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General Physiology & Pathology > Haemostasis > Flashcards

Haemostasis Flashcards

1
Q

Haemostasis is the interaction of

A
  • platelets
  • coagulation factors
  • coagulation inhibitors
  • fribrinolytic processes
  • blood vessels/endothelium/cellular membranes (mononuclear cells)
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2
Q

What is primary haemostasis?

A

occurs immediately (seconds, minutes)

  • vasoconstriction - limits blood flow to the injury
  • platelet adhesion and aggregation - initial framework formation for fibrin
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3
Q

What is secondary haemostasis?

A

occurs minutes after injury

  • activation of coagulation factors - proteins in the blood
  • formation of fibirin mesh - covers the platelet plug
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4
Q

What is fibrinolysis?

A

occurs within minutes to hours of injury

  • activation of fibrinolyisis
  • lysis of clot - smoothes surface in the vessel to restore laminar flow
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5
Q

What is Virchow’s Triad?

A
  • explains the 3 contributing factors to abnormal clotting:
    • abnormalities in the vessel wall*
    • abnormalities in blood flow
    • abnormalities in blood composition

*we have no way of assessing vessel wall integrity; test number and function of platelets, integrity of clotting proteins instead

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6
Q

How do we test functionality of the clotting system?

A
  • cannot assess blood vessel walls
  • test number and function of platelets
  • test integrity of the clotting proteins
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7
Q

The coagulation system is part of which blood component?

A

plasma

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8
Q

What is the trigger that initiates the clotting system/coagulation cascade?

A

exposure of tissue factor to the blood, released when vessel walls are damaged

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9
Q

What is the key protein in controlling the coagulation system?

A

Thrombin - initiates the -ve or +ve feedback loops that turn it off and on, respectively

tf a very important anti-thrombotic agent

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10
Q

What are the 3 phases of coagulation?

A
  1. initiation
  2. amplification
  3. propagation
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11
Q

What happens in the initiation phase of coagulation?

A
  • hole in vessel wall triggers coagulation
    • tissue factor is exposed to blood
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12
Q

What happens in the amplification phase of coagulation?

A
  • activation of FXa triggers prothrombin–>thrombin
    • thrombin postiviely feedbacks on platelets
      • causes platelet activation
      • increases amount of thrombin (thrombin burst)
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13
Q

What happens in the propagation phase of coagulation?

A
  • thrombin burst facilitaties the formation of fibrin
  • fibrin forms the mesh, generating the stable clot that plugs the hole in the blood vessel wall
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14
Q

Thrombin

A
  • essential for fibrinogen –> fibrin
    • critical gor clot formation and reinforcement of the platelet plug
  • if insufficient? bleeding
  • if excessive? thrombosis
  • thrombin is the regulator of haemostasis
    • activates factor 13: cross-linking of fibrin
    • binding to thrombomodulin: inhibits system
    • activates platelets
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15
Q

How is thrombin inactivated?

A
  • binding to thrombomodulin-activated protein c (APC) system
    • downregulates ability to cleave fibrinogen–>fibrin
    • involves protein C and protein S*

**factors that inhibit clotting are given letters; factors that promote clotting are given Roman numerals**

  • irreversible inhibition by binding antithrombin (+ x1000 by Heparin)
  • binding to heparin co-factor II, dermatan sulphate, alpha-2 macroglobulin
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16
Q

What is the haemostatic test fof platelets?

A
  • number
  • function
  • appearance
17
Q

What are the haemostatic tests of the coagulation (and fibrinolytic) system?

A
  • to assess risk of bleeding or clotting, and to monitor anticoagulant drugs
  • global tests:
    • APTT (Activated Partial THromboplastin Time)
    • INR (International Normalized Ratio)
  • specific test:
    • Factor 8 deficiency (haemophilia A - Queen V)
  • genetic tests:
    • gene abnormality
      • mutation does not always mean the protein is non-functional
      • tf abnormality depends on phenotype
18
Q

What is the ACT haemostatic test?

A
  • activated clotting time
  • usually done in OR on cardiopulmonary bypass
19
Q

What is the APTT haemostatic test?

A
  • activated partial thromboplastin time
  • usually in conjunction with a PT/INR
  • pt plasma is arrested with citrate
  • heated, Ca, phospholipid, and TF reagent (pro-thombitic) added
  • measure time to clot
20
Q

What is the PT/INR ratio?

A
  • (patient prothrombin time/mean normal prothrombin time)^ISI
    • ISI = international sensitivity index, reflects sensitivity of reagent to reduction in Vit K dependent factors - therefore it only tells you about factor 7 OR if they are on warfarin which inhibits production of vitamin K
  • used to equate different international testing methods in deteriming prothrombin time
  • normal INR is ~1, on Warfarin ~1-3
21
Q

What are the haemostatic assays?

A
  • factor assays e.g. Factor 8 for haemophilia
  • VWF - von Willebrand factor, a blood glycoprotein related to bleeding disorder VW disease
  • collagen binding assays - functional assessment of vWF protein
  • measure fibrinogen (if abnormal, can’t clot)
22
Q

What is a functional clot based assay?

A
  • blood in test tube, look for clot formation
  • measure time to clot in seconds
  • not truly physiologic because not in vivo (no endothelial surface), cells heated
23
Q

What is a chromogenic assay (haemostatic test)?

A
  • plasma in test tube
  • chromogenic substance in tube produces light when clipped
  • measure light formation
  • may be more reproducible but not physiologically relevant
24
Q

What is an immunological assay (haemostatic test)?

A
  • quantify hoe much protein we have
  • doesn’t tell us about its functionality
    • type I defect is low amount and low function
    • type II defect is normal levels but low function
25
Q

What does an abnormal INR tell you?

A

There is a Factor 7 issue, or the patient is on Warfarin (inhibits production of Vit K)

i.e. Factor VII is vitamin K dependent

26
Q

What is imporant to consider about the APTT?

A

numbers are lab-specific

27
Q

APTT is mainly for monitoring

A

heparin therapy

28
Q

If you have an isolated prolonged APTT

A
  • deficiency of factor 12, 11, 9 (8, cofactor)
  • heparin therapy
  • lupus anticoagulant autoimmune phenomenon
    • Ab directed against the coagulation system prolonging teh APTT
29
Q

Warfarin

A
  • Vitamin K antagonist
  • inhibits production of Vit K dependent factors (2, 7, 9, 10)
30
Q

Heparin

A
  • binds to anti-thrombin
    • turns off factor 2 and 10

General Physiology & Pathology (4 decks)

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