Dommisse, J.

du Toit, E.D.

English

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244 S.A. MEDICAL JOUR~AL 1 March 1969CDe/cde infants born to mothers with anti-C plus anti-D,than if the same mothers had only produced anti-D." Theassumed connection between increased antibody loadingon the red cells and the severity of the disease is quitefeasible, but the primary cause of the development ofmultiple antibodies would seem to be directly linked withthe intensity of the stimulation of the antibodies as a re-sult of repeated episodes of placental bleeds.In the present investigation evidence has also been ob-tained to show that antibodies other than anti-Rh can beproduced in response to frequent episodes of re-immuni·zation. Since this form of complication is most often con-firmed among mothers with significantly raised Rh-anti-body values (Table VII), who as a rule had more severelyTABLE VII. FREQUENCY OF OTHER IMMUNE RED CELL ANTIBODIESAMONG MOTHERS WHO WERE INITIALLY SENSITIZED BY RHFACTORMaternal No. of Immunizing antibody Percentage ofRh-antibody mothers 2 antibodyinhibition index examined Anti-Rh alone Anti-Rh plus systems observedothers·80 units or less 82 82 0 0·0%80-500 units 54 49 5 9·2%500 units or more 33 27 6 18·1%*Rh immunization found in association with immune anti-A, B. KelI, FyAor Jk A .affected infants (Table VI), and a greater incidence ofpossible placental bleeds,' it would seem appropriate toconclude that future studies directed towards the possibleprevention of placental bleeds could lead to an evengreater reduction in foetal wastage.SUMMARYIn this study a new procedure of Rh-antibody quantificationwas introduced which is essentially based on the number ofabsorptions an Rh antibody requires by Rh-positive red cellsbefore it is removed from the serum. By altering the basicprocedure of antibody absorption so that the method can beadapted for routine use, an Rh-antibody inhibition test wasdesigned which offered the best possible approach to standardi-zation. Using the Rh-antibody inhibition test as a means ofquantification, other improvements could be made to measurethe over-all impact of Rh-antibody stress on the infant duringpregnancy. This was accomplished by multiplying the Rh-antibody inhibition value by the recorded duration of preg-nancy.The Rh-antibody inhibition test is of greater significance inthe prognostication of the severity of Rh-haemolytic diseasethan Rh-antibody titrations. Where the Rh-antibody inhibitionindex showed increased intensity of antibody production as aresult of renewed stimulation by foetal Rh-positive red cells,it was often possible to find that antibodies other than anti-Rhwere also frequently produced by the mother. As multipleantibody formation can be regarded as a measure of raisedintensity of immunization, which is associated with the occur-rence of more severely affected Rh-positive infants, it wouldappear that the examination for antibodies other than anti-Rhis justified as a routine follow-up test on selected Rh-immu-nized mothers in whom repeated Rh-antibody increases canbe recorded during pregnancy.REFERENCES1. Vos, G. H. (1969): S. Afr. Med. J., 43. 130.2. Kelsall, G. A., Vos, G. H. and Kirk, R. L. (1958): Brit. Med. I.,2, 468.3. Vos, G. H. (1958): Aust. Ann. Med., 7, 340.4. Race. R. R. and Sanger, R. (1950): Blood Groups in Mall, 1st ed.,p. 169. Oxford: Blackwell Scientific Publications.5. Idem' (1954): Blood Groups in Man, 2nd ed., p. 280. Oxford: Black-well Scientific Publications.6. Vos, G. H. and Kirk, R. L. (1958): Amer. I. Clin. Path., 29, 284.7. Coombs, R. R. A., Mourant, A. E. and Race, R. R. (1945): Lancet,2, 15.8. Tovey, G. H. and Valaes, T. (1959): Ibid., 2, 521.9. Iacobs, W. M. (1962): Obstet. and Gynec., 19, 806.10. Zeitlin, R. A. and Boorman, K. E. (1963): I. Obstet. Gynaec. Brit.Cwlth, 70, 798.11. Crawford, J. W., Cameron, C. and Walker, C. H. M. (1966): Lancet,2, 887.12. Farrell, A. G. W. and Davis, G. S. D. (1967): S. Afr. J. Obstet.Gynaec., 5, 1.13. Vos, G. H. (1969): S. Afr. Med. I. (in the press).14. Nilsson, B. A. (1965): Acta obstet. gynec. scand., supp/. 