HEMOSTASIS

By Prof\ Sameh Shamaa

Prof Of medical Oncology and
Internal medicine
Mansoura Faculty Of Medicine
HEMOSTASIS
HEMOSTASIS
Def:- stoppage of bleeding from the blood
vessels
Mechanisms
(I) v.c of blood vessels
(II) platelet plug formation
(III) Blood coagulation (fibrinogen fibrin)
(IV) Clot retraction
(V) fibrinolysis to dissolve the clot
HEMOSTASIS
PRIMARY HEMOSTASIS

includes the processes that result in the
formation of the platelet plug.
Necessary factors-:
-The blood vessels : the vessel walls esp. the
subendothelial layer.
- The platelets
- 2 plasma glycoproteins:
- fibrinogen
-Willebrand factor ,which
also presents inside the platelets

Mechanisms:

1-v.c of the bl. vessel.
2- Platelets adhesion to subendothelial layer, ( Willebrand
factor is necessary for this stage)
adhesion of platelets- 3- platelets secretion:
their activation and secretion of ADP,adrenaline,
noradrenaline > aggregation & activation of other
platelets.
4- Aggregation of platelets.
5- Formation of capillary plug.


HEMOSTASIS
Exploration of the 1ry homeostasis
1) Important points in the history
of any bleeding patients :

HEMOSTASIS
- Family history
- Duration (recent onset or since childhood)
- Duration of the bleeding episode.
- Circumstance of bleeding
(spontaneous, after trauma, or surgery)


HEMOSTASIS
Type and character of bleeding:
-

- Purpuric spots
(capillary or platelets defect not characteristic of
hemophilia)
- Hematoma, hemarthrosis or large ecchymoses at
the site of trauma :
suggests hemophilia (coagulation defect)
- Sudden severe bleeding from multiple sites after
prolonged surgery or during obstetric procedures
suggests acquired fibrinogen defect

HEMOSTASIS
2) Investigations :
HEMOSTASIS
1) Capillary resistance test of Hess
2) Platelets count
3) Bleeding time
time needed for the platelet plug formation
If . N. ------ Normal 1ry homeostasis .
------ platelet or vascular defect.
HEMOSTASIS
Capillary resistance test of
Hess:

sphygmomanometer cuff above the cubital
fossa and raise the pressure to 100 mm Hg
(or midway between systolic & diastolic if
systolic pressure <100) for 5 - 7' minutes-
deflation '3 minutes later count the
number of petichea in area of 3 cm diameter,
1 cm below the cubital fossa Normally up
10 if more than 20, means platelets or
capillary wall defect
HEMOSTASIS
4) Other tests
only done if there is a prolonged bleeding
time with normal platelet count
- Measurement of capillary resistance
- Measurement of Willebrand factor
- Platelets function tests (Adhesiveness,
Aggregation)
- other tests for platelets (clot retraction,
prothrombin consumption).


HEMOSTASIS
Coagulation of Blood
Def :- represent the conversion of fibrinogen
(soluble protein) to fibrin (insoluble)
meshwork which occludes the point or
vessel rupture.


HEMOSTASIS
First Step :Activation of factor X
BY One of 2 systems:

I-urgent system II-delayed system
(Extrinsic system.) (Intrinsic system.)
HEMOSTASIS
systems of coagulation
I-urgent system. II-delayed system
Extrinsic system. Intrinsic system.
12-20'' (seconds) 4-8' (minutes)
In vivo only. In vivo & in vitro
Due to tissue damage. due to contact with foreign surface


Tissue factor activation of contact system

X < ------------------------------------IX a < ---------------- IX

Xa

2- prothrombin thrombin

3-fibrinogen Fibrin

HEMOSTASIS
EXTRINSIC SYSTEM
FACTORS NICESSORY ARE:
Factor X
Tissue factor and Factor VII
Tissue F.

VIIa VII
Xa X



Blood vessel

HEMOSTASIS
INTRINSIC SYSTEM
Necessary factors: -
XII (Hageman factor)
- Contact system XI
Kallikrene
kininogene
- F. IX
- F. VIII
- F. X
- Ca. ++
- phospholipids of the platelets membrane

HEMOSTASIS
Contact System:
Foreign surface
|--------------------------------------------------|
Kalierne XII kininogene

Fragmentation
XIIa

XI XIa

Rest of intrinsic pathway
IX

HEMOSTASIS
Rest of intrinsic pathway
IX
Platelets
Ca ++
IXa

X VIIIa

VIII
Xa
II IIa



HEMOSTASIS
Second Step: of Coagulation
Thrombin Formation: (IIa)
Factors needed:
- prothrombin (II) Ca++ platelets
- Xa II V Ca++
- V (acceleririe) Xa
- phospholipids
- Ca + + IIa

HEMOSTASIS
3
rd
Step :Fibrin Formation
Fibrin Formation:-
------------------------
IIa
XIII XIIIa

(Fibrinogen) -------------------- Ia
(Soluble fibrin)


Insoluble Fibrin
HEMOSTASIS
Physiological anticoagulants
1- Serine protease inhibitors :inhibit the
coagulation cascade.
2-Neutralizers of activated coagulation
factors (components of protein C system)
HEMOSTASIS
1-Serine protease inhibitors:
1-Antithrombin (III).
2-Heparin and heparin like
substance.
3-Alpha 1 antitypsin.
4-Alpha 2 macroglobulin
HEMOSTASIS
2-Neutralizers of activated
coagulation factors :
(components of protein C
system)

