Case 124 – Update 2

Thank you for all of your input and suggestions. To summarise the case thus far:

  • 68 year old lady referred with a macrocytic anaemia and thrombocytosis:
    • Haemoglobin              87 g/L (115 – 165)
    • White cell count          5.2 x 109/L (4 – 11)
    • Platelets                      538 x 109/L (150 – 450)
    • Mean Cell Volume      108 fl (80 – 100)
  • No reversible cause identified on further investigation, and her blood film demonstrated some dysplastic features:

IMG_2154

We therefore organised a bone marrow aspirate which confirmed trilineage dysplasia, no excess blasts and no excess ring sideroblasts:

 

Cytogenetics has subsequently confirmed a diagnosis of MDS with isolated del(5q) (like many of you suggested – good work!)

 

The patient comes back to clinic for results. How would you communicate her prognosis? What treatment options, if any, would you discuss?

 

Please reply to us (@TeamHaem) on Twitter and always include #TeamHaem to allow others to follow your comments. Please join in the debate and learn about haematological problems along the way. The case will continue to evolve over the coming week so keep checking #TeamHaem on Twitter for more information. 

Please note – all cases on TeamHaem are entirely fictional to protect patient confidentiality.

TeamHaem are not a position of authority.  It is an educational platform to allow discussion and learning.

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Case 124 – Update 1

We are investigating a 68 year old lady referred with a macrocytic anaemia and thrombocytosis. Thanks for all of your helpful input thus far. Tests you have requested to date:

Haemoglobin              87 g/L (115 – 165)

White cell count          5.2 x 109/L (4 – 11)

Platelets                      538 x 109/L (150 – 450)

Mean Cell Volume      108 fl (80 – 100)

 

Folate/B12 – normal

LFTs – normal

Ferritin – normal (with a normal CRP)

Retics – borderline low

Haemolysis screen (LDH, DAT) – negative

Coag screen – negative

 

CT chest, abdomen, pelvis – no evidence of malignancy. No size significant lymphadenopathy and normal liver/spleen. Confirms previous right total hip replacement.

Blood film is prepared and shown below (the BMS comments that there is a lot of platelet clumping and platelet islands, and confirms a thrombocytosis):

IMG_2154

What does the blood film demonstrate? What would be the next step in your investigation of this lady?

 

Please reply to us (@TeamHaem) on Twitter and always include #TeamHaem to allow others to follow your comments. Please join in the debate and learn about haematological problems along the way. The case will continue to evolve over the coming week so keep checking #TeamHaem on Twitter for more information.

Please note – all cases on TeamHaem are entirely fictional to protect patient confidentiality.

TeamHaem are not a position of authority.  It is an educational platform to allow discussion and learning.

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Case 124 – The beginning

You are helping out in new patient haematology clinic. You have just had your post-lunch coffee and are raring to go! The next patient has been referred via the 2ww pathway by their GP for investigation of an abnormal FBC, with concern about an underlying malignancy. They are a 68 year old lady with a PMH of:

  • Hypertension
  • CKD stage 2
  • Mild asthma (PRN salbutamol only)
  • Total hip replacement 2012
  • Provoked DVT secondary to this in 2012 (completed 3 months of anticoagulation with warfarin)

Her FBC from the GP is as follows (normal range in brackets):

Haemoglobin               87 g/L (115 – 165)

White cell count          5.2 x 109/L (4 – 11)

Platelets                        538 x 109/L (150 – 450)

Mean Cell Volume      108 fl (80 – 100)

Haematocrit                0.45 (0.37 – 0.47)

Neutrophils                 3.6 x 109/L (2 – 7.5)

Lymphocytes               1.9 x 109/L (1.5 – 4.5)

How would you approach the clinical assessment of this patient? What further investigations would you organise?

 

Please reply to us (@TeamHaem) on Twitter and always include #TeamHaem to allow others to follow your comments. Please join in the debate and learn about haematological problems along the way. The case will continue to evolve over the coming week so keep checking #TeamHaem on Twitter for more information.

 Please note – all cases on TeamHaem are entirely fictional to protect patient confidentiality.

TeamHaem are not a position of authority.  It is an educational platform to allow discussion and learning.

