Case 140: Update 2

This lady’s blood film shows red cell agglutination at room temperature which resolves with sample
warming to 37 degrees Celsius. There is also polychromasia with spherocytosis. Her
thrombocytopenia is mild but genuine with no platelets clumps.


You suspect this lady has haemolytic anaemia secondary to cold haemagglutinin disease (CHAD) and
arrange for her to be admitted to your hospital’s urgent care centre. You arrange further tests which
support your diagnosis, including:

Direct antiglobulin (Coombs) test: positive (anti-C3d +++)
Bilirubin: 26 umol/L
LDH: 740 U/L
Haptoglobin: undetectable
Reticulocytes: 188 x109/L (5.8%)


A CT chest/abdomen/pelvis is only significant for moderate splenomegaly (17cm) with no associated
lymphadenopathy.


What do you think could be the cause of this lady’s CHAD, and how would you investigate?

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Case 140: Update 1

This lady has a new macrocytic anaemia and is symptomatic. She is also mildly thrombocytopenic.


Her B12 and folate are normal, unfortunately the rest of her biochemistry has haemolysed. Her reticulocyte count is raised at 188 ×109/L. She has no B-symptoms or palpable lymphadenopathy/organomegaly.

She takes no medications, does not drink alcohol, and has a balanced diet.


Given how troubled she is by her symptoms, her GP arranges for this lady to receive a red cell
transfusion. Unfortunately her FBC sample is now a couple of days old so you are unable to obtain a
blood film. You ask the GP to repeat her FBC after a few days with a request for a blood
film. At that point, her FBC and blood film are as follows:


Hb 78 g/L
MCV 104 fL
Plt 135 x109/L
WCC 12.7 x109/L
Neut 5.8 x109/L
Lymph 5.6 x109/L
Mono 1.1 x109/L
Eosino 0.2 x109/L
Baso 0.01 x109/L

What is your main differential at this point and how would you further investigate?

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Case 140: The beginning

You are the on call haematologist and are asked by one of the secretaries to speak to a worried GP
on the phone.


It is regarding a 52 year old lady who saw her GP with a 2 week history of worsening fatigue and
shortness of breath on minimal exertion. Her full blood count is as follows:


Hb 81 g/L
MCV 103 fL
Plt 138 x109/L
WCC 11.2 x109/L
Neut 4.8 x109/L
Lymph 5.1 x109/L
Mono 1.0 x109/L
Eosino 0.3 x109/L
Baso 0.01 x109/L


Her GP is concerned because this lady has no bleeding symptoms and her last haemoglobin done 2
months previously was in the normal range.


What advice would you give her GP?

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Case 139 – Summary

The cases this week were designed to consider the complexities of VTE management in cancer patients. 

VTE is four to seven times as common in the cancer population compared to the general population.

Cancer associated thrombosis is the second commonest cause of death in cancer patients after disease progression.

It is the source of a huge amount of morbidity for patients with associated anxiety regarding treatment delays, bleeding issues or further thrombosis.  It is often a challenging situation to manage as patients may well have bleeding and thrombosis risk factors and may even have this present simultaneously (as seen in short case 2). 

Importantly a good haematologist will consider patient choice, prognosis of the disease and practical considerations such as drug interactions, abnormalities in blood tests, surgery and biopsies.

Role of thromboprophylaxis in cancer patients: (Case 1)

There is no benefit in unselected thromboprophylaxis in ambulatory cancer patients. The number needed to treat for the population as a whole is which is felt to be too high to warrant unselected intervention (NNT 60) from Cochraine review of 3538 patients. The review found no difference in mortality at 12 and 24 months despite reductions in symptomatic VTE rates but it did show possible increased bleeding rates while on prophylaxis.

In 2008 Khorana et al. Devised a validated score to evaluate the risk of thrombosis in a cancer patients. This score suggested if patients scored 3 or more had a high risk of VTE (7.8% over 2.5 months, compared to 0.8% for low risk individuals). The use of this tool is recommended by ASCO, ESMO and BSH guidelines. 

It should be stressed that NICE guidance suggests that all patients with active cancer therapy should be considered for thromboprophylaxis on admission to hospital unless there are contraindications.

NICE also suggest that consideration is given to thromboprophylaxis for ambulatory cancer patients with other thrombotic risk factors. It also advocates  consideration of prophylaxis in pancreatic cancer patients while on chemotherapy and myeloma patients on Thalidomide, Lenolidamide or Pomalidamide.

