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)
3- platelets secretion: adhesion of platelets-
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
(Extrinsic system.)
HEMOSTASIS
II-delayed system
(Intrinsic system.)
systems of coagulation
I-urgent system.
Extrinsic system.
12-20'' (seconds)
In vivo only.
Due to tissue damage.
II-delayed system
Intrinsic system.
4-8' (minutes)
In vivo & in vitro
due to contact with foreign surface
↓
↓
Tissue factor
activation of contact system
↓
↓
X < ------------------------------------IX a < ---------------- IX
↓
Xa
↓
2- prothrombin
thrombin
3-fibrinogen
HEMOSTASIS
Fibrin
EXTRINSIC SYSTEM
FACTORS NICESSORY ARE:
Factor X
Tissue factor and Factor VII
Tissue F.
VIIa
Xa
Blood vessel
HEMOSTASIS
VII
X
INTRINSIC SYSTEM
Necessary factors: XII (Hageman factor)
- Contact system XI
Kallikrene
kininogene
- F. IX
- F. VIII
- F. X
- Ca. ++
- phospholipids of the platelet’s 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
HEMOSTASIS
IIa
Second Step: of Coagulation
Thrombin Formation: (IIa)
Factors needed:
- prothrombin (II)
Ca++
- Xa
II
- V (acceleririe)
- phospholipids
- Ca + +
IIa
HEMOSTASIS
platelets
V
Xa
Ca++
3rd Step :Fibrin Formation
Fibrin Formation:-----------------------IIa
XIII
(Fibrinogen) -------------------Ia
(Soluble fibrin)
HEMOSTASIS
Insoluble Fibrin
XIIIa
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
is the process wherein a fibrin clot, the
product of coagulation, is broken down.Its
main enzyme plasmin cuts the fibrin mesh
at various places, leading to the
production of circulating fragments that are
cleared by other proteases or by the
kidney and liver
HEMOSTASIS
HEMOSTASIS
Measurement
When plasmin breaks down fibrin, a
number of soluble parts are
produced. These are called fibrin
degradation products (FDPs). FDPs
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
HEMOSTA fibrinolysis
HEMOSTASIS
(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.
Affected by factors VII, X, V, II & •
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
Hageman factor'. Affected by factors XII,
XI, IX, VIII, X, II
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
congenital or acquired
platelet factor tests
HEMOSTASIS
Willebrand disease
dosage of factor VIII
PRACTICAL INVESTIGATION OF
HEMOSTATIC TROUBLE
3- ↑Quick + ↑CKT Other tests are N
Acquired defect of several
factors (II, VII, X,V)
defect of factor common for
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
PRACTICAL INVESTIGATION OF
HEMOSTATIC TROUBLE
8-All tests ate Normal:
* Capillary fragility (usually only
ecchymoses ) ---> measurement of
cap.fragility.
* deficient factor XIII
* no hemostatic troubles.
HEMOSTASIS
Thank You
HEMOSTASIS