CASE REPORT

Hemoglobin 2,6 g/dL due to Autoimmune Hemolytic Anemia (AIHA)

Presented by: Dr. Edwin Tohaga

Supervised by : Dr. Bambang Sudarmanto. SpA(K)

Department of Pediatrics Faculty of Medicine Diponegoro University-Dr. Kariadi Hospital Semarang 2012
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Table of Contents
CHAPTER 1....................................................................................................................................... 3 INTRODUCTION.............................................................................................................................. 3 CHAPTER 2....................................................................................................................................... 4 CASE PRESENTATION ................................................................................................................... 4 CHAPTER 3....................................................................................................................................... 7 DISCUSSION .................................................................................................................................... 7 Case Analysis ................................................................................................................................. 7 Diagnostic Aspect .......................................................................................................................... 7 Type of AIHA .............................................................................................................................. 12 Therapeutic Aspec ........................................................................................................................ 13 Aetiologies Aspec ........................................................................................................................ 16 Prognosis ...................................................................................................................................... 18 CHAPTER 4..................................................................................................................................... 19 CONCLUSION AND SUGESTION ............................................................................................... 19 PROBLEM SCHEME .................................................................................................................. 20 REFERENCES ................................................................................................................................. 20

CHAPTER 1 INTRODUCTION

Autoimmune hemolytic anemia (AIHA) is a disease characterized by the presence of autoantibodies directed against antigens on the red cell membrane. This phenomenon leads to premature red cell destruction by reticulo endothelial system phagocytes. In the severe form of the disease hemoglobin drops suddenly to life-threatening levels and, unfortunately, provision of compatible blood for transfusion is very difficult.1,2 AIHA is a rare disorder, the incidence of AIHA is estimated 0,2:100.000 children. The peak incidence occurs in pediatric patients at pre-school age children. Boys are affected 2.5 times more often than girls. Most cases the child has an acute onset and selflimitting. Approximately 50% to 70% of cases are idiopathic cases, some cases of druginduced, and the other occurs simultaneously without the autoimmune diseases, particularly systemic lupus erythematosus. Some cases develop in patients with B cell lymphoma or chronic lymphocytic leukemia (chronic lymphositic leukemia, CLL).3 This patient was the only case that founded for the last five years. In the treatment of AIHA, conventional dose prednisone (2 mg/kg/day), high dose methylprednisolone (3 mg/kg/day) or sometimes intravenous immunoglobulin G (IVIG) therapy are used3-5. Other cytotoxic agents such as cyclosporine, azathioprine, and cyclophosphamide have rarely been reported to be used in refractory autoimmune hemolytic anemia. 4-6 Here, we report an 8 years old girl with AIHA, who was treated with methylprednisolon 4 mg/kg/day and tapered with methylprednisolon oral 3 mg/kg/day successfully.

CHAPTER 2 CASE PRESENTATION

On September 1st 2010, An eight-year-old girl with pale and fever had been diagnosed with anemia gravis at another hospital, she was admited at referal hospital for 3 days with hemoglobin ( Hb) was 4 g/dl, she programed fortransfusion of red blood cell suspensions, but no blood found suitable for the patient. The patient then being transfer to Kariadi Hospital. The patient admited to our hospital with fever, pallor, icteric and hepatomegaly(2cm). Her hemoglobin (Hb) was 2,6 g/dl with her white blood cell (WBC) count was 9.650/mmkand platelet count was 350.000/mmk.During admition she recieve 9 unit of washed red blood cell suspensions and every time she get transfusion, blood crossmacth inkompabilitas mayor always obtained, but she remained transfusion. Post transfusion she always have a fever,improved after administering dexamethason injection, no further simptom found after the injection. At this moment the differential diagnosis was anemia gravis ec thalasemia and paracites infection. Because this examination takes times at least 2 weeks after the last trasfution ( toward thalasemia Hb electroforesis), She was allowed to be discharge and go home with last know Hb was 12 g/dl. Three days later, she returned with a new anemic attack (Hb: 2.6 g/dl ) accompanied with fever, dizzines no convulsion and icteric at the sklera, no apetite, vomite and hepatomegaly ( 2 cm), we found a systolic murmur grade 3/6 sound continued to sternum. Her hemoglobin was 2,6 g/dl, white blood cell was 9.650, platelet count was 350.000,indeks eritrosit was ( mcv (fl) 89, MCH (pg) 29,4, MCHC (g/dl) 32,9), eritrosit was 870.000/mm3), LED I/II(mm) 160/185 RDW(%) 14,9. Retikulosit 0,80 %, Malaria negatif, bilirubin total 1,82 mg/dl,bilirubin direk 0,42 mg/dl, LDH 478 u/l. The assesment was anemia gravis with differesial diagnosis: thalasemia, hemolitic, paracitic infection. She was again programed for recieving a transfusion. During the first 2 days of admission she get three unit of washed red blood cell. Post tansfusion, Hb was 5.56g/dl, white blood cell was 9460/mm3, platelet count was 473.000/mm, eritrosit indexs (MCV(fl) 87.9, MCH(pg) 34.4, MCHC(g/dl) 39.2), erythrocytes was 1.610.000 /mm3), RDW14.8%,and herreticulocytes was 0.8%, TIBC223(ug/dl), Ferritin was > 1200ng/dl, examination of blood smear obtained diffcount E0/B0/St0/Sg74/L21/M, the impression of blood smear was : eritropoetik: mild

