(petechiae) (ecchymosis)

(epistaxis) (hemarthrosis) (muscular bleeding)

(hemostasis)

(platelet-fibrin
mesh work) (fibrinolytic system)

(1,2)

(local cause)
(hemostatic
disorders)




(3-7)
1.


1.1



(FXIII deficiency)
Afibrinogenemia
1.2 15

24
7
2
1.3

1.4 circumcision

1.5 non steroid anti-inflammatory drugs (NSAIDs)
(platelet dysfunction)
(vitamin K deficiency)
1.6
collagen vascular disorders
1.7

(acute leukemia)
1.8

sex linked recessive
(vWD)
autosomal dominant
70 30
(mutation)
2.

2.1

(allergic rhinitis)
2.2
1-2 (petechiae)
(capillary bleeding)
(rash)
( 3 )
(ecchymosis)

(thrombocytopenia) (platelet
dysfunction)
(large deep ecchymosis) (hematoma)
(muscular bleeding) (hemarthrosis)
(loose skin) (abnormal
scars) (joint laxity) Ehlers-Danlos syndrome
(telangiectasias)
hereditary hemorrhagic telangiectasia Osler-WeberRendu disease
Henoch Schnlein purpura (HSP)
2.3
(chronic arthropathy)
(joint
laxity) Ehlers-Danlos syndrome
radius thrombocytopenia with absent radius syndrome (TAR ) Fanconi
anemia
2.4


3.
(screening laboratory)
( 1)
3.1 Complete blood count (CBC)

automate

 atypical lymphocyte
acquired platelet dysfunction with
eosinophilia (APDE) Bernard- Soulier syndrome
3.2 tourniquet test

bleeding time (BT)

3.3 Venous clotting time (VCT)

( clotting factor activity <1%) VCT 15 clot
retraction 1-2 clot
retraction clot lysis clot lysis 24 clot lysis
30 hyperfibrinolysis
mixing VCT
VCT VCT factor VIII
factor IX concentrate 2
3.4 Coagulogram
- Prothrombin time (PT) fibrinogen, prothrombin, factor V,
VII, X >70%, 11.5-14.5 INR (international normalized ratio) 1.3
- Activated partial thromboplastin time (APTT) fibrinogen,
prothrombin, V XII VII 30-38 APTT
VIII 25-30%
- Thrombin time (TT) fibrinogen
9-11 fibrinogen 100 ./. fibrinogen
(dysfibrinogenemia) TT, PT APTT
PT, APTT TT 1.2-1.5

factor VIII clotting activity, platelet aggregation study, von Willebrand factor antigen, ristocetin
cofactor activity von Willebrand factor activity

CBC
Tourniquet test
Bleeding time
Venous clotting time
Mixing venous clotting
time
Clot retraction
Clot lysis
Coagulogram

Venous Clotting Time

+ Factor VIII

+ Factor IX

1.

2. 3
2.1
2.2

1.

2.
, ,
3.

(hematoma)

4.

5.

*
*

,
1-3 .
(petechiae) (small
ecchymosis)

screening laboratory
(1)
1. screening laboratory
CBC
2
1.1 2
1.1.1 Isolated thrombocytopenia
immune thrombocytopenic purpura (ITP)
thrombocytopenia with absent radii (TAR) syndrome
1.1.2 Pancytopenia (inherited bone
marrow failure) (acquired aplastic anemia)
(acute leukemia)
2 (bone
marrow aspiration )
1.2 BT
1.2.1 BT (platelet
dysfunction)
hereditary platelet dysfunction Bernard- Soulier syndrome

Glanzmanns thrombasthenia platelet function test

eosinophilia
APDE
1.2.2 BT
Ehlers-Danlos syndrome (scurvy)
HSP
2.

screening laboratory CBC coagulogram (APTT,
PT,TT) 4
2.1Prolonged APTT hemophilia vWD acquired
autoantibody against factor VIll heparin
2.2 Prolonged PT early vitamin K deficiency, congenital factor
VII deficiency coumarin
2.3 Prolonged APTT PT congenital factor II, V, X deficiency
2 2 idiopathic vitamin K deficiency in
infancy (IVKDI) acquired prothombin complex deficiency (APCD)

2.4 Prolonged APTT PT disseminated intravascular
coagulopathy (DIC) TT
2.5 Prolonged APTT, PT TT dysfibrinogenemia
hypofibrinogenemia afibrinogenemia
2.6 Prolonged APTT TT PT
heparin overdose heparin
:
- hemophilia A B factor VIII IX clotting activity
- vWD vWF antigen, ristocetin cofactor activity, factor VIII assay
multimeric analysis of vWF
- Liver disease liver profile
- DIC fibrinogen, fibrin degradation
products (FDP) D-dimer
-
prothrombin induced by vitamin K absence (PIVKA II)
60

