Coagulation Flashcards
What molecule attaches to naked endothelium, platelts attach with?
Then what happens?
Two types of granules in plts?
vWF; the platelets attachs by glycoprotein Ib/V/XI
Plt’s release granules
Alpha : thromboglobulin, P-selectin-PDGF, PF4, platelet fibrinogin, VWF, thrombospondin
Dense: ADP (causes vaso constriction), ATP, serotonin, Ca2+
What happens after plt’s change shape; what is exposed?
Glanzmann’s is from issue with?
Bernard-Soulier disease is an issue with?
Fibrinogin and GPIIb/IIIa and platelets bind to this; causes primary plug
GpIIb/IIIa complex
GpIb
What coag factors are not made in liver?
Intrinsic pathway is activated by?
Extrinsic pathway activated by?
Patients with low kallikrein and pre-kallirein do they have bleeding?
vWF (made in endothelial cells)
–ve charged glass
Tissue factor
No, elevated PTT
If PT and PTT normal is there an issue with the cascade?
What factor is involved in tertiary hemostatsis?
What breaks down fibrin?
Probably not! Most likely outside of the cascade
Factor XIII–>XIIIa briding thrombin
Plasmin!
Three inhibotors of plamin pathway?
Fibrin broken down into?
Alpha two antiplasmin inhibits plasmin
PAI inhibits plasminogen
TAFI (thrombin activatable fribrinolysis inhibitor) inhbitis plasminogen to TPA/Fibrin
Breaks down into D Dimers awnd Fragment E
What proteins inhibit FV and FVIII?
Antithrombin made where, and bind to?
Activated factor C carried by protein S inhibits FV and FVIII
Liver, bind Heparin and inhibits II to IIa and inhibits Xa
How does plt count work?
Bleeding time was a test for; better test?
Count things less than <13fL (no functional information)
Bleeding time: Plt activity; worthless; use platelet function analysizer
PTT test method; what factors not measured?
PT, method, and pathways?
Negatively charged surface phospholipid and PPP and CaCl added; <40 seconds; intrinsic and common; ALL BUT 7 and 13
PT: Take tissue factor and phospholipids; add citrated PPP and CaCL; <15 seconds; extrinsic andn common
What is INR?
What is Thrombin time, measures what pathway?
Increased in?
Standardized reactivity of tissue factor INR= (patient PT/Normal mean PT) raised to ISI
Thrombin time: Take xogenous thrombin, add PTT, measure clot time; common pathway; No Ca or phospholiped needed
Increased in: increased paraprotein, amyloid, heparin, dysfibrinogenemia
What is Reptilase time?
Increased in?
If patient is on heparine?
If on heparine what is thrombin time and Reptilase time?
Take Bothrops atrox venon, add PPP, measure clot time
Increased in dysfibrinogenemia
Thrombin time increased; reptilase normal
What is a mixing study?
If PTT corrects, think?
If PTT doesn’t correct, think?
Which inhibitor corrects and then prolongs after 1-2 hours?
Will dysfibrinogenemia correct?
Take patient plasma and mix with pooled normal
Measure PT and PTT and at 1 hr interval
If PTT correct= factor deficency
If PTT doesn’t correct=inhibitor
F8!!
Partially; hypofibrinogenemia will completely correct
What does a platelet aggregation nstudy do?
Take patient’s platelet rich plasma and add ristocetin (causes aggregation); looka t light transmission and look for decreased turbidity and increase in transmission
Bernard-Soulier
Defect?
Size of plts?
Increase or decrease in Plts?
PT, PTT, Bleeding time?
Ristocetin aggreation results, mixing?
Flow results?
GPIb/V/IX (CD42); plts cannot bind to vWF
Large plts with pseduonucleolus
Decrease/thrombocytopenia
PT, PTT normal; Bleeding time increased (plts don’t work correctly)
Impaired ristocetein aggregation–corrects if mixed with normal plts
Flow shows decreased CD42a, b, d
Glansman thrombocytopenia problem?
Abnormal protein complex?
Risocetin test results?
Flow?
PT; PTT (and differs from afibrinogenemia)?
GPIib-IIIa cannot bind fibrin (so adhesion but not aggregation); Normal plt count
Decressed aggrecation ADP, collagen, and EPI but NORMAL risocetin
Decreased CD41 (GPIIb) and CD61 (GPIIIa)
Normal in Glansman (afibrinogenemia increased PT and PTT–no fibrin!)
Storage pool deficiency shows:
What agregation changes?
What morphology; EM changes?
Plt agg studies results?
What ATP:ADP ratio?
decreased agg due to alpha/dense granule issues
Normal morphology; no granules EM
Plt agg: NO 2nd way-ADP or EPI; decreased collagen +AA, normal ristocetin
Increased ATP:ADP
Common causes of acquired disorders of platelet function?
Drugs
Uremia: Abnormal adhesion, abnormal aggregation (ADP, Epi, Collagen)
Myeloproliferative disorders
Cardiopulmonary bypass; plt activation, decreased granules
Mechanism of action of Aspirin/NSAIDS?
Aggregation study results?
Block acetylation of platelet cyclooxygenase–> decrease th romboxane formation
Decreased 2nd wave to ADP, EPI, no response to collagen or arachadonic acid
vWF binds to?
Multimers cleaved by?
Where is it made?
Decreased vWF seen in what type of stored blood?
F8 and subeptiehial collagen and GPib
ADAMTS-13
Megakaryocytes (alpha granules and endothelial cells Weibel-Palade bodies)
Type O