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Coagulation & Hemostasis
Keck Hematology
126
Medical
Graduate
02/14/2012

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Term
primary hemostasis
Definition
refers to formation of platelet plug in a vessel hole
Term
secondary hemostasis
Definition
refers to the coagulation cascade and formation of a fibrin plug generated from soluble fibrinogen by enzymatic cleavage
Term
clinical difference btwn defect in fibrin plug and platelet plug
Definition
fibrin plug: deep muscle or joint bleeds. platelet plug: mucosal bleeding, ecchymosis, petechiae
Term
lab difference btwn fibrin and platelet plug defects
Definition
fibrin: PT/PTT elevated, quantitive fibrinogen. Platelet: platelet count, bleeding time, platelet fn assays
Term
Factor I
Definition
fibrinogen
Term
Factor II
Definition
prothrombin
Term
Factor III
Definition
tissue factor
Term
Factor IV
Definition
calcium
Term
Factor V
Definition
cofactor for the generation of the prothrombinase complex
Term
Factor VIII
Definition
"antihemophilic factor"
Term
Factor IX
Definition
christmas factor
Term
Factor XI
Definition
deficiency doesn't cause bleeding except under stress (surgery, trauma). Thrombin enhances 11->11a, which enhances thrombin in turn
Term
Factor XIII
Definition
stabilizes fibrin clot; not reflected in PT or aPTT but by 5M urea clot lysis test. Cross links glutamine and lysine btwn soluble fibrins to make insoluble
Term
TT
Definition
thrombin time: add thrombin to pt's plasma, tests fibrinogen adequacy and inhibitors of thrombin (e.g. heparin) or inhibitors of fibrin polymerization
Term
PT
Definition
prothrombin time: add active tissue factor (factor III). used primarily to monitor anticoagulation therapy. NORMAL in hemophiliacs!
Term
aPTT
Definition
activated partial thromboplastin time: tests rxn to negatively charged surface (glass) beginning w/ factor 12. Calcium independent. MAY NOT DETECT some bleeding disorders
Term
site of synthesis of coagulation factors
Definition
ALL are made in the liver. Platelets make 5, VWF, and PAI-1. Endothelium makes vWF, 7, tPA, uPA.
Term
4 steps of platelet plug formation
Definition
adhesion, aggregation, granule release/amplification, support of coag. cascade.
Term
mechanisms of thrombocytopenia
Definition
decreased or ineffective pdxn, destruction, redistribution, dilution
Term
Von Willebrand's Dz
Definition
vWF deficiency or defect, affects 1% of caucasians. Autosomally inherited.
Term
vWF
Definition
von Willebrand factor; binds platelets to damaged endothelium. carries F8, complete def. is indistinguishible from hemophilia A
Term
2 screening tests for primary hemostasis
Definition
PFA100 and bleeding time (less reliable, poor screening test)
Term
PFA100
Definition
blood is run thru column coated w/ collagen and checks how much time it takes to close aperture. better than bleeding time for checking primary hemostasis.
Term
ristocetin cofactor assay
Definition
tests ability of vWF to bind platelet GPIb (functional test of vWF, esp. HMW multimers)
Term
platelet aggregometry
Definition
tests platelet response to specific agonists
Term
bleeding time assay
Definition
widely variable, interobserver reliability is poor, poor predictor of operative outcome
Term
aPTT procedure
Definition
plasma is separated from blood and put into a citrate tube (binds Ca, prevents clotting). Phospholipid is added (partial thromboplastin), and contact activator is added. Ca is added back in and clotting time is measured.
Term
minimal hemostatic level of F 8,9,11
Definition
30% and up should all clot normally
Term
prolonged aPTT indicates:
Definition
deficiency in F12,11,9, 8,10,5, 2 and fibrinogen. most sensitive for 12,11,9,8, less for 2 and fibrinogen
Term
Hageman factor
Definition
factor 12- deficiency may cause prolonged aPTT but no disease
Term
causes of spurious prolongation of aPTT
Definition
elevated plasma citrate, heparin in tube, or clotted sample that pulls out clotting factors
Term
Inhibitors of clotting in vitro; promotes clotting in vivo
Definition
lupus anticoagulant and anticardiolipin antibodies
Term
workup for prolonged PT
Definition
50-50 mixing study will differentiate btwn factor deficiency and inhibitor
Term
specific tests for secondary hemostasis
Definition
pt's plasma added to factor deficient plasma- clotting time plotted against mix of normal plasma and factor deficient plasma. Must be done once for each factor to be tested.
