|
Hemolytic Uraemic Syndrome
Associated with Pregnancy
S heikh
N.M., Kettern M.A., Ahmed A/H.A.
Department of
Anesthesia/ICU, Hamad Medical Corporation
Doha, Qatar
  Abstract:
Hemolytic uraemic syndrome (HUS) and thrombotic
thrombocytopenic purpura (TTP) are described as
acute syndromes with multisystem abnormalities
and pentad of thrombocytopenia, microangiopathic
hemolysis, neurological symptoms, renal
impairment and fever. Both diseases were
believed to form a continuum of the same
disease, but recently it was found, that they
were having a different pathophysiology, as TTP
patients have a deficiency in von wilbrand
factor (vWF) cleavage protease.
When renal involvement is severe with little or
no neurological manifestation, this
microangiopathy is termed as haemolytic-uraemic
syndrome. If the hemolytic uraemic syndrome is
not associated with diarrhoea, it is called
D-negative or atypical HUS. This subdivision is
of etiological and prognostic importance.
TTP-HUS is associated with high maternal and
fetal morbidity and mortality. Treatment of
these syndromes differs from syndrome of
hemolysis with elevated liver enzymes (HELLP
syndrome) and acute fatty liver of pregnancy
hence accurate diagnosis is important for
optimal therapy.
Plasma transfusion and plasmapheresis have
revolutionized management of TTP and HUS by
increasing survival 80% to 90%.
Here we are reporting a case of D-negative
hemolytic uraemic syndrome associated with
pregnancy causing intrauterine fetal death.
Diagnosis made on clinical and hematological
findings, successfully treated by plasmapheresis
with residual maternal renal impairment.
We are presenting this case, as it is rare
disorder associated with high mortality and
morbidity, to increase awareness about disease,
its diagnosis and management.
Key words: Microangiopathies, hemolytic
uremic syndrome, throm- botic thrombocytic
purpura, HELLP syndrome, fatty liver,
plasmapheresis.
 Introduction:
Thrombotic thrombocytopenic purpura and
hemolytic uremic syndrome are rare thrombotic
microangiopathies characterized by occlusion of
arterioles and capillaries with thrombi.
Thrombocytopenia, hemolysis associated with
varying degree of neurological and renal
impairment is characteristics of this disease.
Until recently both diseases were thought to be
having the same pathophysiology but now it has
been demonstrated that patients with TTP have a
deficiency of plasma protease (1)
responsible for cleavage of large von will brand
factor (vWF). These microangiopathies are
associated with high maternal and fetal
morbidity and mortality(2).
The treatment of this micro-angiopathies is
totally different from that of syndrome of
hemolysis; low platelet elevated liver enzymes
and acute fatty liver during pregnancy, so an
accurate diagnosis is essential for optimal
therapy.
Here we are
reporting a case of hemolytic uraemic syndrome
associated with pregnancy, which was
successfully managed in the surgical intensive
care unit of our hospital.
Illustrative
Case:
Thirty-three years old patient admitted with
intrauterine fetal death (IUFD), dropped her
hemoglobin and platelet count, her coagulation
profiles were normal and there was no vaginal
bleeding.
She underwent vaginal delivery of fetus next day
there was significant blood loss, resuscitated
with packed red blood cell, fresh frozen plasma
and platelet concentrate. She was stable
hemodynamically, but started to become oliguric,
with thrombocytopenia and anaemia in spite of
transfusions so she was transferred to Surgical
Intensive Care Unit.
In Intensive Care Unit she was fully awake, no
neurological abnormality, her vital signs were
stable, blood pressure and central venous
pressure were on higher side. She became anuric,
started on lasix infusion and labetalol infusion
to control her blood pressure. She responded to
lasix and started to pass urine, blood pressure
controlled with labetalol. But serum creatinine
was raising, she was febrile, thrombocytopenic
and anaemic even with transfusion of blood and
blood product according to complete blood count
data. Her lactic dehydrogenase (LDH) were very
high and liver function were normal, coagulation
profiles was not deranged, septic workup was
negative, ultrasound abdomen not showed any
collection only both renal cortex were
hyperechogenic and peripheral smear showed
schistocyte >21%, hemolytic uraemic syndrome
suspected. Hematologist and Nephrologist
confirmed the diagnosis and decided to start
plasmapheresis. On third day of admission she
was passing good amount of urine lasix was
stopped, creatinine levels were stable, LDH
levels decreasing and by sixth day platelet
increased to more then 100,000. Started her on
oral tenormine and Norsac and weaned from
labetalol infusion. Plasmapheresis stopped on
7th day.
She was started
on normal diet and transferred to the ward from
there she was discharged home one week later and
was followed in by the Nephrologist in the
Outpatient Department for her residual renal
impairment.
Discussion:
Thrombotic microangiopathy typically present
with classic pented of thrombocytopenia,
microangiopathic hemolysis, neurological
manifestation, renal impairment and fever (3).
When thrombotic
microangiopathy associated with pregnancy two
entities have to be considered, first thrombotic
thrombocytopenic purpura (TTP)-hemolytic uremic
syndrome (HUS) and secondly severe preeclampsia
with hemolysis, elevated liver enzymes and low
platelets. The differential diagnosis in these
two entities is important for therapeutic and
prognostic reasons. In our case clinical,
hematological parameters and timing of
presentation were suggesting diagnosis of
hemolytic uraemic syndrome.
