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Fundamentals of P > Blood coagulation, Haemostasis, and its Investigation > Flashcards

Blood coagulation, Haemostasis, and its Investigation Flashcards

1
Q

Haemostasis - define

A

Protective process evolved in order to maintain a stable physiology

“An explosive reaction designed to curtail blood loss, restore vascular integrity and ultimately preserve life”

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2
Q

The Horseshoe Crab - define

A

Limulus Polyphemus

‘A primitive coagulation pathway can be initiated by endotoxin’

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3
Q

The Haemolymph contains what

A

The Haemolymph contains amebocytes:

Proteins of the coagulation system
Proteins & peptides of the immune system

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4
Q

Haemostasis - life preserving processes = describe

A

Life preserving processes designed to maintain blood flow
Respond to tissue injury
Curtail blood loss
Restore vascular integrity & promote healing
Limit infection

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5
Q

Haemostasis - 4 components

A 
Four Key Components
Endothelium
Coagulation
Platelets
Fibrinolysis
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6
Q

What makes a Blood Clot?

A

Fibrin mesh
Platelets
Red blood cells

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7
Q

Coagulation - decribe process briefly

A

Vessel damage
& Blood loss

Vascular spasm

Platelet Plug forms

Coagulation

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8
Q

Primary haemostasis - description

A

Primary haemostasis:
Vasoconstriction (immediate)
Platelet adhesion (within seconds)
Platelet aggregation and contraction (within minutes)

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9
Q

Secondary haemostasis - description

A

Secondary haemostasis:
Activation of coagulation factors (within seconds)
Formation of fibrin (within minutes)

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10
Q

Fibrinolysis - description

A

Fibrinolysis:
Activation of fibrinolysis (within minutes)
Lysis of the plug (within hours)

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11
Q

Clot strength in terms of stages

A

Initiation = slow rise ~ 0
Amplification = rapid increase
Stable clot = strongest
Lysis = steady decrease to 0

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12
Q

Characteristic of heamostasis at rest

A

Haemostasis at rest: triggers and cofactors separated

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13
Q

vWF function under shear forces

A

Under shear forces, self-association of plasma VWF occurs surface of platelets + endothelial cells = creating fibrillar structures that further facilitate platelet adhesion

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14
Q

Platelet aggregation function

A

Prevents excessive blood loss at site of injury

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15
Q

When does seconday haemostasis take place

A

This plug of activated platelets, localised to the site of injury, provides the phospholipid surface upon which Secondary Haemostasis takes place

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16
Q

When does primary haemostasis take place

A

Primary hemostasis = when platelets attach to damaged endothelium, adhesion allows the platelets to undergo a shape change = aggregation
Once adhered to each other a temporary platelet plug is created

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17
Q

Brief process of haemostatic plug formation

A

Vessel constriction
Formation of an unstable platelet plug
platelet adhesion
platelet aggregation
(above is primary haemostasis)
Stabilisation of the plug with fibrin blood coagulation (secondary)
Dissolution of clot and vessel repair fibrinolysis

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18
Q

Fibrin mesh function

A

Fibrin mesh binds and stabilises platelet plug and other cells

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19
Q

Fibrinogen (I) function

A

Forms clot (fibrin)

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20
Q

Prothrombin (II) function

A

Its active form (IIa) activates I, V, VII, XIII, protein C, platelets

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21
Q

Tissue factor (III) function

A

Co-factor of VIIa

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22
Q

V (proaccelerin, labile factor)

function

A

Co-factor of X with which it forms the prothrombinase complex

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23
Q

VI function

A

Unassigned - old name of Factor Va

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24
Q

VII (stable factor) function

A

Activates IX, X

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25
Q

VIII (antihaemophilic factor)

function

A

Co-factor of IX with which it forms the tenase complex

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26
Q

IX (Christmas factor)

function

A

Activates X: forms tenase complex with factor VIII

27
Q

X (Stuart-Prower factor)

function

A

Activates II: forms prothrombinase complex with factor V

28
Q

XI (plasma thromboplastin antecedent)

function

A

Activates XII, IX and prekallikrein

29
Q

XII (Hageman factor)

function

A

Activates prekallikrein and fibrinolysis

30
Q

XIII (fibrin-stabilizing factor)

function

A

Crosslinks fibrin

31
Q

von Willebrand factor

function

A

Binds to VIII, mediates platelet adhesion

32
Q

FVII deficiency effect

A

FVII deficiency causes bleeding

33
Q

FXII deficiency effect

A

FXII deficiency not associated with bleeding

34
Q

What does each action in waterfall hypothesis require

A

Each reaction requires:

Ca2+
Phospholipid
± Specific co-factors

35
Q

Describe clotting cascade

A

TF is outside the lumen
Formation of TF-FVIIa complex
Recruitment of FX and formation of thrombin

36
Q

Fibrinolysis (clot dissolution) function

A

Main function:

clot limiting mechanism
repair and healing mechanism

37
Q

Fibrinolysis (clot dissolution) - characteristic of the process

A

Series of tightly regulated enzymatic steps

- feedback potentiation & inhibition

38
Q

Fibrinolysis (clot dissolution) - key players

A

Main Key players:

Plasminogen

Tissue plasminogen
activator (t-PA) & urokinase (u-PA)

Plasminogen activator inhibitor -1 and -2

α2-plasmin inhibitor

39
Q

Formation of plasmin - describe

A

Plasminogen → plasmin
through tissue plasminogen
activator, tPA

40
Q

Formation of plasmin - effect

A

D dimers are generated when cross-linked fibrin is degraded.

FDP (Fibrin degradation products) are generated if non-cross linked fibrin or fibrinogen is broken down.

