Immune Thrombocytopenic Purpura and Intracranial Haemorrhage a Formidable
Chrystal Calderon* and A Perez
Department of Neurosurgery, Eric Williams medical Sciences Complex, Champs Fleurs, Trinidad and Tobago
Submission: July 02, 2020; Published: September 14, 2020
*Corresponding author: Chrystal Calderon, Mailing address: Department of Surgery, EWMSC Champs Fleurs Trinidad and Tobago
How to cite this article: Chrystal C, A Perez. Immune Thrombocytopenic Purpura and Intracranial Haemorrhage a Formidable Medical Challenge. Open Access J Neurol Neurosurg 2020; 14(2): 555881.DOI: 10.19080/OAJNN.2020.14.555881.
To discuss the thought provoking and difficult clinical management of a case of spontaneous intracerebral haemorrhage and immune thrombocytopenic purpura (ITP).
A 6-year-old female, known ITP, presented with a one-day history of traumatic dislodged tooth, with associated neurological symptoms. However, her neurological status was alert and oriented, with absence of focal deficits. The complete blood count showed a platelet count of 26 x 109 /L and was in keeping with her known baseline platelet level. Computed tomography of the brain demonstrated three sites of cerebral contusions with no associated midline shift.
Hours after admission, there was progressive decline in the patient’s clinical status. Additionally, repeat blood investigations showed a downward trend in platelet counts. Aggressive medical management was implemented with the aid of neurosurgery, haematology, paediatrics, and the intensive care unit. Despite various therapeutic modalities, the patient succumbed to her underlying disorder.
On retrospective review, this patient had a severe phenotype of ITP. This was demonstrated by repeated oral mucosa bleeds, gastrointestinal bleeds and episodes of haematuria preceding this last admission. Despite multimodal therapies and the combined efforts of a multi-disciplinary team, the clinical management remained arduous.
Keywords:Immune thrombocytopenic purpura (ITP); Intracerebral haemorrhage; Medical management; Neurosurgical intervention
Abbreviations: ITP: Immune Thrombocytopenic Purpura; GCS: Glasgow Coma Scale
Thrombocytopenia may result from an impairment in platelet production, an increase in platelet consumption and splenic sequestration . ITP is thought to occur following a viral illness and may be self- limiting in children . Traditional terminology categorized the pathological course into acute and chronic phases. It may also be classified as newly diagnosed, persistent or chronic [3,4]. This case patient fell into the group of persistent- which is within 3- 12 months following diagnosis. Her initial diagnosis was established 6 months prior to this ultimate presentation, with prior recurrent visits to the emergency department with bruising over the body, conjunctival haemorrhages, and a lower gastro-intestinal bleed.
We believe there were combined underlying aetiologies- of trauma and spontaneous elements. There was a known history
of minor blunt trauma however, the pattern of haemorrhages on imaging is not consistent with an isolated traumatic injury. Spontaneous non-traumatic intracerebral haemorrhage in the paediatric population is far less common relative to the adult population. ITP will result in cerebral haemorrhage in 0.1%- 1% of cases, and the majority of published cases demonstrate that this will occur within the first 6 months of diagnosis .
A 6-year-old Afro-Caribbean female, known ITP, presented with a one-day history of a traumatic dislodged tooth with persistent bleed. Approximately 24 hours following the injury, the patient started complaining of headaches. The headaches were described as mild to moderate and was associated with nausea and 2 episodes of vomiting. On initial examination, her Glasgow
coma scale (GCS) was 15, with pupils equal and reactive bilaterally.
A complete blood count revealed a platelet count of 26 x 109 /L
and a computed tomography of the brain without contrast was
performed. It showed the presence of the three distinct foci of
hyper-densities in keeping with, cerebral contusions. A left frontal
lobe contusion of 2.6 cm x 2.3 cm, a right frontal lobe contusion
of 1.8 cm x 1.5 cm and left parietal lobe contusion 1.8 cm x 2.3
cm. There was no evidence of midline shift and the dimensions
of the ventricular system remained within normal limits. (Figures
1 & 2). Supportive medical management and neuro- observation
was commenced with the support of haematology and paediatric
medicine. An altered conscious level was noted 12 hours following
admission, with a drop in GCS to 9. An urgent blood panel was
requested showing a platelet count of 18 x 109 /L. Computed
tomography of the brain was repeated. It showed a moderate
increase in size of the cerebral contusions. The left frontal lobe
contusion measured 3.3cm x 2.7cm, right frontal lobe contusion
2.2cm x 1.9 cm and left parietal lobe contusion 2.3cm x 2.7cm.
There was no associated midline shift or ventricle effacement
once more (Figure 3).
