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Case Report
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CASE REPORT
Year : 2019  |  Volume : 20  |  Issue : 2  |  Page : 99-102
 

Anesthesia consideration for cesarean section in chronic myeloid leukemia diagnosed during pregnancy: An interesting case report and brief review of literature


Department of Anaesthesiology, Grant Medical College and Sir JJ Group of Hospitals, Mumbai, Maharashtra, India

Date of Submission26-Jun-2018
Date of Acceptance10-Oct-2018
Date of Web Publication28-Aug-2019

Correspondence Address:
Dr. Veena Ganeriwal
Department of Anesthesiology, Grant Government Medical College and Sir JJ Group of Hospitals, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/TheIAForum.TheIAForum_26_18

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  Abstract 


Chronic myeloid leukemia (CML) is a myeloproliferative disorder with clonal expansion of transformed primitive hematopoietic progenitor cells without loss of their capacity to differentiate. Annual incidence of CML in females ranges from 0.6 to 1.6 per 100,000 populations. In developing countries like India where onset of hematological malignancy occurs in early age, thereby increases chances of concomitant occurrence of CML and pregnancy together. Although the incidence is rare, anesthesia management of pregnant female presenting more so for an emergency cesarean section (C/S) is challenging because of the physiological changes during pregnancy, presence of anemia, coagulopathy, immunosuppressant drugs, leukocytosis, and rarely blast cells in circulation. We report the successful management of a 19-year-old primigravida, recently diagnosed with CML, planned for emergency C/S under general anesthesia in view of meconium-stained liquor with fetal distress.


Keywords: Chronic myeloid leukemia, developing country, general anesthesia, pregnancy


How to cite this article:
Ganeriwal V, Agrawal P, Thote P, Parkar M, Waiker SS. Anesthesia consideration for cesarean section in chronic myeloid leukemia diagnosed during pregnancy: An interesting case report and brief review of literature. Indian Anaesth Forum 2019;20:99-102

How to cite this URL:
Ganeriwal V, Agrawal P, Thote P, Parkar M, Waiker SS. Anesthesia consideration for cesarean section in chronic myeloid leukemia diagnosed during pregnancy: An interesting case report and brief review of literature. Indian Anaesth Forum [serial online] 2019 [cited 2019 Nov 21];20:99-102. Available from: http://www.theiaforum.org/text.asp?2019/20/2/99/265645





  Introduction Top


Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by increased proliferation of granulocyte cells. In India, it constitutes 30%–60% of all adult leukemias. During pregnancy, CML being the most common chronic leukemia, its incidence is <10% of all leukemia.[1] The annual incidence of CML in females ranges from 0.6 to 1.6 per 100,000 populations.[2] CML is more prevalent in males than females with a mean age of diagnosis at 55–65 years.[3] The incidence of CML in younger generation is hardly 3%.

In developing countries like India, CML occurs in younger age compared to developed countries. Hence, the chances of CML in pregnancy though rare can be high and if associated with pregnancy may lead to delayed diagnosis.[1],[4] The diagnosis of CML depends on the presence of the BCR-ABL1 oncogene, resulting from a reciprocal balanced translocation between the long arms of chromosomes 9 and 22, t(9;22) (q34;q11.2), cytogenetically detected as the Philadelphia chromosome (Ph).[5]The majority of cases that occur during pregnancy are diagnosed during routine antenatal check-up. If acute leukemia presents during pregnancy, chemotherapy is generally started and is considered safe during the second and third trimesters.[6],[7] The patient diagnosed with CML during pregnancy, posted for cesarean section (C/S), is a very rare occurrence. We herein describe the successful management of a 19-year-old primigravida, posted for the emergency C/S, diagnosed as a case of CML during the third trimester of pregnancy.


