Anemia & Thrombocytopenia Flashcards
Describe the progression of production sites of Fetal erythropoesis (3)
- Yolk Sac (2-10wks)
- Liver (5wks-5-6 mos)
- Bone Marrow (18wk start-complete by 30 wks)
What would be the primary erythropoesis production site in a 24 wkr?
Liver
The hypoxic state in Utero leads to what?
What happens after birth?
Increased NRBC’s and Increased Reticulocytes.
W/in 72 hrs, NRBC’s disappear. By 7 days Reticulocytes <1%.
True/False. The umbilical vein stays patent long after the umbilical arteries constrict.
True.
Reason: to allow placental transfusion
How much fetal blood does the placenta contain?
~100 mL’s
By 1 min delayed cord clamping, how much fetal blood goes to the neonate?
50%
w/in 15 seconds-25%
Term infant has __- __ mL’s/kg blood volume.
Preterm infant has ___-___mL’s/kg blood volume.
50-100mL/kg
89-105mL/kg (higher plasma vol. RBC mass same as term)
What is normal Hgb range?
14-20g/dL
What is normal Crt range?
~42-60%
Hgb x ___ = Crt
x 3
Fetal–>Maternal transfusion can be caused by:
Amniocentesis
Trauma
How is fetal–>Maternal transfusion diagnosed?
Kleinhauer-Betke test
(detection of fetal Hgb on RBC’s in maternal blood)
Detects both the presence of and the volume of fetal RBC’s.
also flow cytometry avail-but more $$, not used much but more accurate
What is a significant % on KB test?
> 1% of maternal blood volume (or >50mL’s fetal blood)
-ie. if KB 2%, presume fetal transfusion 100mL’s.
When is a KB not useful/valid?
If mom also has a hemaglobinopathy with increased Hgb F
With Monochorionic/Monoamniotic twins, why would an OB choose to deliver them at 30-32 wks?
The longer the gestation, the higher the rate of intrauterine mortality. ~70% twin-twin transfusion.
Name 2 interventions in mono/mono twins to alleviate twin-twin transfusion.
- Serial Amnioreductions
2. Ablation (better overall survival rates)
Name S/S of twin-twin transfusion
- one bright pink baby, one very pale baby
- > 20% difference in BW
- > 5g Hgb difference is suspect (not dx)
The “donor” twin will have:
- Anemia
2. Oligohydramnios
The “recipient” twin will have:
- Polycythemia
2. Polyhydramnios
Would you want to give lots of blood to the donor twin quickly?
No, they are used to anemic state, you could cause them to be compromised. Replace very slowly.
How might the recipient twin need to be helped?
Elective exchange transfusion if high Crt to get it 70-75%.
Which twin is at more risk of cardiovascular and end-organ failure?
Recipient twin. Used to pumping high volume of sluggy blood.
Name 4 types of Hemorrhagic Anemia
- Fetal Hemorrhage
- Placental Hemorrhage
- Umbilical Cord Bleeding
- Hemorrhage r/t delivery
Name 4 reasons for umbilical cord bleeding
- Preemie (weak cord/rupture)
- Precip delivery (Increased cord tension)
- Short/entangled cord
- Abnormal cord insertion or vessels
Name 6 types of hemorrhage r/t delivery
-may be asymmptomatic first 24-48 hrs
- Cephalohematoma (no cross suture lines, restricted by periosteum)
- Subgaleal Hemorrhage (vacuum)
- ICH
- Adrenal/kidney H. (breech)
- Splenic rupture (w/splenomegaly)
- Hepatic hemorrhages
Name 3 reasons for hemolytic anemia
- Immune D/O’s (ABO/Rh)
- Acquired RBC D/O’s (infection)
- Hereditary RBC D/O’s (G6PD, Thalassemia)
What is ABO incompatability?
Result of maternal anti-A or anti-B antibodies that enter Fetal circulation and react with A or B antigens on Erythrocyte surface. (bABy + mOm = ABO)
Why don’t mothers with Blood types A, B, or AB tend to have ABO incompatabilities?
They tend to produce IgM (which doesn’t cross placenta)
Type O blood produces IgG-which does cross.
Do you have to be sensitized to have ABO?
No, can occur with 1st pregnancy.
Is ABO common? Is it usually serious?
Yes, common -12% pregnancies affected.
No, <1% live births w/serious hemolysis. Only a small fraction of the anti-A or Anti-B binds to the erythrocytes.
