ANEURYSM OF THE ABDOMINAL AORTA - David H. Stubbs, MD
BASICS
DESCRIPTION
A permanent localized (i.e., focal) dilatation of the abdominal aorta having at least a 50% increase in diameter compared to the expected diameter of the artery. The clinical presentation of aneurysms relates to location, size, type, and comorbid factors affecting the patient. The majority of aneurysms are asymptomatic. Some present with rupture, others with embolism or thrombosis. The management and indications for surgical repair is dictated by the natural history of the aneurysm, the type, the consequences of repair, and the general status of the patient. There are two types, which are infrarenal (90%) and thoracoabdominal.
• System(s) Affected: Cardiovascular; Hemic/ Lymphatic/Immunologic
• Synonym(s): Aortic aneurysms; AAA
ALERT
Geriatric Considerations
Familial aggregations exist, but pathogenesis relates to interaction of genetic, environmental, and biochemical factors.
- Marfan syndrome
- Ehlers-Danlos syndrome
Pediatric Considerations
Etiology more likely infectious or collagen disorders
GENERAL PREVENTION
Screening: 1-time ultrasound screening for AAA in male patients, ages 65-75 who have ever smoked >100 cigarettes
EPIDEMIOLOGY
• Predominant age: Elderly
• Predominant sex: Male > Female (4:1)
Incidence
• >15,000 deaths per year
• 10th leading cause of death in males >55
- In men >60 years: 2-5%
- In men >65 years: 6%
- In men >75 years: 11%
• In women >65 years: 4%
• High risk groups
- Coronary disease: 5-9%
- Peripheral vascular disease: 10-15%
- 1st degree relative with AAA: 25%
- Males = 40% risk
- Females = 15% risk
- Obese patients >65 years
- Presence of peripheral aneurysms
RISK FACTORS
• Hypertension
• Nicotine
• COPD
• Familial: Siblings of patients with AAA
ETIOLOGY
• Atherosclerosis
• Inflammatory (5-10%)
• Traumatic
• Genetic predisposition (Marfan, Ehlers-Danlos)
ASSOCIATED CONDITIONS
• Marfan syndrome
• Ehlers-Danlos syndrome
DIAGNOSIS
SIGNS AND SYMPTOMS
Physical Exam
Majority of patients with abdominal aortic aneurysm (AAA) are asymptomatic. Many are discovered during radiologic procedures performed for other reasons.
• Pulsatile epigastric mass
• Vague abdominal pain
- May radiate to the back of flank
• Encroachment by aneurysm
- Vertebral body erosion
- Gastric outlet obstruction
- Ureteral obstruction
• Lower extremity ischemia secondary to microembolization or macroembolization of mural thrombus
• The triad of shock, pulsatile mass, and abdominal pain should always suggest rupture of AAA
- Shock may be absent if the rupture is contained.
- Palpable pulsatile mass may be absent in up to 50% of the patients with rupture.
- Pain may radiate to the back or into the groin.
- Rupture associated with 90% mortality rate.
• Unusual presentations
- Primary aortoenteric fistula: Erosion/rupture of AAA into duodenum
- Aortocaval fistula: Erosion/rupture of AAA into vena cava or left renal vein
- Inflammatory aneurysm: Encasement of aneurysm by thick inflammatory rind associated with chronic abdominal pain, weight loss, and elevated ESR
- Surrounding viscera are densely adherent.
ALERT
Geriatric Considerations
More common in this age group and may present atypically
TESTS
Lab
Evaluation for concomitant CAD
• Selective evaluation for CAD is appropriate prior to elective AAA repair (i.e., cardiac clearance).
• Patients with mild, stable cardiac symptoms should have a noninvasive cardiac stress study.
• Coronary revascularization should be performed when the CAD would merit intervention on its own.
Imaging
Screening: 1-time ultrasound screening for AAA in male patients, ages 65-75, who have ever smoked >100 cigarettes
Diagnostic Procedures/Surgery
• Clinical examination
• Ultrasonography is the preferred initial diagnostic tool in suspected AAA, but is not reliable for a diagnosis of a rupture.
