Module 6 Ics

Front 1

Newborn platelet values compared to adults?

Back 1

150K to 450K x 10ˆ9/L

Mean platelet volume (MPV) is 7-9FI

**same across all ages

Front 2

Newborn platelet survival compared to adults?

Back 2

7-10 days

**same across all ages

Front 3

Newborn platelet structure compared to adults?

Back 3

Same number granules

Serotonin and ADP content is ~50% that of adults

Front 4

Newborn platelet adhesion compared to adults?

Back 4

1. ↑ as measured by ↓ bleeding time
-- ↑vWF + large RBCs + ↑Hct

2. ↑ agglutination of cord platelets at birth
-- ↑vWF + ↑ high molec wt VW multimers

3. ↑↑agglutination to ristocetin

Front 5

Newborn platelet aggregation compared to adults?

Back 5

1. ↓ aggregation to epi
-- ↓ number of α-adrenergic receptors

2. variable aggregation to ADP, collagen, and arachidonic acid

Front 6

Newborn platelet activation/secretion compared to adults?

Back 6

No specific abnormalities, however:

Platelets are activated at birth as manifested by elevation of
-- Thromboxane β2
-- β-Thrombomodulin
-- PF4
-- decreased granular content of cord platelets
-- decreased level of epi receptor availability

Activation is multifactorial as thermal changes, hypoxia, acidosis, adrenergic stimulation, and exposure to amniotic fluid are all likely to occur at birth

Front 7

Vessel wall (endothelium) fxns in a newborn?

Back 7

1. Antithrombosis
-- production of prostacyclin via liopoxygenase and cyclooxygenase mediated pathway of unsaturated fatty acids
-- promotion of ATIII neutralization of thrombin by cell surface proteoglycans
-- production of NO --> vascular relaxing factor, inhibitor of platelet activation and platelet adhesion to damaged vessel walls

2. Hemostasis
-- promotes formation of fibrin when injured

Front 8

What is the key step in homostasis?

Back 8

Thrombin formation
-- significantly decreased in newborns --> similar to adult receiving therapeutic doses of anticoagulant

Front 9

Why is thrombin decreased in newborns?

Back 9

Result of:
-- decreased factor and inhibitor production
-- increased clearance
-- increased consumption from activation of the coagulation cascade at birth

Front 10

Coagulation factors in the fetus?

Back 10

Do NOT cross the placenta

Measurable by 10wks of gestational age and continue to increase thereafter

Front 11

Vitamin K factors in the newborn?

Back 11

II, VII, IX, and X

DECREASE at birth and are directly involved in the hemorrhagic disease of the newborn

Front 12

Contact Phase factors in the newborn?

Back 12

XI, XII, Prekallikrein and HMW Kininogen

Decrease at birth and directly responsible for the ↑↑APTT

Front 13

Other coagulation factors in the newborn?

Back 13

Fibrinogen, V, VIII, XIII, and vWF

-- NOT decreased at birth

Front 14

List inhibitors of coagulation.

Back 14

Direct inhibitors
Protein C/Protein S system
Tissue Factor Pathway Inhibitor (TFPI)
Regulation of thrombin by fibrin

Front 15

What are the direct inhibitors of coagulation in a newborn?

Back 15

1. C1 esterase inhibitor
-- increased at birth
2. α2 macroglobulin
-- increased at birth
3. Heparin cofactor II
4. Antithrombin III
5. Fetal anticoagulant (acts via heparin cofactor II)

Front 16

Explain the Protein C/Protein S system and their levels in the newborn.

Back 16

1. Thrombomodulin
-- ↑↑↑ at birth until early childhood

2. Protein C
-- ↓↓↓ at birth until 6mos of age
-- fetal form has excess of single chain protein
-- adult levels reached by early childhood

Protein S
-- ↓ at birth but fxnal activity similar to that of adult

STEP 1: binding of thrombin to thrombomodulin

STEP 2: interruption of fibrinogen, factor V and factor VIII cleavage as well as platelet activation

STEP 3: activation of Protein C in the presence of Protein S and inactivation of Va and VIIIa by proteolytic degradation

Front 17

What does the Tissue Factor Pathway Inhibitor (TFPI) do?

