Hemophilia type A
Hemophilia type A is a rare genetic disorder caused by missing or defective factor VIII (FVIII), a clotting protein in the blood. The disease is usually inherited, but in about one-third of known cases, it is caused by a spontaneous mutation.
Recurrence of CNS bleeding was confirmed to be relatively frequent in patients with severe FV, FX, FVII and FXIII deficiencies. Most patients were managed with replacement therapy alone, surgery is reserved for those with worsening neurological conditions. Results indicate that some rare bleeding disorders (RBDs) require early prophylactic treatment to prevent CNS bleeding. Optimal dosage and frequency of treatment need further evaluation 1).
No explicit recommendations or guidelines exist for patients with hemorrhagic diatheses, such as von Willebrand disease (vWD), hemophilia A and B and idiopathic thrombocytopenic purpura (ITP). Published data regarding the safety of neuraxial techniques in these patients are scarce. Neuraxial anesthesia in patients with vWD is only acceptable when coagulation is optimized (substitution of factor concentrates or hemostatic agents depending on the type of vWD) and monitored frequently during the procedure. The only exception might be obstetric patients with vWD type I as coagulation frequently normalizes at the end of pregnancy. In these patients, neuraxial anesthesia can often be performed without supplementation of clotting factors. Neuraxial techniques in patients with hemophilia A or B are usually contraindicated. The procedure may only be acceptable if serious reasons exist against general anesthesia. Supplementation of the missing factor to normal levels and monitoring during the procedure is essential if neuraxial block is performed. Patients with ITP often present with low platelet counts. Normally, spinal or epidural anesthesia is considered safe if the platelet count is over 80,000/µl. However, the consistently low platelet counts in ITP seem to be less problematic than rapidly falling values due to other diseases, because this is often accompanied by platelet dysfunction or coagulopathy. In several studies, neuraxial anesthesia was successfully performed with platelet counts between 50,000 and 80,000/µl. Nevertheless, the minimum safe platelet count for neuraxial blockade remains undefined in these patients. Evidence-based recommendations for neuraxial anesthesia in patients with hemophilia, vWD or ITP cannot be offered. Each patient has to be treated individually with appropriate caution 2).
Case reports
Hemophilia is generally considered a contraindication to deep brain stimulation (DBS) and other elective intracranial surgery due to the elevated risk of perioperative hemorrhage. Recent case reports of patients with Parkinsonian tremors have suggested, however, that DBS may be safe in patients with hemophilia who undergo appropriate factor replacement.
Palsma et al. described the first case of DBS surgery for medically-refractory essential tremor (ET) in a patient with hemophilia A.
A 68-year-old right-handed man with mild hemophilia A presented for a ten-year history of bilateral (right greater than left), medically-refractory ET. The patient was considered an appropriate candidate for DBS by a multidisciplinary movement disorders conference, and hematology consultation was obtained. Baseline preoperative labs showed a quantitative factor VIII (FVIII) level of 38%. Perioperative management consisted of daily intravenous doses of recombinant FVIII from the morning of surgery to postoperative day ten. The patient underwent uncomplicated unilateral DBS placement in the left ventralis intermedius thalamus. Intraoperative and postoperative imaging showed no hemorrhage. His postoperative course was uncomplicated except for a single self-limited episode of hematuria requiring no intervention.
DBS placement for ET may be safe in patients with coexisting hemophilia A if appropriate FVIII replacement is given, which may be delivered as bolus infusions rather than continuous infusion 3).
A 35-year-old man without any past medical history was admitted with diplopia and ocular motility disorder. computed tomography (CT) and magnetic resonance imaging (MRI) revealed obstructive hydrocephalus and a solid giant tumor of more than 4.0 cm in diameter in the right cerebellopontine angle (CPA). Hemangioblastoma was suspected on cerebral angiography. After ventriculoperitoneal shunt for obstructive hydrocephalus, oozing from the skin incision continued for several days. Hemophilia type A was diagnosed based on the result of laboratory blood coagulability examination. Supplemental administration of factor VIII and coil embolization of the feeding arteries of the lesion on the CPA were performed, and the tumor was subtotally resected without hemorrhagic complications. The histopathological diagnosis was hemangioblastoma. We report this case to emphasize the importance not to overlook previously undiagnosed coagulopathy before surgical excision of hemangioblastoma. And, with appropriate perioperative management for coagulopathy, surgical treatment involving a high risk of perioperative bleeding can be safely undertaken 4).
A 5-year-old severe hemophilic A boy presented with a life threatening left parietal subcortical hemorrhage, for which he underwent craniotomy and evacuation of the hematoma. Recurrent hemorrhage necessitated a repeat craniotomy. This was followed by three episodes of SDH development at the craniotomy site that were treated surgically, and finally controlled with embolization in the subacute period. This case presents a novel option for treating a refractory SDH in patients with coagulation disorders 5).
A 34-year-old man with hemophilia type A presented with a huge intracerebral hematoma (ICH) in the left frontoparietal lobe due to the rupture of an arteriovenous malformation (AVM). Angiography demonstrated the AVM in the frontoparietal lobe fed by the anterior cerebral arteries and the middle cerebral arteries, with a vein draining into the superior sagittal sinus. He developed signs of cerebral herniation due to the huge ICH. An emergent operation was performed to reduce intracranial pressure and to stop bleeding from the AVM under continuous administration of factor VIII. To prevent postoperative hemorrhage, aggressive blood pressure control and continuous administration of factor VIII were performed for 10 days. His neurological status improved so that he could hold a simple conversation. Continuous administration of factor VIII during surgery and intensive Intra- and postoperative therapy resulted in a favorable outcome for this patient with hemophilia type A 6)