Venous Malformation

Determination of Blood Flow Velocity and Transit Time in Cerebral Arteriovenous Malformation using Microdroplet Angiography

Venous Malformation | Johns Hopkins Medicine

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    Canty, J. M. Jr., R. M. Judd, A. S. Brody, and F. J. Klocke. First-pass entry of nonionic contrast agent into the myocardial extravascular space. Effects on radiographic estimates of transit time and blood volume. Circulation 8: 2071–2078, 1991.

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    Coard, K., M. D. Silver, G. Perkins, A. J. Fox, and E. V. Vinuela. Isobutyl-2-cyanoacrylate pulmonary emboli associated with occlusive embolotherapy of cerebral arteriovenous malformations. Histopathology: 917–926, 1984.

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    Colombo, F., F. Pozza, G. Chierego, L. Casentini, G. De Luca, and P. Francescon. Linear accelerator radiosurgery of cerebral arteriovenous malformations: an update [see comments]. Neurosurgery 3: 14–20, 1994.

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    Debrun, G., F. Vinuela, A. Fox, and C. G. Drake. Embolization of cerebral arteriovenous malformations with bucrylate. J. Neurosurg. 5: 615–627, 1982.

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    Deruty, R., I. Pelissou-Guyotat, C. Mottolese, Y. Bascoulergue, and D. Amat. The combined management of cerebral arteriovenous malformations. Experience with 100 cases and review of the literature. Acta. Neurochir. 12: 101–112, 1993.

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    Deveikis, J. P., H. J. Manz, A. J. Luessenhop, A. J. Caputy, A. I. Kobrine, D. Schellinger, and N. Patronas. A clinical and neuropathologic study of silk suture as an embolic agent for brain arteriovenous malformations. AJNR Am. J. Neuroradiol. 1: 263–271, 1994.

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    Divani, A. A. Injection of micro-droplets for flow characterization in arteriovenous malformations prior to embolization. Master thesis. Buffalo: SUNY at Buffalo, 1999, p. 128.

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    Ersahin, A., S. Y. Molloi, and J. W. Hicks. Absolute phasic blood flow measurement in the brain using digital subtraction angiography. Invest. Radiol. 3: 244–253, 1995.

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    Goldman, M. L., M. S. Sarrafizadeh, P. K. Philip, A. M. Karmody, R. P. Leather, N. Parikh, and S. R. Powers. Bucrylate embolization of abdominal aortic aneurysms: an adjunct to nonresective therapy. AJR, Am. J. Roentgenol. 13: 1195–1200, 1980.

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    Gruber, A., P. R. Mazal, G. Bavinzski, M. Killer, H. Budka, and B. Richling. Repermeation of partially embolized cerebral arteriovenous malformations: a clinical, radiologic, and histologic study. AJNR Am. J. Neuroradiol. 1: 1323–1331, 1996.

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    Hessel, S. J., D. F. Adams, and H. L. Abrams. Complications of angiography. Radiology 13: 273–281, 1981.

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    Luessenhop, A. J., and W. T. Spence. Artificial embolization of cerebral arteries: Report of use in a case of arteriovenous malformation. J. Am. Med. Assoc. 17: 1153–1155, 1960.

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    Martin, N. A., and H. V. Vinters. Arteriovenous malformations. In: Neurovascular Surgery. New York: McGraw-Hill, 1994, pp. 875–903.

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    Massoud, T. F., C. Ji, G. Guglielmi, and F. Vinuela. Endovascular treatment of arteriovenous malformations with selective intranidal occlusion by detachable platinum electrodes: Technical feasibility in a swine model. AJNR Am. J. Neuro-radiol. 1: 1459–1466, 1996.

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    Mygind, T. Particulate radiographic contrast material for quantitative representation of blood-flow patterns. II. Theoretical considerations. Invest. Radiol.: 27–39, 1971.

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    Mygind, T., M. Sovak, A. Oigaard, O. Christensen, and A. Jarlov. Soluble contrast particles for radiographic analysis of blood flow. Determination of cardiac output in dogs. Invest. Radiol.: 1–12, 1970.

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    Nakstad, P. H., S. J. Bakke, and J. K. Hald. Embolization of intracranial arteriovenous malformations and fistulas with polyvinyl alcohol particles and platinum fibre coils. Neuroradiology 3: 348–351, 1992.

