Heamatology Flashcards
Macrocytosis causes
Alcohol B12/folate deficiency Myelsdysplastic syndrome Hypothyroidism MM Acute leukaemia Drugs - valproate, phenytoin, metformin, chemo agents, antiretroviral
Microcytosis
Iron deficiency, thalassaemia, anaesmia of chronic disease, vit b deficiency, sideroblastic anaemia
Nucleated red cell
An immature subtype
Due to; BM struggling to keep up with losses or insufficient resources to complete maturation process
Causes- Asplenua Anaemia Hypoxia Sepsis DKA Renal Tx Liver disease Uraemia Thermal injury BM invasion by malignancy
Rouleaux formation of RBC
Form of reversible RBC aggregation Seen with anything that increases ESR Causes- Infection Inflammatory disease of any sort Hyperviscisity stndromes MM Malignancy dehydration Diabetes Chronic liver disease
Target cells (codocytes)
Lots Seen in thalassaemia
Hepatic disease with jaundice
Hb-C disorders
Post splenectomy
Less target cells seen in;
Iron deficiency
Sickle cell
Lead intoxification
Polychromasia
Many colours - immature cells in circulation
A non specific marker of bone marrow stress
A marker of impaired erythrocyte control (like Howell-jolly bodies)
Causes-
Haemorrhage, haemolysis
Recovery of normal BM function eg iron infusion, EPO injection
Failure of BM to sustain normal function eg myelofibrosis, BM infiltration
Failure of RBC control - splenectomy
Howell jolly bodies
Bits of leftover DNA in erythrocytes
Seen post splenectomy
Also - pernicious anaemia, steroid use
Heinz bodies
Lumps of denatured Hb within red cells
Indicate oxidative stress
Causes -
Toxins - solvents, quinidine
Unstable haemoglonins - chronic liver disease, alpha thalassaemia, methylene blue methaemoglobinqemia
Deranged RBC metabolism - dapsone toxicity, Bactrim
Decreased clearance defective RBC - post splenectomy
Blister cells
Blebs on surface of RBCs
Suggestive of oxidative damage
Leukemoid reaction
Hyperproliferation of leukocytes (typically neutrophils)
Usually only lasts 24 hours
Most important aetiology is myeloid leukaemia
Causes -
Infection
Drugs - steroids, GCSF
Increased neutrophil release - stress, trauma, exercise, sepsis
Inflammatory conditions - organ necrosis, empyaema, DKA
Malignancy - myeloproliferative disorders, lymphoma, solid tumours
Decreased neutrophil clearance - splenectomy
Schostocytes
Haemolysis
Cryoprecipitate contains
Fibrinogen
Factor 8, 13
VWF
TRALI diagnostic criteria
Onset within 6 hours of transfusion Hypoxia Bilateral CXR infiltration No other cause identified No preexisting lung injury Absence of risk factors for other causes of ALI
Clinical features of TRALI
Hypoxia Dyspnoea Fever Pulmonary oedema Hypotension Cyanosis
Pathophysiology ofTRALI
Neutrophils sequestered in lung parenchyma
Risk factors for TRALI
Critical illnsee Chronic alcoholism Shock states Smoking High ventilatory pressures Positive fluid balance
Risks of massive transfusion
Usually risks of transfusion (TRALI, reactions, infection, storage lesions)
Risks and complications of large volume resuscitation with blood; overload, overtramafusion, hypothermia. ALI, citrate toxicity)
If o neg used - difficulty cross matchcing in future. Difficulty with matching solid organs
Ghost cells
Clostridium perfingens
Underlying causes of TTP
Infection
Surgery
Pancreatitis
Pregnancy
All lead to endothelial activation
There is low activity of ADAMTS13 - a vWF cleaving protein
Then allows large vWF multimers to accumulate
Plasma exchange removes
Autoantibody Immune complexes Myeloma light chains Cryoglobulins Endotoxins
Indications for plasma exchange
GBS MG NMDA antibody encephalitis TTP Hyperviscpsity syndrome Antiphospholipid syndrome
IVIg action and indications
Actions;
Multiple immunomodulatory and anti inflammatory activities
- modulates complement
- suppression of idiotype antibodies
- neutralisation of super antigens
- suppression of various mediators; cytokines, chemokines, adhesion molecules
Indications; GVHD ITP APLS toxic shock Nec fasc Wegners Pempigus SJS/TEN GBS MG MS
