Hematology Flashcards
What is anemia?
hematocrit value at least 2 standard deviations below the mean for age
What is the normal range of hct in newborns?
45-61%
What is the normal range of hgb in newborns?
15-20%
What are possible etiologies for EARLY anemia?
1) blood loss
2) congenital erythrocyte underproduction
3) acquired erythrocyte underproduction
4) increased destruction
What are etiologies of blood loss in the neonate?
1) sequestered blood/ internal hemorrhage
2) Fetal-maternal
3) Placental
What are potential sites for sequestered blood/ internal hemorrhage?
1) intracranial: subdural, intraventricular, subgaleal
2) organ: adrenal, ruptured liver/spleen, retroperitoneal cavity
3) integumentary: bruising, hemangiomas
What are potential causes of fetal-maternal hemorrhage?
1) fetal maternal hemorrhage
2) ABO incompatability
* in most pregnancies there are fetal cells in maternal circulation (50-75%)
What are potential causes of placentall hemorrhage?
1) abruption
2) abnormal placental insertion (velamentous)
3) placental rupture
4) tight nuchal cord
5) CSX
6) TTTS (acute and chronic)
How is Fetal-Maternal Hemorrhage diagnosed?
diagnosis is by detection of fetal RBC in maternal circulation
- done on maternal blood, adult hgb has different solubility than fetal hgb.
- K-B can calculate volume of fetal blood loss (used to estimate Rhogam dose so that it is sufficent to kill fetal cells)
What is the incidence of volume transfer in fetal maternal hemorrhage?
1 in 400 pregnancies transfer > 30mL
1 in 2000 pregnancies transfer > 100mL
What is the relative occurrence of congenital erythrocyte underproduction?
rare
What are the causes of congenital erythrocyte underproduction?
1) hypothyroidism
2) adrenal insufficiency
3) hypopituitarism
Genetic causes, including:
1) congenital hypoplastic anemia (Diamond-Blackfan)
2) constitutional aplastic anemia (fanconi’s anemia)
What are the causes of acquired erythrocyte underproduction?
1) infection
2) maternal drug ingestion
3) drugs
4) nutritional deficits
5) lead toxicity
What infections are likely to cause acquired erythrocyte underproduction?
1) Parvo B 19 (most common)
2) hepatitis
3) HIV
4) syphillis
What maternal drugs are known to cause acquired erythrocyte underproduction?
azathioprine
What drugs are known to cause acquired erythrocyte underproduction?
chloraphenicol
What nutritional deficits are known to cause acquired erythrocyte underproduction?
1) Fe
2) folic acid
3) Vitamin B 12
What are causes of increased RBC destruction?
1) isoimmunization
2) minor blood group incompatibilities
3) structural abnormalities of the cell
4) RBC biochemical defects
5) infections
What isoimmunization states can lead to increased RBC destruction?
Rh incompatibility
ABO incompatibility
What structural abnormalities of RBCs can lead to increased RBC destruction?
- spherocytosis
- eliptocytosis
What biochemical defects of RBCs can lead to increased RBC destruction?
- G6PD
- pyruvate kinase deficiency
What is the etiology of erythroblastosis fetalis?
Rh incompatibility
What is the incidence of ABO incompatibility?
approximately 3%
What is the cumulative effect of ABO incompatibility with subsequent pregnancies?
may occur in first pregnancy, no sensitization req’d, subsequent pregnancies are not more severely affected
What immunoglobulin do mother’s with type A or B blood produce?
IgM
What immunoglobulin do mother’s with type O blood produce?
IgG; crosses the placenta; reason why mothers who are O tend to have hemolysis
What other effects can be expected with a mother with type B blood and an ABO incompatible fetus?
may also have thrombocytopenia since B antigen is expressed on platelets (usually mild)
What are the laboratory findings a/w ABO incompatibility?
