Haemostasis Flashcards
Haemostasis is the mechanism that _______________
keeps blood in a fluid state
Normal hemostasis is dependent upon the complex interaction of plasma _______ and __________ proteins, ______, and the blood vasculature.
coagulation
fibrinolytic
platelets
Normal haemostasis can be div. into:
The 3 categories are:
_________ hemostasis
________ hemostasis
_________ hemostasis
Primary
Secondary
Tertiary
Normal haemostasis can be div. into:
The 3 categories are:
Primary hemostasis: the formation of the ________
Secondary hemostasis: formation of ________________________
Tertiary hemostasis: the formation of _____________________
platelet plug.
fibrin through the coagulation cascade.
plasmin for breakdown of the clot.
5 major components are involved in haemostasis
◼ Blood ________
◼ Blood ________
◼ Coagulation _______
◼ Coagulation __________
◼ ___________
vessels
platelets
factors
inhibitors
Fibrinolysis
Blood platelets
Are ______ of _______ of ________
(Nucleated or Non- nucleated?)
Produced mainly by the ___________
fragments; cytoplasm; megakaryocytes
Non- nucleated
bone marrow
Blood platelets
Normal platelet count- ____-____ x 109/l
Life span is about ______ days
95-400
7-10
Blood platelets
About ___/3 is trapped in the normal _____
1
spleen
Blood platelets
Measures about ____-_____
Volume about ____-____ fl
3x0.5μm
7-11
Blood platelets
Contains 3 types of storage granules ◼__________
◼__________/_________
◼ __________
Dense granules
Alpha/specific granules
lysosomes
Dense granules:
____________
__________
__________
Nucleotides(ADP,ATP,5-HT)
Calcium
Serotonin
Lysosomes contain _________
catalase
Factor V
Dense or specific granules?
Specific
Platelet-derived growth factor
Dense or specific granules?
specific
Fibronectin
Dense or specific granules?
specific
Β-thromboglobulin
Dense or specific granules?
specific
Heparin antagonist(PF-4)
Dense or specific granules?
specific
Thrombospodin
Dense or specific granules?
Specific
VWF
Dense or specific granules?
Specific
Fibrinogen
Dense or specific granules?
Specific
Calcium
Dense or specific granules?
Dense
Serotonin
Dense or specific granules?
Dense
Nucleotides
Dense or specific granules?
Dense
Platelet function
Main function is the formation of __________ in response to vascular injury
haemostatic plugs
Lack of platelet may lead to spontaneous leakage of blood through vessel walls
T/F
T
Primary haemostasis
Primary hemostasis is defined as the formation of the __________ and involves platelets, the blood vessel wall and __________
primary platelet plug
von Willebrand factor.
Primary haemostasis
Abnormalities result in _________ from mucosal surfaces, ______ or _______ hemorrhages, and prolonged bleeding after venipuncture or wounds
hemorrhage
petechial or ecchymotic
The normal endothelium prevents hemostasis by providing a ________ and by secreting products which inhibit platelets, including ____________ and _________
physical barrier
nitric oxide and prostaglandin I2 (prostacyclin)
The formation of the primary platelet plug involves platelet ______ followed by platelet _______ then _______ to form a platelet plug.
adhesion; activation; aggregation
❖ Platlet-vessel wall interaction ( ______ )
❖ Platelet-platelet interaction ( __________ )
❖ Platelet release reaction
Adhesion
Aggregation
Platelet adhesion
The _____ event in hemostasis is the adhesion of platelets to ___________
1st
exposed subendothelium.
Platelet adhesion
In areas of high shear rate (in the microvasculature), this is mediated ______, which binds to gp ____\ in the platelet membrane.
In areas of low shear rate (e.g. _______), _______ mediates the binding of platelets to the gp _______).
vWf; Ib
Aorta ; fibrinogen
Ia/IIa
Platelet activation
The _____ of platelets to the vessel wall activates them,
❖ platelets to __________,
❖ activate the _____ on their surface
❖ undergo the _____ reaction
❖ platelets synthesize and release _________ and ________ which are potent platelet aggregating agonists and vasoconstrictors
adhesion
change shape
collagen receptor
release
TXA2 and platelet activating factor (PAF),
Collagenous receptor is an
_______ receptor called glycoprotein _____/_____
integrin
PLATELET AGGREGATION
Platelet aggregation is mediated primarily by __________
______has a secondary role
which binds to glycoprotein ______ on adjacent platelets.
fibrinogen
vWf
IIb/IIIa
PLATELET AGGREGATION
This aggregation leads to the formation of the ________, which must be stabilized by the formation of ________.
primary platelet plug
fibrin
Platelet procoagulant activity
❖ Following platelet aggregation and release, the exposed membrane phosplolipid(_____) is then available for the _______ and _______ reactions in secondary haemostasis
PF3
tenase and prothrombinase
Blood coagulation(20 haemostasis)
It’s a biological amplification system characterized by ________ of a cascade of circulating precursors (__________)
culminating in the generation of _________
Sequential activation
coagulation factor enzymes
thrombin
Blood coagulation(20 haemostasis)
This involves
❖ circulating _________, which act as
enzymes [which require _______]
❖ cofactors (_____________),
❖_______ and
❖ platelets (platelets provide a source of _________ and a ___________ upon which the coagulation cascade proceeds)
coagulation factors; activation
factors V and VIII
calcium
phospholipid [PF3] and a binding surface
Defects in the primary hemostasis manifest as more serious bleeding than coagulation cascade
T/F
F
Defects in the coagulation cascade manifest as more serious bleeding than primary hemostasis
Defects in Coagulation
Defects in the coagulation cascade manifest as more serious bleeding than primary hemostasis, including bleeding into ____ (chest, joints) and __________.
cavities; subcutaneous hematomas
Defects in Coagulation
Petechial hemorrhages
are seen in disorders of secondary hemostasis.
