Haemophilia

Haemophilia is an inherited shortage of one of the proteins that turn a soft clot into a firm plug. The blood does clot, but slowly and badly, so the danger is not a scratch: it is what cannot be seen, blood seeping into a joint, into a muscle, inside the skull. The condition is rare and almost always affects men. Over the past thirty years it has changed more than most chronic diseases: a child with the severe form who is treated from the first year of life now grows up with intact joints and lives as long as his classmates.

Why the bleeding does not stop

Stopping a bleed takes two moves. First, platelets stick to the damaged vessel wall and plug the hole with a soft clot; that takes seconds, and in someone with haemophilia it works perfectly well. Then a cascade of a dozen proteins called factors gets going, each switching on the next, until threads of fibrin are laid down that stitch the plug through. It is in that cascade that one link is missing.

Hence everything that is peculiar about the illness. A small cut or a grazed knee bleeds as it does in anyone else and stops by itself, because platelets handle it. But wherever a firm seal is required — deep inside a joint, within a muscle, in the socket of an extracted tooth, in a surgical wound — the soft plug crumbles after a few hours and the bleeding starts again. That delayed rebleed is the signature of haemophilia.

Who inherits it and who is affected

The genes for both factors sit on the X chromosome. A man has only one: if the gene on it is faulty there is nothing to replace it, and he has the disease. A woman has two, and the second one usually works, so she is more often a carrier. The sons of a carrier have a one in two chance of having haemophilia, and her daughters the same chance of being carriers. Every daughter of an affected man is a carrier, while his sons are unaffected, because from their father they receive the Y chromosome.

Two things about this scheme are widely overlooked. First, roughly a third of those affected have no family history at all: the fault arose afresh, and having no affected relatives does not rule the diagnosis out. Second, being a carrier is not always silent. In some women the factor level is low enough that they genuinely bleed: heavy and prolonged periods, haemorrhage after childbirth, easy bruising, slow healing after a dental extraction. For a long time they were dismissed as "just carriers" and left untreated; today they are given the diagnosis and treated on the same footing as men.

There is also an acquired form, in which an adult's body suddenly starts producing antibodies against its own factor. It is very rare, arises mostly in older age, after childbirth or alongside a tumour or an autoimmune disease, and looks alarming: extensive bruising and bleeding in someone who has never had such trouble. It is managed differently and needs urgent assessment.

Two types and three degrees of severity

In haemophilia A factor VIII is missing; in haemophilia B it is factor IX. The symptoms are indistinguishable and only the medicines differ, so the type is always established. Haemophilia A is about four times commoner.

Severity is defined not by how a person feels but by the residual activity of the factor in the blood:

• severe: activity below one per cent of normal. Bleeds occur with no injury at all, most often into joints, and without preventive treatment they recur dozens of times a year;
• moderate: between one and five per cent. Bleeding shows itself after knocks and exertion;
• mild: five per cent and above. A whole life can pass without a single episode, and the condition comes to light at forty after a tooth extraction or a first operation. It is precisely the mild forms that spring a surprise at the worst moment.

What it looks like in real life

The severe form usually announces itself in the first year: large oddly shaped bruises once the child starts crawling and pulling up, prolonged bleeding from a bitten lip or torn frenulum, a swollen joint after ordinary rough and tumble. After that the central event becomes bleeding into a joint, most often the knee, ankle or elbow.

It is recognised by a sensation children describe as tingling or pressure from within, before anything is visible. Then the joint turns hot and tight, straightening it hurts, and the person settles with it half bent. Blood inside a joint does more than hurt: it eats away at cartilage. Several repeated bleeds into the same knee turn it into a "target joint", where each new episode comes more easily than the last, and over the years an arthropathy develops with stiffness and pain. That is why a bleed is treated at once rather than after "seeing how it looks in the morning".

The second typical site is muscle. Blood within the muscle body produces a firm painful swelling with no bruise on the skin, and the volume lost can be substantial. The iliopsoas deserves separate mention: a bleed there disguises itself as pain in the groin, the abdomen or the lower back, the leg stays flexed at the hip and will not straighten, and such bleeding is dangerous both for the blood lost and for the pressure on a nerve.

