Case Report: Aplastic Anaemia in Pregnancy - Management and Follow-up
A 23-year-old primigravida with recently diagnosed aplastic anemia presented for antenatal care. History of UTI, pancytopenia, and transfusions were noted. Hematologist confirmed aplastic anemia with hypocellular marrow. Despite challenges, pregnancy was managed with multidisciplinary approach including repeat bone marrow evaluations. Hematologist advised regular blood counts and transfusions as needed. Close monitoring ensured optimal management throughout pregnancy.
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APLASTIC ANAEMIA IN APLASTIC ANAEMIA IN PREGNANCY PREGNANCY - - A CASE REPORT REPORT A CASE Dr.Sofia.K (Fellow in Reproductive medicine) Dr.V.Geetha ,Dr.Lakshmi , Dr.Kundavi Institute of reproductive medicine, Madras medical mission Monday,15th February 2021(online)
CASE REPORT 23 year old primi presented to IRM at 7weeks +4days for antenatal care with an history of recently diagnosed aplastic anemia.
History of presenting illness History of presenting illness Patient was married at 23 years 3 months after marriage Developed UTI associated with chills and rigor. Evaluated at private hospital and Routine laboratory tests showed pancytopenia Haemoglobin of 7gm/dl, Platelet 37000 & TC-3,600 & 3 units of PRBC transfused
INVESTIGATIONS INVESTIGATIONS Hematologist opinion was obtained Iron Normal Ferritin TIBC Bone marrow aspirate: Hypocellular marrow Dyserythropoiesis Absent iron storage A bone marrow biopsy confirmed the diagnosis of aplastic anemia.
HISTORY HISTORY Menstrual History: Regular menstrual cycles Medical History: Evaluated for giddiness at 20 year and found to have mild anemia and vitamin B12 deficiency treated with vitamin B12 injection Surgical History: NIL Family History: NIL
HISTORY HISTORY Obstetric History : NT scan First trimester screening NORMAL Anomaly Scan serial growth scans Her pregnancy was managed with multidisplinary approach .
INVESTIGATIONS INVESTIGATIONS Repeat bone marrow done at early gestation Hypocellular marrow particles Normoblastic erthyropoiesis Mildy suppressed megakaryopoiesis Myelodysplastic syndrome panel by FISH Negative Chromosomal analysis Normal female karyotype 46XX
HAEMATOLOGIST ADVICE Advised blood count every 2 weeks Haemoglobin < 8gm/dl - 2 units of packed red blood cells Platelet count < 20,000 4 units of platelets According to the Hematologists advice patient was managed accordingly.
HAEMATOLOGICAL PROFILE HAEMATOLOGICAL PROFILE Date GA Hb platelet WBC Blood transfusion 3/12/19 7+4wks 12.7 37000 20/12/19 10 wks 10.6 45000 3840 2/1/20 12 wks 9.1 58000 2670 14/1/20 13+3 wks 7.1 60000 4000 2 PRBC 5/2/20 16+4 wks 7.7 50000 3900 2PRBC 19/2/20 18+4 wks 8.3 50000 3800 28/2/20 19+6 wks 6.8 50000 4000 2 PRBC 29/3/20 23 wks 6.7 38000 4500 2 PRBC 8/4/20 25+4 wks 7.5 26000 4200 1PRBC 15/4/20 26+4 wks 7.2 1 PRBC 27/4/20 28+2 wks 6.5 30000 3900 2 PRBC
MANAGEMENT MANAGEMENT According to hematologist advise patient was transfused with PRBC and platelets Haemoglobin > 8gm/dl platelet > 20,000, To prevent the serious consequences of thrombocytopenia and anemia of the mother and fetus .
MANAGEMENT MANAGEMENT At 35 weeks + 3 days of gestation decision to LSCS was made. 2 days before the lscs patient was Haemoglobin was 9gm and platelets 40,000 patient was transfused with 4 units of random platelets & 1 unit of PRBC Platelet refractoriness checked platelets after one hour -80,000 Antenatal steroids given for fetal lung maturity On the day of LSCS Haemoglobin - 9.9 gm/dl Platelet - 70,000
DELIVERY DELIVERY Patient underwent Elective lscs at 35 weeks and 5 days with 4 units of platelets on flow under antibiotic coverage B A B Y . Alive male 2.470 kgs 9/10,9/10 Histopathology of placenta -: Umblical cord - Three blood vessel Membranes - No specific lesion placenta - Mild congestion
Post operative period Post operative period Post operative period was uneventful POD Hb Platelet TC POD -0 9.9 1,00,000 7100 POD- 1 9.0 1,00,000 5700 POD-2 8.9 1,00,000 6200 POD-3 9.2 1,10,000 5500 Patient was discharged in stable condition on 4th POD. Haemoglobin - 9gm platelets -1 lakh
WHAT IS APLASTIC ANEMIA? WHAT IS APLASTIC ANEMIA? . Aplastic anemia is a rare disease caused by destruction of pluripotent stem cells in bone marrow with an annual incidence of 2 to 6/10,00,000. In contrast to the term 'aplastic anemia', suggesting suppression of erythropoetic cell lines, all cell lines may be affected . Depending on affected cell lines, aplastic anemia is associated with fatigue, bleeding due to thrombocytopenia and recurrent infections due to neutropenia . The diagnosis 'aplastic anemia' is confirmed by hypocellularity of the bone marrow. The remaining cells are morphologically unaffected without malignant infiltration.
