DR. spiro A. Tawil
Consultant Surgeon
F.R.C.S.I.
What is haemostasis?
Platelet
Normal blood flow
Vasoconstriction
1. Vasoconstriction
Primary haemostasis
Loose platelet plug
Collagen
1. Vasoconstriction
2. Primary haemostasis
Primary haemostasis – adhesion of platelets
1. Adhesion
The role of platelets
Primary haemostasis – activation of platelets
Activated
Platelet
Secondary haemostasis – coagulation and
formation of fibrin
Coagulation system
Coagulation factors
 Factor I (Fibrinogen)
 Factor II (Prothrombin)
 Factor III (Tissue
Factor)
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Factor IV (Ca++)
Some new factors involved in coagulatio
Factor V
Protein C
Factor VII
Protein S
Factor VIII
Thrombomodulin
Factor IX
Antithrombin
Factor X
Tissue Factor Pathway Inhibitor
Factor XI
Carboxypeptidase U
Factor XII
Thrombin Activatable Fibrinolysis Inhibitor
Factor XIII
Prothrombin time (PT)
1.Add tissue factor
2.Add Ca++
Initiation
and start the clock
Amplification
Tissue factor
Factor XIa
Factor VIIa / Tissue
factor
Factor IXa
Factor X
Factor Xa
Prothrombin
Fibrinogen
Factor Xa
Thrombin
Fibrin
Thrombus formation
Normal range: 12 to 20 s
Activated partial thromboplastin
time (aPTT)
Initiation
Amplification
Tissue factor
Factor XIa 1. Contact activation
Factor VIIa / Tissue
factor
Factor X
Prothrombin
Fibrinogen
Factor Xa
Factor IXa
2. Add Ca++ and
start the clock
Factor Xa
Thrombin
Fibrin
Thrombus formation
Normal range: 30 to 40 s
Thrombin time (TT)
Initiation
Amplification
Tissue factor
Factor XIa
Factor VIIa / Tissue
factor
Factor IXa
Factor X
Factor Xa
Prothrombin
Fibrinogen
Factor Xa
Thrombin
Fibrin
1. Add a known amount of thrombin
Thrombus formation
Normal range: 15 to 25 s
NovoSev
en
Human/porci
ne factor VIII
FEIBA
Initiation phase of coagulation
Tissue factor
FVIIa
FX
Prothrombin
FXa
TFPI/FXa
Tissue factor pathway
inhibitor (TFPI)
Fibrinogen
Thrombin
Fibrin
Primary
platelet
plug
Fibrin bound thrombin
Amplification phase of coagulation
Tenase complex
FIXa
FVIIIa
FIXa
FVIIIa
Platelet membrane
FX
FV and FVIII
FXa
Activation of more platelets
Generation of more fibrin
Prothrombinase complex
Clot stabilisation
FXa
FVa
FXIIIa
Prothrombin
Antithrombin
Thrombin
FXIII
The protein C system and termination of coagulation
Tenase complex
FIXa
FVIIIa
FX
FVIIIa
FXa
inactive
APC
Prothrombinase
complex
FVa
inactive
FXa
FVa
Protein C
Thrombin
Thrombomodulin
Prothrombin
Thrombi
n
Thrombin
Fibrinogen
Fibrin
Fibrinolysis
Thrombin has a central role in
blood coagulation
The coagulation system is
a complex interaction of
several enzymes, cofactors
and inhibitors in which
thrombin is the
“conductor of the
orchestra” as it is involved
in coagulation,
anticoagulation and
fibrinolysis
Thrombin
 Cleaves fibrinogen to
fibrin
 Induces platelet
aggregation
 Stimulates its own
generation
 Downregulates its own
formation
Fibrinogen binding to thrombin
Fibrinogen binding
site
D
E
Active site
D
Fibrinogen
Fibrinopeptides
Laboratory tests of haemostasis
Test
Purpose
Normal range
Platelet count
No of platelets in the blood
150-300 x 109/l blood
Bleeding time
Functional platelet aggregation <12 min
Activated partial
thromboplastin time
(aPTT)
Activity of all coagulation factors
in the amplification loop
35-45 s*
Prothrombin time (PT) Activity of vitamin K-dependent10-20 s*
coagulation factors
International normalised
Calculated from PT as
the ratio
1.0
ratio (INR)
between PT in patient plasma and
reference sample
Thrombin time (TT)
Activity of thrombin
10-30 s*
Ecarin clotting time
(ECT)
Effect of direct
thrombin inhibitors
20-40 s**
Fibrin degradation
products (FDPs)
Fibrinolytic system
<10 mg/l plasma
D-dimers
Fibrinolytic system
<0.5 mg/l plasma***
* Depends on the amount of thrombin added to the sample
