Hypercoagulability Due to Homocystinuria in a Case of Head and Neck Reconstruction Resolved with Combined Systemic Therapy (2008)

Sir: We thank Drs. Spanio di Spilimbergo et al. for their comments and for reporting their experience with free flap loss and salvage in a patient with homocystinuria. Although individual enzymatic defects in the folate pathway may be rare, when all potential causes are included, homocystinuria affects as much as 10 percent of the population.1 Therefore, it is likely that many more flap failures have occurred as a result of this entity but have gone unrecognized. In fact, the effects of homocystinuria on plastic surgical patients extend beyond microsurgery. For example, homocystinuria is a risk factor of deep venous thrombosis, and thus we advocate measuring homocysteine levels as part of the hypercoaguable evaluation for young, healthy patients who develop a deep venous thrombosis or pulmonary embolus.2 The treatment of homocystinuria is straightforward and significantly reduces the morbidity of affected individuals.3 In the case reported by Spanio di Spilimbergo et al., an anterolateral thigh flap was used to reconstruct a floor-of-the-mouth defect after tumor resection. As in our case, the first free flap was lost despite attempts at regional thrombolytic therapy.4 A second anterolateral thigh flap was attempted and salvaged using aggressive systemic anticoagulation: tissue plasminogen activator, tirofiban, and intravenous heparin. Systemic heparin was continued for 2 weeks after the procedure, and the patient was discharged uneventfully after a 25-day hospitalization. Spanio di Spilimbergo et al. should be commended for their technical expertise and salvage of the second anterolateral thigh flap. Moreover, they should be congratulated for thoroughly investigating the cause of their first flap’s failure and identifying the source of their patient’s hypercoagulability. Unfortunately, homocystinuria is likely to be diagnosed only after a failed free tissue transfer, which then stimulates a hypercoagulabiltiy work-up. In the patient with elevated homocysteine levels, our experience as well as Spanio di Spilimbergo et al.’s suggests that regional thrombolytic therapy is ineffective and aggressive multimodal systemic anticoagulation may be required for flap salvage. However, the morbidity and mortality risks associated with multimodal systemic anticoagulation in any postoperative patient, especially those with fresh anastomoses in the neck, are considerable. Presently, it is unknown whether treatment of homocystinuria can abrogate the risks of microvascular thrombosis. We would predict that the observations of decreased stroke, thrombosis, and myocardial infarction seen in homocystinuria patients treated with vitamin B and folate would also translate into a reduced risk of microvascular thrombosis.3 However, in the rare microsurgical patient with known, controlled homocystinuria, the surgeon should have a low threshold for the use of systemic anticoagulation. Currently, we do not recommend homocystinuria testing in healthy patients before a microsurgical procedure. Instead, during our preoperative screening we obtain a hypercoagulability profile in patients with a history of thrombosis at a young age, thrombosis without a predisposing cause, or resistance to anticoagulation. Brian I. Labow, M.D. Arin K. Greene, M.D. Joseph Upton, M.D. Department of Plastic Surgery Children’s Hospital Boston Boston, Mass.