Case 87 – summary

This week we looked at a case of pulmonary embolism in a lady who was 28 weeks pregnant.

 

Initial management included:

  • ABC
  • ECG – T wave inversion. S1Q3T3 pattern and right bundle branch block.  May also help with identifying an alternative diagnosis
  • Chest x-ray – may identify other pulmonary disease.  If CXR normal, this improves likelihood of V/Q scan giving a definitive result.  If chest x-ray abnormal, CTPA should be performed
  • Duplex ultrasound – bilateral if suspicion of DVT.  If diagnosis of DVT made, now further imaging of chest would be required reducing radiation exposure for mother and baby
  • FBC, coagulation screen, urea and electrolytes and liver function tests.

 

D-dimer

There is a progressive rise in d-dimer levels throughout pregnancy, and this remains elevated in the postnatal period.  The role of d-dimer testing in pregnancy remains controversial.  RCOG guidelines advise not to test d-dimer in pregnancy, as do the American thoracic society guidelines.  The European society of cardiology suggest that a negative d-dimer level can be used to rule out PE in pregnancy, however the d-dimer is unlikely to be with normal range.

 

Pre-test probability assessment such as the WELLS score have not been validated for use in pregnancy.

LEFt rule – can help identify pregnant women with DVT.  (L – Left leg, E- oedema > 2cm calf circumference difference, Ft – first trimester presentation)

Further imaging

Choice of further imaging will depend upon availability within the hospital.

V/Q scan – ventilation component can often be omitted therefore minimising radiation to the fetus.  Main concern is radiation dose to fetus, causing a very small increase in the risk of childhood cancers.

CTPA – more readily available.  Can identify other pathology.  Increased radiation dose to breast tissue, therefore increasing the risk of breast cancer.  Radiation dose to the fetus is less than a V:Q scan.

 

Women should be counselled on options for further imaging.  Factors such as the background risk of breast cancer for that lady, should be taken into account.

 

Treatment

LMWH – should be commenced immediately, until the diagnosis can be excluded.  Dose should be titrated against the womens booking or early pregnancy rate. There have been a number of study’s comparing once daily dosing with BD dosing, with insufficient evidence to favour one option.

Anti-Xa monitoring is not required routinely in pregnancy.  Only women at extremes of body weight (<50kg or >90 kg), or with other complicating factors (renal impairment, recurrent VTE).

Routine platelet count monitoring is not required.

Delivery plan – women should be informed not to adminster any further LMWH once in established labour.  If delivery is planned, by c-section or induction, LMWH should be discontinued 24 hours prior to planned delivery.  Regional anaesthesia should not be undertaken until at least 24 hours after the last dose of LMWH.  LMWH should not be given for 4 hours after the use of spinal anaesthesia, or after epidural catheter has been removed.  Epidural catheter should not be removed within 12 hours of admistraion of LMWH.

Anticoagulation should be continued for at least 6 weeks postnatally, or until 3 months of anticoagulation has been given in total.  Warfarin can be introduce at 5 days postpartum.  DOACs can be consider in women who are not breastfeeding.

 

Massive life threatening PE – consider intravenous unfractionated heparin, thrombolytic therapy, thoracotomy, or surgical embolectomy.   If the patient has received thrombolysis (often anticoagulation alone with not reduce the obstruction in the circulation), the loading dose of unfractionated heparin should be omitted and infusion commenced at an hourly rate.

IVC filter may be consider in patients with recurrent PE despite adequate anticoagulation, or in the peripartum period when anticoagulation is contraindicated.

 

Future pregnancies

Women with previous VTE should be offered thromboprophylaxis throughout the antenatal period.  In this case it would be useful to know the patients family history.  Thrombophilia testing would only be indicated in patients with a positive family history.  The finding of antithrombin deficiency would potentially change management in future pregnancy’s as an intermediate or therapeutic dose would be indicated.  However without a significant family history, there would be no indication for further testing as management would not change for this lady as she would qualify for thromboprophylaxis in future pregnancy’s.  Technically, a positive family history should have been identified by the midwife at the booking in appointment.  Thrombophilia testing should not be undertaken during pregnancy.

 

Posted in Anticoagulation, Related to other specialities, Thrombosis | Tagged , , , , , , ,

Case 87 – the beginning

A 32 year old lady presents to A&E with incresing shortness of breath and chest pain.  She is 28 weeks pregnant.

What further information do you need? Initial management/investigations?

