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 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:

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

Neurological (confusion, CVA)
Pulmonary (SOB, respiratory alkalosis)
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