Case 76 – update 3

Our patient is started on recombinant factor VIII replacement and achieves a trough level of 100%. Neurosurgery is not required. Genetic samples are sent to examine the F8 gene to see where the mutation is as this can help investigate other family members and can also predict inhibitor formation.

 

‘Inhibitors’ are alloantibodies against the VIII replacement rendering them ineffective and therefore cause major interference with treatment of haemophilia when they occur.

 

Here is the family tree of our patient:

Haemophilia family tree

 

Questions

  • What increases the risk of inhibitor formation?
  • Which relatives would you be keen to counsel and test?

 

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.

Posted in Uncategorised

Case 76 – update 2

Factor assays are back. IX, XI and XII are within normal limits for neonates but VIII is <1%. This confirms the diagnosis of severe haemophilia A.

 

The child is transferred to the regional haemophilia centre for intensive VIII replacement and neurosurgical opinion.

 

Questions

  • How is haemophilia A inherited? What may you ask in the family history?
  • As well as a low VIII what other tests would you want to do?
  • How do you treat haemophilia A?

 

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.

Posted in Uncategorised

Case 76 – update 1

Our three day old child is admitted unwell and has deranged clotting with a markedly prolonged APTT. The team wanted an ultrasound scan which confirms a small intraparenchymal bleed. Repeat coagulation testing shows:

  • PT 18s (12-14 adult)
  • APTT 92s (30-38 adult)
  • APTT 50:50 mix with normal plasma 38s
  • Clauss fibrinogen 2.6g/L (2-4)

Liver function tests are within normal limits. The parents are fit and well with no past medical history. The pregnancy was uneventful save for an element of iron deficiency which resolved with supplementation.

Questions

  • Given the clinical history and the coagulation results what are the differential diagnoses?
  • What does 50:50 mix mean?
  • You’re in a district general hospital – what would be your immediate management?

 

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.

Posted in Uncategorised

Case 76 – the beginning

You are working in the emergency department of a district general hospital. Parents bring a three day old child in for assessment as he has been non-specifically unwell, looking pale and feeding poorly. He was born at term by spontaneous vaginal delivery and was allowed home a day later. APGAR scores were 9 at one and five minutes. He has some bleeding around his umbilical stump so a FBC and coagulation screen were checked:

  • FBC – within reference range
  • PT 19s (12-14 adult)
  • APTT 89s (30-38 adult)
  • Clauss fibrinogen 2.5g/L (2-4)
  • Glucose – normal

 

Questions

  • What are your differential diagnosis of the coagulation results?
  • What are you concerned about with the baby?

 

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.

Posted in Uncategorised

Case 75 – summary

Case 75 – Summary!

Thank you for all of the contributions with Case 75, where we encountered a 43 year old who presented with back pain and circulating plasma cells in his peripheral blood.

In summary we established that this young man had a mild leucocytosis (WCC 23) with marked anaemia and thrombocytopenia (Hb 73, Plts 45). He had associated acute kidney injury and hypercalcaemia. He had an IgA paraprotein (18g/l) with a discrepantly high serum free light chain ratio of 6543. B2 microglobulin 8.7 and hypoalbuminaemia 28.

He had >2 x 109/L of circulating cells with the following immunophenotype (CD20+, CD38+, CD138+, CD56-) confirming the diagnosis of primary plasma cell leukaemia (he had no previous history of myeloma). He had a high tumour burden in his bone marrow with 66% plasma cells. He had a normal karyotype (even though he has normal cytogenetics he has high risk disease and this would not influence our future management). Within our case we did not focus upon bone imaging.

He received treated with a bortezomib-based regime (velcade, thalidomide and dexamethasone). We would aim to consolidate with a melphalan autologous stem cell transplant and discussed with transplant team regarding the role of an allogenic stem cell transplant.

Plasma cell leukaemia
Primary plasma cell leukaemia is a rare, aggressive plasma cell dyscrasia with a poor prognosis. It is defined by the presence of >2×109/L peripheral blood plasma cells or plasmacytosis accounting for >20% of the differential white cell count, and does not arise from pre-existing myeloma.

