Haematological emergencies

In this article, we give an overview of the most important and serious haematological emergencies that junior doctors should know about!

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Neutropenic sepsis

Case 1:

  • 54-year-old woman
  • Recent new diagnosis of a high-grade lymphoma
  • Received R-CHOP chemotherapy 7 days ago
  • Presents to ED with a fever of 38c

What could be going on here? What would your management be?

What is neutropenic sepsis?
  • Treatments like R-CHOP are myelosuppressive – patients may become anaemic (low haemoglobin), thrombocytopenic (low platelets), and also neutropenic (low neutrophils)
  • The exact definition of neutropenia can vary, however generally moderate neutropenia is defined as a neutrophil count 0.5-1.0 x10^9/L, and severe as <0.5 x10^9/L
  • Neutropenic sepsis = neutropenia, plus either a raised temperature (>38c) or clinical signs/symptoms of sepsis

Always have a high degree of suspicion for neutropenic sepsis in neutropenic patients/patients with risk factors for neutropenic sepsis, as the clinical signs aren’t always obvious

We have a separate article all about neutropenic sepsis here

  • Neutropenic patients have a weakened immune system, which means they can’t fight off infection as easily
  • Infections in these patients are more likely to be bacterial, and more likely to become disseminated – they can become life-threatening much more quickly!
  • Patients at risk of this should be counselled – e.g. if they spike a temp, go straight to hospital
Management

It’s important to get antibiotics in quickly (before investigations)! Which antibiotic to use will be trust-dependent

  • Usually broad-spectrum e.g. Tazocin
  • Plus gram-negative cover e.g. gentamicin

Why gram negative? Neutrophils also have an additional role in maintaining mucosal membranes – which is why neutropenic patients often get issues like oral mucosal ulceration and colitis – the gut mucosa is less protected. Because that barrier between the gut and the rest of the body is not as intact, patients can get ‘bacterial translocation’ – gut bacteria (which are often gram-negative) get into the bloodstream

Do the sepsis 6, and make sure you get all the cultures! Including from any lines e.g. PICC line

  • Make sure you do a thorough examination, checking for any sources of infection
  • Often you won’t find a clear clinical focus – this is due to a lack of neutrophils, which means you don’t get as much localisation, and infection becomes widespread quickly
  • E.g. your patient might not show a focus on CXR, might not have WCC on urine dip
  • Also, do Covid PCR and viral screens

When to consider granulocyte colony-stimulating factor (G-CSF)?

  • G-CSF = S/C injection that stimulates granulocytes to increase circulating neutrophil count – to help the body fight off infection
  • In this case, it’s a lymphoid malignancy so it is ok to give G-CSF if they are neutropenic (however there are caveats to that, e.g. Hodgkin’s lymphoma)
  • In myeloid malignancies e.g. AML it may actually drive the underlying malignancy! Don’t start without asking the chemo/oncology/haematology team

Thrombotic thrombocytopenic purpura (TTP)

Case 2:

  • A 25-year-old woman presents to ED with fever and headache
  • FBC shows a platelet count of 15 x 10^9/L
  • Lab calls and says that they think they can see schistocytes on the blood film
schistocytes
Blood film showing schistocytes

Schistocytes are literally RBCs that have been sheared in half – multiple causes, including TTP

If TTP is untreated, the mortality rate is 90% within 48 hours

Note – DIC can present similarly, but would also have clotting screen derangement, and usually don’t have such a marked thrombocytopenia

Pathophysiology
  • Lack of ADAMTS13, an enzyme responsible for cleaving large von Willebrand factor (VWF) multimers – usually due to antibodies towards it
  • Lack of this enzyme causes large clumps of uncleaved VWF multimer – this clogs up capillaries
    • Can clump in the brain, kidneys, heart etc.
  • Thrombocytopenia happens due to consumption
  • Anaemia – due to the mechanical shearing of red blood cells through the partially occluded vessels
Pentad of features
  • Thrombocytopenia
  • Microangiopathic haemolytic anaemia (MAHA)
  • Neurological impairment
  • Renal impairment
  • Fever

But note – not all patients will have all of these features!

