HEMOSTASIS

1
HEMOSTASIS
The ability of the body to control the flow of
blood
following vascular injury is
paramount to continued
survival.
- prevention of blood loss - to close the hole
in the vessel permanently - the process of
blood clotting and then the subsequent
dissolution of the clot, following repair of the
injured tissue
2

• normal haemostasis
• complicated relations between the vessel
  wall,
• 
  trombocytes
• 
  and coagulation and fibrinolytic system
• the balanced system the mutual proportions are
  not impaired
• - is
  continuously maintained
• - big biological
  potential of hemostatic system
  necessary regulation !!!
• - dysregulation
  thrombosis, bleeding.. DIC

the systems inhibiting the disseminated thrombosis
the systems supporting the local haemostasis
3
The hemostatic response can be divided into two
reactions
PRIMARY HEMOSTASIS
SECONDARY HEMOSTASIS
?
?
4

• PRIMARY HEMOSTASIS
• vascular constriction
• -the initial phase of the process
• -this limits the flow of blood to the area of
  injury
• - stimulus of the traumatized vessel
• ? nervous reflexes (pain)
• ? local myogenic spasm (direct
  damage)
• - lasts many minutes or even hours
• adhesion, activation and ggregation of
  platelets,
• formation of platelets plug
• platelets - circulate in an inactive form
• are activated, if the endothelium is damaged

5

• a) vascular wall
• - active role , mainly endotelium a subendotelium
• - function mechanical ? VASOCONSTRICTION
• synthetic ? formation
  and accumulation of substantions involved in
  hemostasis
• Important physiological anticoagulant
  instrument
• ?
• Endothelium no tissue factor (strong activator
  of coagulation)
• - nontrombrogenic barrier-

? ? ? intact , watter-repellent endothelium ? ?
?
6

• b) plateletes ? 2/3 blood pool
• ? 1/3 lien
  pool
• - c. membrane receptors .
  glykoproteins (GP), - primary plug
• 
  fc. - bond to subendotel
• 
  - bond to other plateletes
• fosfolipids (PF3
  - bond to factors of coagulation cascade
• surface for
• coagulation
  
  

Function of trombocytes 1. formation of
primary plug, stop bleeding immediately 2.
providing surface fosfolipids 3. release
factors (ADP, serotonin)
7
SECONDARY HEMOSTASIS

• over 40 different substances (in the blood
  and in tissues)
• balance between
• ? fa promoting coagulation .
  procoagulants
• ? fa inhibiting coagulation ...
  anticoagulants
• - the activation of plasma coagulation factors
• resulting in the formation of fibrin
• - fibrin reinforcement of the initial platelet
  aggregate
• is essential to prevent bleeding from larger
  lesions

8

9
(No Transcript)
10
INITIATION OF COAGULATION FORMATION
OF PROTHROMBIN ACTIVATOR
Prothrombin activator can be formed in two
basic ways
intrinsic pathway
intrinsic pathway
- they are initiated by different mechanisms -
the both converge on a common pathway, that leads
to clot formation - both pathways involve
numerous proteins .. clotting factors
11
the extrinsic mechanism for initiating clotting
12
the intrinsic mechanism for initiating
clotting blood coming in contact with collagen
or with a wettable surface
13

• plasminogen plasmin
• PLASMIN digests the fibrin
• fibrinogen, factor V, factor VIII,
• prothrombin, factor XII
• - hypocoagulability of the blood
• is activated by
• 1. thrombin
• 2. activated factor XII,
• 3. lysosomal enzymes.
• - activator systems
• also occur within the blood itself,
• especially the thrombin formed
• during the clotting process

14
DISSEMINATED INTRAVASCULAR COAGULATION

• pathophysiological process/syndrom and not a
  disease
• inappropriate excessive and uncontrolled
  activation of haemostatic process (coagulation,
  fibrinolysis)
• (on more places in circulation)
• systemic circulation of thrombin and plasmin
• characterised by consumption of clotting factors
  and platelets within circulation resulting in
  varying degrees of microvascular obstruction due
  to fibrin deposition
• and resulting in bleeding

15

• is a syndrome arising as a complication of
  many different serious illnesses (shock, sepsis)
• acute, chronic (rare) form
• ? in its acute form, DIC is usually an explosive,
  often life-threatening disorder
• ? when it is relatively mild or subclinical, DIC
  may not be so easy to spot
• clinical manifestation of DIC relates to
  occlusion of the microvessels during the
  obstructive phase of the syndrome
• and hemorrhage secondary to consumption of
  plasma and cellular components in the hemorhagic
  phase
• the perpetuation of the process may be due to
  continuation of the stimulus and/or consumption
  of the natural inhibitors of hemostasis

