Coag For Ap/cp Boards

Front 1

Clues to a defect in primary hemostasis

Back 1

Immediate bleeding
Mucosal bleeding
Menorrhagia
Epistaxis
Easy bruising

Front 2

Clues to a defect in secondary hemostasis

Back 2

Delayed bleeding
Bleeding into joints and soft tissue

Front 3

Bernard-Soulier Syndrome

Back 3

AR
Giant platelets
Defect in GLYCOPROTEIN 1b/9
(plt receptor for vWF)
does NOT aggregate in response to ristocetin

Front 4

How to distinguish BS from vWD?

Back 4

Both will NOT aggregate in response to ristocetin

BUT

with the addition of normal plasma, vWD will aggregate. BS won't.

Front 5

What other diseases are associated with GP1b/9?

Back 5

ITP!
60% of cases of ITP have an autoantibody, usually to GP1b/9 or GP2b/3a

Velocardiofacial syndrome: microdeletion 22q11

Front 6

What is the treatment for ITP?

Back 6

NOT PLATELETS

Steroids are first line

Front 7

Glanzmann's thrombasthenia

Back 7

AR or autoimmune

Defect in glycoprotein 2b/3a
Causes problems with platelet aggregation
Will NOT show aggregation by ADP, epinephrine, collagen, TXA2 or thrombin.
WILL aggregate with ristocetin (through vWF)

Front 8

What does glycoprotein 2b/3a do?

Back 8

it is an integrin on the platelet surface that acts as a receptor for fibrinogen. 2b & 3a come together in the presence of calcium

Front 9

Platelet receptors

Back 9

Front 10

Coagulation cascade

Back 10

Front 11

What conditions will you have this abnormality in platelet aggregation studies?

Back 11

Bernard-Soulier
vWD

= Abnormal aggregration in response to ristocetin.
(Ristocetin causes vWF to bind to gp1b receptor)

Front 12

What is ristocetin?

Back 12

Was used as an antibiotic, but caused clotting. Now only used in vitro. Enhances binding of vWF to platelet receptor gp1b, in an unknown fashion.

Front 13

What is shown in this platelet aggregation study?

Back 13

NORMAL platelet aggregation :-)

ADP and epinephrine exhibit two waves of aggregation, primary and secondary . The secondary wave is due to release of endogenous ADP.

Front 14

Disease?

Back 14

Glanzmann's thrombasthenia

Front 15

Disease?

Back 15

Storage pool disease or defective release of storage pool contents (aspirin-like defect)

**Secondary waves to ADP and epinephrine absent

Front 16

What are in the granules of platelets?

Back 16

Dense granules: ADP, Ca, Serotonin

Alpha granules:growth factors, Platelet factor 4, fibronectin, Beta Thromboglobulin, von Willebrand Factor, Fibrinogen and Coagulation factors V and XIII

Lambda granules: similar to lysosomes and contain several hydrolytic enzymes.

Front 17

pattern?

Back 17

Abnormal response to ADP, epi, collagen.These are all dependent on binding to the ADP receptor (specifically P2Y12).

This pattern of abnormalities suggest either an abnormality of the P2Y12 receptor [rare] or a drug effect such as Clopidogrel [common.]

If bleeding, give platelets.

Front 18

These aggregation traces were obtained from a 33-year-old woman referred for investigation of life-long menorrhagia and prolonged bleeding after dental surgery. There was a family history suggestive of a bleeding disorder but no conclusion had ever been reached.

Back 18

The obvious abnormalities in these series of aggregation traces are the lack of second wave aggregation with ADP and adrenaline [remember these are weak agonists] but in addition the aggregation with collagen and ristocetin is abnormal [reduced.]
This suggests either platelet storage pool disorder or an abnormality of platelet granule release.

Front 19

These aggregation traces were obtained from an 18-year-old student under investigation for easy bruising. She had a prolonged closure time of >300s with PFA100

Back 19

The obvious abnormalities are an absent response to arachidonic acid and reduced secondary wave aggregation with ADP and Adrenaline. Collagen is also reduced.

These findings suggest a defect in the Thromboxane A2 pathway. Possibilities include drugs such as aspirin, NSAIDs, food stuffs that contain salicylates or a true defect in the TxA2 pathway.

Front 20

Clinical clues to dx of vWD

Back 20

Easy bruising
Nose bleeds
Menorrhagia

Jt bleeding uncommon; possibly type 3

Front 21

Lab test abnormalities in vWD

Back 21

Low F8
PT: normal
PTT: prolonged
Plt agg: abnormal response to ristocetin; normal responses to others.
PFA: abnormal collagen/adrenaline closure time and in most cases (but not all) a normal collagen/ADP time.

