Acute recurrent appendicitis in a hemophiliac Nepalese girl: beyond just… avoidance of formidable cuts! – A case report

Hemophilia denotes a hereditary bleeding disorder resultant to a deficiency or malfunctioning of clotting factors VIII and IX. Classified into two main types: Hemophilia A and B, any surgical procedure performed on these patients requires a careful and coordinated planning by both the surgical and anesthetic teams in order to ensure proper optimization and a secured outcome. More importantly, when operating on a hemophiliac child in an emergency, strategies have to surpass beyond just steps to circumvent surface bleeding. In this case report, we outline perioperative management strategies for these patients’ undergoing appendectomy. This case report has been reported in line with the SCARE checklist[ 1 ]. HIGHLIGHTS A rare female hemophilic child successfully underwent emergency laparoscopic appendectomy. Success relied on a seamlessly coordinated multidisciplinary team effort. A thorough perioperative plan was essential. A strict adherence to established hematological and surgical guidelines was crucial. A rare female hemophilic child successfully underwent emergency laparoscopic appendectomy. Success relied on a seamlessly coordinated multidisciplinary team effort. A thorough perioperative plan was essential. A strict adherence to established hematological and surgical guidelines was crucial.

Hemophilia is known to present with a wide gamut of symptoms consequent to bleeding ranging from skin bruises, muscle compartment bleed, hemarthrosis, and genitourinary bleed to a potentially life-threatening intracranial and gastrointestinal hemorrhage[ 2 ]. Categorized into type A (factor VIII) and type B (factor IX) based on factor deficiency, its severity is estimated measuring the factor activity in blood[ 2 ]. The commoner variant hemophilia A follows a severity classification that identifies a factor activity of 40%–150% as normal, 5%– < 40% as mild, 1%–5% as moderate and <1% as severe hemophilia respectively[ 3 ]. Regardless of severity, any hemophiliac individual can suffer a potential risk of bleeding during an operation owing to the consumption of coagulation factor by the procedure[ 4 ]. Therefore, The World Federation of Hemophilia (WFH) recommends the performance of surgeries in hemophiliacs in centres with adequate laboratory and blood bank support wherein preoperative evaluation should include factor VIII level estimation along with coagulation profile. Additionally, pre- and postprocedural screening for inhibitor is suggested along with immediate factor VIII transfusion [ 2 , 5 ] . The global incidence of Hemophilia A continues to demonstrate a striking male predominance of 90.2% based on the reports of the Annual Global Survey of WFH, 2023[ 6 ]. Corresponding data from Nepal, confirmed a total of 686 cases wherein only 40% were children below 18 years[ 6 ]. Therefore, managing perioperative hemostasis in a hemophiliac girl presenting with an acute surgical condition can pose a rare and unique challenge. The suggested line of management for surgical patients with mild disease is desmopressin (DDAVP), a vasopressin analogue either intravenously or subcutaneously at a dose of 0.3 mcg/kg in order to expect 3- to 6-folds raise in FVIII levels with its peak action occurring within an hour. The use of DDAVP when prolonged is limited with events like tachyphylaxis, water retention and hyponatremia[ 7 ]. Therefore, a duration under 3–5 days in adults and a single daily dose not exceeding 3 days is recommended in children[ 5 ]. For patients with moderate or severe disease undergoing surgery, clotting factor concentrates (CFCs) are imperative to achieve and maintain the necessary factor levels throughout the perioperative period for adequate hemostasis[ 5 ]. However, CFCs although effective, are expensive, not readily available and contribute to the inhibitor development following repeated use that necessitates screening after 4–12 weeks[ 5 ]. Consequently, a practice combining both DDAVP and factor VIII is under investigation before its superiority concerning safety and efficacy can be established compared to each modality in isolation[ 8 ]. Additionally, antifibrinolytic agents such as tranexamic acid (inhibitor of conversion of plasminogen to plasmin) that stabilize the clot has been recommended by WFH as an alternative either as a standalone or adjuvant therapy to minimize mucocutaneous bleeding[ 4 ]. The considerations from a surgical standpoint include avoidance of intramuscular and arterial injections that could result in bleeding or hematoma in general[ 4 ]. And in female hemophiliacs, early suspicion and evaluation for gynecological conditions mimicking acute appendicitis like Mittelschmerz pain and endometriosis could avoid an unnecessary procedure altogether. Intraoperative considerations include avoidance of muscle relaxants like succinylcholine, that cause muscle