Cp 2 Coagulation

Front 1

Primary vs secondary hemostasis

Back 1

Primary: platelets/fibrin/clot

Secondary: coagulation factors

Front 2

Match symptom with primary vs secondary hemostatic defect:

A. petechiae

B. small ecchymoses

C. hemarthosis

D. menorrhagia

E. deep soft tissue hematomas

F. extensive postop bleed

G. delayed onset of bleeding

Back 2

Primary: menorrhagia, petechiae, bleeding immediately follows trauma, spreading deep soft tissue hematomas [A, D]

Secondary: hemarthrosis, deep soft tissue ecchymoses, delayed/extensive post-op bleed, gingival bleeds [B, C, E, F, G]

Front 3

Symptoms of a primary hemostatic disorder

Back 3

Mucosal (gingival/epistaxis) and cutaneous bleeding (petechiae,ecchymoses)

Menorrhagia/metrorrhagia

Patients tend to bleed immediately after vascular trauma

Hint 3

Ecchymoses: usually develop without noticeable trauma and DO NOT spread into deeper tissues

Menorrhagia/metrorrhagia: 15%caused by bleeding diathesis (vWD, ITP, platelet function defect)

Front 4

A patient has petechiae with normal platelet counts and PT/PTT. What's the next step?

Back 4

PFA-100

Front 5

What do the following have in common?

Factor V Leiden

Protein S deficiency

Protein C deficiency

AntithrombinIII deficiency

Prothrombin mutation (G20210A)

Lupus anticoagulant

Pregnancy

Plasmin defects

Back 5

Hypercoagulable states/diseases

Front 6

Wilms tumor and coagulation

Back 6

Associated with acquired vWD

Front 7

Thrombomodulin plus F2a = ?

Back 7

Activates protein C

PC --> APC

Front 8

Factor V Leiden results in what symptoms?

Back 8

Hypercoagulable state

Front 9

In primary hemostasis, platelets tether to areas of injury via __ (platelet) connections to __.

Back 9

Gp1b binds vWF

Front 10

Where does vWF bind?

Back 10

Binds collagen and Gp2b/3a

Front 11

Where does vWF come from?

Back 11

Platelet alpha granules and endothelial Wiebel Palade bodies

Front 12

What is GpIV?

Back 12

A collagen receptor

Front 13

Together with GpIV, GpIb leads to intracellular release of _.

Back 13

Calcium

Front 14

What does calcium do?

Back 14

Activates PLA2 (PL --> AA)

Alpha and dense granule release

PKC activation

- activates Gp2b/3a)

- actin polymerization

Front 15

PKC activation leads to __.

Back 15

Activates Gp2b/3a)

Promotes actin polymerization

Front 16

PLA2 is activated by _.

Back 16

Calcium

Front 17

PLA2 takes _ and forms _.

Back 17

PL

AA

Front 18

AA forms into __ by the action of __.

Back 18

Prostaglandin

COX

Front 19

Alpha granules contain _.

Back 19

vWF, fibrinogen

Front 20

Dense granules contain _.

Back 20

5HT, ADP, Ca2+

Front 21

Name the disease associations (1-15)

Back 21

1) vWD 2) Bernard Soulier

4) Ehlers Danlos, Marfans

7) Thromboxane synthase def

8) Alpha storage pool disorders (gray plt syndrome)

9) Delta storage pool disease

12) Glanzmann thrombasthenia

13) Congenital afibrinogenemia

14) Scott syndrome: defect in flippase

15) Wiskott-Aldrich syndrome

Hint 21

3) Collagen R defects

5) Impaired liberation of AA

6) COX def

10) Purine /TXA2receptor or G protein defects

11) Defects in PIP metabolism

Front 22

Glanzmanns

Back 22

12

Front 23

Bernard Soulier

Back 23

2

Gp1b is 2nd most expressed integrin (25K on plt surface, MC is GpIIb/IIIa at 50K)

Front 24

Scott syndrome

Back 24

14) Scott syndrome: defect in flippase,leaves PS on inner leaflet, phosphatidyl choline on outside --> factors can’t kick start coagulation cascade

Front 25

Wiskott-Aldrich syndrome

Back 25

15) Wiskott-Aldrich syndrome- a defect in cdc42 geneblocks GpIb-mediatedfilopodiaformation (Gp1b --> cdc4(g protein) --> WASP --> actin polymerization). It also hassomething to do w granule release. This dz also affects T cells.

