Haematology Flashcards
What is the first line medication for neutropenic sepsis?
Tazocin- needs to be given within the first half an hour
If penicillin allergic- give Meropenem
Ideally get the cultures first, but need first dose of antibiotics first
Where do you take blood cultures?
Need to take cultures from peripheral vein and indwelling lines
Common infection in patients with haematological malignancies?
Diarrhoea- perianal infections
What should you consider in patients with neutropenia if they are not responding to antibiotics?
Atypical infections- especially fungal infections
What biomarkers would indicate fungal disease?
B-D glucan
Galactomannan
Aspergillus PCR
With neutropenic sepsis, if patient is still not recovering what should you consider?
Vancomycin for gram positive cover
If BP dropping- could give Gentamicin (gram negative sepsis, usually from urine/gut)
Contact ITU and get your senior involved
How long do blood cultures take to come back?
48 hours
Prophylactic medication
Aciclovir- varicella and herpes reactivation
Posaconazole- prevent fungal infection
Co-trimoxazole- prevent PCP
What to give people who are going on chemotherapy to reduce neutropenia
G-CSF (granulocyte colony stimulating factor)
Bone pain (femur), headache, fatigue and nausea
Often used in prophylactic lymphoma where neutropenia is expected
Do NOT give in Leukemia- stem cell disease (AML/CML)
What would make you suspicious of a thrombosis in the PICC line? What symptoms?
Swelling
Erythema
Normally upstream of the line. A week or two after it has been put in
Investigate?- doppler ultrasound
Management= Enoxparin (LMWH)
What is the complication we are trying to prevent with irradiated blood products?
Transfusion associated graft vs host disease
You might accidentally transfuse lymphocytes.
Common chemotherapy in chronic lymphocytic leukemia
Fludarabine (purine analogue)
When is cryoprecipitate used?
To replace fibrinogen
DIC or major hemorrhage
What is tumor lysis syndrome?
Any patient with haematological malignancy can get TLS
Potassium, phosphate and uric acid rises
Calcium is low because phosphate binds to calcium
Cells are full of potassium and uric acid
Release all of those cellular components
How can you prevent TLS?
Patient is given lots of IV fluids!!
Strict input/output monitoring
Allopurinol
Xanthine oxidase inhibitor
Xanthine oxidase makes uric acid
Also
Rasburicase (urate oxidase)a recombinant version of urate oxidase, an enzyme that metabolizes uric acid to allantoin. Allantoin is much more water-soluble than uric acid and is, therefore, more easily excreted by the kidneys
generally preferred now for patients at a higher risk of developing TLS
What can you give women who are about to undergo chemotherapy to stop their periods?
Norethisterone used to stop menstruation (synthetic oral progestin)
Do NOT give COCP- increase thrombotic risk
How to preserve fertility before chemotherapy?
Egg collection (have to wait for a cycle, hormone treatment) if it cancer doesn’t need immediate treatment
Sperm storage in men- cryopreserved
Can give gnrh blockers- shuts down system and reduces damage to eggs
How to prevent mucositis
Mouth care is very important
Can get serious impairing ability to eat
Chlorhexidine
Difflam (pain relief)
What is the difference between acute and chronic in blood cancers?
Chronic= mature cells (more differentiated)
Acute= higher up the chain in hemopoesis (less differentiated)
Symptoms in blood cancers?
Can be non-specific and widely spread across the body:
Weight loss
Infections
Run down
Weak
Picked up on a blood film
Lymphoma= B symptoms
- Night sweats
- Weight loss
- Fever
Can also find unexplained itching with Lymphoma
What are the common infectious causes of lymphadenopathy?
Viral: Epstein-Barr virus (EBV), Cytomegalovirus (CMV), HIV.
Bacterial: Staphylococcus aureus, Streptococcus pyogenes, Mycobacterium tuberculosis.
Parasitic: Toxoplasma gondii.
List three common neoplastic causes of lymphadenopathy
Lymphoma: Hodgkin and non-Hodgkin lymphoma.
