Case 96 – update 2

An USS abdomen has been performed which confirms mild hepato-splenomegaly. CXR was reported as normal. Faecal elastase, TTG, TFTs, ILGF1 all normal.

You phone the haematology registrar to look at the blood film in view of the abnormal FBC.

Questions:

1. Please comment on the blood film features and what are your differentials?

2. What other blood tests or investigations might be helpful?

3. What is your next step?

Here are the blood films:

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 Uncategorised

Case 96 – update 1

This 13 month old boy was born at 39/40 by normal delivery. His birth weight was 2.6kg. He is normally fit and well with no significant problems and no previous hospital admissions. He is up to dates with all his immunisations. He was exclusively breastfed till 6 months of age. There is no significant family history and his 5 year old sister is fit and well.

There have been no fevers, but vomiting a couple of times a day and green loose stools 1-2 times per day in recent weeks.

On examination, there is no lymphadenopathy, though you can feel a 2cm liver and a palpable spleen tip. There is no petechial rash. You suspect the rash on the arm could be an abscess but you are not sure. There are the odd basal crackles on chest auscultation. You also think he may or may not look slightly unusual.

You admit him for dietitian input and to establish a feeding plan.

You get these initial blood results:

Hb 85

Platelets 52

MCV 89

WBC 35

Neut 14

Lymphocytes 11

Monocytes 8.3

U&Es and LFTs are unremarkable. CRP 22, ESR 15.

Questions:

1. What do you think of these results?

2. What further information & investigations would you like?

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 Uncategorised

Case 96 – the beginning

Welcome to our new #TeamHaem case.

You are an SHO in a general paediatric outpatient clinic. Your next patient is a new GP referral – a 13 month old boy who has not been putting on weight for the past 3 months. Mum has had trouble with weaning and he has been having intermittent vomiting and loose stools, and Mum feels his abdomen has been more distended. The GP thought it might have been lactose intolerance but despite changing his diet, he is still not putting on weight.

On first impression he does not look unwell, though slightly pale. You plot his growth chart, and his weight, length and head circumference are all < 0.4th centile, whilst previously he had always trended around the 9th centile. Mum also said he has a lump/rash on his arm which has been coming and going. He’s also been coughing for the past few weeks & always seems to have a cold.

Questions:

1. What further history would you like to obtain?

2. What clinical examination findings might be useful to take this forward?

3. What investigations would you like to carry out?

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 Uncategorised

Case 95 – summary

Thankyou for all your help this week.

This week we had a look at mantle cell lymphoma (MCL). MCL is a type of none Hodgkin’s lymphoma, and comprises between 3 and 10% of NHL, and often has features of both high and low grade lymphomas.

It has the chromosomal abnormality t(11;14)(q13;q32) which results in an over expression of cyclin d1.

MCL is more common in men and usually presents in the older population. Patients will often present with widespread lymphadenopathy, which not infrequently involves extranodal sites. Bone marrow/peripheral blood/splenic involvement are common at diagnosis.

The clinical course for patients presenting with MCL is variable. In some cases the MCL may behave more aggressively from the outset, whereas others may have an initial more indolent course. Patients who have blastoid MCL histologically usually have a more aggressive lymphoma, with a shorter survival and a lower response rate to treatment.

Although CNS involvement is uncommon at presentation, CNS relapse can occur in in up to 7.8% of patients. This is more likely if the patient has blastoid MCL or MCL with a high Ki67 on histology. Patients with CNS involvement have a poor prognosis.

When working up a patient it is important to ensure they have certain investigations completed

  • FBC and film to look for evidence of involvement, this can be sent for flow cytometry if suspected.
  • LDH
  • Hep B (SA and core Ab), hep C status prior to immunotherapy
  • HIV
  • If no peripheral blood involvement bone marrow aspirate and trephine to help establish staging
  • CT N/C/A/P to establish baseline lymphadenopathy
  • LP with cytology and flow if suspicion of CNS disease
  • MRI brain can also be useful to assess CNS disease.

Scoring systems

The MIPI is used to prognosticate disease into low medium and high risk categories. A link to the calculator can be found below. But age, LDH,ECOG and peripheral blood white cell count all play a part. Ki67 can also be included if using MIPIc

http://www.european-mcl.net/en/clinical_mipi.php

Some studies have shown that up to 92% of patients may have GI involvement, upper and lower GI endoscopy can be performed to assess, although this may not affect treatment. However in a patient with what appear to be otherwise stage 1A disease, or with other GI symptoms/bleeding this should be considered.

Once tissue has be acquired for diagnosis, if through bone marrow or peripheral blood flow cytometry can be performed. MCL usually expresses – CD5+,CD19+,CD22+,CD79b+,FMC7+, light clonal light chain expression is usually moderate. CD10 is occasionally positive.

