Case 147 summary: VITT

Many thanks for following our case this week of a young patient with VITT – a syndrome which emerged in Spring 2021 and offered significant challenges to treat

Following extensive roll-out of vaccines to protect against SARS-CoV-2, concerns arose around cases of thrombosis at unusual sites and thrombocytopenia. There were several case reports assimilated in different countries associated with the ChAdOx1 nCoV-19 (Oxford–AstraZeneca) vaccine. In the UK, an expert panel was convened to offer advice on the investigation and management of these patients and clinical experience quickly grew. The condition was termed Vaccine-induced immune thrombocytopenia and thrombosis (VITT).

Key clinical features (Clinical Features of Vaccine-Induced Immune Thrombocytopenia and Thrombosis | NEJM):

  • Onset of symptoms 5 – 30 days after vaccination (median 14 days)
  • Thrombosis (cerebral venous sinus thrombosis, DVT/PE and splanchnic vein thrombosis for the most part)
  • Thrombocytopenia (any level below lower limit of normal) – median 47 per cubic millimeter
  • Elevated D-dimer – median level 24,000
  • Anti-PF4 antibodies by ELISA

Investigations for thrombosis should be guided by clinical symptoms

Cases should be reported to the MHRA’s COVID-19 Yellow Card scheme

Management (COVID-19 rapid guideline: vaccine-induced immune thrombocytopenia and thrombosis (VITT) (magicapp.org))

  • Anticoagulation
    • Start as soon as benefit outweighs risk of bleeding using a non-heparin drug. Local experience in high bleeding-risk situations has been to use argatroban, and then fondaparinox or a DOAC once bleeding risk has reduced
    • Platelet transfusion or fibrinogen replacement may need to be considered for surgical intervention/bleeding
  • Managing the immune response
    • IVIg 1 g/kg – consider 2nd dose at 48h – 72h depending on response
    • Consider corticosteroids if response to IVIg is insufficient
    • Consider plasma exchange with fresh frozen plasma (1 volume exchange a day) as an alternative to a second dose of intravenous immunoglobulin – continue for up to 5 days, or until platelets recover
    • Consider rituximab for people with VITT that has not responded to a second dose of intravenous immunoglobulin or plasma exchange – 375 mg/m2 for 4 weekly doses

There are a group of high risk patients for whom prognosis is very poor: CVST with secondary bleeding, low platelets (<30) and/or thrombosis at multiple sites. These patients will likely benefit from more intensive treatment with plasma exchange and steroids up front

Ongoing management

Guidance states to continue anticoagulation for at least 3 months, and when anti-PF4 antibodies are no longer detected. This will likely be an individualised decision based on site of thrombosis and patient factors

In terms of second vaccine against SARS-CoV-2, the consensus is to give an alternative, mRNA vaccine once clotting has stabilised and at least 12 weeks has elapsed from the implicated dose.

Aetiology

The mechanism that links the vaccines and VITT is still uncertain. The detection of anti-PF4 antibodies suggests a similar process to HITT but without heparin as a trigger. The most likely hypothesis is that some element of the vaccine is binding to PF4 and triggering an immune response.

References/further reading:

Clinical Features of Vaccine-Induced Immune Thrombocytopenia and Thrombosis | NEJM

COVID-19 rapid guideline: vaccine-induced immune thrombocytopenia and thrombosis (VITT) (magicapp.org)

Greenbook COVID-19 chapter 14a (publishing.service.gov.uk)

vitt_patient_information_v4-20210420.pdf (b-s-h.org.uk)

Thrombosis UK | The Thrombosis Charity wishes to increase awareness of thrombosis among the public and health professionals and to raise research funds to improve patient care. Helping people who suffer from VTE, DVT, PE and clots.COVID vaccines and blood clots: what researchers know so far (nature.com)

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 147 – Update 3

Our 34 year-old female patient with VITT has responded well to plasma exchange, IVIg and anticoagulation and is now in neuro-rehabilitation with a normal FBC and is due to be discharged. The rehab medicine team wish to have your advice on:

  1. How long to continue anticoagulation for (she is on dabigatran 150mg BD)?
  2. Should she have the 2nd dose of her COVID vaccine?