Investigations
  • FBC: Low platelets (usually 10-30), anaemia
  • Blood film: Schistocytes
  • Haemolysis markers
  • Coag screen – normal
  • ADAMTS13 assay
  • Consider other investigations for underlying causes – e.g. virology, autoimmune screen, ECG
Management
  • Start treatment based on history, examination and blood film results
  • Plasma exchange (the mainstay of management) – aim to start within 4-8 hours – this replaces ADAMTS13
  • Steroids – to stop the production of antibodies to ADAMTS13
  • Supportive care

APML

Case 3:

  • 27-year-old male
  • Presents to ED with fever and bruising
  • Hb 92, WCC 1.9 (neutrophils 0.3), platelets 38
  • PT 23, APTT 50
  • Lab call saying they think they can see blasts on the film
blasts
Blood film – there are very large cells (called blast cells – immature white cells), and the nucleus of these cells is very diffuse and bi-lobed (called a buttock cell)
The cell in the middle is packed with Auer rods
Bundles of these rods are pathognomic for a myeloid malignancy 

Buttock cells with coagulopathy – classical of acute promyelocytic leukaemia (APML) – this leukaemia is classically associated with DIC

What is APML?
  • Incidence of AML is 3-5,000/year, of which 5-10% are APML (highest rates in young adults)
  • Generally good prognosis, but this only applies if the patient survives the first few days, as the coagulopathy is the most likely thing to kill them
  • APML is caused by the translocation t(15:17) – of retinoids acid receptor alpha
  • This stops promyelocytes from differentiating
  • Therefore, you treat it with retinoic acid (trans) which allows the cells to replicate
Investigations
  • Blood film
  • BMAT (if coagulopathy allows)
  • Karyotype
  • FISH
  • RT-PCR

But start treatment based on the morphology on the blood film!

Management
  • Immediate: Management of DIC (see below), supportive products e.g. FFP, management of concomitant infection, consider TLS
  • All-trans-retinoic acid (ATRA) + anthracycline/cytarabine
  • OR arsenic trioxide
  • Chronic remission is achieved in 80-95% of patients who survive the first 48 hours

Dissemination intravascular coagulation (DIC)

  • Increased tissue factor, which causes excess thrombin production
  • Can be secondary to many pathologies e.g. sepsis, malignancy, infection, trauma
  • Essentially out of control haemostasis
    • Consumption of platelets and clotting factors, hyperfibrinolysis causes bleeding
    • Consumption of anticoagulants e.g. protein C/S, anti-thrombin, and excess antifibrinolysis – causes thrombosis
Clinical features
  • Thrombosis and bleeding
  • Microvascular thrombosis can lead to organ failure
Diagnosis
  • Schistocytes on blood film
  • Low platelets
  • Reduced fibrinogen
  • Increased D Dimer
  • Deranged PT
Management
  • The main treatment is to treat the underlying cause!!
  • If bleeding, then give FFP

Hyperleukocytosis and leukostasis

Case 4:

  • 40-year-old woman
  • Presents to ED with fever and SOB
  • Hb 70, WCC 120, plts 35
  • CXR:
leuco

Given the very high WCC, you should be worried about leukostasis – here there has been infiltration of WCC into the lungs. This problem is more common in acute leukaemias – blast cells are big sticky cells, which can clump and cause congestion

Presentation
  1. Neurological (confusion, CVA)
  2. Pulmonary (SOB, respiratory alkalosis)
  3. Cardiac (angina, sometimes MI)
Diagnosis
  • WBC >100 (but it can occur with a WCC lower than this)
  • Signs of tissue hypoxia
  • Blood film
Management
  • Fluids and leukapheresis (spin off the white cells)
  • Then cytoreduction (either chemotherapy or hydroxycarbamide) – brings the white cell count down
  • 20-40% mortality within 1 week of presentation – needs urgent treatment!