COAG changes in pregnancy
Low platelets
Low factor 9
Low protein s
Increase factors 5 7 8 9 10 12 vWF
Increased fibrinogen
No change factor 2 and 5
Unchanged protein c
Ferritin
Gold standard for assessment of iron stores
Only cause of low level is iron deficiency
High levels -
- acute phase reactant
- pregnancy
- malignancy
- iron overload
- chronically transfused disease states (sickle cell, thalassaemia)
- haemophagocytic syndrome; VERY high levels; may be congenital or acquired (infections eg EBV CMV HIV, neoplastic eg lymphoma, autoimmune eg SLE
Transferrin
Binding protein and part of innate immune system
Decreased in inflammatory states
May rise in response to iron deficiency state
Transferrin saturation -
If less than 20% there is iron deficiency state, if over 45% there is iron overload state
Causes of thrombocytopaenia
Decreased production
- BM suppression due to alcohol, chemo, myelofibrosis, virus, nutritional deficiency, liver disease
Pseudothrobocytopaenia - improper sampling and clumping
Dilution - MBT, massive resus
Increased destruction
SLE, ITP. DIC, drugs, TTP, APLS, HELLP, circuits
Sequestration - hypersplenism, hepatic sequestration, extremes of temp
Management of thrombocytopaenia
Minimise destruction - withhold heparin, manage sepsis, address specific aetiologies (TTP, HELLP)
Maximise production -
Nutrition, rationalise drugs that are BM toxic, correct BM failure if possible
Protect from complications -
Postpone non essential invasive procedures
Cover essential procedures with platelets
Storage lesions
occur after 2-3 weeks
RBCs unergo a structural and function change
Changes include -
- reduced deformability
- reduced 23DPG -> left shift and decreased O2 delivery
- increased adhesiveness
- decreased concentration of NO
- reduced ATP
- accumulation of pro-inflammaory bioactive substances
Is it better to use newest blood?
NEJM 2017 - transfusion of freshest blood vs standard care (mean 22 days)
- no difference in death at 90 days or secondary outcomes
- subgroup analysis - higher APACHE group had higher 90 day mortality with fresher blood
Bottom line - no need to use newest blood, no harm from using older blood
Plasmacytosis
Increased plasma cells -
due to;
plasma cell disorder - MM, Waldenstroms macroglobulinaemia, solitary plasmacytoma
Other causes - pulmonary TB, cirrhosis, adenoCa of colon, syphillis
Hyperviscosity syndrome
Often due to waldenstroms (IgM) but can be due to any plasmcytosis
Clinical presentation -
- severe headaches (due to increased ICP from venous occlusion)
- fluctuating level of consciousness
- stroke
- seizures
- coma
- constitutional symptoms - fatigue, malaise, letheragy
- haemorrhagic symptoms - epistaxis, mucosal bleeding
- blurred vision (retinal vein occlusion)
- renal failure
- aggravated heart failure
Lab -
- leucocytosis (suggestive of malignancy)
- high plasma count
- high globulin level
Mx - plasmaaphesesis
Smudge cells
deformed lmyphocytes associated with CLL
Pathogenesis of anaemia of chronic disease
inflammation -> cytokine release -> increase hepcidin -> reduced iron release from BM and macrophages and reduced absorption of iron
Findings in iron deficieny anaemia
Low MCV low iron low ferritin (only cause) high transferrin (a binding protein - increases as a reaction) tranferrin saturation <<20%
Findings in anaemia of chronic disease
may be microcytic or normocytic low iron normal ferritin low transferrin normal transferrin saturation
Causes of high ferritin
acute phase protein
pregnancy
malignancy
iron overload
chronically transfused states - sickle cell
chronic inflammatory states - chronic liver/renal disease, HIV
haemophagocytic lymthohistiocytosis
- causes a VERY high ferritin
- may be congenital or acquired; infection (|eBV, CV, HIV), neoplastic (lymphoma), autoimmune (SLE)
Types of leukaemias
AML -
- acute proliferation of immature myeloid precursor cells
- acute promyelocytic anaemia is characterised by dense cytoplasmic granules and Auer rods
ALL - childhood, good prognosis
CLL -
