PEDIATRIC CASE REPORTS

Stefanus Gunawan
Hemophilia Treatment Center
RD Kandou Hospital
Faculty of Medicine Sam Ratulangi University

CASE 1

JL, Minahasan, male, 3 months

Referred from surgeon
Prolonged bleeding + Post-op cleft-lip

PRIOR DATA (PRE-OP)

Hb 13.1 g/dl
Hct 37.9 %
WBC 8.400/mm3
Plt 589.000/mm
BT 9 (N:3-10 )
CT 6 (N:4-10 )

FURTHER EXAMINATION

No history of bleeding
No family history

PHYSICAL FINDINGS

Compos mentis
7.2 kg; 62 cm
good nutrition
BP 80/50 mmHg
Pulse 100 bpm,
regularly
Respiratory 30 x/m
Temperature
36.6C

Anemic (-)
Upper Lip:
bleeding from
surgical site
Thorax &
Abdomen: no
abnormality
Skin: no bruising

LAB FINDINGS

After consultation:
Hb 11.1 g/dl
Hct 34.9 %
WBC 7900/mm3
Plt 446,000/mm3
PT 12 (10.8-14.4); INR 1.02
aPTT 65 (26.4-37.6)
FVIII 2.3%

Assessment
Mild-bleeding postop labioschizis e.c
Haemophilia A
(moderate)

Treatment
Factor VIII: 20
IU/kgbw/12hr
Tranexamic acid
50mg/kg/dy
Wound care

FOLLOW UP

No more bleeding after 2 days

Discharged

COST ANALYSIS IN JKN*

F VIII
Bleeding type

PASIEN

Target
desired
level
(%)

Weight
(kg)

# Faktor
VIII
needed
(IU)

40

7.2

560

FVIII cost

Tariff (INACBG+Top up)

B class
Hospital Reg3

Balance

Surgery (Minor)
Bleeding
Dy 1-2

2,500,000

10,444,300
#

7,944,300#

(excl. other medicines

& service)

LEARNING POINT

Elective surgery
Comprehensive medical history including
family history should be taken
Hemostatic screening test if indicated
CBC,

Blood smear
aPTT, PT
CT not sensitive
Rapaport SI. Blood.1983;61: 229-231
Chee YL et al. Br J Haematol.2008;140:496-504
Laine C et al.Ann Intern Med.2009;151:ITC1-1
10

CASE 2

LS, male, Chinese, 5 years

Diagnosed as hemophilia from 1 yr (FVIII IU)
Prolonged

wound healing

Hemophilia A (moderate) + phimosis

Need to circumsized

11

PEDIGREE

12

PHYSICAL FINDINGS

Compos mentis
29 kg; 130 cm
good nutrition
BP 100/70 mmHg
Pulse 80 bpm,
regular
Respiratory 24 x/m
Temperature 36C

Anemic (-)
Thorax & Abdomen
no abnormality
detected
Extremity no
hemarthrosis
Genital: phimosis

13

LABORATORY FINDINGS

Hb 13.1 g/dl

Hct 37.9 %
WBC 8400/mm3

Plt 589,000/mm3

PT12.9
(10.8-14.4)
INR 1.02
aPTT 66.7 (26.437.6)
Factor VIII 2%

14

Assessment: Hemophilia A (moderate) +

phimosis, pro circumcision

Planning
Advocation to board of director
F VIII replacement pre-post circumcision

15

FOLLOW UP &
FVIII REPLACEMENT SCHEME

-1 hr: F VIII 750 IU (25 IU/Kgbw)

0 hr: circumcision done
+1 hr: no bleeding
F

VIII 750 IU/12 hour (25 IU/Kgbw)

Tranexamic acid 3 x 500 mg IV
Amoxicillin 3 x 500 mg P.O
Wound care

+5 hr: bleeding (oozing) R/F VIII 750 IU (25

IU/Kgbw)

