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Flashcards in Coagulation Deck (113)
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1

What does vWF bind to on the platelets?

Glycoprotein Ib/V/IX

("1B59")

Damanged endothelium-->circulating vWF in plasma attaches to endothelium, platelets attach to vWF using GPIb/V/IX

2

HIGH YIELD!

Platelets have alpha granules and delta (dense) granules. What do they contain?

*hint* dense only have 4 things whereas alpha has a lot so easiest to memorize contents of dense granule

Dense Granule:

-ADP dense granule which causes vasoconstriction

- ATP

- Serotonin

- Ca++

Alpha Granule:

- thromboglobulin

- P-selectin

- PDGF

- PF4

- platelet fibrinogen

- thrombospondin

- VWF

3

After vWF attaches to endothelium and platelets, platelets release their granules and change shape with expose their fibrinogen receptors. What receptor binds fibrinogen? What drugs inhibit this receptor?

Glycoprotein IIb/IIIa

GPIIbIIIa inhibitors: Abciximab-Reopro, Integrilin,

Aggrastat

4

Where is vWF made (two sites)?

Endothelial cells (Weibel-Palade bodies) and megakaryocytes (alpha granules)

5

Coagulation cascade is divided into intrinsic and extrinsic pathways based on in vitro methods. What activates these pathways?

•Intrinsic path activated by blood in contact with negative charged glass

•Extrinsic path activated by tissue factor (subendothelium)

6

What are the steps of fibrinolysis (breaking down clot)?

Tissue plasminogen activator (TPA) cleaves plasminogen to plasmin

Plasmin cleaves fibrin into fibrin split products

7

What are the there inhibitors of fibrinolysis?

1. Alpha two antiplasmin inhibits plasmin

2. PAI inhibits plasminogen

3. TAFI (thrombin activatable fibrinolysis inhibitor)

inhibits binding of plasminogen and TPA to fibrin

8

How does protein C function?

Thrombomodulin binds to thrombin to activate protein C; with its carrier, protein S, activated protein C inhibits FV and FVIII

9

How does antithrombin function?

Liver-produced AT binds to heparin and inhibits conversion of II to IIa; also inhibits Xa action

10

Technically, how does the PTT test work?

Method

– Take negatively charged surface phospholipid (partial thromboplastin)

– Add PPP + calcium chloride

– Measure the time to clot

Normally < 40 seconds

Measures intrinsic & common pathway

Measures all factors except 7 and 13

11

Technically, how does the PT test work?

Method

– Take tissue factor and phospholipids

– Add citrated patient’s platelet-poor plasma (PPP) & calcium chloride

– Measure the time to clot

Normally < 15 seconds

• Measures the extrinsic and common pathways

12

Technically, how does the thrombin time work?

Method

– Take exogenous thrombin

– Add PPP

– Measure time to clot

Measures common pathway

Measures conversion of fibrinogen to fibrin

• Doesn’t need Ca or phospholipid

• increased paraprotein, amyloid, heparin, dysfibrinogenemia

13

Technically, how does the reptilase time work?

Method

– Take Bothrops atrox venom

– Add PPP

– Measure time to clot

increased reptilase time in dysfibrinogenemia

• If patient is on heparin, they will have an increased TT but nl reptilase time

• Reptilase measures conversion of fibrinogen to fibrin, but is

insensitive to heparin

• heparinase + protamine will correct TT that is increased in a patient on heparin

14

Which factor inhibitor will correct with an immediate mixing study but then prolongs after 1-2 hours (time dependent prolongation)?

Factor VIII inhibitor

15

What happens in mixing studies with:

1) dysfibrinogenemia

2) hypofibrinogenemia

1) Partially corrects

2) Completely corrects

16

What disorder is characterized by a defect in GPIb/V/IX (CD42), shows LARGE platelets with pseudonucleolus, has impaired ristocetin aggregation?

Bernard Soulier

17

What does Bernard Soulier show on flow cytometry?

Decreased CD42a, CD42b and CD42d

(which corresponds to GPIb, V, and IX)

18

What disorder is characterized by a platelet aggregation problem because platelets can't bind fibrinogen and this is from abnormal GP IIb-IIIa receptor?

Glanzmann thrombasthenia

19

What platelet disorder shows impaired ristocetin aggregation on PFA?

Bernard Soulier

20

What platelet disorder shows impaired aggregation with ADP, collagen and epinephrine but NORMAL ristocetin?

Glanzman thrombasthenia

21

What are the flow cytometry findings in Glanzmann thrombasthenia?

Decreased CD41 and CD61

(corresponds to GPIIb and GPIIIa respectively)

22

What is the main differential with Glanzmann thrombasthenia and how do you tell them apart?

Glanzmann and Afibrinogenemia

*Glanzmann's has normal PT and PTT

Afibrinoginemia has increased PT and PTT

23

What disorder is has giant platelets AND WBC inclusion, is autosomal dominant mutation in myosin heavy chain 9 gene, has thrombocytopenia but very little bleeding and normal PMN function?

May Hegglin Anomaly

24

What is the mutation in May Hegglin anomaly?

Myosin heavy chain 9 gene

25

HIGH YIELD!

What disorders can cause giant platelets?

• ITP, May Hegglin, gray platelet syndrome, Bernard Soulier, Montreal plt syndrome, DiGeorge syndrome

• Mediterranean macrothromocytosis

• Sebastian, Fechner, Epstein, and Alport syndromes

26

What platelet disorder is characterized by decreased platelet aggregation due to deficiencies in either dense granules/alpha granules or both?

Storage Pool Deficiency

normal morphology, no granules on EM

27

This platelet aggregation suggests what disorder?

Storage Pool Deficiency

NO 2nd wave wtih ADP and Epinephrine

DECREASED collagen and AA

NORMAL ristocetin

INCREASED ATP:ADP ratio

28

What disorder is characterized by no alpha granules, large gray platelets with no granules, results from cardiopulmonary bypass and platelet aggregation studies are blunted with everything except ADP and epinephrine?

Gray Platelet syndrome

29

What is the dysfunction in Quebec platelet disorder?

No alpha granules (similar to gray platelet syndrome)

30

What disorder is X linked, NO DELTA GRANULES on EM, platlets are small and granulated and is characterized by thrombocytopenia, infection, eczema and increased risk of malignancy?

Wiscott Aldrich syndrome

(Chediak Higashi and Hermansky Pudlak also no delta granules)