A CASE OF APLASTIC ANEMIA WITH

CRBSI IN ESRF
Presented by: Muhammad Ridhwan Hakim B Zainurin
Reviewed by: Cik Nabilah Husna binti Aziz
◦ Aplastic anemia is a rare and heterogeneous disorder. It is defined as pancytopenia
with a hypocellular bone marrow in the absence of an abnormal infiltrate or marrow
fibrosis.
◦ Pancytopenia, most often idiopathic.
(Sally et al 2015, BJH Guidline) .
Severe Classification (Camitta criteria)
Severe Aplastic anemia Non-Severe Aplastic Anemia
◦ 2-of 3 Blood count criteria ◦ Not fulfilling any of other criteria
Very severe aplastic Anemia
◦ ANC neutrophil count <200u/L
Ref:Neal 2018, The new england journal of medicine

ANC* Platelets ARC* BM cellularity

< 500/uL < 20,000/uL < 40,000/uL < 25% for age
◦ Bone marrow biopsy shows
hypocellular marrow without
abnormal cells.
1. Radiation & Chemotherapy treatments
• Use to kill cancer cells, also damage healthy cell (stem cell)

2. Exposure to chemical
• Solvents (benzene)
• Industrial pesticides (Organophosphates & carbamate)

3. Use of certain drug

• Antibiotic ( cephalosphorine, dapsone)
• Other drug(chloramphenicol, carbamazepine, felbamate, phenytoin, quinine, and phenylbutazone )

4. Viral infection
• Hepatitis, cytomegalovirus, parvovirus

5. Autoimmune disorder
• Immune system attack stem cell (SLE)
• thymoma

6. Genetic defect
• Fanconi anemia, telomere disease and other germline mutation

Idiophatic
• Unable to identify cause
 •Chest pain
•Fatigue
Low HB (Anemia) •Shortness of breath
•Dizziness
•Pallor

•Fever
Low WBC •Infection
(Leukopenia) •Flu-like illness

•Prolong bleeding
Low Platelet •Easy bruising
(Thrombocytopenia •Red spot
. Full blood count
• Pancytopenia. Usually the haemoglobin concentration and neutrophil and platelet counts are uniformly depressed.
In the early stages, isolated cytopenia, particularly thrombocytopenia, may occur or monocytopenia may occur .

Reticulocyte count
• Reticulocytopenia; automated reticulocyte counting will over-estimate the count compared with the levels set in the
Camitta criteria (Camitta, 1984) for defining disease severity, which were defined on manual counts.

Blood film examination

• Frequent macrocytosis and anisopoikilocytosis. Neutrophils may show toxic granulation. Platelets are mainly small in
size. Exclude presence of dysplastic neutrophils, abnormal platelets, blasts and other abnormal cells, such as ‘hairy’
cells

Hb Fetal%
• HbF; measure pre-transfusion in children – important prognostic factor in children. Note that the level is often
elevated in constitutional syndromes

Peripheral blood chromosomal breakage analysis: diepoxybutane test (DEB Test)

• For possible Fanconi Anemia if patient aged <50 years, but it would also be indicated to screen older patients if FA is
clinically suspected.
Vitamin B12 and folate
• Documented vitamin B12 or folate deficiency should be corrected before a final diagnosis of AA is confirmed.
• Bone marrow aplasia due to vitamin deficiency is exceedingly rare

Liver function tests

• Liver function tests should be performed to detect antecedent/on-going hepatitis

Viral studies: hepatitis A/B/C, EBV, CMV, HIV and Parvovirus

• AA due to hepatitis is rare, it usually occurs 2–3 months after an acute episode of hepatitisIn post-hepatic AA the
serology is often negative for the known hepatitis viruses.
• CMV should be assessed if SCT is being considered. Anti-nuclear antibody and antidouble stranded DNA

Pancytopenia in systemic lupus erythematosus may

• (i) be autoimmune with a cellular bone marrow

• (ii) with a hypocellular marrow

Chest X-ray and other radiology

• Useful at presentation to exclude infection and for comparison with subsequent films.
• X-rays of the hands, forearms and feet may be indicated if an IBMFS is suspected.

