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

General Principles of Hemostasis - Krafts Flashcards

1
Q

How is hemostasis a balancing act?

A
  • Balance between:
    • Pro-clotting
      • plugs up holes in blood vessels
    • Anti-clotting
      • keeps clotting under control
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2
Q

What are the three (simplistic) steps of clotting?

A
  1. Vascular constriction
  2. Form platelet plug (primary hemostasis)
  3. Make fibrinogen (secondary hemostasis)
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3
Q

Why is vessel constriction important in clotting?

A
  • Blood loss decreases
  • Platelets and factors meet
    • help components come in contact with each other
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4
Q

What are the basic steps of platelets forming a plug?

A
  • Proteins are exposed in endothelium
    • collagen
  • Platelets adhesion to proteins
    • via collagen
  • Platelets change shape and release granules
    • attract more platelets
  • Platelets aggregate
  • Phospholipids are exposed
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5
Q

What is fibrin important for?

A
  • Fibrin seals up plug
    • Tissue factor is exposed
    • Cascade begins (fibrinogen → fibrin)
    • Cascade makes fibrin
    • Fibrin solidifies plug
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6
Q

How do you keep clotting from getting out of control?

A
  • Breakdown formed clot
    • fibrin chunks (remodeling)
    • t-PA
    • plasmin
  • Inhibit formation of clots
    • cascade inhibition
      • TFPI
      • ATIII
      • Proteins C, S
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7
Q

What are the four membrane glycoproteins that are important in platelet adhesion and aggregation in clot formation?

A
  • Phospholipids
    • activate coag factors
  • GP Ia
    • binds collagen
  • GP Ib
    • binds vWF
  • GP IIb-IIIa
    • binds fibrinogen
    • mediates interactions between platelets
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8
Q

What do each of the roman numerals stand for in the coagulation cascade?

A
  • Proenzymes that become activated
    • activate more enzymes
  • Activated enzymes have “a”
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9
Q

What are the three parts of the Coagulation Cascade? Why are they named accordingly?

A
  • Intrinsic
    • components are sitting in the blood
  • Extrinsic
    • have to add tissue factor
  • Final Common Pathway
    • two arms meet
    • form one pathway
    • “meet me at 10”
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10
Q

What is the whole point of the Coagulation Cascade?

A

MAKE FIBRIN!

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11
Q

What molecule activates fibrinogen → fibrin?

A

Thrombin

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12
Q

What molecule activates prothrombin → thrombin?

A

Xa

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13
Q

How does the coagulation cascade start?

A

Tissue Factor becomes exposed.

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14
Q

Where does tissue factor come from?

A
  • “Hidden” cells exposed during injury
  • Microparticles floating around in blood
  • Endothelial cells and monocytes
    • during inflammation
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15
Q

What does tissue factor bind to in the coagulation cascade?

A

VIIa

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16
Q

What molecule activates X → Xa?

A

TF + VIIa complex

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17
Q

What happens immediately after X → Xa in the extrinsic pathway?

A
  • Xa inhibits the TF-VIIa complex
  • Shuts down extrinsic pathway after it “kickstarts” Xa
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18
Q

What most likely converts the co-factors VIII→VIIIa and V→Va?

A

Thrombin

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19
Q

How are clots broken down?

A
  • Plasmin breaks down clot into FDPs
    • fibrin degradation products
  • Plasminogen → Plasmin
    • via t-PA
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20
Q

What are the three ways you can stop the coagulation cascade?

A
  • Protein C (w/ Protein S)
    • cleaves VIIIa
    • cleaves Va
  • Antithrombin III
    • affects factors on both sides (mostly intrinsic)
    • give co-factors “bear hug” and prevents them from working properly
  • TFPI
    • acts on TF+VIIa complex
21
Q

What are the two platelet lab tests?

A
  • Count
    • Done by particle counter
    • Normal = 150-450 x 10^9
  • Morphology
    • Size
    • Granulation
22
Q

What are the two zones of a normal platelet?

A
  • Granulomere (center)
  • Hyalomere (surrounding)
23
Q

What is the Template Bleeding Time test?

A
  • Inflate blood pressure cuff
  • Make incision
  • Measure time it takes to stop bleeding
24
Q

Why would one perform a Template Bleeding Time?

