Hyperferritinemia in pregnancy induced hypertension and eclampsia.L Raman, AB Pawashe, P Yasodhara
National Institute of Nutrition, Indian Council of Medical Research, Jamai, Qsmania (PO), Hyderabad., India
Correspondence Address: Source of Support: None, Conflict of Interest: None PMID: 0001432830
Source of Support: None, Conflict of Interest: None
A study of serum iron and ferritin levels in Indian women with pregnancy induced hypertension (PIH) (mild/severe) and eclampsia compared with controls of similar gestational ages, revealed that mean serum iron was elevated slightly in PIH and significantly in eclampsia as compared to controls. Mean ferritin levels were significantly elevated both in PIH and eclampsia as compared to controls indicating that ferritin measurement in PIH and eclampsia would not reflect iron nutritional status. Lack of significant changes in liver enzymes and in hemoconcentration in PIH and eclampsia indicate that liver damage and altered hemodynamics only play a partial role in causing hyperferritinemia. Possible role of placental ferritin, being released as a result of placental damage in these conditions seems to be an area needing further research.
Keywords: Anemia, Hypochromic, epidemiology,etiology,Eclampsia, blood,complications,Erythrocyte Volume, Female, Ferritin, blood,Hemoglobins, analysis,Human, India, epidemiology,Iron, blood,Liver Function Tests, Pre-Eclampsia, blood,complications,Pregnancy, Pregnancy Complications, Hematologic, epidemiology,etiology,
Hypovolemia and hemoconcentration are known to occur in pregnancy induced hypertension (PM) and eclampsia resulting in altered homeostatic mechanisms during pregnancy. Recent reports suggest that there is significant hyperferrimia and hyperferritinemia occurring in PIH and eclampsia attributed to altered liver function or intravascular hemolysis resulting in release of iron from RBCs, . However, the sample size was small (11 subjects, only one with eclampsia),. Plasma ferritin is known to be a reliable indicator of iron nutritional status. In view of the high prevalence of iron deficiency in the population an investigation was undertaken to see if there were any alterations in the hematological parameters including ferritin status in PIH and eclampsia.
Fasting blood samples for ferritin assay were obtained from 34 normal (between 28-38) weeks of gestation), 33 with mild PIH (BP - 140190mm, edema andlor traces of proteinuria) and 28 women with severe PIH (BP 11 Omm diastolic; andlor ++ or +++ proteinuria). In 29 eclamptics, blood samples were obtained in between convulsions. Hemoglobin was measured by cyanmethemoglobin method and serum iron by the method described by ICSH 1971.
Serum ferritin was measured by a sandwich ELISA technique that was developed using polyclonal antiferritin raised in rabbit against the human liver ferritin obtained from International Centre for Control of Nutritional Anemia (ICCNA, USA) and HRP antiferritin conjugate5. This method has been standardised against reagents obtained from ICCNA and International Committee for Standardization in Hematology (ICSH, UK). Serum glutamate pyruvate transaminase (SGP7), serum glutamate oxaloacetate transaminase (SGOT) were assayed in a subsample by using the kit obtained from Stangen Immunodiagnostics, Hyderabad. Gammaglutamyl transferase (GT) was assayed by the method of Rosalky and Tarlow  in 6 cases of PIH in whom SGOT and SGPT were found to be beyond the normal range and also in 6 controls. Students t test was applied to compare the differences in the values between the controls and PIHs.
From the earlier data on plasma volume, the ratio of plasma: red cell volumes were calculated to assess the extent of hemoconcentration in PIH
As shown in [Table - 1], no significant differences were observed in the hemoglobin, serum iron and ferritin levels between mild and severe P1H. Therefore, the data were pooled and compared with the controls. Mean hemoglobin and serum iron, though slightly elevated in mild and severe PIH were not significantly different from the controls whereas in eclampsia both these parameters were significantly elevated (P < 0.01 and P < 0.05) as compared to controls.