2, 44.THE INCIDENCE AND TREATMENT OF SEVERE PREGNANCY ANAEMIAIN THE CAPE TOWN AREA*J. DOMMISSE, M.B., CH.B., M.R.C.O.G. AND E. D. DU Ton, M.B., CH.B., Department of Obstetrics and Gynaeco-logy and the Cape Provincial Blood Gr0l!ping Laboratory, Groote Schuur Hospital and the University of Cape TownAnaemia is so commonly encountered in the pregnantpatients under the care of our hospital and municipalantenatal clinics that it was decided to undertake asurvey to determine the incidence of anaemia in preg-nancy, the type of anaemia encountered and a logicalapproach to its prevention and treatment.The type of anaemia encountered in a particular geo-graphical area will vary. This may depend on dietaryor other factors, for example the presence of an endemicdisease such as malaria. ._Folic acid has been widely advocated as importantin preventing anaemia and it was therefore necessary todetermine the incidence of megaloblastic anaemia in thiscommunity before accepting this therapy.The following is a brief and preliminary report of theresults of this survey.'Paper presented at the Interim Congress of the S.A. Society of Obstetri-cians and Gynaecologists, Hermanus, April 1968.METHODHaemoglobin estimations were performed by the labora-tory on all patients booking for confinement at bothhospital and municipal antenatal clinics. A total of 45,350haemoglobin estimations were performed. The incidenceof moderate anaemia -(haemoglobin 8 - 9·9 G /100 ml.)was 10·1 % and of severe anaemia (haemoglobin 4 - 7·9G/lOO m!.) 0'5%.'The 244 patients with severe anaemia were referredto a special clinic for complete investigation. If, onarrival at the clinic, the haemoglobin was confirmed tobe less than 8 G /100 ml. and the patient had receivedno previous haematinic therapy, full investigations, in-cluding bone-marrow aspirations, were performed. Thus,100 patients were fully irlVestigated.Table I gives details of these 100 patients.1 Maart 1969 S.A. TYDSKRIF VIR GENEESKU DE 245500Marrow40020(8)Bone•• Grade 3 MegaloblasticJ( Grade 1 Megaloblastico Iron Deficiency Only~s.-.l--80nrI Marrow ~ic:iencyBone M."owIron Stor.. %60300(21)SerumI,on~g/100""oJ((384)200100••Red Cell Folates m....gl mlFig. 3. Red cell and serum folates compared.oI·0:IIIIII2· ---...:--------t----o----o--- -------------• I 0 •"lIIIIIIIIIII3·Folate.•o4' 0disease. The over-all incidence of urinary tract infectionon culture of mid-stream urine specim n wa 1000.Fig. 2 illustrates the means of the diagnostic criteriain patients who had iron-deficiency anaemia, and in allthese cases there was a complete absence of stainableiron ;", the bone-marrow specimens.Fig. 2. Diagnostic criteria means in the 86 cases of iron-deficiency anaemia.Fig. 3 depicts the values of the red cell folates andthe folates in patients with grade 1 and grade 3 megalo-blastic erythropoiesis. As can be seen, both levels werevery low in the patients with florid megaloblastic ery-oSerumIRON DEFICIENCYAtM.EMIA..::15..0..~....C» u;;Cl ....0 ~.... gc ..gC» ~UL z wC» i 0a.. ..~..i~... u.. zz ..... u~ ::;u Q"Z~0u:I u·..0TABLE I. DETAILED INVESTIGATION OF A AEMIA IN PREGNANCYI 100 PATIENTSTotal haemoglobin estimations performed 45,350Total patients referred for detailed investiga-tion (Rb. less than 8 G/lOO mL) .... 250 (0·5%)Total complete investigations including bone-marrow examination 100Race Coloured 86Bantu 8White 6Parity Primigravida 14Gravida 2 - 4 33Gravida 5 plus 53Age in years < 20 1320 - 30 48> 30 39RESULTSThe aetiology of the 100 severe cases of anaemia is shownin Fig. 1.Fig. 1. :Pinal diagnosis on bone marrow.There was an overwhelming preponderance of iron-deficiency anaemia, accounting for 86% of the casesinvestigated.Only 3 patients showed florid megaloblastic erythro-poiesis arid an additional 10 patients had mild megalo-blastic erythropoiesis (grade 1) in the presence of iron-deficiency anaemia. One patient had haemoglobin-Hthropoiesis, but in about half the patients with earlymegaloblastic erythropoiesis these parameters were withinnormal limits. In addition, 8 patients with normoblasticerythropoiesis had either a Iow serum folate or a lowred cell folate level, possibly indicating folic-acid defi-ciency.One may conclude that 21 patients had some evidenceof folic-acid deficiency but only 3 had megalobla ticanaemia. On the other hand, as detailed later, the evi-246 S.A. MEDICAL JOURNAL 1 March 1969Fig. 5. Graphic comparison of response between Imferon (22 patients) and oral iron(38 patients).8after Total Dose Imferon6rise on Ferro - gradumet--- Hb rise-Hb54Treatmentof3WeeksIt was thus decided to compare the response to oraliron with the response to total-dose intravenous Imferon.An oral