Leukaemia: Chronic lymphocytic leukaemia (CLL), acute lymphoblastic leukaemia (ALL).
Metastatic cancer: Breast, lung, or gastrointestinal carcinomas
What are the common autoimmune causes of lymphadenopathy
Systemic lupus erythematosus (SLE): Generalised lymphadenopathy.
Rheumatoid arthritis: Chronic inflammation-related.
Sarcoidosis: Non-caseating granulomas affecting lymph nodes.
How to investigate haematological malignancy?
Routine bloods
- FBC, UE, LFT, CRP, Ca2+
- Haematinics, retics, Blood film
Special bloods
- LDH, urate, B2M (beta 2 microglobulin), PV (plasma viscocity)
- Ig +/- SFLC
- PB immunophenotyping
Imaging
- CT scan
- PET scan (lymphoma/myeloma)
- MRI spine/pelvis (myeloma)
Invasive
- Tissue biopsy
- BM aspirate and trephine
Types of Leukaemia
- Acute myeloid leukaemia- Auer rod blood film (buzz word)
- Acute Lymphoblastic leukaemia
- Chronic myeloid leukaemia- Philadelphia chromosome translocation
- Chronic lymphocytic leukaemia
Types of Myeloproliferative neoplasms
Still cancers but softer. Not the same as acute leukaemias.
Essential thrombocythaemia- biggest risk is thrombosis
What are some advantages of central venous acess?
More than one drug at a time (multi lumen)
Continuous infusion (>24 hours)
Can give nutrition via central catheters
Less invasive for frequent treatment
Home treatment
Long term (over months) therapy
Reduced risk of extravasation (vesicants)
What are some disadvantages of central venous access?
Risk of pneumothorax during insertion
Infection (insertion and use)
Bleeding (during procedure of insertion)
Thrombosis of line
Misplacement (could go arterial or into jugular vein), CXR to check, use ultrasound when inserting
What is neutropenic sepsis defined as?
Neutrophil count of 0.5 x 10^9 per litre or lower
Causes of pancytopenia
Inherited/acquired
Inherited
- Aplastic anaemia
- Fanconi anaemia
- Diamond-Blackfan anaemia (don’t worry about detail)
- Ataxia pancytopenia syndrome (don’t worry about detail)
Acquired
- Excessive alcohol consumption
- Cancers- leukemia, lymphoma, myeloma, myelodysplastic syndrome, metastatic bone marrow cancer
- Hyposplenism
- PNH (paryxysmal nocturnal haemoglobinuria)
- Chemotherapy- methotrexate
Investigations for pancytopenia
- FBC
(Macrocytic, normocytic, or microcytic anaemia can suggest different causes (e.g., vitamin B12/folate deficiency, bone marrow failure, etc.) - Blood film (Blast cells may indicate acute leukaemia.
Atypical lymphocytes suggest infections like infectious mononucleosis (EBV).
Tear-drop cells may indicate myelofibrosis.
Schistocytes might point to haemolytic anaemia or thrombotic microangiopathies.) - Bone marrow aspiration and biopsy (LDH levels are also useful in suspecting a malignancy)
- Autoimmune test- RA/lupus
- Infection disease testing- HIV and Hep C can cause pancytopenia. Mono, TB and malaria.
What is pancytopenia?
Decrease in all peripheral blood cell lines (Low red blood cells, neutrophils and platelets)
Most common causes for pancytopenia
Chemotherapy
Immunosuppressants (steroids don’t tend to cause pancytopenia)
B12/folate deficiency- key for making DNA
Alcoholic liver cirrhosis
What type of bleeding do you get with thrombocytopenia?
Epistaxis
Mucosal bleeding
(clotting problems)
What is the difference between clotting and platelet type bleeding?