**Depends on the amount of ecarin added to the sample
*** May also be expressed as fibrinogen equivalent units (FEU)
FRESH BLOOD COMPONENTS
 WHOLE BLOOD
 RED BLOOD CELL IN ADDITIVE SOLUTION
 PLATELETS
 FRESH FROZEN PLASMA (FFP)
 CRYOPRECIPITATE
PLASMA FRACTION
 HUMAN ALBUMIN
 PROTHROMBIN COMPLEX CONCENTRATES
 IMMUNOGLOBULIN PREPARATION (90% Ig G)
RED CELL SEROLOGY
 ABO ANTIGENS
 RHESUS ANTIGENS (Rh)
 OTHER RED CELL ANTIGENS
 Kell antigens
 Duffy antigens
 Kidd antigens
PRETRANFUSION TESTING
 TYPE AND SCREEN
 CROSS- MATCHING
 EMERGENCY REQUIREMENTS FOR BLOOD
ORDERING BLOOD IN AN EMERGENCY
 Immediately take samples for cross-matching
 Inform the blood bank of the emergency,the volume
of blood required,and where blood is to be delivered
 One individual should take responsibility for all
communications with the blood bank, and should
ensure that it is clear who will be responsible for the
blood delivery
 In cases of exsanguinations use emergency group O
Rh(D)-negetive blood.
 Do not ask for cross-matched blood in an emergency
BLOOD ADMINISTRATION
 Before administrating blood 2 staff members (one
of whom must be a doctor or trained staff nurse)
must check
 the patient’s full identity
 the blood pack,compatability label and report form
 the blood pack for signs of haemolysis or leakage from
the pack.
 Any discrepancies means that the blood must not
be transfused and that the laboratory must be
informed
TRANSFUSION ERRORS
 Almost all deaths from transfusion reaction are
due to ABO incompatility
 Errors in patient identification at the time of blood
sampling or administration are the major cause
 When taking the initial blood sample
 check the patient’s identity verbally and on the wrist
identification band
 label the sample fully before leaving the bedside
 make sure that the blood request form is clearly and
accurately completed.
ADVERSE EFFECTS OF TRANSFUSION
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HYPOCALACAEMIA
HYPERKALEMIA & HYPOKALAMIA
HYPOTHERMIA
ADULT RESPIARATORY DISTRESS SYNDROME (ARDS)
AUTOLOGOUS TRANSFUSION
 PREOPERATIVE DONATION
 ISOVOLAEMIC HAEMODILUTION
 CELL SALVAGE
TRANSFUSION REQUIREMENTS IN SPECIAL
SURGICAL SETTINGS
 MASSIVE TRANSFUSION
 THROMBOCYTOPENIA
 COAGULATION FACTOR DEFICIENCY
MASSIVE BLOOD TRANSFUSION
 This is defined as the transfusion of the equivalent of the the
circulating blood volume within a 24hour period (in practice
10-20 units in an adult)
 Common identifications for massive blood transfusion are
major trauma, gastrointestinal bleeding and obstetrics
complications.
 Major problems associated with massive blood transfusion
include
 underlying coagulopathy
 thrombocytopenia
 lack of coagulation factor 5 & 8
 hyperkalaemia
 hypothermia
METHODS TO REDUCE THE NEED FOR
BLOOD TRANSFUSION
 ACUTE VOLUME REPLACEMENT
 HYDROXYETHYL STARCH (HES)
 DEXRAN 70
 DEXTRAN40
 UREA-BRIDGED GELATIN (HAEMACCEL
MECHANISM FOR REDUCED BLOOD USE IN
SURGERY
 PREOPERATIVE
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* Surgery elective – Correct the Haemoglobin level.
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Stop drugs that interfere Haemostasis
 INTRAOPERATIVE
Posture
Use of Vasoconstrictors
Use of tourniquets
Use of anti-fibrinolytic drugs eg Aprotinin
Using Fibrin Sealant
POST OPERATIVELY
 Blood can be salvaged from drains into collection devices that
permit reinfusion
 Decision to transfuse post operatively should depend
* Age of the patient
* Ability to tolerate lower levels of anaemia
* Rate & amount of continuing blood loss
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Clinical Scenarios
 A 65 year old man has undergone a left
nephrectomy 3 days ago. He required 3 units of
packed cells intra-operatively. He looks pale
and is dyspnoeic but his vital signs and
urinary output are satisfactory. You check his
FBP. Hb is 7 PCV 0.28.
