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Haemostasis &

Coagulation


`THE DOCTOR WAS IN SUCH A HURRY TO OPERATE ON MY FATHER,

LIKE A CHILD WANTING A LOLLYPOP'
When an incision is made , the blood clots

A 68 year old woman with a history of a 12 kg weight loss over the past

six months presents to the emergency room with a history of passing

bright red blood per rectum. Her pulse is 95, her blood pressure 120/70.

She has not seen a physician in 40 years.

Study Questions:
What history and physical exam information would you gather to assess

this patient's coagulation system?

If there is a problem present, what would be the most likely?
What laboratory tests would you order to assess this patient's

coagulation system?
A 24 year old man is in the operating room for a massive liver injury

sustained when his motorcycle hit a truck. After one hour of surgery he

has received 15 units of packed cells and has developed diffuse oozing

from the surface of his liver. Clots are no longer forming. His body

temperature is 34oC.

Study Question:
What are the most common coagulation difficulties associated with

massive transfusion? What is the management of each?

HAEMOSTASIS
OBJECTIVES

Mechanism of coagulation

Tests

Abnormal thrombosis

Abnormal bleeding

HAEMOSTASIS

Keeps blood in fluid state & in circulation

Prevents blood loss
Haemostasis

Four interconnected mechanisms form the basis of hemostasis:
(a) blood vessel contraction
(b) platelet plug formation (primary hemostasis)
(c) clot stabilization with fibrin cross-linking (secondary hemostasis)
(d) endogenous fibrinolysis.

What is involved in

Haemostasis?

Blood vessels
Platelets
Plasma coagulation factors
Inhibitors
Fibrinolytics
Events in Haemostasis

Vascular spasm
Formation of platelet plug
Formation of fibrin plug - Blood clot
Re-establishment of endothelium

Haemostasis

Vasoconstriction

Clean cut vessels > crushed vessels
Partially transected > completely cut
Veins are easily compressed
Danger areas of bleed
Haemostasis

Platelet plug - White bodies or microthrombi
Contact with subendothelial collagen
swell
irregular with pseudopods
release ADP, thromboxane A2 , phospholipids , HMWK
sticky & aggregate

Haemostasis

Fibrin clot:
Severe trauma - 15-20 secs

Minor trauma - 1-2 mts

Retraction - 20-60 mts
Haemostasis

COAGULATION

3 steps:
Prothrombin activator

Prothrombin Thrombin

Fibrinogen Fibrin

Haemostasis

Pathways

Intrinsic - XI = slow

Extrinsic - VII = fast

Common pathway
factor V
Xa Prothrombin activator
phospholipid, calcium
Haemostasis

Extrinsic

Tissue extract factor VII factor X

Intrinsic

surface contact VI
XI XI a XI a IX a X
HMWK phospholipid

calcium



BOTH ARE ESSENTIAL

HAEMOSTASIS

ACTIVATED PLATELETS

Prothrombin activator {rate limiting factor}
{THROMBOPLASTIN}

CALCIUM
PROTHROMBIN THROMBIN

FIBRINOGEN FIBRIN MONOMERS
CALCIUM XII

FIBRIN POLYMERS STABLE

CLOT
HAEMOSTASIS

PRODUCTION OF CLOTTING FACTORS
Fibrinogen liver
I , VII, IX, X liver with vit K
VII , V, XI endothelium
XI I platelets

HAEMOSTASIS

THROMBIN

Intensely proteolytic
Activates factor V ,VII , XI I
Releases phospholipid from endothelium & platelet
Activates protein C




HAEMOSTASISCONTROL

Fibrinolysin or Plasmin
Plasminogen activator

DIGESTS

ACTIVATES

fibrin

factor XII

fibrinogen kinin
factor VI complement
factor V,XII
prothrombin

Inhibited by- alpha 2 plasmin inhibitor .

HAEMOSTASIS

Why does not blood clot normally ?

Endothelium

Fibrin & Antithrombin

smooth

thrombin fibrin [85-90%]

glycocalyx antithrombin
thrombomodulin
prostacyclin
heparin sulfate
tissue plasminogen activator
ADP ase
HAEMOSTASIS

Why does not blood clot normally?
Heparin Thrombin
Alpha 2 macroglobulin Thrombin
C 1 inhibitor XI a, Kallikrein
Alpha 1 antitrypsin XI a, Elastase
Protein C Va, VII a

Tests of blood coagulation

1. Bleeding time:

2.Clotting time:

{modified Ivy's method}

{Lee & White method}

N = 1-6 mts

N = 6-10 mts in glass

platelet plug

N = 20-60 mts in

Prolonged in:

siliconized tubes

Thrombocytopenia

Measures intrinsic &

Thrombasthenia

common pathway

Von-Wil ebrand's disease
Tests of blood coagulation

Prothrombin time: { Quick's one stage test }


calcium

oxalated blood from patient

clot

tissue thromboplastin

N = 12 secs

extrinsic & common pathway

Prothrombin time contd. .

