Does iron-deficient erythropoiesis in pregnancy influence fetal iron supply?

BACKGROUND: It was investigated whether the iron status in newborns is negatively influenced by iron-deficient erythropoiesis of the mother during pregnancy. METHODS: The iron status is characterized by hemoglobin, erythrocyte zinc protoporphyrin and serum ferritin values. Iron-deficient erythropoiesis of the mother is characterized by erythrocyte zinc protoporphyrin values. Measurement of erythrocyte zinc protoporphyrin was performed in 103 non-anemic females within 24 hours after delivery. The iron status of their newborns was measured in cord blood. RESULTS: Erythrocyte zinc protoporphyrin concentrations were normal in 62% and elevated in 38% of the females, hence 39 women had iron-deficient erythropoiesis. There were no significant differences in mean values of the iron status parameters between neonates born to females with iron-deficient erythropoiesis and neonates born to females not having iron-deficient erythropoiesis. No correlation was found between maternal erythrocyte zinc protoporphyrin values and any of the neonatal parameters. CONCLUSION: It is concluded that fetal iron supply is not negatively influenced by iron-deficient erythropoiesis in the mother.

Erythrocyte zinc protoporphyrin testing in pregnancy.

BACKGROUND: To compare the usefulness of serum ferritin, hemoglobin and erythrocyte zinc protoporphyrin estimations as indicators of the need of iron supplementation in pregnancy. METHODS: In 97 healthy pregnant women serum ferritin, hemoglobin and erythrocyte zinc protoporphyrin concentrations were measured at each trimester period. Iron supplementation was prescribed at hemoglobin values below 113 g/L. RESULTS: Neither in the first nor in the second trimester differences in serum ferritin and erythrocyte zinc protoporphyrin values have been found between women who got iron therapy prescribed and women who did not get iron therapy, whereas already in the first trimester hemoglobin values were lower in the group that got iron therapy. These results indicate that hemodilution rather than iron deficiency determined which women got iron therapy. In the third trimester 14 out of 80 women without iron supplementation had depleted iron stores and a significant erythrocyte zinc protoporphyrin increase, indicating evolving iron deficiency anemia. However, only five of them showed hemoglobin levels below 113 g/L and got iron therapy. Low serum ferritin levels were found in 23% of the women at booking and in 92% in the third trimester. Serum ferritin levels neither predicted the development of iron deficient erythropoiesis nor of anemia. CONCLUSIONS: Iron deficiency can neither be diagnosed nor predicted by serum ferritin or hemoglobin measurements at booking or later on in pregnancy. Erythrocyte zinc protoporphyrin measurements can be of help in determining which women have iron deficient erythropoiesis and may benefit by iron therapy.

Influence of iron deficiency anaemia on haemoglobin A2 levels: possible consequences for beta-thalassaemia screening.

Iron deficiency modulates the synthesis of HbA2, resulting in reduced HbA2 levels in patients with iron deficiency anaemia. The diagnosis heterozygous beta-thalassaemia is based on a raised HbA2 level. Patients with beta-thalassaemia and concomitant iron deficiency can show normal HbA2 levels. It is of clinical importance to know the quantitative effect of iron-deficient erythropoiesis on the levels of HbA2 in order to be able to determine which iron-deficient patients with normal HbA2 levels have to be retested after iron therapy in thalassaemia screening programmes. In this study, HbA2 levels in 150 patients with iron-deficiency anaemia and 71 healthy controls have been measured. A linear correlation is found in the patient group between HbA2 and Hb, HbA2 and MCV, and HbA2 and erythrocyte zinc protoporphyrin (ZPP). In future studies, the correlation between HbA2 and erythrocyte parameters in patients with heterozygous beta-thalassaemia and concomitant iron deficiency has to be examined. We recommend that ZPP be measured in these studies too, as ZPP levels may be a better indicator of concomitant iron deficiency than Hb or MCV in thalassaemic patients.

