3. Blood (2) Flashcards
Haemostasis:
prevention of blood loss/stopping blood
If a vessel is severed, haemostasis is achieved by:
- Rupture of vessel —-> wall of vessel contracts, sticks
together - Contraction results from: (3)
- nervous reflexes initiated by pain
- local smooth muscle spasm (main factor)
- local humoral factors from traumatized tissues and blood platelets (Thromboxane A2)
- Smaller vessels: platelets mainly responsible for
vasoconstriction by releasing _______ _____ and
forming a “plug” - Spasm lasts several hours —-> time to form platelet plug and _____ clot.
Thromboxane
fibrin
What do they contain? (6)
What forms part of the platelet membrane? (3)
Dead platelets are removed by macrophages, particularly in the ______.
spleen
What is the process of the Formation of the platelet plug?
Platelets are also activated by: (4)
- thromboxane A2
- ADP
- serotonin
- thrombin
What are the features of activated platelets? (6)
What is on the surface of activated platelets? (2)
What are the platelet-limiting factors and anti-platelet
pharmaceuticals?
What are the multiple injuries of micro-vessels?
What is blood coagulation?
Blood coagulation = Secondary Haemostasis
- Coagulation = transformation of blood from a liquid to a semi-solid, gel state = clot
What is blood coagulation initiated by? (3)
- extravascular cells
- platelets
- damaged vessel walls
What is the ultimate effect of blood coagulation?
conversion of fibrinogen (soluble plasma
protein) to fibrin (insoluble fibres) = clot
Fibrin clot adheres to the damaged vessel
surface and platelet plug, traps blood cells,
fills the breach and blocks the vessel (~20
minutes).
What are the clotting factors?
All clotting factors, except tissue factor, are produced by the _____ and are present in the blood as inactive precursors (______)
liver
(zymogens)
When activated, factors IIa (thrombin), VIIa, IXa, Xa, XIa and XIIa are:
proteolytic enzymes that activate other clotting
factors, by cutting the proteins
Four factors, II, VII, IX and X, can only be produced if
______ ____ is available in the liver.
Vitamin K
- Factor XIIIa is also an enzyme, but it _____-_____ fibrin.
cross-links
What is fibrinogen?
Fibrinogen (FI) is not an enzyme or a co-factor. When the
fibrinogen protein is cut by thrombin (FIIa) it becomes
insoluble and forms fibres, called fibrin, which is the clot.
Five clotting factors VIIa, IXa, Xa, XIa and XIIIa
require _____ as a cofactor. (Blocking ____ prevents
coagulation in blood collection tubes.)
Ca2+
Two protease clotting factors, IXa and Xa require
platelet _________ for full activity.
Phospholipid
- Three protease clotting factors VIIa, Xa and IXa require
clotting “________” proteins.
“co-factor”
The cofactor proteins are, respectively, _____ ____ (TF,
FIII —-> TF/FVIIa), FVa (FVa/FXa) and FVIIIa
(FVIIIa/FIXa).
tissue factor
Clotting proteins are inactive in plasma to avoid ______________ clots and tissue factor is absent.
Spontaneous
What is the general coagulation sequence?
- 3 different coagulation pathways form fibrin, 1 physiological, 2 “biochemical”:
What is the process of cell-based coagulation? (3)
Fibrin Formation and Crosslinking: (4)
Once the clot is formed: (2)
Platelets secrete growth factors
- Fibroblast cells grow around and into the clot
- ______ tissue forms (1-2 weeks)
- Fibroblasts become _______ cells
- Clot is removed (_______)
Clot Retraction and Fibroblast Invasion
Scar
endothelial
fibrinolysis
Fibrinolysis and Dissolution of the Clot:
Vessel injury —> blood oozes out of the vessel. To stop this:
Biochemical (laboratory) measurement of clotting:
Primary haemostasis:
Secondary hemostasis: (3)
—> Bleeding time
Extrinsic pathway —-> Prothrombin Time (PT)
Intrinsic pathway —> Partial Thromboplastin Time (PTT)
also —> Whole blood clotting time
Bleeding Time Test Measures Platelet Function:
Prothrombin Time (PT) test – Extrinsic Pathway, what must be added to the blood?
Explain the Prothrombin Time (PT) test – Extrinsic Pathway?
- Blood is collected into citrate or EDTA tube (to chelate Ca2+). Removal of Ca2+ prevents coagulation in blood collection tube.
- Blood is _______ to separate the plasma.
- Plasma is mixed with Ca2+, tissue factor and phospholipid.
- Time to make a clot is measured —-> usual range = _________
- Tests function of factors VII, X, V, II & fibrinogen = _____ pathway.
- ____ is often expressed as INR (international normalized ratio) or prothrombin ratio.
- INR = (Patient’s PT/Normal PT)
Normal INR = _____
Biochemical ________ Pathways
centrifuged
12-15s
extrinsic pathway
0.8-1.2
Coagulation
What is the Partial Thromboplastin Time (PTT) test
– Intrinsic Pathway?
Factor XII is a plasma
protein that activates (cuts)
itself after binding to
negatively-charged surfaces
and molecules, including
* in vitro: glass, silica, kaolin etc.
* in vivo: collagen, platelets, denatured proteins, nucleic acids, microbes
FXIIa activates FXI and also
stimulates inflammation.
What is the full intrinsic coagulation pathway?
- Blood is collected into _______ or EDTA tube (to chelate Ca2+) and centrifuged.
- Plasma is mixed with phospholipid,
Ca2+ and a factor _____ activator
(kaolin, silica…) - Time to form a clot is measured -
usual range is less than ____ seconds. - Tests function of factors XII, XI, IX,
VIII, X, V, II = intrinsic pathway - These factors can also be activated
by _______
citrate
XII
39
inflammation
What is a whole blood clotting time test? (4)
What does the extrinsic and intrinsic pathway start with?
What are the Mechanisms of Anticoagulation?
- Clots should not form in healthy/unbroken
blood vessels.
* 90% of thrombin is immobilised in the fibrin clot. - Endothelial cells inhibit coagulation by
* Their smooth endothelial surface and glycocalix layer,
which repel platelets and clotting factors
* Stimulating vasodilation (prostacyclin and NO)
* Stimulating fibrinolysis (secretes tPA)
* Producing molecules that inhibit clotting factors,
especially thrombin
* Producing molecules that break down clotting factors
How does Thrombomodulin produce anti-coagulation?
How does Antithrombin & heparin produce anti-coagulation?
How does Tissue Factor Pathway
Inhibitor (TFPI) produce anti-coagulation?
What are the therapeutic anticoagulants? (5)
Coagulation disorders: (2)
Hypercoagulability
Hypocoagulability
Hypercoagulability (risk of thrombosis)
* 3 main causes:
- Haemodynamics
- Vessel injury
- Excess pro-coagulants vs anticoagulants
What are the Haemodynamics of Hypercoagulability? (3)
What are the vessel injuries associated with Hypercoagulability?
Hypercoagulability - Excess Pro-coagulants vs
Anticoagulants: (4)
How does Hypocoagulability (bleeding risk) affect platelet cells?
How does Hypocoagulability affect the Extrinsic Pathway?
Vitamin K deficiency has a major disruptive effect on the extrinsic pathway because of its
effect on factor VII, but also disrupts the intrinsic pathway to a lesser extent because it
decreases production of factor IX, in addition to decreasing ___ and ________.
FX
thrombin
How does Hypocoagulability affect the Intrinsic pathway? (2)
