Differences: DBA and TEC

2. Differences: DBA and TEC • DBA may be considered premalignant syndrome • Laughing: Pediatric Boards

3. Both DBA and Fanconi Anemia can have: Thumb abnormalities, urogenital defects, severe anemia DBA will typically be ISOLATED ANEMIA Caution!

4. Think about it • 12 month old • Severe anemia (Hbg 3) • Recent viral illness • Reticulocytosis • TEC in recovery phase

5. Question 5 • Name the syndrome which is characterized by microangiopathic hemolytic anemia caused by a giant hemangioma. • A: Stendhal Syndrome • B: Kasabach-Merritt Syndrome • C: Capgras Syndrome • D: Cotard Syndrome

6. Kasabach-Merritt Syndrome • Giant hemangioma • Serves as trap for platelets • Localized consumptive coagulopathy • Risk for DIC • Bone marrow is normal • Tx: • Address hemangioma • Support with transfusions

7. White blood cells

8. Leukemoid Reaction • Differentiated from leukemia by B.M. Biopsy • Leukocyte alkaline phosphatase (LAP) • Increased in leukemoid reaction • Down Syndrome • Transient leukemoid reaction as neonate • 20-30% of these: leukemia in 1st 3 yrs of life

9. Reilly (Alder-Reilly) Bodies • WBC metachromatic prominent granules • Stained with toluidine blue • Pathognomonic for Hurler syndrome

11. Question 6 A previously healthy 4 year old girl is seen for petechiae and diffuse bruises. She is anxious but afebrile, alert and not in any distress. She is noted to have bleeding from the gums and moderately severe epistaxis. Lab studies reveal: Hgb 12.5; WBC 7 with a normal diff; platelets 4000. Part of the initial management would include . . . . . A. Immediate bone marrow exam for suspected leukemia B. Blood cultures and IV antibiotics C. Careful PE, review of the smear and consideration of IVIG therapy D. Type and cross match and infusion of FFP E. Emergency splenectomy following platelet transfusion

12. Bleeding Disorders

13. Bleeding Disorders • Mucocutaneous bleeding • Purpura • Petechiae • Ecchymoses • Deep tissue bleeding • Joint bleeds Disorders of Platelets Coagulopathies

14. Bleeding Disorders • Bleeding in either may be • Trauma • Surgery • Hematuria • Guaiac-positive stools • Menorrhagia • CNS bleeding • Epistaxis • More likely to be nose picking, dry mucous membranes or rarely HTN

15. Bleeding Disorders • Evaluation • CBC c diff • Platelet count • PT • PTT • Bleeding time or closure time

16. Platelet Disorders • Isolated Thrombocytopenia • Idiopathic or immune thrombocytopenias • Hypersplenism • DIC • Consumption • Intracardiac defect or bypass • Washout from exchange transfusion • Local microangiopathic disease • HUS • Local thrombosis • Renal vein thrombosis

17. Platelet Disorders • ITP • Look at the smear! • Large platelets = platelet destruction • Hx • Recent viral infection • Tx • IVIG • Anit-D antibody • Only if pt is Rh positive • Splenectomy when unresponsive • Bone marrow • When unresponsive

18. Platelet Disorders • Isoimmune Thrombocytopenia in the Newborn • Fetal platelets cross the placenta into maternal circulation • Maternal IgG produced against the platelet antigen • Suspect when • Maternal platelets normal • Risk • Cephalohematoma • Bleeding from umbilicus • ICH • Tx • Washed maternal platelets • IVIG

19. Platelet Disorders • Decreased production = decreased or absent megakaryocyte precursors • TAR syndrome • Thrombocytopenia-absent radius • Amegakaryocytic thrombocytopenia • Leukemoid reactions • CHD • FTT • In both conditions, thrombocytopenia resolves with age

20. Platelet Disorders • Qualitative or functional platelet disorders • Normal number and clotting studies but poorly functioning platelets • First ask for history of . . . • Drug exposure • Uremia • Hypothyroidism • Hyperbilirubinemia • IBD • Von Willebrand disease

21. Question 7 A 16 month old boy is brought to the ER with persistent crying and refusal to move his right arm. The history is negative for fever and trauma. Past history is significant for bleeding from his circumcision and easy bruising. PE shows boggy, tender swelling of the right elbow with marked decrease in ROM. The Hb is 11.2; WBC, plts and inflammatory markers are normal. You plan would be . . . . A. Obtain a skeletal survey to r/o child abuse B. Admit the patient for evaluation of a bone tumor C. Request an orthopedic consultation for aspiration of the elbow joint. D. Obtain a FH, PT, PTT, factor assay and consider factor replacement therapy E. Close monitoring of the patient w/o intervention for the presumptive diagnosis of HSP