Primary plasma cell leukaemia has different clinical, laboratory and biological in comparison to myeloma as listed below:

Clinical features:
Younger age at presentation
More advanced disease at presentation (>80% with Stage III disease)
More extensive bone disease
Extramedullary involvement is more common e.g hepatosplenomegaly, lymphadenopathy, plasmacytomas, leptomeningeal disease

Laboratory features:
Leucocytosis and more marked cytopenias in comparison to multiple myeloma
Higher incidence and severity of renal impairment, hypercalcaemia and LDH/B2 microglobulin

Blood film: commonly leucoerythroblastic along with circulating plasma cells
Bone marrow biopsy: typically high tumour burden

Immunophenotype: CD38+, CD138+. In comparison to multiple myeloma more likely to be:
• CD56- (likely due to higher incidence t(11;14)
• CD117-, HLA-DR-
• CD20+, CD23+

Cytogenetics:
There are usually multiple genetic abnormalities (and often high risk abnormalities) present at diagnosis as opposed to the gradual acquisition of genetic events that occur in end stage myeloma / secondary plasma cell leukaemia. In primary plasma cell leukaemia the genetic aberrations present result in bone marrow microenvironment-independent tumour growth.

Common cytogenetic abnormalities:
• IgH translocations – most commonly t(11:14), t(14:14), t(14:16)
• Hypodiploidy
• Del(17p), del (13q), del(1p21), ampl(1q21)

Management:
Given the rarity of this condition there is a paucity of data on treatment regimens and participation in a clinical trial, if available, is recommended. However, bortezomib are known to be associated with better outcomes as it more rapidly reduces tumour load and has been found to overcome some adverse cytogenetics including del(17p) and t(4;14).

Bortezomib-based therapies:
There is no evidence to guide a particular bortezomib-based regimen and various regimens are used internationally reflecting different countries historic use and also access to first line immunomodulating or novel agents.

Regimens commonly in used for first line therapy include:
• VTD – bortezomib, thalidomide and dexamethasone
• RVD – lenalidomide, bortezomib and dexamethasone
• PAD – bortezomib, doxorubicin and dexamethasone
• VCD – cyclophosphamide, bortezomib, dexamethasone

Commonly in the UK VTD is used as first line therapy. Whereas thalidomide is often replaced by lenalidomide in this regime in Europe where Lenalidomide is available as first line. Lenalidomide has been shown to be more efficacious than Thalidomide in multiple myeloma.

Supportive therapies
• Blood transfusions
• Antimicrobial prophylaxis
• Prophylaxis against tumour lysis syndrome should be instituted
• Bisphosphonates
• Consideration for radiotherapy for problematic plasmacytomas

Autologous Haematopoietic Stem Cell Transplant:
Autologous stem cell transplant improves both progression-free survival and overall survival and should be encouraged if the patient is considered fit to undergo the procedure providing they have achieved at least a partial response. Conditioning regimens are melphalan-based. Trials have discussed the potential role for consolidative treatment (e.g further cycles of VTD but this is not available within the UK) or maintenance therapy (e.g lenalidomide)

Allogenic Haematopoietic Stem Cell Transplant
Unfortunately the prognosis following autologous stem cell transplant remains poor and allogenic stem cell transplants are associated with reduced risk of relapse in comparison (albeit with higher rates of TRM). This could therefore be considered in young, fit individuals following discussion within the MDT. However, there remains to be limited data in this area and ideally this should be performed as part of a clinical trial.

References:
Niels et al. How I treat plasma cell leukaemia. Blood. 120(12), 2376-2389. 2012.

Posted in Myeloma/paraproteins | Tagged , , , , , ,

Case 75 – update 3

Bortezomib-based regimes are associated with better outcomes as it more rapidly reduces tumour load and reverses complications.

What would you combine Bortezomib with in our patient?

How would you consolidate this treatment if response achieved?

Would the cytogenetics results influence your treatment options?

Please reply with #Teamhaem so everyone can be involved!

