Hemostasis:
Hemostasis:
Hemo/Stasis
Hemo=‫خون‬
Stasis=‫سکون‬
:‫مثلث هموستاز‬
Platelets
Blood Vessels
Hemostatic Factors
Causes of Bleeding(1)
Thrombocytopenia:
Primary:
• ITP
• Neonatal Isoimmune
• TAR Syndrome
• Wiskott-Aldrich Syn.
Secondary:
*Malignancy
*Aplastic Anemia
*DIC
*Sepsis
*HUS
*Hypersplenism
*Autoimmune(SLE)
Causes of Bleeding(2)
Coagulopathy:
Primary:
• vWF Deficiency
• Hemophilia
• Platelet dysfunction
Secondary:
• DIC
• Anticoagulants
• Vit K deficiency
• Hepatic Failure
• Renal Failure
• Maternal
Anticonvulsant
Causes of Bleeding(3)
Vascular(Non-Hematologic)
•
•
•
•
•
•
•
Child Abuse
Vasculitis
Ulcer
Varices
Ehlers-Danlos Syndrome
Telangiectasia
Angiodysplasia
‫تقسیم بندی هموستاز‪:‬‬
‫‪)1‬هموستاز اولیه‪:‬چند ثانیه بعد از آسیب عروقی ایجاد‬
‫میشود و از خونریزی از عروق کوچک و ونولها‬
‫جلوگیری میکند‪.‬‬
‫‪)2‬هموستاز ثانویه‪:‬چند دقیقه بعد از آسیب عروقی ایجاد‬
‫میشود و از خونریزی از عروق بزرگ جلوگیری‬
‫میکند‪.‬‬
Differences of Primary and
Secondary Hemostasis:
Manifestations
Onset of
Bleeding
Site of Bleeding Superficial
Secondary
Hemostasis:
Delayed-hours or
days
Deep)joints,…)
Physical Exams Petechia,Echymosis
Hematoma,Hemarthrosis
Family History
AR or X-link R
Response to
Therapy
Primary
Hemostasis:
Immediate
AD
Immediate;
Local pressure
Systemic
Therapy
Estimation of BT with desired
Platelet count
BT= 30.5- Platelet count (minute)
3,850
Vitamin K Related Factors:
•
•
•
•
Factor II
Factor VII
Factor IX
Factor X
Prolonged PTT
• No clinical bleeding
???
• Mild or rare bleeding
???
• Frequent,Severe Bleeding
???
Prolonged PTT
• No clinical bleeding
Factor XII , HMWK , PK
• Mild or rare bleeding
Factor XI
• Frequent,Severe Bleeding
Factors VIII and IX
Prolonged PT
• ???
• ???
• ???
Prolonged PT
• Factor VII Deficiency
• Vitamin K Deficiency(Early)
• Warfarin anticoagulant ingestion
Prolonged PT and PTT
• ???
• ???
• ???
Prolonged PT and PTT
• Factor II,V,X Deficiency
• Vitamin K Deficiency(Late)
• Warfarin anticoagulant ingestion
Prolonged TT
• ???
• ???
• ???
Prolonged TT
• Mild or rare bleeding: Afibrinogenemia
• Frequent,Severe Bleeding:Dysfibrinogenemia
• Heparin like inhibitors or heparin administration
Prolonged PT and/or PTT not
corrected with normal plasma
• Specific or nonspecific inhibitor
Syndromes
Clot Solubility in 5 M urea
• Factor XIII deficiency
• Inhibitor
Secondary Hemostasis Approach:
1)What is diagnosis?
2)What is hemostatic level of Factor?
3)What is blood distribution of factor?
4)Which products contain desired factor?
5)What is half life of coagulation factor?
APPROACH TO
COAGULATION DISORDERS
Clinical approach
1.
2.
3.
4.
Is the bleeding significant ?
Local Vs Systemic ?
Platelet Vs Coagulation disorder ?
Inherited Vs Acquired ?
Laboratory Approach
1.
2.
3.
4.
5.