T/F
F
Not seen
Defects in Coagulation cascade
These disorders do share common bleeding symptoms with defects in primary hemostasis, including _________ and _________________-
epistaxis and bleeding after surgery or
wounds
___________ and ________
this may be the 1st sign of a hemostatic
defect
epistaxis and bleeding after surgery or
wounds
Defects in Coagulation cascade va defects in primary haemostasis
it may be impossible to distinguish between defects in these 2 pathways based on clinical signs alone.
T/F
T
Coagulation factors
Factor 1——— ________
II————-_________
III- ___________
V———–________
VII——— ________
VIII—-_________
IX——- ____________
X ——-____________
XI——- ________________
XII—— __________(______)
XIII—–___________
HMWK (Fitzgerald factor)
fibrinogen
prothrombin
Tissue factor
labile factor
Proconvertin
Antihaemophylic factor
Christmas factor
Stuart power factor
plasma thromboplastin antecedent
Hageman (contact) factor
Fibrin stabilizing factor
Coagulation invivo depends on enzyme
complex:
◼__________
◼__________
◼____________
◼__________
Protease
Cofactor
Phospholipid
Calcium
Coagulation invivo depends on enzyme
complex:
Extrinsic tenase—-(_____,_____ ____,_______ →Xa
Intrinsic tenase —-(_____,_____,_____,______ ) →Xa
VIIa, TF, PL, Ca2+
IX, VIII, PL, Ca2+
Coagulation invivo depends on enzyme
complex
Prothrombinase complex—-(_____,_____,______,_______)
Xa
Va
Pl,
Ca2+
Physiological limitations of Blood
coagulation
Unchecked blood coagulation could lead to serious ____________(_______)
vascular occlusion(thrombosis)
Coagulation factors inhibitors
TFPI (synthesized by _______ cells, its present in ______ and ______ and accumulates at sites of injury caused by local platelet activation)
endothelial
plasma & platelets
Coagulation factors inhibitors
◼ TFPI inhibits:
_____
______
_____
Xa
VIIa
TF
Coagulation factor Inhibitors
__________
_________
_____________
________
________
Antithrombin III
Heparin cofactor II
C1 esterase inhibitor
Protein C
Protein S
Coagulation factor Inhibitors
Antithrombin III: effects is enhanced by ________
heparin
Protein C inhibits _____________
FVa &FVIIIa
Thrombin binds to ___________, and this complex activate _______
(________ is a cofactor)
thrombomodulin
protein C
protein S
Blood flow: activated factors are
rapidly ______ by the blood and
destroyed by the _________
cells
diluted
liver parenchymal
Tertiary hemostasis
Tertiary hemostasis is defined as the
formation of _______, which is the
main enzyme responsible for
__________(______________)
plasmin
fibrinolysis
breakdown of the clot
Fibrinolysis
It’s a normal haemostatic response to injury ensuring the _________ of the _______
dissolution of the fibrin clot.
Fibrinolysis
___________ (tpA) binds to ________ —ensures that ________________
Tissue plasminogen activator
fibrin; fibrin generation is
localized to the fibrin clot
Fibrinolysis
APC stimulates fibrinolysis by _____________
destroying
plasma inhibitors of tpA
Fibrinolysis
Thrombin inhibits fibrinolysis by __________________________
activating thrombin-activated fibrinolysis inhibitor(TAFI)
Plasmin is capable of digesting:
◼________
◼ _______
◼_____
◼_____
Fibrinogen
Fibrin
FV
FVIII
Therapeutic fibrinolytic agents
◼_________________
◼ _________ (initially from human urine)
◼ _________ (from haemolytic
streptococci)
Recombinant tPA
Urokinase
Streptokinase
Inhibitors of plasmin
◼___________________ (PAI)
◼________________
Plasminogen activator inhibitor
Alpha2 antiplasmin
Tests of Haemostasis
Defective haemostasis with abnormal
bleeding may result from:
◼ ________ disorder
◼______________
◼ Defective ___________
Vascular
Thrombocytopaenia
blood coagulation
Tests of haemostasis
_______
______
________
Thrombin time
APTT
PT
Tests of haemostasis:Thrombin time
•normal range: ___-____secs.
•Prolongation due to ____________
•FDPs(_______)
◼ Associated disorder:
______
________
14-16
dysfibrinogenaemias
Fibrin degradation products
DIC; Heparin RX
Tests of haemostasis
APTT(_________________)
•Measures the ______ pathway, its global test of haemostasis
•normal range ___-____ secs
•Prolonged in:_________, _______,_____
Activated Partial Thromboplastin Time (aPTT)
intrinsic
30-40
Haemophilia
Von willbrand disease
DIC
Thrombin time
It measures the time it takes for _______________________________________________
a clot to form after the addition of thrombin, a protein involved in the clotting process.
Tests of haemostasis: PT
measures the ______ pathway and the common pathway:
•_____,______,_____,______,______
•Normal range—___-___secs
Prolonged in:
◼_______
◼______ therapy
◼_____
extrinsic
FVII, X, V, III & fibrinogen
10-14
Liver disease; Warfarin; DIC
Tests of haemostasis
Fibrinogen assay: indication is _______ deficiency,
Fibrinogen is (Increased or Reduced?) in DIC
fibrinogen
Reduced
Tests for Haemostasis
Bleeding Time: Normal range is _____________
3-8 minutes
Tests of haemostasis
________ assay
_________ Time
__________ count
Fibrinogen
Bleeding
Platelet