Coagulation Flashcards
What is primary hemostasis
the activation and action of platelets in the formation of the initial clot or platelet plug
What initiates primary hemostasis
vascular injury which causes the release of procoagulant factors
What are the anticoagulant properties of the endothelium
secretion of prostacyclin, nitric oxide, heparin sulfate, tissue factor pathway inhibitor, tissue plasminogen activator
smooth continuous surface inert to PLT and coag factors
expression of continuous surface inert to PLT and coagulation factors
expression of cell membrane thrombomodulin
What does prostacyclin
platelet inhibitor
What does nitric oxide do
vascular relaxing
What are the procoagulant properties of the endothelium
exposure of collagen
vasoconstriction caused by harm and factors released by the platelets
secretion of VWF
sub-endothelial cells contain TF
What does thromboxane A2 do
causes calcium to be released and promotes PLT aggregation and vasoconstriction
What are the purpose of dense PLT granules
fuse with plasma membrane to secrete contents
contain ADP, ATP, Ca, Mg, serotonin
What are the purpose of alpha PLT granules
secrete contents into surface-connected canalicular system that releases contents to external environment
contains PF4, B thromoglobulin, platelet derived growth factor, endothelial growth factor, transforming growth factor, factors V, XI, VWF, fibrinogen
What is used to monitor the intrinsic pathway
PTT
What is used to monitor the extrinsic pathway
PT
What are the vitamin K dependant factors
II, VII, IX, X
What factors are in the common pathway
I, II, XIII
What factors are in the extrinsic pathway
III, VII, X
What factors are in the intrinsic pathway
VIII, IX, X, XI, XII
What is a zymogen
inactive form of an enzyme
What is a serine protease
active form of the clotting factor whose activity depends on the amino acid serine at activation site
What factors are the serine proteases
kallikrein, II, VII, IX, X, XI, XII, plasmin, protein C
What is the role of pf3
during platelet activation they are converted to arachidonic acid and the thromboxane A2 which promotes the release of calcium which allows propagation of the cascade
What is the role of VWF
stabilizes factor VIII
What are regulators of coagulation
fibrinolytic system
regulatory mechanisms of coagulation - tissue factor pathway inhibitor, protein c system, anti-thrombin, protein Z dependent protease inhibitor
what activates plasminogen
tissue plasminogen activator
what does plasminogen act on
fibrin
What inhibits plasminogen
alpha-2 antiplasmin
What does tissue plasminogen activator work on
fibrin bound plasmin at site of thrombus
what inhibits tissue plasminogen activator
PAl-1
what is the purpose of urokinase
prevents fibrin clots in renal collecting ducts
what inhibits urokinase
PAI-1
What is unfractionated heparin
a mix of glycosamines from pig intestines
indirect anticoagulant that accelerates the action of antithrombin
monitored via PTT or anti-Xa
What is low molecular weight heparin
fractionated heparin
monitored through anti-Xa only
What is fondaparinux
synthetic formulation of active sequence of heparin
increases antithrombin activity
monitored through anti-Xa
What is coumadin
acts on liver to impair production of vitamin K factors
monitored via PT
What is dabigatran
a direct thrombin inhibitor
monitored via TT
What is rivaroxaban and apixaban
inhibits FX
monitored via anti-Xa
What is the testing window for PTT
4 hours
What is the testing window for PT
24 hours
What are interferences in coagulation testing
clots
underfilled
heparin
hemolysis
prolonged tourniquet application
lipemia
cold storage
heat
What is the principle of mechanical end-point clot detection
measures the variation in amplitude of the oscillation of a steel ball
as clot is formed ball moves less
What is the principle of photo-optical end-point clot detection
as the clot is formed the change in transmittance is detected by the instrument
What is the principle of the chromogenic end-point detection
a chromogenic labelled oligopeptide is used to detect activity of factors, when the oligopeptide is cleaved by the factor it puts of a signal
What is the principle of light -absorbance end-point detection
when microparticles agglutinate there is a decrease in transmittance which causes an increased absorbance proportional to the antigen of interest
What reagents are used for PT
tissue thromboplastin (recombi) and calcium
What causes prolonged PT
abnormalities/deficienceies in the extrinsic and common pathway
vitamin K deficency
What causes decreased PT
myocardial infarction, multiple myeloma, drug therapy
What is the reference range for PT
0.8-1.2
What is the therapeutic range for PT
2.0-3.5
What is the critical value for PT
> 5.0
What are the reagents used for PTT
calcium, negatively charged contact activator
What cause prolonged PTT
abnormailties/deficiencies in the intrinsic and common pathway
circulating anticoagulants
liver disease, vitamin K deficiency
What is the reference range for PTT
26-38 sec
What is the therapeutic range for PTT
low: 59-83
high: 84-88
What is the critical value for PTT
> 120 sec
What can cause decreased fibrinogen
congenital afibrinogenemia. DIC, systemic fibrinolysis, pancreatitis, severe hepatic dysfunction
What is the critical value for fibrinogen
<1.0g/L
What is the principle of a mixing study
patient plasma is mixed 1:1 with normal plasma before testing to determine if the normal plasma corrects any prolonged PT/PTT results
How do we remove heparin from a sample
hepzyme
What is an inhibitor screen
tests to see if an inhibitor is delayed or immediate. Patient plasma is mixed and tested then incubated at 37 and tested alongside unmixed patient plasma that was also incubated
What is the purpose of platelet aggregation studies
assess platelet function
What occurs in a platelet aggregation study
