1474 Stroke June 2016 Methods Patient Selection

Intracerebral hemorrhage (ICH) is still the deadliest type of stroke and accounts for 10% to 20% of all cerebrovascular events. Hematoma expansion occurs in about one third of patients and is strongly associated with poor outcome. As a potentially modifiable determinant of ICH prognosis, hematoma expansion represents an appealing target for acute ICH treatment. The relationship between acute inflammation, white blood cell (WBC) count and ICH pathophysiology is complex. ICH is associated with leukocytosis, but the inflammatory activation represented by leukocytosis may, in turn, play a role in ICH severity. The results of multiple studies suggest that higher WBC counts accompany more severe ICH as measured by reduced consciousness, higher baseline hematoma volume, and intraventricular hemorrhage presence. Leukocyte count has also been associated with higher risk of early neurological deterioration, increased long-term mortality, and poor functional outcome. However, Di Napoli et al found that leukocytosis does not independently predict poor ICH prognosis when controlling for other outcome determinants including age, baseline hematoma volume, and admission Glasgow Coma Scale. Leukocytes interact with platelets, endothelium, and coagulation factors and have been widely recognized as important contributors to facilitating hemostasis in physiological and pathological conditions. Acute leukocytosis shifts the hemostatic balance in favor of coagulation and may therefore play an important role in the arrest of bleeding after an ICH occurs. To test the hypothesis that acute leukocytosis limits the extent of bleeding after acute ICH, we investigated whether acute leukocytosis reduced the risk of subsequent hematoma expansion. Background and Purpose—Acute leukocytosis is a well-established response to intracerebral hemorrhage (ICH). Leukocytes, because of their interaction with platelets and coagulation factors, may in turn play a role in hemostasis. We investigated whether admission leukocytosis was associated with reduced bleeding after acute ICH. Methods—Consecutive patients with primary ICH were prospectively collected from 1994 to 2015 and retrospectively analyzed. We included subjects with a follow-up computed tomographic scan available and automated complete white blood cell count performed within 48 hours from onset. Baseline and follow-up hematoma volumes were calculated with semiautomated software, and hematoma expansion was defined as volume increase >30% or 6 mL. The association between white blood cell count and ICH expansion was investigated with multivariate logistic regression. Results—A total of 1302 subjects met eligibility criteria (median age, 75 years; 55.8% men), of whom 207 (15.9%) experienced hematoma expansion. Higher leukocyte count on admission was associated with reduced risk of hematoma expansion (odds ratio for 1000 cells increase, 0.91; 95% confidence interval, 0.86–0.96; P=0.001). The risk of hematoma expansion was inversely associated with neutrophil count (odds ratio, 0.90; 95% confidence interval, 0.85–0.96; P=0.001) and directly associated with monocyte count (odds ratio, 2.71; 95% confidence interval, 1.08–6.83; P=0.034). There was no association between lymphocyte count and ICH expansion (odds ratio, 0.96; 95% confidence interval, 0.79–1.17; P=0.718). Conclusions—Higher admission white blood cell count is associated with lower risk of hematoma expansion. This highlights a potential role of the inflammatory response in modulating the coagulation cascade after acute ICH. (Stroke. 2016;47:1473-1478. DOI: 10.1161/STROKEAHA.116.013176.)

[1]  M. Elkind,et al.  Monocyte Count and 30-Day Case Fatality in Intracerebral Hemorrhage , 2015, Stroke.

[2]  M. Selim,et al.  The HEP Score: A Nomogram-Derived Hematoma Expansion Prediction Scale , 2015, Neurocritical Care.

[3]  Chad M. Miller,et al.  Admission Leukocytosis in Intracerebral Hemorrhage: Associated Factors and Prognostic Implications , 2015, Neurocritical Care.

[4]  R. Veltkamp,et al.  Neuroinflammation after intracerebral hemorrhage , 2014, Front. Cell. Neurosci..

[5]  D. Dwivedi,et al.  Neutrophil Extracellular Traps Promote Thrombin Generation Through Platelet-Dependent and Platelet-Independent Mechanisms , 2014, Arteriosclerosis, thrombosis, and vascular biology.

[6]  Qing-Wu Yang,et al.  Inflammation in intracerebral hemorrhage: From mechanisms to clinical translation , 2014, Progress in Neurobiology.

[7]  J. Broderick,et al.  Peripheral monocyte count is associated with case fatality after intracerebral hemorrhage. , 2014, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[8]  S. Greenberg,et al.  Predicting hematoma expansion after primary intracerebral hemorrhage. , 2014, JAMA neurology.