W/ABO, is DAT positive?
Is Indirect antiglobulin test positive?
DAT usually positive, can be negative.
Indirect Antiglobulin test positive.
When should a baby w/ABO be checked for anemia post-discharge?
2-3 wks
What is the other name for Rh incompatibility?
Erythroblastosis Fetalis
When does Rh incompatibility happen?
Rh+ mom (RBC w/D Antigen)
& Rh- baby (RBC w/Anti-D Antibodies)
Is sensitization necessary for Rh incompatability?
What is the incidence of Rh incompatibility after Rhogam came out?
No, can happen first known pregnancy (hx of unknown miscarriage, transfusion)
Increased incidence w/subsequent pregnancies.
11/10,000
Can fetuses inherit Rh +/- from mom or dad?
Yes. They can either match mom or dad’s blood typing.
When is Rhogam given?
1st at 28 wks or w/trauma/fall, etc
Then at birth (if infant is Rh+)
What is the cause of the varying degrees of Rh dz (jaundice-death)?
The degree of Anemia from hemolysis.
Name the 3 types of Hemolysis
- Mild
- Moderate
- Severe
Which type of Hemolysis is most common?
Mild
Describe Mild Hemolysis
Hgb >14g/dL; Cord bili <4g/dL
Positive DAT w/minimal hemolysis
Jaundice-tx w/phototherapy usually
Describe Moderate Hemolysis
Hgb <14g/dL; Cord bili >4g/dL
Moderate Anemia w/hemolysis
Hepatosplenomegaly, jaundice
Tx: early exchange & intensive photo. tx
What is the incidence of severe hemolysis?
Describe Severe Hemolysis.
~25%-of affected infants
Hgb <14g/dL; cord bili >14g/dL
Moderate Anemia w/hemolysis
Hydrops as early as 20-22 wks
Early detection via MCA doppler at 24 wks
Tx: Amniocentesis, early induction, intrauterine fetal blood transfusions, photo tx, exchange, IVIG PRN
In severe hemolysis, why are intrauterine fetal blood transfusions done?
To prevent hydrops
How is a minor blood incompatibility Dx’d?
DAT+ in absence of Rh and ABO incompatibility w/Neg Maternal DAT
How common is Kell sensitization?
Fairly common, 20%
Name the order of minor blood group incompatabilities.
D c,E (Rh Antigens) Kell (K, k) Duffy Kidd
If a mom has anti-Kell, be prepared for what?
A baby w/Severe hemolysis at delivery (regardless of what US says)
*Amnio and antibody titer may underestimate hemolysis severity
Name an autoimmune dz that can cause anemia.
What happens?
Lupus
Passive transfer of IgG antibody
When would you suspect Auto-immune anemia?
Neonatal hemolysis
+DAT (Absence of Rh or ABO incompatibility)
Antiglobulin + hemolysis in mother
How do you tx mom/baby w/auto-immune anemia?
Mom: Prednisone
Baby: Exchange, Phototherapy
Infection can cause non-immune hemolytic dz. From what infections?
CMV, Toxoplasmosis, Syphilis, bacterial sepsis
*can also have thrombocytopenia
What signs would you see on non-immune hemolytic dz?
How would you tx?
Jaundice (T & C elevated), Hepatosplenomegaly
Supportive tx
Is hemolysis r/t infection always early?
No, may be weeks later
Name the 2 dominantly inherited abnormal RBC morphology d/o’s
- Spherocytosis
2. Eliptocytosis
How is Spherocytosis dx’d?
When is it comfirmed?
Blood smear (although can also be seen w/ABO-so r/o) After 3 months (when HgbF is gone)
What happens in Eliptocytosis?
Mutations of the RBC membrane that weaken it’s structure–>cell destruction.
Name the 2 RBC enzyme abnormalities
- G6PD
2. PK
In general, what is G6PD?
An enzyme deficiency.
Sex-linked, X-chrom.
Males>females affected
Mediterranean, African, Middle-Eastern, Asian descent
*provides measure of protection from Malaria (US=increase hyperbili, anemia)
What is PK deficiency?
Autosomal Recessive
Affects all ethnic groups
Rare compared to G6PD
What is the pathophys of G6PD?
RBC’s lack enzyme to regenerate GSH–>oxidative injury–>Heinz bodies bind to denatured cell membrane–>hemolysis
In what situation might you suspect G6PD?
