Eur J Vasc Surg 8, 366-368 (1994)

CASE REPORT

Fatal Haemorrhage Associated with Neurofibromatosis

F. J. Mullan ~, B. M. Herron 2 and R. C. Curry ~

1 Vascular Surgery Unit and 2 Department of Histopathology, Belfast City Hospital, Belfast, U.K.

Case Report

A 54-year-old male pedestrian was admitted follow- ing a road traffic accident in which he sustained a compound, severely comminuted fracture of the left humerus and a compound fracture of the left tibia. The arm injury was associated with severe contusion of the soft tissues which were extensively involved by diffuse neurofibromatosis (Fig. 1). The left hand was

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Fig. 1. Amputated left arm showing gross distortion due to diffuse subcutaneous and intramuscular neurofibromata.

cold and mottled with no pulses palpable below the axilla, suggesting a major vascular injury at the frac- ture site. Profuse haemorrhage from the upper arm was controlled initially by compression bandaging, although a large subcutaneous haematoma devel- oped in the left pectoral region. There was no clinical or radiological evidence of intrathoracic or intraperi- toneal haemorrhage. It was rapidly established that the left arm had been functionally almost useless due to the pre-existing diffuse neurofibromatosis and it was therefore decided to proceed to primary ampu- tation. The tibial fracture was first treated by internal fixation.

In the course of the upper limb amputation (which was too high for tourniquet control) further profound haemorrhage was encountered from nu- merous dilated thin-walled vascular channels in the subcutaneous tissue. The axillary artery was also abnormally thin-walled, with extensive traumatic lacerations but showing no evidence of vasospasm. Haemostasis was initially achieved by ligation of the axillary vessels and closing the stump around gauze packs. Following the operation the patient developed a severe coagulopathy and recurrent haemorrhage which was controlled by radiological embolisation of the axillary artery. The patient required 88 units of blood and blood products in the first 24 hours. He subsequently developed multiple organ failure and died 27 days after the initial injuries.

At post mortem many of the features of neurofi- bromatosis were present. There was marked kyphos- coliosis and hundreds of discrete neurofibromata were present throughout the body. There was also diffuse proliferation of neural tissue (diffuse neurofi- bromatosis) infiltrating skin, subcutaneous tissue, muscles, fat and many of the viscera. Numerous thin- walled, ectatic blood vessels were present throughout the skin, subcutaneous tissue and muscle. These were in direct relation to the abnormal neural pro- liferation.

Histological examination of the axillary artery showed distortion of the lumen and infiltration of the wall by diffuse neurofibromatosis (Fig. 2).

Discussion

Von Recklinghausen introduced the concept of mul- tiple neurofibromatosis in 1882, based on his obser- vation of patients with multiple nerve sheath tumours. ~ Different variants have since been de-

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Fatal Haemorrhage 367

Fig. 2. (a) Cross-section of normal subclavian artery (H&E, magnification x250); (b) Cross-section of patient 's subclavian artery showing infiltration of the tunica adventitia and tunica media by the diffuse neurofibromatous (arrowed) process (H&E, magnification x250).

scribed. Classical neurofibromatosis or von Reckl- inghausen disease is known as neurofibromatosis type-1 (NFM-1) and has three major features:

1. Multiple neural tumours; 2. Numerous cafe au lait spots; 3. Pigmented iris hamartomas (Lisch nodules).

NFM-1 is associated with abnormalities of chromo- some 17. 2 Central neurofibromatosis or type-2 (NFM- 2) presents as bilateral acoustic neuromata and is as- sociated with abnormalities of chromosome 22. 3 Neurofibromatosis is an autosomal dominant in- herited disease occurring in about one in 3000 live births. 4

Vascular lesions associated with neurofibromato- sis were first reported in 19445 and six types of lesion are now recognised (Table 1). 6" 7 Pure intimal lesions

Table 1. Types of vascular lesion associated with neurofibroma- tosis

1. Pure intimal.

2. Intimal aneurysmal.

3. Nodular.

4. Advanced intimal.

5. Epithelioid cell.

6. Pericapillary.

involve small arteries whereas intimal aneurysmal type involves medium sized arteries.

Salyer and Salyer found vascular lesions in almost half of neurofibromatosis patients examined at autopsy. 8 These consisted of vascular stenoses, aneurysms, arteriovenous fistulae and spontaneous

vascular ruptures. Severe haemorrhage is an uncom- mon complication of neurofibromatosis largely ignored in medical and surgical textbooks. Most re- ported cases have been associated with complications of gastrointestinal, retroperitoneal and intrathoracic tumours. There may, in addition, be associated but quite distinct arterial anomalies and these are some- times complicated by spontaneous rupture. Rarely there are co-existing coagulopathies. 9" 10

The neurofibromatous tissue itself often has a very bizarre vascular structure. As in the present case thin-walled ectatic blood vessels lie in a loose neural stroma which replaces the normal adipose tissue. The vessels tend not to retract on sectioning. They are easily avulsed and lacerated by sheering forces during trauma or operative dissection, ligatures cut through them easily and electro-cautery is largely ineffective because of their size and fragility. 11 Estab- lished haemorrhage can therefore be extremely diffi- cult to control.

References

1 CRUMI" T. Translation of case reports in (Ueber die multiplen fibrome der haut und ihre beziehung zu den multiplen neuro- men by F von Recklinghausen). Adv NeuroI 1981; 29: 1-9.

2 BARKER D, WRIGHT E, NGUYEN K, et al. Gene for von Reck- l inghausen neurofibromatosis is in the pericentromeric region of chromosome 17. Science 1987; 236: 1100-1102.

3 ROULEAU GA, WERTELECKI W, HAINES JL, et al. Genetic linkage of bilateral acoustic neurofibromatosis to a DNA marker on chro- mosome 22. Nature 1987; 329: 246-248.

4 RICCARDI VM. Von Recklinghausen neurofibromatosis. N Engl J Med 1981; 305: 1617-1627.

5 REIdBI F. Les Vaisseaux et les glandes endocrines dans le syn- drome sympathicotonique dans la maladie de Recklinghausen. Schweiz Z Pathol Bakteriol 1944; 7: 168-236.

6 FEYRTER F. Uber die vasculare Neurofibromatose, nach Untersu- chungen am menschlichen Magen-Darmschlauch. Virchows Archiv Bd 1949; 317: 221-265.

7 RATZENHOFER M. Zur Kenntnis der Organveranderungen bei

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368 F.J. Mullan et aL

Recklinghausenscher Neurofibromatose. Verh Dtsch Ges Pathol 1954; 38: 236-244.

8 SALVER WR, SALVER DC. The vascular lesions of neurofibroma- tosis. Angiology 1974; 25: 510-519.

9 FARAH GR, Aw~m AS. Massive bleeding in neurofibromatosis associated with congenital hypofibrinogenaemia. Eur ] Surg Oncol 1985; 11: 57-60.

10 KITAO T, MIYABO S, HITTORI K. Hemophilia associated with von Recklinghausen's disease. South Med J 1976; 69: 16-39.

11 FRANOS DMA, MACKIE W. Life-threatening haemorrhage in patients with neurofibromatosis. Aust NZ ] Surg 1987; 57: 679- 682.

Accepted 19 August 1992

Eur J Vasc Surg Vol 8, May 1994