Acquired haemophilia: a rare autoimmune bleeding disorder

Haemophilia is usually an inherited condition. The NHS explains that it is caused by a lack of a clotting factor, a protein that helps blood to clot, that most people are born with it, and that it can be developed later in life, although this is very rare. In the acquired form, the immune system makes antibodies, called inhibitors, that attack factor VIII, so the blood can no longer clot normally. A 2020 international recommendations paper describes the condition as acquired haemophilia A and notes that it occurs in men and women without a previous history of bleeding.

Because it is not inherited, people often have no family history and no personal history of bleeding. That is why the first episode can be a shock. The same paper says approximately half of patients have concomitant disorders, most often other autoimmune disorders or malignancy, and that about 1 to 5% of cases are diagnosed during pregnancy or within a year of childbirth. The other half have no identifiable cause.

A published discussion says acquired haemophilia should be suspected in any patient with no personal or family history of bleeding who presents with sudden-onset bleeding without a trigger, or with excessive bleeding after mild trauma. The consensus paper describes the bleeding pattern as characteristic: bleeding under the skin is the most common, seen in about 80% of patients, followed by bleeding into muscle, the gut, the urinary tract and the space behind the abdomen. Joint bleeds, the hallmark of congenital haemophilia, are much less common.

Typical features therefore include large bruises appearing without injury, swollen painful muscles, nosebleeds, blood in the urine or stool, and heavy bleeding after surgery, dental work or childbirth. The paper notes that bleeding ranges from life-threatening to mild or none, and that around 10% of patients do not present with bleeding at all.

Large unexplained bruises, bleeding that will not stop or any sudden internal bleeding need prompt medical assessment. The NHS advises people with haemophilia to call 999 or go to A&E for a head injury, a serious injury, blood in the poo or very dark poo, vomiting or coughing up blood, or a sudden bad headache with confusion, and the same warning signs should prompt emergency help for anyone with unexplained bleeding. Do not drive yourself.

If you are on a blood thinner, a bleed has many possible explanations, and doctors will consider those first. Tell clinicians about all medicines, because anticoagulants and antiplatelet drugs alter the picture.

The key blood test is the APTT, a clotting time that is unusually long when factor VIII is blocked, while the prothrombin time is usually normal. The consensus paper says that patients typically present with acute or recent bleeding, an isolated prolonged APTT, reduced factor VIII activity and the presence of autoantibodies detected by the Bethesda assay or an enzyme-linked immunosorbent assay. A mixing study, in which the patient plasma is mixed with normal plasma, shows that the APTT does not correct, indicating an inhibitor rather than a simple deficiency.

Doctors also look for a trigger. This usually involves checking for other autoimmune disease, medicines, a recent pregnancy, and for cancer, including blood and solid tumours. A prolonged APTT should never be ignored before an operation or in a person who is bleeding, the consensus paper stresses.

Management is by or in conjunction with a haemophilia centre. The NHS says that people diagnosed with haemophilia are referred to their local haemophilia centre for treatment.

Two things need to happen: bleeding has to be controlled, and the antibody has to be removed. For bleeding, the 2020 consensus recommends bypassing agents, namely recombinant activated factor VII, activated prothrombin complex concentrate or recombinant porcine factor VIII, in bleeding patients. These medicines work around the blocked factor VIII. Ordinary factor VIII replacement, which is used for inherited haemophilia, may be ineffective because the antibody neutralises it, although a published discussion says it can be used when the inhibitor level is low.

To remove the antibody, the consensus recommends immunosuppressive therapy, including corticosteroids, cyclophosphamide and rituximab, or combinations of these. It reports a median time to remission of 5 weeks, with considerable variation between individuals, and says that factor VIII activity at presentation, inhibitor level and antibody type are prognostic markers. Treating an underlying cause, such as a cancer or other autoimmune disease, may also remove the inhibitor.

Because there are no comparative trials, the authors say treatment decisions rest on expert experience and referral to expert centres is often recommended. Avoiding injuries and unnecessary invasive procedures is also an early priority while the inhibitor is present.

Acquired haemophilia is a serious condition but many people achieve remission. A published discussion gives estimated mortality of 7.9 to 22%, with most deaths from bleeding occurring within the first weeks after presentation, which underlines the importance of rapid diagnosis. Older people, who often have other illnesses and may be on anticoagulants or antiplatelet drugs, face particular risks from both the bleeding and the immunosuppression.

After remission, follow-up blood tests are needed because the inhibitor can return. Contact your haemophilia centre promptly if bruising or bleeding returns.

Once treatment is established, most people can resume normal activities, although the immunosuppression has infection risks that the team will discuss. The NHS advice for haemophilia generally, which includes checking with the haemophilia team before taking new medicines, avoiding aspirin, ibuprofen and other NSAIDs, taking care of teeth and gums, and wearing a medical alert bracelet, is sensible to discuss with your specialist while an inhibitor is present.

The Haemophilia Society is the UK charity the NHS points to for information and support for people with haemophilia and other bleeding disorders.