[The incidence of irregular antibodies in pregnancy: a prospective study in the region of the 's-Hertogenbosch]. / Het vóórkomen van irregulaire antistoffen in de zwangerschap; een prospectief onderzoek in de regio 's-Hertogenbosch.

OBJECTIVE: To determine the incidence and clinical relevance of irregular erythrocyte antibodies (IEA), in multiparous women and in primigravidal with a history of blood transfusion. DESIGN: Prospective longitudinal cohort study. METHODS: In the 's-Hertogenbosch area, the Netherlands, both primigravidae with a previous blood transfusion and multiparous women were tested for IEA in addition to the regular blood tests during the first trimester of pregnancy. If IEA were discovered, the partners were tested for the presence of the antigen involved. Blood samples of children of positive fathers were tested immediately post partum for signs of haemolytic disease of the newborn (HDN). RESULTS: During a 2.5-year period (August 1995-January 1998) a total of 2392 pregnant women were screened for IEA: 2204 multiparous women and 188 primigravidae women. In 65 women 81 IEA were discovered. In the group of 30 children positive for the antigen involved, 12 (40%) had clinical symptoms of HDN; intrauterine death was diagnosed once, one child died immediately after delivery. One child had signs of hydrops fetalis and two children needed an exchange transfusion. Phototherapy and/or regular blood transfusion were given to 7 children. Most cases of HDN were caused by anti-D, anti-Kell and anti-c antibodies. CONCLUSION: Non-RhD-IEA were found in 1.6% of pregnant women screened. First-trimester screening for IEA is recommended as it can be of help in early diagnosis and treatment of HDN.

Combined use of erythrocyte zinc protoporphyrin and mean corpuscular volume in differentiation of thalassemia from iron deficiency anemia.

In a retrospective study the diagnostic value of erythrocyte zinc protoporphyrin (ZPP) measurement as a means of distinguishing iron deficiency anemia from thalassemia syndromes in patients with microcytosis was explored. ZPP values were increased in all patients with iron deficiency and in part of the patients with thalassemia. The combined measurement of erythrocyte mean corpuscular volume (MCV) and ZPP resulted in a correct classification of patients with iron deficiency and with thalassemia in more than 95%. The predictive value of this method is better than the results obtained by using formulae derived from red cell indices. In population screening programs for thalassemia syndromes, in which MCV determination is used as the initial test, the ZPP test is recommended as a second test, in order to discriminate between patients with microcytosis due to iron deficiency and patients with microcytosis due to thalassemia syndromes.

Zinc protoporphyrin as screening test in female blood donors.

Erythrocyte zinc protoporphyrin (ZPP) was measured in 102 women blood donors to evaluate its usefulness in screening for evolving iron deficiency anemia, a reason for the deferral of donors. The results were compared with serum ferritin determinations. Five women were deferred before their first donation and eight women were deferred after one or two donations. Women with increased ZPP values all had low serum ferritin concentrations, indicating iron-deficient erythropoiesis that was caused by iron depletion. The positive predictive value of an increased ZPP in predicting deferral of the donor after one or two donations was 75%, whereas a serum ferritin concentration < or = 12 microg/L predicted deferral in 26% of the donors. The results indicate that the ZPP test can be recommended as a feasible and inexpensive predonation test to determine a subset of donors with iron-deficient erythropoiesis at risk of developing iron deficiency anemia.

Dependency of MCV and haemoglobin concentration on plasma vitamin B12 levels in relation to sex and age.