In our short case one the patients Khorana score is 1 (score for bladder cancer 1-8 -2% risk over 2.5 months of VTE). He had some bleeding risk factors to consider such as his history of active haematuria and iron deficiency at present. He was also planned to start chemotherapy which cause thrombocytopenia.  It was decided no thromboprophylaxis was indicated.

Management of Cancer associated thrombosis: (Case 1)

It is important to have a sound understanding of the literature with regards to anticoagulation to be able to apply the principles to practice. 

Here is a quick summary of the important trials in this area:

CLOT trial 2003: Dalteparin Vs VKA  –  Recurrent thrombosis reduced in Dalteparin group (9% Vs 17%) and similar bleeding risk (4% Dalteparin Vs 6% VKA). Minor criticism of this trial is in VKA arm 50% of recruited patients in VKA arm had poor time in INR range.

CATCH trial 2015: Tinzaparin Vs VKA  – Reduced recurrence rates in Tinzaparin group with major bleeding rates the same (2%) but lower clinically relevant non major bleeds in Tinzaparin group.

This established LMWH is superior to VKA in management of cancer associated thrombosis.

HOKUSAI VTE 2018: Edoxaban 60mg OD (After 5 days LMWH) Vs LMWH. No difference VTE recurrence rates (12.8% Edoxaban Vs 13.5% LMWH). Increased major bleeding rates in trial (6.9% Edoxaban Vs 4% LMWH) when analysed these were particularly GI bleeds and convincingly on subgroup analysis were linked to urothelial and GI malignancy patients. ICH rates in both groups were the same.

SELECT-D 2018: Rivaroxaban (15mg BD for 21 days then 20mg OD) Vs LMWH. Reduced VTE recurrence rates (4% Rivaroxaban Vs 11% LMWH). Increased major bleeding on Rivaroxaban (6% Rivaroxaban vs 4% LMWH) and clinically relevant non major bleeding. This finding lead to stopping recruitment for upper GI malignancy cancer patients early. In this trial again ICH rates were not increased with Rivaroxaban.

ADAM VTE 2019: Apixaban (10mg BD 7 days to 5mg BD) Vs LMWH. Primary outcome in this trial was Major bleeds with 0% in Apixaban group compared to 1.4% in LMWH group. These rates were low compared to other DOAC Vs LMWH trials and this may be due to selection of patients and small study population of 287 patients. This trial also confirmed statistically significant lower VTE recurrence rates of (0.7% Apixiban Vs 6.3%).

CARVAGGIO 2020: Apixiban (10mg BD for 7 days to 5mg BD) Vs LMWH. Recurrent VTE rates 5.6% Apixaban Vs 7.9% LMWH) statistically significant for non inferiority of Apixaban in this setting. Major bleeding rates same (3.8% Apixaban Vs 4% LMWH) this included Major GI bleeds. It did find an increase in clinically significant non major bleeding rates in Apixiban group and these were mainly in genitourinary and upper airway bleeds. Older patients >75 years appeared to have more major bleeding on Apixiban on subgroup analysis. 

These trials have established DOACs are non inferior to LMWH in terms of recurrent VTE. DOACs may be associated with increased clinically relevant minor bleeding and it seems that patients with GI malignancy are at increased risk of major bleeding on these drugs. 

Recent ESMO guidelines sensibly suggest particular patient groups where care should be taken with DOACS:

Frail patients – None of the DOAC trials included patients with ECOG <2.

Luminal GI cancers, Genitourinary cancers, nephrostomy tubes or those with known Gastritis, Oesophagitis or Colitis – Increased bleeding risk on DOACs.

Thrombocytopenia – Patients will require interruption of DOAC if plt <50. 

Pharmacokinetic considerations – CYP3A4 pathway used for metabolism of DOACS. Many anti cancer drugs can interact with this pathway including Biclutamide, TKI, Paclitaxel  plus supportive medications such as Azol anti fungals.

Poorly controlled vomiting and patients with GI resection – May affect absorption of DOACs 

The patients choices and values may also need to be considered and often a patient has a clear idea of which anticoagulant they would prefer and the decision making and the risk/ benefit need to be shared with the patient.

