Classic hemophilia or hemophilia A is a congenital bleeding diathesis in which the affected individual may present with spontaneous hemorrhage or persistent bleeding even after minor trauma. Knowledge about the disease process, multidisciplinary team approach, and timely management can lead to favorable outcome in these patients. We report management of a child with hemophilia A for suturing of lacerated upper lip mucosa following trauma. A review of literature with recommendations for perioperative management, especially in the setting of emergency surgery, is also provided.
Keywords: Anesthesia, emergency surgery, factor VIII, hemophilia, trauma
Classic hemophilia or hemophilia A is an X-linked recessive hereditary disorder characterized by defective or deficient clotting factor VIII (FVIII) which affects the male progeny. The incidence is 1/5000 male live births. The affected individual may present with spontaneous hemorrhage specifically into the joint cavities or uncontrollable bleeding even after minimal injury. In pediatric age group, the child's physical activity increases as the age advances which results in more exposure to trauma and bleeding. In toddlers, laceration of tongue and mouth is a common presentation due to biting of tongue or lip during a fall or trauma. Profuse bleeding from open wounds in children with hemophilia A results in significant blood loss because of delayed formation of soft and friable clot. Moreover, rebleeding or delayed bleeding during the physiologic lysis of clots can also occur after a period of apparent hemostasis. Hence, trivial trauma can sometimes lead to life-threatening hemorrhage in hemophilia patients. So, local as well as systemic approach is essential to manage such patients till the complete healing occurs. Exogenous administration of FVIII concentrate temporarily replaces the missing clotting factor. Hence, prompt transfusion of recombinant FVIII concentrate and early surgical intervention can transmogrify the outcome in these patients.
A 5-year-old, 17 kg boy was brought in emergency with excessive bleeding for 30 min following injury while playing, involving mucosa of the upper lip. At 1.5 years of age, he was incidentally diagnosed of having pink Tetralogy of Fallot for which he underwent surgical repair. The patient was also diagnosed as a case of hemophilia A since then. The patient's factor replacement history revealed moderate disease (2% FVIII activity) with a negative inhibitor titer assay within the last month and two previous episodes of acute bleeding following fall from height which was successfully treated with FVIII concentrate (Hemofil-M, Baxter). He had no previous history of spontaneous bleeding into joints; no other members of the family had any clinical disease.
On examination, his pulse rate was 130 beats/min, blood pressure was 84/50 mm of Hg. As the bleeding did not respond to pressure maneuvers (compression with damp gauge pieces), hematologist opinion was sought for and transfusion of recombinant FVIII concentrate was started in the emergency after securing a peripheral line with 22-gauge cannula. Since the child was not cooperative, suturing under monitored anesthesia care was planned. High-risk consent for surgery and anesthesia was obtained from the parents. Inside the operation theater, another 22-gauge peripheral line was secured and packed red blood cells transfusion was also started. Monitoring included pulse oximetry, electrocardiogram, and noninvasive blood pressure. He was preoxygenated with nasal prong at 4 L/min and neck was turned on one side and intermittent suction was done on dependent cheek with a red rubber catheter [Figure 1]. Injection ranitidine 1 mg/kg, injection ondansetron 0.15 mg/kg, and injection glycopyrrolate 8 µg/kg were administered intravenously. Infusion of loading dose of injection tranexamic acid 15 mg/kg was started before the induction of anesthesia. Anesthesia was induced with slow intravenous ketamine 2 mg/kg. Suturing of the bleeding mucosa with resorbable suture was performed and hemostasis achieved.
Simple (red) rubber catheter with blunt tip and side hole.
During surgery, meticulous suctioning and mopping were done to prevent aspiration of blood. Postoperatively, he was transferred to recovery room and nursed in the left lateral position with oxygen via face mask till he became fully conscious. Eight hours after surgery, the patient received another dose of FVIII concentrate and thereafter twice a day for 5 days. The postoperative period was uneventful. After 7 days, he was discharged from the hospital.
A child with hemophilia A presenting for emergency surgery poses a challenge to the surgeon as well as anesthesiologist. Bleeding tendency in the affected individual is inversely proportional to FVIII level in the body. Normal plasma levels of FVIII ranges from 0.5 to 1.5 IU/ml or 50–150% (1 IU/ml = 100% of FVIII in 1 ml of normal plasma), and the hemostatic level is more than 30–40%. FVIII activity in patients with mild, moderate, and severe hemophilia A are 5-<40%, 1–4%, and <1% of normal, respectively. Coagulation studies in patients with hemophilia A reveal high activated partial thromboplastin time (APTT) but normal platelet count, bleeding time, and prothrombin time. All patients with classic hemophilia, regardless of the severity of the disease, are at risk of excessive bleeding after trauma or during surgery.
Intracranial hemorrhage accounts for major cause of mortality in hemophilia patients. Besides that, morbidity and mortality in hemophilia patients are also increased due to bleeding from injury, gastrointestinal or genitourinary tract.
