Heme Flashcards
When is physiologic Nadir for Hgb?
Term: 8-10 wks. Pre-term 6-8 wks.
*Note f-Hgb has half the half-life, that’s why
Microcytic Anemia DDX
*TAILS*: Thalassemia Anemia of CD IDA Lead poisoning Sideroblastic anemia.
Macrocytic Anemia DDX
- Megaloblastic: B12 def, Folate def
- Marrow Failure: Myleodysplasia, Fanconi, Diamond-Blackfan, Aplastic
- Other: Hypothyroid, DS, liver disease, drugs (AZT, etoh), Normal Newborn
Normocytic Anemia DDX
- Anemia of CD
- Chronic renal failure
- Transient erythroblastopenia of childhood (TEC)
- Malignancy/marrow infiltration
- Other: HIV, HLH
- Bleeding/hemolysis (except if massive reticulocytosis then macro)
Classify hemolytic disorders
(based on problem in RBC)
Problem INTRINSIC to the Red Cell
• Membranopathy: hereditary spherocytosis, elliptocytosis
• Enzymopathy: G6PD deficiency, PK deficiency
• Hemoglobinopathy: Hb SS, SC, S-βthal
Problem EXTRINSIC to the Red Cell
• Immune hemolysis: autoimmune, iso-immune, drug-induced.
• Non-immune hemolysis: HUS, TTP, DIC, Burns, Wilson, Vit E def, etc.
IDA: why does cow’s milk lead to IDA
Iron is absorbed at 50% efficiency from breast milk and 10% from cow’s milk. Excessive cow’s milk also
interferes with balanced nutrition, and causes GI blood loss.
Limit cow milk intake to 16-24 oz/day.
IDA: causes
1) Inadequate iron endowment at birth
2) Insufficient iron in diet
3) Blood loss
GI tract (cow milk, parasitic infection, varices, Meckel’s, polyp, ulcer, H pylori)
Epsitaxis, menorrhagia, rarely pulmonary or renal loss
4) Malabsorption of iron
Celiac disease, antacids, giardiasis, IBD, IRIDA.
IDA: treatment
- Usual dose is 4-6 mg/kg/day of elemental iron. Vit C helps with absorption.
- Check CBC + retics within 1-2 weeks of treatment
A positive response:
– Rapid subjective improvement within 2 days
– Reticulocytosis within 3-7 days
– Increased hemoglobin (usually 7 to 30 days)
– Repletion of iron stores (usually by 3 months).
Features on CBC indicative of IDA
Microcytotic, hypochromic MCV/RBC >13 (Mentzer index) is suggestive of iron def, (<13 suggests thal trait). Increased RDW Thrombocytosis Pencil cells
Difference bw IDA and alpha-that trait?
1) Iron studies: alpha normal, IDA abnormal
2) RDW: alpha normal, IDA high.
3) RBC count: alpha increased (~5), MCV very low.
Mentzer index (MCV/RBC):
alpha <13, IDA >13
4) Plt: alpha normal, IDA increased
Note: Hb electrophoresis is normal in both.
Typical age group for “Transient Erythroblastopenia of Childhood” (TEC)
1-3 years
Often after a viral trigger (not necessarily parvo)
• Onset gradual, may become severe
• Recovery is spontaneous within 1-2 months
• A single transfusions may become necessary.
• The main ddx is diamond-blackfan anemia (vs aplastic crisis)
Which anemia is associated with goat milk intake
Folate deficiency macrocytic/megaloblastic anemia
Types of hemolytic anemias caused by ‘membranopathy’
hereditary spherocytosis, elliptocytosis
Types of hemolytic anemias caused by ‘enzymopathy’
G6PD deficiency, PK deficiency
Types of hemolytic anemias caused by ‘Hemoglobinopathy’
Hb SS, SC, S-βthal
Hereditary Spherocytosis Treatment
- Splenectomy: corrects the anemia + normalizes the RBC survival, even though the spherocytes persist.
- should be deferred until after age 5y if possible to minimize risk of sepsis. Partial splenectomy may achieve a balance.
Most common presentation of h. spherocytosis in a newborn?
Jaundice
Most common complication of hereditary spherocytosis?
Gallstones
What can cause a false negative in G6PD testing?
If done while hemolysing.
Must be done few weeks after.
G6PD treatment
- Supportive care + avoidance of acute triggers
(Splenectomy is not useful.) - Most common oxidants: sulfas, nitrofurantoin, dapsone, naphthalene (moth balls), anti-malarials, rasburicase, fava beans, and infection.
Types of AIHA (Auto-Immune Hemolytic Anemia)
3 types
1) Warm (IgG, extravascular hemolysis)
2) Cold (IgM, called “cold agglutinin disease”)
3) Biphasic (Donath-Landsteiner IgG, called “paroxysmal cold hemoglobinuria”).
