Hemostasis and

coagulation

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 Hemostasis  
1.  Vascular phase
2.  Platelet phase
3.  Coagulation phase
4.  Fibrinolytic phase

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 Coagula'on    

Hemorrhage :
blood vessel rupture
platelet abnormalities
aquired or congenital abnormalities
Coagulation : - Primary : platelet function and
vasoconstriction
- Secondary : coagulation protein and series
enzymatic reactions

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 Classified  Coagula'on  factors  
1.  The fibrinogen group : F I, V, VIII XIII.
FV and VIII : labile  will increase during pregnancy
and inflammation
2.  The prothrombin group : F II, VII , IX , X
Dependent on Vit K during synthesis ,stable
3. The contact group : F XI, XII , prekallikrein , High
Moleculer Weight Kininogen ( HMWK) are involved in
the intrinsic pathway , moderately stable , not
consumed during coagulation

HIS-2015 4
 Platelet  func'on  at  the  site  injury    

•  1.Reac'on    1  (  ADHESION  )  
•  2.Reac'on    2  (  Aggrega'on  )  
•  3.  Reac'on  3    (  Realized    granule  release)  
•  4.  Reac'on    4    (  Stabiliza'on  of  the  clot  )  

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Schematic diagram of platelet
morphology

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Vascular system

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 Hemostasis
Primer

Hemostasis
Sekunder
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Hemostasis    

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 Cell-based model Hemostasis

1.  Initiation : TF primary initiator of coagulation fibrin

formation : intrinsic and extrinsic pathway
1.  Amplification: platelet adhere to extravascular matrix
component at the site of injury

2.  Propagation : “Tenase” (F.VIIIa/IXa) and

“prothrombinase” complexes  on the platelet surface
and large-scale thrombin generation takes place

Thromb Haemost 2001;85:958-65

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 Interaksi    
Hemostasis System kuat  &  
teratur  

Endotel
Protein Pembuluh
Darah
Koagulasi

Sistem
Fibrinolisis

Antikoagulan
Trombosit

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 Deficiency  
Coagula8on  
factor  
vWD   Hiperfibrinolysis    

Bleeding    
TIC   Hemophilia  
disorders  

Hepa8c  diseases   An8coagulan  

Therapy    
Platelet    
disorders  
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 Bleeding Disorders

Hereditary o  Def./Disfunction thrombosit

o  Def. Coagulation factor
o  von Willebrand Diseases
Acquired o  Hiperfibrinolysis

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 Lab.examination Bleeding
Disorders
Hemostasis Secundary
Primary Hemostasis

o  Bleeding Time* o  PT
o  Trombocyte count(CBC) o  APTT
o  Peripheral blood smear* o  TT
o  Platelet : MPV o  Fibrinogen conc.
o  PFA* o  PFA*

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 Interpreta8on  of  coagula8on    
screening  test  
Result Cause

PT >>, aPTT Normal Def. F VII, early stage of VKDB or liver disease

PT Normal, aPTT >> Def. F VIII, F IX, XI, Lupus anticoagulant

PT >>, aPTT >> :

TT Normal Def. F II, V, X, VKDB, Liver disease

TT >> Afibrinogenemia, Heparin, DIC

David M Keeling. Bleeding disorder. In : ABC of hematology. 3rd ed.2007

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HIS-2015 16
 Introduc8on  Hemophilia    
•  X linked recessive disorders

HEMOPHILIA. A
•  Is a bleeding disorder that results from a
deficiency in coagulation factor VIII (FVIII).

HEMOPHILIA B
•  Is a bleeding disorder that result from a deficiency
in coagulation factor IX (F IX)

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 Epidemiologi  
• Prevalence of hemofilia increase ( ? )
• Biostatistik:
  Population Indonesia 220 million ,
  Expected prevalence of hemofilia : 20.000
  Known cases : 1737 ( 2013 )

UNDERDIAGNOSIS ?
HIS-2015 18
                  Prevalence  of    hemophilia    
                     (Indonesia,  2012)  

20
156

18 35
9 4
2 22
6
3
2 1 6
58
11 289
157 62
257
57 16
278
116

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Data : Indonesian Hemophilia Society, Mar ch 2012
PREVALENCE    OF  HEMOPHILIA    
INDONESIA    (2013)  

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Data : Indonesian Hemophilia Society, 2013
GENETIC  FACTOR  of    HEMOFILIA  

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 FAMILY  HISTORY  

FATHER : HEMOPHILIA FATHER : NORMAL

MOTHER : NORMAL MOTHER : CARIER

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FATHER : HEMOPHILIA
MOTHER : KARIER
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Pathophysiology  
•  Fac.VIII & IX with phospholipid and Ca : 
complex  F X-activating

•  After injury: initial hemostatic  formation of the

platelet plug , together with the generation of the
fibrin clot

•  Hemophilia A& B “ clot formation delayed

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 CLINICAL  MANIFESTATION  :  
Symptoms  