If using lymph node/other affected tissue/bone marrow trephine IHC can be performed to establish diagnosis. MCL is usually CD20+,CD5+,BCL2+,cyclinD1+,SOX1+ and CD10-,CD23-,BCL6-

Cytogenetics can also be used to establish diagnosis and some cytogenetic abnormalities may be able to predict a poorer prognosis.

t(11;14)(q13·3;q32·33) is the cytogenetic abnormality behind MCL cases and can be detected by FISH, however many patients may have other cytogenetic abnormalities. Complex karyotypes are usually associated with a poorer prognosis and, as with other disorders, TP53 mutations confer a poorer prognosis

Treatment

Each patient needs careful assessment to decide if treatment is needed. In patients with an indolant, fairly asymptomatic disease a watch and wait approach may be adopted. As with other low grade lymphomas, indications for treatment can include bone marrow failure, bulky disease, symptomatic organomegaly, B symptoms and GI bleeding from MCL involvement.

Clinical trials should be offered to patients where available when considering treatment.

Considerations for type/intensity of treatment include age,comorbidities and performance status.

For first line treatment, in fit patients who would be suitable for an autologous SCT, to ensure a greater chance of achieving an optimal response a regime containing high dose cytarabine plus rituximab should be used.

For first line treatment in those patients not fit for auto SCT RCHOP and R-bendamustine are commonly used. In those less fit patients other immunochemotherapy regimes such as R-chlorambucil can be considered.

Regardless of upfront treatment with or without auto SCT rituximab maintainence treatment can be used and aim to increase duration of response to treatment.

CT can be used to assess response to treatment. MRD for t(11;14) has also be shown to be helpful in prognosticating patients, but is not widely used.

Options for 2nd line treatment can include brutonkinase inhibitors, R-CHOP and R-BENDA+/-cytarabine. Auto SCT (following treatment) if not done at first line and patient fit can be done. Consideration for ALLO SCT in younger fitter patients can also be made following 2nd line treatment.

Other drugs including venetoclax (BCL2 inhibitor) are currently being trialed for use in MCL and look promising.

Thankyou for your participation this week. Is there anything you would like to ask/add/and knowledge you would like to share?

For further reading we would recommend the BSH guidelines

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 Chronic leukaemia, Laboratory morphology, Lymphoma | Tagged , ,

Case 95 – update 2

We have monitored our patient for a year. Unfortunately at his most recent appointment he has begun to complain of weight loss of 7kg, drenching night sweats and fatigue.

What would you want to do next? Are there any investigations you would want to organise?

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 Chronic leukaemia, Lymphoma | Tagged , ,

Case 95 – update 1

So we have found our patient has a lymphocytosis on repeat bloods, we have no historical results.

He denies and weight loss, sweats or tiredness.

On examination you can feel an enlarged spleen 4cm below the costal margin, but you can not palpate any lymphnodes.

A repeat fbc has been done and results show

  • Hb 137
  • Plt 175
  • Wcc 23
  • Neut 5
  • Lymphocytes 16.5
  • HIV negative
  • EBV IgG positive, IgM negative
  • CMV IgG positive, IgM negative

He has been referred to haematology with those results.

Blood film shows

Angular, pleomorphic lymphoid population with v high NC ratio, clumped chromatin, and occasional nuclear clefts. About 1/3 contain nucleoli

Flow cytometry has been requested

Here are some of the results.

  • What can you tell from these results? What are the possible diagnosis?
  • What would do next? Are there any other tests you would want to organise?

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 Chronic leukaemia, Laboratory morphology, Lymphoma | Tagged ,

Case 95 – the beginning

Welcome to our new case!

This week we start in GP. We have a 59 year old gentleman who A&E have asked you to follow up as he was found to have a slight lymphocytosis on some bloods that were done following an attendance with diarrhoea, which turned out to be food poisoning from undercooked barbecue chicken.

The bloods were taken 2 weeks ago.

  • Hb 135
  • Plt 180
  • Wcc 22
  • Neuts 4
  • Lymph 15

What questions would you like to ask the patient?

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 Chronic leukaemia, Lymphoma | Tagged

Case 94 – update 1

Our patient has undergone emergency surgical decompression for severe C3/4 spinal cord compression secondary to a lesion in his C3 vertebral body. He is recovering well on the neurosurgical ward.

Initial investigations were unremarkable.

Results update:

Following discussion, the further investigations below were requested and all found to be within their normal ranges:

Serum calcium, immunoglobulins, serum electrophoresis, serum free light chains, beta 2 microglobulin, LDH, HIV, Hepatitis B, Hepatitis C.

