Hematology Flashcards
What is the genetic basis behind Sickle Cell Disease?
Mutation of a valine to a glutamine resulting in an abnormal beta globin chain.
Sickle Cell Trait - HbSHb
Sickle Cell Anemia - HbSS
Sickle Cell Disease - HbSS or Sickle Hgb C or Sickle B thalessemia
What features would make you most suspicious for langerhans cell histiocytosis?
- bony lucencies
- exophthalmos
- diabetes insipidus
- difficult to treat, scaly, seborrheic dermatitis of the scalp, diaper, axillary or post-auricular regions
may also see chronically draining ears, HSM, growth retardation, weight loss, fever or FTT
How is a diagnosis of LCH confirmed?
Biopsy of affected area
How is LCH treated?
- Curettage and bone graft
- Low dose radiation therapy
- Corticosteroid injection
- Systemic multiagent chemotherapy (i.e vinblastine/etoposide)
What are the CPS suggested guidelines for treatment of anemia of prematurity?
If on respiratory support:
115, 100, 85 (week 1, week 2, week 3 postnatal)
If not on respiratory support:
100, 85, 75
In children who have had a splenectomy, what are the prophylaxis guidelines as per CPS?
- birth to 5 years of age: 125 mg BID penicillin VK, or 10 mg/kg/dose BID amoxicillin
- > 5 yoa: 250-300 mg BID penicillin V, or 250 mg BID amoxicillin
What additional vaccines should be considered in a child with sickle cell anemia?
- Hib - 5th dose
- Polysaccharide pneumococcal-23 - 2 doses
- Annual influenza
- Quadrivalent meningococcal vaccine q 5 years
- Men-B x 2 doses
- Salmonella typhi if travelling to high risk area
How often should children with sickle cell anemia receive transcranial dopplers?
• Yearly between the ages of 2 and 16
What annual screening should be done for children with sickle cell anemia?
- Yearly retinopathy screening starting at age 10
- Yearly screening for asthma
- Yearly screening for nephropathy starting at age 10 (UA and urine albumin: creatinine ratio)
What transfusion goals should be set for children with sickle cell anemia?
• Should try and maintain Hgb S <30%, total hgb no greater than 125
Remember to also:
• Test for alloantibodies + RBC phenotyping
• If chronic transfusion: annual infection screen (HepB, HepC, HIV)
• Iron overload monitoring if >100 mg/kg of RBC (ferritin)
What organisms are children with SCD at greater risk of falling ill from?
Encapsulated bacteria
“Some Nasty Killers Have Some Capsule Protection”
Strep pneumoniae, Neisseria meningitidis, Klebsiella pneumoniae, Haemophilus influenzae, Salmonella typhi, Cryptococcus neoformans, Pseudomonas aeruginosa
What is your management of acute chest crisis?
- Pain control: opioids, Tylenol, NSAIDs
- Oxygen
- Bloodwork to assess hematocrit, group and type, and sickling load in preparation for possible transfusion (5 mL/kg)
- Hydration - to prevent hyperviscosity (10 mL/kg NS bolus)
- Blood culture and antibiotics (CTX and vanco)
- Incentive spirometry and SABA as required
What are the 3 most common respiratory organisms in cases of acute chest crisis in SCD?
- streptococcus pneumonia
- mycoplasma
- chlamydia
How to determine of a child with SCD has aplastic anemia or splenic sequestration?
- presence or absence of large spleen
- retics will be low in aplastic anemia, high in splenic sequestration
- bilirubin will be low in aplastic crisis, high in splenic sequestration
What neurological complications are possible in the setting of sickle cell disease?
- Headaches
- Cerebral sinovenous thrombosis (CSVT)
- Posterior reversible leukoencephalopathy syndrome (PRESS)
- Cognitive Impairment - deficits in intelligence, attention, executive function, memory, language and visual-motor
- Academic failure, decreased QOL (silent strokes)
What does the CPS suggest with respect to treatment of ITP in children?
- For children without active bleeding
- Observation as the 1st-line, with PO corticosteroids or IVIG as 2nd-line options
- Consider the individual’s bleeding risk (e.g., activity level), logistics (e.g., household distance from hospital) and social issues (e.g., reliability of follow-up)
- For children with moderate bleeding
- IVIG (0.8 g/kg to 1.0 g/kg) OR corticosteroids
- IV anti-D Ig only in Rh+ children (NOT first-line)
- For children with severe bleeding(e.g., prolonged epistaxis, GI bleeding or ICH)
- Admit, IV steroids and IVIG is indicated
- Tranexamic acid (25 mg/kg/dose 3 to 4 times per day (to a maximum of 1500 mg per dose or 4500 to 6000 mg per day)
- Plt tx only for acute, life-threatening bleeds or in children requiring immediate surgery
What is the genetic basis behind thalassemia alpha and thalassemia beta?