preparation, Ferro-Gradumet, containing 105mg. of elemental iron as a single daily dose, was used.This was easy to control and previous studies' had shownit to be both effective and well tolerated.Intravenous Irnferon was administered on an outpatientbasis at the recommended dosage (0·3 x wt. in lb.81110inHbGm.dence of folic-acid deficiency in theother 18 patients was probably ofno significance in relation to theanaemia, which was basically dueto severe iron deficiency.ASSESSMENT OF TREATMENTFolic-Acid DeficiencyIn an attempt to ascertain whe-ther patients with evidence of folic-acid deficiency in addition to iron-deficiency anaemia required folicacid, it was decided to treat suchpatients with iron only. This wasdone while keeping a careful watchon their haematological progress,as the development of megaloblas-tic anaemia can be acute and resultin rapid deterioration.It was only possible to do thisadequately in 4 patients, as theother patients required urgenttransfusion for obstetrical reasons.The remarkable response to irontherapy is illustrated in Fig. 4. The serum folates and redcell folates were repeated on 2 of these patients once thehaemoglobin had been corrected, and in both cases werefound to be still below normal. None of these patientsdeveloped anaemia later in pregnancy or in the puerperium.A fifth patient treated with folic acid alone failed torespond and was transfused.5'---;----:-------::----;-------::-------::--_6 L-------- rnlnsfused8 weeks4 weeks 6 weeks2 weeks43HbRise2inGms %---Post pqtal Hb 13-3P.c.v. 31'5Serum FeAt. 3- tRed CeI Folate '29- Folic Acid Therapy- Iron Therapy---------.------------ Serum Folate 1·4R.d e.. Folate 11e.,W •• ks871110HbGm,Fig. 4. Response to iron therapy.Iron-Deficiency AnaemiaIron-deficiency anaemia will respond in most casesto the oral administration of iron. In many cases, how-ever, the response is unsatisfactory, due either to patientsfailing to take their tablets regularly or, occasionally, topoor intestinal absorption.~ =Ferro - GradumetWeeks after institution of Therapy~ =Total Dose ImferonFig. 6. Histogram showing response with Imferon andoral iron.1 Maart 1969 S.A. l'YDSKRIF VIR GENEESKUNDE 247x haemoglobin deficit in % Haldane) diluted in normalsaline. Phenergan, 50 mg., was given before administra-tion. The concentration never exceeded 30 ml. /1,000 m!.and was always started slowly. To date we have ad-ministered intravenous Imferon to 80 pregnant patientswithout major side-effects or need to discontinue theadministration.The results of this comparison are shown in Figs. 5and 6 and it is evident that intravenous Imferon has pro-duced a more rapid and complete response.In addition, this method facilitates subsequent follow-up investigations, as the factor of patient or absorptionfailure is excluded. Probably the major advantage oftotal-dose intravenous Imferon is the rapid repletion oftissue and bone-marrow iron stores. To accomplish thisby oral means, medication should be continued for 6months.' This correction is most important, particularlywith regard to the patient's future health and pregnan-cies.DISCUSSIONThe Iow incidence (3%) of megaloblastic anaemia in se-vere pregnancy anaemia (haemoglobin less than 8 G/lOOml.) is striking. Giles; in an extensive investigation, foundthat in severe anaemia (haemoglobin less than 50%) 165of 255 cases had megaloblastic anaemia. In the Trans-vaal, Edelstein et al." studied 100 anaemic Bantu patientsfollowing delivery and found that 78 % showed morpho-logical evidence of deficiency of antimegaloblastic fac-tors.Megaloblastic anaemia is particularly prevalent nearterm and in the puerperium, and most of our cases werebetween 24 and 34 weeks pregnant. However, any patientwho developed severe anaemia later in her pregnancy wasalso included in the series, so that this is probably not avery significant factor.The most likely explanation is that as megaloblasticanaemia is basically due to a dietary deficiency of folicacid, associated with certain other precipitating factors, thediet of our patients, even in the lower socio-economicgroups, is not lacking in folic acid. Fruit and vegetablescontaining folic acid are relatively cheaply available inthe Cape Town area and form part of the basic diet ofBOEKBESPREKINGSPSYCHOTHERAPY TECHNIQUETechnique of Psychotherapy. 2nd ed. Vols. I and H. ByL. R. Wolberg, M.D. Pp. xiv + x + 1411. £11.4.0. London:William Heinemann Medical Books. 