|Year : 2021 | Volume
| Issue : 2 | Page : 81-89
Pregnancy in thalassemia, anesthetic implication and perioperative management- A narrative review
Abhishek Singh1, Karuna Sharma2, Vineeta Venkateswaran1, Anjan Trikha1
1 Department of Anesthesiology, Pain Medicine and Critical Care, All India Institute of Medical Sciences, New Delhi, India
2 Department of Anesthesia and Critical Care, Geetanjali Medical College and Hospital, Udaipur, Rajasthan, India
|Date of Submission||28-Aug-2021|
|Date of Acceptance||02-Sep-2021|
|Date of Web Publication||01-Oct-2021|
Dr. Abhishek Singh
Department of Anesthesiology, Pain Medicine and Critical Care, Room Number 5011, Teaching Block, Anesthesia Office, Ansari Nagar East, AIIMS, New Delhi - 110 029
Source of Support: None, Conflict of Interest: None
Advancement in the treatment of thalassemia has increased the life span of female patients, with the result that they are reaching the reproductive age group and expecting childbirth. Anesthesia is challenging in such patients due to ineffective erythropoiesis and multiple system involvement as a result of iron overload and chelation therapy. Careful management of the preconception phase, various conception strategies, and multidisciplinary management of pregnancy and childbirth can lead to a healthy and successful outcome of pregnancy. This review provides an overview of the pathophysiology and clinical manifestation of alpha and beta-thalassemia in pregnancy and its successful management. All available literature related to thalassemia was searched in major databases like PubMed, Embase, Scopus, and Google Scholar. Original articles, review articles, book chapters, guidelines, case reports, and correspondence were reviewed for pathophysiology, clinical manifestations, and anesthetic management of thalassemia during pregnancy with keywords like thalassemia, Cooley's anemia, thalassemia and pregnancy, anesthetic management of thalassemia, labor analgesia in thalassemia, and transfusion in thalassemia.
Keywords: Anesthetic concern, perioperative management, thalassemia
|How to cite this article:|
Singh A, Sharma K, Venkateswaran V, Trikha A. Pregnancy in thalassemia, anesthetic implication and perioperative management- A narrative review. J Obstet Anaesth Crit Care 2021;11:81-9
|How to cite this URL:|
Singh A, Sharma K, Venkateswaran V, Trikha A. Pregnancy in thalassemia, anesthetic implication and perioperative management- A narrative review. J Obstet Anaesth Crit Care [serial online] 2021 [cited 2021 Nov 29];11:81-9. Available from: https://www.joacc.com/text.asp?2021/11/2/81/327414
| Introduction|| |
Hemoglobinopathies are the most common inherited disease of hemoglobin structure and function. Thalassemia refers to the group of hemoglobinopathies, which are characterized by partial or complete suppression of synthesis of either one of the alpha or beta globin chains of the hemoglobin molecule, due to genetic mutations. This change results in reduced hemoglobin levels, microcytosis, and anemia. Depending upon the affected gene and its effect on the globin chain, various types of thalassemia have been described. The most common and clinically significant types are alpha and beta-thalassemia.
Globally, 15 million people are affected by thalassemia, and men and women are affected equally. Alfa thalassemia is prevalent in the African and southeast Asian race, whereas beta thalassemia is prevalent in the Mediterranean, African, and southeast Asian races. In India, approximately 10000 children are born with thalassemia which accounts for nearly 10% of the worldwide incidence of thalassemia-affected children. Beta thalassemia is prevalent throughout India with the average carrier frequency being 3%–4%. The prevalence varies from 3.5% in Bengal and 4.3% in south India to 6.5% in Punjab and 8.4% in Tamil Nadu, and 10%–15% in Gujrat, with increased prevalence in certain communities like Sindhis, Punjabis, Bengalis, Gujratis, Mahars, Saraswats, Gaurs, and Kolis. Over 7% of pregnant women carry a significant variation of hemoglobin globally. Amongst these, beta and alpha thalassemia constitute 90% and 4.3%, respectively. Pregnancy in patients with beta-thalassemia was rare before 1960 as these patients had poor life expectancy and suffered from reduced growth and fertility. The clinical outcome of these patients has improved significantly after the late 1970s due to advancements in blood transfusion and iron chelation therapy. Now female patients have been surviving up to child-bearing age and coming at various stages of pregnancy management and delivery. The anesthetic management of a pregnant patient with thalassemia poses a significant challenge to the clinician and requires the coordinated effort of hematologists, cardiologists, obstetricians, and anesthetists.