anisositosis, mild poikilositosis (tear drop cells), eritroblast(+), normocytic. Granulopoetik: normal, no blast cell form. Trombopoetik: normal. On the third day of admition she was looks pale again and repeated laboratory examination results, Hb after transfusion was4.16g/dl, white blood cell 9460/mm3, platelete count 473.000/mm3,index eritrosit (MCV(fl) 87.9, MCH(pg) 34.4, MCHC(g/dl) 39.2), erythrocytes 1.610.000/mm3), RDW 14,8%. Detailed examination of the blood smear reviealed an autoaglutination that give clues to the existence of an autoimmune disorder, she was programmed to do work up diagnosis for evidence of hemolityc and comb test and the result was positive at this time the assessment was change to autoimmune hemolytic anemias (AIHA) and then given immunosuppression therapy by administering metilpredsinolonoral 4-3-3 tab with paracetamol 3 x 200 mg and vitamin b compleks 3 x 1 tab, and still gived blood trasfusion, although every time there was always an inkomptabilitas major, transfusion complications in the form of fever is still occuring every transfusion. On the fourth day of admission, the therapi was change to injection of metilprednisolon 3 x 15 mg and the dose was change again in the day 6thof admission to methylprednisolon IV 4 x 20 mg. On the seventh day of admission the patient looks improved, no more pale, but new problem was found with fever that not respon to therapy. From the laboratorium finding, Hb was 9.20g/dl, hematokrit 25,8 %, white blood cell 21.400/mm3, platelete count 157.000/mm3, index eritrosit (MCV(fl) 85.30, MCH(pg) 30.4, MCHC(g /dl) 35.6, erythrocytes3.030.000/mm3), RDW 14,8%. We add assesment with febris and susp nosocomial infection and add the therapy with antibiotic injection, cefotaxim 3 x 750 mg iv On the eighth day of admission we have a new problem with a bleeding in gastrointestinal, with a clinical sign we found that nasogastric tube looks brownish. Our assesment was add with gastrointestinal bleeding and therapy was add with ranitidin inj 3 x 20 mg. On the thirteenth day of admission we found good clinical finding with no more pale and icteric, from physical examination we found no more murmur on cor auscultation and no more hepatomegaly. Hb was 10.90 g/dl, hematocrit 31,9 %, white blood cell 24.700/mm3, platelete count 251.000/mm3, index eritrosit (MCV(fl) 90.50, MCH(pg)

30.9, MCHC(g /dl) 34.2, erythrocytes 3.520.000/mm3), RDW 15,8%. No additional therapy was given. On the sixteenth day of admission no more complain and the condition was improved with no more pale and from physical examination was normal. Hb was 10.70g/dl, hematokrit 31,3 %, white blood cell 14.600/mm3, platelete count 216.000/mm3, index eritrosit (MCV(fl) 91.30, MCH(pg) 31.20, MCHC(g /dl) 34.20, erythrocytes 3.430.000/mm3), RDW 22,80%. The patient was already recieved 14 day injection of methylprednisolon and programed for discharge from hospital and continue therapy with tampering out with methylprednisolon for another 14 days. The second admition was carried ou for 2 weeks and get transfusion during admited for 8 times with the washed red blood cell. After two weeks of administering methylprednison, Her Hb was 10.70g/dl, hematokrit 31,3 %, white blood cell 14.600/mm3, platelete count 216.000/mm3, index eritrosit (MCV(fl) 91.30, MCH(pg) 31.20, MCHC(g /dl) 34.20, erythrocytes 3.430.000/mm3), RDW 22,80%. Patients prognosis was quo ad vitam ad bonam, quo ad sanam ad bonam, quo ad fungsionam ad bonam. One week following her discharge from hospital, the patient was follow up as an out patient in hematologic clinic. She was denied having another anemia attack, she already have a normal daily activities. Her physical examination were within normal limit.