Posted in Myeloma/paraproteins | Tagged , ,

Case 75 – update 2

Our patient has >2×109 plasma cells in peripheral blood without a history of myeloma consistent with a diagnosis of primary plasma cell leukaemia (pPCL). Flow is typical of  pPCL – myeloma markers with CD56- and CD20+. Our patient had a normal karyotype, which is slightly unusual for pPCL.

What cytogenetic abnormalities would you typically expect for pPCL in comparison to newly diagnosed multiple myeloma?

How would you treat this patient?

Please reply with #Teamhaem so everyone can be involved!

Posted in Myeloma/paraproteins | Tagged ,

Case 75 – update 1

Thanks for everyones contributions. The following results are now back:

 

SFLC kappa: lambda ratio: 6543.

Igs and serum electrophoresis: Immuneparesis and IgA kappa paraprotein 18

B2 microglobulin 8.7. Albumin 28.

Bone marrow biopsy: 66% plasma cells morphologically.

Flow cytometry (blood and BM): CD 20+, CD38+, CD138+, CD56-

MRI in progress

 

 

What is the diagnosis?

What’s the criteria for plasma cell leukaemia?

How do we differentiate between myeloma and primary plasma cell leukaemia?

What are the cytogenetics results likely to be?

 

Please reply with #Teamhaem so everyone can be involved!

 

 

 

 

 

 

Posted in Myeloma/paraproteins | Tagged , , , ,

Case 75 – the beginning

A 43 year old man presents to A+E with severe back pain. He also has a 2 month history of progressive fatigue. On examination he has pallor, splenomegaly and marked tenderness to L2-L5.

How would you further assess this patient? What initial investigations would you perform?

Please reply via twitter using the hashtag #teamhaem

Posted in Myeloma/paraproteins | Tagged , ,

Case 74 – summary

Thankyou for your input this week!This week we had a look at a few abnormalities that can be seen on coagulation screens in a pre procedure setting.
The first thing to say is there is no replacement for a good old fashioned bleeding history! Patients may have a significant bleeding history, as seen in our second case, but with a normal coagulation screen. 
With all patients a medication history and family history, if there is a bleeding tendency, should be asked.

Our first patient was found to have a prolonged aptt and intrinsic factors were checked. These revealed a low factor XII, which is of no clinical significance and shouldn’t produce a bleeding tendency.

Our second case was slightly more interesting with a significant operative bleeding history but apparent normal coagulation screen. A number of tests were normal, but a 2-stage factor VIII was low. Patients with haemophilia may have a discrepant 1 and 2 stage assay, and their bleeding may be out of proportion to their apparent 1 stage factor 8. Certain genetic mutations have been associated with this – e.g. Factor VIII A3 domain mutation. Below is a link to a nice case report of this. 
http://onlinelibrary.wiley.com/store/10.1046/j.1365-2141.1999.01460.x/asset/j.1365-2141.1999.01460.x.pdf;jsessionid=C0FFE34DDCDD2563BFFB0DA5EA5A88FD.f03t04?v=1&t=j0mrvh9i&s=2678df26547954b719a0f070ac9e3c11886921a2
Our 3rd case this week looked at a patient with vasculitis who was on plasma exchange, who had a prolonged APTT. When a patient is on exchange it is important to enquire whether they are being exchange with as clotting factors can be depleted.

The thrombin time on this sample was >300, with a normal reptilase and protamine time. Thus indicating heparin contamination. 

A peripheral blood sample was taken showing a normal coagulation screen.

So that was a whistle stop tour of a couple of clotting cases, highlighting the importance of a good history!

Is there anything you want to ask?

Join us on Twitter @TeamHaem and let us know what your thoughts are, what questions you have and what you want to do as we see this case evolve over the next week. Remember to use #teamhaem on all your posts to help us follow the case! 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

Posted in Acquired bleeding, Anticoagulation, Inherited bleeding | Tagged , , , , , , ,

Case 74 – part 3

We have our 3rd and final case of the week!
A 40 year old man who has a vasculitis ,who has been requiring plasma exchange, needs to have a new line put in for exchange.
The renal team are concerned about doing this as the clotting is deranged.
PT 13 APTT 75 FIB 5.7
What do you want to ask them, what would you do next?