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 147 – Update 2

We have a 34 year-old female patient presenting with headache, thrombocytopenia (plt 25) and intracranial haemorrhage requiring a decompressive craniectomy. She had the ChAdOx1 nCoV-19 (AstraZeneca) vaccine 13 days ago.

D-dimers are significantly elevated at 35,283 and subsequent CT venogram has confirmed significant sigmoid sinus thrombosis. Anti-PF4 antibodies have been sent but will take a few days to come back.

There is high clinical suspicion of Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT).

The patient is stable and the neurosurgeons are happy to commence anticoagulation.

What anticoagulant would you use, if any?

What other treatment would you implement, if any?

Why would the anti-PF4 ELISA be positive in the absence of heparin?!

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 147 – Update 1

We have a 34 year-old female patient who has presented with headache, thrombocytopenia (plt 25) and intracranial haemorrhage requiring a decompressive craniectomy which was supported with 2 pools of platelets pre-operatively and a further pool intra-operatively. She is now on the neurosurgical ICU and is stable, but remains intubated and ventilated.

You have collated other results:

U&Es, LFTs, bone profile, CRP all normal

Coag screen: PT 13, APTT 35, Clauss Fibr 4.1 (within normal ranges for your lab)

Film: True thrombocytopenia. No fragments, no primitive cells. No large platelets. No clear morphological cause for thrombocytopenia ?ITP

You have also collected some more information from GP records:

No significant past medical history, no regular meds, no known alcohol excess

Only recent GP record (13 days ago) is for her first ChAdOx1 nCoV-19 (AstraZeneca) vaccine

Are there any further investigations you would suggest?

Would you consider any other treatment at this time?

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Case 147 – the beginning

It is 4am and you are peacefully dreaming about the educational opportunities at #BBTS2021 when you are awoken by the neurosurgical SpR on-call. They would like advice around product support for a patient they wish to take to theatre for an emergency decompressive craniectomy.

The patient is a 34 year old lady who presented to A&E with a severe headache and has subsequently dropped her GCS to 9/15. CT head has demonstrated a large intracranial bleed with mass effect and midline shift. FBC on admission:

  • Hb 151
  • WCC 5.8
  • Plt 25

They are planning transfer to theatre imminently, and the procedure cannot be safely delayed.

Is there any other information you require pre-operatively?

What advice would you give to support the platelet count?

Are there any other investigations which may be helpful?

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.

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

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Case 145 – summary

Antiphospholipid syndrome (APS) is an acquired autoimmune disease characterised by laboratory criteria (persistent antiphospholipid antibodies) and clinical criteria (venous/arterial/micro-thromboses and/or pregnancy morbidity).

Catastrophic antiphospholipid syndrome (CAPS) is a rare manifestation of APS, which is characterised by rapid onset of multi-organ thromboses in the context of antiphospholipid antibodies or known APS. Prompt identification of this disease and intervention significantly improves prognosis (recovery rates range from 50 to 80% if treated effectively).

This summary focuses on CAPS.

Epidemiology

  • Extremely rare disease
  • Female > male
  • Occurs in both paediatric and adult patients


Clinical manifestations

  • Occurs as first presentation of APS (50% of cases) or in the context of known APS
  • Primary or secondary
    • Secondary APS/CAPS usually due to underlying SLE
  • Precipitating factor often identified, e.g. infection, malignancy, surgery
  • Rapid onset (within a week) of multiple organ thromboses
    • Microvascular thromboses predominates: renal failure, ARDS, ischaemic encephalopathy, cutaneous mainfestiations (livedo reticularis, necrosis, ulceration)
    • Large-vessel arterial thromboses: stroke, myocardial infarction
    • Large vessel venous thromboses: DVT, PE, thrombosis at unusual sites (e.g. CVST)
  • Systemic inflammatory response syndrome