 What would you do?
 A 34 year old man presents in the resuscitation
room of the A/E department. He is anxious, short
of breath, sweating and his BP is 80 systolic, Pulse
120. There is a stab wound on the right side of the
chest. A chest drain was inserted by the SHO and
1000mls of blood drained immediately.
 What would you do with respect to his fluid
 A 57 year old man needs a left hemicolectomy for
carcinoma. He declares himself to be a Jehovah’s
witness and refuses a blood transfusion under any
circumstances.
 What will you do?
Case 1
 It is Friday at 4:40pm
 Lab calls
 You are patient is being preped for urgent surgery.
 INR 6.5
 What to do ?
Vitamin K
 Warfarin affects factors II,VII,IX and X
 These are the vitamin K dependent factors
 Can reverse warfarin effect
 Takes time
 Available forms ?
Reversing INR wityh vitamin K
 Depends on clinical scenario
 Complete reversal
 Partial reversal (too high INR)
 IV or oral forms prefered
 For complete reversal 5-10 mg IV q12h for 2 doses will
reverse completely in 36-48 hours.
 1-2 mg will decrease INR to therapeutic
 Level within 12-24 hrs
Case 2
 You are on call for ENT and are asked to see an 18
year old girl with refractory nosebleed.
 The nose is packed and bleeding does not stop.
 You notice a few bruises
 Blood sent off to lab.
 The lab calls at 6:00 Pm with a “critical” platelet
count of 10
 What is likely diagnosis
 What to do ?
ITP Immune thromboctopenic purpura
 What is needed for diagnosis
 Bone marrow examination
 Anti platelet antibodies
 When isolated and very low ITP is most likely
diagnosis
 Could be a part of another disease but not likely (SLE ,
inf mono)
 Does it require hospitalization ?
ITP continued
 If mucosal bleeding platelets are less than 6
 Needs action
 Steroids
 IVIG
 Anti D
 What about splenectomy
 New treatments
 Rituximab
 TPO agonists
Case3
 A 48 year old woman appears in emerg with jaundice
of 3 weeks duration
 Exam – jaundice - some RUQ pain an palpation
 Blood tests
 CBC Hgb 125, WBC 7.6 Plat 345
 INR 2.6 ptt 42
 What is likely diagnosis
 What to Do ?
Vitamin K deficiency
 Obstructive jaundice
 Malabsorption of Vit K dependent factors
 Older people at risk
 Post surgery at risk
 Treatment
 Oral or IV Vitamin K
Case 4
 A 54 year old male comes to office feeling unwell.
 Exam
 Mild jaundice, some telangectasis on skin
 Mod ascites.
 CBC - Hgb 110 WBC 2.5 plat 68
 INR 1.6 Ptt 41 TT 25
 What is likely diagnosis ?
Hepatic dysfunction - Cirrhosis
 Liver makes and degrades
 Coagulation is affected by decreased production and
impaired degradation of activated factors
 Chronic DIC
 Splenomegaly
 Trearment only if bleeding
 Liver transplant
Case 5
 18 year old male scheduled for tonsillectomy
 History of easy bleeding
 Exam normal no bruises
 CBC normal
 INR 1.1 PTT 45
 What is likely diagnosis ?
 How to diagnose ?
Hemophilia
 X linked bleeding disorders characterized by
spontaneous development of large hematomes in
deep tissues.
 May lead to joint bleeding, or into other closed
structures
 Joint cavity bleeding leads to deformed joints
 bleeding may be spontaneous or asssociated with
mild or moderate injury
Hemophilia types
 Hemophilia A
 absent or decreased factor VIII
 Hemophilia B
 lack of factor IX
 similar in symptoms to Hemophilia A
 Hemophilia A is 10 times more common than
hemophilia B
Case 6
 17 year old girl with mennorhagia
 History of easy bruising
 Possible history of easy bruising
 CBC normal
 INR 1.1 PTT 32 (2 sec prolonged)
 What is diagnosis
 How to diagnose ?
 Treatment ?
Von Willebrand’s Disease
 Most frequent inherited bleeding disorder
 1% - 1/100 of western population
 less severe than hemophilia
 Disease results from a decrease or absence of Von
Willebrand factor for platelet adhesion
 Affects primary hemostasis
Von Willebrand’s Disease and Factor VIII
 VW factor produced in megakaryocytes and
endothelial cells
 Coded on chromosome 12
 Autosomal dominant inheritance
 Large molecule, and multimeric
 Monomers undergoglycolisation and
multimerization before secretion
 Different multimer size = disease