41
Q

Uses of tPA and streptokinase

A

tPA and a bacterial activator, streptokinase, are
used in therapeutic thrombolysis for myocardial
infarction (Clot busters)

42
Q

Describe haemostasis and thrombosis in relation to one another

A

Haemostasis and Thrombosis: a Balance
Normal haemostasis: a state of equilibrium

Fibrinolytic factors,
anticoagulant proteins

VS

Coagulation factors,
platelets

43
Q

Cuase of thrombosis

A

↑ Coagulation
factors,
platelets

and

↓ Fibrinolytic factors,
anticoagulant proteins

44
Q

Chronic venous insufficiency effects

A

Atrophic changes
Hyperpigmentation
Ulceration
Infection

45
Q

Cause of bleeding

A

↑ Fibrinolytic
factors,
Anticoagulant
proteins

and

↓ Coagulation factors,
Platelets

46
Q

Define ecchymosis

A

Easy bruising
(ecchymosis) = a discoloration of the skin resulting from bleeding underneath, typically caused by bruising

Virtually all bleeding disorders and often in normals

47
Q

Principles of clotting tests

A

Incubate plasma with reagents necessary for coagulation:
Phospholipid, co-factors
Trigger or activator
Calcium

Measure time taken to form fibrin clot

48
Q

Prothrombin time (PT) - define and describe characteristics

A

Prothrombin time (PT) is a blood test that measures how long it takes blood to clot

Sensitive to extrinsic pathway and to a lesser extent common pathway
TF driven

49
Q

APTT (Activated Partial Thromboplastin Time) - define and describe characteristics

A

The partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT or APTT) is a blood test that characterizes coagulation of the blood

Sensitive to intrinsic pathway and to a lesser extent common pathway
Contact activated

50
Q

TT (Thrombin Time) - define and describe characteristics

A

Thrombin time (TT), a blood test that measures the time it takes for a clot to form in the plasma of a blood sample containing anticoagulant, after an excess of thrombin has been added.

Sensitive to defects in conversion of fibrinogen to fibrin

51
Q

Overview of Coagulation Pathways

A

Activated partial thromboplastin time
(APTT) = 1. Surface activating agent (e.g. kaolin)
2. Phospholipid
3. Calcium

= Intrinsic pathway

PT = 1. Thromboplastin
Tissue factor
Phospholipid
2. Calcium

= Extrinsic pathway

both feed into

Thrombin time = thrombin

= common pathway

All combining to form

= fibrin clot

52
Q

Accuracy of haemostasis laboratory tests depends on what

A

Accuracy of haemostasis laboratory tests depends on the quality of the specimen submitted

53
Q

Effect of under filling the tube

A

Under filling the tube yields grossly inaccurate results.

54
Q

Problems with blue-top tube = pre-analytical error

A

Partial fill tubes

Vacuum leak and citrate evaporation

55
Q

Problems with phlebotomy = pre-analytical error

A

(using a needle to take blood from a vein)

Heparin contamination
Wrong label
Slow fill
Underfill
Vigorous shaking
Difficult venepuncture
56
Q

Laboratory errors = pre-analytical error

A

Delay in testing
Prolonged incubation at 37°C
Freeze/thaw deterioration

57
Q

Biological effects that are pre-analytical errors

A

Hct ≥55 or ≤15

Lipaemia, hyperbilirubinaemia, haemolysis

58
Q

Mixing studies - describe

A

Mix patient and normal plasma in equal volumes (50:50 mix)
Repeat abnormal coagulation test
Test normalises – factor deficiencies
Test remains abnormal – inhibitor (usually antibody)

59
Q

What tests do you do if you obtain an normal PT + abnormal APTT, include results

A

Repeat at 50:50 mix

If 50:50 abnormal:
Test for inhibitor activity:
Specific factors: VIII,IX, XI
Non-specific (anti-phospholipid Ab)

If 50:50 mix normal
Test for factor deficiency:
Isolated deficiency in intrinsic pathway (factors VIII, IX, XI)
Multiple factor deficiencies (rare)

60
Q

What tests do you do if you obtain an abnormal PT + normal APTT, include results

A

Repeat at 50:50 mix

If 50:50 abnormal:
Test for inhibitor activity:
Specific: Factor VII (rare)
Non-specific: Anti-phospholipid (rare)

If 50:50 mix normal:
Test for factor deficiency:
Isolated deficiency of factor VII (rare)
Multiple factor deficiencies (common) (Liver disease, vitamin K deficiency, warfarin, DIC)

61
Q

What tests do you do if you obtain an abnormal PT + abnormal APTT, include results

A

Repeat at 50:50 mix

If 50:50 abnormal:
Test for inhibitor activity:
Specific : Factors V, X, II, I (rare)
Non-specific: anti-phospholipid (common)

If 50:50 mix normal:
Test for factor deficiency:
Isolated deficiency in common pathway: Factors V, X, Prothrombin, Fibrinogen
Multiple factor deficiencies (common) (Liver disease, vitamin K deficiency, warfarin, DIC)

62
Q

What tests do you do if you obtain an abnormal PT + abnormal APTT, include results

A

Repeat a normal test

If abnormal:
Dysfibrinogenaemia
Abnormal fibrinolysis
(e.g. α2 anti-plasmin def)
Elevated FDPs
If normal:
Von Willebrand’s disease
Platelet disorder
FXIII deficiency
Non-coagulation defect (e.g. vascular disorder)
63
Q

D-dimer Testing - characteristics

A

A measure of the D-dimer, a fibrin degradation product

Found elevated in the situation of enhanced fibrinolysis (Thrombosis, DIC)

Not specific for thrombosis also elevated as an acute phase reactant

A Negative result is useful if clinical suspicion of VTE is low

Fundamentals of P (62 decks)

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