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case 123 summary

Our case this week looked at a 44 year old gentleman with a new diagnosis of AML.

He presented with pancytopenia and blasts with auer rods on peripheral blood.

Investigations confirmed a diagnosis of AML.  PML – RARA was negative, and cell markers inkeeping with AML (CD33+, CD34+, CD13+, CD19+, CD56+, HLA-DR, CD17+, CD64+).  Cytogenetic and molecular studies showed t(8:21), C-KIT positive, FLT3 negative and NPM1 negative.  We decided to treat this patient initially with DA+myelotarg.

Initial investigations should include:

  • FBC
  • Clotting screen including fibrinogen and D-dimers
  •  Urea and electrolytes
  •  Liver function tests
  •  Urate
  •  CMV serology (in those patients who may be transplant candidates)
  •  HLA class 1 and 2 tissue typing for potential allogeneic stem cell
    transplant candidates
  • Marrow aspirate and trephine where possible for morphological
    assessment
  • Marrow EDTA sample for immunophenotyping
  • Marrow sample for cytogenetic and molecular analysis

 

Risk Stratification

A number of factors are known to affect prognosis of patients with AML including:

  1.  age
  2. peripheral white cell count
  3. marrow cytogenetics
  4. response to induction chemotherapy
  5. molecular studies

 

Cytogenetic abnormalities

  • Good risk:  t(8;21), inv(16), t(16;16), t(15;17)
  • Standard: Any patient not in either good or poor risk groups.
  • Poor risk: -5, -7, del(5q), abnormal (3q) or complex (5 or more abnormalities)..

 

Molecular markers

  • FLT3-ITD +, NPM1 – Poor Risk
  • FLT3-ITD +, NPM1+ Intermediate Risk
  • FLT3-ITD -, NPM1 – Intermediate Risk
  • FLT3-ITD -, NPM1 + Good Risk

 

Core binding factor

CBF in acute myeloid leukaemia represents 5-8% of all AMLs and has a relatively favourable prognosis.  In general CBF patients have a higher CR rate and an extended CR time. Therefore many centres may opt to treat with chemotherapy, rather than chemo + transplantation.

However the presence of C-KIT mutation ALONE is associated with a higher risk of relapse and shorter survival.  Studies have reported contradictory results with regards to prognostic significance of KIT mutation in combination with CBF.  Some studies suggest a decreased remission rate and survival whilst others suggest no effect of KIT mutation in CBF-AML.   It has also been proposed that C-KIT in AML patients with T(8:21) confers a poorer prognosis however no definite conclusions can be made in AML inv(16).

Treatment options may include

  • Trial
  • DA
  • DA+ myelotarg (as per NICE guidance in the UK)
  • DA+ midostaurin (if FLT3 positive)
  • CPX – (AML with previous MDS, AML with previous CMML, therapy associated-AML, AML with genetics consistent with MDS)
  • IHD inhibitors – (IHD1 ivosidenib, ID2 enasidenib)
  • Venetoclax (not currently available in UK)
  • Allogeneic stem cell transplant
  • TKI ???

 

There are no definitive answer to how all AML patients should be treated.  Individualised treatment plans are essential to improving outcomes in this population.  Below is a brief synopsis of treatments currently available/in trials with lots of references if anyone wants to do some further reading!

Myelotarg

NICE guidance for myelotarg

  • untreated de novo CD33+ AML
      • start with induction therapy when either the cytogenetic test confirms that the disease has favourable, intermediate or unknown cytogenetics (that is, because the test was unsuccessful) or when their cytogenetic test results are not yet available and
      • start with consolidation therapy when their cytogenetic test confirms that the disease has favourable, intermediate or unknown cytogenetics (because the test was unsuccessful)

 

Myelotarg has shown significant survival benefit for favourable and intermediate cytogenetic risk groups when assessed separately or together.  A consistent observation of myelotarg is a lack of benefit in patients with adverse risk. Therefore optimal use of myelotarg requires rapid identification of risk groups in order to allow avoidance of myelotarg in the adverse risk groups

Midostaurin

The addition of FLT3 inhibitor Midostaurin to treatment in patients who are FLT3 positive has been founds to improve 4 year overall survivial to 51% versus 44% in the group that recieved placebo.  Disease free survival has been reported at 26.7 months versus 15.5 months.