Front 22

Type 1 vWD

Back 22

Most common; mildest; may be asx
HETEROZYGOUS (homoz is type3)
Quantitative defect

Front 23

Type 2 vWD

Back 23

20%
AD
Qualitative defect
Normal levels but structurally abnormal

FOUR SUBTYPES: A B M N

Front 24

Type 2A vWD

Back 24

Decreased ability to bind GP1 receptor
Decreased plt adhesion & aggregation
Low ristocetin cofactor activity
Cannot form large multimers

Front 25

Type 2B vWD

Back 25

GAIN OF FUNCTION
Enhanced binding to GP1 = spontaneous binding to platelets --> rapid clearance of plts & lrg multimers
So may have thrombocytopenia & lack large multimers

***
Pt plt-poor plasma + formalin donor plts: low ristocetin activity
Pt plt-rich plasma: Abnormally LOW levels of ristocetin cause aggregation. Because large multimers are bound to platelets.
CANNOT use desmopressin as a treatment for bleeding as can lead to clots & low plts

Front 26

Type 2M vWD

Back 26

Decreased ability to bind GP1 (thus low activity with ristocetin) but has NORMAL large multimers

Front 27

Type 2N vWD
Normandy

Back 27

Abnormal binding to F8

Normal vWF levels
Normal ristocetin activity
DECREASED F8 to levels seen in hemophilia A

Front 28

Type 3 vWD

Back 28

Most severe (HOMOZYGOUS)
NO vWF production
Extremely low F8 levels, to those seen in hemophilia A
(Hemophilia A is XR, Type3vWD is AR)

Front 29

Platelet-type vWD
Pseudo-vWD

Back 29

AD defect in platelet
GP1 receptor on plt membrane increased affinity for vWF
plt aggs + lrg multimers removed from circulation causing thrombocytopenia and low multimer levels
SIMILAR FINDINGS TO TYPE 2B

Front 30

Acquired vWD

Back 30

Autoantibodies
A form of vWD occurs in patients with aortic valve stenosis, leading to gastrointestinal bleeding (Heyde's syndrome).
Acquired vWD has also been described in the following disorders: Wilms' tumour, hypothyroidism

Front 31

Which ABO blood group has normally LOW levels of vWD and may be misdiagnosed with Type 1 vWD?

Back 31

O

Front 32

When is desmopressin useful in treating vWD?

Back 32

Type 1, Type 2A
Desmopressin (DDAVP) stimulates release of von Willebrand factor from the Weibel Palade bodies of endothelial cells and increases the levels of vWF as well as coagulant Factor VIII.

CONTRAINDICATED in Type 2B; ineffective in others

Front 33

describe pattern of vWF multimers in type 1, 2a, 2b, 3

Back 33

Front 34

What 2 vWD have an increased RIPA test?

Back 34

2B (gain of fxn gp1b/9)(decreased large forms)

Plt type (gain of fxn gp1b/9 for vWF)(decreased large forms)(Mimics 2B but needs higher ristocetin level, and also aggregates with cryo)

Front 35

What vWD type mimics hemophilia A? Why? How to tell apart?

Back 35

vWD 3. most severe form of vWD. No vWd and therefore looks like no F8 either.

But type 3 vWD is AR vs. XR in hemophilia. So they could give you a picture that looks like hemophilia, but in a female.

Front 36

genetic defect hemophilia A?

Back 36

xq28 inversion intron 22

Front 37

What is it in EDTA that causes platelet clumping and pseudothrombocytopenia?

Back 37

antibodies to gp2b/3a! (what usu binds to fibrinogen)

Front 38

how can you tell DIC from TTP/HUS based on labs?

Back 38

DIC has low fibrinogen

Front 39

mutation in factor V leiden?

Back 39

Arg --> Gln @ 506

Front 40

mutation facrot V cambridge?

Back 40

Arg --> thr @ 306

Front 41

Mutation sickle cell dz?

Back 41

Glu --> Val on 11 (Beta chain gene)

Front 42

test results for antiphospholipid syndrome

Back 42

elevated PTT

Front 43

2 diseases with low platelets AND thrombosis

Back 43

APLS
HIT

Front 44

treatment of HIT

Back 44

Stop heparin
DO NOT give platelets
DO NOT give warfarin
DO give thrombin inhibitors, and monitor with PTT