Prolonged in:
1. Oral anticoagulant drugs
2. Liver disease, obstructive jaundice
3. Vit K deficiency
4. D I C
5. Deficiency of factor VI , X, V, II
SPECIFIC FOR FACTOR VII
[ With X & V APTT is also prolonged]
PARTIAL THROMBOPLASTIN TIME

[ activated ]

Contact activation

KAOLIN
+

of factor XI + pt's = Clot

CEPHALIN

blood

phospholipid

Intrinsic & Common pathway

Partial thromboplastin time

[activated ] contd.....

Prolonged in:
1. D I C
2. Liver disease
3. Massive transfusion of stored blood
4. Heparin
5. Circulating anticoagulants
6. Deficiency of clotting factors other than VI
7. Haemophilia
THROMBIN TIME

PLASMA + THROMBIN CLOT
Assesses fibrinogen
Prolonged in :
1. Hypofibrinogenemia

DIC CONGENITAL
2. FDP
3. Heparin [ assess with REPTILASE test ]
4. Dysfibrinogenaemia

PLATELET COUNT

N = 150 - 300 x 10 9 / L
80 x 10 9 / L Bleeding may fol ow trauma
< 40 x 10 9 / L Spontaneous haemorrhage
< 10 x 10 9 / L Lethal haemorrhage
PRIMARY SCREENING TESTS

Bleeding time
Platelet count
P T
A P T T

Specific tests- Factor VII , XI I, fibrinogen
Tests for fibrinolysis

ABNORMAL HAEMOSTASIS

Normal haemostasis

PT

APTT TT

Platelet count Disorder of platelet

function.

1 n

n

n

n

Mild coagulation
disorder

Factor VII deficiency

2 long

n

n

n

Early oral
Anticoagulation
12-36 hrs

3 n

long

n

n

Factor VII , IX, XI, XI deficiency
Prekal ikrein, HMWK
Deficiency, vWD,
circulating
anticoagulant
ABNORMAL HAEMOSTASIS

PT

APTT TT

Platelet

count

Vit K deficiency
Oral anticoagulants

4 long

long

n

N

Heparin, Fibrinogen

5 long

long

long

N

Deficiency, Liver
disease, Fibrinolysis

6 n

n

n

Low

Thrombocytopenia

7 long

long

n

Low

Massive transfusion
Liver disease

8 long

long

long

low

DIC

SURGICAL SCREENING
HAEMOSTASIS

In a patient who bleeds:

LIVER
IMMUNOLOGIC
RENAL

COMPLETE

CARDIAC

WORK UP

SEVERE INFECTION
DRUGS

Best screening test - HISTORY

NATURAL ANTICOAGULANTS

Antithrombin II
Protein C and protein S
NATURAL ANTICOAGULANTS

Antithrombin II
This is an inhibitor of thrombin, its action being potentiated by heparin.
Congenital antithrombin II deficiency is inherited as an autosomal

dominant.

Heterozygotes may suffer from recurrent DVT, pulmonary embolism,

and mesenteric thrombosis.

Homozygotes present in childhood with severe arterial and venous

thrombosis.

NATURAL ANTICOAGULANTS

Protein C and protein S
These are synthesised in the liver and are dependant on vitamin K.
Protein C degrades factors Va and VII a and promotes fibrinolysis by

inactivating plasminogen-activator inhibitor I.

Protein S is a cofactor for protein C and enhances its activity.
Hereditary protein C defciency may occur, patients being more

susceptible to DVT, PE, superficial thrombophlebitis, and cerebral

venous thrombosis
ANTICOAGULANT DRUGS

Warfarin
Warfarin is a coumarin derivative which is administered orally.
It is a vitamin K antagonist and in effect induces a state analogous to

vitamin K deficiency.

It interferes with the activity of factors II, VII, IX and X. It delays

thrombin generation, thus preventing the formation of thrombi.

