Maria Reyna- Xavier University Hospital Department of Pediatrics

Calang, Caryl Vin Feril, Jonhrey Sanchez, Irene

 General: To present a case of aplastic anemia Specific: To identify and diagnose aplastic anemia based on clinical presentation To discuss differential diagnoses of aplastic anemia To discuss the epidemiology, etiology, pathophysiology, diagnosis, prognosis and treatment of aplastic anemia

A.P. 11 8/12 old Male Filipino Muslim Marantao, Lanao del Sur

 Fever (Tmax 38C) Paracetamol (16.7mg/kg/dose)

 Fever Body weakness Pallor Dizziness Anorexia

 Fever Body weakness Pallor Dizziness Anorexia

 Headache Nausea and vomiting Gum and lip bleeding Fast breathing

CBC and Blood typing Chest X-ray APL Na+ and K+ Urinalysis IgG and IgM TyphiDot

CBC and Blood Typing

Result Reference Range

WBC
RBC Hematocrit

3.1
1.2 11

4.50-13.50 x 109/L
3.69-5.90 x 1012/L 35 45 %

Hemoglobin
Platelet Count Neutrophils

3.4
26 54

11.50 25.50 gm/ L

150 390 x 109/L 37 - 72%

Lymphocytes
Monocytes Blood Typing

42
4

20 50%
8 - 14%

Type O Rh positive

ANC

1,674

Chest X-ray APL

Chest X-ray Hazy densities at the retrocardiac area. Heart is normal in size. Trachea is at the midline. Diaphragm and costophrenic sulci are unremarkable. Bony thoracic cage appears intact.
Impression

Blood Chemistry
Result Reference Range

Na+

142.5

135 - 155 mg/dL

K+

4.22

3.5 - 5.3 mmol/L

Serology

IgG ang IgM TyphiDot Negative

Urinalysis
Result Physical Examination Color Transparency Chemical Parameters Specific Gravity pH Sugar Protein Microscopy WBC RBC Epithelial Cells Reference Range

Yellow Clear

1.000 5.0 Negative Negative

0 1/hpf 0 1/hpf Rare 0 2/hpf 0 2/hpf 0 2/hpf

 Tranexamic Acid (8 mg/kg/dose) Vitamin K 1 amp IV Penicillin G IV drip (103,333 mg/kg/day)

 Blood Transfusion 1 unit FWB (1st unit) CBC 6 hours post BT

CBC
Result Reference Range

WBC
RBC Hematocrit

2.9 (3.1)
1.8 (1.2) 17 (11)

4.50-13.50 x 109/L
3.69-5.90 x 1012/L 35 45 %

Hemoglobin
Platelet Count Neutrophils

5.5 (3.4)
21 (26) 58 (54)

11.50 25.50 gm/ L

150 390 x 109/L 37 - 72%

Lymphocytes
Monocytes ANC

39 (42)
3 (4) 1,682 (1,674)

20 50%
8 - 14%

 Blood Transfusion 1 unit FWB (2nd unit) CBC 6 hours post BT

CBC
Result Reference Range

WBC
RBC Hematocrit

3.6 (2.9)
2.5 (1.8) 23 (17)

4.50-13.50 x 109/L
3.69-5.90 x 1012/L 35 45 %

Hemoglobin
Platelet Count Neutrophils

7.5 (5.5)
31 (21) 25 (58)

11.50 25.50 gm/ L

150 390 x 109/L 37 - 72%

Lymphocytes
Monocytes ANC

69 (39)
6 (3) 900 (1,674)

20 50%
8 - 14%

 fever and gum bleeding subsided The condition persisted

 Blood Transfusion 1 unit FWB (3rd unit) CBC 6 hours post BT

CBC
Result Reference Range

WBC
RBC Hematocrit

3.1 ( 3.6)
3.70 ( 2.5) 34 ( 23)

4.50-13.50 x 109/L
3.69-5.90 x 1012/L 35 45 %

Hemoglobin
Platelet Count Neutrophils

11.3 ( 7.5)
102 ( 31) 31 ( 25)

11.50 25.50 gm/ L

150 390 x 109/L 37 - 72%

Lymphocytes
Monocytes ANC

61 ( 69)
8 ( 6) 961 (900)

20 50%
8 - 14%

 Blood Transfusion 1 unit FWB (4th unit) Gum and lip bleeding Epistaxis

 Condition persisted Referred

Headache Nausea and vomiting Body weakness Anorexia Pallor Dizziness Fast breathing

