Clinical Cases in Haematology Flashcards
List abnormalities
Anaemia
Neutrophilia
Thrombocytosis
Hyperviscosity
Circulating lymphoplasmacytoid lymphocytes may be significant to diagnosis
What kind of anaemia is it?
Normocytic
What does plasma viscosity measure?
Viscosity of plasma - the more viscous the thicker and harder it is to flow
What causes an increase in plasma viscosity?
Plasma gets more viscous when there is more protein in it. The common proteins that can go up are reactive ones- such as C-reactive protein, and fibrinogen; but the proteins are not that big or at that high a concentration so viscosity doesn’t go that high. Immunoglogulins are bigger and so marked increases in them caused by a malignancy that produces them can increase viscocity much more. The biggest of the immunoglobulins is IgM as it has a pentameric structure and so for a given concentration causes the greatest rise in viscosity.
What tests would help distinguish different causes?
Serum electrophoresis would be the most useful. Proteins migrate based on size and charge (alpha fastest then beta then gamma regions). ‘Gamma’ globulins are therefore an old name for immunoglobulins if there was a peak in the gamma region then the lab would go on to perform immunofixation to identify the isotype (IgG, IgA, IgM) and if clonal (clonal will be either kappa or lambda restricted but not both).
He has an IgM kappa paraprotein of 55g/L.
What is the likely diagnosis?
Waldenstroms macroglobulinaemia
What procedure might help in the short term to improve his symptoms?
Plasmapheresis (removal of plasma, replacing it with albumin) will remove IgM paraprotein
And in the longer term, how do we treat Waldenstrom’s Macroglobulinemia?
Treat the cause ie kill the cells making the paraprotein either with chemo plus rituximab or BTK inhibitor eg ibrutinib.
How might the pathophysiology explain the confusional state?
Hyperviscous blood has different physical properties - it doesn’t flow so well. This results in vascular stasis and hypoperfusion. In the brain this can cause confusion. It also explains the other clinical features of Hyperviscocity syndrome. SOB hypoxia resp distress, hypotension and the venous stasis (eg retinal bleeds) and leads to platelet dysfunction at these lower flow rates and bleeding problems can result - mucosal bleeding.
State the abnormalities
Pancytopenia (combination of anaemia, neutropenia and thrombocytopenia), a macrocytic anaemia, high number of circulating blasts
Blood film shows most of the circulating white blood cells are lymphoblasts
What is the diagnosis?
Acute Lymphoblastic leukaemia - can’t tell if it is B or T cell- immunophenotyping would be required. Acute leukaemias result from proliferation of cells that can’t differentiate - ie primitive or blast cells which were seen on the film.
Why is she bleeding and bruising?
She has thrombocytopenia - a defect in primary haemostasis
Why does she have adenopathy and hepatomegaly?
These organs have been infiltrated with blasts. Lymphoblasts are produced in the bone marrow , they are the progeny of abnormal haematopoietic stem cells. The normal counterpart of these cells would enter the circulation and go to lymphoid organs such as lymph nodes, spleen and liver and undergo maturation. Similarly these malignant cells could follow a similar route.
Why might she be confused (there could be several reasons)?
She could have sepsis with hypotension (hypoperfusion) or hypoxia- she is neutropenic so more prone to bacterial/fungal infection
She could have had a CNS bleed due to the thrombocytopenia eg subdural haematoma
She could have CNS infiltration with lymphoblasts - ALL can enter CNS and treatment includes specific CNS directed components as not all drugs cross the blood brain barrier. These include intrathecal chemotherapy (given directly into the CSF) by lumbar puncture.
What are the abnormalities?
FBC: Macrocytic anaemia, neutrophilia, mild thrombocytosis. Blood film shows leucoerythroblastic changes, plasma cells in the circulation
Biochemistry: Renal impairment raised CRP (suggests inflammation/infection), Hypercalcaemia, low albumin, raised Alk Phos (could be liver, could be bone)
What do you think is the haematological diagnosis here?
Myeloma
Many of the CRAB criteria present here and plasma cells seen so Myeloma is the diagnosis.
C=calcium high, R= renal dysfunction, A=anaemia, B=bone disease (lytic- not proven this case but Alk Phos is high and bone pain symptoms)
Why might she have impaired renal function?
Several potential reasons contributing :
Hypercalcaemia causing dehydration (through polyuria);
sepsis causing renal hypoperfusion;
myeloma producing light chains causing cast nephropathy;
myeloma protein toxic effect on proximal tubular cells;
NSAID related nephropathy;
urate (increased levels due to tumour burden) nephropathy;
myeloma can result in amyloid deposition too.
Likely here it is due to hypercalcaemia, sepsis related hypovolaemia, NSAIDs nephropathy and possibly cast nephropathy.
What might be contributing to her confusional state?
Hypercalcaemia, sepsis (multifactorial -hypotension, possibly chest source and hypoxia), possibly hypervicosity would all be reasonable potential explanations
What are the abnormalities?