Laboratory features

  • Persistent antiphospholipid antibodies
    • Lupus anticoagulant (LA): detected using functional assay, e.g. dRVVT
    • Anti-cardiolipin antibodies
    • Anti-beta2-glycoprotein I antibodies
  • Prolonged aPTT (if lupus-sensitive reagent used)
  • Mild thrombocytopenia is common
  • Minimal/absent MAHA – should only see a few fragments (if any!)
  • Anti-nuclear antibodies (especially with underlying SLE)

Diagnostic criteria for CAPS

  1. Evidence of involvement of three or more organs/tissues
  2. Rapid onset of multi-organ thromboses simultaneously or within one week
  3. Histological evidence of microvascular thrombosis affecting at least one organ
  4. Laboratory evidence of antiphospholipid antibodies

All four required for definite CAPS diagnosis; however, criterion 3 not readily available in acute phase, so probable diagnosis can be made from criteria 1, 2 and 4.


First-line Treatment

  • Given rarity of disease entity, treatment is not standardised
  • Essential elements of treatment
    • Anticoagulation
      • Unfractionated heparin or LMWH in acute phase
      • After recovery from CAPS, long term warfarin is the preferred anticoagulant of choice
    • High dose corticosteroids
      • e.g. IV methylprednisolone followed by oral prednisolone
  • Optional additional front-line treatment options
    • Plasma exchange
    • Intravenous immunoglobulin
      • Started after final day of PEX to avoid removal
    • Cyclophosphamide in patients with underlying SLE

Treatment of refractory CAPS

  • Treatment of refractory CAPS heavily relies on case reports and small case series
  • Treatment options include
    • Rituximab (anti-CD20)
    • Eculizumab (terminal complement inhibitor)

References

Kazzaz NM, McCune WJ, Knight JS. Treatment of catastrophic antiphospholipid syndrome. Curr Opin Rheumatol. 2016;28(3):218-227.

Nayer A, Ortega LM. Catastrophic antiphospholipid syndrome: a clinical review. J Nephropathol. 2014;3(1):9-17.

Ortel TL, Erkan D, Kitchens CS. How I treat catastrophic thrombotic syndromes. Blood 2015;126(11):1285–1293.



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Case 146 – summary

Marginal zone lymphoma is a type of low grade B-cell non-Hodgkin lymphoma. It can be sub-classified as nodal, splenic, and extra-nodal (EMZL) of mucosa-associated lymphoid tissue (MALT). They make up 5-15% of all non-Hodgkin lymphomas in the Western world.

EMZL account for around 2/3 of MZL. The commonest site is the stomach (where there is a strong association with Helicobacter pylori infection), followed by eyes and associated tissues, lungs, and salivary glands.

Tissue biopsy is essential for diagnosis, and immunohistochemistry must show CD20 positivity. The diagnosis is further supported by histological appearances and IHC negativity for markers of other lymphomas, including CD5, CD10, MYD88, cyclin D1. Staining for H. pylori is essential in order to guide treatment – if negative, other diagnostic means should be pursued e.g. serology, urea breath test, stool antigen test.

Additional investigations are recommended such as full blood count, hepatic/renal function tests, LDH, beta-2 microglobulin, serum protein electrophoresis and immunofixation, hepatitis/HIV testing. Bone marrow biopsy is recommended but its use varies. The ideal modality for staging is not universally agreed, and both CT or PET-CT are used. For gastric EMZL, oesophagogastrodudodenoscopy (OGD) is essential in order to collect biopsies from multiple sites (the disease is often multifocal). Endoscopic ultrasound may be of use to examine for perigastric lymphadenopathy, although often imaging will suffice.