- presents with B symptoms, BM failure, splenomegaly and autoimmune haemolytic anamia
- richters transformation -> diffuse large B cell lymphoma associated with poor prognosis
CML - linked to philadelphia chromosome
- typically beings with chronic phase -> accelerated phase -> blast crisis
- presents with wt loss, splenomegaly, fever, night sweats
Classification of lymphoma
Hodkins - seen in young
- reed-sternberg cells are characteristic on hisology
Non-hodgkins -
- heterogeneous group with 30 different subtypes
- may be low grade or high grade
Low - follicular (most common), waldenstrom macroglobulinaema, mantle cell lymphoma
High - most common is diffuse b cell lymphoma
- Burkitts - fast growing, high risk of TLS
Multiple myeloma
plasma cell malignancy
present with bone pain, fractures, BM faliure, renal failure
Types of haematopoietic stem cell transplant
Source of stem cells -
- peripheral
- bone marrow
- umbilical cord blood
Donor of cells -
- autologous - re-infusing peripheral blood of patient from during time of remission
- allogenic - donor; more intensive myeloablative regimens and immunosuppresion
Patterns of infection following HSCT
Pre-engraftment - <30days
- at risk of bacterial infections due to neutropenia
Early post-engraftment - 30-100days
- cell mediated immunity impaired
- risk of fungal and viral infections (CMV, PJP, aspergillus)
Late post-engraftment -
- impaired reticuloendothelial, cell medicated and humoral factors
- at risk of mycobacteria and viruses
Problems following HSCT -
INfection GVHD Graft failure Diffuse alveolar haemorrhage Idiopathic pneumonia syndrome Engraftment syndrome cryptogenic organising pneumonia veno-occlusive disease Posterior reversible encephalopathy syndrome post transplant lymphoproliferative disorder TTP
GVHD
incidence 30-50% post allogenic Tx
- increases with advancing age of donor and recipient, inadequate immunosuppresion, HLA mismatch, use of peripheral blood as stem cell source
Acute - presents 7-28days after Tx with rash (esp on palms and soles), dirrhoea and intrahepatic cholestasis
Is staged and graded -
- each system staged 0-4
- then combined to give clinical grade
Prophylaxis is with immunosuppressants
treatment is high dose methyl pred
Chronic GVHD
multi-organ syndrome which occurs >100 days after Tx
May be limited or extensive
Can involve - skin, eyes, lungs, salivary glands, neuromuscular system, liver
Treatment is difficult as need to increase immunosuppresion but try to avoid infections
idiopathic pneumonia syndrome
usually seen 3/52 after Tx
diffuse infiltrates on CXR
high mortality
Engraftment syndrome
also known as capillary leak syndrome
- presents 4-5 days after autologous Tx with fever, rash, non-cardiac pulm oedema
Use of GCSF increases prevalence and must be stopped
cryptogenic organising pneumonia (or bronciolotis obliterans organising pneumonia)
occurs 1-3/12 after Tx
Presents with SOB, fever, cough
Treatment is with steroids and response usually good
Other causes -
- follow on from many types of pneumonia
- drugs
- connective tissue disordrs
- organ tx (BM and lung)
- malignancies
- radiotherapy
Is an important cause of peripheral consolidation on HRCT
- presents with flu-like illness
Definitive Dx is with lung biopsy and negative mirco
- PFT will show reduced DLCO
NB - it is DIFFERENT to bronchiolitis obliterans - non reversible due to fibrosis and inflammation
Veno-occlusive disease (sinusoidal obstruction syndrome)
Triad of -
- painful hepatomegaly
- jaundice
- ascites
Presents 3/52 after Tx
Other features - wt gain, encephalopathy, bleedings, hepato-renal sydrome
Doppler will show reduced or reversed portal flow
Posterior reversible encephalopathy syndrome
Characterised by headache, seizures, visual loss
T2 MRI (CSF bright) shows diffuse hyperintensity in parieto-occipital white matter
Acute oncological emergencies
Neutropenic sepsis - Abx in1 hours, consider antigungals if no improvement in 4-7days
