Bleeding Disorders (Autoimmune) - TTP, ITP

Question 1

What is TTP?

Answer 1

Thrombotic thrombocytopenia

Question 2

what is the pathological factor in TTP?

Answer 2

dysfunctional ADAM TS13 protein which is a vwf cleaving protease.

consequently: **vwf aggregates causing endothelial damage **which propagates development of thrombosis in small blood vessel.

network of fibrin deposited is macroangiopathic and lysis RBC - hemolytic anemia w/ schistocytes

Question 3

ADAM TS 13

Answer 3

VWF PROTEASE

Question 4

Functions of VWF

Answer 4

1- protects factor viii from liver metabolism - disorder of secondary hemostasis
2- platelets binds to collagen w/ help of vwf - disorder of primary haemostasis

Question 5

Describe the pathogenesis of common thrombocytopenia: ITP,TTP, DIC

Answer 5

ITP - Endothelial defect
ITP - Antiplatelet antibodies
DIC - Excess thrombin

Question 6

How Would TTP present?

Answer 6

Purpuric Rash
Fever
Menorrhagia
AKI
Neurological Sx
Haemolytic Anemia (jaundice, schistocytes, hepatosplenomegaly and lymphadenopathy)

Question 7

How to investigate TTP

Answer 7

FBC - Thrombocytopenia
Blood film - Schistocytes
Serum ADAM 13

Question 8

Investigating TTP

Answer 8

1st Prednisolone
2nd - caplacizumab (vwfi)

3-plasma exchange

4- Rituximab (Anti-B cell monoclonal antibody)

Consider - folic acid

Then long term - Aspirin

Question 9

Why does TTP not affect APTT/PT

Answer 9

Because it affects primary haemostasis - platelet disorder

Question 10

What the clinical difference between TTP and ITP

Answer 10

Clinically presenting TTP will have
Nx,
Lymphadenopathy
hepatosplenomegaly
and jaundice whilst ITP will not.

Also ITP will often be present in very young children 2-6/ post viral infection

Question 11

What is ITP

Answer 11

Immune thrombolytic purpura

Question 12

what is the pathological factor in ITP?

Answer 12

Autoimmune disease via

Auto IgG Ab which destroy integrin complex (glycoprotein 11b/111a) found on platelets.

These complexes are receptor/binding point for fibrinogen and vwf.

Lack of complex = Less Platelet plug formation

Question 13

How would an ITP patient present

Answer 13

Often in children

Usually self limiting
purpuric rash
no systemic sx

If Extremely sever - Primary haemostasis sx

Question 14

ITP DX

Answer 14

FBC AND BLOOD SMEAR
THROMBOCYTOPENIA
iNCREASED wcc

Bloodsmear - normal / exclude ddx

Serologyy - Quantitative IgG

Question 15

TX ITP

Answer 15

1st - Prednisolone
+ IV IG infusion

2nd - Rituximab

Acute attack -
Prednisolone
+ IV IG infusion + plasmapheresis