Interactive talk on common hematological and oncological emergencies - which if not noticed early can lead to irreversible complications and death . Intended to be used for educational purposes for the fertile minds in medicine .

1. Emergencies in Pediatric
Hematology
Akshat Jain MD, MPH’15
Division of Pediatrics , Pediatric Hematology
Oncology and Stem Cell Transplantation
Steven and Alexandra Cohen Children's Medical center
of New York

2. Emergencies in Pediatric Hematology
– Bleeding emergencies
– Sickle cell emergencies
– Anemia in a Neonate
– Transfusion emergencies

3. Identifying abnormal “bleeding”
• Epistaxis unrelieved by 15 minutes of
pressure, both nostrils, requiring an
ER visit, documented drop of Hb.
• Bleeding after procedures
(circumcision, dental extractions, T
and A-delayed bleed)
• Ecchymoses/bruising inconsistent
with the degree of trauma.
• Menstrual periods( amount, pads,
duration)

4. Cause of bleeding in a child !
• Coagulation
a. Primary hemostasis
b. Secondary hemostasis
• Vascular ( Non hematologic)
Eg. Child Abuse ,Vasculitis

5. Causes of Bleeding - Coagulopathy:
Congenital :
• VWF Deficiency
• Hemophilia
• Platelet dysfunction
Acquired :
• DIC
• Anticoagulants
• Vit. K deficiency
• Hepatic Failure
• Renal Failure
• Maternal
Anticonvulsant

6. Characteristic Primary
hemostasis
Secondary hemostasis
Onset Spontaneous and
immediate
Delayed after trauma
Usual site Skin, mucous membranes Deep tissues /
hemarthrosis
Other sites Rare Retroperitoneum, CNS
Examples Thrombocytopenia,
platelet defects (vWD)
Factor deficiency or
inhibitor
Case with Bleeding ? Think -

7. Case 1 : A healthy full term newborn has a completely normal
physical exam except for a few petichiae. Platelet 50,000.
THINK
Production defects:
Small platelets
Genetic - TAR, Trisomy 13, 18 Wiskott-
Aldrich
Infections- viral, bacterial.
Infiltration (Gauchers, Niemann Pick ,
Myelofibrosis , Osteopetrosis) ,Leukemia
Destruction :
Large platelets
Allo-immune-
Platelet group incompatibility.
Auto-immune: Mat ITP
Drugs (thiazide ,tolbutamide), SLE ,Infections
Loss: Kasabach- Merritt syndrome
(hemangiomas, DIC/TTP)

8. Kasabach-Merritt , TAR

9. Case 2 -Photo Quiz
What’s different in this peripheral
smear ?
Normal Abnormal

10. ITP

11. ITP
• Usually acute onset; immune mediated; post viral
• Peak 2-5 years of age, males=females
• Spontaneous bruises, petechiae
• PE –no lymphadenopathy (LN), hepatosplenomegaly.
• CBC- other cell lines normal, large platelets on smear
• Treat if platelet < 10,000 or wet ITP, avoid NSAIDS, Aspirin.
• Treat- IVIG best response, 48-72 hours; Side effects.
– Anti-D (WInRho) Rh+ ,hemolysis, quick response
– Steroids good response, SE, inexpensive, need BM
• BM- Increased megakaryocytes, otherwise normal

12. Case 3
• 10 year old male treated with Valproic acid for seizures presents with fever.
Well appreaing with no skin lesions, lymphadenopathy or
hepatosplenomegaly.
Labs - WBC 5K , Hb 12gm, Platelet 65,000.
BUN 12, Creatinine 0.6 md/dl.
• What is the Most likely cause:
– ITP (Immune thrombocytopenic purpura)
– HUS (Hemolytic Uremic Syndrome)
– HS Purpura (Henoch- Schonlein Purpura)
– ALL (Acute lymphoblastic leukemia)
– Drug induced purpura

13. Bleeding Disorders
Coagulation cascade

14. Bleeding Hemophiliac

15. The bleeding hemophiliac
Hemophilia –
– A (“classic”): factor 8 deficiency
– B (“christmas disease”): factor 9 deficiency
– Both coded on X chromosome
– Disease due to absent or dysfunctional protein
– Clinically INDISTINGUISHABLE
– Prevalence: 1 in 7500 males