When it is a matter of hours

Call an ambulance at once (in Europe the single number is 112) or go to the emergency department if a person with haemophilia has:

• a head injury of any kind, even with no loss of consciousness and no visible wound;
• sudden severe headache, vomiting, drowsiness, confusion, a squint or seizures: this is how bleeding into the brain shows itself;
• bleeding or swelling in the neck, the mouth or under the tongue, a changed voice, difficulty swallowing or breathing;
• vomiting blood or coffee-ground material, or black tarry stools;
• severe pain in the abdomen or the groin;
• a deep wound, a fracture, a major injury;
• increasing swelling of a limb with numbness, pallor and loss of sensation: the tissues are being compressed by the blood that has leaked out.

The rule is simple: give the usual treatment first, if it is to hand, and only then call for help — waiting for a doctor to decide is not an option. Do not drive yourself. Take the medication and the document stating the diagnosis, the type and the contact details of your centre. In all other situations — an ordinary joint or muscle bleed, blood in the urine, bleeding that home treatment will not settle — contact your haemophilia centre the same day.

How the diagnosis is made

The first step is the basic clotting screen. In haemophilia one result is prolonged, the activated partial thromboplastin time, while the prothrombin time and the platelet count are normal. Next the activity of factors VIII and IX is measured: that is the diagnosis, and it also sets the severity. Separately, the blood is checked for antibodies against the factor.

Von Willebrand disease looks similar; it is the commonest inherited bleeding disorder and affects men and women equally, and the same tests exclude it. Genetic testing pins down the exact variant and is useful above all to female relatives, who need to know whether they are carriers.

Where haemophilia is already known in the family, testing is planned in advance: a blood sample from the cord at birth and, if wished, testing before birth. In a woman expecting a boy at risk, delivery is conducted gently, without ventouse or forceps.

What treatment looks like now

The foundation of treatment is replacing the missing protein. Factor concentrate is given into a vein; preparations may be synthetic or plasma-derived, and both undergo viral inactivation. Extended half-life products allow injections to be spaced further apart.

The great shift of recent decades has been the move from treating bleeds as they happen to prophylaxis: the medicine is given regularly so that the factor level never falls to the critical point and the bleeds simply do not occur. In children with the severe form prophylaxis starts early, before the first joint damage, and it is what has changed the outlook of the disease.

For haemophilia A there is a drug injected under the skin that stands in for the missing factor; it suits children and people who have developed antibodies alike. In mild haemophilia A a medicine that makes the body release its own stores of factor is sometimes enough. For bleeding from mucous membranes — the nose, the gums, after a tooth extraction, with heavy periods — a drug is used that stops the clot dissolving. Gene therapy has also arrived: a single administration after which the liver begins making the factor itself. The method is young, not available to everyone, and requires long-term follow-up.

Inhibitors, antibodies the body makes against the infused factor, are the most troublesome complication of treatment. The usual products stop working, and the switch is either to bypassing regimens or to a long course that teaches the immune system to tolerate the factor. Antibody levels are therefore checked regularly, especially in the first years.

A separate chapter of history: plasma-derived concentrates used before viral inactivation methods existed infected many patients with HIV and hepatitis C. This does not apply to present-day products, but anyone whose treatment began in those years should make sure they have been tested for both — hepatitis C can now be cured.

Living with haemophilia

The rules look dull right up until you compare the joints of those who kept to them with the joints of those who did not.

• Treat a bleed immediately. At home, at the first sensation in the joint, without waiting for swelling; then rest, cold, gentle support and the limb raised.
• Avoid aspirin and other non-steroidal anti-inflammatory drugs: they hamper the platelets further still. For pain, paracetamol and whatever the doctor advises.
• No intramuscular injections. Vaccines are given with a fine needle under the skin, with pressure held over the spot for a few minutes; vaccination itself is important, and hepatitis vaccines especially so.
• Keep moving. Strong muscles protect joints, and immobility ruins them. Swimming, cycling and walking are good; boxing, wrestling, rugby and anything involving blows to the head are not.
• Look after the teeth, and tell the dentist in advance so that any procedure can be covered with treatment.
• Discuss any operation, however minor, and any new medicine.
• Wear a bracelet or carry a card with the diagnosis, the type and the centre's contact details: if you are unconscious, it is the only thing that will speak for you.

Online consultation

An online appointment is not the tool for the middle of a bleed — then you follow the plan and call for help — but for the time in between, when there is room to think. The doctor can judge whether bruising, joint pain or very heavy periods fit a clotting disorder and which tests would settle it. They can help a woman from a family with haemophilia understand what carrier status means for her and for any children she may have. And they can plan the run-up to surgery or a dental extraction, decide what to do about repeated bleeds into the same joint, shape a sensible level of activity, and go through what to pack before a trip.

This material is for information only and does not replace medical advice.