Demonstration of the defect
Identification of the defect(s)
Assessment of severity
Consequential studies eg. carrier detection
Monitoring of treatment
Screening Tests
1. Platelet count & morphology
2. Bleeding Time(BT)
3. Prothrombin Time(PT)
4. Activated Partial Thromboplastin Time(PTT)
5. Thrombin Time
(TT)
Collection of blood sample
1. Minimum circulatory stasis
2. Clean venous puncture
3. Proper anticoagulant
4. Proportion of blood to anticoagulant
5. Separation of plasma and storage
6. Effect of stress, pregnancy, drugs
7. Effect of PCV on the proportion of plasma
to anticoagulant
Prolonged PT/APTT
•
•
•
•
Coagulation factor deficiency/inhibitor
Test plus control plasma - 1:1
Repeat PT/APTT
> 50% correction
– Yes - Factor deficiency
– No - inhibitor
timed incubation
abnormally increasing
specific inhibitor
no change
Lupus Anticoagulant
HMWK
VII
XII
PK
XI
APTT
IX
PT
VIII
X
PT - 
APTT, TT, PLC - N
* Factor VII deficiency
* Anticoagulant therapy
V
II
I
TT
HMWK
VII
XII
PK
XI
APTT
IX
PT
VIII
X
APTT - 
PT, TT, PLC - N
* Factor deficiency
* vWD
* Inhibitors
* Heparin therapy
V
II
I
TT
Mixing tests with APTT
APTT of test plasma +
Aged plasma
Adsorbed plasma
Diagnosis
No correction
Corrected
VIII
Corrected
No correction
IX
Corrected
Corrected
XI,XII
Prolonged APTT, BT
von Willebrand’s disease
Ristocetin Induced Platelet Agglutination
VIII:C
vWF:Ag
vWF multimeric analysis
Type 1 - Partial deficiency of vWF
2A - Absence of large and interm. multimers
2B - Absence of large multimers
2M- multimers normal, pl. function 
2N -  affinity for FVIII
3 - severe deficiency of vWF
HMWK
VII
XII
PK
XI
APTT
IX
PT
VIII
X
PT, APTT - 
TT, PLC - N
*
*
*
*
V
II
I TT
Common Pathway Factor deficiency
Vitamin K deficiency
Oral anticoagulant therapy
Liver disease
Mixing tests with PT
PT of test plasma +
Aged plasma
adsorbed plasma
Diagnosis
Corrected
Not corrected
X
Not corrected
Corrected
V
Not corrected
Partial
II
HMWK
VII
XII
PK
XI
APTT
IX
PT
VIII
X
PT, APTT, TT - 
PLC - N
* Hypo / dysfibrinogenemia
* Heparin
* Liver disease
* Systemic hyperfibrinolysis
V
II
I
TT
HMWK
VII
XII
PK
XI
APTT
IX
PT
VIII
APTT, PT,TT all 
PLC - low
* DIC
- FDP
- D-dimer
- Fibrin monomer
X
V
II
I
TT
HMWK
VII
XII
PK
XI
APTT
IX
PT
VIII
PT, APTT- 
TT - N
PLC - 
Massive transfusion
with stored blood
X
V
II
I
TT
HMWK
VII
XII
PK
XI
APTT
IX
PT
VIII
X
PT, APTT,TT-N
PLC - 
V
II
I
Thrombocytopenia
Pseudo vs True
Bone marrow biopsy to differentiate
 production
 destruction
TT
PT, APTT, TT, PLC - Normal
• Factor XIII deficiency
• Thrombasthenia
– congenital
– drug induced
• Disorders of vascular
hemostasis
• Factor XIII - clot
solubility
• Platelet function
–
–
–
–
BT
clot retraction
1 minute platelet count
aggregation
• Tourniquet test
Asymptomatic Patient
Routine screening tests shows
prolonged APTT
– Inhibitor - lupus anticoagulant
– Factor XII deficiency
– Mild congenital factor deficiency
Antiphospholipid Antibody Syndrome
Criteria by Branch and Silver 1996
• Clinical
– Recurrent abortion
– Recurrent venous
thrombosis
– Recurrent arterial
thrombosis
– Persistent
thrombocytopenia
– Livedo reticularis
• Laboratory
– IgG/IgM anticardiolipin Ab
– Lupus anticoagulant
• Diagnosis
– 1 clinical + 1 lab criteria
– Lab result must be positive
on at least 2 occasions
more than 3 months apart
Lupus Anticoagulant
• Kaolin clotting time
• Dilute Russel’s viper venom time
• Platelet neutralization test
• Tissue thromboplastin inhibition test