Direct Coombs: weakly positive, or negative
Indirect Coombs: positive
What is the incidence of Rh incompatibility?
before Rhogam 1%, now 11/10,000
What is the cumulative effect of Rh incompatibility with subsequent pregnancies?
primary response (with first pregnancy) is IgM (not transmitted), followed by production of IgG (transmitted). With repeat exposure IgG response is more rapid (worse over time and with future pregnancies)
What is the effect of ABO and Rh incompatibility?
Rh incompatability may be protective; as it destroys the fetal cells before the MOB can mount an immune response
What is the effect of an Rh negative mother and a Rh positive fetus?
if the mother is Rh negative and fetus is positive, there is a transplacental hemorrhage and the MOB will produce anti-D (resulting in fetal hemolysis)
What are the minor group incompatibilities?
- other Rh antigens (c, E) are most common
- Kell (K and k), infrequent; “kell kills”
- Duffy; “duffy dies”
- Kidd
- Lewis; “Lewis lives”
What are the associated risks with an exchange transfusion?
1) blood hypersensitivity
2) multiple donor exposure
3) umbilical line
4) infection
5) bleeding
6) clots
7) air embolism
8) hypocalcemia
What is the expected volume of blood in a newborn?
80-100mL/kg; term infants are closer to 80, PT closer to 100
What are the indicated treatments for severe hemolytic disease?
- phototherapy
- ABO: IVIG (reduces need for exchange transfusion)
- Exchange transfusion
What type of blood is ordered to complete an exchange transfusion?
whole blood; request hct ~ 55%
What is the effect of citrated blood that is used in an exchange transfusion?
decreased Ca levels; entire clotting cascade is Ca dependent
What orders are indicated s/p exchange?
bili, hct, plt, maybe Rx levels
- NPO for awhile
- monitor lab work Q6h
- may require a second exchange
What is physiologic anemia?
occurs in every baby; there is a large RBC mass at birth (r/t relative hypoxic intrauterine environment). At birth and with first breathes, increases PaO2, erythropoiesis ceases (for a period of time bc it is not needed); fetal RBCs have a shorter life span
What is the physiologic nadir of a FT infant?
nadir to hgb of 9-12; 10-12 weeks
What is the physiologic nadir of a PT infant?
nadir hgb is 7-8; presents much earlier
What is one of the most limiting nutritional factors in the making of new RBCs?
protein deficiency
What are the causes of anemia of prematurity?
physiologic anemia processes, iatrogenic blood loss, disease, nutritional state, fetal-neonatal erythropoiesis
What are the physiologic contributors to anemia of prematurity?
1) low set point of O2 sensor (liver to kidney switch)
2) rapid body growth
3) shortened RBC span
4) Left shifted ODC at birth
5) low plasma EPO levels
6) cardiovascular factors: systemic and local
What are the non-physiologic contributors to anemia of prematurity?
1) laboratory blood loss
2) inadequate nutrient intake: protein, vitamins and calories
3) non laboratory blood loss and hemorrhage
4) infection/sepsis
What is the indicated treatment of anemia of prematurity?
1) minimize blood draws
2) good nutrition (protein & Fe)
3) Rh-Epo
What do RBCs of anemia of prematurity look like?
- normocytic ( normal size RBC)
- normochromic (RBC hgb concentration)
- hyporegenerative (stunted erythropoietin response)
What is the effect of Epo on anemia of prematurity look like?
- won’t limit early treatment, may limit later transfusion needs
- no proof that you’ll improve your outcomes (might just delay nadir
- may improve hgb
What is the reticulocyte count?
a measure of how quickly RBCs are being produced
How is reticulocyte count calculated?
% of RBCs in blood that are reticulocytes (# of retic divided by total hct) x 100
What are normal ranges for newborn reticulocyte count?