Warfarin is usually administered for 3?6 months following DVT or PE
Lifelong warfarin is required for recurrent venous thromboembolic

disease,some prosthetic heart valves, congenital deficiency of

antithrombin II , deficiency of protein C or protein S,

ANTICOAGULANT DRUGS

Heparin
Heparin potentiates the action of antithrombin I I.
Standard unfractionated heparin is administered i.v. or s.c. and has a half

life of about 1 h.

Low molecular weight heparin is used subcutaneously and has a longer

biological half life.

Heparin does not cross the placenta and is, therefore, the drug of choice

when anticoagulation is required during pregnancy.

Bleeding due to overdose is managed by stopping the heparin and

administering protamine sulphate intravenously.

Side effects of heparin include thrombocytopaenia,hypersensitivity

reactions, alopecia, and osteoporoi
DISORDERS OF

HAEMOSTASIS AND

COAGULATION

CONGENITAL

HAEMOPHILIA A and B.
Von WILLEBRAND'S disease.
Defencies of factorXI and XI ,prekallikrien,HMWkininogen.
Defencies of factorVII,V and thrombin.
Disorders of fibrinogen like a or hypofibrinogenemia or

dysfibrinogenemia.

Factor XI I defeciency.
ACQUIRED

VITAMIN K DEFECIENCY.
ANTICOAGULANT DRUGS.
HEPATIC FAILURE.
RENAL FAILURE.
THROMBOCYTOPENIA.
THROMBOCYTOPATHY.
HYPOTHERMIA.
DIC.

APPROACH
HISTORY

H\O bleeding,easybruising.
Frequent or unusual mucosal bleeding.
Metromenorrahgia.
Haematuria.
Epistaxis.
Previous h\o prolonged bleeding asso with invasive procedures.
Positive family history.
Drug history like intake of NSAIDS,aspirin,etc.

EXAMINATION

Ecchymotic patches or petechiae on skin.
Joint deformities.
Adenopathy.
Hepatospleenomegaly.
Hypermobility of joints.
Increased elaticity of skin.
SCREENING TESTS

CBC.
Platelet count.
PT.
aPTT.
Bleeding time.
Fibrinogen level.
Thrombin time.
Platelet function tests.
Specific factor assays.

PROTHROMBIN TIME

Measures function of factor VII,X, prothrombin and thrombin,fibrinogen

and fibrin.

Prolongation occurs when levels of factor V,VII or X fall.
Seen in warfarin therapy and vit.k defeciency.
aPTT

Detects decreased levels ofHMWkininogen,prekallikrien,XI ,XI,IX,VII ,V,X.
Increased in heparin therapy.

CONGENITAL

DISORDERS
HAEMOPHILIA A
HAEMOPHILIA A

Deficiency of factor VII .
X linked recessive disorder with males being affected exclusively.
Severe bleeding if factor level<2%.Moderate bleeding with levels b\w

2%-5%.Mild bleeding with factor levels b\w 5%-30%.

Patient has large haematomas and haemarthroses.
Bleeding is prolonged for hours or days after injury.
Lab tests show a prolonged Aptt with decreased factor VII level,normal

PT,bleeding time and vWF levels.

HAEMOPHILIA A

Desmopressin may temporarily raise factor VII levels in mild disease.
Can be given intranasal y or iv and is ineffective in treating severe disease.
Antifibrinolytic therapy with EACA and tranexemic acid with or without

desmopressin is also effective in dental extarctions or paediatric patients.

CRYOPRECIPITATE is a good source of factorVII .
One bag contains 80 units of factor VII and 1U\kg increases levels by2%.
Specific factor VII concentrates are more popular now.
Give 50U\kg stat then 30U\kg every 8 hrs for the first 2 days after surgery

or injury.
CONGENITAL

DISORDERS
HAEMOPHILIA B

HAEMOPHILIA B

Xlinked bleeding disorder with a deficiency of factor IX.
Patient presents with deep bleeding and haemarthroses.
Lab tests show increased Aptt with decreased factor IX levels, normal

PT, BT,platelet count and factor VII .

Tt is by prothrombin complex concentrate which contains factor IX and

all of the vit k dependent factors.

HighPurity factor IX concentrate is also available.
CONGENITAL

DISORDERS
VON WILLEBRAND'S DISEASE

Von WILLEBRAND'S DISEASE

Most common congenital bleeding disorder.
vWF is an important stimulus for platelet aggregation and carrier

protien for factor VII .

Type 1 is inherited as autosomal dominant and is characterized by

quantitative defect in vWF.

Type 2 has variable inheritance and there is qualitative defect in vWF.
Type3 is autosomal recessive disease with absent levels of vWF.
Patients present with mucosal bleeding,petechiae,epistaxis and

menorrhagia.