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    Nishi, S., W. Taki, I. Nakahara, K. Yamashita, A. Sadatoh, H. Kikuchi, H. Hondo, K. Matsumoto, H. Iwata, and Y. Shimada. Embolization of cerebral aneurysms with a liquid embolus, EVAL mixture: report of three cases. Acta. Neurochir. 13: 294–300, 1996.

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    Ohnishi, K., M. Saito, H. Koen, T. Nakayama, F. Nomura, and K. Okuda. Pulsed Doppler flow as a criterion of portal venous velocity: Comparison with cineangiographic measurements. Radiology 15: 495–498, 1985.

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    Reichle, F. A., M. Sovak, R. L. Soulen, and G. P. Rosemond. Portal vein blood flow determination in the unanesthetized human by umbilicoportal cannulation. J. Surg. Res. 1: 146–150, 1972.

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    Rudin, S., L. R. Guterman, W. E. Granger, D. R. Bednarek, and L. N. Hopkins. Application of region-of-interest imaging techniques to neurointerventional radiology. Radiology 19: 870–873, 1996.

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    Rudin, S., B. B. Lieber, A. K. Wakhloo, D. R. Bednarek, L. R. Guterman, and L. N. Hopkins. Quantitative flow velocity measurements in vessels, aneurysms, and arteriovenous malformations (AVMs) using droplet path tracing with a biplane pulsed fluoroscopy system. Proc. SPIE 303: 268–279, 1997.

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Spotlight On: Johns Hopkins Combines Health Data with Patient Input to Reduce Venous Thromboembolism

Venous Malformation | Johns Hopkins Medicine

Many patients being admitted to hospitals today are at risk of developing a potentially deadly medical condition that’s ly not even on their radar. According to the U.S.

Surgeon General, this problem affects up to 600,000 patients in the United States each year, with 100,000 of those cases resulting in death — more than AIDS, breast cancer, and motor vehicle accidents combined.

The condition? Venous thromboembolism (VTE), more commonly known as blood clots.

Deep vein thrombosis (DVT) occurs when a blood clot forms in a deep vein and becomes potentially fatal if it breaks loose to the lungs, called a pulmonary embolism (PE), where it may block some or all of the blood supply to the lungs. Patients who are suffering from cancer, having surgery, or dealing with major traumas fractures are at the highest risk.

In 2005, when Johns Hopkins Medicine set out to reduce the incidence of blood clots across its health system, it formed the VTE Collaborative, a group that today includes, among others, a hematologist, a surgical nurse, an anti-coagulation pharmacist, a trauma surgeon, and researchers. Brandyn Lau, an assistant professor of radiology and health sciences informatics at the Johns Hopkins University School of Medicine, also joined the group to contribute his expertise in applying health information technology to improve patient care.

Lau has chosen to focus on VTE because this deadly condition is highly preventable. “There’s strong evidence that shows that best-practice prophylaxis reduces risk of blood clots in hospitalized patients by about 60 percent. That is a huge risk reduction,” says Lau.

Johns Hopkins Medicine’s commitment to the Patient Safety Movement Foundation Actionable Patient Safety Solutions (APSS) #12 aims to reduce embolic events. Lau is passionate about the idea of improving practices in this way. “When you think about improving practices, you’re improving the care for thousands or tens of thousands of patients, which is an incredibly rewarding experience.”

To fulfill its commitment to APSS #12, the VTE Collaborative targeted three areas: risk assessment, prescription of preventive therapy, and administration of prescribed preventive therapy. The system it created ensures that:

  • Upon admission, every Johns Hopkins patient is assessed for their individual risk of developing a blood clot
  • that assessment, patients are prescribed the appropriate prevention therapy for their risk level
  • Complete administration of prescribed, risk-appropriate preventive therapy is monitored and, if the patient misses a dose for any reason, active intervention to provide information on the symptoms, risk factors, and preventive measures for blood clots

Johns Hopkins chose to build a specialty-specific VTE risk-assessment tool into Epic, its electronic health record system which is also used in many hospitals around the country.

The information derived from the risk assessment determines the appropriate prevention therapy and then makes a prescription recommendation to the patient’s doctor.

To further improve prescribing practices, residents in the Departments of Surgery, Medicine, and Gynecology and Obstetrics receive individualized feedback about their VTE prophylaxis prescribing habits monthly which has ensured that more than 95 percent of patients are prescribed appropriate care to prevent blood clots.

