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Thrombosis In The Pediatric Patient: Unique Risk Factors, Diagnosis & Management Issues
Surgeon General's Workshop on Deep Vein Thrombosis
1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 19 | 20
Thrombosis In The Pediatric Patient: Unique Risk Factors, Diagnosis & Management Issues. Surgeon General’s Workshop on DVT May 8-9, 2006 Bethesda, Maryland
Marilyn J. Manco-Johnson, MD & Neil A. Goldenberg, MD Departments of Pediatrics and Medicine, Mountain States Regional Hemophilia & Thrombosis Center University of Colorado at Denver & Health Sciences Center & The Children's Hospital, Denver, CO, US
SLIDE 2: DVT is the Most Common Blood Clot in Children (n=84)
Pie chart showing the following percentages:
- DVT=63%
- CSVT=18%
- Isol PE=5%
- RVT=6%
- IAS=10%
SLIDE 3: Although Rare, DVT is a Health Risk During Childhood, Especially for Newborn Infants & Adolescents
- Newborn 5.1/100,000
- Childhood VT 0.7/100,000
- Childhood Stroke 2/100,000
- Adolescent 10/100,000
- Elderly 5-15,000/100,000
DVT is an Important Cause of Death in Children
- 2.2% (9/405) Monagle et al. Pediatr Res 2000;47:763-6
- 3.8% (3/79) Nowak-Göttl et al. Arch Dis Child 1997;76:F163-7
- 1% (1/100) Van Ommen et al. J Thromb Haemost 2003;1:2516-23
- 2.2% (13/584) Composite
DVT Has a High Risk of Pulmonary Embolism in Children
- 18% (11/61) Nuss et al. Pediatrics 1995;96:291-4.
- 17% (69/405) Monagle et al. Pediatri Res 2000;47:763-6.
- 17% (80/466) Composite
SLIDE 5: DVT in Children Can Be Recurrent
- Monagle P, et al Pediatr Res 2000;47:763-6
8.1% (33/405) median 2.8 yrs
- Van Ommen, et al J Thromb Haemost 2003;1:2516-22
8% (8/100) after 1 year
18% (18/100) after 7yrs
10% (51/505) Composite
SLIDE 6: Children with DVT are More Likely to Have Multiple Thrombophilia Traits
Mountain States Regional Hemophilia & Thrombosis Center
Number of Children Seen 2001-2003 293
Thrombosis 131
Family Study 162
Thrombophilia testing:
- No abnormality: 19%
- Single trait: 27%
- Two traits: 27% Multiple traits in 54% evaluated
- Three traits: 5%
- Four traits: 22%
DVT recurrence is more likely with multiple thrombophilia traits!
SLIDE 7: LMWH Dosing Is More Variable in Children & Requires More Monitoring
| Theraputic Dose of Enoxaparin (mg/kg Q12h by age cohort) | 1.00 | 1.25 | 1.375 | 1.5 | 1.625 | 1.75-2.0 |
|---|---|---|---|---|---|---|
| Birth to < 1 month N=11 | 0% | 9% | 9 % | 36% | 28% | 18% |
| 1 month to < 1 year N=12 | 8% | 8% | 0% | 59% | 8% | 17% |
| 1 year to < 6 years N=16 | 0% | 31% | 25% | 44% | 0% | 7% |
| 6 years to < 12 years N=12 | 0% | 75% | 17% | 8% | 0% | 0% |
| 12 years to < 21 years N=43 | 5% | 88% | 5% | 0% | 2% | 0% |
SLIDE 8: Post Thrombotic Syndrome (PTS) Causes Disability in Children & Adolescents
Stage1: Swelling: DVT age 16 years; FVL, OCP
Stage 2: Visible Collaterals DVT age 14 yrs; APA, prolonged bus ride
Stage 3: Induration, hyperpigmentation DVT age 13 years; FVL, APA
Stage 4: Stasis ulcers; DVT age 10 yrs; PC, tibial fracture
12.4% (50/405) median 2.8 yrs Monagle P, et al Pediatr Res 2000;47:763-6
59% (10/17) pain 41% (7/17) abn PE IVC Hausler M, Arch Dis Child 2001;85:228-33.