In a retrospective study of 872 men and 1474 women we determined the relationship between serum vitamin B12 concentration and mean values for Hb and MCV, which were known for 68% of the men and 72% of the women. In both sexes there was a distinct decrease in the mean Hb at serum vitamin B12 concentrations < 0.05 nmol/l. However, the mean MCV was already raised by 4-5 fl at serum vitamin B12 levels < 0.16 nmol/l in men and < 0.11 nmol/l in women, and the percentage of patients with macrocytosis (defined as MCV > 100 fl) also increased significantly at these levels. To find out whether these relationships were age-dependent, male and female patients were split into groups of 20-70 years old and older persons. The mean MCV in men aged 20-70 years increased at a serum vitamin B12 level < 0.16 nmol/l, whereas in older men an increase in mean MCV occurred only at vitamin B12 levels < 0.11 nmol/l. In women, the mean MCV for both age groups increased significantly at a serum vitamin B12 level < 0.11 nmol/l. We conclude that haematological signs of B12 deficiency arise at different serum vitamin B12 concentrations in men and women and that only in men is there an age dependency.

Antineutrophil cytoplasmic autoantibodies with myeloperoxidase specificity in a patient with anti-glomerular basement membrane disease.

An unusual case is described of a patient with both anti-glomerular basement membrane (GBM) disease and anti-neutrophil cytoplasmic autoantibodies with myeloperoxidase specificity (MPO-ANCA) presenting with acute renal failure. Four years before a seronegative arthritis of the left wrist was diagnosed. Tests for ANCA by indirect immunofluorescence were repeatedly negative. The diagnosis was made by renal biopsy and by testing the serum with specific enzyme-linked immunosorbent assays (ELISA) for MPO-ANCA and anti-GBM antibodies. To our knowledge, this is the first patient presenting with such findings in the Dutch literature.

A patient with postpartum primary hypothyroidism and acquired von Willebrand's disease.

Patients with hypothyroidism often complain about easy bruising. We describe a patient with a postpartum acquired bleeding tendency. Hypothyroidism was suspected and confirmed biochemically. After substitution therapy with levothyroxine the bleeding tendency recovered completely. The coagulation disorder appeared to be based on an acquired von Willebrand's disease, secondary to the hypothyroidism. In patients with von Willebrand's disease underlying diseases have to be excluded.

Highly variable anticoagulant response after subcutaneous administration of high-dose (12,500 IU) heparin in patients with myocardial infarction and healthy volunteers.

BACKGROUND: In this study, the anticoagulant response of 12,500 IU heparin s.c. was investigated in patients with myocardial infarction and healthy volunteers to determine variabilities in response and modifying factors. METHODS AND RESULTS: On the fourth day after thrombolytic therapy, blood samples were taken before and at frequent intervals until 10 hours after the injection of 12,500 IU heparin s.c. Plasma anti-Xa activity, anti-IIa activity, and the activated partial thromboplastin time (APTT) were measured in addition to body weight and thickness of the abdominal subcutaneous fat layer. Contrary to expectations, the increase of anti-Xa activity, anti-IIa activity, and APTT compared with baseline (predrug) levels was very small, with an average maximal APTT of 42.6 seconds (SD, 12.4 seconds; range, 30.4-70.7 seconds). Subsequently, the influence of the length of the injection needle on the anticoagulant effect of 12,500 IU heparin s.c. was studied in 10 healthy volunteers to find a factor that could be responsible for the poor response in the patients. The length of the injection needle did not influence the anticoagulant effect of heparin. Large interindividual and intraindividual variabilities were seen in the volunteers. The majority of volunteers had minimal prolongation of the APTT, but very strong prolongation was also seen (maximal APTT, 163 seconds). There was no correlation between the abdominal skinfold thickness and anti-Xa activity, anti-IIa activity, or APTT (p > 0.05), but in the patient study, there was a correlation between weight and anti-Xa activity and anti-IIa activity (p < 0.05), and in the volunteer study, there was a correlation between weight and anti-Xa activity and APTT (p < 0.05). CONCLUSIONS: Subcutaneous administration of heparin in a fixed dose for prophylactic and therapeutic purposes may be inadequate because of the large interindividual and intraindividual variations in anticoagulant effect.

Terminal deoxynucleotidyl transferase positive subpopulations occur in the majority of ANLL: implications for the detection of minimal disease.