Join us on Twitter @TeamHaem and let us know what your thoughts are, what questions you have and what you want to do as we see this case evolve over the next week. Remember to use #teamhaem on all your posts to help us follow the case! 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

Posted in Acquired bleeding, Anticoagulation | Tagged , , , , ,

Case 74 – part 2

So our second case starts with a phone call from the anaesthetic consultant in the pre op clinic.
He has a 20 year old man that needs a wide excision of a suspicious mole on his back. 
He has been looking through his medical history and the patient had a tonsillectomy aged 8 and had significant bleeding post operatively requiring a blood transfusion.

He also had a tooth extraction age 16 which required repacking and suturing due to bleeding.
The anaesthetist has done a coag screen pt 13 aptt 34 fib 3.5

Fbc normal

U&e and lft normal
What would you do next? Do you want to ask any other questions?

Join us on Twitter @TeamHaem and let us know what your thoughts are, what questions you have and what you want to do as we see this case evolve over the next week. Remember to use #teamhaem on all your posts to help us follow the case! 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

Posted in Acquired bleeding, Inherited bleeding | Tagged , , , , , ,

Case 74 – part 1

Welcome to our new teamhaem cases!This week we will run through some short cases with pre operative coagulation screen abnormalities!
Our first patient is a 25 year old male who has been admitted to the surgical assessment unit with abdominal pain. The team think he has appendicitis and want to take him to theatre later today
He has had routine bloods done which show HB 135g/l plt 300 wcc 16 neut 11

Pt 13 aptt 55 fib 4.0
What do you want to ask in the history?

What tests do you want to do?
Join us on Twitter @TeamHaem and let us know what your thoughts are, what questions you have and what you want to do as we see this case evolve over the next week. Remember to use #teamhaem on all your posts to help us follow the case! 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

Posted in Acquired bleeding, Inherited bleeding | Tagged , , , , ,

Case 73 – summary

This week our case involved the care of a 10 year old girl with SCD who had transfered her care to the UK. She presented in outpatient clinic for the first time and we had to determine her management. During subsequent screening she went on to have elevated transcranial Doppler results that lead to exchange transfusions. She then was changed to hydroxycarbamide therapy at her request after 2 years and full counselling. 

An approach to a new SCD patient in clinic:

History:

  • Current symptoms: pain, infections?
  • Previous admissions particularly focussed questions on any previous chest crisis/sequestration events.
  • Previous transfusion history.
  • Development and puberty – refer to endocrine if no signs after 14 years females and 14.5yrs males.
  • Enuresis?
  • Pica?
  • Neurological issues?
  • Drug history – Penicillin v and folic acid?
  • Knowledge of local service and who to call for advice if concerns
  • Family history – ? Any other family members at risk
  • ? Registered on to National haemoglobinopathy database – leaflet available if patient not already registered.

Examination:

  • Growth and development. Pubertal features if of appropriate age.
  • Check for murmur, jaundice, pallor and spleen size. 
  • BP – if elevated this is a risk factor for CVA in children.

Investigations/Management:

  • Urinalysis – only needed annually
  • FBC, Retics
  • Film (only indicated at first visit unless concerns)
  • U&E and LFTs (baselines to compare if unwell) – interestingly 50% of SCD children will have gallstones by age 10 years. 
  • Blood group and extended phenotyping including ABO,RhDCcEe, Duffy type, S s including U typing if indicted, Kidd and Kell. Genotype may also be indicated looking for variety RHCE genes that are commoner in SCD population. Genotype will be required if had transfusion in last 3 months as serology won’t work.
  • HPLC and a confirmatory test using another technique required if first presentation.
  • Echo if murmur or low o2 sats.
  • TCD screening indicated 2-16 years annually.
  • MRI Brain indicated if headaches, developmental concerns or elevated TCD.
  • MRI hip/shoulder if persisting pains in these areas as at risk of AVN. 
  • Penicillin V should be Rx from 3 months old as it has been shown that as Hb F falls there is a risk of hyposplenism.
  • Folic acid.
  • If travelling needs Men ACWY vaccines and malaria prophylaxis.
  • Ensure had all childhood vaccinations including pneumococcal vaccine and the pneumococcal vaccine should be repeated 5 yearly. 
  • Annual flu vaccination
  • Hep B vaccination
  • Consider annual blood borne viral screening in regularly transfused patients.