Histopathology have called through a provisional report, our patient’s C3 biopsy is ‘highly suspicious for plasmacytoma’.

Questions:

  • What histopathological features would support a diagnosis of plasmacytoma?
  • How would you prioritise further investigations for our patient? Why?
  • How would you explain this result to our 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.

Posted in Uncategorised

Case 94 – the beginning

Welcome to our new #TeamHaem case!

You are the junior doctor in A+E. The next patient to be seen is a 38 year old man who has presented with severe neck pain. He works as a builder and has been sent home from work today for being ‘clumsy’ on site. The triage nurse shows you that his latest observations are stable but that his pain score is 9/10, despite taking oral analgesia 1 hour ago.

Questions:

  • What questions would you ask him?
  • What would you look for on examination?

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 93 – summary

This case highlighted a number of issues in the management of VTE.

1) The investigation of a patient with newly diagnosed DVT

One of the most useful parts in the history taking is the identification of a provoking factor. We know that those with provoked DVT have relatively low risk of recurrence after an initial period of intensive anticoagulation. However frequently patients have ‘soft’ provoking factors or no provoking factors or relapsing-remitting provoking factors e.g. inflammatory bowel disease. Guidance from ISTH can help us decide on whether a provoking factor has occurred.

In those with a clearly provoked VTE e.g. following surgery or hospital admission then investigation into underlying causes may not be needed. A full history and examination should be performed in all patients.

In those with unprovoked VTE the addition of CT abdomen and pelvis was studied in addition to standard of care and in the SOME trial a routine CT scan did not offer any clinical benefit. Patients should have a systematic history and examination in addition to urinalysis, CXR and routine age-appropriate cancer screening. In addition to malignancy features of autoimmune disease should be asked about. Basic laboratory tests should be performed such as FBC, U&E, LFT and bone profile. Further investigations can be performed as guided by history, examination and blood tests. Tests such as autoimmune screening, immunoglobulins, thyroid function, inflammatory markers, ferritin and tumour markers are controversial but can be used on a case-by-case basis.

2) Deciding which anticoagulant to use

Various factors need to be considered and the final approach needs to be individualised to the patient after discussion with them. Factors that may need to be taken into account include:

  • Presence of active cancer – LMWH generally better option if undergoing chemotherapy. DOACs are increasingly used in patients with malignancy.
  • Need for reversal agent – currently warfarin and dabigatran have reversal agents but anti-Xa reversal agent Andexanet alfa has been approved by FDA for reversal of rivaroxaban and apixaban)
  • Preferring oral vs parenteral
  • Extremes of body weight – DOACS generally advised against over 120kg
  • Ability to absorb – if absorption issues then parenteral anticoagulant or an anticoagulant that can be monitored reliably may be preferred
  • Ability to monitor – warfarin and LMWH are easily monitored. DOAC levels can be checked but interpretation is not always straightforward and titration of dose is not generally possible
  • Interacting medications
  • Preference to take once daily – warfarin, LMWH and rivaroxaban are all once daily
  • History or at risk of heavy menstrual bleeding – rivaroxaban has been associated with higher risk in non-randomised comparative studies
  • Not wanting to take any injections – rivaroxaban and apixaban do not require any period of LMWH
  • Ease of monitoring and facilities to do so (community vs hospital visits etc.)
  • Presence of antiphospholipid syndrome – currently warfarin and LWMH are the preferred option here
  • Local policies – this may dictate prescribing
  • Cost – this may dictate prescribing
  • Presence of renal failure – in the presence of severe renal failure warfarin is the best option for treatment of VTE although apixaban has been used for AF in dialysis-dependant patients. All other DOACs have limits and dose reductions depending on the degree of renal failure.
  • Presence of liver disease and coagulopathy – LMWH may be the best option here
  • Current or potential pregnancy – DOACs and warfarin are contraindicated in pregnancy but generally most are happy to become pregnant whilst on warfarin but to change to LMWH as soon as possible
  • History of gastritis and GI bleed – dabigatran has more GI side effects and rivaroxaban has possibly more GI bleeding.
  • Presence of coronary artery disease – dabigatran may have more cardiac side effects

 

Whatever anticoagulant is used patients should be counselled on the risks and benefits and expected side effects. They should be told what medicines to avoid and when next to have blood test monitoring if appropriate. They should be given advice on who to contact if any problems.

3) The use of compression hosiery

Again, another controversial issue with some people advocating its use and others avoiding. Generally use grade 2 stockings 30-40mmHg at ankle and change 3-6 monthly or after 100 washes. Patients should start wearing once the acute swelling has reduced – around two weeks post DVT and may need refitting if swelling reduced. The SOX trial in 2014 enrolled patients with a first DVT  and they wore stockings at least three days a week and they were randomised against sham stockings. The incidence of post-thrombotic syndrome was 14.2% in stockings group versus 12.7% in sham stockings group.