CHAPTER 3 DISCUSSION
Hemolytic anemia is a condition wherein the red blood cells (RBC) are broken down or destroyed in the blood vessels or in other parts of the body. When the breakdown of RBC becomes faster, the body produces more RBC to make up for the loss. When the rate at which the body breaks down RBC exceeds that rate at which the body produces RBC, anemia is then experienced.Immune hemolytic anemia is a kind of hemolytic anemia characterized by the immune systems early destruction of red blood cells. This condition involves the formation of antibodies that target the bodys own red blood cells. The antibodies detect the red blood cells as foreign material and destroy them. The body may obtain these antibodies through various means, such as by blood transfusion, complications arising from a disease, and a baby having a different blood type from its mother. These antibodies may also result from negative reaction to medicines. When the antibodies form because of disease complications or reaction to medicines, the condition is called secondary immune hemolytic anemia. Sometimes, the cause of the formation of antibodies could not be determined. An example of such case is idiopathic autoimmune hemolytic anemia. This constitutes about half of the immune hemolytic anemias known. Autoimmune hemolytic anemia in children may be associated with

immunodeficiency syndrome, malignancy, and multisystem autoimmune disorders. Sometimes no underlying disease can be detected, as in our case.

Case Analysis Diagnostic Aspect

Autoimmune hemolytic anemia (AIHA) is a hemolytic anemia due to formation of autoantibodies attached to the erythrocyte membrane causing destruction (hemolysis) of erythrocytes leading to shortened erythrocyte age.1,2,3 There are three types of AIHA can be distinguished from the clinical characteristics and serologis, the type of warm (warmautoimmune hemolyticanemia, WAIHA), type (cold agglutinin disease), and hotcold type of Donath-Landsteiner or paroxysmal cold hemoglobinuria(PCH).1,4,5 These three types of abnormalities can occur as idiopathic (primary) and accompanies other

diseases (secondary). AIHA can also occur following administration of certain drugs (druginduced).1 AIHA is a rare diseases, the incidence of AIHA is estimated 0,2:100.000 children. The peak incidence occurs in pediatric patients at pre-school age children. Boys are affected 2.5 times more than girls. Most cases the child has an acute onset and selflimitting. Approximately 50% to 70% of cases are idiopathic cases, some cases of druginduced, and the other occurs simultaneously withoutv autoimmune diseases, particularly systemic lupus erythematosus. Some cases develop in patients with B cell lymphoma or chronic lymphocytic leukemia (chronic lymphositic leukemia, CLL).1 Patients first referred with anemia, and history was obtain from the onset of disease which is occurvery quickly. There was no history of previous bleeding and no any risk factors that can provide information about the prevailing conditions, from physical examination found a pale and jaundiced, and the enlargement of the organ with an impressiv elaboratory evidence of anemia gravis. When program transfusion of blood components, from the first transfusion in comtabilitas was the major problem and then to reduce the transfusion risk we used wash erythrocytes. Post-transfusion the patient always suffer fever as a result of transfution reaction, but the transfusion remain to be done. By administering corticosteroid post transfusion the conditions was improve. During treatment the patient has received 9 times transfusion, Hb last inspection has been increased up to 12.6 gr, work up diagnosis still been done to find the cause of anemia, search towards a parasitic infection carried by fecal examination was negative, then traced by looking towards thalassemia, laboratory of Hb electrophoresis was required uncontaminated blood samples of blood donors, so it was decided to do the examination 2 weeks later. Because the child's condition improved and the time required for examination still long, the patient were discharge. Three days post-hospital care children were admitted again due to anemia attack, Hb was 2.4g/dl, a transfusion given for emergency treatment, examination of blood smear suggested proved for autoaglutinasi proces. This became the basic for the search towards hemolytic anemia caused by the presence of autoimmune diseases, and comb test was performed with positive results. Patients diagnosed with AIHA and programmed therapy methylprednisolon injection 4x20mg continued for 2 weeks tapered out with methylprednisolon oral at a dose of 4-2-2tab/ day with alternate dose. Children treated for 2 weeks and go home with oral methylprednisolon treatment. Patients were programmed to

