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Anesthetic management of Cesarean delivery in a patient with hypoplastic anemia and severe pre-eclampsia

[L’anesthésie pendant une césarienne chez une patiente qui présente une anémie hypoplasique et une prééclampsie sévère]

From the Department of Anaesthesiology, University of Hong Kong, Queen Mary Hospital, Hong Kong, China.

Address correspondence to: Dr. Andrew Y. C. Wong, Department of Anaesthesiology F2, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, China. Fax: 852-2855-3384; E-mail: wongyca{at}so-net.com.hk

	Abstract

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Purpose: To describe the anesthetic management of Cesarean delivery in a patient with hypoplastic anemia and severe pre-eclampsia.

Clinical features: A 28-yr-old parturient with a history of thrombocytopenia was admitted with signs of pre-eclampsia (blood pressure of 140/90 mmHg, heavy proteinuria and moderate bilateral ankle edema) at 25 weeks of gestation. Laboratory studies revealed pancy-topenia (hemoglobin 6.4 g·dL^–1, white cell count 3.43 x 10⁹·L^–1, platelet count 20 x 10⁹·L^–1) and bone marrow biopsy showed hypoplastic anemia. As pre-eclampsia worsened, a Cesarean delivery was performed at 27 weeks with prophylactic platelet transfusion and meticulous blood pressure control. The procedure was uneventful, conducted under general anesthesia with an estimated blood loss of around 600 mL and a live female baby was delivered. Postoperatively her blood pressure and neurological symptoms improved but thrombocytopenia remained at discharge.

Conclusions: Hypoplastic anemia is rare in pregnancy but it poses an increased risk for both mother and fetus. The mother is at risk of life-threatening episodes of bleeding and infection and a multidisciplinary team approach (obstetrician, anesthesiologist, hematologist and pediatrician) is essential. An accurate assessment of the hematological condition should be made and abnormalities corrected before surgery. Regional anesthesia may not be possible in this circumstance.

	Introduction

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HYPOPLASTIC anemia is a serious hematological disorder characterized by pancytopenia in the peripheral blood and hypocellularity in the bone marrow. Fortunately it is rare in pregnancy since the mother is at risk of life-threatening episodes of bleeding and infection. Maternal anemia can also lead to intra-uterine growth retardation and death of the fetus, while maternal infection can cause chorioamnionitis leading to preterm delivery. We describe a patient with both hypoplastic anemia and severe pre-eclampsia. The case was managed by a team of obstetricians, anesthesiologists, hematologists and pediatricians. As the pre-eclampsia worsened, Cesarean section was performed at 27 weeks. Anesthetic management of a patient with these serious co-existent disorders for Cesarean delivery has not been previously described in the literature.

	Case report

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A 28-yr-old parturient with a seven-year history of thrombocytenia was admitted at 25 weeks of gestation with a blood pressure of 140/90 mmHg, heavy proteinuria and moderate bilateral ankle edema. She was being managed by a private practitioner who had diagnosed thrombotic thrombocytopenic purpura (TTP). She had never had any bone marrow examination and denied easy bleeding or bruising. On admission, laboratory studies showed hemoglobin (Hb) of 6.4 g·dL^–1 (normal range: 11.5–16.5 g·dL^–1), white cell count (WCC) 3.43 x 10⁹·L^–1 (normal range: 4–11 x 10⁹·L^–1), platelet count 20 x 10⁹·L^–1 (normal range: 150–400 x 10⁹·L^–1), prothrombin time (PT) 10.5 sec (normal range: 11.3–13.2 sec), activated partial thromboplastin time (APTT) 23 sec (normal range: 27.6–37.6 sec), albumin 28 g·L^–1 (normal range: 42–54 g·L^–1), aspartate aminotransferase (AST) 36 U·L^–1 (normal range: 12–28 U·L^–1), lactate dehydro-genase (LDH) 473 µmoL·L^–1 (normal range: 200–360 µmoL·L^–1), urate 473 µmoL·L^–1 (normal range: 160–380 µmoL·L^–1) and 5.7 g of protein in a 24-hr urine collection. She had also developed episodes of spontaneous epistaxis and gum bleeding since admission. The hematologist was consulted. With a working diagnosis of TTP, a double-lumen catheter was inserted into her right internal jugular vein under ultrasound guidance and daily plasmapheresis was initiated. The platelet count increased to 54 x 10⁹·L^–1 and there was no more epistaxis or gum bleeding. The bone marrow biopsy, however, showed a reduced cellularity compatible with hypoplastic anemia and consequently plasmapheresis was stopped. The patient started to develop blurred vision, headache and epigastric pain. Oral nifedipine 40 mg twice daily was being used for blood pressure control which averaged 170/100 mmHg. A case conference was held and she was scheduled for a semi-emergent Cesarean section at 27 weeks after two doses of im betamethasone 12 mg to hasten fetal lung maturity. In view of severe pre-eclampsia and co-existent thrombocytopenia, general anesthesia was chosen.