16

FOLLOW UP &
FVIII REPLACEMENT SCHEME

Day +1
Bleeding (+)
F VIII 50 IU/kgbw/12 hr (1500IU)
Wound dressing+Tranexamid acid
Day +2
No more bleeding
FVIII 25 IU/kg/12hr, others cont
Day +3
No bleeding discharged
Tranexamic acid p.o only
17

LEARNING POINT

WFH Protocol for circumcision

Alternative protocols

18

CIRCUMCISION IN HEMOPHILIA
WFH 2003

12 hrs prior to
surgery
Oral tranexamic
acid 25-30
mg/kg/day
7
days

2 hrs prior to
surgery
F VIII 20 U/kg
(25 U/kg for
severe cases)*, IV
bolus

Surgery
+ 10 mg/kg
tranexamic acid (or
0.3 mcg/kg DDAVP
infusion for mild
cases)

*Double doses for

hemophilia B

19

8 & 16 hrs after

surgery:
F VIII 10 U/kg (12.5
U/kg for severe cases)

Day 2-3#: F VIII 15

U/kg/day bid + DDAVP
for mild, 25 U/kg/day
tid for moderate, 40
U/kg/day qid for severe
cases

#Hemophilia B, double
doses of factor are used
twice, but DDAVP is not
used
20

SEVERE & MODERATE CASES

Day 4-7: severe*: F

VIII 30 U/kg/day tid
moderate: 20
U/kg/day tid#

Day 8-10: severe: 20

U/kg/day bid
moderate: 10
U/kg/day bid# +
DDAVP

*Severe hemophilia B, day 4-7:

double doses twice; day 8-14: once,
& every other day thereafter
#Moderate Hemophilia B, double
doses, without DDAVP

Day 11-14:
severe: 10
U/kg/every
other day
moderate: 10
U/kg/every
other day#

21

MILD CASES

Day 4: F VIII
15 U/kg/day
tid

Day 5-7:
10 U/ kg/day
bid + 1 dose
DDAVP

Thereafter,
10 U/kg/every
other day,
once or twice

*Double doses for

hemophilia B, once,
without DDAVP
22

WFH GUIDELINES
ON MINOR SURGERY (2012)
SUGGESTED PLASMA FACTOR PEAK LEVEL AND DURATION OF ADMINISTRATION
(WHEN THERE IS SIGNIFICANT RESOURCE CONSTRAINT)
Hemophilia A
Desired level
(IU/dL)
Pre-op

40-80

Post-op

20-50

Hemophilia B
Duration (days)

Desired level
(IU/dL)

Duration (days)

40-80
1-5^

20-50
^

1-5^

depends on type of procedure

23

ALTERNATIVE PROTOCOLS

Izmir protocol (Turkey)

Oral tranexamic acid, fibrin glue
5 doses factor concentrate
Level of 90-100%: 1 h before
operation, then at 12 h
Level of 50-60%; 24h, 36h, 48h
discharge
Outcome: 3/50 (6%) bleeding
Yilmaz D, et al. Haemophilia 2010;16:888-91.
24

24 h before circumcision: Oral

tranexamic acid 15 mg/kg, tid for 7
days
1 h before surgery, FVIII 40 IU/kg
Repeat same dose at 12 h after
surgery, day 2-10, once/day
Nafil H, et al. Med Sante Trop. 2013;23:111-2.

25

2 doses of FVIII concentrate (25

U/kg), 1 hour before circumcision, 1
hour before removal of dressing
Gelatin sponge
Outcome: 1/25 bleeding, no
additional risk to develop inhibitor
Elalfy MS, et al. Pediatr Hematol Oncol 2012;29:485-93.

26

Enhancing local hemostasis: risk

of postoperative bleeding, less
factor consumption
Fibrin

glue
Gelatin sponge
(Glubran) skin tissue adhesive
Haghpanah S et al. Ann Hematol. 2011;90:463-8.