IVC Filters in cancer associated thrombosis: (Case 2)

BSH guidelines suggest these can be considered as an option for patients with an acute VTE and an absolute contraindication to anticoagulation. These are not a permanent substitute to anticoagulation and need to be inserted with clear plan for removal.

IVC filters that are left in situ can lead to serious complications due to stent migration, perforation of IVC and occlusion can occur in up to 20% of patients who have stents left in for 5 years.

In short case 2 the patient had a PE and DVT in the context of haemorrhagic cerebral metastasis with neurological deficit. It was unlikely that she would ever be considered suitable for anticoagulation and hence an IVC filter was unlikely ever to be able to be removed. The patient also had a poor prognosis from her metatstatic malignancy and hence this intervention was felt to be inappropriate in her case.

BSH guidelines also support the use of IVC filters when need for urgent surgery and VTE within last 4 weeks due to high recurrence rates during interruption of anticoagulation. This would clearly be important to consider for any cancer surgery in patients with recent thrombosis. 

Many thanks for your help this week I hope it was interesting and that you feel more confident in the recent literature surrounding this area of practice.

References:

Akl  EA, Kahale  LA, Hakoum  MB, Matar  CF, Sperati  F, Barba  M, Yosuico  VED, Terrenato  I, Synnot  A, Schünemann  H. Parenteral anticoagulation in ambulatory patients with cancer. Cochrane Database of Systematic Reviews 2017, Issue 9. Art. No.: CD006652. 

Venous thromboembolism in over 16s: reducing the risk of hospital-acquired deep vein thrombosis or pulmonary embolism. NICE guideline [NG89] Published date: 21 March 2018.

Khorana AA et Al. Development and validation of a predictive model for chemotherapy associated thrombosis. Blood, 111, 4902-4907.

Watson, H.G., Keeling, D.M., Laffan, M., Tait, R.C., Makris, M. and (2015), Guideline on aspects of cancer‐related venous thrombosis. Br J Haematol, 170: 640-648.

Moik F, Pabinger I, Ay C. How I treat cancer-associated thrombosis. ESMO Open 2020;4:e000610. doi:10.1136/ esmoopen-2019-000610

Key N et al. Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update Journal of Clinical Oncology 38, no. 5 (February 10, 2020) 496-520.

Guidelines on use of Vena cava filters. Br J Haematol, 136 :90-595.

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Case 139 – short case 2 update 2

Thanks for your input with regards to IVC filter decision making.

You ask a few more questions and establish that the patient has declined any further investigation for her likely metatataic malignancy and the oncology team advise her prognosis is weeks to months.

Knowing the patients wishes for no further intervention and her poor prognosis it isn’t felt she is an appropriate candidate for an IVC filter.

She has also developed right arm weakness presumably secondary to her haemorrhaging brain metastasis. You agree to stop anticoagulation given her neurology. The patient is informed of the difficult situation with regards to PE and brain haemorrhage and is also in agreement with this plan.

Many Thanks for your help with the two short cases this week. A summary of important issues to consider in cancer associated thrombosis will follow this weekend.

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Case 139 – short case 2

You are the haematologist on call and phoned at 5pm on a Friday about a 75 year old lady who presented to the acute admissions unit with confusion. She was diagnosed with Hypercalcaemia and a subsequent CT is suggestive of metastatic Lung Adenocarcinoma. She has a past medical history of Type two diabetes, AF on Apixiban, Gallstones, Diverticular disease and has an elevated BMI with a weight of 130kg.

The medical team contact you as she has had a staging CT that shows a segmental PE in right lung and a CT Brain that shows probable cerebellar metastasis with one metastasis showing possible small haemorrhage. Her right leg is swollen and clinically there is suspicion of a DVT.

They are concerned about the new VTE while she is “on Apixiban” and had planned to change her to treatment dose LMWH but wanted your approval for this before starting this given the possible bleed on CT Head.

They tell you her FBC is normal and her coagulation screen is normal apart from an elevated fibrinogen and D-Dimer. Her renal function is Normal.

What are your initial thoughts regarding anticoagulation?

Are there any other investigations that may help in this case?

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Case 139 – short case 1 update 3

After careful consideration you opted for weight based LMWH due to concerns about Thrombocytopenia and he has a bladder cancer with history of haematuria.

A month later his platelet count has recovered but he has developed new dyspnoea. He is found to have a new segmental PE on CTPA. He has been on LMWH weight based with normal renal function eGFR >90. He has no active bleeding and his Hb has improved to 111 following Iron replacement.

