Coagulation Flashcards
1
Q
Briefly describe Coagulation
A
- critical process
- designed to stem blood loss from injury: formation of thrombus
- complex interaction of multiple factors
2
Q
Define Haemostasis
A
the balance between coagulation & anticoagulation
3
Q
What is the purpose of the coagulation cascade ?
A
- conversion of fibrinogen to fibrin
- acheived by activation of a serine protease called thrombin
- strengthens platelet aggregation at wound site to help prevent bleeding
4
Q
What is fibrin ?
A
- insoluble protein that forms a mesh over a cut or lesion
5
Q
Describe coagulation factors
A
- all designed with roman numberals
- Factor 10 is written as FX & when activated = FXa
- majority exist as zymogen pro-enzymes, when activated they are then converted into active serine proteases
6
Q
What coagulation factors are exceptions?
A
- FVIII & FV = glycoprotein co-factors
- FXIIIa = transglutaminase - acts to cross-link fibrin monomers/polymers to strengthen them
7
Q
Describe Factor VIII
A
- Inactive form bound to von Willebrand’s factor (vWF)
- thrombin cleaves vWF to from FVIIIa that can stablilse FIXa
8
Q
What is a FVIII Deficiency called ?
A
Haemophilia A
9
Q
What is another name for a FIX deficiency?
A
- Haemophilia B
- or christmas disease named after Stephen Christmas -> first case described 1952
10
Q
A
11
Q
Describe the role of phospholipids in coagulation
A
- key role in haemostasis
- mostly supplied by platelets & released following adhesion & aggregation
- also found in tissue cells
- promote assist in activity of coagulation factors
12
Q
What are some inhibitors of coagulation?
A
- there are naturally occuring anti-coagulants present in the blood
- Protein C + S = vitami K dependent proteins made in the liver
- protein C activated through thrombin-thrombomodulin complex inhibits Va & VIIIa
12
Q
Describe the activity of Thrombin
A
- promotes platelet aggregation/release
- activates FV
- activates FXI leading to FIX activation
- converts soluble fibrinogen to insoluble fibrin
13
Q
Describe Fibrinolysis
A
- process whereby fibrin is degraded by plasmin
- the inactive form of plasmin is found in plasma & called plasminogen
14
Q
When is warfarin used?
A
- treatment of deep vein thrombosis, pulmonary embolism, heart valve replacement
- monitored by Prothrombin time (PT)
- patient’s result is compared to control
14
Q
Describe Warfarin
A
- derivative of coumarin
- Vitamin K antagonists - target FII, FVII, FIX & FX, protein C & S
- inhibits post ribosomal y-carboxylation of glutamate residues on these proteins in the liver
15
Q
Describe Automated Coagulation Testing
A
- Sysmex CS-5100 system
- Primary tube sample volume check identifies potential inaccuracies caused by improper sample collection
- detects haemolysis, icterus & lipaemia with a pre-analytic scan of patient samples
- 400 PT tests/hour
16
Q
Describe PT tests
A
- 0.1 ml patient or control plasma
- 0.2 thromboplastin/ calcium chloride mixture
- assay 37 degrees
- measure time taken for clot to develop
17
Q
What are some reasons for prolonged PT result?
A
- warfarin therapy
- vitamin K or FVII deficiency
- liver disease
- lupus-like anticoagulation inhibitors
18
Q
What is the equation from INR for warfarin monitoring?
A
INR = [PT Patient/PT control] ^ISI
19
Q
What does INR stand for ?
A
international normalised ratio
20
Q
What does ISI stand for?
A
International sensitvity index
21
Q
Describe Heparin
A
- acdic mucopolysaccharide with an average molecular weight of 15,000-18,000 Daltons
- acts to potentiate the activity of anti-thrombin
- only given via IV
- affects platelet function
- LMWH = low molecular weight heparin = interacts more with antithrombin. to inhibit FXa rather than thrombin
22
Q
How is heparin activity monitored?
A
lab test called Activated Partial Thromboplastim Time (APTT)
23
What should the APTT for DVT therapy be ?
1.5-2.5 times the normal control
24
Describe the process of Activated Partial Thromboplastin Time (APTT)
- 0.1ml patient or control plasma
- 0.1ml APTT reagent
- incubate 37 degrees for 3m
- 0.1ml CaCl 2-
- assay at 37 degrees
- measure time taken for clot to develop
- normal range = 30-40 secs
25
Describe Anticoagulant therpay in practise
- initial heparin-monitored by APTT until desired ratio 1.5
- patient started on warfarin, heparin stopped when full effect of warfarin is achieved
- too high a dose of heparin - can be reversed by protamine sulphate
26
Describe Haemophilia A
- Results from spontaneous mutation (common)
- sex-linked
- results in absence/low conc. of FVIII
- 50% patients = missense/frameshift mutation
- 50% = inversion of the end of X-chromosome = results in severe clinical form
27
What are some clinical features of haemophilia A?
-many large/deep bruises
- pain, swelling or tightness in joints
- nosebleeds without cause
- unexplained & excessive bleeding from cuts or injuries
28
What is the lab diagnosis for Haemophilia A ?
- extended APTT
- PT should be normal
- Low plasma FVIIIa concentration
29
How is haemophilia A treated?
- historically = FVIII concentrates
- recombinant FVIII prep, heat or solvent treated
- DDVAP - vasopressin , for milder forms only, raises circulating plasma FVIII
30
Describe Haemophilia B
- christmas disease
- results in deficiency of FIX
- FIX encoded for a gene on X chromosome which is very close to gene for FVII
- Bleeding episodes treated with high purity FIX concentrates
31
Describe von Willebrand's Disease
- vWF protein produced by platelets & endothelial cells
- 2 main roles; stabilises FVIII complex in plasma & acts as an adapter protein for platelets to bind collagen
- point mutation or inversion of gene region in reduction vWF or abnormal function
- excessive blood loss from superficial cuts or nose bleeds