Clotting- bruising, swollen joints
Platelet type bleeding- petechial rash (blood blisters on mucosal membranes and skin), mucosal bleeding
Features of fanconi syndrome
- Cafe au lait spots
- Curved spine or short stature
- Learning disabilities
- Constipation and weakness
Febrile neutropenia vs neutropenic sepsis
Febrile neutropenia
- Fever in a patient who is neutropenia
Neutropenic sepsis
- Hypotension, tachycardia
- Acidotic
Importance of LDH
Increased cellular turnover
Not specific-
What anaemia does B12 deficiency cause
Macrocytosis with hypersegmented neutrophils
Where is B12 absorbed?
Terminal ileum
If you administer folate first then the B12 will drop
Subacute demyelination of the spinal cord
Why do you have to be careful with transfusing patients with B12 deficiency?
1 unit at a time- otherwise will go into heart failure
What test tells you how well the bone marrow is functioning?
Reticulocyte count
Lots of reticulocytes, more of a purple colour on a blood film- polychromasia (lots of different colours)
How long are patients under surveillance for before they are discharged with high grade lymphoma?
3 years
Can you cure myeloma?
No you keep patients under surveillance
What are symptoms of relative (decreased plasma volume) polycythemia vera?
- Dry mucous membranes
- Decreased skin turgor
- Orthostatic hypotension
What are types of myeloproliferative disorders?
Essential thrombocythemia
Polycythemia vera
Myelofibrosis
Chronic myeloid leukaemia
All of these disorders involve dysregulation at the
multipotent haematopoietic stem cell
What is the genetic mutation in myeloproliferative disorders?
Many patients have a specific point mutation in one copy
of the Janus kinase 2 gene (JAK2)
- a cytoplasmic tyrosine kinase on chromosome 9,
which causes increased proliferation and survival of
haematopoietic precursors
We now have specific drugs targeting the aberrant protein
What is a paraprotein?
An abnormal monoclonal protein produced by a single clone of plasma cells
Paraprotein/M spike/M protein are all the same thing
We produce polyclonal antibodies to cover all infections- why patients get sick with myeloma because they have immunoparesis (don’t make enough of the other immunoglobulins to cover infection)
What is the most common immunoglobulin found in myeloma?
IgG
How can you diagnose myeloma?
- Serum electrophoresis (M spike) M-spike on SPEP: Indicates overproduction of a monoclonal immunoglobulin.
- Light chain assay with a ratio of 2:1
For the above two just need a normal blood test
- Bone Marrow Biopsy: Confirms diagnosis by identifying ≥10% clonal plasma cells and assessing marrow architecture.
- Additional Testing: Cytogenetics (FISH), CRAB criteria evaluation, and imaging (to detect bone lesions).
What are plasma cells?
Mature B lymphocytes
If a patient has high levels of IgM what symptom should you be worried about?
Hyper viscosity as IgM immunoglobulins are the largest in size
Should you put down bence jones proteins as an investigation for myeloma?
NO
It is no longer being used. If you can find light chains in the serum why look in the urine
What is the main result commonly seen on FBC with myeloma?
Anaemia
Don’t commonly see thrombocytopenia and low WCC
What percent of clonal plasma cells need to be seen on biopsy for it to be called myeloma?
> 10%
When do you start to treat myeloma?
When plasma cells seen are >10%
15g/l
Or there is symptomatic myeloma (CRABBI)
What is MGUS?
Monoclonal gammopathy of undetermined significance (MGUS, also known as benign paraproteinaemia and monoclonal gammopathy) is a common condition that causes a paraproteinaemia and is often mistaken for myeloma
Think about it like a spectrum with MGUS on one side and symptomatic myeloma on the other
IMWG guidelines
Take a look
If a patient has CRABBI symptoms, what should you make sure you do first?
Rule out underlying causes
How do you manage a spinal cord compression and what could be causing it in myeloma?
Give 16mg STAT of Dexamethasone straight away while ordering a WHOLE spine MRI
No one will mind if they have one dose of steroids and it turns out to not be a spinal cord compression
Plasmacytoma- can be shrunken with radiotherapy
What two symptoms should you ask about with a lymphoma?