• CT scans are the preferred preoperative study. Avoid contrast if the patient has significant renal insufficiency. CT scans assist in the diagnosis of an inflammatory aneurysm.
• MRI: Similar to CT and avoids contrast. MR angiography may replace arteriograms.
• Aortography: Does not define outside dimensions of aneurysms.
• Indications for aortography
- Associated renovascular hypertension
- Symptoms of visceral angina
- Significant iliofemoral occlusive disease
- Peripheral aneurysms
- Horseshoe or pelvic kidney
- Prior colectomy
DIFFERENTIAL DIAGNOSIS
• Abdominal masses transmitting aortic pulse
• Other causes of abdominal pain (e.g., peptic ulcer disease)
• Other causes of back pain (e.g., arthritis, metastatic disease)
TREATMENT
STABILIZATION
• The treatment of AAA is elective repair.
• The prevention of AAA is elective repair.
GENERAL MEASURES
• Control hypertension
• Treat atherosclerotic risk factors
• Stop smoking
SURGERY
• Repair when
- Rupture occurs
- Size >5.5 cm (or >6 cm in poor surgical risk patients)
- Expansion >0.5 cm/6 months
- Symptoms occur
• Poor surgical risk patients
- Class III-IV angina; LVEF 30%; recent CHF or MI; severe valve disease
- Serum creatinine >3 mg/dL
- PaO2 50 mm Hg; FEV1IL
- Cirrhosis with ascites
- Diffuse retroperitoneal fibrosis; hostile abdomen
- Physiologic age > chronological age
• Endovascular aneurysm repair
- There are currently 3 devices approved by the FDA for marketing. Late complications of these devices continue to occur.
- Long-term CT surveillance is required.
- Adequate iliac/femoral access
- Infrarenal non-aneurysmal neck length of at least 1 cm at the proximal and distal ends of the aneurysm
- Morphology suitable for endovascular repair
- One of the following: A diameter >5 cm, a diameter of 4-5 cm, and an increase in size by 0.5 cm in the past 6 months.
- Health status adequate to undergo the 2-hour plus implementation procedure
FOLLOW-UP
PROGNOSIS
• Aneurysms usually expand over time (Laplace's Law: T (wall tension) = Pressure Radius. Wall tension is directly related to blood pressure and the radius of the artery.) When wall tension exceeds wall tensile strength, rupture occurs.
• Surgical Outcomes:Morbidity 32%; cardiac (MI) 11%; mortality 4.2%
• Risk of morbidity and mortality increase with age
• Operative mortality is inverse to surgeon volume, hospital volume, specialty (vascular vs general surgeon)
• Non-repair (natural history of AAA >5.5 cm); 57% mortality within 1.5 years
• Mean expansion is 0.4 cm per year
• Rupture risk is increased by:
- Diastolic hypertension
- Tobacco use
- Diameter >6 cm
- COPD
- Familial history
• Ruptured aneurysms
- 8% die before receiving definitive care and 50% of the remaining die during their treatment or hospitalization.
COMPLICATIONS
• Rupture
• Associated dissection
• Thrombosis
• Embolization distally
PATIENT MONITORING
• Hypertension control
• Lipid control
• Recurrent assessment of smoking status
• Perioperative complications
- MI: 5%
- Renal failure: 6%, chronic dialysis: 1%
- Pulmonary failure: 5-8%
- Microembolism (trash foot): 1-4%
- Ischemic colitis: 0.5-1%
- Wound infection: 2%
- Graft infection: 0.5%
- Stroke: 0.5-1%
- Paraplegia: 0.2%
• Postsurgical monitoring
- Anastomotic aneurysm
- Graft infections
- Aortoenteric fistula
- Graft limb occlusion
- Additional aneurysms: Thoracic, thoracoabdominal, femoral
REFERENCES
1. Irvin TT. Abdominal pain: A surgical audit of 1190 emergency admissions. Br J Surg. 1989;76:1121.
2. Johnston W, Rutherford RB, Tilson MD, et al. Suggested standards for reporting on arterial aneurysms. J Vasc Surg. 1991;13:452.