 

However either myelotarg or midostaurin can be chosen.  They cannot be used in combination and this once again highlights to need to clarify cytogenetic/molecular status before instigating treatment.

 

CPX

CPX is a dual drug liposomal encapsulation of cytarabine and daunorubicin.  Clinical studies have shown prolonged drug exposure and prolonged survival compared to DA 3+7, in older patients with newly diagnosed secondary AML.

This study included patients with the following diagnosis

  • therapy-related AML,
  • AML with a history of myelodysplastic syndrome [MDS] with and without prior hypomethylating agents,
  • AML with a history of chronic myelomonocytic leukemia [CMML],
  • de novo AML with MDS-related cytogenetic abnormalities

 

IDH inhibitors

IDH1 and IDH2 mutations are seen in approximately 15-20% of patients diagnosed with AML and these mutations are targeted by ivosidenib and enasidenib.  The mutations more frequently occur in patients of older age, with a normal karyotype and NPM1 mutation.  These treatment have been used so far in relapsed/refractory AML.  Enasidenib has been found to be effective salvage treatment inducing responses of approximately 40% of patients with IDH2 mutations.  There are ongoing phase 1/2 trials in newly diagnosed AML, which include these treatment upfront.

 

Venetoclax

Venetoclax has been approved in the United states by the FDA for use in combination with hypomethylating agents or low dose cytarabine as front line therapy for older patients with AML or those unfit for intensive treatment.  Venetoclax is a promising treatment for AML and to date has produced some deep and durable responses, with promising overall survival.  The challenges come with tumour lysis syndrome, continuation of treatment (i.e. do both treatments need to be continued lifelong), and predicting who will have a poor response to treatment

Dasatinib

Ongoing phase III trial currently.  Inital studies found acceptable toxicity and favourable outcomes with OS of 74.7%,

 

References

Prognostic Importance of C-KIT Mutations in Core Binding Factor Acute Myeloid Leukemia: A Systematic Review.
Ayatollahi H1, Shajiei A2, Sadeghian MH2, Sheikhi M3, Yazdandoust E2, Ghazanfarpour M4, Shams SF2, Shakeri S2.  Hematol Oncol Stem Cell Ther. 2017 Mar;10(1):1-7. doi: 10.1016/j.hemonc.2016.08.005. Epub 2016 Sep 3.
The importance of relative mutant level for evaluating impact on outcome of KIT, FLT3 and CBL mutations in core-binding factor acute myeloid leukemia.
Allen C1, Hills RK, Lamb K, Evans C, Tinsley S, Sellar R, O’Brien M, Yin JL, Burnett AK, Linch DC, Gale RE.  Leukemia. 2013 Sep;27(9):1891-901. doi: 10.1038/leu.2013.186. Epub 2013 Jun 20.
The Addition of Gemtuzumab Ozogamicin to Induction Chemotherapy in Acute Myeloid Leukaemia : An Individual Patient Data Meta-analysis of Randomised Trials in .  Lancet Oncol. 2014 August ; 15(9): 986–996. doi:10.1016/S1470-2045(14)70281-5.

Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation
Richard M. Stone, M.D.,  et al. August 3, 2017
N Engl J Med 2017; 377:454-464

CPX-351 (cytarabine and daunorubicin) Liposome for Injection Versus Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary Acute Myeloid Leukemia  Jeffrey E. Lancet et al.  Journal of Clinical Oncology 36, no. 26 (September 10, 2018) 2684-2692.
Stein EM, DiNardo CD, Fathi AT, et al: Ivosidenib or enasidenib combined with induction and consolidation chemotherapy in patients with newly diagnosed AML with an IDH1 or IDH2 mutation is safe, effective, and leads to MRD-negative complete remissions. 2018 ASH Annual Meeting & Exposition. Abstract 560. Presented December 3, 2018.
How we use venetoclax with hypomethylating agents for the treatment of newly diagnosed patients with acute myeloid leukemia.  Brian A. Jonas & Daniel A. Pollyea
Leukemia volume 33, pages2795–2804(2019)
Adding dasatinib to intensive treatment in core-binding factor acute myeloid leukemia-results of the AMLSG 11-08 trial.  Paschka P et al.  Leukemia. 2018 Jul;32(7):1621-1630. doi: 10.1038/s41375-018-0129-6. Epub 2018 Apr 17.
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Case 123 update 2

The plan is to commence treatment with DA+myelotarg

Cytogenetic and molecular studies show

t(8:21)

C-KIT positive

FLT3 negative

NPM1 negative

Would this change your management?