Reviews should be 3 monthly up to age 2 years then minimum 6 monthly to 5 years and can be extended depending on clinical picture.

TCD screening:

TCD screening indicated 2-16 years annually. 

If TCD results 170-199 cm/sec warrants at repeat in 1-4 months maybe sooner if less than 10 years. 

If > 200cm/sec may be a role in quick repeat scan prior to Rx depending on individual circumstances. If persistently abnormal to commence regular transfusions. Can review Tx after minimum of 1 year and consider transferring to hydroxycarbamide. If changing to HC needs slow taper of Tx after reaching HC max tolerated dose.

MRI/MRA Brain important if abnormal TCD to detect any subclinical infarcts  (39% by 18 years will have evidence of silent infarcts) and assess for vasculopathy. As any evidence of this will lead to a regular transfusion plan for secondary stroke prevention. 

Risk factors for CVA in children: 

  • TCD >200cm/sec
  • Previous infrarcts
  • Cerebral vasculopathy
  •  Recurrent Sepsis
  • Rapid rise in Hb level
  • Renal disease, Diabetes and Blood pressure

Evidence base that influenced the above:

  • SIT trial 2014 (1) : Established TX as effective in secondary CVA prevention. RCT ,29 centres internationally with children 5-15 years with at least one infarcts on screening MRI scan. 196 children in total.Arms were std care (observe. no HC) Vs Tx >90g/l with aim HbS <30%. Results: 58% Relative risk reduction in recurrent infarcts in Tx group. Also improvements in QOL, priapism, AVN, Acute chest crisis and painful crisis (all stat significant) . NNT to prevent 1 CVA was 13. Though infarcts were still seen in Tx group suggesting in secondary CVA prevention transfusion not always effective. 
  • STOP trial 1998 (2) : Established role of Tx in primary stroke prevention. RCT with children SCD 2-16 years no previous CVA and Doppler USS abnormal >200cm/sec in MCA or ICA. High doppler pt randomised to std care Vs Tx with Hb S <30 and target Hb <120. Exchange or top up could be used. Once reached targets above transfused 3-4 weekly. Results:Trial stopped early as 92% RRR in Tx arm of CVA. NNT in treatment group 7 to prevent 1 CVA. 
  • STOP 2 2005 (3): stopping Tx in patients for primary prevention not safe. Extension of STOP study where children with high TCD who had normal dopplers after 30 or more months on Tx were recruited and any other children fulfilling same criteria. Must have normal TCD x2 and have had Tx for at least 24 times in the 30 month period and had HbS <30% on at least 20 out of 30 months. Assigned to a stop Tx group vs ongoing Tx. Results: trial stopped early as more CVA or abnormal Doppler results in STOP group (16 events: 14 abnormal doppler and 2 CVA in Stopped group vs none in ongoing Tx group) stat significant finding  P< 0.001
  • SWiTCH 2012(4): No excess CVA in secondary prevention CVA patients changed to HC but stopped early as liver iron loading between two arms equivalent. RCT recruited 134 patients non- inferiority trial looking at SCD patients with prev CVA and iron overload on transfusion for at least 18 months. Arms compared HC and venesection to Tx and chelation. Results: There were 7 CVA out of 67 pt in HC arm Vs none in Tx arm with CVA – still non inferior when trial stopped early due to evidence of equivalent iron loading.
  • TWiTCH 2015 (5): confirms non inferior to transfer to HC after at least 1 year of regular Tx in patients with previously abormal TCD and no vasculopathy. Multicentre trial in USA and Canada, 121 patients age 4-16 years with abnormal TCD and non severe vasculopathy. Hydroxycarbamide arm patients started at 20mg /kg/ day and titrated to max tolerated dose with overlap median of 6 months with transfusion. Results: primary endpoint of similar TCD measurements at 2 years, P value 0.023. Some criticism that primary endpoint too short to establish if difference in groups. 

