G gamma beta + type of hereditary persistence of fetal haemoglobin in association with Hb C.

This report describes a Negro family with the G gamma beta + type of hereditary persistence of fetal haemoglobin. Family members with levels of haemoglobin F of 17 to 23% had normal red cell indices, balanced globin chain synthesis, and a pancellular distribution of the fetal haemoglobin, showing that these subjects have a form of HPFH. The production of Hb A and C in addition to the large amount of Hb F in one family member showed that there was an active beta A gene in cis to the HPFH determinant, while structural analysis of the Hb F revealed the presence of only G gamma chains. The criteria for the diagnosis of G gamma beta + HPFH, and the relevance of such conditions to the control of globin gene expression, are discussed.     

Hereditary persistence of fetal hemoglobin presenting as fetal-maternal hemorrhage.

This report describes a case of hereditary persistence of fetal hemoglobin (HPFH) presenting initially as a marginal placental abruption in a primiparous woman at 27 weeks gestation. Persistent but erratic elevation of percent hemoglobin F positive cells, as determined by a modified Kleihauer-Betke method, complicated the remainder of her pregnancy. The clinical impression of placental abruption with possible extension could not be documented by ultrasound or examination of the placenta at delivery. Hemoglobin electrophoresis followed by quantitative fetal hemoglobin first suggested the diagnosis of HPFH, which was confirmed seven months postpartum. Furthermore, the magnitude of percent positive F-cells could be profoundly altered by subtle changes in pH of the acid elution reagent. This case demonstrates that positive acid elution tests for maternal-fetal transfusion may be caused by elevated maternal hemoglobin F. Erratic results, elevated quantitative hemoglobin-F and sensitivity to reagent pH should alert the pathologist to this diagnosis and alter clinical management.     

Mild sickle-cell anaemia in Iran associated with high levels of fetal haemoglobin.

Sixteen subjects, with sickle-cell anaemia, all Iranians (ages 3 to 56 years), with very mild symptomatology are reported. Some of the subjects had been totally asymptomatic. Splenomegaly was noted in 9 cases. There was an increase in the mean level of fetal haemoglobin (18%); this is the probable explanation for the mild phenotype. In 29 subjects with sickle-cell trait, the level of HbF was also significantly raised as compared with normal (1-6% vs. 0-6%). The mechanism of increased synthesis of HbF is unknown. The findings are similar to those reported in the Shiite Moslems of Saudi Arabia suggesting that in these populations there is a genetically-determined ability to produce high levels of Hb F in the presence of the sickle-cell gene.     

The therapeutic reactivation of fetal haemoglobin

Unusually high levels of fetal haemoglobin production can ameliorate sickle cell disease and beta thalassaemia. Although efforts directed at the pharmacological stimulation of fetal haemoglobin as an approach to managing these conditions have met with limited success, there is wide variation in individual responses. Whether this reflects the particular mutations that underlie these conditions or other genetic factors remains to be determined, as does the ideal combination of agents to achieve this end. These results are encouraging, however, in particular in view of the recent demonstration that other monogenic diseases, Duchenne muscular dystrophy, for example, might be amenable to the same therapeutic strategy.      

Massive acute thymic haemorrhage and cerebral haemorrhage in an intrauterine fetal death

Massive acute thymic haemorrhage in the neonate occurs extremely rarely and is associated with haemorrhagic disease of the newborn. A 30 year old woman with an unremarkable previous obstetric history presenting at 37 weeks and 4 days gestation with the complaint of loss of fetal movement was found to have a male fetus with findings at necropsy of massive acute thymic haemorrhage, acute intracranial haemorrhage, and hydrops fetalis. This is the first report of massive acute thymic haemorrhage in utero. Massive thymic haemorrhage should be added to the reported causes of lethal non-immunological hydrops.     

Automated technique for the estimation of fetal haemoglobin

An automated alkali denaturation technique which measures fetal haemoglobin is described. This method offers greater speed and a lower standard deviation than comparable manual methods.     

