sickle-cell disease in pregnant immigrantssickle-celldisease inpregnantimmigrants sickling, but this...

Postgrad. med. J. (November 1968) 44, 836-843.

Sickle-cell disease in pregnant immigrants

A. E. R. BUCKLEF.R.C.S., F.R.C.O.G.

Consultant, Department of Obstetrics and Gynaecology,Lewisham General Hospital, London, S.E. 13

SummaryThirteen pregnancies in nine patients with sickle-cell disease, sickle-cell/haemoglobin C diseaseand sickle-cell/thalassaemia are reported. Therewas one maternal death and one stillbirth. Crisesoccurred in three of the four patients with sickle-cell disease but in only one of the three patientswith sickle-cell/haemoglobin C disease.

IntroductionThe clinical features of sickle-cell disease have

been recognized for many years, the diseasebeing described by Herrick (1910), later Syden-stricker (1924) reported on a large series ofcases. In 1931, Yater & Mollari described a casewith fatal outcome; Kobak, Stein & Daro (1941)made a detailed study of pregnancy in associa-tion with sickle-cell disease. The demonstrationby Pauling et al. (1949) of an abnormal haemo-globin in the erythrocytes of patients with thedisease led rapidly to the identification of addi-tional haemoglobin variants and the introductionof filter-paper electrophoresis by Spaet (1953)allowed of identification of abnormal haemo-globins in general hospital practice, so allowingseparation of cases which may previously havebeen included as sickle-cell disease but whichwere, in fact, cases of sickle-cell/haemoglobin Cdisease or cases of sickle-cell/thalassaemia.An increasing number of papers has since

appeared dealing with the problem in the preg-nant woman (Adams, Whitacre & Diggs, 1953;Eisenstein, Posner & Friedman, 1956; Curtis,1959; Abrams & Schwartz, 1959; Anderson etal., 1960). These papers have described casesoccurring in the United States of America andthe West Indies and to date there has been littleinformation concerning cases in the United King-dom (Reiss, 1962; Apthorp, Measday & Leh-mann, 1963). Routine ante-natal haemoglobinelectrophoresis screening of negro women hasbeen reported from the United States of America(Curtis, 1959; Cotter & Prystowsky, 1963), fromthe West Indies (Anderson et al., 1960) and from

the United Kingdom (Buckle, Hanning & Holman,1964). The results obtained from such screeningshow a comparable incidence of cases of sickle-cell disease, sickle-cell/haemoglobin C diseaseand sickle-cell/thalassaemia, an incidence of0 18% for these three conditions being reportedby Buckle et al. (1964) in immigrants into theUnited Kingdom from West Africa, the WestIndies and the Mediterranean littoral. The condi-tions will, therefore, be infrequently encounteredin association with pregnancy and individual ex-perience in management necessarily limited. Inthe present paper, the course, outcome and man-agement of thirteen pregnancies in patients withsickle-cell anaemia or variants will be described.

The general problemIt is not within the compass of this paper to

detail the problem of sickle-cell diseases. It willsuffice to mention that these disorders, whichare inherited, may give rise to symptoms earlyin life and may involve almost every system inthe body.The basis of the disease is the presence of the

abnormal sickle haemoglobin molecule which, inits reduced state, comes out of solution, formingaggregates. A multi-molecular combination of thishaemoglobin, being less soluble then single mole-cules, will form a solid gel, leading to rigiditywithin the erythrocyte and this rigidity is reflec-ted in distortion of the cell, which becomes asickle cell. Because of the abnormal shape, thesickle-cell is liable to mechanical destruction andphagocytosis, leading to haemolytic anaemia. Thesickle cells can cause damage by blocking bloodvessels, the occlusion of small vessels leading tothe crises of sickle-cell disease. Infarction mayoccur by primary occlusion of small vessels bysuch tangles of erythrocytes or by embolism fromnecrotic bone marrow. The sickling phenom-enon, which occurs with diminished oxygentension, is favoured by a lowering of pH and byincrease in body temperature. The oxygen tissuesmay be low enough in most tissues to induce