DAT- hemolytic anemia w/infection or admin. of drugs
How can G6PD be dx’d?
Peripheral blood smear
What is the major manifestation of G6PD?
Hyperbilirubinemia (rarely present at birth)
Jaundice > Anemia (prolonged hyperbilirubinemia)
> ___% kenicterus cases are from G6PD?
> 30%
Is G6PD on all NBMS?
No. Being pushed though.
The term infant has about ___-___% HgbF
60-90%
HgbF % falls to ____ by 6 months age?
~5%
What is postnatal Hgb?
HgbA
HgbA has how many alpha/beta chains?
2 Alpha, 2 Beta
Name the 2 major causes of RBC Aplasia.
Are these common in NICU?
- Diamond-Blackfan Anemia (congenital hypoplastic anemia)—severe Anemia in NB period
- Transient Erythroblastopenia of Childhood (TEC)—rare before 6 mos
Describe Physiologic Anemia
Increased O2 content decreases Erytrhopoetin–>decreased Erythropoesis
When and what is the Nadir in a term infant?
Wks 6-12
Hgb 9.5-11 g/dL
When and what is the Nadir in a preterm infant?
Wks 5-10
Hgb 8-10 g/dL
When does RBC begin to increase?
When tissue O2 demand exceeds supply, Hgb is produced
What are the symptoms of Physiologic Anemia?
Asymmptomatic
Does Fe admin prevent Physiologic Anemia?
No, only stores Fe for future use.
Name 4 causes of Anemia of Prematurity
- Physiologic decrease in Hgb
- Heightened deficiencies of Folate, Vit B12, Vit E-essential in erythrocyte integrity
- Iatrogenic blood loss
- Underlying Dz. (Rh, ABO)
Name the tx’s for Apnea of Prematurity
- Limit lab testing
- Delayed cord clamping (30 sec preemie)
- Optimize nutrition
- Iron Supplement
- EPO
- PRBC transfusions
What is the calculation for when a premature infant will deplete his iron stores?
1.5 x cord Hgb level = + % of BW needed
True/False: Fe deficiency has negative neurodevelopmental sequelae.
True
What are the 2 types of Fe supplement we use?
- Fer-in-sol
- Poly-vi-sol
(usually transitioned to poly in prep for home)
How much Fe do most formulas provide?
2mg/kg/day
How much Fe do you want a preemie to get?
2-6 mg/kg/day (feeds + fe supp)
What is the Fe concentration in Poly-vi-sol?
10 mg/kg
What is the usual transfusion amount/kg?
10-20 mL’s/kg
3 mL’s/kg transfusion will raise Hct by ~?
10 mL’s/kg transfusion will raise Hgb by ~?
about 3% (would increase Hgb by 1 g/dL)
about 3 g/dL (would increase Crt by 10%)
Name the 5 risks of blood transfusion
- Graft vs Host
- Infection (CMV)
- Suppress own RBC production
- Transfusion associated NEC
- Fluid overload (s/s pulm. edema)
Irradiation of transfusion products reduces what?
CMV and Graft/host dz
Leukocyte reduction of transfusion products reduces what?
CMV infection
Is there concrete guidelines for stopping feedings with/before transfusions r/t NEC?
No, great variance. Studies suggest it’s the Anemia not the transfusion causing the NEC.
What number Defines Thrombocytopenia
Platelet count <150
What number defines Mild thrombocytopenia?
Platelet count 100-150
What number defines Moderate Thrombocytopenia?
Platelet count 50-99
What number defines Severe Thrombocytopenia?
Platelet count <50
Where do platelets come from?
Megakaryocytes in the bone marrow
Who has a greater chance of developing thrombocytopenia, <800 gms or >800 gms?
<800 gms –85%
Is congenital thrombocytopenia rare?
Yes
True/False: Immune acquired thrombocytopenias are not Uncommon
True
Name the signs you may see in a baby with Thrombocytopenia
- Bruising
- Purpura or Petechiae
- Bleeding from needle sticks
- Oozing from line sites
- Asymmptomatic
How is early-onset Thrombocytopenia defined?
< 72 hrs
W/early-onset thrombocytopenia in an ill-appearing infant, what are the 3 differentials?
TORCH infection
Birth Asphyxia
Sepsis
W/early-onset thrombocytopenia in a well-appearing infant, what are the 3 differentials? (mild-mod, & severe)
Mild-mod: Placental insufficiency, genetic D/O’s, Autoimmune
Severe: Neonatal Alloimmune Thrombocytopenia, Genetic D/O’s
How is late-onset thrombocytopenia defined?
