Hematology Flashcards
What is the treatment for PE?
LMWH
What is the most common transfusion related infection
CMV
What is the confirmatory test for AIHA?
DAT
What is the treatment for AIHA?
Steroids
What does the buffy layer of blood contain?
WBC and platelets
What proteins make up normal adult hemloglobin?
Alpha and beta (and some delta)
α + β (A) = 97%; α + δ (A2) = 2%
What proteins make up normal fetal hemoglobin?
Alpha and gamma
α + γ (F)
At birth, what percentage of HbF do you have?
70%
30% HbA
At what age does the Hb pattern resemble that of an adult (HbF <2%)?
6 months
What is the composition of the following hemoglobins: HbF HbA HbA2 HbC HbS HbH HbBart
NORMAL HEMOGLOBINS
Hb F = α2γ2
Hb A = α2β2
Hb A2 = α2δ2 (normally up to 3% of adult Hb).
BETA CHAIN VARIANTS
Hb C = α2βC2 (a variant of the β chain).
Hb S = α2βS2 (a variant of the β chain).
Hb D and Hb E and HbOArab and 1000 others (other variants of the β chain).
TETRAMERS
Hb H = β4 (observed in α-thal)
Hb Bart = γ4 (observed in α-thal)
Where is an embryo, then fetus’ blood made?
Yolk sac then Liver
Yolk sac at 3 weeks
Migrates to the liver at 2 months
Bone marrow at 6 months.
What is a normal Hb range for men, women, newborns?
Men 140-180
Women 120-160
Newborns up to 200
When is the physiologic nadir for hemoglobin and why does it happen?
8-10 weeks for term babies
6-8 weeks for preterm babies
In utero there is hypoxemia, which results in upregulation of EPO and increased fetal Hb
When you are born, saturation goes up and EPO is suppressed
8-10 weeks represents fetal RBC life span
What is the best way to classify anemias?
1) Decreased production OR increased destruction
-CHECK RETICS
2) If decreased production
Microcytic, normocytic, macrocytic
3) If increased destruction
Bleed, hemolysis, splenomegaly
What is the differential diagnosis for microcytic anemia?
Cells are small because there is inadequate production of hemoglobin.
Iron deficiency anemia Thalassemia Sideroblastic anemia Lead Anemia of chronic disease (usually normocytic)
What is the differential diagnosis for normocytic anemia?
They are normal cells, just not enough
Usually due to something impairing adequate marrow synthesis.
Anemia of chronic disease
Chronic renal failure
Transient erythroblastopenia of childhood
Malignancy/marrow infiltration
Acute bleed (retic response can take 2-3 days)
Other: HIV, HLH
What is the differential diagnosis of macrocytic anemia?
Difficulty with DNA production. Cell division lags behind, cytoplasm continues to grow
Vitamin B12 deficiency
Folate deficiency
Marrow failure: Myelodysplasia, Diamond-Blackfan, Fanconi anemia, Aplastic anemia (These may be normocytic early on)
Massive reticulocytosis
Normal newborn
Hypothyroidism
Down syndrome
Chronic liver disease
Drugs (alcohol, AZT).
What is the differential diagnosis of hemolytic anemia?
Problem Intrinsic to the Red Cell
Membrane: hereditary spherocytosis, elliptocytosis
Enzymes: G6PD deficiency, PK deficiency
Hemoglobin: Hb SS, SC, S-βthal
Problem Extrinsic to the Red Cell
Non-immune hemolysis: HUS, TTP, DIC, Burns, Wilson, Vit E def, etc.
Immune hemolysis: autoimmune, iso-immune, drug-induced.
What are the three most important tests for anemia?
CBC
Retics
Peripheral blood smear
What are the following blood film findings associated with:
Target cells Pencil cells Howell-Jolly bodies Basophilic stippling Heinz bodies Hb H bodies
Target cells-iron deficiency, post splenectomy, liver disease, hemoglobinopathies
Pencil cell-iron deficiency
Howell-Jolly bodies-asplenia, megaloblastic anemia, hemolysis
Basophilic stippling- lead poisoning or thalassemia
Heinz bodies- denatured Hb seen in G6PD, thalassemia
Hb H bodies-β4 tetramers seen in Hb H disease.
What are the main causes of iron deficiency?