- start with anti-pseudomonal beta-lactam with addition of vanc/aminoglycoside or fluroquinolone if resistance suspected
Neutropenic enterocolitis (typhlitis) - abdo pain, fever and diarrhoea due to mucosal wall damage - usually needs conservative Mx (TPN)
Respiratory failure - many causes
AKI - many causes
TLS
Causes of respiratory failure in a haem onc patient
Non infectious - general
- ARDS
- aspiration
- pulmonary oedema
- chemo-induced toxicity
- cryptogenic organising pneumonia
- pulmonary infiltration - leukaemia or thumour
Non infectious specific to HSCT -
- diffuse alveolar haemorrahge
- idiopathic pnemonia syndrome
- engraftment syndrome
Infectious -
- bacterial - psuedomonas, klebsiella, acinetobacter, staph, enterococcus, strep, leigonella, mycoplasma
- viral - flu, adenovirus, parainfluenza, RSV, CMV, HSV, VZV
- fungal - candida, aspergillus, PJP
- mycobacterium - TB
Tumour lysis syndrome
- definition
- characteristics
- risk factors
oncological emergency
caused by rapid lysis on tumour cells -> release of intracellular contents into circulation
Characterised by -
raised K, PO4, urate, LDH
low Ca
Increased risk with - (can be divided into patient and tumour factors)
- large tumour mass
- organ infiltration by tumour
- bone marrow involvement
- pre-existing renal disease or dehydration
- tumours sensitivity to chemo
- high intensitiy of chemo
- acidic urine
- nephrotoxin exposure
- unchecked K and PO4 replacement
- pre-exisiting gout
TLS - prevention and treatment
Prevention -
Hydration to achieve u/o 1-1.5ml/kg/hr to reduce chance of uric acid precipitating in renal tubules
Avoid K containing fluids
Allopurinol - 300-600mg/day
- decreases uric acid formation by blocking xanthine oxidase enzyme
Rasburicase - a recombinant urate oxidase enzyme that converts uric acid to allantoin (10x more soluble that uric acid)
Alkalinization of urine - not common - aim is to reduce the liklihood of uric acid precipitating in the tubules
Treatment of TLS
repeated dose of rasburicase
Careful management of fluids and electrolyes
Specific Mx of hyperK, HypoCa and hyper PO4
Haemodilysis for standard indications
Causes of hepatosplenomegaly
malaria myelofibrosis sarcoidosis amyloidosis CML chronic liver disease kala-azar (viscaeral leischmaniasis)
the above list also cause massive splenomegaly
pernicious anamia acromegaly thyrotoxicosis SLE obesity viral infections eg EBV metabolic storage diseases
Massive splenomegaly
malaria myelofobrosis sarcoid amyloid CML chronic TB thalassaemia major polycythehmia Waldenstroms macrogolobulinaemia
abnormal bleeding
normal PT normal APTT
vWB disease
platelet dysfunctoin
fibrinolysis disorder
SHould order platelet function studies
normal APTT, abnormal PT
Exrinsic pathway failure
warfarin
vit K def
liver diease
isolated factor VII def
Abnormal APTT, normal PT
Intrinsic pathway failure
?factor deficiency or anticoagulant factor - answered by mixing studies
factor deficiency fixes with mixing
- vWB disease - de factro factor 8 deficiency
- factor 8 (haemophilia A)
- factor 9 (haem B)
- factor 11 (hame C - 8% ashkenazi jews)
- factor 12 - very rare
Doesnt fix; presence of anticoagulant factor -
NOrmal TT and RT - antiphospholipid antiodies
High TT, normal RT -heparin
High TT, high RT -low fibrinogen, abnormal fibrinogen, amyloid
Thrombophilia screen
antithrombin protein c protein s factor 5 leiden lupus anticoagulant - antiphospholipid syndrome anti Beta 2 glycoprotein antibody (APS) anticardiolipin antibody (APS) prothrombin gene mutation
Antithrombin III deficiency
consequences are thrombosis and loss of heparin effect
management is supplementation of ATIII with purified factor or FFP
Causes -
inherited ATIII defects
Acquired -
- reduced production - liver disease, oral contraceptive, eclampsia
- loss of protein - nephrotic syndrome, plasmapheresis with albumin, extnesive blood loss
- increased consumption - DIC, acute thrombosis, extra-corporeal circuits
TEG values
R value = reaction time (s); time of latency from start of test to initial fibrin formation (amplitude of 2mm); i.e. initiation