Treatment involves H. pylori eradication triple therapy with a proton pump inhibitor for 4 weeks and 2 antibiotics for 10-14 days – regardless of H. pylori status. Urea breath test or stool antigen test should be checked 6 weeks after commencing treatment – if still positive, an alternative eradication regime should be sought. In positive cases, this therapy will result in remission in 75%.

Follow up should be by OGD and biopsy every 3-6 months for a minimum of 2 years. If evidence of residual or recurrent lymphoma, watchful waiting is advised unless the patient is showing symptoms or signs of disease progression. In these cases, radiotherapy can be considered for localised disease. Otherwise chemo-immunotherapy is indicated – agents vary but involve rituximab either as single agent or in combination with another agent such as chlorambucil, bendamustine, and lenalidomide.

References:

Marginal zone lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. https://www.annalsofoncology.org/article/S0923-7534(19)35465-1/fulltext

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Case 146 – update 4

Our patient undergoes involved-field radiotherapy to her stomach and perigastric lymph nodes with good clinical and radiological results – however, her surveillance biopsies remain positive for residual lymphoma. As she is asymptomatic, she resumes a watchful waiting approach.

After 9 months, she notices a lump in her neck and unfortunately this is confirmed to be marginal zone lymphoma.

How would you proceed at this point?

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Case 146 – update 5

Repeat CT scanning at this point shows recurrence of this lady’s perigastric lymphadenopathy, as well as bilateral neck and left axillary nodes.

She is commenced on systemic treatment with rituximab and chlorambucil, which she tolerates well without major side effects.

She remains in remission 4 years down the line. Well done, team!

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Case 146 – update 3

This lady has had a partial response after eradication therapy but is asymptomatic, so continues active monitoring with 3-monthly OGDs.

After about 12 months, she becomes symptomatic again with abdominal discomfort. CT scanning shows gastric wall thickening and perigastric lymphadenopathy only. Biopsy shows progression of her previously diagnosed lymphoma.

What treatment would you offer at this point?

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Case 146 – update 2

This lady has been diagnosed with stage IE extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), Helicobater pylori positive. She has completed 4 weeks of triple eradication therapy with lansoprazole, amoxicillin and clarithromycin, and her H. pylori test is now negative.

Unfortunately, her follow-up OGD and biopsy at 3 months show residual lymphoma.

How would you proceed at this point?

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Case 146 – update 1

You have arranged for this lady to have a CT chest/abdomen/pelvis which, apart from thickening of the stomach lining, is unremarkable.

Her final biopsy results are reported as follows:

“There is a diffuse atypical lymphoid infiltrate of medium sized cells with open chromatin. There are numerous plasma cells with distinct cytoplasmic immunoglobulin globules. IHC reveals predominantly B-cells positive for CD20 and CD79a and negative for CD5, IRF4, cyclin D1, CD10, and BCL6. Staining for H. pylori reveals numerous positive organisms. In situ hybridisation for Ig light chains shows lambda-restricted plasma cells. EBV negative.”

What is the diagnosis and what are her treatment options?

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Case 146 – the beginning

You are about to see a new patient in the Haematology clinic.

She is a 58-year old lady with a background of hypertension. Ramipril is her only medication. She is otherwise fit and well.

She has been referred to you by a gastroenterology colleague. She presented to them with dyspepsia, and a gastric biopsy via oesophagogastroduodenoscopy (OGD) has been provisionally reported as showing lymphoma.

How would you proceed at this point and what further information would you like?

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Case 145 – continued

The critical care team inform you that while he was on LMWH prophylaxis whilst an inpatient for his acute appendicitis, he has not had any further heparin exposure in the last three weeks.

Further investigations are arranged with results as follows:

Blood film – a few red cell fragments (<1 per high power field) and polychromasia. Mild thrombocytopenia. No other diagnostic features.

