; 3: mothers with mild hemolytic disease of the infant, and 4: mothers with severe hemolytic disease of the infant. 925 cases were submitted for the ABO incompatibility tests in 2 years; the babies' sequelae were reported in 131 ABO-incompatible cases. If the tests were done in late pregnancy, severe cases of hemolytic disease of the newborn corresponded to mothers' antenatal antibodies in MESA grade 4, and mild cases to MESA grade 3.     

Incidence of neonatal hyperbilirubinemia: a population‐based prospective study in Pakistan

Objective To estimate the incidence of neonatal jaundice and hyperbilirubinemia in a poor urban community in Karachi, where 70% of births occur at home. Methods Home‐based pregnancy and newborn surveillance were conducted from September 2004 to July 2006 in a multi‐ethnic population by trained community health workers. Newborns were visited several times at scheduled intervals until 59 days of life; any baby with jaundice was referred to the local clinic. Clinical assessments of jaundice were assigned by a physician and recorded using an adapted Kramer scale. Blood for plasma bilirubin was obtained if parents consented. Results Of a birth cohort of 1690 young infants during the study period, 466 infants (27.6%) were referred to our centre with jaundice. Of these, 64% were 0‐6 days old. Bilirubin was measured in 125 of 466 (27%) jaundiced newborns. Overall detected rate of hyperbilirubinemia (bilirubin >5 mg/dl) among 1690 newborns was 39.7/1000 live births (95% CI 29.3–47.6). Rate of plasma bilirubin levels in the range of 15–20 mg/dl was 13/1000 live births (95% CI 7.6–18.4); levels >20 mg/dl were observed in 3.5/1000 live births (95% CI 0.4–5.5). The proportion of newborns with bilirubin ≥15 mg/dl was significantly higher among those assigned a Kramer score of 4–5 compared to those receiving a score of 1–3 (P‐value 0.00004). Conclusion A significant burden of untreated severe neonatal jaundice, causing potential neurological sequelae, exists in developing countries such as Pakistan. WHO guidelines are needed for screening and appropriate management of neonatal jaundice in developing countries.     

Donor-derived red blood cell antibodies and immune hemolysis after allogeneic bone marrow transplantation

Six cases of immune hemolytic anemia attributed to donor-derived red cell antibodies after allogeneic bone marrow transplantation (BMT) are reported. In 2/6 cases, severe intravascular hemolysis was seen, 6/6 required increased red cell transfusion, and 1/6 was treated by plasma exchange. All recipients were receiving cyclosporine to prevent graft-v- host disease. Investigations showed that in each case, the donor lacked ABO or Rho(D) red cell antigens present in the recipient. The direct antiglobulin test was positive in 6/6. Relevant serum antibody (anti-A, four cases; anti-B, one case; anti-D, one case) was first detected one to three weeks after BMT. Eluates made from recipient red cells showed the same specificity as serum antibody. Maximum hemolysis occurred nine to 16 days after BMT, suggesting that active production of antibody by "passenger" donor lymphocytes was the likely mechanism of hemolysis, rather than passive transfer of antibody in the marrow infusion. Retrospective analysis of 21 consecutive cyclosporine-treated BMT patients receiving marrow lacking ABO or D antigens present in the recipient showed that (1) 15/18 patients tested had red cell antibody production against recipient red cell antigens; (2) despite the frequent presence of antibody specific for recipient red cell antigens, only 3/21 patients developed clinically significant hemolysis; (3) clinical hemolysis could not be predicted by donor or recipient red cell antibody titers. We conclude that although red cell antibody against recipient antigens is frequently produced after minor ABO and D mismatched BMT in cyclosporine-treated recipients, only 10% to 15% of cases develop clinically significant immune hemolysis. The data presented show that the most likely source of antibody is "passenger" donor lymphoid cells.     

Immune-mediated hemolytic anemia under oxaliplatin

The induction of autoimmune hemolysis is a rare side effect of oxaliplatin. A 68-year-old patient was referred to our hospital because of progedient jaundice and exertional dyspnea. One day before she had received the 5th consecutive week of treatment of the 8th cycle of a chemotherapy according to FUFOX protocol with oxaliplatin and 5-fluorouracil because of metastasized adenocarcinoma of the sigma. Laboratory values revealed hemolytic anemia associated with thrombocytopenia and neutropenia. In the further clinical course a rapid decline of the hemoglobin (hb) level could be observed associated with a significant increase of hemolysis parameters. A direct Coombs test was positive consistent with oxaliplatin-mediated autoimmune anemia (AIHA) and a pulse therapy with steroids was started accompanied by transfusions resulting in a normalization of red blood cell and white blood cell counts. Chemotherapy was switched to an oxaliplatin-free regimen because of progressive tumor disease and induction of immune pancytopenia. Oxaliplatin-induced AIHA requires an immediate diagnosis since reexposition results in a more severe hemolysis. The direct Coomb's test represents the essential hallmark of the diagnosis.     

