Miscellaneous

Question 1

What is the molecular basis of PNH?

Answer 1

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

Question 2

Which GPIs are especially importnat in complement regulation?

Answer 2

CD55 and CD59 leading to increased complement sensitivity of PNH cells

Question 3

How does the complement system respond to PNH cells?

Answer 3

Intravascular haemolysis
promotion of inflammatory mediators
systemic Hb release

Question 4

How does PNH cause thrombosis?

Answer 4

Platelet activation through increased exposure of PS for PL surface for coagulation binding
NO depletion
Red cell and platelet microparticles

Question 5

What is the targeted treatment of PNH?

Answer 5

Eculizumab - monoclonal antibody which targets C5 - MAC is not formed

Question 6

What are the 3 antibodies seen in antiphospholipid syndrome?

Answer 6

lupus anticoagulant
anti cardiolipin
anitb2gpi

These must be present on 2 occasions 3months apart

Question 7

What is needed for diagnosis of antipospholipid syndrome?

Answer 7

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

Question 8

What does antiphospholipid syndrome cause?

Answer 8

Acquired thrombophilia - 2-4% of new strokes
causes of 1/3 strokes in <50
Can be secondary to SLE

Question 9

What is antiphospholipid antibody syndrome?

Answer 9

It is an acquired autoimmune thrombophilia characterised by vascular thrombosis, recurrent pregnancy losses with laboratory evidence

Question 10

What is the first test considered for APS?

Answer 10

dRWT - Dilure Russel’s Viper Venom test

Factor V and X are directly activated and clotting time is measured - normal time is 23-27seconds

Question 11

What is the confirmatory test?

Answer 11

Sensitive aPTT you increase the concentration of phospholipid - if APTT nromalises with increasing phospholipid conc then APS

Question 12

What is the significance of antiphosphlipid antibodies?

Answer 12

They are insufficient to cause disease, is thought that second hit is needed to produce thrombosis

Question 13

What is the management of APS?

Answer 13

You anti-coagulate them, warfarin is usually used however INR can be affected by presence of antibodies

Question 14

How can pregnancy loss be avoided?

Answer 14

LMWH has some use in increasing live births

Question 15

What are some causes of haemorrhagic disease of the newborn?

Answer 15

Vitamin K deficiency due to:
Low fetal liver stores
Maternal medications depleting stores
Reduced synthesis due to undeveloped gut bacteria

Question 16

What are the 3 stages of presentation?

Answer 16

Early <24hr
Classic 1-7 days
Late>7 days

Question 17

What are the common signs of HDN?

Answer 17

Intracranial haemorrhage
GI haemorrhage
Bleeding after circumcision
Bruising/purpura

Question 18

What is the management?

Answer 18

Establish diagnosis with PT
Vit K iv if bleeding
FFP if severe bleeding

Question 19

What is now given as prophylaxis?

Answer 19

IM vit k at birth

reduces rate from 1:400 to 1:400,000

Question 20

What are the 2 mutations observed in essential thrombocytopaenia?

Answer 20

JAK2 50-60%

CALR 20-30%

Question 21

What is the pentad of signs seen in TTP?

Answer 21

MAHA and low platelets!
Neurological dysfunction
renal failure
fever

Question 22

What are the causes of TTP?

Answer 22

Idiopathic - without predisposing condition - familial Upshaw schulman - reduced/absent ADAMTS13
Secondary - secondary to causes such as cancer/sepsis/HIV/pregnancy/pill/and drugggggs

Question 23

What is HIT?

Answer 23

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

Question 24

What is the HIT score?

Answer 24

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

Question 25

WHat is the pathogenesis of HIT?

Answer 25

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