1-Protein C: synthesized in the
liver, vit. K dependant, activated by
thrombin.
2-Thrombomodulin.
3-Protein S and C4b-binding
protein.
HEMOSTASIS
Fibrinolysis
, the clot fibrin is the process wherein a
, is broken down.Its coagulation product of
cuts the fibrin mesh plasmin enzyme main
at various places, leading to the
production of circulating fragments that are
or by the proteases cleared by other
liver and kidney
HEMOSTASIS
HEMOSTASIS
Measurement
When plasmin breaks down fibrin, a
number of soluble parts are
fibrin produced. These are called
(FDPs). FDPs degradation products
compete with thrombin, and so slow
down the conversion of fibrinogen to
fibrin (and thus slows down clot
formation).
Exploration of the coagulation
(I) whole blood clotting time
Normally 4-10 minutes
Generally ---> N. in platelets defects.
= coagulation defect

But not very sensitive: - only +ve when blood
coagulation is very defective

HEMOSTASIS HEMOSTA fibrinolysis
(Hyperfibrinolysis), SIS
(2) One stage prothrombin time:
general exploration or the extrinsic pathway
(Quick time)
N : 16-18 sec.
addition of tissue thromboplastin +
ca++ to decalcified plasma ---> measure
the time till coagulation occur.
& II , V , X VII, Affected by factors
fiboinogen (only severe defect)




HEMOSTASIS
(3) partial thromboplastin time (PTT)
or CKT(cephaline koalin time)
General exploration of the intrinsic pathway
clotting time of recalcified plasma in the
presence of phospholipid (cephaline),
while koalin powder for activation of
, XII Hageman factor'. Affected by factors
II , X , VIII , IX , XI

HEMOSTASIS
(4) Thrombin time
detect the defects in the conversion of
fibrinogen ---> fibrin
Measured by addition of thrombin to citrated
patients plasma
If polonged
Abnormalities of fibornogen
(hypo or hyper or dysfibrinogenemia)
Heparin
Presence of some abnormal proteinswhich inhibits the
polymerisation of monomers of fibrin. (e.g myeloma
protein


HEMOSTASIS
(5) Deficiency of F XIII (fibrin stabilizing
factor ) detected by noting the solubility of fibrin
in 5M urea or 1% monochloroacetic acid (can't
dissolve fibrin in the presence of factor XIII).In
congenital defect of f. XIII ---> dissolution of the
clot in <10.
(6) Assay for each cogulation factor is
available


HEMOSTASIS
(7) Detection of coagulation inhibitors:

1-Inhibitors for a specific factor (especially F. VIII)
usually ---> severe hemorrhage
2- Inhibitors against platelets or tissue
phospholipids ---> prolongation of tests of
coagulation (Quick or CKT) e.g L.E
but usually no hemorrhagic manifestations
3- if there is of Quick test or CKT or thrombine:-
50% of normal plasma + 50% of patient plasma
(incubation at 370c for I hour) repeat the test
If become normal ---> factor defect
if no correction ---> presence of inhibitors.

HEMOSTASIS
PRACTICAL INVESTIGATION OF
HEMOSTATIC TROUBLE
B.T
Platelets count
Quick test
CKT
Thrombin time
Dosage of fibrinogen

HEMOSTASIS
PRACTICAL INVESTIGATION OF
HEMOSTATIC TROUBLE
I- B.T, platelets ( 80.000; mm3)

Thrombocytopenia

2- B.T, platelets normal

Qualitative platelets abnormalities Willebrand disease
congenital or acquired

platelet factor tests dosage of factor VIII
HEMOSTASIS
PRACTICAL INVESTIGATION OF
HEMOSTATIC TROUBLE
3- Quick + CKT Other tests are N

Acquired defect of several defect of factor common for
factors (II, VII, X,V) 2 pathways ex. X or V or II

4- Quick N., CKT: either:
I- Hemophilia Aor B.
2- Rarely ---> defect of one factor of the contact system
(XII, or XI or others)
HEMOSTASIS
PRACTICAL INVESTIGATION OF
HEMOSTATIC TROUBLE
5- Quick , CKT N

isolated defect of factor VII


in 3, 4..5 dosage of the factors with suspected deficiency,
also search for inhibitors. Ex:

- Quick, normal dosage of factors--->
hyperfibriongenemia which inhibit the test
- Quick +CKT + no F. defect --->? Inhibitors, e.g.
antiphospholipides.

HEMOSTASIS
PRACTICAL INVESTIGATION OF
HEMOSTATIC TROUBLE
6-T.T either:
* heparine in the blood or in the tube. Here T.T
can be corrected by adding either
a- toluidine blue
b-Reptilase time (incomplete thrombin not
sensitive to heparin and not inhibited by
antithrombin III).
* If (a-b also defective) ---> troubles of fibrin
polymerisation :either due to abnormal fibrin
(dysfibrinogenimia) or inhibition e.g by --->
myeloma protein or F.D.P.
HEMOSTASIS
PRACTICAL INVESTIGATION OF
HEMOSTATIC TROUBLE
7- fibrinogen
* congenital afibrinogenimia or
hypofibrinogenimia
Acquired hypofibrinogenimia e.g.liver
cirrhosis.
consumption of fibrinogen: e.g. D.I.V.C,
fibrinolysis

HEMOSTASIS

8-All tests ate Normal:
* Capillary fragility (usually only
ecchymoses ) ---> measurement of
cap.fragility.
* deficient factor XIII
* no hemostatic troubles.



PRACTICAL INVESTIGATION OF
HEMOSTATIC TROUBLE
HEMOSTASIS

HEMOSTASIS