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HEMOSTASIS
By Prof\ Sameh ShamaaProf 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 systemExtrinsic system. Intrinsic system.12-20'' (seconds) 4-8' (minutes)In vivo only. In vivo & in vitroDue 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 XTissue 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 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
VIIIXa
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
3rd 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
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
HEMOSTASISHEMOSTA 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.
• 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 hemorrhage2-Inhibitors against platelets or tissue
phospholipids ---> prolongation of tests of coagulation (Quick or CKT) e.g L.E
but usually no hemorrhagic manifestations3- 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 defectif 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 diseasecongenital 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 eithera-toluidine blueb-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
Thank You
HEMOSTASIS