Page 263 - Medicine and Surgery

P1: KPE
BLUK007-06 BLUK007-Kendall May 25, 2005 18:6 Char Count= 0

Chapter 6: Disorders of the kidney 259

present in the same patient. The characteristic features thereisadeficiencyofthisenzyme,ULvWFmultimers
of TTP–HUS are microangiopathic haemolytic anaemia accumulate and cause platelet aggregation.
(MAHA)andthrombocytopenia,withvariablerenaland Lack of other inhibitors or antibodies against them
neurological abnormalities. have also been postulated.

Incidence/prevalence Clinical features
HUS is one of the commonest causes of ARF in children. Patients may present with some or all of the following.
Haemolytic anaemia with mild jaundice, lethargy.

Age Thrombocytopenia which may result in purpuric rash
More common in children and young adults. or bleeding.
Acute renal failure (usually oligo-/anuric).

Neurological abnormalities including headache and
Geography
confusion, seizures and coma.
Clusters and epidemic foci suggest an infective trigger.
Fever.

Aetiology
Microscopy
There appear to be inherited and acquired forms of HUS
Thrombi mainly composed of platelets are found in ar-
and TTP.
terioles and fibrin deposits are seen in the endothelium
The epidemic form of HUS has been associated with a

of glomerular capillaries. This causes a focal segmen-
variety of bacterial and viral agents, including a vero-
tal glomerulonephritis. Widespread hyaline thrombi are
toxin (also called Shiga toxin) produced by Escherichia
seen in TTP.
coli (O157:H7).
Many cases of TTP are idiopathic.

There is an association of TTP–HUS with later stages Investigations

of pregnancy, SLE and certain drugs. TTP-HUS should be suspected in any case of throm-
bocytopenia and microangiopathic haemolytic anaemia
Pathophysiology (without another clinically apparent cause)
FBC and peripheral blood film: Anaemia, thrombo-
There are several postulated mechanisms.
It has been suggested that an initial toxic insult to the
cytopenia, film shows schistocytes and ‘helmet cells’
vascular endothelium may induce platelet activation. (fragments of red blood cells) and increased reticu-
This results in intravascular coagulation and haemol- locytes. Direct antiglobulin test must be negative (to
ysis of red blood cells. Certain individuals appear to be exclude an immune cause). Clotting profile should be
moresusceptible,perhapsduetoinheritedoracquired normal.
abnormalities of their coagulation/platelet activation U&Es to look for renal failure and hyperkalaemia.
systems. Dipstick may show some proteinuria and be positive
In E. coli O157 associated HUS, the verotoxin ap-
for blood because of haemoglobinuria, but urine mi-
pears to act by several mechanisms, including a di- croscopy usually shows few red cells.
rect platelet-aggregating effect, a toxic effect on the Serum bilirubin and LDH are raised and haptoglobins
endothelium and neutrophil activation. are very low due to the haemolysis.
InfamilialTTPpatientshaveahereditarydeficiencyof

vonWillebrand Factor (vWF) cleaving protease, and Management
many patients with non-familial TTP have an anti- Early diagnosis and treatment is needed to prevent irre-
body directed against this enzyme. vWF is produced versible renal failure and to reduce mortality. The treat-
by endothelial cells and forms Ultra Large (ULvWF) ment of choice is plasma exchange with fresh frozen
multimers which circulate in the plasma and promote plasma. Without this, TTP-HUS in adults had a ∼90%
aggregation of activated platelets. VWF cleaving pro- mortality. In contrast, HUS in children due to O157 of-
teasebreaksthesemultimersdownrapidly;however,if tenresolves spontaneously with supportive therapy, e.g.