Keywords
intra cerebral hemorrhage - ITP - craniotomy - splenectomy
Introduction
Intracerebral hemorrhage (ICH) is a life-threatening complication of immune thrombolytic
purpura (ITP). ITP results in cerebral hemorrhage in only 0.1 to 1% of cases.[1] Spontaneous nontraumatic ICH is uncommon in the adult population compared with the
pediatric population.[2] Management of ICH in these patients is highly challenging due to deranged hematology.
Also, there is limited literature about managing life-threatening ICH due to ITP,
especially in the adult population. In literature search, we found only five adult
cases of intracranial hemorrhage in ITP[3]
[4]
[5]
[6]
[7]
[8] ([Table 1]).
Table 1
Registries of patient with ITP who had developed intracerebral hematoma
|
Sr. no.
|
Author (year)
|
No. of adult patients
|
Age/sex
|
Medical Mx
|
Splenectomy
|
Neurosurgical management
|
Outcome
|
|
1
|
Carpenter et al (1959)3
|
2
|
Age not specified
|
Plt/S
|
No
|
No
|
Death
|
|
2
|
Nagler et al (1986)4
|
1
|
32/M
|
Plt/S
|
No
|
No
|
Survived
|
|
3
|
Awerbuch and Sandyk (1987)5
|
1
|
26/F
|
Plt/S/IVIG
|
No
|
No
|
Survived
|
|
4
|
Brenner et al (1988)6
|
2
|
25/F
32/M
|
S/Plt
S/Plt
|
Yes
Yes
|
No
No
|
Death
Survived
|
|
5
|
Lee and Kim (1998)7
|
3
|
28/F
81/F
22/F
|
Plt/S
S
Plt/S/IVIG
|
Yes
No
Yes
|
Yes
No
No
|
Survived
Died
Survived
|
|
6
|
Gellens et al(2018)8
|
1
|
29/M
|
Plt/R
|
No
|
Yes
|
Survived
|
Abbreviations: IVIG, intravenous immunoglobins; Plt, platelets; S, splenectomy.
The decision about the emergency craniotomy in a patient with signs and symptoms raised
intra-cranial tension (ICT) is often deferred due to very low platelet counts.[2] The availability of modern drugs to improve the platelet count takes time to enhance
platelet function before the surgery. In this tricky situation, a timely splenectomy
can rapidly improve platelet functions.[9] It can help decide safe and early craniotomy, which can change the overall outcome
in these patients. We described a life-threatening spontaneous ICH in an adult patient
with chronic ITP who underwent emergency splenectomy followed by craniotomy to evacuate
hematoma with an excellent clinical outcome.
Case Report
A 30-year-old male patient was brought to emergency medical services (EMS) with a
sudden severe headache with vomiting. He was a known case of ITP diagnosed a few years
back and was not taking any medication. At the time of arrival to EMS, he was fully
conscious and well-oriented to time, place, and person. His pupils were bilaterally
3 mm in size and briskly reacting to the light. His Glasgow coma scale was 15/15,
and his power was an MRC (Medical Research Council) scale of 5/5 in all four limbs.
Emergency computed tomography (CT) scan revealed a large right frontal ICH with significant
perilesional edema, mass effect, and midline shift of approximately 13 mm ([Fig. 1A]). Hematological investigation revealed a platelet count of approximately 2,000/µL
and a low hemoglobin level. Ultrasonography scan of the abdomen revealed splenomegaly.
Because of preserved neurology and abnormal hematological parameters, the patient
was initially treated conservatively in the form of intravenous antiepileptics, antiedema
measures, diuretics, and steroids. He received one unit of single donor platelets
(SDP), and the count increased from 2,000/µL to 3,000/µL. However, after 36 hours
of treatment, he became progressively drowsy and developed left-sided weakness. A
repeat CT scan brain revealed an increase in perilesional edema, mass effect, and
midline shift ([Fig. 1B]). Due to progressive neurological deficit and increased perilesional edema, decompressive
surgery was imminent. However, surgery was out of the question because of meager abnormal
platelets count of 3,000/µL. After consultation with a physician, hematologist, and
general surgeon, the decision was taken about emergency splenectomy. The patient underwent
an emergency open splenectomy under general anesthesia with an SDP cover. During surgery,
no abnormal bleeding was observed. Six hours later, the platelet count was 85,000/µL,
so craniotomy was decided.
Fig. 1 Computed tomography (CT) scan of the brain plain study showing large right frontal
intracerebral hematoma with perilesional edema, mass effect, and midline shift (A). Repeat CT scan brain plain study after 36 hours showing increase size of the hematoma,
perilesional edema, mass effect and midline shift (B).
He underwent cranial surgery under general anesthesia. The right-extended hemicoronal
incision was taken, the scalp flap was elevated, and the left frontoparietal craniotomy
was performed. The brain was full and weakly pulsatile. The intracerebral hematoma
was evacuated out. The brain became completely lax and nicely pulsatile at the end.
Dura closed primarily, the bone flap kept back, and the wound closed in layers.
Postoperatively, the patient was extubated after 24 hours. His consciousness improved,
and his left limb power improved to an MRC scale of 5/5. On the seventh postoperative
day, he was fully conscious and well-oriented to time, place, and person without neurological
deficits. His platelet counts progressively increased from 85,000 to 600,000/µL. His
repeat CT scan brain revealed significant resolution in the mass effect and midline
shift ([Fig. 2]). At 6 months of follow-up, he was neurologically intact.
Fig. 2 Postoperative computed tomographic scan of the brain showing almost near complete
evacuation of the hematoma with operative changes.