ANCA – negative
ANA – weak positive with negative extractable nuclear antibodies
Anti-cardiolipin IgG 62 U/mL (0-10)
Anti-beta2-glycoprotein IgG 41 U/mL (0-7)

CT TAP has been requested to exclude underlying malignancy.

Given the degree of renal impairment and the require for invasive procedures (line insertions, etc.), you advise the critical care team to commence an unfractionated heparin infusion with anti-Xa monitoring due to the prolonged baseline aPTT.

What is the most likely diagnosis here?

What would you advise regarding the patient’s antiplatelet therapy – should this continue if starting UFH?

Given the most likely diagnosis, what treatment options are available and which ones would you initially recommend?

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Case 145 – the beginning

You are on-call for haematology and receive a call from the critical care team regarding a 36-year-old male with a complex medical history. With the exception of an episode of uncomplicated acute appendicitis 3 weeks ago which required a laparoscopic appendicectomy, he was otherwise previously fit and well. He was admitted to hospital 7 days ago with right hemiparesis and dysphasia – imaging demonstrated thrombus within the left middle cerebral artery. He received systemic thrombolysis with altepase with a good neurological response and was then commenced on aspirin 300 mg daily.

Three days into his admission while he was being worked up for the cause of his stroke, he developed central chest pain – troponin T was significantly elevated at 623 ng/L. Cardiology took him to the cath lab for a primary PCI; however, his coronary arteries appeared patent on angiography. ECG showed sinus rhythm and his echocardiogram was unremarkable with good LV function.

Over the next three days, he developed shallow skin ulcers affecting his shins and an acute kidney injury. He then deteriorated suddenly with features of acute respiratory distress syndrome and was transferred to intensive care where he was immediately intubated and ventilated. The admitting critical care doctor notices that his right leg is swollen and doppler ultrasound confirms a proximal DVT. CTPA did not demonstrate any associated large PE.

Prior to commencing anticoagulation, the critical care team note that his coagulation profile (below) is abnormal and call for advice both on the safety of anticoagulation and for advice on any further investigations for this very thrombotic patient.

What advice would you give them on anticoagulation? What would be your choice of anticoagulant in this patient and why?

What further investigations would you recommend?

Full blood count
Hb 102            (130-180)
MCV 99           (80-100)
Platelets 123   (150-450)
WCC 14.2        (4.0-11.0)
Lymph 2.1       (0.5-3.5)
Neut 10.8        (2.0-8.0)
Eosin 0.3         (0.1-0.5)
Baso 0.1          (0.0-0.1)
Mono 1.0        (0.2-1.2)
Retic 120         (20-80)

Coagulation
PT 15               (11-15)
APTT 61           (25-35)
Fibrinogen 6.7 (1.5-5.0)


Biochemistry
Na 142            (133-146)
K 5.9                (3.5-5.3)
Creat 310        (45-85)
Bili 35              (0-21)
ALT 49             (0-40)
ALP 102           (30-130)
CRP 113           (0-5)

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Case 144 – Summary

The case this week focused on the use of Viscoelastic Haemostatic assays (VHA). The patient had a ruptured AAA. Initial TEG testing was normal but she continued to bleed. Repeat TEG showed she had developed shortened R time and increased MA that responded to product replacement with FFP and platelets. She had an increased Ly 30 % but the team were uncertain about the use of TXA. Eventually a repeat TEG showed Ly 30 % > 70% and TXA was given to good effect and haemostasis was achieved.

VHA are uniquely placed to diagnose hyperfibrinolysis and there is no equivalent conventional lab test to detect this. In TEG studies 10-34% of patients having a major haemorrhage have Hyperfibrinolysis and this can lead to unnecessary mortality and morbidity for patients.

