How to treat a patient with appendicitis and hemophilia?

Treatment of Appendicitis in Patients with Hemophilia

Patients with hemophilia and appendicitis require urgent appendectomy with prophylactic bypassing agents (recombinant activated Factor VII or activated prothrombin complex concentrate) administered perioperatively to achieve hemostatic Factor VIII levels of 50-100 IU/dL, followed by maintenance dosing every 8-12 hours until complete healing. 1, 2

Preoperative Hemostatic Management

Factor Replacement Strategy

• Administer bypassing agents prophylactically before any surgical intervention in hemophilia patients, as invasive procedures and surgery require coverage with bypassing agents 1
• For congenital hemophilia A patients, give Factor VIII concentrate to achieve hemostatic levels of 50-100% (50-100 IU/dL) prior to appendectomy 3, 2
• Subsequent maintenance doses of 20-50 IU/kg Factor VIII should be administered every 8-12 hours until bleeding is controlled and surgical healing is complete 3
• Recombinant activated Factor VII (rFVIIa) at 46-150 mcg/kg every 2-24 hours or activated prothrombin complex concentrate (aPCC) are first-line bypassing agents for patients with inhibitors or acquired hemophilia 1

Critical Preoperative Assessment

• Measure Factor VIII levels after initial dosing to confirm adequate replacement (target >50%) before proceeding to surgery 3
• Do not delay surgery for inhibitor eradication in acute appendicitis - instead, use bypassing agents to achieve hemostasis 1
• Exclude intraabdominal or retroperitoneal hemorrhage before surgery, as these can mimic appendicitis in hemophilia patients 2

Surgical Approach

Operative Technique Selection

• Both laparoscopic and open appendectomy are acceptable, with the choice dictated by surgeon expertise 1
• Two-incision laparoscopic appendectomy is particularly effective in hemophilia patients due to minimal trauma and faster recovery characteristics 2
• Operative intervention should be performed as soon as reasonably feasible once adequate factor replacement is achieved 1

Timing Considerations

• Urgent appendectomy is required for perforated appendicitis to provide adequate source control, even in hemophilia patients 1
• Surgery should not be delayed for inhibitor eradication if appendicitis is present, as the mortality risk from untreated appendicitis outweighs bleeding risk with appropriate factor coverage 1

Antimicrobial Therapy

• Administer antimicrobial agents effective against facultative/aerobic gram-negative organisms and anaerobes to all patients with appendicitis 1
• Continue antibiotics for minimum 3 days or until clinical symptoms and signs of infection resolve 1
• For critically ill patients with healthcare-associated infections, consider meropenem 1g every 8 hours or alternative carbapenem regimens 1

Perioperative Monitoring and Management

Factor Level Monitoring

• Monitor Factor VIII levels continuously throughout the perioperative period to ensure adequate hemostasis 2
• Management must rely on clinical assessment as there are no validated laboratory tests to determine therapeutic levels of bypassing agents 1
• Continue bypassing agent therapy for 24-72 hours depending on bleeding site, type, and severity 1

Prevention of Iatrogenic Bleeding

• Even minor procedures such as peripheral venous access may result in significant bleeding in hemophilia patients 1
• Central venous access requires coverage with bypassing agents 1
• Avoid invasive procedures without adequate Factor VIII coverage 3

Special Considerations by Hemophilia Type

Acquired Hemophilia A

• Use bypassing agents (rFVIIa or aPCC) as first-line therapy rather than Factor VIII concentrates, as inhibitors render replacement therapy ineffective 1
• Recombinant activated Factor VII showed 90% effectiveness in non-surgical cases and 86% in surgical cases in acquired hemophilia 1
• Do not use desmopressin (DDAVP) for major surgery - reserve only for minor bleeding with very low titer inhibitors, as efficacy is unpredictable and adverse events (hyponatremia, seizures) are concerning 1

Congenital Hemophilia A

• Factor VIII concentrate replacement is definitive treatment, achieving hemostatic levels of 50-100 IU/dL 3
• For patients already on emicizumab prophylaxis, continue therapy perioperatively as it provides continuous thrombin generation 4
• Approximately 20-35% of severe hemophilia A patients have inhibitors requiring bypassing agents 4

Common Pitfalls to Avoid

• Do not delay Factor VIII replacement while awaiting confirmatory testing - treat based on clinical diagnosis when acute appendicitis is present 3
• Do not use Factor VIII concentrates in acquired hemophilia unless bypassing therapy is unavailable and inhibitor titer is very low 1
• Combination therapy with rFVIIa and aPCC should be restricted to life- or limb-threatening bleeds due to thrombotic risk 1
• Tranexamic acid is contraindicated with aPCC administration 1

Postoperative Management

• Continue factor replacement or bypassing agents until complete surgical healing 3
• Monitor for signs of continued bleeding: unchanged/decreased hemoglobin despite transfusion, increasing hematoma dimensions, bleeding at new sites 1
• If bleeding persists despite one bypassing agent, switch to the alternative agent 1
• Consider plasmapheresis or immunoadsorption for refractory bleeding episodes 1