A
  • Evaluate platelet response to vascular injury
  • Some platelet disorders have a long bleeding time
  • Only test that looks at how platelets work inside the patient’s arm as they are stopping the blood flow
    • ***test does not measure coagulation
25
Q

What test is an alternative to the template bleeding time that uses a platelet function analyzer to measure how quickly platelets occlude small holes in a membrane?

A

Closure Time (CT)

(“in-vitro bleeding time)

26
Q

What is the Platelet Aggregation test?

A
  • Add aggregating agents to patient’s sample (plasma with platelets)
    • e.g. ADP
  • See if platelets aggregate
  • Measure decrease in sample turbidity
    • get clear solution
  • Helps find platelet function abnormalities
27
Q

What are the general steps in Coagulation Lab Tests?

A
  • Measure how well patient can make fibrin by:
    • draw blood into citrate tube
    • Spin tube, decant plasma
    • Add reagents to plasma
    • Watch for formation of fibrin
      • normal time of formation OR
      • prolonged time
28
Q

What is a Prothrombin Time (PT) test?

A
  • Plasma + thromboplastin
    • thromboplastin acts as Tissue Factor
    • measure how fast fibrin is formed
  • Measure extrinsic pathway
    • and final common pathway
29
Q

What is special about the Extrinsic pathway? What is unique about it?

A
  • Factor VII
    • made by liver
    • needs Vitamin K to work
    • decreased by Coumadin
    • shortest half-life
30
Q

What would make the PT increased?

A
  • decreased VII, X, V, II, I
  • Coumadin
    • affects vitamin K-dependent factors
  • Heparin
    • works with antithrombin III (potentiates it)
  • DIC
    • disseminated intravascular coagulation
    • use up all coag factors
31
Q

When should you order a PT?

A
  • Never!
  • Order INR instead.
32
Q

What is an INR?

A
  • Just a corrected PT
  • Stands for international normalized ratio
33
Q

When should you order an INR?

A
  • To assess liver function
  • To monitor Coumadin therapy
  • To diagnose DIC
  • To assess pre-op status
34
Q

What is a Partial Thromboplastin Time (PTT) test?

A
  • Plasma + phospholipid
    • phospholipid is part of thromboplastin molecule
  • Measures intrinsic pathway
  • APTT = same thing
    • activated partial thromboplastin time
    • don’t worry about differences
35
Q

What things would make the PTT increased (prolonged)?

A
  • Hemophilia A
    • missin VIII
  • Hemophilia B
    • missing IX
  • DIC
    • missing all the factors everywhere
  • Heparin
  • Inhibitors
    • antibodies that influence intrinsic pathway
36
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
37
Q

What is a Thrombin Time test?

A
  • Plasma + thrombin
  • Measures conversion of fibrinogen ⇒ fibrin
  • Bypasses intrinsic and extrinsic pathways
38
Q

What would increase TT?

A
  • decreased fibrinogen
  • increased FDPs
39
Q

When should you order a Thrombin Time test?

A
  • When the PTT is prolonged, and you want to rule out a fibrinogen problem
    • rare
40
Q

What is a PTT Mixing Study?

A
  • Pooled plasma + patient plasma + phospholipid
  • If PTT corects: something missing
    • something was added in the pooled plasma that pt was missing
  • If PTT doesn’t correct: inhibitor
    • antibody that messes up test
41
Q

When should you order a mixing study?

A
  • When PTT is prolonged, but TT is normal
  • If PTT corrects = factor deficiency
  • If PTT doesn’t correct = inhibitor present
42
Q

What is a Fibrin Degradation Product Assay?

A
  • Measures FDPs (fibrin degradation products)
    • including D-dimers
  • VERY sensitive
43
Q

What happens to fibrin in a clot? What perfoms this?

A
  • Cross-links to form sturdy clot
  • Done via XIII
44
Q

What does the D-dimer test measure?

A
  • Cross-linked fibrin broken down by plasmin
    • products = d-dimers
45
Q

When should you order an FDP assay?

A
  • To rule out a clot
  • Not to rule in a clot
  • SUPER SENSITIVE
46
Q

What causes increased FDPs?

A
  • Thrombi
  • Minor clotting
47
Q

What is a Fibrinogen Assay?

A
  • Measure fibrinogen
48
Q

What causes decreased fibrinogen?

A
  • DIC
  • Massive bleeding
49
Q

When should you order a fibrinogen level?

A
  • To diagnose DIC
  • **To follow patients with massive bleed

IHO Week 6 - WLB (8 decks)

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