Haem/Onc Flashcards
Haemophilia
Treatment
- Analgesia + Avoid NSAIDS, aspirin, IM injections
- Joints - protect + RICE
-
Factor replacement is KEY
a. 30-100units/kg depending to location, severity of bleed - TXA 15mg/kg
- Activated PCC (II, VII, IX, X)
a. If pt has developed inhibitors - Cryo (VIII, XIII and VWF + fibrinogen)
- FFP (all factors + fibrinogen)
- Factor VII (VII + vWF)
- DDAVP - if mild (factor levels > 5%)
a. Restores Factor VIII + VWF into circulation
b. 0.3mcg/kg IV
Haemophilia Severity grading
Severity grading
Severe <1% factor
- Frequent bleeding, esp joints + muscles
Mod 1-5% factor
- can bleed after minor injury, severe bleeds with mod trauma + surgery
Mild >5-40% factor
- bleeding with major trauma / surgery
Haemorrhage Risk Score
HAS BLED
Orbit Score
Haemorrhage risk whilst taking Anti-coagulants
https://www.mdcalc.com/calc/10227/orbit-bleeding-risk-score-atrial-fibrillation
Not statistically superior to HASBLED but validated for DOACs
Acquired Haemophilia
- Malignancy
- Pregnancy / Post partum
- Autoimmune
- Drugs
- Idiopathic
HUS
OVERVIEW
Triad of MAHA + ARF + Thrombycytopaenia
Clinically similar to TTP but ARF > neuro symptoms
TYPES OF HUS
* Diarrhoea-associated (D+ HUS) - >90%
* Preceding infection with a verocytotoxin-producing bacteria, typically E.coli O157:H7
* Non-diarrhoeal/ atypical (D- or aHUS) - rare
* poorer prognosis / familial / complement dysregulation
* Pregnancy (term or post-partum)
* Drugs – quinine, mitomycin, ciclosporin, tacrolimus, ticlopidine, caboplatinum, gemcitabine
* Transplantation – renal, haematological stem cell transplantation
* HIV
* Combined methylmalonic aciduria and homocystinuria (a vitamin B12 metabolism disorder)
* Strep. pneumoniae associated (P-HUS)
* Anti-T immunoglobulin M (IgM) in the serum reacts with the antigen on red blood cells, platelets, and glomeruli causing hemolysis, thrombocytopenia and renal damage
Classic pentad: (FAT R/N)
Common presentation includes bloody diarrhoea +/- crampy AP, fever +/- vomiting
- Fever
- Anaemia (microangiopathic haemolytic)
- Thrombocytopenia
- Renal problems (88% have renal problems, 15% haematuria) – more likely in HUS
- Neurological problems (headaches, confusion, seizures) – more likely in TTP
Examination
Shock - hypotension, tachycardia, poor CRT, cool peripheries
Dehydration - fontanelle, mucous membranes, skin turgor
Overload - oedmea, hypertension
CNS - agitation, confusion, ALOC
Ix
MAHA + ARF + thrombocytopaenia
* Bloods
* FBC - anaemia
* Blood film - shistocytes
* Low PLT
* Increased reticulocytes
* Low haptoglobins
* Increased LDH
* High Br (unconj), urinary urobilinogen
* Increased urea and creatinine levels (greater in HUS)
* CMP
* LFTs
* Coombs +ve
* VBG
* Urine and Stool MC+S (E coli)
Management
* Supportive care and monitoring are the mainstays
* Avoid nephrotxins
* ABx may worsen toxin production
* HTN - trial duiretics + vasodilatory agents
* PLT contra-indicated unless requiring surgery
* Plasmapheresis
* may worsen P-HUS
* Rx underlying cause and complications
* No good evidence for steroids, heparin, aspirin, antioxidants, fluid restriction or diuretics, anti-hypertensives