However they can be useful to alleviate symptoms.

4) Diagnosis of recurrent DVT

There is no validated risk score and USS and d-dimer are also not validated. If the recurrence is in the contralateral leg then the diagnosis is usually straightforward. USS is operator dependant and some factors can be used to determine new clot vs old such as extent and appearances but this is not easy. In real life the clinical features, d-dimer and ultrasound findings need to be triangulated. A good review on recurrent DVT is here.

Recurrent DVT investigation.jpg

When someone has a recurrent thrombosis it is important to think about:

  • Are levels required to assess compliance and efficacy?
  • Check compliance with patient
  • Check correct dose, weight, taking with food (if needed), timings
  • Check no medications that may reduce effect
  • On other medications e.g. chemotherapy or hormones that may increase hypercoagulability?
  • Consider
    • Looking for malignancy
    • Looking for pro-thrombotic state e.g. heparin-induced thrombocytopenia (if on heparin), paroxysmal nocturnal haemoglobinuria, myeloproliferative neoplasm and anti-phospholipid syndrome
    • Looking for anatomical abnormality e.g. May Thurner

The treatment of recurrent DVT depends on the circumstance and some options are given:

  • On warfarin but subtherapeutic? Give LWMH and once improving reintroduce warfarin with more intense monitoring and lower threshold for LMWH if subtherapeutic. Investigate why warfarin subtherapeutic. Could also increase target range to reduce likelihood of being subtherapeutic. A DOAC may be a better option here.
  • On warfarin but therapeutic (ensure therapeutic leading up to event)? Give LWMH and once improving reintroduce warfarin with more intense monitoring and lower threshold for LMWH if subtherapeutic. Increase target INR range.
  • On full dose DOAC? Give LWMH and once improving start warfarin.
  • On half dose DOAC? Give full dose.
  • On LWMH? Escalate dose by 20-25%
  • If cancer – start LMWH
  • If new MPN – use LWMH then warfarin and consider cytoreduction.
  • If PNH – consider eculizumab
  • If vascular abnormality refer to vascular surgeons

5) Duration of therapy

For provoked DVT generally 3-6 months anticoagulation is sufficient assuming the risk factors have gone. Patients should be counselled about risk in the future and symptoms to look out for. In unprovoked DVT treatment duration is less clear. Male sex, obesity and extent of DVT are all risk factors for recurrence. Consider long term anticoagulation in all unprovoked – reduces risk by 80-90%

  • Distal do not need long term
  • If don’t want need to way up risks and benefits
  • Bleeding risk factors include: ETOH, hypertension, CKD, cirrhosis, previous bleed, over 65s, aspirin too)
  • Options include
    • Stop and no monitoring
    • Stop and d-dimer monitoring e.g. DASH score (or similar)
    • Stop and thromboprophylaxis during high risk events
    • Extended anticoagulation with reduced dose
    • Extended anticoagulation same dose

6) IVC filters

General points:

To prevent PE in patients who can’t be anticoagulated. Once inserted should start anticoagulation when no contraindication due to risk of recurrence and filter blocking, however no known benefit for starting anticoagulation for filter alone as patients with filter and anticoagulation still get VTE therefore decision to restart should be made on underlying condition not filter alone. Filter and anticoagulation reduces risk of PE but increases risk of DVT and no difference in overall survival. If anticoagulation fails – intensify first. Free-flowing thrombus is not an indication for filter. Remove filter in two months and definitely less than three months. Consider filter if:

  • Pre op and VTE in last month where anticoagulation must be interrupted and surgery can’t be delayed
  • Pregnant and contraindication to anticoagulation or within two weeks of delivery
  • Chronic thromboembolic pulmonary hypertension pre pulmonary endarterectomy
  • Platelets too low for treatment

Complications:

  • Recurrent DCT 20%
  • IVC thrombus 10%
  • Post thrombotic syndrome 15-40%
  • Pneumothorax
  • Migration
  • Misplaced
  • Entrapment of guidewires

7) Cancer-associated VTE

LMWH has the most established use in this scenario having superiority to warfarin (CLOT trial). Edoxaban and rivaroxaban have been studied, however these may be less easier to manipulate during thrombocytopenia, interactions may not be easy to spot and during chemotherapy absorption may be altered and vomiting may occur. In the pilot data with use of rivaroxaban there was more bleeding in the rivaroxaban arm. The risks and benefits of oral agents should be discussed with patients and in those that find LMWH painful and difficult DOACs may be an option.