Back 17

STEP 1: TFPI/Xa complex binds to VIIa and inactivates VIIa

STEP 2: prevents further generation of thrombin

Front 18

What are the components of the fibrinolytic system in a newborn?

Back 18

1. t-PA and PAI are ↑↑ in the newborn but ↓↓ in the cord blood at birth

2. α2-antiplasmin: 80% adult level

3. Plasminogen: 50% of adult level

The fibrinolytic system is activated by the birth process

Front 19

What are the common chief complaints that might indicate a hemostatic disorder in a newborn?

Back 19

1. oozing from unbilicus
2. bleeding into the scalp
3. large cephalhematoma
4. bleeding after circumcision
5. bleeding at venipuncture sites
6. intracranial hemorrhage
7. sites of invasive procedures (mucous mbrn, bladder, etc)
8. joint bleeding is rare

Front 20

What are the most common causes of bleeding in healthy infants?

Back 20

immune mediated thrombocytopenia

Vitamin K deficiency

congenital factor deficiency

Front 21

What is the most common hemostatic abnormality in newborns?

Back 21

thrombocytopenia
-- indicative of an underlying pathologic process

Front 22

Thrombocytopenia incidence in newborns?

Back 22

-- approx 22% of all newborns admitted into NICU

-- about 50% of affected infants have counts <100 x 10ˆ9/L
-- 20% have counts <50 x 10ˆ9/L

In 75% of sick newborns, thrombocytopenia is present by day 2 of life, reaches its nadir by day 4, and recovers to >150 x 10ˆ9/L by day 10 in 86% of affected infants

Front 23

What is the risk for serious bleeding in a newborn w/ thrombocytopenia?

Back 23

Depends on:
-- platelet count (<50 x 10ˆ9/L)
-- presence of a platelet fxn defect
-- maturity of infant (highest risk in premature)

Front 24

What processes are implicated in the development of thrombocytopenia?

Back 24

1. decreased production
-- rare, responsible for less than 5% of thromboctopenia in newborns

2. increased destruction
-- directly implicated in the majority of infants

3. increased pooling in the spleen

Front 25

How do we manage thrombocytopenia?

Back 25

Depends on underlying disorder and may require combination of modalities

PLATELET TRANSFUSION
-- indicated in bleeding infant, regardless of cause
-- 10-20ml/kg concentrate

IVIG
-- for infants w/ thrombocytopenia induced by placental passage of autoAb
-- indicated to block trapping of platelets by the splenic RES system

Front 26

Other qualitative platelet disorders in a newborn?

Back 26

PREVENT NORMAL AGGREGATION:
-- salicylates
-- indomethacin
-- nitric oxide

INCREASED PLATELET AGGREGATION
-- maternal diabetes
-- diet deficient in essential fatty acids and vitamin E
-- perinatal aspiration of aamniotic fluid

Front 27

Congenital factor deficiencies in the newborn and bleeding incidence?

Back 27

Usually only severe deficiencies are associated w/ signif bleeding in the newborn
-- do not bleed perinatally unless hemostatically challenged

Front 28

Factor dificiencies in the newborn?

Back 28

1. Factor VII and IX
-- two sex-linked d/o's
-- also known as hemophilia A and B
-- most frequent

2. Deficiencies of factors II, V, VII, XI, XII, prekallikrein or HMWK
-- rare, autosomal recessive
-- normally seen in families w/ hx of consanguinuity
-- deficiencies of XII , prekallikrein, and HMWK do not result in hemorrhagic complications

Front 29

How do we diagnose factor deficiencies in the newborn?

Back 29

Measurement of plasma concentration of coagulatoin proteins

Use molecular techniques prenatally

Evaluate the parents

Front 30

What are the most frequent sites of bleeding?

Back 30

penis (circumcision)

umbilicus

intracranial hemorrhage
-- rare in full tern newborns w/o signif primary promblems
-- should raise possibility of primary hemostatic disorders

Front 31

What is the usuall treatment of choice for congenital factor deficiencies?

Back 31

Usually NOT plasma or FFP

Several specific concentrates produced by either recombinant techniques or highly purified and treated against infectious organisms are now available for the majority of congenital deficiencies.

Front 32

List acquired hemostatic disorders possible in a newborn.

Back 32

1. DIC
2. Liver disease
3. Vitamin K deficiency
4. Other

Front 33

Describe DIC in the newborn.