Genetic basis and morphology
The structure of adult hemoglobin consists of two alpha (α) and two non-alpha or β globin chains that are attached with four iron-containing heme complexes. There are two α-globin genes located on each chromosome 16, and one non-α-globin gene (normally β-globin gene) on each chromosome 11. The α-chains are encoded by four co-dominant alleles, whereas the β-chains are encoded by two co-dominant alleles; thus, altogether six alleles code for the globin chain. Co-dominance implies that the alleles are equally expressed in the synthesis of hemoglobin polypeptides. Thalassemia is generally inherited as an autosomal recessive disease; hence, the phenotype is fully expressed in individuals who are homozygous for both defective alleles. Approximately 200 gene mutations have been diagnosed in patients with beta-thalassemia that range from transcription to mRNA translation. The genetic aberration responsible for beta-thalassemia consists of small nucleotide substitution in the gene cluster; beta gene deletions and rarely, deletion of regulatory elements have also been identified. Alpha thalassemia usually results due to the deletion of one or both alpha genes from the chromosome. Beta-thalassemia occurs due to a defect in beta-globin chains of the HbA molecule. It usually manifests around 4–6 months of age as fetal hemoglobin decreases significantly to be replaced by HbA during this period.
Hemoglobin is a tetrameric structure with two pairs of globin (polypeptide) chains. Globin chain can be α, β, γ, δ, ε, and ζ. Different types of hemoglobin are produced by a combination of these chains in pre- and postnatal life. Normal adult Hb (HbA) is made of 2α and 2β chains. HbA2 is a normal variant of adult Hb made of 2α and 2δ chains. It is found in small quantities in the blood. Another major type of Hb is HbF (2α and 2γ) which is found in fetal life and almost completely replaced by adult Hb after 1 month postnatally. Hemoglobin Portland (2ζ, 2γ), Hb Gower 1 (2ζ, 2ε), and Hb Gower 2 (2α, 2ε) are embryonic Hb found in early fetal life (3 to 10 wks of gestation). The thalasemias are generally characterized as α-, β-, γ-, δ -, δβ-, or εγδβ-thalassemias, depending upon chain whose synthesis is impaired.
β-thalassemia consists of three main variants: First, Thalassemia Major which is also called as “Cooley's Anemia” and “Mediterranean Anemia;” Second is Thalassemia Intermedia and Thalassemia Minor which are also referred as “β-thalassemia trait,” “β-thalassemia carrier,” or “heterozygous β-thalassemia;” Third is Hb E/β-thalassaemia which is caused by co-inheritance of Haemoglobin E allele from parent and β-thalassaemia allele from another [Table 1].
|Table 1: Various forms of thalassemia (α,β) depending upon the number and type of globin gene affected|
Click here to view
Alpha thalassemia results are due to reduced or absent production of alfa chains. Patients with 2 out of 4 functional alleles are generally called as “thalassemia trait.” The presence of only one functional allele (1/4) leads to an intermediate form of alpha thalassemia manifested by the occurance of variable amounts of HbH. The absence of all functional alleles leads to the most severe form of alpha thalassemia called Bart's hydrops fetalis syndrome [Table 1].
Pathophysiology and clinical features
Thalassemia usually presents as microcytic hypochromic anemia which may be transfusion-dependent or non-transfusion-dependent. Patients with transfusion-dependent thalassemia require frequent blood transfusion for survival; however, even the non-transfusion-dependent patient may need a blood transfusion during periods of stress like pregnancy.
