Module 1 - 2/3/4th week mixed Flashcards
Definition and classification of APLS
APS is an AI disease, where Abs react with phospholipids/ CSM glycoproteins, leading to in-vivo increased risk of arterial & venous thrombosis
•primary APS occurs in the abscence of other AI disease
•secondary APS occurs in conjunction with diseases eg SLE, RA, scleroderma etc
•catastrophic APS is a very rare variant which causes multi organ thrombosis and is always fatal
What antibodies are present in APLS?
Lupus anticoagulant antibodies, anti-cardiolipin antibodies and other APS Abs target lipoprotein surface antigens and components of the coagulation/fibrinolytic systems.
APLS criteria
The revised Sapporo classification diagnoses APS when one clinical and one laboratory finding are met, between 12weeks and 5years of each other.
Clinical criteria for APL
Vascular events – a history of one or more arterial/venous thrombosis episodes, objectively diagnosed by imagining, with no evidence of vessel wall inflammation
Obstetric events – requires only one of the following:
o >3 spontaneous and unexplained abortions prior to
10weeks gestation
o >1 miscarriage beyond 10weeks gestation
o >1 premature birth due to pre-eclampsia, eclampsia
or placental insufficiency
Lab criteria for APL
- ELISA to detect anti-cardiolipin antibodies at medium or high titres, at least twice in more than a 12 weeks period
o illness etc can induce transient APS Abs production
in normal people - Prolonged coagulation in dilute Russell’s viper venom time demonstrates lupus anticoagulant only when
o normal plasma addition does not correct the
prolongation
o addition of phospholipids (dilution of antibody) does
correct the prolongation
Causes of placental insufficiency?
- placental insufficiency can be due to HTN/ T2DM
* in ACS, placental insufficiency leads to intra-uterine growth restriction
Common clinical presentation of placental insufficiency
•vascular
o VTE prevalence is roughly 30%
o recurrence rate of untreated patients is 10%; this
carries a higher mortality rate
o cerebral thrombosis is most common arterial
thrombosis event
o digital necrosis and gangrene may also be seen
• cardiac – valvular heart disease
• neuro – TIA/stroke, vascular dementia
• skin – livedo reticularis (rash that appears reticular) (purple pearls)
• renal – vasculopathies → chronic renal ischaemia
rare clinical findings in APLS
Thrombocytopenia (splenic sequestration following Abs binding to Plt PL)
pulmonary HTN
peripheral thrombosis
catastrophic APS
APLS treatment
- heparin and low dose aspirin are being used as prophylaxis to prevent (recurrent) miscarriages
- steroids should only be used in treatment of coexisting AI disease, not to treat APS (side effects).
What is APLS associated with?
intra-uterine growth restriction, premature births, HELLP syndrome (haemolysis, eleveated liver enzymes, low platelets)
VTE & PE similarities
- Identical pathophysiology
- incr thrombus size leads to destruction of venous valves
- destruction of venous valves gives rise to post-phlebitic
syndrome
- predisposing Rf leads to thrombus formation in veins
thrombi form legs/pelvis embolise to pulmon. circulation
- 90% of PEs attributable to leg thrombi; 10% pelvic
about 50% of people with DVT develop a subsequent PE - Similar risk factors
pregnancy, HRT, orthopaedic surgery, thrombophilia, flights etc (Basically, Virchow’s triad) - Identical therapeutic goals
- Similar treatment strategies
Symptoms and signs of DVT /PE
symptoms of inflammation
pain, swelling, redness, warmth
unilateral signs
leg – pitting oedema, tenderness, muscle induration
lung – pleuritic chest pain, haemoptysis
systemic upset – pyrexia, tachycardia
Simplified wells score for DVT
ONE POINT: active cancer, paralysis, bed>3d, surgery within 4wk, vein tendereness, swollen leg, calf swollen>3cm, pitting oedema, collateral veins, previous DVT
Alternative diagnosis -2
Low risk/unlikely <1 Moderate 1-2 High/likely >2
Protocol for wells score showing high risk pnt
if someone has a high risk from history, negative d-dimer does not mean no DVT. high risk patients should always have an ultrasound
Protocol for wells score showing low risk pnt
If -ve d-dimer, probably don’t have a DVT because d-dimers have a high negative predictive value
If +ve d dimer but -ve US, probably confirms the diagnosis; but ultrasound is only sensitive 97% of the time – they may still require venogram/serial ultrasound within 1 week if the history points to very high risk.
Why are venograms are rarely used these days in DVT?
invasive, expensive, dangerous contrast mediated effects on kidney (especially in HTN, T2DM)
reserved for people with high risk from history and normal USS – this may suggest recurrent DVT (which USS is poor at picking up)
o recurrence is diagnosed if vessel diameter has enlarged by 2mm or more from previous venogram
Simplified wells score for PE
DVT, tachy >100, immobility or surgery 4 weeks ago, previous VTE, haemoptysis, Ca, most likely than alternative diagnoses = 1 point each. PE is deemed unlikely if score is <1.
What is the diagnostic ability of a v/q scan?
- V/Q is only diagnostic in 30% of cases, but it should be used before CTPA in the interest of decreasing radiation exposure
- V/Q may be influenced by any coexisting lung disease
What is the test of choice in a massive PE?
TTE
• you are looking for signs of RV stress/dilation in the emergency situation with TTE
• then confirm diagnosis with VQ of spiral CT
• avoid CTPA because it increases risk of major bleeding in massive PE patients
Other investigations for PE (explain each one)
ABG
ECG
Potential targets for new anticoagulants
o TFPI/PC/APC analogues
o f9, f10a, thrombin, tafi inhibitors
o rThrombomodulin
Requirements for new anticoagulants
efficacy – proven in arterial/venous thrombosis
safety – wide therapeutic window, low bleeding risk,
predictable response, antidote presence
convenience – oral, fixed dosage, few interactions, rapid on-&offset of action, no need for monitoring
Comparin warfarin, UH and LMWH
UFH and LMWH have rapid onset (warfarin does not)
UFH has rapid offset
LMWH has the most predictable response and limited interactions.
However, UFH and warfarin have antidotes but LMWH doesn’t.
The only unique advantage of warfarin is that its oral.
They all cost alot.
UH vs LMWH
UH - IV, higher incidence of HIT. LMWH - SC,
Give some examples of new anticoagulant agents in clinical practice
Synthetic pentasaccharides,
F10a inhibtors
Thrombin inhibitos
PC analogues
Give example of anticoagulants that shares the same pentasaccharide sequence as UFH and LMWH for the binding to antithrombin?
Fondaparinux
• vte prevention
• but requires parenteral (SC) admin
• excreted by kidney so cant be used in renal failure
• not reversible by protamine, but does NOT cause HIT (as with UFH / LMWH)
idraparinux
• longer half life than fondsparinux (designed to be injected weekly instead of daily)
• Its chemically related to heparin. Its a factor Xa inhibitor & binds antithrombin and accelerates its inhibition of factor Xa.
Give an example of novel f10inhibitor and thrombin inhibitor
rivaroxaban
• licensed for orthopaedic vte prophylaxis, stroke prophylaxis in AF •no antidote, but annexa 4 trials have shown promising for andexanet
dabigatran
• licensed for orthopaedic vte prophylaxis, stroke prophylaxis in AF