The patient’s height and pre-pregnancy body weight were 150 cm and 53 kg respectively. Her body weight had now risen to 76 kg and she had bilateral lower limb edema up to the thighs, severe facial edema, urine protein 4+ and a Mallampati grade 2 airway. One unit of packed red blood cells had been transfused since admission. Preoperative laboratory results showed a Hb of 10.8 g·dL^–1, WCC 4.33 x 10⁹·L^–1, platelet count 10 x 10⁹·L^–1, PT 8.6 sec, APTT 20.6 sec, albumin 25 g·L^–1, AST 61 U·L^–1, LDH 1073 U·L^–1 and urate 473 µmoL·L^–1. The patient was premedicated with oral ranitidine 150 mg in the evening before and morning of the operation day and 30 mL of oral sodium citrate 0.3M on arrival in the operating room. The patient was placed in the left lateral tilt position on the operating table. The first non-invasive blood pressure reading was 167/111 mmHg. A fetal heart rate of 130·min^–1 was measured with a hand-held ultrasound device. Her edematous state made iv cannulation extremely difficult and an 18-gauge (G) iv and 22-G intra radial artery cannula were inserted under local anesthesia. The double-lumen central line was left unused. In order to reduce the risk of intracranial hemorrhage at intubation and intraoperative major hemorrhage since the platelet count was low (10 x 10⁹·L^–1), 10 U of platelets were transfused before induction. Hydralazine 5 mg was given intravenously 20 min before induction. Rapid sequence induction was performed with alfentanil 0.8 mg, thiopentone 375 mg and suxamethonium 100 mg. A grade 1 view of the larynx was obtained on direct laryngoscopy with a McCoy blade and endotracheal intubation was performed with a size 7.0 mm internal diameter cuffed endotracheal tube. Anesthesia was maintained with oxygen, nitrous oxide, isoflurane and atracurium. Intraoperative monitoring included continuous electrocardiogram, invasive blood pressure, pulse oximetry, airway pressure, capnography and isoflurane measurement. The central venous pressure (CVP) was not monitored as it has been shown to be unreliable in severe pre-eclampsia.^1–3 A live female baby weighing 735 g was delivered three minutes after skin incision, with Apgar scores 5 and 8 at one and five minutes respectively. Due to gross prematurity and severe intra-uterine growth retardation, an experienced neonatologist was present at delivery and the baby was electively intubated and transferred to the neonatal intensive care unit. Intravenous morphine 3 mg was administered and the patient’s intraoperative blood pressure was stable until wound closure with the systolic ranging from 140 to 160 and diastolic 70 to 80 mmHg. Four more units of platelets were transfused close to the end of surgery in order to minimize the amount or risk of postoperative oozing or hemorrhage. The operation took 32 min from skin incision to wound closure. The blood loss was estimated to be around 600 mL. At emergence, titrated doses of esmolol to a total dose of 80 mg were given to attenuate the stress of extubation. Neuromuscular block was reversed with neostigmine 2.5 mg and atropine 1.2 mg and the trachea was extubated with the patient awake. She received another 4 mg of morphine in the recovery room. The blood pressure was stable at around 140/60 mmHg in the recovery room. A patient-controlled analgesia (PCA) pump with morphine was provided for postoperative pain control. A gross neurological examination was normal.