A Surprise in the Data

An unexpected issue revealed itself when Lau examined data on medication dose administration. “We found that 12 percent of doses of medication to prevent blood clots are not administered to patients,” says Lau. “It was absolutely shocking.”

In 60 percent of cases where the doses were skipped, the documented reason was patient refusal.

In collaboration with peers at hospitals around the country, Lau finds this high rate of refusal typical, even though many hospitals are unaware it’s even an issue.

  “Most hospitals only look at whether the first dose is administered, not whether the doses continue to be administered or missed,” explains Lau. “If the medication dose isn’t administered, it can’t possibly be effective.”

VTE prophylaxis typically comes in the form of blood thinners administered in a shot once or even multiple times per day. Combine this discomfort with the fact that the danger of blood clots isn’t widely understood, and it becomes clear why some patients and nurses de-prioritize this part of their care.

With funding from the Patient Centered Outcomes Research Institute, the group set about developing comprehensive VTE education. To make sure the information was truly what patients need and want, the group started there – with the patients.

The group partnered with more than 400 individuals across the country and asked what they understood about blood clots, what they wish they had known before they developed the condition, and how they would have d to have had that information delivered.

While there wasn’t a single preference, the group identified three formats that were prioritized by patients: paper, video, and in-person conversations with a clinician.

The patients were clear about their preferences. With the printed paper, patients didn’t want more than a single sheet, front and back. The video needed to be shorter than 10 minutes. For the discussions, patients just wanted a nurse or a doctor whom they could talk to, ask questions, and get answers from in real time.

In the end, the VTE education covered just the basics – symptoms, risks factors, and preventive measures for blood clots – but it was the information patients needed to make an informed decision, and dose administration improved by almost 50 percent.

When it came to delivering this information, the VTE Collaborative again returned to the data.

Delivering VTE education to every patient would be an inefficient use of resources in the 60 percent of cases where patients were receiving all of their doses.

The system instead triggers an alert when a nurse documents a missed dose in Epic so a nurse educator from the VTE Collaborative can coordinate the education bundle.

Spreading the word

The strategies have shown measurable and reproducible improvements in VTE outcomes at The Johns Hopkins Hospital. To help other hospitals achieve the same success, the Johns Hopkins VTE Collaborative has published the educational bundle, which includes the two-page educational form and the 10-minute video. These tools are freely available at

Lau understands that hospitals have limited resources. “We’ve done a lot of the heavy lifting here to develop tools and a data-reporting structure that we as an institution are very happy to share with other hospitals that are using the same type of electronic health record system.”

Lau and the VTE Collaborative are pleased with the project. “We didn’t reduce missed doses by 100 percent but, at the very least, our mission is to make sure patients are informed about the care that’s being offered so they can make an informed decision about what is right for them.”


Vascular Malformations of the Brain – NORD (National Organization for Rare Disorders)

Venous Malformation | Johns Hopkins Medicine


Beers MH, Berkow R., eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:244-45; 1427; 1482.

Smith WS, Johnston SC, Easton JD. Cerebrovascular Diseases. In: Kasper, DL, Fauci AS, Longo DL, et al. Eds. Harrison’s Principles of Internal Medicine. 16th ed. McGraw-Hill Companies. New York, NY; 2005:2392-93.

Marchuk DA, Berg JN. ENG and ALK1 and Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Syndrome) and Vascular Morphogenesis. In: Epstein CJ, Erickson RP, Wynshaw-Boris, eds. Inborn Errors of Development. 1st ed. Oxford University Press. New York, NY; 2004:319-28.

Johnston MV. Acute Stroke Syndromes. In: Behrman RE, Kliegman RM, Jenson HB. Eds. Nelson Textbook of Pediatrics. 17th ed. Elsevier Saunders. Philadelphia, PA; 2005:2036-37.

Solomon RA, Pile-Spellman J, Mohr JP. Vascular Tumors and Malformations. In: Rowland LP. Ed. Merritt’s Neurology. 10th ed. Lippincott Williams & Wilkins. Philadelphia, PA. 2000:367-71.

Guttmacher AE, McDonald JE. Hereditary Hemorrhagic Telangiectasia. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:418.


Arteriovenous malformation

Choi JH, Mohr JP. Brain arteriovenous malformations in adults. Lancet Neurol. 2005;4:299-308.

