childhood stroke gita v. massey, md coagulation update 2006 september 30, 2006
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Childhood StrokeChildhood Stroke
Gita V. Massey, MDGita V. Massey, MD
Coagulation Update 2006Coagulation Update 2006
September 30, 2006September 30, 2006
The challenge……………..The challenge……………..
How to cover this How to cover this enormous topic in 30 enormous topic in 30 minutes and give minutes and give some insightful advice some insightful advice to the practicing to the practicing hematologist…………hematologist………………
What the experts say…….What the experts say…….
Jordon, LC; Stroke in Childhood. The Neurologist; 12, 94-102; 2006Jordon, LC; Stroke in Childhood. The Neurologist; 12, 94-102; 2006deVeber, G; In pursuit of evidence-based treatments for paediatric stroke. deVeber, G; In pursuit of evidence-based treatments for paediatric stroke. The Lancet Neurology; 4, 432-436; 2005The Lancet Neurology; 4, 432-436; 2005Lynch, JK and Han CJ; Pediatric Stroke: What do we know and what do we Lynch, JK and Han CJ; Pediatric Stroke: What do we know and what do we need to know? Sem in Neurology; 25,410-423; 2005need to know? Sem in Neurology; 25,410-423; 2005deVeber, G; Arterial ischemic strokes in infants and children: and overview deVeber, G; Arterial ischemic strokes in infants and children: and overview of current approaches; Sem in Thromb and Hemost; 29, 567-573; 2003.of current approaches; Sem in Thromb and Hemost; 29, 567-573; 2003.
EpidemiologyEpidemiology
Incidence 8/100,000/year (1.3-13)Incidence 8/100,000/year (1.3-13)
Incidence in neonates 1/4,000/yearIncidence in neonates 1/4,000/year
Incidence increasingIncidence increasing– More sensitive imagingMore sensitive imaging– Effective Rx for predisposing condition (CHD, Effective Rx for predisposing condition (CHD,
prematurity, tumors)prematurity, tumors)
Death in 6% (top 10 causes of death in children)Death in 6% (top 10 causes of death in children)
Neurologic deficits in 2/3Neurologic deficits in 2/3
20-30% recurrence risk20-30% recurrence risk
Children are not little adults……Children are not little adults……
Incidence is rareIncidence is rare
Subtle neurologic Subtle neurologic presentationpresentation
Underdiagnosis and Underdiagnosis and delay in diagnosisdelay in diagnosis
Multiple types of Multiple types of strokestroke
Multiple risk factorsMultiple risk factors
Type of StrokeType of Stroke
STROKE
Acute Ischemic Stroke(AIS)
Hemorrhagic Stroke(HS)
Cerebral Venous Thrombosis (CVT)
Infection
Dehydration
Prothrombotic states
Vascular malformations
ITP/Hemophilia
Brain tumors
Acute Ischemic StrokeAcute Ischemic Stroke
Incidence is 3/100,000, yearIncidence is 3/100,000, year
Neonates account for 25% of AIS – Neonates account for 25% of AIS – median age 5 yrsmedian age 5 yrs
Male predominance (60%)Male predominance (60%)
Predominance in African-American Predominance in African-American populationpopulation
Clinical Features of AISClinical Features of AIS
Canadian RegistryCanadian Registry– 51% hemiparesis51% hemiparesis– 48% seizures48% seizures– 17% speech disorder17% speech disorder– 50% headache, lethargy, confusion50% headache, lethargy, confusion
NeonatesNeonates– <25% hemiparesis<25% hemiparesis– Lethargy and seizures predominateLethargy and seizures predominate– No symptoms (early hand dominance)No symptoms (early hand dominance)
Vascular Risk FactorsVascular Risk Factors
Vascular
Arteriopathies Vasospastic VasculitisSystemic vascular
disease
Transient
Progressive
Infectious
Connective tissue disease
Drugs
Embolic Risk FactorsEmbolic Risk Factors
Embolic
Congenital Heart Disease
Acquired HeartDisease
Trauma
Cyanotic Heart Disease
PFO
Cardiomyopathy
Arrhythmia
Intravascular Risk FactorsIntravascular Risk Factors(The Hematologist’s Domain)(The Hematologist’s Domain)
Intravascular
Hematologic Disorders
Prothrombotic States
Metabolic
Sickle cell
Iron deficiency
Leukemia
Acquired
Congenital
Hyperhomocysteinemia
Hyperlipidemia
The Acquired Prothrombotic StatesThe Acquired Prothrombotic States
LupusAnticoagulants
Pregnancy
Meds
Acquired
The Congenital Prothrombotic The Congenital Prothrombotic StatesStates
Lipoproteina
MTHFR
PT20210
Plasminogen
Protein S
APC resistance
Protein C
ATIII
Congenital
The Confusing Realm of The Confusing Realm of Prothrombotic StatesProthrombotic States
How much do they How much do they contribute?contribute?