Posted in Anticoagulation, Related to other specialities, Thrombosis | Tagged , , , , , , ,

Case 86 – part C2

Thanks for your help with this short case. We examined this blood film of an unwell female:TTP film

The most striking abnormality is red cell fragmentation. This can be seen in:

  • AIHA/Evans’ syndrome
  • DIC
  • Pregnancy-associated (HELLP, pre-eclampsia, malignant hypertension, fatty liver of pregnancy)
  • Drugs – quinine, simvastatin, tacrolimus/ciclosporin, interferon, clopidogrel
  • Malignant hypertension
  • Infections – viral (CMV, adenovirus, HIV) and bacterial (meningococcus, clostridium perfringens, pseudomonas)
  • Lupus nephritis
  • Scleroderma/SLE
  • PAN/vasculitis
  • PNH
  • HUS/aHUS
  • Malignancy-associated MAHA and post-transplant
  • Catastrophic antiphospholipid syndrome
  • G6PD deficiency
  • Mechanical valves
  • B12 deficiency
  • Thrombotic thrombocytopenic purpura
  • Homograft rejection – microthrombi in transplant
  • Thalassaemia major

Therefore fragmentation needs to be interpreted with the clinical context but if there is associated thrombocytopenia there needs to be urgent patient review to rule out thrombotic thrombocytopenic purpura. The main cause of TTP is an auto-antibody which depletes ADAMTS13. Rarely patients can have a congenital deficiency of ADAMTS13. There are other types of TTP – sometimes called thrombotic microangiopathies which are not due to ADAMTS13 deficiency (e.g. post transplant, malignancy, HIV, pancreatitis). ADAMTS13’s role is to cleave high molecular von Willebrand factor but without this HMW vWF circulates and causes platelet aggregation and micro-thrombi, which in turn cause red cell breakdown due to shear stress.

TTP can present non-specifically. Classically there is fever, neurological impairment and renal impairment but not all of these may be present and there needs to be an index of suspicion. Seeing the above blood film should prompt urgent clinical review by a haematologist. Treatment is with urgent plasma exchange. This needs to happen urgently and if not available FFP infusion is a holding measure. Ideally solvent-detergent FPP which is virally inactivated should be used has there will be high volumes infused. Patients need specialist care and discussion/transfer to a centre that treats TTP is required. Bearing in mind that the incidence is 6/million/year this may not be too often!

For further summary on TTP please click here or visit the BSH guidance on TTP.

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 Laboratory morphology, Platelet disorders, Thrombosis, Transfusion | Tagged , , , , ,

Case 86 – part 3A

A 32 year old female presents with headaches, visual disturbance and fever.

  • Hb 92g/L
  • MCV 99fl
  • Platelets 38×109/l
  • WCC and differential – mild neutrophilia

TTP film

Questions

  • Name some features of the blood film?
  • What are the differential diagnosis?
  • What further investigations would you want?
  • What questions would you want to ask her?

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 Laboratory morphology, Thrombosis, Transfusion | Tagged , , , , ,

Case 86 – part B2

Thanks for joining in with this short case. We reviewed the blood film of an 82 year old. The FBC was done for diabetes monitoring. There was no recent transfusion and no new medications.

Cold agglutination - annotated

The film showed red cell agglutination(3) along with a normal neutrophil(1), lymphocyte(2) and monocyte.

Cold agglutination of red cells occurs due to an IgM antibody attaching to the red cells (often on the I antigen (occasionally on the i antigen (if EBV-related) or P antigen). The antibody generally only attaches in the cold (hence why we see this on the blood film (unless it is 37 degrees Celsius where you work!). The antibody can cause red cell agglutination as we see on the blood film or red cell lysis or both. If patients become cold the antibody binds (mostly in the peripheries). Cold agglutination can occur in:

  • Infections e.g. mycoplasma, EBV – Mostly polyclonal IgM antibodies which develop in response to infective organisms and cross react with RBC antigens. Haemolysis 2-7/52 after infection – mild and self-limiting. Can also see in other autoimmune disease and solid organ malignancy(Sometimes called secondary CHAD or cold agglutinin syndrome)
  • Non-Hodgkin lymphoma with an associated IgM kappa paraprotein e.g. lymphoplasmacytic lymphoma/Waldenström’s macroglobulinaemia
  • Cold haemagglutinin disease – there is an IgM kappa paraprotein – usually at low level which does not meet the criteria for lymphoma (often  monotypic B cells can be found by flow of bone marrow)

