Congenital vascular malformations, which represent developmental abnormalities of vascular or development, may affect capillaries, veins, arteries, lymphatics, or any combination of these vascular channels. Characteristically, these lesions “grow in parallel with the growth of the patient.” However, there are certain scenarios in which the vascular malformation can be “aggravated,” generating unwanted symptoms and potential complications. Inciting factors include time, trauma, hormonal changes (puberty, the menstrual cycle, pregnancy), infection, thromboses, and surgical intervention. Unwanted associated symptoms include thromboses, bleeding, inflammation, increased size of lesions, functional impairment, tissue hypertrophy, hypertrophic nodules, pathologic fracture, and other morbidities.

Tissue Overgrowth

Capillary malformations generally remain macular for many years; however with time, soft tissue, gingival, and skeletal overgrowth, as well as lesional thickening and nodules, can develop [1–4]. The soft tissue overgrowth occurs in the region of the capillary malformation, predominantly in the V2 distribution, and one study suggests the onset may be delayed with early pulsed dye laser treatment [4]. The exact mechanism of the above progression is not fully understood; however, the provoking factor for capillary malformations to evolve as described is time, since the incidence of hypertrophy and lesional changes increases with age. Tark et al. observed histologic findings suggestive of arteriovenous malformations in resected hypertrophic nodules from adults with longstanding capillary malformations [5]. These later-stage lesions are resistant to pulsed dye laser treatment, in contrast to laser in infants, which has been shown to achieve a more favorable response [6].

Hormonal Changes: Puberty, Menstrual Cycle, and Pregnancy

Vascular malformations may remain quiescent for years, and then patients may notice a sense of fullness and intermittent pain, which may progress. Frequently this correlates with peripubertal changes. The onset of puberty is preceded biochemically by hormonal changes, which may affect a vascular malformation, manifesting as pain or discomfort. Recent evidence suggests the onset of pubertal development is occurring earlier [7–9]. The circulating hormones may trigger signs of puberty and accompanying problems in patients with vascular malformations. Kulungowski et al. reviewed hormone receptor expression in vessels of vascular malformations (arteriovenous, lymphatic, and venous) and found increased expression of growth hormone receptor, speculating that this may be contributory to puberty-related changes in vascular malformations [10]. Patients may notice increased fullness, pain, and cyclical changes associated with the menstrual cycle. “Growth spurts” during puberty may also magnify limb length discrepancies. The use of estrogen-containing birth control pills may lead to unwanted thromboses, especially in women with a predisposing thrombophilia [11].

Pregnancy poses many challenges to patients with vascular malformations, especially lower extremity malformations. Pregnancy related complications have been studied in women with hereditary hemorrhagic telangiectasia. The rates of miscarriage and congenital anomalies were considered to be comparable to that of the general population. Wain et al. reported the results of a survey of 560 pregnancies in 226 patients with HHT [12], and De Gussem and colleagues reported the results of a retrospective study via telephone interviews of 87 women with HHT (representing 244 pregnancies) [13]. Hemothorax (2.1 %), hemoptysis (1.1 %), transient ischemic attack (possibly from a paradoxical embolus), intracranial hemorrhage, cardiac failure (in patients with hepatic AVMs), increased telangiectasias, and epistaxis were described [12–14].

Pregnancy-related complications such as intrapartum/peripartum hemorrhage and/or thrombosis, increased varicosities (e.g., vulvar), and seizures have been described in women with Klippel-Trenaunay syndrome [15–18]. Successful pregnancies in women with Klippel-Trenaunay syndrome have been reported [19, 20]; however, precautions such as prophylactic anticoagulation and high-risk surveillance are recommended [21, 22]. Anatomic variations such as May-Thurner syndrome place women at increased risk of thrombosis, especially in the setting of pregnancy, immobilization, or exposure to estrogen-containing birth control pills [11, 23, 24]. Prophylactic anticoagulation should therefore be considered in such patients.

Although the risk of intracerebral hemorrhage from intracerebral vascular malformations in pregnancy is rare, it is generally appreciated that pregnancy increases the hemorrhagic risk of AVM. In one case report, a pregnant woman with a developmental venous anomaly experienced a neurologic event, presumably due to dehydration-related thrombosis with secondary hemorrhage [25, 26].

Trauma

Trauma to a vascular malformation may cause infection, bleeding, thrombosis, fracture, or other problems. Some patients report lymphedema following sports trauma. This may be related to damage to fragile subcutaneous lymphatic vessels, e.g., in the shins.

Iatrogenic Provoking Factors: Surgery and Endovascular Therapy

Boccara et al. investigated if surgical intervention may provoke clinical aggravation of lymphatic malformations (LM) in pediatric patients. This retrospective review of 26 cases revealed that postoperative delayed wound healing, lymphatic oozing, and functional impairment were frequent [27]. Additionally, Trenor and Chaudry warn that rib biopsy can induce chronic pleural effusion in patients with complicated lymphatic anomalies [28]. Patients with vascular anomalies associated with profound thrombocytopenia (e.g., Kasabach-Merritt phenomenon in Kaposiform Hemangioendothelioma) are at risk of bleeding; thus, biopsy of these lesions and surgical intervention overall should be performed with caution.

Careful planning and staged interventional procedures by experienced interventional radiologists can abrogate serious treatment-related complications. In one series of 116 evaluable patients with venous malformations who underwent sclerotherapy with alcohol and/or sodium tetradecyl sulfate, the complications included peripheral nerve injury, deep vein thrombosis, muscle contracture, infection, skin necrosis, and others, most of which ultimately resolved [29]. Pulmonary embolism, hemoglobinuria, renal complications and coagulopathy, contour deformities, and hyperpigmentation (following bleomycin sclerotherapy) have also been reported as possible sequelae from sclerotherapy [30–34]. Foam sclerotherapy is noted to have a lower complication rate, and alcohol the highest [33, 35, 36].

Delayed wound healing, wound dehiscence, and recurrence were the most common sequelae of surgical intervention for vascular anomalies of the vermilion in a series of 38 patients [37].

In summary, there are many potential “provoking factors” which can aggravate congenital vascular malformations. It is essential to be aware of these issues and to mitigate complications when feasible.