Abdominal ultrasound scan and echocardiogram

• An enlarged spleen and/or lymph nodes raise the possibility of a malignant hematological disorder as the cause
of the pancytopenia.
• In younger patients, abnormal or anatomically displaced kidneys are features of FA
1. Direct progenitor cell death due to marrow toxins (benzene)
2. Underlying Hematopoietic Stem Cell abnormality
– Post Immunosuppression(meds), low stem cell persist and
macrocytosis may not return to normal
– Late clonal abnormalities
3. Immunologic destruction of hematopoietic stem cells
– Clinical response to immunosuppressive therapies
4. Fault in the genetic stem cells making it unable to divide and
differentiate sufficiently to produce the blood cells.

Ref: Neal 2018, The new england journal of medicine

◦1. Stem cell transplant (hematopoietic
stem cell transplantation)
◦2. Immunosuppressant
◦3. Blood transfusion
◦4. Bone marrow stimulant (ESA)
◦5. Antibiotics & antiviral
◦6. Eltrombopag (refractory aplastic
anemia)
◦7. Androgen
Ref: Neal 2018, The new england journal of medicine
Ref:Neal 2018, The new england journal of medicine
Ref:Neal 2018, The new england journal of medicine
CASE PRESENTATION
 Patient’s Information

Malay, Female
56 years old
(~50 kg)

WARD 8F

Date of admission:
27/7/19

Date of discharged:
Mrs. IS 21/8/19
CHIEF COMPLAINTS
Elective admission for tenckoff insertion

HISTORY OF PRESENTING COMPLAINTS

Fever
Pedal edema up to midshin
Previous history of CRBSI 9-23/7/2019
PAST MEDICAL HISTORY PAST MEDICATION HISTORY
1. ESRF for LTP CAPD T. Folic acid 1/1 OD
-- temporary HD T Vitamin b complex 1/1 OD
-- under f/up visiting specialist at HHT T. Ferrous fumarate 400mg OD
2. HPT T. Calcium carbonate 1g TDS
3. HPL
3. Gout
4. Anemia
SOCIAL HISTORY COMPLIANCE ALLERGY
• Married Good compliance to medication NKDA
• Prev: farming work -never miss dose
• Non Smoker
• Non Alcoholic
 Vital signs charting

Blood pressure
200 Fluid overload
Blood pressure (mmHg)
150

100

50
Hemodialysis
0

13/8.
27/7
29/7
31/7
2/8.
4/8.
6/8.
8/8.
10/8.
11/8.

15/8.
17/8.
19/8.
21/8.
Date Systolic BP
Diastolic BP
 Pulse rate
100

0
20
40
60
80

27/7
29/7
31/7
2/8.
4/8.
6/8.
8/8.
Pulse Rate

Date

10/8.
11/8.
Vital signs charting

13/8.
15/8.
17/8.
19/8.
21/8.
 Vital signs charting
Temperature
41
Temperature (degree

Tab Paracetamol
1g STAT Tab Paracetamol 1g STAT

40 Tepid sponging

39
celcius)

38

37 IV Cloxacillin
1g QID Temperature
36
IV Piperacillin / Tazobactam 2.25g QID IV Meropenam 500mg OD
27/7
28/7
29/7
30/7
31/7
1/8.
2/8.
3/8.
4/8.
5/8.
6/8.
7/8.
8/8.
9/8.
10/8.
11/8.
12/8.
13/8.
14/8.
15/8.
16/8.
17/8.
18/8.
19/8.
20/8.
21/8.
Date
1.Cover for catheter related blood
stream infection (CRBSI)
2.Pancytopenia sec to hematological
malignancy(aplastic anemia)
3.Underlying of hypertension, and
hyperlipidemia
LAB INVESTIGATION
FULL BLOOD COUNT
15/1/1 1/8 5/8 8/8 12/8 14/8 18/8 21/8
8 20/1/18 9/7 23/7 27/7 D1 29/7 D3 D6 2/8 D7 D10 D13 D17 D18 D23 D16

