IOD Inherited and Acquired Thrombotic Disorders Flashcards
CP CVT/PE?
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
Types?
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
Long term complications of VTE?
Risk of recurrence increases as you go on
Post-thrombotic syndrome-PulHT, eczema, varicoses, stents and anticoagulation
Virchows triad?
Endothelial injury
line, trauma, surgery, cancer pts
Stasis
immobility, less flow
Blood components Platelets Coagulation factors Coagulation inhibitors Fibrinolytic factors
which factor is most important in arterial thrombosis?
vessel wall injury
Which factors are most important in VT ?
stasis and blood coagulation
Haemostatic plug formation?
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
contents arterial?
Platelet based: white thrombus
Platelet-VWF interactions critical
Associated with atheroma and changes in blood vessel wall
pathophysiology arterial?
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.
contents venous?
Fibrin based: red thrombus
Coagulation factors critical
Associated with venous stasis – flow and blood constituents
pathophys venous?
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
what balance is important?
bt fibrinolytic proteins/anticoagulant proteins and coagulation factors/platelets
What is thrombosis?
A multifactorial disorder with genetic and acquired rfs-risk increases cumulatively
acquired rfs?
immobility, surgery, OCP, age, obesity, APL and myeloproliferative disorders
inherited rfs?
antithrombin, protein c/s FVL deficiencies
mixed rfs?
high factor VIII, IX, XI fibrinogen, homocysteine
inherited thrombophilias?
Factor V Leiden Prothrombin mutation Protein C deficiency Protein S deficiency Antithrombin deficiency High factor Vlll levels Hyperhomocysteinaemia
haemostatiic plug?
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
-
pathway?
see ppt
Protein C inhibits?
VIII and Va
Antithrombin inhibits?
Xa and thrombin IIa
Factor V Leiden?
Usually binds to activated Protein C-breaks clotting cascade
but in resistance, the binding site changes shape-so reaction slows and clotting continues
What should we assess on?
Cumulative risk of inherited conditions and acquired rfs to plan interventions
Age and sex?
More in women before 60
rare under 18
risk increases with age
elderly causes?
Decreased mobility Reduced muscular tone Increasd frequency of risk-enhancing disease (eg. Malignancy) Aging tissues: Vein walls and valves Subcutaneous tissues
Risk with COCP?
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
HRT?
2-4-fold increased risk of VTE
Risk highest shortly after starting, probably due to other prothrombotic states
irrespective of type/mode
stasis?
Prolonged immobility eg surgery, travel Stroke Cardiac failure Pelvic obstruction Dehydration Hyperviscosity Polycythaemia
Longhaul flight over 4 hours 1 in 6000-cumulative with rfs
Biggest risk in hospitals?
surgery-75% for knee
investiagtions?
Inherited thrombophilia testing in lab Direct assays Protein C Protein S Antithrombin levels Mutation analysis for prothrombin gene mutation and factor V Leiden
investigation of APL syndrome?
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.