AIHA: treatment
- Warm AIHA:
- supportive care, transfusions (“least incompatible”), steroids, ?IVIG, rituximab, splenectomy.
- Cold or biphasic AIHA:
- supportive care, transfusions prn. If severe: plasmapheresis.
Etiology of SS anemia
Single nucleotide substitution (GTG for GAG, valine for glutamic acid) at codon 6 of the beta-globin gene on chromosome 11
• QUALITATIVE DEFECT (as opposed to quantitative )
SS anemia: List as many acute complications as you can
- Acute vase-occlusive crises
- Infections: strep pneumo, OM (staph, salmonella), Parvo aplastic crises
- ACS (50%)
- Stroke (10% by 20)
- Splenic Sequestration
SS anemia: List as many chronic complications as you can
- immunodeficiency sec to asplenia
- resp: lung disease of SCD (asthma-like), pHTN
- Neuro: sequelae from stroke
- Retinopathy
- Cholelithiasis (40%), Renal Insufficiency (20%), Priapism (10-40%)
- Osteonecrosis of femoral head (50-60% by adult)
Rates of functional asplenia in SS
30% of SS by 1 y and 90% by 6 y.
SS ACS: management
- IV Antibiotics (cephalosporin and macrolide)
- O2
- hydration
- incentive spirometry
- bronchodilators.
- Simple transfusion for hypoxia needing O2 or a Hct<18%.
- Exchange transfusion for progressive multilobe infarcts and hypoxia.
- Recurrent ACS: consult resp for PFTs.
SS ACS: features + causes
Def: fever and infiltrate. Hypoxia not necessary for the dx.
Causes:
- 16% are due to bacterial infections (mostly atypicals) and 6% due to viral.
- 10% are due to fat embolism (after bone marrow infarction from a VOC.)
- Too much analgesia for VOC can cause hypoventilation leading to ACS.
SS: splenic sequestration dx
- sudden enlargement of the spleen + 20 pt drop in Hb with reticulocytosis.
- Can result sudden circulatory collapse and death.
**
Occurs in children with SS <3 y, with other types at any age. Recurrence is frequent.
SS anemia: splenic sequestration managt
- NS bolus, blood transfusions.
- 2+ splenic sequestrations –> splenectomy.
SS anemia: list 5 preventative care measures
1) Penicillin prophylaxis should begin at 3 mo- 5 years.
2) Pneumococcal vaccination
– Prevnar-13 at 2, 4 and 12 mo
– Pneumovax-23 should be given at 2 y and 5 y.
3) TC doppler should begin at 2 y- 16 y for all SS and S-β0 thals.
4) Routine screening for end-organ damage should begin in middle-childhood.
5) Evaluated by SC program by 3 mo. Parent education re fever mgt and spleen palpation
SS anemia: 5 indications for transfusion
Simple transfusion:
1) Aplastic crisis
2) Splenic sequestration
3) Pre-op (high risk surgeries)
4) Stroke – if low Hb, awaiting exchange
5) ACS – if low Hb, awaiting exchange
6) Also used chronically to prevent stroke by keeping HbS under 30%.
7) Persistent priapism, with caution
Exchange transfusion:
- Reserved for stroke, severe ACS, and pre-op some major surgeries.
- transfusions NOT indicated for vaso-occlusive crisis.
What increases risk of stroke in SS anemia
Hx of ACS (recent, frequency)
Other RFs include SS genotype, low baseline Hb, previous TIA, high blood pressure,
SS anemia: 2 disease modifying tx
1) hydroxyurea
2)
Questions to ask for BLEEDING HX
(+age group based)
Neonate: Cord separation, IVH, subgaleal hemorrhage, procedural
• Infant: Vaccines, circumcision
• Toddler: Intracranial bleed after small trauma, joint or soft tissue bleeds
• Child: Epistaxis, joint or soft tissue bleeds, exfoliation of primary dentition
• Adolescent/Adult: Menorrhagia, peripartum bleed
• All: Bleed requiring transfusion, excessive bleed during surgery
• Family Hx: Consanguinity
• Other History: Recent drug use (including natural + OTC), recent viral illness or diarrhea (for thrombocytopenia)
Thrombocytopenia: DDX based on physiology
1) Decreased production:
- marrow infiltration (leukemia)
- marrow injury (aplastic anemia)
- congenital syndromes of ineffective thrombopoiesis (eg TAR, hereditary thrombocytopenias, Wiskott-Aldrich syndrome)
2a) Increased destruction, Immune:
- ITP, SLE, NAIT, Infection, Heparin, drugs (eg VPA, anticonvulsants, chemo).
2b) Increased destruction, Non-Immune:
- DIC, HUS, TTP, Infection, Kasabach-Merritt syndrome, artificial heart valve.