How are you going to monitor response in this patient?

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Case 123 update 1

 Our 44 year old male presented with the following full blood count

Hb 62

WCC 35

plt 22

Blood film identified blasts, with auer rods.

Blood film shows blasts cells, auer rods noted, thrombocytopenia and anaemia.

Differential has included AML and APML

 

Flow cytometry on peripheral blood:

CD33+, CD34+, CD13, CD19, CD56, HLA-DR+, CD117+, CD64+

What is your immediate management for this patient?

 

Longer term management?

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Case 123

44 year old man present to GP with fatigue, SOB and petechial rash.

What investigations would you perform?  Level of urgency??

Please reply to us (@TeamHaem) on Twitter and always include #TeamHaem to allow others to follow your comments. Please join in the debate and learn about haematological problems along the way. The case will continue to evolve over the coming week so keep checking #TeamHaem on Twitter for more information.

Please note – all cases on TeamHaem are entirely fictional to protect patient confidentiality.

TeamHaem are not a position of authority.  It is an educational platform to allow discussion and learning.

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Team Haem saves Christmas: The Summary

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

The haemolysis is self-limiting

No more parasites are seen

The pitted red cells that have lost malaria

Are being chomped up in the spleen

 

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

The DAT is clearly negative

Steroids were not given today

Jingle can go back to work

All elves shout hooray!

 

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

SUMMARY

With a parasite count of >5%, poor Jingle had severe malaria

As per NICE and WHO recommendations, IV artesunate was started.  This cleared the parasites quickly.

Delayed haemolysis is a recognised complication of IV artesunate therapy.  There is no clear evidence to guide management and all data comes from case reports/series.  Some clinicians have given steroids, and a proportion do seem to be autoimmune, although it is likely to be self-limiting.

It appears that most of the haemolysis is due to the destruction of red cells that become pitted following death of the parasites.

Further reading:

Lalloo, D.G., Shingadia, D., Bell, D.J., Beeching, N.J., Whitty, C.J. and Chiodini, P.L., 2016. UK malaria treatment guidelines 2016. Journal of Infection72(6), pp.635-649.

https://cks.nice.org.uk/malaria#!topicSummary

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TeamHaem Saves Christmas Part 3

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

Whilst sorting through the letters

Poor Jingle remembers a bite

A sneaky mosquito from an envelope

Then that naughty insect took flight

 

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

The parasites numbered 7%

Treatment was started straight away

Intravenous artesunate

Should keep the malaria at bay

 

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

Father Christmas is feeling better

Because Jingle has improved

No fevers and no more aches

He’s started singing Christmas tunes

 

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

But alas that’s not the end

Of this very sorry tale

For poor Jingle’s wee is dark

And he’s looking very pale!

 

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

Please review the blood film….

What is going on and what could be the mechanism?

What shall we do!

 

image005

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TeamHaem Saves Christmas Part 2

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

Father Christmas is so worried

Jingle sorts out both his lists

He checks on who’s behaving

And makes sure no-one’s missed.

 

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

Blood cultures have grown nothing

The blood film’s ready for review

There is no clear infectious cause

Please we all need help from you!

 

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

Please review the blood film and suggest next steps

What tests should be performed?

What treatment would you recommend?

 

Falciparumimage003

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TeamHaem help us save Christmas 2019! 🎄❄️ Part 1

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

A day or two ago 

Father Christmas needed help

Jingle, his top packing elf,

Just wasn’t feeling himself

 

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

His temperature was high

He was shaking head to toe

Mumbling, stumbling and confused

To the hospital he did go, Oh!

 

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

‘Oh my muscles are so achy’

‘My head is pounding bad!”

They took some blood tests from his arm

And his platelets were down a tad.

 

Jingle bells, jingle bells

Jingle all the way

Oh what fun it is to tweet TeamHaem’s case today!