 

Features

  • Acrocyanosis – purple extremities secondary to stasis and agglutination.
  • Livedo reticularis
  • Raynaud’s phenomenon
  • Jaundice; mild splenomegaly
  • Worse in cold – get anaemic
  • Features of haemolysis e.g. haemoglobiniuria
  • No symptoms – incidental finding
  • Erroneously elevated MCV (red cells stick together and low RBC with raised MCHC – repeat at 37oC resolves this

 

Laboratory – need to think of the following questions

  1. Is the patient haemolysing?
    • Check FBC/film/bilirubin/haptoglobin/DAT/LDH/reticulocytes
  2. Is the haemolysis immune
    • Check DAT – in cold haemolysis the DAT will usually only be positive for C3d and not IgG (the IgM antibody leaves the red cell leaving complement 3d)
    • Check red cell panel to see if underlying specificity to I antigen etc.
  3. Is there an underlying cause
    • E.g. recent viral infection or lymphoma (may want to check viral serology, immunoglobulins/serum protein electrophoresis and work up for lymphoma e.g. CT scan and bone marrow if concerns)

If cold haemolysis is suspected a direct agglutination test should be done and titre (if the cold antibody is >1:500 this suggests CHAD). Thermal amplitude can also be performed and if CHAD it is usually ≥30°C.

Our patient

He had evidence of red cell agglutination on the blood film but had a normal FBC (once warmed at 37oC) and no biochemical evidence of haemolysis. The DAT was positive for C3d but the antibody was <1:64 and thermal range was low. He had no symptoms or signs of lymphoma but did have an IgM kappa paraprotein at low level consistent with MGUS. He was advised to stay warm in the cold and report any features of anaemia or haemolysis (and if required a transfusion this should be through a blood warmer). Otherwise no further treatment was advised for his asymptomatic cold agglutinins.

References

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 Anaemia, Laboratory morphology, Lymphoma | Tagged , , , ,

Case 86 – part B1

An 82 year old gentleman has a routine blood count for diabetes monitoring. This is the blood film.

Cold agglutination

 

Questions:

  • What do you see on the blood film?
  • What questions do you want to ask the patient?
  • Any further investigations?

 

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 Anaemia, Laboratory morphology, Lymphoma | Tagged , , , ,

Case 86 – part A2

This short case focused on the diagnosis of thalassaemia over iron deficiency. The below factors can help, but there are many overlapping factors and this is more of a guide rather than absolute. Factors that may make this unreliable include co-existing B12/folate deficiency, co-inheritance of alpha thalassaemia trait in addition to beta thalassaemia or use of drugs that alter the MCV e.g. hydroxycarbamide. Thalassaemic disorders are not confined to certain parts of the world. The platelet count may be elevated in iron deficiency. If the MCV is disproportionately low compared to the haemoglobin this also points towatds thalassaemia.

Thal vs iron deficiency

The blood film showed mainly target cells (1). There were occasional spherocytes and some polychromasia. The red cells were small (compared to mature lymphocyte nucleus -2).

Leica Picture

The main differential of a low MCV are:

  • Iron deficiency
  • Anaemia of chronic disease
  • Thalssaemia
  • Lead poisoning
  • Inherited sideroblastic anaemia

She had normal iron stores (ferritin 46μg/l) with no clinical or laboratory evidence of inflammation. Family history revealed her mother was always anaemic. She is from Malaysia.

HPLC revealed a variant haemoglobin in the A2 position. Haemoglobin E runs in this position and this was confirmed on acid and alkaline electrophoresis. The haemoglobin in the A0 time is likely degradation product.

Case 86b.jpg

HbEE

Haemoglobin E is a variant haemoglobin affecting the beta globin gene. There are two beta globin genes and in one is affected by HbE then the patient has HbAE (heterozygous haemoglobin E disease). Homozygous HbE disease is where both beta globin genes are affected and is common in Southeast Asia. It is generally an asymptomatic condition. Patients have mild microcytic anaemia and mild haemolysis. There may be no anaemia at all. They may have mild splenomegaly but this does not usually result in symptoms. The main issue is in pre-pregnancy counselling. Her partner should be tested for any significant haemoglobin disorder. When haemoglobin E is combined with other haemoglobinopathies it can result in a more serious disease – for example if a child inherits haemoglobin E from the mother and an absent/dysfunctional beta globin gene from the father then the child develops HbE/β0 thalassaemia which can be transfusion-dependant.

