Coagulation studies Flashcards
when is aPTT used? (active partial thromboplastin time)
- Identify factor deficiencies in intrinsic pathway (XII, XI, IX, VIII, X, V, II, I)
- Monitor heparin therapy
When is PT used? (prothrombin time)
- Identify factor deficiencies in extrinsic pathway (VII, X, V, II, I)
What is clotting factor I & function
Fibrinogen
> thrombonin substrate
What is clotting factor II & function
Prothrombonin
> serine protease
What is clotting factor III & function
Tissue factor
> co-factor to inc. enzymatic activity
What is clotting factor IV & function
Calcium
> mineral
Why is citrate the anticoagulant of choice when testing clotting functions in specimens*
because it reversibly binds to Ca2+ unlike EDTA
- add more Ca2+ so citrate unbounds
Hypercholesterolemia & cause
.
friedwald equation
.
Hyperlipidemia / Hyperlipoprotemia . cause
. hi cholesterol OR TG
- familial cholesterolemia
- diabetes
Combined Hyperlipidemia / Hyperlipoprotemia
Hi choesterol AND hi TG
Hypolipoproteinemia / Hypolipidemia
.
Hypertriglyceridemia
.
Define Pupura
bleeding under the skin
Define petechiae
small bleeds under skin (3mm)
Define ecchymoses
larger bleeds under skin (>3mm)
Define haemarthrosis
bleeding into joint = joint swelling
Define epistaxis
nose bleed
Define haematemesis
vomiting of blood
Define haematoma
bleeding confined to particular organ
Define Maelena
blood in faeces
Define menorrhagia
heavy menstrual bleeding
What does the 1º & 2º haemostasis involve?
1º: platelets
2º: plasma coagulation factors- requiring +ve & -ve charges = complexes
How does the 1º haemostatic plug form?
- vasular injury = endothelial damaged= exposes collagen
- von Willebrand factor (vWF) (in blood/released from damaged endothel) sticks to collagen (subendothelial matrix) & elonagate = expose binding sites
- Plt bind to vWF via glycoprotein (GP) 1b-V-IX => plt become activated = change shape = discoid (flat shape) 4. GP IIb-IIIa exposed on plt => fibrinogen binds to these on adjacent plt > stabilise plt
- procoagulant contents released => recruit more plt & further aggregation
What do activated plt release?
- Dense bodies: Seretonin, ADP, Ca2+
- Alpha granules: fibrinogen, vWF, PF4, PDGF, thrombospondin
- thromboxane A2 > activate more plt
what is Fibrinolysis & Describe process
a. digestion of fibrin clot
b. plasminogen activated to plasmin => digest fibrinogen & fibrin
3 phases of fibrinogen formation ie. endpoint of 2º haemostasis
- proteolysis
- polymerisation: form fibrin polymers
- stabilisation: FXIIIa forms covalent bonds in b/w D-dimers ≠ break = stable fibrin polymer
Describe how you form fibrin from fibrinogen w/ thrombin
thrombin cleaves Fibrino peptides on E domain of fibrinogen => E domain is +ve charged & D domain is -ve
Describe the intrinsic & common pathway (T E N = X)
- FXII is activated by -ve charged surface => FXIIa
- FXIIa activates FXI => FXIa
- FXIa activates FIX => FIXa:FVIII complex (or intrinsic tenase)
- Complex activates FX => FXa:FV
- FXa:FV activates prothrombin => thrombin (enzyme)
- Thrombin cleaves fibrino peptides on E domain of fibrinogen => fibrin
Describe the extrinsic & common pathwaay
- Vessel injury
- Tissue release factor (or intrinsic tenase) like thromboplastin (tiss. factor on PL)
- TF:FVIIa complex is formed => activating FX => FXa:FV
- FXa:FV activates prothrombin => thrombin (enzyme)
- Thrombin cleaves fibrino peptides on E domain of fibrinogen => fibrin
3 roles of haemosatic system
- keep blood & prevent excess blood loss
- keep thrombosis to the site
- fibrinolysis (digest fibrin clot for remodelling)
4 substances that activate plt
- thromboxane a
- ADP
- Collagen
- Thrombin
a deficiency in vWF can lead to a deficiency of F_ because _
FVIII
bc vWF cirlulates (bound to) FVIII
plt aggregates by
fibrinogen binding to GP IIb-IIa on adjacent plt
which measurement to use to determine platelet function
platelet aggregation
list th 5 laboratory assays for 1º haemostasis
- [ptl] (150-400 x10^9/L)
- bleeding time
- plt function analyser (measure clot time w/ PFA-100)
- vWF
- plt aggretonomy
list the clotting factors from I-VII
I: fibrinogen II: prothrombin III: tissue factor IV: Calcium V: labile factor (cofactor) VII: stable factor (serine protease) * NO FACTOR VI
characteristics of Fibrinogen group
- FI, V, VIII, XIII
- procoag. factors => thrombosis
characteristics of Prothrombin group
- FII, VII, IX, X
- Vitamin K dependant
- stable in blood storage
- inhibited by warafin (PT = ext.)
characteristics of contact group
- FXI, XII
- activated when in contact with -ve charged surfaces
list th 5 laboratory assays for 2º haemostasis
- PT
- aPTT
- thrombin time
- factor assays
- Fibrinogen assays
organ/site of production for factors
liver
Why is vitamin K important for FII, VII, IX, X?
- bc is required to make FII, VII, IX, X functional
- bc Vit. K is needed by glutamic acid (Gla) => undergo gamma carboxylation so that Ca2+ can bind to Gla => complex can bind to -ve PL (remain at site of damage)
4 Things to avoid when preparing coagulation assays
- use citrate not EDTA
- use plastic tubes not glass (bc can activate CF)
- mix well to prevent specimens clotting
- avoid under-filling tubes = keep ratio constant ie 9 blood : 1 citrate