3. Lederle FA, Wilson SE, Johnson GR, et al. Aneurysm detection and management Veterans Affairs cooperative study group. Immediate repair compared with surveillance of small abdominal aortic aneurysms. N Engl J Med. 2002;346:1437-1444.
4. Mason JJ, Owens DK, Harris RA, Cooke JP, Hlatky MA. The role of coronary angiography and coronary revascularization before non-cardiac vascular surgery. JAMA. 1995;273:1919.
5. Porter JM, ed. The Year Book of Vascular Surgery. New York, NY: Mosby-Year Book; 1997.
6. Rutherford B, ed. Vascular Surgery. 14th ed. Philadelphia: WB Saunders; 1995.
7. Szilagyi DE, Smith RF, DeRusso FJ, Elliott JP, Sherrin FW. Contribution of abdominal aortic aneurysmectomy to prolongation of life. Ann Surg. 1966;164:678.
Wednesday, December 31, 2008
ANEURYSM OF THE ABDOMINAL AORTA
ANEMIA, SIDEROBLASTIC
ANEMIA, SIDEROBLASTIC - Anne C. Nofziger, MD
BASICS
DESCRIPTION
A heterogeneous group of disorders characterized by microcytic, hypochromic anemia, impaired heme biosynthesis causing ineffective erythropoiesis, and ringed sideroblasts in the bone marrow. Severity and course may range from severe progressive to indolent asymptomatic anemia; onset may be congenital or late in life.
GENERAL PREVENTION
Pyridoxine prophylaxis with INH therapy
EPIDEMIOLOGY
• As a group, sideroblastic anemias (SA) are uncommon, and specific incidence/prevalence information is difficult to find.
• Acquired forms more common than hereditary forms (1), usually occur in older adults; present in 25-30% of alcoholics with anemia (2)
• Several hundred X-linked cases described (3) Hereditary forms variably severe, usually manifest in childhood
RISK FACTORS
• Male gender (X-linked SA)
• Family history of hereditary SA
• Chronic alcohol abuse
• Gastric bypass surgery (1 case report) (4)
Genetics
• Usually X-linked
- Defect in aminolevulinic acid synthase (ALAS-2 mutation), the first and rate-limiting enzyme in heme biosynthesis
- With congenital ataxia: hABC7 gene mutations (mitochondrial transport protein)
• Rarely autosomal dominant or recessive; gene(s) unknown
• Mitochondrial cytopathy
- Heterogeneous, involve deletions in mtDNA
- Unpredictable maternal inheritance
• See "Etiology"
PATHOPHYSIOLOGY
• Impaired heme biosynthesis within mitochondria
• Ineffective erythropoiesis
• Increased GI absorption of iron (Fe overload)
• Enhanced apoptosis in bone marrow
• Possibly, reactive oxygen species play a role
ETIOLOGY
Acquired SA
• Reversible
• Drugs and toxins
- Ethanol (SA is a later finding in multifactorial anemia related to alcoholism)
- INH
- Chloramphenicol
- Cycloserine
- Zinc toxicity (Cu deficiency)
• Nutritional deficiencies
- Pyridoxine deficiency
- Copper deficiency
Post-gastrectomy
Prolonged parenteral nutrition
Prolonged zinc supplementation
• Hypothermia
• Acquired idiopathic sideroblastic anemia (AISA)
- Pure sideroblastic anemia (PSA)
Only the erythroid line affected
- Refractory anemia with ringed sideroblasts (RARS)
Myelodysplasia, other cell lines also affected
- Associated with hematologic malignancies, myeloproliferative disorders
Hereditary SA
• X-linked
• Autosomal dominant, recessive, maternal inheritance
• Mitochondrial cytopathy
- Wolfram syndrome
- Pearson syndrome
Congenital SA
Disproportionately male, sporadic, mild to severe, kindreds too small to analyze inheritance
ASSOCIATED CONDITIONS
• Alcoholism
• According to mutation, e.g., severe congenital ataxia (hABC7 mutation), pancreatic dysfunction (Pearson syndrome)
• Iron overload or "erythropoeitic hemochromatosis" (2) develops over time in all but reversible and x-linked/ataxia forms.