control every 2 weeks for 3 months. One month post-treatment of children remain healthy and show no signs of anemia towards the attack. The first step in the diagnosis of anemia is detection with reliable, accurate tests so that important clues to underlying disease are not overlooked and patients are not subjected to unnecessary tests for and treatment of nonexistent anemia. Detection of anemia involves the adoption of arbitrary criteria. WHOs criterion for anemia in adults is an Hb value of less than 12.5 g/dL. Children aged 6 months to 6 years are considered anemic at Hb levels less than 11 g/dL, and children aged 6-14 years are considered anemic when Hb levels are less than 12 g/dL. The disadvantage of such arbitrary criteria is that a few healthy individuals fall below the reference range, and some people with an underlying disorder fall within the reference range for Hb concentration.6 Diagnosis is made by first ruling out other causes of hemolytic anemia, such as G6PD, thalassemia, sickle-cell disease, etc. Clinical history is also important to elucidate any underlying illness or medications which may have led to the disease Evidence of hemolysis in patients can be searched with the following examination7 : Increased red cell breakdown
o o o o o o

Elevated serum bilirubin (unconjugated) Excess urinary urobilinogen Reduced plasma haptoglobin Raised serum lactic dehydrogenase (LDH) Hemosiderinuria Methemalbuminemia

Increased red cell production:

o o

Reticulocytosis Erythroid hyperplasia of the bone marrow

Specific investigations o Positive direct Coombs test

Standard blood studies for the workup of suspected hemolytic anemia include the following:

Complete blood cell count Peripheral blood smear

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Serum lactate dehydrogenase (LDH) study Serum haptoglobin Indirect bilirubin

Peripheral smear findings can help in the diagnosis of a concomitant underlying hematologic malignancy associated with hemolysis. For example, smears in CLL are characterized by an abundance of small lymphocytes and smudge cells (ruptured CLL cells). A peripheral smear may demonstrate spherocytes, suggesting congenital spherocytosis or autoimmune hemolytic anemia (AIHA). Changes in the LDH and serum haptoglobin levels are the most sensitive general tests because the indirect bilirubin is not always increased. Unconjugated bilirubin is a criterion for hemolysis, but it is not specific because an elevated indirect bilirubin level also occurs in Gilbert disease. With hemolysis, the level of indirect bilirubin usually is less than 3 mg/dL. Higher levels of indirect bilirubin indicate compromised hepatic function or cholelithiasis. Serum LDH elevation is a criterion for hemolysis. LDH elevation is sensitive for hemolysis, but is not specific since LDH is ubiquitous and can be released from neoplastic cells, the liver, or from other damaged organs. Although an increase in LDH isozymes 1 and 2 is more specific for red blood cell destruction, these enzymes are also increased in patients with myocardial infarction. Other laboratory studies may be directed by history, physical examination, peripheral smear, and other laboratory findings. Ultrasonography is used to estimate the spleen size, since the physical examination occasionally does not detect significant splenomegaly. Chest radiography, electrocardiography (ECG), and other studies are used to evaluate cardiopulmonary status.

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These were an algorithm for hemolitic anaemia evaluation

Figure 114:Algorithm for the evaluation of hemolytic anemia. (CBC = complete blood count; LDH = lactate dehydrogenase; DAT = direct antiglobulin test; G6PD = glucose-6-phosphate dehydrogenase; PT/PTT = prothrombin time/partial thromboplastin time; TTP = thrombotic thrombocytopenic purpura; HUS = hemolytic uremic syndrome; DIC = disseminated intravascular coagulation)

Patients from the early arrival has actually been shown signs of hemolytic, with a history of suddenly pale without a history of prior bleeding, there is jaundice, liver enlargement, anemia and decreased erythrocyte. Work-up diagnosis in patients starting from the anemia gravis which occur repeatedly in short time (3days) provide an indication of anemia hemolitic occurred, conducted bloodsmear, with the impression of blood smear was (eritropoetik: anisositosis mild, mild poikilositosis (tear dropcells), eritroblas t(+), normocytic, Granulopoetik: normal, no blast cells form, Trombopoetik: normal. from the results above there is no clue as to the condition of anemia that occurs hemolitic, but from re-evaluation of the child obtain the section on the picture cell autoaglutinasi red blood. Patients were then followed up with examination of the comb test and obtain positive results and confirm the evidence for the diagnosis of AIHA.