27

SARDJITO HOSPITAL/GAJAHMADA UNIVERSITY

PROTOKOL PEMBERIAN AHF PADA OPERASI SIRKUMSISI
PADA PENDERITA HEMOFILIA A
BB.kg

Nama # MR Umur....thn/bln
Kadar factor VIII =.%

Inhibitor (tgl pemeriksaan)

Jikamasihperdarahan

Hari

H0

H+1

H+2

H+3

H+4

H+5

H+6

Tanggal
Jam

Tranexamic acid,
iv, bolus

- 30
mnt

Operasi

+ 12

+ 24

+ 36

+ 48

+ 60

+ 72

+ 84

15 mg/kg=...........mg

AHF, iv bolus
25 U/kg=.....U

PROTOKOL DAPAT DIUBAHSESUAI KONDISI PERDARAHAN

Supervisor

Dokter yangmerawat

28

COST ANALYSIS IN JKN*

PWH
Bleeding type
Weight
(kg)

Tariff (INA# Faktor FVIII total cost CBG+Top up)

B class Hospital
VIII
Reg-3
needed/kg
(IU)

Deficit

Circumcision
WFH 2012
(minor surgery)
Sarjito/UGM
Patient

30

120(-290)

17,500,000

225
200

33,600,000
28,800,000

19,859,600
-8,940,400

29

WFH RECOMMENDATIONS:
CIRCUMCISION OF PWH

Should not be considered as a minor procedure

Should not be performed without taking adequate
precautions
All necessary laboratory tests should be done
to

confirm factor deficiency

level of factor
presence of inhibitors

Informed consent
Blood products (FC, PRC, FFP, etc)
Other medications (tranexamic acid, DDAVP, analgesics,
antibiotics, etc)
Generally risk of postoperative bleeding in PWH 15-20%
30

CASE 3

DJ, male, 10 yrs,Gorontaloneese

Refered from Ampana Hospital Central

Sulawesi: 24 hrs by land
Chief complaint: unconscious

31

HISTORY

Head trauma
Hit bedhandle
Dy
Vomit
Weakness
-7
right limb

Hospitalised
Ampana
Dy
Less conscious
Seizure
-6
R/FVIII 750IU
once

Arrived
RDK
Dy 0Unconsciou
s
No seizure

32

PEDIGREE

33

PHYSICAL FINDINGS

Severe ill, GCS 9 (E2M6V1)

30 Kg; 131cm good nutrition
BP 110/70 mmHg
Pulse 124 bpm, regular
Respiratory 24 x/m, thoracoabd
Temperature 38.2C

34

PHYSICAL FINDINGS

Anemic (-), icteric (-)

Pupil round, isochors, 3-3 mm, reflex +/+
Thorax (heart, lung) & Abdomen: NAD
Extremity warm, CRT < 2
Motoric 1 5
1

Physiologic reflexes /N
Pathologic reflex: +/+
Spastic (-), clonus (-)

35

LABORATORY FINDINGS

Hb 13.1 g/dl
Hct 38.2 %
WBC 12,900/mm3
Plt 560,000/mm3
PT 12.3 (10.8-14.4); INR 0.97
aPTT 31.0 (26.4-37.6)
Factor VIII <1%

36

Intracerebral haemorrhage
frontotemporoparietalis sinistra, subdural
haemorrhage, subarachnoid haemorrhage

37

Assessment: ICH + severe hemophilia A +

susp. bacterial infection
Treatment:
Oxygen

1L/m
IV NaCl 0.45% in D5% 50ml/m
F VIII 2 x 1500IU (50 IU/kg/12hr)
Tranexamid acid 3 x 750 mg, IV
Furosemid