Summary

Our patient was diagnosed with an unprovoked DVT and was started on rivaroxaban. Whilst on treatment he had a recurrence which lead to the diagnosis of pancreatic malignancy. He was started on LMWH but needed urgent surgery (within two weeks of recurrence), so an IVC filter was inserted with instructions to stop LMWH 36 hours pre surgery and restart as soon as bleeding risk reduced (usually after 48-72 hours). At 48 hours prophylactic LWMH was introduced and then escalated to treatment dose BD until he was established on once a day. Once there was no bleeding and no further intervention planned the filter was removed three weeks later. He had a total of six months anticoagulation with LMWH and during repeat imaging he was declared cancer free. He had a monitoring scan two years later and remained cancer-free and off anticoagulation with no VTE recurrence. He was educated on the signs and symptoms to look out for and advised to be on prophylactic LMWH during times of risk.

Conclusion

Management of VTE is not straightforward. There are a number of debated issues:

  • Treatment of isolated distal DVT
  • Biomarkers for DVT diagnosis
  • Treatment of recurrent DVT
  • Investigations of the newly diagnosed patient
  • Use of compression hosiery
  • How long should patients be on treatment
  • Risk factors: provoked vs unprovoked
  • Incidental VTE
  • Role of inherited thrombophilia screening
  • Localised thrombolysis

The above issues may need to be discussed with patients and uncertainty acknowledged in order to promote shared decision making.

 

References

Posted in Anticoagulation, Thrombosis | Tagged , , , , , , , ,

Case 93 – update 4

Our patient has had one left leg DVT which was treated with rivaroxaban. He had no symptoms of malignancy. Two months later he presents again with increased leg swelling and pain and has the thrombosis has increased compared to previous. A recurrent DVT is diagnosed despite compliance with anticoagulation. He has a CT scan which suspects pancreatic malignancy and he undergoes surgery two weeks later. Because of the high risk of bleeding during the procedure and the likelihood he will require a significant amount of time without anticoagulation postoperatively he has an IVC filter inserted.

 

Post operatively he recovers well and after two weeks he is back on full dose anticoagulation and the IVC filter is removed.

Three months after the recurrence he is deemed cancer free and has no more treatment planned.

 

Questions

  • What is the optimal anticoagulation for cancer-associated VTE?
  • How long should patients be anticoagulated for?

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 Anticoagulation | Tagged , , , ,

Case 93 – update 3

Our patient has his d-dimer checked which is positive and has an ultrasound scan of the left leg which has confirmed a clot. On review of the images the clot is more extensive that previously. This combined with the clinical history is strongly suggestive of recurrent thrombosis.

When someone has a recurrent thrombosis it is important to think about:

  • Are levels required to assess compliance and efficacy?
  • Check compliance with patient
  • Check correct dose, weight, taking with food (if needed), timings
  • Check no medications that may reduce effect
  • On other medications e.g. chemotherapy or hormones that may increase hypercoagulability?
  • Consider
    • Looking for malignancy
    • Looking for pro-thrombotic state e.g. heparin-induced thrombocytopenia (if on heparin), paroxysmal nocturnal haemoglobinuria, myeloproliferative neoplasm and anti-phospholipid syndrome
    • Looking for anatomical abnormality e.g. May Thurner

 

Our patient now reports some upper abdominal discomfort and a CT scan reveals a mass at the head of the pancreas. Following a MDT discussion this is very likely to be a  pancreatic malignancy and surgery is indicated. His surgeon recommends surgery as soon as possible and does not want to wait for more than three weeks. The surgery planned would be a Whipple’s procedure.

 

Questions

  • How do you manage anticoagulation around elective but urgent surgery?
  • What anticoagulant do you recommend?
  • Any other interventions need considering?
  • What about post-operatively?

 

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 Anticoagulation, Thrombosis | Tagged , , , ,

Case 93 – update 2

We discussed what anticoagulant to start in our patient with a newly diagnosed DVT. There are a number of options and the main ones will include:

  • LMWH then warfarin
  • LWMH then dabigatran
  • Rivaroxaban
  • Apixaban
  • LMWH then edoxaban

 

Various factors need to be considered and the final approach needs to be individualised to the patient after discussion with them. Factors that may need to be taken into account include:

  • Presence of active cancer – LMWH generally better option if undergoing chemotherapy. DOACs are increasingly used in patients with malignancy.
  • Need for reversal agent – currently warfarin and dabigatran have reversal agents but anti-Xa reversal agent Andexanet alfa has been approved by FDA for reversal of rivaroxaban and apixaban)
  • Preferring oral vs parenteral
  • Extremes of body weight – DOACS generally advised against over 120kg
  • Ability to absorb – if absorption issues then parenteral anticoagulant or an anticoagulant that can be monitored reliably may be preferred
  • Ability to monitor – warfarin and LMWH are easily monitored. DOAC levels can be checked but interpretation is not always straightforward and titration of dose is not generally possible
  • Interacting medications
  • Preference to take once daily – warfarin, LMWH and rivaroxaban are all once daily
  • History or at risk of heavy menstrual bleeding – rivaroxaban has been associated with higher risk in non-randomised comparative studies
  • Not wanting to take any injections – rivaroxaban and apixaban do not require any period of LMWH
  • Ease of monitoring and facilities to do so (community vs hospital visits etc.)
  • Presence of antiphospholipid syndrome – currently warfarin and LWMH are the preferred option here
  • Local policies – this may dictate prescribing
  • Cost – this may dictate prescribing
  • Presence of renal failure – in the presence of severe renal failure warfarin is the best option for treatment of VTE although apixaban has been used for AF in dialysis-dependant patients. All other DOACs have limits and dose reductions depending on the degree of renal failure.
  • Presence of liver disease and coagulopathy – LMWH may be the best option here
  • Current or potential pregnancy – DOACs and warfarin are contraindicated in pregnancy but generally most are happy to become pregnant whilst on warfarin but to change to LMWH as soon as possible
  • History of gastritis and GI bleed – dabigatran has more GI side effects and rivaroxaban has possibly more GI bleeding.
  • Presence of coronary artery disease – dabigatran may have more cardiac side effects

 

Our patient prefers an oral option and would like a tablet to take once a day as he would find it easier to remember. He starts on rivaroxaban 15mg BD with a plan to drop to 20mg od after three weeks. He notices an improvement in his symptoms. He is asymptomatic and has no signs or symptoms of malignancy or autoimmune disease. He has a chest X-ray which is normal. Urinalysis is unremarkable and FBC, U&E, LFT and calcium are all within the reference range.

 

Two months later he attends again with extensive left leg swelling after having an initial improvement.

Questions

  • How do you counsel patients about to start anticoagulation? Any dos and don’ts?
  • Do you offer compression hosiery routinely?
  • His leg is worse again – how do you proceed?

 

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 Anticoagulation, Thrombosis | Tagged , , ,

Case 93 – update 1

Our patient has a confirmed proximal DVT and we recognised the important points in the clinical evaluation by looking for provoking factors:

  • Malignancy
  • Family history
  • Periods of immobility
  • Recent surgery or hospital stays
  • Hormonal therapy or pregnancy
  • Nephrotic syndrome
  • Autoimmune or other inflammatory disorder

In our patient nothing obvious came to light. He’d been on a short train journey and his cousin also had a DVT – neither enough to make us wonder about a convincing risk factor.

He needs treatment for the DVT. His renal and liver function are normal.

Questions

  • How do you decide which anticoagulant to use?
  • What risks and side effects would you tell him?
  • What investigations may you wish to perform to look for causes of VTE?

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 Anticoagulation, Thrombosis | Tagged , ,

Case 93 – the beginning

Welcome to our new #TeamHaem case.

You are the acute medicine senior house officer working in ambulatory care. A GP has referred a 58 year old gentleman with left leg swelling and is concerned about deep vein thrombosis (DVT). He has never had a blood clot before. Blood tests reveal a positive d-dimer and an ultrasound scan confirms a clot in the femoral vein extending into the external iliac vein.

Questions:

  • What further information in the history is useful to know here?
  • What would you look for on examination?

 

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 92 – summary

Thanks for your help with the cases.

This week we have looked at three different scenarios regarding bleeding or bruising presenting in the paediatric population.

The cases although different have some common themes:

Coagulation testing in paediatrics is challenging for several reasons:

  1. lack of local reference ranges for tests due to ethical concerns.
  2. physiological differences in coagulation factor and other coagulation protein levels (Factor II, VII, X, IX, XII don’t reach adult range until 6 months with other differences such as elevated factor VIII and VWF levels, reduced platelet function and low protein C and S levels at birth). Children’s reference ranges should be used until age 16.
  3. Sampling much more challenging particularly in babies. Platelet function and nucleotide testing not recommended before 1 year due to challenges of obtaining samples and interpreting results. Stress of venipuncture in children can also affect VWF results. Difficulties in obtaining samples can lead to pre activated samples.

With the above in mind when faced with a child with bleeding or bruising given limitations of the tests the focus should be on good history and examination.

Testing should focus on excluding major bleeding disorders rather than investigating for milder conditions that are unlikely to be cause of presentation. Repeat testing can be helpful if results unclear particularly with VWF tests that are affected by acute trauma and stress. Platelet nucleotide and function should not be performed in young babies as not possible to interpret results with certainty.

History points to consider:

  • Is the bruising or bleeding consistent with history given? – NAI clearly may have inconsistent story but equally bleeding disorders may also cause bruising with apparently minimal trauma.