16. Basics of managing the bleeding
hemophiliac
• Rx -
– Respective recombinant factor replacement (both F8 and F9 deficiency)
– DDAVP (mild factor 8 deficiency)
– Antifibrinolytics (amicar)
• FUNDAMENTAL PRINCIPLE:
– Recombinant factor 8 dosing:
• 1 unit/kg of factor 8 raises the activity level 2%
– Recombinant factor 9 dosing:
• 1.5 unit/kg of r-factor 9 raises the acvity level 1%
Life threatening Emergencies
– FFP (factor 9 deficiency)
– Cryoprecipitate (factor 8 deficiency)

17. Case 4 - What's Wrong ?
8 yo male with jaundice , Hgb- 8 gms , Elevated reticulocyte count
Elevated total bilirubin , Abnormal cells on peripheral blood smear
examination

18. Emergencies in Pediatric Hematology
– Bleeding emergencies
– Sickle cell emergencies
– Anemia in a Neonate
– Transfusion emergencies

19. Sickle cell emergencies

20. •Crises
•Infection
•Stroke
•Sequestration
•Acute chest syndrome

21. Sickle cell crises
• Vasoocclusive crisis- dactylitis, long bones, back,
chest.
• Aplastic crisis
– remember Parvovirus B19!

22. Sickle Cell Disease (SCD)
• General principles :
– Gentle hydration
– Anti-inflammatory medications and narcotics .
– STAT CBC w Reticulocyte count , Type and cross.
– Supplemental oxygen ( controversial ) .

23. Can You Prevent a Pain Crisis?
• Avoid extremes of temperatures; be prepared for
sudden changes in temperature
• Adequate hydration
• Avoid swimming in cold water
• Related to menstrual bleeding; consider
contraception

24. Pain crisis Management
• Warm, moist soaks , Never cold packs
• Increase oral hydration
• Ibuprofen
• Opoids
• Prefer not giving combinations preps – Percoset ,
Tylenon#3

25. Bacteremia and Sepsis
Functional asplenia develops after
repeated splenic infarctions in
the 1st year of life.
Leads to an increased risk of
sepsis, particularly with
Streptococcus pneumoniae.
Prior to PPV 23, the risk of
pneumococcal disease was 10%
in children < 5years of age.
300 times greater than the general
population.

26. PROPS I study
Prophylaxis with Penicillin Protects Infants with SCA
from Pneumococcal Sepsis
Gaston et al. NEJM 1986 314:1593-159

27. Management of Fever
• Fever is an emergency!
• Do not use antipyretics for fever at home .
• If temp >100.4 F (38.0 C) → ER visit .
• Basic labs: CBC, U/A, cultures, CXR .
• Empiric IV antibiotics (e.g., ceftriaxone 75 mg/kg) .
• Observe for 3 hours .
• Follow up in 24 hours
– Give second IV antibiotic dose in 24 hours.
• Admit if: toxic appearing, hemodynamic instability, WBC >30,000/µL
or <5,000/µL, prior history of sepsis, temp > 40 C, social concerns .
• Consider adding vancomycin if any of the above .

28. Stroke in SCD
Occurs in 5 – 10% of children with
HbSS
Thrombotic or infarctive event
involving large intracranial
arteries
Presents with weakness, aphasia,
seizures, LOC
Often results in permanent
neurological damage and long-
term disability

29. Rates of Stroke in HbSS by
Age
Ohene-Frempong et al Blood. 1998

30. STROKE
• Can be ischemic (younger) or hemorrhagic (older ) .
– Administer oxygen and IV fluids .
– CBC w retic, Type and cross .
– CT Scan brain .
– Alert Blood bank STAT - exchange transfusion .

31. Secondary Prevention of
Stroke
 Without transfusion 70% recur within 3
years of initial stroke
 Chronic transfusion therapy with an aim
to keep HbS<30% at all times
 Recurrence only 10% on chronic
transfusion

32. Splenic Sequestration
Blood can pool in
spleen, causing
hypovolemia.
-I.V. Fluids,
-Transfuse only to 8
or 9 g/Dl – NOT
MORE

33. Spleenic sequestration

34. Case 5
• 12 year old female with SS disease complains of right sided
chest pain and upper back pain for one day.
• P/E reveals slightly reduced breath sounds and a Pulse OX of
86 %. CXR shows an infiltrate on the right lower lobe.
• What is your diagnosis?
• What will you do next?