2.5%- 6.5% at birth, should fall by 2 weeks to 0.5%-2%
How can a reticulocyte count be helpful diagnostically?
can be used acutely in a baby that has hemolysis of chronic cases of anemia (have been retic-ing for awhile; and then production ceased in response to an O2 rich environment)
How should anemia be treated?
- biggest concern is delivery of oxygen to the tissues
treatment is based on infant’s volume status
What is the treatment for anemia in a newborn that is hypovolemic?
acute blood loss has occurred; give volume expanders for a temporary fix (10-20mg/kg of volume)
What is the treatment for anemia in a newborn that is euvolemic?
occurs with chronic blood loss; simple PRBC transfusion only when symptomatic
What is the treatment for anemia in a newborn that is hypervolemic?
occurs with anemia and hydrops; isovolemic PRBC exchange
What are the clinical manifestations of acute and severe anemia during the intrauterine period?
1) decreasing fetal movement, sinusoidal FHR pattern
2) if chronically anemic > hepatospleenomegaly
What are the clinical manifestations of acute and severe anemia during the postnatal period?
1) pale
2) tachycardiac
3) hypotension
4) tachypnea
5) acidosis
What are the clinical manifestations of acute and severe chronic anemia?
1) pale
2) tachycardia
3) poor pattern of growth
4) tachypnea or increased respiratory support
Why is protein so important in hematopoesis?
facilitates the making of new cells
Why is Fe and vitamin E so important in hematopoesis?
decreased retic count, decreased RBC life span
What is the expected result of a blood transfusion to your hematocrit and hgb?
a 3mL/kg will raise hct approximately 3%
a 10mL/kg will raise hgb by approximately 3g
How do you determine when an infant’s Fe stores will be depleted?
BW + cord hgb (gm/dL) = % growth until Fe depletion
% growth + BW = wt at which Fe stores at birth will be gone
What is the physiologic effect of Fe deficiency?
has negative neurodevelopmental sequelae even when the infant is not quite iron deficient
When should Fe supplementation begin?
around 2 weeks of life
What is the recommended Fe dose for routine maintainence?
2-4mg/kg/day
What is the recommended Fe dose for treatment?
4-6mg/kg/day
What are the associated risks with Fe treatment?
damaging to the liver
What are the associated risks with blood transfusion treatment?
1) GvHD: seen in pts with primary immune deficiency (ex: Di George)
2) infection: incidence of CMV seropositivity in adult pop is 60% (doesn’t mean active infx)
3) suppresses production of endogenous hematopoesis
4) transfusion related NEC
5) fluid overload
How can the risk of GvHD be limited when giving a PRBC transfusion?
irradiation of blood products
How can the risk of CMV transmission be limited when giving a PRBC transfusion?
leukocyte reduce: because the virus lives on WBCs
irradiate
How can you maximize infant blood volume in order to reduce need for subsequent PRBC tx?
delayed cord clamping
How can you limit donor exposure in order to increase safety with PRBC tx?
1) quad packs, directed donor
2) autologous transfusion from the placenta
What criteria should be considered when considering transfusing an older patient?
1) pattern of growth
2) O2 requirement
3) spells
4) retic
5) if surgery is coming up
6) if you can’t get enough good Fe in
7) active septic state causing increased RBC destruction
Where are platelets derived from?
megakaryocytes
What is the clinical range determining thrombocytopenia?
< 150k; severe is < 50k
What is the incidence of congenital thrombocytopenia?
rare; occurs frequently in sick infants (about 35%)
What is considered in the differential with the etiology of thrombocytopenia?
1) increased plt destruction
2) decreased production
What is considered early onset thrombocytopenia?
first 72h
What is the differential in an ill appearing infant with a variable degree of thrombocytopenia in < 72 h of life?
1) Sepsis (bacterial, viral)
2) TORCH infx
3) Birth asphyxia
What is the differential in an well appearing infant with a mild to moderate degree of thrombocytopenia in < 72 h of life?
