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