1 x 20 mg, IV
Mannitol 75 cc in 30 3x/dy
Cefotaxime

3 x 1 gr, IV
Paracetamol 3 x500 mg prn, IV

Consult neurosurgery: Elective trepanation

38

Dy+1-+3
GCS 10
R/ FVIII 50
IU/kg/12hr
others cont

Dy +4-+7
GCS 11
R/ FVIII 25
IU/kg/12hr
Mannitol &
Frusemide stop
Rehabilitation

DY +8-+9
GCS 12 no fever
R/ FVIII 20
IU/kg/12hr
Cefotaxime
stop

39

Dy +10-+13
GCS 15
Motoric Right
R/ FVIII 10
IU/kg/12hr

Dy +14
Status quo
discharged by
parents own

40

COST ANALYSIS IN JKN*

F VIII
Bleeding type

PASIEN

Target
desired
level
(%)

Weight
(kg)

50-80
30-50
20-40

30

Tariff (INA# Faktor FVIII total cost CBG+Top up)

B class
VIII
Hospital Regneeded
3
(IU)

Deficit

CNS Bleeding
Dy 1-3
Dy 4-7
Dy 8-14

19,800

95.040.000

19.859.600

41

-75.180.400

LEARNING POINTS

Approach PWH with suspect of ICH

WFH Guidelines for ICH

42

APPROACH TO SUSPECT ICH

Nagel K, et al. Blood Coagul Fibrinolysis 2012;24:23 27.

43

WFH GUIDELINES
ON CNS BLEEEDING (2012)
SUGGESTED PLASMA FACTOR PEAK LEVEL AND DURATION OF ADMINISTRATION
(WHEN THERE IS NO SIGNIFICANT RESOURCE CONSTRAINT)
Hemophilia A

Hemophilia B

Desired level
(IU/dL)

Duration (days)

Desired level
(IU/dL)

Duration (days)

Initial

80-100

1-7

60-80

1-7

Maintenance

50

8-21

30

8-21

44

WFH GUIDELINES
ON CNS BLEEDING (2012)
SUGGESTED PLASMA FACTOR PEAK LEVEL AND DURATION OF ADMINISTRATION
(WHEN THERE IS SIGNIFICANT RESOURCE CONSTRAINT)
Hemophilia A

Hemophilia B

Desired level
(IU/dL)

Duration (days)

Desired level
(IU/dL)

Duration (days)

Initial

50-80

1-3

50-80

1-3

Maintenance

30-50

4-7

30-50

4-7

20-40

8-14

20-40

8-14

45

Neurosurgery:
Failure

of conservative-replacement
therapy
Severe-life threatening ICH
Cermelj M et al.Haemophilia. 2004;10:405-7
Wu XJ et al. Br J Neurosurg. 2009;23:455-7

46

Klinge et al:

744 children with hemophilia 30 episodes of

ICH: 57% due to head trauma

Haemophilia 2008;14:952-5

Mortality due to ICH in PWH:

1960-1991: 29.2%

2001: 18.2%

2003: 8.6%

De Tezanos-Pinto. Haemostasis.1992;22:259-67

Nuss. Am J Hematol.2001;68:37-42
Antunes. Haemophilia.2003;9:573-7
47

WFH RECOMMENDATIONS:
ICH IN PWH
A medical emergency. Treat first
before evaluating
All post-traumatic head injuries,
confirmed or suspected, &
significant headaches must be
treated as intracranial bleeds
Do not wait for further symptoms
to develop or for laboratory or
radiologic evaluation
48

Immediately raise the patients factor

level when significant trauma or early
symptoms occur
Further doses will depend on imaging
results
Maintain factor level until etiology is
defined
If a bleed is confirmed, maintain the
appropriate factor level for 10-14 days
(Level 4)
49

CT scan or MRI of the brain should

be performed
Neurological consultation should be
sought early (Level 4)
ICH may be indication for prolonged
2nd-prophylaxis (3-6 mo), especially
where high risk of recurrence
observed (e.g. HIV +) (Level 3)
50

THANK YOU

51