This patient is a 34-year-old Filipino man who presented with dizziness, loss of appetite, vomiting, and generalized weakness. His history and lab results are consistent with a diagnosis of aplastic anemia. Aplastic anemia is a bone marrow failure where the production of red blood cells, white blood cells, and platelets is suppressed, leading to pancytopenia. Treatment options include supportive care like transfusions, immunosuppressive drugs, and bone marrow transplant, with outcomes varying based on a patient's age and availability of a histocompatible donor.

1. CASE MANAGEMENT Group 1

2. GENERAL DATA J.G., 34 y/o, male Filipino, from Dagupan City admitted for the first time at PMC on November 2, 2009.

3. INFORMANT: Patient RELIABILITY: 80 % CHIEF COMPLAINT: Dizziness

4. HISTORY OF PRESENT ILLNESS 5 days prior to admission dizziness associated with loss of appetite Vomiting non-billous non-projectile amounting to 5-10 ml per bout. generalized body weakness

5. HPI..cont Few hours PTA Dizziness---px can’t walk and stand alone Consultation --admission

6. Past Medical History Year 2000 Dizziness Philippine General Hospital due ---- diagnosed to have “ Paroxysmal Nocturnal Hemoglubinuria” Medication: Folic acid OD and Vit B6 & B1 OD September 2009 Skin discoloration At Philippine General Hospital Px already had 14x blood transfusion(4-5bags/time)

7. Family History Mother has breast cancer Father has hypertension. 3 siblings have anemia.

8. Social, Personal, and Environmental History P atient is a farmer Lives with his wife and 3 children Alcoholic drinker Smoker

9. Review of system +Dizziness +loss of appetite +Vomiting +generalized body weakness

10. PHYSICAL EXAMINATION SKIN: (+) jaundice HEENT: Pale palpebral conjunctivae ABDOMEN: Globular , liver span - 13cm

11. Vital signs BP - 110/80 mmHg HR - 78 bpm RR - 16 cpm TEM - 36.8 C( upon admission 37.8)

12. Laboratory test

13. Hematology : Parameter Result Normal value Total WBC 2.9 4-10 x 10 9 /L SEGMENTERS 0.39 0.40-0.80 LYMPHOCYTES 0.16 0.20-0.40 MONOCYTES 0.04 0.04-0.10 EOSINOPHILS 0.01 0.02-0.06 Total RBC 0.51 4-6x10 12 /L HEMOGLOBIN 21 140-180g/L HEMATOCRIT 0.06 0.40-0.54 PLATELET 78 150-450 x 10 9 /L

14. Blood chem Result Normal value Urea nitrogen 4.8 mmol/L 2.2-8.2mmol/L Creatinin 1.9 5-17 Phos Alk 32.8 10-35 SGPT 50.9 5-47

15. HBsAg screening Nonreaction

16. What are you impression?

17. APLASTIC ANEMIA

18. DIFFERENTIAL DIAGNOSIS Role out Leukemia--- WBC increased in BM Multiple Myeloma--- plasma cell increased in BM Lymphoma(Hodgkins)--- Lymphocyte increased in BM

19. APLASTIC ANEMIA What happens when the bone marrow shuts down?

20. What is Aplastic Anemia ? - Aplastic Anemia is a bone marrow failure disease .

21. APLASTIC ANEMIA Aplastic anemia is a severe, life threatening syndrome in which production of erythrocytes, WBCs, and platlets has failed. The disease is characterized by peripheral pancytopenia and accompanied by a hypocellular bone marrow.

22. Peripheral blood Smear Peripheral blood Smear

23. HYPOCELLULAR BONE MARROW IN APLASTIC ANEMIA

24. Aplastic Anemia patients Aplastic Anemia patients have decreased amounts of: - Red Blood Cells - White Blood Cells - Platelets

25. Functions of Blood Cells Red Blood Cells Carry oxygen to all body organs White Blood Cells Fight infection and keep you healthy Platelets Help control bleeding

26. Clinical Manifestations Symptoms caused by suppression of any or all bone marrow elements Low Red Blood Cell Fatigue, Headache, Inability to Concentrate, Dyspnea ,Pale skin Low White Blood Cell Frequent or prolonged infections Viral Infections, Bacterial Infections Low Platelets Easy Bruising, Petichiae, Nosebleed and bleeding gums,Prolonged bleeding

27. PATHOGENESIS Stem cell failure resulting from: 1-An acquired intrinsic stem cell defect 2-An environmental cause Immune mechanisms Growth factor deficiency Defects in the microenvironment