What would you do now?

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Case 139 – short case 1 update 2

The decision was made not to give thromboprophylaxis in the poll. As previously provoked DVT and also history of ongoing bleeding and iron deficiency with risk of thrombocytopenia on the chemotherapy. His Khorana score was 1 (Intermediate risk 1.8-2% chance of VTE).

You are called about the same patient a month later. His second cycle of treatment has been delayed as his platelet count is 70.

He has presented with a swollen right leg and a Doppler USS has confirmed a DVT. The medical team tell you the patient is keen for a DOAC over LMWH and are keen to hear your thoughts on the use of DOACs in cancer associated thrombosis.

What anticoagulation options would you consider for this patient? What is your preference and why?

What should the team do about the thrombocytopenia and anticoagulation? Any platelet thresholds you may use to advise the team?

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Case 139 – short case update 1

You establish the patient apart from his new cancer diagnosis and previous DVT is usually well. BMI 30.

His full blood count is normal apart from microcytic anemia Hb 101, MCV 77, plt 300, Wcc 9. He has been having some intermittent haematuria and this is ongoing he has just started oral iron replacement.

He has no family history of DVT. His DVT 10 years ago happened in context of trauma where he needed a right hemiarthroplasty.

The oncology consultant tells you the cisplatin gemcitibine regimen can cause thrombocytopenia but he will be having regular FBC checks and chemotherapy would be delayed if plt <100. It can also lead to renal impairment but at present the patients eGFR >90 and again they will monitor.

What is his Khorana score? – what does this mean?

Please answer the poll question about your final thromboprophylaxis decision.

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Case 139 – the beginning of short case 1

This week we are going to have two short cases to discuss the tricky management of cancer associated VTE. It would be great to hear your thoughts and suggestions as like so much of practice there are likely several approaches that can be adopted. Please remember to use #TeamHaem in your responses and look forward to your thoughts.

Short case 1 :

You are called about a 60 year old man with newly diagnosed muscle invasive bladder cancer. The MDT have suggested Neoadjuvant chemotherapy with Cisplatin based chemotherapy and Radical cystectomy. Past medical history includes a DVT 10 years ago.

His Oncologist wants advice regarding thromboprophylaxis as he recently attended a talk where he remembered that high risk oncology outpatients should receive thromboprophylaxis. He thought as the patient has had a previous DVT he should need prophylaxis and is seeking guidance from you the on call the Haematology SpR.

What additional history would be useful to assist in you decision making?

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Case series 138 – Summary

This week, we covered a series of cases in various clinical settings with patients presenting with very high white cell counts (>50 x 109 / L). The differential diagnosis is wide, including both haematological (hyperleukocytosis) and non-haematological (leukemoid reactions) causes. Rarely, a high WCC represents a haematological emergency and requires emergency treatment.

Leukemoid reaction vs CML

Leukemoid reactionChronic myeloid leukaemia
DefinitionWCC >50 x 109 / L due to non-leukaemic causesMyeloproliferative neoplasm => uncontrolled production of granulocytes
Aetiologyserious infections/sepsis, drugs (e.g. G-CSF), solid organ malignancyBCR-ABL1 fusion gene (Ph chromosome)
Clinical featuresclear precipitant (e.g. severe sepsis), patient is usually very unwell due to underlying causeusually relatively well (unless in blast crisis), incidental finding, splenomegaly, fatigue, weight loss
Pathologic featuresneutrophilia, left shifted granulocytes, toxic granulation of neutrophilsleukocytosis (often >100) with neutrophilia, basophilia (universal finding) and eosinophilia, left shifted granulocytes, “myelocyte bulge”, normocytic anaemia, thrombocytosis

Causes of hyperleukocytosis (leukaemic WCC >50 x 109 / L)

Mature lymphoid neoplasms: CLL, indolent NHLs (e.g. marginal zone, follicular), B- and T-PLL (rare and more aggressive)

Chronic myeloid neoplasms: CML, CMML, other rare myeloproliferative neoplasms (e.g. chronic neutrophilic leukaemia)

Acute lymphoblastic leukaemia

Acute myeloid leukaemia: FLT3 mutated, myelomonocytic/monocytic subtypes

Complications of hyperleukocytosis

Epidemiology: Complications of hyperleukocytosis usually affect patients with AML or ALL. They are very uncommon in patients with CLL and CML (with the exception of CML in blast crisis). Symptoms more commonly occur with a blast count > 100 x 109 / L.