  Case Report Top


A 19-year-old female with 33 weeks of pregnancy presented with fever, chills, and abdominal pain. Her investigations revealed hemoglobin (Hb) – 9.5 gm%, leukocytosis with shift to left – 200 × 103/mm, differential leukocytes count neutrophils – 42%, metamyelocyte – 12%, myelocyte – 2%, lymphocyte – 15%, eosinophils – 2%, monocyte – 2%, basophils – 0%, band forms – 27%, raised lactate dehydrogenase – 920 mIU/ml, raised reticulocyte count – 7.70%, and platelet count – 880 × 103/mm. Ultrasound abdomen was suggestive of moderate hepatosplenomegaly. The bone marrow smear showed features suggestive of chronic myeloid leukemia. The diagnosis was confirmed by fluorescent in situ hybridization showed Philadelphia chromosome (BCR ABL) {t(9;22) (q34;q11)}. The patient was started on tablet hydroxyurea 500 mg thrice a day. Her repeat total leukocytes counts after 1 month came down to 20,800/mm3, Hb was 9.0 gm%, and platelet counts were adequate. She was followed up till term and was scheduled for planned normal vaginal delivery. On the scheduled day, labor was induced, but the decision for the emergency C/S was taken after 15 h of labor induction, in view of meconium-stained liquor with fetal distress. Investigations showed Hb of 9.0 gm%, white blood cells (WBC) count of 28,300/mm3, and platelet count of 430 × 103. Coagulation profile showed prothrombin time (PT) of 18 s and international normalized ratio (INR) of 1.4. After considering anesthetic risks and benefits in the given situation, general anesthesia with endotracheal intubation was planned. Adequate blood and blood products were confirmed, and the patient was prepared for the emergency C/S. In operation theater, noninvasive monitors including electrocardiogram, noninvasive blood pressure, and pulse oximeter (SpO2) were attached to the patient. Under adequate monitoring, the patient was premedicated with intravenous (iv) glycopyrrolate 0.2 mg. Rapid sequence induction and intubation were performed using propofol 80 mg iv and suxamethonium 75 mg iv. Anesthesia was maintained with O2, N2O, and 1%–2% sevoflurane. Fentanyl 80 mcg iv was given after delivery of the baby. The baby had birthweight of 2320 g with good Apgar score. At the end of the surgery, the patient was reversed with neostigmine 2.5 mg and glycopyrrolate 0.4 mg iv. The entire procedure was uneventful. Intraoperatively, the patient was hemodynamically stable, and recovery was smooth. Postoperative period was uneventful, and the patient was started on tablet imatinib after 2 weeks of breastfeeding [Table 1].
Table 1: For hemoglobin, platelet, and white blood cell count

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  Discussion Top


Leukemia in pregnancy is a rare condition, with its annual incidence being 1–2/100,000 pregnancies.[1],[3],[8] The coincidence of CML and pregnancy is uncommon because CML occurs mostly in older age groups. CML presenting for the first time in pregnancy is less common in the developed world, but it is still a distinct possibility in the developing world due to the lack of basic health services and poor health awareness. This case was diagnosed with CML for the first time in her late second trimester. Another factor in delaying in the diagnosis is physiological changes of pregnancy, which masks the physical and laboratory findings of neoplasm. The disease diagnosis is occasionally an incidental finding during the routine blood investigations done during pregnancy[9] or sometimes as in our case when patient presents in prenatal unit with fever and weight loss.

CML has three phases (long chronic phase, followed by accelerated and blast phase). Clinical manifestations may include anemia and splenomegaly in 20%–70% cases and hepatomegaly in 10%–15% of patients with associated symptoms such as fatigue, weight loss, lethargy, fever, and excessive sweating. The patient may also have symptoms and signs pertaining to thromboembolic events because of leukocytosis and thrombocytosis. Sometimes, it may progress to acute or blast phase. The diagnosis of CML is based on peripheral hematologic examination showing mild-to-moderate anemia which is present in one third of patient, elevated WBC count (>20,000–100,000/mm3), left shift of hematopoiesis with predominance of neutrophils, and the presence of bands, myelocytes, metamyelocytes, promyelocytes, and blasts (usually ≤5%). Basophils and/or eosinophils are frequently increased. Thrombocytosis is common, but thrombocytopenia is rare and when present suggests a worse prognosis, disease acceleration, or an unrelated etiology.[5]

Management in cases of CML diagnosed during pregnancy depends on stage of pregnancy, without compromising the outcome of mother and fetus, as it is a well-known fact that during normal pregnancy if anything benefits mother, then fetus is also benefitted by the same. Treatment goals for CML include hematologic, molecular, and cytogenetic remission.

