Pediatric Thrombosis & Pediatric Thrombosis & ThrombophiliaThrombophilia

Bryce A. Kerlin, M.D.Bryce A. Kerlin, M.D.Director, Hemostasis & Thrombosis CenterDirector, Hemostasis & Thrombosis Center

Disclosures:Disclosures:

• Bayer HealthCare, LLCBayer HealthCare, LLC– US Clinical Advisory BoardUS Clinical Advisory Board

• Hemophilia & Thrombosis Research Hemophilia & Thrombosis Research SocietySociety– Grant SupportGrant Support

Objectives:Objectives:

• Understand which children are at Understand which children are at greatest risk of thrombosisgreatest risk of thrombosis

• Principles of evaluation and treatment of Principles of evaluation and treatment of thrombotic episodesthrombotic episodes

• Considerations for Thrombophilia Considerations for Thrombophilia evaluationevaluation

EpidemiologyEpidemiology

Overall Thrombotic Risk Overall Thrombotic Risk ModelModel

• Patients with low-level of baseline hyper-Patients with low-level of baseline hyper-coagulability (no thombophilia)coagulability (no thombophilia)– Clinically overt precipitating eventsClinically overt precipitating events

• Patients with high-level of baseline hyper-Patients with high-level of baseline hyper-coagulability (multiple thrombophilias)coagulability (multiple thrombophilias)– Sub-clinical triggersSub-clinical triggers– Appearance of “idiopathic” or “unprovoked” eventAppearance of “idiopathic” or “unprovoked” event

Age/Illness

Thrombosis threshold

Th

rom

bo

sis

Ris

k

Inherited Thrombophilia

i.e. FVLeiden

Interaction between Inherited Interaction between Inherited and Acquired Risk Factorsand Acquired Risk Factors

Slide courtesy S. Cataland & E. Varga.

EpidemiologyEpidemiology

• Highest incidence Highest incidence of thrombosis in of thrombosis in childrenchildren– NeonatesNeonates– AdolescentsAdolescents

0

5

10

15

20

25

30

35

40

0 5 10 15 20 25 30 35 40 45 50

Age (Y)

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10

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Adapted from: Andrew, Monagle, Brooker, Eds. “Thromboembolic Complications during Infancy and Childhood”: © 2000 BCDecker.

Neonatal EpidemiologyNeonatal Epidemiology

• Highest risk group in the pediatric populationHighest risk group in the pediatric population• Thrombosis IncidenceThrombosis Incidence

– 2.4/1000 NICU Admissions2.4/1000 NICU Admissions

• Catheters associated with:Catheters associated with:– 80+% of Venous Thrombi80+% of Venous Thrombi– 90% of Arterial Thrombotic Complications90% of Arterial Thrombotic Complications

• Renal Vein ThrombosisRenal Vein Thrombosis– Most common non-catheter related thrombotic Most common non-catheter related thrombotic

complicationcomplication

Schmidt B & Andrew M. Neonatal Thrombosis: Report of a prospective Canadian and International Registry. Pediatrics 96:939, 1995.

Older Children & AdolescentsOlder Children & Adolescents

Andrew, Monagle, Brooker, Eds. “Thromboembolic Complications during Infancy and Childhood”: © 2000 BCDecker.

““Other” Co-Morbid Other” Co-Morbid PredispositionsPredispositions

• CathetersCatheters• ObesityObesity• Diabetic Diabetic

KetoacidosisKetoacidosis• SepsisSepsis• Oral ContraceptivesOral Contraceptives

• Nephrotic SyndromeNephrotic Syndrome• Cystic FibrosisCystic Fibrosis• Short Gut SyndromeShort Gut Syndrome• InfectionsInfections• PregnancyPregnancy• Autoimmune Autoimmune

DiseaseDisease

Virchow’s TriadVirchow’s Triad

Neonatal RiskNeonatal Risk

• Intimal Injury:Intimal Injury:– CathetersCatheters– PolycythemiaPolycythemia– ShockShock– Perinatal AsphyxiaPerinatal Asphyxia

• Abnormal Blood Abnormal Blood Flow:Flow:– CathetersCatheters– Congenital Heart Congenital Heart

DiseaseDisease

• Developmentally Developmentally Prothrombotic:Prothrombotic:– Decreased levels of Decreased levels of

Natural Anti-Natural Anti-coagulants:coagulants:

• Protein C, Protein S, Protein C, Protein S, AntiThrombin IIIAntiThrombin III

– Decreased levels of Decreased levels of Fibrinolytic Proteins:Fibrinolytic Proteins:

• Esp. PlasminogenEsp. Plasminogen

Upper Extremity DVTs:Upper Extremity DVTs:

0%

20%

40%

60%

80%

100%

NB Children Adults

UE

LE

Other

Adapted from: Andrew, Monagle, Brooker, Eds. “Thromboembolic Complications during Infancy and Childhood”: © 2000 BCDecker.