Disseminated intravascular coagulation: can occur in either ALL or AML

Tumour lysis syndrome: more common in ALL than AML, usually complication of treatment but can occur spontaneously

Leukostasis: more common in AML than ALL, respiratory features (pulmonary infiltrates, hypoxaemia), neurological features (visual blurring, confusion, headahes, reduced GCS), associated with early mortality

Management of symptomatic hyperleukocytosis: supportive care (fluids, rasburicase, avoid red cell transfusions if possible) and cytoreduction (one or more of hydroxurea, leukapheresis, induction chemotherapy)



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Case series 138 – part 3

You are a GP registrar working in primary care. It’s 5 pm on Friday and you are going through the last few blood results before the weekend. The final patient is a normally fit and well 69 year old man who had bloods done as part of an NHS Health Check.

Full blood count
Hb 128             (130-180)
MCV 92            (80-100)
Platelets 138   (150-450)
WCC 220          (4.0-11.0)
Lymph 212      (0.5-3.5)
Neut 6.0          (2.0-8.0)
Eosin 0.4         (0.1-0.5)
Baso 0.1          (0.0-0.1)
Mono 1.5         (0.2-1.2)

The last FBC from his last Health Check 5 years ago was completely normal.

You call the patient at home and he tells you that he feels “champion”.

The BMS has made a blood film.

Questions

1) What is the differential diagnosis here?

2) How would you report the blood film?

3) Does the patient need to be admitted to hospital? If so, why? If not, how urgently should they be seen by haematology?

4) Is this patient at risk of leukostasis (i.e. symptomatic hyperviscosity due to high WCC)?

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Case series 138 – part 2

You are the critical care registrar on call and get called to A+E to review a 65 year old patient in resus.

The patient is in extremis with sats of 88% on 15 L non-rebreath mask and is septic with haemodynamic instability. His wife is present and says that he’s normally fit and well but has gradually deteriorated over the last 3 weeks with a sudden deterioration in the last 48 hours. He tested negative for COVID-19 three days ago.

A portable chest x-ray is arranged.

As you are about to organise transfer to intensive care, the haematology laboratory calls with abnormal blood results.

Full blood count
Hb 78               (130-180)
MCV 92            (80-100)
Platelets 46     (150-450)
WCC 390           (4.0-11.0)
Manual differential in progress.

An urgent blood film is made by the BMS.

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Case series 138 – Part 1

You are the surgical SHO on call and get called by A+E to see a 23 year old patient with severe abdominal pain. The patient is septic and being treated with broad spectrum antibiotics and fluid resuscitation. Examination demonstrates severe abdominal tenderness with guarding, rebound tenderness and generalised abdominal rigidity. An urgent CT scan is performed which confirms perforated appendicitis.

As you prepare to get the patient to theatre, the haematology laboratory calls with abnormal blood results.

Full blood count
Hb 108               (130-180)
MCV 92            (80-100)
Platelets 670     (150-450)
WCC 75           (4.0-11.0)
Lymph 4.4      (0.5-3.5)
Neut 70          (2.0-8.0)
Eosin 0.1         (0.1-0.5)
Baso 0.1          (0.0-0.1)
Mono 3.4        (0.2-1.2)

The BMS has made an urgent blood film:

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Case 137 – Summary

Thank you for your help in the management of our 53 year old man who presented with all of the CRAB constellation of symptoms of multiple myeloma (hypercalcaemia, renal impairment, anaemia and lytic bone lesions).

We talked a bit about hypercalcaemia where other more common causes include hyperparathyroidism and malignancy of the breast, lung, oesophageal, head and neck, skin, cervix, breast, kidney, and bladder. It can lead to problems including fatigue, confusion, memory problems, depression, nausea, vomiting, abdominal pain, weight loss, thirst, polyuria, constipation, abdominal pain and renal colic, or renal impairment.  It can also lead to a shortened QT interval; prolonged PR interval and cardiac arrhythmias such as ventricular fibrillation which is why if a patient has severe hypercalcaemia of unknown cause (>=3.4mmol/L), emergency hospital admission for management of this should be arranged.