Pattern of Bruising or bleeding:

  • Bruises consistent with a pattern like a hand would be consistent with NAI.
  • Bruising over shins much less concerning than sites that are not exposed such as the abdomen .

Bleeding history and challenges to haemostasis:

  • Birth: stump bleeds ( suggestive XIII deficiency), cephalohaematomas.
  • Vaccines: significant bleed or bruise post IM injections
  • Mucosal bleeding: VWD
  • Surgery: circumcision, tooth extraction

General Health:

  • Liver disease?
  • Sepsis- DIC picture
  • Recent Infection – Henoch scholein purpura, ITP

Family History:

  • Bleeding issues
  • Hypermobility

Ethnicity:

  • Consanguineous relationships – recessive bleeding traits.
  • Ashkenazy Jewish population – factor XI deficiency

Drug History:

  • Anticoagulants
  • Steroids
  • Maternal drug Hx – Vit K def more common if taking some antiepileptic medications

Diet:

  • Breast fed – risk for Vit k deficiency
  • Poor diet – Vit C deficiency

Hypermobility – Ehlers Danlos

Examination points to consider:

  • Sites of bruising and age – abuse and bleeding disorders varied ages of bruises
  • Petechia? – ITP or HSP?
  • Joint bleeds? – Haemophillia
  • Hypermobility? Scars?- Ehlers Danlos

Investigations:

These are dependent on history and examination and are not needed in all cases. For example if a child has a clear belt buckle shaped bruise that is consistent with NAI further tests won’t be needed. A baby who had clearly prolonged PT and history of breastfeeding may only require Vit K and repeat Coag not the full range of factors.

Basic screen:

  • PT/APTT
  • Thrombin time
  • Fibrinogen
  • 50:50 mix of prolonged Coag times
  • Factor VIII,IX,XI
  • VWD screen
  • Other tests such as factor XIII and platelet function depends on history and presentation.

 

Notes on Specific cases this week:

  1. Vitamin K deficiency resulting in intracranial haemorrhage:

Levels of Vitamin K dependent coagulation factors (II,VII,IX, and X ) are low at birth and these factors are functionally inactive without vitamin K. Vitamin K deficiency classically prolongs PT in isolation but in severe cases may prolong APTT.

It should always be considered as a cause of neonatal bleeding and vitamin K should be given even prior to coagulation results being available in cases of severe bleeding.

Vitamin K deficiency bleeding (VKDB) risk factors are exclusive Breastfeeding (Breast milk does not contain VitK), missing treatment at birth, mother on drugs such as phenytoin that interfere with Vit K metabolism or babies with Liver disease who don’t use vit K the body stores or bowel problems who don’t absorb the vitamin K.

There are 3 types of vitamin K deficiency:

  • Early: first 24 hours after birth commonly due to maternal medications
  • Classical: 1-7 days post delivery
  • Late: 2-12 weeks of age but can be seen up to 6 months. These babies are otherwise well and sadly up to 60% present with significant intracranial bleeds as first event.

Management of vitamin K prophylaxis is varied and there are several approaches.

If a mother is on antiepileptic such as phenytoin she should be counselled about risks and given choice to change medication. She should receive 20mg vit K per day in last 4 weeks of pregnancy and IM 1mg Vit K given at birth.

IM vit K 1mg was traditionally given at birth but there was a single study that linked this to possible childhood cancer ( though no further studies have shown no link). Oral regimens give 2mg at birth and then daily for the next 3 months instead.

Any infant presenting with possible bleeding related to vitamin K deficiency should receive IV or S/C vit K (avoid IM route). This should occur before confirmation.

Octoplas 15ml/kg should be used to correct coagulation anomalies. Care should be taken to avoid volume overload and changes in BP due to rapid volume expansion.

2. Ehlers Danlos

This is a group of 13 different inherited conditions that affect the connective tissues, usually collagen.

The commonest type is classical Ehlers Danlos. This condition causes a defect in type V collagen leading to fragility of collagen fibrils. In classical ED under an electron microscope collagen flowers can be seen due to defects in collagen fibres.

Given the classical clinical presentation of Hypermobile joints, skin elasticity and easy bruising with atrophic scaring the diagnosis is often given on clinical grounds. Skin biopsy and microscopy was the previous diagnostic test however Genetic tests can be performed looking for mutations in COL5a or COL5A2 genes if needed (The condition is autosomal dominant).

A patient will often have fragile skin and inspection will show scars with wide defects or over shins, elbows and knees. They will demonstrate Hypermobile joints and a useful clinical tool is the Beighton score which if >5 suggests hyper mobility. They may also have easy bruising and stretchy skin. There is often a family history of hyper mobility and hernias or prolapses due to weak collagen.