Patients with the alpha thalassemia trait are usually asymptomatic and often diagnosed only while investigating for microcytic hypochromic anemia or during pregnancy. HbH has an increased affinity for oxygen than normal adult hemoglobin leading to reduced delivery of oxygen to the peripheral tissue. These patients may require frequent blood transfusions, may develop jaundice, splenomegaly, and suffer from infections, growth retardation, and iron overload. Alpha thalassemia major or Hb Bart represents the most severe form of alpha thalassemia in which the affected fetus develops severe anemia and heart failure as well as excess fluid around the heart, lung, skin, and subcutaneous tissue which can be seen on ultrasound as fetal hydrops. Fetuses with Hb Bart are incompatible with life, and the affected fetus either dies during intrauterine or in the early postnatal period. Bart's syndrome also has some serious maternal manifestations. There is an increase in maternal complications in these pregnancies, such as; placentomegaly, severe preeclampsia with vomiting, hypertension, generalized edema (peripheral and pulmonary both), and proteinuria. Uncontrolled hypertension can lead to eclampsia dystocia, retained placenta, and postpartum hemorrhage. Sometimes, it may become desirable to deliver fetuses affected by Hb Bart, as early delivery may help to prevent the development of severe symptoms in the mother. On the other hand, the course of pregnancy in women suffering from other types of alpha thalassemia does not vary significantly from normal women.
Beta thalassemia intermedia and minor
Patients who receive beta-thalassemia genes from both parents with varying degrees of mutations usually develop beta-thalassemia intermedia. This condition may be transfusion-dependent or transfusion-independent, depending upon the degree of mutation. Beta-thalassemia minor denotes heterozygous carriers who are generally non-transfusion-dependent.
The clinical course of the disease in transfusion-independent beta-thalassemia is minor and intermedia is usually benign. The anemia is mild with microcytic and hypochromic red blood cells. These patients may develop moderate anemia during pregnancy but usually tolerate pregnancy and delivery uneventfully. However, the incidence of fetal growth restriction and oligohydramnios is greater than in nonthalassemic patients. Blood transfusion is generally reserved for pregnant patients experiencing hemorrhage or those with hemoglobin below 8 g/dL. The anesthetic management of non-transfusion-dependent thalassemia minor and intermedia patients is no different from that of a normal patient.
In beta-thalassemia, there are reduced or absent beta-globin chains which leads to precipitation of excess alpha chains in red cell precursors which interferes with red cell maturation and leads to early destruction in the bone marrow. This manifests as ineffective erythropoiesis which is a hallmark of the disease and subsequent hemolysis of distorted cells in peripheral circulation leading to anemia [Figure 1]. Increased erythropoietin production in response to anemia causes hypertrophy of bone marrow resulting in skeletal changes affecting the skull and long bones in addition to variable degrees of hepatosplenomegaly. Early transfusion therapy cuts off the erythropoietin drive and allows for normal growth and development in such patients. Iron overload due to repeated blood transfusion causes severe damage to the liver, endocrine organs, and myocardium. Cardiac failure and ventricular arrhythmias are often the main cause of death.
Various systemic manifestations due to ineffective erythropoiesis and multiple blood transfusions are mentioned in [Table 2]. Congestive cardiac failure is the most common cardiac complication causing death. Dilated cardiomyopathy and pulmonary hypertension are the major cause of heart failure in beta-thalassemia major and intermedia, respectively. Cardiac arrhythmias with prolonged QT and QTc interval which increase the risk of ventricular tachycardia, torsades de Pointes, and sudden cardiac death have also been diagnosed. Pulmonary hypertension has been documented in up to 75% of patients with beta-thalassemia major and in 50% with beta-thalassemia intermedia. There is pulmonary fibrosis due to iron overload leading to restrictive lung disorder with reduced total lung capacity. Renal abnormalities include low molecular weight proteinuria, high creatinine clearance, increased urinary excretion of magnesium, calcium, phosphate, uric acid, and raised biomarkers of proximal tubular injury. The anterior pituitary is affected in the majority of the cases of beta-thalassemia. Children usually present with growth retardation and short stature which poorly respond to growth hormone therapy., Hypogonadism and reduced fertility are also common manifestations that require hormone replacement therapy., Glucose intolerance and diabetes mellitus are also seen in these patients. Iron overload also leads to hypothyroidism and hypoparathyroidism, the effect of which can be reversed by effective chelation therapy.