 

What are our first steps?

 

Elf blood count: Hb 110, WBC 13, Neut 11, PLT 99

(Please note, elf physiology is extremely similar to humans)

 

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Case 121 – Summary!

This week we followed our patient with relapsed/refractory DLBCL through CAR T-cell therapy. We managed her cytokine release syndrome (CRS) and she is in remission thus far.

CAR T-cell therapy

Chimeric Antigen Receptor (CAR) T-cells are modified T cells in which the receptors are targeted against a specific tumour antigen. There a several ‘brands’ of CAR T-cells directed against CD19 which hold great promise in the treatment of relapsed/refractory B cell malignancies, including diffuse large B cell lymphoma (DLBCL), which has previously represented an area of unmet need.

Within the UK, eligibility and appropriateness for CAR T-cell therapy is discussed in MDT meetings at designated CAR T centres. Current products are licensed in DLBCL after two or more prior lines of treatment. Patients often require bridging therapy due to the timeframe of organising CAR T cell therapy (including MDT discussion, cell harvest, manufacture and production) and the therapy used is often down to clinician choice.

Patients receive lymphodepleting conditioning prior to infusion of CAR T-cell therapy. There is increasing recognition of specific toxicities related to CAR T-cell therapy:

 

Cytokine-release syndrome (CRS) is an escalated immune response triggered by CAR T-cell release of inflammatory mediators (cytokines) which often presents with fever, hypotension, hypoxia with or without evidence of end-organ dysfunction.

The severity of CRS can be graded according to the ASBMT Consensus Grading System

Table 1Table from Neelapu SS. Managing the toxicities of CAR T‐cell therapy. Hematological Oncology. 2019;37(S1):48–52. https://doi.org/10.1002/hon.2595

Centres which administer CAR T-cell therapy should have an algorithm for assessment and management of patients receiving CAR T-cell therapy to ensure early recognition and intervention of acute toxicities.

Management will often be guided by the grade of CRS. Supportive measures should be used including anti-pyretics, IV fluids and oxygen. It is vitally important to consider infection and treat accordingly.

Hypotension or hypoxia refractory to adequate fluid challenges or oxygen therapy, or those with Grade 2 CRS, can be considered for management with tocilizumab, an anti-IL-6 therapy. Depending on response patients may require intensive care admission with cardiovascular support. Corticosteroids can be considered for patients with Grade 3 or 4 CRS or those refractory to treatment above.

Patients receiving CAR T-cell therapy should be monitored closely with assessment of fluid balance, organ systems and CRS grade at least twice daily, or more frequently if there is a change in clinical status

 

Immune effector cell-associated neurotoxicity syndrome (ICANS) represents a toxic encephalopathic state and often presents with CNS signs including confusion, impaired higher cognitive function and delirium.

The severity of CRS is often graded using the ASBMT consensus grading system which incorporates the ICE score (Immune effector Cell‐associated Encephalopathy).

Table 2Table from Neelapu SS. Managing the toxicities of CAR T‐cell therapy. Hematological Oncology. 2019;37(S1):48–52. https://doi.org/10.1002/hon.2595

Management of ICANS is based on toxicity grade and options include supportive care, anti-IL-6 therapy (tocilizumab) when associated with CRS, or corticosteroids if not.

Patients receiving CAR T-cell therapy should be monitored closely with assessment of fluid balance, organ systems and ICANS grade at least 8 hourly, or more frequently if there is a change in clinical status. Both CRS and ICANS are reversible in most patients with the correct treatment, and so close monitoring and awareness of local policy is key.

There is also increasing recognition of medium term toxicities related to CAR T-cell therapy including prolonged cytopenias, risk for opportunistic infections, and B‐cell aplasia and hypogammaglobulinaemia.

 

References/further reading:

  • Neelapu SS. Managing the toxicities of CAR T‐cell therapy. Hematological Oncology. 2019;37(S1):48–52. https://doi.org/10.1002/hon.2595
  • Yakoub-Agha, I et al. Management of adults and children undergoing CAR t-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE). Haematologica Nov 2019, haematol.2019.229781; DOI: 10.3324/haematol.2019.229781

 

Please reply to us (@TeamHaem) on Twitter and always include #TeamHaem to allow others to follow your comments. Please join in the debate and learn about haematological problems along the way. The case will continue to evolve over the coming week so keep checking #TeamHaem on Twitter for more information.