VHA Background:

The ideas behind Viscoelastic Haemostatic Assays (VHA) are old and in fact “whole blood assays” as they were known were first described by Prof Hartert in 1948. These were mainly research tools due to long sample processing times and the susceptibility to external vibration. These issues started to be overcome and over the past few years these have gradually made there way into clinical use. It should be acknowledged that the evidence base is limited. A 2014 NICE DG13 only recommends the use of TEG and ROTEM post cardiac surgery and states there is insufficient evidence to recommend the routine adoption of ROTEM and TEG in trauma and post partum haemorrhage. The research has continued and in 2018 a BSH guideline was published on their use as an adjunct to usual care. Many hospitals in the UK have access to VHA and these are being used in settings other than the accepted role post cardiac surgery.

BENEFITS VHA:

  • SPEED – Traditional coagulation tests are slow and can lag behind in rapidly evolving clinical situations like haemorrhage. Viscoelastic assays are quick taking 30 mins but a rapid TEG is available in 15 minutes.
  • HYPERFIBRINOLYSIS DIAGNOSIS- uniquely placed to diagnose this issue and allow correction with TXA like in case 144.
  • LIVER DISEASE ? Recognised for some time that PT/APTT prolongation in liver disease for example don’t correlate with bleeding risk due to fall in protein C or S levels. Viscoelastic assays may help in this setting.
  • PLATELET FUNCTION – Useful for platelet inhibition testing for anti platelet agents – may yield important information regarding drug resistance.
  • PATIENT BLOOD MANAGEMENT – Good evidence to show can reduce blood product use in a variety of settings.

Difficulties VHA:

  • STANDARDISATION – Poorly standardised no generalised reference ranges.
  • TRAINING ISSUES – Older Viscoelastic assays rely on pipetting rather than cartridges so issues with user were common.
  • REPLACING TRIED AND TESTED TESTS – Temptation this is used as replacement for tried and tested lab tests rather than adjunct to care.
  • INCREASES COST OF CARE – Additional costs to testing with unclear benefit in some settings such as trauma.
  • INTERPRETATION/ COMPLEXITY – Specialised test needs someone who understands to interpret and apply to clinical situation and this may be difficult in stressful situations like Major haemorrhage.
  • ONLY INFORMATION ON SECONDARY HAEMOSTASIS- No use in assessing vascular issues or primary haemostasis as evidenced by the normal traces seen in VWD, Lupus, HITT or Protein C or S deficiencies.
  • ACTING ON SINGLE RESULT – Generally trends helpful in these assays rather than a one off result often tempting to over interpret one abnormal trace.

Types of VH Assay:

All are VHA’s are useful tests and there is little difference between ROTEM and TEG. They are based on the same technology both are viscoelastic methods that provides graph of clotting process.

  • Thromboelastography (TEG) – Whole blood into cup with activator. Cup moves around pin that is static and resistance recorded using torsion wire.
  • Thromboelastometry (ROTEM) – Like TEG uses whole blood in cup but this time pin moves and cup is static. Change in optical density detected.
  • SONOCLOT – Plastic probe on electromagnetic transducer vibrates vertically resistance as blood clot forms is measured.

Each system has its own nomenclature and interpretation system. Our hospital in the case had TEG so we will focus on this for the interpretation. There is a good summary in BSH guidance if your hospital uses other systems.

INTERPRETING TEG:

  • CK TEG OVERVIEW:

R time – Time taken for the pin to start to detect resistance and is when fibrin starts to form. Long R suggests prolongation in PT/APTT. FFP is the agent of choice to address this.

K time- Time for clot to form and fibrin to polymerise.

MA – Maximum clot strength. Depends on PLT and FFP. Referring to CFF trace will help assess if platelet dysfunction or fibrinogen issue mainly to blame for reduced MA.

Ly30 – Defines the amount of fibrinolysis. If prolonged Tranexamic acid will help here. If MA increased alongside increased LY 30 this is functional fibrinolysis and doesn’t need TXA.

