MOD: Hemostatis I and II

Question 1

Platelet components

Answer 1

Alpha granules (protein storage eg thromboglobulin etc) and Dense granules (ATP, serotonin, calcium etc), and PF3 (platelet factor 3 surface marker) hidden in inner memb that becomes exposed when platelet activated

Question 2

What are two platelet receptors

Answer 2

GP1B: VWF receptor (von willebrand factor), adhesion
GP2B: (mostly fibrinogen receptor), step 2 aggregation

Question 3

What prevents blood from clotting in vessels?

Answer 3

House collagen in endoth, so when broken can come out, neg charge of both endoth and plasma prots keeps them away from ea other, thrombomodulin etc

Question 4

Clotting mech:

primary hemostasis platelet adhesion

Answer 4

Endoth cell dmg rel collagen which binds to VWF, which concentrates platelets in dmg region

Question 5

What events happen in primary hemostasis?

Answer 5

Platelets, adhesion & aggregation

Question 6

Platelet structure

Answer 6

discoid if inactiv, purple on smear, pseudopodia if active

Question 7

How does platelet adhesion of damaged endoth occur

Answer 7

subendoth collagen exposed, binds vWF, platelets also bind VWF via GP1b, platelets activated and secr granules, serotonin and ADP cause vasoconstr to slow flow,
-GP2b changes shape and binds fibrinogen, causing platelets to aggregate, forming plug

Question 8

What catabolizeds von willebrand multimers?

Answer 8

ADAMTS13 (missing in TPP)

Question 9

Von Willebrand Factor?

Answer 9

Multimer prot in megakaryoctyes and endoth cells, and stored in endoth cell Weibal-Palade bodies (which also hold P selectin)

• its also the primary transport protein for factor VIII in the serum (so VWF allows factor 8 to circul8)
• binds GP1b on one side and subendoth collagen on the other

Question 10

What does <150k platelets mean?

>450k?

Answer 10

Thrombocytopoenia <150k

Thrombocytosis >450k

Question 11

What are the labs to test platelets?

Answer 11

CBC bn 150k-450k, MPV
Periph blood smear
Bleeding time, replaced by:
Platelet fxn analyzer-100 (PFA-100), cartridge in collagen coated with ADP or epi, measure time it takes for platelets to occlude cartridge, req VWF

Question 12

Sx of platelet issues?

Answer 12

longer clotting time on test,

mucosal bleeding, purpura, post-ob bleeding

Question 13

Immune Thromobocytopenic purpura aka ITP

Answer 13

Autoimmune clearance of platelets via autoantibodies to them

Question 14

drugs that can cause clotting issues

Answer 14

Aspirin COX inhibition decr TXA and inhibs platelets,

Plavix inhibs ADP receptor

Question 15

Bernard-Soulier Syndrome

Answer 15

lack gp1b VWF receptor on plaletets, probs with adhesion so incr bleeding time on PFA-100 etc

• v v large platelets!
• usu young pt with bleeding disorder and assoc anemia

Question 16

Glanzman Thrombesthenia

Answer 16

Def in GP2 fibrinogen receptor so plalets cant aggregte/bind

Question 17

Gray Platelet syndrome

Answer 17

alpha storage granule deficiency, look gray, incr bleeding time, purpura and some bleeding

Question 18

Von Willebrand Disease sx

Answer 18

-usual platelet disorder sx

Question 19

Acquuired platelet issues

Answer 19

CPB cardiopulm bypass, myeloma ab’s on platelts, MPN incr platelet count , etc etc

Question 20

Inherited VWD genetics?

Types?

Answer 20

all types AD except type 3 is AR
type 1 decr conc of normal VWF, most common
type 2 normal conc but abnormal VWF
type 3 complete VWF absence so low factor 8 (hemophilia A phenotype)
autoimm issues can also remove VW factor

Question 21

Abnormal Ristocetin cofactor test means?

Answer 21

VWD!!!

Can also use VWF multimer test, large are more hemostatic

Question 22

When would you not evaluate VWF?

Answer 22

stren exercise/stress

2nd3rd trim of pregnancy

Question 23

VWD Tx

Answer 23

• best for type 1; desmopressin (stim VWF release into bloodstream), dont give for type2b bc causes thrombocytopenia (already have normal quantity)
• for other types: factor 8 first

Question 24

What is TPP (Thrombotic Thrombocytic Purpura)

Answer 24

Loss of ADAM gene causes failture to make large multimers of VWF into smaller, causes too muc platelet activation and thrombosis

• causes the pentad: fever, thrombocytopen, microangiopathic hemolytic anem w schistiocytes, mental status changes, renal failure
• PRIMARY aggregation problem (secondary hemostasis coag is normal)
• fatal if untreated, so give plasma to replace ADAM

Question 25

How to distinguish TTP from DIC?

Answer 25

In DIC, PTT etc tests will be abnormal, but will be NORMAL IN TTP!