Quite a lot!!
FBC: Haemolyic anaemia seems likely - retic response and no bleeding history; neutrophilia; thrombocytopenia but normal coag screen so DIC not the cause. Film is interesting - red cell fragmentation suggesting the red cells are being damaged extrinsically
Biochem: Renal impairment, other features supporting haemolysis - raised bilirubin, LDH and low haptoglobins. Normal CRP so infection seems unlikely
Coombs’ test is negative
This rules out AIHA
There is evidence of red cell fragmentation on the blood film and haemolysis.
What is MAHA (microangiopathic haemolytic anaemia) and how does it result in fragmentation?
Micro (small) angio (blood vessels) pathic so pathology is occurring in small blood vessels. Something is causing damage to the endothelial lining with resultant micro thrombi’ This will result in organ damage (in this case kidney and brain and heart) and damage to the red cells trying to get through these damaged small vessels which will result in their fragmentation.
Can you find a unifying diagnosis that causes neurological problems, haemolysis and renal impairment?
There are several different situations that can cause MAHA- most commonly DIC but also in pregnancy (preeclamsia, HELP), mechanical heart valves, HUS (haemolytic uraemic syndrome), TTP (thrombotic thrombocytopenic purpura), burns, valve haemolysis, malignant hypertension.
TTP would explain it best given the clinical pattern of organ involvement(neuro and renal), lack of a coagulopathy (as would be seen in DIC) and a thrombocytopenia. HUS and TTP can be difficult to distinguish sometimes, but HUS causes more severe renal damage and often associated with E coli O157 serotype. Hence the haematologist writing the film report was asking if any history to suggest GI upset as needed more clinical information to make the diagnosis. As TTP is a medical emergency and needs urgent and specific management with plasma exchange, blocking small molecules that stop vwf/plt aggregates forming and immunosuppression need started urgently. You need to be aware of the condition but not how to treat it!
How might the pathophysiology explain the confusional state?
Damage to small vessels in CNS is part of the underlying pathophysiology so caused the confusion and subsequent fit
List the abnormalities?
Pancytopenia with a markedly disproportionate neutropenia, renal impairment with a very raised CRP and low albumin
Why is he pancytopenic?
Chemotherapy induced most probably NHL can involve marrow but marked neutropenia is more typical and the timing fits (nadir is usually 10 days post chemo)
Why is his neutropenia more profound than the other cytopenias?
To do with cell turnover of the different cell types- neutrophils have the fastest so go down the quickest (but also recover quickly on regeneration)
How long is this likely to persist?
Post RCHOP likely only to be a few days from around days 10-12 post chemo
What might be the cause for his confusion?
Infection
Metabolic upset
What is endotoxic shock and how might it contribute to his renal impairment?
Endotoxin is a molecule found in the cell wall of gram negative bacteria. Endotoxic shock is the complex inflammatory response to gram negative infection resulting in hypotension, renal dysfunction and ultimately cardiovascular collapse, multiorgan failure and DIC
What other tests would you do and what treatment(s) would you start in A&E?
Start Sepsis 6 a combination of 3 things you measure/test for and 3 actions- lactate, cultures,monitor renal output, give fluids, iv antibiotics and oxygen therapy
I’d probably also check Creatinine Kinase (CK) as potentially had a long lie so worry about rhabdomyolysis contributing to renal dysfunction
Why is he on warfarin?
Mitral valve replacement
What is the target INR and acceptable therapeutic range for warfarin in this case?
Target 3 range 2.5-3.5 but can vary depending on valve type and position
Why might his INR be high?
Antibiotics seems most likely either interferes with warfarin metabolism or gut flora gut flora synthesis vit K, or
Might be confused and taken the wrong dose – tablets are colour coded for different strength and patient may have more than one strength at home in confusion might be taking the same number but wrong strength
diet change so less Vit K intake so balance of anticoagulation might shift too
alcohol intake changed – always worth getting an alcohol history
What might be contributing to his confusion?
Sepsis, hypoxia, hyperglycaemia all potential but bleeding due to high inr can cause a subdural.
This is the most important to exclude acutely given the neurological findings
What further tests would you do and why?
Blood sugar, sepsis 6 investigations, blood gases (might hold off that till INR reversed), CXR and send him for an urgent head CT after you have reversed his warfarin.
How would you reverse his warfarin?
Urgent reversal of warfarin is indicated with a multifactor concentrate (called a PCC or prothrombin complex concentrate) which contains factors II, VII, XI and X. This is superior to FFP and provides more complete reversal as much higher quantities of deficient factors can be given than in FFP.
Remember to also give Vitamin K too, as the factors in the PCC will be consumed and so levels fall again over the next 12 hours (and INR rise) unless new factors are synthesised or a further dose is given. If you give Vitamin K at the same time as the PCC it will overcome the effect of warfarin and allow active factors II, VII, XI and X to be synthesised by the liver so endogenous factor production will rise as the PCC factors are consumed.