ProphylaxisProphylaxis• Aspirin:Aspirin:

– Most experience in Congenital Heart Disease with vascular Most experience in Congenital Heart Disease with vascular shunt devicesshunt devices

• Low-Dose Heparin:Low-Dose Heparin:– 3-5 Units/hr3-5 Units/hr– Commonly usedCommonly used– Improves duration of catheter patencyImproves duration of catheter patency

• Patency most likely represents absence of local thrombusPatency most likely represents absence of local thrombus

• Heparin Capping:Heparin Capping:– Broviac / Hickman CVLsBroviac / Hickman CVLs– Implantofix / Port-a-cath CVLsImplantofix / Port-a-cath CVLs

Andrew M. Developmental Hemostasis: Relevance to Newborns and Infants. In: Nathan and Oski’s Hematology of Infancy and Childhood 5 th Ed. (1998).

Evaluation & ManagementEvaluation & Management

Signs & SymptomsSigns & Symptoms

• DVT:DVT:– Poorly Functioning Poorly Functioning

CathetersCatheters– Edematous extremityEdematous extremity– Plethoric extremityPlethoric extremity– Warm extremityWarm extremity– Painful extremityPainful extremity

• PE:PE:– Cough, SOB, Cough, SOB,

HemoptysisHemoptysis– TachycardiaTachycardia

Diagnostic AlgorithmDiagnostic AlgorithmConsider:1. Venography

as the gold standard (MRV)

2. D-dimer in all cases

3. CT Angio-gram for patients with Pulmonary Sx

Therapeutic GoalsTherapeutic Goals

• Prevent thrombus growth and/or Prevent thrombus growth and/or embolizationembolization

• Restore blood flow (rapidly, when Restore blood flow (rapidly, when necessary)necessary)

• Minimize long-term sequelaeMinimize long-term sequelae

Thrombolysis &Thrombolysis &ThrombectomyThrombectomy

• Thrombolysis:Thrombolysis:– Reserved for patients with life-, organ-, or limb-threatening thrombiReserved for patients with life-, organ-, or limb-threatening thrombi– Contraindicated for patients at increased risk of hemorrhage:Contraindicated for patients at increased risk of hemorrhage:

• Recent surgery or traumaRecent surgery or trauma• Stroke – limited pediatric dataStroke – limited pediatric data

– Should be administered under the supervision of an experienced Should be administered under the supervision of an experienced HematologistHematologist

• Surgical Thrombectomy:Surgical Thrombectomy:– Can be curativeCan be curative– High risk, technically difficult procedureHigh risk, technically difficult procedure– May cause further intimal damage – relapse?May cause further intimal damage – relapse?– Preferred for patients with increased risk of hemorrhagePreferred for patients with increased risk of hemorrhage

Andrew M et al. Fibrin Clot Lysis by Thrombolytic Agents is Impaired in Newborns Due to a Low Plasminogen Concentration. Thromb Haemost 68:325, 1992.

Andrew M. Developmental Hemostasis: Relevance to Newborns and Infants. In: Nathan and Oski’s Hematology of Infancy and Childhood 5 th Ed. (1998).

IVC FiltrationIVC Filtration• Overwhelming opinion in the literature is Overwhelming opinion in the literature is

avoidance in the majority of Pediatric Patientsavoidance in the majority of Pediatric Patients– Inadequate dataInadequate data

• Generally reserved for:Generally reserved for:– Anticoagulation Contraindicated in setting of Anticoagulation Contraindicated in setting of

proven DVTproven DVT– Anticoagulation Failure (PE despite adequate Anticoagulation Failure (PE despite adequate

anticoagulation)anticoagulation)• When needed, temporary filters preferredWhen needed, temporary filters preferred

– Inadequate long-term follow-up dataInadequate long-term follow-up dataAndrew M et al. Guidelines for antithrombotic therapy in pediatric patients. JPeds 1998;132:575-88.Kinney TB. Update on Inferior Vena Cava Filters. JVascIntervRadiol 2003;14:425-40.Monagle P et al. Antithromotic Therapy in Children: The 7 th ACCP Conference on Antithrombotic &

Thrombolytic Therapy. Chest 2004;126:645S-87S.Ku GH & Billett HH. Long lives, short indications: The case for removable inferior cava filters.