[9]  A. Mócsai Diverse novel functions of neutrophils in immunity, inflammation, and beyond , 2013, The Journal of experimental medicine.

[10]  S. Greenberg,et al.  Hematoma Expansion following Acute Intracerebral Hemorrhage , 2013, Cerebrovascular Diseases.

[11]  S. Greenberg,et al.  CTA Spot Sign Predicts Hematoma Expansion in Patients with Delayed Presentation After Intracerebral Hemorrhage , 2012, Neurocritical Care.

[12]  B. Phillips-Bute,et al.  Correlation of leukocytosis with early neurological deterioration following supratentorial intracerebral hemorrhage , 2012, Journal of Clinical Neuroscience.

[13]  R. Keep,et al.  Intracerebral haemorrhage: mechanisms of injury and therapeutic targets , 2012, The Lancet Neurology.

[14]  Bertrand Tavitian,et al.  Noninvasive molecular imaging of neuroinflammation , 2012, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[15]  S. Tsirka,et al.  The CCL2‐CCR2 system affects the progression and clearance of intracerebral hemorrhage , 2012, Glia.

[16]  P. Koudstaal,et al.  International Epidemiology of Intracerebral Hemorrhage , 2012, Current Atherosclerosis Reports.

[17]  L. McCullough,et al.  Peripheral leukocyte counts and outcomes after intracerebral hemorrhage , 2011, Journal of Neuroinflammation.

[18]  S. Greenberg,et al.  Body Mass Index and Etiology of Intracerebral Hemorrhage , 2011, Stroke.

[19]  N. Roglans,et al.  Tissue factor pathway inhibitor 2 is induced by thrombin in human macrophages. , 2011, Biochimica et biophysica acta.

[20]  Ji-Eun Kim,et al.  Thrombomodulin phenotype of a distinct monocyte subtype is an independent prognostic marker for disseminated intravascular coagulation , 2011, Critical care.

[21]  Eric E. Smith,et al.  Defining hematoma expansion in intracerebral hemorrhage , 2011, Neurology.

[22]  Brian Y. Hwang,et al.  Advances in Neuroprotective Strategies: Potential Therapies for Intracerebral Hemorrhage , 2010, Cerebrovascular Diseases.

[23]  E. Connolly,et al.  Neuroprotective Strategies for Intracerebral Hemorrhage: Trials and Translation , 2010, Stroke.

[24]  W. Ruf,et al.  Neutrophils release brakes of coagulation , 2010, Nature Medicine.

[25]  K. Preissner,et al.  Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases , 2010, Nature Medicine.

[26]  T. Steiner,et al.  Options to Restrict Hematoma Expansion After Spontaneous Intracerebral Hemorrhage , 2010, Stroke.

[27]  I. Ott,et al.  Modulation of tissue factor and tissue factor pathway inhibitor-1 by neutrophil proteases , 2008, Thrombosis and Haemostasis.

[28]  B. Furie,et al.  Mechanisms of thrombus formation. , 2008, The New England journal of medicine.

[29]  Jian Wang,et al.  Inflammation after Intracerebral Hemorrhage , 2007, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[30]  E. Tremoli,et al.  Human polymorphonuclear leukocytes produce and express functional tissue factor upon stimulation 1 , 2006, Journal of thrombosis and haemostasis : JTH.

[31]  P. Thiagarajan,et al.  Leukocyte adhesion and thrombosis , 2006, Current opinion in hematology.

[32]  C. Esmon The interactions between inflammation and coagulation , 2005, British journal of haematology.

[33]  A. Dávalos,et al.  Early neurologic deterioration in intracerebral hemorrhage , 2004, Neurology.

[34]  R P McEver,et al.  Adhesive Interactions of Leukocytes, Platelets, and the Vessel Wall during Hemostasis and Inflammation , 2001, Thrombosis and Haemostasis.

[35]  B. Bouchard,et al.  Platelets, leukocytes, and coagulation , 2001, Current opinion in hematology.

[36]  B. Furie,et al.  Interactions of neutrophils and coagulation proteins. , 1997, Seminars in hematology.

[37]  R. Kelley,et al.  Acute leukocyte and temperature response in hypertensive intracerebral hemorrhage. , 1995, Stroke.

[38]  J. Weinberg,et al.  Thrombomodulin expression by human blood monocytes and by human synovial tissue lining macrophages. , 1991, Blood.

[39]  Adnan I Qureshi,et al.  Intracerebral haemorrhage , 2011, Radiopaedia.org.

[40]  A. Osborn CT Angiography “Spot Sign” Predicts Hematoma Expansion in Acute Intracerebral Hemorrhage , 2009 .