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sickling, but this requires time and the cells havenormally become re-oxygenated before sicklingoccurs.The haemoglobinopathy will be severe where

only genes for sickle haemoglobin are present.With one gene for sickle haemoglobin and onefor haemoglobin C (sickle-cell/haemoglobin Cdisease), the amount of haemoglobin S is suchthat molecular aggregation may occur and thelife span of the erythrocytes is reduced, thoughhaemolysis is less than in the homozygous sickle-cell disease. The condition may remain undiag-nosed unless there is superadded stress such asinfection or during pregnancy. In sickle-cell/thalas-saemia, where haemoglobin S and F are present,the clinical course, particularly during pregnancy,may be benign.

In general, in sickle-cell disease, there will bechronic anaemia, jaundice, weakness, fatigue,bone and joint pain, and abdominal pain. Signsinclude fever, bone tenderness, occasional splen-omegaly, hepatomegaly, underdevelopment andmalnutrition. Symptoms date from early child-hood and the condition may well have been diag-nosed before pregnancy. The same is not neces-sarily true of sickle-cell/haemoglobin C disease orof sickle-cell/thalassaemia and routine screeningof patients likely to be affected is desirable.

Effects of pregnancy on sickle-cell diseasesThere have been conflicting reports on the

seriousness of pregnancy occurring in patientswith the sickle-cell diseases. Smith & Conley(1954) suggested that pregnancy was more hazar-dous in patients with sickle-cell /haemoglobin Cdisease, a view which received support frompapers by Edington (1957) and Molina & Marks(1957). Eisenstein et al. (1956) reported a post-partum maternal death in a patient with sickle-cell disease. Curtis (1959) found no exacerbationof symptoms and no mortality in nine patientswith sickle-cell disease, whereas four of sixteenpatients with sickle-cell/haemoglobin C diseasedied during pregnancy or after delivery; threecases of sickle-cell /thalassaemia had uneventfulpregnancies. Anderson and her colleagues, repor-ting from the West Indies on nine cases of sickle-cell disease, seven cases of sickle-cell/haemoglob-in C disease, and one case of sickle-cell/thalas-saemia without maternal death during pregnancyor after delivery, agreed that symptoms in sickle-cell/haemoglobin C disease might be manifestfor the first time during pregnancy but felt thatthe hazards, in their cases at least, appeared tobe less than in other reports.

In general, pregnancy appears not to influencethe natural course of sickle-cell disease, whereas

haemolytic and infarctive crises may be manifestfor the first time in cases of sickle-cell/haemo-globin C disease during pregnancy. In sickle-cell/ thalassaemia, the condition appears to run abenign course during pregnancy. The maternalmortality generally is higher in cases of sickle-cell/haemoglobin C disease.

Effect of sickle-cell diseases on pregnancySpontaneous abortion in 19% of cases of sickle-

cell disease and 16-39% of cases of sickle-cell/haemoglobin C disease was reported by Curtis(1959) and the total foetal survival in his serieswas 52% in the former condition and 65% in thelatter. Anderson et al. (1961) reported three abor-tions and two still-births in thirty-nine pregnanciesin patients with sickle-cell disease and sickle-cell/haemoglobin C disease and Reiss (1962), fromthe United Kingdom, reported four pregnanciesin immigrants with sickle-cell/haemoglobin Cdisease, without foetal loss. He also reported aperi-natal loss of four of six children born to onepatient with sickle-cell disease, but this figure mustbe treated with reserve as the total included onetwin and one triplet pregnancy. McCurdy (1964)found no increase in frequency of maternalcomplications such as pre-eclampsia, ante-partum haemorrhage or post-partum infection insuch cases, but reported a 34-6% foetal loss insickle-cell disease and a 15-5% loss in sickle-cell/haemoglobin C disease.The increase in peri-natal mortality in these

cases may be related to foetal anoxia consequenton sickling in the maternal venous sinuses. Curtis(1959) suggested that, consequent on sluggishmaternal flow and variable oxygen tension, theplacenta might be an ideal site for clumping ofsickle-cells and thrombosis. Both placental biopsyand biopsy of the uterine muscle at the time ofCaesarian section have confirmed marked sick-ling in the maternal vessels in these cases (Buckle,unpublished observation).