* RRT (acidosis, fluid overload not responding to duiresis, high K or uraemia)
Complications
AKI - oliguria or anuria, hypertension and hyperkalaemia
Cardiac - hypertensive cardiomyopathy / myocarditis, APO
CNS - seizures, coma, cortical blindness
Coagulopathy - bleeding
GI - severe colitis +/- bleeding, bowel necrosis or perforation, peritonitis, intussusception, pancreatitis
Tumour Lysis Syndrome
TLS occurs when destruction of malignant cells occurs too quickly for homestatic mechanisms to cope
Spontaneous OR associated with ALL, NHL and Burkitts most commonly
NB as chemo regimes get better, may see more TLS
Hallmarks
- LOW Ca
- HIGH uric acid, PO4, K
- AKI from CaPO4 or uric acid crystals in kidneys
Mx
* Hydration
* 0/9% saline or 1/2 saline
* Aim UO > 1ml/kg/hr
* Alkalinise urine
* If metabolic acidosis present
* Aim pH > 7.0
* Stop when urine pH >8.5
* Hyperuricaemia
* Allopurinol 10mg/kg
* Rasburicase 0.2mg/kg
* CI in G6PD - triggers haemolytic crisis
* Complications: MetHb
* Electrolyte Mx
* Hyperkalaemia Rx
* DO NOT replace Calcium unless cardiac or neuro Sx
* PO4 binders
* Dialysis or RRT if renal failure, uncontrolled electrolytes despite conservative measures
Superior Vena Cava Obstruction
SVC susceptiple to compression as thin walls and low pressure
- Extrinsic
- Malignancy -Lung, Lymphoma
- Goitre
- Intrinsic
- Thrombus
- Device related - CVC / PPM
- Post radiation fibrosis
- Fungal infections
Signs
- Life-threatening
- Tracheal obstruction
- Cerebral oedema => inc ICP + altered mental status
- Haemodynamic collapse
- Other Sx
- Facial oedema, arm swelling
- Dyspnoea, voice change, cough
- Dysphagia
- Headache worse with bending forward
- Dizziness / syncope
- Pemberton’s sign - After lifting hands in the air for one minute => dvpt of facial plethora/ cyanosis +/- inspiratory stridor +/- non-pulsatile elevation of the JVP - indicates thoaric inlet obstruction
Radiology
- CXR
- UL lesion - Pancoast tumour
- Widened mediastinum
- Promiment right hilar nodes
- Aortic nipple (enlarged left sup intercostal vein)
- CT - contrast
Mx
- Supportive
- O2
- Head up 30 degrees
- Dexamathasone
- Thrombolysis if indicated
- DXT
- SVC Stent
- Tissue diagnosis + Chemotherapy
- Surgery
*
MTP
Definition
- >1 blood volume in 24 hrs
- > 50% blood volume in 4 hrs
- Child: >40mL/kg
Adult BV = 70ml/kg and Child BV = 80ml/kg
Goals:
- Restoration of tissue perfusion and O2 carrying capacity via blood volume and Hb
- Avoid hypothermia, coagulopathy, acidosis and hypocalcaemia
- Definitive care - IR or surgery
Parameters
- Temp > 35.0
- pH > 7.2, BE <-6, Lactate < 4mmol/l
- Ion Ca >1.1mmol/l
- Hb - interpret clinical
- PLT >50 x 109 and >100 x 109 if HI or ICH
- PT/aPTT <1.5 x normal
- Fibrinogen >1.0g/L
Complications of transfusion
- Febrile Non-haemolytic transfusion reaction
- TACO
- TRALI
- Acute haemolytic transfusion reaction
- Anaphylaxis
- Transfusion related bacterial infection/sepsis
Haemolytic anaemias
Increased - LDH, Br (unconj), Reticulocytes
Decreased - Haptoglobin
Blood film - Schistocytes
Methhaemalbumin = severe intravascular haemolysis
**Classification of causes **
* RBC Defects
* Membrane
* Hereditary spherocytosis, H Elliptocytosis
* Haemoglobinopathy - Sickle, Thalassaemia
