D. Williamson

Risk of venous thromboembolism associated with a G to A transition at position 20210 in the 3'-untranslated region of the prothrombin gene.

The odds ratio for the FII 20210G/A mutation in 504 patients with venous thromboembolism compared to controls was 2.0 (95% CI 1.0–4.0) and, for factor V Leiden, 5.8 (95% CI 3.3–10.3). 3/504 patients were heterozygous for both mutations. None of the patients had combined natural anticoagulant deficiency and the FII 20210G/A mutation. We conclude that the FII 20210G/A mutation is present in 2.6% of the population and the relative risk of venous thromboembolism in carriers is 2.0.

Unstable Haemoglobin Haemolytic Crises: Contributions of Pyrexia and Neutrophil Oxidants

Summary. Pyrexia and the production of oxidants by phagocytic cells have been examined as two possible causes of haemolytic crises associated with infections in carriers of unstable haemoglobins. Three unstable haemoglobins were examined, both in red cells and after purification. Incubation at 40°C rather than 37°C resulted in only a slight increase in autoxidation rate, but a considerable increase in the rate of precipitation of the haemoglobins as Heinz bodies. Oxidants produced by activated neutrophils were capable of oxidizing haemoglobin both in solution and red cells, though there was no preferential effect on the unstable as opposed to the normal haemoglobin.

Hemoglobin Palmerston North β23 (B5) VAL→phe a New Variant Identified in a Patient with Polycythemia

Hemoglobin Palmerston North is a new slightly unstable hemoglobin with increased oxygen affinity. The mutation, β23 Val→Phe, was readily apparent on separation of the tryptic peptides by HPLC.

Two de novo mutations in one β globin chain: hemoglobin Atlanta-Coventry, β75 Leu→Pro and β141 Leu deleted

Reverse phase HPLC analysis of a hemolysate from a patient with hemolytic anemia revealed the presence of three different β globins. Reverse phase Peptide mapping and amino acid analysis indicated that one was normal βA (66%), one was β Atlanta (675 Leu→Pro, 23%) and the third, β Atlanta-Coventry, contained two mutations β75 Leu→Pro and β141 Leu deleted.The parents and four siblings of the propositus had only βA chains, while two of his children inheriteg the β Atlanta and β Atlanta-Coventry chains from him, and βA Chains from their mother. His third child was normal, possessing only βA chains.

Haemoglobin Manukau β67[E11] Val→Gly : transfusion-dependent haemolytic anaemia ameliorated by coexisting alpha thalassaemia

Summary Haemoglobin Manukau (β67 Val→Gly) is a novel haemoglobin variant presenting in two brothers as non‐spherocytic haemolytic anaemia which became transfusion dependent by 6 months of age. The severity of clinical expression seems to be modulated by coexisting alpha thalassaemia: the severely affected children have a normal complement of alpha globin genes with an unusual genotype (‐α3,7/ααα3,7), while their father, who carries the abnormal gene with minimal symptoms, has homozygous α+ thalassaemia (‐α3,7/ ‐α3,7) Another unusual feature of this case is the association of the β67 Val→Gly mutation with modification of β141 Leu to a residue (believed to be hydroxyleucine) that is not detected by standard amino acid analysis. This finding offers an explanation for the previous report of an association of another mutation at this site (Hb Sydney β67 Val→Ala) with Hb Coventry (deletion of β141 Leu).

Hemoglobin Collingwood β60 (E4) VAL→ALA a New Unstable Hemoglobin

Hemoglobin Collingwood is a new unstable hemoglobin variant arising from the substitution of the internal valine at position 660 (E4) by alanine. The variant retains normal oxygen binding characteristics and is not associated with clinical symptoms, though there is evidence suggesting increased red cell turnover.

Two Unstable Hemoglobins in One Individual: Hb Atlanta (β75 Leu→Pro) and Hb Coventry (β141 Leu deleted)

A 25-year-old male had a life long history of a hemolytic anemia which was shown to be due to the presence of an unstable hemoglobin, Hb Atlanta β75 Leu4→Pro. Two dimensional peptide maps of isopropanol precipitated globin also showed the presence of a second variant, Hb Coventry β141 Leu deleted. HPLC separation of the tryptic peptides consistently demonstrated both the abnormal and normal β9 and β14 peptides in the digest of total globin. Neither of the abnormal peptides was apparent on similar maps of globin from his parents or his two siblings. The proportion of the variants measured from the peptide maps was 11% β-Coventry, 34% β-Atlanta and the remainder β-A. The possible basis for the presence of three 6β-globins is discussed and it is concluded that this is likely to be due to some mechanism other than a β-δ crossover.

A New Unstable and Low Oxygen Affinity Hemoglobin Variant: Hb J-Auckland [β25(B7)Gly → Asp]

Hb J-Auckland is a new hemoglobin variant with the amino acid substitution beta 25(B7)Gly----Asp. It is mildly unstable and has a low oxygen affinity. The propositus and a son, both heterozygous for Hb J-Auckland, have marginally low Hb values but no apparent clinical symptoms.

DETECTION OF ABNORMAL HAEMOGLOBINS BY THE TECHNICON H6000 AUTOMATED CELL COUNTER

PREISLER, H.D., EPSTEIN, J., BARCOS, M., PRIORE, R., RAZA, A., BROWMAN, G.P., VOGLER, R., WINTON, E., GRUNWALD, H., RAI, K., BRENNAN, J,, BENNETT, J., GOLDBERG, J., GOTTLIEB, A., CHERVENICK, P., JOYCE, R., MILLER, K., LARSON, R., D.’ARRIGO, P., DOEBLIN, T., STEIN, M., BLOOM, M., STEELE, R. & LEE, H. (1 984) Prediction of response of acute nonlymphocytic leukaemia to therapy with ‘high dose’ cytosine arabinoside. British Journal of Haematology, 58, 19-32. PREISLER, H., BARCOS, M.. REESE, P., PRIORE, R.L. & POTHIER, L. (1983) Recognition of drug resistance during remission induction therapy for acute non-lymphocytic leukemia: utility of day 6 bone marrow biopsy. Leukemia Research, 7, 67-75.

Hemoglobin A2 Fitzroy δ 142 ALA → ASP: A New Delta-Chain Variant

HbA2 Fitzroy is a new delta-chain variant with the amino acid substitution δ 142 (H2O) Ala→Asp. This variant was detected solely due to its abnormal electrophoretic mobility.