Current seriesNine patients, observed over a total of thirteen

pregnancies, form the basis of this paper. Thebreakdown of the haemoglobin genotype is shownin Table 1. One case (Case 4) did not have thisinvestigation performed until necropsy, deathhaving taken place suddenly, 40 hr after normalvaginal delivery; the remainder were identifiedby routine ante-natal screening. Brief clinicaldetails are mentioned below and the more impor-tant points are summarized in Tables 2 and 3.

Case 1 (Hospital No. D 41453)A 34-year-old primigravida from Barbados.

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Genotype SS. There was a history of jaundicesince childhood but no other relevant medicalhistory. Ante-natal booking was at 16 weeksof pregnancy and the patient was admitted 1week later with joint pains. Examination showedhepatomegaly and splenomegaly and there wereold scars on the legs. Hb 92 g/ 100 ml. Totalbilirubin 1-lg/100ml. Serum iron slightly in-creased. The patient was commenced on oralalkalies and given supplementary folic acid, 5 mgdaily. She was allowed home and no further crisesoccurred during pregnancy. The haemoglobinlevel varied between 7-2 and 9-6 g/ 100 ml.Assessment for induction at 39 weeks' gesta-tion showed the cervix to be unfavourableand delivery was effected by lower segmentCaesarian section, operation being carried outunder general anaesthesia. One pint of bloodwas transfused during operation and intravenoussodium bicarbonate given in place of oral alkaliuntil the patient was again taking food bymouth. Intravenous magnesium sulphate, 2 ml of50% solution, was given 6-hourly from the timeof operation for 24 hr. A post-operative pyrexiafor 3 days was noted and the patient given acourse of ampicillin. No organisms were culturedfrom a urine specimen or from a high vaginalswab. The oral alkali regime was continued untilthe patient left hospital. The infant was a live-born male, weighing 2-8 kg.

TABLE IHaemoglobin genotype of patients and outcome of pregnancy

Haemoglobin genotype

SS SC S/Thalassaemia

Total cases 4 3 2Total previous 6 4 1pregnanciesTotal pregnancies 5 5 3currently observedAbortions - - -Still-births 1 - -Neonatal deaths -

Maternal deaths 1 - -

Average birth weight 2 54 2-68 3-1of new-born infant(kg)

Case 2 (Hospital No. D 13410)A 28-year-old Nigerian, gravida 2. Genotype

SS. There was no relevant medical history butthe patient was a poor witness. During the firstpregnancy (elsewhere), there had been joint andbone pains on numerous occasions. Vaginal

delivery at 37 weeks' gestation had resulted inthe birth of a live female, weight 2-5kg.During the second pregnancy, at this hospital,

the patient booked into the ante-natal clinic at20 weeks. There was no hepatomegaly or spleno-megaly though there were old leg ulcers. Hb 9 g/100 ml. Oral alkali and supplementary folic acidwere commenced. She was admitted at 30 weeks'gestation with bone and joint pains, the haemo-globin at this time being 8-2 g/ 100 ml, with areticulocyte count of 20%. The total bilirubinlevel was 05 mg/ 100 ml. The oral alkali was in-creased and her condition rapidly settled but3 weeks later there was a sudden rise in tempera-ture with signs of left lower lobe pulmonary con-solidation (?embolic ?pneumonic) and the patientwent into premature labour. The foetal heartsounds ceased at the onset of the second stageof labour and the patient delivered herself of afresh still-born male infant, weight 1 8 kg. Thepuerperium was uneventful, alkali therapy beingdiscontinued at the time of discharge fromhospital.The patient again attended 12 months later