63% (96/153) Kuhle S, et al. Thromb Res 2003;111:227-33.
70% (23/33) Van Ommen, et al J Thromb Haemost 2003;1:2516-22
29% (179/608) Composite
SLIDE 9: DVT Therapy is Frequently Delayed in Children Due to Under-Recognition.
Two charts showing Treatment Delay Results in Poor DVT Resolution and Long-Term Pain.
Results of 81 DVT in Children treated with Anticoagulation
SLIDE 10: Teen Age is a Risk Factor for PTS
Line chart showing Teen Age is a Risk Factor for PTS
SLIDE 11: Overweight Predisposes to PTS in Children & Teens
Photos showing how Overweight Predisposes to PTS in Children & Teens (January 2004 and October 2004)
Stage 3: Skin induration, venous eczema
Overweight Predisposes to PTS in Children & Teens
88% rate of overweight in children with PTS
Overweight children have RR of 7 for PTS
SLIDE 12: Inflammation is the Most Common Risk Factor; DVT without a Risk Factor is Rare in Children
Pie chart showing
- Lupus anticoag=40%
- Central venous catheter=24%
- Acute infection=13%
- Chronic inflamm=10%
- Other=8%
- Idiopathic=5%
SLIDE 13: Inflammatory Markers* at Diagnosis Predicts a Poor Outcome of Thrombosis in Children
Probability of a Poor DVT Outcome: Positive Likelihood Ratio 6.1
All children
- 51%
Children with inflammation
- 90%
* FVIII, DD, Goldenberg, et al NEJM, 2004;351:1081-8
SLIDE 14: The Newborn Infant Has a Unique Hemostatic Balance:
BLEEDING
- lower Thrombin Generation
- lower Fibrin Tensile Strength
- lower Platelet Aggregation
THROMBOSIS
- higher Rate of Thrombin Generation & Thrombin Regulation
- higherTF Expression, Whole Blood Clotting & Hematocrit
- higher Platelet Adhesion
SLIDE 15: Thrombosis May Be Devastating in Neonates
Photos of thrombosis in Neonates
SLIDE 16: Children Have an Excellent Chance for Recovery From Severe DVT
Now 18 years old, this "Gifted & Talented" HS Senior with severe protein C deficiency (compound heterozygous, <1%) is going to college.
SLIDE 17: Outcome of In Utero Thrombosis with Severe Thrombophilia is Good with Treatment
[Photo]
CXR on Infant with Respiratory Infection
PMH: normal pregnancy, labor and delivery; well until acute respiratory illness
FH: negative for bleeding, thrombosis
Left: Organized IVC clot, left adrenal hemorrhage
Right: Organized right atrial clot
Thrombophilia eval: Homozygous Factor V Leiden, Heterozygous Protein C Deficiency; D-dimer, F 1+2, TAT persistently elevated
SLIDE 18: Critical Issues in DVT in Children
- DVT is an important and increasing problem in infancy, childhood and adolescence.
- Health and cost burdens of DVT and its long-term complications are disproportionately higher in children:
- Children will live 60 - 80 years following DVT.
- PTS limits aerobic activities that are necessary for normal childhood development.
- DVT trials specific for children are urgently needed.
SLIDE 19: DVT is the Most Common Blood Clot in Children (n=84)
Time-Limited Risk Factors: Trauma, surgery, immobility Indwelling Catheters Infection, Post infectious APA Surgically Correctible Congenital Heart Disease Leukemia, Cancer, Chemotherap Steroids On-Going Risk Factors: Genetic Thrombophilia Primary or Secondary APAS Inflammatory Diseases Prosthetic Cardiac Valves Sickle Cell Anemia
Pie chart showing
- DVT=63%
- CSVT=18%
- Isol PE=5%
- RVT=6%
- IAS=10%
SLIDE 20: Clot Formation is Accelerated in the Newborn
Picture of CloFAL Assay
Picture of newborn and adultCloFAL Assay