New clinical manifestation of seizures presented within the
next couple of hours, and the patient remained in status epilepticus
for approximately 45 minutes. Examination findings showed a
dilated (5 mm), unreactive left pupil and a reactive, 3mm right
pupil. Her vital signs were deranged with elevated systolic blood
pressures (123-132 mmHg), tachypnoea and bradycardia (56- 60
beats per minute). Neurosurgical intervention was planned with
a bi-frontal decompressive craniectomy to aid with the increasing
cerebral edema. Paediatric intensive care physicians and
anesthesiologists were asked to consult on the case. The ultimate
decision was for resuscitative methods – including endotracheal
intubation, additional sedative and anticonvulsant medications
and achieving a suitable platelet count of 50- 100 109 /L for safe
surgical intervention. Attempts at improving the platelet count
failed over the upcoming days. The patient was transfused with a
total of 18 units of platelets. She was also administered intravenous
immune globulins, corticosteroid medication and tranexamic
acid. The platelet count remained low, fluctuating between 11-
14 x 109 /L. The course in paediatric intensive care unit was
complicated with the development of central diabetes insipidus
and radiological evidence of a right pulmonary haemorrhage. Her
GCS was assessed as 3 and pupils were dilated and unreactive
bilaterally on day 3 following admission. She underwent initial
brainstem death testing and unfortunately succumbed to her
condition on day 8.
ITP is an uncommon hematological condition occurring in
both the adult and paediatric age groups. The incidence in adults
and children are estimated as 0.2- 0.4 new cases per 10,000 /
annum and 0.2 – 0.7 new cases per 10,000/ annum, respectively
. The pathology of the disease stems from the imbalance of
platelet consumption and production. An autoimmune condition
develops where autoantibodies are formed against platelets
and their precursor, megakaryocytes. Autoantibodies binding
to the platelet membrane proteins leads to direct damage and
promotes the removal of these platelets from circulation by
phagocytosis in the liver and spleen . Megakaryocyte depletion
impairs the production of new platelets in the bone marrow and
hence, cannot compensate for the depletion taking place in the
circulatory system [6,7]. Based on this background, it is clear that
these patients will tend to bleed even from minor injury. These
include the presence of easy bruising over the limbs and trunk,
bleeding from mucus membranes, and difficult to control bleeds
from traumatic injury. ITP is diagnosed based on laboratory blood
investigation demonstrating an isolated thrombocytopenia of less
than 100 x109/L and an absence of any underlying predisposing
conditions . The normal platelet count usually lies within the
range of 150 x 109 /L and 450 x 109 /L; a count between 10-20
x 109 /L places a patient at risk for spontaneous haemorrhage
[1,3]. Based on World Health Organization (WHO) bleeding scale
this case patient falls into the highest category, Grade 4 – with
central nervous system bleeding on imaging study. This is denoted
as life-threatening, with a likelihood of permanent functional
impairment [9-11]. Fortunately, the probability of a fatal bleed or
a severe bleed in a child is low – with an evaluation of 0 %- 3 [4,8].
In children, some of the common associations of spontaneous
intracerebral haemorrhage include arteriovenous malformations,
cavernous angiomas, cerebral aneurysms, brain tumors and
hematological conditions [12,13]. The latter, which includes
coagulopathies, sickle cell disease and hemophilias, represent a
substantial risk factor in approximately 10-30% of cases [5,14].
The most common cerebral site affected is the supra-tentorial
region, with lobar haemorrhages. A poor prognostic outcome in
these cases are directly correlated to the site of haemorrhage as
with infratentorial bleeds, a low GCS on presentation, and younger
children (<3 years) [12,15,16].
Surgical intervention was considered in this case patient,
with a possible bifrontal craniotomy to attenuate the effects of an
elevated intracranial pressure. However, attempts at optimization
for safe surgical intervention faired unfavorable with falling
platelet counts. This is despite the use of several units of platelets,
and a combination of drugs- intravenous immunoglobulins, high
dose corticosteroid therapy and tranexamic acid - as recommended
[17,18]. Further steps to be considered was an emergency
splenectomy, which has shown to lead to a sustained rise in
platelet count post operation . We believe following through
with a craniectomy or splenectomy in this thrombocytopenic
state would have led to devastating intra-operative complications.
The presence of an intracranial haemorrhage in ITP has
devastating mortality rates, with estimations of 25%- 55% [5,20].
Additionally, there is noteworthy neurological morbidity that may
persist in non-fatal cases. This was a challenging neurosurgical
and haematological case to manage and it could not be done in
isolation. It required the combined efforts and decision-making
of neurosurgeons, haematologists, physicians, and anaesthetists.
Unfortunately, the patient succumbed to the sequelae of events
despite these efforts.
Intracranial haemorrhage resulting from ITP in the paediatric
population is not frequently seen in clinical practice. It carries
significant morbidity and mortality even with urgent aggressive
management- usually requiring a multi-disciplinary team. Our
case patient proved to be refractory to combination drug therapy
and platelet transfusions with no notable rise in platelet levels
during her course in-hospital. This case was a medical challenge
in optimization for safe surgical intervention.
(2018) US Department of Health and Human Services, National Institute of Health, National Cancer Institute. CTCAE (Common Terminology Criteria for Adverse Event) v5.0. National Cancer Institute Division of Cancer Treatment and Diagnosis.