Transcript Thrombotic complications in pediatric patients

Thrombotic complications in
pediatric patients
‫• בן ‪15‬‬
‫• אושפז במחלקת ילדים ב‪ 5.96-‬עקב דלקת ריאות‪.‬‬
‫• באשפוז התקבלה אנמנזה של מאורע פתאומי של הפרעה‬
‫בדיבור‪ ,‬מלווה ברעד כשנתיים לפניכן‪.‬‬
‫• מאז המאורע התרשמו ההורים מירידה בתפקוד עם קשיים‬
‫בריכוז והילד‪ ,‬שהיה עד אז תלמיד טוב‪ ,‬הפסיק ללמוד‪.‬‬
‫• אשפוז שני ב‪ 9.96-‬עקב כאבי ראש פרונטלים‪ ,‬סחרחורות‬
‫ובחילות‪.‬‬
‫• במשפחה‪ :‬הורים‪ ,‬שני אחים ואחות ללא מחלות ידועות‪.‬‬
‫• ב‪ :MRI-‬אוטם באזור הגלובוס פלידוס‬
‫• בבירור של קרישיות‪-‬יתר‪:‬‬
‫• הטרוזיגוטי ל‪Factor V Lieden-‬‬
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‫חליל‬
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‫לאחרונה‪:‬‬
‫• במחלקת תינוקות‪ :‬ילוד עם קונטרקטורות של‬
‫שורשי כפות ידיים‪ ,‬הידיים (בעיקר השמאלית)‬
‫צמודות לגוף‪.‬‬
‫• ב‪ US-‬מח‪ :‬ממצאים בעד‪:‬‬
‫‪Rt. Periventricular infarction‬‬
:‫במחלקת ילדים‬
9 ‫ילד בן‬
CNS ‫ עם מעורבות‬ALL ‫רלפס של‬
‫סימנים נוירולוגים‬
,jugularis ( cerebral vein thrombosis CT-‫ב‬
(sigmoid, transverse, SSS
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‫ילדה בת ‪17‬‬
‫חצי שנה על גלולות למניעת הריון‬
‫עישון ‪ 3‬סיגריות ליום‬
‫כחודשיים לפני האשפוז ביד שמאלית‬
‫אושפזה עקב אירוע פתאומי של חולשה‪-‬נימול ביד‬
‫שמאלית והפרעה בדיבור‬
‫ב‪ :MRI-‬אוטם פרונטו‪-‬פריאטלי מימין‪,‬בטריטוריה של ענף‬
‫של ה‪middle cerebral artery-‬‬
‫‪Young stroke ‬‬
16 ‫בן‬
Acute otitis media
Mastoiditis
Viral meningitis
Inflammatory bowel disease
Common variable immunodeficiency
sigmoid sinus thrombosis :CT
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Thrombotic events in children
• Age-related features
• Adults guidelines not optimal for children
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Presentation may be more extensive
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Over 50% of events: in upper venous system,
secondary to central venous lines (CVLs)
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More unusual locations
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Essentially in all children: severe underlying
disorders.
5. Different underlying pathology (for example,
Congenital Heart Disease)
6. Patients with homozygous Protein S or Protein
C deficiency present at birth with purpura
fulminans, entity essentially unknown in adult
population.
7. Hemostatic system of the young differs from the
adult.
Incidence of thrombotic complications
in children appear to be increasing:
• Unlike venous thromboembolism in adults,
VTE in children is usually a complication of
a primary illness or therapy.
• As survival rates for major childhood
illnesses such as CHD and cancer
improve, the incidence of VTE is
increasing dramatically.
Risk factors:
Multiple in the majority of patients.
Age distribution:
Two age groups together account for
approximately 70% of thrombosis:
Early infancy:
• Risk approximately 40 times greater than
in any other age during childhood:
• Small vesell diameter, high hematocrit,
immature hemostatic system with
decrease reserve capacity to insults.
