Use of cell salvage and HBOC-201 in a pregnant Jehovah’s Witness with sickle beta+thalassaemia undergoing emergency caesarean section

Background

Jehovah’s Witness (JW) patients typically refuse red blood cell transfusion, even in the setting of severe anaemia or major surgery. An increased mortality has been shown to correlate with declining levels of haemoglobin (Hb) in this population.1 Among JW patients, some may accept the use of minor blood fractions, intraoperative cell salvage and Hb blood substitutes, though this is a personal decision not universally agreed on by all JW patients. HBOC-201 (Hemopure), a bovine-Hb-based oxygen carrier, serves as a bridge in patients with life-threatening anaemia when blood transfusion is not an option while the body regenerates its own blood, but carries potential risks including myocardial and cerebrovascular ischaemia.2 With the same oxygen-carrying capacity as whole blood, HBOC-201 promotes both oxygen diffusion and delivery to increase oxygen transfer between red blood cells and tissues. The utility and safety of HBOC-201 in sickle cell disease (SCD) is still largely unexplored and based on case reports and small case series; given that it scavenges nitric oxide, it could potentially induce vasoconstriction and exacerbate vaso-occlusive crises.3–6

Intraoperative cell salvage is the process of collecting and washing blood shed from the operative field and reinfusing as autologous blood. Cell salvage use in patients with SCD is controversial due to the possibility of re-administering sickled blood and further reducing oxygen-carrying capacity.7 In obstetric patients, salvaged blood contamination by amniotic fluid may theoretically result in disseminated intravascular coagulation (DIC), emboli and pulmonary hypertension. Though, with advanced filtration techniques and a growing body of reports supporting the safety of this practice in obstetric patients, the American College of Obstetricians and Gynecologists has endorsed the use of cell salvage in obstetric haemorrhage.8

Case presentation

A gravida 1, para 0 woman in her late 20s at approximately 27 weeks gestation presented for emergency caesarean section (C-section) due to pre-eclampsia with refractory severe hypertension with elevated transaminases. Her medical history was significant for sickle beta+thalassaemia. Prepregnancy, she maintained a baseline Hb of 10–12 g/dL. She experienced multiple vaso-occlusive pain crises as a child, which were managed at home with conservative therapy. She was hospitalised once for a pain crisis 6 years prior and never received red blood cell (RBC) transfusion. During her pregnancy, she experienced more frequent pain crises and her Hb decreased to 8 g/dL. The patient is a JW and declined allogeneic blood products.

She had an uncomplicated pregnancy until 25 weeks gestation when she presented to her obstetrician for mild hypertension and a Hb of 5.1 g/dL. She was admitted to a local hospital for pre-eclampsia evaluation. After 1 week, she was transferred to our academic tertiary care centre for high-risk obstetric care. We consulted a multidisciplinary team comprised of obstetric, haematology, maternal fetal medicine, anesthesiology, blood bank and laboratory specialists, in addition to discussion with the patient and her family, to arrive at a comprehensive and individualised consensus treatment plan.

On admission to our hospital, she had a blood pressure of 175/107 mm Hg (from prepregnancy baseline <120/80), which was managed with labetalol 40 mg intravenously and magnesium sulfate 2 g/hour intravenously for seizure prophylaxis. Admission laboratory findings were notable for aspartate aminotransferase (AST) of 202 IU/L, alanine transaminase (ALT) of 79 IU/L, lactate dehydrogenase of 1109 IU/L, total bilirubin of 2.6 mg/dL, ferritin of 946 ng/mL and platelets of 148 thou/mm (table 1). Hb at admission was 6.4 g/dL (from baseline 10 g/dL; figure 1). Random urinary protein/creatinine ratio was 1.39 mg/mg. She was diagnosed with pre-eclampsia/haemolysis with elevated liver enzymes and low platelets (HELLP). Admission pelvic ultrasound showed fetal growth restriction with absent end diastolic flow. In preparation for emergent delivery for pre-eclampsia/HELLP, the patient was given two doses of betamethasone for fetal lung maturity.