Hussain MS, Qureshi AI, Kirmani JF, et al. Update on endovascular treatment of cerebrovascular diseases. J Endovasc Ther. 2004;11 Suppl 2:II32-42.

Brown RD Jr, Flemming KD, Meyer , et al. Natural history, evaluation, and management of intracranial vascular malformations. Mayo Clin Proc. 2005;80:269-81.

Schauble B, Cascino GD, Pollock BE, et al. Seizure outcomes after stereotactic radiosurgery for cerebral arteriovenous malformations.

Yamada S, Brauer FS, Colohan AR, et al. Concept of arteriovenous malformation compartments and surgical management. Neurol Res. 2004;26:288-300.

Cavernous malformation

Raychaudhuri R, Batjer HH, Awad IA. Intracranial cavernous hemangioma: a practical review of clinical and biological aspects. Surg Neurol. 2005;63:319-28.

Byrne JV. Cerebrovascular malformations. Eur Radiol. 2005;15:448-52.

Yasui T, Komiyama M, Iwai Y, et al. A brainstem cavernoma demonstrating a dramatic, spontaneous decrease in size during follow-up: case report and review of the literature. Surg Neurol. 2005;63:170-73; discussion 173.

Baumgartner JE, Ater JL, Ha CS, et al. Pathologically proven cavernousangiomas of the brain following radiation therapy for pediatric brain tumors. Pediatr Neurosurg. 2003;39:201-07.

Zhou LF, Mao Y, Chen L. Diagnosis and surgical treatment of cavernous sinus hemangiomas: an experience of 20 cases. Surg Neurol. 2003;60:31-36; discussion 36-37.

Venous angiomas

Bilaniuk LT. Vascular lesions of the orbit in children. Neuroimaging Clin N Am. 2005;15:107-20.

Chiller KG, Frieden IJ, Arbiser JL. Molecular pathogenesis of vascular anomalies: classification into three categories based upon clinical and biochemical characteristics. Lymphat Res Biol. 2003;1:267-81.

Metry DW. Potential complications of segmental hemangiomas of infancy. Semin Cutan Med Surg. 2004;23:107-15.

Tille JC, Pepper MS. Hereditary vascular anomalies: new insights into their pathogenesis. Arterioscler Thromb Vasc Biol. 2004;24:1578-90.

Vein of Galen malformations

Kubi N, Levy BI. Understanding angiogenesis: a clue for understanding vascular malformations. J Neuroradiol. 2004;31:365-68.

Greene AK, Burrows PE, Smith L, et al. Periorbital lymphatic malformation: clinical course and management in 42 patients. Plast Reconstr Surg. 2005;115:22-30.

Gupta AK, Varma DR. Vein of Galen malformations: review. Neurol India. 2004;52:43-53.

Punt J. Surgical management of paediatric stroke. Pediatr Radiol. 2004;34:16-23.


Freedom RM, Yoo SJ, Perrin D. The biological “scrabble” of pulmonary arteriovenous malformations: considerations in the setting of cavopulmonary surgery. Cardiol Young. 2004;14:417-37.

Woods CG. Human microcephaly. Curr Opin Neurobiol. 2004;14:112-17.

Marchuk DA, Srinivasan S, Squire TL, et al. Vascular morphogenesis: tales of two syndromes. Hum Mol Genet. 2003; 12 Spec No 1:R97-112.

Sabba C, Pasculli G, Cirulli A, et al. Hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease). Minerva Cardioangiol. 2002;50:221-38.

Ataxia telangiectasia with vascular abnormalities in the brain parenchyma: report of an autopsy case and literature review. Pathol Int. 2001;51:271-76.


McKusick VA, ed. Online Mendelian Inheritance In Man (OMIM). The Johns Hopkins University. Cerebral Cavernous Malformations; CCM. Entry Number; 116860: Last Edit Date; 11/2/2005.


The Johns Hopkins Venous Thromboembolism Collaborative: Multidisciplinary team approach to achieve perfect prophylaxis

Venous Malformation | Johns Hopkins Medicine

Volume 11, Issue S2

Venous thromboembolism (VTE) is an important cause of preventable harm in hospitalized patients.

