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 is a leucoerythroblastic blood film?
Literally LEUCO (white cells) ERYTHRO (red cells) BLASTIC (primitive cells)
So it is the presence of primitive white and red cells(ie cells that should only be seen in the marrow) cells in the bloodstream. It doesn’t necessarily mean blasts of these lineages are seen though - myelocytes are primitive white cells which are usually seen, and nucleated red cells are the primitive red cells.
What are the causes of a leucoerythroblastic film?
Things that stress the marrow sufficiently to cause immature cells to be released prematurely such as severe infection, severe trauma, severe hypoxia.
Damage to the marrow by marrow infiltration - that could be a primary marrow malignancy such as myeloma, lymphoma or it could be secondary malignancy such as metastatic breast cancer.
Marrow fibrosis can also cause this - myelofibrosis is a myeloproliferative neoplasm that can cause this too.
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)
What are the common causes of hypercalcaemia?
Malignancy - myeloma /high grade lymphoma commonly but also secondary cancers (eg lung renal breast),
hyperparathyroidism can cause chronic hypercalcaemia (usually adenoma rarely adenocarcinoma)
These two causes account for the vast majority
Mild hypercalcaemia can be caused by drugs typically vitamin D (cod liver oil supplements rich in Vit D), calcium supps , Lithium or thiazide diuretics.
Rarer causes – the list gets long and include sarcoidosis, TB, addisons, thyrotoxicosis etc
What are the clinical features of hypercalcaemia?
Polyuria polydipsia, bone pains/osteoporosis, ‘abdominal moans’: constipation, pancreatitis, gastric ulcers, nausea and vomiting; ‘psychiatric groans’: confusion, dementia depression fatigue . Chronic hypercalcaemia (ie not seen in cancer usually) can cause renal stones), can cause short QTc and so arrythmias Hence ‘stones,bones,abdominal moans, and psychiatric groans’
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.