1) Inadequate iron endowment at birth
- Preterm
2) Insufficient iron in diet
- Only breastmilk after 6 months
3) Blood loss
- GI tract (cow milk, parasitic infection, varices, Meckel’s, polyp, ulcer, H pylori)
- Epsitaxis
- Menorrhagia
4) Malabsorption of iron
- Celiac disease
- Antacids
- Giardiasis
- IBD
- IRIDA.
Why is there an increased risk of Pb toxicity in iron deficiency?
Pica
What type of iron is better absorbed-heme iron or non-heme iron?
Heme iron
What is the typical pattern of lab results in iron deficiency anemia?
Inadequate retic response Low MCV High RDW High platelets Target cells, pencil cells Hypochromasia High transferrin/TIBC High soluble transferrin receptor (not affected by inflammation) Serum iron-not a good test because affected by diurnal variation, diet, stress, infection
What is the Mentzer index?
MCV/RBC <13=thal
MCV/RBC >13=iron deficiency
How do you treat IDA?
4-6 mg/kg/day elemental iron
Reduce cows milk to 16-24 oz
Use vitamin C/orange juice to improve absorption
Treat for 3 months
When will you see response to iron treatment?
Reticulocytosis within 3-7 days
Increased hemoglobin (usually 7 to 30 days): expect Hb increases by 10 in 4 weeks
Repletion of iron stores (usually by 3 months).
When do you use IV iron?
Malabsorption
If there is not an adequate response to iron therapy in IDA (e.g. no Hb response in 2 weeks), what are the possible explanations?
Non-compliance Wrong diagnosis Ongoing blood loss Infection Mal-absorption.
What are some features of iron deficiency anemia?
Pica
Koilonychia-spoon nails
Cheilosis-cracking at corners of mouth
Psychomotor retardation
What is thalassemia?
Group of anemia disorders due to diminished or absent normal globin chain production
What are the 4 different types of alpha thalassemia?
3 α genes:
- Silent carrier state
- Normal/mildly reduced Hb/MCV
- Hb electrophoresis normal
2 α genes:
- Alpha thal trait or minor
- Normal/mildly reduced Hb
- Low MCV
- Moderate anemia (Hb 70-100)
- Hypochromia
- Microcytosis
- Target cells
- Heinz bodies
- Splenomegaly
- Jaundice
1 α gene:
- Hb H disease
- 60-70% HbA, 30-40% HbH, 2-5% HbA2, 2-5% HbF
No alpha genes:
HbBart disease
All the gammas stick together γ4
Leads to hydrops
What is a normal Hb electrophoresis?
90-98% HbA
2-3% HbA2
2-3% HbF
What is the Hb electrophoresis patter in alpha thalassemia?
1) Alpha thalassemia carrier/trait (3 or 2 alpha genes)=NORMAL
There is a proprotional reduction in all types of Hb (HbA, HbA2, HbF) and therefore, the percentages stay the same
2) HbH disease (1 alpha gene): 60-70% HbA, 30-40% HbH, 2-5% HbA2, 2-5% HbF.
What are the differences between iron deficiency anemia and Alpha-thal trait?
1) In alpha thal, the iron studies (serum iron, TIBC, ferritin, and marrow stores) are normal.
2) In alpha thal, RDW is normal, in IDA it is high.
3) In alpha thal, the RBC count is increased, usually around 5, and the MCV is very low.
There are many small cells. The Mentzer’s index (MCV/RBC) is >13 in IDA, and under 13 in thal trait.
4) In IDA, platelets are often increased.
Why are patients from SE asia more likely than Africans to have children with HbH disease or HbBart?
Because SE asians have cis mutations (2 alpha deletions on one chromosome)
Africans have trans deletions (one on each chromosome)
What are the different types of beta thalassemia?
Beta gene defect can be B0 (absent production) or B+ (reduced production)
Type is determined by clinical phenotype!
Beta thalassemia minor (one defective gene)
Hypochromia Microcytosis Target cells Basophilic stippling Mild or no anemia.
Beta thalassemia intermedia (two defective genes B0/B+, B+/B+)
Severe hypochromic microcytic anemia with Hb 70-90
Hepatosplenomegaly
Bone changes-mastoid hyperplasia, frontal bossing
Iron overload
Some need for transfusions
Beta thalassemia major (B0/B+, B0/B0) Severe anemia (Hb <70) Abnormal growth Iron overload Need for transfusion.
Do you need to treat beta thal minor?
No
Offer genetic counseling
What is the typical hemoglobin electrophoresis in Beta thal minor?