when she booked at the ante-natal clinic at 18weeks' gestation. Hb 9-2 g/ 100 ml. The alkaliregimen and supplementary folic acid werecommenced but the patient was admitted at 29weeks' gestation with pain under the left costalmargin. Haemoglobin level at this time was 7-5 g/100ml and the total bilirubin 4-7mg/lO0ml.She was treated with intravenous magnesiumsulphate during the painful episode and the oralalkali continued. Her symptoms rapidly subsidedand the total bilirubin 3 weeks later was under1 mg/ 100 ml. Labour commenced spontaneouslyat 37 weeks' gestation and the patient deliveredherself of a live male infant, weight 2-3 kg. Alkaliwas continued until her discharge after a normalpuerperium.

Case 3 (Hospital No. D 18709)A 29-year-old Jamaican, gravida 3. Genotype

SS. There was no relevant previous historyobtained but the patient stated that during bothprevious pregnancies (elsewhere) she had jointpains throughout pregnancy. Term vaginaldelivery had taken place, both infants being live-born.

In her third pregnancy, observed at thishospital, she attended for ante-natal booking at12 weeks. There was no hepatomegaly or spleno-megaly and no old scarring on the legs. Thehaemoglobin was 8 g/ 100 ml. She was commencedon alkali and supplementary folic acid andremained well, without crisis, throughout preg-nancy, the haemoglobin level varying between

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TABLE 3

Laboratory investigations

Haemoglobin BilirubinCase Haemoglobin (g/100 ml) (mg/100 ml) Serum UrineNo. genotype total iron culture Stool

Lowest Highest maximum

I SS 7-2 9-2 11 Slightly E. coli Negativeincreased

2 SS (a) 7-4 8-7 0-3 Normal Negative Negative(b) 7-0 9-8 4-7 Normal Negative Negative

3 SS 8-2 9 3 1 0 Slightly Negative Negativeincreased

4 SS 108 12*2 1-8 Normal Negative Negative5 SC 91 10X4 - E. coli Negative6 SC (a) 8-5 9 9 0 5 Normal Negative Negative

(b) 8X2 9 5 1-2 Normal Negative Negative7 SC (a) 7-8 9 9 0X6 Slightly Negative Negative

decreased(b) 9.4 9-6 0 4 Slightly Negative Negative

decreased8 S/Thalassaemia(a) 10-5 120 - Negative Negative

(b) 11-7 13-7 Negative Negative9 S/Thalassaemia 8-2 9 0 2-0 Normal Negative Negative

(a) First observed pregnancy.

8-2 and 9-3 g/ 100 ml. Spontaneous onset oflabour at 38 weeks was followed by normalvaginal delivery of a live male infant, weight2-6 kg. The puerperium was uneventful andalkali was discontinued at the time of dischargefrom hospital (this patient was admitted 9 monthslater under the care of the physicians with acrisis and pulmonary infarct).

Case 4 (Hospital No. B 81737)A 40-year-old Jamaican, gravida 4. Genotype

SS. No relevant medical history was obtainedand the three previous pregnancies had appar-ently been uneventful, although the patient was apoor historian. The patient attended for ante-natal booking at 16 weeks' gestation. There wasno hepatomegaly and no splenomegaly and thehaemoglobin was lOg/100ml. Routine screeningfor abnormal haemoglobins had not been insti-tuted at the time of this patient attending. Duringthe ante-natal period, the haemoglobin levelvaried between 9-2 and 10-4g/100ml. She wasadmitted for bed rest at 36 weeks on accountof hypertension and was induced 2 weeks lateron this finding. During the time in the ward shehad complained once of pain in the arm. Un-complicated vaginal delivery of a live female,weight 32 kg followed induction. After delivery,the patient complained again of pain in thearms and thighs; 40 hr after delivery, the patient

(b) Second observed pregnancy.

got out of bed, fell to the floor, lost conscious-ness and died within a few minutes. Post-mortemexamination of the blood confirmed the patientas being of genotype SS, death resulting frombone marrow infarction with pulmonary, fatembolism.

