Antenatal erythropoietin and intra-operative cell salvage in a Jehovah's Witness with placenta praevia

Antenatal erythropoietin and intra-operative cell salvage in a Jehovah's Witness with placenta praevia

BJOG: an International Journal of Obstetrics and Gynaecology May 2003, Vol. 110, pp. 524– 526 CASE REPORT Antenatal erythropoietin and intra-operati...

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BJOG: an International Journal of Obstetrics and Gynaecology May 2003, Vol. 110, pp. 524– 526

CASE REPORT

Antenatal erythropoietin and intra-operative cell salvage in a Jehovah’s Witness with placenta praevia Alison de Souzaa, Michael Permezela,b, Mark Andersona, Andrew Rossa, James McMillanc, Susan Walkera,b,* Case report A 34 year old parous Jehovah’s Witness was booked at 13 weeks of gestation to her regional hospital. All antenatal investigations were normal, including her haemoglobin concentration (128 g/L). However, a mid-trimester ultrasound scan demonstrated an anterior low lying placenta completely covering the internal os. Her antenatal course was uneventful until 28 weeks of gestation when she had a small painless antepartum haemorrhage. She was haemodynamically stable, her uterus was lax and non-tender and her cervix long and closed on speculum examination. A cardiotocogram was reactive. Corticosteroids were administered to bring about fetal lung maturity and the woman was transferred to the Mercy Hospital for Women. Her haemoglobin concentration was 109 g/L, her Kleihauer test was negative and she had a normal coagulation profile but mild iron deficiency. An ultrasound scan showed normal fetal growth and wellbeing, but confirmed a major degree of placenta praevia, with the placenta positioned centrally over the internal os. The woman was admitted to hospital and advised regarding the risk of major obstetric haemorrhage and the need for caesarean section. Consistent with her religious beliefs, she refused to accept all blood products, but consented to crystalloid or non-human colloid solutions for resuscitation. She was administered iron supplements and remained in hospital. She continued to have small episodes of vaginal bleeding. At 29 weeks of gestation, her haemoglobin concentration was unchanged. She was asked to consider recombinant

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Mercy Hospital for Women, East Melbourne, Victoria, Australia b University of Melbourne Department of Obstetrics and Gynaecology, Victoria, Australia c Perfusion Services Pty Ltd, Parkdale, Victoria, Australia * Correspondence: Dr S. Walker, University Department of Obstetrics and Gynaecology, Mercy Hospital for Women, Clarendon Street, East Melbourne, 3002, Victoria, Australia. D RCOG 2003 BJOG: an International Journal of Obstetrics and Gynaecology doi:10.1016/S1470-0328(02)01661-0

erythropoietin. After discussion with church leaders, she agreed to its administration as long as it was not suspended in human albumin. Erythropoietin was subsequently administered at a dose of 50 iu/kg twice weekly. Apart from mild flu-like symptoms, the woman had no ill effects. A parenteral iron infusion was administered at 30 weeks of gestation. Erythropoietin resulted in a rise in haemoglobin concentration from 109 g/L at 28 weeks of gestation to 133 g/L six weeks later. The woman was also asked to consider intra-operative cell salvage. She was reviewed by an anaesthetist and clinical perfusionist, and consented to a ‘cell saver’, provided that the blood remained in a continuous extracorporeal circuit, and that the circuit itself was primed with non-blood products. At 34 weeks of gestation, the woman experienced several episodes of antepartum haemorrhage, resulting in a semi-elective caesarean section under general anaesthesia. Arterial and central venous catheters were inserted. The cell salvage device was a Cobe autotransfusion system. Simultaneously, an extracorporeal circuit was set up with a Cobe roller pump, with tubing 28 ft long and 1/4 inches in diameter, giving a total capacity of 550 mL. All circuit components were heparin bonded (Carmeda) and the circuit was primed with Hartmann’s solution. After cannulation of the right internal jugular vein with a 7.5 French gauge sheath cannula, the primed circuit was connected and the pump was run at 50 mL/minute, simultaneously drawing off 1 mL/minute of acid citrate dextrose at the proximal takeoff point. The distal end of the circuit was connected to a blood collection bag, which in turn was connected to a 14-gauge cannula in the left cubital fossa. This resulted in a total extracorporeal volume of 1000 mL in a closed circuit, allowing a greater degree of haemodilution with about 3 L of crystalloid, and resulted in a pre-operative haemoglobin concentration of 105 g/L. All blood salvaged was collected into the autotransfusion system, where each bowl was washed free of amniotic fluid and debris with 2 L of normal saline, delivered to a re-infusion bag and immediately re-infused into the woman. About 350 mL of blood was re-infused. Suction of amniotic fluid and blood for delivery of the baby was separate and not connected to the cell saver, www.bjog-elsevier.com

