hemostasis/coagulation Flashcards
3 major components to the hemostatic system
the vascular wall, platelets, and coagulation proteins
3 steps of the platelet response to vascular injury (primary hemostasis)
adhesion, activation, aggregation
platelet adhesion involves activation of a surface membrane receptor, _____, an adhesive protein, ____, and an appropriate surface, _____
glycoprotein Ib/IX
von Willebrand factor
subendothelial collagen
in fibrin clot formation (secondary hemostasis), soluble coagulation proteins within plasma are activated to generate ____ in an ____ reaction
thrombin; amplification
what does thrombin convert
thrombin converts fibrin to fibrinogen
fibrin adds ____ to the clot after fibrin monomers are covalently cross-linked by _____
stability; Factor XIII
sequence of the intrinsic pathway
activation of Factor XII by kallikrein
activation of Factor XI by Factor XIIa
Factor XIa activates Factor IX
sequence of extrinsic pathway
activation of Factor VII by tissue factor
sequence of the common pathway
activation of X to Xa
conversion of prothrombin (II) to thrombin
conversion of fibrinogen (I) to fibrin
regulatory systems in secondary hemostasis
serine protease inhibitors (antithrombins)
protein C pathway (controls Va and VIIIa)
fibrinolysis (removes excess clot)
antithrombins inhibit the activity of thrombin and other serine proteases (like ______) of the coagulation cascade by forming an inactive ______
factors IXa, Xa, XIa, and XIIa
enzyme-inhibitor complex
one of the best known antithrombins is _____, a molecule which, in the presence of _____, becomes activated so that it can form a complex with thrombin, thus destroying the ability of thrombin to participate in generation of _____
antithrombin III
heparin
fibrin monomers
protein C system regulates the major cofactors of the coagulation cascade, _____
factors Va and VIIIa
activated _____ is the major effector enzyme of the protein C system and ____ is a major cofactor
protein C; protein S
_____ promotes coagulation through resistance to enzymatic inactivation by the Protein C/S complex
Factor V Leiden mutation
in the presence of fibrin, _____ can bind to _____ and convert it to the activate enzyme which breaks down fibrin monomers into fibrin degradation products
tissue plasminogen activator (TPA) ; plasminogen (active enzyme = plasmin)
common lab screening tests used to evaluate hemostasis
prothrombin time (PT) international normalized ratio (INR) partial thromboplastin time (PTT) platelet count bleeding time
clinical manifestations of disorders of primary hemostasis include _____ and/or ______; laboratory manifestations include _____ and _____
mucocutaneous bleeding (petechial); bleeding associated with trauma prolonged bleeding time; thrombocytopenia
clinical manifestations of disorders of secondary hemostasis include _____ and/or _____; laboratory manifestations include a _____ and/or _____
soft tissue bleeding; bleeding associated with trauma
prolonged PT and/or PTT; thrombin time
clinical manifestations of disorders of the regulatory system include _____ and/or ______; laboratory manifestations are often ____ in screening tests
soft tissue bleeding; bleeding associated with trauma
normal
congenital disorders associated with bleeding
von willebrand disease hemophilia A (factor VIII deficiency) hemophilia B (factor IX deficiency)
two most frequent congenital bleeding disorders
von willebrand disease and hemophilia A
von willebrand disease is an _____ disorder associated with production of decreased amounts of a _____ (quantitative abnormality) or production of a protein with _____ (qualitative abnormality), or both
autosomal dominant; normal protein; abnormal function
predominant clinical manifestation of von willebrand disease is _____
mucocutaneous bleeding
hemophilia A is an ______ disorder that is due to decreased production of _____
X-linked recessive; Factor VIII
clinical hallmark of hemophilia A is _____
recurrent soft tissue bleeding
hemophilia B is an ____ disorder that is due to decreased production of ____
X-linked recessive; Factor IX
refers to a decrease in platelet count
thrombocytopenia
bleeding due to thrombocytopenia typically appears as _____ and _____
petechial hemorrhages in skin and mucous membranes
disorder characterized by immune-mediated destruction of platelets; autoantibodies are directed at the platelet membrane antigens
immune thrombocytopenic purpura (ITP)
____ and ____ are common targets of immune thrombocytopenic purpura (ITP)
GPIb/IX ; IIb/IIIa
thrombotic thrombocytopenic purpura (TTP) is characterized by _____ with formation of _____ throughout the circulation
intravascular platelet activation; platelet-rich microthrombi
cause of TTP is due to a deficiency of a _____, called _____ that normally degrades very high molecular weight multimers of von willebrand factor
metalloproteinase; ADAMTS 13
regulators of primary hemostasis (platelets)
NO, prostacyclin (PGI2), and ADPase
as part of the regulation of coagulation, antithrombins inhibit _____, protein C inhibits _____ and plasmin does what?
serine proteases (like thrombin, factors 9a-12a)
cofactors Va and VIIIa
plasmin removes excess fibrin clot
screens for activity of proteins in the extrinsic pathway (factors V, VII, II, X, and fibrinogen)
prothrombin time (PT)
prothrombin time (PT) is a measurement of the time needed to ____ in the presence of added _____
form a clot; tissue thromboplastin (tissue factor)
used to monitor patients on anticoagulation therapy (coumadin/warfarin)
international normalized ratio (INR)
INR is a ratio of:
patient prothrombin time / control prothrombin time
screens for activity within the intrinsic pathway (factors XII, XI, IX, VIII, X, V, II and fibrinogen)
partial thromboplastin time (PTT)
PTT is a measurement of the time needed for plasma to form a clot in the presence of added ______ to activate _____
ground glass or kaolin (negatively charged activators of factor XII)
to activate contact-dependent Factor XII
normal range for platelet count is _____
150,000 to 400,000 per microliter
the term _____ refers to a decrease in platelet number; ____ and _____ denote an increase in platelet number
thrombocytopenia
thrombocytosis and thrombocythemia
specialized tests of hemostasis
mixing studies
factor assays
circulating anticoagulant
platelet aggregation testing
if mixing study corrects clotting time, a _______ is felt to be present
deficiency of some factor(s)
if the mixing study does not correct the clotting time, an ____ is felt to be present
inhibitor (factor-specifc or lupus anticoagulent type)
classification of bleeding disorders
primary vs. secondary hemostasis
congenital vs. acquired
regulatory disorder
mild vs severe
classification of vWD
type I- quantitative deficiency (partial)
type II- qualitative deficiency
type III- quantitative deficiency (complete absence)
most common hereditary cause for serious bleeding
hemophilia A
mechanisms of thrombocytopenia
- decreased platelet production
- increased destruction
- sequestration
- congenital vs acquired
ITP clinical features
petechial hemorrhages
gingival bleeding
ecchymoses (bruises)
bleeding with trauma or surgery
factor VIII complex is composed of _____ and _____
vWF; factor VIII procoagulent
lab features of vW disease
prolonged BT/PFA-100 and PTT
leb features of hemophilia A
prolonged PTT and decreased factor VIII
schistocytes in peripheral blood smear; increased bilirubin and LD, reflecting intravascular hemolysis
TTP (thrombotic thrombocytopenic purpura)
