Transcript Heme/Onc Part 2 - LSU School of Medicine

DBA
TEC
Age
Infancy
1-3y/o
Inherited?
Inherited?
Acquired
Antecedent illness
No
Viral illness
Abnormal
facies/anomalies
Yes: 25-50%
No
RBC Adenosine
Deaminase
High
Normal
MCV
High
Normal
(?high in recovery)
Hgb F
High
Normal
(?high in recovery
Differences: DBA and TEC
DBA
TEC
Spontaneous Recovery Rarely
Almost always
Transfusion
Common
Uncommon
Steroids
Helpful
No
Incidence
Rare
Common

DBA may be considered premalignant syndrome
• Laughing: Pediatric Boards
Both DBA and Fanconi Anemia can have:
Thumb abnormalities, urogenital defects,
severe anemia
DBA will typically be ISOLATED ANEMIA
Think about it

12 month old
 Severe anemia (Hbg 3)
 Recent viral illness
 Reticulocytosis

TEC in recovery phase
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

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
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
Reilly (Alder-Reilly) Bodies

WBC metachromatic prominent granules
 Stained with toluidine blue

Pathognomonic for Hurler syndrome
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
Bleeding Disorders




Disorders of Platelets
Mucocutaneous bleeding
Purpura
Petechiae
Ecchymoses


Coagulopathies
Deep tissue bleeding
Joint bleeds
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
Bleeding Disorders

Evaluation
 CBC c diff
 Platelet count
 PT
 PTT
 Bleeding time or closure time
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
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
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
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
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
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
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
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
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
Coagulopathies

Hemophilia
 Secondary hemophiliac
arthropathy
○ Knees
○ Elbows
○ Ankles
 Contractures
 Painful arthritis
 Compartment syndrome
○ Intramuscular bleeding
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
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
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
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
Thrombosis
Disruption in the
balance of
procoagulant and
antithrombotic factors
 Rare in children

 Infants and
adolescents

Incidence increasing
 Due to use of
indwelling lines
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
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
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
Thrombosis

Factor V Leiden
 Mutations lead to protein C resistance
○ Can’t degrade procoagulant factors

Factor II prothrombin gene variant
 Increased factor II

Methylene tetrahydrofolate reductase
(MTHFR) gene mutation
 Thermolabile variant
 Increased plasma homocyteine levels

Genetic testing may be done
 Not affected by anticoagulants
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.
B.
C.
D.
E.
Chromosomal analysis
Bone Marrow Biopsy
CBC with peripheral smear
CBC with reticulocyte count
CBC with diff
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
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
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