Elevated HbA2 and HbF (the extra alpha chains combine with delta and gamma)
90-95% HbA
5-7% HbA2
2-10% Hb F
What is the hemoglobin electrophoresis pattern in betal thal intermedia?
20-40% HbA
5% Hb A2
60-80% HbF
What is the hemoglobin electrophoresis patter in beta thal major?
95% HbF
No Hb A
What is the treatment for B thal major?
Regular transfusions and iron chelation.
Monitoring for complications of iron overload (cardiomyopathy, endocrine, hepatitis)
Bone marrow transplantation
What are risk factors for lead poisoning?
Living in old home (before 1978)
Pica
What features do you see on blood smear with Pb poisoning?
Basophilic stippling
In Pb deficiency, what happens to zinc protophyrin?
High
How do you treat Pb toxicity?
Removal from exposure
Chelation
Correction of IDA
What are features of anemia of chronic disease?
Caused by inflammatory cytokines and hepcidin, which Inhibits intestinal absorption of iron
Ferritin is often high/normal, TIBC is low
What is Diamond Blackfan anemia?
Congenital pure RBC aplasia
What are the clinical features of Diamond Blackfan anemia?
Normocytic anemia that presents in first few months of life
Associated anomalies:
- Craniofacial malformations
- Thumb or upper limb abnormalities
- Cardiac defects
What are the laboratory and BM features of Diamond Blackfan Anemia?
Anemia
Normal wbc and plts
Low retics
Bone marrow with reduced erythroid precursors.
Are patients with Diamond Black Fan anemia at increased risk of cancer?
Yes, especially leukemia
How do you treat Diamond Black Fan ?
1/2 respond to long term steroid therapy
1/2 need chronic transfusions
In what group of children is transient eryhtroblastopenia of childhood most common?
Usually appears in otherwise healthy children (1-3 years)
Often after a viral trigger
Over what time period do children with TEC recover?
Recovery is spontaneous within 1-2 months
How do you differentiate between DBA and TEC and aplastic crisis?
DBA – younger than 1 year, elevated MCV (esp at recovery), increased Hb F and ADA. More severe anemia, 50% have congenital anomalies
TEC-recovers in 1-2 months, normal HbF (can be elevated in 20%)
Aplastic anemia-hemolytic disease, parvovirus B19, recover to baseline
What should you do if you are following a patient with TEC and their MCV or HbF remain elevated?
Refer to hematology to rule out DBA
What deficiencies cause megaloblastic anemia?
Folate or Vitamin B12
Both are required to make DNA
Results in continuing cell growth without division
What are risk factors for Vitamin B12 deficiency?
Strict vegetarian diet Picky eaters Prolonged breastfeeding if mom deficient Ileal resection (that is where B12 is absorbed) Abnormal intestinal transport Congenital IF (absorption requires IF) Gastrectomy (absence of IF) Malabsorption (celiac) Transcobalamin deficiency (transports B12)
What are risk factors for folate deficiency?
Decreased intake (excessive goat milk) Intestinal malabsorption (celiac, IBD, anticonvulsants, septra) Increased requirements (chronic hemolytic anemia, pregnancy).
What findings would you see on blood smear with megaloblastic anemia?
Megaloblastic changes
Howell-jolly bodies
Hypersegmentation of neutrophil nucleus
What features do you see in megaloblastic anemia?
Mild jaundice due to ineffective erthropoiesis
Glossitis
In B12 deficiency: peripheral neuropathy
What is the treatment for folate deficiency?
200-400 ug/day
What are dietary sources of folate?
Fruits, vegetables, milk, fortified bread/pasta/flour
What are dietary sources of vitamin B12?
Meat and dairy
What type of milk does not have folate in it?
Goat’s milk
What is the inheritance patter of hereditary spherocytosis?
Most AD
1/3 spontaneous mutation
What are the clinical features of hereditary spherocytosis?
Neonatal jaundice
Chronic hemolysis
Gall stones***most common complication
Splenomegaly
What investigations support a diagnosis of hereditary spherocytosis
Smear
DAT negative
High MCHC >350
Osmotic fragility rarely necessary
When should patients with HS get a splenectomy?
Moderate hemolysis, symptomatic disease
After age 5 to minimize risk of sepsis
G6PD is most common in which ethnicities?
Africa, Middle East, South Asia and the Mediterranean
What is the genetics of G6PD?