35. ACS
Gladwin MT, Vichinsky E. N Engl J Med 2008;359:2254-2265.

36. Definition- Diagnostic criteria for ACS
• ACS is defined as radiographic evidence of consolidation: a new
segmental radiographic pulmonary infiltrate, AND at least one of
the following:
1. Temperature ≥38.5°C
2. >2 percent decrease in SpO2 (O2 saturation) from a documented
steady-state value on room air (FiO2 = 0.21)
3. PaO2 <60 mmHg
4. Tachypnea (per age-adjusted normal)
5. Intercostal retractions, nasal flaring, or use of accessory muscles of
respiration
6. Chest pain
7. Cough
8. Wheezing

37. Management of Acute Chest Syndrome
• Antibiotics to cover pneumococcal, Mycoplasma, Chlamydia,
• Bronchodilator,
• Oxygen,
• Incentive spirometry,
• Transfusion,
• Steroids (controversial),
• NSAID’s
• Avoid overhydration .

38. Prevention of ACS
• Adequate pain control
• Optimize pain control while minimizing sedation (PCA)
• Incentive spirometry
• Continuous pulse oximetry
• Ambulation

39. Priapism
• Caused by sickling of cells within the penis.
 Results in a sustained erection
 Painful; can lead to damage of penile tissues
Mx. pointers – Don’t transfuse them.
 Emergency evacuation of the hematoma rx of choice.
 Oxygen
 Vasodilators – pseudoephedrine

40. Pathologic Neonatal Anemia
Think of :
1. Hemorrhage
2. Hemolysis
3. Inadequate Production

41. Work up

42. Case 6
• 1 week old male
• Not Jaundiced
• Hgb is 4
• Retic count is 0.5%
What test do you want to order next?

43. Pathologic Anemia in Neonates
• Can be divided into three categories:
1. Hemolysis
2. Inadequate Production
3. Hemorrhage

44. Differential Diagnosis

45. Case 6
• Low/Absent Reticulocyte count, think
marrow dysfunction/failure and get a
biopsy.

46. Inadequate Red Blood Cell
Production
• Can be caused by:
1. Lack of specific substrates or their carriers
2. Lack of an appropriate marrow environment
3. Lack of specific growth factors

47. Reticulocyte Count
• If Low (0-2%) – Obtain Bone Marrow
- Diamond-Blackfan
- Fanconi’s Anemia
- Congenital Dyserythropoetic Anemia
- Refractory Sideroblastic Anemia
- Transcobalamin II Deficiency
- Other BMFS
• If High (>5-10%) – Coomb’s Test

48. Case 7
• 1 week old female
• Jaundiced
• Hgb is 9
• Retic count is 7%
What test do you want to order next?
Direct Coombs test

49. Case 7
• Coomb’s is positive! So think
- Isoimmunization…

50. Isoimmunization
• ABO or Rh incompatibility is the most common cause of
hemolytic disease in the newborn period
• Other minor blood group incompatibilities include c, C, e,
G, FGya (Duffy), Kell, Jka, MNS, Vw

51. • If Coombs is negative, Look at the Smear

52. Case 8 -
• A 6 year old girl who has hereditary spherocytosis presents with a 1
week history of fever. Physical examination and history reveal
abdominal pain, vomiting, fatigue and pallor. Her hemoglobin is
typically about 10 g/dL with a reticulocyte count of 9%, but now, her
hemoglobin is 4 g/dL and the reticulocyte count is 1%. Her bilirubin is 1
mg/dL. Of the following, the MOST likely cause for this girl’s present
illness is infection with
– Coxsackie virus
– Epstein-Barr virus
– Hepatitis A virus
– Influenza A virus
– Parvovirus B19

53. Hereditary Spherocytosis

54. Blood Smear
• Specific RBC Dysmorphology
- Elliptocytosis
- Stomatocytes
- Fragmentation
- Basophilic Stipling
- Spherocytes
Obtain an osmotic fragility test

55. Hereditary Elliptocytosis

56. Case 9
• A previously normal African-
American child visited Africa
and was given malarial
prophylaxis. He experienced
pallor, fatigue, and dark urine.
His hemoglobin level decreased
from 14.8 to 9 g/dL. The most
likely diagnosis is
– Hereditary spherocytosis
– Sickle cell disease
– Hepatitis
– G6PD deficiency
• Blister cells
• Bite cells
• Blister cells
• Bite cells

57. G6PD Deficiency
• Acute Hemolytic Anemia is the most dramatic
presentation of G6PD deficiency.
• Acute intravascular hemolysis occurs after oxidative
stress.
• Stresses include:
– Primaquine or sulfa drugs
– Naphthalene (mothballs)
– Fava beans
– Infection