Back 33

Clinical spectrum continually changing due to improved perinatal care

Accumulation of several factors, those most important being:
-- intensity/duration of activation of the hemostatic system
-- degree of assoc blood flow impairment
-- extent of liver fxn or dysfxn

Front 34

How do we diagnose DIC in the newborn?

Back 34

Since the coag system is activated at birth, certain markers like ATII/thrombin complex determination CANNOT be used

Decreased factor V, VII, and fibrinogen are more likely diagnostic since their conc is similar to adults

NO Dx test can confirm or exclude DIC in the neonatal period.

Front 35

DIC treatment in the newborn?

Back 35

Control underlying disorder

Factor replacement not indicated unless there is evidence of bleeding

Maintain:
-- platelet count >50K/mm3
-- fibrinogen >1g/L
-- PT values at levels normal for postnatal and gestational age

Front 36

Liver disease in the newborn?

Back 36

Coagulopathies encountered are due to failure of hepatic synthetic fxns superimposed to:

-- physiologic immaturity
-- activation of coag and fibrinolysis
-- poor clearance of activated coag factors
-- loss of hemostatic proteins into the ascitic fluid
-- thrombocytopenia (↓platelet production + splenic sequestration + ↑ clearance)

**Increased PT and decreased Plasma proteins commonly found

Front 37

Common causes of liver disease in newborns?

Back 37

ciral hepatitis
hypoxia
total parenteral nutrition
shock
fetal hydrops

Front 38

Treatment for liver disease-induced hemostatic disorders in the newborn?

Back 38

FFP
cryoprecipitate
exchange transfusion for clinical bleeding

Pts w/ persistent liver failure: liver transplant

Front 39

What occurs in the absence of Vitamin K?

Back 39

1. Decreased prothrombin activity
2. Increased PT on day 2 to 4 of life
3. Return to normal by day 5-7

Admin of vitamin K soon after birth prevents the decrease in PT activity during the first 3-4 days of life

Front 40

VitK deficiency lab test in the newborn?

Back 40

Screening
-- PT
-- APTT

Factor assays

Decarboxylated forms of VK-dependent factors

Protein induced by VK antagonists (PIVKA)

Direct measurement of VK

Front 41

Forms of vitamin K?

Back 41

VK1: phytonadione
-- green leafy vegetables

VK2: metaquinanone
-- produced by intestinal flora

VK3: menadione
-- synthetic water soluble

Front 42

Vitamin K prophylaxis recommendations for newborns?

Back 42

Single dose of 0.5 to 1mg IM at birth

OR

Oral dose of 2-4mg at birth w/ subsequent dosing for breast-fed infants

Front 43

How do we treat Vitamin K deficiency?

Back 43

VK should be admin SQ or IV but not IM to avoid hematoma formation at the site of injection

Plasma should be admin to infants w/ serious bleeding manifestations

Front 44

Describe classic Vitamin K dependent bleeding (VKDB).

Back 44

INCIDENCE
-- 1/10k births

TIMING
-- Day 2 to 7 of life

CAUSES
-- poor placental transfer of VK
-- marginal VK in breast milk
-- inadequate milk intake
-- sterile gut (rare in formula fed infants)

BLEEDING (in order)
1. ICH
2. GI
3. umbilicus
4. ENT region
5. Injection sites
6. Circumcision

Front 45

Describe early VKDB.

Back 45

INCIDENCE
-- very rare

TIMING
-- first 24 hours of life

CAUSES
-- maternal use Rx interfering w/ VK metabolism

BLEEDING (in order)
1. ICH
2. GI
3. Umbilicus
4. intra-abdominal
5. Cephalhematoma

Front 46

Describe late VKDB.

Back 46

INCIDENCE
-- 4-10/10k births

TIMING
-- weeks 2 to 8

CAUSES
-- disorders interfering with VK supply

BLEEDING (in order)
1. ICH (>50%)
2. GI
3. skin
4. ENT region
5. injection sites
6. urogenital tract
7. intrathoracic

Front 47

Other causes of aberrant coagulation system activation?

Back 47

Activation w/ or w/o consumption of platelets has been observed in:
-- respiratory distress syndrome
-- use of extracorporeal mbrn oxygenation (ECMO)