16

• in initiation ..may be adequate
  compensation
• ...defects only in the
  laboratory tests
• severe the initiating disorder... uncontrolled
  acute DIC ... systemic bleeding state ... end
  organ failure
• ACUTE (OVERT) FORM
• a hemorrhagic disorder.multiple
  ecchymoses,mucosal bleeding, and depletion of
  platelets and clotting factors
• CHRONIC (NONOVERT) FORM
• - involves thromboembolism accompanied by
  evidence of
• activation of the coagulation system
• - coagulation factors may be normal, increased,
  or moderately
• decreased, as may the platelet counts

17
pathogenesis of DIC
18

• Patophysiology of DIC
• - contemporary excess of thrombin a plazmin
  in blood
• oscilation of hemocoagulation balance to
  extrems hypo- hypercoagulation( thrombosis /
  bleeding )
• PRIMARY DISEASE
• ?
• 
  activation of coagulative cascade
• fibrinemia
• microvascular thrombosis
• 
  consumption of trombocytes
  
  
  coagulat.
  factors ff., inhibitors
• 
  aktivation of
  fibrinolysis
• 
  
• 
  degradation of ff. a inhibitors
• MODS /MOF
  
  BLEEDING

TF
TROMBIN
PLASMIN
19

• mechanisms which may inappropriately
• activate haemostatic system
• 1.? activation of coagulation sequence by
  release of tissue thromboplastins (tissue
  factor) into systemic circulation
• (extensive trauma, surgery, malignancy ,
  intravascular haemolysis)
• 2.? induction of platelet activation
• (eg septicaemia, viraemia, immune
  complexes)
• 3. ? vessel wall endothelial injury
• causing platelet activation followed by
  activation of the
• haemostatic systém (.e.g Gram-negative
  sepsis, extensive burns,
• prolonged hypotension, hypoxia or
  acidosis)

20
pathogenesis of DIC

• DIC occurs when monocytes and endothelial cells
  are activated or injured in certain
  diseases
• ? monocytes and endothelial cells generate
• tissue factor on the cell surface
• ? activating the coagulation cascade
• acute DIC...? explosive generation of thrombin
• ? depletes clotting factors and platelets
• ? activates the fibrinolytic system

21

• BLEEDING into the subcutaneous tissues, skin, and
  mucous membranes
• OCCLUSION of blood vessels caused by fibrin in
  the microcirculation
• significant platelet and coagulation factor
  consumption
• ? ? ? BLEEDING may become a major feature
• chronic DIC... less explosive, compensatory
  responses
• ? the likelihood of bleeding
• ? hypercoagulable state
• - changes can be detected by testing the
  coagulation system
• - thromboembolism

22

• clinical features
• presentation varies
• mixture of thrombotic, haemorrhagic or mixed
• manifestations in various organ systems
• major problem and presenting feature of acute
  DIC is
• bleeding ( think of trombosis !!!)
• when occurs in patients with MOF prognosis is
  poor
• in some patients, DIC may be an agonal event
  and should
• not be treated
• presentation in pregnancy may be more sudden
  and
• unexpected

23

• CONDITIONS ASSOCIATED WITH DIC
• INFECTION
• ? bacterial
• ? viral CMV, hepatitis viruses, HZV
• OBSTETRIC
• ? amniotic fluid embolism
• ? placental abruption
• ? eclampsia
• ? retained dead fetus
• ? septic abortion

24

• INTRAVASCULAR HAEMOLYSIS
• ? haemolytic transfusion reaction
• ? massive transfusion
• ? minor haemolysis
• TRAUMA OR BURNS most frequent !!!
• VENOMS AND TOXINS
• HEPATIC DISEASE
• PROSTHETIC DEVICES
• ? intra-aortic balloon pump
• ? Leveen shunt
• ? cardiopulmonary bypass

25

• VASCULAR DISORDERS
• ? hereditary telangiectasia
• ? thrombotic thrombocytopaenic purpura
• ? vasculitis
• ? AV fistula
• ? angiosarcoma
• ? malignant hypertension
• MALIGNANCY
• ? adenocarcinoma prostate, lung, breast,
  pancreas
• ? haematological acute promyelocytic leukaemia,
  myeloproliferative disease, myeloma

26
laboratory findings

• results may be variable and difficult to
  interpret
• ( no specific test)
• significant DIC can be present despite normal
  PT, APTT and TT but conversely patients may have
  laboratory features of DIC without any clinical
  sequelae
• the key tests in diagnosis are those that provide
  evidence for excessive conversion of fibrinogen
  to fibrin within the circulation and its
  subsequent lysis
• platelet- fibrin clots create a mesh in the
  microcirculation in which passing red cells may
  be traumatized, resulting in haemolysis

27
diagnosis
combination of the clinical picture with
supportive pattern of laboratory tests of the
haemostatic system evidence for the diagnosis
thrombocytopenia,hypofibrinogenaemia,
prolongation of the APTT, PT,TCT, elevation of
fibrin degradation products ( D- Dimer test)
- in chronic DIC,the laboratory findings are
different from acute DIC - many of the usual
tests of haemostasis are normal or near normal
28
diagnosis of acute DIC

