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Hematology 1 - Hemostasis Vol. I

omarys's version from 2018-11-06 10:22

Section 1: The coagulation cascade

Question Answer
Thromboplastin is AKATF (factor III)
Factor VIIa-TF as a complex activates- (2)Factor IX and X (7+3=10 (and 9))
Factor IX and factor ___ work as a complex; they activate factor ___.VIII ; X (8,9,10)
Factor X activates prothrombin (II) to thrombin (IIa) using ___ as cofactor. Va (10/5=2)
Factor XII is AKA ___ and is responsible for activating factor ___.Hageman factor ; XI
Factor XI can activate ___, but ___ is also activated by ___.IX ; IX ; VIIa-TF (7+3=10 (and 9 for some reason...take it or leave it))
Factors that are part of the intrinsic pathway are- (4)VIII, IX, XI, XII
PTT checks the coagulation cascade starting from factor ___; so it will be longer if ___, ___ or ___ are damaged.XII ; VIII ; IX ; XI
PT checks cascade activated thru ___ so it will be longer if e.g. factor ___ is damaged.TF ; VII
TT checks cascade activated thru ___, so it will be longer if there is damage to fibrinogen. II (thrombin)(IIa activates fibringoen to fibrin)
The Xa-Va complex (Va is co-)(which activates prothrombin) is AKAprothrombinase complex
The IX-VIII complex (VIII is co-) is AKApro-tenase complex (or intrinsic Xase; compare with VIIa-TF, which is termed extrinsic Xase)
Factor Xa (poz fb) can also activateV, VIII, XI

Section 2: Thrombophilia / thrombosis and hypercoagulability

Question Answer
Does warfarin increase or decrease coagulation?Decreases coagulation (increases risk of bleeding), bc "warfare" means blood spillin
TorF: Both vitamin K and vitamin K epoxide reductase act as anticoagulants.False. Vit K and the enzyme that reactivates it (=epoxide reductase) ENHANCE the clotting ability of 2, 7, 9 and 10.
Thrombophiliain VENOUS system (VTE), e.g. DVT
Virchow's triad:stasis, hypercoagulable state, endothelial injury
Congenital thrombophilia may be caused by- (4)protein S or C deficiency ; aPCR ; prothrombin (II) mutation ("GOF") ; antithrombin III mutation ("LOF")
Proteins S and C inactivate factors ___ and ___.8 ; 5 (S with a / is 8; 5 is C cuz idk)
Whose half-life is longer, protein C or S?S (line is probs longer)
Warfarin ___ blood clotting by blocking an enzyme called vitamin K ___ ___ that ___ vitamin K1.decreases ; epoxide reductase ; reactivates (Without sufficient active vitamin K1, clotting factors II, VII, IX, and X have decreased clotting ability.)
Other than its effect on the clotting factors, warfarin also damages-proteins S and C (C decreases first)
aPCR is when-there's a mutation in factor V --> factor V Leiden --> protein C is unable to effectively bind factor V and inactivate it
Vitamin K is also involved insynthesis of proteins S and C
A GOF mutation in a gene that leads to a mild increase in likelihood of thrombosisG20210 prothrombin mutation
In ppl w factor V Leiden (___), the ___ (time) decreases, e.g. in homozygotes it is less than in heterozygotes.(aPCR) ; PTT
Happens in homozygous protein C deficiencyneonatal purpura fulminans (can worsen into skin necrosis)
Protein C deficiency is a ___ condition marked by increased risk of ___.rare ; VTE
Happens in heterozygous protein C deficiencyWarfarin-induced skin necrosis
Warfarin (Coumadin) prevents the production of ____ _________ dependent clotting factors. As a result, clotting occurs at a much ___ rate.Vitamin K ; slower
The first to be damaged when vitamin K function is compromisedprotein C (also involved are factors II, VII, IX, and XI and protein S)kinda paradoxical because vitamin K is important for both pro- (the factors) and anticoagulation agents (proteins C and S)
In the first few days after warfarin-induced skin necrosis (w protein C deficiency as a background condition), there is ___ likelihood of thrombosis.increased (because protein C is the first to be compromised)
What medication increases the likelihood of VTE?birth control pills

Section 3: Bleeding disorders & lab tests

Question Answer
In a hematoma the blood (usually ___) pools in tissues.liquid - emphasis here is on accumulation in TISSUE and taking up volume- in muscles, joints, cranium
In a bruise/contusion, the blood pools in a ___ ___ under the ___ and can be in the form of ___ (___), a ___ (_________) or ___ ().thin layer ; skin ; petechiae (up to 4 mm) ; purpura (4-10mm) ; ecchymosis (>10 mm)
Tests for all cascade, thru contact/intrinsic pathwayPTT (high in e.g. VIII, IX, XI def)
Tests the beginning of the cascade, thru the TF/extrinsic pathwayPT (high in e.g. VII def; should add TF&Ca++ if using this test)
TTartificial activation of thrombin, to test for fibrinogen amounts (i.e. TT will be high if fibrinogen is faulteh)
The difference bwn petechiae and small angiomas is that the formersdon't disappear/turn white when you apply pressure on them.
The difference bwn a petechia and a vasculitis lesion is that the latterwill be raised and palpable
Purpura are common in ppl whotake aspirin, suffer from CT diseases, old ppl after trauma
Ecchymoses are usuallyblack and blue

Section 4: ?