 Birth History born to a 40y G10P10, via NSD at home, attended by a hilot Birth rank 4/10 Growth and Development sit at 7 mos talk at 12 mos walk at 14 mos Grade IV student

 Medical Conditions/Past Illnesses/Hospitalizations 2003 (3y) Inguinal Hernia (Iligan City) = herniorrhaphy, left Feb 2012 (11y) Dengue Fever (Amai Pakpak Hosp) No known food and drug allergies Immunization BCG1; Hepatitis B 1, 2, 3; DPT 1, 2, 3; OPV 1, 2, 3; measles; MR

(+) hypertension (+) diabetes mellitus (-) asthma (-) PTB exposure (-) hematologic diseases (-) cancer

 General: (-) change in weight (+) fatigue Skin: (-) jaundice (+) dryness Head: (-) injury or trauma

Eyes: (-) pain (-) diplopia (-) blurring vision Ears: (-) tinnitus (-) discharges (-) difficulty hearing Nose and Sinuses: (-) nasal stuffiness and congestion

 Throat and Mouth: (-) frequent sore throat (-) dry mouth and hoarseness (-) dysphagia Neck: (-) pain, stiffness (-) swelling Respiratory: (-) wheezing (-) cough Cardiovascular: (-) palpitations (-) orthopnea

Gastrointestinal: (-) heart burn (-) hematochezia (-) melena (-) constipation Genitourinary: (-) nocturia and urinary frequency (-) gross hematuria Peripheral Vascular: (-) claudication (-) leg cramps

 Musculoskeletal: (-) limitation of ROM (-) muscle pain (-) joint stiffness Neurologic: (-) memory loss (-) fainting, seizures (-) tingling sensation and tremors

Endocrine and Metabolic: (-) heat or cold intolerance (-) excessive thirst or hunger Mental Status: (-) change in mentation (-) depression (-) anxiety

 Conscious, coherent, not in respiratory distress, in pain

Blood Pressure: Pulse Rate: Respiratory Rate: Temperature: O2 Sat

100/60 mmHg 112 beats/min 32 cycles/min 36.8 C 100%

Height: Actual Weight: BMI:

112 cm 30 kg 23.9 kg/m2 (z-score 2)

 pale. No jaundice and cyanosis. Nail beds are pale without clubbing. (+) petechial rashes at abdomen Skin is cold and dry with good skin turgor. Capillary refill Time: <2 seconds. No signs of tenderness.

 Head Skull is normocephalic without any deformities. No lumps and lesions.

 Ears No discharges, foreign bodies and swelling of the ear canal. No signs of tenderness. No lumps or masses.

 Eyes Anicteric sclerae. Pale palpebral conjunctivae

 Nose and Sinuses No alar flaring. No bleeding and discharges. No sinus tenderness.

 Mouth and Throat Lips are dry, pale with blood clots and cracks. Pale oral mucosa with no ulcerations and lesions. Pale gums with blood clots. Uvula and tongue at midline with no deviation and lesions. Tonsils are not swollen.

Supple. No cervical lymphadenopathies.

Symmetrical chest. No intercostal retractions and use of accessory muscles. Equal chest expansion. Resonant on all LF. Clear breath sounds on all lung fields. No rales nor wheezes.

Adynamic precordium. No palpable thrills and heaves. Tachycardic at 112 beats per minute with regular rhythm. Distinct S1 and S2. No murmurs.

Flat with umbilicus in midline. No hernias and visible veins. No visible peristalsis and pulsations. Normoactive bowel sounds at 16 clicks per minute. No bruits heard. Tympanitic in all quadrants. No shifting dullness. No tenderness on light and deep palpation. No palpable masses. Nonpalpable spleen and kidneys.

No costovertebral angle tenderness.

No deformities, atrophies and clubbing. No signs of joint and muscle tenderness. Good range of motion on all joints.

No peripheral edema. Full pulses. CRT<2s

Responds appropriately to stimuli. No observable mannerisms, in pain. Conscious. Oriented to time, place and person.

 Rapid alternating movements - not assessed Romberg test - not assessed Pronator drift - not assessed Gait - not assessed (-) nystagmus

Negative Kernig and Brudzinski signs.

 CN I: Not assessed CN II: Both pupils brisk and equally reactive to light and accomodation. Positive direct and consensual light reflex on both eyes. Pupils constricting from 4mm to 3mm in diameter. (+) multiple retinal hemorrhages, OU CN III, IV, VI: No ptosis and nystagmus. Extraocular movements intact. CN V: Can open and close mouth.

