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S3B5 Pathology > Coagulation I > Flashcards

Coagulation I Flashcards

1
Q

What is reflex vasoconstriction?

A

occurs immediately after an injury to restrict blood flow to the injured area

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2
Q

What initiates reflex vasoconstriction? Augmented?

A
  • Initiated: reflex neurogenic mechanisms
  • Augmented: transient local secretion of endothelin
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3
Q

What are the 3 overall steps to primary hemostasis?

A
  1. Adhesion
  2. Activation
  3. Platelet aggregation
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4
Q

What happens during the adhesion stage of primary hemostasis?

A

exposure subendothelial collagen & vWF

vWF binds to both collagen & platelet receptor GPIb/IX/V complex

this activates the platelets & initiates a signaling cascade

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5
Q

What are the two components to the activation stage of primary hemostasis?

A
  1. Platelets undergo shape change (increase SA)
    1. smooth disks to spiky & conformational change surface GPIIb/IIIa → increases affinity for fibrinogen & PL on membrane
    2. PL serve to assemble coagulation factor complexes
  2. Release of platelet granule contents
    1. recruit additional platelets & helps to activate multiple coagulation factors
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6
Q

Platelet activation is triggered by what substances?

A

thrombin (through activation PAR)

ADP also recruits platelets

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7
Q

Activated platelets produce what potent inducer of platelet aggregation?

A

thromboxane A2 (TxA2)

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8
Q

Describe the process of platelet aggregation

A

When GpIIb/IIIa binds to fibrinogen, this forms bridges between adjacent platelets, leading to aggregation

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9
Q

Is platelet aggregation reversible?

A

the initial round is reversible

when thrombin stabilizes the platelet plug, this leads to irreversible platelet contraction

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10
Q

How do ADP & thromboxane A2 help platelet aggregation?

A

binding of platelet GpIIb/IIIa receptor to fibrinogen

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11
Q

What process is shown in the provided image?

A

platelet activation

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12
Q

How is secondary hemostasis initiated?

A

same time platelets are being activated, local activation of coagulation cascade is initiated by exposure of tissue factor (TF)

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13
Q

How does TF initiate coagulation cascade? This is what pathway?

A

extrinsic pathway

  • TF binds to circulating VII → VIIa
  • VIIa activates IX → IXa & X → Xa
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14
Q

What molecules initiates the intrinsic pathway? When?

A
  • circulating factor XII autoactivates when exposed to collagen/activated platelets
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15
Q

What is the result of the intrinsic & extrinsic pathways?

A

activation of series of proteolytic enzymes → generation thrombin & soluble fibrinogen → insoluble fibrinogen → fibrin polymerizes & cements platelets into hemostatic plug → plug is crosslinked by factor XIII

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16
Q

What is the most important coagulation factor?

A

thrombin

many enzymatic controls of hemostasis & link clotting to inflammation and repair

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17
Q

What are thrombin’s 4 most important functions?

A
  1. conversion fibrinogen → cross-linked fibrin = insoluble clot
    1. activates XI, V, & VII → amplify coagulation cascade
    2. activate XIII → cross-links fibrin
  2. activation platelets (via activation PARS)
  3. Pro-inflammatory effects
  4. Anticoagulant effect
    1. in normal endothelium changes from pro-coagulant to anticoagulant
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18
Q

Why is it important that thrombin acts as an anticoagulant in normal endothelium?

A

prevents clotting form spreading beyond the site of injury

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19
Q

What are the 4 major counter-regulatory mechanisms that limit the hemostatic process to the site of injury?

A
  1. Dilution of factors by blood flowing past the injury (& washed by liver)
  2. Requirement for negatively charged phospholipids for activation of many factors
  3. activation fibrinolytic system - via t-PA (most active when bound to fibrin)
  4. free palsmin in blood is rapidly inhibited by alpha2-antiplasmin inhibitor to limit fibrinolysis
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20
Q

What is the function of t-PA?

A

t-PA converts inactive plasminogen to active plasmin

plasmin breaks down fibrin & fibrinogen

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21
Q

What are the 3 groups of anticoagulant properties of normal intact vascular endothelium?

A
  1. Platelet inhibitory effects
  2. Anticoagulant effects
  3. Fibrinolytic effects
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22
Q

What platelet inhibitory effects are exhibited by normal intact vascular endothelium?