Question Answer
Weather changes are frequentnoh
___ is the only biomolecule that can convert ___ to ___.Thrombin (II) ; fibrinogen ; fibrin (I) (das why it's important to regulate THROMBIN effectively)
Factors ________ are ____ly ___ and are all dependent on _______ for synthesis.2, 7, 9, 10 ; negative ; charged ; vitamin K
GGCX?Gamma glutamyl carboxylase (a liver enzyme that needs vitamin K; responsible for carboxylation of 2, 7, 9, 10 so they form the 'sandwich')
Vitamin K helps ___ turn Glu to Gla (gamma carboxy glutamic acid) in ________ so as to make them more ______.GGCX ; 2, 7, 9, 10 ; negatively charged (helps bind em to Ca++ ions)
A carboxyl group is R-COOH
The source of Ca++ isdense granules (from activated platelets)
The 3rd (and ____) part of the 'sandwich' isplatelet membranes (phosphatidylserine)(made more neg by flip flop - induced by Ca++)
Why ya need to inject vitamin K to newborns?They got none in gut flora (if not, they'll have 2,7,9,10 w/o Gla - hard to form sandwich)
In the Glu-->Gla reaction, vitamin K is ____ and needs to be ______ to be active again. This is done by ________, which _____ blocks..oxidized ; reduced ; vitamin K epoxide reductase ; warfarin/coumadin
To prevent coagulation in a tube, add ________________ agents.calcium-absorbing
Other than the poz fb for 5,8,11, thrombin (2) activatesplatelets
The thrombin burst happens thanks to
Protein levels in blood from highest to lowestfibrinogen > prothrombin > factor VII > factor IX > factor X > other COfactors mostly (5, 8)

Section 5: Extrinsic pathway

Question Answer
Factor ___ has a pretty short half-life so it needs to be regulated well since it's effectively the one that starts this pathway.7
TF-VIIa ___________activates other VII's (but some VIIa's (active) are already found in bloodstream)
TF can bind bothVII (and activate it to VIIa) or VIIa

Section 6: Intrinsic pathway

Question Answer
Factor XI can be activated thru both ______ and ______.thrombin (II) ; the intrinsic pathway (XII)
What activates XII into XIIa?contact with neg' charged molecules (collagen, poly-P molecules, molecules from act' neutrophils; found on act' platelets/neutrophils & on artificial valves, etc.)
Fibrinogen > fibrin monomers > fibrin polymer w jelly consistency > ____/____ does cross linkstransglutaminase / Factor XIII (needs calcium to work)
Other functions of XIII?wound healing (its def. should be on the DD if wound healing problem) ; egg implantation
Factor XIII comes into the picture only after ___'s done its thangthrombin (II)

Section 6: Regulation of hemostasis

Question Answer
TFPI has _____ in its _____.Kunitz domains (1-3) ; centre
K2 of TFPI bindsXa
TFPI-Xa complex can bind ____ thru the domain ____.TF:VIIa complex ; K1
TFPI10 - 7 = 3
TFPI can also bind an already formedTF:VIIa:Xa
TFPI effectless thrombin (IIa) production
AT3 inhibits/degrades10a and 2a (and 9a)
Protein C degradesCF 5a & 8a
Example of GAGHeparan sulfate (expressed on surface of HEALTHY endothelial cells)
AT3 is not very ____; it becomes so once it ______.GAGs
Why isn't AT3 active in areas of active coagulation?cuz the endothelium is damaged there (no GAGs for AT3 to be active; but once there's collateral damage the GAGs are there to activate AT3)
______ is a type of GAGheparin
So in essence, a GAG/GAG-related molecule is ____-____.anticoagulant
The GAG is like a snek that coils around AT3 andeither Xa or IIa (thrombin)
LMWH helps AT3 inhibit _______ ONLYXa
enoxaparin / _____ is an ______ medication that-clexane ; anticoagulant - helps AT3 bind Xa (not IIa)
Clexane is given _____ and is commonly used insubcutaneously - gynecology/obstetrics
A pentasaccharide sequence is the-smalles subunit of heparin that can help AT3 function - but only for binding/inactivation Xa (same as LMWH)
LMWH ________ than heparinis easier to manipulate/has more predictable pharmacokinetics
LMWH is also safer cuz heparin is more likely to induceHIT (thrombocytopenia)
LMWH vs heparin- the formeris admin. subcutaneously more than IV; has longer half-life; has higher bioavailability
HEALTHY endoth. cells also express-EPCR (binds PC)
HEALTHY endoth. cells also ALSO express-thrombomodulin (binds Xa and neutralizes it)
The thrombin-thrombomodulin complex binds EPCR-protein C, which-releases an ACT' protein C (that binds protein S, its co-)
Protein Ca (& co-f' S) degrade5a and 8a
So...thrombin is a chraytah?yea, it both poz fb's and (indirectly, thru EPCR-PC) degrades 5a and 8a. Also it helps AT3 too. Too much thrombin = tips balance towards anticoagulation
EPCR-PC will bind thrombin-thrombomodulin if there'sCa++

Section 7: Fibrinolysis

Question Answer
DAMAGED endoth. cells can secretetPA (to produce plasmin, to DEGRADE the clot)
Who's tPA's nemesis?PAI (plasminogen activator inhibitors 1&2)
Who's TAFI and whose side is it on?Thrombin-activatable fibrinolysis inhibitor; on fibrin's side/PAI's side
So thrombin is also pro-coagulation in terms offibrinolysis inhibition (other than coagulation induction)
Plasmin + fibrin =FDPs, e.g. D-dimers
Each fibrin (in the polymer) is made up of(D-----E-----D)(D-----E-----D)(D-----E-----D)
Each D-dimer is made up ofTwo D domains from 2 DIFFERENT fibrins
In bleeding disorders, we might wanna tryinhibiting the fibrinolytic system (e.g. thru TXA)
TXATranexamic acid/hexakapron (usually admin. after traumatic bleeding- decreased bleeding and MORTALITY)
TXA is a _____ analogue that binds ______ riiight where it's spozed to work on ______.lysine ; plasmin ; fibrin

Section 8: Other

See summary pic for thrombin