* Enzyme Deficiency - G6PD, pyruvate kinase
* Other
* Autoimmune - 95% positive Coomb’s test
* ABx - penicillins, cephalosporins
* ABO incompatibility
* SLE, RA, UC
* Malignancy - lymphoma, CLL
* Mechanical - prosthetic valve, runners
Classification by site of haemolysis
* Intravascular
* MAHA
* March
* Chronic cold agglutinin
* PNH
* Extravascular
* Autoimmune
* Rh Incompatibility
* Chronic haemolytic dsorder
Cx
Pigment gallstones
Haemolytic anaemia - Bloods
Inc. Reticultocytes
Inc Br
Inc LDH
Dec Haptoglobin
MetHb if severe
Jaundice DDx
Hereditary Spherocytosis
Hx - episodic jaundice, neonatal jaundice
FHx - jaunduce, splenectomy, early cholcystectomy
OE - jaundice, splenomegaly
Bloods - dec Hb, inc retic, -ve Coombs, +ve Osmotic fragility (membrane)
Mx
Evaluate for fever, illness
May need blood
Splenectomy if severe
G6PD
Intermittent haemolysis + oxidative stress
X-linked (boys)
Risk
Fava bean, moth balls
Drugs - sulfa drugs, dapsone, nitrofurantoin, anti-malarials
Mx
Stop offending agent
Post Splenectomy
Encaspulated bacteria
- HiB, S.pneumo, N. meningitidis
Need pre-op vaccines, post penicillin
Prophylaxis until age 5 - highest risk before 5 yrs old
Thrombotic Thrombocytopaenic Purpura
One of the MAHA syndromes
Rapidly progressive, 90% mortality without treatment
Deficiency of ADAMTS13 enzyme causes
- abN platelet clumping
- abN formation of large multimers of VWF
- extensive microthrombi + haemolysis + end organ effects
Hereditary vs acquired
Epi
1:100,000-1:500,000
F>M 2:1
Most common betw 30-40yrs, 90% <60 years old
Sx/Signs
* Classic pentad (FATRN)
CNS Sx in 75%
* Headache, AMS, focal deficits, seizures, fluctuating symptoms and signs
Bleeding 45%
* Usually cutaneous
GI in 40%
* N/V/AP
Fever 20%
Bloods
FBC
* Shistocytes, increased reticulocytes
* Anaemia, thrombocytopaenia
Haemolysis
* Coomb’s negative
* Dec haptoglobins
* Inc LDH, Br (unconj), urobilinogen
Coags
- Normal Fibrinogen, D-dimer, coags
UECs
- May have AKI
ADAMST13 antibodies
Decreased ADAMST13 activity
* - < 10% severe deficiency - supports TTP
* 10-20% - maybe
* >20% TTP unlikley
Mx
ICU/Haem referral
Plasmapheresis - removes vWF and ADAMST13 multimers
Plasma exchange with FFP replacement
Corticosteroids 1mg/kg/day
Monoclonal antibody
PLT transfusion - only if life threatening bleeding
Poor prognosis:
GCS < 14
Elevated troponin
High levels of ADAMST13 antibodies
Low levels of ADAMST13 activity
Causes MAHA
(DIC, HUS, TTP, malignant HTN, Malignancy, VICC, PET, HELLP)
Thrombocytopaenia
Anaemia
Fragmentation of RBCs - Shistocytes
Elevated LDH
Elevated reticulocytes
Elevated Br
True vasculitis absent
Febrile Neutropaenia
FEBRILE to 38.3 or >38.0 for 1hr +
ABSOLUTE NEUTROPHIL COUNT <0.5
Timeline: 3-14 days post chemo
Fever in the cancer patient
- Infection (30%)
- DVT/PE
- Chemo / medication
- Direct tumour burden
- Transfusion reaction
Pericardial Effusion in the Cancer pt
- Malignancy (lung, Breast, Haem, Melanoma)
- Hypoalbuminaemia
- Radiation
- Chemotherapy
Hypercalcaemia
Serum levels >3mmol/l symptomatic
Calc Correction for low albumin
Corr = Total + 0.02 (40 - albumin)
Sx: Stones, Bones, Moans, Groans
Signs: ECG - short QT interval
Mx
Excretion
- IVF