> 72 hrs
What is the differential in an ill-appearing infant with late-onset thrombocytopenia?
Sepsis, NEC, inborn error of metabolism
What is the differential in a well-appearing infant with late-onset thrombocytopenia?
Drug-induced thrombocytopenia
thrombosis
Fanconi-Anemia (inherited, affects all types of blood cells)
What is NAIT?
Neonatal Alloimmune Thrombocytopenia
When should it be considered?
Any infant with initial Platelet count <50 in well-appearing infant.
What happens in NAIT?
Passive transfer of maternal Allo-antibodies attach paternally-derived platelet antigens that are present on the neonate’s platelets.
When an infant has NAIT, is does mom have Thrombocytopenia?
No, her Plt ct is normal.
How can NAIT be tested for?
Maternal and Paternal blood samples; Antigen testing HPA 1, 3, 5 (catches most cases)
*The baby can be screened too, but high false-positive rate.
How is NAIT tx’d?
- Cranial US (25% ICH-often in utero)
- Random donor Plt transfusion <30 or <100 w/IVH
- IVIG if dx confirmed
- Corticosteroids
- If other options have not increased plt in 1-2 days: Matched (Antigen Neg platelets): either maternal OR Donor HPA matched.
If a platelet transfusion of 5-10mg/kg is given, how much would you expect the platelet count to increase?
50,000-100,000
What does ITP stand for?
Immune Thrombocytopenic Purpura
What happens/why does baby get it?
Mom has Auto-Immune Thrombocytopenia or is developing it during pregnancy.
*Maternal Autoantibodies are passively transferred to fetus in utero which react with it’s platelets.
In OB pts with ITP, ___% of the infants had low platelet count at birth?
25%
What condition might mask maternal and neonatal thrombocytopenia?
HELLP
How is ITP tx’d?
- Screen infants born to mothers w/autoimmune dz’s
- Cranial US
- Normal Plt count: Observe them
- Mild to Mod (50-100k): Trend down < 30, tx w/IVIG
- Severe (< 50k): < 30 tx w/IVIG (first line); transfuse w/random donor platelet transfusion
What is the normal Platelet transfusion amount?
10-15 mL’s/kg aliquot
When is Platelet transfusion recommended for infant < 33wks in the first WOL?
After the first WOL (if clinically stable)?
<50,000
<30,000
What is transfusion associated lung injury?
When does it show up?
Hypoxia and bilateral pulmonary lung infiltrates.
W/in first 6 hrs of transfusion.
There’s a strong A/W ________and Platelet transfusion in NICU population.
Mortality
chicken/egg concept
Name 4 reasons Neonates have excessive bleeding
- Platelet D/O’s
- Neonatal hemophilia or clotting factor D/O’s
- Vit K deficiency syndroms
- DIC
What is a normal PT?
Is it an extrinsic or intrinsic pathway?
What does it affect?
PT is elevated in?
10-16 sec (Prothrombin Time)
Extrinsic
Vit K dependent factors
Liver Dz, and DIC
Which pathway is PTT?
When would you see an elevated PTT?
Term= 25-60 sec, Preemie= up to 80 sec.
(Partial Thromboplastin Time)
Vit K deficiency, Liver failure, DIC, factor deficiencies
What factor is Fibrinogen?
Factor 1
What is a D-dimer?
Firbrin degradation products (fibrin split products)
What does INR stand for?
If it is high, what is more likely to happen to baby?
If it is low, what is more likely to happen to baby?
International Normalized Ratio
High-Bleed (just more likely to, does not indicate active bleeding)
Low-Clot
Name the 6 screening tests for coagulation
PT PTT Fibrinogen D-Dimer Platelets INR
What is Von Willebrand Factor?
Primary plasma protein required for platelet adhesion/aggregation
What happens in Von Willebrand Dz?
Absent or decreased amounts of OR Abnormal VWF function–>defects in platelet adhesion/aggregation–>increased bleeding risk
VWF is the carrier protein for which factor?
Factor 8
How does VWF present in NB period?
Rarely presents itself in NB period, s/s similar to Thrombocytopenia (bleeding/bruising)
How is VWD treated?
Replace VWF concentrates from plasma (FFP).
Desmopressin or antifibrinolytic agents (rarely used in NB’s)
Factor 8 is known as?