Please note – all cases on TeamHaem are entirely fictional to protect patient confidentiality.

TeamHaem are not a position of authority.  It is an educational platform to allow discussion and learning.

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Case 121 – update 3!

We manage our patient with CAR T-cell therapy related CRS/ICANS with supportive care, including organ support from our critical care colleagues, and tocilizumab (anti-IL-6) therapy. She responds well to therapy and is stepped down to the haematology ward for ongoing care.

She is now 2 weeks following infusion of CAR T-cell therapy and observations are stable and she feels well.

How would you monitor this patient on discharge from hospital? What long term toxicities may you encounter?

 

Please reply to us (@TeamHaem) on Twitter and always include #TeamHaem to allow others to follow your comments. Please join in the debate and learn about haematological problems along the way. The case will continue to evolve over the coming week so keep checking #TeamHaem on Twitter for more information.

Please note – all cases on TeamHaem are entirely fictional to protect patient confidentiality. 

TeamHaem are not a position of authority.  It is an educational platform to allow discussion and learning.

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Case 121 – Update 2!

We suspect cytokine-release syndrome (CRS) in our patient 5 days post CAR T-cell infusion. We manage her with aggressive fluid boluses, low-flow nasal cannula oxygen and paracetamol. We also complete a septic screen and cover her with broad-spectrum antibiotics. Her observations initially improve and she remains on the haematology ward. The next afternoon at 2pm you are asked to review the patient again.

She continues to spike high-grade fevers despite regular paracetamol and oxygen requirement has increased to 40% via facemask.

On further assessment, you also note that our patient appears a little muddled and less orientated.

What would be your next steps in the acute investigation and management of this patient?

 

Please reply to us (@TeamHaem) on Twitter and always include #TeamHaem to allow others to follow your comments. Please join in the debate and learn about haematological problems along the way. The case will continue to evolve over the coming week so keep checking #TeamHaem on Twitter for more information.

 Please note – all cases on TeamHaem are entirely fictional to protect patient confidentiality.

 TeamHaem are not a position of authority.  It is an educational platform to allow discussion and learning.

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Case 121 – Update 1!

Our 48 year old patient with relapsed/refractory DLBCL is referred for consideration of CAR T-cell therapy. She is managed with IVE chemotherapy as a ‘bridging treatment’ and is subsequently admitted for CAR T-cell infusion.

You are the on-call haematology SpR. You are called at 2am regarding our patient. She is 5 days post CAR T-cell infusion, and the SHO on-call is concerned she is ‘septic.’ Current observations are:

Temp 39.2

BP 84/60

HR 78

SpO2 92% O/A

What would be your next steps in the acute investigation and management of this patient?

 

Please reply to us (@TeamHaem) on Twitter and always include #TeamHaem to allow others to follow your comments. Please join in the debate and learn about haematological problems along the way. The case will continue to evolve over the coming week so keep checking #TeamHaem on Twitter for more information.

 Please note – all cases on TeamHaem are entirely fictional to protect patient confidentiality.

TeamHaem are not a position of authority.  It is an educational platform to allow discussion and learning.

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Case 121 – The Beginning!

Welcome to another TeamHaem clinical case! Get involved and help shape the care of our fictional patient……

You review a 48 year old patient in lymphoma clinic. She was diagnosed with stage IVA diffuse large B cell lymphoma (DLBCL), with no evidence of MYC rearrangement, and completed treatment with six cycles of R-CHOP. End-of-treatment PET-CT demonstrated complete metabolic remission (CMR).

6 months following this she re-presented with stage IV relapsed disease and is currently post 2 cycles of R-GDP as ‘salvage chemotherapy.’ On review of a CT scan to assess disease response, she has progressive disease. She has no significant co-morbidity and ECOG performance status is 0.

What are the treatment options for this lady? Would you arrange any further investigations at this point?

 

Please reply to us (@TeamHaem) on Twitter and always include #TeamHaem to allow others to follow your comments. Please join in the debate and learn about haematological problems along the way. The case will continue to evolve over the coming week so keep checking #TeamHaem on Twitter for more information.