References

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 Anaemia, Haemoglobinopathy, Laboratory morphology | Tagged , , , , , , ,

Case 86 – part A1

Welcome to #TeamHaem. This week we are going to look at some blood film morphology.

A 21 year old female student has a full blood count done due to fatigue.

  • Hb 100g/L
  • MCV 74fl
  • MCH 21.7pg
  • Platelets 250×109/l
  • WCC and differential – normal
  • Ferritin 46μg/l
  • CRP<5mg/l

Leica Picture

Questions

  • Name some features of the blood film?
  • What are the differential diagnosis?
  • What further investigations would you want?
  • What questions would you want to ask her?

 

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 Anaemia, Haemoglobinopathy, Laboratory morphology | Tagged , , , , , , ,

Case 85 – summary

So, our patient has had quite a week! Thanks to your efforts, he is safely back on the ward, conscious and improving. 

Recap:

We have managed an emergency presentation of an unconscious patient with severe hypercalcaemia, hyperviscosity and an AKI.

We investigated and unconvered an underlying, previously unknown, diagnosis of IgA Myeloma. 

We involved other medical specialties and appropriately escalated his care to level 2 (HDU). 

We considered the ethical implications of treating a patient who lacks capacity to make decisions about his care. 

We touched on the legal framework of best interests decisions in the UK (Mental Capacity Act, 2005). 

We discussed specific management considerations for severe hypercalcaemia:

  • Volume expansion with intravenous 0.9% NaCl (initial rate 200-300ml/hr to maintain urine output >100ml/hr, if no oedema/overload)
  • IV bisphosphonates (caution in AKI) but remember there is a lag in their action of 2-3 days
  • s/c calcitonin in severe, refractory cases (rapid action within 24 hours but effect lost due to tachyphylaxis)

We considered the specific management of hyperviscosity syndrome:

  • Exclude other underlying CNS pathology ?acute intracranial haemorrhage
  • Assess fundi
  • Volume expansion/hydrate
  • Steroids
  • Plasma exchange
  • Treat underlying cause

Beyond initial blood tests, we discussed the pertinent investigations to consider in suspected Myeloma:

  • Imaging (see BSH guidance 2017)
  • Bone marrow biopsy including aspirate, trephine, flow and cytogenetics 

Our MDT considered a bortezomib-based chemotherapy regime appropriate in this case and initiated treatment alongside VTE prophylaxis. 

Outcome:

Our patient received 4 days of plasma exchange following his emergency admission. He commenced definitive chemotherapy for Myeloma on day 2.

After his last plasma exchange his salient bloods included:

  • Adjusted calcium 2.40
  • Paraprotein 5g/L
  • Creatinine 83

His GCS is now 15. 

He is aware of his new diagnosis and is being supported by his friends, ward staff and the specialist Myeloma nursing team. 

Thank you for your help!

Further reading:

http://www.bloodjournal.org/content/bloodjournal/119/10/2205.full.pdf&nbsp;

Join us soon for our next case on Twitter #TeamHaem

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

Case 85 – update 2

We rejoin our patient on HDU…

He remains unconscious and lacks capacity to currrently make decisions regarding his further management. 

Based on our team’s suspicion of an underlying plasma cell disorder, that may be driving our patient’s hypercalcaemia, AKI and hyperviscosity, a best interests decision is made to urgently investigate. 

2% lidocaine and a couple of bone marrow needles later… we obtained a bone marrow aspirate, trephine and samples for flow cytometry and cytogenetics. 

Having looked at the aspirate morphology, we felt our suspicions were justified as plasma cells appeared in increased numbers. We even spotted a Dutcher body – immunoglobulin-filled cytoplasm invaginating into the plasma cell nucleus to give the appearance of an  intranuclear inclusion. 

He has received his first plasma exchange and is planned for daily exchange over the next 48 hours or until his GCS improves.

Our patient improved slightly with intravenous fluid and steroids and has woken up enough to pull out his nasopharyngeal airway! He remains drowsy. He is not able to communicate with us at present. 

HDU have inserted a urinary catheter and arterial line to aid our ongoing patient monitoring.

We have prescribed more intravenous saline to balance our patient’s polyuria – which we think may be a symptom of his hypercalcaemia. 