4-11x109/L
WBC 2.40 4.4 3.6 2.6 2.4 2.7 3.4 2.3 1.6 3.3 2.9 2.9 3.9
11.5-
16.5g/100mL
HB 81 68 53 76 75 68 79 56 86 77 64 68 62 76
150-400x
109/L
PLT 75 109 131 119 134 111 63 44 43 29 58 106 115 122

BASO 0.5-2.0% 0 0.4 0.2 0.6 0.4 0.8 0.7 0.3 0.4 0 0 0.4 0 0.3

EOSI 1.0-6.0% 0 10.7 1.6 7.60 8 6.4 0 0.6 15.1 11 0 0 0 0

LYMP 20.0-40.0% 51.5 23.9 16.8 19.7 23 22.9 20.4 27.6 24.9 29.9 28.9 45.6 33.3 17.1

MONO 2.00-10.00% 36.4 31.3 8.9 18.3 13.4 15.3 4.8 4.9 15.1 15.2 12.5 17.2 20.7 23.9

NEUT 40.0-80.0% 12.1 33.7 72.5 53.8 55.2 54.6 74.1 66.6 44.5 43.9 58.6 36.8 46 58.7

ANC 2.0 – 7.0 x109/L 0.04 0.24 4.83 2.22 6.66 3 2 0.72 1.78 1.93 1.33 1.05 1.31 2.26
 31/7 D5
Erythrocytes Severe anaemia. Normochromic
normocytic RBC. RBC anisocytosis.
Some crenated cells. Occasional
elliptocytes. No RBC agglutination or
spherocytes seen. No polychromasia.
Leucocytes Leucopenia. No blast cells.
Platelets Thrombocytopenia. No platelet
clumps.
Comment Pancytopenia for investigation. To
relate clinically.
Suggestion For Bone Marrow Aspiration/ Trephine
Biopsy if clinically indicated.
Impression: Aplastic anemia
14/8 D19
Normochromic normocytic
anaemia, some macrocytes, burr
cells, elliptocytes,
Leucopenia, no suspicious cell.
Thrombocytopenia, no platelet
clumping.
Pancytopenia for investigation.
To relate clinically.
To review bone marrow
aspiration and trephine biopsy.
 BM Aspiration 6/8-15/8
Interpretation Hypocellular marrow. To
consider secondary
causes eg: infection,
drugs, autoimmune
disease.

Suggestion To review trephine

biopsy.

BM Aspiration 6/8
Interpretation Status -Arrived-

Impression: Aplastic anemia

 Normal 16/1/ 20/1/ 7/7 23/7 27/7 30/7 1/8 5/8 6/8 7/8 8/8 15/8 16/8
level 18 18 D1 D3 D5 D10 D11 D12 D13 D20 D21
Urea 1.7-8.3 32.1 26.4 52.9 18.5 26.5 27.9 4.9 18.3 8.8 14 17.8 5.3 6.6
mmol/L
Na 135-145 138 113 136 136 134 132 134 134 133 132 135 134
mmol/L
K 3.5-5.0 4.2 null 4.8 3.9 5.2 5.2 2.9 3.6 3.4 3.6 3.8 3 3
mmol/L
Cl 96-106 110 112 86 103 105 102 98 99 99 98 98 100 99
mmol/L
SCr 64-122 522 439 1358 774 1153 1277 368 827 489 690 881 280 420
μmol/L
ClCr 105-150 8.37 9.95 3.22 5.64 3.78 3.42 11.8 5.28 8.93 6.33 4.96 15.6 10.4
mL/min
 Normal 27/7 5/8 6/8 8/8 11/8 12/8 16/8 17/8
range 20/7 21/7 D1 D10 D11 D13 D16 D17 D 21 D22
10-13.5
PT sec 13.1 14.9 13.9 14.8 14.2 12.8 12 13.1 12.7 12.1
26-42
APTT sec 51.3 45.7 46.2 55 56.6 52.9 52.7 180 53 51.7
INR 0.96 1.13 1.03 1.13 1.07 0.94 0.85 0.96 0.92 0.87