1) placental insufficiency (including PIH)
2) Genetic disorders
3) Autoimmune
What is the differential in an well appearing infant with a severe degree of thrombocytopenia in < 72 h of life?
1) Neonatal alloimmune thrombocytopenia
2) Genetic disorders
3) Autoimmune
What is the differential in an ill appearing infant in > 72 h of life?
1) Sepsis (bacterial, viral, fungal)
2) NEC
3) Inborn error of metabolism
What is the differential in an well appearing infant in > 72 h of life?
1) Drug induced thrombocytopenia (ex: heparin)
2) Thrombosis
3) Fanconi anemia
What are the 4 steps in platelet production?
1) production of thrombopoietin Tpo
2) proliferation of megakarocyte progenitors
3) megakaryocyte maturation
4) generation and release of plt
Why is overall plt production less in neonates?
neonates have higher Tpo levels, but megakaryocytes are smaller and produce fewer plt
What is the mechanism of thrombocytpoenia with intrauterine hypoxia?
underproduction r/t lower levels than expected of Tpo
What is the mechanism of thrombocytpoenia with sepsis?
underproduction: body attempts to up regulate production but is unsuccessful
When should Alloimmune Thrombocytopenia (NAIT) be considered?
in any neonate with initial plt count < 50k in an otherwise well appearing infant
What lab work is diagnostic for NAIT?
collect blood from mother and father; antigen testing HPA 1,3,5 will catch most cases; neonate can be screened for platelet antibodies that high false positive rate
What is the indicated treatment for NAIT?
1) brain MRI (most bleeding occurs where it cannot be seen)
2) random donor plt tx (if initial count is < 30k or < 100k with IVH)
3) IVIG if diagnosis is confirmed (helps to decrease rate of destruction)
4) if other tx is not effective in 1-2d: matched (antigen negative plts)- maternal tx or donor plt HPA matched
How do infants with Autoimmune Thrombocytopenia present?
- early onset
- mod- severe thrombocytopenia
- maternal h/o ITP or autoimmune disease
(all infants with maternal h/o autoimmune dz should be screened)- in OB pts with ITP, 25% of infants had low plt count at birth
What is the treatment for Autoimmune Thrombocytopenia?
1) IVIG
2) cranial imaging
3) plt tx
4) follow until stable
What are the risks a/w plt tx?
1) plt tx thresholds are highly variable
2) thresholds and effects in neonatal pop is poorly studied
3) GvHD
4) CMV
5) associated lung injury (hypoxemia and pulmonary infiltrates within 6h of plt tx)
6) bacterial contamination
7) strong association b/w the number of plt tx and risk for death
What is the current recommendation for plt tx threshold in an otherwise clinically stable newborn?
< 30k
What is Cushing’s Triad?
indicator of increasing ICP
1) bradycardia
2) hypertension- progressively increasing systolic (or widened pulse pressures)
3) abnormal respiratory effort
What are anticlotting factors?
- Protein C
- Protein S
- Antithrombin
- Antithrombin III
- Thrombomodulin
Why are infants at an increased risk for thromobosis?
fibrinolysis decreased d/t low plasminogen levels
What are additional risk factors for thrombosis in neonates?
1) umbilical lines
2) asphyxia
3) sepsis
4) polycythemia (dehydration, IDM, CHD)
5) shock
6) Protein c or S deficiency
7) Antithrombin III deficiency
8) factor V Leiden
What clinical syndromes increase an infant’s risk for thrombosis?
1) renal vein thrombosis (renal fx, renal mass, IDM, polycythemic)
2) renal artery thrombosis
3) sagittal sinus thrombosis
4) stroke (seizures)
What is the management for thrombosis?
antithrombolitic therapy; TPA controversial, heparin gtt
What is the PT test?
prothrombin time
- evaluation of the extrinsic pathway
- evaluation of vitamin K dependent factors (II, VII, IX, X)
What is the normal range for a PT test?