We have just heard back from the cytogenetic and flow labs and we now feel confident that our patient does have an underlying plasma cell Myeloma, as we have isolated an aberrant plasma cell population that comprises 25% of the sample.

We established that a haematopathological finding of >10% plasma cells is consistent with a diagnosis of Myeloma. 

We are now considering giving an intravenous bisphonate to aid his severe hypercalcaemia but are being cautious given his AKI. 

We remain concerned about our patient.

Problems:

1) too much calcium

2) far too much protein

3) far, far too drowsy

Emergency MDT meeting question:

  • Should we treat his newly diagnosed Myeloma?
  • If so, with what and when?

Join our MDT on Twitter! #TeamHaem

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

Case 85 – update 1

Thank you for all your help so far on the medical admissions unit.

Assessment
Our patient was initially assessed using an ABCDE approach:
A) Snoring, requiring an airway adjunct (nasopharangeal airway)

B) RR16, chest clear to auscultation, sats 97% room air

C) HS I+II+0, HR 90 regular, BP 150/95, Cap refill 2 secs, no urine output

D) Unresponsive. BM 7. Pupils 2mm equal, reactive to light. Apyrexial

E) Soft abdomen, no obvious tenderness. No obvious trauma/bleeding/injuries/rash
We then discussed some initial investigations. You correctly identified that this was an emergency situation in which we had extremely limited background information about our patient.

First steps
Initial blood tests were taken
An urgent non-contrast CT head was requested
Critical care were contacted to review our patient

Investigations
The lab struggled with our patient’s samples and reported that they were ‘breaking the analyser’ as they were ‘too thick’, an ABG could not be processed; which made us question whether this could be a presentation of hyperviscosity syndrome.

The FBC came back relatively quickly and you notice that the requested blood film looked very blue compared to other samples – which you correctly identified could be a sign of a paraproteinaemia.

You pointed out that we need to be cautious with regard to top-up blood transfusions if we are considering a diagnosis of hyperviscosity syndrome, as this can further increase plasma viscosity and be dangerous for our patient.

Hb 73 

MCV 102.8 

Plt 123

WCC 5.87 

Neut 4.08 

CRP 60

 PT 12 

APTT 30

Fib 3.7

Na 140 

K 4.8 

Ur 23 

 Creat 204

 Co2 19

Total protein 115 

Albumin 37 

 Mg 1.0

 IgA 53

IgG 1.3

IgM 0.13

Paraprotein 45g/L

 Ad. Ca 4.33 

Phosphate 1.36 

                                                           
CT Head (non-contrast) No evidence of bleed/mass/infarct. Lytic lesions noted throughout skull

Next steps…
We have transferred our patient to a level 2 bed on HDU for monitoring, as he remains unresponsive and is tolerating an airway adjunct. We now have a bag of intravenous saline running in an attempt to dilute his hyperviscous blood.

We have summarised his current issues

1) Severe hypercalcaemia

2) Likely hyperviscosity syndrome

3) AKI (no know urine output at present)

4) Possible new underlying diagnosis of IgA Myeloma (serum immunofixation, lytic lesions on CT head)

Questions
· What do you know about the causes and symptoms of hypercalcaemia?

· What do you know about the causes and symptoms of hyperviscosity syndrome?

· What could be the causes of an AKI in this case?

· How would you prioritise the next steps in his management?

Share your thoughts on Twitter #TeamHaem
 

Posted in Myeloma/paraproteins | Tagged , , ,

Case 85 – the beginning

Welcome to our new case. We need your help urgently.

Our patient is a 55 year old man who is drowsy and confused. His friend is extremely worried and has brought him to the Medical Admissions Unit front door for help.

Our patient has been a bit muddled for a few days but is now barely responding to voice and is snoring loudly. His friend reports that our patient does not drink any alcohol, he does not take any recreational drugs or regular prescription medications.

Yesterday, our patient mentioned to his friend that he has an urgent Haematology clinic appointment next week – but his friend is not sure why.

Questions

  • How would you further assess our patient?
  • What initial investigations would you perform?

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, TeamHaem cases 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 Myeloma/paraproteins | Tagged

Case 84 – summary

Thank you for all your help with this weeks case!

This week we looked at a case of a patient with type 1 Gaucher’s disease . She was found to be mildly anaemia with a mild thrombocytopenia.

A CT scan revealed splenomegaly and blood tests showed a raised serum ACE and ferritin which are typically found in Gaucher’s disease.