TTP-HUS often occurs
in postpartum period symptoms often delayed for
48 hours or more after delivery(4).
TTP-HUS used to be
considered as a variant of the same disease but
recent evidence suggests, that patients with TTP
are having a deficiency of protease enzyme,
responsible for cleavage of larger vWF(5).
Till this test is freely available, the
differentiation between this two diseases is
based on involvement of neurological symptoms in
TTP and more severe renal impairment in HUS(6).
As our patient was having renal shutdown,
thrombocytopenia, fever and hemolysis without
CNS symptoms, the diagnosis was hemolytic-uraemic
syndrome.
HUS was first
described in 1955(7).
HUS is subdivided in two forms: the typical
form, which is associated with infectious
diarrhea and an atypical or D-negative form
without diarrhea(8).
This subdivision is important for diagnosis and
prognostic value(9).
Our case was D-negative hemolytic-uremic
syndrome.
TTP-HUS is
associated with high maternal and fetal
mortality and morbidity. Weiner in review of 40
cases of TTP and HUS reported maternal mortality
of 44% and associated fetal loss rate of 80%(10).
Plasma transfusion
and plasmapheresis have revolutionized the
management of TTP and HUS.
The use of plasma
transfusion as first line of therapy during
pregnancy yielded response rate of 64%(11).
Plasmapheresis should be started as early as
possible. Onundarson et al demonstrated initial
response rate to plasmapheresis was 81%; seventy
four percent of initial nonresponders died and
38% of those responded initially needed
additional therapy(12).
Other therapies have
a lower response rate, glucocorticoids are less
effective than plasma transfusion(13).
Other treatments include immunoglobulin,
vincristine(14),
cyclosporine and azathioprine(15).
Lastly to mention in spite of hazard of
thrombosis, massive hemorrhage can occur in TTP
and HUS. It is advisable to infuse platelets in
case of life threatening bleeding(16).
Spleenectomy has been reported to induce
long-term remission inpatients refractory to
plasmapheresis.
Our case responded
initially to plasmapheresis and did not require
any other additional therapy.
Conclusion:
Early accurate diagnosis with aggressive
treatment with plasmapheresis is cornerstone of
management of TTP and HUS.
|
Figure 1: Serum Creatinine
and Platelet Counts
|
References:
1. Tsai HM, lian E,.Antibodies to
von will brand factor cleavage protease in
thrombotic thrombocytopenic purpura. N Eng J Med
1998; 339: 1585.
2. Robert S, Egerman, Andrea G,
Steven A, Sibai MB. Thrombotic thrombocytopenic
purpura and haemolytic uremic syndrome: Review
of 11 cases. Am J obstet Gynecol 1996; 175:
950-6.
3. Ridoffi RL, Bell WR.
Thrombotic thrombocytic purpura: Report of 25
cases and review of literature. Medicine
(Baltimore) 1981; 60: 413-28.
4. George JN. The association of
pregnancy with thrombotic thrombocytopenic
purpura-hemolytic uraemic syndrome. Curr opin
Hematol 2003; 10: 339.
5. Furlan M, Robles R, Galbusera
M. Von will brand factor cleaving protease in
thrombotic thrombocytopenic purpura and
hemolytic uraemic syndrome Eng J med 1998; 339:
1578.
6. Wun T, Bahuo WF. Thrombotic
thrombocytopenic purpura. In http://www.emedicine.com/MED/topic
2265.htm.
7. Gasser C, Galltier E, Steek A.
Hemolytic-uremic syndrome: Bilateral necrosis of
renal cortex in acute haemolytic anemia. Schweiz
med wochenchr 1955; 85: 905.
8. Fitzpatrick NM, Walters MDS,
Trompeter FS. Atypical hemo- lytic uraemic
syndrome in childhood pediatr 1993; 122: 532.
9. Biega T, Prausser R.
Hemolytic-uremic syndrome. In http:// www.
emedicine.com/MED/hmt.
10. Wiener CP. Thrombotic
microangiopathy in pregnancy and postpartum
period.seim Hematol 1987; 24: 119-29.
11. Davies GE. Thrombotic
thrombocytopenic purpura in pregnancy with
maternal survival: A case report. Br J obstet
1984; 91: 396-8.
12. Onundarson PT, Rowe JM, Heal
JM, Francis CW. Response to plasma exchange and
spleenectomy in thrombotic thrombo- cytopenic
purpura: A 10 years experience at single
institution. Arch Int med 1992; 152: 791-6.
13. Bell WR, Braine HG, Ness PM,
Kicker TS. Improved in throm- botic
thrombocytopenic purpura–hemolytic uraemic
syndrome. Eng J med 1991; 325: 398-403.
14. Levin M, Grunwald HW. Use of
vincristine in refractory thrombotic
thrombocytopenic purpura. Acta Hematol 1999; 85:
37-40.
15. Moake JL, Rudy CK, Troll JH.
Therapy for chronic relapsing thrombotic
thrombocytopenic purpura with prednisolone and
azathioprine. Am J Hematol 1985; 20: 73-9.
16. George JN, EL Harake M.
Thrombocytopenia due to enhance platelet
destruction by non-immunological mech. I n
Beutler E, Lichman MA, Coller BS, Kipps TJ
editors. Williams’s hemato- logy 5th ed. New
York: McGraw Hill 1995: 1290. |
