Normal Hemostasis Flashcards
Hemostasis
coagulation or hemostasis is the process involved when blood clots in reponse to an injury
3 stages of normal coagulation
- primary hemostasis
- secondary hemostatsis
- fibrinolysis
Primary hemostasis
injury-> damaged vessels initiate hemostasis:
contraction of vessels: minimizes blood flow to wound area & brings platelets & coag factors closer to vessel wall
Megakaryoblast MK1
6-24 microns scant basophilic cytoplasm no visible granules round nucleus visible nucleoli
Promegakaryocyte MK2
cytoplasmic granule development begin
membrane demarcation begins
nucleus lobulated
no visible nucleus
Megakaryocyte MK3
cytoplasmic RNA (blue) disappear so it is more purple
proplatelets-groups of platelets break off into circulation
granular cytoplasm
large, multilobed nucleus
Mature Megakaryocyte
after proplatelets have been released
all that is left is the nucleus, which is phagocytized by macrophages & broken down
Platelet Structure
peripheral zone: phospholipid layer w/ protein
structural zone: microtubules etc
organelle zone: granules & organelles
membrane systems
Formation of Platelet plug involves:
platelet adhesion platelet activation platelet shape change platelet secretion of granules platelet aggregation
Platelet Adhesion
damaged vessels exposes flowing blood to subendothelial connective tissue that is composed of adhesive molecules 3 components: 1. vWF -links platelet to subendothelial 2. platelet membrane receptorGPlb 3. collagen fibers
Platelet adhesion: vWF
synthesized by endothelial cells & megakaryocytes
absorbed onto the surface of the platelet bound to its receptor GPlb
becomes a bridge connecting the platelet to the collagen fibers
Platelet Activation
leads to :
shape change, secretion of granules into surrounding tissue, formation of aggregates
only activated plts are able to proceed w/ formation of plug
Platelet Agonists
an agent that induces plt activation
each agonist binds to the plt surface at its specific receptor site
ADP, serotonin, platelet activating factor, TXA2
collagen, thrombin (!), epinephrine
Platelet shape change
adhesion of platelets to collagen fibers via vWF triggers shape change:
pseudopods, become extremely sticky
Platelet secretion
release of granules into surrounding area
granules: alpha & dense granules
Alpha granules
thrombospondin- promotes plt to plt interaction
vWF- plt adhesion
plt-derived growth factor (PDGF) -promotes smooth muscle growth
Dense granules
ADP- promotes plt aggregation
Calcium- regulates plt activation/aggregation
Serotonin-promotes vasoconstriction
Platelet Aggregation
attachment of plt to one another
activation leads to secretion of substances stored in granules - ADP etc
Platelet plug
primary hemostatic plug
fragile & easily dislodged
plug is stabilized to vessel wall via 2ndary hemostasis
Secondary Hemostasis
rapid reinforcement of plt. plug w/ fibrin clot
requires coagulation factors
Coagulation factors
inactive coag factors - zymogens
almost all are made in the liver & are proteins
classification of coag factors
- fibrinogen group
- prothrombin group
- contact group
Fibrinogen group
includes factors: I (fibrinogen) V - heat liable VIII XIII all factors are consumed during process of coag present in plasma & absent in serum
Prothrombin Group
includes factors: II (prothrombin) VII IX X factors are not consumed during coag (except II) Vit K dependent!
Vitamin K dependent factors
II, VII, IX, X
makes it possible for these factors to bind to calcium
Intrinsic pathway
contact
XIIa + HMWK + PK
XIa + Ca2+
IXa + VIII + PL+ Ca2+ (intrinsic complex)
Extrinsic pathway
vessel injury
TF+ VII + Ca2+ (extrinsic complex)
Common pathway
X
Xa + V + PL + Ca2+ = prothrombin complex
prothrombin (II) is then converted to thrombin (IIa) via above complex
thrombin then converts fibrinogen (I)->fibrin & XIII-> XIIIa
forms crossliked fibrin
Fibrinolysis
when clot is no longer needed
enzymatic cleavage of fibrin to soluble fragments
fragments are then removed by macrophages
Plasminogen (PLG)
as clotting begins, plasminogen binds to fibrin throughout the clot
Plasminogen Activators
tissue plasminogen activator (tPA) & urokinase type plasminogen activator (uPA)
both activate plasminogen to plasmin
Plasmin
initiates fibrinolysis
plasmin digests fibrin by hydrolysis - cleaves fibrin
FDP/FSP
fibrin degradation or split products
fragments from fibrinolysis that are rapidly cleared from circulation by the liver
consists of : X,Y,D, E
these fragments exert an antithrombin effect
Tissue factor pathway inhibitor (TFPI)
glycoprotein found on endothelial surfaces & serves as an anticoagulant by inhibiting factors VIIa & Xa (extrinsic & common pathway)
Activated Protein C (!) & Protein S
proteins C & S are both Vit K dependent inhibitors, synthesized in the liver
together they inactivate factors Va & VIIIa (common pathway)
Serine Protease Inhibitors
known as serpins
inhibit target by trapping the enzyme w/ the serpin & resulting in loss of activity
Antithrombin III (AT), ALpha2-macroglobulin, alpha1-antitrypsin, Heparin cofactor II,
Antithrombin III (AT)
binds & directly inactivates thrombin, & factors: IXa, Xa, XIa & XIIa, kallikrein, plasmin
MOST CLINICALLY SIGNIFICANT INHIBITOR
effect is enhanced 3-4x using heparin
Alpha2-macroglobulin
inhibits kallikrein, plasmin, thrombin, Xa
Alpha1-antitrypsin
inhibits factors XIa, thrombin, kallikrein, plasmin
Heparin cofactor II (HCII)
inhibits thrombin
not as broad spectrum as AT
CI-inhibitor
inhibitory of the esterase activity of Ci from the complement cascade
also inhibits F-XIIa (!)
Protein Z
vit K dependent
enhances the inhibitory function against F-Xa
Fibrinolytic activator
TPA- tissue plasminogen activator