Heterogeneity of sickle cell anaemia in Arabs: review of cases with various amounts of fetal haemoglobin.

A study is presented on eleven patients with homozygous sickle cell anaemia. They are non-Sheeah Arabs from the United Arab Emirates on the south-eastern coast of the Arabian Peninsula. The proportions of fetal haemoglobin in these patients are variable, and there is a marked variation in the severity of their disease condition; these facts are not related. African sickle cell gene admixture is a likely affecting factor.     

Delay in the fetal globin switch in infants of diabetic mothers

In the normal fetus, a switch from production of hemoglobin F (alpha 2 gamma 2) to hemoglobin A (alpha 2 beta 2) occurs at 28 to 34 weeks of gestation. In the fetus with beta-hemoglobinopathy or beta-thalassemia, this switch proceeds despite the morbidity that results when production of beta-globin is abnormal or reduced. Since insulin has recently been shown to induce renewed expression of some inactive genes, we studied globin biosynthesis during the natural evolution of the fetal globin switch under conditions of hyperinsulinemia, which occurs in infants of diabetic mothers. Such infants develop in a hyperglycemic environment, which produces reactive hyperinsulinemia. The normal increase in beta-globin production from pre-switch levels did not occur in 9 of 10 such infants at term, as compared with 11 normal infants, in whom the switch occurred by 36 to 39 weeks of gestation (P less than 0.0001). The delay in the switch from gamma-globin to beta-globin in this unique clinical setting may allow identification of physiologic factors that can modulate developmental gene suppression.     

The effect of haemorrhage on haemoglobin concentration, blood volume and arterial pressure in kittens and cats

1. The arterial haemoglobin concentration in kittens less than 24 hr old was inversely related to body weight. There was about twice as much haemoglobin/unit body weight at birth as in adult cats. Haemoglobin concentrations were minimal at 3-6 weeks of age.2. In animals lightly anaesthetized with sodium pentobarbitone, arterial pressure rose from 52 mm Hg at birth in kittens to 133 mm Hg in adult cats. Blood volume decreased from 73 ml./kg at birth to 60 ml./kg in adults.3. When kittens less than a fortnight old were subjected to stepwise blood letting, arterial pressure fell proportionately with blood volume; in older kittens and in cats, arterial pressure was less well maintained at similar proportionate reductions of blood volume than in young kittens.4. The responses to haemorrhage of kittens and cats were compared with those of rabbits similarly treated and with those of adult cats anaesthetized with urethane and chloralose reported in the literature.     

Disorders of haemoglobin in China.

A large scale survey of haemoglobinopathies and thalassaemia has been carried out in China, involving 900,000 people in 28 provinces. It has resulted in the finding of many new variants and some interesting cases of thalassaemia, and in a study on the chemical structure of abnormal haemoglobins and DNA analysis of thalassaemia. We report here data on haemoglobin disorders in the Chinese, mainly the characterisation of the geographical distribution of haemoglobin variants, the analysis of globin genes of alpha, beta, gamma, or delta beta thalassaemia, and the progress in prenatal diagnosis of alpha and beta thalassaemia conducted in the authors' laboratory.     

Assessment of reproductive risk and intentions by mothers of children with hemophilia

Thirty-five mothers of children with hemophilia were studied in order to ascertain the impact of hemophilia on family planning. Attitudes about reproductive risks and prenatal diagnosis were also examined. The most important factors influencing family planning in this group were parental fulfillment and availability of medical care and education for their affected child. Although 79% of mothers viewed their reproductive risk as moderate to very high, 57% indicated that their reproductive plans had not changed even with this knowledge. While 43% of the group would consider prenatal diagnosis, only 17% would terminate a pregnancy if the fetus was found to have hemophilia. Of those interested in prenatal diagnosis, the majority were interested in knowing if the fetus was affected but would not consider termination of the pregnancy. The majority of mothers in the group did not view having a child with hemophilia as an insurmountable burden on their lives. Therefore, the disease appeared to have little impact on family planning.