High-Dose Intravenous IgG for the Treatment of Severe Rhesus Alloimmunization

The value of intravenous immunoglobulin (IVIG) in the treatment of 24 severely Rh-sensitized pregnant women was studied. IVIG was infused at a daily dose of 0.4 g/kg maternal body weight for 4-5 consecutive days, and was administered again 15-21 days later until delivery, depending on the evolution of the hemolytic disease. Our population was divided into 3 groups according to the time of onset of therapy: group 1 (n = 8), before 20 weeks' gestation; group 2 (n = 7), 20-28 weeks, and group 3 (n = 9), after 28 weeks. Initial mean anti-D level was significantly higher in group 1 (25.9 +/- 12.9 IU/ml) than in the other 2 groups, whose mean values were, however, higher than 10 IU/ml. Amniotic-fluid total bilirubin levels before the onset of therapy were pathologic, and in 55% of the cases they coincided with zone 3 of Liley's chart. Hydrops fetalis at the onset of treatment accounted for the only 3 fetal deaths in groups 1 and 2. None of the fetuses developed hydrops during treatment. Six of the 9 neonates in group 3 were depressed at birth (1-min Apgar below 7). However, at 5 min only 1 newborn showed an Apgar below 7. Mean birth weight was over 2,500 g in all the cases. Neonatal hematological condition in group 2 (50% of the babies required only phototherapy) was better than in the other 2 groups (transfusional therapy). There was a significant fall in maternal anti-D titers and intrauterine hemolysis after IVIG treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

孕妇产前抗体效价预测新生儿溶血病

目的：探讨O型及Rh阴性孕妇血清中抗体效价来预测新生儿溶血病的关系。方法：采用血型血清学方法,对1256对夫妇血型不合的O型及Rh阴性孕妇检测ABO、RhD血型、抗体筛选、抗体效价。效价≥64的建议服中药治疗,定期检测抗体效价。对新生儿（出生0～7d）发生黄疸后,抽静脉血检测溶血3项。结果：1244名O型孕妇血清中IgG抗-A（B）效价≥64者564例,占45.3%;对12名Rh阴性孕妇血清中产生抗D抗体5例,效价均≥64,占41.6%,7例抗体筛选阴性。IgG抗-A（B）效价≥64并发生ABO-HDN占49.5%。ABO-HDN占产前的比例（279/1244）为22.4%。结论：动态监测夫妇血型免疫抗体效价,及时采取措施以降低孕妇体内IgG抗体效价,降低新生儿发病率,减少并发症,提高人口素质。     

Exchange Transfusion for Severe Neonatal Hyperbilirubinemia: 17 Years’ Experience from Vojvodina,Serbia

This study aimed to evaluate the frequency of the main risk factors for severe neonatal hyperbilirubinemia, to determine the incidence of exchange transfusion (ET) in the Autonomous Province of Vojvodina (the northern part of Serbia) and to describe the experience with ET performed in premature and term infants during the past 17 years. We performed a retrospective data analysis of 398 newborn infants who underwent a double volume ET from 1997 to 2013. During the 17 year study period, a decreasing incidence of ET, expressed per thousand newborns, was observed. A total of 468 double volume ET were performed: 328 (82.4 %) infants had one treatment and 70 (17.6 %) had repeated treatments. A total of 262,830 mLs of blood were transfused, an average of 660 mLs per child. There were 221 male and 177 female infants, with a sex ratio 1.25:1. The frequencies of risk factors for developing hyperbilirubinemia were as follows: (1) 38 % RhD incompatibility; (2) 38 % ABO incompatibility (26 % group A infant of group O mother, 12 % group B infant of group O mother); (3) 7 % low birth weight/preterm birth; (4) 17 % other factors. Risk factors for neurotoxicity were identified in 56.3 % of infants. No deaths or complications were reported arising from the treatment. ABO and Rh incompatibilities were found to be the main risk factors for severe neonatal hyperbilirubinemia in Vojvodina. Exchange transfusion, used as therapy for severe hyperbilirubinemia, trended downwards over the period of this study.     

IgG Subclasses of Anti-A and Anti-B Antibodies Bound to the Cord Red Cells in ABO Incompatible Pregnancies

IgG subclasses were determined in 138 A or B infants weighing over 2,500g, born to O mothers. Direct antiglobulin test (DAT) was positive in 43 infants and negative in 95 with anti-A and/or anti-B antibodies detected by heat elution test. In 59 out of 131 infants without ABO hemolytic disease (ABO-HDN), no IgG subclass was detectable. In the 72 others, IgG1 was found in 29/72, IgG2 in 63/72, and IgG3 was not detected. In 7 infants with ABO-HDN, DAT was positive in 4 and negative in 3. In conclusion, in DAT-positive infants without HDN, IgG1 or IgG2 may be bound to erythrocytes, but the amount of IgG1 is too small to cause hemolysis. In DAT-positive ABO-HDN the amount of IgG1 is sufficient to cause hemolysis. In DAT-negative ABO-HDN, IgG3 is responsible for hemolysis, even though undetectable by DAT.     