A series of 60 acute nonlymphocytic leukemias (ANLL) was analyzed for the expression of terminal deoxynucleotidyl transferase (TdT). The detected TdT+ cells were studied in detail by use of double marker analyses for TdT and differentiation markers, such as myeloid markers (CD13 and CD33), B cell markers, T cell markers, and the precursor antigen CD34. In 15 (25%) of these leukemic cell samples, we found no TdT+ cells or low percentages of CD10+TdT+ cells; the latter probably represent precursor B cells. In the other 45 (75%) ANLL myeloid marker+TdT+ CD10- cells were detected, ranging from 0.1-10% (n = 24) or over 10% (n = 21) of mononuclear cells. Interestingly, a higher frequency of CD34 positivity was found on the TdT+ cells as compared to the TdT- cells, suggesting that the TdT+ cells represent an immature leukemic subpopulation. Therefore, it may be speculated that the TdT+ subpopulation contains the clonogenic ANLL cells. In two patients, in whom immunologic marker analysis was performed at initial diagnosis as well as at relapse, an expansion of the TdT+ subpopulation was documented at relapse, which may reflect a reduced differentiation capacity of the leukemic cells. Previous studies on a series of nonleukemic bone marrow and blood samples revealed that normal counterparts of myeloid marker+TdT+ cells are rare in bone marrow (less than 0.03%, if they occur at all) and that such cells are not detectable in blood. Therefore myeloid marker TdT double stainings may be useful to monitor the TdT+ leukemic subpopulation in patients with a TdT+ ANLL during and after chemotherapy. Our preliminary results on the follow-up of two such patients support this hypothesis.

Immune reactions in patients with superficial bladder cancer after intradermal and intravesical treatment with bacillus Calmette-Guérin.

The immune reactivity of patients with strongly recurrent superficial bladder cancer was followed after combined intravesical and intradermal bacillus Calmette-Guérin (BCG) immunotherapy. All patients in this study were previously treated without success with intravesical chemotherapy. The BCG treatment regimen consisted of weekly administrations with BCG (RIVM) for six consecutive weeks, both intravesically and intradermally. In this study, sera and peripheral blood leukocytes (PBL) of patients were tested serially. Besides BCG-antigen-specific reactions, e.g. skin reactivity to purified protein derivatives of Mycobacterium tuberculosis (PPD), antibody formation and antigen stimulation of PBL in vitro, non-antigen-specific immune reactivities were also measured, e.g. mitogen response and spontaneous cytotoxic activity of PBL. In addition the antibody response to bladder carcinoma antigens and the cytotoxic activity of PBL for the bladder carcinoma cell line T24 and the natural-killer-sensitive K562 cell line were investigated. The results obtained from the various assays were evaluated for their prognostic value in relation to the length of the tumor-free interval after the BCG treatment. Because sera and PBL were only obtained during the first 6 months after the BCG treatment, the immune reactivity was compared to the clinical results at that same time. At 6 months after therapy 12 out of 40 BCG-treated patients were tumor-free whereas 28 out of 40 showed a recurrence. Skin reactivity to tuberculin PPD was measured in 40 patients during a period of 3-6 months after therapy. Of patients who showed a recurrence of the tumor within 6 months, 48% of them showed a transient response or developed no response at all to PPD. In the group of patients with a longer tumor-free period (n = 10), only one patient lost the response to tuberculin PPD. Although PBL of a limited number of patients were tested, it was observed that the cytotoxicity to the bladder carcinoma cell line T24, and the natural-killer-sensitive K562 cell line increased in a number of the patients (7 out of 14, and 9 out of 14 respectively). Reactivity of PBL to mitogens and subset distribution (ratio T-helper: T-suppressor/cytotoxic) were not influenced by the BCG treatment. Antibody response to mycobacterial antigen was detected in 9 out of 23 patients investigated. Of these 9 patients, 8 belonged to the group with a recurrence of the tumor within 6 months (n = 17). There was no correlation between the skin reactivity and the antibody response to tuberculin PPD.(ABSTRACT TRUNCATED AT 400 WORDS)