Haem

Question 1

What is the triad of HUS

Answer 1

Thrombocytopenia

Renal failure

Microangiopathich haemolytic anaemia (MAHA)

Question 2

Types of HUS

Answer 2

Typical (epidemic) or atypical

Question 3

Causes of Typical HUS

Answer 3

Infection with verotoxin producing enterococci e.g
E.coli 0157

Shigella

Question 4

Causes of atypical HUS

Answer 4

Rarer - poor diagnosis

Strep pneumoniae, CMV, HIV
Bone marrow transplant
Solid organ transplant
Qunine, heroin, ciclosporin
Malignancy
Pregnancy

Question 5

Pathophys of HUS

Answer 5

Toxin causes haemorragic colitis–> bloody diarrhoea and prodomal illness

AKI develops within a week –> direct injury to renal vascular epithelium

Platelet aggregatraion, micro thrombi

Hypertension and fluid overload commonly follow

Atypical - complement dysreguation

Question 6

Ix for HUS

Answer 6

FBC
Film –> reticulocytes, haemolysis, thrombocytopenia

Direct Coombs test - immune and non immune mediated

LDH - raised in haemolysis

HIV,

Renal screen

Question 7

Managig HUS

Answer 7

Supportive
Treat infectious cause - cipro for ecoli and shigella

Plasma exchange as difficult to tell from TTP
Recommended in atypical

In epidemia HUS - PEx, IVIg, steroids, antiplatelts have no role

Question 8

Which has worse prognosis, typical or atypical

Answer 8

atypical -25% (50% is ESRD)

Question 9

How does HUS differ from TTP,

Answer 9

spectrum of same disease process

Question 10

Featrues of TTP

Answer 10

Thrombocytopenia
MAHA
Fluctuating neurology
Renal impairment
Fever

Clotting now, DIC is late

Question 11

Pathology of TTP

Answer 11

deficiency of vWF cleaving protease (vWF-CP) or ADAMTS 13.

Can be genetic, lack of enzyme or acquired, presence of antibody

vWF activates and binds platelets in repsonse to injury
Inactivated when cleaved by vWF-CP.

With TTP , lack of vWF-CP means no cleavage.

Fibrin is deposited and thrombus propogated creating ischaemia. Red cells shred as they pass the fibrin/platelet mesh (MAHA)

Question 12

TTP management

Answer 12

PEx wth octaplas (FFP with ultrao large vWF)
Keep going for two daya after platelemt recovery
Removes antibodies

High dose pulsed methylpred

Rituximab in acute life threatening refractory disease

Low dose aspirin once plts>50

Red cell transfusion and folate.

Question 13

Threshold for neutropenia

Answer 13

0.5-1.0

NICE say 0.5 neutrophil count

Question 14

Neutropenic sepsis definition

Answer 14

neutropenia plus temp greater than 38

Question 15

Abx for neutropenic sepsis

Answer 15

Commonly tazocin with gent

If CVP add vanc

Question 16

What is TLS

Answer 16

Tumour lysis syndrome
Breakdown of malignant cells with 
High K
High PO3
Low Ca

Question 17

Pathophys of TLS

Answer 17

Cell lysis:

Release of K and PO

Binds Ca by PO, CaPO crystlises n tissue and renal tubules

Release of nucleic acids, metabolism –> rise in uric acid

AKI, arrhytmias, seizures, death

Question 18

Risk factors for TLS

Answer 18

High tumour load
High turnover of tumour cells
High LDH
High sensitivity to chemo
Pre-existing renal dysfunction +/- low urine output

Associated with acute leukaemias and high grade lymphoma e.g Burkitts

Question 19

Prevent TLS

Answer 19

Hydrate 3 litres per day
Avoid other uric acid forming agent - dieuretics, coffee, alcohol

Allopurinol - xanthine oxidase inhibitory
Rasburicase - urate oxidase preparation iv

Question 20

Management TLS

Answer 20

High hydration and urine output
100mls/hr/m2 BSA
Avoid furosemide

Rasburicase has a role in treating as well as preventing
Allopurinol does not
Electrolyte abnormalities corrected
RRT

Question 21

Is there a role for urine alkalinisation in TLS

Answer 21

No

Question 22

What are the causes of methaemoglobinaemia? How would it represent on an A-A gradient and what would the patients sats be?

Answer 22

It can be congenital (cytochrome b5 reductase deficiency) or acquired.
Acquired causes include exposure to drugs including:
Nitrates
Certain local anaesthetics – e.g. prilocaine, benzocaine
Certain antibiotics – e.g. dapsone
Analine dyes

Normal A-a gradient

Pa02 would be normal/high and O2 sats would be low as a result of the absorption spectrum of methaemoglobin
detected on pulse oximetry

Question 23

Why does methaemoglobinaemia cause hypoxia?

Answer 23

The ferrous ion Fe+2 in haem is oxidized to the ferric state Fe+3. Fe+3 ions have poor oxygen affinity. The remaining ferrous ions have increased oxygen affinity causing a left shift of the oxygen disassociation curve and reduced oxygen delivery to tissue.

Question 24

What is the treatment for methaemoglobinaemia?

Answer 24

Administer supplemental oxygen.

Intravenous methylene blue is a specific antidote, facilitating the reduction of methaemoglobin.

The role for hyperbaric oxygen and exchange transfusion remains anecdotal.