IOD Inherited and Acquired Thrombotic Disorders

Question 1

CP CVT/PE?

Answer 1

Pulmonary embolism
SOB
Pleuritic chest pain
Haemoptysis
Haemodynamic instability
Calf swelling >3 cm compared to the other leg
Measured 10cm below tibial tuberosity
Collateral (nonvaricose) superficial veins present
Localized tenderness along the deep venous system
Pitting oedema, confined to symptomatic leg

Question 2

Types?

Answer 2

Deep vein thrombosis (DVT)
Incidence 1/1000 per year

Pulmonary embolism (PE) 
50 – 70 % of above knee DVT embolise

Hospital acquired thrombosis
Up to 60% of VTE is associated with a hospital admission

Question 3

Long term complications of VTE?

Answer 3

Risk of recurrence increases as you go on

Post-thrombotic syndrome-PulHT, eczema, varicoses, stents and anticoagulation

Question 4

Virchows triad?

Answer 4

Endothelial injury
line, trauma, surgery, cancer pts

Stasis
immobility, less flow

Blood components
Platelets
Coagulation factors
Coagulation inhibitors
Fibrinolytic factors

Question 5

which factor is most important in arterial thrombosis?

Answer 5

vessel wall injury

Question 6

Which factors are most important in VT ?

Answer 6

stasis and blood coagulation

Question 7

Haemostatic plug formation?

Answer 7

Response to injury
Vessel constriction

Formation of unstable platelet plug

- platelet adhesion
- platelet aggregation

Fibrin stabilisation of the plug with fibrin
- blood coagulation

Dissolution of clot and vessel repair
- Fibrinolysis

Question 8

contents arterial?

Answer 8

Platelet based: white thrombus
Platelet-VWF interactions critical
Associated with atheroma and changes in blood vessel wall

Question 9

pathophysiology arterial?

Answer 9

Artery. The primary trigger of arterial thrombosis is rupture of an atherosclerotic plaque. This involves disruption of the endothelium and release of constituents of the plaque into the lumen of the blood vessel.

Question 10

contents venous?

Answer 10

Fibrin based: red thrombus
Coagulation factors critical
Associated with venous stasis – flow and blood constituents

Question 11

pathophys venous?

Answer 11

By contrast, in venous thrombosis, the endothelium remains intact but can be converted from a surface with anticoagulant properties to one with procoagulant properties.Venous thrombosis can be triggered by several factors: abnormal blood flow (such as the absence of blood flow); altered properties of the blood itself (thrombophilia); and alterations in the endothelium

Question 12

what balance is important?

Answer 12

bt fibrinolytic proteins/anticoagulant proteins and coagulation factors/platelets

Question 13

What is thrombosis?

Answer 13

A multifactorial disorder with genetic and acquired rfs-risk increases cumulatively

Question 14

acquired rfs?

Answer 14

immobility, surgery, OCP, age, obesity, APL and myeloproliferative disorders

Question 15

inherited rfs?

Answer 15

antithrombin, protein c/s FVL deficiencies

Question 16

mixed rfs?

Answer 16

high factor VIII, IX, XI fibrinogen, homocysteine

Question 17

inherited thrombophilias?

Answer 17

Factor V Leiden
Prothrombin mutation
Protein C deficiency
Protein S deficiency
Antithrombin deficiency
High factor Vlll levels
Hyperhomocysteinaemia

Question 18

haemostatiic plug?

Answer 18

Response to injury
Vessel constriction

Formation of unstable platelet plug

- platelet adhesion
- platelet aggregation

Fibrin stabilisation of the plug with fibrin
- blood coagulation

Dissolution of clot and vessel repair
- Fibrinolysis
-

Question 19

pathway?

Answer 19

see ppt

Question 20

Protein C inhibits?

Answer 20

VIII and Va

Question 21

Antithrombin inhibits?

Answer 21

Xa and thrombin IIa

Question 22

Factor V Leiden?

Answer 22

Usually binds to activated Protein C-breaks clotting cascade

but in resistance, the binding site changes shape-so reaction slows and clotting continues

Question 23

What should we assess on?

Answer 23

Cumulative risk of inherited conditions and acquired rfs to plan interventions

Question 24

Age and sex?

Answer 24

More in women before 60
rare under 18
risk increases with age

Question 25

elderly causes?

Answer 25

Decreased mobility
Reduced muscular tone
Increasd frequency of risk-enhancing disease (eg. Malignancy)
Aging tissues:
Vein walls and valves
Subcutaneous tissues

Question 26

Risk with COCP?

Answer 26

acquired increase in resistance to activated protein C
Reduction in protein S levels
Reduction in antithrombin
Possible protective effect with progesterone on oestrogen mediated lowering of protein S levels
risk can be upto 2-3x more

Question 27

HRT?

Answer 27

2-4-fold increased risk of VTE
Risk highest shortly after starting, probably due to other prothrombotic states
irrespective of type/mode

Question 28

stasis?

Answer 28

Prolonged immobility eg surgery, travel
Stroke
Cardiac failure
Pelvic obstruction
Dehydration
Hyperviscosity
Polycythaemia

Longhaul flight over 4 hours 1 in 6000-cumulative with rfs

Question 29

Biggest risk in hospitals?

Answer 29

surgery-75% for knee

Question 30

investiagtions?

Answer 30

Inherited thrombophilia testing in lab
Direct assays
Protein C
Protein S
Antithrombin levels
Mutation analysis for prothrombin gene mutation and factor V Leiden

Question 31

investigation of APL syndrome?

Answer 31

B2 glycoprotein AB in APL protein
Lupus-calcium-not clotting-blocking clotting factor interaction with PL membrane in APL syndrome
Blood-AB activated in system-more clotting in vivo-blocked in vitro.