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IHO Week 6 AJL > General Principles of Hemostasis- Krafts > Flashcards

General Principles of Hemostasis- Krafts Flashcards

1
Q

What are the three steps in clotting?

A

(1) Blood vessel constricts
- Blood loss decreases
- Platelets and factors meet

(2) Platelets form a plug
- Proteins are exposed
- Platelets adhere
- Granules release contents
- Platelets aggregate
- Phospholipids are exposed

(3) Fibrin seals up the plug
- Tissue factor is exposed
- Cascade begins
- Cascade makes fibrin
- Fibrin solidifies plug

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2
Q

What are the two mechanisms of anti-clotting?

A

(1) Cascade inhibition
- TFPI
- ATIII
- Proteins C, S

(2) Clot lysis
- t-PA
- Plasmin

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3
Q

What are the platelet membrane molecules we need to memorize?

A

Phospholipids (activate coag factors)
GP Ia (binds collagen)
GP Ib (binds vWF)
GP IIb-IIa (binds fibrinogen)

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4
Q

What is the end goals of the coagulation cascade?

A

Make fibrin!!!

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5
Q

Why are the two arms of the cascade named intrinsic and extrinsic?

A

Intrinsic- everything you need for the cascade is in the blood

Extrinsic- Need extrinsic factor for cascade to go

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6
Q

Where does tissue factor (TF) come from?

A
  • “Hidden” cells exposed during injury
  • Microparticles floating in blood
  • Endothelial cells and monocytes (during inflammation)
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7
Q

What does thrombin do?

A

Thrombin converts:
VIII –> VIIIa (Intrinsic)
VII –> VIIa (Extrinsic)
V –> Va (Intrinsic)

These are cofactors in the cascade

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8
Q

What happens in the SEXtrinsic pathway?

A

Simple pathway….

  • Exposed TF complexes with VIIa (which was converted from thrombin from VII)
  • TF/VIIa complex converts X –> Xa

COMMON PATHWAY
-Xa converts prothrombin to thrombin

-Thrombin converts fibrinogen to fibrin –> CLOT!!!

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9
Q

What happens after a little bit of thrombin is produced via the Extrinsic pathway?

A

Xa has a negative feedback on the TF/VIIa complex essentially shutting down the extrinsic pathway……

But, you have some thrombin there to start the intrinsic pathway

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10
Q

What are the factors we need to remember on the Extrinsic side?

A

Exposed TF
TF/VIIa complex

TF, 7

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11
Q

Explain the SINtrinsic pathway…..

A
  • Thrombin converts XI to XIa
  • XIa converts IX –> IXa
  • IXa complexes with VIIIa (thrombin converts VIII to VIIIa)
  • IXa/VIIa complex converts X –> Xa
  • V is converted to Va by thrombin
  • Va complexes with Xa

COMMON PATHWAY
-Xa/Va converts prothrombin to thrombin

-Thrombin converts fibrinogen to fibrin –> CLOT!!!

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12
Q

What are the factors/cofactors we need to remember for the SINtrinsic pathway?

A

XI to XIa
VII to VIIa (cofactor)
V to Va (cofactor)

11, 9, 10, 5

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13
Q

What are the little chunks of broken up clot called?

A

Fibrin Degradation Products (FDP)

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14
Q

What converts clots to FDP’s?

A

Plasmin

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15
Q

How is plasmin formed?

A

Plasminogen is converted to plasmin using t-PA

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16
Q

What does Protein C do?

A

Blocks Va and VIIIa cofactors…..less clotting

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17
Q

What does ATIII do?

A

Blocks XIa, IXa, Xa, Thrombin, and VIIa….less clotting

18
Q

What does TFPI do?

A

Tissue Factor Pathway Inhibitor

Blocks TF……less clotting

19
Q

What are the two important platelet lab tests?

A

Count: 150-450 x10^9

Morphology: size and granulation

20
Q

What is the dark center part of the platelet called? Outer light layer?

A

Granulomere

Hyalomere

21
Q

What is the Template Bleeding Time (Bleeding Time)?

A

This evaluates patients response to vascular injury….this is the one you use a blood pressure cuff and slice the patient and time how long it takes them to clot…..lots of factors that effect this test.

22
Q

What is an alternative to the Bleeding Time test? How does it work? Are there any advantages of this test?

A

Closure time:
Machine measures how quickly platelets occlude small holes in a membrane “in vitro” bleeding time

Better at detecting aspirin related bleeding and von Willenbrand disease

23
Q

How and why do you do a platelet aggregation test?

A

How: add aggregating agents to patients sample and see if it aggregates, measure the decrease in sample turbidity…..always repeat an abnormal test

Why: To find platelet function abnormalities

24
Q

How do coagulation tests work?

A

Draw blood into citrate tube
Spin tube, decant plasma
Add reagents to plasma
Watch for formation of fibrin

This test is either normal or prolonged

25
Q

What pathway is being tested with Prothrombin Time?

A

Extrinsic Pathway

26
Q

How does the PT test work? What factor is it basically testing?

A

You add thromboplastin to a patients plasma, thromboplastin acts like TF which stimulates the extrinsic pathway to go

Factor VII

27
Q

How is PT essentially testing Factor VII?

A

Factor VII is the most dependent on K so when you throw Coumadin in the mix you run out of Factor VII which prolongs PT

28
Q

Fun facts about FII?

A
  • Made by liver
  • Needs K
  • Dec. by Coumadin
  • Short half-life
29
Q

How do you increase PT?

A
  • Dec. VII, X, V, II, I
  • Coumadin
  • Heparin
  • DIC
30
Q

When should you order a PT?

A

Never!!! Order an INR which is just a corrected PT

31
Q

When should you order an INR?

A
  • To assess liver function
  • To monitor Coumadin therapy
  • To diagnose DIC
  • To assess pre-op status
32
Q

How do you do a Partial Thromboplastin Time? Which arm is this testing?

A

Take the patient’s plasma and add back in phospholipid

Measures the intrinsic pathway

33
Q

When should you order a PTT?

A
  • To investigate a history of abnormal bleeding
  • To monitor heparin therapy
  • To diagnose DIC
  • To diagnose an antiphospholipid antibody
  • To assess pre-op status
34
Q

What is a Thrombin Time? What does it assess?

A

Patient’s plasma + thrombin

Assesses conversion of fibrinogen to fibrin (bypasses intrinsic and extrinsic pathways)

35
Q

What causes PTT increase?

A
  • Hemophilia A (VIII)
  • Hemophilia B (IX)
  • DIC
  • Heparin
  • Inhibitors
36
Q

How do you get an increased Thrombin Time?

A
  • Decreased fibrinogen

- Increased Fibrin Degredation Products (FDP)

37
Q

When should you order a Thrombin Time?

A

When PTT is prolonged…..do this to rule out fibrinogen problem….this is really rare

38
Q

What is a PTT Mixing study? When do you do it?

A
  • Take pooled plasma + patient plasma + phospholipid….if PTT corects there’s something missing, if it doesn’t correct there’s an inhibitor.
  • Do this test when: PTT is prolonged but TT is normal
39
Q

What does Fibrin Degredation Product Assay measure? Why do you do the test?

A 
Measures FDPs (including D-dimers) 
VERY SENSITIVE

Use it to to RULE OUT a clot….FDPs increase in thrombi and normal minor clotting

40
Q

What causes a decrease in fibrinogen?

A

DIC

Massive bleeds

IHO Week 6 AJL (3 decks)

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