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

Emergencies in Pediatric Hematology

– Bleeding emergencies

– Sickle cell emergencies

– Anemia in a Neonate

– Transfusion emergencies

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)

Cause of bleeding in a child !

• Coagulation

a. Primary hemostasis

b. Secondary hemostasis

• Vascular ( Non hematologic)

Eg. Child Abuse ,Vasculitis

Causes of Bleeding - Coagulopathy:

Congenital :

• VWF Deficiency

• Hemophilia

• Platelet dysfunction

Acquired :

• DIC

• Anticoagulants

• Vit. K deficiency

• Hepatic Failure

• Renal Failure

• Maternal

Anticonvulsant

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 -

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)

Kasabach-Merritt , TAR

Case 2 -Photo Quiz

What’s different in this peripheral

smear ?

Normal Abnormal

ITP

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

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

Bleeding Disorders

Coagulation cascade

Bleeding Hemophiliac

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

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)

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

Emergencies in Pediatric Hematology

– Bleeding emergencies

– Sickle cell emergencies

– Anemia in a Neonate

– Transfusion emergencies

Sickle cell emergencies

•Crises

•Infection

•Stroke

•Sequestration

•Acute chest syndrome

Sickle cell crises

• Vasoocclusive crisis- dactylitis, long bones, back,

chest.

• Aplastic crisis

– remember Parvovirus B19!

Sickle Cell Disease (SCD)

• General principles :

– Gentle hydration

– Anti-inflammatory medications and narcotics .

– STAT CBC w Reticulocyte count , Type and cross.

– Supplemental oxygen ( controversial ) .

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

Pain crisis Management

• Warm, moist soaks , Never cold packs

• Increase oral hydration

• Ibuprofen

• Opoids

• Prefer not giving combinations preps – Percoset ,

Tylenon#3

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.

PROPS I study Prophylaxis with Penicillin Protects Infants with SCA

from Pneumococcal Sepsis

Gaston et al. NEJM 1986 314:1593-1599

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/µLor <5,000/µL, prior history of sepsis, temp > 40 C, social concerns .

• Consider adding vancomycin if any of the above .

Stroke in SCDOccurs 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

Rates of Stroke in HbSS by

Age

Ohene-Frempong et al Blood. 1998

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 .

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

Splenic Sequestration

Blood can pool in

spleen, causing

hypovolemia.

-I.V. Fluids,

-Transfuse only to 8

or 9 g/Dl – NOT

MORE

Spleenic sequestration

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?

ACS

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

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

Management of Acute Chest Syndrome

• Antibiotics to cover pneumococcal, Mycoplasma, Chlamydia,

• Bronchodilator,

• Oxygen,

• Incentive spirometry,

• Transfusion,

• Steroids (controversial),

• NSAID’s

• Avoid overhydration .

Prevention of ACS

• Adequate pain control

• Optimize pain control while minimizing sedation (PCA)

• Incentive spirometry

• Continuous pulse oximetry

• Ambulation

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

Pathologic Neonatal Anemia

Think of :

1. Hemorrhage

2. Hemolysis

3. Inadequate Production

Work up

Case 6

• 1 week old male

• Not Jaundiced

• Hgb is 4

• Retic count is 0.5%

What test do you want to order next?

Pathologic Anemia in Neonates

• Can be divided into three categories:

1. Hemolysis

2. Inadequate Production

3. Hemorrhage

Differential Diagnosis

Case 6

• Low/Absent Reticulocyte count, think

marrow dysfunction/failure and get a

biopsy.

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

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

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

Case 7

• Coomb’s is positive! So think

- Isoimmunization…

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

• If Coombs is negative, Look at the Smear

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

Hereditary Spherocytosis

Blood Smear

• Specific RBC Dysmorphology

- Elliptocytosis

- Stomatocytes

- Fragmentation

- Basophilic Stipling

- Spherocytes

Obtain an osmotic fragility test

Hereditary Elliptocytosis

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

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

G6PD Deficiency

Bite CellsWhen a macrophage in the spleen identifies an RBC with

a Heinz body, it removes the precipitate and a small piece

of the membrane

Heinz BodiesInclusions of denatured Hgb

• If no Jaundice

– Acute Blood loss due to

- Obstetric Complications

- External Hemorrhage

- Internal Hemorrhage

- DIC/Sepsis

- Bleeding Dyscrasias

If no Jaundice…

Infections

• Bacterial Infections

• Parvovirus B19

• TORCH Infections

• Syphilis

• Malaria

• HIV

Get Blood Culture, Maternal Serum for IgG, HIV, RPR/FTA

Differential Diagnosis

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?

Case 10

• What does the smear show?

• What tests do you want to order next?

Case 10

• Hypochromic, microcytic RBC’s, so think chronic bleed

or thalessemia.

• Obtain a Hgb electrophoresis and a Kleinhaur-Betke

stain.

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.

Pathologic Anemia in Neonates

• Can be divided into three categories:

1. Inadequate Production

2. Hemolysis

3. Hemorrhage

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

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)

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

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%

I’m going to leave you with the following quiz

that highlights the common and usually

missed presentations of many oncologic

diagnoses !!

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?

Quiz 1

• Opsoclonus Myoclonus ?

• Unilateral proptosis in childhood ?

• Proptosis with black eyes ?

• Bone pain and arthritis +/- neutropenia ?

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 ?

THANK YOU !