Visual changes and headaches (microvascular changes)
Why should you be cautious with giving RBCs for patients with myeloma?
Hyper viscous blood
One unit at a time
What is the pathophysiology of amyloidosis?
Plasma cells mutate and begin to produce abnormal light chain proteins
Light chains become misfolded
Typically affects the heart and/or kidneys
What staining is done for amyloidosis?
Congo red staining with green apple colouring if positive
What is Waldenstrom’s macroglobulinaemia?
Waldenström’s macroglobulinaemia (WM) is a type of blood cancer where abnormal B-cells produce excessive amounts of IgM paraprotein. This IgM protein is larger than other immunoglobulins, leading to hyperviscosity (thickened blood), which can cause circulation problems like headaches, blurred vision, and dizziness.
What should you tell patients when they are diagnosed with myeloma?
It is an incurable disease but it is very treatable
(Essentially you keep trying treatment after treatment, will not be unusual for a patient to be on the 6th line)
When should you be suspicious of fractures?
Takes minimal effort to fracture (sneezing and vertebral fracture)
Should you do a skeletal survey?
NO
Whole body MRI instead
You have to lose a lot of cortical bone for it to show up (lytic lesion)
What surgeries can take place without disruption to anticoagulants?
Minor skin surgeries, cataract surgeries and dental extractions
What are the three main broad symptoms you can ask about with a patient presenting with lymphoma/leukemia
Pancytopenia
Fatigue- low RBCs
Fever- low neutrophils
Bleeding- low platelets
What drug is given to patients with chronic myeloid leukemia?
Key Points of Relationship:
Philadelphia chromosome (BCR-ABL1 fusion) is the genetic hallmark of CML.
Imatinib directly targets the abnormal protein (BCR-ABL1) produced by the Philadelphia chromosome, thereby controlling the disease.
Imatinib therapy represents a targeted treatment approach, demonstrating the success of molecularly targeted therapies in haematological malignancies.
In summary, the Philadelphia chromosome is the genetic abnormality responsible for CML, and imatinib is the targeted therapeutic agent that specifically inhibits the pathogenic effects of the BCR-ABL1 fusion protein.
What are the three categories of polycythaemia?
Relative
- Dehydration
- Stress (Gaisbock syndrome)
Primary (abnormal proliferation of erythroid precursors)
- Polycythaemia rubra vera
Secondary (increased EPO)
- COPD
- Altitude
- OSA
- Excessive EPO- tumour secretion
What are symptoms/signs of polycythemia vera? (EPO low)
- Pruritis
- Erythromelagia
- Headaches/visual disturbance
- Sweats
- Gout
- Thrombosis
- Subconjuntival suffusion
- Ruddy complexion
- Tinnitus
Investigations for suspected polycythemia vera
FBC- RBC, raised hematocrit, raised haemoglobin, raised red cell mass with low/low-normal plasma volume
History of secondary causes
EPO level (low)
JAK2- if negative consider sleep studies (other causes)
USS abdomen (splenomegaly, renal masses, uterine masses (secondary polycythaemia through increased blood loss)
Management for polycythaemia
Aims??
Reduce the risk of thrombotic events
Manage symptoms and address underlying causes
Therapeutic phlebotomy
Low-dose aspirin
Cytoreductive therapy (hydroxyurea) In those patients who are high risk (>60, cardiovascular risk factors)
Venesection in the acute phase
Lifestyle modifications- smoking cessation, weight control, BP control
What is the difference between cytoreductive therapy and venesection?
Venesection is a quick fix that removes blood to lower cell counts temporarily.
Cytoreductive therapy is a long-term treatment that uses medication to reduce blood cell production and manage the disease at the source.
Complications of polycythaemia vera?
Ischaemic stroke
Myocardial infarction
Pulmonary embolism
Progression to myelofibrosis or acute myeloid leukaemia
Gastrointestinal haemorrhage
Budd-Chiari syndrome