• clinical findings
• multiple bleeding sites,
• ecchymoses of skin, mucous membranes
• visceral hemorrhage, ischemic tissue
• laboratory abnormalities
• coagulation abnormalities prolonged prothrombin
  time, activated partial thromboplastin time,
  thrombin time
• decreased fibrinogen levels increased levels
  of FDP (eg, on testing for FDP, D dimer)
• platelet count decreased, schistocytes on
  peripheral smear

29
diagnosis of chronic DIC

• clinical findings
• - signs of deep venous or arterial thrombosis or
  embolism
• - superficial venous thrombosis, without varicose
  veins
• - multiple thrombotic sites at the same time
• - serial thrombotic episodes
• laboratory abnormalities
• - modestly increased prothrombin time
• - shortened or lengthened partial
  thromboplastin time
• - normal thrombin time
• - high, normal, or low fibrinogen level
• - high, normal, or low platelet count
• - increased levels of FDP (eg, on testing for
  FDP, D dimer)

30
therapy

• Blood component in haemorrhaging patient
• !!!! the use of heparin only in selected causes
  !!!
• FFP .contains all the coagulation factors, main
  inhibitors, antithrombin III, protein C, in near
  normal quantities and should be used if
  haemorrhage is occurring.
• Cryoprecipitate..contains VIII complex as well
  as fibrinogen , factor XIII in concentrated form
• Platelet transfusion .. in the presence of
  life-threatening haemorrhage

31
TREATMENT
- treatment of the underlying disease is the
mainstay of management of either acute or
chronic DIC ! - additionally, acute DIC is
treated with blood products TREAT THE UNDERLYING
DISEASE - avoid delay - treat vigorously (eg,
shock, sepsis, obstetrical problems)
32
manage the acute DIC

• !!! No treatment !!! blood components as
  needed
• ?fresh frozen plasma
• ? cryoprecipitate
• ? platelet
  transfusions
• ? anticoagulants (see "with thromboembolism"
  below)
• after bleeding risk is corrected with blood
  products

without bleeding
with bleeding
with ischemia
33
manage the chronic DIC

• no specific therapy needed but prophylactic drugs
• (eg, low-dose heparin, low-molecular-weight
  heparin)
• may be used for patients at high risk of
  thrombosis
• ? heparin or low-molecular-weight heparin,
• ? trial of warfarin sodium (Coumadin).

without thromboembolism
with thromboembolism
34
management of sudden massive obstetric haemorrhage

• is similar to other cases of DIC
• except!!!
• the onset is more likely to be fulminant and
  unexpected
• is associated with greater
  depletion
• of coagulation factors,
  especially fibrinogen
• ( marked fibrinolysis)
• fresh blood is possibly warranted
• !once the uterus has been emptied and contracted,
  the haemostatic failure quickly resolves!

35
(No Transcript)
36
Schéma probíhající
hemokoagulace
a degradace fibrin polymerové síte
? ? ? tkánový faktor
plazmatický koagulacní systém


PROTROMBIN
tPA x PAI

PLASMIN
TROMBIN
X
antitrombin heparin

degradace trombocytu
Fibrin polymer
degradacní produkty
.
Valenta J., Dg. a terapie akutního por. krvácení,
2002
37
Schéma probíhající
hemokoagulace
a degradace fibrin polymerové síte
? ? ? tkánový faktor
plazmatický koagulacní systém


PROTROMBIN
tPA x PAI

PLASMIN
TROMBIN
X
antitrombin heparin

degradace trombocytu
Fibrin polymer
degradacní produkty
.
Valenta J., Dg. a terapie akutního por. krvácení,
2002
38

• Patofyziologie DIC aktivace všech systému
  hemostázy
• - kolísání hemokoagulacní rovnováhy k
  extrémum hypo- hyperkoagulace ( tromby /
  krvácení )
• ZÁKLADNÍ ONEMOCNENÍ
• ?
• 
  aktivace koagulacních systému
  ( koagul. faktoru, desticek)
• 
  fibrinémie
• a mikrovaskulární
  trombóza
• 
  konzumpce trombocytu,
• 
  
  
  koagulacních faktoru ff., inhibitoru
• 
  aktivace
  fibrinolýzy
• 
  
• 
  biodegradace ff. a inhibitoru
• ( MULTI) ORGÁNOVÉ SELHÁNÍ
  MNOHOCETNÁ KRVÁCIVÁ DIATÉZA

TF
TROMBIN
FIBRINOGEN ? fibrin ?
tkáne bohaté na tPA
PLASMIN
39
(No Transcript)
40

• intrinsic and extrinsic pathway

41
(No Transcript)