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

di Spilimbergo, Stefano Spanio M.D., D.M.D.; Rampazzo, Antonio M.D.; Squaquara, Roberto M.D.; Penzo, Michelangelo M.D.; Padula, Ernesto M.D.

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Plastic and Reconstructive Surgery: April 2008 - Volume 121 - Issue 4 - p 1508-1509
doi: 10.1097/01.prs.0000305361.01499.f6
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We read with great interest an article recently published in Plastic and Reconstructive Surgery about a case of free flap failure in a patient with homocystinuria.1 The authors faced multiple arterial thrombi during toe-to-hand transfer in their young patient. They tried thrombectomy and multiple local infusions of streptokinase and tissue plasminogen activator, but eventually they could not save the flap.

We experienced a similar case in a patient operated on for a squamous cell carcinoma of the floor of the mouth. After resection, he was reconstructed with a free anterolateral thigh musculocutaneous flap. Unfortunately, this flap failed due to venous and arterial thromboses. We tried to overcome the problem with arterial infusion of 1000 IU of streptokinase with opened veins and 4000 IU of subcutaneous heparin postoperatively, but we had no success and explained this failure as a technical error.

We then decided to perform another anterolateral thigh musculocutaneous flap from the contralateral side. At this stage, multiple arterial thromboses after every anastomosis with the facial, lingual, and superior thyroid arteries presented. Sometimes thrombosis was evident even before anastomosis. Intraoperative Doppler ultrasound of the carotid artery showed normal flow.

Due to this unknown hypercoagulable state, we started with empirical systemic therapy: 50 mg of tissue plasminogen activator intravenously, 0.1 μg/kg per minute continuous intravenous infusion of tirofiban (inhibits platelet aggregation) for 12 hours, and 8000 IU/day of continuous intravenous infusion of heparin. Arterial thrombosis resolved in about 10 minutes, and we then successfully performed vessel repair.

From the twelfth postoperative hour until the seventh postoperative day, prophylactic intravenous heparin was administered. From the seventh to the fourteenth postoperative day, 2000 IU of subcutaneous heparin was given three times a day.

The postoperative course was uneventful, and after 25 days the patient was discharged. A coagulation work-up was positive for elevated serum homocysteine, consistent with moderate homocystinuria. We agree with the authors that hypercoagulability syndromes2–5 should be included in the differential diagnosis of flap loss, and we think that when faced with this problem only an associated systemic therapy with thrombolytic, antiaggregant, and heparin can resolve the problem. Bleeding could be the main disadvantage, so the whole history, examination, and risk-benefit ratio should be taken into consideration.

Stefano Spanio di Spilimbergo, M.D., D.M.D.

Antonio Rampazzo, M.D.

Roberto Squaquara, M.D.

Unità Operativa di Chirurgia Maxillo-Facciale

Michelangelo Penzo, M.D.

Unità Operativa di Cardiologia

Ernesto Padula, M.D.

Unità Operativa di Chirurgia Maxillo-Facciale

Ospedale S. Bortolo

Vicenza, Italia


1. Labow, B. I., Greene, A. K., and Upton, J. Homocystinuria: An unrecognized cause of microvascular failure. Plast. Reconstr. Surg. 120: 6e, 2007.
2. Ayala, C., and Blackwell, K. E. Protein C deficiency in microvascular head and neck reconstruction. Laryngoscope 109: 259, 1999.
3. Wilson, K. M., McCaw, R. B., Leo, L., et al. Prothrombotic effects of hyperhomocysteinemia and hypercholesterolemia in ApoE-deficient mice. Arterioscler. Thromb. Vasc. Biol. 27: 233, 2007.
4. Bick, R. L. Coagulation abnormalities in malignancy: A review. Semin. Thromb. Hemost. 18: 353, 1992.
5. Nand, S. Hemostasis and cancer. Cancer J. 6: 1, 1993.

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