General Flashcards
Inheritance of Haemophilia & who does it present in
X linked recessive
So mostly males (unless female has carrier Mum and affected Dad)
Types of Haemophilia & main mechanism of bleeding
A - factor 8 def
B - factor 9 def
Acquired: AutoAb to F8
Lvl of Haemohilia factor considered normal/severe
Normal >50%
Severe <1%
Causes Increased APTT (normal PT)
Mixing corrects: no inhibitor but intrinsic deficiency
Non correcting: inhibitor present (inc VWD)
?Heparin (if so: TT should be up, repitalise normal
Causes Prolonged PT (normal APTT)
Mixing corrects; F7 def
Mixing doesn’t correct: F7 inhibitor
(also check ?Liver, ?DIC, ?Warfain)
Causes prolonged both pathways (which test and what causes)
Thrombin Time
Prolonged: fibrinogen disorders
Normal: common pathways (2, 5, 19) - trial vit K
Any suspected bleeding disorder, check these 3 things first
Have they HAD thrombosis?
HITS: PF4
APLS: LAC, anti-cardiolipin, B2 glycoprotein
DIC
If the PT (extrinsic) pathway is involved, consider these 3 things first
Liver
DIC
Warfarin
(Also consider HITS, APLS etc)
Inheritance VWD & who does it present in
AD
Males/females equal
Often only notice prolonged bleeding post op etc or known FHx
Types of VWD & differences
T1: lower amt F8 (>50% normal but 30-50% can be LLN or VWD)
T2: decreased F8 protein fxn (T2N is severe)
T3: very low lvls (homozygote - rare but severe)
Rx haemophilia A/B
1) Recombinant factor (eg prophylaxis, short half life) - 1A) extended half life versions
2) Immune tolerance induction to eradicate inhibitors
3) Bypass agents:
- FEIBA
- Recomb F7a (O/L extrinsic pathway)
- Emicizumab: mimics F8 binding (bridges 9a + 10 binding)
4) Gene Rx
Rx VWD
Desmopression
F8, vWF
(if bleeding F8 + TxA)
Acquired haemophilia - presentation on labs
Prolonged, non correcting APTT
Haemophilia A/B - presentation on labs
Prolonged APTT (correcting)
Acquired haemophilia - Rx
FEIBA
Factor 7a
IS (RTX, cyclophosphamide, IVIg)
CD marker of stem cells
CD34
Blast cell marker / stem cell
CD3?
Universal T cell marker
t (9;22)
CML
Philadelphia chromosome - 22 letters, 9 vowels
t (15;17)
APML
P = 16th letter
Sickle cell - inheritance & types
AR
HbSS - homozygote
Compound heterozygote
eg w/ Beta (0) thal (HbSBeta)
or HbC (HbSC) - milder less sickling
SLiM criteria in MM
- Plasma cells >60% (sixty) in BM
- Light chain ratio >100 (either one)
- MRI have multi focal lesions
Differentiating MGUS from other myeloma
Smouldering only needs 1 of
- BM plasma cells 10-60%
- Paraprotein >30g/L
- No CRAB/SLiM
Active myeloma
- BM plasma cells usually >10%
- CRAB/SLiM criteria met
- Plasma cells >60% (sixty) in BM
- Light chain ratio >100 (either one)
- MRI have multi focal lesions
mAb to work up for pre-transfusion as affects RBC
Daratumumab (antiCD38)
PP about Daratumumab
Anti-CD38
Needs pre-transfusion RBC work up at lab
RCHOP components
Rituximab
Cyclophosphamide
Doxirubicin
Vincristine
Prednisolone
Thrombophilia screen includes (& highest risk, most common)
- Factor V Leidan (most common, presents w/ preg VTE, 8% popn hetero & if FHx then Rx post-partum, homozy ante/post natal, no increase CAD risk tho)
- Prothrombin (2nd most common, homozygot same risk as F5L)
- Anti-thrombin def (highest risk of PE but low numbers, often already on AC)
- Protein C, protein S (activated protein C resistance
- Plasminogen, fibrinogen
Cell lines - myeloid & lymphoid
t(8:14)
Rx
BURKITTS
- very aggressive, HIV w/ preserved CD4
- Assoc w/ MYC translocations (c/s 8)
- EBV
- Starry night sky on film
- high risk TLS
t (14;18)
Rx
FOLLICULAR LYMPHOMA
- 30% spontaneous remit
- Obintuzumab (v potent CD20) - continue after Rx to prolong PFS
+ Bendamustine (alkyaltor & purine analogue) - high risk OI
or CHOP
Thalassemia: how to tell Beta thal
Usual is HbA (α2β2)
In B-trait (B+/B0) - mildly increased HbA2 (α2δ2), mild inc HbF
TDT B0/B0: 90% HbF (α2ɣ2), can have HbE variant
HbA
97% of normal human Hb
α2β2
HbA2
α2δ2
2% normal human Hb, mildly increased in Beta-thal trait
HbF
α2ɣ2
0.5% normal human Hb, far more in first half pregnancy
Can be 90% of Hb in TDT beta thal
HbH
β4
Found in 3 gene deletion alpha thal (–/-α) - still non transfusion dependent
Hb Barts
ɣ4
Tetramers - found in 80% trans -α/-α and 100% cis alpha thal
Comprise 90% of Hb in 4 gene deletion alpha thal not compatible with life, as need some alpha even for HbF. Fetal death.
CLL deletion of importance & Rx impications
p53, 17p, TP53
If +ve: BK-inhibitor (Ibrutinib)
Can combine Venetoclax, RTX + BTK - very potent
If -ve (consider IGHV status - mutation is positive)
Obinutuzumab + Veneteclax if frail or IGHV -
If fit <65y: Chemo (FCR) - fludarabine, cyclophosphamide, RTX
BTK-inh - Names, Toxicities
BTK in CLL - need to take indefinitely (also some indolent lymphomas)
Ibrutinib:
- 10% AF risk - switch to Acalabrutinib
- low risk OI (but not zero)
- good in p53 mutations which traditional chemo is resistant to
Acalabrutinib:
- more selective for BTK-rec so less off target effects but no additional benefit
- not well absorbed if on PPI
Venetoclax - MoA
BCL2 inhibitor
BCL2 is an anti-apoptotic protein (pro survival signal)
Overexpressed in some haem malignancies - inhibits apoptosis
BH3 mimetic to inhibit BCL2
TLS within hours. Can only use for 18m
Clots - consider tests
- APLS - anticardioplipin, anti B2 glycoprotein, LAC, antithrombin III
- JAK2 mutation (if odd location eg CVST)
Intravasc haemolysis - causes
- Complement cascade activation (eg PNH, ABO blood transfusion)
- Mechanical damage to RBC - schistocytes (MAHAs)
- Severe oxidative stress - G6PD
Extravasc haemolysis - causes
- Warm AIHA
- Drug induced
- Hereditary spherocytosis
- Haemoglobinopathies
Most anaemias haemolysed within RE system (liver/spleen)
TTP - Rx (Acq/Inh)
- PLEX (but send off ADAMTS13 level prior)
- FFP (to replace ADAMTS13)
- IS - GC (RTX)
- Don’t give platelets
In inherited - no Ab so no need for PLEX/IS - just give FFP
