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 may be considered premalignant syndrome

• Laughing: Pediatric Boards

DBA TEC

Spontaneous Recovery Rarely Almost always

Transfusion Common Uncommon

Steroids Helpful No

Incidence Rare Common

CAUTION!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 illnessReticulocytosis

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 plateletsLocalized consumptive coagulopathy

○ Risk for DICBone marrow is normal

Tx:Address hemangiomaSupport with transfusions

White blood cells

Leukemoid Reaction Differentiated from leukemia by B.M.

Biopsy Leukocyte alkaline phosphatase (LAP)

Increased in leukemoid reaction Down Syndrome

Transient leukemoid reaction as neonate20-30% 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 6A 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 leukemiaB. Blood cultures and IV antibioticsC. Careful PE, review of the smear and consideration of IVIG

therapyD. Type and cross match and infusion of FFPE. Emergency splenectomy following platelet transfusion

Bleeding Disorders

Bleeding DisordersDisorders of Platelets Coagulopathies

Mucocutaneous bleeding Purpura Petechiae Ecchymoses

Deep tissue bleeding Joint bleeds

Bleeding Disorders Bleeding in either may be

TraumaSurgeryHematuriaGuaiac-positive stoolsMenorrhagiaCNS bleeding

EpistaxisMore likely to be nose picking, dry mucous

membranes or rarely HTN

Bleeding Disorders Evaluation

CBC c diffPlatelet countPTPTTBleeding time or closure time

Platelet Disorders Isolated Thrombocytopenia

Idiopathic or immune thrombocytopeniasHypersplenismDICConsumption

○ Intracardiac defect or bypassWashout from exchange transfusionLocal microangiopathic disease

○ HUSLocal thrombosis

○ Renal vein thrombosis

Platelet Disorders ITP

Look at the smear!Large platelets = platelet

destructionHx

○ Recent viral infectionTx

○ 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 circulationMaternal IgG produced against the platelet antigenSuspect when

○ Maternal platelets normalRisk

○ Cephalohematoma○ Bleeding from umbilicus○ ICH

Tx○ Washed maternal platelets○ IVIG

Platelet Disorders Decreased production =

decreased or absent megakaryocyte precursorsTAR 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 7A 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 abuseB. Admit the patient for evaluation of a bone tumorC. Request an orthopedic consultation for aspiration of the elbow joint.D. Obtain a FH, PT, PTT, factor assay and consider factor replacement therapyE. 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 PTTVariable degrees of deficiency and diseaseMild

○ 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 systemsMusculoskeletal

- Hemarthroses- Soft tissue bleeding with

intramuscular hematomasCNSUrinary

Coagulopathies Hemophilia

Secondary hemophiliac arthropathy○ Knees ○ Elbows○ Ankles

ContracturesPainful 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 antigenVon Willebrand factor ristocetin cofactor activityFactor VIII levels

TreatmentDDAVP

○ Causes release of factor stores from platelets and endothelial cells

○ QuantitativeFactor 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

Thrombotic disorders

Thrombosis Disruption in the

balance of procoagulant and antithrombotic factors

Rare in childrenInfants 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 historyPast history of thrombosisRecurrent spontaneous abortionsThrombosis during pregnancyNephrotic syndrome

Thrombosis Protein C

Vitamin K dependentInhibits procoagulant factors Va and VIIIaDecreases clot formation

Protein SCofactor 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

RareCells with an increased sensitivity to complementLeads 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 variantIncreased factor II

Methylene tetrahydrofolate reductase (MTHFR) gene mutationThermolabile variantIncreased plasma homocyteine levels

Genetic testing may be doneNot affected by anticoagulants

Question 8An 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 analysisB. Bone Marrow BiopsyC. CBC with peripheral smearD. CBC with reticulocyte countE. CBC with diff

Pancytopenia

Pancytopenia Definition

Reduction in all three formed elements of the blood

Results from a number of disease processesBone marrow failureDepressed 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