|Table 2: Systems affected, clinical manifestation and anesthetic implications in thalassemia|
Click here to view
Extramedullary erythropoiesis results in a spectrum of craniofacial abnormalities consisting of prominent zygomatic bones, frontoparietal bossing, depressed nasal bridge, and maxillary overgrowth with dental malocclusion or protrusion; these changes are collectively called “chipmunk facies.” Bony overgrowth and extramedullary hyperplasia may cause pressure effect on neural structures in the orbit and middle ear, hampering vision and hearing, respectively. The pressure effect on the spinal cord and cauda equina may result in a spectrum of neurological symptoms ranging from mild sensory-motor deficit to paraplegia, bladder bowel incontinence, and impotence. Poor bone mineralization, osteomalacia, osteopenia, and microfractures are common and are the result of bone marrow hyperplasia and marrow cavity expansion. Thalassemia is also well documented as a hypercoagulable state. The presence of low levels of protein C, protein S, antithrombin III, in addition to changes in the red cell membrane as well as endothelial and platelet activation contribute to increased thrombotic tendency. Beta thalassemia intermedia patients are more prone to develop venous thromboembolic events like portal vein thrombosis, pulmonary embolism, deep vein thrombosis, etc., whereas beta thalassemia major patients are more prone to arterial thrombosis. Multiple blood transfusions render thalassemia patients susceptible to numerous blood-transmitted diseases such as hepatitis C, hepatitis B, and HIV. Simultaneously, other manifestations of disease like chronic anemia, iron overload, and splenectomy make these patients susceptible to bacterial infection.
Diagnosis is generally made on the basis of clinical features (discussed with respective thalassemia types above), various hematological markers, and qualitative (type) and quantitative (amount) analysis of Hb [Table 3]. Molecular diagnosis of a particular type of thalassemia can be done by PCR-based technology. Hematologic investigations include complete blood count (CBC), RBC indices (MCV, MCH), serum iron, ferritin, total iron binding capacity, and percentage saturation of transferring and peripheral blood smear (PBF), which helps in ruling out other causes of microcytic anemia, especially iron-deficiency anemia [Figure 2]. Typical findings of PBF are the presence of microcytosis, hypochromia, target cells, +/- inclusion bodies, increased reticulocytes, crenated and nucleated RBC, and basophilic stippling. Recently, magnetic resonance imaging (MRI) has been adopted to evaluate iron accumulation in the liver and heart and guide chelation treatment.
- Blood transfusion
- Chelation therapy
- Stem cell transfer/Bone marrow transfer
- γ Globin induction
- Gene therapy.
Blood transfusion is considered the mainstay of treatment. Leukocyte-depleted blood with extended antibody typing is generally used to reduce the risk of alloimmunization., Physiological changes associated with pregnancy may have a deleterious effect on the thalassemic mother and the fetus. An increase in plasma volume during pregnancy can worsen the anemia. Patients with thalassemia intermedia who had a minimal manifestation of the disease before pregnancy may require blood transfusion for the first time during pregnancy so as to maintain hemoglobin level above 10 g/dL. A well-managed transfusion regimen in pregnancy is known to reduce hyperactive erythropoiesis, excessive gastrointestinal iron absorption as well as the high rate of pregnancy loss, prematurity, and intrauterine growth restriction. The cardiovascular changes associated with pregnancy and labor may cause severe cardiac deterioration and left ventricular impairment in women with beta-thalassemia major. Women with diagnosed cardiac dysfunction or significant arrhythmias should be advised against planning pregnancy.
Repeated blood transfusion carries an inherent risk of complications such as iron overload, adverse transfusion reactions, and risk of transmission of blood-borne infections. Iron overload is a serious complication and if untreated, may result in mortality by the second or third decade of life. It is generally managed by iron-chelating agents like desferrioxamine, deferiprone, and deferasirox. These drugs carry certain side effects such as vertebral dysplasia, growth retardation, visual disturbances (with desferrioxamine), gastrointestinal symptoms, rashes (with deferasirox), and agranulocytosis (with deferiprone). Splenectomy has been shown to reduce transfusion requirements but increases the risk of postoperative infection and thrombotic events. Recent advances in treatment modalities include stem cell transplantation, gene therapy, and fetal hemoglobin inducers.
As reported by Fforde, pregnant women with thalassemia are often on several drugs of which some may be teratogenic, like deferiprone. Deferasirox in animal studies has not shown any teratogenicity but there is limited safety data regarding its use in pregnancy. The authors recommend that whenever possible, deferiprone and deferasirox should be discontinued at least 3 months before conception. Desferrioxamine should be avoided in the first trimester of pregnancy due to lack of safety data but can be used safely after 20 weeks of gestation in low doses. Transfusion-dependent pregnant women not on chelation therapy need peripartum chelation therapy to avoid free radical damage and cardiac dysrhythmia due to toxic iron species during labor.
