Hemodynamic Disorders: Hemostasis Flashcards
normal hemostasis includes
- platelets
- endothelium
- plasma clotting factors
function of platelets
- maintenance of vascular integrity
- platelet plug formation
- platelet phospholipid complex expression (leads to promotion of coagulation cascade)
- promotion of endothelial repair
name 2 platelet inhibitors
- cyclooxygenase inhibitors (aspirin)
2. ADP receptor antagonists (ticlopidine and clopidogrel)
what are other platelet inhibitors
- phosphodiesterase inhibitors (dipyridamole)
2. glycoprotein (GP) IIB/IIIa receptor antagoinsts
mechanism of phophodiesterase inhibitors
increases [ ] of cAMP and cGMP
function of endothelium
- metabolic transfer
- barrier functions
- synthesis of mediators of interactions between endothelium and blood components
- thomboresistance - prevents clotting
- mediation of vascular repair
examples of endothelial thromboresistance
- heparin-like molecules
- PGI2 and nitric oxide (NO) synthesis
- plasminogen activation
- ADP degradation
- thrombin inactivation
- thrombomodulin production
- protein S synthesis
where do heparin-like molecules act at
at interface of endothelial cells and plasma
function of heparin-like molecules
activate antithrombin III
activated antithrombin II cleaves
thrombin, factors Xa and IXa
what is thrombomodulin
endothelial surface protein
thrombomodulin is a receptor for
thrombin
thrombomodulin binds thrombin and coverts it to an
activator of protein C
activated protein C (APC) cleaves factors
VA and VIIIa
protein S is a cofactor for
activated protein C
other functions of activated protein C
- contributes to significant reduction of mortality in patients with severe sepsis
- attenuates various deleterious events induced by lipopolysaccharide (LPS)
activated protein C has associated —- and — effects
anti-inflammatory
profibrinolytic
activated protein C inhibits
tumor necrosis factor-alpha (TNF-alpha) production
events initiated by endothelial disruption
- vasoconstriction (neurogenic, endothelin)
- platelet adhesion and aggression
- release of TxA2
- initiation of coagulation
- fibrinolysis
what are the 3 distinct phases of the newest representation
- initiation
- propagation
- termination
what are initiation
-chemical or mechanical damage to tissue
function of initiation
- exposes tissue factor (TF) to the plasma circulation
- induces TF expression by monocytes, activated endothelium
Tissue factors interacts with a small amount of
preexistant factor VIIa in the plasma
interaction of TF and preexistant factor VIIa form
extrinsic tenase (TF/VIIa/IX/X) on a phospholipid surface
rapid inactivation of the extrinsic tenase by
tissue factor pathway inhibitor (TFPI)
extrinsic tenase generates small amounts of factors
IXa and Xa
Xa cleaves
prothrombin (II) to form small amounts of thrombin (IIa)
initial small amounts of thrombin activates
cofactor proteins
factors V and VIII to VA and VIIIa
platelets
cofactor activation initiates assembly on
platelet phospholipid surface of intrinsic tenase (VIIIa/IX/X) which leads to Xa activation
function of prothrominase (Va/Xa/II/Ca++)
accelerates thrombin formation (IIa)
thrombin and fibrinogen form
fibrin
function of fibrin
- removal of fibrinopeptide A and B
- cross-linking
termination
formation of thrombin/thrombomodulin complex activates protein C which inactivates Va and VIIIa
how is extrinsic tense inactivated
spontaneous decay of TFPI
inactivation of Xa and thrombin (IIa) by
antithrombin III
prothrombin time (PT) is a measure of
extrinsic pathway of coagulation
Prothrombin Time measures factors
VII, X, V, II and fibrinogen
prothrombin time is a mixture of
thromboplastin (tissue factor) plasma, calcium ion
expect a clot to form in —s when using PT
12 seconds
partial thromboplastin time is a measure of
intrinsic pathway of coagulation
PTT measures factors
XII, XI, IX, VIII, X, V, II, fibrinogen
PTT is a mixture of
phospholipid platelet substitude (partial thromboplastin), plasma, calcium ions
a clot form in —s with PTT
25 seconds
name 2 disorder of hemostasis
- antithrombotic (hemorrhagic) disorder
2. prothrombotic (hypercoaguable) states
what are the antithrombotic (hemorrhagic) disorders
- classic hemophilia
- Christmas disease
- von Willebrand’s disease
- disseminated intravascular coagulation with consumption coagulopathy etc.
what are the prothombotic (hypercoaguable) states
- hereditary thrombophilia
- lupus anticoagulant
- HIT syndrome (heparin induced thrombocytopenia and thrombosis syndrome)
- disseminated intravascular coagulation (DIC)
hereditary thrombophilia is most often present in
adolescents or young women
hereditary thrombophilia presents with
- venous thrombosis
- recurrent thromboembolism
name 2 hereditary thrombophilia
Factor V Leiden
Prothrombin 20210A transition
Methylene Tetrahydrofolate Reductase Mutation
Factor V Leiden has a mutation in
factor V
causes resistance to activated protein C
what are the 3 Hereditary THrombophilia deficiencies
- antithrombin III deficiency
- protein C deficiency
- protein S deficiency
Genes implicated in hereditary thrombophilia
- factor V Leiden and other factor V variants
- prothrombin 20210G-A polymorphism
- hyperhomocysteinemia and homocystinuria
- antithrombin 3
- protein C
- protein S
- numerous others
lupus anticoagulant has a prolonged — test
partial thromboplastin time
in lupus anticoagulant what interfers with PTT test
antiphopholipid antibodies
symptoms of Lupus Anticoagulant
- increased venous and arterial thrombosis
- sometimes associated with autoimmune diseases such as SLE
what is HIT syndrome
heparin-induced thrombocytopenia (and thrombosis)
HIT syndrome is caused by
antibodies to the complex of heparin and platelet factor 4 (PF4)
HIT syndrome is related to what kind of therapy
therapy with high molecular weight heparin (avoided by using low molecular weight heparin)
HIT syndrome is clinically characterized by
heparin induced thrombocytopenia followed by thrombotic complications (cause too much clotting)
disseminated intravascular coagulation (DIC) is caused by
- an obstetric complication caused be:
- retained dead fetus
- premature separation of placenta (abruptio placentae)
DIC is gram —- species
negative
DIC can lead to what type of trauma
- leg surgery
- hemolytic transfusion rxns
DIC can cause what type of malignancy
lung, pancrease, other
what is DIC
widespread deposition of fibrin in microvasculature
what factors are involved with DIC
factor VII, V, II and fibrinogen
what is consumption of coagulopathy
- depletion of platelets and coagulation factors
- associated with DIC
DIC has prolongation of
- prothrombin time (V,II, fibrinogen)
- PTT (VIII, V, II, fibrinogen)
- thrombin time (fibrinogen)
DIC has presence of
fibrin-fibrinogen degradation (split) products (FDP)
