Coagulation studies

Question 1

when is aPTT used? (active partial thromboplastin time)

Answer 1

1. Identify factor deficiencies in intrinsic pathway (XII, XI, IX, VIII, X, V, II, I)
2. Monitor heparin therapy

Question 2

When is PT used? (prothrombin time)

Answer 2

1. Identify factor deficiencies in extrinsic pathway (VII, X, V, II, I)

Question 3

What is clotting factor I & function

Answer 3

Fibrinogen

> thrombonin substrate

Question 4

What is clotting factor II & function

Answer 4

Prothrombonin

> serine protease

Question 5

What is clotting factor III & function

Answer 5

Tissue factor

> co-factor to inc. enzymatic activity

Question 6

What is clotting factor IV & function

Answer 6

Calcium

> mineral

Question 7

Why is citrate the anticoagulant of choice when testing clotting functions in specimens*

Answer 7

because it reversibly binds to Ca2+ unlike EDTA

- add more Ca2+ so citrate unbounds

Question 8

Hypercholesterolemia & cause

Answer 8

.

Question 9

friedwald equation

Answer 9

.

Question 10

Hyperlipidemia / Hyperlipoprotemia . cause

Answer 10

. hi cholesterol OR TG

1. familial cholesterolemia
2. diabetes

Question 11

Combined Hyperlipidemia / Hyperlipoprotemia

Answer 11

Hi choesterol AND hi TG

Question 12

Hypolipoproteinemia / Hypolipidemia

Answer 12

.

Question 13

Hypertriglyceridemia

Answer 13

.

Question 14

Define Pupura

Answer 14

bleeding under the skin

Question 15

Define petechiae

Answer 15

small bleeds under skin (3mm)

Question 16

Define ecchymoses

Answer 16

larger bleeds under skin (>3mm)

Question 17

Define haemarthrosis

Answer 17

bleeding into joint = joint swelling

Question 18

Define epistaxis

Answer 18

nose bleed

Question 19

Define haematemesis

Answer 19

vomiting of blood

Question 20

Define haematoma

Answer 20

bleeding confined to particular organ

Question 21

Define Maelena

Answer 21

blood in faeces

Question 22

Define menorrhagia

Answer 22

heavy menstrual bleeding

Question 23

What does the 1º & 2º haemostasis involve?

Answer 23

1º: platelets

2º: plasma coagulation factors- requiring +ve & -ve charges = complexes

Question 24

How does the 1º haemostatic plug form?

Answer 24

1. vasular injury = endothelial damaged= exposes collagen
2. von Willebrand factor (vWF) (in blood/released from damaged endothel) sticks to collagen (subendothelial matrix) & elonagate = expose binding sites
3. 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
4. procoagulant contents released => recruit more plt & further aggregation

Question 25

What do activated plt release?

Answer 25

- Dense bodies: Seretonin, ADP, Ca2+ - Alpha granules: fibrinogen, vWF, PF4, PDGF, thrombospondin - thromboxane A2 > activate more plt

Question 26

what is Fibrinolysis & Describe process

Answer 26

a. digestion of fibrin clot | b. plasminogen activated to plasmin => digest fibrinogen & fibrin

Question 27

3 phases of fibrinogen formation ie. endpoint of 2º haemostasis

Answer 27

1. proteolysis 2. polymerisation: form fibrin polymers 3. stabilisation: FXIIIa forms covalent bonds in b/w D-dimers ≠ break = stable fibrin polymer

Question 28

Describe how you form fibrin from fibrinogen w/ thrombin

Answer 28

thrombin cleaves Fibrino peptides on E domain of fibrinogen => E domain is +ve charged & D domain is -ve

Question 29

Describe the intrinsic & common pathway (T E N = X)

Answer 29

1. FXII is activated by -ve charged surface => FXIIa 2. FXIIa activates FXI => FXIa 3. FXIa activates FIX => FIXa:FVIII complex (or intrinsic tenase) 4. Complex activates FX => FXa:FV 5. FXa:FV activates prothrombin => thrombin (enzyme) 6. Thrombin cleaves fibrino peptides on E domain of fibrinogen => fibrin

Question 30

Describe the extrinsic & common pathwaay

Answer 30

1. Vessel injury 2. Tissue release factor (or intrinsic tenase) like thromboplastin (tiss. factor on PL) 3. TF:FVIIa complex is formed => activating FX => FXa:FV 4. FXa:FV activates prothrombin => thrombin (enzyme) 5. Thrombin cleaves fibrino peptides on E domain of fibrinogen => fibrin

Question 31

3 roles of haemosatic system

Answer 31

- keep blood & prevent excess blood loss - keep thrombosis to the site - fibrinolysis (digest fibrin clot for remodelling)

Question 32

4 substances that activate plt

Answer 32

- thromboxane a - ADP - Collagen - Thrombin

Question 33

a deficiency in vWF can lead to a deficiency of F_ because _

Answer 33

FVIII | bc vWF cirlulates (bound to) FVIII

Question 34

plt aggregates by

Answer 34

fibrinogen binding to GP IIb-IIa on adjacent plt

Question 35

which measurement to use to determine platelet function

Answer 35

platelet aggregation

Question 36

list th 5 laboratory assays for 1º haemostasis

Answer 36

1. [ptl] (150-400 x10^9/L) 2. bleeding time 3. plt function analyser (measure clot time w/ PFA-100) 4. vWF 5. plt aggretonomy

Question 37

list the clotting factors from I-VII

Answer 37

``` I: fibrinogen II: prothrombin III: tissue factor IV: Calcium V: labile factor (cofactor) VII: stable factor (serine protease) * NO FACTOR VI ```

Question 38

characteristics of Fibrinogen group

Answer 38

- FI, V, VIII, XIII | - procoag. factors => thrombosis

Question 39

characteristics of Prothrombin group

Answer 39

- FII, VII, IX, X - Vitamin K dependant - stable in blood storage - inhibited by warafin (PT = ext.)

Question 40

characteristics of contact group

Answer 40

- FXI, XII | - activated when in contact with -ve charged surfaces

Question 41

list th 5 laboratory assays for 2º haemostasis

Answer 41

1. PT 2. aPTT 3. thrombin time 4. factor assays 5. Fibrinogen assays

Question 42

organ/site of production for factors

Answer 42

liver

Question 43

Why is vitamin K important for FII, VII, IX, X?

Answer 43

- 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)

Question 44

4 Things to avoid when preparing coagulation assays

Answer 44

- 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