Hemostasis:
Hemostasis:Hemo/Stasis
Hemo=خون Stasis=سکون
هموستاز :مثلث
Blood Vessels
Platelets
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
هموستاز بندی :تقسیم
1) اولیه عروقی: هموستاز آسیب از بعد ثانیه چندو کوچک عروق از خونریزی از و میشود ایجاد
میکند ونولها جلوگیری .
2) ثانویه آسیب: هموستاز از بعد دقیقه چندایجاد عروق عروقی از خونریزی از و میشود
میکند جلوگیری .بزرگ
Differences of Primary and Secondary Hemostasis:
ManifestationsManifestations Primary Primary Hemostasis:Hemostasis:
Secondary Secondary Hemostasis:Hemostasis:
Onset of Bleeding
Immediate Delayed-hours or days
Site of Bleeding Superficial Deep(joints,…)
Physical Exams Petechia,Echymosis Hematoma,Hemarthrosis
Family History AD AR or X-link R
Response to Therapy
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. Is the bleeding significant ?
2. Local Vs Systemic ?
3. Platelet Vs Coagulation disorder ?
4. Inherited Vs Acquired ?
1. Demonstration of the defect
2. Identification of the defect(s)
3. Assessment of severity
4. Consequential studies eg. carrier detection
5. Monitoring of treatment
Laboratory Approach
1. Platelet count & morphology
2. Bleeding Time(BT)
3. Prothrombin Time(PT)
4. Activated Partial Thromboplastin Time(PTT)
5. Thrombin Time (TT)
Screening Tests
Collection of blood sample1. 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
• Coagulation factor deficiency/inhibitor• Test plus control plasma - 1:1• Repeat PT/APTT• > 50% correction
– Yes - Factor deficiency– No - inhibitor
Prolonged PT/APTT
timed incubationabnormally increasingspecific inhibitor
no changeLupus Anticoagulant
PT
TT
APTT
PT - APTT, TT, PLC - N
HMWKXII
PKXI
IX
VIII
VII
X
VIII
* Factor VII deficiency* Anticoagulant therapy
APTT - PT, TT, PLC - N
* Factor deficiency* vWD* Inhibitors* Heparin therapy
PT
TT
APTT
HMWKXII
PKXI
IX
VIII
VII
X
VIII
Mixing tests with APTT
APTT of test plasma +Aged plasma Adsorbed plasmaDiagnosis No correction Corrected VIII
Corrected No correction IX
Corrected Corrected XI,XII
Prolonged APTT, BT
von Willebrand’s disease
Ristocetin Induced Platelet AgglutinationVIII:CvWF:AgvWF 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
PT
TT
APTT
PT, APTT - TT, PLC - N
HMWKXII
PKXI
IX
VIII
VII
X
VIII
* 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
PT
TT
APTT
PT, APTT, TT - PLC - N
HMWKXII
PKXI
IX
VIII
VII
X
VIII
* Hypo / dysfibrinogenemia* Heparin* Liver disease* Systemic hyperfibrinolysis
PT
TT
* DIC- FDP- D-dimer- Fibrin monomer
APTT
APTT, PT,TT all PLC - low
HMWKXII
PKXI
IX
VIII
VII
X
VIII
PT
TT
APTT
PT, APTT- TT - NPLC -
HMWKXII
PKXI
IX
VIII
VII
X
VIII
Massive transfusion with stored blood
ThrombocytopeniaPseudo vs True
Bone marrow biopsy to differentiate production destruction
PTAPTT
PT, APTT,TT-NPLC -
HMWKXII
PKXI
IX
VIII
VII
X
VIII TT
• Factor XIII deficiency
• Thrombasthenia– congenital
– drug induced
• Disorders of vascular hemostasis
• Factor XIII - clot solubility
PT, APTT, TT, PLC - Normal
• 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 SyndromeCriteria 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
• Kaolin clotting time
• Dilute Russel’s viper venom time
• Platelet neutralization test
• Tissue thromboplastin inhibition test
Lupus Anticoagulant