Please note – all cases on TeamHaem are entirely fictional to protect patient confidentiality.

TeamHaem are not a position of authority.  It is an educational platform to allow discussion and learning.

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Case 120 – Summary!

Thank you for everyone’s contributions this week. We discussed the management of a 57 year old lady who was suffering a major haemorrhage secondary to a road traffic accident.

The key points of managing a major haemorrhage (from haem perspective) are highlighted below:

  1. Identify Major Haemorrhage
    1. Early recognition essential to enable prompt provision of blood products
    2. Definitions:
      1. Bleeding which leads to heart rate >110bpm +/- systolic BP <90mmHg (NB be aware of patients baseline HR / SBP as individuals may be significantly compromised at the above parameters if their baseline levels vary from the general population)
      2. Loss of 1 blood volume in 24 hours / 50% blood volume in 3 hours / 125ml blood loss in 1 minute (NB these definitions are generally considered less useful as often detected retrospectively)
  1. Activate major haemorrhage protocol
    1. All hospitals within the UK should have a protocol
    2. Typically involves senior clinician, senior nurse, anaesthetist, transfusion lab, porter
    3. Ideally the team leader should designate one member of staff to liaise with the haematology lab

 

  1. Initial Management
    1. ABC approach and local control of bleeding
    2. Bloods:
      1. FBC, coag and clauss fibrinogen, biochem
      2. Group and save (x2 different times)
        1. Minimum identifiers: name, DoB, unique patient identifier number
        2. If unknown patient: Unique patient identifier number and gender
      3. Transfusion support (see below)
      4. Ascertain if on anti-platelets / anticoagulation (if possible)

 

  1. Transfusion Support
    1. Urgent blood / blood component transfusion. Major haemorrhage packs should be available as part of the major haemorrhage protocol. The documented ‘packs’ below are a guide and will vary slightly between hospitals such as 1 pool platelets may be available in pack. Need to switch to group specific / cross-matched packed red cells (PRCs) asap. Use cell salvage if available. Ongoing PRCs and components should be guided by blood results and near patient tests as soon as available alongside the ongoing clinical situation.
    2. Pack 1 of major haemorrhage pack
      1. PRCs and FFP in 1:1 ratio or 2:1 ratio (based on PROPPR trial – which improved deaths from bleeding but note no benefit in overall survival)
      2. 4 units PRCs
        1. If female of child bearing potential (<50 yrs) give Group O Rh D-ve Kell-ve
        2. If adult male or female >50yrs can consider Group O Rh D+ve
        3. Switch to group specific as soon as possible
      3. 4 units FFP
        1. Ideally Group AB but often in short supply in which case Group A (negative for high-titre anti-B)
    3. Pack 2 of major haemorrhage pack
      1. PRCs and FFP in 1:1 or 2:1 ratio (4 units PRCs : 4 units FFP)
      2. 1 pool platelets (consider giving platelets earlier if known to be on anti-platelets)
      3. Consider cryoprecipitate
    4. Transfusion based on blood results / near patient tests
      1. Aim to do traditional coagulation tests (PT, APTT, clauss fib) approximately every 30 mins. Be aware that these tests are not real-time so don’t represent the current clinical picture
      2. TEG / ROTEM provide real time results but should be used alongside traditional coag tests.Aim parameters
        1. Falling Hb: PRCS
        2. PTr / APTTr >1.5 : FFP 15-20ml/kg
        3. Clauss fibrinogen <1.5 (2 if obstetric haemorrhage) : 2 ppols of cryoprecipitate
        4. Platelets <50 : 1 pool platelets
  1. Pharmacological agents
    1. Tranexamic acid
      1. If trauma <3hrs / or risk of major haemorrhage / or not contraindicated as per CRASH 2 trial which demonstrated increased overall survival with TXA use. Give 1g TXA bolus then further 1g over 8 hours.
    2. Reversal agents for anti-coagulation (i.e protamine for heparin, praxbind for dabigatran)
  1. Other supportive measures
    1. Optimisation of hypothermia (aim >36.5C), acidosis, hypocalcaemia to reduce coagulopathy.
  1. Measures post major haemorrhage
    1. When bleeding has ceased – DEACTIVATE PROTOCOL (inform blood bank)
    2. Return unused stock to blood bank
    3. Monitor for complications from transfusions such as TACO
    4. Consider VTE prophylaxis when considered safe from bleeding perspective

 

References:

  1. Hunt BJ et al. A practical guideline for the haematological management of major haemorrhage. British Journal of Haematology. 170 (6). 788-803. 2015.
  2. Norfolk D. Handbook of Transfusion medicine 5th Edition. TSO. 2013.
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Case 120 – Update 4!