A bone marrow biopsy was consistent with a diagnosis of Gaucher’s disease, and a glucocerebrosidase enzyme activity assay was reduced confirming the diagnosis of Gaucher’s disease. Genetic testing can also be done for homozygosity in N370S GBA gene which is found in the majority of cases of type 1 Gaucher’s disease.

Gaucher’s disease is a lipid storage disorder where glucosylceramide will accumulate in macrophages, and results from a deficiency in lysosomal hydrolase glucocerebrosidase.
Gaucher’s disease is an inherited autosomal recessive condition, and phenotype can vary greatly, with some patient’s not being diagnosed until very late in life, whereas other are diagnosed in infancy.

The prevalence of Gaucher’s disease varies in different populations and for type 1 Gaucher’s disease can be 1:50000-1:100000, and up to 1:850 in the Ashkenazi Jewish population. Type 3 Gaucher’s disease is most common in the Norrbottnian area of Sweden with a prevalence of 1:50000.

There are different types of Gaucher’s disease.

Type 1 Gaucher’s disease, as in our case, can present in childhood or adulthood, and some patient’s may have signs/symptoms for a few years before the diagnosis is made. This type of Gaucher’s does not usually result in brain or spinal cord involvement. Patient’s may present with anaemia, thrombocytopenia and hepatosplenomegally. There may also be lung and bony involvement – resulting in bone pain and fractures.

Type 2 and 3 Gaucher’s disease are known as nuronopathatic types as they will typically have nerve and spinal cord involvement. Patient’s can get the symptoms of type 1 Gaucher’s disease, but in addition will have central nervous symptom effects, such as seizures. Type 2 Gaucher’s disease will usually present in infancy. Type 3 Gaucher’s disease may progress slower than type 2.

In the severest cases Gaucher’s disease can cause in utero problems such as hydrops fetalis, organomegally and neurological problems and babies may die shortly after birth.

Treatment is with enzyme replacement therapy. An oral glucosylceramide inhibitor can also be considered.

Has anyone got any questions, or any knowledge they would like to add?

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, Bone marrow failure, Laboratory morphology, Related to other specialities | Tagged , , , , ,

Case 84 – update 2

So we have the results of our patient’s bone marrow and it looks to be consistent with Gaucher’s disease!

Our patient has a raised serum ACE and ferritin which is typical of Gaucher’s disease.

Our bone marrow shows the typical ‘crushed silk’ appearance of Gaucher’s cells.

Questions:

  • What tests would you do to confirm this?
  • What is Gaucher’s disease?
  • What types of Gaucher’s are there?
  • What type of Gaucher’s disease do we think our patient has?
  • What symptoms and lab findings can be associated with Gaucher’s disease?

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, Bone marrow failure, Laboratory morphology, Related to other specialities | Tagged , , , , ,

Case 84 – update 1

So we have an update:

We have found our patient is thrombocytopenic, and has a mild normocytic anaemia.

Our patient has been slightly tired for a year or so, but still manages to do her demanding job as a PE teacher. She has no past medical history and is on no regular medication

The patient does notice she is bruising easily but does not have any bleeding problems. A bleeding score is 1 (isth-ssc), and our patient says her job can be quite physical, so put it down to that. She denies any night sweats/weight loss. There is no parental history of bleeding problems. Our patient’s father was born in Israel and moved to England when he was 2, our patient’s mother was born in the England.

On examination:

  • Chest clear
  • HS I+II+O
  • Abdo soft, the spleen can just be felt below the costal margin
  • There are no rashes.
  • The patient has a few cutaneous bruising on arms and shins, none >2cm, no palpable haematomas.

We have done a number of blood tests:

  • Blood film – thrombocytopenia, but morpholocicaly normal red/white cells/platelets. No plt clumps.
  • B12/fol normal
  • U+E – normal
  • LFT – normal
  • Auto immune screen including RH factor, ANA, ENA,ANCA negative
  • Coag
    • PT 13.4
    • APTT 33
    • CLAUS FIB 3.7
    • VWD screen, factor XIII, PFA-100 normal
  • HIV/hep B/hep C negative
  • EBV IgG positive, IgM negative
  • CMV IgG and IgM negative
  • An ultrasound abdo has been done and shows splenomegaly with a 16.5 cm spleen. Liver appears normal. Renal tract normal.

Questions:

  • What are your thoughts now?
  • Is there anything else you would like to know?
  • What should we 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, Bone marrow failure, Laboratory morphology, Related to other specialities | Tagged , ,

Case 84 – the beginning

Welcome to our new case!