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Establishing the diagnosis in patients, based on existing theories done not systematically. Steps that should be done in a work-up diagnosis is by standart examining to determine the signs of hemolytic. Examination of blood smear preparations should provide more detail, we should seach for spherocytes cell, which is a typical sign of the condition of AIHA, from the impression of clinical pathology it was not metioned.

Figure 3: Spherocytes cell

Signs of hemolytic it was already presence, wich the condition of anemia Hb 2.4 g% 0.80% Reticulocytes, total bilirubin 1.82 mg / dl, director Bilirubin 0.42 mg / dl, LDH 478 u / l, and positive results comb test. But the tests was conducted not directly but with a gap of more than 1 day, after verification of hemolytic. In this patients the diagnosis was established within three days on the second treatment. In the first treatment steps are not taken, leading to this condition recurring.

Type of AIHA
The clinical presentation of AIHA is not different from other forms of acute haemolytic anaemia or acute crisis of a chronic haemolytic anaemia. Frequently, patients are jaundiced and suffer from clinical signs of anaemia, such as pallor, fatigue, shortness of breath and palpitations. In contrast, haemoglobinuria as a sign of intravascular haemolysis is rare, but the patient must explicitly be asked for that symptom. In case of cold agglutinins, cold exposure may lead to agglutination of RBC in the circulation as reflected by cyanotic discolouring of the acra, such as toes, fingers, ears and nose. After warming up, the cyanotic discolouring disappears quickly and in contrast to a Raynaud phenomenon, no reactive hyperaemia occurs. The presence of a disease frequently reported
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to be associated with AIHA supports the suspected diagnosis. Since many of these diseases are accompanied by anaemia, the diagnosis of a mild AIHA can easily be missed. This was the algorithm for distinguishedtype of AIHA

Figure 216. Diagnostic algorithm in AIHA. LDH indicates lactate dehydrogenase; DAT, direct antiglobulin test; and CT, computed tomography.

Type AIHA in patients based on the signs, symptoms and laboratory examination, the patient tipe was a warm type. Symptoms and signs show that patient never had a cyanotic colour at the extrimities that can lead to cold AIHA and laboratory from the DAT test ( comb test) perform at room temprature sugested that it was a Warm AIHA, also tests support the presence a slow on set of symptoms to first treatment condition, physical examination obtain from patient there were organ enlargemen of hepatomegaly, jaundice and fever.

Therapeutic Aspec1,4,5,7,8,11,13
Therapy in children with AIHA essentially distinguished by the type of AIHA occurring. 1. In patients with warm type AIHA performed:

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a. Transfusion If possible be avoided, because of the difficulty of finding a suitable blood (cross-matching) and short-age of blood transfusion. However, the use of blood transfusions performed in certain circumstances to avoid cardio pulmonary compromise. Transfusion guidelines include:
-

Must be a suitable donor is selected Washed packed red cells from a donor who used at least eritrosit showed agglutinationin serum of patients