X-linked
What findings on smear are indicated of G6PD?
Blister cells-RBCs appear blistered and bitten (bite cells)
Heinz bodies
When is the G6PD assay falsely negative?
Patients who are actively hemolysing (because the older cells are dead)
What are the most common oxidants triggering hemolysis in G6PD?
Sulfas Nitrofurantoin Dapsone Naphthalene (moth balls) Anti-malarials-chloroquine Rasburicase Fava beans Infection.
Absent radius is found in which aplastic anemia?
Fanconi anemia
What are the 3 types of autoimmune hemolytic anemia?
1) Warm (IgG, extravascular hemolysis)-makes kids sick
2) Cold (IgM, called “cold agglutinin disease”)
3) Biphasic (Donath-Landsteiner IgG, called “paroxysmal cold hemoglobinuria”).
How do you diagnose autoimmune hemolytic anemia?
Positive DAT
What are some etiologies of AIHA?
Idiopathic Secondary to drugs Infection Lupus Immunodeficiency Lymphoproliferative diseases (lymphoma, ALPS)
Cold and biphasic AIHA are associated with which infections?
EBV, mycoplasma, CMV, HIV
How do you treat warm AIHA?
STEROIDS
Splenectomy
If need to, transfuse
How do you treat cold or biphasic AIHA
Supportive care
Transfusions
Plasmapheresis if severe
What are the most common causes of hemolysis in the newborn?
Rh D allo-immunization (Hemolytic disease of the newborn)-MOST SEVERE
ABO incompatability (mOm O, bABy AB), Other blood groups (Kell, Duffy, Lewis)
Non-immune hemolysis (HS, G6PD, and rarely alpha-thal major).
What is the severity of Rh incompatability at the time of birth is best predicted by?
Cord hemoglobin
What is the triad of HUS?
Microaniopathic hemolytic anemia
Thrombocytopenia
Renal impairment
List 3 causes of HUS
E.coli O157:H7 toxin.
Shigella
Strep Pneumoniae
What is the pentad of TTP?
Microaniopathic hemolytic anemia Thrombocytopenia Renal impairment Fever Neurologic impairment-DIFFERENTIATES FROM HUS
What causes TTP?
Congenital or acquired deficiency of ADAMTS13
What is TTP?
A thrombotic microangiopathy caused by severely reduced activity of the von Willebrand factor-cleaving protease ADAMTS13. It is characterized by small-vessel platelet-rich thrombi
What does bloodwork look like in DIC?
High INR, high PTT, LOW FIBRINOGEN, fragmented red cells
What is the genetic mutation that causes sickle cell disesase?
Caused by a single nucleotide substitution (GTG for GAG, valine for glutamic acid) at codon 6 of the beta globin gene on chromosome 11
What does the sickledex test measure?
Detects HbS by looking at its solubility
After what age can you use the sickle dex?
After 3 months (need high percentage of HbS for it to be positive; before 3 months, lots of HbF)
What is the relative severity of the different types of sickle cell disease?
SS > S-β0 > SC > S-β+ > S-HPFH
What is the expected life expectancy of HbSS?
45 years
By what age are 90% of HbSS patients functionally asplenic?
6 years
What are the two most common organisms causing osteomyelitis in SCD?
Salmonella and Staph aureus
What are the indications for chronic transfusion in SCD?
History of stroke (goal is to maintain HbS <30%)-pRBC FOR LIFE
Abnormal TCDs (flow velocity greater than can detect children at risk of overt stroke when they have flow velocities greater than 200 cm/sec)
When should you screen with TCDs?
Annually between 2-16 years
What are risk factors for stroke in SCD?
SS genotype Low baseline Hb Previous TIA High blood pressure Multiple ACS Abnormal TCD
What antibiotics should you use to treat ACS?
Cephalosporin + macrolide
How is lung disease associated with SCD different from asthma?
May not respond to ICS
Below what age do you see splenic sequestration?
<3 years
When do you perform splenectomy in HbSS?
Over 2 splenic sequestrations
What are the indications for cholecystectomy for SCD?
Abdominal Pain
Cholestatic jaundice
History of acute cholecystitis
What are the long term complications of SCD?
Stroke/Silent infarct Retinopathy PHTN Lung disease of SCD Osteonecrosis of femoral/humeral head Nephropathy (papillary necrosis) Iron overload
What screening should be done in SCD?