22. Coagulopathies • Deficiency in factors • Causes • Decreased production • Genetic defects • Acquired conditions • Overutilization of factors • Testing • PT • Extrinsic and common • PTT • Intrinsic and common • Make sure you check age related values

23. Coagulopathies • Hemophilia A (VIII) and B (IX) • X-linked recessive • Males • Prolonged PTT • Variable degrees of deficiency and disease • Mild • 5-30% factor activity • Bleeding with surgery or major trauma • Moderate • 1-5% factor activity • Localized hemorrhage in response to trauma • Severe • <1% factor activity • Spontaneous soft tissue hemorrhages or bleeding with minor trauma

24. Coagulopathies • Hemophilia • Presentation • Birth • Circumcision • 12-18 months • Increased mobility and bleeding with minor trauma • Most commonly affected systems • Musculoskeletal • Hemarthroses • Soft tissue bleeding with intramuscular hematomas • CNS • Urinary

25. Coagulopathies • Hemophilia • Secondary hemophiliac arthropathy • Knees • Elbows • Ankles • Contractures • Painful arthritis • Compartment syndrome • Intramuscular bleeding

26. Von Willebrand Disease • Most common heritable bleeding disorder • Bleeding time or closure time is increased with or without an increase in the PTT • Most are AD • Most are asymptomatic and found incidentally • If symptomatic • Abnormal mucosal bleeding • Frequent epistaxis • Menorrhagia

27. Von Willebrand Disease • What does VWF do? • Responsible for the adherence of platelets to damaged endothelium • Required for normal Factor VIII function • Types • I and III • Quantitative • I is most common • II • Qualitative

28. Von Willebrand Disease • Testing • Von Willebrand factor antigen • Von Willebrand factor ristocetin cofactor activity • Factor VIII levels • Treatment • DDAVP • Causes release of factor stores from platelets and endothelial cells • Quantitative • Factor replacement • Donor blood products • Qualitative

29. Acquired Disorders • Inhibitors • Testing • Mix patients plasma with normal plasma • PT or PTT will fail to correct • Example • Lupus anticoagulant • Actually predisposes to thrombosis • 10% of patients with Lupus • Also acquired after some medications or other infectious organisms • Persists for months

30. Thrombotic disorders

31. Thrombosis • Disruption in the balance of procoagulant and antithrombotic factors • Rare in children • Infants and adolescents • Incidence increasing • Due to use of indwelling lines

32. Thrombosis • Increased risk • Retardation of blood flow • Severe dehydration • Immobilization • Endothelial damage • Indwelling catheters • Family history • Past history of thrombosis • Recurrent spontaneous abortions • Thrombosis during pregnancy • Nephrotic syndrome

33. Thrombosis • Protein C • Vitamin K dependent • Inhibits procoagulant factors Va and VIIIa • Decreases clot formation • Protein S • Cofactor required for anticoagulant activity of protein C • Deficiency of either leads to clot formation

34. Thrombosis • Antithrombin III • Inhibitor • Complexes with thrombin, factor Xa and factor IXa • Deficiency lead to loss of inhibition and thrombosis • Paroxysmal Nocturnal Hemoglobinuria • Rare • Cells with an increased sensitivity to complement • Leads to • Abdominal and back pain • Chronic intravascular hemolysis • Intermittent hemoglobinuria • Diffuse venous thrombosis

35. Thrombosis • Factor V Leiden • Mutations lead to protein C resistance • Can’t degrade procoagulant factors • Factor II prothrombin gene variant • Increased factor II • Methylenetetrahydrofolatereductase (MTHFR) gene mutation • Thermolabile variant • Increased plasma homocyteine levels • Genetic testing may be done • Not affected by anticoagulants

36. Question 8 An infant you are seeing in the newborn nursery is born with hypoplastic thumbs and some abnormal skin pigmentation. You suspect that the patient may have Fanconi’s anemia. What test should confirm the diagnosis? A. Chromosomal analysis B. Bone Marrow Biopsy C. CBC with peripheral smear D. CBC with reticulocyte count E. CBC with diff

37. Pancytopenia

38. Pancytopenia • Definition • Reduction in all three formed elements of the blood • Results from a number of disease processes • Bone marrow failure • Depressed marrow function and increased cellular destruction

39. Aplastic Anemia • Insult to the bone marrow • Drugs • Toxins • Solvents • Radiation • Autoimmune • Postinfectious • Idiopathic • 50% • Bone marrow failure • Death from infection or bleeding unless there is an intervention

40. Fanconi Anemia • Autosomal recessive • Signs • Pancytopenia • Marrow hypoplasia • Congenital anomalies • Abnormal skin pigmentation • Growth retardation • Skeleton • Absent or hypoplastic thumb • CNS • GU • Testing • Fragility of the chromosomes • Breaks, gaps and rearrangements • Treatment • Frequent transfusions • Bone marrow transplant