Guidelines for the management of pregnancy in thalassemia patients
The Green-top guideline for thalassemia and pregnancy (2014) and NHM guidelines for prevention and control of hemoglobinopathies in India (2016) give an overview on management of thalassemia including prevention, early diagnosis, and treatment strategy. A brief review of various components of Green top guidelines is given below:
Prevention of disease by prenatal diagnosis and genetic counseling
- Patients planning for pregnancy should visit the thalassemia clinic to be screened for end-organ damage.
- Screening for liver, thyroid, heart, and kidney function.
- ABO, full blood genotype, and antibody titer should be done.
- Genetic counseling and option for in vitro fertilization with donor sperm is suggested if the partner is a carrier for the disease
- Preimplantation genetic diagnosis (PGD) should be considered if both partners have hemoglobinopathy, so that a homozygous or compound heterozygous pregnancy can be avoided.
- Preconceptional chelation therapy can reduce and optimize body iron burden and prevent end-organ damage.
Ante partum care
- All the pregnant patients should come for antenatal visit monthly till 28 weeks of gestation and every fortnightly after that.
- A multidisciplinary team should look after such patients from the beginning of the pregnancy.
- Thalassemia patients suffering from diabetes should undergo monthly evaluation of serum fructosamine level and should be followed up in a specialist diabetic pregnancy clinic.
- The cardiac condition should be evaluated at 28 weeks of gestation and thereafter when needed.
- Hypothyroid patients should undergo thyroid function evaluation during pregnancy.
- HBsAg negative women who are transfusion-dependent or may need a transfusion in the future are recommended to undergo hepatitis B vaccination. Their hepatitis C status should be determined.
- Postsplenectomy women should undergo penicillin prophylaxis and should be vaccinated for hemophilus influenzae type B and pneumococcal vaccine if they have not received it before.
- All women should be given folic acid preconceptionally to prevent neural tube defects.
Thalassemia major pregnant women should receive blood transfusion at regular intervals to target Hb at 10 g/dL.
- Worsening of anemia and fetal growth retardation requires a regular blood transfusion.
- National guidelines should be followed when determining the timing of delivery.
- All the staff consisting of obstetricians, anesthesiologists, hematologist, and senior midwifery should be informed as soon as thalassemic pregnancy women are admitted to the delivery suite.
- In pregnant patients with the presence of red cell antibodies, blood should be kept ready after cross-matching for delivery to avoid delay in its availability when needed.
- Thalassemia major pregnant patients should be given desferrioxamine 2 g over 24 h for the duration of labor
- Electronic fetal monitoring should be done continuously during the intrapartum period.
- Active management of the third stage of labor is recommended to minimize blood loss.
- Women should be offered an early scan at 7–9 weeks of gestation. In addition to the routine first-trimester scan (11–14 weeks of gestation) and a detailed anomaly scan at 18–20 weeks of gestation, women should be offered serial fetal biometry scans every 4 weeks from 24 weeks of gestation.
The catecholamine surge associated with labor pain can cause severe cardiac deterioration and left ventricular impairment in pregnant women with beta-thalassemia major, and this may have deleterious effects on the mother as well as the fetus. Effective labor analgesia is advocated to avoid such complications. Pharmacological as well as nonpharmacological techniques can be used for labor analgesia in such patients. Pharmacological techniques usually comprise central neuraxial analgesia and inhalational agents. Central neuraxial techniques are considered the gold standard for labor analgesia and consist of epidural and combined spinal-epidural analgesia (CSE). Both modalities can be safely used in thalassemic patients. Amongst inhalational agents, entonox (50% N2O and 50% O2) can be used with proper oxygen saturation monitoring but should be avoided in those with evidence of pulmonary artery hypertension. Halogenated inhalational agents like desflurane, isoflurane, and sevoflurane need further studies before they can be used in clinical practice.
Women with thalassemia major are considered at high risk for venous thromboembolism. The Green-top guidelines recommend administration of thromboprophylaxis with low molecular weight heparin in hospital as well as for 7 days postdischarge after vaginal delivery and for 6 weeks after cesarean section. The guidelines state that oral desferrioxamine should be restarted in breastfeeding mothers as soon as the initial 24-h infusion of desferrioxamine is completed after delivery. But, if the mother plans not to breastfeed, then desferrioxamine infusions are continued till discharge from the hospital or till her previous iron chelation regimen is started under hematology guidance.
