Week 5 Flashcards
What are the 3 component of the haemostatic system that help prevent blood loss?
Blood vessels, platelets, Plasma Proteins :blood clotting
What is considered Primary haemostasis?
Blood vessels & Platelets
What is considered Secondary haemostasis?
Platelets & Plasma Proteins
What does haemostasis mean?
the process to prevent and stop bleeding
What are the 3 functions of platelets?
Adhesion (reversible), Aggregation (irreversible), Secretion (irreversible)
Which factor is activated by both intrinsic and extrinsic pathways?
X marks the spot
Which factor acts as a co-factor with FX?
Factor V (V fits into X)
Which factors are in the common pathway?
FII and FI
Which factor(s) are in the extrinsic pathway?
FVII
Which factor(s) are in the intrinsic pathway?
FXII, XI, IX, VIII (TENET)
Which factor crosslinks fibrin?
FXIII
Intrinsic pathway is measured by what test
APTT
Extrinsic pathways is measured by what test
PT
What does APTT and PT stand for?
APTT - Activated partial thromboplastin time.
PT - Prothrombin Time
It is called an intrinsic pathway because …
FXII is found IN blood
It is called an extrinsic pathway because……
Tissue factor is not found in blood
What is normally contained in a clot-base pro-coagulant screen? (5)
PT, APTT, thrombin clotting time (TCT), Fibrinogen Assay (FIB), platelet count
Which test monitors for warfarin and which one for heparin?
Warfarin - PT
Heparin - APTT
The PT test is most sensitive to levels of what factor?
FVII
What is International Normalised Ratio (INR)?
a calculation based on results of a PT. Used to monitor warfarin.
In the APTT test a Reagent contains ________ that
activates Factor _______ which then Initiates an _______ cascade
phospholipid, FXII, intrinsic
A PT test consists of what 3 things?
PPP + PT reagent + Ca++
Which factor gets activated in a PT test?
FVII
An APTT test is prolonged with <30% normal activity of what 3 factors?
- FVIII
- FIX
- FXI
In a TCT test Bovine thrombin reagent cleaves
________ to form ______ polymer
fibrinogen, fibrin
A prolonged TCT test occurs in the presence of what 3 things?
- Low fibrinogen
- Heparin
- FDPs
What are the 3 principal regulators of the coagulation regulatory system?
i. Tissue factor pathway inhibitor (TFPI)
ii. Protein C pathway
iii. Antithrombin (AT)
TFPI only functional if which factor is activated
X
Protein C pathway is _____ dependent anticoagulant proenzyme
vitamin K
What activates protein C?
thrombomodulin
APC acts as an anticoagulant by proteolytically inactivating which factors?
FVa & FVIIIa
APC acts as an anticoagulant and is enhanced by
Protein S
Protein S is a glycoprotein dependent on which vitamin?
Vit K
Protein C pathway is a natural __________
Anticoagulant
Which protein deficiencies result in risk of recurrent DVT and risk of pulm embolism
Protein C & S
AT is a serine protease inhibitor (serpin)
→binds an neutralises all serine proteases except ________
FVIIa
Heparin cofactor II → serpin that inactivates ________primarily
thrombin
AT & Heparin cofactor II both require ______ for effective anticoag activity In vivo heparin from EC
heparin
Therapeutic heparin: ↑ ability of AT to neutralise serine proteases by _______ fold
1000
What are the 6 different ways to classify bleeding symptoms?
Localised (single site) vs Generalised (multiple sites)
Mucocutaneous (systemic) vs Anatomic (soft tissue)
Acquired vs Congenital
List examples of mucocutaneous (systemic) bleeding.
Thrombocytopaenia Qualitative platelet disorder Von Willebrand disease Vascular disorder Eg: purpura, petechiae, eccymoses
List examples of Anatomic (soft tissue) bleeding
Excessive bleeding after : minor trauma, dental extraction, surgery, bleeding into muscles, joints etc.
Draw the trauma triad of death.
slide 24 week 5
What are the key elements of the “triad of death” in acute
coagulopathy of trauma?
Liver disease predominantly affects which dependent factors
Vit K dependent factors
What are the vitamin K dependent coag factors? and what are the anticoag factors?
II, VII, IX, X (TV stations)
C,S,Z
List some situations where Vit K deficiency may be seen.
Fad diets
Biliary duct obstruction
Newborn (minimal vit K in milk)
Which anti coagulant is a vit k antagonist?
warfarin, ratsack
Which test would you use to monitor warfarin?
PT
What are 3 things you could use to reverse warfarin therapy if needed?
Vitamin K
Fresh frozen plasma
Prothombinex
List 3 congenital coagulopathies
Von Wilebrand Disease
Haemophilia A
Haemophilia B
Von willebrand Disease is a carrier molecule for which factor?
FVIII
What is the name of the VWF cleaving protease?
ADAMTS-13
When the endothelium is damaged what does the produced VWF bind to?
collegen
What is the most common mucocutaneous bleeding disorder
Von Willebrand Disease
Besides FBC
PT & PTT what other tests would be conducted for VW Disease? (besides specialised tests)
PTT mixing tests
Fibrinogen or Thrombin Time (TT)
What are 4 specialised tests for Von Willebrand Disease
Quantitative Immunoassay (Ag –Ab based) VWF:RCo ristocetin cofactor activity Ability to bind to platelets - functional Also called Ristocetin Cofactor Assay FVIII activity assay VWF multimer analysis Gel electropheresi
Is Haemophilia a X-linked or Y-linked recessive pattern?
X-linked - females are normally just carriers
Haemophilia A is a deficiency in which factor?
FVIII
FVIII deficiency slows the production of __________ which leads to __________
thrombin, haemorrhage
Is Haemophilia usually a quantitative or qualitative disorder?
quantitative but can sometimes be qualitative
The severity of haemophilia A correlates with level of what activity
F VIII activity
List the lab findings for Haemophilia A:
FBC, APTT, FVIII & IX, PT, vWF
FBC - Normal APTT - prolonged FIII & IX - low or absent PT- Normal vWF - Normal
How do we treat Haemophilia A
Clotting factor therapy
What is the most common acquired form of haemophilia? (acq. coagulopathy 2nd to disease)
Autoantibodies to FVIII
What test can you do to differentiate inhibitor from deficiency?
Mixing studies
In mixing studies if you combine patient plasma+normal plasma and it corrects the prolonged APTT what does that mean?
There was a FVIII deficiency
In mixing studies if you combine patient plasma+normal plasma and the APTT remains prolonged what does that mean?
Inhibitor (e.g. autoAb)
Haemophilia B is a deficiency in which Factor?
FIX deficiency
How do you test single factor assays?
Use the plasma deficient in specific factors and combine with the patients. If it is still prolonged then that is the deficient factor, If it is corrected it is not the factor.
What specimen do we use for coagulation assays?
3.2% sodium citrate
Do you centrifuge for PPP or PRP?
PPP - used in factor assays
List 4 steps usually visible on a platelet aggregometry trace.
- Baseline
- Agonist added
- Primary wave of aggregation
- Secondary wave of aggreation