ThrombHaemost 2005;93:17-22.Streiff MB. Vena caval filters: A review for intensive care specialists. JIntensiveCareMed

2003;18:59-79.

HeparinHeparin• Standard HeparinStandard Heparin (vs. Low Molecular Weight) (vs. Low Molecular Weight)

– Easily reversible (Protamine Sulfate)Easily reversible (Protamine Sulfate)– Short T½ Short T½ – Dose Variability:Dose Variability:

• Infants have higher dose requirements than older childrenInfants have higher dose requirements than older children– Bolus: 75-100 Units/kg (vs. 50-75)Bolus: 75-100 Units/kg (vs. 50-75)– Maintenance: Mean = 28 Units/kg/hour (vs. 20)Maintenance: Mean = 28 Units/kg/hour (vs. 20)

– Monitoring:Monitoring:• Frequent (ACT, aPTT, anti-Factor Xa)Frequent (ACT, aPTT, anti-Factor Xa)

– IV Access requiredIV Access required– Disadvantages:Disadvantages:

• Frequent monitoring is necessaryFrequent monitoring is necessary• Risk of hemorrhageRisk of hemorrhage• Risk of HIT/TRisk of HIT/T

– Thrombocytopenia or Platelet Count <50% baselineThrombocytopenia or Platelet Count <50% baseline

Andrew M. Developmental Hemostasis: Relevance to Newborns and Infants. In: Nathan and Oski’s Hematology of Infancy and Childhood 5 th Ed. (1998).

Hirsh J et al. Heparin and Low-Molecular-Weight Heparin. Chest 114:489S, 1998.

HeparinHeparin

• Standard Heparin (vs. (vs. Low Molecular Weight ~ Low Molecular Weight ~ Lovenox/EnoxaparinLovenox/Enoxaparin))– Irreversible (partial w/ protamine)Irreversible (partial w/ protamine)– Long T½Long T½– Dose Variability:Dose Variability:

• Infants have higher dose requirements than older children Infants have higher dose requirements than older children – ~1.6 mg/kg/dose (vs. 1) ~1.6 mg/kg/dose (vs. 1)

– Monitoring:Monitoring:• Infrequent (anti-Factor Xa)Infrequent (anti-Factor Xa)

– No IV access necessaryNo IV access necessary– Limited SQ sites for administration?Limited SQ sites for administration?– Disadvantages:Disadvantages:

• ComplianceCompliance• Osteoporosis?Osteoporosis?

Massicotte P et al. Low-Molecular-Weight Heparin in Pediatric Patients with Thrombotic Disease:A Dose Finding Study. J Pediatr 128:313, 1996.

Cruickshank MK et al. A Standard Heparin Nomogram for the Management of Heparin Therapy.Arch Intern Med 151:333, 1991.

CoumadinCoumadin (Warfarin) (Warfarin)• Frequent monitoring is necessary:Frequent monitoring is necessary:

– Infants are exquisitely sensitive due to relative Vitamin K deficiencyInfants are exquisitely sensitive due to relative Vitamin K deficiency– INR affected by:INR affected by:

• DietDiet– Breast Milk is low in Vit KBreast Milk is low in Vit K– TPN (pediatric) and Commercial Formulas are high in VKTPN (pediatric) and Commercial Formulas are high in VK

• Medications affecting p450 metabolismMedications affecting p450 metabolism• Intercurrent illnesses (esp. gastroenteritis or Abx Rx)Intercurrent illnesses (esp. gastroenteritis or Abx Rx)

• Should be avoided during the first year of life when possibleShould be avoided during the first year of life when possible– Higher risk of hemorrhageHigher risk of hemorrhage– Dose instabilityDose instability

• Less risk of osteopeniaLess risk of osteopenia• Oral administrationOral administration

Bovill E et al. Vitamin K1 Metabolism and the Production of des-Carboxy Prothrombin and Protein C in the Term and Premature Neonate. Blood 81:77, 1993

Schmidt B et al. Report of Scientific and Standardization Subcommittee on Neonatal Hemostasis: Diagnosis and Treatment of Neonatal Thrombosis. Thromb Haemost 67:381, 1992.