APLASTIC ANEMIA IN PREGNANCY The first report of Aplastic anemia in Pregnancy was publised by Ehrlich in 1888 Pathophysiology of pregnancy associated AA high levels of hormones during pregnancy The level of placental lactogen ,erythropoietin- stimulate the function of hemopoiesis Increased estrogen during pregnancy - inhibits erythropoiesis Aitchison RG, Marsh JC, Hows JM, Russell NH, Gordon-Smith EC. Pregnancy associated aplastic anaemia: a report of five cases and review of current management.Br J Haematol. 1989;73:541 545. doi: 10.1111/j.1365-2141.1989.tb00294.x.[PubMed] [CrossRef] [Google Scholar]
APLASTIC ANEMIA IN PREGNANCY Haemorrhage and sepsis due to pancytopenia are the major reasons for death in pregnant women with aplastic anemia Immunosuppressive agents or hemopoietic stem cell transplantation are contraindicated during pregnancy. Supportive care remains the first line treatment for pregnant women
Classification of AA: Classification of AA: camitta camitta criteria criteria
CAUSES CAUSES OF APLASTIC ANEMIA APLASTIC ANEMIA INHERITED- Fanconi's anemia Dyskeratosis congenita Shwachman-Diamond syndrome Reticular dysgenesis Amegakaryocytic thrombocytopenia Familial aplastic anemias Preleukemia (monosomy 7, etc.) Nonhematologic syndrome (Down, Dubowitz, Seckel)
CAUSES CAUSES OF APLASTIC ANEMIA APLASTIC ANEMIA ACQUIRED- Radiation Drugs and chemicals Viruses (non-A, non-B, non-C Hepatitis, EBV, Parvovirus B19, HIV-1) Immune diseases (Eosinophilic fasciitis, Thymoma, Hyperimmunoglobulinemia, Graft-versus-host disease) Paroxysmal nocturnal hemoglobinuria, Pregnancy Idiopathic
PATHOPHYSIOLOGY PATHOPHYSIOLOGY Bone marrow failure results from severe damage to the hematopoietic cell compartment. There is replacement of the bone marrow by fat. An intrinsic stem cell defect exists for the constitutional aplastic anemias Extrinsic damage to the marrow follows massive physical or chemical insults such as high doses of radiation and toxic chemicals Immune mediators like Helper T cells, TNF, IFN- may be involved in the pathogenesis.