Term
Thrombin time evaluates
Definition
rate of conversion of fibrinogen to fibrin, which depends on amount of fibrinogen and quality of fibrinogen
Term
reptilase test
Definition
can confirm that inability to clot is due to heparin
Term
paraproteinemia
Definition
inhibits polymerization, causes problems in 1' and 2' hemostasis, causes prolonged thrombin time
Term
causes of prolonged thrombin time
Definition
congenital afibrinogenemia, dysfibrinogenemia, heparin, xs fibrinogen degredation products (as in DIC), paraproteinemia, renal failure, amyloidosis
Term
Dilute whole blood clot lysis time
Definition
screens for accelerated fibrinolysis; measures time to clot breakdown in a sample of plasma (euglobulin lysis time) or whole blood (DWBCLT). Shortened in advanced cirrhosis, also venous thrombosis and renal dz
Term
Tissue factor
Definition
receptor for 7a and also vital for angiogenesis, constitutively expressed on subendothelium and bone marrow derived microparticles. induced by cytokines, LPS, and VEGF
Term
TFPI
Definition
Tissue Factor Pathway Inhibitor complexes F10a and F7a to shut down clotting via their pathway. This forces the TF;F7a complex to activate factor 9 instead
Term
function of vitamin K
Definition
converts glutamic acid into gamma carboxy glutamic acid
Term
hemophilia A
Definition
factor 8 deficiency
Term
Hemophilia B
Definition
factor 9 deficiency
Term
thrombin amplifies its own production how? (2 ways)
Definition
activates factor 11, activates platelets leading to increased surface for coag cascade
Term
antithrombin
Definition
important anticoagulant; major scavenger of xs thrombin. knockout -> death! deficiency-> clots! activated by GAGs on endothelial surface. can neutralize F10a and F9a
Term
Ptn S
Definition
cofactor for APC; allows APC to clip factors 8a and 5a
Term
Activated Protein C
Definition
APC comes from PC that has been converted by the thrombin-TM complex on ET. Inhibits F5 and F8, and PAI-1 (to increase fibrinolysis). Inhibited by APCI
Term
Dense granules (platelet)
Definition
contain ADP, ATP, serotonin, and Ca (platelet agonists!)
Term
alpha granules (platelet)
Definition
vWF, F5, F11, etc.
Term
TPO
Definition
thrombopoietin, mpl ligand on plateletes and megakaryocytes, secreted constitutively by liver. cellular levels vary w/ platelet and MK size
Term
pseudothrombocytopenia
Definition
an error in diagnosis of thrombocytopenia, look at the edge of a PBS to see the platelets in these cases
Term
Immune thrombocytopenia
Definition
antibodies to platelets reduce their amount, but more young platelets are made, allowing sufficient clotting for most pts
Term
ITP
Definition
Idiopathic (immune) Thrombocytopenic Purpura is caused by antibodies against common platelet antigens (i.e. platelet transfusions are of little use). May be caused by drugs, infection, or autoimmune dz. Splenic MPs phagocytose platelets. Often cured by splenectomy.