 CN VII: Able to wrinkle forehead, frown, and close both eyes without facial deviation. CN VIII: Able to hear whispered and spoken words on both ears. CN IX, X: Positive gag reflex. CN XI: Able to turn head left and right against resistance. CN XII: Tongue and uvula at midline.

 Symmetric muscle bulk with good tone. No fasciculation, atrophy and tremors. Weakness at left lower extremities
Able to respond to light touch.

 Negative Babinski reflex.

+ +

History 11 y.o., male, Filipino Fever Body weakness Dizziness, headache Anorexia, nausea and vomiting Gum and lip bleeding, epistaxis Dyspnea No history of injury/trauma No family history of hematologic d/o and cancer No previous exposure to chemotherapy or radiation therapy

Physical Examination Drowsy, weakness Tachypneic Pallor (+) petechial rashes at abdomen (+) blood clots at gum areas and lower lip area (-) organomegaly (+) multiple retinal hemorrhages, OU Hyperreflexia, left lower extremities Weakness at left lower extremities

History 11 y.o., male, Filipino Fever Body weakness Dizziness, headache Anorexia, nausea and vomiting Gum and lip bleeding, epistaxis Dyspnea No history of injury/trauma No family history of hematologic d/o and cancer No previous exposure to chemotherapy or radiation therapy

Physical Examination Drowsy, weakness Tachypneic Pallor (+) petechial rashes at abdomen (+) blood clots at gum areas and lower lip area (-) organomegaly (+) multiple retinal hemorrhages, OU Hyperreflexia, left lower extremities Weakness at left lower extremities

History 11 y.o., male, Filipino Fever Body weakness Dizziness, headache Anorexia, nausea and vomiting Gum and lip bleeding, epistaxis Dyspnea No history of injury/trauma No family history of hematologic d/o and cancer No previous exposure to chemotherapy or radiation therapy

Physical Examination Labs: CXR Retrocardiac pneumonia Na 143.5, K 4.22 CBC prior to BT WBC : 3.1 x109/L RBC : 1.2 x1012/L Hct : 11% Hgb : 3.4 g/L Differential Count Neutrophils : 54% Lymphocytes : 42% Monocytes : 4% Platelet Count : 26 x109/L ANC = 1,674 HBsAg Nonreactive Typhidot Negative

History 11 y.o., male, Filipino Fever Body weakness Dizziness, headache Anorexia, nausea and vomiting Gum and lip bleeding, epistaxis Dyspnea No history of injury/trauma No family history of hematologic d/o and cancer No previous exposure to chemotherapy or radiation therapy

Physical Examination Labs: CXR Retrocardiac pneumonia Na 143.5, K 4.22 CBC prior to BT WBC : 3.1 x109/L RBC : 1.2 x1012/L Hct : 11% Hgb : 3.4 g/L Differential Count Neutrophils : 54% Lymphocytes : 42% Monocytes : 4% Platelet Count : 26 x109/L ANC = 1,674 HBsAg Nonreactive Typhidot Negative

Nathan and Oskis Hematology of Infancy and Children, 6th Edition

Aplastic anemia Inherited bone marrow failure Hypoplastic myelodysplastic syndrome Virus-associated aplastic anemia

Nathan and Oskis Hematology of Infancy and Children, 6th Edition Harrisons Principles of Internal Medicine, 17th Edition

Myelodysplasia Paroxysmal nocturnal hemoglobinuria Myelofibrosis Myelophthisis Bone marrow lymphoma Hairy cell leukemia
Nathan and Oskis Hematology of Infancy and Children, 6th Edition Harrisons Principles of Internal Medicine, 17th Edition

SLE, Sjgren syndrome Hypersplenism Vit B12 or folate deficiency Overwhelming infection Storage disease Alcoholism Sarcoidosis, Brucellosis, Tuberculosis, Leishmaniasis
Nathan and Oskis Hematology of Infancy and Children, 6th Edition Harrisons Principles of Internal Medicine, 17th Edition

Leukemia Hemophagocytic lymphohistiocytosis Fanconi Anemia Metastatic solid tumors Osteopetrosis Myelofibrosis

Nathan and Oskis Hematology of Infancy and Children, 6th Edition Harrisons Principles of Internal Medicine, 17th Edition

Pancytopenia
History and PE
History/Laboratory evidence of: CBC with differential Peripheral smear

Reticulocyte count Sickle cell anemia Thalassemia Heridetary Spherocytosis

Transient aplastic crisis (parvovirus)

