(Stroke. 1998;29:2002-2003.)
© 1998 American Heart Association, Inc.
Depressed Platelet Status in an Elderly Patient With Hemorrhagic Stroke After Thrombolysis for Acute Myocardial Infarction
R. T. F. Cheung, MBBS, PhD, MRCP
Division of Neurology,
Department of Medicine,
Queen Mary Hospital,
Hong Kong
To the Editor:
I read with great interest the above-titled article by Serebruany and
colleagues.1 This report is special because prospective
data are available regarding the changes of platelet functions before
the occurrence of hemorrhagic stroke following
thrombolysis.1 I would like to make the following comments
and report the case of an elderly Chinese man who developed a
cerebellar hematoma after thrombolysis for acute myocardial infarction
(MI) when thrombocytopenia was induced by low-molecular-weight
heparin.
First, hemorrhagic stroke is a major complication of thrombolysis for
acute MI, even though patients with a recent history of stroke were
excluded from clinical trials on thrombolysis in acute
MI.2 3 In general, hemorrhagic stroke after thrombolysis
in acute MI occurs within the first 24 to 48 hours of treatment; the
hematoma is commonly lobar in location and occasionally multifocal; and
the risk of hemorrhagic stroke is greater with tissue plasminogen
activator than streptokinase.2 3 I wonder whether the
index patient of Serebruany et al1 had a history of recent
transient ischemic attack or a history of stroke longer than 6 months.
I also wonder whether his arterial blood pressure was high when he was
treated with tissue plasminogen activator. The platelet count was
normal, but the activated partial thromboplastin time was mildly
prolonged at 36 hours after thrombolysis,1 and I am
interested in knowing about any disturbance in his coagulation and/or
platelet count immediately after the development of neurological
symptoms at 44 hours.
Second, I have two concerns when reviewing the comprehensive platelet
function tests. Although many platelet functions of the index patient
were rather "abnormal" compared with the mean results of the group
of patients with acute MI and those of the control group, the absolute
results were either within or very close to the lower limit of the
"normal" range provided by the two groups of subjects (see the
Table1 ). It would be interesting to speculate why
hemorrhagic stroke did not occur in the other patients and control
subjects whose results were more abnormal than those of the index
patient in some platelet function tests. In addition, the platelet
functions appeared to improve spontaneously in all patients, including
the index patient, after thrombolysis. Nevertheless, the hemorrhagic
stroke occurred at 44 hours after thrombolysis in the index patient,
when his platelet functions were improving (see the
Figure1 ). While it is unfortunate that the results of
platelet function tests at a later time were unavailable, I wonder
whether the authors can explain the timing of hemorrhagic stroke in
relation to the changes in platelet functions of the index patient.
Finally, I would like to briefly describe a 76-year-old Hong Kong
Chinese man whose depressed platelet count contributed to the
occurrence of hemorrhagic stroke after thrombolysis for acute MI. This
patient, who had no history of stroke or transient ischemic attack,
presented initially with chest pain and ECG changes indicating acute
inferior MI. Streptokinase (1.5 million U IV) was given over a 1-hour
period, and his chest pain subsided, together with complete resolution
of the ECG changes. Subsequently, he was given subcutaneous
low-molecular-weight heparin and oral aspirin (300 mg loading dose
followed by 150 mg daily). Serial cardiac enzymes confirmed acute MI.
Forty-six hours after his first MI, his chest pain recurred with ECG
changes of acute anterior MI. A second dose of streptokinase was given,
and once again his chest pain subsided, together with complete
resolution of the ECG changes. Ten hours after the second dose of
streptokinase, he awoke with a headache, confusion, and dizziness.
Urgent CT of his brain revealed a right cerebellar hematoma 2.5 cm in
diameter; blood tests revealed coagulopathy and thrombocytopenia, and
his platelet count was reduced to 89 000/mL. His arterial blood
pressure remained stable throughout the admission. The cerebellar
hematoma was managed conservatively, together with cessation of
low-molecular-weight heparin and aspirin and transfusion of fresh
frozen plasma and platelet concentrate. He was discharged without
neurological deficit, and his latest platelet count was 269 000/mL.
The thrombocytopenia was probably induced by treatment with
low-molecular-weight heparin,4 and the antiplatelet
antibody was negative. I wonder whether the authors have encountered
thrombocytopenia following thrombolysis and use of heparin in patients
with acute MI.
References
1.