Factor 9 is known as?
Hemophilia A
Hemophilia B
How is Hemophilia transmitted?
X-linked. Males>Females
w/known family Hx, can be Dx’d before symptoms.
What happens in Hemophilia?
Absence of Factor 8 & 9–>Reduced Thrombin on Plts at site of bleeding–>Clot w/poor structural integrity–>Increased risk Fibrinolysis
What is the incidence of severe Hemophilia A (Factor 8 deficiency)?
What is the incidence of Hemophlia B (Factor 9 deficiency)?
1: 10,000
1: 30,000
When can Hemophilia manifest itself in the NB period?
With Severe Hemophilia w/Factor level <1%
Name Clinical Manifestations of severe hemophilia
Intra or extracranial bleeding
Prolonged bldg from venipuncture/heelstick
Prolonged bldg after circ (most common in asymptomatic infants)
Excessive bruising
Muscle hematomas after IM’s like vaccines
Bleeding after surgery
How is Severe Hemophilia tx’d?
Factor replacement Tx
What labs are used to Dx severe hemophilia? Does this work in a preemie?
Elevated PTT, abnormal factor levels
Misleading in preemie, deficient in these anyway.
What causes Vit K deficiency in a NB?
Insufficient intestinal colonization by bacteria, poor absorption
Low Vit K in breastmilk
What is the most common cause of bleeding in an otherwise healthy infant?
Vit K deficiency
Infants who do not recieve Vit K at birth are ____ x’s more likely to develop late VDKB
81 x’s >
What lab is elevated w/VKDB?
3-4 fold PT (is specfic to Vit K)–the PT is greater than PTT–
Early VKDB happens?
Can be from?
w/in 24 hrs
Poor maternal Vit K transfer, maternal meds
Classic VKDB happens?
From?
1-7 days
Physiologic deficiency, lack Vit k in breastmilk or inadequate feeding
Late VKDB happens?
From?
2-12 wks Inadequate VitK intake (usually exclusively breastfed) Fat malabsoption (biliary atresia, CF, Alpha 1 anti-trypsin)
How do you tx VKD?
How long does the measure last?
0.5-1mg Vit K IM at birth
1 month
DIC is a ___________ coagulopathy defined as?
Consumptive: Uncontrolled activation and consumption of Platelets, Pro-coagulant, Anti-coagulant, Fibrinolytic proteins.
What are the most common causes of DIC?
How do they present?
Sepsis, NEC (each present with thrombocytopenia initially and most prominently)
Hypoxia/Acidosis (present with Fibrinogen deficiency)
Liver failure
How is successful treatment of DIC defined?
Improvement of coagulation w/in 72 hrs, and resolution of thrombocytopenia in 7-10 days
What symptom is the first to show and last to leave with DIC?
Thrombocytopenia
What are the indications for using FFP?
Bleeding, DIC, Vit K deficiency, Factor 8 Deficiency, Factor 9 deficiency
What are 2 main factors in FFP?
Factor 5 and factor 8
What are the indications for Cryoprecipitate?
Factor 8 deficiency, VWF deficiency,
What are the components of Cryoprecipitate?
Fibrinogen, Factor 8, Factor 9, VWF, Fibronectin
What are the indications for Platelets?
Thrombocytopenia, Bleeding
What are the components of Platelets?
Platelets +/- some WBC’s (how graft vs host can happen)
What is the pathophys of Thrombosis in NB?
Hypercoagulability, Disturbances in blood flow, Endothelial damage/disruption
Why are infants at greater risk of Thrombosis vs. older children?
Decreased fibrinolysis d/t low plasminogen levels
What can put baby at risk of Thrombosis?
What deficiencies can put baby at risk of Thrombosis?
Umbilical lines (site of insertion or tip), Asphyxia, Sepsis (w/DIC), Polycythemia (Dehydration, IDM, CHD), Shock
Protein C or S deficiency, ATIII deficiency, Factor V Leiden
What are some clinical types of Thrombosis?
Renal vein thrombosis, renal artery thrombosis, sagittal sinus thrombosis, stroke (seizures)
How is Thrombosis Dx’d?
US w/doppler, CT, MRI
How is Thrombosis Tx’d?
Anticoagulant Tx:
Heparin infusion
Low-molecular-weight heparin (enoxaprin SQ
Warfarin (PO)
Thrombolysis if complete occlusion or ischemia:
Systemic TPA