1967.Numerous changes nnd additions have been made to the o~e­volume 1957 edition of Technique of Psychotherapy, revealingthe strides made in psychotherapeutic practice. There are newchapters on behavioural, existential and Kleinian therapies;indications and effectiveness of various types of psychotherapy;causes of failure in psychotherapy; therapy in children andadolescents; and religion and psychotherapy.In this revised edition the 'working-through' process and thedoctor-patient relationship are considered more importantthan 'intellectual' -insight in reconstructive (analytic-type)psychotherapy. Somatic therapies and their indications arealso included, as well as an extensive bibliography.The author displays a refreshingly eclectic, though analytic-ally oriented, approach to psychotherapy. D.S.V.the group investigated, in contrast to the groups quotedabove.The response to iron therapy in patients with additionalevidence of folic-acid deficiency confirms the statementby Dawson' that the presence of megaloblastic erythro-poiesis in the marrow of a patient with iron-deficiencyanaemia does not mean that the response to iron therapywill be suboptimal or that the patient's anaemia willimprove on vitamin B" or folic acid.The reason for the better response to intravenous ironthan to oral iron is probably partly due to patient failure,although every possible precaution was taken to avoidthis. In certain cases there may have been inadequateintestinal absorption. In either case the more liberal useof intravenous Imferon is justified, and the early correctionof tissue and bone-marrow iron stores is an additionaladvantage.SUMMARYA total of 45,350 hnemoglobin estimations were performed onpatients attending antenatal clinics in thc Cape Town area. Theincidence of severe anaemia (haemoglobin less than 8 G / 100ml.) was 0·5%. Detailed investigation, including bone-marrowaspiration, was performed on 100 such patients with severeanaemia.By far the commonest cause of the anaemia was irondeficiency, and only 3 cases of megaloblastic anaemia wereencountered. Certain patients with evidence of folic-acid defi-ciency responded to iron therapy alone. Total-dose intravenousImferon was found to be safe and more effective than oraliron in the treatment of established iron-deficiency anaemia.All pregnant patients should receive supplementary irontherapy during pregnancy, but folic acid is only indicated inthis area in certain selected cases.We should like to thank Dr J. G. Burger, Medical Superin-tendent of Groote Schuur Hospital, for permission to publish;Dr D. McKenzie and the Staff of the Pathology Laboratories,Red Cross Children's Hospital, for the folate investigations;and Mr L. van Zyl, senior technician of the Provincial BloodGrouping Laboratory.REFERENCES1. Israel, M. C. G. and Cook, T. A. (1965): Lancet, 2, 654.2. BothweU, T. H. and Finch, C. A. (1962): Iron Metabolism. London:Churchill.3. Giles, C. (1966): J. Clin. Path., 19, 1.4. Edelstein, T., Zai1, S. S., Faulding, G. E. and Metz, J. (1967):S. Afr. Med. J., 41, 300.5. Dawson, D. w. (1962): J. Obstet. Gynaec. Brit. Cwlth, 69, 38.BOOK REVIEWSVASCULAR DISTURBANCESVascular Diseases. By M. J. Tsapogas, M.D., M.Ch., V. V.Kakkar, ER.C.S., ER.C.S. (Edin.) and E. N. Gleave,F.R.C.S., F.R.C.S. (Edin.). Pp. 178. lllustrated. £2.10.0:London: H. K. Lewis. 1968.This is a comparatively short but surprisingly complete accountof most of the common vascular disturbances encountered inpractice. The presentation of the material is to be highlycommended and it is a work that is eminently readable.The descriptions of the various pathological states and theirclinical features are of necessity short and limited, but clearand very much to the point. As stated in the preface, thisbook is based largely on personal clinical experience, andthis particular feature is evident throughout the subjectmaterial.This book is to be particularly recommended for studentand general practitioners, and would serve as the basis ofknowledge for specialists desirous of acquiring a more detailedknowledge of vascular diseases. F.Z.

The incidence and treatment of severe pregnancy anaemia in the Cape Town area

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The incidence and treatment of severe pregnancy anaemia in the Cape Town area

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