Volume

of

blood

transfusion

should

be

sufficient

to

avoid

cardiopulmonary compromise. Typically a liquots 5 ml/kg is used and transfused with a speed of 2ml/kg/hour b. Corticosteroids Corticosteroids are first-line therapy for WAIHA. Oral prednisone 2-6 mh / kg / day or intravenous methylprednisolone 2-4 mh / kg / day for 3 days followed by oral prednisone. The use of high doses of corticosteroids given to few days later on tappering off in 3-4 weeks. c. Gammaglobulin intravena Administered at a dose of 1-5g/kg with a varied response. Considered in patients with severe hemolysis requiring transfusion. d. Rituximab Administered at a dose of 375mg/m2 once weekly for 4 weeks when patients with severe disease do not respond to steroids or steroid-dependent, and the refractory state. e. Splenectomy Splenectomyis thevsecond-line therapy is indicated if the hemolysis is rapid while the high-dose corticosteroid therapy, rituximab, and transfusions are not able to maintain hemoglobin levels are safe for patient. f. Plasmapheresis Plasmapheresis can slow the speed of hemolysis in patients with severe WAIHA. g. immunomodulatoryagents Drugs that can administered, among others, mycophenolate mofetil, cyclosporine, and danazol. Mycophenolatemofetil is effective in patients with
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AIHA with autoimmune or lympho proliferative diseases underlying. Danazol may decrease the expression of Fcrecept or activity of macrophages. h. Antimetabolite Azathioprine and 6-mercaptopurine take 4-12 week stop rovide steroid-sparing effect. i. Alkylating agent Cyclophosphamide can be given only in severe circumstances that are not responsive to steroids, and immunomodulatory or rituximab. j. Inhibitor of mitosis Vincristine and vinblastine are rarely administered, but they are used to suppress hemolysis while awaiting immunomodulatory or cytotoxic agents start working. 2. Cold type AIHA Control of underlying diseases Transfusion given when there is a significant and symtomatic hemolysis. Warm the patient room Plasmapheresis efficient for the treatment of disorders of IgM because IgM is widely available intravascular. Drug therapy can be given in severe circumstances. Drugs that can given, among others, rituximab and cyclophosphamide. Steroids provide a small effect on CAD. 3. Hot Cold type AIHA Keeping patient warm. Patient respond to corticosteroid. Plasmapharesis is also effective weight given to the state.

In these patients after being diagnosed with AIHA treatment program performed, in addition from giving a blood transfusion was also done methylprednisolon injection at a dose of 3x15mg given over 2 days and then the dose was changed to 4x20mg daily for 2 weeks and then tapered with oral methylprednisolon 4-2-2 tablet per day given for 2 weeks. The result was good Methylprednisolon injection administered at a dose of 80mg/day which means given 4mg/kg/day, for 2 weeks and there are side effects of therapy which is

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gastrointestinal bleeding, symtom improved by administering a ranitidin injection of 3 x20 mg for 5days. The first defense against this disease is treatment with steroids, specifically prednisone, during therapy. produced. Prednisone is a corticosteroid that is synthetically

Corticosteroid is a kind of steroid that the adrenal cortex naturally

produces. Corticosteroids have a wide range of physiological applications. They are used to treat conditions like skin diseases, adrenal problems, brain tumors, and others. There are generally two classes of corticosteroids glucocorticoids and mineralocorticoids. Glucocorticoids act as anti-inflammatory agents, and they also control the metabolism of fats, carbohydrates, and protein. Mineralocorticoids control the levels of water and electrolytes in the body. Prednisone possesses both glucocorticoid and mineralocorticoid properties and effect. It is generally used as an immunosuppressant; the mechanism of prednisone in fighting immune hemolytic anemia is to suppress the immune system. In most cases, administering prednisone to the patient is enough to help control the anemia effectively, either completely or partially. Therapy has been performed according to the theory, which are given methylprednisolon injectionwith dose 4 mg/kgbw/day, followed by oral methylprednisolon with dose 3 mg/kgbw/day. The dose was still in normal limit dose for therapy and proven to respond well.

Aetiologies Aspec This table represent the most common aetiologies for autoimmune haemolytic anaemia14:

Tabel 1. Aetiologies of autoimmune haemolytic anaemia Autoantibody (incidence)14 Warm antibody AIHA (1:100000) Primary (idiopathic) Secondary Lymphoproliferative disease (lymphoma) Autoimmune diseases (SLE, colitis ulcerosa)
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Acute leukaemia Solid malignancy (ovarian carcinoma) Cold antibody AI HA (1:1000000) Primary (idiopathic): frequently herald of occult lymphoma Secondary Lymphoproliferative disease (M. Waldenstrom, lymphoma) Infection (mycoplasma, EBV) Biphasic haemolysins (rare) Idiopathic Secondary Postviral,siphilis Mixed forms with warm and cold antibodies Idiopathic Secondary Autoimmune diseases (SLE)