Discussion
ITP is an uncommon hematological condition in adults and pediatric age groups. The
incidence in adults and children is approximately 0.2 to 0.4 new cases per 10,000/annum
and 0.2 to 0.7 new cases per 10,000/annum, respectively.[9] Thrombocytopenia is defined as a platelet count below the lower limit of normal
(< 150,000/µL for adults). Degrees of thrombocytopenia can be further subdivided into
mild (platelet count 100,000–150,000/µL), moderate (50,000–99,000/µL), and severe
(< 50,000/µL).[10] The acronym ITP stands for “immune thrombocytopenia” and has, by international agreement,
replaced the term ITP. It is because ITP is no longer idiopathic. The cause of ITP
is an autoimmune reaction against platelets and megakaryocytes.[11]
[12] The immune response involves different pathogenetic mechanisms. The most common
causes include (1) the formation of autoantibodies 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.[13]
[14]
[15] (2) Megakaryocyte depletion impairs the production of new platelets in the bone
marrow, and relative thrombopoietin deficiency leads to impaired thrombopoiesis.[16]
[17]
[18]
[19] (3) Reduced regulatory T lymphocytes lead to immune dysregulation causing direct
damage to the platelets.[20]
Based on international consensus again, ITP should only be diagnosed if the platelet
counts are repeatedly below 100,000/µL. The therapy and therapeutic goals change with
the duration and severity of the disease. Therefore, the traditional distinction of
“acute” and “chronic” ITP was abandoned, and a new division into three condition and
treatment phases was developed and adopted from the guidelines into newly diagnosed
(< 3 months), persistent (3–12 months), and chronic (> 12 months).[21] Treatment of ITP depends on the severity of the bleeding. Numerous bleeding scores
have been developed to assess the bleeding severity.[22] The World Health Organization (WHO) bleeding scale or the National Cancer Institute
Common Terminology Criteria for Adverse Events (NCI-CTCAE) is often used.[23]
[24]
[25] They are well-established in clinical practice and familiar to most physicians,
including nonhematological specialists.
ICH is a fatal complication of this pathology. Spontaneous nontraumatic ICH is uncommon
in the adult population compared with the pediatric population. Due to deranged hematology,
managing ICH in these patients is highly challenging. The severity of bleeding in
adults should be graded according to the NCI-CTCAE and classified into four grades.[9] Our patient had grade 4 severity of bleed, which was life-threatening, so surgical
intervention was considered. There is a clear indication for splenectomy for all patients
with persistent or chronic thrombocytopenia and severe bleeding (WHO III, IV) who
do not respond sufficiently to all other treatment modalities. In emergencies (e.g.,
life-threatening bleeding that does not respond to steroids and intravenous immunoglobulins),
splenectomy is even the therapy of choice because treatment with thrombopoietin receptor
agonist (TRAs) or rituximab is not immediately effective but needs some time to increase
the platelet counts and stop the bleeding (often > 1 week). There is no compelling
indication for splenectomy.[26]
[27] Neurosurgical intervention in ITP is usually craniotomy with evacuation of the bleed.
It is usually warranted when the patient's platelet counts are greater than 70,000/µL.[9] Also, other factors that should be considered are hemorrhage in an accessible location
for evacuation, level of consciousness deterioration, and new-onset neurological deficit.[5]
Very few adult cases of ITP with ICH have been reported in the literature, as it is
more common in children. Carpenter et al[3] reported the first case of this kind in 1959, where the patient was treated with
platelets and splenectomy. However, no neurosurgical intervention resulted in the
patient's death. Later in 1998, a case report published by Lee and Kim.[7] showed that neurosurgical intervention was done after splenectomy when the platelets
increased and the patient survived. A recent case report by Gellens et al[8] in 2018 mentions splenectomy and drug romiplostim as a second-line measure for rapid
increase in platelets prior to neurosurgical intervention. In our case report, the
patient underwent craniotomy and bleed evacuation after splenectomy after his platelets
count improved.
The presence of an intracranial hemorrhage in ITP has devastating mortality rates,
with estimations of 25 to 55%.[28] It was a challenging neurosurgical and hematological case. It required the combined
efforts and decision-making of neurosurgeons, hematologists, physicians, and anesthetists.
Due to active efforts from a multidisciplinary team, the patient recovered completely
without any neurological deficit.
The spleen derived autoantibodies bind with antigen, primarily gpIIb/IIIa and gp1b/IX
on the surface of the platelets. FcyR expressing splenic macrophages internalize antibody-coated
platelets, degrade them, and present them to autoreactive CD4 + T cells. These activated
cells interact with B cells through the CD40/CD40L interaction leading to somatic
hypermutation and class switching. Auto reactive B cells than differentiate in to
antiplatelets antibody producing plasma cells that either stay in the spleen or migrate
to the blood and bone marrow. Megakaryocytes in the bone marrow express platelets
glycoprotein such as gpIIb/IIIa and gp1b/IX and autoantibodies against these antigens
impair platelet production and contribute megakaryocytes apoptosis that leads to thrombocytopenia.
Thus, splenectomy immediately halts destruction of platelets and production of plasma
cells results in improved platelets counts.[29]
Conclusion
ICH is a devastating complication of ITP, both in adults and children. Management
of such cases is equally challenging. It carries significant morbidity and mortality.
In a life-threatening situation, a timely decision of emergency splenectomy followed
by craniotomy can result in an excellent clinical outcome. Our case advocates the
importance of a multidisciplinary team approach and aggressive decision-making in
a clinal scenario.