Infants should be evaluated in a SCD program by 3 months
Penicillin prophylaxis should begin at 3 months and continue until at least 5 years.
Appropriate pneumococcal vaccination
Prevnar-13 at 2, 4 and 12 mo
Pneumovax-23 should be given at 2 y and 5 y.
Transcranial doppler should begin at age 2 y and continue yearly until 16 y for all SS and S-β0 thals.
Routine screening for end-organ damage should begin in middle-childhood.
- PFTs
- Echo
- Urine ACR
- Eye exam
What are the indications for simple and exchange transfusion in SCD?
Simple transfusion: Aplastic crisis Splenic sequestration-need to be careful Pre-op (high risk surgeries) Stroke – if low Hb, awaiting exchange ACS – if low Hb, awaiting exchange Also used chronically to prevent stroke by keeping Hb S under 30%.
Exchange transfusion:
Stroke
Severe ACS-if Hb near 100; want to avoid making them too viscous with simple tx
Pre-op some major surgeries.
When does iron overload in SCD patients receiving chronic transfusion?
After 1 year of monthly transfusions
How do you monitor compliance with hydroxyurea?
MCV
HbF
HbS
What are congenital causes of neutropenia?
GSD type Ib
Severe congenital (not necessarily Kostmann)
Cyclic neutropenia
Fanconi Anemia, Schwachman-Diamond
What are acquired causes of neutropenia?
Infection:
-Viral (EBV, parvovirus, HHV6), bacterial.
Drug-induced
-Anti-epileptics, anti-psychotics, myelotoxic agents
Autoimmune
- Primary: autoimmune neutropenia of childhood*
- Secondary: SLE, neonatal due to maternal autoimmune disease
Chronic idiopathic
Sequestration
Nutritional:
-B12 or folate deficiency
What is autoimmune neutropenia of infancy?
Kids between age 0-10 years
Normal WBC count but can have severely low ANC
Only minor infections (cellulitis, OM, URTI, gastro)
Lasts 6-24 mo.
What are the acquired causes of pancytopenia?
Exposures (chemotherapy, benzene, antiepileptics, radiation, many others) Viruses (EBV, HIV, CMV, HBV, HCV) Autoimmune diseases (SLE, others) Pregnancy Paroxysmal Nocturnal Hemoglobinuria Infiltrative (Leukemia, metastatic solid tumor, myelofibrosis) Myelodysplasia Macrophage Activation Syndrome/HLH Acquired Aplastic Anemia
What are inherited causes of pancytopenia?
Fanconi Anemia
Shwachman-Diamond Sydrome
Dyskeratosis Congenita
Diamond-Blackfan Anemia (usually just anemia)
Congenital Amegakaryocytic Thrombocytopenia
Primary Hemophagocytic Lymphohistiocytosis
Unclassified inherited bone marrow failure
How are the clinical features of Fanconi anemia?
Dysmorphic Café au lait macules Short stature Thumb/Hip abnormalities Absent radius, no thumb Horseshoe kidney Progressive marrow failure
How is Fanconi inherited?
AR
What is the risk of malignancy with Fanconi
15% AML/MDS
Head/neck carcinoma
Liver tumors
What are the clinical features of Shwachman-Diamond ?
Short stature Skeletal abnormalities (metaphyseal widening) Pancreatic insufficiency Bone marrow dysfunction Most have neutropenia 1st
How is Shwachman-Diamond inherited?
AR
What malignancies are associated with Shwachman-Diamond ?
MDS
Leukemia
What is the differential for thrombocytopenia?
Decreased production Increased destruction (immune and non-immune) Sequestration Consumption Platelet loss or dilution
Decreased production: marrow infiltration (leukemia), marrow injury (aplastic anemia), congenital syndromes of ineffective thrombopoiesis (eg TAR, hereditary thrombocytopenias, Wiskott-Aldrich syndrome)
Increased destruction, Immune: ITP, SLE, NAIT, Infection, Heparin, drugs (eg Valproate, anticonvulsants, chemo).
Increased destruction, Non-Immune: DIC, HUS, TTP, Infection, Kasabach-Merritt syndrome, artificial heart valve.
Sequestration: Hypersplenism from liver disease, storage disease, portal vein thrombosis.
Consumption: thrombosis, eg clot around central line, type 2B von Willebrand disease.
Platelet loss or dilution (after massive dilution for major trauma or scoliosis surgery).