Pregnant patients with thalassemia may present for elective or emergency surgery. For elective surgery, these patients should undergo in-depth laboratory and clinical examination as well as preoperative optimization.
There are no guidelines regarding ideal perioperative hemoglobin level. However, RCOG considers 10 g/dL as safe and appropriate. All patients with low hemoglobin levels should undergo blood transfusion preoperatively depending upon the risk severity of the procedure and expected blood loss. Detailed systemic examination and organ function tests should be done for evaluating systemic manifestation of thalassemia. They should also be investigated for side effects related to multiple blood transfusion and chelation therapy.
Careful airway examination should be done preoperatively as the probability of difficult intubation due to the presence of maxillary hypertrophy can be as high as 19%. Placement of laryngeal mask may also be difficult due to the presence of a high arched palate. However, in the majority of patients with adequate disease management, facial abnormalities are less evident; as a result, preoperative airway examination may be normal with uneventful intraoperative orotracheal intubation.
The cardiovascular function should be thoroughly investigated and poor effort tolerance should warrant evaluation by echocardiography. The presence of pulmonary hypertension, heart failure, and cardiomyopathy may need further evaluation by cardiac catheterization. A multidisciplinary team consisting of a hematologist, anesthetist, cardiologist, surgeon, and pulmonologist is needed while managing such cases.
Besides routine ASA monitoring (pulse oximetry, noninvasive blood pressure, ECG, capnography), such cases require advanced cardiovascular hemodynamic monitoring like transesophageal or transthoracic echocardiography, minimally invasive cardiac output monitors like esophageal Doppler monitor and pulse contour analysis devices.
In patients with pulmonary hypertension, every effort should be made to avoid hypercarbia, hypoxia, and acidosis intraoperatively. Preoperative pulmonary function, renal function, liver function, and electrolyte levels should be checked, and any abnormalities should be optimized before proceeding with surgery.
Perioperative blood loss should be minimized, and blood conservation strategies may be utilized. Strategies such as preoperative blood donation, human erythropoietin administration, and intraoperative tranexamic acid use have shown successful results in reducing blood loss and the need for blood transfusion. If transfusion is indicated, leukocyte-depleted packed red blood cells should be used.
As thalassemia patients are immunocompromised and susceptible to infection, perioperative broad-spectrum antibiotic prophylaxis should be given, and the patient should be monitored postoperatively for any evidence of infection. As hypercoagulability is frequently seen in thalassemia, thromboprophylaxis measures should be undertaken. The presence of osteomalacia and osteoporosis, as well as thin and fragile skin, increases the risk of pathological fractures and leg ulcers, therefore, patient transfer and positioning should be done carefully. Anesthetic implications in accordance with systems involved in thalassemia are mentioned in [Table 2].
- For nonobstetric surgery
The anesthesia technique and drugs used should be tailored according to surgery and clinical condition. Both neuraxial and general anesthesia has been used successfully. Standard anesthesia techniques with intravenous agents, inhalational agents, and opioids have been used with minimal side effects. Spinal, epidural, and combined spinal epidural, all have been used successfully., Skeletal involvement may cause difficulty in performing neuraxial procedures. Preexisting neurological deficits, when present, should be evaluated thoroughly and are a relative contraindication for the neuraxial block. Routine preoperative coagulation test and platelet count should be performed before attempting any regional technique as abnormal coagulation values and thrombocytopenia may be encountered in these patients. Continuation of folic acid and vitamin B12 in mothers with beta-thalassemia prevents superimposed megaloblastic anemia.
- For Cesarean delivery
Planned cesarean delivery is advisable for these patients as it avoids the cardiovascular stress associated with labor and overcomes the high incidence of cephalopelvic disproportion due to the short stature found in thalassemic patients.
Factors favoring cesarean delivery include cephalopelvic disproportion, abnormal fetal lie, and severe cardiac disease. If vaginal delivery is planned, a hemodynamic manifestation of Valsalva maneuvers, the second stage of labor, and risk of transmission of infection should be taken into consideration. While selecting the anesthesia technique for cesarean delivery, the high incidence of difficult intubation due to maxillofacial deformities in planned general anesthesia should be weighed against the possibility of a complicated neuraxial block due to skeletal deformities, osteoporosis, intraspinal extramedullary hemopoiesis, and splenomegaly-induced thrombocytopenia.