- LOOP diuretic (thiazide makes worse)
- Dialyse - refractory + CHF/fluid overload
Osteoclast inhibition (dec Ca release)
- Bisphosphonate - Pamidronate 90mg IV
- Calcitonin - PRN for cardiac dysrhythmias - takes 24-48 hrs to work
Cancer presentations DDx to consider
Cancer +
- Fever
- SOB - effusion, SVC, PE
- AMS - raised ICP, hyperviscosity syndrome
- ARF - post-renal failure, tumour lysis
- BP - spinal mets
- AP - necrotising enterocolitis
Febrile Neutropaenia Antibiotic Guidelines
- Start antibiotics ASAP
- Wide spectrum covergage with pip-tazo, meropenem or imipenem
- Add vancomycin - hypotension, suspected line sepsis, mucositis, a history of MRSA, or recent antibiotic use
- Add aminoglycoside - septic shock +/- suspected/ proven antibiotic resistance
- Add IV acyclovir - herpetic infection or encephalopathy
- Consider anti-fungal - fever >4 days
Febrile Neutropaenia Risk Stratification
MASCC vs CISNE
The MASCC Score will identify more patients as low risk, but will have more treatment failures / bounce-backs than the CISNE score
Neutropaenia causes - general
- Overconsumption
- Sepsis
- Autoimmune disease (SLE, rheumatoid arthritis, etc)
- Underproduction by bone marrow
- Malnutrition – alcoholism, anorexia, etc
- Myelodysplastic syndrome
- Post-viral: varicella, measles, rubella, influenza, hepatitis, Epstein-Barr virus, HIV
- Drug induced: clozapine, methimazole, sulfasalazine, bactrim, b-lactam antibiotics, NSAIDs, ticlopidine, cephalosporins, chemotherapy
Pemberton’s sign
After lifting hands in the air for one minute => dvpt of facial plethora/ cyanosis +/- inspiratory stridor +/- non-pulsatile elevation of the JVP - indicates thoracic inlet obstruction
Transfusion related-graft vs host diease
RISK = haem malignancy + non-irradiated blood products
Coag Interpretation
DIC causes
- Sepsis - Gram -ve, Viral Haemorrhagic fevers
- Hepatic failure
- Obstetric - PET, HELLP, Amniotic fluid embolus, IU foetal death
- Trauma - Massive blood loss, major HI, rhabdo
- Malignancy - prostate, mucinous, ac promyelocytic leukaemia
- Immune - T/F rxn, anaphylaxis, transplant rejection
- Shock
- Snake envenomation
Other - pancreatitis, large vessel aneurysm, giant haemangiomas, connnective tissue disorders i.e. APL syndrome
Sickle Cell Complications
DVT RF
- External Compression - pregnancy, masses
- Vessel wall - trauma, surgery, vasculilitis
- Intra-luminal - FB, lines, prosthetic valves
- Blood
a. Stasis - immobility, travel, POP, obese, AF
b. Hormones - OCP, pregnancy (up to 12/52 post)
c. Hyperviscosity
d. Smoking
e. DM
f. Active mlignnacy
g. Nephrotic syndromes
f. Defects of haemostasis - Plt, coags, APL, FV Leiden
PERC Rule out Criteria
Wells score for DVT
< 1pt - 62% pts - 3-9% have DVT
>2pts - 39% pts - 20-35% have DVT
Pancytopaenia
Von Willebrand Disease
Most common inherited bleeding disorder
vWF is a glycoprotein, when activated binds to PLT glycoproteins -> PLT adhesion
Type I - dec production vWF glycoprotein + low FVIII
Type II - dysfunctionsl vWF
Type III - no vWF + low FVIII
Clinical presentation
Easy bruising
Skin and mucosal bleeding
Ix
Normal PLT, coags, INR
Mx
Desmopressin
vWF concentrates
Topical Haemostatic agents
ITP
Haemolysis Causes
