HEMOSTASIS

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HEMOSTASIS

• By Prof\ Sameh Shamaa
• Prof Of medical Oncology and Internal medicine
• Mansoura Faculty Of Medicine

HEMOSTASIS
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HEMOSTASIS

• Def- stoppage of bleeding from the blood vessels
• Mechanisms
• v.c of blood vessels
• platelet plug formation
• Blood coagulation (fibrinogen fibrin)
• Clot retraction
• fibrinolysis to dissolve the clot

HEMOSTASIS
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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

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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 gt
  aggregation activation of other platelets.
• 4- Aggregation of platelets.
• 5- Formation of capillary plug.
•  

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Exploration of the 1ry homeostasis

• Important points in the history of any bleeding
  patients

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

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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

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

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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
  lt100) 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
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• 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).

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Coagulation of Blood

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

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First Step Activation of factor X

• BY One of 2 systems

I-urgent system II-delayed
system (Extrinsic system.) (Intrinsic
system.)
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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 lt ------------------------------------IX a lt
  ---------------- IX
• ?
• Xa
• ?
• 2- prothrombin thrombin
• 3-fibrinogen Fibrin

HEMOSTASIS
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EXTRINSIC SYSTEM

• FACTORS NICESSORY ARE
• Factor X
• Tissue factor and Factor VII
• Tissue F.
• VIIa VII
• Xa X
• 
  Blood vessel

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INTRINSIC SYSTEM

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

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• Contact System
• Foreign surface
• --------------------------------------
  ------------
  Kalierne XII kininogene
• Fragmentation
• XIIa
• XI XIa
• Rest of intrinsic pathway
• IX

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• Rest of intrinsic pathway
• IX
• Platelets
• Ca
• IXa
• X VIIIa
• VIII
• Xa
• II IIa

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Second Step of Coagulation

• Thrombin Formation (IIa)
• Factors needed
• - prothrombin (II) Ca platelets
  
• - Xa II V Ca
• - V (acceleririe) Xa
• - phospholipids
• - Ca IIa

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3rd Step Fibrin Formation

• Fibrin Formation-
• ------------------------
• IIa
• XIII XIIIa
• (Fibrinogen) -------------------- Ia
• (Soluble fibrin)
• 
  
• Insoluble Fibrin

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Physiological anticoagulants

• 1- Serine protease inhibitors inhibit the
  coagulation cascade.
• 2-Neutralizers of activated coagulation factors
  (components of protein C system)

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1-Serine protease inhibitors

• 1-Antithrombin (III).
• 2-Heparin and heparin like substance.
• 3-Alpha 1 antitypsin.
• 4-Alpha 2 macroglobulin

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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.

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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

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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).

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Exploration of the coagulation

• whole blood clotting time
• Normally 4-10 minutes
• Generally ---gt N. in platelets defects.
• ? coagulation defect
• But not very sensitive - only ve when blood
  coagulation is very defective

HEMOSTASIS
HEMOSTA fibrinolysis (Hyperfibrinolysis), SIS
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• (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 ---gt measure the
  time till coagulation occur.
• Affected by factors VII, X, V, II fiboinogen
  (only severe defect)

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• (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
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• Thrombin time
• detect the defects in the conversion of
  fibrinogen ---gt 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

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• (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 ---gt
  dissolution of the clot in lt10.
• (6) Assay for each cogulation factor is available

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• (7) Detection of coagulation inhibitors
• 1-Inhibitors for a specific factor (especially F.
  VIII)
• usually ---gt severe hemorrhage
• 2- Inhibitors against platelets or tissue
  phospholipids ---gt 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 ---gt factor defect
• if no correction ---gt presence of inhibitors.

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PRACTICAL INVESTIGATION OF HEMOSTATIC TROUBLE

• B.T
• Platelets count
• Quick test
• CKT
• Thrombin time
• Dosage of fibrinogen

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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

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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 ---gt defect of one factor of the
  contact system (XII, or XI or others)

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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---gt
  hyperfibriongenemia which inhibit the test
• - ?Quick ?CKT no F. defect ---gt? Inhibitors,
  e.g. antiphospholipides.

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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) ---gt troubles of fibrin
  polymerisation either due to abnormal fibrin
  (dysfibrinogenimia) or inhibition e.g by ---gt
  myeloma protein or F.D.P.

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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

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PRACTICAL INVESTIGATION OF HEMOSTATIC TROUBLE

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

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Thank You
HEMOSTASIS