The critical steps in delivery of optimal VTE prevention care include (1) assessment of VTE and bleeding risk for each patient, (2) prescription of risk‐appropriate VTE prophylaxis, (3) administration of risk‐appropriate VTE prophylaxis in a patient‐centered manner, and (4) continuously monitoring outcomes to identify new opportunities for learning and performance improvement. To ensure that every hospitalized patient receives VTE prophylaxis consistent with their individual risk level and personal care preferences, we organized a multidisciplinary task force, the Johns Hopkins VTE Collaborative. To achieve the goal of perfect prophylaxis for every patient, we developed evidence‐based, specialty‐specific computerized clinical decision support VTE prophylaxis order sets that assist providers in ordering risk‐appropriate VTE prevention. We developed novel strategies to improve provider VTE prevention ordering practices including face‐to‐face performance reviews, pay for performance, and provider VTE scorecards. When we discovered that prescription of risk‐appropriate VTE prophylaxis does not ensure its administration, our multidisciplinary research team conducted in‐depth surveys of patients, nurses, and physicians to design a multidisciplinary patient‐centered educational intervention to eliminate missed doses of pharmacologic VTE prophylaxis that has been funded by the Patient Centered Outcomes Research Institute. We expect that the studies currently underway will bring us closer to the goal of perfect VTE prevention care for every patient. Our learning journey to eliminate harm from VTE can be applied to other types of harm. Journal of Hospital Medicine 2016;11:S8–S14. © 2016 Society of Hospital Medicine

Venous thromboembolism (VTE), which encompasses deep venous thrombosis and pulmonary embolism, is an important cause of preventable morbidity and mortality.1 Each year it is estimated as many as 600,000 American's suffer VTE and as many as 100,000 die.

2 Consequently, patient safety and healthcare quality, accrediting organizations such as The Joint Commission, and federal agencies such as the Centers for Disease Control and Prevention and Agency for Healthcare Research and Quality (AHRQ) have made VTE prevention a priority.3-5

Despite widespread recognition that VTE prophylaxis is an important patient safety measure, poor performance is common.

The ENDORSE (Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting) study of over 68,000 hospitalized patients in 32 countries noted only 58.5% of surgical patients and 39.

5% medical patients received American College of Chest Physicians (ACCP) guideline‐appropriate VTE prophylaxis.6 In 2005, an audit of the surgical services at The Johns Hopkins Hospital found that only 33% of 322 randomly selected patients were prescribed prophylaxis consistent with the ACCP guidelines.

Achieving defect‐free VTE prevention requires attention to each step in the process: (1) assessment of both VTE and bleeding risk, (2) prescription of risk‐appropriate VTE prophylaxis, and (3) administration of risk‐appropriate VTE prophylaxis.

In 2005, to improve our VTE prevention performance at Johns Hopkins Hospital, the Center for Innovations organized a VTE Collaborative of 2 physicians, 1 nurse, and 1 pharmacist dedicated to VTE quality improvement.

Since then, the group has grown dramatically, adding a clinical informatics expert and numerous other members and coming under the auspices of The Armstrong Institute for Patient Safety.

Recognizing that many, though not all, VTEs are potentially preventable,7, 8 the mission of the Johns Hopkins VTE Collaborative is to ensure that all hospitalized patients receive risk‐appropriate, best‐practice VTE prophylaxis. This article chronicles the innovative strategies that the Johns Hopkins VTE Collaborative has employed over the past decade to improve our hospital's performance in VTE prevention (Table 1).

Strategies to improve VTE prophylaxis ordering
Paper‐based patient risk assessment forms (before computer order entry)
Mandatory evidence‐based specialty‐specific computer clinical decision support “smart order sets”
Group data and competitions
1‐on‐1 provider feedback
Pay for performance
Individualized feedback with resident scorecards
Strategies to improve VTE prophylaxis administration
Identification of missed doses as a major contributor to preventable VTE
Identification of physician, nurse and patient contributors to missed doses
Collaboration with patients to create patient‐centered educational materials
Novel web‐based module for nursing education
Real‐time missed doses alert
Targeted 1‐on‐1 patient education
  • NOTE: Abbreviations: VTE, venous thromboembolism.

With the support of hospital leadership, the VTE Collaborative held a series of events in 2005 with medical and surgical providers to review the current evidence supporting VTE prophylaxis and achieve consensus on appropriate practice based upon the 2004 ACCP VTE Prophylaxis Guideline.

The result was the development of 5 evidence‐based, paper VTE prophylaxis order sets that guided the ordering provider on the assessment of VTE and bleeding risk and facilitated the selection of risk‐appropriate VTE prophylaxis.

