Miscellaneous Flashcards
What is the molecular basis of PNH?
There is somatic mutation of the og the PIG-A gene in the bone marrow which leads to disruption to glycosylphosphatidylinositol biosynthesis (GPI) leading o a deficiency of all GPI anchored proteins on the cell membrane
Which GPIs are especially importnat in complement regulation?
CD55 and CD59 leading to increased complement sensitivity of PNH cells
How does the complement system respond to PNH cells?
Intravascular haemolysis
promotion of inflammatory mediators
systemic Hb release
How does PNH cause thrombosis?
Platelet activation through increased exposure of PS for PL surface for coagulation binding
NO depletion
Red cell and platelet microparticles
What is the targeted treatment of PNH?
Eculizumab - monoclonal antibody which targets C5 - MAC is not formed
What are the 3 antibodies seen in antiphospholipid syndrome?
lupus anticoagulant
anti cardiolipin
anitb2gpi
These must be present on 2 occasions 3months apart
What is needed for diagnosis of antipospholipid syndrome?
1 clinical, 1 lab
Clinical:
Pregnancy loss - death of a normal foetus >10 weeks, 1 premature birth due to pre-eclampsia/placental infart or 3+ consecutive unexplained miscarriages
1 case of objectively confirmed thrombosis
What does antiphospholipid syndrome cause?
Acquired thrombophilia - 2-4% of new strokes
causes of 1/3 strokes in <50
Can be secondary to SLE
What is antiphospholipid antibody syndrome?
It is an acquired autoimmune thrombophilia characterised by vascular thrombosis, recurrent pregnancy losses with laboratory evidence
What is the first test considered for APS?
dRWT - Dilure Russel’s Viper Venom test
Factor V and X are directly activated and clotting time is measured - normal time is 23-27seconds
What is the confirmatory test?
Sensitive aPTT you increase the concentration of phospholipid - if APTT nromalises with increasing phospholipid conc then APS
What is the significance of antiphosphlipid antibodies?
They are insufficient to cause disease, is thought that second hit is needed to produce thrombosis
What is the management of APS?
You anti-coagulate them, warfarin is usually used however INR can be affected by presence of antibodies
How can pregnancy loss be avoided?
LMWH has some use in increasing live births
What are some causes of haemorrhagic disease of the newborn?
Vitamin K deficiency due to:
Low fetal liver stores
Maternal medications depleting stores
Reduced synthesis due to undeveloped gut bacteria
What are the 3 stages of presentation?
Early <24hr
Classic 1-7 days
Late>7 days
What are the common signs of HDN?
Intracranial haemorrhage
GI haemorrhage
Bleeding after circumcision
Bruising/purpura
What is the management?
Establish diagnosis with PT
Vit K iv if bleeding
FFP if severe bleeding
What is now given as prophylaxis?
IM vit k at birth
reduces rate from 1:400 to 1:400,000
What are the 2 mutations observed in essential thrombocytopaenia?
JAK2 50-60%
CALR 20-30%
What is the pentad of signs seen in TTP?
MAHA and low platelets!
Neurological dysfunction
renal failure
fever
What are the causes of TTP?
Idiopathic - without predisposing condition - familial Upshaw schulman - reduced/absent ADAMTS13
Secondary - secondary to causes such as cancer/sepsis/HIV/pregnancy/pill/and drugggggs
What is HIT?
It is when the platelet count drops on heparin administration to <30-50% of previous value within 5 days
There may be thrombo-embolic complications such as VTE/heparin induced skin lesions/venous gangrene
What is the HIT score?
Thrombocytopenia <30, 30-50, ~50
Timing - <5 days, >10days, 5-10 days
Thrombosis - none, progress/recurrence, new clot/skin necrosis
oTher cause - definite, possible, none seen
WHat is the pathogenesis of HIT?
Administration of heparin induces development of HIT antibodies. When heparin is bound to platelet factor 4 (PF4) formation of antibodies occurs in HIT. These are normally IgG to the PF4/Heparin complex. Platelets are activated via fc receptors and release procoagulant microparticles