Case 5 (Hospital No. D 39069)A 21-year-old Gambian, gravida 4. Genotype

SS. There was no relevant medical history. Thethree previous pregnancies (elsewhere) had beenuneventful. In the fourth pregnancy (at thishospital), the patient attended for ante-natalbooking at 14 weeks' gestation. There was nohepatomegaly but the spleen was enlarged andthere were old scars on the legs. The haemo-globin level was 10 6 g/ 100 ml. She was commen-ced on oral alkali and supplementary folic acidand remained well throughout pregnancy apartfrom one attack of fleeting joint pain at 34weeks' gestation, hospital admission not beingnecessary. Labour commenced spontaneously at38 weeks' gestation, the patient delivering herselfof a live male infant, weighing 3-2 kg. The puer-perium was uneventful and alkali treatment wasdiscontinued at the time of discharge fromhospital.

Case 6 (Hospital No. D 8141)An 18-year-old Jamaican, gravida 1. Genotype

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SC. There was a history of pneumonia at theage of 16 years. The patient attended for ante-natal booking at 20 weeks' gestation, no hepato-megaly, splenomegaly or old leg ulceration beingnoted. The haemoglobin was 85g/100ml Alkalitreatment with supplementary folic acid wascommenced. The haemoglobin level varied be-tween 8-5 and 99g/100ml during the remainderof pregnancy and no crisis occurred. At term, thecervix was unfavourable for induction; accord-ingly, lower segment Caesarian section wascarried out under general anaesthesia, alkali andmagnesium sulphate being given as outlined inCase 1. A live male infant, weighing 30 kg wasdelivered. The patient had a post-partumpyrexia for which no cause could be found. Shewas given a course of ampicillin and discharged,afebrile, on the 12th day after operation. Therewas no crisis during the puerperium.The patient re-attended for booking at 20

weeks' gestation some 10 months later. She wasagain put on a similar regimen of managementand no crisis occurred during pregnancy. Deliv-ery was effected by elective lower segmentCaesarian section at 39 weeks gestation, a livefemale infant weighing 2-3 kg being delivered.The post-partum course was uneventful and theregimen of management during and after operationwas as previously outlined.

Case 7 (Hospital No. D 2470)A 24-year-old gravida 3 from St Vincent's.

Genotype SC. The patient gave a history of anEsch. coli septicaemia following a spontaneousabortion, at which time her abnormal haemo-globin state had been discovered. She had oneprevious full-term pregnancy (elsewhere) andboth pregnancy and delivery had apparently beenuneventful.The patient attended for ante-natal booking at

16 weeks' gestation. There was no hepatomegaly,but the spleen was enlarged and there were oldscars on the legs. The haemoglobin at bookingwas 8-6g/100ml. She was commenced on alkaliand supplementary folic acid and the haemo-globin varied between 7-8 and 9.9g/100ml dur-ing pregnancy; there were no crises. Labourcommenced spontaneously at 38 weeks and thepatient delivered herself of a live female infant,weight 2-6 kg. The puerperium was uneventful,free from crisis and the haemoglobin afterdelivery was 10-5 g/ 100 ml.

This patient re-attended for ante-natal booking18 months later. A similar regimen was institutedand pregnancy was uneventful. She went intolabour spontaneously at 37 weeks and delivereda live male infant weighing 2-3 kg. The puerper-

ium was uneventful, tubal ligation being carriedout on the 5th post-partum day under generalanaesthesia.

Case 8 (Hospital No. B 22357)A 23-year-old gravida 2 from Granada.

Genotype S/Thalassaemia. There was no relevantmedical history and the previous pregnancy hadended in a spontaneous abortion at 10 weeks. Inthe current pregnancy, the patient attended forante-natal booking at 14 weeks. There was nosplenomegaly and no hepatomegaly and thehaemoglobin level was 10 5 g/ 100 ml. Pregnancywas entirely uneventful and labour commencedspontaneously at 39 weeks' gestation, a live femaleinfant weighing 3 0 kg being delivered. The puer-perium was uncomplicated.