We start in the GP surgery with a 21 year old woman.

She has been feeling tired for a while so has come to get checked. Your colleague did some bloods on the previous visit and she has come for the results

  • Hb 110g/l
  • Wcc 9.0
  • Neuts 5.0
  • Plt 92
  • MCV 97

Questions:

  • What would you do next?
  • Is there any history you would like?
  • Are there any tests you would 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, Bone marrow failure, Laboratory morphology, Related to other specialities | Tagged

Case 83 – summary

Many thanks to everyone who contributed to our case.

This week the case centred on a pregnant female who was an obligate carrier of Haemophillia A (Her Father was affected). She had a factor VIII level of 54%. She was a carrier of intron 22 inversion. The free fetal DNA testing in this case confirmed she is carrying a male fetus. In this situation CVS would be offered or Amniocentesis for pre natal diagnosis but the patient declined.

She was keen for an elective c-section as she lives some way from the specialist centre and after careful discussion this was arranged for 37 weeks. A comprehensive care plan was agreed with MDT:

  • Premise is to assume baby may have Severe Haemophillia A
  • C-section planned for 37 weeks safe to proceed if factor VIII >50% and also safe for spinal if threshold reached. To deliver between 9-5 and inform MDT on initiation of section.
  • VTE prophylaxis safe if VIII level >60%
  • Mechanical VTE prophylaxis and adequate hydration to be encouraged.
  • If admission in spontaneous labour no fetal blood has sampling or fetal scalp electrodes. No forceps or ventousse.

At delivery:

  • Urgent cord blood for factor VIII level.
  • Oral vitamin K not IM.
  • Any bleeding concerns contact Haem consultant on call.
  • Neonatal team to review on delivery.
  • Cranial USS will be required if affected baby.
  • Actively managed third stage of labour.

She had a successful C-section and factor VIII level at delivery on the neonate is 36%. This is slightly lower than may be expected for a neonate but certainly excludes severe Haemophillia A a repeat sample at 6 months confirmed factor VIII level of 85%.

This case hopefully highlighted the importance of MDT working when caring for a pregnant patient.

Ideally this lady should have had pre-natal counselling and reproductive options discussed with her given her obligate carrier status. It is important when caring for patients with severe Haemophillia to contemplate extended family and offer genetic screening as appropriate particularly to females of childbearing potential.

Carriers of severe Haemophillia A should receive genetic counselling  and the options of preimplantation genetic diagnosis discussed. In England the NHS will find 3 cycles of pre implantation genetic diagnosis with a success rate of around 30%.

Other options for diagnosis:

  • Free fetal DNA to determine sex from 9 weeks gestation.
  • Carriers of Haemophillia A and male fetus should be offered Pre natal diagnosis via CVS at 11-14 weeks gestation.
  • Third trimester amniocentesis could also be considered for a male fetus.

If no diagnostic testing must treat male fetus as affected by Haemophillia A.

Antenatal care needs a coordinated MDT approach. In the case of Haemophillia A factor VIII levels generally rise during pregnancy from 6 weeks to around 2-3x baseline by term. Falling by day 2-3 post partum. Most carriers will have a level of 50-60% but lyonisation and ABO blood group can affect an individuals level.

Factor levels should be checked at booking and pre procedure as well as in third trimester to assist in planning for delivery. It should be noted that individuals carrying Haemophillia have an increased bleeding risk even when levels are between 40-60%. They are also at higher risk of PPH.

Factor VIII levels should be >50% for delivery and epidural. They should be >60% for LMWH prophylaxis.

If levels of VIII are low then DDAVP (0.3 micro grams per kg based on pre pregnancy weight)  should be given as a trial. Tachyphalaxis can occur with repeat doses. DDAVP is contraindicated if any evidence of pre-eclampsia. A fluid restriction should be kept to 1 litre post treatment. If trial of DDAVP fails then recombinant factor VIII should be used with levels checked before and after doses and after 4-6 hours. Tranexamic acid should also be used. Treatment should be continued for 3-5 days post delivery depending on circumstances.

Intrapartum care should be agreed with MDT and an anaesthetic opinion as well as obstetric advice is vital. A plan should be written and agreed before 37 weeks.