Incidence of moderate/severe anemia (Hb 9 gm%) was 17.6% in the controls, 14.3% in PIH and 11.1 % in eclampsia. Mean serum ferritin was significantly higher in both P1H and eciampsia (P < 0.01) as compared to the control group. In eclampsia, the mean level was four fold higher than the controls and also significantly higher as compared to the levels seen in PIH (P < 0.01). Thirty five percent of the controls showed evidence of iron deficiency as reflected by both ferritin (10 ng/ml) and serum iron (< 60 ug/df) in both PIH and eclampsia, the diagnosis of iron deficiency was possible only in terms of low serum iron rather than low serum ferritin.
Liver function tests done in the subsample indicated that both SGPT and SGOT though within the upper limit of the normal range, were significantly elevated in severe PIH (P <0.01 and P <0.005) and in eclampsia (P<0.001) as compared to the controls [Table - 2] Gamma GT assayed in samples showing elevated SGIDT and SGOT did not show any difference both PIH and eclampsia as compared to the control values.
Plasma/RBC volume ratios did not show any difference between controls and PIH except in moderate/severe anemia (Hb 9 gm/dl) where hemoconcentration was more obvious in PIH as compared to controls [Table - 3]
Normally both serum iron and ferritin show a decrease with advancing gestation due to hemodilution and depletion of iron stores to meet the increasing needs of the growing conceptus. In developing countries, the depletion is of much higher order due to a high prevalence of iron deficiency anemia.
However, in the present study, highly elevated levels of serum iron and ferritin were observed in eciampsia and PIH despite relatively lesser changes in the mean hemoglobin levels. Similar increase in serum iron and ferritin have been reported earlier in severe PIH and eclampsia,. In this study, whereas 35% of controls showed evidence of iron deficiency and anemia, the deficiency status was masked in both PIH and eciampsia due to elevated serum iron and ferritin.
Elevated serum ferritin occurs in a variety of clinical conditions associated with non-utilization of iron and destruction of tissues such as in hemolytic anemia, hepatic damage, inflammation and neoplasms due either to repeated transfusion or to suppression of erythropoiesis leading to accumulation of storage iron. In liver disease, serum ferritin increases due to leakage of tissue ferritin from damaged hepatocytes in the circulation.
Observations in the present and earlier studies suggest that PIH and eclampsia are yet other conditions where hyperferritinemia is a common feature. However, a comparatively lesser degree of hyperferritinemia and ferrimia was observed in the present study as compared to earlier reports by Entman et al and this could be due to associated iron deficiency commonly seen in the population. However, only 7-10% of the subjects with PIH and eciampsia had ferritin below 10 ng/ml. Thus ferritin cannot be used as an index of iron nutritional status in these conditions.
Earlier studies have indicated that despite hypovolemia in PIH, hemoconcentration was not of significant order due to concomitant decrease in red cell volume as a result of chronic iron deficiency in the population. In the present study, though there is evidence of hemoconcentration as evidenced by higher hemoglobin and lesser degree of anemia, it may not entirely account for the elevated serum iron (two fold) and ferritin (four fold) especially in eclampsia.
Subclinical hepatic damage is known to occur in PIH and eciampsia and this is reflected by elevated liver enzymes. The hepatic damage may result in the leakage of ferritin into circulation resulting in hyperferritinernia, more so in eciampsia due to the acute damage. In the present study, both SGPT and SGOT were within the upper limit of normal range. Also GT an indicator of active hepatic dysfunction, did not show any elevation either in PIH or eclampsia similar to observations in an earlier study suggesting that there is possibly no severe impairment of the liver function which would account for hyperferritinemia seen in eclampsia.
Thus, it is possible that hyperferritinemia seen in eclampsia may in addition to hypovolemia and hemoconcentration be related to placental damage resulting in release of placental ferritin in the circulation similar to other enzymes like heat stable alkaline phosphates . Further studies are on, to characterize the nature of ferritin in eclampsia and it's role in placental dysfunction.
The authors are thankful to the Director, National Institute of Nutrition and Dr. MK Nair for providing antiferritin antibodies. They also thank Dr. JK Cook, ICCNA, Kansas, USA for the kind gift of human liver ferritin. Technical assistance of Mrs. M Vijayalakshmi and secretarial assistance of Mrs. Sudha Srinivasan is gratefully acknowledged.
[Table - 1], [Table - 2], [Table - 3]