We have already discussed myeloma in previous cases but as myeloma represents approximately 10% of haematological malignancies and patients may remain under follow up for a long period of time, it is always good to revisit. This case went on to develop therapy related MDS which is a very rare complication of treatment. 

Almost all cases of myeloma evolve from MGUS (monoclonal gammopathy of undetermined significance) which progresses to malignancy at approximately 1% per year, depending on the size and type of the paraprotein as well as underlying cytogenetics.

Paraprotein and serum free light chains are used to help diagnose myeloma and to monitor response to treatment, usually monthly during treatment and 3-4 monthly when not on treatment. Approximately 2% of patients have non-secretory disease with no measurable paraprotein or abnormal serum free light chain. 

Diagnosis:

  1. >= 10% clonal plasma cells in bone marrow or plasmacytoma proven on biopsy

+>=1 of the following

  1. Any of the CRAB criteria thought likely related to the plasma cell disorder
  2. bone marrow clonal plasma cells >=60%
  3. SFLC ratio >=100 but involved FLC>=100mg/L
  4. >1 focal lesion on MRI

Staging is with the Revised International Staging System R-ISS

Stage 1

All of:

  1. albumin >=35
  2. Beta 2 microglobulin <3.5
  3. No high risk cytogenetics: t(4;14), t(14;16), del(17p)
  4. Normal LDH

Stage 2

Not stage 1 or 3

Stage 3

  1. Beta 2 microglobulin >5.5

And 1 of

  1. High risk cytogenetics
  2. Raised LDH

Imaging

Low dose whole body CT, PET or MRI are best to detect bone disease

First line treatment for transplant eligible patient

VTD followed by autologous stem cell transplant is the current UK NICE recommendation

VRd followed by autologous stem cell transplant followed by lenalidamide or bortezomib based maintenance may be used elsewhere eg in the US

Supportive management includes aciclovir, co-trimoxazole, prophylactic antibiotics, VTE prophylaxis, zolendronic acid, pain management and input from the MDT, particularly the nurse specialists. 

The increase in therapy‐related MDS and AML in patients with myeloma has long been recognised and again more recently in patients on lenalidomide maintenance therapy, but the risk is low and the benefits outweigh the risk from myeloma by far.

Our patient developed pancytopenia several years after his autologous stem cell transplant and we undertook a bone marrow biopsy.  We looked at some morphological features of MDS in the bone marrow including abnormal myelopoiesis with pseudo Pelger-Huet neutrophils and hypogranular form, abnormal erythropoiesis with intercellular bridging and abnormally shaped nuclei and ringed sideroblasts.  This was in keeping with MDS with multi-lineage dysplasia and ring sideroblasts, but as he had previously had cytotoxic therapy, it was classified as therapy related MDS. 

Risk Stratification in MDS

IPSS‐R prognostic score values

Prognostic variable00·511·5234
CytogeneticsV Good
Good
IntermediatePoorV Poor
BM blast %≤2
>2–<5
5–10>10
Hb (g/l)≥100
80–<100<80


Plts  (×109/l)≥10050–<100<50



Neuts (×109/l)≥0·8<0·8

IPSS‐R cytogenetic prognostic subgroups

Very good−Y, del(11q)
GoodNormal, del(5q), del(12p), del(20q), double including del(5q)
Intermediatedel(7q), +8, +19, i(17q), any other single or double independent clones
Poor−7, inv(3)/t(3q), double including ‐7/del(7q), complex: 3 abnormalities
Very PoorComplex: >3 abnormalities

Therapy-related MDS is associated with higher risk cytogenetic abnormalities and a poorer prognosis. Our patient was young and fit and had mild anaemia and very poor risk cytogenetics giving him an IPSS-R of 5.  As he had high risk disease we discussed him at the MDT where the decision was made to aim for an allogeneic bone marrow transplant.

References

Rajkumar S, Multiple myeloma: 2020 update on diagnosis, risk-stratification and management, American Journal of Haematology, 2020;95:548–567.

NICE Clinical Knowledge Summaries; Hypercalcaemia  https://cks.nice.org.uk/topics/hypercalcaemia/

Killick S et al, Guidelines for the diagnosis and management of adult myelodysplastic syndromes, British Journal of Haematology, 2014; 164;4, 503-525

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case 137 – Update 5

It is now nearly 3 years since our patient completed his treatment for myeloma and you noticed that he had started to become a little anaemic with Hb 97, neuts 1.9 and plts 120.