Finding an aetologies for this diseases will be helpfull to avoid the recurencies in the future. The causes of AIHA are poorly understood. The disease may be primary, or secondary to another underlying illness. The primary illness was idiopathic (the two terms being used synonymously). Idiopathic AIHA accounts for approximately 50% of cases. 9 Secondary AIHA can result from many other illnesses. Warm and cold type AIHA each have their own more common secondary causes. The most common causes of secondary warm-type AIHA include lymphoproliferative disorders (e.g. chronic lymphocytic leukemia, lymphoma) and other autoimmune disorders (e.g. systemic lupus erythematosis, rheumatoid arthritis, scleroderma, ulcerative colitis). Less common causes of warm-type AIHA include neoplasms other than lymphoid, and infection. Secondary cold type AIHA is also primarily caused by lymphoproliferative disorders, but is also commonly caused by infection, especially by mycoplasma, viral pneumonia, infectious mononucleosis and other respiratory infections. Less commonly, it can be caused by concomitant autoimmune disorders.10 Drug-induced AIHA, though rare, can be caused by a number of drugs, including -methyldopa and penicillin. This is a type II immune response in which the drug binds to macromolecules on the surface of the RBCs and acts as an antigen. Antibodies are
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produced against the RBCs, which leads to complement activation. Complement fragments, such as C3a, C4a and C5a, activate granular leukocytes (e.g. neutrophils), while other components of the system (C6, C7, C8, C9) can either form the membrane attack complex (MAC) or can bind the antibody, aiding phagocytosis by macrophages (C3b). This is one type of "penicillin allergy". From the history taken from the patient, we cannot determine which was the real aeteologies, because we found no drug use history before, and according to the alloanamnesis from the parent, this condition was occur suddenly without any possible cause. One examination that could give us clue, whether this is primary or secondary cause perhaps doing bone marrow pucture that can rule out hematologic malignancy. But we did not perform this prosedure because the patient parent was refused to act.

Prognosis
Autoimmune hemolytic anemia (AIHA) in children is usually characterized by a good prognosis; the disease often presents as anacute, self-limited illness, with good response to short-term steroid therapy in nearly 80% of patients.8 However, in some cases, AIHA can be characterized by a chronic course and an unsatisfactory control of hemolysis, thus requiring prolonged immuno suppressive therapy. Especially in children younger than 2 years of age or in teenagers, the clinical course of the disease may show either resistance to steroids or dependence on high-dose steroids, 2 with sub sequent development of severe side effects on growth, bone mineralization, and the endocrine system. The mortality rate in these children with primary AIHA has been reported to be on the order of 10%.8 The patient was an eight years old girl, respond to short term steroid therapy, so Patients prognosis was quo ad vitam ad bonam, quo ad sanam ad bonam, quo ad fungsionam ad bonam.

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CHAPTER 4 CONCLUSION AND SUGESTION

An eight-year-old girl with pale and fever had been diagnosed with anemia gravis at another hospital, she was admited at referal hospital for 3 days with hemoglobin ( Hb) was 4, she programed for transfusion of red blood cell suspensions, but no blood found suitable for the patient. The patient then being transfer to Kariadi Hospital. At Kariadi hospital admited for 2 times. The first admission, patient was hospitelized for 9 days, recieve transfusion of 9 unit Wash eritrosit, the assesment was cannot be ruled out, waiting for laboratorium confirmation and the patient was discharge. 3 days later the patient return with anemia attack problem, at this time the diagnosis can be ruled out as AIHA and given apropriate therapy using streoid injection for 2 week and tapered for another 2 week with metylprednisolon oral. The patient was improved after therapy and follow up been done with result the patient was in good condition after discharge. Problem was occur when tried to do work up diagnosis, the miss assesestment in the first admission were nearlycausedafatalcondition. Sugestion
1. When dealing with the anemic condition that occurs suddenly, do not forget to

evaluate the state of hemolytic anemia.

2. Diagnosis should be performed simultaneously to prevent the deterioting condition. 3. Using evaluation algorithm can simplify the way we think of diseases.

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PROBLEM SCHEME

A Girl, 8 years old, with AIHA

Destruction of eritrosit

Anaemia Gravis

Incompatibility

Haepatomegaly Icteric pale

Transfusion reaction

Hematologic disorder

Fever

infection

Curative : - Methylprednisolon inj -Antibiotic inj - Care - Love - Stimulation

Promotive Preventive Rehabilitativ ee Optimal growth and development

Evaluation: Respiratory function Kardial function Hematologyc fuction Aeteologyc factor

according to genetic potency

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