Title: Thrombotic complications in pediatric patients
1Thrombotic complications in pediatric patients
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- Rt. Periventricular infarction
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- ?-CT cerebral vein thrombosis (,jugularis
(sigmoid, transverse, SSS
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- Acute otitis media
- Mastoiditis
- Viral meningitis
- Inflammatory bowel disease
- Common variable immunodeficiency
- sigmoid sinus thrombosis CT
9Thrombotic events in children
- Age-related features
- Adults guidelines ?not optimal for children
10- Presentation may be more extensive
- Over 50 of events in upper venous system,
secondary to central venous lines (CVLs) - More unusual locations
- Essentially in all children severe underlying
disorders.
11- Different underlying pathology (for example,
Congenital Heart Disease) - 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.
12Incidence 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.
13- Risk factors
-
- Multiple in the majority of patients.
14Age 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.
15- Around puberty, late teenage years
- Hormonal changes
- Oral contraceptives
- Pregnancy
16Venous thromboembolism
- From the data in the literature
- 4 ? idiopathic
- 12 ? only one risk factor
- 84 ? two or more risk factors
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18- Upper limb DVT more frequently associated with
CVLs. - Long term parenteral nutrition using CVL high
risk situation - Gold standard for diagnosis venography
- CVLs predispose to thrombosis by introducing
foreign surface, damaging the endothelium,
disturbing blood flow, content of fluid
infusions)
19Central 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.
20Consecuences
- NOT TRIVIAL
- Can lead to repeat anesthesia for CVL
replacement - Lethal Pulmonary embolism
- Superior Vena Cava Syndrome
- Chylothorax
21Long 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
22Right atrial thrombosis
- Children tend to be young
- CVLs 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
23Paradoxical emboli
-
-
- VTE can also present as stroke with
paradoxical emboli (in children with
right-to-left shunt)
24Cerebral 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
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30Thrombotic complications in ALL
- Disease process itself
- L-Asparaginase
- Effect of other chemotherapeutic agents
31Congenital / 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
32ARTERIAL THROMBOEMBOLIC DISEASE
- Kawasakis disease
- Surgery
- Arterial catheters
- Takayasus arteritis
- Arterial occlusion of transplanted organs
- CNS arterial thromboembolic events
33CNS 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
34Clinically
- Infarcts in utero
- Newborns lethargy, seizures, rarely focal
neurological deficit appreciable. - Older children may present with hemiparesis,
with or without seizures. - TIAs not unusual.
- MRI / MRA diagnostic test of choice.
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36Kawasakis disease
- 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.
37- 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.
38Takayasus 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).
39Other 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.
40- 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 age-appropriate
reference ranges.
41Hypercoagulable states
- Collection of clinical conditions that shift the
balance between the pro and the anticoagulant
forces in favor of coagulation. - Virchow triad- Risk factors for thrombogenesis
- Vessel wall
- Disturbances in blood flow
- Changes in constituents of blood
42Blood coagulation
- Crucial role ? Tissue factor - factor
VII - Major reaction ? Conversion
- Prothrombin?Thrombi
n - Thrombin ? Procoagulant activity
- Neutralized by
Antithrombin - Induce anticoagulation
43Thrombotic 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).
44- 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.
45Pathogenesis of thrombosis
- Breakdown in the balance between thrombogenic
factors and protective mechanisms.
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47Thrombotic disorders
- Patients clinically suspected can be divided
in 2 categories - Inherited
- Acquired
- Heterogeneous group of diseases with increased
risk of thrombotic complications.
48Suspicion 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.
49Risk factors for thrombosis (1)
- Acquired
- Surgery
- Trauma
- Immovilization
- Increasing age
- Malignancy
- Nephrotic Syndrome
50Risk factors for thrombosis (2)
- Antiphospholipid antibodies
- Hyperhomocysteinemia
- Previous thrombotic event
- Pregnancy Puerperium
- Oral contraceptives
- Drugs (L-Asparaginase)
- Myeloproliferative disorders
- Paroxysmal Nocturnal Hemoglobinuria
- Hormonal replacement therapy
51Inherited risk factors (1)
- Common
- Factor V Leiden
- Prothrombin 20210
- Elevated levels of coagulation factors (II, VIII,
IX, XI)
52Inherited risk factors (2)
- Rare
- Antithrombin
- Protein S
- Protein C
53Inherited risk factors (3)
- Very rare
- Dysfibrinogenemia
- Homocystinuria
54Inherited risk factors (3)
- Other
- Plasminogen deficiency
- Thrombomodulin mutations
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56Thrombophilia 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
57Thrombophilia studies (2)Hematology (Molecular
Biology) laboratory
- Factor V Leiden
- Prothrombin 20210
- MTHFR mutation
58Thrombophilia studies (3)Immunology laboratory
- Anticardiolipine Ab IgM-IgG
- Anti ß2 Glycoprotein 1 IgM-IgG
- Antinuclear Ab - Anti DNA
59Thrombophilia studies (4)Biochemistry laboratory
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61thank you