You asked for more information. Film showed MCV 112 but film fairly unremarkable otherwise. Renal, liver, bone profile, LDH, paraprotein and SFLCs normal.

You asked for a bone marrow biopsy. Some pictures are shown below:

What features do you note and what are your thoughts?

How would you risk stratify this patient and what further information do you require to do this?

How might you manage this patient?

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Case 137 – Update 4

Thanks for all your help with management of this chap. We have confirmed his diagnosis of multiple myeloma on bone marrow biopsy and completed imaging with plain films of his long bones as he has already had a whole spine MRI.

He was aggressively rehydrated and given IV bisphosphonate and his calcium improved. We started him on a pulse of steroids pending starting treatment with VTD chemotherapy and his renal function and hypercalcaemia improved significantly.

We started VTD chemotherapy and additional supportive treatment included VTE prophylaxis with LMWH which we changed to rivaroxaban when his renal function normalised, acyclovir to prevent shingles, and co-trimoxazole. We also thought about levofloxacin prophylaxis.  We asked him to get a dental review as soon as possible and started him on monthly zolendronic acid.

He responded quickly to treatment and his paraprotein was undetectable with a normal serum free light chain ratio after 4 months. His cytogenetics came back showing only a t(11;14) which was pleasing. He went on to have an autologous stem cell transplant and remained under regular review.

However, it is nearly 3 years since he completed his treatment and you notice that he has started to become a little anaemic with Hb 97, neuts 1.9 and plts 120.

What is your differential?

What actions do you take?

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Case 137 – Update 3

You have undertaken a bone marrow biopsy and the aspirate (shown below) and flow are back.

There is a population of abnormal CD20+, CD38+, CD138+, CD56+ cells.

Cytogenetics awaited

His calcium is a little better at 3.1 but his renal function is fairly static with a creatinine of 185 and urea 8.3.

LDH is normal. 

B2m 5.6

Albumin 36

What would be your choice of treatment?

What supportive management would you undertake along side this?

It’s a Friday evening and you can’t start definitive treatment until next week.  Anything you want to do in the meantime?

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Case 137 – Update 2

You have treated our gentleman with AKI and hypercalcaemia with IVT and once well hydrated, you added an IV bisphosphonate.  His calcium is a little better at 3.2 and his renal function is also a little better with creating improved to 190.

We discussed that it is important to recognise and treat hypercalcaemia as it can be related to drowsiness, confusion, weakness, constipation, vomiting, polydipsia, polyuria, dehydration, shortened QT interval, prolonged PR interval and arrhythmias.  NICE guidelines suggest admission for urgent management if hypercalcaemia is severe (>3.4mmol/L) or symptomatic. 

We have discussed some of the more common causes of hypercalcaemia and our differential included malignancies, particularly lung cancer, multiple myeloma, and renal cell carcinoma as well as breast and colorectal cancers and also hyperparathryroidism. 

We have finally got back the results we have been waiting for

Bloods: Serum electrophoresis: IgG K paraprotein 13.2g/L, K light chains 9802

MRI whole spine: extensive lytic lesions throughout spine and right clavicle. Compression fracture at T4. No concerns regarding nerve impingement or cord compression.

What is your next course of action?

What further investigations do you need to do?

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Update 1

Your 53 year old male patient seems very vague and his partner tells you that he has been very forgetful and low in mood recently. He feels weak and achey and has to force himself to go downstairs to eat. He has not left the house for 2 weeks. 

He can’t remember when he last opened his bowels but he is thirsty so is drinking and peeing plenty.  He doesn’t really know if he has lost any weight. He has felt under the weather for a few months now.

He had a back injury 8 months ago.  He can’t really remember what happened, just that it seems to have gotten worse rather than improved over time. 

Medication: Paracetamol and ibuprofen for back pain

Examination: No organomegaly or lymphadenopathy

Bloods:

FBC: Hb 78g/L but otherwise fairly normal.

Blood film: some rouleaux but otherwise fairly unremarkable.

Retics 84

LFTs normal

Cre 284

Urea 15.2

Haptoglobin normal

Coombs test negative

Ferritin, B12 and folate normal

CRP 14

What is on your list of differentials for hypercalcaemia?

Why is hypercalcaemia an emergency?

How do you manage hypercalcaemia?

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