58. G6PD Deficiency
Bite Cells
When a macrophage in the spleen identifies an RBC with
a Heinz body, it removes the precipitate and a small piece
of the membrane
Heinz Bodies
Inclusions of denatured Hgb

59. • If no Jaundice
– Acute Blood loss due to
- Obstetric Complications
- External Hemorrhage
- Internal Hemorrhage
- DIC/Sepsis
- Bleeding Dyscrasias
If no Jaundice…

60. Infections
• Bacterial Infections
• Parvovirus B19
• TORCH Infections
• Syphilis
• Malaria
• HIV
Get Blood Culture, Maternal Serum for IgG, HIV,
RPR/FTA

61. Differential Diagnosis

62. Case 10
• 1 week old male
• Jaundiced
• Hgb is 9
• Retic count is 7%
• Coomb’s is negative
What test do you want to order next?

63. Case 10
• What does the smear show?
• What tests do you want to order next?

64. Case 10
• Hypochromic, microcytic RBC’s, so think chronic bleed
or thalessemia.
• Obtain a Hgb electrophoresis and a Kleinhaur-Betke
stain.

65. Case 11
• A 4 week old female Twin A, being seen in your
clinic for anemia.
• Born at 34 weeks, birth weight was 4lb 15oz.
• An U/S 6 days prior to birth showed both babies
to be moving well
• Twin B was stillborn. Doctors told parents that
Twin A had given blood to Twin B.

66. Pathologic Anemia in Neonates
• Can be divided into three categories:
1. Inadequate Production
2. Hemolysis
3. Hemorrhage

67. Hemorrhage
• Common cause of anemia in neonates
• Can occur before birth or during delivery
• Associated with obstetric accidents and maternal
hemorrhage
• Can also be due to internal hemorrhage or recurrent
phlebotomy losses

68. Transfusion Medicine
• Platelet transfusion
– Platelet count < 10,000
– Active bleeding in setting of
significant thrombocytopenia
– Platelet count of 50,000
adequate for most surgical
procedures
– Single apheresis unit will
generally raise platelet count by
30,000
• Anticipate low yield with
splenomegaly, DIC, sepsis
– Relative contraindications
• ITP, TTP, and HIT
– Indications of plasma
transfusions
• Coagulation factor deficiency
– Consider factor concentrates
if available
• Rapid reversal of warfarin effect
• Hemorrhage in patients with liver
disease
• DIC (controversial)

69. Transfusion Emergencies -Transfusion Reactions
– Acute hemolytic reaction
• Intravascular hemolysis (hemoglobinuria)
– Fever, chills, pain, nausea, dyspnea, hypotension
– May lead to ARF, DIC, and death
• ABO incompatibility (human error) is most common cause
– Proper labeling and patient identification is essential for prevention
• STOP transfusion and notify blood bank immediately
– Delayed hemolytic reaction
• Occur days to weeks later
• Caused by RBC antibodies not detected by pretransfusion testing
– Febrile non-hemolytic reaction
• Common in patients with multiple prior transfusions
• Caused by cytokines or recipient antibodies to donor leukocytes

70. Transfusion Reactions
 Hypotensive reaction
 Caused by bradykinin generation
 Hypotension and tachycardia shortly after beginning transfusion ; BP returns to
baseline upon interruption
 Usually safe to resume at slower rate upon recovery
 Bacterial contamination
 Septic shock ; high mortality
 Rare but unpredictable
 Transfusion-related acute lung injury (TRALI)
 Occurs during or shortly after transfusion
 Presents as pulmonary edema in absence of heart disease
 Resolves within 48-72 hours
 Mortality rate is 10%

71. I’m going to leave you with the following quiz
that highlights the common and usually
missed presentations of many oncologic
diagnoses !!

72. Quiz 1 - What comes to mind with
each of these presentations
• Fever of unknown origin in a teenager with
weight loss and itching ?
• Infant less than 2 years of age with failure
to thrive and irritability ?
• Mass in the abdomen found by the
babysitter?

73. Quiz 1
• Opsoclonus Myoclonus ?
• Unilateral proptosis in childhood ?
• Proptosis with black eyes ?
• Bone pain and arthritis +/- neutropenia ?

74. Quiz 1
• Bone pain and swelling shortly after
trauma ?
• Bone Pain , weight loss and sick with
normal blood counts ?
• Pancytopenia and young red and white
cell precursors on the blood smear ?

75. THANK YOU !