fasciculations increasing the risks of muscle and joint hemorrhage in addition to close monitoring and maintenance of vital signs mainly blood pressure and heart rate, the instabilities of which may contribute to the surgical site bleeding[ 4 ]. The choice of surgical technique is crucial in determining the extent of bleeding. Minimal access techniques such as laparoscopic appendectomy or trans umbilical laparoscopic appendectomy (TULA) have been shown to offer favourable outcomes in these patients [ 9 , 10 ] . During appendectomy, avoidance of rough dissection and judicious use of electrocautery even for the skin and subcutaneous tissues is recommended considering its safety and hemostasis compared to a traditional scalpel[ 11 ]. The use of energy devices for intra peritoneal vessel sealing along with factor VIII replacement is recommended for optimal hemostasis[ 11 ]. In our experience, minimizing suction trauma, avoiding blind grasping, careful handling of mesoappendix (especially during electrocoagulation with minimal tissue trauma) and active surveillance of retroperitoneal and pelvic bleeding during the surgery are essential in this situation. Estimation of intraoperative bleeding should be performed by both the surgeon and the anesthesiologist. Blood loss (within 10%), similar to that in the nonhemophilic patient, is labeled as excellent, while 10–25% greater than expected for a nonhemophilic patient, judged clinically insignificant, is labelled as good. Additionally, blood loss in excess of 25%–50% over expectation, requiring an unplanned dose of FVIII transfusion is labeled as fair, while increased blood loss (>50% over expectation) requiring intervention, not explained by any issue other than hemophilia, or associated with unexpected hypotension or shift to Intensive Care Unit (ICU) is labeled as poor.[ 5 ] Based on these parameters and judgment of the involved team, we labeled the index case as “good” hemostasis[ 5 ]. The port site skin closure was achieved with the use of topical skin adhesive instead of traditional skin sutures or metallic clips, aiming to avoid unnecessary suture bites and bleeding during postoperative suture removal. Resultantly, no wound complications were observed whatsoever. The recommendations follow that during extubation the ETT be checked for blood stains to rule out injury to the airway. Even extubating in a deeper anesthetic plane may be considered to avoid cough reflex and minimize the chances of airway bleeding[ 4 ]. Postoperatively, NSAIDs and cyclooxygenase-1 inhibitors are best avoided due to the association of stress ulcers with the former and platelet dysfunction with the latter to further mitigate the risks of bleeding[ 12 ]. Likewise, postoperative monitoring mandates intense vigilance to detect surface, intraabdominal or muscular bleeding[ 12 ]. Regular assessment of FVIII level postoperatively maintaining the desired factor VIII level of at least 60–80 IU/dL in 1–3 days, 40–60 IU/dL in 4-6 days and 30–40 IU/dL in 7–9 days is suggested[ 12 ].

This case highlights a multidisciplinary approach in the management of a female child with hemophilia A undergoing emergency laparoscopic appendectomy. The necessary surgical procedure was carried out successfully with adequate preoperative workup, early CFC administration, a suitable anesthetic technique and proper intra and postoperative care. Early recognition, tailored perioperative planning and adherence to established hemophilia management protocols can lead to a successful outcome as witnessed in the current case.

An 8-year-old girl presented with a history of sudden and progressively increasing pain over the right lower abdomen for 7 hours with no specific aggravating or relieving factors. She had experienced similar pain twice in the past 9 months, both managed conservatively. Both the times, acute uncomplicated appendicitis was diagnosed but operation was deferred in view of risk of bleeding. She was a diagnosed case of hemophilia A with a past history of prolonged bleeding following trivial trauma and easy bruising intermittently. With an existent maternal family history of same, she had undergone a complete hematological work up elsewhere that had confirmed factor VIII deficiency. She had however, never required any medications or blood product transfusions in the past. Physical examination revealed a tender and guarded right lower abdomen. Her hemogram showed hemoglobin: 12.2 gm%, leucocytosis (Total leukocyte count: 15 700 cells/cu.mm and differential leukocyte count: polymorphs: 82%, lymphocytes: 15%, eosinophils: 1%, and monocytes: 2%) and elevated C-reactive protein (CRP): 90 mg/L. Her biochemical tests were normal and so was serum platelets (Platelets count: 1, 64 000 cells/cu.mm). Coagulation studies showed normal prothrombin time (PT-Test:14 s/control:14 s, INR: 1.0) and prolonged activated partial thromboplastin time (aPTT -Test: 45 s/control: 33 s) with subsequent correction on mixing