The indicated coagulation defect should be corrected as soon as possible and must not be delayed while results of diagnostic tests are awaited. The surgery in patients with hemophilia A should take place in a center with adequate laboratory support for perioperative assessment of FVIII level including inhibitor screening and optimal blood bank support to provide sufficient quantities of FVIII concentrates. As our patient needed emergency surgery, FVIII assay and inhibitor screening were not feasible preoperatively. Postoperative monitoring for bleeding was done with hemoglobin and APTT levels along with FVIII level and FVIII antibody assay.
Emergency bleeding incidents such as in case of trauma or emergency surgery require immediate intervention with a major dose of FVIII concentrate infusion to ensure hemostasis. Moreover, the consumption of coagulation factors is highly increased during surgery. Hence, the replacement of recombinant FVIII concentrate must occur before or in parallel with any intervention in a patient with hemophilia. The recommended plasma factor level and duration of administration for major as well as minor surgeries are shown in Table 1. Life-threatening hemorrhages require replacement therapy to achieve a plasma level equal to that of normal, i.e., 100 IU/dl or 100%. The dose of FVIII concentrate is calculated according to the World Federation of Hemophilia 2012 (WFH) guidelines: Patient's body weight (in kg) × desired factor level (IU/dl) × 0.5 or weight (in pound)/4.4 × desired factor level (IU/dl). In the absence of an inhibitor, plasma FVIII level increases approximately 2 IU/dl per infused IU/kg body weight. As FVIII assay was not available to us in emergency, we started slow IV infusion of 850 units (17 kg × 100 IU/dl × 0.5) of FVIII at 100 units per min considering the severe bleeding from mucosal trauma to achieve desired factor level of 100% as per the hematologist's advice. Since the half-life of FVIII is approximately 8–12 h, it must be administered twice daily.
WFH recommendation of desired factor VIII levels and duration of factor VIII administration for major and minor surgeries
Desmopressin, a synthetic vasopressin analog, increases the plasma levels of FVIII and Von Willebrand factor in patients with mild to moderate hemophilia A. A single IV infusion (0.3 μg/kg diluted in 50–100 mL of isotonic saline and infused over 30 min) increases the level of FVIII 3–6 times with peak response in 90 min. However, it is ineffective in patients with severe hemophilia A or patients with high FVIII antibody titers.
Tranexamic acid and ε-aminocaproic acid are useful as an adjunct therapy in hemophiliacs and are valuable in controlling bleeding from mucosal surface as it promotes clot stability by their antifibrinolytic activity. Tranexamic acid can be used as IV infusion, oral tablet, 4.8% solution as mouth wash, and application of solution or paste of crushed tablets directly to the site of bleeding.
Although vascular access does not cause excessive bleeding, it is better to place it with care and intramuscular medications and arterial puncture should be avoided. Smooth induction of anesthesia is preferable and succinylcholine is avoided to prevent muscle fasciculation, which may worsen muscle and joints hemorrhagic state. Postinduction manipulation or intubation of the airway can cause submucosal hemorrhages, which can become a life-threatening condition and nasal intubation is more traumatic and bleeding from the site can also lead to aspiration. Hence, tubes should be previously greased with lubricant to decrease friction with the mucosa and proper care is needed with the insertion of feeding tubes or temperature probes because tongue and airway muscles bleeding may rapidly lead to airway obstruction. We avoided tracheal intubation in our patient to prevent any insult to the airway mucosa. We placed the child supine with head turned on one side and continuous suctioning from dependent cheek was done with a nontraumatic red rubber catheter to prevent aspiration of secretions and blood. Pressure points were padded with cotton during positioning of the extremities to prevent intramuscular hematomas or hemarthrosis.
Hemodynamic conditions should be maintained as close as possible to normal range during anesthesia as hypertension and tachycardia can result in increased bleeding from surgical area. Tracheal extubation needs to be performed in deep plane of anesthetic without cough reflex with extreme vigilance about pharyngeal aspiration. Although guidelines do not recommend regional anesthesia in patients with hemophilia, literature review revealed that neuraxial blocks as well as peripheral nerve blocks have been performed safely in a patient with moderate to severe hemophilia with maintenance of FVIII level within a safe range throughout the perioperative period.
For closure of the mucosal wound, absorbable suture-like vicryl was used in our patients as it avoids need for the postoperative removal and the possibility of bleeding during suture removal.
Postoperatively, we used paracetamol for analgesia as nonsteroidal anti-inflammatory drug can predispose Hemophilia patients to gastrointestinal complications like ulcer, bleeding and perforation.
To conclude, we successfully managed a child with classic hemophilia with sublabial oral mucosal injury for emergency suturing. Management according to WFH guidelines, prompt surgery and less manipulation of airway possibly led to good outcome in our case.
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