•  Easy  bruising,large  
hematoma  wiyh  minor  
trauma    
•  Hemarthroses  
•  Joint    sweeling  &  pain  
•  Prolonged    bleeding  
•  Abdominal  pain  
HIS-2015 25
Signs  
•  Hemarthroses  
•  Muscle  bleeding  
•  Subcutaneous  
bleeding    
•  oral  mucosal  
bleeding  
•  Melena  ,hematuri
a  
HIS-2015 26
  Laboratory  finding  

•  Reduce  level  of  factor  VIII  or  IX  

•  APTT  is  two  to  three  'mes    
•  Platelet  count    
•  Bleeding  'me    
Normal
•  Prothrombin  'me        
•  Thrombin  'me            

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 Treatment  
A.Replacement   2.Tranexamic  acid    
•  1.Desmopressin     3.Fibrin  glue:  
fibrinogen,thrombin  ,FXIII  
acetate  (DDAVP)    mild  
f  VIII  hemophilia    
•  2.Recombinant  FVIII  or   C.Prophylaxis  
FIX  :  for  correc'on   D.Suppor>ve  care  
factor  moderate  and   E.Inhibitors    
severe  hemophilia   F.Comprehensive  care  
B.  Adjuvant  therapy  :    
1.Epsilon  amino  caproic  acid  
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• Give factor q 12 hours for 2-3 days after major surgery, continue with daily infusions for 7-10 days
• Trough factor levels with q 12 h dosing after major surgery should be at least 50-75%
• Most joint and muscle bleeds can be treated with “minor” (50%) doses for 1-3 days without monitoring

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Adjuvant        

An8fibrinoly8c  therapy:  
1.Aminocaproic  acid:  100  
g/Kg/dose  (  max.5  g /
dose)  iv/po  -­‐  q6h  
2.Tranexamic  acid  :25  mg/
Kg/dose  ,  max.1.5  g /
dose  PO  q8h  or  10  mg/
kg/dose  max,1  g /dose  –  
iv  q8h  

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        Treament regimen guidelines for
therapy of hemophilic bleeding
Bleeding  site                  op'mal  factor                dosage(iu/kg)  
                                                                 level  (%)  
-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐-­‐  
Hematoma                                  20-­‐30    10-­‐15  
Hemarthrosis          30-­‐50  15-­‐25  
GI  tract                                                        40-­‐60    20-­‐30  
Retropharyng/tongue      60-­‐100  30-­‐50  
Intracranial            80-­‐100  30-­‐50  
Retroperitonial          60-­‐100  30-­‐50  
Hematuria                                    30-­‐50  15-­‐25  
Minor  bleeding          20-­‐30  10-­‐15                                  

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 Treatment and Prevention of complication

•  P: protection/ dilindungi
bandage, ortosis/bracing
•  R: rest/ istirahat/ immobilisasi
splinting
•  I: ice application/ terapi dingin
•  C: compression/ penekanan ringan
•  E: elevation/
 Supervised rehabilitation
program.

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 Basic  principles  of  bleeding  treatment  episodes  in  
hemophilia  A  
1. Treat bleed early with factor
replacement therapy within 2 hours of the onset
symptoms
2. Treat veins with care. A hemophiliac’s veins are
his lifeline
3. Avoid products that cause platelet dysfunction
4. Home therapy with clotting factor is usually
begun when a child is 3-5 years old.
5. The concept of comprehensive care at a
hemophilia treatment center is state of the art
approach to hemophilia treatment
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Specific  hemorrhage  

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 specific hemorrhage

Muscle hemorrhage

•  First give patients the

appropriate dose of FVIIIK
and then evaluate

•  Raise FVIII level to 40% first

symptom/trauma.

•  A second infusion to rise fctor

level 40 % often required
within 24 hours.

•  Should be monitored
neurovascular compromise

HIS-2015 35
 specific hemorrhage

Iliopsoas hemorrhage

•  Problem often presents as an

acute abdomen or as hip pain.

•  Sign may include pain in lower

abdomen,groin,and/or lower
back,and pain on extension,
paresthesia
•  Immediately raise FVIII
80-100%.maintain VIII >50%.

•  Hospitalize for
observation,treat anemia
•  CT scan for confirm the
diagnosis.
This is a form of muscle hemorrhage
•  Limit activity until pain with unique presentation
resolves,physical therapy
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 specific hemorrhage

CNS hemorrhage/head trauma

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 specific hemorrhage

Throat and neck hemorrhage and

severe tosillitis
•  This is true medical
emergency, immediately raise
FVIII level 80-100% when
symptom or significant
trauma occur.

•  Maintain FVIII at least 50%

for 1-2 weeks until
hemorrhage resolves.

•  CT scan or MRI should be

performed.