5/8 D10 4/8 D9

Vitamin >1200 Uibc 27.8-63.6 <10.0

B12
folate >15 >54.6 TIBC 44.1

Ferritin 11.0-306 >1500 Iron 10.7-32.2 34.1

TSAT 77%
LIVER PROFILE
Normal level 15/1/ 30/7 1/8 2/8 4/8 5/8
18 D10 D12 D13 D15 D16
Serum Albumin 35-52g/L 29 25 23

ALP 53-141 61 78 74 2250 1218 633

u/L
ALT <45 u/L 49 158 81 121 92 84

AST <75 u/L 31 14 148 117 74

7/8 Ultrasound Hepatobiliary: simple right liver cyst

 Range 11/7 23/7 29/7 2/8 11/8
CRP <1 61.9 11.2 8.7 40.5 32.8

Impression: High indicates sign of infection

range 4/8 COOMB’S test 5/8

Reticulocyte count 0.2-6% 0.6 Direct Antiglobulin test Positive (+2)

Indirect Antiglobulin test negative

TRO: Hemolytic anemia

 CULTURE AND SENSETIVITY TEST
Sampling Result Source M/organism Sensitivity Resistance
Date Date

28/7 1/8 Blood Aerobe No Growth N/A N/A

D2 D6 (Peripheral, Red, Blue)
2/8 8/8 Blood Aerobe No Growth N/A N/A
D7 D13 (Peripheral, Red, Blue)
2/8 6/8 Sputum ESBL Ertapenam
D6 D11 Klebsiella pneumonia
6/8 13/8 Bone marrow No Growth N/A N/A
D11 D18
7/8 13/8 Blood Aerobe No Growth N/A N/A
D12 D18 (Peripheral, Red, Blue)

14/8 21/8 Sputum Multiresistance Polymycin B Meropenam

D19 D26 organism Ciprofloxacin Piperacillin/
Acinetobacter spp tazobactam
WARD MEDICATION
 MEDICATION DATE START DATE STOP INDICATION REMARKS
IV Piperacilin/ Tazobaactam 4.5mg CRBSI
28/7 4/8
STAT/ 2.25mg QID
CRBSI
IV Cloxacillin 1g QID 2/8 5/8
CRBSI Due to temperature
IV Meropenam 500mg OD 4/8 5/8
spiking
C Fluconazole 200mg OD 4/8 7/8 CRBSI empirical for fungal
IV Piperacilin/ Tazobaactam 4.5mg CRBSI
5/8 7/8
STAT/ 2.25mg QID
EBSL Klebsiella
IV Meropenam 500mg OD 7/8 20/8
Pneumonia
T Paracetamol 1g STAT/ TDS 28/7 2/8 Spiking temperature

T Ferrous Fumarate 400mg OD 2/8 DC Anemia

T Folic Acid 5mg OD 2/8 DC Anemia

T Vitamin B Complex 1/1 OD 2/8 DC Anemia

T Calcium Carbonate 500mg BD 2/8 DC Phosphate binder

S/C EPO (Recormon) 2000u 2x week 31/7 19/8 Anemia

S/C EPO (Recormon) 4000u 2x week 19/8 DC Anemia

C. Danazol 200mg OD 14/8 DC Aplsatic anemia

T. Frusemide 80mg OD 20/8 DC Fluid overload

PHARMACEUTICAL
CARE ISSUE
Aplastic Anemia
Goal of therapy Management based on EBM Management in Ward