What is the differential for Neonatal Thrombocytopenia?
Decreased production:
-TAR (thrombocytopenia absent radii syndrome) in which megakaryocytes are absent in the bone marrow.
Non-immune destruction:
TORCH eg CMV
NEC, RDS, and transiently after maternal pre-eclampsia. (In general, a sick neonate).
Clot
Immune destruction:
Maternal ITP – check mom’s CBC
NAIT - alloantibody directed against an antigen on the newborn’s platelets made by mother
What is NAIT?
- Analogous to Rh disease
- 98% of humans have the HPA antigen on platelets
- 2% of women who lack this antigen will produce antibodies against the fetus‘plts
What is more severe–maternal ITP or NAIT?
NAIT-Hemorrhage can be severe. ICH and hydrocephalus can occur.
When does maternal ITP resolve?
After a few months when antibodies catabolized
Do you need to treat maternal ITP?
Rarely
If there is bleeding, IVIg can be given
How do you treat NAIT?
First line:
-Washed maternal platelets
Second line:
-HPA-negative/PLA-1 negative platelets
Third line:
-IVIg
What percentage of children with ITP get ICH?
<1%
Below what number of plaletets are you at increased risk of ICH in ITP?
<10
What are the indications for bone marrow in ITP?
Low Hb Low WBC Blasts Lymphadenopathy Hepatosplenomegaly Suspicious history such as long fevers, bone pain or weight loss
How long does acute ITP take to resolve?
6 months
What are risk factors for chronic ITP?
- 1/3 progress to chronic ITP
- Insidious onset, higher initial count and older age (adolescent)
What anticipatory guidance do you give to families for ITP?
Avoid contact sports
Avoid NSAIDs and aspirin
How do you counsel families on treatment options in ITP, if platelets <10?
1) Oral steroids for 4 days
- Benefits-po
- Side effects: hyperphagia, irritability, insomnia, can mask leukemia/upgrade risk
2) IVIG
- May work slightly faster then steroids (within 24 hours)
- Side effects: headache, nausea, vomiting, aseptic meningitis, allergic reactions
3) Observe
- ALWAYS if plt >10
What are the indications for splenectomy in ITP?
1) Older child (> 4 yr) with severe ITP that has lasted >1 yr and whose symptoms are not easily controlled with medical therapy is a candidate
2) Life-threatening hemorrhage and platelet count cannot be corrected rapidly with other means.
What is a bleeding work up?
CBC, PTT, INR
Factor levels as indicated
Platelet count normal but primary hemostasis problem suspected, do PFA-100
If PFA abnormal: vWD, liver disease, hereditary or acquired platelet disorders.
Which factors are in the intrinsic pathway?
8, 9, 11, 12
HEMOPHILIAS
Which factors are in the extrinsic pathway?
7
Which factor does not affect INR/PTT?
Factor XIII
What factor increases PTT, but is not a coagulation disorder?
Factor XII deficiency
Can you diagnose hemophilia within the first 72 hours of life?
No
Factor VIII often elevated after birth
What is the differential for
1) Normal INR and elevated PTT
2) Elevated INR and normal PTT
3) Both elevated
4) Both normal
1) Normal INR and elevated PTT
- Factor 8, 9, 11 deficiency
- Factor 12 deficiency-but not coagulopathic
- vWD
- Heparin
- APLA
2) Elevated INR and normal PTT
- Early Vit K
- Factor 7 deficiency
- Early liver disease
- Warfarin
3) Both elevated
- Late vit K deficiency
- Liver disease
- DIC
- Dys/afibr.
- Factor 2 deficiency
- Excess Hep/warf
4) Both normal
- Factor 13
- PAI deficiency
What are the differences between UFH and LMWH?
UFH
- Fast onset and offset
- Not affected by renal function
- Can be given IV
- Cheap
- Monitor with anti-Xa or aPTT
LMWH
- More predictable
- Can be given at home
- Less frequent monitoring
- Monitor with anti-Xa
Why is heparin not effective in antithrombin III deficiency?
Heparin binds to the enzyme inhibitor antithrombin III; inactivates thrombin and other factors in the coagulation cascade
When do the different types of hemorrhagic disease of the newborn present?
Early-first 24 hours
Classic-: from 1 day to 1 week
Late: from 2 weeks to 2 months or longer
What is the etiology of early HDNB?
Maternal anticonvulsants
Maternal antiTB meds
How can you prevent early HDNB?