K = kinetics (s); time taken to achieve a certain level of clot strength (amplitude of 20mm); i.e. amplification
alpha = angle (slope between R and K); measures the speed at which fibrin build up and cross linking takes place, hence assesses the rate of clot formation; i.e. thrombin burst
TMA = time to maximum amplitude(s)
MA = maximum amplitude (mm); represents the ultimate strength of the fibrin clot; i.e. overall stability of the clot
A30 or LY30 = amplitude at 30 minutes; percentage decrease in amplitude at 30 minutes post-MA and gives measure of degree of fibrinolysis
CLT = clot lysis time (s)
TEG response to changes
Increased R time => FFP
Decreased angle => cryopreciptate
Decreased MA => platelets (consider DDAVP)
Fibrinolysis => tranexamic acid (or aprotinin or aminocaproic acid)
Heparin - pharmacology
heterogeneous mix of mucopolysaccharides
subcut dose take 1-2hours to reach peak effect
Mechanism -
- enhances activity of ATIII by factor of 1000
- ATIII inactivates several factors - Xa and thrombin
LMWH vs UFH -
- inactivation of thrombin depends on heparin molecule lenght - clexane does not affect it
- inactivation of Xa is independent of length so both effect it
interactions with heparin
potentiated by -
- sodium valproate
- hyroxycholoroquine
Effects of heparin antagonised by -
- antihistamines
- digoxin
- nicotine
- tetracyclines
chronic complications of heparin
HITS - occurs 5-10days after start of heparin
- mostly associated with UFH, more frequent in elderly
- type 1 - mild, reversed by cessation of heparin, occurs in 10% patients
- type 2 - severe, associted with thrombosis in 30% cases, due to formation of antibodies to the complex made up of platelet factor 4 (PF4) and heparin
osteopaenia
mineralocorticoid
alopecia
elevation of AST and ALT
Protamine
1mg reverses 100units
given slowly
Side effects -
- catastrophic hypotension due to vasodilatation
- pulmonary hypertension
- anaphylaxis
Resistance to heparin therapy
due to -
- increased heparin-binding protein levels (all of them are acute phase reactants)
- low antithrombin III levels
- increased heparin clearance
- high factor VII levels
Management -
- change to LMWH
- give FFP or cryo
- given ATIII concentrate
tirofiban
reversible inhibition of P2Y12 ADP receptor -> inhibition of cAMP dependent platelet activation
Biliary clearane
duration of action 3-5 days
Dabigatran/rivaoroxiban
Dabigatran - direct thrombin inhibitor - renally excreted can use dialysis to clear lower bleeding risk than warfarin new antidote - praxbind (monoclonal antibody)
Rivaroxiban -
- factor Xa inhibitor
- prevents thrombin generation
- bad in both liver and kidney disease
- not able to dialyse
Drugs that increase bleeding risk with Xa inhibitors
ca channel blockers fluconazole immunosuppresants macrolides (clarithro, erythro) amioderone tamoxifen
INdications for IVC filter
Absolute contraindication to anticoagulation in patient with high risk DVT/PE
COmplication of anticoag -> needs to be reversed
Inability to achieve full anticoagulation
PE while fully anticoagulated
Extended indications - no evidence, but may get placed – trauma, burns, cancer pt, clot induced pulmoary HTN
IVIg actions
modulates; B and T cells, macrophages, cytokines networks and complement
Regulates cell growth
IVIg indications
Haematological
- idiopathic thrombocytopenic purpura (ITP)
- post plasma exchange course completion
- antiphospholipid syndrome (APLS)
- chronic graft versus host disease (hypogammaglobulinaemia)
Infections
- toxic shock syndromes (staphyloccocal and streptococcal)
Vasculidities
- Kawasaki disease
- Wegener’s granulomatosis
- Microscopic polyangiitis
Dermatological
- pemphigus vulgaris
- bullous pemphigoid
- SJS/TEN (controversial)
Neuromuscular
- GBS (AIDP)
- dermatomyositis
- myasthenia gravis
- chronic inflammatory demyelinating peripheral neuropathy (CIDP)
- Eaton-Lambert syndrome
- Stiff Person Syndrome
- Multiple sclerosis
Renal transplant rejection (controversial)