Because there were no validated VTE or bleeding risk assessment tools at the time we developed our order sets, we used specialty‐specific VTE risk factors derived from the 2004 ACCP Guideline.

To identify patients inappropriate for pharmacologic prophylaxis, we used exclusion criteria derived from contemporary randomized clinical trials of pharmacologic prophylaxis in the target populations (ie, active bleeding, abnormal activated partial thromboplastin time not due to a lupus inhibitor) or mutually agreed upon thresholds after discussion with individual provider groups (platelet count


Online Mendelian Inheritance in Man (OMIM)

Venous Malformation | Johns Hopkins Medicine

A number sign (#) is used with this entry because of evidence that primary intraosseous vascular malformation (VMPI) is caused by homozygous mutation in the ELMO2 gene (606421) on chromosome 20q13.

Primary intraosseous vascular malformation, previously called intraosseous hemangioma, is a rare malformation that usually involves the vertebral column and the skull. The most commonly affected bones in the skull are the mandible and the maxilla, and life-threatening bleeding after a simple tooth extraction is frequent (Vargel et al., 2002).

Vargel et al. (2002) reported 2 consanguineous Turkish families containing 4 persons with VMOS. The phenotypic expression was remarkably similar in both families.

Characteristic findings included severe blood vessel expansions within the craniofacial bones and midline anomalies such as diastasis recti, supraumbilical raphe, and hiatus hernia. Malformation was restricted to the mandibular and maxillary areas in the prepubertal years; rapid expansion started after age 12 or 13 years.

A 15-year follow-up of 1 patient demonstrated that the vascular malformation did not extend beyond the craniofacial region despite severe involvement of almost all bones in the skull.

Detailed clinical and radiologic evaluation provided neither evidence of soft tissue involvement nor any sign of gross arterial, venous, or combined malformations, indicating that bone changes are a primary rather than a secondary effect due to any other vascular anomaly in the craniofacial region.

Cetinkaya et al. (2016) studied 8 affected children from 5 unrelated consanguineous families with VMPI, including 4 from the 2 Turkish families originally reported by Vargel et al. (2002). All of the children appeared unaffected at birth, but developed a painless swelling of the mandible in early childhood that progressed with age.

Follow-up of the affected members of the Turkish families showed that enlargement of facial bones accelerated during early puberty and caused severe facial asymmetry. The mandible and maxilla were involved in all patients; other affected bones included the nasal bones, calvaria, sphenoid, clivus, and, less frequently, the clavicles, ribs, and vertebrae.

Ectopic tooth eruption occurred in all affected individuals, and removal of teeth and facial bones provided temporary symptomatic relief and slowed disease progression. All patients also exhibited gingival bleeding, requiring endovascular embolization and/or percutaneous sclerotherapy, and 5 of them had chronic anemia due to repeated bleeding episodes.

One of the Turkish patients died at age 27 due to spontaneous massive bleeding.

In 5 of 6 patients who underwent angiography, there was abnormal organization of vessels and late-phase capillary pooling in affected bones, indicating slow-flow lesions of capillary or venous origin; magnetic resonance angiography performed in 1 patient showed hypervascular lesions of the facial bones.

Compression of organ compartments by the expanding vascular lesions resulted in various complications, including exophthalmos in 7 patients, which was associated with some loss of vision in 5 patients, spinal cord compression with paraplegia in 1 patient, and increased intracranial pressure in 3 patients, associated with brain herniation and death in 1 patient. Primary extraosseous findings were supraumbilical raphe, diastasis recti, and umbilical hernia.

Using tissue samples from 2 Turkish patients with VMPI, Vargel et al.

(2002) found that an antibody against a universal proliferation marker, MKI67 (176741), detected nonproliferative, single-layered endothelial cells, suggesting that this abnormality is a vascular malformation rather than a hemangioma.

Staining of alpha-actin (102610) with an antibody against perivascular tissues such as smooth muscle cells and/or pericytes showed that pathologic vessels lost their surrounding supportive tissues, as seen in other types of vascular anomalies.

Cetinkaya et al. (2016) performed histologic analysis of mandibular tissue from a Turkish patient with VMPI and observed irregular, thin-walled, dilated and engorged vascular channels, accompanied by abundant adipose tissue among bone trabeculae. In contrast, patient fibular tissue obtained for mandibular reconstruction was normal.