Tumour lysis syndrome (TLS)

Case 5:

  • 60-year-old man – bleeped to review at 0300 following syncopal episode/fall
  • Recently started on chemotherapy for bulky DLBCL (diffuse large B cell lymphoma – a high-grade lymphoma)
  • Background: CKD, but on repeat bloods, he is noted to have AKI, hyperkalaemia, and hypocalcaemia
  • Tachycardic on examination
What is TLS?
  • Metabolic syndrome is caused by the breakdown of malignant cells
  • When those cells get destroyed (either by auto-lysis or due to chemo), release cellular contents into the circulation
  • TLS causes a high burden of uric acid, phosphate, and potassium – can cause arrhythmias etc.
  • Uric acid crystals form in the renal tubules, meaning the TLS metabolites can’t be excreted, causing a downwards spiral of acute kidney failure
  • It is a fairly rare complication, however, when it does happen it often has severe consequences, a third of patients need dialysis
Risk factors
  • High tumour burden
  • High-grade tumour
  • Existing renal impairment
  • Age
  • Treatment with highly active, cell cycle-specific agents
  • Use of other drugs that increase uric acid levels, e.g. alcohol, thiazides, cisplatin

All patients receiving chemotherapy for haem malignancies should be risk-assessed for TLS. Based on the risk assessment, they may then have prophylactic treatment

  • Low risk: Monitoring, regular fluid status evaluation, low threshold for IVI
  • Intermediate risk: Offer up to 7 days of allopurinol prophylaxis, along with increased hydration
  • High risk: Prophylaxis with rasburicase, plus increased hydration
  • Allopurinol: xanthine oxidase inhibitor – prevents uric acid from being formed
  • Rasburicase: converts uric acid into allantoin, which is much more soluble than uric acid
Diagnosis
  • Lab-based – look at uric acid levels, potassium etc.
    • High uric acid (≥476 umol/l or 25% increase from baseline)
    • High potassium (≥6.0 mmol/l or 25% increase from baseline)
    • High phosphorus (≥1.45 mmol/l (adults) or ≥2.1 mmol/l (children) or 25% increase)
    • Low calcium (≤1.75 mmol/l or 25% decrease from baseline)
  • Clinical – e.g. AKI, cardiac arrhythmia, seizures (poor prognosis)
Treatment
  • Cardiac monitoring
  • MDT – involve ICU, haematology, renal
  • IV fluid
  • Rasburicase
  • May need dialysis e.g. if severe hyperkalaemia

Acute chest syndrome

Case 6:

  • 19-year-old man with known HbSS (sickle cell disease)
  • He is on a regular transfusion programme, hydroxycarbamide and iron chelation therapy, penicillin prophylaxis, and folic acid
  • Presents with 1-week history of generalised pain not responding to regular oral analgesia
  • In particular, worsening right arm and rib pain
  • Afebrile, HR 96, BP 126/82, RR 24, sats 92% room air
  • Chest: Some right basal crackles
Initial management
  • O2
  • Analgesia
  • Regular obs
  • Urgent bloods including group and save           
    • Should highlight to the lab that you have a sickle cell patient in – they have a high chance of having allo-antibodies complicating cross-match
  • Check renal and liver function, inflammatory markers
  • CXR

Reviewed the patient later:

  • Chest pain worsening, sats 80% room air, RR 33
  • CXR: Left basal pneumonia and interstitial shadowing
  • ABG: pCO2 5.1, pO2 8.1

This is an emergency!

  • ACS is an acute illness characterised by fever and/or respiratory symptoms accompanied by a new pulmonary infiltrate on CXR
  • Severe hypoxia is a useful predictor of severity and outcome
  • Can occur on admission (i.e. present with it), or may develop later on in admission for acute pain
  • It can be triggered by PE, fluid overload, opiates, infection
  • This can be a LIFE-THREATENING condition, and early recognition of progression to acute respiratory failure is vital
  • Up to 20% need ventilation
Pathophysiology

There is an initial insult – e.g. infection, infarction –> reduced oxygenation –> HbS polymerisation –> decreased pulmonary blood flow that exacerbates vaso-occlusion –> more severe hypoxia

It’s a vicious cycle! Can deteriorate very rapidly

Investigation and management
  • All SCD patients with acute pain crisis should have at least 4-hourly obs including sats, daily clinical exam
  • CXR, FBC, renal/liver function, blood group, cultures if febrile, ABG, atypical screen, sputum MC&S
  • Inform the haematology team, and outreach/ITU teams
  • Thromboprophylaxis
  • Monitoring, IVI, IV antibiotics, analgesia, chest physio, transfusion if necessary

References

Written by Dr Sarah Halligan (IMT1)

Webinar and review by Dr James Clark, Haematology SpR

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