Around puberty, late teenage years:
• Hormonal changes
• Oral contraceptives
• Pregnancy
Venous thromboembolism
From the data in the literature:
• 4%  idiopathic
• 12%  only one risk factor
• 84%  two or more risk factors
• Upper limb DVT more frequently
associated with CVLs.
• Long term parenteral nutrition using CVL:
high risk situation
• Gold standard for diagnosis: venography
• CVL’s predispose to thrombosis by
introducing foreign surface, damaging the
endothelium, disturbing blood flow, content
of fluid infusions)
Central Venous lines (cont.)
• Leading cause of thromboembolic disease in
children.
• Incidence underestimated, perhaps because of
different diagnostic modalities.
• Symptoms:
Catheter malfunction, requirement of local
thrombolytic therapy to restore patency,
recurrent sepsis, multiple CVL replacements,
development of superficial collaterals, swelling,
pain.
Consecuences:
NOT TRIVIAL
• Can lead to repeat anesthesia for
CVL replacement
• Lethal Pulmonary embolism
• Superior Vena Cava Syndrome
• Chylothorax
Long term problems:
• Postphlebitic syndrome
• Recurrent thrombosis
• Side effects of long-term anticoagulants
Canadian registry of 525 children:
Death from untreated thrombosis: 2.9%
Recurrent thromboembolic disease: 3.3%
Postphlebitic syndrome: 12.8%
Urgent need to develop safe strategies for
preventing CVL-related thrombosis
Right atrial thrombosis
• Children tend to be young
• CVL’s present in over 80% of cases
• Most common underlying disease: CHD
• Patients may be asymptomatic
• Diagnosis: on routine echocardiography or
present with CVL malfunction, sepsis, CHF
Paradoxical emboli
VTE can also present as stroke with
paradoxical emboli (in children with
right-to-left shunt)
Cerebral vein thrombosis
Largest group of affected children:
• Newborns within 1st month of life
• Most common symptoms: headache, seizures,
lethargy, intermittent hyper-excitability.
• Most common underlying disorders: Cardiac
disease, thrombophilia
• Diagnostic test of choice: MRI / MRV
Thrombotic complications in ALL:
• Disease process itself
• L-Asparaginase
• Effect of other chemotherapeutic agents
Congenital / acquired
Cardiac disease
Cardiac catheterization
risk of at least 40% in small children if heparin is
not used.
Mechanical prosthetic valves
• Considerable risk.
• Require lifelong anticoagulation
Cardiomyopathies
ARTERIAL THROMBOEMBOLIC
DISEASE
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Kawasaki’s disease
Surgery
Arterial catheters
Takayasu’s arteritis
Arterial occlusion of transplanted organs
CNS arterial thromboembolic events
CNS arterial thromboembolic
events
• CT-MRI have greatly facilitated diagnosis
• Incidence of ischemic stroke: 0.063 – 1.2 per
10,000 children per year.
• Thirty percent 1st month of life
• Predisposing disorders:
sickle cell anemia
CHF
prematurity
leukemia
Clinically:
• Infarcts in utero
• Newborns: lethargy, seizures, rarely focal
neurological deficit appreciable.
• Older children: may present with hemiparesis,
with or without seizures.
• TIA’s not unusual.
• MRI / MRA: diagnostic test of choice.
Kawasaki’s disease
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Fever
Lymphadenopathy
Conjunctivitis
Mucositis
Rash
Incidence of aneurysms and / or thrombosed
coronary arteries: 15-30%
• Two percent die from rupture of coronary
arteries or AMI.
Surgery:
• Procedures for CHD (Fontan operation)
Arterial catheters:
• Placed for diagnostic, therapeutic and
monitoring purposes, most common cause in
pediatric patients.
Arterial occlusion of transplanted organs:
• Small children: hepatic, renal arteries.
Takayasu’s arteritis
• Rare chronic, idiopathic, inflammatory
disease of large arteries, predominantly
affecting asian females.
• Clinical presentation: limb or organ
ischemia due to gradual stenosis of
related arteries.