Regular Tx: exchange Vs top up?

BSH guidance advises that either exchange or top up may be indicated for primary stroke prevention. 

Points to consider:

  • In this case the patients baseline Hb was on the higher side possibly increasing the risk of hyperviscosity if simple top ups used. This would also make reducing HbS to <30% challenging without getting Hb higher than advised 100-110 target. 
  • Iron overload: should have 3 monthly ferritin and liver scans 1-2 years to quantify overload if concern.Worsened overload in top up compared to exchange.
  • Access problems- need line for exchange.
  • Alloimmunisation rates similar for both techniques even though often more blood used in exchange.

If exchange used ideally blood should be ABO,Rh and Kell matched, Hb S neg, allo ab neg and less than 7 days old. 

Patients on regular Tx should have HepB vaccines and annual blood borne viral monitoring. 

Hydroxycarbamide initiation after primary stroke prevention: 

TWiTCH supports changing from regular transfusion to Hydroxycarbamide after a minimum of 1 year of regular transfusion. Discussions regarding when and if this should occur need to be made on an individual basis.

Transfer to HC therapy should be gradual with initiation at 20mg/kg/day and slow titration to max tolerated dose with weaning blood transfusion volumes once MTD reached. 

Patients should be counselled regarding need to stop Hydroxycarbamide 3 months prior to conception and that it has no effects on fertility. 

References:

Excellent overview of SCD in CNS disease:

DeBaun and Kirkham. Central nervous system complications and management in sickle cell disease. Blood 2016;127(7):829-838.

Useful UK guidelines:

Davis et al. Guidelines on red cell transfusion in sickle cell disease. Part I principles and laboratory aspects. BJH 2017 176 (2) 179-191.

Davis et al. Guidelines on red cell transfusion in sickle cell disease. Part II indications for transfusion. BJH 2017 176 (2) 192-209.

NHS screening programme. Sickle cell disease in childhood. Standards and guidelines for clinical care. 2nd edition October 2010. 

Papers:

1) DeBaun et al. Controlled trial of transfusions for silent cerebral infarcts in sickle cell anaemia. NEJM 2014;371:699-710.

2) Adams et al. Prevention of first stroke by transfusions in children with sickle cell anaemia and abnormal results in transcranial Doppler ultrasonography. 

3) Adams et al.Discontinuing prophylactic transfusions to prevent stroke in sickle cell disease. NEJM 2005;353:2769-2778.

4) Ware et al. Stroke with transfusions changing to hydroxyurea (SWiTCH). Blood 2012;119(17) 3925-3932.

5) Ware et al. Hydroxycarbamide versus chronic transfusion for maintenance of transcranial flow velocities in children with sickle cell anaemia – TCD with transfusions changing to Hydroxyurea. (TWiTCH): a multicentre open label phase 3 non-inferiority trial. Lancet 2016 387; 10019 661-670.

Posted in Anaemia, Haemoglobinopathy, Transfusion | Tagged , , ,

Case 73 – update 2 

Given the girls high Right MCA doppler at screening the patient started regular transfusion for prevention of CVA. This was initiated due to Adams et al 1998 NEJM paper that showed a 92% risk reduction in patients with high dopplers and SCD. She has had a good response to exchanges and so far has not developed any allo antibodies or had any haemolytic reactions. She has an MRI brain that shows no evidence of cerebral vasculopathy. 

After two years of regular exchange transfusion the patient and her mum ask you about the possibility of changing treatment. Her mum feels that the visits for exchange are interfering with school. 

What are the treatment options for this girl two years into successful exchange treatment? 

What evidence may support a change in treatment?

How should a change in treatment be initiated if warranted? 

Reference:

Adams et al. Prevention of a first stroke by transfusions in children with sickle cell anaemia and abnormal results on trans cranial Doppler ultrasonography. NEJM; 339, 5-11.

Posted in Anaemia, Haemoglobinopathy, Transfusion | Tagged , , ,

Case 73 – update 1

Thanks for all your suggestions so far. When the patient was seen for the first time the following was established:

History:

She is now age 10 and moved to the UK from west Africa a few months ago with her parents. She has a cousin with sickle cell disease but has no siblings. 