Question 26

HUS (Hemolytic Uremic Syndrome)

Answer 26

pediatric disease similar to TTP, but with renal failure instead of mental status change, caused by Shiga toxin in E coli O157:h7, no VWF involved, plasma exchange wont work (supportive tx only)

Question 27

``` Antiphospholipid Syndrome (Lupus anticoagulant) HIT (Heparin Induced thrombocytopenia) ```

Answer 27

Anti-phospholipid syndrome: ab's to platelet phospholipids, causes platelet activation thus thrombosis - elevated aPTT (but this disorder isnt a bleeding disorder), dx with russel venom viper test (dRVVT) - HIT: ab to PlateletFactor 4 (PF4) and heparin causes platelet activation thus thrombosis

Question 28

What IS desmopressin

Answer 28

exogenous vasopressin to stim rel of preformed VWF in endoth/megakaryocytes to boost conc in periphery

Question 29

How do you distinguished acquired VWD (assoc with some other diseases) vs inherited?

Answer 29

In inherited, pts have family history of bleeding (so fam history, duh), wont have easy bruising but may have DVT

Question 30

If you see the PENTAD of fever thrombocytopenia, microangiopathic hemolytic anemia (schistocytes), mental status changes, renal failure, what might this suggest?

Answer 30

TTP!!!

Question 31

What does secondary hemostasis form?

Answer 31

fibrin clot | cascade involves intrinsic and extrinsic paths converrging to common (prothrombin (II) and fibrinogen (I)

Question 32

where are the non-VWF other clotting factors made?

Answer 32

liver!

Question 33

what ARE the clotting factors?

Answer 33

serine proteases

Question 34

what happens in hemo 2 cascade

Answer 34

endoth dmg exposes Tissue factor (TF), which complexes with VII (7) which turns into VIIa, starts off secondary hemostasis in vivo, turns IX to IXa (crossover path where extrinsic crosses over to activate intrinsic path), IXa combines with VIII to convert X to Xa But in vitro, 7a converts 10 to 10a, complexes to 5 to convert 2 to 2a, which then converts fibrinogen to fibrin

Question 35

what does fibrin do w platelets | what vitamin do u need

Answer 35

stabilizes platelet plug | -need presence of vitamin K to carboxylate (add negative charge) to some of the factors)

Question 36

What does thrombin do?

Answer 36

converts fibrinogen to fibrin, activates 5 and 8, converts 11 to 11a, converts 13 to 13a to make more stable fibrin clot (starts tertiary hemostasis)

Question 37

TFPI (tissue factor pathway inhibitor)

Answer 37

rel by damaged tissue and shuts off extrinsic path, so need factor 11a to keep activating factor 9 (since extrinsic pathway wont do it), so we need thrombin which converts 11 to 11a

Question 38

What does tertiary hemostasis start with

Answer 38

formation of cross linked fibrin, factor 13a forms to stabilize clot (looks like net)

Question 39

What does tPA (tissue plasminogen activator) do? | What is it inhibited by?

Answer 39

recruits plasminogen into plasmin at site of clot (lyses fibrin into fibrin split products, such as D-DIMER!!!) -Inhib by Plasminogen activator inhibitor (PAI) and alpha-2 antiplasmin, which inhibs breakdown of fibrin

Question 40

What are some natural anticoagulants

Answer 40

protein c-activated by binding to thrombomodulin, then activated protein binds to protein S, which activates 8a and 5a

Question 41

What does antithrombin do?

Answer 41

inhibits serine proteases, esp 2a thrombin and 10a

Question 42

What are 5 basic tests of clotting factors?

Answer 42

``` PT PTT TT Fibrinogen test Mixing studies ```

Question 43

PT

Answer 43

Prothrombin time! functional test of extrinsic and common paths so all must be present to have normal PT, if prolonged could be liver disease, malabs of vit k (or warfarin, a vit k antagonist), could be fibrin/fibrinogen degrad prods -INR calculated from PT to montior warfarin

Question 44

PTT

Answer 44

Partial thromboplastin time! fxnl test of intrinsic and common path heparin etc etc

Question 45

Diffs in PT vs PTT

Answer 45

diff activators | PT uses TF, PTT uses clay coating

Question 46

TT

Answer 46

Thrombin time! fxnl test of fibrin generation add exoenous thrombin and Ca to plasma and measure conversion of fibrinogen to fibrin (increased in fibrinogen disorders, which can also be in liver dis)

Question 47

Fibrinogen test

Answer 47

fxnl assay that adds LARGE amoutn of thrombin and measures conversion of fibrinogen to fibrin, low if low conc of dysfuxn of fibrinogen -can use mass assay like ELISA immunoassay

Question 48

When are Mixing studies used? | procedure?

Answer 48

When theres a prolonged PT/PTT to determine if its due to deficiency of a factor or inhibition of a factor -mix pt plasma with normal plasma: factor deficiency would show >50% activity, if inhibitor of factor then will show clotting time that doesnt correct, must mean an ab (or drug like heparin) is present

Question 49

What are disorders of secondary hemostasis?

Answer 49

A type of hemorrhagic disroder, show hemarthrosis (bleeding into joints), echymoses (large bruises), delayed post-op or trauma bleeds, examples are Hemophila A and B

Question 50

Hemophilia A | Missing factor, genetics, test results, and tx?

Answer 50

FACTOR 8 DEFICIENCY! X linked recessive, severe for most INCREASED PTT! Tx by replacing missing factor!

Question 51

Hemophilia B | Deficient factor, genetics, test results?

Answer 51

deficiency in factor 9 | same genetics and clinical stuff as HEMOPHILIA A

Question 52

DIC (disseminated intravascular coagulation) histo

Answer 52

Schistiocytes (fragments) and thrombocytopenia (v few platelets in smear), microangiopathic hemolytic anemia on smear (unlike TTP)

Question 53

DIC sx and tests?

Answer 53

excessive clotting AND fibrinolysis, bleeding and/or thrombosis increases on ALL THREE TESTS! PT/PTT/TT decreased fibrinogen increased FSP like D-DIMERS

Question 54

DIC assocs?

Answer 54

assoc with blood cancers like APL, sepsis etc etc etc

Question 55

Other thrombotic disorders

Answer 55

Antithrombin deficiency APCR (acctivatd protein c resistance) usu due to factor 5 Leiden mutation Protein C def (need to inactiv8 factor 5 and 8) Protein S def (cofactor for protein C) Hyperhomocystinemia (mutation in MTFH receptor)