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
Dyskeratosis congenita
X-linked recessive/AD/AR
Telomere maintainence
- Reticular/lacy rash, leukoplakia & nail dystrophy
- BM failure 90%
- Eye abn 50%- epiphora, cataracts, strabismus
- Skeletal/dental abnormalitis
Coats’ plus syndrome
mutations in the CTC1 gene; results in short telomeres
- Vasculature ectasia: Retinal telangiectasia, GI bleeding and portal HTN
- Intracranial calcification, leukodystrophy, brain cysts,
- Osteopenia,
Additional manifestations of DC, which include sparse and graying hair, dystrophic nails, and anemia
Revesz Syndrome
Dystrophic nails, leukoplakia, aplastic anemia, retinopathy & cerebellar hypoplasia
Hoyeraal-Hreidarsson syndrome
aplastic anemia, immunodeficiency, microcephaly, growth retardation, and cerebellar hypoplasia
Findings on this film?
Howell Jolly Bodies
- Splenectomy/functional asplenia (sickle cell)
- Fragments of RBC nucleus
Heparin induced thrombocytopenia- cause/Rx
Naturally occurring GAG produced by basophills/mast cells
Treatment for cardioembolic stroke (3mo)/ VST(3-6)
HIT = formation of platelet factor 4 antibodies
Treatment of VWF?
- Desmopressin – increases the amount of circulating VWF by release from endothelial cells
May increase level of VWF + F8 by 3-5 x over 8-10 hours
- 1c type does not respond - Tranexamic acid
Antifibrinolytic agent
Prevents dissolution of haemostatic plug
Treatment of VWF?
- Desmopressin – increases the amount of circulating VWF by release from endothelial cells
May increase level of VWF + F8 by 3-5 x over 8-10 hours
- 1c type does not respond - Tranexamic acid
Antifibrinolytic agent
Prevents dissolution of haemostatic plug
Differences between haemophilia & VWF
Haemophilia A
- Boys
- Deep tissue bleeds
- Normal bleeding time
vWF
- Boys = girls
- More common
- More mucosal bleeding
Types of VWF
Type 1 (80%)- quant deficiency
- AD
- ↓ VWF activity/Rco
- All multimers present but decreased number
Type 2 (20%) - qualitative deficiency
2A (10-20%): ↓activity/Rco, NF8, dec. large monomers
2B (5%) - ↓activity/^Rco, NF8, dec. large monomers
2M (↓activity/Rco)
2N (normal activity/Rco, low F8, normal electrophoresis)
Type 3- complete deficiency (AR)
- No vWF
- Low F8
- Undetectable electrophoresis
Types of VWF
Type 1 (80%)- quant deficiency
- AD
- ↓ VWF activity/Rco
- All multimers present but decreased number
Type 2 (20%) - qualitative deficiency
2A (10-20%): ↓activity/Rco, NF8, dec. large monomers
2B (5%) - ↓activity/^Rco, NF8, dec. large monomers
2M (↓activity/Rco)
2N (normal activity/Rco, low F8, normal electrophoresis)
Type 3- complete deficiency (AR)
- No vWF
- Low F8
- Undetectable electrophoresis
Symptoms of renal vein thrombosis
Most common spontaneous TE in neonates - 25% of cases are bilateral
Clinical manifestations =
1) haematuria
2) abdominal mass
3) thrombocytopaenia (consumptive)
Common in insulin dependant DM
Most important risk factor for VTE in paediatrics?
Most important RF – 90% neonatal VTE 60% of childhood VTE
CVCs may damage endothelial lining and/or cause blood flow disruption
Peak incidences of VTE in paediatric population
Infants <1yr highest
Adolescents 2nd peak
MOA Heparin, monitoring, SFx
Inhibits Xa & thrombin
Ix: APTT/ anti Xa level
- Reversal with protamine sulfate
Risks:
Bleeding
Osteoporosis
Heparin-induced thrombocytopaenia (HIT)
LMW Heparin
- smaller protein
- less effect on thrombin
Ix: anti fXa level
Less easily reversed, delayed onset of action
Prolonged half life if ESRF
Less risk of HIT/osteoporosis
MOA Warfarin, monitoring, SFx
Decreased activation of vit K, TV factors, protein C & S
Monitoring
- INR (5-7 days to reach therapeutic level)
- Note FVII and protein C are reduced first
SFx:
Bleeding
Teratogenic T1 mainly
(chondrodysplasia punctate – nasal hypoplasia, excessive calcifications in epiphyses and vertebrae)
Sx/Ix in TTP
TTP: Ab mediated destruction of ADAMTS-13
Fever
Microangiopathic haemolytic anaemia
Thrombocytopaenia
Abnormal renal function
CNS changes
Ix: DAT pos anaemia, abnormal RBCs (schistocytes, spherocytes, helmet cells), high retics, low plts, low MMP, elevated BUN/creat
Rx Fanconi Anemia
Ca/endo monitoring
HSCT
Androgens- oxymetholone
GCSFm + EPO
High risk antibodies (maternal) for haemolytic disease of the newborn?
Anti-D, anti-c, anti-Kell
Dx on film?
Low Hb, microcytosis, RDW normal
Teardrop cells
Target cells
B-Thalassemia
Dx on film?
Low Hb, microcytic, raised RDW
Pencil cells, anisocytosis, hypochromasia
Iron deficiency anemia
Dx(s) on film?
Spherocytes, Howell-Jolly bodies
Hereditary spherocytosis if EMA binding reduced/FHx
Warm haemolytic anemia if DAT positive, low haptoglobin (90% of AIHA)
Dx on this film?
Cold AIHA
Half life of clotting factors?
Factor 8 = 12h (shortest)
Factor 9 - 24h/1d
Factor 10 = 30h
Factor 7/fibrinogen = 2-4d
Prothrombin= 3.5d
Factor 13 = 5-7d (longest, stabilises fibrin)
What clotting factors are reduced in neonates?
- Vitamin K dependent factors – 2, 7, 9, 10 and contact factors 11, 12 reduced by 50% adult values
- Anticoagulant proteins – antithrombin, protein C, protein S
Differences between coagulation disorders/blood vessel & platelet disorders
Coagulation (clotting factors i.e haemophilia)
- Soft tissue/joint haematomas
- Delayed bleeding
- FHx bleeding
- Mainly male patients
Platelet/BV (inc VWBD)
- Petechiae & ecchymoses
- Persistent bleeding from superficial wounds
- Rare FHx
- Mainly female
Conditions with raised APTT/PT
APTT = INTRINSIC pathway
– VIII (haemophilia A), IX (haemophilia B) X, XI, XII factor deficiencies (corrects on mixing test)
- Lupus anticoagulant (non-correction on mixing test)
- Heparin (prolonged thrombin time, normal reptilase)
PT/INR = EXTRINSIC pathway
- Assesses common pathway and factor FVII
- Factor VII deficiency / inhibitor
- Vitamin K deficiency (mild) or early liver disease
- Warfarin
What haematological conditions is desmopressin used in?
Haemophilia A
- Stimulates release of endogenously produced FVIII – peaks after 30-60 minutes
VWB
-increases the amount of circulating VWF by release from endothelial cells
Master transcription factor for erythropoiesis?
GATA1
- Differentiates stem cells to erythroid or myeloid lineage
- Linked to AML/TMD in T21& Diamond-Blackfan