Term
3 As of platelet function
Definition
Adhesion to disrupted endothelium, Activation (become sticky), Aggregation (recruit other platelets to clot)
Term
Glycoprotein 1B9
Definition
ptn on the surface of platelets that reversibly binds vWF on damaged endothelium. Induced by fast flow in bloodstream
Term
Glycoprotein 6
Definition
ptn on surface of platelets that stably binds endothelium
Term
Weibel palade bodies
Definition
storage for vWF multimers in endothelium
Term
ADAMTS13
Definition
cuts HMW vWF into smaller, less sticky pieces for constitutive circulation. deficiency--> thrombotic thrombocytopenic purpura (TTP) with lots of clotting
Term
platelet agonists in vivo
Definition
collagen w/ GP6, cWF w/ GP9B, thrombin, ADP, and epinephrine
Term
Platelet suppressors in vivo
Definition
endothelial NO, endothelial prostacyclin, and CD39 (breaks down ADP)
Term
Glycoprotein IIb/IIIa
Definition
expressed on platelets, upregulated in activation, binds fibrinogen or vWF, vital for platelet aggregation
Term
workup for vW dz
Definition
vWF Ag quantification detects circulating levels from lo and hi MW multimers. Ristocetin cofactor assay gives functional assessment of vWF action. vWF multimer assay looks at proportions of each multimer. F8 level. Ristocetin induced platelet aggregation (RIPA) uses pt's plasma and platelets checks sensitivity of platelet vWF binding
Term
ristocetin induced platelet aggregation (RIPA)
Definition
uses pt's platelets and plasma and assesses sensitivity of platelet vWF binding
Term
types of vW dz
Definition
1: too little vWF. 2:dysfunctional vWF (several subtypes). 3: complete lack of vWF
Term
vWF multimer assay
Definition
gel electrophoresis separates multimers of vWF, checks for appropriate proportions of HMW vWF
Term
hemophilia A
Definition
X linked disorder of Factor 8
Term
DDAVP
Definition
synthetic desmopressin stimulates endothelial release of vWF is great for treating vW dz in anticipation of bleeding (period, dentist) but can only be used a couple days at a time (tachyphylaxis)
Term
vWD Tx
Definition
DDAVP, Cryoprecipitate, purified vWF:8, anti fibrinolytics, and estrogen
Term
Bernard Soulier syndrome
Definition
autosomal recessive, platelet GP 1B9 deficiency. PBS: mild to moderate thrombocytopenia, large platelets. Low RIPA, nl RCo . Corresponds with vWD
Term
Gray Platelet Syndrome
Definition
lifelong mucocutaneous bleeding, autosomal recessive def of alpha granules
Term
Glanzmann's thrombasthenia
Definition
autosomal recessive defect in platelet GP IIb/IIIa. Normal platelet count, severe mucocutaneous bleeding, Fe deficiency, prolonged bleeding time, absent aggregation to any agonist except ristocetin.
Term
Aspirin MOA
Definition
irreversibly inhibits COX1 , prevents formation of TXA2.
Term
Protein C cofactors
Definition
Thrombomodulin, Ptn S, and F5a
Term
megaloblastic anemia
Definition
MCV is over 100 fL, indicates dfx in DNA pdxn and cell division, could be B12 or folate def. Retics will be lo, bili hi, cells all over body have trouble dividing.
Term
heparan
Definition
GAG that activates antithrombin to prevent thrombin from promoting clotting
Term
Thrombin
Definition
induces ET to release tPA, ET derived relaxing factor and prostacyclin; induces monocytes to express uPA receptors; complexes with TM to activate ptn C; induces platelet mediated clot retraction
Term
plasmin
Definition
a very active serine protease from plasminogen; degrades fibrin, F5, F8, and deactivates platelets. a-2-PI inhibits it, uPA and tPA activate it. Active in angiogenesis.
Term
tPA
Definition
tissue plasminogen activator; comes from ET, dissolves clots, converts plasminogen to plasmin. released in response to increased venous pressure
Term
PAI
Definition
Plasminogen Activator Inhibitor. Does whjat it says.
Term
Annexin II
Definition
binds ET and allows conversion of plasminogen to plasmin
Term
a2PI deficiency
Definition
excessive fibrinolysis by plasmin that mimics hemophilia symptomatically w/ bleeding into joints
Term
D- dimer
Definition
cross linked fibrins from clot breakdown; its presence tells you 3 things: you have functional thrombin that made fibrin, F13 cross linked it, and plasmin was activated to break down the clot.
Term
TAFI
Definition
Thrombin activated fibrinolysis inhibitor; cuts off lysine residues that plasminogen and tPA would bind to, making the clot more stable.