At least 2 of the ff: WBC<500/uL Platelets<20,000/uL Reticulocytes<1%

Severe aplastic anemia

Mild/moderate aplastic anemia

Sickle cell anemia Thalassemia Heridetary Spherocytosis

Transient aplastic crisis (parvovirus)

At least 2 of the ff: WBC<500/uL Platelets<20,000/uL Reticulocytes<1%

Severe aplastic anemia

Mild/moderate aplastic anemia (hypoplastic anemia) Repeat in 2-3 weeks

Referral to hematologist Bone marrow studies

Normal CBC

Transient aplastic crisis (parvovirus)

WBC<500/uL Platelets<20,000/uL Reticulocytes<1%

Severe aplastic anemia

Mild/moderate aplastic anemia (hypoplastic anemia) Repeat in 2-3 weeks

Referral to hematologist Bone marrow studies

Normal CBC

Idiopathic

Infectious agents

Congenital

Rule In
Body weakness Dizziness, headache Anorexia, nausea and vomiting Gum and lip bleeding, epistaxis Dyspnea Drowsy, tachypneic Pallor (+) petechial rashes at abdomen (+) blood clots at gum areas and lower lip area (+) multiple retinal hemorrhages Pancytopenia

Rule Out
No family history of hematologic disorders and cancer No skin nodules No previous exposure to chemotherapy or radiation therapy Cannot be totally ruled out

Rule In
Fever Body weakness Dizziness, headache Anorexia, nausea and vomiting Gum and lip bleeding, epistaxis Dyspnea Drowsy, tachypneic Pallor (+) petechial rashes at abdomen (+) blood clots at gum areas and lower lip area (+) multiple retinal hemorrhages Pancytopenia

Rule Out
No organomegaly Nonreactive HBsAg serology Negative Typhidot serology

Rule In
Body weakness Dizziness, headache Anorexia, nausea and vomiting Gum and lip bleeding, epistaxis Dyspnea Drowsy, tachypneic Pallor (+) petechial rashes at abdomen (+) blood clots at gum areas and lower lip area (+) multiple retinal hemorrhages Pancytopenia

Rule Out
No organomegaly No previous exposure to chemotherapy or radiation therapy Cannot totally rule out

Rule In
Body weakness Dizziness, headache Anorexia, nausea and vomiting Gum and lip bleeding, epistaxis Dyspnea Drowsy, tachypneic Pallor (+) petechial rashes at abdomen (+) blood clots at gum areas and lower lip area (+) multiple retinal hemorrhages Pancytopenia (-) organomegaly

Rule Out
No previous exposure to chemotherapy or radiation therapy Cannot totally rule out

ON ADMISSION

On admission
Diet as tolerated, no dark-colored food IVF of 1 L PNSS at KVO CBC, U/A, CT Scan Brain Plain Initial medications:
Paracetamol 250/5, AD:12.5 mkdose

COMPLETE BLOOD COUNT

PARAMETER Total WBC Total RBC Hemoglobin Hematocrit MCV MCH MCHC Platelet Count Differential Count Neutrophils Lymphocytes Monocytes Eosinophils Basophils RDW-CV ANC L 36.9 H 52.8 9.2 0.7 0.4 0.5 1033 % % % % % % 37.0 72.0 20.00 50.00 8.0 14.0 0.00 6.00 0.0 1.00 11.5 14.5 RESULT L 2.8 L 2.46 L 7.20 L 19.5 79.3 29.30 36.9 L 27 UNIT x 109/L x 1012/L g/dL % fL Pg g/dL x 109/L REF. RANGES 4.50 11.00 3.69 5.90 13.50 17.50 41.00 53.00 80.0 100.0 26.10 33.30 31.0 37.0 150 390

 Transfuse 3 units of platelet concentrate and 1 unit of PRBC Medications:

Tranexamic Acid 500mg IVTT, 16.6 mkdose

Cranial CT Scan

Cranial CT Scan
Radiologist Linear densities are seen in the right temporal lobe,both frontal and both parietal lobes. There is effacement of the sulci at the right temporo-parietal lobes Neurologist Multiple Intracranial parenchymal bleed secondary to bleeding dyscrasias with increased intracranial pressure

Subarachnoid Hemorrhage, Right Temporal, Both Frontal and Both Parietal Lobes

1ST HOSPITAL DAY

Problem # 1:

T/C Aplastic Anemia

Problem # 1: T/C Aplastic anemia

(+) epistaxis (-) hematemesis (-) gum bleeding

Problem # 1: T/C Aplastic anemia

conscious, coherent
BP : 110/70 HR : 86 RR : 23 Temp. : 37.1C

Problem # 1: T/C Aplastic anemia

Skin: Brown, no lesions HEENT: Anicteric sclerae Pale conjunctivae Pale lips

Problem # 1: T/C Aplastic anemia

Chest and Lungs: Clear breath sounds Equal chest expansion
Heart: Distinct heart sounds Normal rate & regular rhythm

Problem # 1: T/C Aplastic anemia

Abdomen: Soft and nontender normoactive bowel sounds
Ext: Full pulses CRT< 2 secs

URINALYSIS
PARAMETER Physical Examination Color Transparency Chemical Parameters Yellow Turbid RESULT

Specific Gravity
pH

1.010
8.0

Sugar
Protein

Negative
Negative

PARAMETER
Microscopic/Urine Flowcy WBC RBC Epithelial Cells Cast Bacteria

RESULT

UNIT

REF. RANGES

1 59 3 0 6,922

/hpf /hpf /hpf /lpf /hpf

0 2/hpf 0 2/hpf 0 2/hpf 0 3/lpf 0 20/hpf

Problem # 1: T/C Aplastic anemia

Day 13 of illness Afebrile Not tachypneic

Problem # 1: T/C Aplastic Anemia

Pharmacologic
Tranexamic Acid 500 mg IV q 8
Diphenhydramine 50 mg cap Paracetamol 325mg, 1 tab Transfuse 3 units of platelet concentrate
Q 4 T 37.8 PRN for headache

Problem # 1: T/C Aplastic Anemia

Non-pharmacologic
Diagnostics
CBC, UA with hyphal elements Chest XRAY

Supportive care
Trauma precaution Limit visitors

Problem # 2:

Intracranial Bleed

Problem # 2: Intracranial Bleed (-) headache (-) vomiting (-) dizziness (-) blurring of vision

Problem # 2: Intracranial Bleed

conscious, coherent BP : 110/70 HR : 86 RR : 23 Temp. : 37.1C

Problem # 2: Intracranial Bleed

Skin: Brown, no lesions HEENT: Anicteric sclerae Pale conjunctivae Pale lips

Problem # 2: Intracranial Bleed Chest and Lungs: Clear breath sounds Equal chest expansion
Heart: Distinct heart sounds Normal rate & regular rhythm

Problem # 2: Intracranial Bleed Abdomen: Soft and nontender normoactive bowel sounds
Ext: Full pulses CRT< 2 secs

Problem # 2: Intracranial Bleed Neurologic: GCS 15 conscious, coherent no observable mannerisms perception logical Motor 5/5 upper ext, 4/5 lower ext Sensory intact Cranial nerves intact

Problem # 2: Intracranial Bleed

No neurologic deficits GCS 15

Problem # 2: Intracranial Bleed

Pharmacologic
Tranexamic Acid 500 mg IV q 8 Lactulose 20 cc at bedtime Diazepam 5mg IVTT PRN Paracetamol 325mg, 1 tab
Mannitol 100cc q 6 Q 4 T 37.8 PRN for headache

Problem # 2: Intracranial Bleed

Non-pharmacologic
Diagnostics
U/A

Supportive care
Avoid emotional stresses Elevate head of bed at 30 Trauma precaution Limit visitors

2ND HOSPITAL DAY

Problem # 1:

T/C Aplastic Anemia

Problem # 1: T/C Aplastic Anemia

(-) epistaxis (-) hematemesis (-) gum bleeding

Problem # 1: T/C Aplastic Anemia

conscious, coherent BP : 90/60 HR : 85 RR : 25 Temp. : 36.4C

Problem # 1: T/C Aplastic Anemia

Skin: Brown, no lesions HEENT: Anicteric sclerae Pale conjunctivae Pale lips

Problem # 1: T/C Aplastic Anemia

Chest and Lungs: Clear breath sounds Equal chest expansion
Heart: Distinct heart sounds Normal rate & regular rhythm

Problem # 1: T/C Aplastic Anemia

Abdomen: Soft and nontender normoactive bowel sounds
Ext: Full pulses CRT< 2 secs

COMPLETE BLOOD COUNT

PARAMETER Total WBC Total RBC Hemoglobin Hematocrit RESULT L 2.2 L 2.55 L 7.80 L 21.50 UNIT x 109/L x 1012/L g/dL % REF. RANGES 4.50 11.00 3.69 5.90 13.50 17.50 41.00 53.00