CASE REPORT

which collected blood obtained only after delivery of the placenta and membranes. Caesarean section was performed through a midline skin incision and, in view of a poorly formed and extremely vascular lower segment, a classical uterine incision was performed. The placenta was not incised. A baby boy was delivered by breech extraction. His weight was 2700 g. His Apgar scores were 4 at 1 minute, 6 at 5 minutes and 10 at 10 minutes. Blood loss after removal of the placenta was moderate and was quickly controlled after closure of the uterus. Haemoglobin concentration immediately postoperatively was 120 g/L. The woman made an uneventful recovery. The infant was initially admitted to the neonatal intensive care unit with hyaline membrane disease, pneumothorax and persistent pulmonary hypertension of the newborn. Erythropoietin was administered prophylactically. He was discharged fully breastfeeding to the referring hospital at 17 days of age.

Discussion A refusal to receive blood or blood products can make treatment of Jehovah’s Witnesses difficult when the obsterician is faced with severe obstetric haemorrhage. Their belief is based on interpretation of the biblical passages, ‘‘Only flesh with its soul — its blood — you must not eat’’ (Genesis 9: 3,4) and ‘‘Abstain from . . . fornication and from what is strangled and from blood’’ (Acts 15: 19 –21)1. Several recent changes in the outlook of Jehovah’s Witnesses suggest that the distinction between acceptable and unacceptable treatments may be more subject to personal conviction and preference now than previously. Members can now remain silent about their medical treatment and avoid expulsion from the church. In addition, while ‘primary components’ of blood must be refused, Jehovah’s Witnesses can now ‘conscientiously decide’ whether to accept transfusions of fractions derived from whole blood, such as albumin, globulin, interferon and — perhaps in the future — haemoglobinbased blood substitutes2. Nevertheless, primary blood components (red and white cells, platelets and plasma) must still be refused, and even autologous blood is only acceptable for re-infusion by some patients if kept in a continuous extracorporeal circuit3. Jehovah’s Witnesses will therefore accept only volume expanders such as crystalloids and Haemaccel. In this case report, we suggest two further treatments suitable for Jehovah’s Witnesses. Erythropoietin is an endogenous glycoprotein that stimulates the production of red blood cells, and is normally synthesised in the interstitial peritubular cells of the kidney in response to hypoxaemia. Recombinant human erythropoietin is purified from a Chinese hamster ovary cell line into which the gene coding for human erythropoietin D RCOG 2003 Br J Obstet Gynaecol 110, pp. 524 – 526

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has been inserted. It is similar to human erythropoietin in biological and chemical properties except for some microheterogeneities in the 4-carbohydrate chains4. Its major use has been in anaemia associated with chronic renal insufficiency, where the anaemia can be corrected in a dose-dependent and predictable manner without significant side effects. Erythropoietin has also been successfully used in patients with anaemia associated with malignancy, chemotherapy4, the acquired immune deficiency syndrome5, prematurity and chronic inflammatory disease6. It has received considerable attention as a performance enhancing drug among athletes by improving oxygen carrying capacity4. Recombinant human erythropoietin is administered at doses of 50 – 200 iu/kg subcutaneously two or three times per week. To optimise the haemoglobin response, oral or parenteral iron supplementation is recommended. A rise in haemoglobin of 10 g/L over one month can be expected. Increases greater than 20 g/L in one month require a reduction in the dose, and treatment should stop if the haemoglobin concentration exceeds 140 g/L, due to the risk of thrombosis. The cost of erythropoietin is approximately A$45 per dose. Pre-operative administration of erythropoietin has been shown to reduce the need for allogenic blood transfusion in patients undergoing cardiac surgery. In these patients, increasing the preoperative haemoglobin concentration facilitates both preoperative autologous donation of blood, as well as the more efficient use of acute normovolaemic haemodilution. A larger blood loss can therefore be tolerated before allogenic blood transfusion becomes necessary7. In the woman in our case report, erythropoietin given antenatally significantly elevated the haemoglobin concentration before her caesarean section. In addition, deliberate modest haemodilution of blood allowed a larger blood loss to be safely tolerated, given the absence of recourse to blood transfusion. Intra-operative cell salvage is a technique increasingly used in cardiac, vascular, orthopaedic and hepatobiliary surgery where heavy blood loss is anticipated8. The technique involves the rapid collection, washing and reinfusion of blood lost from the operative field, and is considered acceptable to some Jehovah’s Witnesses, provided the equipment is set up to maintain a continuous extracorporeal circuit3. Intra-operative cell salvage has been considered relatively contraindicated in obstetrics because of the fear of re-infusing blood containing amniotic fluid to cause amniotic fluid embolism. Adequacy of the washing process to minimise this risk is difficult to assess, as the pathophysiology of amniotic fluid embolism is uncertain9. A tissue factor derived from amniotic fluid is thought to be responsible for the disseminated intravascular coagulation; other investigators believe other fetal components in the amniotic fluid, such as fetal squames, lanugo and phospholipids, may play a role10.