3) Sequestration:
- Hypersplenism from liver disease, storage disease, portal vein thrombosis.
4) Consumption:
- thrombosis, eg clot around central line, type 2B vonWillebrand disease.
5) Platelet loss or dilution
- eg. after massive dilution for major trauma
Neonatal Thrombocytopenia: DDx based on physiology
1) Decreased production: congenital syndromes.
- TAR (thrombocytopenia absent radii syndrome) in which megakaryocytes are absent in the bone marrow.
2) Non-immune destruction:
- TORCH eg CMV
- NEC, RDS, and transiently after maternal pre eclampsia. (In general, a sick neonate).
3) Immune destruction:
- Maternal ITP – check mom’s CBC
- NAIT - alloantibody directed against an antigen on the newborn’s platelets made by mother
Most common cause of isolated thrombocytopenia in children
ITP: immune thrombocytopenic purpura
ITP: 4 indications for BMA
1) Low WBC
2) Low Hgb
3) Blasts on the peripheral smear
4) Lymphadenopathy
5) Hepatosplenomegaly
(or suspicious history such as long fevers, bone pain or weight loss.)
ITP: counselling
1) Reassure parents about the chances of recovery and rarity of serious events.
2) Avoid contact sports and restrict activities if possible. 3) Avoid NSAIDs and aspirin.
ITP: Management
1) Counselling
2) Increasing plt count (3-4 ways)
- (transfusion, steroids, IVIG, Anti-D)
3) Splenectomy
4) Immunomodulation:
- CSA, MMF, rituximab, vincristine,
cyclophosphamide, others
5) Increase Production – Thrombopoietin analogues
CPS Statement:
- Treat based on severity (mild, mod, severe) and NOT based on plt count.
ITP: ways to increase platelets
1) Platelet transfusions:
– not effective (destroyed immediately); should only be used in cases of actual intracranial hemorrhage
2) Oral steroids x 4 days.
3) IVIG may work slightly faster then steroids.
4) Anti-D
— works by coating red cells in people who are Rh+ (so it can only be used in 80% of people) and causing an immune hemolysis. It keeps the spleen busy
chewing red cells so that the platelets can slip by.
ITP: 2 indications for splenectomy
1) older child (> 4 yr) with severe ITP >1 yr + symptoms not controlled with medical tx
2) life-threatening hemorrhage (intracranial hemorrhage) complicates acute ITP, plt count not corrected other means
Heparin acts on what part of the fibrinolysis/coag pathway?
Activates on Antithrombin (which anti-coagulates)
Warfarin: mechanism of action
Activates Vit-K dependant clotting factors
How to clinically differentiate primary hemostasis problem from secondary hemostasis?
Primary: mucocutaneous bleeds (oral, nasal), petechiae
Secondary: deep bleeds (muscular bleeds, joints, large hematomas)
Vit K: What does CPS recommend (dose and timing) for newborn
All be given 0.5 to 1.0 mg of IM vit K within 6 hrs of birth. Those who refuse: give IM dose as 2 mg PO, and repeat at 2-4 wk, 6-8 weeks.
Types (and timing) of Vit-K def bleeding (newborn)
• Early HDNB:
- first 24 hours. - Usually due to maternal anticonvulsants or antiTB meds. Give vit K to mother.
• Classic HDNB:
- from 1 day to 1 week. - Observed in up to 2% of infants not received vit K proph at birth.
• Late-onset HDNB:
- 2 weeks to 2 months or longer. - breast-fed infants not received vit K prophylaxis. - Present with IC bleeding.
vWD : types
- Type 1 : quantitative. (most common, mild, women)
- Type 2: qualitative (many subtypes)
- Type 3 (AR, consanguinity)
vWD: testing
1) CBC, coags, PFA.
2) - vWillebrand antigen (to test quantity),
- ristocetin cofactor (to test quality or function of vWF),
- factor VIII level
- blood group (because levels vary with BG).
vWD: management (tx, counselling)
- Desmopression acetate (DDAVP): IV or IN
- need DDAVP challenge - Factor VIII-vWF concentrate (Humate P – human plasma derived)
- OCP and treatment for anemia (eg iron) if needed for menorrhagia.
- General supportive care: avoid contact sports, wear helmets with any wheels or contact, avoid anti-platelet meds such as Advil/ASA
- Antifibrinolytics (eg TXA) useful for mucocutaneous bleeds.
Hemophilia: types (deficiencies)
- Hemophilia A = Factor VIII deficiency = Classic hemophilia, 85% of cases.
- Hemophilia B = Factor IX deficiency = Christmas disease, 15% of cases.
Hemophilia: severity classification
MILD disease (5-30% factor activity level):
- may have bleeding after surgery or trauma.