-
urea clot solubility vWD
HSP

 1 (3-8)

Suspected coagulation defect

Suspected vascular or platelet

CBC with platelet count, APTT, PT

CBC with platelet count

Decreased
platelet
counts

Normal
Platelet
counts

Prolonged
APTT

Prolonged
PT

Prolonged
APTT& PT

Prolonged
APTT,PT&
TT

Hemophilia A,B
Pancytopenia

Isolated
thrombocytopenia

Prolonged
APTT&PTTT
with decreased
platelet counts

- Factor XI def.
- vWD
- Heparin effect

Bleeding time

Prolonged

Normal
- HSP

ITP
- TAR syndrome
- BMA is considered

Liver disease
- Early Vit. K def
- Factor VII def.
- Excessive coumarin

- Severe liver disease

- Vit K def.
- Congenital factor
def. (II, V, X)
- High dose heparin
or coumarin

APDE

- other

- Congenital
Aplastic anemia

vascular

platelet

defect

dysfunction - Acute leukemia

Dysfibrinogenemia
Afibrinogenemia
Hypofibrinogenemia
- DIC
- Hemangioma
(KMS)

- vWD
BMA is considered
HSP = Henoch-Scholein purpura, APDE = Acquired platelet dysfunction with eosinophilia, VWD = von Willebrand disease,
BMA = Bone marrow aspiration, ITP = Immune thrombocytopenic purpura, TAR = Thrombocytopenia with absent radii
syndrome,
DIC = Disseminated intravascular coagulopathy, KMS = Kasabach-Merrit syndrome


4 (8,9)
1. (Local treatment)

adrenalin, gel foam,
fibrin glue tranexamic acid 2
15-30 1-2 48
15-30 4-6
24-48
(partial
weight bearing)
3-7
2. (Replacement therapy)(10-17)
( 4,5 6)
Cryoprecipitate fibrinogen
(level IV evidence, grade B recommendation)
Fresh frozen plasma coagulopathy DIC, Idiopathic
Vitamin K deficiency in infancy (IVKDI), liver disease (level IV evidence, grade B
recommendation) TTP, hemolytic uremic syndrome (HUS)
(level I evidence, grade A recommendation)
Cryo-removed plasma factor II, VII, X (level IV
evidence, grade B recommendation)
Platelet concentrate bone
marrow failure DIC (level IV evidence, grade B recommendation)
Factor concentrate factor VIII concentrate,
prothrombin complex concentrate (PCC) factor IX complex factor IX concentrate (level
IV evidence, grade B recommendation)
Activated prothrombin complex concentrate recombinant activated factor VII
recombinant activated factor
VII

(level IV evidence, grade B recommendation)

10

Whole blood
Packed red cells
FFP, FDP
Cryoprecipitate
Cryo-removed plasma
Platelet concentrate
Factor VIII concentrate
Lyophilized cryoprecipitate
Factor IX concentrate PCC

20 ./.
10 ./.
10 ./.
0.2 /.**
10 ./.

10%*
10%*

VIII 15-20%, fibrinogen 80-100 ./.

( cryoprecipitate)
10-15% IX 7-10%
0.2 /. 20,000-40,000/.
1 /. factor VIII:C 2%
1 /. factor VIII:C 2%
1 /. factor IX:C 1%

* 1 1 /. 70 .
** cryoprecipitate FVIII:C 40-60 / 0.2 /. FVIII:C 15-20%
cryoprecipitate FVIII:C 80-100 / 0.1 /. FVIII:C 15-20%

5 *

1.
**
2. ( ileopsoas)

3. ,
, , ,
ileopsoas
4.

(%)

20-30
40-60

20-30
( 3-7 )
40-50
( 1 )

80-100

80-100

40-50
( 1-2 )

* Factor VIII concentrate 1 /. VIII 2%

PCC factor IX concentrate 1 /. IX 1%
FFP, FDP 10 ./. VIII 10-15%, IX 7-10%
Dry cryoremoved plasma 10 ./. IX 7-10%
Cryoprecipitate 0.1 /. VIII 10%

11

Heat-treated lyophilized cryoprecipitate ( 200 ) 1 /. VIII 2%

**

FVIII:C
(/.)
40-60

30-50

20-30

20-30

FVIII:C 50%

FVIII:C 30%

FVIII:C 30%
12 .
FVIII:C 30%

3. (Medications) ( 7)
3.1 Antifibrinolytic agents Tranexamic acid mucous
membrane bleeding hematuria
10 ././ 6 20-25 ././
3-4 5% solution transmin (250 . 50 .) 4

