Haematology Flashcards
Complications post splenectomy & prevention of infection
Risk sepsis 5%, most in 2yrs
- Higher risk if Hbopathies, immunodeficiency, storage disease/haemolytic anemia
Organisms
80% encapsulated bacteria
- Strep Pneumo
- H.Influenzae
- N.Meningitides
Protozosl
Capnoytophaga/C.Cynodegmi (animal bite)
Rx: broad spec- cephalosporin + vanc
Prevention:
Pneumococcal
- Prevenar 13 x1: >12mo
- Prevenar 23 x2: 4-5yr, then 5 yrs post
Meningococcal: ACWY/B x1
Annual influenza vaccine
AB prophyaxis: oral amoxicillin, pen V until 16yrs or lifelong if severe immunocompromise/high risk
DDx for splenomegaly & definition
> 2cm below L) costal margin
(usually 2-3x normal size to be felt)
Structural: harmatoma, polysplenia, cyst, haemangioma
Haem: IDA, EM haematopoesis, haemolysis
Storage disease: lipidoses, MPS, CHO defects
Immunological: autoimmune conditions
Malignancy: leukaemia, lymphoma, mets
Congestive: CCF/portal HTN
Infection
Hypo vs hypersplenism & causes.
Hypersplenism
- Increased function- sequestration/destruction of cells, increased BM activity/haematopoesis
- Banti syndrome: obstruction in hepatic/splenic or portal veins = hypersplenism, Rx splenectomy vs portocaval shunt depending on site of obstruction
Hyposplenism
- Neonate/premature
- Haemolysis, sickle cell disease (6mo onwards)
- Autoimmune diseases
- GI/hepatic disorders
- Meds: methyldopa, steroids, PN,radiation
- Ix: Howell-Jolly/Heinz bodies on film, poor technetium uptake, reduced IgM memory B cells
What Dx contributes to activated protein C resistance?
Protein C/S (cofactor): degrade 5a/8a
- leads to HYPERCOAGULABLE state as prolonged clot degradation
Factor 5 Leiden (APC resistance)
- Most common inherited risk factor for thrombosis (5% of white population)
- F5 = procoagulant clotting factor that amplifies the production of thrombin
Ix: APC resistance assay- should prolong APTT in F5L in doesnt, genetics
What Dx contributes to activated protein C resistance?
Protein C/S (cofactor): degrade 5a/8a
- leads to HYPERCOAGULABLE state as prolonged clot degradation
Factor 5 Leiden (APC resistance)
- Most common inherited risk factor for thrombosis (5% of white population)
- F5 = procoagulant clotting factor that amplifies the production of thrombin
Ix: APC resistance assay- should prolong APTT in F5L it doesn’t, genetics (FISH)
Rx: long term anticoagulation if homozygote, education- COCP avoidance heterozygotes
Prothrombin 20210 features
Second most common thrombophilia
- Gain of function mutation at position 20210
- 30% higher than standard levels
- Precursor of thrombin- elevated levels = more clot
Protein C/S, antithrombin deficiency features/Rx
Rare but strong cause of thrombophilia
- Counter-regulatory protein
- Stops formation prothrombin - thrombin (inhibits 5a/8a)
- Deficiency = more clots
Ix: Protein C/S/AT chromogenic clotting assay
Rx: FFP, protein C/S replacement
Risk of VTE with F5L vs Protein C/S/AT and prothrombin mutations
AT: 16x risk
Protein C: 7x risk
Protein S: 5x risk
F5L: 4-5x risk
Prothrombin: 3-4x risk
Methaemaglobinemia- types, Rx
Hereditary
- AR, cytochrome B5 reductase deficiency
- AD HbM diseases (altered globin gene)
- Diminished reduction of Hb Fe3+ to HbFe2+
- Lifelong cyanosis, otherwise asymptomatic
Acquired
- Ingestion of drugs
Methaemaglobinemia- types, Rx
Hereditary
- AR, cytochrome B5 reductase deficiency
- AD HbM diseases (altered globin gene)
- Diminished reduction of Hb Fe3+ to HbFe2+
- Lifelong cyanosis, otherwise asymptomatic
Acquired
- Ingestion of drugs
Pathophys/Ix for NAIT
Common cause of low platelets
Maternal platelt ABs reacting against paternal
- HPA1-a, 5b, 15b highest in europeans,
- HPA4b Asians
Can occur in first pregnacy
Risk of IVH up to 20%
Rx: platelet transfusions
Alpha thalassemia trait findings?
αo mutation = no α-chains
α+ mutations = decreased α-globin chain
Minima: 1 defective- asymptomatic
Minor: 2 defective - mild anemia
HbH: 3x defective - mod anemia, transfusion dependant
Barts: 4x defective- FDIU/hydrops
B thalassemia path findings?
Decreased HbA (need to replace with HbA2/F)
B thal minor
(B+/B) = increased HbA2 or (B+/B0) = increased HbA2 & F
B thal intermedia
(B+/B+) = increased HbF
B thal major
(B0/B0) = no HbA, severe anemia
Fanconi anemia Sx
Most common inherited aplastic anemia (AR)
- Chromosomal fragility, oxidative damage to RBCs
- 3-14yrs onset, most haem > physical
Marrow failure <10yrs
- Elevated AFP
- Hypocellular/fatty BMA
- Dx: chromosomal breakage studies (DEB/mitomycin C)
Hyperpigmentation of trunk/neck/axilla & groin
Cafe au lait spots, vitiligo
ABSENT RADII/ supernumary or bifid thumbs
Short stature, abnormal genitalia/underdeveloped in males
Microcephaly, small eyes
Renal, cardio, gastro malformations
Child presents with profound anaemia at 4mo, noted to have triphalangeal thumb & high arched palate.
Ix: macrocytic anemia, increased HbF/i-antigen, increased erythrocyte adenosine deaminase (ADA) activity, low retics
Diamond Blackfan Anaemia
AD- RPS19 gene (ribosomal subunit of RBC)
- Normochromic/macrocytic anemia 2-6mo
+/- hydrops 25% - Craniofacial abnormalities 50%
- Skeletal abnormalities 30%
- Renal tract & cardiac abnormalities 30-40%
- Predisposed to MDS, AML, sarcomas
Ix: as above, normal other cell lines
Rx: steroids 80% response, transfusions - good prognosis 75% at 40yrs
Pearson Marrow-Pancreas Syndrome
Mitochondrial disorder
FTT
Exocrine pancreas dysfunction
Liver and renal tubular defects
Malabsorption
Myopathy
Macrocytic anaemia, sideroblasts/vacuolated erythroblasts & elevated HbF
2y/o child presenting with significant normocytic anemia and low reticulocytes, borderline neutropenia- 1-2 weeks after viral URTI
TEC
> 1yr, post viral illness, no other abnormalities, normal MCV (DBS macrocytic)
HbF/i-antigen & ADA normal
Treatment of Fanconi Anaemia
Monitor endocrine, blood counts
Supportive
- Androgens 50% response
- G-CSF/EPO
Curative- HSCT
Shwachman-Diamond Syndrome
AR- SBDS gene
- Ribosomal dysfunction
- Pancreatic insufficiency (2nd most common cause)
- Neutropenia 85-100%, anaemia 50%, thrombocytopenia/pan 25%, MDS 10-30%
- Flared ribs/delayed bone maturation & FTT