10-16 sec
When is a PT test elevated?
liver disease and DIC
What is the PTT test?
partial thromboplastin time
- evaluation of intrinsic pathway
What is the normal range for a PTT test?
FT: 25-60 secs; PT: up to 80 secs
When is a PTT test elevated?
1) vitamin K deficiency
2) liver failure
3) DIC
How should an INR be evaluated?
- if high: more likely to bleed
- if low: more likely to clot
When is an INR ordered?
to monitor efficacy of heparin therapy
What is the fibrinogen test?
fibrinogen is a protein produced in the liver to help in clot formation
When is a D Dimer or fibrin degredation product test indicated?
to evaluate the products in the blood that are needed to remodel and remove the clot
What would the lab work look like in a patient with Hemophilia A or B?
- very high PTT
- normal PT
- normal fibrinogen
- negative to high D dimer
- normal platelets
What would the lab work look like in a patient with thrombocytopenia?
- normal to high PTT
- normal PT
- normal fibrinogen
- negative to high D dimer
- low to very low platelets
What would the lab work look like in a patient with Vit K deficiency?
- high to very high PTT
- very to severely high PT (PT >PTT)
- normal fibrinogen
- negative to high D dimer
- normal platelets
What would the lab work look like in a septic pt?
- low to very high PTT
- high to very high PT
- normal to low fibrinogen
- high to very high D dimer
- low to very low platelets
What would the lab work look like in a hypoxic patient?
- high to very high PTT
- normal to very high PT
- normal to very low fibrinogen
- very high to severely high D dimer
- low to very low platelets
What would the lab work look like in a patient with DIC?
- high to severly high PTT
- high to severely high PT
- normal to severly low fibrinogen
- very high to severely high D dimer
- low to very low platelets
What is an APT test?
to evaluate “whose blood it is” MOB or babe; helpful in evaluating pseudohemorrhage in the newborn
What is the etiology of vitamin k deficiency in the first day of life?
1) refusing injection
2) maternal anticonvulsants
3) antibiotics
What is the etiology of classic vitamin k deficiency in the first week of life?
poor vitamin K intake, usually breastfed
What is the etiology of late vitamin k deficiency in the first eight weeks of life?
1) fat malabsorption (biliary atresia, CF, alpha 1 antitrypsin)
2) poor intake
3) antibiotics
What is DIC?
consumptive coagulopathy; uncontrolled activation and consumption of plt, procoagulant, anticoagulant and fibrinolytic proteins
What are the most frequent causes of DIC?
- sepsis
- NEC
- hypoxia/ acidosis
- liver failure
What is the treatment for DIC?
treat the underlying cause, transfusion support and keep up the factors
What is the pathology of bleeding d/t liver failure in the newborn?
1) failure of protein synthesis
2) consumption of clotting factors
3) inhibition of normal coagulation, failure to clear degradation products
What is the indicated treatment for bleeding d/t liver failure?
successful treatment is dependent on treatment of liver failure
What are the indications for a PRBC tx?
1) hypovolemia
2) anemia
What are the components in a PRBC tx?
RBCs + some WBCs, no immunoglobulins or clotting factors
What are the indications for FFP tx?
1) bleeding
2) DIC
3) vit K deficient
4) factor IX deificient
What are the components in FFP?
all clotting facotrs, fibrinonectin, albumin, plasma proteins
What are the indications for a cryo tx?
1) VIII deficiency
2) von Wildebrand
What are the components in cryo?
FIBRINOGEN, VIII, XIII, vWF, fibrinonectin
What are the indications for a plt tx?
1) thrombocytopenia
2) bleeding
What components are in plt tx?
platelets with some WBCs
What is the risk for cord injury with a velamentous cord insertion?
the umbilical cord abnormally inserts into the fetal membranes and into the placenta, leaving the vessels exposed (no Wharton’s Jelly) and therefore, a great risk of rupture