MOD disease (1-5%):
- occasional hemarthroses & spontaneous hematomas
SEVERE disease (less than 1%):
- spontaneous bleeding into joints and deep tissues.
Hemophilia: management
(• Prophylactic factor after delivery can be considered; not routine)
- Give vitamin K! – lots of pressure on IM site
- Education: parents are taught to give IV factors. Ports may be necessary.
- Acute treatment: for severe: factor should be given immediately, even before evaluation.
• Factor replacement: patients who develop target joints should be placed on a regimen of prophylactic factor replacement to avoid progression.
– For minor, achieve factor levels of 50%.
– For major hemorrhage, achieve factor level of 100%.
– 1 U/kg of FVIII = 2% rise in levels.
– 1 U/kg of FIX = 1% rise in levels.
• DDAVP can be used for mild/moderate hemophilia A → challenge first
List 5 neonatal presentations of hemophilia
- Intraventricular hemorrhage
- Circumcision bleeding
- IM hematoma after vit K injection
- Bleeding at the umbilical stumb
- Large caput or subgaleal bleed
- Excessive bleeding with phlebotomy
Indications for transfusions
- pRBC
- plt
- FFP
- Cryo
Transfuse Red Blood Cells:
- For Hb 70-100: signs of impaired oxygen delivery. Few situations.
- For Hb < 70, likely to be appropriate.
Transfuse Platelets:
- If plt < 10. (except ITP)
- If plt < 20 and fever or coagulopathy
- If plt < 50 for surgery, epidurals, LPs
- If plt < 100 for neurosurgery or head trauma
Transfuse FFP:
- For emergency reversal of warfarin
- For active bleeding or surgery, and coags > 1.5x normal
Transfuse Cryoprecipitate (factor 8, fibrinogen, vWF):
- For bleeding in pt with fibrinogen less than 0.8 to 1.0.
- For bleeding with vWD or hemophilia ONLY if factor or DDAVP is unavailable.
Most common reaction to transfusion
urticaria
fever
alpha Thal subtypes
Based on # of defective a-genes
1 –> carrier
2 –> trait (cis vs trans), (minor disease)
3 –> HgH disease (moderate disease)
excess beta –> clumping/tetramers –> hypoxia:
- hemolysis in marrow + extravascular
- High O2 affinity –> not released. –> severe anemia
- Triggers increase RBC production –> HSM
4 –> hydrops fetalis (Barts)
- in fetal: gamma chain tetramers –> extreme O2 affinity (don’t release)
- hypoxia –> Cardiac Failure + HSM + edema
- incomp w life –> transf, BM Tx
alpha-thalassemia: CBC features
- low Hgb
- Low MCV
- Low MCH
(Mentzer index: MCV/RBC <13 )
Smear:
- microcytic, hypochromic, target cells
beta-thalassemia subtypes
Minor: 1 defective beta (b0, or b+)
Intermedia: 2 defective (function): b+b+
Major: 2 defective (loss) b0b0
how can you differentiate alpha and beta TRAIT based on testing
Hgb electrophoresis is normal in alpha and abnormal in beta.
Diamond Blackfan Anemia: presentation
▪ Pallor with profound anemia usually becomes evident by 2 to 6 months of age; 90% of cases are recognized in the first year of life
▪ Growth retardation occurs in about one-third of children
▪ Congenital malformations are detected in about 35% to 45% of children
▪ Most commonly, craniofacial abnormalities (hypertelorism) and thumb abnormalities (flattening of thenar eminence, triphalangeal thumb)
Diamond Blackfan anemia: Labs
● Anemia (macrocytic, low retic, insufficient RBC precursors)
● Otherwise normal bone marrow
● Erythrocyte ADA activity is ↑ (helps to distinguish from TEC)
● Thrombocytopenia and neutropenia can present initially
● RBC precursors are markedly ↓ in BM, Serum iron levels are ↑
● unlike in Fanconi A, there is no ↑ in chromosomal breaks when lymphocytes are stressed with
alkylating agents
Diamond Backfan Anemia: DDX
● Transient erythroblastopenia of childhood (TEC)
- Macrocytosis, congenital anomalies, fetal red cell characteristics, and elevated erythrocyte ADA are generally associated with DBA and not with TEC
● Fanconi anemia - usually pancytopenia and absent radius
● Schwachman Diamond
● Myelodysplastic syndrome
● ParvoB19 – need to rule this out when diagnosing DBA
● HIV, as well as drugs, immune processes, and Pearson syndrome should also be ruled out
Diamond Blackfan Anemia: Tx
● Corticosteroids are mainstay of treatment
● If fail steroids → transfusions
● Stem cell transplant is curative
Hemophilia: complications
1) Intracranial bleeding: neurologic sequelae
2) Intramuscular bleeding: can lead to compartment syndrome
3) Intra Articular bleeding: can lead to arthritis and reduced ROM