3.2 Desmopressin DDAVP (1-deamino 8D-arginine vasopressin)
( >5-40%) vWD
type 1(18) (level IV evidence, grade B recommendation)

DDAVP (4 ./.) 0.3 ./. ( 20 .)
0.9% 15-20 . 10-15
30-60 FVIII:C, vWF 3
DDAVP
24-72 DDAVP
antifibrinolysis

12

3.3 -1 mixed micelle 1

. , APCD 13 1-2 . , 2-5 . , 5-10 . -1

3.4 Heparin or Low molecular weight heparin (LMWH) severe DIC

conservative treatment gangrene
3.5 Corticosteroid(19,20)
(ITP) (level I evidence, grade B recommendation)
corticosteroid
- Prednisolone 1-2 mg/kg/day ( 60 mg/day) 14

- Prednisolone 4 mg/kg/day 7
- Methylprednislone 30 mg/kg/day 3
3.6 Intravenous immunoglobulin (IVIG) (20,21) non-modified Fc portion IVIg
Fc portion RE system (level I evidence, grade B
recommendation) IVIg IVIg
24 corticosteroid
IVIg corticosteroid IVIg
IVIg 0.8-1
/./ 2 24-48
75 acute ITP

13

 7
Drug
Indication
Tranexamic acid
Mucosal bleeding
(avoid in patient with hematuria)
Desmopressin (DDAVP) 1. Mild hemophilia A, vWD
2. Uremia
3. Hereditary platelet dysfunction
with
bleeding
except
Glanzmanns
thrombasthenia
Vitamin K 1 mixed 1. Vitamin K deficiency state
micelle
2. APCD
Heparin or LMWH

1. Severe DIC not response to

conservative treatment
2. Venous thrombosis

Dose
10-25 mg/kg/dose oral or
intravenous(IV) q 6 hr
0.3-0.4 mcg/kg/dose in NSS 30
ml IV infusion in 20 min
(maximum response in 30-60
min) 12 hr.

1-5 mg IV or IM repeat dose

q 2-4 wk in severe
malabsorption state
Heparin 50-100 unit/kg in NSS
in 30 min then 12-25 unit /kg/hr
continuous infusion
LMWH 1 mg/kg subcutaneous
q 12 hr

4. (General care)

(subcutaneous)
10-15

1.
1.1

1-2 . (large deep ecchymosis)
(hematoma) (muscular bleeding) 1-3

14

 (hemarthrosis)

1.2

sex-linked recessive
1.3 (chronic arthropathy)

1.4. venous clotting time

venous clotting time
mixing venous clotting time
coagulogram APTT PT TT
factor VIII/IX clotting activity (FVIII:C,FIX:C)
1.5 (DNA analysis)

2.

3
2.1 (treatment on demand)
(hepatitis B, C
HIV antibody, HIV antigen, syphilis) fresh frozen plasma, cryoprecipitate, cryo-removed
plasma heat-treated lyophilized cryoprecipitate /
half life 12
. 24 .

cryoprecipitate
cryoprecipitate normal saline 10 .
serum protein 9 g/dl

volume overload 80-100
%
12 .

2.2 (early treatment)

(factor concentrate)

15

 (.)

10 90,000 10 /
120,000

.
2.3 (prophylactic treatment)
1-3

3.

16


1.

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2.

Lanzkowsky P. Disorders of coagulation. In : Lanzkowsky P. ed. Manual of pediatric

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3.

Scott JP. Bleeding and Thrombosis. In: Kliegman RM, Greenbaum LA, Lye PS,eds.
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Saunder 2004:909-928

4.

, . Hereditary Hemostatic and Thrombotic Disorders

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5.

Lusher JM. Clinical and Laboratory Approach to the Patient with Bleeding. In : Nathan
DG, Oski SH, eds. Nathan and Oskis Hematology of Infancy and Childhood 6th ed.
Philadelphia, WB. Saunder 2003:1515-26

6.

Grabowski EF, Corrigan JJ. Hemostasis : general considerations. In Miller DK, Baehner
RL, eds. Blood diseases of infancy and childhood. St. Louis. Mosby. 1996:849-63

7.

Allen GA, Glader B. Approach to the bleeding child. Pediatr Clin N Am 2002;49:123956
, . Bleeding Tendency. ,
, , ,
. .
, 2545:69-71

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18