1. To improve signs Based on Guidelines for the diagnosis and management of C. Danazol 200mg OD
and symptoms
adult aplastic anemia T. Ferrous fumarate 400mg OD
2. To prevent Elderly patients with AA should be individually assessed and T. Folic acid 5mg OD
complications their specific wishes respected, as quality of life is paramount in T. Vitamin B complex 1/1 OD
this patient group. 1 pint of Pack Cell
• Immunosuppressive therapy IST is considered the treatment of 1 pint of platelets
choice. Anti –thymocyte globulin (ATG) and Cyclosporin(CsA) S/C Erythropoetin Beta
result in a more rapid recovery of blood counts but, (Recormon)2000-4000 3xweek
alternatively, CSA alone or oxymetholone can be considered.
Patients unfit for, who decline or who are intolerant of IST
should be offered best supportive care.
(Sally et al 2015, BJH Guideline) .

However for patient lacking both, human leukocyte antigen

(HLA) -matched donor and access to immunosuppressive
therapy(IST), were treated with danazol and modern support
therapy shows response rate of 46% remission. Thus remains an
acceptable therapeutic option for AA patients.
(Jaime et al 2011, Annals of Hematology) .
Management based on EBM Management in Ward

Based on KDOQI Clinical Practice Guidelines and Clinical C. Danazol 200mg OD

Practice Recommendations for Anemia in Chronic Kidney Disease T. Ferrous fumarate 400mg OD
Management of anemia in patients with CKD with preexisting hematologic disorders associated with T. Folic acid 5mg OD
anemia may present specific problems because of multifactorial causes. In some patients, anemia may T. Vitamin B complex 1/1 OD
result predominantly from low indogenous erythropoietin levels and can be corrected readily by 1 pint of Pack Cell
administration of ESAs. In other disorders, impaired marrow function, ineffective erythropoiesis, and 1 pint of platelets
shortened red blood cell survival may contribute to anemia and ESA hyporesponsiveness. S/C Erythropoetin Beta
(Recormon)2000-4000 3xweek
For supportive therapy,(Blood product support)
• Blood transfusions should be given to improve quality of life and symptoms.
• Transfusion of platelets. Regular platelet transfusion support may be required for AA patients. The need
for iron chelation therapy should be decided on an individual patient basis.
• Haemopoietic growth factors. Haemopoietic growth factors, such as erythropoiesis-stimulating agents
and granulocyte colony-stimulating factor (G-CSF), are usually ineffective in supporting blood counts
in AA patients.
(Sally et al 2015, BJH Guideline) .
Catheter Related Blood
Stream Infection
(CRBSI)
Goal of therapy Management based on EBM Management in Ward

1. To eradicate Based on IDSA guideline, It is recommended that initiation of broad IV Piperacillin/ Tazobactam
infectious 2..25mg QID
spectrum antibiotic for empiric therapy should cover both Gram
organisms
positive and Gram negative organisms. IV Cloxacillin 1 g QID

2. To improve signs
and symptoms
3. To prevent
complications
Possible microbes
Gram-negative bacilli
Klebsiella spp
Acinetobacter spp
Pseudomonas aeruginosa
Escherichia coli
Coagulase-negative Staphylococcus
Staphylococcus aureus
(Methicillin sensitive or resistant)
Enterococcus faecalis
(Ampicillin sensitive or resistant)
Enterococcus faecium
(Vancomycin sensitive or resistant
-For Gram positive organisms, Vancomycin should be initiated until
culture and sensitivity result is available.
• Loading Dose: 25-30 mg/kg, and subsequent doses based on TDM. (target
level: 15-20 mcg/ml)
• 1st Gen cephalosporin, Cefazolin can be used in the setting of low
prevalence of MRSA already given (2/52) in previous admission.
-For Gram negative organisms, 3rd Gen cephalosporin, carbapenem
and b-lactam/b-lactamase combination can be used.
• IV Ceftazidime 1g OD already given (5/7) in previous admission .
Renal Pharmacy Handbook 3rd Edition, 2018
Based on Malaysia Guide To Antimicrobial Therapy In ICU 2017
The empirical therapy (non renal dose) is
IV Cefepime 2g q8h or IV Piperacillin/ Tazobactam 4.5g q6h (
PLUS
IV Cloxacillin 2g q4h
With optional of IV Fluconazole as anti fungals
Management based on EBM Management in Ward