Well done team – with your input I’m pleased to say she has now stabilised and has stopped bleeding!!! To achieve this she has been transfused:

  1. 8 units red blood cells
  2. 8 units FFP
  3. 1 pool of platelets
  4. 2 pools cryoprecipitate

She undergoes surgery to stabilise her pelvis and is likely to be an inpatient for some time whilst she undergoes rehabilitation.

Questions:

  1. Now she is stable what would be the threshold to transfuse red blood cells? What her Hb target?
  2. What methods would you use to reduce her risk of thromboembolism?
  3. How would you ensure your hospital is managing major haemorrhages appropriately?

Please reply to us (@TeamHaem) on Twitter and always include #TeamHaem to allow others to follow your comments. Please join in the debate and learn about haematological problems along the way. The case will continue to  evolve over the coming week so keep checking #TeamHaem on Twitter for more information.

Please note – all cases on TeamHaem are entirely fictional to protect patient confidentiality.

TeamHaem are not a position of authority.  It is an educational platform to allow discussion and learning.

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Case 120 – Update 3!

Thank you for everyone’s ongoing input. Our patient is more haemodynamically stable but continues to have ongoing bleeding. She is now receiving group specific/compatible blood products. She has currently received:

  1. 6 units packed red cells.
  2. 6 units FFP
  3. 1g tranexamic acid with a further 1g TXA being infused

A repeat FBC / coagulation screen is in progress. Her latest TEG is below (dotted line is normal TEG for comparison).

TEG

R time: 8min (4-8min), K time: 5min (1-4min), a-angle: 30 (47-74), MA: 35 (55-73mm)

Questions:

  1. What blood products would you give based on the TEG?
  2. Based on the traditional FBC / coagulation screen what values would you be aiming for? e.g PT/APTT/fibrinogen/platelets greater than ?

Please reply to us (@TeamHaem) on Twitter and always include #TeamHaem to allow others to follow your comments. Please join in the debate and learn about haematological problems along the way. The case will continue to  evolve over the coming week so keep checking #TeamHaem on Twitter for more information.

Please note – all cases on TeamHaem are entirely fictional to protect patient confidentiality.

TeamHaem are not a position of authority.  It is an educational platform to allow discussion and learning.

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Case 120 – Update 2!

Thanks for everyone’s contributions so far!

Our 57 year old female patient is haemorrhaging following a road traffic accident. The multidisciplinary team are trying to establish source control of the bleeding. The major haemorrhage protocol has been activated. She has received packed red cells and FFP in a 1:1 ratio. She has received the following products:

  1. 4 units packed red cells: 1 unit Group O D negative, 3 units Group O D positive
  2. 4 units FFP: 2 units Group AB and 2 units Group A (negative for high-titre anti-B)

The baseline blood results are now available:

Hb 81, Plts 60, WCC 5. PT 19, APTT 42, Clauss Fib 1.4

The ABO group and D status result is available for interpretation (antibody screen in progress):

Forward Group Reverse Group
Anti-A Anti-B Anti-D1 Control A1 cells B cells
5 0 5 0 0 5

Questions:

  1. What ABO group is this patient? What is the Rh D status?
  2. What is the potential impact of the potential blood products that have already been given? How would you manage this?

Please reply to us (@TeamHaem) on Twitter and always include #TeamHaem to allow others to follow your comments. Please join in the debate and learn about haematological problems along the way. The case will continue to  evolve over the coming week so keep checking #TeamHaem on Twitter for more information.

Please note – all cases on TeamHaem are entirely fictional to protect patient confidentiality.

TeamHaem are not a position of authority.  It is an educational platform to allow discussion and learning.

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