W7: Assessing Haemostasis :((((( Flashcards
5 steps of haemostasis
vessel spasm
platelet plug formation
coag
clot retraction
clot dissolution
define coag
fluid blood converted into a gelatinous clot.
converts platelet plug into a more stable clot.
how is thrombin generated?
from prothrombin at sites of tissue injury
what does thrombin catalyse?
conversion of fibrinogen to fibrin
diff btwn intrinsic and extrinsic
E - need molecules from tissue
I - molecules already in blood
what does plasmin do?
plasmin cleavage of crosslinked fibrin creates d-dimers (fibrin degradation prods)
what might cause bleeding disorders (insufficient haemostasis)?
defs of platelet no or function, or defs in coag factors
what might cause thrombosis (inapprop haemostasis)?
arterial - inapprop stim of platelets (rupture of atherosclerotic plaques)
venous - defs in inhibitors of coag factors
S&S of thrombotic disorders (depending on location of thrombus)
coronary arteries: chest pain
carotids arteries: FAST
deep veins of legs: unilateral leg pain
S&S of bleeding defects: pts present w/
easy bruising (purpura/petechiae/ecchymoses)
mucosal bleeding (epistaxes, menorrhagia, GI, GU)
haemarthrosis
complications w surgery/trauma/venepuncture
what is a bruise?
micro or macroscopic tearing
leaked blood cell are phagocytosed & degraded -> colour changes:
red-blue: Hb
green: biliverdien
yellow: bilirubin
golden: hemosiderin
sizes of haematomas
Petechiae - <3mm
Purpura – 3mm – 1cm
Ecchymoses - >1cm
issues w/ platelet plug formation are what type of disorders?
primary haemostatic
abnormal bleeding may result from 4 causes…
vascular defects (weak vessels – leak)
decr platelet number (thrombocytopenia)
decr platelet function (disorders of platelet function)
decr coagulation
primary haemostatic disorders vs coag disorders: e.g.
thrombocytopenia, VWD
haemophilia
primary haemostatic disorders vs coag disorders: bleeding
immediate
delayed
primary haemostatic disorders vs coag disorders: petechiae
yes
no
primary haemostatic disorders vs coag disorders: epistaxes
common
uncommon
primary haemostatic disorders vs coag disorders: menorrhagia
common uncommon
primary haemostatic disorders vs coag disorders: haemarthroses
no
yes
primary haemostatic disorders vs coag disorders: intramuscular haematomas
uncommon
common
primary haemostatic disorders vs coag disorders: gender
equal
>80% male
haemostatic investigations: blood film/smear
morphology
clumping platelets
haemostatic investigations: FBC
EDTA removes Ca - so clotting can’t occur
thrombocytosis vs thrombocytopenia
haemostatic investigations (platelet tests): bleeding time
normal = 3-8 min
haemostatic investigations (platelet tests): PFA-100
replaced bleeding time
mem coated w/ molecules that would activate platelets, aggreg would decr flow, if platelets not activated, no effect on flow
haemostatic investigations (platelet tests): platelet aggregation studies
aggreg of platelets, gaps btwn clumps, so light can pass thru
see how diff activators affect aggreg
haemostatic investigations (platelet tests): flow cytometry
haemostatic investigations (platelet tests): aspirin-specific tests
serum thromboxane & aspirinworks
5-40% of ppl don’t respond to aspirin (don’t want to be taking it & experiencing side effects, if it doesn’t work for you)
Test if they do respond by measuring thromboxane levels
Need to know before surgery if someone’s taking aspirin (bc aspirin reduces clotting)
haemostatic investigations (coag tests): PT
assesses extrinsic pathway. Many clotting factors in extrinsic pathway require vit K for their synthesis, therefore, the prothrombin time can be used to assess pts on warfarin. (warfarin use ↓).
Warfarin blocks vit K cycling, so less CFs prod
normal value for PT
11-16 sec
haemostatic investigations (coag tests): aPTT
assesses intrinsic pathway, which is initiated by exposure of collagen (due to vessel damage)
normal value for aPTT
30-40 sec
haemostatic investigations (coag tests): TT
assesses final stages of common pathway
no ca needed (ca independent)
normal values for TT
15-19 sec
normal platelet count
normal PT
normal aPTT
normal TT
- Disorder of platelet function
- Factor XIII deficiency
- Disorder of vascular haemostasis
- Severe bleeding w/ normal haemostasis
normal platelet count
long PT
normal aPTT
normal TT
- Deficiency or defect of the extrinsic pathway.
- Rare FVII deficiency
- Start of oral anti-coagulant therapy (Warfarin)
normal platelet count
normal PT
long aPTT
normal TT
Deficiencies or defects of intrinsic pathway
FVIII / IX (Haemophilia A / B), FXI, FXII, prekallikrein, HMWK.
- Von Willebrands Disease
- Anti-coagulants
normal platelet count
long PT
long aPTT
normal TT
Vit K deficiency
- Oral anti-coags (Warfarin)
- Deficiencies in FV, VII, X and II
normal platelet count
long PT
long aPTT
long TT
Heparin
- Liver disease
- Fibrinogen deficiency
- Hyperfibrinolysis
low platelet count
normal PT
normal aPTT
normal TT
thrombocytopenia
low platelet count
long PT
long aPTT
normal TT
Massive transfusion
- Liver disease (could affect thrombopoietin prod & CF prod)
low platelet count
long PT
long aPTT
long TT
DIC
acute liver disease
haemostatic investigations (further tests): factor assays
testing for deficiencies
If pt plasma diluted in normal plasma the prolonged clotting time should be corrected.
Diluting in various plasmas that are deficient in specific CFs can indicate which factor missing/reduced.
haemostatic investigations (Further tests): inhibitor assays
If pt plasma is added to normal plasma & incubated for 2h, any inhibitors present in pt plasma will cause the normal plasma to have prolonged clotting times.
haemostatic investigations (Further tests): PCR
Families w/ bleeding disorders may undergo risk assessment by analysis of
Pedigree
Phenotype
Genotype
Mutations commonly identified by PCR amplification of DNA.
Most commonly used for analysis of Haemophilia A/B & von Willebrands Disease.
D-dimer assays:
Raised w/ fresh venous thrombosis.
Also elevated in cancer, inflammation after surgery or trauma, but -ve result helps exclude DVT.
which CFs are involved in intrinsic?
12
11
9
8
(10)
which CFs are involved in extrinsic?
3
7
(10)
which CFs are involved in common?
1
2
5
10
13