MCV
MCH MCHC Platelet Count

84.3
30.60 36.3 21

fL
Pg g/dL x 109/L

80.0 100.0
26.10 33.30 31.0 37.0 150 390

Differential Count
Neutrophils Lymphocytes Monocytes Eosinophils Basophils RDW-CV ANC L 20.5 H 70.7 L 7.4 1.4 0.0 13.7 451 % % % % % % 37.0 72.0 20.00 50.00 8.0 14.0 0.00 6.00 0.0 1.00 11.5 14.5

URINALYSIS
PARAMETER Physical Examination Color Transparency Chemical Parameters Specific Gravity pH Sugar Protein 1.010 7.0 Negative Negative Yellow Turbid RESULT

PARAMETER
Microscopic/Urine Flowcy

RESULT
0
0 0 0 18

UNIT
/hpf
/hpf /hpf /lpf /hpf

REF. RANGES
0 2/hpf
0 2/hpf 0 2/hpf 0 3/lpf 0 20/hpf

WBC
RBC Epithelial Cells Cast Bacteria

NEGATIVE FOR HYPHAL ELEMENTS

CHEST XRAY
Heart is normal in size. Lung fields are clear Hemidiaphragms and sulci are intact. Negative Chest XRAY

Problem # 1: T/C Aplastic Anemia

No episodes of bleeding
Risk for infection and bleeding tendencies

Problem # 1: T/C Aplastic Anemia

Pharmacologic
Tranexamic Acid 500 mg IV q 8 Diphenhydramine 50 mg, 1 cap

Transfuse 1 unit of PRBC

Problem # 1: T/C Aplastic Anemia

Non-pharmacologic
Diagnostics
BMA CBC

Supportive care
Trauma precaution Limit visitors

Problem # 2:

Intracranial Bleed

Problem # 2: Intracranial Bleed

(-) headache (-) vomiting (-) dizziness (-) blurring of vision

Problem # 2: Intracranial Bleed

conscious, coherent
BP : 90/60 HR : 85 RR : 25 Temp. : 36.4C

Problem # 2: Intracranial Bleed

Skin: Brown, no lesions HEENT: Anicteric sclerae Pale conjunctivae Pale lips

Problem # 2: Intracranial Bleed

Chest and Lungs: Clear breath sounds Equal chest expansion
Heart: Distinct heart sounds Normal rate & regular rhythm

Problem # 2: Intracranial Bleed

Abdomen: Soft and nontender normoactive bowel sounds
Ext: Full pulses CRT< 2 secs

Problem # 2: Intracranial Bleed

Neurologic: conscious, coherent no observable mannerisms perception logical Motor 5/5 upper ext, 4/5 lower ext Sensory intact Cranial nerves intact

Problem # 2: Intracranial Bleed

Bleeding probably did not progress. GCS 15

Problem # 1: Intracranial Bleed

Pharmacologic
Tranexamic Acid 500 mg IV q 8 Lactulose 20 cc at bedtime Diazepam 5mg IVTT PRN Mannitol 100 cc q 6 Paracetamol 325mg, 1 tab
Q 4 T 37.8 PRN for headache

Problem # 2: Intracranial Bleed

Non-pharmacologic
Diagnostics
CBC

Supportive care
Avoid emotional stresses Elevate head of bed at 30 Trauma precaution Limit visitors

3RD HOSPITAL DAY

Problem # 1:

T/C Aplastic Anemia

Problem # 1: T/C Aplastic Anemia

(-) epistaxis (-) hematemesis (-) gum bleeding

Problem # 1: T/C Aplastic Anemia

conscious, coherent
BP : 110/70 HR : 84 RR : 22 Temp. : 36.8C

Problem # 1: T/C Aplastic Anemia

Skin: Brown, no lesions HEENT: Anicteric sclerae Pink conjunctivae Pink lips

Problem # 1: T/C Aplastic Anemia

Chest and Lungs: Clear breath sounds Equal chest expansion
Heart: Distinct heart sounds Normal rate & regular rhythm

Problem # 1: T/C Aplastic Anemia

Abdomen: Soft and nontender normoactive bowel sounds
Ext: Full pulses CRT< 2 secs

Bone Marrow Aspiration

Panhypocellular Marrow Aplastic anemia

Bone Marrow Aspiration

hypocellular bone marrow with fatty replacement and relatively increased nonhematopoietic elements, such as plasma cells and mast cells

Bone Marrow Aspiration

hypocellular bone marrow with fatty replacement and relatively increased nonhematopoietic elements, such as plasma cells and mast cells