In her second observed pregnancy 5 yearslater, the pregnancy was again entirely unevent-ful and vaginal delivery of a living female infantweighing 3-3 kg took place at 39 weeks' gestation.There was no anaemia during pregnancy and thepuerperium was uncomplicated.Case 9 (Hospital No. B 54658)A 30-year-old gravida 2 from Jamaica. Geno-

type S/Thalassaemia. There was a long-standinghistory of jaundice and investigation under thecare of the physicians had revealed her abnormalhaemoglobin state. In her first pregnancy (else-where), there had apparently been no abnorm-ality.

In her second pregnancy, at this hospital, thepatient attended ante-natal booking at 24 weeks'gestation. There was no hepatomegaly but thespleen was palpable. The haemoglobin was 9 g/100 ml. There was a persistent anaemia through-out pregnancy, which was otherwise unevent-ful. The patient commenced labour spontaneouslyat 39 weeks and delivered herself of a live femaleinfant, weight 4-0 kg. The puerperium was un-eventful.

Patient management during pregnancyThe patients have been seen at frequent inter-

vals during the ante-natal period and carefullyobserved, particularly from the haematologicalpoint of view, blood examination being carriedout at each attendance. An adequate diet, withspecial regard to a good protein intake, has beenadvised but, in so far as these patients generallyhave adequate iron stores (Monitt, 1963), oraliron only was given during pregnancy and norecourse was had to parenteral iron. Serum ironlevels have been estimated (see Table 3).As crises may result from a rise in temperature,

the patients have been warned to report any ill-ness and have, where necessary, been given anti-

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A. E. R. Buckle

biotic cover for such illnesses. In addition, routinescreening of the urine has been carried out dur-ing pregnancy to exclude chronic pyelonephritis,for patients with sickle-cell/haemoglobin Cdisease have been reported as having this condi-tion more frequently than other patients(McCurdy, 1964). Stool examination has also beenroutinely carried out (Table 3).The continuing demand on the haemotopoietic

function of the bone marrow means that supple-mentary folic acid should be supplied and thisis particularly the case during pregnancy, wherethere is the additional demand from the foetus.A daily dose of 5 mg of folic acid has thereforebeen given throughout pregnancy.As mentioned earlier in this paper, sickling

occurs with falling oxygen tension and is fav-oured by a lowering of the pH or a rise in thebody temperature. Greenberg & Kass (1958) drewattention to the effect of acidosis on sickling andLehmann (1963) pointed out that, without localacidosis, stasis or firm intravascular wedging ofthe sickled blood, infarctive crises do not occur.He felt that alkali treatment played its part inthe prevention of sickling rather than in the treat-ment of the crisis. Stasis encourages sickling be-cause the cell loses oxygen and there is a rise ofacid metabolites, but the greater the alkalireserve, the longer stasis would have to last toresult in sickling. Lehmann further pointed outthat, for a painful and lasting crisis, the cellshave to be bound together by clotting plasma.Intravenous magnesium sulphate may delay theincrease in viscosity and also, if clotting has takenplace, prevent further strengthening of the clot,so allowing gradual reduction in its size. On thisbasis he advocated a regimen of intravenous mag-nesium sulphate during crisis, followed by oralmagnesium and this to be followed by a regimenof oral sodium bicarbonate.Our patients have been kept on oral sodium

bicarbonate throughout pregnancy, sufficientbeing given to keep all urine specimens alkaline.The patients have been instructed to test everyspecimen with litmus paper and it has beenpossible to obtain full co-operation on this point.The average amount of sodium bicarbonate givenhas been 2 g 6-hourly during the day and 4 g atnight. During crises, the patients have been ad-mitted and alkali treatment, possibly in increasedamount, continued and intravenous magnesiumsulphate given as outlined above.Blood transfusion has been avoided whenever

possible; although available at the time of opera-tion, it has only been necessary to transfuse onepatient. It was reported by Went & McIver (1958)that when transfusion took place, there was a

diminished reticulocytosis which returned tousual levels when the haemoglobin had returnedto the pre-transfusion level.