CLINICAL PRESENTATION CLINICAL PRESENTATION Low RBC Low platelets Low WBC (Anemia) (Thrombocytopenia) (Leukopenia) Pallor Fatigue Dyspnoea Dizziness Chest pain Bleeding is the most common early symptom Easy bruising petechie epistaxis heavy menstrual flow Infections Fever. Flu- like illness
Effects of anemia in pregnancy Effects of anemia in pregnancy maternal complications maternal complications During pregnancy : -Preterm labour -Pre eclampsia -Cardiac failure During labour -Uterine inertia -Post partum Hemorrhage -Shock Puerperium -Sub involution -Puerperal sepsis -Failing lactation -Pulmonary embolism
Neonatal complications Prematurity Intra uterine growth retardation Low birth weight Poor APGAR score Fetal distress Neonatal Anemia
INVESTIGATIONS INVESTIGATIONS BLOOD CBC Peripheral smear Reticulocute count B 12/folate LFT Virology FLOW CYTOMETRY FOR PNH BONE MARROW ASPIRATE AND BIOPSY
LAB FINDINGS LAB FINDINGS Severe pancytopenia with relative lymphocytosis Normochromic ,normocytic RBCs Mild to moderate anisocytosis and poikilocytosis Decreased reticulocyte count Hypocelullar bonemarrow with > 70% yellow marrow
BM BIOPSY BM BIOPSY HYPOCELLULAR, INCREASED FAT SPACES HYPOCELLULAR, INCREASED FAT SPACES
NORMOCELLULAR BONE MARROW NORMOCELLULAR BONE MARROW
DIFFERENTIAL DIAGNOSIS DIFFERENTIAL DIAGNOSIS Paroxysmal noctural hemoglobinuria Inherited marrow failure Myelodysplastic syndrome(MDS)
MANAGEMENT MANAGEMENT 1. Identification and elimination of underlying cause 2.supportive therapy 3.Hemotopoietic stem cell transplantation 4.Immunosuppressive treatment 5.Androgens 6.Growth factors (GM,CSF,G-CSF,EPO)
SUPPORTIVE THERAPY SUPPORTIVE THERAPY Supplementation of blood products Prevention and treatment of haemorrhage Prevention and treatment of infection
BONEMARROW TRANSPLANTATION BONEMARROW TRANSPLANTATION Treatment of choice Correction of haematopoetic defect The best therapy for the younger patient with fully histocompatible sibling donor. Long term survival rates :80-90% Donor stem cells > 4 x 10 5-15% risk of graft failure in multitransfused patients
IMMUNOSUPPRESSION IMMUNOSUPPRESSION As most of patients lack suitable donor, it is the treatment of choice for them. Antithymocyte globulin (ATG) Antilymphocyte globulin (ALG) Cyclosporin Intensive immunosuppression : cyclophosphamide corticosteroids
IMMUNOSUPPRESSION IMMUNOSUPPRESSION Increasing age and the severity of neutropenia are the most important factors weighing in the decision between transplant and immunosuppression in adults who have a matched family donor. Older patients do better with Anti thymocyte globulin and cyclosporine, whereas transplant is preferred if granulocytopenia is profound.
MANAGEMENT OF AA MANAGEMENT OF AA - - PREGNANCY PREGNANCY Little research has been published about therapy for aplastic anemia during pregnancy. In fact, only case reports and series with small sample sizes are available. In young non-pregnant patients first choice therapy for aplastic anemia is allogenic stem cell transplantation with a five-year survival of 70 to 80% However, stem cell transplantation is not feasible during pregnancy because of the teratogenic effects of the immunotherapy and radiotherapy for the unborn child Aitchison RG, Marsh JC, Hows JM, Russell NH, Gordon-Smith EC. Pregnancy associated aplastic anaemia: a report of five cases and review of current management. Br J Haematol. 1989;73:541 545. doi: 10.1111/j.1365-2141.1989.tb00294.x. [PubMed] [CrossRef] [Google Scholar]
MANAGEMENT OF AA MANAGEMENT OF AA - - PREGNANCY PREGNANCY . Pregnancy termination to start bone marrow transplantation was not recommended because of the relatively good prognosis for both mother and child. During pregnancy supportive therapy with erythrocyte and platelet transfusions is a widely used, reasonable alternative
CONCLUSION CONCLUSION Aplastic anaemia is a serious condition which may manifest during pregnancy. The seriousness depends on the degree of bone marrow suppression. Most pregnant patients will have full-term pregnancies with a healthy child with supportive care Fortunately,aplastic anaemia has a low mortality due to treatment
CONCLUSION CONCLUSION As described in this case,the benefit of transfusions to prevent bleeding should be weighed against the likelihood of developing HLA antibiodies and hemochromatosis in the mother. In case the patient responded insufficiently to supportive therapy, immunotherapy with ATG,CsA or methylprednisolone can be started.
patient with severe AA was treated throughout the course of pregnancy with haemopoietic growth factor in combination with an immunosuppressive agents and supportive transfusion
During severe aplastic anemia or complications caused by supportive therapy (PRBC and platelet tranfusion) ATG, cyclosporine can be used
Conservative transfusion management is critical to prevent alloimmunization.
PROPHYLACTIC MEASURES PROPHYLACTIC MEASURES Prophylactic platelet transfusion at delivery. Prophylactic analgesics and antibiotic coverage during delivery. Assisted second stage of labour in cases of vaginal delivery. In post-partum period,perineal infection should be avoided.
TAKE HOME MESSAGE TAKE HOME MESSAGE A multidisplinary - team approach to the management of aplastic anemia in pregnancy involving the obstetrician ,the hematologist ,Anaesthetist and neonatologist is necessary to Coordinate antenatal care Optimize maternofetal outcomes & Plan peripartum interventions Good supportive care and blood transfusion resulted in successful outcome in our patient.
Obstetrics,Haematologist,Neonatologist ,Anaesthetist & lab services, Madras Medical Mission