COMPLETE BLOOD COUNT

PARAMETER Total WBC Total RBC Hemoglobin Hematocrit RESULT L 2.7 L 3.49 L 10.90 L 29.30 UNIT x 109/L x 1012/L g/dL % REF. RANGES 4.50 11.00 3.69 5.90 13.50 17.50 41.00 53.00

MCV
MCH MCHC Platelet Count

84.00
31.2 37.2 20

fL
Pg g/dL x 109/L

80.0 100.0
26.10 33.30 31.0 37.0 150 390

Differential Count
Neutrophils Lymphocytes Monocytes Eosinophils Basophils RDW-CV ANC L 22.1 H 65.1 L 12.1 0.7 0.0 13.1 596.7 % % % % % % 37.0 72.0 20.00 50.00 8.0 14.0 0.00 6.00 0.0 1.00 11.5 14.5

Blood Chemistry
PARAMETER CREA UREA Nitrogen RESULT L 0.38 L 18 UNIT mg/dL mg/dL REF. RANGES 0.8-1.3 19-44

Problem # 1: Aplastic Anemia

Reduction below normal levels of platelets, neutrophils and lymphocytes.

Problem # 1: Aplastic Anemia

Pharmacologic
Cyclsoporine 100mg, 1 tab PO BID Folic Acid 1 ml, OD Prednisone 10 mg, 1 tab OD

Problem # 1: Aplastic anemia

Non-pharmacologic
Diagnostics
CBC with reticulocyte count

Supportive care
Avoid emotional stresses Elevate head of bed at 30 Trauma precaution Limit visitors

Problem # 2:

Intracranial Bleed

Problem # 2: Intracranial Bleed

(+) headache (-) vomiting (-) dizziness (-) blurring of vision

Problem # 2: Intracranial Bleed

conscious, coherent
BP : 110/70 HR : 84 RR : 22 Temp. : 36.8C

Problem # 2: Intracranial Bleed

Chest and Lungs: Clear breath sounds Equal chest expansion
Heart: Distinct heart sounds Normal rate & regular rhythm

Problem # 2: Intracranial Bleed

Abdomen: Soft and nontender normoactive bowel sounds
Ext: Full pulses CRT< 2 secs

Problem # 2: Intracranial Bleed

Neurologic: conscious, coherent no observable mannerisms perception logical Motor 5/5 upper ext, 4/5 lower ext Sensory intact Cranial nerves intact

Problem # 2: Intracranial Bleed

Day 13 of illness

afebrile
No neurologic deficits noted

Problem # 2: Intracranial Bleed

Pharmacologic
Tranexamic Acid 500 mg IV q 8 Lactulose 20 cc at bedtime Diazepam 5mg IVTT PRN Mannitol Paracetamol 325mg, 1 tab
Q 4 T 37.8 PRN for headache

Problem # 2: Intracranial Bleed

Non-pharmacologic
Diagnostics
CBC with reticulocyte count

Supportive care
Avoid emotional stresses Elevate head of bed at 30 Trauma precaution Limit visitors

 a physiologic and anatomic failure of the bone marrow

marked decrease or absence of blood-forming elements in the marrow pancytopenia

congenital or acquired

Incidence rate ~ 2 per 1,000,000 persons per year Frequency 15-25 years old then 65-69 years old Prevalence Far East Multifactorial
genetic predisposition chloramphenicol in Asia (?) poorly regulated exposure of workers to benzene impure water use in Thailand (infectious?)

Male:Female incidence ratio ~ 1

 Severe aplastic anemia

bone marrow cellularity < 25% 2 of the ff cytopenias: granulocyte count < 500/mm3 <200 mm3 very severe AA platelet count < 20,000/mm3 reticulocyte count < 20,000/mm3

 exposure to an inciting antigen, cells and cytokines of the immune system destroy stem cells in the marrow pancytopenia -interferon (-IFN)

Acquired Autoimmune Drugs Toxins Viruses PNH

Autoimmune/CTD Thymoma Pregnancy Iatrogenic Hereditary

 T cells
secrete -IFN and TNF
potent inhibitors of both early and late HPC suppress hematopoiesis mitotic cycle apoptosis

secrete IL-2
polyclonal expansion of the T cells activation of the Fas receptor apoptosis

 -IFN
mediates hematopoietic suppressive activity through IRF-1
inhibits the transcription of cellular genes and their entry into the cell cycle

induces production of the toxic gas NO

additional toxic effects on the HPC

 Direct cellcell interactions

oligoclonal expansion of CD41 and CD81 T cells genetic predisposition to marrow failure