Management and administration of chemotherapeutic drug in CML diagnosed during pregnancy depend on the duration of pregnancy and aims at control of severe leukocytosis. During pregnancy, treatment is difficult because of the potential effects of chemotherapy on the fetus. Most of the cases reported in the literature were diagnosed before pregnancy and the patient had conceived while undergoing treatment for CML. In this case, the patient presented with fever with chills and pain abdomen with moderate hepatosplenomegaly in her third trimester and was diagnosed with CML.

During the first trimester, control of leukocytosis can be achieved by leukapheresis,[2] while to reduce the CML burden during the second and third trimester and till delivery, hydroxyurea at daily doses of 0.5–1 g is proven to be safe and effective. It is also used in combination with tyrosine kinase inhibitors to get complete cytologic and hematologic response. Another modality includes treatment with interferon-alpha which is immune modulator and is safe to administer throughout pregnancy and is the treatment of choice for a patient who is diagnosed with CML during pregnancy as it neither inhibits DNA synthesis nor crosses the placental barrier.[10] In case if interferon therapy is not well tolerated, then hydroxyurea remains the choice of drug for treatment except during the first trimester.[11] During pregnancy, the common complications of CML treated with hydroxyurea therapy are preeclampsia, intrauterine growth restriction, and stillbirth, but in our patient, who was diagnosed with CML during the third trimester, started with hydroxyurea 500 mg tds. No adverse effect was observed in the mother and fetus.

The common cause for all these obstetric complications is placental insufficiency due to the leukostasis resulting from the uncontrolled myeloproliferation seen in CML, and hence, if left untreated during pregnancy, then chances of low birth weight babies, fetal prematurity, and maternal/perinatal mortality are increased.[12] The patient posted for emergency C/S having leukemia during pregnancy possess multiple challenges for an anesthesiologist. An understanding of normal maternal-fetal physiology is critical in the diagnosis, surgical and anesthesia management, and postoperative care of pregnant women.

Leukocytosis and thrombocytosis lead to increase in blood viscosity, which may increase the risk of infection, thromboembolic events, and hemorrhage. During normal pregnancy, there is reduction in total platelet count with decreased fibrinolytic activity, and hence, both coagulation and fibrinolysis are augmented and remain balanced to maintain hemostasis. The aim before any surgical intervention and providing anesthesia to CML patient is to reduce leukocyte load so as to prevent tumor lysis syndrome with chemotherapeutic drugs. The interaction between cytotoxic drugs and anesthesia drugs is unpredictable. The presence of blast cells and coagulopathy are contraindication for regional anesthesia while general anesthesia is relatively contraindicated in hyperleukocytosis and at initiation of chemotherapeutic treatment.[13] Patient with leukemia suffers from anemia, coagulation disorder, and immunosuppression because of immunomodulator drug therapy.

Meyer et al. reported a case of massive subcutaneous hemorrhage resulting from multiple epidural punctures in patient with thrombocythemia due to CML.[14]

Kimura et al. reported two cases of thrombocytosis due to myeloproliferative disease, where general anesthesia was given along with epidural block in a patient who received myelosuppressive therapy resulting in normal platelet count and only general anesthesia in the second patient with increased platelet count.[15]

The guideline for anesthesia management for C/S in a patient of CML, diagnosed during pregnancy, is limited as there are only a few reported cases. In most of the cases, normal vaginal delivery was preferred, and only in few cases reported in literature, elective C/S was done. The presence of blast cells indicates that disease is in acute phase and thereby increased incidence of blast cell seedling into CSF if central neuraxial block is preferred for lower segment C/S (LSCS). Hence, it is contraindicated in patient with acute leukemia and in blast crisis (presence of >30% blast cell in circulation). Owsiak et al. preferred general anesthesia over central neuraxial blockade considering the fact that the presence of circulating blast cells may lead to iatrogenic inadvertent intrathecal seeding.[16]

In our patient, though her leukocyte count and platelet count came down to near normal at term, her PT was 18 s and INR was 1.4, and the patient came for emergency LSCS in view of fetal distress; considering all these facts, we preferred giving general anesthesia.

