Chapter: Drug therapy
Article: 3 of 7
Update: Feb 08, 2021
Author(s): Wohlgemuth, Walter A.
Chronic bleeding is a common problem in patients with very extensive venous malformations (VM), as it often affects not only one limb but also the intestinal mucosa of the rectum, sigmoid colon and/or descending colon. This intestinal involvement manifests itself in the form of a continuous massive, often circular submucosal venous malformation directly below the mucosa, often extending from the anus into the colon. Submucosal venous malformations near the mucosa tend to bleed. In the ENT area as well, especially the mouth and tongue as well as the upper airways, chronic bleeding foci are found in venous malformations. Less frequently, the bladder mucosa is affected, with recurrent hematuria.
Chronic bleeding is more often found in patients with extensive or multifocal venous malformations or in VMCM patients.
Patients with venous malformation of the rectum or colon may suffer additionally from acquired thrombosis of the portal vein. This is caused by mesenteric venous thromboembolism via communicating veins from the venous malformation in the colon, usually via thrombi into a dysplastic, massively dilated inferior mesenteric vein. The resulting portal venous hypertension further increases the venous pressure in the submucosal venous malformation located on the colonic and rectal mucosa. This leads to a further increased risk of bleeding.
Patients with blue rubber bleb nevus syndrome (Bean syndrome) also have frequent chronic intestinal bleeding. In this case, the lesions of the venous malformation are much smaller but usually more frequent, and the extent of the intestine affected is also greater. In Bean syndrome the spots of intestinal VM extend discontinuously into the upper gastrointestinal tract, especially in the small intestine.
Patients with extensive venous malformations may also have additional chronic bleeding from an involved bladder mucosa or from gynecologic or other bleeding sources with venous malformation (usually vaginal).
The basic principle of therapy in bleeding patients with vascular anomalies is first of all the invasive elimination of the cause of bleeding by closure of the submucosal venous malformation.
Endoscopically controlled sclerotherapy (colon) or sclerotherapy by the direct puncture technique (rectum) of the venous malformation in the intestinal mucosa or bladder is technically possible but difficult and requires several sessions, sometimes in combination with endoscopic ligatures or laser therapy (urinary bladder).
Extensive, recurrent bleeding that cannot be treated in this way or cases with very extensive involvement, e.g., in blue rubber bleb nevus syndrome, may require partial bowel resection, if necessary with intraoperative bowel opening and preparation as well as resection of individual lesions, to be performed at an interdisciplinary, specialized center.
Urologic or gynecologic bleeding is treated analogously by direct minimally invasive, endoscopic intervention or open surgery. Combination therapies are common.
The prophylactic administration of heparin prior to major surgery is particularly important for bleeding prophylaxis when LIC turns into disseminated intravascular coagulation disorder (DIC), where all coagulation factors are very quickly consumed. Bleeding then results because the body cannot produce the coagulation factors fast enough. Therefore, in the case of abnormal laboratory findings (high D-dimers, low fibrinogen), extensive LIC and large VM, the administration of heparin at least 3 days prior to surgery is necessary to prevent the transition into DIC.
In cases of pronounced LIC and large venous malformations that threaten to turn into DIC with clinically manifest bleeding, the administration of antifibrinolytics (such as epsilon-aminocaproic acid or tranexamic acid) is not very effective. Coagulation factors should be substituted with equal amounts of heparin. According to the published literature, antifibrinolytics have also been shown to be less effective in the case of bleeding in KMP.
Another group of patients who may be prone to recurrent, sometimes arterial bleeding are patients with arteriovenous malformations (AVM) that are at an advanced clinical stage (Schobinger grade 3) and thus have ischemic ulcerations or wounds. These chronic wounds, mostly on the lower extremity (owing to the additional high venous hydrostatic pressure caused by the arteriovenous fistulas), do not heal for a long time. The high local blood pressure can cause severe bleeding from these wounds. In this case, treatment of the wounds (including bacterial superinfection) and treatment of the AVM itself by means of embolization and, if possible, open resection are necessary.
The general principles of drug treatment of bleeding otherwise do not differ from bleeding therapy for other reasons. First and foremost, volume replacement is required for shock treatment and the source of bleeding must be stopped (minimally invasively by angiography, open surgery, or endoscopically). Additional coagulation factor substitution, in some cases with administration of fresh plasma and/or corpuscular blood components, is unavoidable.