The options of delivery need careful discussion but a vaginal delivery is not contraindicated though induction may be needed if concerns about distance from specialist care centre. The optimal mode of delivery is uncertain but there is an increased risk of ICH in babies born with assisted vaginal delivery especially ventose. There is a suggestion of lower risks of ICH with planned Caesarean section and this should be offered to mothers for discussion depending on other additional risk factors.

During labour fetal blood sampling, fetal scalp electrode use and mid cavity or ventouse should be avoided. IM vitamin K should not be given oral used instead until confirmation of babies Haemophillia status via urgent cord blood.

Post delivery tranexamic acid is recommended for mothers until bleeding post delivery stops or lightens to normal menstrual period. This is felt to be safe with breast feeding. Women should be advised lochia passage can occur for long period upto 58 days post delivery.

If the baby is affected then cranial USS is recommended due to increased rates of ICH in these babies. MRI may be considered if suspicion of ICH. Prophylaxis may be considered for premature babies or those with traumatic delivery on a case by case basis.

There is a highly comprehensive guideline available on which the above case advice has been taken:

Pavord S et al. RCOG Green top guideline no 71. Management of inherited bleeding disorders in pregnancy. BJOG 2017;124:e193-e263. 

Posted in Inherited bleeding, Paediatric haematology, Related to other specialities | Tagged , , , , , , ,

Case 83 – update 3 

Our pregnant patient had a factor VIII level of 54%. She is a carrier of intron 22 inversion as predicted from family history.  The free fetal DNA testing confirms she is carrying a male fetus. The patient has decided that she does not wish to undergo CVS for diagnosis.

She was keen for an elective c-section as she lives some way from the specialist centre and after careful discussion this was arranged for 37 weeks. A comprehensive care plan was agreed with MDT:

  • Premise is to assume baby may have Severe Haemophillia A 
  • C-section planned for 37 weeks safe to proceed if factor VIII >50% and also safe for spinal if threshold reached. To deliver between 9-5 and inform MDT on initiation of section.
  • VTE prophylaxis safe if VIII level >60%
  • Mechanical VTE prophylaxis and adequate hydration to be encouraged.
  • If admission in spontaneous labour no fetal blood has sampling or fetal scalp electrodes. No forceps or ventousse.

At delivery:

  • Urgent cord blood for factor VIII level.
  • Oral vitamin K not IM.
  • Any bleeding concerns contact Haem consultant on call.
  • Neonatal team to review on delivery.
  • Cranial USS will be required if affected baby.
  • Actively managed third stage of labour. 

She has a successful C-section and factor VIII level at delivery on the neonate is 36%

Does this exclude baby being affected by severe Haemophillia A? 

What should you tell the parents?

What are the generally expected levels of factors in neonates? 



Posted in Inherited bleeding, Paediatric haematology, Related to other specialities | Tagged , , , , , , ,

Case 83 – update 2

Our pregnant patient returns to clinic she is now 13 weeks pregnant. 

Her factor VIII level was 54%. She is a carrier of intron 22 inversion as predicted from family history. 

The free fetal DNA testing confirms she is carrying a male fetus. The patient has decided that she does not wish to undergo CVS for diagnosis.

Is the patients factor VIII level safe for intervention / delivery?

When should her factor VIII level be re-checked?

What should be considered when formulating a birth plan with the patient? 

Any interventions that should be avoided during delivery?

Posted in Inherited bleeding, Related to other specialities | Tagged , , , , , ,

Case 83 – update 1

After consideration of her family tree you realise  if there are no non-paternity issues she is an “obligate carrier” of Haemophillia A. 

After counselling and discussion she agrees to having genetic testing for herself. She is willing to have free fetal DNA testing for fetal sex that can be carried out after 11 weeks. She also consents to checking her factor VIII level. 

A discussion regarding the next steps for diagnosis if the fetus is a male occurs. The lady is not keen to undergo CVS due to miscarriage risk and is clear she would continue with the pregnancy regardless of the outcome. 

She is otherwise well and all her booking bloods are satisfactory. Her bleeding history is unremarkable she has had a dental extraction a few years ago without complication and has not had any other bleeding. 

You agree to review her in clinic with the results of the above tests. 

What is the commonest mutation seen in Haemophillia A patients? 

If the patient was keen for CVS for pre natal diagnostic testing what level of factor VIII would you aim for to minimise bleeding risks? 

What treatment would you use if required to increase maternal factor VIII in preparation for CVS? 

Posted in Inherited bleeding, Related to other specialities | Tagged , , , , ,