Studies on hemolytic anemia in pregnancy with evidence for autoimmunization in a patient with a negative direct antiglobulin (coombs') test

Three patients were studied who had acquired hemolytic anemia during pregnancy. One patient had a relapsing hemolytic anemia of pregnancy with a negative direct antiglobulin test. Previously reported cases have been presumed to be antibody-mediated because of rapid destruction of transfused blood, transient hemolysis in the newborn, and a favorable response to corticosteroid therapy. Our findings with the complement-fixation antibody consumption (CFAC) test offer support for an immune pathogenesis, since we documented abnormal concentrations of IgG on the patient's red cells during pregnancy and also on a sample of cord blood. The hemolytic anemia responded partially to prednisone during pregnancy and resolved postpartum. A repeat CFAC test postpartum revealed a marked reduction in the number of IgG molecules per red cell on the mother's cells, and IgG was no longer detectable on the infant's red cells. The other patients had serologic abnormalities characteristic of an autoimmune hemolytic anemia with an IgG warm autoantibody. The patients were followed closely during pregnancy because of previous reports of life-threatening morbidity in mothers, as well as stillbirths, neonatal death, and seriously affected infants. An amniocentesis was performed in one patient because of persistent hemolysis in spite of prednisone therapy. The mothers and their infants did well, but serologic abnormalities and mild hemolytic anemia persisted in both mothers. Therefore, an elective splenectomy was performed with significant improvement in both instances.     

Hemolytic anemia caused by graft-versus-host reaction in ABO-nonidentical renal transplants from blood group O donors

Acute hemolytic anemia is one of the side effects associated with cyclosporin and tacrolimus therapy, and three mechanisms have been described to account for hemolytic anemia in patients receiving these drugs: drug induced hemolysis, autoimmune hemolysis and alloimmune hemolysis resulting from donor lymphocytes derived from the allograft (passenger lymphocyte syndrome). We report four cases of renal transplant recipients who developed alloimmune hemolytic anemia due to minor ABO incompatibility while under treatment with cyclosporin (two) and tacrolimus (two). The anti-erythrocyte antibodies responsible for hemolysis were of the IgG isotype and showed anti-A or anti-B specificity. These findings suggest that the hemolysis could be related to alloantibodies derived from the clonal development of donor B lymphocytes in the recipients (microchimerism). In summary, hemolytic anemia due to ABO-minor incompatibility occurs infrequently after renal transplantation. Risks are higher for patients A, B or AB blood group receiving an O blood group graft under treatment with cyclosporin or tacrolimus. Follow-up of these patients is warranted for the early detection and optimal management may be achieved by reduction of immunosuppression and change to mycophenolate mofetil.     

Does Anti-Jra Cause Hemolytic Disease of the Newborn?

Abstract. A Jr(a-) Japanese female developed anti-Jr^a during her first pregnancy. Both father and infant red cells were Jr(a+), and anti-Jr^a was eluted from the infant's red cells. The antibody was determined to be IgGl. Hemolysis could not be definitively established from the clinical data. The pitfall of using the presence of jaundice as the sole evidence for hemolysis is emphasized. We conclude that the present case, and other previously reported cases, do not unequivocally establish that anti-Jr^a causes significant hemolytic diesease of the newborn (HDN). Amniocentesis probably should not be performed during the pregnancy of mothers sensitized to Jr^a antigen. Jr^a HDN is probably a mild disease, like ABO HDN.     

Immunoglobulin serum levels in very low birth weight infants treated with different intravenous preparations

Summary Parenteral human immunoglobulin (IVIG) administration is widely used in low birth weight (LBW) infants for prevention and therapy of neonatal infection. In previous studies, IVIG preparations containing IgG and low IgM concentrations were commonly used. In this study we compare immunoglobulin serum levels in two groups of healthy preterm infants receiving prophylactically standard IVIG (Sandoglobulin, 0.1 mg/kg IgM) or IgM-enriched IVIG (Pentaglobin, 30 mg/kg IgM). Immunoglobulin levels were assayed by rate nephelometry at birth and at 3, 5, 7, and 14 days after birth. The two groups of patients were matched for gestational age (31±2.3 weeks), birth weight (1320±340 g), and serum IgG (4.1±1.9 g/l) and IgM (0.22±0.18 g/l) levels at birth. Significantly higher IgM levels were observed at 3 and 5 days after IgM-enriched IVIG administration (p<0.01). Higher IgG levels were attained and persisted for 2 weeks after standard IVIG administration (p<0.01). These data indicate different IgG and IgM target levels in LBW infants treated with different immunoglobulin preparations.