AnticoagulationAnticoagulation

AcutelyAcutely• High Risk:High Risk:

– Standard HeparinStandard Heparin

• Low Risk:Low Risk:– EnoxaparinEnoxaparin

ConvalescentConvalescent• Short Courses:Short Courses:

– EnoxaparinEnoxaparin– WarfarinWarfarin

• Chronic Chronic Anticoagulation:Anticoagulation:– WarfarinWarfarin– EnoxaparinEnoxaparin

Duration of TherapyDuration of Therapy• Highly individualizedHighly individualized

– Further investigation is neededFurther investigation is needed

• Supportive Care or Therapy should be monitored with Supportive Care or Therapy should be monitored with objective studiesobjective studies– Short courses of 2-6 weeks may be adequateShort courses of 2-6 weeks may be adequate

• Relapse, extension, or residual thrombus indicates Relapse, extension, or residual thrombus indicates need for long-term therapy (minimum of 3-6 months)need for long-term therapy (minimum of 3-6 months)

• If continued risk (CHD/catheter/protein defect) is If continued risk (CHD/catheter/protein defect) is present a longer course should be consideredpresent a longer course should be considered

• Indefinite therapy for:Indefinite therapy for:– first relapse with protein defectfirst relapse with protein defect– second relapse withoutsecond relapse without

Andrew M et al. Guidelines for Antithrombotic Therapy in Pediatric Patients. J Pediatr 132:575, 1998.

Anticoagulant DurationAnticoagulant Duration

• ““Risk Group” Stratification:Risk Group” Stratification:– Ongoing Multi-institution StudyOngoing Multi-institution Study

• Low Risk:Low Risk:– Brief Inciting EventsBrief Inciting Events– 6 wks (Thrombus Resolution and no thrombophilia)6 wks (Thrombus Resolution and no thrombophilia)vs.vs.– 3 mos (Residual Thrombus or thrombophilia)3 mos (Residual Thrombus or thrombophilia)

• High Risk:High Risk:– Multiple Thrombophilia or “High Risk” Lab ProfileMultiple Thrombophilia or “High Risk” Lab Profile– Early thrombolysis followed byEarly thrombolysis followed by– 6 mos vs. 12 mos6 mos vs. 12 mos

• End Points:End Points:– Recurrent TE and/or Post-Phlebitic SyndromeRecurrent TE and/or Post-Phlebitic Syndrome

Multi-institutional studies in progress.

Ending TherapyEnding Therapy

• Thrombus Resolved or 6 Thrombus Resolved or 6 monthsmonths– Whichever 1Whichever 1stst

• D-dimer assay one month D-dimer assay one month after end of therapy: after end of therapy: If positive If positive resume anticoagulation and re-resume anticoagulation and re-evaluate after an additional 18 evaluate after an additional 18 months.months.

Figure 2. Cumulative Incidence of and Hazard Ratios (HRs) for Main Outcomes. The graph compares the outcomes among patients who had a normal D-dimer level with those among patients who had an abnormal level and either resumed or stopped anticoagulation therapy.

Palareti et al. D-Dimer testing to determine the duration of anticoagulation therapy. NEJM 2006;355:1780-9.

Long-Term Follow-upLong-Term Follow-up

• Post-phlebitic Post-phlebitic SyndromeSyndrome– Chronic Venous Chronic Venous

InsufficiencyInsufficiency• Pain w/ walking or ADLsPain w/ walking or ADLs• Chronic edemaChronic edema• Venous ulcerationVenous ulceration• Varicosities (collateral Varicosities (collateral

vessels)vessels)

• Recurrent TERecurrent TE– Pulmonary Pulmonary

HypertensionHypertension– Life-Threatening Life-Threatening

Embolic DiseaseEmbolic Disease

Thrombophilia StudiesThrombophilia Studies

Thrombophilia HistoryThrombophilia History

• Co-morbid Medical ConditionsCo-morbid Medical Conditions• FMHx:FMHx:

– Deep Venous Thrombosis / Pulmonary EmbolismDeep Venous Thrombosis / Pulmonary Embolism– Anticoagulation – why?Anticoagulation – why?– Early Myocardial Infarction or Cerebral Vascular Early Myocardial Infarction or Cerebral Vascular

AccidentAccident– Frequent pregnancy loss, SGA, or prematurityFrequent pregnancy loss, SGA, or prematurity– Sudden Unexplained DeathSudden Unexplained Death– Autoimmune DiseasesAutoimmune Diseases

HemostasisHemostasis

Platelet

ClottingFactors

VesselWall

Natural-Coagulants

Anti-Coagulant SystemAnti-Coagulant System

Thrombin

Prothrombin

Tissue Factor+

fVIIa

f IXa +

fVIIIa, Ca, PLf IX

fXa +

fVa, Ca, PL

fX

Trigger Guard: Tissue Factor Pathway Inhibitor

Cleaver: Protein C / Protein S Complex

Inhibitor: Anti-Thrombin III

Fibrinogen Fibrin Drano: Fibrinolytic System

Slippery Pipes: Endothelium

Thrombophilia in Adults w/ Thrombophilia in Adults w/ DVTDVT

• Protein Deficiencies:Protein Deficiencies:– Anti-Thrombin IIIAnti-Thrombin III ~4.8%~4.8%– Protein CProtein C ~4.3%~4.3%– Protein SProtein S ~4.3%~4.3%

• aPC ResistanceaPC Resistance– Factor VFactor VLeidenLeiden ~40%~40%

• Elevated Prothrombin LevelsElevated Prothrombin Levels– Prothrombin G20210AProthrombin G20210A ~16%~16%

Total:Total: ~69.4%~69.4%

Seligsohn U & Lubetsky A. Medical Progress: Genetic Susceptibility to Venous Thrombosis. NEJM 344:1222-31, 2001.

Prevalence Test Affected/tested

Study Population

Factor V Leiden 8/171 4.7 % 4 %

Prothrombin G20210A 4/171 2.3 % 2 %

Protein S deficiency 2/171 1.2 % 0.3 %

Protein C deficiency 1/171 0.6 % 0.3 %

Antithrombin deficiency 0/171 0.0 % 0.02 %

Lipoprotein (a) >30mg/dl 8/107 7.5 % 7 %

Revel-Vilk. J Thromb Haemost 1 (2003), 915-921

Prevalence of inherited thrombophilia Prevalence of inherited thrombophilia in children with DVTin children with DVT

Slide courtesy L. Michaels

The diagnosis of an inherited The diagnosis of an inherited thrombophilia does not change thrombophilia does not change

treatment recommendationstreatment recommendations1st episode DVT: Duration of

anticoagulation transient risk factor 3 months (1A)

idiopathic 6-12 months (1A) consider indefinite therapy (2A)

thrombophilia (non-LA)

6-12 months (1A) consider indefinite therapy (2C)

7th ACCP evidence based guidelines

Slide courtesy L. Michaels

Justification for ScreeningJustification for Screening

Blood 2001;97:858-862.

Laboratory Studies at time of Laboratory Studies at time of Acute ThrombosisAcute Thrombosis

• DIC Screen:DIC Screen:– CBC, PT, aPTT, Thrombin Time, Fibrinogen, D-CBC, PT, aPTT, Thrombin Time, Fibrinogen, D-

dimerdimer

• Protein C ActivityProtein C Activity• Protein S ActivityProtein S Activity• Antithrombin III ActivityAntithrombin III Activity• Consider:Consider:

– Mixing Studies for PT & aPTT if prolongedMixing Studies for PT & aPTT if prolonged– dRVVT, StaClot, ACL Ab, dRVVT, StaClot, ACL Ab, ββ22-GPI Ab-GPI Ab

Antiphospholipid Antibody Antiphospholipid Antibody SyndromeSyndrome

• Autoimmune Acquired Prothrombotic Autoimmune Acquired Prothrombotic DisorderDisorder

• Very High Risk for recurrent Very High Risk for recurrent thromboembolic diseasethromboembolic disease– both venous and arterialboth venous and arterial

• Indefinite duration anticoagulation Indefinite duration anticoagulation recommended +/- immunosuppressionrecommended +/- immunosuppression