Term
DIC definition
Definition
disorder of hemostasis resulting from excess generation of thrombin (usually from triggering of intrinsic system by TF)
Term
Lab Dx criteria for DIC
Definition
Thrombocytopenia, ^D-Dimer, ^fibrin monomer, low-nl fibrinogen, positive protamine test
Term
Kasabach Merritt syndrome
Definition
localized DIC syndrome, livable
Term
nl PTT
Definition
30" give or take 5"
Term
nl PT
Definition
12"
Term
AMICAR
Definition
epsilon amniocaproic acid, binds lysine residues, acts as an antifibrinolytic. blocks tPA and plasminogen
Term
Inherited thrombophilias
Definition
Deficiency in AT, Ptn C, or Ptn S; APC resistance, PT gene mutation, homocysteinemia, or elevated F8, F11.
Term
APC resistance
Definition
(factor 5 leiden) arginine target of ptn S/APC cleavage is mutated, preventing breakdown of f5a and increasing risk of thrombus 5x
Term
re-bleeding
Definition
hallmark of factor 13 deficiency; pts will bleed, clot, and then begin bleeding again later
Term
factors unique to the intrinsic pathway
Definition
12,11,9,8
Term
factors in the common pathway
Definition
X,V,II,I
Term
factors unique to the extrinsic pathway
Definition
7
Term
factors requiring Ca and vitamin K
Definition
F2,7,9,10
Term
cofactor for protein C
Definition
ptn S
Term
Tenase
Definition
refers to the complex of F9 and F8 together
Term
prothrombinase
Definition
refers to complex of F10a and F5a
Term
what test is used for coumadin/warfarin monitoring?
Definition
PT tests levels of F7, which has the shortest halflife of the vitamin K dependent factors
Term
clopidagrel
Definition
Plavix; blocks ADP receptor on platelets
Term
platelet collagen receptor
Definition
GP1a/2a
Term
conformational change in platelet exposes
Definition
GP2b/3a
Term
Abciximab
Definition
glycoprotein IIb/IIIa receptor irreversible inhibitor
Term
GP 2b/3a inhibitors
Definition
abciximab, eptifabitide, tirofiban
Term
ADP receptor inhibitors
Definition
clopidogrel and ticlopidine
Term
TXA2 receptor blocker
Definition
Dipyridamole
Term
Sx of platelet disorder
Definition
small bleeds (petechiae, purpura, epistaxis, mucocutaneous bleeds)
Term
Sx of secondary hemostasis disorder
Definition
bleeding into joints, large ecchymoses
Term
unfractionated heparin vs. LMW heparin
Definition
unfractionated: effective, reversible, rapid, short t/2, unpredictable, inpatient, more HIT. LMW:effective, fixed dosing, more predictable, less HIT, subQ, not fully reversible, difficult for obese or renal pts
Term
fondaparinux
Definition
pentasaccharide; selective inhibitor of F10a, can be used in pts with HIT
Term
warfarin
Definition
blocks vitamin K epoxide reductase, oral, outpatient, dietary precautions, unpredictable. OD may cause warfarin necrosis w/ microvascular clots
Term
rivaroxaban and apixaban
Definition
oral factor 10a inhibitor, broad therapeutic index
Term
prothrombin inhibitors
Definition
argatroban, lepirudin, bivalrudin, dibagitran
Term
Thienopyridines
Definition
ticlopidine and clopidogren irreversibly inhibit ADP receptor on platelets; both prodrugs activated in hepatic metabolism
Term
First line anti-platelet therapy
Definition
aspirin blocks COX1 irreversibly and blocks platelet aggregation for up to 5 days
Term
level of TPO in aplastic anemia
Definition
elevated
Term
level of TPO in ITP
Definition
normal
Term
normal distribution of platelets
Definition
1/3 of platelets are in a normal spleen at any given time
Term
daily platelet turnover rate
Definition
0.1
Term
normal platelet survival time
Definition
10 days
Term
Infections associated with autoimmune thrombocytopenia
Definition
H. pylori, Hep C, and HIV
Term
pseudo- vWD
Definition
gain of function mutation to the GP1b9, "mops up" vWF from the body
Term
Jewish bleeding disorder
Definition
factor 11 deficiency
Term
lupus anticoagulant
Definition
inhibits phospholipid dependent in vitro coagulation tests, esp. PTT. Causes arterial and venous thrombosis, fetal death. It is an antibody against clotting proteins that, when combined, develops affinity for phospholipid.
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