121214 defects of coagulation

Question 1

platelets have what type of granules

Answer 1

dense (signal 1 platelet to next platelet): ADP, ATP, serotonin, Ca

alpha: coagulation proteins (fibrinogen, vWF), growth factors, etc

Question 2

when you turn on activating receptors on platelets–their downstream effects?

Answer 2

integrin activation (fibrinogen)
granule secretion
cytoskeletal rearrangements (shape change)

Question 3

steps of platelet adhesion

Answer 3

endothelial damage, then collagen exposed, then vWF sticks, then platelets adhere

Question 4

consequences of platelet activation

Answer 4

granule release–signal to other platelets

activation of GPiib/iiia—allows platelet cohesion

membrane procoagulant expression, leading to thrombin and a clot

Question 5

cell based coagulation steps

Answer 5

initiation
amplification
propagation
thrombin causes transformation of fibrnogen to fibrin and cross-linking

Question 6

vit K dependent clotting factors

Answer 6

pro-coagulant: 2,7,9,10

anticoagulant: protein C, protein S

Question 7

factor 13a

Answer 7

increased by thrombin

stabilizes polymerized fibrin

Question 8

lab would need to throw in tissue factor for which clotting test?

Answer 8

PT

Question 9

what factor is important in PTT but not in normal physiology?

Answer 9

factor 12/contact factor

Question 10

fibrinolytic system

Answer 10

t-PA
plasminogen
alpha antiplasmin
D-dimer

Question 11

thrombocytopathy occurs commonly due to

Answer 11

anti-platelet drugs

Question 12

causes of thrombocytopenia (increased destruction types)

Answer 12

immune clearance
sepsis, DIC, TTP
hypersplenism

Question 13

coagulopathy ex

Answer 13

inherited: vWillebrand disease, hemophilia
acquired: DIC, anticoagulants, hepatic failure, vitamin K deficiency

Question 14

mucosal bleeding is a sign of

Answer 14

platelet defect or VWF

Question 15

deep tissue bleeding is a sign of

Answer 15

factor deficiency

Question 16

generalized oozing at venipuncture sites

Answer 16

consider DIC

Question 17

bruising is a sign of

Answer 17

it;s nonspecific

Question 18

timing of bleeding–immediate vs delayed suggest what?

Answer 18

immediate–platelet dysfxn

delayed–suggests hemophilia more

Question 19

PE-what to look for in the case of suspected bleeding disorders

Answer 19

petechia (severe platelet deficiency)

signs of liver disease (b/c liver produces coagulation proteins)–spenomegaly (pts w splenomegaly can have thrombocytopenia)

Question 20

screening tests for bleeding disorders

Answer 20

platelet phase:
platelet count (and blood film)
PFA-100

coagulation phase:
prothrombin time (PT)
partial thromboplastin time (PTT)
fibrinogen
inhibitor screening (1:1) mix

Question 21

further laboratory evaluation of platelet defects

Answer 21

quantitative:
peripheral blood film
lab studies for associated disorders (such as vit B12, PF4 ELISA)

Question 22

if immune mediated peripheral destruction is the cause for thrombocytopenia, and it’s Fab mediated, what does the blood film look like?

Answer 22

normal

Question 23

ex of non Fab mediated immune thrombocytopenia

Answer 23

heparin induced thrombocytopenia
immune complex disease (HIV)
TTP (auto antibody to ADAMTS13)

Question 24

immune thrombocytopenic purpura mechanism

Answer 24

childhood type–auto antibody to platelet surface glycoproteins

adult type–usually no obvious antecedent viral illness (as opposed to in children)

Question 25

what can you see on blood film for ITP?

Answer 25

platelets that are large

Question 26

heparin induced thrombocytopenia-pneumonic?

Answer 26

``` 4T's: thrombocytopenia timing thrombosis no oTher ```

Question 27

heparin induced thrombocytopenia-mechanism?

Answer 27

neo-epitope (heparin-PF4) causes transient autoimmune disease. IgG/PF4/heparin complex activates platelet via the Fc receptor. associated with thrombotic events moderate thrombocytopenia

Question 28

how to diagnostically evaluate heparin induced thrombocytopenia?

Answer 28

PF4-heparin ELISA

Question 29

thrombotic microangiopathy ex

Answer 29

TTP hemolytic uremic syndrome (Shiga toxin associated-HUS) DIC, sepsis etc

Question 30

classic PENTAD of TTP

Answer 30

lab abnormalities (required for diagnosis): microangiopathic hemolytic anemia thrombocytopenia organ dysfxn (not required for diagnosis): renal failure mental status changes fever TTP is a clinical diagnosis

Question 31

idiopathic TTP is due to

Answer 31

auto antibody to ADAMTS13 protein

Question 32

role of ADAMTS13

Answer 32

regulates vWF/platelet interactions

Question 33

PFA-100 fxn

Answer 33

screens for platelet and VWF function gives you occlusion time as a test, however, it's sensitivity/specificity is lower than required for a good test

Question 34

fxns of vWF

Answer 34

support platelet adhesion ot exposed collagen at sites of injury carrier for factor 8--maintains factor 8 in circulation

Question 35

lab eval for von willebrand dis

Answer 35

quantitation of VWF by immunoassay: VWF:Ag quantitation of VWF fxn: VWF:RCo (the ristocetin cofactor assay)

Question 36

platelet function defects--ex of platelet receptor disorders?

Answer 36

congenital absence of: GPIb-Bernard Soulier syndrome GPIIb/IIIa-Glanzman's thrombasthenia

Question 37

platelet fxn defects can be what types?

Answer 37

platelet receptor disorders that are congenital acquired disorders (drugs to inhibit platelet fxn, etc)

Question 38

PT method

Answer 38

tissue factor, phospholipid and calcium are added to citrated plasma and clotting time is measured

Question 39

INR

Answer 39

normalizes reported PT so that result is comparable across labs intended for warfarin monitoring

Question 40

1:1 mix

Answer 40

pt plasma is mixed with normal plasma containing 100% of all factors. clotting time is obtained if clotting time corrects to normal, factor deficiency is likely if clotting time still prolonged, then inhibitor is likely

Question 41

differential of isolated long PTT, and what tests would you run?

Answer 41

factor deficiency: factor 8,9,11,12, contact factors (factor 12 deficiency isn't a physiological bleeding problem) von Willebrand disease (8) inhibitors: heparin (inhibitis Xa, thrombin) lupus anticoagulant specific factor inhibitor repeat PTT, perform 1:1 mix

Question 42

differential of isolated long PT

Answer 42

factor deficiency: factor 7 combination of factors-vit K deficiency/oral anticoagulant, liver disease or inhibitors (rare)

Question 43

prolonged PT and PTT differential

Answer 43

factor deficiency: - isolated factor (10,5,2, fibrinogen) - multiple factor deficiency (liver disease, vitamin K deficiency if severe, DIC) inhibitors: - isolated factor inhibitor (10,5,2) - drugs (heparin,..) - lupus inhibitor

Question 44

factors not tested by screening tests

Answer 44

``` factor 13 physiologic anticoagulants (antithrombin, protein C, protein S, factor V Leiden) ```