Types of trace on TEG:

  • Citrated Kaolin (CK) – Kaolin only the “standard” TEG
  • Heparinise (CKH) – Kaolin and Heparinase. Useful to detect if heparin affecting results.
  • Functional fibrinogen (CFF) – Tissue factor and platelet inhibitor. Shows the function of fibrinogen. Results should show 20-30% contribution by fibrinogen. 
  • Rapid TEG (CRT) – Kaolin and tissue factor. Result in 10-15 mins so useful in MHP. Tells the MA but no R time as uses Kaolin and tissue factor to activate coagulation. 
  • Platelet mapping – ADP and Arachidonic acid.

REFERENCE TABLE FOR ACTIONS WITH VARIOUS RESULTS ON TEG: (Reference ranges vary according to local standards hence not used in table)

Profile/TestTEG Measure ResultActions
CKRProlonged**check CKHeparinase R time?Heparin contamination
Otherwise consider FFP
CK or CRTMADecreased**Check CFF MA if normal give PLT. If abnormal CFF Cryo or consider both Plt/Cryo
CKLY30Increased*Consider TXA 
*If MA on CK is increased then TXA not indicated as likely reactive Hyperfibrinolysis
CFFMADecreasedCryo 
CKHeparinaseRIf R time shorter than CK R timeSuggests Heparin in sample

Evidence for VHA use in trauma:

Interestingly as mentioned earlier although the use of VHA is fairly widespread in the context of trauma the evidence base for VHA driven Major Haemorrhage protocols is actually fairly weak. There has been a recent large RCT of 390 patients (ITACTIC study) with major bleeding comparing conventional coagulation test driven MHP to VHA driven MHP. This failed to show improved patient mortality or reduced massive transfusion in first 24 hours for the VHA group. This study perhaps shows that although tempting to adopt novel therapies on the basis they seem superior the evidence for VHA driven MHPs is still lacking. Enthusiasts for the role VHA has would suggest this is due to poor interpretation of the VHAs. In the centres that used VHA in ITACTIC study were not familiar in applying the technique in a pressurised situation that may have affected outcomes.

In reality VHA may have a role to play but certainly this doesn’t replace the use of conventional haemostatic tests at present. VHA is advocated in American college of surgeons advanced trauma life support recommendations. It has a 1C recommendation in European guidelines of major bleeding and coagulopathy following trauma 4th edition. The same European guidelines give conventional coagulation driven MHP protocols a rating of 1A. Therefore VHA are adjuncts to usual care and do not replace laboratory tests in major haemorrhage at this stage.

There are some other things we do know about VHA in trauma and these are outlined below:

  • There is evidence to suggests a Normal VHA is useful to rule out need for transfusion. (2B recommendation from BSH guideline on VHA).
  • Low clot strength (MA) and Ly30 >3% can be used as increased risk factor for transfusion. (2C recommendation BSH guideline on VHA).
  • Use of VHA seems to reduce transfusions used in terms of Red cells and FFP. (Gonzalez et al).
  • There is no basis to withhold TXA based on VHA results in trauma. (1B BSH guideline on VHA)
  • BSH guidelines state there may be a reduction in mortality when using VHA driven MHP based on Gonzalez et al study. This however as discussed above has not been found in more recent large multi-centre study ITACTIC.

I hope this case has been helpful and thank you for your contributions to the case. Please feel free to post any comments.

References:

NICE DG13 – detecting, managing and monitoring haemostasis: vistoelastometric point of care testing. (ROTEM, TEG and Sonoclot systems. 20/8/14.

Curry et al. The use of viscoelastic haemostatic assays in the management of major bleeding. British Journal of Haematology (2018) 182; 789-806.

The use of viscoelastic haemostatic assays in goal-directing treatment with allogeneic blood products – A systematic review and Meta-analysis. Scandinavian journal of trauma, resuscitation and emergency medicine. (2017) 25:39.

Gonzalez E et al. Goal directed haemostatic resuscitation of trauma -induced coagulopathy: a pragmatic randomised clinical trial comparing a viscoelastic assay to conventional coagulation assays. Ann Surg 2016;263:1051-9.