• Strict Diagnostic CriteriaStrict Diagnostic Criteria

Antiphospholipid SyndromeAntiphospholipid Syndrome

• Clinical criteria (Clinical criteria (≥1 must be present)≥1 must be present)::

1. Vascular thrombosis:1. Vascular thrombosis: - - ≥ 1≥ 1clinical episode of, objectively confirmed, arterial, venous, or clinical episode of, objectively confirmed, arterial, venous, or

small vessel thrombosissmall vessel thrombosis

2. Pregnancy morbidity:2. Pregnancy morbidity:

- - ≥ 1 ≥ 1 unexplained fetal death @ unexplained fetal death @ ≥ ≥ 10 weeks EGA10 weeks EGA

- - ≥ 1 ≥ 1 premature birth (premature birth (≤ ≤ 34th week of gestation) due to eclampsia, 34th week of gestation) due to eclampsia, severe pre-eclampsia, or placental insufficiencysevere pre-eclampsia, or placental insufficiency

- - ≥ 3 ≥ 3 unexplained consecutive spontaneous abortions @ <10 weeks unexplained consecutive spontaneous abortions @ <10 weeks EGAEGA

Revised Sapporo/Sydney Criteria. JTH 2006;4:295-306

Antiphospholipid SyndromeAntiphospholipid Syndrome

• Laboratory criteria (Laboratory criteria (≥1 must be present)≥1 must be present)::– LA (+) LA (+) ≥ 2 ≥ 2 occasions, at least 12 weeks apart, according occasions, at least 12 weeks apart, according

to ISTH guidelines:to ISTH guidelines:• prolonged PL-based clotting assay, lack of correction with prolonged PL-based clotting assay, lack of correction with

1:1 mix, and correction with excess PL1:1 mix, and correction with excess PL

– ACLA and/or anti-ACLA and/or anti-ββ2 glycoprotein-I antibody:2 glycoprotein-I antibody:• medium or high IgG and/or IgM isotype titer medium or high IgG and/or IgM isotype titer ≥ 2 ≥ 2

occasions, at least 12 weeks apartoccasions, at least 12 weeks apart

• Standardized ELISA assaysStandardized ELISA assays

Revised Sapporo/Sydney Criteria. JTH 2006;4:295-306

Consider Thrombophilia Consider Thrombophilia StudiesStudies

• Factor V LeidenFactor V Leiden– and/or activated protein C and/or activated protein C

resistance resistance

• prothrombin G20210A prothrombin G20210A mutationmutation

• tPA deficiencytPA deficiency• PAI-1 elevationPAI-1 elevation• MTHFR A1298C mutationMTHFR A1298C mutation• euglobulin clot lysis timeeuglobulin clot lysis time• plasminogen deficiencyplasminogen deficiency• high plasminogen activator inhibitorhigh plasminogen activator inhibitor• heparin cofactor II deficiencyheparin cofactor II deficiency• spontaneous platelet activationspontaneous platelet activation• platelet receptor polymorphismsplatelet receptor polymorphisms• factor VII–activating protease (FSAP) factor VII–activating protease (FSAP)

variant Marburgvariant Marburg II

• elevated thrombin-activatable fibrinolysis elevated thrombin-activatable fibrinolysis inhibitor inhibitor

• thrombin-activatable fibrinolysis inhibitor thrombin-activatable fibrinolysis inhibitor AFI-438 G/AAFI-438 G/A

• thrombomodulin polymorphismsthrombomodulin polymorphisms

• other factor V polymorphismsother factor V polymorphisms

• endothelial protein C receptor mutationsendothelial protein C receptor mutations

• Protein Z / ZPInhibitorProtein Z / ZPInhibitor

• lipoprotein (a)• elevated factor VIII, IX, XI• elevated fibrinogen• hyperhomocysteinemia

and/or MTHFR C677T polymorphism

In patients with VTE, family In patients with VTE, family history is a poor predictor history is a poor predictor

of test resultsof test results

Family historyFamily history Patients with positive testing for Patients with positive testing for inherited thrombophiliainherited thrombophilia

NegativeNegative 32%32%

PositivePositive 42%42%

Van Sluis. J Throm Haem 2006;4: 2182-7

Healthy Children w/ Healthy Children w/ Family History of DVT or Family History of DVT or

ThrombophiliaThrombophilia• Screening is rarely indicated:Screening is rarely indicated:

– Risk assessment limited by heterogeneity of Risk assessment limited by heterogeneity of genotype and phenotypegenotype and phenotype

– No guidelines for managementNo guidelines for management– Potential risk of anticoagulation outweighs benefitPotential risk of anticoagulation outweighs benefit– May inhibit ability to obtain life/disability insuranceMay inhibit ability to obtain life/disability insurance– Ethical concerns: autonomy, assent, consentEthical concerns: autonomy, assent, consent– Appropriate age for screening unknownAppropriate age for screening unknown– Unnecessary anxietyUnnecessary anxiety

Anticipatory GuidanceAnticipatory Guidance

• Good Hydration HabitsGood Hydration Habits– Note to School!Note to School!

• Regular ExerciseRegular Exercise• Heart Healthy Diet & LifestyleHeart Healthy Diet & Lifestyle• Avoidance of prolonged sedentary activity:Avoidance of prolonged sedentary activity:

– Planes, Trains, & AutomobilesPlanes, Trains, & Automobiles• Non-estrogen contraceptionNon-estrogen contraception

– Progestins (1Progestins (1stst or 2 or 2ndnd generation vs 3 generation vs 3rdrd)?)?• Family planningFamily planning

– Discuss need for prophylaxis w/ OB 1Discuss need for prophylaxis w/ OB 1stst

Screening sometimes helpful:Screening sometimes helpful:

JPAG 2006;19:313-6.

HTRS: TERegistryHTRS: TERegistry

• Large Multi-Institutional DatabaseLarge Multi-Institutional Database

• Clinical and Demographic DataClinical and Demographic Data

• Thromboembolic Disease in Children Thromboembolic Disease in Children and Adultsand Adults

• EpidemiologyEpidemiology

• OutcomesOutcomes

• Adverse EventsAdverse Events

PI: Bryce Kerlin – Sponsor: Hemophilia & Thrombosis Research Society (HTRS)

SummarySummary

• Pediatric thrombosis is most common in Pediatric thrombosis is most common in infants and adolescentsinfants and adolescents

• Co-morbid Diseases increase likelihood of Co-morbid Diseases increase likelihood of thrombosisthrombosis

• The upper extremity circulation is most The upper extremity circulation is most commonly affectedcommonly affected

• Diagnosis should be confirmed with:Diagnosis should be confirmed with:– D-dimerD-dimer– Venous Doppler UltrasonographyVenous Doppler Ultrasonography– CT AngiogramCT Angiogram

SummarySummary

• Initial treatment should be standard or low Initial treatment should be standard or low molecular weight heparinizationmolecular weight heparinization

• Short courses may be completed with Short courses may be completed with heparin, longer courses may benefit from heparin, longer courses may benefit from transition to Warfarintransition to Warfarin

• Duration of anticoagulant therapy is Duration of anticoagulant therapy is individualized based on underlying co-individualized based on underlying co-morbiditiesmorbidities

• Patients should be followed closely for Patients should be followed closely for recurrent disease and/or post-phlebitic recurrent disease and/or post-phlebitic syndromesyndrome

SummarySummary

• All thrombosis patients should be screened All thrombosis patients should be screened for for treatabletreatable molecular thrombophilias molecular thrombophilias

• Some patients may benefit from additional Some patients may benefit from additional screeningscreening

• Asymptomatic patients and family members Asymptomatic patients and family members not at increased risk for thrombosis should not at increased risk for thrombosis should not routinely be screenednot routinely be screened

Hemostasis & Thrombosis Hemostasis & Thrombosis CenterCenter

• Services:Services:– Acute Thromboembolic DiseaseAcute Thromboembolic Disease

• Consultation, Recommendations, Consultation, Recommendations, (Co)Management(Co)Management

– Outpatient ManagementOutpatient Management• Anticoagulation therapy & monitoringAnticoagulation therapy & monitoring• Long-term follow-upLong-term follow-up• Post-Thrombotic Syndrome managementPost-Thrombotic Syndrome management• Resources for FamilyResources for Family

Hemostasis & Thrombosis Hemostasis & Thrombosis CenterCenter

Call (614) 722-3250 to arrange Call (614) 722-3250 to arrange referrals.referrals.

Hematologists are available for Hematologists are available for consultation 24/7 via hospital operator.consultation 24/7 via hospital operator.