The patient stayed in the high dependence area within the labour suite for 24 hr before discharge to the postnatal ward. During this time, the patient’s blood pressure remained stable at around 165/95 with normal neurological examinations. The first postoperative laboratory results showed a Hb of 8.3 g·dL^–1 and a platelet count of 160 x 10⁹·L^–1. There was a marked reduction in edema and her body weight had decreased to 73 kg by day two postoperatively. PCA provided satisfactory pain control and was stopped on postoperative day two with a total consumption of 24.8 mg of morphine. Symptoms of headache, blurred vision and epigastric pain started to improve within 24 hr and had resolved by postoperative day seven, the day of discharge. However, the pancytopenia had failed to improve. Having received 2 U of blood, as suggested by the hematologist, the Hb increased from 8.3 to 12.1 g·dL^–1. The other laboratory results at discharge were WCC 4.7 x 10⁹·L^–1, platelet count 14 x 10⁹·L^–1, albumin 25 g·L^–1, AST 44 U·L^–1, LDH 830 U·L^–1 and urate 270 µmoL·L^–1. Body weight at discharge was 73.9 kg.

	Discussion

TOP Abstract Introduction Case report Discussion References

 
Severe pre-eclampsia is often associated with thrombocytopenia, but it is important to look for other concomitant causes for the thrombocytopenia in pregnancy.⁴ In the present case, the patient had been diagnosed with TTP by her private practitioner before pregnancy. TTP is a rare thrombotic microangiopathy characterized by occlusion of arterioles and capillaries by microemboli. The affected patients have varying degrees of renal or neurologic impairment accompanying the universal findings of thrombocytopenia and microangiopathic hemolysis evidenced on peripheral blood smear. Plasma transfusions and plasmapheresis have revolutionized the management of TTP, significantly decreasing the high maternal and fetal mortality and morbidity rate.⁵ Hypoplastic anemia is characterized by diminished hematopoietic precursors in the bone marrow and results in a deficiency of circulating erythrocytes, granulocytes and platelets. In aplastic anemia, the precursors are absent or severely reduced, Hb can easily drop to around 3 g·dL^–1 and, in severe cases, the neutrophil and platelet count drop to < 0.5 x 10⁹·L^–1 and < 20 x 10⁹·L^–1 respectively.⁶ The presented patient had a Hb level of 6.4 g·dL^–1 on admission and probably already had hypoplastic anemia resulting in thrombocytopenia before pregnancy. Pregnancy seems to have a detrimental effect on the disease process.⁷ A parturient with hypoplastic or aplastic anemia is at increased risk of hemorrhage and infection and there are a number of case reports and reviews of aplastic anemia in pregnancy.^7–9 It has a very variable clinical course and outcome,¹⁰ and termination of pregnancy is usually advised for those with severe disease. There are case reports on successful management of pregnancy in bone marrow failure syndromes such as Diamond-Blackfan anemia and Shwachman-Diamond syndrome.¹¹ In these reports, the patients required Cesarean section, but there were no details on the anesthetic management.

Close monitoring of hematological variables and appropriate replacement therapy is important. White cell transfusion is required only for serious infection. Plasmapheresis is not a treatment for hypoplastic anemia and was stopped once the diagnosis was recognized not to be TTP. Thrombocytopenia in hypoplastic anemia is treated with platelet transfusion, but repeated platelet transfusion may become ineffective due to platelet refractoriness and cross-immunization.⁸

This patient’s pregnancy was also complicated by severe pre-eclampsia. There has been research on the association between maternal anemia and pre-eclampsia. Kadyrov’s group found that maternal anemia and pre-eclampsia are associated with different patterns of placental trophoblast invasiveness.¹² In the case described, the patient’s blood pressure control had been unsatisfactory since admission and she had started developing headache, blurred vision and epigastric pain. Her AST and LDH levels were escalating, and we were concerned that she would develop HELLP syndrome. In view of this, a conference among the specialty teams involved in her care (obstetrics, anesthesiology, hematology and pediatrics) led to a decision to undertake a semi-emergent Cesarean delivery at 27 weeks. There has been no case report or review of the anesthetic management of Cesarean section in hypoplastic or aplastic anemia. Hara et al. described the management of a patient with myelodysplastic syndrome,¹³ which has a similar peripheral hematological picture as hypoplastic anemia. The patient had pre-anesthetic laboratory studies of Hb 6.6 g·dL^–1, WCC 3.8 x 10⁹·L^–1 and platelet count 40 x 10⁹·L^–1 and was transfused with 800 mL lecukocyte poor red cells and 10 U of platelets. Another 10 U of platelets were given intraoperatively. The intraoperative blood loss was 1520 mL, including amniotic fluid. In the present case, the patient’s pre-anesthetic platelet count was 10 x 10⁹·L^–1. Since platelet transfusion is indicated for major surgery such as Cesarean section, 10 U of platelets were transfused and intraoperative blood loss was moderate (around 600 mL).

