Improved treatment of sudden hearing loss by specific fibrinogen aphaeresis

Abstract

The etiology of sudden sensorineural hearing loss is still unclear and is thought to result from disturbances of microcirculation, infectious causes, or autoimmune disorders. So far standard therapy did not show clear improvement over spontaneous remission rate, which is assumed to be about 50% [Nakashima et al., Acta. Otolaryngol. Stockh. 514:14-16, 1994; Schuknecht and Donovan, Arch. Otorhinolaryngol. 243:1-15, 1986; Harris and Sharp, Laryngoscope 100:516-524, 1990; Mayot et al., Clin. Immunol. Immunopath. 68:41-45, 1993; Gussen, Ann. Otol. Rhinol. Laryngol. 85:94-100, 1976]. Elevated blood viscosity due to high fibrinogen levels is supposed to cause decreased cochlear blood flow and thus initiate sudden hearing loss. The specific lowering of fibrinogen immediately decreases plasma viscosity exactly to the desired extent and should lead to improved cochlear blood flow [Suckfüll et al., Acta. Otolaryngol 119:763-766, 1999; Suckfüll, Lancet 360:1811-1817, 2002; Walch et al., Laryngol. Rhino. Otol. 75:641-645, 1996; Suckfüll et al., Otol. Neurotol. 23:309-311, 2002]. In a prospective uncontrolled pilot study on 36 patients with unilateral sudden onset sensorineural hearing loss (SHL) we tried to establish that 1-3 specific fibrinogen aphaereses alone improve recovery of hearing and that it is possible to lower fibrinogen to the target of 80-100 mg/dl without important side effects. Pure tone audiometry was carried out immediately before and after each aphaeresis as well as at 2 and 4 weeks and 6 months after treatment. Sixteen patients recovered spontaneously before undergoing fibrinogen adsorption. All 20 aphaeresis patients improved during immunoadsorption; in 60% of patients auditory thresholds returned to normal after the first immunoadsorption and treatment could be discontinued, in another 20% of patients complete recovery was reached after 4 weeks. The mean plasma fibrinogen concentration of the 20 patients before the first aphaeresis session was 308.1 +/- 51.5 mg/dl. Immediately after the first treatment session, the fibrinogen concentration was lowered to 100.7 +/- 25.3 mg/dl (P < 0.001). The second and third sessions also showed highly significant reductions in plasma fibrinogen. No important side effects were seen. In conclusion, specific fibrinogen adsorption is a promising new treatment modality that should be tested in a prospective, randomized controlled trial in patients with sudden hearing loss.

Sudden Deafness and Right-to-Left Shunts

“…The reason why border-zone infarcts occur in cases with major arterial occlusion may be that a hypoperfusion status, caused by slow blood flow, is unable to wash out small emboli that would disappear under normal cerebral perfusion [12]. Based on this observation, slow cochlear blood flow that is highly susceptible to blood pressure fluctuations and impairments in blood flow may play an important role in embolisms of the internal auditory artery [13]. When small emboli stray into the internal auditory artery, sudden death may result from an embolism that should have been washed out in other cerebral vessels under normal perfusion.…”

“…When small emboli stray into the internal auditory artery, sudden death may result from an embolism that should have been washed out in other cerebral vessels under normal perfusion. Indeed, specific fibrinogen and low-density lipoprotein apheresis techniques have been attempted to improve whole blood and plasma viscosity, and to increase the release of nitric oxide to improve blood flow by vasodilatation [13]. …”

Role of Genetic and Acquired Prothrombotic Risk Factors in Genesis of Sudden Sensorineural Hearing Loss

“…Many risk factors have been investigated, particularly cardiovascular ones such as diabetes, smoking, increased blood viscosity, elevated fibrinogen, triglycerides, LDL, total cholesterol and several mutations including the glycoprotein la [Ohinata et al, 1994;Suckfüll et al, 2002;Ullrich et al, 2004].…”

Apheresis for idiopathic sudden hearing loss: Reviewing the evidence

“…All 20 apheresis patients improved during immunoadsorption; 60% of patients' auditory thresholds returned to normal after the first immunoadsorption and treatment could be discontinued, while complete recovery was reached after 4 weeks in another 20% of patients. Both these studies demonstrated significantly lowered levels of fibrinogen, and fibrinogen and cholesterol, respectively, after apheresis [20,21]. Valbonesi et al [9] conducted another uncontrolled trial, treating 60 ISHL patients with Rheopheresis (cascade filtration).…”

“…Within the HELP group, patients with high levels of fibrinogen seemed to benefit more. Ullrich et al [21] conducted an uncontrolled trial, using fibrinogen apheresis to treat 20 ISHL patients of whom 80% recovered fully under apheresis. Fibrinogen apheresis is a highly specific immunoadsorption, extracting only fibrinogen.…”