- Thalassemia alpha: genetic changes that affect the alpha chain (Chromosome 16)
- silent trait - single mutation
- cis/trans trait - alpha thal minor
- 3 mutations - alpha thal major
- 4 mutations - hemoglobin barts (hydrops)
- Thalassemia beta: genetic changes that affect the beta chain (Chromosome 11)
- single mutation B+ or B0 - betal thal minor
- B+/B0, B+/B+ - beta thal intermedia
- B0/B0 - beta thal major/Cooley’s anemia (transfusion dependent)
What clinical findings are expected in cases of beta thalassemia major?
- expansive extramedullary hematopoesis - chipmunk cheeks, hair-like projections on x-ray of skull, frontal bossing
- HSM
- depressed nasal bridge
- hypothyroidism
- FTT
- diarrhea
- pallor/jaundice
What treatment options are available for beta-thalessemia major?
- blood transfusion
- iron chelation
- splenectomy
- folate, iron and B12 supplementation
- hydroxyurea
What are the potential complications of beta-thalessemia major?
- Iron overload (#1 complication) - 2⁰ to hemolysis and repeat transfusions; multi system effects
- Bone marrow expansion :. May get spinal cord compression, osteoporosis/penia, fractures, AVN
- Chronic hepatitis, Hemochromocytosis
- Neurocognitive & learning delays
- Growth failure
What are the measures of severity for hemophilia?
- Severe <1%
- Moderate 1-5%
- Mild 5-25%
Which children with hemophilia require lifelong prophylaxis?
- Severe forms
* Those who have had their first joint bleed
What are the treatment options for hemophilia?
• Severe Hemophilia - treat with prophylactic rVIII concentrates, then PRN if bleeds
• Moderate Hemophilia - treat PRN with prophylactic rVIII concentrates
• Mild Hemophilia - DDAVP
- stimulates release of VW protein from endothelial cells and platelets
- VW carries factor VIII so you can boost their levels quite easily with DDAVP for bleeding episodes.
• Antifibrinolytic therapy (TXA and epsilon aminocaproic acid (EACA)) can be used with factor therapy to treat those with a mucosal source of bleeding
What are inhibitors and how do you manage their presence?
• Inhibitors = antibodies directed against factor VIII or factor IX that block the clotting activity
- Failure of a bleeding episode to respond to appropriate replacement therapy is usually the first sign of an inhibitor.
• Many patients who have an inhibitor lose it with continued regular infusions
• May also treat with immune tolerance induction (= regular (daily or several times weekly) infusions of variable doses of factor VIII or IX administered for a period of weeks to years in an effort to tolerize the immune system to factor VIII or IX)
Can immunizations be given to patients with hemophilia?
Yes, using a very small gauge needle (at least 23) and applying firm pressure afterwards for at least 5-10 mins
What are the classic findings in cases of hemolytic uremic syndrome?
- Thrombocytopenia
- Renal dysfunction
- Microangiopathic hemolytic anemia
What are potential causes of HUS?
- Infectious: i.e. E coli O157:H7 or neuraminidase streptococcus
- Genetic: ADAMTS13, complement factor H, I , B abnormality
- Medication: clopidogrel, calcineurin inhibitors
Treatment for HUS?
- Transfusion with washed RBCs (IgM if not washed may worsen course)
- DO NOT transfuse platelets
- Support re: renal dysfunction - diuresis, dialysis
- Management of hypertension
- Eculizumab
What are the different forms of von Willebrand Disease?
- Type 1 - mild, AD, prolonged mucocutaneous bleeding
- Type 3 - severe, AR, significant mucocutaneous bleeding that can mimic hemophilia
- Type 2 - difficult to diagnose
What is the best test for vWD?
- Ristocetin cofactor assay
- vWF antigen
- PT/PTT
- factor VIII activity
What is the most commonly inherited disorder of the RBC membrane?
Hereditary Spherocytosis (>Northern Europeans, but present in most populations)
What feature on CBC is unique to hereditary spherocytosis?
Markedly high MCHC (>350)
Which blood factors are not blood products, but recombinant products?
Factor VIII and Factor IX
What infectious agents does Canadian Blood Services screen for?
HIV, HTLV 1/2, Hep B/C, WNV, Bacterial infections by culture, CMV, Syphilis
What are the approximate risks of contracting HIV, Hep C and Hep B from donated blood products?
- HIV: 1 in 10 million
- Hep C: 1 in 5 million
- Hep B: 1 in 1 million
What are the characteristic features of Schwachman-Diamond Syndrome?
“Patrick Swayze takes a NAPP”
- Neutropenia
- Anemia
- Pancreatic insufficiency - improves with age
- Poor growth (FTT, recurrent infections)
What are the features of TARS?
- Thrombocytopenia
- Absent radius
- Eosinophilia
- Congenital heart disease i.e. ToF, ASD, VSD
What are the features of Diamond-Blackfan?
- Normochromic MACROcytic anemia, presenting in infancy
- Congenital abnormalities: -fan -> tri-/biphlangic thumbs, snub nose, hyperteloric, high-arched palate
- Neutropenia
- Thrombocytopenia
What is the main concern in patients with G6PD?
- Genetic abnormality that results in deficient Glucose-6-phosphate dehydrogenase placing the RBCs at greater risk of oxidative stress
- Results in breakdown of RBCs in times of stress, or exposure to free-radical producing medications or foods i.e. favism