Front 26

dxby EM, difficult to test for bc hard to keep NL plts fr degranulating ImKuzBvanMcQ7cooki@

Back 26

8)Alpha storage pool disorders (gray platelet syndrome)

Front 27

eptifibatide

Back 27

3) abciximab, tirofiban, eptifibatide-inhibit fibrinogen binding to GpIIb/IIIa, agonists in the PFA will not induceaggregation (weo ristocetin),these drugs are far more potent than aspirin, ITP (2/2 to drug-dependent Abs)is a possible sdeeffect

Front 28

prasugrel

Back 28

2) clopidogrel, ticlodipine,prasugrel- thienopyridinederivatives that inhibit the ADP P2Y12 receptor, they also affect plt response to collagen, epinephrine, and thrombin

Front 29

ibuprofen

Back 29

1) Aspirin (irreversible- takes 5-7d fordrug to wear off- the lifespan of plts), NSAIDs (reversible- ibuprofen, forexample, only takes 24h to wear off). Note: though aspirin irreversible, itonly blocks one of many pathways, thus, plts are NOT totally inactivated

Front 30

SSRI

Back 30

4) SSRIs: pts may be more prone to GIT or post-op bleed

Front 31

clopidogrel

Back 31

2

Front 32

tirofiban

Back 32

3

Front 33

ticlodipine

Back 33

2

Front 34

F12 is activated by _.

Back 34

F2a

Hint 34

Front 35

12a activates _.

Back 35

11

Hint 35

Front 36

11a activates _.

Back 36

9

Hint 36

Front 37

8 is activated by _.

Back 37

2

Hint 37

Front 38

10 is activated by _.

Back 38

VIIa/TF

9a/8a

Hint 38

Front 39

Red 1

Back 39

Hemophilia

Front 40

Red 2

Back 40

Factor 13 deficiency

Hint 40

It is diagnosed by urea clot solubility-non-covalent fibrin clot is soluble in urea, FXIII defproven when clot solubilizes to 5M urea

Front 41

Red 3

Back 41

3a) Hypofibrinogenemia-heterozygote, low but not usu clin signiffibrinogen.

3b) afibrinogenemia arehomozygous or compound heterozygous for fibrinogen alpha chain gene mutations.PT/PTT generally not affected bc fibrinogen is not a rate limiter.

4) Dysfibrinoginemia-fibrinogen polymerizes slowly, activity usu ↓/NL but [fibrinogen] is ↑/NL when measured immunologically (eg,radial immunodiffusion,ELISA, or nephelometry). Dx: lowratio of functional to immunologic fibrinogen. 60% will not have sx butPT/PTT may be funny, 25% bleed, 10% thrombose(fibrin polymerizes & breaks-down slowly), 5% show pregcomplications e

Front 42

Red 5

Back 42

5) In prostate cancer, incr urokinaseleads to bleeding. This is a rare example of bleeding in cancer, as cancer usu a.w hypercoagulablestates

Front 43

Red 6

Back 43

6) Alpha 2-antiplasmin(A2AP) deficiency- can be congenital or acquired (cirrhosis, also seentransiently following liver transplant as it takes time for liver fxn tocome back)

Front 44

Hypercoagulable states lead to _ thrombi.

A. venous

B. arterial

C. both

Back 44

A. Venous

Note: Arterial TE are not usu associated with hypercoagstates- these are caused by atherosclerosis/trauma

Front 45

Prothrombin (G20210A) mutation causes _.

Back 45

Hypercoagulable state

Front 46

Protein S is bound in serum to _.

Back 46

C4b binding protein

Front 47

Protein S does what?

Back 47

S for Support

It support F5/8 cleavage by activated protein C (APC)

Front 48

Protein C is activated by _.

Back 48

Thrombomodulin

Front 49

5M urea does what?

Back 49

Causes polymerized fibrin clots to become solube. Covalent linked fibrin does not so it can be used to test F13 deficiency.