Rare disordersRare disorders
Age related Age related differencesdifferences
Acute differencesAcute differences
Dietary variationsDietary variations
The Diagnostic Work-UpThe Diagnostic Work-Up
HistoryHistory– Trauma, infection, palpitations, mental status Trauma, infection, palpitations, mental status
chages, underlying diseasechages, underlying disease– Previous DVT’s, family historyPrevious DVT’s, family history
Physical ExamPhysical Exam– Marfanoid body habitusMarfanoid body habitus– Cutaneous lesionsCutaneous lesions
Café au lait spotsCafé au lait spots
xanthomaxanthoma
The Diagnostic Work-UpThe Diagnostic Work-Up
Laboratory StudiesLaboratory Studies– CBC, comprehensive metabolic panel, ESRCBC, comprehensive metabolic panel, ESR– Toxicology and infectious studiesToxicology and infectious studies– The hypercoagulation studiesThe hypercoagulation studies
Imaging StudiesImaging Studies– CTCT– MRI/MRA/MRVMRI/MRA/MRV– EchoEcho
The hypercoagulation profileThe hypercoagulation profile
Implicated in 38%-75% of childhood stroke Implicated in 38%-75% of childhood stroke patientspatients
ExpensiveExpensive
Rare disordersRare disorders
Transient disordersTransient disorders
What can you do about it?What can you do about it?– B12, folate, B6 in hyperhomocystenemiaB12, folate, B6 in hyperhomocystenemia– Niacin in lipoprotein aNiacin in lipoprotein a
TherapyTherapy
Absence of RCTAbsence of RCT
Adapted from adultsAdapted from adults
Treat underlying risk factorTreat underlying risk factor
Prevent recurrencePrevent recurrence
Consensus on……Consensus on……
Sickle cell diseaseSickle cell disease
Acute therapyAcute therapy– Exchange transfusionExchange transfusion
Preventive therapyPreventive therapy– Blood transfusion every 3-6 weeks to maintain Blood transfusion every 3-6 weeks to maintain
HbS<30%HbS<30%– ?HU, stem cell transplant?HU, stem cell transplant– Transcranial dopplersTranscranial dopplers
Current recommendations……Current recommendations……
Neonatal AIS – no therapyNeonatal AIS – no therapyDissecting vasculopathy – anticoagulation Dissecting vasculopathy – anticoagulation 3-6 months3-6 monthsCardiogenic embolism – anticoagulation Cardiogenic embolism – anticoagulation but no consensus on length of timebut no consensus on length of timeVasculopathy – ASA (no consensus on Vasculopathy – ASA (no consensus on dose 1-5mg/kg/day)dose 1-5mg/kg/day)Recurrent stroke – consider Recurrent stroke – consider anticoagulationanticoagulation
Current practice…..Current practice…..
Most (>50%) will use LMWH/UH 5-7 days Most (>50%) will use LMWH/UH 5-7 days in non neonatal period followed by ASAin non neonatal period followed by ASA
Thrombolytic agents are rarely used in Thrombolytic agents are rarely used in pediatrics and their use is recommended pediatrics and their use is recommended only in conjuction with clinical trials.only in conjuction with clinical trials.
Outcomes of Childhood AISOutcomes of Childhood AIS
1991 – 85% long-term sequelae1991 – 85% long-term sequelae
2001 – 60% long-term sequelae2001 – 60% long-term sequelae
Hemiparesis, speech, learning and behaviorHemiparesis, speech, learning and behavior
WORSE IF…..WORSE IF…..– Multiple risk factorsMultiple risk factors– CHD/progressive vasculopathyCHD/progressive vasculopathy– Larger infarctLarger infarct– Stroke after neonatal periodStroke after neonatal period– Seizures with strokeSeizures with stroke
What do we need for the future?What do we need for the future?
Prospective cohort Prospective cohort studiesstudies– Standard evaluation of Standard evaluation of
risk and outcomerisk and outcome– Develop therapy and Develop therapy and
prevention strategiesprevention strategies
Incidence studiesIncidence studies
Case control studies Case control studies of risk factorsof risk factors
Outcome studiesOutcome studies