studies. Factor VIII levels were measured to be 35.5% (normal 50–150%). Abdominal ultrasound showed a blind-ending, tubular, a-peristaltic, non-compressible, hypoechoic structure arising from caecum with wall-to-wall diameter of 7.33 mm in the right iliac fossa suggestive of inflamed appendix, which was surrounded by echogenic mesentery without evidence of surrounding collection. Based on anesthetic evaluation she was classified as American Society of Anaesthesiologists (ASA) class 2E and administered 500 IU of Factor VIII transfusion approximately 30 minutes prior to the onset of operation. Laparoscopic appendectomy was planned using 3 mm instruments in order to avoid bleeding with the use of little incisions. Procedure was planned under general anesthesia with endotracheal intubation. She was induced with fentanyl, a titrated dose of propofol, and vecuronium as a muscle relaxant. Intubation was achieved without trauma on the first attempt with a cuffed endotracheal tube (ETT) of size 5.5 mm internal diameter and fixed at 16 cm. Anesthesia was maintained using isoflurane in addition to intravenous paracetamol for analgesia and an infusion of Co-amoxicillin–clavulanate for antibiotic prophylaxis. A standard three port laparoscopy was performed using umbilicus as the optical port. Bipolar diathermy was utilized for skin and sub-cutaneous hemostasis. Once into the peritoneal cavity, blunt dissection, tearing, and teasing movements were completely avoided. Deliberate care was practiced while handling the mesoappendix, carefully dissecting and dividing the appendicular vessels initially with bipolar vessel sealer and later with hook electro diathermy making blood loss to a bare minimum as shown in the Fig. 1 . Figure 1. (A) Port placement using 3 mm working ports and 10 mm optical port at the umbilicus. (B) Use of atraumatic bowel grasper for gentle handling of appendix. (C) Precise and deliberate gentle handling of mesoappendix: use of hook diathermy for vessel division after bipolar vessel coagulation. (D) Application of absorbable endo loops twice proximally at the appendix base and once distally. (A) Port placement using 3 mm working ports and 10 mm optical port at the umbilicus. (B) Use of atraumatic bowel grasper for gentle handling of appendix. (C) Precise and deliberate gentle handling of mesoappendix: use of hook diathermy for vessel division after bipolar vessel coagulation. (D) Application of absorbable endo loops twice proximally at the appendix base and once distally. The appendicular base was ligated using absorbable endo loops twice proximally and once distally. Appendectomy was performed between the ligatures using 3 mm laparoscopic scissors and retrieved trans umbilically directly using a port now changed into a 10 mm after port site dilatation. Peritoneal irrigation was done with normal saline followed by suction till dry. Port sites were repaired with 3-0 polyglactin sutures for muscles, 4-0 polyglactin sutures for subcutaneous tissues and tissue adhesive for skin. The operation lasted for approximately 1 hour and she remained hemodynamically stable throughout. An estimated blood loss >10% than expected for a non-hemophilic patient was observed in Fig. 2 . Figure 2. (A) Trans umbilical retrieval of appendectomy specimen under direct vision, ligated appendix stump in the background. (B) Relook to confirm haemostasis at the right iliac fossa and retro-peritoneum. (C) Retrieved appendectomy specimen. (D) Topical application of skin adhesive to the port site skin incision to avoid suture removal later. (A) Trans umbilical retrieval of appendectomy specimen under direct vision, ligated appendix stump in the background. (B) Relook to confirm haemostasis at the right iliac fossa and retro-peritoneum. (C) Retrieved appendectomy specimen. (D) Topical application of skin adhesive to the port site skin incision to avoid suture removal later. In the immediate post operative period, she was administered intravenous injection ondansetron. Reversal of anesthesia was done using neostigmine and glycopyrrolate. She was subsequently extubated after gentle suctioning of the oropharynx making a clear noted of the ETT being non-blood-stained. She was then transferred to the postanesthetic care unit where in close monitoring of vital signs were performed. Post-operative analgesic cover was provided using intravenous fentanyl and paracetamol strictly avoiding intramuscular injections and nonsteroidal anti-inflammatory drugs (NSAIDs). Factor VIII was transfused on the first postoperative day 12 hours later and intravenous Tranexamic acid was used (10 mg/ kg/dose) thrice daily until discharge. Her post operative period remained largely uneventful. The feeds were initiated on gradual return of bowel activity along with continuation of supportive measures and ambulation, that she tolerated well. She was discharged on the third postoperative day with a normal hemogram. On subsequent follow-ups, she remained symptom-free.