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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.

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Thrombotic complications in pediatric patients

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  1. Thrombotic complications in pediatric patients

  2. 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 בריכוזוהילד, 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.

  3. ב-:MRIאוטם באזור הגלובוס פלידוס • בבירור של קרישיות-יתר: • הטרוזיגוטי ל-Factor V Lieden

  4. בדראן איבטיסם מג'ד 3 חליל 15 רוזין 8 אמג'ד 13

  5. לאחרונה: • במחלקת תינוקות: ילוד עם קונטרקטורות שלשורשי כפות ידיים, הידיים(בעיקר השמאלית)צמודות לגוף. • ב-US מח: ממצאים בעד: Rt. Periventricular infarction

  6. במחלקת ילדים: • ילד בן 9 • רלפס של ALL עם מעורבות CNS • סימנים נוירולוגים • ב-CTcerebral vein thrombosis (,jugularis (sigmoid, transverse, SSS

  7. ילדה בת 17 • חצי שנה על גלולות למניעת הריון • עישון 3 סיגריות 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 ה-middle cerebral artery • Young stroke 

  8. בן 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 theadult.

  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. Upper limb DVT more frequently associated with CVLs. • Long term parenteral nutrition using CVL: high risk situation • Gold standardfor diagnosis: venography • CVL’s predispose to thrombosis by introducing foreign surface, damaging the endothelium, disturbing blood flow, content of fluid infusions)

  18. 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.

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

  20. 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

  21. 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

  22. Paradoxical emboli VTE can also present asstrokewith paradoxical emboli(in children with right-to-left shunt)

  23. 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

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

  25. 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

  26. ARTERIAL THROMBOEMBOLIC DISEASE • Kawasaki’s disease • Surgery • Arterial catheters • Takayasu’s arteritis • Arterial occlusion of transplanted organs • CNS arterial thromboembolic events

  27. 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

  28. 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.

  29. Kawasaki’s 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.

  30. 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.

  31. 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).

  32. 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.

  33. 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.

  34. 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

  35. Blood coagulation Crucial role Tissue factor - factor VII Major reaction  Conversion ProthrombinThrombin Thrombin  *Procoagulant activity * Neutralized by Antithrombin * Induce anticoagulation

  36. 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).

  37. 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.

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

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

  40. Suspicion of underlying thrombophilia: • Unexplained thrombosis in younger than 40-45 years of age. • Recurrent thromboembolic event. • Thrombosis of visceral, cerebral orcutaneous vessel. • Positive family history. • Thrombosis in unusual sites.

  41. Risk factors for thrombosis (1) Acquired: Surgery Trauma Immovilization Increasing age Malignancy Nephrotic Syndrome

  42. 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

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