The abnormal mandibular vessels were lined by a single layer of endothelial cells and were negative for MKI67, consistent with the diagnosis of vascular venous malformation rather than a proliferative or neoplastic process.

In addition, the VMPI tissue was negative for markers of mature vascular smooth muscle cells (vSMCs), suggesting that vSMCs in VMPI form an immature smooth muscle layer incapable of withstanding blood pressure.

Cetinkaya et al. (2016) analyzed genomewide homozygosity-by-descent haplotypes in 4 families with VMPI, including 2 Turkish, 1 Saudi, and 1 Iraqi, and identified a single homozygous region spanning 3.27 Mb between DNA markers rs6065774 and rs401976 on chromosome 20q13.12 (chr20:43,655,782-46,924,866; GRCh37).

Exclusion Studies

By homozygosity mapping in 2 Turkish families with VMPI, Vargel et al.

(2002) excluded the following loci and/or genes from involvement in VMOS: multiple cutaneous venous malformation (VMCM1; 600195) on 9p21; venous malformation with glomus cells (VMGLOM; 138000) on 1p22-p21; hereditary hemorrhagic telangiectasia type 1 (HHT1; 187300) and type 2 (HHT2; 600376) on 9q34.1 and 12q11-q14, respectively; and cerebral cavernous malformation type 1 (CCM1; 116860), type 2 (CCM2; 603284), and type 3 (CCM3; 603285) on 7q11.2-q21, 7p15-p13, and 3q25.2-q27, respectively.

By massive parallel sequencing targeting the critical homozygous region for VMPI on chromosome 20q13, Cetinkaya et al. (2016) identified homozygosity for a splice site mutation in the ELMO2 gene (606421.

0001) in affected individuals from 2 Turkish families originally reported by Vargel et al. (2002). Two other homozygous mutations identified in the ELMO2 gene included another splice site mutation (606421.0002) in 2 affected sisters from a Saudi family and a 1-bp deletion (606421.

0003) in an affected individual from a North American family. Cetinkaya et al. (2016) also identified a complex rearrangement at 20q13 involving a 5,398-bp deletion and a 330-bp insertion in an affected Iraqi female.

All available parents were heterozygous for the respective mutations, and unaffected sibs were either heterozygous or did not carry the mutation.


Spinal Arteriovenous Malformations

Venous Malformation | Johns Hopkins Medicine

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Arteriovenous malformations (AVMs) occur when the connections between the veins and arteries don't form correctly and the vessels become entangled. Usually, these abnormalities develop in the fetus, or in a newborn baby.

AVMs can occur anywhere in the body. When they happen in the spinal cord and brain, they are called neurological AVMs, and are more ly to affect different parts of your body. This is because the brain and spinal cord make up the central nervous system. 

What causes spinal AVMs?

AVMs are equally common among different races and ethnicities, and in both sexes. Most people don't even know that they have a spinal AVM—it may be found during treatment or diagnosis for another condition. 

Spinal AVMs can cause problems with circulation because they interfere with your body's blood flow. Normally, your arteries transport oxygen-rich blood away from your heart and to cells throughout your body.

Your veins carry that blood, with its oxygen stores used up, back to your lungs and heart.

But the malformations of your arteries and veins in spinal AVMs don't allow this natural cycle to occur because of missing capillaries, which regulate blood flow.

Spinal AVMs can lead to a serious situation if they rupture, causing bleeding into surrounding areas. They can also cause symptoms by compressing parts of your spinal cord. 

What are the symptoms of spinal AVMs?

Spinal AVMs often don’t cause any symptoms. When they do, they're usually minor and hard to notice. In a few people, however, the symptoms can be severe enough to affect their ability to function.

These are the most common symptoms of a spinal AVM:

  • Muscles that feel weak or become paralyzed
  • Problems with balance and coordination (ataxia)
  • Pain or unusual sensations throughout your body, such as tingling or numbness

How are spinal AVMs diagnosed?

If you have symptoms, your healthcare provider may use these tests to find out if you have a spinal AVM:

  • Angiography (X-rays used along with a dye injected into your artery)
  • MRI scans
  • CT scans
  • Magnetic resonance angiography

How are spinal AVMs treated?

Treatment depends on the location and type of AVMs you have and the symptoms they cause. You may require surgery by a neurosurgeon to remove the AVM. Or, endovascular embolization may be used instead.