Serebruany VL, Gurbel PA, Shustov AR, Dalesandro
MR, Gumbs CI, Grabletz LB, Bahr RD, Ohman EM, Topel EJ, for the
GUSTO-III Investigators. Depressed platelet status in an elderly
patient with hemorrhagic stroke after thrombolysis for acute myocardial
infarction. Stroke. 1998;29:235–238.[Abstract/Free Full Text]
2.
The GUSTO Investigators. An international randomized
trial comparing four thrombolytic strategies for acute myocardial
infarction. N Engl J Med. 1997;329:673–682.[Abstract/Free Full Text]
3.
Cheung RTF. Neurological complications of heart
disease. Baillieres Clin Neurol. 1997;6:337–355.[Medline]
[Order article via Infotrieve]
4.
Warkentin TE, Levine MN, Hirsh J, Horsewood P, Roberts
RS, Gent M, Kelton JG. Heparin-induced thrombocytopenia in patients
treated with low-molecular-weight heparin or unfractionated heparin.
N Engl J Med. 1995;332:1330–1335.[Abstract/Free Full Text]
Response
Victor L. Serebruany;
MD;
PhD Paul A. Gurbel, MD, FACC
for the GUSTO-III Investigators,
Sinai Center for Thrombosis Research,
Baltimore, Maryland
We thank Dr Cheung for his interest and comments regarding our
GUSTO-III case report.1 Indeed, they are the only
prospective data available that support the concept of platelet
hypofunction as a risk factor for intracranial hemorrhage after
systemic thrombolysis for MI. Dr Cheung correctly points out that known
cerebrovascular disease and systemic hypertension are risk factors for
intracranial hemorrhage following thrombolytic therapy with any agent.
Neither of these risk factors was present in our patient. Coagulopathy,
either induced or spontaneous, also can increase hemorrhagic events but
was not observed significantly in the index patient. Moreover, the
platelet count in our patient was stable throughout the hospital
course.
Dr Cheung also correctly points out that a few of the acute MI patients
exhibited slightly higher platelet aggregation than our patient in
response to collagen and ristocetin; however, the index patient
represented the lowest level in 7 of 14 of receptor expression and
function tests. Clearly, there is heterogeneity of platelet activity in
acute MI, and not all patients have highly active
platelets.2 Our major concern, and the stimulus for this
report, involves the uniform dosing regimens of antiplatelet agents in
many clinical trials, particularly those involving the elderly, without
accounting for the variability of baseline platelet function.
Occurrence of stroke depends on multiple factors.3
Platelet hypofunction may be just one of them. Later after
thrombolysis, the pattern of platelet characteristics was similar
between the described patient and the rest of the acute MI group;
however, platelet function remained well below the mean. The GUSTO-III
platelet study assessed platelets in a prospective manner over the
first 24 hours after the start of thrombolysis.4 It is
possible that the clinical manifestations of the intracranial
hemorrhage occurred well after the initial onset of bleeding.
References
1.
Serebruany VL, Gurbel PA, Shustov AR, Dalesandro
MR, Gumbs CI, Grabletz LB, Bahr RD, Ohman EM, Topel EJ, for the
GUSTO-III Investigators. Depressed platelet status in an elderly
patient with hemorrhagic stroke after thrombolysis for acute myocardial
infarction. Stroke. 1998;29:235–238.
2.
Serebruany VL, Gurbel PA, Shustov AR, Ohman EM, Topol
EJ. Heterogeneity of platelet aggregation and major surface receptor
expression in patients presenting with acute myocardial infarction.
Am Heart J. In press.
3.
Gore JM, Granger CB, Simoons ML, Sloan MA, Weaver WD,
White HD, Barbash GI, Van de Werf F, Aylward PE, Topol EJ, Califf RM,
for the GUSTO-I Investigators. Stroke after thrombolysis: mortality and
functional outcomes in the GUSTO-I trial. Circulation. 1995;92:2811–2818.[Abstract/Free Full Text]
4.
Gurbel PA, Serebruany VL, Shustov AR, Bahr RD, Carpo
C, Ohman EM, Topol EJ, for the GUSTO III Investigators. Effects of
reteplase and alteplase on platelet aggregation and major receptor
expression during the first 24 hours of acute myocardial infarction
treatment: the GUSTO III Platelet Study. J Am Coll Cardiol. 1998;31:1466–1473.[Abstract/Free Full Text]