Regional anesthesia has some advantages over general anesthesia in pre-eclampsia with normal coagulation and there is an increasing use of spinal anesthesia in such patients.^14–17 Platelet function is an important factor when making a decision about regional anesthesia. Thrombocytopenia has been regarded as a contraindication for neuraxial regional techniques. The other platelet function tests include bleeding time, thromboelastography (TEG) and platelet function analysis (PFA). Bleeding time is however, highly operator-dependent, lacks sensitivity and specificity and has poor diagnostic value even when platelet function is altered.¹⁸ TEG has not undergone all the validation procedures mandatory for conventional hemostasis tests (intra- and inter-observer variability, repeatability, calibrations, quality controls), and is not recommended in counterbalancing a low platelet count.¹⁹ PFA evaluates in vitro primary hemostasis by measuring the time required for whole blood to occlude an aperture in the membrane of a test cartridge, which is coated with platelet agonists. It has high reliability and could be used as a method of evaluating platelet function in pre-eclamptic patients with low platelet counts.²⁰ This device is unfortunately unavailable in our department. The present patient presented with severe thrombocytopenia on admission despite a normal clotting profile. We felt that the risk of neuraxial hematoma formation with regional anesthesia was very high and that general anesthesia was the best option. It is generally accepted that patients with a platelet count lower than 50 x 10⁹·L^–1 need platelet transfusion before major surgery.²¹ The same threshold is also recommended for patients with aplastic anemia and myelodysplasia.²² There are no agreed guidelines on dose of prophylactic platelet transfusion in thrombocytopenic patients. Studies on platelet dose for prevention of major bleeding complications are lacking.²³ Norol et al. demonstrated the dose-effect of platelet transfusions and suggested a platelet dose of 1.5 U for each 10 kg body weight in patients without clinical factors favouring platelet consumption and receiving random platelet concentrates.²⁴ Thus 10 U of platelets were transfused before the start of surgery.

Since severe pre-eclampsia can cause airway problems and labile blood pressure,^1,25 an arterial line was inserted before induction for close monitoring of blood pressure. The arterial line is also useful for assessing the patient’s response to vasodilators and anesthetic drugs. CVP was not monitored in our patient as, in addition to the risks of insertion, a poor correlation between CVP and pulmonary catheter wedge pressure (PCWP) has been shown in cases of severe pre-eclampsia.^1–3 Hydralazine is a direct vasodilator which lowers arterial pressure and systemic vascular resistance, increasing cardiac output and heart rate without affecting PCWP. It can be used to blunt the hypertensive response during intubation,¹ but it has a slow onset and delayed peak effect. It was given 20 min before anesthesia induction. To further blunt the hemodynamic effect of intubation 0.8 mg of alfentanil, a short-acting opioid with a very fast onset, was given at induction. The patient’s blood pressure remained stable from induction to delivery. Tachycardia and hypertension at emergence were controlled with bolus doses of esmolol, a selective ß-1 receptor antagonist with a rapid onset and offset of action. Esmolol is not recommended at induction, as it can cause severe fetal bradycardia after maternal administration.²⁶

In summary, we have presented a parturient with hypoplastic anemia and severe pre-eclampsia. A multi-disciplinary team approach involving the obstetrician, anesthesiologist, hematologist and pediatrician was important. Prophylactic hematological treatment was deemed necessary to ensure safe perioperative management without serious complications.

	Footnotes

 
Accepted for publication April 26, 2004. Revision accepted Juin 9, 2004.

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This Article Abstract Résumé de cet Article Full Text (PDF) Submit a scholarly reply Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wong, A. Y. C. Articles by Irwin, M. G. Search for Related Content PubMed PubMed Citation Articles by Wong, A. Y. C. Articles by Irwin, M. G.