She has not had any previous chest problems apart from a course of antibiotics for a chest infection a few years ago. She does get pains in her legs but never needed hospital admissions for pain.

Since her move to the UK she has had a few episodes of leg pains intermittently. These settle with rest and paracetamol plus ibuprofen. She has had a few days off school because of this. Her mum feels the cold weather is to blame.

She has never had blood transfusions.

Her mum is unsure if she has been vaccinated.

No concerns with her development. 

She has never had TCD measurements. 

 She has no sign of puberty at present. 

She has no symptoms of picca,enuresis or dyspnoea.

On examination:

She is between 9th and 25th centile for height and 25th centile for growth when you plot it on a growth chart.

Her blood pressure and pulse are normal for age. She has oxygen saturations of 97% on air. 

Her chest is clear, heart sounds are normal and she has no palpable spleen. 

Investigations:

Her urinalysis is normal.

She has a baseline echo arranged given slightly low oxygen saturations this shows no signs of pulmonary hypertension. 

She has a blood film that was reviewed and showed prominent sickle cells and Howell jolly bodies. There were a few target cells but not the predominant feature.

Her Baseline Hb is around 90

HPLC confirms Hb SS. This sample was sent to another lab for confirmation as this was her first attendance to the hospital.

She has a high retic count and normal ZPP.

She has blood phenotyping given the possible need for transfusion. This includes full ABO, Rr,Ee,Cc,Ss (U type if s neg ),Fya,Fyb,Jka,Jkb typing. Genotyping for Rh group could also be considered as variant RhCE is more common in these patients.

She has a full viral screen performed.

Management:

You introduce her to the haemoglobinopathy specialist nurse and she is going to have a home visit and discuss the national haemoglobinopathy register with the family. 

You prescribe penicillin V and folic acid. 

You speak to her GP regarding need for repeat prescriptions for penicillin and folic acid.

 You also arrange catch up childhood immunisations and inform them of the need for 5 yearly pneumococcal vaccinations, annual flu vaccinations and arrange for hepatitis B vaccines. 

Her TCD is booked for next week and is to be performed annually. 

You are feeling rather pleased that you remembered to cover so much in your first meeting. 

A week later……

You get a call from the TCD list saying that the patient has a Right MCA velocity of 210 msec

What is she at risk from?

What evidence supports management in this situation?

Should we transfuse her? If so how?

What requirements should be met as a minimum if she is to have a blood transfusion?

Posted in Anaemia, Haemoglobinopathy, Transfusion | Tagged , , ,

Case 73 – the beginning

A 10 year old girl attends paediatric outpatient clinic with a history of Sickle Cell Disease. She was born abroad and has just moved to the UK. 

What history should you establish? 

What should you note on examination?

How would you confirm the diagnosis and monitor her disease?

Posted in Anaemia, Haemoglobinopathy, Transfusion | Tagged , , ,

Case 72- summary

Answers

A – hereditary elliptocytosis

B – hairy cell leukaemia

C – metastatic prostate cancer

Case A

The first case, we started with something relatively straightforward:

img_1615

This was a blood film of a 21 year old pregnant women who was anaemic.

Numerous elliptocytes are noted on this blood film.  The patient had been noted to be anaemic on routine pregnancy bloods.  Frequently, hereditary elliptocytosis is discovered by chance from a blood film, or a marginally raised bilirubin.  As suggestive by one of our followers, reviewing blood films of first degree relatives may be useful as the inhertiance is autosomal dominant.   HE is due defects in either the structure or quantity of the cytoskeletal proteins responsible for maintaining the biconcave morphology of RBCs. Mutations in either alpha- and beta-spectrin are most commonly responsible, but mutations in other cytoskeletal proteins (band 4.1 and glycophorin) are also described.

For patients with mild haemolysis, anaemia may increased during pregnancy, infections and folate deficiency.

 

Other causes of acquired elliptocytic or fragmented red cells need to be excluded including haematinic deficiency and MAHA.