platelet rich plasma is stirred monitoring for changes in light transmission as various agonists are added
What are the platelet aggregation study results for VWF disease
ADP, collagen, epinephrine, AA are all normal
Ristocetin is variable based on typw
I- abnormal
2A- abnormal
2B- normal
3- absent
What are the platelet aggregation study results for bernard soulier
ADP, collagen, epinephrine, AA are all normal
ristocetin is absent
What are the platelet aggregation study results for Glanzmans
ADP, collagen, epinephrine, AA are all absent
ristocetin demonstrates aggregation followed by disaggregation
What are the platelet aggregation study results for storage pool diseaseq
ADP, collagen, epinephrine, AA are all variable with collagen
ristocetin is normal
What are the platelet aggregation study results for alpha granule deficency
ADP, collagen, epinephrine, AA are all decreased
ristocetin is normal
What does the ristocetin cofactor assay test
ensures all coagulative components are present
if aggregation occurs then the patient has VWF
What does reptilase time test
if the patient has adequate fibrinolysis
prolonged - hypofinbrinogenemia or dysfibrinogenemia
What can cause factor deficiencies
liver disease, vitamin K deficiency, auto immune
What is vonwillebrand disease
a congenital bleeding disorder with auto dominant inheritance pattern that causes a deficiency of VWF which in turn causes decreased FVIII
What are test results for vonwillebrand disease
PT/PTT normal to prolonged
PLT count normal
Bleeding time prolonged
vWF assay low
FVIII assay low
Ristocetin aggregation variable
Ristocetin cofactor negative
What is hemophilia A
a congenital bleeding disorder with X-linked recessive inheritance that effects FVIII
What are test results for hemophilia A
PT normal
PTT prolonged
TT prolonged
bleeding time normal
What is hemophilia B
an X-linked bleeding disorder that effects FIX
What are test results for hemophilia B
PT normal
PTT prolonged
bleeding time normal
What is Hemophilia C
auto dominant bleeding disorder that effects FXI
What are test results for hemophilia C
PT normal
PTT prolonged
TT normal
bleeding time normal
What is hypofibrinogenemia
auto-recessive or acquired disorder leading to low levels of fibrinogen
What are test results for hypofibrinogenemia
PT abnormal
PTT abnormal
TT abnormal
FIB abnormal
BT abnormal
What is afibrinogenmia
an auto recessive disorder that causes the absense of functionally detectable fibrinogen in plasma
What are test results for afibrinogenmia
PT abnormal
PTT abnormal
TT abnormal
FIB abnormal
BT abnormal
PLT adhesion/aggregation abnormal
What is dysfibrinogenemia
auto dominant disorder that cause the alteration of the structure of fibrinogen effecting the interaction of fibrinogen with other molecules
What are test results for dysfibrinogenemia
PT normal
PTT normal
BT normal
TT prolonged
PLT function normal
reptilase time very prolonged
What are contact factor deficiencies
auto recessive disorder effecting FXII, HMWK, prekallekrein
What are test results for contact factor deficiencies
PT normal
TT normal
BT normal
PTT abnormal
Factor assay decerased
What is factor XIII deficiency
a deficience that effects FXIII keading to decreased cross linking
What are test results for factor XIII deficiencey
factor assay abnormal
clot dissolving in 5M urea or 1% monochloroacetic acid
What is APC resistance
auto dominant disorder causing a defect in FV so it cannot be bound by APC (FV cannot be regulated)
What is Prothrombin G20210A mutation
a mutation in prothrombin causing elevated plasma prothrombin levels
What is lupus anticoagulant
a nonspecific inhibitor which prolongs PTT by binding to the commercial phospholipid reagent that causes risk of thrombosis
What is the dilute russel viper venom time
used to detect lupus anticoagulant by initiating the coagulation cascade by activating FX. confirm reagent is rich in phospholipid and neutralizes LAC shortening the time
What is megakaryocyte hypoplasia
a decrease in megakaryocytes which in turn causes a decrease in PLT
What is ITP
IgG antibodies attach to PLT causing them to be removed by the spleen. PLT are often large and abnormal due to accelerated production
What is neonatal thrombocytopenia
mother develops antibodies to fetal PLT
What is drug indiced thrombocytopenia
caused by salicylates, acetaminiohen, penicillin, sulfa drugs, quinidine, phenobarbital
What is heparin induced thrombocytopenia
an adverse effect of UFH that causes an IgG antibody to be made. The antibody complexes with heparin and then the complex binds to platelet receptors which leads to PLT activation
What is Bernard Soulier Syndrome
dective platelet function leads to nosebleeds, bruising, and bleeding. Manifested in infancy or childhood it is a autosomal recessive disorder in which the GPIb complex is missing which means PLT cant bind to VWF causing defective adhesion
What are lab results for bernard soulier syndrome
PT/PTT normal
PLT count low
bleeding time prolonged
PLT aggregation shows no response to ristocetin
PLT have cytoplasmic vacuoles visible on electron microscope
What is Glazmanns thrombasthenia
an autosomal recessive disorder that causes severe hemorrhage. There is an absence of GPIIb/IIIa receptors on the platelets causing defective aggregation
What are lab tests for Glazmanns thrombasthenia
PT/PTT normal
PLT count/morph normal
bleeding time prolonged
PLT affregation normal with ristocetin
What is dense granule deficiency
can be associated with albinism or not. Dense granule membranes are present but unable to pack granule contents. Usually only cause bruising though it does effect PLT aggregation studies
What is alpha granule deficency
an autosomal recessive disorder causing the absence of alpha granules leading to an agranular appearance
What are lab tests for alpha granule deficency
PT/PTT normal
PLT count decreased
agranular PLT
bleeding time prolonged