Postoperative analgesia with a multimodal approach including an emphasis on regional analgesia techniques should be preferred. This may consist of a combination of regional blocks, patient-controlled analgesia, epidural analgesia, and oral or intravenous analgesic drugs such as NSAIDs, paracetamol, opioids, and ketamine. Recently, nerve blocks like transverses abdominis plane block, and ilioinguinal-iliohypogastric nerve blocks have gained importance as they carry no risk of respiratory depression, maternal sedation, or prolonged analgesia.
| Conclusion|| |
Perioperative management of the parturient with thalassemia major is challenging and complicated because of multiple organ system involvement, multiple blood transfusions resulting in iron overload, and physiological changes of pregnancy. Pregnancy appears to be safe and uneventful in patients with non-transfusion-dependent thalassemia intermedia and minor, but a multidisciplinary approach is needed for preoperative investigation, optimization, and uneventful perioperative management.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Greer JP, Arber DA, Glader B, List AF, Means RT, Paraskevas F. Wintrobe's Clinical Hematology. 13th
ed. PA, USA: Lippincott Williams and Wilkins; 2014.
Madan N, Sharma S. Sood SK, Colah R, Bhatia HM. Frequency of beta-thalassemia trait and other hemoglobinopathies in northern and western India. Indian J Hum Genet 2010;16:16-25.
] [Full text]
Sinha S, Black ML, Agarwal S, Colah R, Das R, Ryan K, et al
. Profiling β-thalassaemia mutations in India at state and regional levels: Implications for genetic education, screening and counseling programmes. Hugo J 2009;3:51–62.
Mohanty D, Colah RB, Gorakshakar AC, Patel RZ, Master DC, Mahanta J, et al
. Prevalence of β-thalassemia and other hemoglobinopathies in six cities in India: A multicentre study. J Community Genet 2013;4:33-42.
Dewan K, Shukla S, Singh D, Sharma S, Trivedi SS. Antenatal carrier screening for thalassemia and related hemoglobinopathies: A hospital based study. J Med Soc 2018;32:118–22. [Full text]
Butwick A, Findley I, Wonke B. Management of pregnancy in a patient with β thalassaemia major. Int J Obstet Anesth 2005;14:351-4.
Propper RD, Cooper B, Rufo RR, Nienhuis AW, Anderson WF, Bunn HF, et al
. Continuous subcutaenous administration of deferoxamine in patients with iron overload. N Engl J Med 1977;297:418-23.
Modell B, Letsky EA, Flynn DM, Peto R, Weatherall DJ. Survival and desferrioxamine in thalassaemia major. BMJ 1982;284:1081–4.
Firth PG. Anesthesia and hemoglobinopathies. Anesthesiol Clin 2009;27:321–36.
Giardine B, Borg J, Higgs DR, Peterson KR, Philipsen S, Maglott D, et al
. Systematic documentation and analysis of human genetic variation in hemaglobinopathies using the microattribution approach. Nat Genet 2011;43:295–301.
Weatherall DJ. The thalassemias. In: Stamatoyannopoulos G, Nienhuis AW, Majerus PH, Varmus H, editors. The Molecular Basis of Blood Diseases. 2nd
ed. Philadelphia, PA: W.B. Saunders; 1994. p. 157–205.
Rachmilewitz EA, Giardina PJ. How I treat thalassemia. Blood 2011;118:3479–88.
Staikou C, Stavroulakis E, Karmaniolou I. A narrative review of peri-operative management of patients with thalassaemia. Anaesthesia 2014;69:494-510.
Saxena R, Banerjee T, Aniyery RB. Thalassemia and its management during pregnancy. World J Anemia 2017;1:5-17.
Joshi DD, Nickerson HJ, McManus MJ. Hydrops fetalis caused by homozygous alpha-thalassemia and Rh antigen alloimmunization: Report of a survivor and literature review. Clin Med Res 2004;2:228-32.
Gibbons R, Higgs DR, Olivieri NF, Wood WG. Clinical features: The b thalassaemias. In: Weatherall DJ, Clegg DJ, editors. The Thalassaemia Syndromes. Oxford: Blackwell Science; 2001. p. 287–356.
