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 recognize 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 hemophilia specialists and the orthopedic surgeons.
Higher risk in patients with hemophilia B.
The allergic reaction to factor IX generally indicates that the patient is developing or has developed a factor IX inhibitor.
Hemophilia 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 hemophilia and not receiving prophylactic therapy (defined as the regular, continuous administration of a hemostatic agent/agents with the goal of preventing bleeding in people with hemophilia while allowing them to lead active lives and achieve quality of life comparable to non-hemophilia individuals).[38]
Medium risk if moderate hemophilia and not receiving prophylactic therapy.
Low risk if mild hemophilia.
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 hemophilia A. The use of recombinant factor VIIa seems to be safe and effective for providing adequate hemostatic cover in patients with inhibitors undergoing orthopedic surgery procedures.[146][147]
Pseudotumor is a potentially limb- and life-threatening condition. The "tumor" 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 pseudotumor can become massive, causing pressure on adjacent vital organ(s) and neurovascular structures and may cause pathologic fractures. Management should be coordinated between hemophilia specialists and the orthopedic surgeons.
High risk if severe hemophilia and not receiving prophylactic therapy (defined as the regular, continuous administration of a hemostatic agent/agents with the goal of preventing bleeding in people with hemophilia while allowing them to lead active lives and achieve quality of life comparable to non-hemophilia individuals).[38]
Low risk if severe hemophilia and receiving prophylaxis.
Medium risk if moderate hemophilia.
Low risk if mild hemophilia.
The risk increases in all patients with trauma or surgery.
Risk is low for mild to moderate hemophilia, and medium for severe hemophilia.
Likelihood is higher in hemophilia A than in hemophilia B.
About 30% of patients with hemophilia A develop inhibitors to infused factor VIII, whereas the inhibitor incidence for hemophilia B is up to 5%.[38]
Risk factors for the development of inhibitors include:[18][21][39][40][41][42][43][44][45][46][47][48]
Disease severity - more common in severe hemophilia, but may also occur in patients with mild to moderate hemophilia
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 titer ≥5 Bethesda units (BU); however, it should be noted that overall high responders may have a low titer result (a titer <5 BU) at any particular test without it altering their overall classification.
Patients with low-titer inhibitors may be treated with high doses of factor VIII or factor IX, whereas those with high-titer inhibitors need treatment with bypassing agents (e.g., recombinant factor VIIa or anti-inhibitor coagulant complex [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 hemophilia 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.[148][149]
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.[150]
The Centers for Disease Control and Prevention implemented a program 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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