A
  • shields platelets from vWF & collagen
  • prostacyclin (PGI2), nitric oxide (NO), adenosine diphosphatase (degrades ADP) inhibit platelet adhesion & aggregation
  • endothelial cells bind & change activity of thrombin from procoagulant to anticoagulant
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23
Q

What anticoagulant effects are exhibited by normal intact vascular endothelium?

A
  • thrombomodulin & protein C receptor bind thrombin & protein C in a complex - thrombin can no longer activate coagulation factors & platelets
    • thrombin cleaves & activates protein C
  • Heparin-like molecules bind & activate antithrombin
  • Tissue factor pathway inhibitor (TFPI) most potent inhibitor of factor VIIa-tissue factor complex
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24
Q

What is antithrombin? It is enhanced by what molecules?

A

protein that inhibits factors IIa, Xa, VIIa, IXa, Xia, kallikren, and XIIa

enhanced by heparin or heparin-like molecules → give antithrombin its anticoagulant properties

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25
Q

What fibrinolytic effects effects are exhibited by normal intact vascular endothelium?

A

synthesize t-PA

key component fibrinolytic system

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26
Q

What is the main initiator of the clotting cascade in the body?

A

Tissue factor - amplified by feedback loops involving thrombin

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27
Q

Clotting in vitro is initiated by what substances?

A

adding phospholipids, calcium & either negatively-charged substance (intrinsic pathway) or source of tissue factor (extrinsic pathway)

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28
Q

Hemostasis testing should occur at what ratio of what substances?

A

citrulated plasma (blue top)

9:1 ratio blood:antcoagulant

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29
Q

How is a PT acquired?

A

tissue thromboplastin & calcium added to citrulated plasma

time to form a clot in tube recorded in seconds

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30
Q

PT asses what factors?

A

integrity of extrinsic & common pathway

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31
Q

PT is useful for what type of monitoring/screening?

A

monitoring warfarin-type anticoagulants

screening for vitamin K deficiency

32
Q

A prolonged PT can be due to deficiencies in what factors?

A
  • fibrinogen (<100mg/dl)
  • prothrombin (II)
  • VII
  • X
  • V
33
Q

Warfarin causes a decrease in what factors?

A
  • II
  • VII
  • IX
  • X
34
Q

What is the most useful test to monitor Warfarin therapy?

A

PT

35
Q

Other than factor deficiencies, what are the other reasons for a prolonged PT?

A

FDP (fibrin degradation products)

D-dimer (plasmin breakdown product)

act as circulating anti-thrombins

36
Q

Can you use PT to monitor heparin?

A

yes, but less sensitive than APTT or TT

37
Q

PT is not affected by deficiencies in what factors?

A
  • XII
  • XI
  • IX
  • VIII
  • HMWK
  • prekallikrein
38
Q

What is the INR?

A

calculated value using the measured PT result, the ISI (international sensitivity index) of the reagent & the MRI (mean reference interval)

developed to better standardize monitoring of warfarin therapy - consistency from one lab to another

39
Q

What is the purpose of the lines on the test tubes used to collect blood to screen for hemostasis?

A

max fill & min fill

overfill - too much blood per anticoagulant

under-fill - too much anticoagulant per blood

want ration 9:1 blood:anticoagulant

40
Q

What type of blood is used to screen for hemostasis?

A

platelet poor plasma

(has been spun down)

want to get normal platelets out of there so they do not confound the test

41
Q

Even if you fill the tube to the correct level for 9:1 blood:anticoagulant, what other variable can alter test results?

A

significant increases & decreases in Hct

42
Q

Why is calcium added to the sample when performing PT?

A

sodium citrate binds calcium in blood as its mechanism as an anticoagulant

adding a bunch of calcium overcomes this anticoagulant & allows the clotting process to begin

43
Q

How is an Activated Partial Thromboplastin Time (APTT) acquired?

A

an activator or “contact” factors is added with phospholipids (“partial thromboplastin”) to citrated plasma & incubated for specified time at 37 degrees C

calcium is added & the time to formation of clot is measured in seconds

44
Q

APTT assess what factors?

A

integrity of intrinsic & common pathway

45
Q

APTT is prolonged by deficiencies in what factors?

A
  • XII
  • XI
  • IX
  • X
  • VIII
  • V
  • thrombin (II)
  • fibrinogen (I)
  • prekallikrein & high molecular weight prekallikrein
46
Q

What is the most common cause of prolonged APTT in hospitalized patients?

A

heparin (antithrombin)

47
Q

What is the new standard for assessing heparin therapy?

