Kelsey, Jen, Matt G, Jeremy, Nichole, Ryan, Sue CPC Case 6 Kelsey, Jen, Matt G, Jeremy, Nichole, Ryan, Sue

History 7 year old male Paternal aunt died of leukemia at age 29 Short thumbs since birth All vaccines up to date Symptoms starting 3 weeks prior Pale Lethargy leading to decreased activity No weight loss No appetite change Mother denies cough, fever, vomiting, sweats, or diarrhea

Physical Exam Brown Macules on hands Short thumbs observed bilaterally HEENT Exam: Unremarkable Chest: Lungs clear HR 118: Normal (60-100bpm) sinus tachycardia without gallops rubs or murmurs Temp: 38.5C (101.3F) Low grade fever BP: 120/72

Brown Macules

Differential Diagnosis?

Differential Diagnosis Hypothyroidism Infection Leukemia Anemia Sickle Cell Anemia Spherocytosis Childhood Depression

Hypothyroidism Yes: No: Fatigue-sleeping more Small thumbs Constipation Rough dry skin Short stature Headaches Vision problems

TSH ($58) Normal: not hypothyroidism

Differential Diagnosis Hypothyroidism Infection Leukemia Anemia Sickle Cell Anemia Spherocytosis Childhood Depression

CBC ($41) Test Normal Range Result Quick look Platelet Count 150 - 400 89 low Hemoglobin 13 - 18 8.4 Hematocrit 43 - 52 31 RBC 4.2 - 5.9 3.4 RDW 11 - 15 16 high MCV 70 - 100 104 WBC 3.4 - 10.7 low?

Infection Most commonly respiratory and urinary WBC not elevated No respiratory symptoms No UTI symptoms WBC not elevated

Leukemia Low RBC Low hematocrit No: Low hemaglobin Weight loss Normal WBC

Differential Diagnosis Hypothyroidism Infection Leukemia Anemia Sickle Cell Anemia Spherocytosis Childhood Depression

Anemia Low RBC Low hemaglobin Low hematocrit What type?

Iron ($61) Normal: Not anemia of chronic disease Not iron deficient anemia

Peripheral Blood Smear Anemia Peripheral Blood Smear Run Reticulocyte # test If normal retic values, check MCV If Increased: think hemolytic MCV results: Decreased Normal Increased Fe deficiency thallassemia Anemia of chronic disease Aplastic Anemia - Folate/B12 deficiency (Pernicious anemia) Indication:

Peripheral Blood Smear ($81) Normal or negative Rules out: Sickle cell anemia Spherocytosis: mild anemia with RBC spherically shaped

BLOOD SMEAR Sickle Cell Anemia Crescent Shaped RBC Megaloblastic Anemia Large RBC B12 deficiency Spherocytosis Hereditary, mild anemia Small RBC lacking light center BLOOD SMEAR

Peripheral Blood Smear Anemia Peripheral Blood Smear Run Reticulocyte # test If normal retic values, check MCV If Increased: think hemolytic MCV results: Decreased Normal Increased Fe deficiency thallassemia Anemia of chronic disease Aplastic Anemia - Folate/B12 deficiency (Pernicious anemia) Indication:

Reticulocyte Count ($24) Normal: Not a hemolytic anemia

Peripheral Blood Smear Anemia Peripheral Blood Smear Run Reticulocyte # test If normal retic values, check MCV If Increased: think hemolytic MCV results: Decreased Normal Increased Fe deficiency thallassemia Anemia of chronic disease Aplastic Anemia - Folate/B12 deficiency (Pernicious anemia) Indication:

Folate ($0)/B12 ($40) Since the MCV was high: Folate: Normal B12: normal- not severe pernicious anemia

Peripheral Blood Smear Anemia Peripheral Blood Smear Run Reticulocyte # test If normal retic values, check MCV If Increased: think hemolytic MCV results: Decreased Normal Increased Fe deficiency thallassemia Anemia of chronic disease Aplastic Anemia - Folate/B12 deficiency (Pernicious anemia) Indication:

Bone Marrow Biopsy ($300) Due to low platelets, RBC and WBC Markedly hypocellular for age (5%) all cell lines present in decreased numbers; no atypical infiltrates or granulomas identified. Indicates anemia Would indicate leukemia if WBC precursors were high and other precursors were low

markedly hypocellular for age (5%) all cell lines present in decreased numbers; no atypical infiltrates or granulomas identified.

Causes of Aplastic Anemia Autoimmune disorder Benzene radiation Drugs such as: Chloramphenical, carmizapine Viral hepatitis Systemic lupus Idiopathic Congenital – Fanconi’s

Cytogenetics ($0) Multiple chromosomal breaks and chromatin fragments Confirms fanconi which inhibits DNA repair mechanisms resulting in breaks in the chromosomes

Cytogenetics Cytogenetic analysis of peripheral blood lymphocytes shows multiple chromosomal breaks and chromatid fragments

Fanconi or Constitutional Aplastic Anemia Most common form of aplastic anemia Inherrited autosomal recessive Other family members should be tested Light brown lesions-Café a lait Skeletal abnormalities, especially thumbs Hepatosplenomegdally not present Development of cancers is common due to an inability to repair DNA Could have been the cause of his aunt’s leukemia

Treatment Cytokine therapy Palogenic stem cell transplants Cyclophosphamide Radiation No pets, antiseptic soaps, contact sports due to lack of platelets Prevention: vaccinations are immportant to avoid infections

Summary of Tests Bone marrow-aspirate and biopsy ($300) Complete blood count ($41) Cytogenetics ($0) Folate ($0) Iron ($61) Peripheral Blood Smear ($81) Reticulocyte count ($24) Thyroid stimulating hormone ($58) Vitamin B12 ($40) Total cost $604

Question 1 You should get a bone marrow biopsy: Any time you suspect anemia When there are decreased RBC When all cells are decreased Never

Question 2 Aplastic Anemia can be caused by: Spontanious and unknown causes Congenital changes Viral Hepatitis All of the above

Question 3 Precautions you should advice patients with Fanconi to take include: No pets Antiseptic soaps No contact sports All of the above

Question 4 A cytogenics test was ordered in order to confirm fanconi which: Spontaneously causes mutations in DNA Makes repair enzymes over reactive Inhibits repair mechanisms Lyses cells

Question 5 The reticulocyte count is typically _____ and the MCV is typically ____ in aplastic anemia. High, low Low, high Normal, high Normal, normal