Patients with haemolysis should be given folate replacement and supportive treatment during exacerbations of anaemia.  Splenectomy is only indicated in severe haemolytic anaemia.

 

 

 

Case B

A 40 year old gentleman present with the following FBC:

  • WCC 2.9×109/L (4-11)
  • Neuts 0.9×109/L (1.7-7)
  • Lymphocytes 1.4×109/L (1.5-4.5)
  • Monocytes 0.2×109/L (0.2-1)
  • Eosinophils 0.3×109/L (0-0.5)
  • Basophils 0.1×109/L (0-0.1)
  • Hb 55g/L (130-180)
  • MCV 88fL (82-98)
  • Platelets 31×109/L (150-450)

His bone marrow trephine is reviewed:

 

This patient was given a diagnosis of hairy cell leukaemia.  Typically blood counts will show a monocytopenia, and may have evidence of a pancytopenia.  Bone marrow aspirate is often unsuccessful, therefore trephine biopsy is essential.  Trephine biopsy typically demonstrates the “fried egg appearence” – the hairy cells typically have a clear zone surrounding, leaving plenty of room between cells.  Typically there is a diffuse interstitial infiltrate.   The reticulin is usually increased.  Agents used for immunohistochemistry include anti-CD20, annexin A, DBA44 and CD11c.  TRAP (tartrate-resistant acid phosphatase) can also be tested by means of a monoclonal antibody on the trephine biopsy.

It is important to appreciate there is also limited normal haematopoiesis on this bone marorw trephine, resulting in the pancytopenia demonstrated on the peripheral blood count.

 

Case C

This was 58 yr old gentleman presents to GP feeling tired.  Bloods show Hb 78, wcc 2.1, platelets 52. Blasts were seen on film, aspirate dry tap.

 

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This patient had a PSA of >3000, suggest metastatic protate carcinoma.  This trephine shows a diffuse infiltrate of non-haematopoietic cells.  Typically prostatic involvement is suggested by cribiform, microglandular pattern, with fibrosis and new bone formation.  It is essential to first note the lack of megaryocytes/erythroid islands/ and granulopoeisis.  The gladular pattern can be appreciated as weel as thickening of the trabeculae in keeping with new bone formation.  IHC can help confirm the diagnosis and stains for PSA, PSAP, and cytoekeratin markers are available.

 

 

Thanks to all our followers that also contributed pictures to our morphology week!

Media preview

Cabot ring, stained with giemsa 7.2 – microtubular remnants of mitotic tubules that are involved in mitosis.  Cabot rings have been observed in megaloblastic anemia, lead poisoning, severe anemia, leukemia, myelodysplastic syndromes, and other cases of dyserythropoiesis

Media preview

A case of dual pathology – AML and plasma cell dyscrasia.

 

We always welcome interesting pictures – so remember to tweet @teamhaem the next time you come across something of interest!

Join us again next week for another case!

 

Posted in Anaemia, Chronic leukaemia, Lymphoma, Related to other specialities | Tagged , , , , ,

Case 72 – case C

Sticking with bone marrow trephine! What do you think of this one?

58 yr old gentleman presents to GP feeling tired.  Bloods show Hb 78, wcc 2.1, platelets 52. Blasts were seen on film, aspirate dry tap.  What other investigations would you suggest?

 

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Posted in Related to other specialities | Tagged , , ,

Case 72 – case B

A 40 year old gentleman present with the following FBC:

  • WCC 2.9×109/L (4-11)
  • Neuts 0.9×109/L (1.7-7)
  • Lymphocytes 1.4×109/L (1.5-4.5)
  • Monocytes 0.2×109/L (0.2-1)
  • Eosinophils 0.3×109/L (0-0.5)
  • Basophils 0.1×109/L (0-0.1)
  • Hb 55g/L (130-180)
  • MCV 88fL (82-98)
  • Platelets 31×109/L (150-450)

His bone marrow trephine is reviewed:

How would you describe this trephine?

What further tests would you do to make a diagnosis?

Posted in Chronic leukaemia, Lymphoma | Tagged , , ,