Aessopos A, Farmakis D, Karagiorga M, Voskaridou E, Loutradi A, Hatziliami A, et al
. Cardiac involvement in thalassemia intermedia: A multicenter study. Blood 2001;97:3411–6.
Tai DY, Wang YT, Lou J, Wang WY, Mak KH, Cheng HK. Lungs in thalassaemia major patients receiving regular transfusion. Eur Res J 1996;9:1389–94.
Ponticelli C, Musallam KM, Cianciulli P, Cappellini MD. Renal complications in transfusion-dependent beta thalassaemia. Blood Rev 2010;24:239–44.
Gamberini MR, De Sanctis V, Gilli G. Hypogonadism, diabetes mellitus, hypothyroidism, hypoparathyroidism: Incidence and prevalence related to iron overload and chelation therapy in patients with thalassaemia major followed from 1980 to 2007 in the Ferrara Centre. Pediatr Endocrinol Rev 2008;6:158-69.
Delvecchio M, Cavallo L. Growth and endocrine function in thalassemia major in childhood and adolescence. J Endocrinol Invest 2010;33:61–8.
Abu Alhaija ESJ, Hattab FN, Al-Omari MAO. Cephalometric measurements and facial deformities in subjects with beta- thalassaemia major. Eur J Orthod 2002;24:9–19.
Nemtsas P, Arnaoutoglou M, Perifanis V, Koutsouraki E, Orologas A. Neurological complications of beta-thalassemia. Ann Hematol 2015;94:1261-5.
Orvieto R, Leichter I, Rachmilewitz EA, Margulies JY. Bone density, mineral content, and cortical index in patients with thalassemia major and the correlation to their bone fractures, blood transfusions, and treatment with desferrioxamine. Calcif Tissue Int 1992;50:397–9.
Taher AT, Otrock ZK, Uthman I, Cappellini MD. Thalassemia and hypercoagulability. Blood Rev 2008;22:283-92.
Viprakasit V, Origa R. Genetic basis, pathophysiology and diagnosis; Chapter 1. In: Cappellini MD, Cohen A, Porter J, Taher A, Viprakasit V, editors. Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT). 3rd
ed. Cyprus: Thalassaemia international federation (TIF); 2014. Publication no. 20. p. 158-69.
Prabhu R, Prabhu V, Prabhu RS. Iron overload in beta thalassemia- A review. J Bio Sci Technol 2009;1:20–31.
Leung TY, Lao TT. Thalassaemia in pregnancy. Best practice and research. Clin Obstet Gynecol 2012;26:37–51.
Savona-Ventura C, Bonello F. Beta-thalassemia syndromes and pregnancy. Obstet Gynecol Surv 1994;49:129–37.
Tuck SM. Fertility and pregnancy in thalassemia major. Ann N Y Acad Sci 2005;1054:300-7.
Chiruka S, Darbyshire P. Management of thalassaemia. Paediatr Child Health 2011;21:353–6.
Fforde R. Management of beta thalassaemia in pregnancy. Obstet Gynaecol 2014;16:148.
Royal College of Obstetrician and Gynaecologists. March 2014. Management of Beta Thalassaemia in Pregnancy. Green-top Guideline No. 66.
National health mission. Guidelines for prevention and control of hemoglobinopathies in India. 2016.
Voyagis GS, Kyriakis KP. Homozygous thalassemia and difficult endotracheal intubation. Am J Hematol 1996;52:125–6.
Pérez Ferrer A, Ferrazza V, Gredilla E, de Vicente J, de la Rua A, Larrea A. Bloodless surgery in a patient with thalassemia minor. Usefulness of erythropoietin, preoperative blood donation and intraoperative blood salvage. Minerva Anestesiol 2007;73:323-6.
Taher AT, Musallam KM, Cappellini MD, Weatherall DJ. Optimal management of β thalassaemia intermedia. Br J Haematol 2011;152:512-23.
Petrakos G, Andriopoulos P, Tsironi M. Pregnancy in women with thalassemia: Challenges and solutions. Int J Womens Health 2016;8:441-51.
Ahemed SA, Denu ZA, Getinet Kassahun H, YilikalFentie D. Efficacy of bilateral transversus abdominis plane and ilioinguinal-iliohypogastric nerve blocks for postcaesarean delivery pain relief under spinal anesthesia. Anesthesiol Res Pract 2018;2018:1948261.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]