This is less invasive than surgery in which a radiologist uses a catheter (small, thin tube) to inject an embolizing material to close off certain vessels. Radiation therapy is also an option.

Focused energy is used to damage and seal off the abnormal vessels.

Your doctor may also give you medicines to treat symptoms, such as back pain, caused by AVMs. 

What are the complications of spinal AVMs?

If spinal AVMs aren't treated, they may cause damage to your spinal cord because it can't get the oxygen it needs from your blood. A spinal AVM may also bleed.

Living with spinal AVMs

Even though a spinal AVM may not always cause symptoms, it can still be dangerous, particularly if it starts to cause symptoms. Your health care provider should check any suspicious symptoms you have. These may include:

  •  Muscles that feel weak
  •  Muscle paralysis
  •  Difficulty with balance and coordination (ataxia)
  •  Unusual sensations, such as numbness or tingling, or pain

Key points about spinal AVMs

  • Arteriovenous malformations (AVMs) occur when the connections between veins and arteries don't form correctly and the vessels become entangled. 
  • AVMs can occur anywhere in your body. But when they happen in the spinal cord and brain, called neurological AVMs, they are more ly to affect different parts of your body.
  • Pay attention to the following symptoms of spinal AVMs and seek medical help for:
    • Muscles that suddenly feel weak or become paralyzed
    • Any problems you may be having with balance and coordination
    • Pain or unusual sensations, such as numbness or tingling in your body

When should I call my healthcare provider?

Your doctor should evaluate any signs or symptoms that indicate a problem with your nervous system, such as headaches that won't go away, seizures, and difficulty controlling your muscles.

Next steps

Tips to help you get the most from a visit to your healthcare provider:

  • Know the reason for your visit and what you want to happen.
  • Before your visit, write down questions you want answered.
  • Bring someone with you to help you ask questions and remember what your provider tells you.
  • At the visit, write down the name of a new diagnosis, and any new medicines, treatments, or tests. Also write down any new instructions your provider gives you.
  • Know why a new medicine or treatment is prescribed, and how it will help you. Also know what the side effects are.
  • Ask if your condition can be treated in other ways.
  • Know why a test or procedure is recommended and what the results could mean.
  • Know what to expect if you do not take the medicine or have the test or procedure.
  • If you have a follow-up appointment, write down the date, time, and purpose for that visit.
  • Know how you can contact your provider if you have questions.


Developmental Venous Anomalies

Venous Malformation | Johns Hopkins Medicine

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A developmental venous anomaly (DVA) is an unusual or irregular arrangement of small veins that may look  the spokes of a wheel. The veins drain into a larger central vein. DVAs are benign (not cancerous).

DVAs also may be called venous angiomas or benign variations in venous drainage. Some doctors refer to them as caput medusae, a Latin term that means head of Medusa because the clump of veins resembles snakes on the head of the Greek mythological character named Medusa.

These unusual vein formations can occur anywhere in the body but are found most often in the brain or spinal cord. By some estimates, as many as 1 in 50 people has at least one DVA.

What causes developmental venous anomalies?

Developmental venous anomalies (DVAs) are congenital malformations of blood vessels – this means a person is born with them.

What are the symptoms of developmental venous anomalies?

Developmental venous anomalies (DVAs) generally do not cause symptoms. Many people do not know that they have one.

How are developmental venous anomalies diagnosed?

Developmental venous anomalies (DVAs) have no symptoms and may only be found when you have imaging tests to look for the cause of other health problems. Imaging tests may include MRI or MRA, conventional angiogram, or specific types of CT scans that show areas of blood flow.

Most people may never know they have a DVA, and it will only be found after their death, if an autopsy is done.

How are developmental venous anomalies treated?

Generally, developmental venous anomalies (DVAs) do not require treatment. These veins do a necessary job of getting blood in and the brain, so they do not need to be surgically removed or closed. Because they are normal and not dangerous, long-term imaging is generally not necessary.

Key points about a DVA

  • A developmental venous anomaly (DVA) is an irregular arrangement of small veins that may look the spokes of a wheel that drain into a larger central vein.
  • DVAs are congenital—a person is born with them.
  • DVAs are not dangerous, and most people do not know if they have them.
  • DVAs may only be found when doing imaging tests to look for the cause of other health problems.
  • DVAs do not need to be treated.