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Several studies have evaluated cell salvage devices in removing amniotic fluid. A substantial reduction or elimination of tissue factor11 and a-fetoprotein12,13 has been reported after cell salvage processing. While significant reductions in the concentration of squamous cells, fetal erythrocytes and lamellar bodies have been reported between the pre-wash and post-filtration samples, substantial quantities remain. The use of a leucocyte reduction filter in concert with the cell salvage device appears to reduce further the concentration of fetal squames and lamellar bodies, but not fetal erythrocytes9. It is thus important to ensure that a Kleihauer test is performed after transfusion of salvaged erythrocytes, and anti-D administered as appropriate. A further safety measure instituted in our patient was the use of a double suction set up. The wall suction was used for aspiration of amniotic fluid during delivery of the infant, and the cell salvage suction was used only after delivery of the placenta and membranes. This might be expected to further reduce the risk of amniotic fluid embolism. Despite the absence of adverse events reported with cell salvage during caesarean section in the 174 women reported in the literature thus far14, this number is obviously inadequate to assess the risk of amniotic fluid embolism, given its estimated incidence of 1:8000 to 1:80,000 deliveries. For the majority of pregnant women, therefore, intra-operative cell salvage is probably inappropriate, in view of the fact that the blood loss at caesarean section is usually modest, there is pregnant women withstand moderate haemorrhage well, a safe and reliable allogenic transfusion service and there may be difficulty in having a serviced cell salvage device readily available as well as, skilled perfusion staff in the obstetric unit. In some women with a high risk of lifethreatening haemorrhage, in whom blood transfusion is not an option, cell salvage may have a role.

References 1. Watch Tower Bible and Tract Society. Family Care and Medical Management of Jehovah’s Witnesses. Ingleburn, New South Wales: Watchtower, 1995. 2. Muramoto O. Bioethical aspects of the recent changes in the policy of refusal of blood by Jehovah’s Witnesses. BMJ 2001;322:37 – 39. 3. Chikada M, Furese A, Kotsuka Y, Yagyu K. Open heart surgery in Jehovah’s Witness patients. Cardiovasc Surg 1996:4311 – 4314. 4. Jelkmann W. Use of recombinant human erythropoietin as an antianaemic and performance enhancing drug. Curr Pharm Biotechnol 2000;1:11 – 31. 5. Ifudu O. Maximizing response to erythropoietin in treating HIV associated anaemia. Cleve Clin J Med 2001;68:643 – 648. 6. Santoso JT, Lin DW, Miller DS. Transfusion medicine in obstetrics and gynaecology. Obstet Gynecol Surv 1995;50:470 – 481. 7. Spahn DR, Casutt M. Eliminating blood transfusions: new aspects and perspectives. Anaesthesiology 2000;93:242 – 255. 8. Napier JA, Bruce M, Chapman J, et al. Guidelines for autologous transfusion. II: Perioperative haemodilution and cell salvage. British Committee for Standards in Haematology Blood Transfusion Task Force. Autologous Transfusion Working Party. Br J Anaesth 1997; 78(6):768 – 771 (June). 9. Potter PS, Waters JH, Burger GA, Mraovic B. Application of cell salvage during caesarean section. Anesthesiology 1999;90: 619 – 621. 10. Waters JH, Biscotti C, Potter PS, Phillipson E. Amniotic fluid removal during cell salvage in the caesarean section patient. Anaesthesiology 2000;92:1531 – 1536. 11. Bernstein HH, Rosenblatt MA, Gettes M, Lockwood C. The ability of the Haemonetics 4 Cell Saver System to remove tissue factor from blood contaminated with amniotic fluid. Anesth Analg 1997;85(4): 831 – 833 (October). 12. Fong J, Gurewitsch ED, Kump L, Klein R. Clearance of fetal products and subsequent immunoreactivity of blood salvaged at cesarean delivery. Obstet Gynecol 1999;93(6):968 – 972 (June). 13. Catling SJ, Williams S, Fielding AM. Cell salvage in obstetrics: an evaluation of the ability of cell salvage combined with leucocyte depletion filtration to remove amniotic fluid from operative blood loss at caesarean section. Int J Obstet Anesth 1999;8:79 – 84. 14. Weiskopf RB. Erythrocyte salvage during caesarean section. Anesthesiology 2000;92:1519 – 1522. Accepted 19 September 2002

D RCOG 2003 Br J Obstet Gynaecol 110, pp. 524 – 526