Prior to C-section, her wishes were clarified with regard to blood product administration. She declined transfusion of any allogeneic whole blood components but was willing to accept fractions such as albumin, as well as intraoperative cell salvage and HBOC-201.

The C-section was performed under spinal anaesthesia with 12 mg of hyperbaric 0.75% bupivacaine mixed with 20 µg of fentanyl and 100 µg of morphine. The magnesium infusion was discontinued on arrival in the operating room (OR) due to a supratherapeutic level. Intravenous volume expansion with plasma-lyte A and albumin was started as soon as the patient arrived in the OR. No sedatives were given. Supplemental oxygen was provided via nasal cannula at 2 L/min. Multiple measures were taken to avoid hypothermia, including increasing forced air warmer, warmed intravenous fluid and warm blankets.

Meticulous surgical care to ensure haemostasis was practiced. After membrane rupture, clear amniotic fluid was suctioned out of the surgical field to minimise incorporation during cell salvage. After delivery of the neonate and placenta, cell salvage was initiated. The rest of the surgery remained uncomplicated with an estimated blood loss of 525 mL, which was saved using cell salvage. Salvaged blood was washed and filtered to minimise amniotic fluid contamination, but not assessed for morphological changes such as hypoxia-induced sickling or haemolysis prior to infusion. A total volume of 125 mL salvaged blood was immediately transfused back to the patient through a warmed intravenous line. The haematocrit level of the salvaged blood was not measured, but likely very dilute due to severe baseline anaemia, as her Hb was 5.2 g/dL prior to C-section. After transfusion of the salvaged blood, point-of-care venous blood gas failed to report a Hb level. A complete blood count drawn at the same time later reported a Hb of 4.2 g/dL. This roughly 1 g/dL decrease in Hb was likely multifactorial and owing to blood draws, operative blood loss and a net fluid intake of 500 mL. One unit of HBOC-201 was then transfused in the OR without adverse reactions. The patient remained haemodynamically stable throughout the surgery. The newborn weighed 775 g with Apgar scores of 4 and 7 at 1 min and 5 min after birth, respectively.

The patient was transported to the intensive care unit (ICU) after the surgery for postoperative care. A second unit of HBOC-201 was administered on arrival to the ICU. On a follow-up complete blood count, the Hb increased to 4.9 g/dL. She had no signs of haemolysis postoperatively. The patient received acetaminophen 650 mg orally and oxycodone 5 mg orally, every 4 hours as needed for pain relief. Labetalol orally was continued to maintain a systolic blood pressure less than 160 mm Hg. She was given ferrous sulfate 325 mg orally daily with vitamin C (iron was not provided intravenously per patient request), folate 1 mg orally daily, vitamin B₁₂ 1000 μg IM daily and epoetin alfa 20 000 units SQ daily (until Hb >7 g/dL) as per our institution’s protocol to support red cell production for a JW patient with severe anaemia. The patient did not experience severe adverse reactions to HBOC-201 nor to the cell salvage product. Additional units of HBOC-201 were not administered given the patient’s postoperative haemodynamic stability and lack of end organ complications, as well as out of consideration for the patient’s plan to breastfeed her newborn, given the lack of data surrounding HBOC-201 administration in breastfeeding mothers. Phlebotomy was minimised and blood was drawn in paediatric tubes to limit iatrogenic blood loss. Her Hb steadily increased throughout her inpatient stay, and on postoperative day 9, she was discharged with a Hb of 6.6 g/dL, AST of 23 IU/L, ALT of 9 IU/L, total bilirubin of 2.2 mg/dL and blood pressure of 121/81 mm Hg.

Outcome and follow-up

At 1-month follow-up, she had recovered well and reported continuation of vitamin C, vitamin B₁₂, folic acid and multivitamin with iron. Her blood pressure had remained stable in the 120s/80s since her discharge, and her Hb was 10.2 g/dL.