Management at the time of deliveryWhere vaginal delivery has been anticipated,labour, if not commencing spontaneously, hasbeen induced at or shortly before term in orderto avoid the additional placental hypoxia whichmay occur in post-term delivery. After the spon-taneous or induced commencement of labour,intravenous dextrose-saline has been commenced,oral alkali continued and intravenous magnesiumsulphate given 6-hourly in a dose of 2 ml of a50% solution, the regimen continuing throughoutlabour and for the first 24 hr of the post-partumperiod, after which time the patient has returnedto the oral alkali regimen. If any urine specimenduring labour has been of acid reaction, intrav-enous sodium bicarbonate has been substitutedfor the oral alkali.

In those cases where elective Caesarian sectionhas been advisable because of the difficulty ofinduction of labour, an identical routine hasbeen employed. Anaesthesia has been standardthiopentone-scoline-gas-oxygen-pethidine, greatcare being taken to avoid hypoxia. It has beenthought advisable to give prophylactic antibioticto any patient delivered in this way.

Management in the puerperiumThe oral alkali and supplementary folic acid

have been continued after delivery until the timeof discharge from hospital. The question of con-tinuation beyond this time has not been thoughtnecessary and in many instances not possible asthe patients have been difficult to contact. Bloodhas been taken from the father of the child inorder to give some idea of the likely genotypeof the child. Contraceptive advice has been givento these, as to all other patients in the unit, butin view of problems in ensuring that oralcontraception is taken correctly, intrauterinedevices have been preferred. In selected cases,post-partum tubal ligation has been carried out.

DiscussionSymptoms in sickle-cell disease commence in

early childhood and the natural history of thecondition is of chronic ill-health with haemolyticanaemia, painful or haemolytic crises interrupt-ing the condition from time to time. In sickle-cell/haemoglobin C disease, symptoms may bemanifest for the first time during pregnancy oras a result of infection. The deleterious aspectsof the conditions are two-fold, namely the haemo-

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Sickle-cell disease in pregnant immigrants 843

lytic anaemia and the crises. As Lehmann (1963)pointed out, the former is no more severe thanin other congenital or acquired haemolyticanaemias and required protection from infectionand supplementary folic acid to maintain haemo-topoiesis. The infarctive crises, resulting from de-oxygenation of the abnormal cells, are favouredby local acidosis, vascular stasis and intravascu-lar wedging of the sickled cells. After Greenberg& Kass (1958) had drawn attention to the role ofacidosis in sickling crises, an alkali regimen wasused in treatment (Scott & Ferguson, 1960). Theadditional use of magnesium with the object ofpreventing the conversion of partially sickledand sludged cells into a firm plug was advocated(Anstall et al., 1959; Huntsman, Hurn & Leh-mann, 1960) but it was later reported (Apthorpet al., 1963) that alkali treatment alone wasequally effective in the prevention of infarctiveepisodes, although the latter authors gave intra-venous magnesium in the early stages of acuteepisodes or during operation.As mentioned earlier in this paper, reports are

conflicting on the seriousness of the associationof the sickle-cell disease and pregnancy and itis not possible to draw any conclusions fromthe cases in the present series because of thesmall number involved. Further reports will berequired before firm comment can be made. Theimpression gained from questioning the patientshas been that, although not symptom-free onthe regimen outlined, they have been very muchless troubled during and after delivery when somanaged than when not on alkali treatment. Theone maternal death occurred in a patient whohad not been managed by the alkali regimen andwho died from pulmonary fat embolism shortlyafter delivery. As this occurs independently ofpregnancy, it is not possible to know whetherthe patient would not have succumbed even ifshe had been on treatment. The one stillbirthin the series occurred in a patient who went intopremature labour after possible pulmonaryinfarction and the foetal heart ceased shortlybefore delivery. Later pregnancy in the samepatient has been successful.

ReferencesABRAMS, J. & SCHWARTZ, I.R. (1959) The Sickle-cell diseases

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