Management of Ehlers Danlos is supportive. Advice includes avoiding skin trauma and contact sport should be avoided due to dislocation risk. Cardiac echo should be considered to ensure cardiac valves not affected. If pregnant then additional care should be taken as high risk for perineal tear and prolapse.

In our case the patient had easy bruising and advice should be to avoid trauma as much as possible. She should have an echo and be advised to inform obstetric team if ever pregnant due to increased perineal tearing rate. Family can be referred to local genetic service if they are concerned.

3. Factor XII deficiency and probable NAI:

Factor XII deficiency s autosomal recessive and affects 1 in a million of the population. Occasionally patients with this condition have poor wound healing but this does not cause bleeding problems.

In this case the factor XII deficiency does not explain bruising and given the bruises suspicious location on the abdomen it is likely NAI is the cause for the presentation.

If NAI is considered you may need to perform testing for rarer bleeding conditions even if initial screen is negative for legal reasons. It is important if NAI is thought to be an issue that advice is sought from experts at an early stage and any testing done in major centre so results can be as accurate as possible.

References:

AE Thomas The bleeding child; is it NAI?. Arch Dis Child 2004, 89, 1163-1167.

CDC website vitamin K deficiency bleeding

The investigation and management or neonatal haemostasis and thrombosis. BJHaem 2002, 119, 295-309.

Ehlers Danlos association website

Factor XII deficiency – Haemophillia.org website

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Case 92- update part C

We have a 7 year old boy who has presented with bruises over abdomen and one on his ear.

Social services have been contacted as there is concern this may be an NAI.

The boy is otherwise well has no family history of bleeding disorders and has no bleeding history of note.

 

The boy was asked to attend the tertiary centre for coagulation tests to be performed. This is because of concerns regarding delay in transportation of samples. If further special tests like platelet function required would also need to be taken at site that can perform the tests.

 

Tests taken and results:

 

  • Full blood count, blood film – Normal
  • PT 13 sec (Normal) APTT 50 sec (Prolonged), thrombin time – Normal, Clauss fibrinogen 3.2 (Normal)
  • Von Willebrand screen – Normal
  • Lupus screen – Normal
  • 50:50 mix APTT – 37 Sec (Normal)
  • FVIII level – 100% (Normal)
  • FIX level – 96% (Normal)
  • FXI level – 110% (Normal)
  • FXII level – 30% (Low)

What is the likely cause for the prolonged APTT?

 

Does this explain the bruises in this case?

 

Would you perform any other tests in this case?

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

Case 92 – part C

Thanks for your help with case 2 the patient has been diagnosed with Ehlers Danlos and will have an echo arranged to check for any cardiac problems.

You now receive a call from the local district general hospital regarding a 7 year old boy who has presented with bruises over abdomen and one on his ear. They have called the tertiary centre in line with regional policy as initial FBC and coagulation screen was normal apart from a prolonged APTT of 50 seconds. They wonder if this finding is significant?

Social services have been contacted as there is concern this may be an NAI.

The boy is otherwise well has no family history of bleeding disorders and has no bleeding history of note.

What tests would you ask for to clarify long APTT?

Would you ask them to perform further tests locally or send the child to your centre?

What is the differential at this stage for the prolonged APTT?

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

Case 92 – part B

Thanks for your help with case 1 the baby is improving. The following morning you as the Haematology registrar have been referred a 5 year old girl who presented due to parental concern with easy bruising. The bruising was noted since she was about one but become more evident since she started school. She has small bruises of varied age over forearm and shins. She has no past medical history of note. She has a maternal grandma who “bruises easily”

What history would you take?

What would you look for in the examination?

What investigations would you consider?

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

Case 92 – update part A

Thanks for your help so far

An 8 week old baby boy born at 40+2 by Normal vaginal delivery has a CT that confirms a subdural haemorrhage.

Results: (With age adjusted reference ranges)

  • FBC – Hb 120 (Low) MCV 120 (upper normal) plt 200 (Normal) Wcc 15 (Normal) Retics 220 (upper normal range)
  • Coag – PT 74 secs (High) APTT 55 sec (upper normal) Fib 2 (Normal). PT corrects on mixing.
  • Film– unremarkable with normal platelet morphology.

The team give Vitamin K 1mg IV as severe bleeding.

The mother is well apart from epilepsy. She has no previous pregnancies. She is not in consanguineous relationship. She reports the boy was well no bleeding of umbilical stump or mucocutaneous bleeding noted. He was on 50th centile for weight. He is exclusively breastfed.

What is the most likely cause of this presentation?

How should this be managed?

What is the relevance of maternal epilepsy in this case?

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