thrombotic disorders

Question 1

what are the 3 elements of haemostasis

Answer 1

1y haemostasis

blood coagulation

fibrinolysis

Question 2

3 parts of 1y haemostasis

Answer 2

vasoconstriction - at the site of endothelial insult

platelet adhesion - to exposed sub-endothelial collagen through GP Ia

platelet aggregation - through release of thromboxane and subsequently ADP

Question 3

what triggers 1y haemostasis

Answer 3

tissue damage

Question 4

2 main parts of coagulation

Answer 4

insoluble fibrin formation

fibrin cross linking

Question 5

what is a thrombus

Answer 5

clot that arises in the wrong place

Question 6

what is thromboembolism

Answer 6

movement of clot along a vessel

Question 7

virchow’s triad

Answer 7

stasis

hypercoagulability

vessel damage

–> thrombosis

Question 8

examples when components of virchow’s triad may be upset

Answer 8

stasis - bed rest, travel

hypercoagulability - pregnancy, trauma

vessel damage - atherosclerosis

Question 9

3 main types of thrombosis

Answer 9

arterial
venous
microvascular

Question 10

what is an arterial clot

Answer 10

‘white clot’ - platelets and fibrin

results in ischaemia and infarction

2y to atherosclerosis

Question 11

examples of arterial thromboembolism

Answer 11

coronary thrombosis - MI, unstable angina

cerebrovascular TE - stroke, TIA

peripheral embolism - acute limb ischaemia

Question 12

risk factors for arterial thrombosis

Answer 12

age 
smoking 
sedentary lifestyle
HT
DM
obesity 
hypercholesterolaemia 

FHx

Question 13

management of arterial thrombosis

Answer 13

1y prevention - lifestyle modification, treatment of vascular risk factors

acute presentation - thrombolysis, anti-platelet/anticoagulant drugs

2y prevention - treatment of identified risk factors

Question 14

what is a venous thrmobus

Answer 14

‘red thrombus’ - fibrin and red cells

results in back pressure

principally due to stasis and hypercoagulability

Question 15

examples of venous thromboembolism

Answer 15

limb DVT
PE
visceral venous thrombosis 
intracranial venous thrombosis 
superficial thrombophlebitis - superficial veins

Question 16

risk factors for venous thrombosis

Answer 16

stasis/hypercoagulability: 
increasing age 
pregnancy 
Hormonal therapy - HRT/COCP
tissue trauma 
immobility 
surgery 
obesity 
systemic disease
FHx

Question 17

systemic disease linked to venous thrombosis

Answer 17

cancer
myeloproliferative neoplasm (MPNs)
AI disease: 
- IBD
- connective tissue disease e.g. SLE
- antiphospholipid syndrome: arterial and venous thrombosis

Question 18

diagnosis of venous thrombosis

Answer 18

pretest probability scoring: Wells score, Geneva score

lab testing if pretest probability low - D dimer

imaging if low pretest probability but +ve D dimer; pts w/ high pretest probability go straight to imaging

Question 19

imaging for venous thrombosis

Answer 19

doppler US for upper and lower limb veins

long images and suspected PE: V/Q scan, CT pulmonary angiogram - gold standard for PE

Question 20

why is CT pulmonary angio gold standard for imaging PE

Answer 20

gives you detail on the clot pattern as well as whether there is evidence of right heart strain and anatomical detail

Question 21

aims of management for venous thrombosis

Answer 21

prevent clot extension

prevent clot embolisation

prevent clot recurrence in long term treatment

Question 22

drug treatment for venous thromboembolism

Answer 22

anticoagulants - LMWH, coumarins (warfarin), DOACs (prevent clot extending but don’t break down the clot)

thrombolysis only in selected cases e.g. massive PE (streptokinase, tenecteplase, alteplase)

Question 23

heritable thrombophilia

Answer 23

common:
factor V Leiden
prothrombin G20210A

rare:
antithrombin deficiency - highest thrombogenicity
protein C deficiency
protein S deficiency

Question 24

factor V Leiden and pathway

Answer 24

in the presence of thrombin, protein C is activated (promoted by thrombomodulin)

activated protein C w/ protein S subsequently inhibits activated factor VIII and V

Question 25

what happens if an individual has factor V Leiden mutation

Answer 25

actions of activated protein C in inhibiting factor V are blocked

activated protein C resistance means there is an ongoing drive towards thrombin generation and fibrin clot formation

Question 26

naturally occurring anticoagulants and deficiency

Answer 26

anti-thrombin protein C and S

deficiency of either means factor VIIIa and Va aren’t inhibited

their drive towards thrombin and fibrin generation continues

Question 27

antithrombin deficiency

Answer 27

antithrombin potentiates the formation of complexes between heparin and serine protease and therefore has a direct blocking effect on thrombin

if antithrombin is deficient then thrombin generation continues and you get fibrin clot formation

Question 28

clinical utility of heritable thrombophila

Answer 28

majority aren’t predictive of recurrent event

screening of asymptomatic family members not recommended - wouldn’t commence long term anticoagulation anyway unless they develop VTE

limited thrombophilia screening restricted to high risk heritable thrombophilia (antithrombin deficiency)

Question 29

what are microvascular thrombus

Answer 29

platelets and/or fibrin

results in diffuse ischaemia

principally in DIC

Question 30

what is DIC

Answer 30

disseminated intravascular coagulation

diffuse systemic coagulation activation; consumption of platelets and clotting factors leeding to bleeding

activation of coagulation leading to microvascular thrombosis deposition

Question 31

when does DIC occur and what does it cause

Answer 31

septicaemia, malignancy, eclampsia

tissue ischaemia: gangrene, organ failure