28. Pathophysiology of aplastic anemia

29. Epidemiology Incidence: 5-10 persons:10 6 per year Aplastic anemia may occur in all age groups and both genders

30. Etiology : Hereditary 1-Schwacman – Diamond Syndrome 2-Fanconi’s anemia syndrome Autosomal recessive disorder congenital developmental anomalies progressive pancytopenia increase risk of malignancy 3-Dyskeratosis congenita characterized by mucous membrane leukoplasia dystrophic nails, reticular hyperpigmentation development of aplastic anemia during childhood

31. Etiology: Acquired 1-Idiopathic 2- Drugs: dose related idiosyncratic Nonsteroidal analgesics Sulfonamides Thyrostatic drugs Some psychotropics Penicillamine Allopurinol Chlorampenicol

32. Etiology: Acquired 3-Radiation- Damages DNA 4-Chemicals- BENZENE 5-Viruses- Hepatitis – most common 6-Pregnancy 7-PNH ( Paroxysmal Nocturnal Hemoglobinuria ) 8-Disorders of immune system- SLE.

33. What causes Paroxysmal Nocturnal Hemoglobinuria Defect in PIG-A gene which is required for the biosynthesis of cellular anchors, so partial or complete inability to construct Glycosylphosphatidylinositol(GPI) anchor for the attachment of CD55, CD59 Diagnosis: Ham’s test , sucrose hemolytic test , Flow cytometry using antibodies against cell surface antigens CD55, CD59 which are lacking in disease

34. Clinical manifestations of PNH Thrombosis Hepatic vein most common common cause of fatality Cerebral vein thrombosis sagittal sinus in particular Abdominal veins Dermal veins Pulmonary embolism unusual

35. Clinical manifestations of PNH Relative/absolute bone marrow failure present to some degree in all patients relative granulocytopenia/thrombocytopenia decreased capacity to form myeloid colonies Two stage model somatic mutation in PIG-A gene some cause for bone marrow failure

36. Diagnosis of AA: Lab findings Peripheral blood Smear Bone marrow biopsy Pancytopenia Normocytic-normochromic anemia (may be slightly macrocytic) Low reticulocyte index Empty fatty spaces Few hematopoietic cells Lymphocytes and plasma cells Hypocellular bone marrow

37. CLASSIFICATION Designation Criteria PBS BM biopsy Severe aplastic anemia -2 / 3 values- Neutro < 500/  L -Platelets < 20,000/ ul- -Reticulocyte index < 1% -Marked hypocellular < 25% cellularity -Moderate hypocellular <25-50% -normal cellularity with <30% of remaining cell hematopoietic Very severe aplastic anemia As above but neutrophils < 200/  L Infection present

38. Presentation of Anemia, Neutropenia and Thrombocytopenia Hemorrhagic lesion of the gums in a patient with aplastic anemia caused by infection with Capnocytophaga ochraceus; such lesions are easily confused with those of herpes simplex.

39. 26-year-old woman with acute aplastic anemia and 1 day of facial pain/swelling. Mouth open involuntarily due to perioral edema. Needle aspirate of small purplish area near right alar revealed P. aeruginosa.

40. Aplastic anemia. Oral leukoplakia in dyskeratosis congenita.

41. Treatment Options Bone Marrow Transplant Growth Hormones Immune Suppressive Therapy Supportive Care

42. TREATMENT 1-Withdrawal of the etiologic agent 2-Supportive treatment transfusion of the blood products, CMV seronegative should be given transfusion from the family members should be avoided to prevent sensitization. pooled donor platelets but leads to sensitization in refractory cases need HLA matched transfusion packed cells filtrated to remove leukocyte and platelets iron overload : give chelating therapy deferoxamine CMV prophylaxis Staph. Aeureus * hospitalization * menses

43. 3.Allogeneic BMT This is the best therapy for the young patient with a fully histocompatible sibling donor usually indicated for most patients with severe disease. -Preferably from sibling -Curative in 60-90% of patients -Applicable only for a third of patients

44. 4.SPLENECTOMY Removal of the spleen does not increase hematopoiesis but may increase neutrophil increase platelet counts two- to threefold improve survival of transfused red cells platelets in highly sensitized individuals

45. 5.Immunosuppression Antithymocyte globulin(ATG) induces hematologic recovery (independence from transfusion and a leukocyte count adequate to prevent infection. Cyclosporin + ATG Corticosteroids High dose cyclophosphamide 6. G-CSF/ GM-CSF/ EPO **Response rate 50-70% Occurs 2-3 months post Rx.

46. Newer *Mycophenolate mofetil (MMF) - cytotoxic to T cells *Monoclonal Ab against IL-2 receptor which is present on activated lymphocytes

47. Outcomes Age, Younger is better BMT < 20 yr with a sib… 75% 20 - 40 yr with a sib…60% < 20 yr unrelated BMT… 40% 20 - 40 yr unrelated BMT…35% Immunosuppression - 60 - 80%

49. Thank you ?