Casper et al. Clinical validation of precision medicine protocols: the last mile is the longest. intensive care med (2021) 47;80-82.

Baksaas-Arsenal K et al. Viscoelastic haemostatic assay augmented protocols for major trauma haemorrhage (ITACTIC): a randomised controlled trial. Intensive care med (2020)

Rossaint R et al. The European guideline on management of major bleeding and coagulopathy post trauma: fourth edition. 2016. Crit care 20:100.

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Case 144 -update 4

The clinical team looking after the lady are not happy to give tranexamic acid as they feel it will be a thrombotic risk.

They do accept advice to give 4FFP and a pool of platelets given the long R time and low MA. 

Blood results from arrival in theatre are now available:

Hb 74, plt 54, PT 25 seconds (12 sec to 14.8 sec) , APTT 49 (27sec -41 sec), Fib 1.4g /l (1.9g/l -8g/l)

They have repeated the TEG and call you again.

The Blue line is the CK TEG from arrival in theatre.

The Purple line is the new CK TEG post FFP, Cryoprecipitate and RBC.

R time (min) 5 (5-10)

Angle (degrees) 53 (53-72)

MA (mm) 60 (50-70)

Ly30 (%) 70 (0-8)

What advice would you give the team ?

Are there any other results you could check that can worsen a major haemorrhage situation?

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Case 144 – update 4

The clinical team looking after the lady are not happy to give tranexamic acid as they feel will be a thrombotic risk.

They do accept advice to give 4FFP and a pool of platelets given the long R time and low MA.

Blood results from arrival in theatre are now available:

Hb 74, plt 54, PT 25 seconds (12 sec to 14.8 sec) , APTT 49 (27sec -41 sec), Fib 1.4g /l (1.9g/l -8g/l)

They have repeated the TEG and call you again.

The Blue line is the CK TEG from arrival in theatre.

The Purple line is the new CK TEG post FFP, Cryoprecipitate and RBC.

R time (min) 5 (5-10)

Angle (degrees) 53 (53-72)

MA (mm) 60 (50-70)

Ly30 (%) 70 (0-8)

What advice would you give the team ?

Are there any other results you could check that can worsen a major haemorrhage situation?

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Case 144 – update 3

The lady has been taken to theatre but the team have noted she is becoming more unstable despite ongoing replacement with the Major Haemorrhage packs

She had 4 RBC 4 FFP and you advised 2 cryo following initial lab tests. Her TEG was normal at that time point.

She has been given a further 2 RBC and 2 FFP but is still haemodynamically unstable in theatre.

They decide to send further lab tests which are awaited and repeat the TEG.

They call you to ask for advice with the CK TEG trace below:

Green line : Patients Initial CK TEG

Blue line : Patients CK TEG in theatre (heparinise cup also run no evidence of heparin contamination)

R (min) 9.4 (5-10)

Angle (degrees) 48 (53-72)

MA (mm) 40 (50-70)

Ly30 (%) 45 (0-8)

What does the TEG show?

Would you advise anything further based on TEG results?

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Case 144 – update 1

You establish the patients isn’t on any anticoagulants or antiplatelet agents. She has no cardiac history and the team don’t know about her blood group. She had an ABG that shows a Hb of 64.

You advise the team that they should be aiming to keep her APTTR and PTR <1.5, Fibrinogen >1.5, Hb >80 and plt >50.

In the hospital there is a Thromboelastography (TEG ) available as a viscoelastic Haemostatic assay and you suggest this may be helpful to guide the situation. 

What are the benefits of viscoelastic haemostatic assays compared to traditional coagulation screens?

What are the potential difficulties with TEG and other similar viscoelastic haemostatic assays such as ROTEM or Sonoclot?

What are the differences between the different assays TEG, ROTEM and Sonoclot?

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