IV meropenam spectrum cover for aerobic gram positive, negative and anaerobes Pt temperature cont to spike,
C. Fluconaole for possible fungal infection as temperature spiking is unsettled. thus change to Iv Meropenam
All empirical theraphy is given Culure and Sensetivity (C+S) result is obtained 500mg OD(1day only), and
revert back IV Piperacillin/
Duration:
Tazobactam 2..25mg QID and
At least 2 weeks. 4-6 weeks in persistent fungemia and bacteremia (<72 hours) after
add C. Fluconazole 200mg OD
catheter removal or with suppurative thrombophlebitis
Changing to definitive antibiotic therapy should be done based on C+S results, and duration
based on organisms. -Sputum C+S showed ESBL
MSSA: 3 weeks Klebseilla pneumonia sensitive
MRSA: 3 weeks to Ertapenem. Treatment
Fungal: 2 weeks after negative culture change to definitive/ pathogen
Monitoring parameter: specifc -IV Meropenem 500 mg
Clinical signs and symptoms OD for 2 weeks duration
Vital signs(Temp)
WBC

Renal Pharmacy Handbook 3rd Edition, 2018

Reference: Malaysia Guide To Anti
Microbial Therapy 2017
Reference: IDSA 2009
DRUG RELATED
PROBLEM
Date Issue Recommendatiion Status

5/8 Polypharmacy of IV Cloxacillin and IV To discontinue IV Iv Cloxacillin is

Meropenam Cloxacillin immediately discontinued.

IV Cloxacillin is not discontinued upon

starting IV Meropenam
7/8 Inappropiate choice of antibiotic To change IV Tazosin to IV Meropenam is started
IV Meropenam
based on C+S result Klebsiella pneumonia immediately
EBSL (6/8)
Pt still on IV tazosin and febrile

21/8 Inappropriate drugs. To withhold double missedPt discharged

Latest serum hematinics -inform MO regarding
-iron intervention
-folate
-vitamin B 12
Are high and pt still on double hematinics
◦ Patient is discharged with ◦ Patient looking well
◦ T. Calcium carbonate 1g BD ◦ Able to ambulate herself
◦ Cap. Danazol 200mg OD ◦ For TCA at Hosp Hulu Terennganu
◦ T. Ferrous fumarate 400mg OD ◦ 24/8 wound inspection
◦ 1/9 CAPD Traning
◦ T. Folic acid 0.5mg OD
◦ T. Vitamin B complex 1/1 OD
◦ T. Frusemide 40mg OD
◦ T. Colchicine 0.5mg OD
Counselled patient and caretaker on CKD
PT currently on supported HD, Long term plan for CAPD

1. General information of kidney

◦ Functions
◦ Factors of failure
◦ Complication of CKD
2. Types of renal replacement therapy
◦ Hemodialysis
◦ Peritoneal dialysis
◦ Renal transplant
3. Drug therapy in CKD (indication, administration and possible side effects)
4. To reduce intake of foods with high phosphate such as canned foods, and condensed milk.
5. Importance of adherence to fluid restriction and medication
6. Discourage use of traditional/herbal medicines
1. Renal Pharmacy Handbook 3rd Edition, 2018

2. Sally et al 2015, British Journal of Heamatogy Guidline

3. Aplastic Anemia, 2018, Neal S. Young, The new england journal of medicine.

4. Danazol as first line therapy for aplastic anemia, Jaime –perrez ,2011, Annals of Hematology

5. Drug Information Handbook. 27th Edition.

6. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Anemia in
Chronic Kidney Disease

7. Ioannou, S., Hatzis, G., Vlahadami, I., Voulgarelis, M.(2010),Aplastic anemia associated with
interferon alpha 2a in a patient with chronic hepatitis C virus infection: a case report. J Med
Case Rep. 4(268)
THANK YOU