Complications
Large bleeding into the deep flexor muscle group within a closed space in the extremities may result in compartment syndrome with neurovascular compromise. This is a musculoskeletal emergency.
May occur following trauma or a spontaneous muscular bleed.
Extremely important to recognise early in order to avoid permanent neuromuscular damage.
Early signs include pain, swelling, decreased range of motion, and increased warmth.
Late signs include worsening pain, pallor, absent or diminished pulses, and sensory deficit.
The initial treatment is aggressive factor replacement therapy (not fasciotomy), but the patient also requires direct, continuous observation and monitoring of the need for fasciotomy. Management should be coordinated between haemophilia specialists and the orthopaedic surgeons.
Higher risk in patients with haemophilia B.
The allergic reaction to factor IX generally indicates that the patient is developing or has developed a factor IX inhibitor.
Haemophilia B patients with factor inhibitors and a history of anaphylaxis to factor IX should be monitored carefully for the development of nephrotic syndrome and recurrent severe allergic reactions during immune tolerance induction with factor IX concentrates.[36][38]
High risk if severe haemophilia and not receiving prophylactic therapy (defined as the regular, continuous administration of a haemostatic agent/agents with the goal of preventing bleeding in people with haemophilia while allowing them to lead active lives and achieve quality of life comparable to non-haemophilia individuals).[38]
Medium risk if moderate haemophilia and not receiving prophylactic therapy.
Low risk if mild haemophilia.
These complications occur secondary to recurrent bleeding into the joint or muscle and may be prevented by the use of prophylactic factor VIII or factor IX infusions, or emicizumab for haemophilia A. The use of recombinant factor VIIa seems to be safe and effective for providing adequate haemostatic cover in patients with inhibitors undergoing orthopaedic surgery procedures.[148][149]
Pseudotumour is a potentially limb- and life-threatening condition. The 'tumour' grows as a chronic, encapsulated cystic mass subsequent to inadequate management of recurrent bleeds in soft tissue/muscles or bones.[60] Often occurs in muscle adjacent to bone, which can be secondarily involved. The pseudotumour can become massive, causing pressure on adjacent vital organ(s) and neurovascular structures and may cause pathological fractures. Management should be coordinated between haemophilia specialists and the orthopaedic surgeons.
High risk if severe haemophilia and not receiving prophylactic therapy (defined as the regular, continuous administration of a haemostatic agent/agents with the goal of preventing bleeding in people with haemophilia while allowing them to lead active lives and achieve quality of life comparable to non-haemophilia individuals).[38]
Low risk if severe haemophilia and receiving prophylaxis.
Medium risk if moderate haemophilia.
Low risk if mild haemophilia.
The risk increases in all patients with trauma or surgery.
Risk is low for mild to moderate haemophilia, and medium for severe haemophilia.
Likelihood is higher in haemophilia A than in haemophilia B.
About 30% of patients with haemophilia A develop inhibitors to infused factor VIII, whereas the inhibitor incidence for haemophilia B is up to 5%.[38]
Risk factors for the development of inhibitors include:[19][22][39][40][41][42][43][44][45][46][47][48]
Disease severity - more common in severe haemophilia, but may also occur in patients with mild to moderate haemophilia
Environmental factors - treatment intensity, infection, age, type of product
Genetic mutations - in particular, those that result in absence of a gene product; immune response genes have also been implicated in inhibitor development. People with a family history of developing inhibitors to infused factor VIII and people of African-Caribbean or Hispanic descent are more likely to develop inhibitors.
Patients are classified as low responders or high responders on the basis of inhibitory antibody levels, and this classification contributes to treatment decisions.[1] High responders have a lifetime history of titre ≥5 Bethesda units (BU); however, it should be noted that overall high responders may have a low titre result (a titre <5 BU) at any particular test without it altering their overall classification.
Patients with low-titre inhibitors may be treated with high doses of factor VIII or factor IX, whereas those with high-titre inhibitors need treatment with bypassing agents (e.g., recombinant factor VIIa or Factor VIII inhibitor bypassing fraction [an activated prothrombin complex concentrate (aPCC)]).
Ultimately, the goal is to eradicate the inhibitor by immune tolerance induction (ITI). The necessity of ITI is now under debate, with the availability of emicizumab for effective prophylaxis. Studies are required.
Of patients with haemophilia who received factor VIII and factor IX concentrates in the late 1970s and early 1980s, 70% to 90% became infected with hepatitis C virus, hepatitis B virus, and HIV. This was due to the preparation of concentrates from pools of plasma collected from thousands of donors.[150][151]
Improved factor concentrate safety and purity has been achieved by a combination of plasma donor screening, heat or chemical viral inactivation methods, monoclonal antibody and other purification techniques, and recombinant gene technology.[152]
In the US, the Centers for Disease Control and Prevention implemented a programme called Universal Data Collection (UDC) to monitor blood safety. Patients enrolled in UDC receive free blood testing for hepatitis A, B, and C, and HIV.
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