 Immunosuppressive therapy an unexpected improvement in pancytopenia was observed in aplastic anemia patients following failure of engraftment in allogeneic bone marrow transplantation the need for immunosuppressive preparative therapy was realized for successful engraftment in about half of hematopoietic stem cells in identical twin bone marrow transplantation performed for aplastic anemia

 Final common pathway decrease in blood cell formation in the marrow

marrow CD34+ cells (multipotential hematopoietic progenitors) colony-forming unitgranulocyte-macrophage (CFUGM) burstforming uniterythroid (BFUE) long-term culture-initiating cells

 Potential mechanisms (acquired)

1. direct toxicity to hematopoietic multipotential cells 2. a defect in the stromal microenvironment of the marrow required for hematopoietic cell development 3. impaired production or release of essential multilineage hematopoietic growth factors 4. cellular or humoral immune suppression of the marrow multipotential cells 5. progressive erosion of chromosome telomeres

 Little evidence for

stromal microenvironmental defect deficit of critical hematopoietic growth factors telomerase mutations with consequent telomere shortening

Autoimmunity
cytotoxic T-cell-mediated immune suppression of very early CD34+ hematopoietic multipotential progenitor or stem cells reduced hematopoiesis

Toxic exposure Drug exposure Viral infection

 Idiopathic - 70% Secondary Incidence: 2 per million per year M:F ratio -1:1

 Acquired AA
gradual, symptoms related to pancytopenia
anemia thrombocytopenia leukopenia

No hepatosplenomegaly/lymphadenopathy

Anemia Reticulocytopenia Leukopenia Thrombocytopenia Fetal hemoglobin

 Bone marrow:
marked depression or absence of hematopoietic cells replacement by fatty-tissuecontaining reticulum cells, lymphocytes, plasma cells and usually tissue mast cells

Chromosomal analysis Bone marrow cultures Chromosome breakage assay Flow cytometry (CD59) Telomere length

Liver function chemistries Renal function chemistries Viral serology testing Quantitative immunoglobulins, C3, C4 and complement Autoimmune disease evaluation HLA typing

 Supportive Care

 Supportive Care Specific Therapy Hematopoietic stem cell transplantation (HSCT) Immunosuppressive Therapy

 Recommendations
Moderate aplastic anemia:
Observe with close follow-up and supportive care

If the patient develops:

Severe aplastic anemia Severe thrombocytopenia with significant bleeding Chronic anemia requiring transfusion treatments Serious infections severe aplastic anemia

 Recommendations
Severe aplastic anemia:
Allogeneic bone marrow transplantation when HLA-matched sibling donor available In the absence of an HLA-matched sibling marrow donor: ATG, cyclosporine A (CSA), methylprednisolone and growth factors

 Recommendations
Severe aplastic anemia:
If no response or waning of response and recurrence of severe aplastic anemia HLA-matched matched unrelated bone marrow, peripheral blood or umbilical cord blood transplantation High-dose cyclophosphamide and cyclosporine therapy without stem cell transplantation

 Antithymocyte globulin
ATGAM anti-thymocyte globulin Thymoglobulin

Methylprednisolone Prednisone
taper following an 8-day course of IV methylprednisolone

G-CSF CSA
continued for one year then decrease the dose

 Contraindications
Serum creatinine > 2 mg% Concurrent pregnancy Sexually active females who refuse contraceptives Concurrent hepatic, renal, cardiac, or metabolic problems

 Adverse reactions
thrombocytopenia headache, myalgia arthralgia, chills and fever chemical phlebitis itching and erythema Leukopenia Serum sickness

 Principal side effects

renal dysfunction tremor hirsutism hypertension gingival hyperplasia

 Uncommon side effects

significant hyperkalemia hyperuricemia hypomagnesemia hepatotoxicity lipemia CNS toxicity gynecomastia.

Contraindications
Hypersensitivity to CSA

 human recombinant granulocyte colony stimulating factor (G-CSF)

stimulates granulopoiesis

1. Survival rates are greater than 90% with either immunosuppressive therapy or stem cell transplantation 2. Immunosuppressive therapy improves hematopoiesis and achieves transfusion independence in the majority of patients 3. Clonal hematopoietic disorders including PNH, myelodysplasia and leukemia may develop in up to 10% of patients treated with immunosuppressive therapy (IST).

 Moderate Aplastic Anemia

supportive therapy with very close follow-up progression treat as severe anemia