•  To prevent hemorrhage with

severe tonsillitis may be
indicate to give antibiotic

HIS-2015 38
 specific hemorrhage

Acute abdomen /Acute

gastrointestinal hemorrhage
•  Give appropriate dose of
FVIIIK and evaluate.

•  Immediately raise FVIII level

to 80-100%. Maintain FVIII at
least a 50% until etiology is
defined.

•  Treat anemia or shock as

needed.

•  Treat origin of hemorrhages .

•  EACA or tranexamic acid may

use as adjunctive therapy as
long as the possibility of renal
bleeding has been eliminated

HIS-2015 39
 specific hemorrhage

Opthalmic trauma or hemorrhage

•  Give  the  pa'ent  the  

appropriate  dose  of  factor  
VIIIK  and  then  evaluate.  

•  Immediately  raise  FVIII  level  

80-­‐100%.  Maintain  a  factor  
level  at  least  50%.  

•  Evalua'on  by  
ophtalmologist  and  
hematologist  is  required  

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 specific hemorrhage

Oral hemorrhage

•  Bleding may be controlled with

use of EACA or tranexamic acid
alone or with the use of FVIIIK
and either EACA or tranexamic ac.

•  Evaluate and treat for anemia as

indicated.

•  The application of topical such as

thrombin on the bleeding mucous
membran may be effective and
also ice.

•  A soft, cold diet for 24 hours is

recommended.

•  Consult to the dentist or

otolaryngologist

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 specific hemorrhage

Epistaxis

•  Factor replacement usually

not required because the
formation of a platelet plug
often adequate.

•  Place his head forward to

avoid swallowing blood and
have him gently blow out
weak clots. Apply firm
pressure to the fleshy part of
the nose for at least 10-20
minutes.
•  For bleed related allergy URI
efinefrin drop 5%-1%, 2
drop/nostril b.i.d for 5 days

•  Watch for anemia if bleeding

is prolonged
•  EACA or tranexamic acid may
be helpful as well as normal
saline solution or gel
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 specific hemorrhage

Soft tissue hemorrhage

•  Most  superficial  sod  'ssue  bleed  
does  not  required  replacement  
therapy.  The  applica'on  of  firm  
pressure  and  ice.  

•  Evaluate  for  severity  and  possible  

muscular  or  neurovascular  
involvement.If  this  suspected  treat  
with  factor  to  80-­‐100%  immediately  

•  A  young,ac've  child  with  hemophilia  

commonly  has  numerous  bruises.  
Parents  are  some'mes  wrongfully  
accused  of  child  abuse  

HIS-2015 43
 specific hemorrhage

Lacerations and Abrasions

•  Deep  lacera'on  required  raising

FVIII level to 50%, then
suturing. Removal of sutures
usually requires another
infusion of FVIII.

•  Superficial laceration can be

treated by cleaning the wound
followed by application of
pressure and steri-strips.

•  Aberation require cleaning

and pressure

HIS-2015 44
 specific hemorrhage

Renal hemorrhage

•  Avoid use of anti-fibrinolytic

agent.

•  Painless hematuria should be

treated with complete bedrest and
vigorous hydration (1-1/2 x
maintenance) for 48 hours.

•  If there is pain or persistent gross

hematuria, give FVIII raise to 50
%.

•  Prednison , if hematuria (gross or

microscopic) persist or if there are
repeated episode

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Factor  XI  Deficiency(  Hemophilia  C  )  

•  Autosomal deficiency
•  Mild and moderate bleeding symptoms
•  In Israel 1-3/1000 are homozygous
•  The bleeding not correlated with the amount of
Factor XI
•  Severe deficiency  minimal or no symptoms

HIS-2015 46
Treatment  

•  There  is  no  concentrate  factor  XI  

•  Fresh  Frozen  Plasma  (FFP)  
•  Minor  surgery    local  pressure  
•  Plasma  infusion  1U/kg    increase  plasma  
 concentra'on  by  2  U/dl  
 The  infusion  of  10  -­‐15ml/kg  plasma    
 sufficient  to  control  moderate  hemorrhage  

HIS-2015 47
 Outreach  Programme  2012  

3 Diagnosing
new  
pa8ents  
2   Factor  assay  
Establishing   Educa'on  
local   session  
1   diagnos'c  
facility  
Recollec'ng  
data  :  
unknown  
diagnosis   Na'onal  
Hemophilia  
Registry  
HIS-2015 48
 Comprehensive  care  of    
Hemophilia    
Pediatric  
Hematologist    
Volunteers/  
Donators   Adult  
Hematologist  

Nurse   Clinical  
Pathologist  
Hemophilia  
pa'ent  

Nutri'onist   Physio-­‐
therapist  

Psychiatrist   Orthopedic  
surgeon  

Den'st  
HIS-2015 49
TERIMA  KASIH    

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