Spencer et al. described a CML parturient who had multiple medical problems such as myocardial infarction, congestive heart failure, diabetes mellitus, asthma, two previous C/S, mild preeclampsia with poorly controlled leukemia. As per her preference, general anesthesia was given for C/S and outcome was uneventful.[17]


  Conclusion Top


CML though rare, its course is not affected in pregnancy. Female with CML on chemotherapy becoming pregnant is usual, but a young pregnant woman diagnosed with CML during pregnancy is uncommon. The treatment and decision-making should involve multidisciplinary team constituting medical oncologist, obstetrician, neonatologist, and anesthesiologist. In the absence of appropriate guidelines regarding anesthesia, the goals of care should be to benefit the mother's life, treat curable malignant disease of pregnant women, and try to protect the fetus and newborn from harmful effects of anesthesia and chemotherapeutic drugs.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Bansal S, Prabhash K, Parikh P. Chronic myeloid leukemia data from India. Indian J Med Paediatr Oncol 2013;34:154-8.  Back to cited text no. 1
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2.
Ali R, Ozkalemkaş F, Ozkocaman V, Ozçelik T, Ozan U, Kimya Y, et al. Successful pregnancy and delivery in a patient with chronic myelogenous leukemia (CML), and management of CML with leukapheresis during pregnancy: A case report and review of the literature. Jpn J Clin Oncol 2004;34:215-7.  Back to cited text no. 2
    
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Sawyers CL. Chronic myeloid leukemia. N Engl J Med 1999;340:1330-40.  Back to cited text no. 3
    
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Malhotra P, Varma S. Chronic myeloid leukaemia in India. Lancet 2007;370:1127.  Back to cited text no. 4
    
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Kantarjian H, Cortes J. Chronic myeloid leukemia 124e-2. Oncology and Hematology: Harrison's Principles of internal Medicine. 19th edition. Mcgraw-Hill Education Part 7. 2015. p. 620-760.  Back to cited text no. 5
    
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Caligiuri MA, Mayer RJ. Pregnancy and leukemia. Semin Oncol 1989;16:388-96.  Back to cited text no. 6
    
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Zuazu J, Julia A, Sierra J, Valentin MG, Coma A, Sanz MA, et al. Pregnancy outcome in hematologic malignancies. Cancer 1991;67:703-9.  Back to cited text no. 7
    
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Firas AS, Demeckova E, Mistrik M. Leukemia in pregnancy. Bratisl Lek Listy 2008;109:364-6.  Back to cited text no. 8
    
9.
Apperley J. Issues of imatinib and pregnancy outcome. J Natl Compr Canc Netw 2009;7:1050-8.  Back to cited text no. 9
    
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Rizack T, Mega A, Legare R, Castillo J. Management of hematological malignancies during pregnancy. Am J Hematol 2009;84:830-41.  Back to cited text no. 10
    
11.
Thauvin-Robinet C, Maingueneau C, Robert E, Elefant E, Guy H, Caillot D, et al. Exposure to hydroxyurea during pregnancy: A case series. Leukemia 2001;15:1309-11.  Back to cited text no. 11
    
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Rohilla M, Rai R, Yanamandra U, Chaudhary N, Malhotra P, Varma N, et al. Obstetric complications and management in chronic myeloid leukemia. Indian J Hematol Blood Transfus 2016;32:62-6.  Back to cited text no. 12
    
13.
Groeben H, Heyll A, Peters J. Pathophysiologic and anesthesiologic characteristics of patients with leukemia. Anaesthesist 1992;41:438-47.  Back to cited text no. 13
    
14.
Meyer HH, Mlasowsky B, Ziemer G, Tryba M. Massive hemorrhage following multiple epidural punctures as a late complication in thrombocythemia. Anasth Intensivther Notfallmed 1985;20:287-8.  Back to cited text no. 14
    
15.
Kimura Y, Yamaguchi S, Nagao M, OkudaY, Kitajima T. Anesthetic management of two patients with essential thrombocythemia. Mausi Jpn J Anesthesiol 2001;50:545-7.  Back to cited text no. 15
    
16.
Owsiak JN, Bullough AS. Chronic myeloid leukemia in pregnancy: An absolute contraindication to neuraxial anesthesia? Int J Obstet Anesth 2016;25:85-8.  Back to cited text no. 16
    
17.
Spencer J, Gadalla F, Wagner W, Blake J. Caesarean section in a diabetic patient with a recent myocardial infarction. Can J Anaesth 1994;41:516-8.  Back to cited text no. 17
    



 
 
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