A

heparin assay

anti-Xa or Xa inhibition test

48
Q

APTT is prolonged by what type of inhibitors?

A
  • lupus anticoagulant
  • fibrin degradation products (FDP)
  • specific factor inhibitors
  • direct thrombin inhibitors
49
Q

How can improper storage lead to increased APTT time?

A

factor VIII is labile & will deteriorate if has been sitting at room temp >4 hr

50
Q

APTT is not affected by deficiencies in what factors?

A

VII

51
Q

Shortened APTT or PT may be due to what probable causes?

A
  • traumatic blood draw & subsequent activation coagulation cascade prior to testing
  • may indicated elevated risk of thrombosis due to elevated levels one or more factor
52
Q

How is a Thrombin Time (TT) acquired?

A

thrombin is added to plasma & the time to form a clot is measured in seconds

53
Q

TT asses what factors?

A

the time it takes thrombin to convert fibrinogen to fibrin

54
Q

What is the most sensitive test to use for detection of heparin?

Why is it not used to monitor therapy?

A

TT

too sensitive - if heparin is present, TT will often be >60s

55
Q

Other than heparin, TT may be prolonged by what situations?

A
  • afibrinogenemia
  • hypofibrinogenemia
  • dysfibrinogenemia
  • inhibitors
    • paraproteins (inhibit polymerization)
    • fibrin degradation products
  • direct thrombin inhibitors
    • argatroban
    • lepirudin
56
Q

What is the clotting factor in the highest concentration in plasma?

A

fibrinogen

(largely absent in serum)

57
Q

What are the two types of fibrinogen assays?

A

functional or antigenic

58
Q

What are the possible causes of decreased fibrinogen levels?

A
  • afibrinogenemia or hypofibrinogenemia
    • dysfibrinogenemia if functional assay is performed
  • heparin
59
Q

What are the possible causes of increased fibrinogen levels?

A

inflammation or malignancy

60
Q

What is the minimal fibrinogen level for hemostasis?

A

75-100 mg/dL

61
Q

How are fibrin degradation products formed?

A

plasmin-mediated degradation of fibrin & fibrinogen

62
Q

Fibrin degradation products may be elevated in what situations?

A
  • DIC, thrombosis, significant bleeding
  • mucin-secreting adenocarcinomas
  • cirrhosis
    • diseased clearance by liver
63
Q

What is a D-dimer? How is it formed?

A

subtype FDP

formed from plasmin-mediated degradation of mostly cross-linked fibrin

64
Q

D-Dimer may be elevated in what situations?

A
  • DIC, thrombosis or significant bleeding
  • mucin-secreting adenocarcinomas
  • cirrhosis
    • decreased clearance FDP
65
Q

What is bleeding time used to assess?

A

screen for capillary integrity & platelet function

not great- poor predictor bleeding risk

USELESS as pre-op screen bleeding risk

66
Q

How is a bleeding time acquired?

A

shallow cut on arm of patient at rest

measure time until bleeding stops

67
Q

Bleeding time can be affected by what variables?

A
  • age
  • hydration
  • temperature of room
  • direction of cut
  • location on arm
  • etc
68
Q

When are mixing studies used?

A

evaluation prolonged PT, APTT or both

differentiate factor deficiency from inhibitor as cause of prolongation

69
Q

How is a mixing study performed?

A

mix patient plasma 1:1 with normal pooled plasma to replace clotting factors to at least 50% normal

this is sufficient for normal hemostasis

70
Q

D-dimer is not specific, but a normal D-dimer effectively rules out what issue?

A

thrombosis

(PE/DVT)

71
Q

If the PT normalizes after the mixing study, what is likely the problem with the patient?

A

factor deficiency

I, II, V, VII, X

72
Q

If the PT corrects after the mixing study, but elongates again after incubation, what is likely the issue with your patient?

A

Factor V inhibitor

73
Q

If the APPT normalizes after the mixing study, what is likely the problem with the patient?

A

factor deficiency

VIII, IX, XI, XII

74
Q

If the APPT corrects after the mixing study, but elongates again after incubation, what is likely the issue with your patient?

A

Factor VIII inhibitor

75
Q

If the PT remains elongated after the mixing study, what is likely your patient’s issue?

A

inhibitor

(e.g. specific factor inhibitor)

76
Q

If the APPT remains elongated after the mixing study, what is likely your patient’s issue?

A

inhibitor - lupus anticoagulant

S3B5 Pathology (13 decks)

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