Tt is by desmopressin or cryoprecipitate.
ACQUIRED

DISORDERS
VITAMIN K DEFECIENCY

Platelet disorders

Thrombocytopaenia
This may be due to a failure of platelet production or increased

destruction or sequestration of platelets, and abnormal platelet

function.

Abnormal platelet function may cause bleeding despite a normal

platelet count.

Abnormal platelet function may occur with: drugs, e.g. aspirin, non-

steroidal antiinflammatory drugs carbenicillin, and ticarcillin;

uraemia;septicaemia; and von Willebrand's disease.
Blood vessel wal

abnormalities

Blood vessel wal abnormalities
These are rare and may be due to scurvy, steroids, Cushing's syndrome,

or Henoch-Schonlein purpura.

VITAMIN K DEFICIENCY

Vit k is required for the reaction that attaches a carboxyl gp to glutamic

acid.

Causes of def are inadequate dietary intake,
Malabsorption,obstructive jaundice,biliaryfistula,
Oral antibiotics and TPN.
Tt is parenteral administration of vit k if there is no active bleeding.
Administration of FFP rapidly corrects the coagulation deficit and is

given in patients with ongoing bleeding.

Correction of the etiology.
ACQUIRED

DISORDERS
HEPATIC INSUFFICIENCY

HEPATIC INSUFFICIENCY

Liver is the site of synthesis of all clotting factors except factorVII ,vWF.
Hepatic failure will result in coagulopathy.
Asso with platelet dysfunction.
Tt is by giving vitk,FFP,cryoprecipitate and platelets.
ACQUIRED

DISORDERS
HYPOTHERMIA

HYPOTHERMIA

Usually seen in a lengthy open surgery on the abdomen or thorax.
The coagulopathy is because of defect in platelet function,fibrinolytic

activity,coagulation cascade enzyme.

Intraoperatively all efforts should be made to keep the temp normal by

warming fluids,heated ventilation and warm environment.
ACQUIRED

DISORDERS
MASSIVE TRANSFUSION

MASSIVE TRANSFUSION

Defined as more than 10 units of transfused blood or replacement of

the pts total blood volume within 24 hrs.

Pts have thrombocytopenia,low fibrinogen and prolonged PT.
These changes result from low temperature of blood,increased citrate

level,increased k level,low pH,decreased ca level.

Tt is by infusion of FFP,PLATELETS.
POST-OP THROMBOSIS

WHY?

1. NO MUSCLE CONTRACTION

2. FIBRINOGEN , PLATELET,vWF, FACTOR VII

3. DECREASED ANTITHROMBIN I I

4. SEPSIS

5. DAMAGE TO VEINS

POST-OP THROMBOSIS

PREVENTION:
Intermittent compression or electrical stimulation
Aspirin, dextran, di-pyridamole
Low dose heparin, low molecular weight heparin
Early mobilization
Hydration
T E D stockings
Surgery in patients on

anticoagulants

DRUG

BLEEDING

ELECTIVE

EMERGENCY

RISK

SURGERY

SURGERY

1 .HEPARIN Low / Moderate Discontinue high dose Same as elective

Give low dose heparin

High risk

Discontinue 6 ? 12 hrs Discontinue

before surgery

Give Protamine sulphate

2. L M W H -- Discontinue 12 ? 24 hrs before surgery especial y in high risk

group



Surgery in patients on

anticoagulants

DRUG

BLEEDING ELECTIVE

EMERGENCY

RISK

SURGERY

SURGERY

3. WarfarinLOW

Adjust dose to I N R < 2.5 Discontinue warfarin

MODERATE `'

Discontinue warfarin



FFP to decrease INR



to < 2.5.

HIGH

Discontinue & al ow P T to Discontinue warfarin
normalize. Substitute with FFP , Vit K to

heparin .

normalize PT.
Surgery in patients on

anticoagulants

Aspirin:

Discontinue 1 week before surgery.
Platelet transfusion
DDAVP

In emergency surgery

Fibrinolytics:
Wait for half life
6 min for TPA
23 min for Streptokinase
16 min for Urokinase
EACA: Only in emergency.

Weigh benefit Vs risk

CONCLUSION

The more exotic these approaches become, the more one is compelled

to emphasize that gentle handling, precise dissection and accurately

applied haemostasis constitute much the art of surgery.

Injecting, burning, stuffing, and scorching wounds is not likely to lead to

a higher plateau of accomplishment.

John A Collins , M.D