• Diagnosis: angiography. Aortic lesions in
2/3 (aortic arch, carotids, renal arteries
primarily affected).
Other predisposing risk factors:
Nephrotic syndrome
• Incidence of thrombosis: 4-28%
Surgery / Trauma
• In contrast to adults, surgical procedures
in children usually no significant risk,
even in the presence of prothrombotic
disorder.
• Following puberty, risk begins to increase.
• Pediatric patients with thromboembolic
complications should be investigated for a
congenital and/or acquired prothrombotic
state, regardless of the presence of acquired
risk factors.
• Family history – Investigation of parents
• All results should be compared to ageappropriate reference ranges.
Hypercoagulable states:
• Collection of clinical conditions that shift the
balance between the pro and the anticoagulant
forces in favor of coagulation.
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Virchow triad- Risk factors for thrombogenesis:
Vessel wall
Disturbances in blood flow
Changes in constituents of blood
Blood coagulation
Crucial role
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Major reaction 
Tissue factor - factor VII
Conversion
ProthrombinThrombin
Thrombin  * Procoagulant activity
* Neutralized by Antithrombin
* Induce anticoagulation
Thrombotic process
• Thrombi may form in any part of the
cardiovascular system (veins, arteries, heart,
microcirculation)
• Complications of thrombosis:
-effects of local obstruction of the vessel
-distant embolization
-consumption of hemostatic elements
(less often).
Arterial thrombi: under conditions of high
flow, composed mainly of platelets
aggregation bound together by fibrin
strands.
Venous thrombi: in areas of stasis.
Composed of red cells with large amounts
of interspersed fibrin and fewer platelets.
Pathogenesis of thrombosis
Breakdown in the balance
between thrombogenic factors
and protective mechanisms.
Thrombotic disorders
Patients clinically suspected can be
divided in 2 categories:
• Inherited
• Acquired
Heterogeneous group of diseases with
increased risk of thrombotic complications.
Suspicion of underlying
thrombophilia:
• Unexplained thrombosis in younger than 40-45 years
of age.
• Recurrent thromboembolic event.
• Thrombosis of visceral, cerebral or cutaneous
vessel.
• Positive family history.
• Thrombosis in unusual sites.
Risk factors for thrombosis (1)
Acquired:
Surgery
Trauma
Immovilization
Increasing age
Malignancy
Nephrotic Syndrome
Risk factors for thrombosis (2)
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Antiphospholipid antibodies
Hyperhomocysteinemia
Previous thrombotic event
Pregnancy – Puerperium
Oral contraceptives
Drugs (L-Asparaginase)
Myeloproliferative disorders
Paroxysmal Nocturnal Hemoglobinuria
Hormonal replacement therapy
Inherited risk factors (1)
Common:
• Factor V Leiden
• Prothrombin 20210
• Elevated levels of coagulation factors
(II, VIII, IX, XI)
Inherited risk factors (2)
Rare:
Antithrombin
Protein S
Protein C
Inherited risk factors (3)
Very rare:
Dysfibrinogenemia
Homocystinuria
Inherited risk factors (3)
Other:
Plasminogen deficiency
Thrombomodulin mutations
Thrombophilia studies-2006 (1)
Hematology (Coagulation) laboratory:
• Blood count +
peripheral blood smear
• PT-PTT
• Fibrinogen
• Thrombin time
• Lupus anticoagulant
• APC-R
• Antithrombin
• Protein S
• Protein C
• Factor IX
• Factor VIII
• Factor XI
Thrombophilia studies (2)
Hematology (Molecular Biology) laboratory
• Factor V Leiden
• Prothrombin 20210
• MTHFR mutation
Thrombophilia studies (3)
Immunology laboratory
• Anticardiolipine Ab IgM-IgG
• Anti β2 Glycoprotein 1 IgM-IgG
• Antinuclear Ab - Anti DNA
Thrombophilia studies (4)
Biochemistry laboratory
• Homocysteine