Bleeding & Hemostasis Flashcards
components of the hemostatic system
- circulating blood (contains platelets and coagulation factors)
- endothelium
- subendothelial matrices
how is hemostasis regulated
balance of pro and antithrombotic properties
- prevents inappropriate thrombosis
- allows rapid hemostasis if injured
steps of hemostasis
- vasoconstriction
- primary hemostasis
- secondary hemostasis
- fibrinolysis
primary hemostasis
formation of a platelet plug
involves:
- platelets
- vWF
- endothelium
resting endothelial cell properties
- inactive
- have an ANTIcoagulant surface to prevent platelet adherence
- no expression of tissue factor or exposure of collagen
- normal vWF levels
anticoagulant endothelial cell membrane
when inactive - endothelium has a neutral outer phospholipid membrane and a procoagulant inner membrane (negatively charged)
maintained by flippase and floppase enzymes
how does endothelium change when vascular injury occurs
- activated
- scramblase enzyme flips the phospholipids so that the outer membrane becomes procoagulant
- facilitates adhesion of circulating platelets
platelets
anuclear, discoid shaped fragments of megakaryocytes
primary effectors of hemostasis - secretes granules that facilitate hemostasis
SHORT lifespan (7-10 days)
steps of platelet activation
- initiation (adhesion)
- extension (activation)
- stabilization (aggregation)
platelet initiation/adhesion
- vascular injury causes exposure of collagen + vWF
- circulating platelets tether to vWF and collagen
- platelets roll along endothelium
- adhesion of a platelet monolayer over injured endothelium –> forms platelet plug
platelet extension/activation
- additional platelets adhere to platelet plug
- platelets get activated by adhesion and soluble agonists
- changes platelet from low to high affinity state
high affinity platelets
- increased granule release
- procoagulant membrane formation
- integrin activation (aIIbB3)
platelet stabilization/aggregation
- aIIbB binds to fibrinogen to initiate aggregation
- allows fibrinogen, fibrin, and vWF to bind to aIIbB3
- initiates outside-in signaling leading to:
- clustering of integrins
- actin remodeling
- clot retraction - stabilizes platelet plug
secondary hemostasis
formation of a stable fibrin clot
involves:
- coagulation factors
coagulation factors
factors that circulate as inactive zymogens
requires activation via coagulation cascade
some may require activation by vitamin K
what is used as the docking site for the assembly of coagulation complexes
pro-coagulant phospholipid membrane on cell surface
coagulation cascade
series of zymogen cleavage into active clotting factors
allows for signal amplification and multiple points of regulation
extrinsic pathway
initiated by endothelial injury
- injury exposes tissue factor (III)
- tissue factor binds to factor VII
- factor VII activates factor X
intrinsic pathway
- factor XII activates factor XI
- factor XI activates factor IX
- factor IX activates factor VIII
- factor VIII activates factor X
common pathway
- activated factor X (from intrinsic and extrinsic), V, and C cleave prothrombin (factor II) into thrombin
- thrombin cleaves fibrinogen (factor I) into fibrin
- thrombin activates factor XIII
- factor XIII binds active C to create fibrin cross links that stabilize the clot
how does coagulation in vivo typically work
mostly via the extrinsic pathway
tissue factor (III) + factor VII are the main initiators of clotting in vivo
thrombin
pro-inflammatory:
- activates platelets
- activates TF V, IX, XI, XIII
- cleaves fibrinogen into fibrin
- crosslinks fibrin
has some anticoagulant and fibrinolytic properties
fibrinolysis
breakdown and removal of clot
goal is to reestablish blood flow after vascular healing
HIGHLY regulated balance of proteolytic and inhibitory proteins
plasminogen/plasmin
- plasminogen gets cleaved into plasmin by activators
- plasmin cleaves fibrin to form fibrin degradation products (FDPs) and D-dimers
FDPs vs D-dimers
FDPs: breakdown product of all fibrin
D-dimers: breakdown product of cross-linked fibrin only
what are primary hemostatic disorders
abnormalities in PLATELET number or function
can also be caused by vWF or endothelial abnormalities
what are secondary hemostatic disorders
abnormalities in COAGULATION FACTORS
can be acquired or congenital
hyperfibrinolysis
RARE
excessive or rapid clot breakdown
clinical signs of primary hemostatic disorders
SMALL body bleeds
- petechiae/ecchymosis
- epistaxis
- gingival bleeding
- hyphema
- hematuria
- melena
- CNS/pulmonary hemorrhage
clinical signs of secondary hemostatic disorders
LARGE body bleeds
- hemoabdomen
- hemothorax
- hemoptysis
- hemarthrosis
- hematoma
- SQ/IM bleeding
- CNS/pulmonary hemorrhage
causes of primary hemostatic disease
- thrombocytopenia
- von willebrand’s disease
causes of thrombocytopenia
- destruction of platelets - IMTP
- decreased production
- increased consumption
- sequestration
diagnosed on platelet count
von willebrand’s disease
inherited vWF disorder
type 1: decreased vWF
type 2: decreased & abnormal vWF
type 3: marked reduced or absent vWF
diagnosed on vWF assay
causes of acquired secondary hemostatic disease
- anticoagulant rodenticide toxicity
- liver failure
- heat stroke
- DIC
- shock
- severe hypothermia
- hemodilution
- acidemia
- drug ingestion
causes of congenital secondary hemostatic disease
hemophilia A: factor 8 deficiency (males only, GSDs)
hemophilia B: factor 9 deficiency
hageman factor deficiency: factor 12 deficiency (NO clinical bleeding but has prolonged aPTT)
primary hemostatic disorder diagnostics
- platelet count - CBC + manual slide review
- vWF assay
- buccal mucosal bleeding time
- platelet function testing
secondary hemostatic disorder diagnostics
- PT/aPTT
- ACT
- viscoelastic testing
- single factor analysis/assay
hyperfibrinolysis diagnostics
- viscoelastic testing
- FDPs or D-dimers
platelet count
CBC + manual review
check for clumping - causes artificially low platelet count on CBC
count on high power (100x) with oil immersion
1 platelet per high power field = 15,000 platelets
vWF assay
measures concentration and function of vWF
antigen assay - type 1 vs type 3
collagen binding - type 2
buccal mucosal bleeding time (BMBT)
highly subjective test of primary hemostatic disorder
dogs: 3-4 min
cats: <2 min
only do once thrombocytopenia has been ruled out
PT
prothrombin time
tests extrinsic & common pathways
aPTT
partial thromboplastin time
tests intrinsic & common pathways
ACT
activated clotting time
tests intrinsic & common pathways
less sensitive than aPTT
viscoelastic testing (TEG)
visual representation of hemostasis
measures:
1. time to form initial fibrin clot
2. time to reach certain clot firmness
3. rate of fibrin accumulation and cross linking
4. clot strength
5. rate of fibrinolysis