Administering vit K to mother in late pregnancy.
Who gets classic HDNB?
Up to 2% of infants who have not received vit K prophylaxis at birth.
Who gets late HDNB?
Breast-fed infants who have not received vit K prophylaxis.
What is the most common presentation of late HDNB?
ICH
What is the schedule for po vit K?
2 mg po at birth
Repeated at 2-4 weeks and at 6-8 weeks.
What are the 3 types of vWD?
Type 1 vWD: quantitative deficiency of normal vWF.
Type 2 vWD: qualitative problems
Type 2A: Abnormal vWF proteolysis. There is absence of the large multimers, leading to defective adhesion.
Type 2B: Enhanced platelet binding affinity of vWF to GPIb leading to clearance from circulation+ thrombocytopenia. DO NOT USE DDAVP
Type 2M: There is decreased binding to platelets.
Type 2N: there is decreased binding of VWF to factor VIII (therefore factor VIII gets degraded). It mimics hemophilia and is often misdiagnosed as such, but it is autosomal rather than X-linked.
Type 3: RARE. Autosomal recessive disorder characterized by complete absence of vWF and severe bleeding.
What tests should you order for suspected vwD?
CBC
Coags
PFA.
Von Willebrand antigen (to test quantity of vWF)
Ristocetin cofactor (to test quality or function of vWF)
Factor VIII level
Blood group (because normal levels of vWF vary with blood group).
A disproportionate decrease of Ristocetin over vWF points to a type 2 problem (qualitative)
What factors can affect vWF levels?
vWF levels can vary with age, race, blood group, stress, trauma, pregnancy
How do you treat vWD?
DDAVP
Factor VIII-vWF concentrate (humate P)
OCP for menorrhagia
Supportive care:
Avoid contact sports
Avoid ASA, advil
What two treatments will not work in vWD type 2B?
DDAVP
Factor VIII-vWF concentrate (humate P)
What factor deficiencies cause hemophilia A and B?
Hemophilia A = Factor VIII deficiency = Classic hemophilia, 85% of cases.
Hemophilia B = Factor IX deficiency = Christmas disease, 15% of cases.
How can women get hemophilia?
It is X-linked. Women are carriers, but can have disease with lyonization, homozygosity, or Turner syndrome.
How does hemophilia present?
- Hemorrhage into soft tissues and joints.
- Iliopsoas bleeds
- Neonates may present after profuse bleeding with circumcision, and up to 5% may present with intracranial hemorrhage.
- Most patients do not have soft tissue hematomas until after they learn to roll over or crawl.
What are the three levels of severity of hemophilia?
Mild disease (5-30% factor activity level) may have bleeding after surgery or trauma.
Moderate disease (1-5%): occasional hemarthroses and spontaneous hematomas, at particular risk after even mild challenges.
Severe disease (less than 1%): spontaneous bleeding into joints and deep tissues.
When do children with hemophilia get prophylactic factor replacement?
Old wisdom was replace in patients who have had a few bleeds or target joins; now there is argument that all should receive prophylaxis
The following are targets for replacement:
For minor bleeds, achieve factor levels of 50%.
For major hemorrhage, achieve factor level of 100%.
DDAVP can be used for mild/moderate hemophilia A, but challenge first
If there is no response to factor in a patient with hemophilia what must you consider?
15% of patients develop IgG antibodies
Patient no longer responds or requires more than usual replacement
How do you treat inhibitor formation in hemophilia?
Desensitization therapy
What are 4 ways that a neonate can present with hemophilia?
IVH Bleeding after circumcision Hematoma with IM vit K Subgaleal hemorrhage Bleeding at umbilical stump Excessive bleeding with phlebotomy
What are the indications for rBC transfusion?
Hb <70
Hb 70-100 with O2 requirement
What are the indications for platelet transfusion?
If plt < 10
If plt < 20 and fever or coagulopathy
If plt < 50 for surgery, epidurals, LPs
If plt < 100 for neurosurgery or head trauma
What are indications for FFP?
For emergency reversal of warfarin
Massive transfusion
For active bleeding or surgery, and coags > 1.5x normal
When are indications for cryoprecipitate?
- For bleeding in pt with fibrinogen less than 0.8 to 1.0.
- DIC
- For bleeding with vWD or hemophilia ONLY if factor or DDAVP is unavailable.
What is the purpose of leukoreduction for pRBC?