Hint 49

Front 50

How do F2 and F13 work regarding fibrin clot formation?

Back 50

F2a snips fibrinopeptides from fibrinogen to produce D to E linkage

F13a creates covalent D to D links

Hint 50

Front 51

Plasminogen is activated by _. It is inhibited by _.

Back 51

tPA, urokinase

Platelet activator inhibitor (PAI-1)

Alpha 2-antiplasmin

Hint 51

Front 52

Plasmin cleaves _ into _.

Back 52

Onfibrinogen, generates D & E fragmentsOnclot, generates D-dimerheld together w E domainNotethat if you detect D/E fragments + D-dimer, pt in fibrinolytic & thrombotic state (ex DIC)

Hint 52

Front 53

Aminocaproic acid

Back 53

antifibrinolytic,used to tx bleeding Tranexamicacid-same MOA, 8Xeffective

Hint 53

Front 54

Warfarin

Back 54

Blue 1

Front 55

Blue 2?

Back 55

2) Heparin: UFH: binds AT3 to 2a/9a/10a/11a/12a (UFH-T1/2 1.5h)LMWH: binds Xa alone (lovenox/enoxaparin(LMWH, T1/2 4-5h), fondaparinux(T1/2 17-21h))

Front 56

Protamine sulfate can neutralize _.

Back 56

Protamine sulfate can neutralize UFH/LMWH but NOT fonda

Front 57

HIT

Back 57

HIT most likely to occur w UFH, some w LMWH, not at all w fondaparinux -

Front 58

lepirudin

Back 58

4) Direct thombin inhibitors: lepirudin(irreversible, T1/2 90-120 min, renal metab, in CKD T1/2 52h!), bivalirudin(reversible), agatroban(short-acting, reversible, liver metab-good for pts w CKD), dabigitran, all do not cause HITa(TM)"R!

Front 59

rivaroxaban

Back 59

3) Direct Xa inhibitors: rivaroxaban, apixaban(both have xa inname), irreversible, renal metab, T1/2 15h, metabd byCYP3A4

Front 60

Mixing study

Back 60

•combinedpt plasma w plasma known to have 100% activity of all factors in 1:1 or 4:1ratio. –IfPT/PTT normalize, a factordeficiencyis at play. If it doesn’t, an inhibitor ispresent.–Note:if PT is prolonged, a mixing study is rarely performed bc an inhibitor to FVIIis so rare–4:1pt to ctrl can be useful for when weak inhibitors are present, as these maycorrect with a 1:1 mix.

Front 61

Euglobulin lysis time (ELT)

Back 61

An old test, rarely usedAcidify pt plasma à precipitate forms that is devoid ofATIII, alpha 1-antiplasmin, alpha 1-antitrypsinExtract precipitate and re-dissolveAdd thrombin in 37C water bath for 2 hrIf clot falls apart, it means there is aproblem in clot stabilityIt cannot give you an exact diagnosisSome patients will be normal foreverything except this test, hard to say what to do...

Front 62

Anti-phospholipid syndrome clinical criteria

Back 62

Clinicalcriteria:1 ormore premature (<34w) 2/2eclampsia-preE orplacental insufficiency1 ormore preglosses >10 wksEGA**3 ormore preglosses <10

Hint 62

Front 63

Anti-phospholipid syndrome lab criteria

Back 63

Twopositive tests, either a lupus anticoagulant (StaClotLA, dRVVT) or anti-PL Ab (B2GP1, cardiolipin, both>40IU or 99th percentile (they are present normallybut in lower concentrations), such that a weakly abNL test should not be called +)Mustbe same test (even for IgM, not sure where this comes from but Dr. Gailani saidit, I can’t find it stated anywhere and Laposata doesn’t agree with it) separated by >12weeksPositivetests must occur w.i 5years of clinical event (thrombosisin 2000 but anti-cardiolipin+ in 2014x2 does not = APS):#1

Hint 63

Front 64

vWD factors to consider

Back 64

vWF antigen

Ristocetin Cofactor

CoF to antigen ratio

F8 levels

Multimer analysis

RIPA

Platelet count

Hint 64