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Thrombotic complications in pediatric patients

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Title: Thrombotic complications in pediatric patients Author: liliana.schliamser Last modified by: user0123 Created Date: 3/14/2006 9:12:04 AM Document presentation ... – PowerPoint PPT presentation

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Title: Thrombotic complications in pediatric patients


1
Thrombotic complications in pediatric patients
2
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  • ?-CT cerebral vein thrombosis (,jugularis
    (sigmoid, transverse, SSS

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    ?? ?-middle cerebral artery
  • Young stroke ?

8
  • ?? 16
  • Acute otitis media
  • Mastoiditis
  • Viral meningitis
  • Inflammatory bowel disease
  • Common variable immunodeficiency
  • sigmoid sinus thrombosis CT

9
Thrombotic 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.

12
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.

13
  • Risk factors
  • Multiple in the majority of patients.

14
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.

15
  • Around puberty, late teenage years
  • Hormonal changes
  • Oral contraceptives
  • Pregnancy

16
Venous thromboembolism
  • From the data in the literature
  • 4 ? idiopathic
  • 12 ? only one risk factor
  • 84 ? two or more risk factors

17
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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)

19
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.

20
Consecuences
  • NOT TRIVIAL
  • Can lead to repeat anesthesia for CVL
    replacement
  • Lethal Pulmonary embolism
  • Superior Vena Cava Syndrome
  • Chylothorax

21
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

22
Right 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

23
Paradoxical emboli
  • VTE can also present as stroke with
    paradoxical emboli (in children with
    right-to-left shunt)

24
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

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30
Thrombotic complications in ALL
  • Disease process itself
  • L-Asparaginase
  • Effect of other chemotherapeutic agents

31
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

32
ARTERIAL THROMBOEMBOLIC DISEASE
  • Kawasakis disease
  • Surgery
  • Arterial catheters
  • Takayasus arteritis
  • Arterial occlusion of transplanted organs
  • CNS arterial thromboembolic events

33
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

34
Clinically
  • 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.

35
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36
Kawasakis 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.

38
Takayasus 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).

39
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.

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.

41
Hypercoagulable 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

42
Blood coagulation
  • Crucial role ? Tissue factor - factor
    VII
  • Major reaction ? Conversion
  • Prothrombin?Thrombi
    n
  • Thrombin ? Procoagulant activity
  • Neutralized by
    Antithrombin
  • Induce anticoagulation

43
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).

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.

45
Pathogenesis of thrombosis
  • Breakdown in the balance between thrombogenic
    factors and protective mechanisms.

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Thrombotic disorders
  • Patients clinically suspected can be divided
    in 2 categories
  • Inherited
  • Acquired
  • Heterogeneous group of diseases with increased
    risk of thrombotic complications.

48
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.

49
Risk factors for thrombosis (1)
  • Acquired
  • Surgery
  • Trauma
  • Immovilization
  • Increasing age
  • Malignancy
  • Nephrotic Syndrome

50
Risk 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

51
Inherited risk factors (1)
  • Common
  • Factor V Leiden
  • Prothrombin 20210
  • Elevated levels of coagulation factors (II, VIII,
    IX, XI)

52
Inherited risk factors (2)
  • Rare
  • Antithrombin
  • Protein S
  • Protein C

53
Inherited risk factors (3)
  • Very rare
  • Dysfibrinogenemia
  • Homocystinuria

54
Inherited risk factors (3)
  • Other
  • Plasminogen deficiency
  • Thrombomodulin mutations

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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

57
Thrombophilia studies (2) Hematology (Molecular
Biology) laboratory
  • Factor V Leiden
  • Prothrombin 20210
  • MTHFR mutation

58
Thrombophilia studies (3) Immunology laboratory
  • Anticardiolipine Ab IgM-IgG
  • Anti ß2 Glycoprotein 1 IgM-IgG
  • Antinuclear Ab - Anti DNA

59
Thrombophilia studies (4) Biochemistry laboratory
  • Homocysteine

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