Most important=reduces viral transmission (CMV)
Reduces febrile non-hemolytic reactions
Reduces allo-immunization
When do you use irradiated blood (kills all nucleated cells)?
Immunocompromised (BMT, SCID, T cell deficiency)
Reduces risk of GVHD
What is the most common acute transfusion reaction?
Allergy
Febrile non-hemolytic reaction
What are the most common fatal transfusion reactions?
TRALI
Sepsis
What is the most common pathogenic infection from transfusions?
Parvovirus
How do you manage a transfusion reaction?
Stop the transfusion
Keep IV running
Send blood and samples to lab
Provide supportive care
List transfusion-acquired infections from most to least common
Transfusionmedicine.ca
What are transfusion thresholds in neonates?
Without resp support
Week 1: 100
Week 2: 85
>Week 3: 75
With resp support
Week 1: 115
Week 2: 100
>Week 3: 85
How much iron do you use to treat anemia of prematurity?
2 mg/kg
Name 4 indications for splenectomy
Traumatic splenic rupture
Severe hemolytic anemia
Refractory ITP
Hypersplenism
Name 3 long-term complications of splenectomy
Infection < 5 years, pneumococcal/meningococcal/H.flu/malaria/babesiosis
Thrombo-embolic complications
Pulmonary hypertension
What vaccines should patients with splenectomy get and when?
PCV13 (prevnar) at 2, 4, 6, 12-15 months
- One dose of PCV13 if >24 months and missed initial series
- All patients should get PCV13 even if they received PCV7 or 10 previously
PPV23 (pneumovax) at 2 years and 7 years (or at splenectomy and then 5 years later)
MCV4 at 2, 4, 6, 12 mo (menveo) and then q5 years
4CMenB
Hib as in regular schedule
Influenza
If a baby has HbF and HbS on electrophoresis, what is the diagnosis?
Sickle cell disease
List 5 preventive care measures in sickle cell disease
Prevnar, Pneumovax
Meningococcal vaccine
Penicillin
Hydroxyurea
What are two treatments that modify the SCD?
BMT
HU
What is the only complication of HbSC that is more common than in HbSS?
Retinopathy
What are the risks of transfusion in SCD?
Iron overload
Alloimmunization
Infection
Final Hct should not exceed 100% otherwise too viscous
What two hematologic disorders are associated with absent radius?
TAR Fanconi anemia (also absent thumb)
What are the features of dyskeratosis congenita?
Reticulated skin hyperpigmentation
Nail dystrophy
Mucosal/tongue leukoplakia
What are the steps in hemostasis?
1) Vasoconstriction
2) Primary hemostasis
- Platetlet plug formation
- Platelet activation and aggregation
- Requires vWF
3) Secondary hemostasis
- Fibrin polymerization
4) Thrombus and antithrombotic events
When does TAR resolve?
Born with thrombocytopenia
Treat with tx
Resolves by 3 years of age
Which factors are in the common pathway?
2, 10
What are the important components of the anticoagulation system and where do they act?
Protein C/S act on Factor 8 and 5
Antithrombin acts on factor 10 and factor 2
How does warfarin work?
Acts on the vitamin K dependent factors
Initially decreases protein C and S-can make you prothrombotic initially!
What type of vWD can be mistaken for ITP?
Type 2B
What type of vWD can be mistaken as hemophilia A?
Type 2N
How does DDAVP work in treating vWD?
It causes release of VWF from endothelium
Before prescribing DDAVP for vWD what should you do?
DDAVP challenge test to see if it works!
Measure vWF, ristocetin, PFA before and after
What are side effects of DDAVP?
Tachycardia
Facial flushing
Hyponatremia
Tachyphalaxis
What is in cryoprecipitate?
Factor 8, 13
vWF
Fibrinogen
What would you advise a child with hemophilia regarding immunizations?
Apply pressure x 10 mins
When do we give CMV negative blood?
Post BMT patients
CMV negative recipients
Prothrombotic work up
INR/PTT CBC Fibrinogen Protein C, S AT 3 level FVL mutation Lupus anticoagulant ACLA
What do you use to treat patient with vWD and acute bleed?
Humate P (first choice) (Cryoprecipitate if above not available) DDAVP-if minor bleed and known vWD type
List 2 long term complications of hemophilia
Arthropathy
Inhibitor formation
Neurocognitive and/or behavioral dysfunction if past ICH
