22nd July 2024

Acquired haemolysis

Autoimmune haemolytic anaemia (AIHA)

In AIHA, extravascular haemolysis occurs due to the presence of autoantibodies against RBCs. This is categorised as either warm or cold AIHA according to the temperature at which this occurs.

Haemolytic markers are raised, and a positive Coombs test is expected.

Drug-induced haemolysis

Many drugs have been found to cause haemolysis, and these can occur by immune (i.e. AIHA) or non-immune mechanisms. Examples include penicillins, cephalosporins, NSAIDs, sulfasalazine, quinine and rifampicin.

Microangiopathic haemolytic anaemia (MAHA)

This is a type of intravascular haemolysis where RBCs are damaged and haemolyse due to mechanical damage whilst circulating. This can be caused by endothelial abnormalities within blood vessels leading to microthrombi, which causes trauma to the RBCs.

Causes include disseminated intravascular coagulation (DIC), haemolytic uraemic syndrome (HUS), thrombotic thrombocytopaenic purpura (TTP), eclampsia/HELLP (haemolysis, elevated liver enzymes and low platelets) syndrome, mechanical valves and vasculitides.

The blood film will show schistocytes (a fragmented part of an RBC) (Figure 6) and there is marked reticulocytosis.

Clinically, it can present differently depending on the primary cause, and treatment will depend on the diagnosis.

Image Source: Wikimedia Commons (2014). Microangiopathic haemolytic anaemia_(Schistocytes_and_spherocytes, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Microangiopathic_haemolytic_anaemia_(Schistocytes_and_spherocytes).jpg (Accessed: 16 January 2024)

Thrombotic thrombocytopaenic purpura

This is often thought of as a pentad of clinical features: haemolytic anaemia, thrombocytopaenia, renal injury, fever and neurological symptoms.

Reduced functional levels of ADAMTS13 (the enzyme that cleaves large multimers of von Willebrand factor, vWF, into smaller molecules) leads to platelet aggregation on the endothelium of small vessels and, therefore, thrombosis. This causes thrombocytopaenia due to increased platelet consumption. This can be acquired (with autoantibodies directed at ADAMTS13) or a hereditary deficiency of the enzyme. Levels can be checked, however treatment will need to be instigated urgently before results are available.

First-line treatment is plasma exchange, and medical treatment can include glucocorticoids, rituximab and caplacizumab (anti-vWF).

Haemolytic uraemic syndrome

This is defined by the triad of microangiopathic haemolytic anaemia, thrombocytopaenia and acute kidney injury.

It is more commonly found in children than in adults and is predominantly caused by shiga toxin-producing E. coli (STEC) 0157:H7, and mostly associated with diarrhoea, although this usually resolves prior to the development of other features. This can be confirmed with a stool culture or PCR for STEC and a stool assay for shiga toxin.

The infection is self resolving, and treatment is mostly supportive with IV fluid replacement, RBC or platelet transfusion and dialysis if required. In severe or atypical cases other treatments may be required, depending on the underlying cause. HUS is a notifiable disease.

Infections

A variety of infections can cause haemolytic anaemia. These include malaria (most commonly falciparum), babesiosis, bartonellosis and viral infections (e.g. dengue, yellow fever, Epstein-Barr virus, EBV).

Paroxysmal nocturnal haemoglobinuria (PNH)

PNH is a rare, acquired clonal abnormality in haematopoietic stem cells, which have reduced complement inhibitors (CD55 and CD 59) on their surface. This leaves cells derived from these stem cells prone to haemolysis through the complement system.

Patients can present with a wide range of symptoms, classically with more noticeable dark urine in the morning (although haemolysis does occur at lower levels throughout the day as well), symptomatic anaemia, jaundice, and unusual sites of venous thrombosis (e.g. abdominal or cerebral). It can also be associated with bone marrow failure and, therefore, symptoms of pancytopaenia such as recurrent infection, bleeding or bruising.

Specific investigations for PNH include sending blood for flow cytometry to detect reductions in CD55 and CD59 and bone marrow biopsy to evaluate any degree of bone marrow failure.

Treatment options include eculizumab (anti-complement monoclonal antibody) and anticoagulation and in patients with co-existing bone marrow failure, stem cell transplant is a curative option.