• Rarely, coexisting iron deficiency masks SA.
DIAGNOSIS
PRE HOSPITAL
Often an incidental finding
SIGNS AND SYMPTOMS
• Moderate to severe anemia
- Fatigue
- Dizziness
- Diminished exercise tolerance
- More symptomatic in older patients with comorbid conditions
• Specific to cause
- Pyridoxine deficiency (peripheral neuropathy, dermatitis)
- Alcoholism
• Manifestations of iron overload
History
• Toxin or drug exposures
• Family history of anemia, especially in men
Physical Exam
• No pathognomonic physical findings
• Mild-moderate hepatosplenomegaly at diagnosis in 1/3-1/2 of patients with AISA (2)
TESTS
Lab
• CBC
- Low MCH
- Low MCHC
- Low MCV (may be normal or high, esp. in myelodysplasia)
- High RDW
- Hgb highly variable
- Siderocytes in peripheral smear (occasional)
- WBC normal; may be reduced if hypersplenism, myelodysplasia
- Platelets normal; may be reduced if hypersplenism, myelodysplasia
- Low reticulocyte count
• Iron studies
- Ferritin increased
- Transferrin saturation increased
- Serum transferrin decreased
- Reticuloendothelial iron increased
• Serum copper, ceruloplasmin, serum zinc if suspected as cause
• Liver enzyme derangements possible depending on cause (EtOH, cirrhosis, Fe overload)
• Molecular studies identify specific mutations causing hereditary SA syndromes
• Myelodysplasia: Morphologic and cytogenetic evaluation required for prognosis
Diagnostic Procedures/Surgery
• Bone marrow examination confirms diagnosis of SA
• Liver biopsy is best; test to assess degree of iron overload.
• See "Pathological Findings"
Pathological Findings
• Bone marrow examination is the key diagnostic modality (1)[C]
- Normoblastic erythroid hyperplasia
- Perls' Prussian blue iron stain: Ringed sideroblasts, >10% of erythroblasts with increased number of abnormally large granules ringing the nucleus
- Electron microscopy: Iron-overloaded mitochondria within erythroblasts
- Iron-laden macrophages
• Liver biopsy
- Iron deposition as in hereditary hemachromatosis
- Micronodular cirrhosis by 3rd or 4th decade
DIFFERENTIAL DIAGNOSIS
• Thalassemias
• Iron deficiency anemia
• Anemia of chronic disease
• Myelodysplastic syndromes
• Lead toxicity with anemia
TREATMENT
GENERAL MEASURES
Treatment is largely supportive
• Pyridoxine supplementation improves symptoms in responsive cases (1)[B]
• Eliminate toxins, causative drugs
• Periodic transfusion: Maintain acceptable hemoglobin to alleviate symptoms and allow normal growth and development (children) (1)[B]
• Prevent end-organ damage from severe iron overload (1)[B]
- Phlebotomy preferred modality if anemia is mild or moderate
- Iron chelation in patients with more severe anemia, or requiring more transfusions
Diet
Address relevant nutritional deficiencies
Activity
As tolerated
SPECIAL THERAPY
Allogeneic stem cell transplantation has been successful in a few cases in younger patients with myelodysplastic syndromes.
IV Fluids
RBC transfusion when necessary
MEDICATION (DRUGS)
First Line
• Trial of pyridoxine is indicated because it has few drawbacks and is very beneficial in responsive cases (1)[B]
- Pyridoxine 50-100 mg PO daily
- Maintenance: Minimum dose to maintain acceptable hgb.
- Supplement folate to compensate for increased erythropoiesis if effective
- Response likely if SA caused by alcohol abuse, pyridoxine antagonists, or some forms of hereditary x-linked SA.
• Chelation therapy for iron overload (1)[B]
• Deferoxamine 40 mg/kg/d in continuous 12-24-hour daily infusions
- Limit ascorbate intake to 200 mg/d
- Auditory/visual toxicity very rare
• Defirasirox is a new oral once-daily iron chelator
- No long-term safety data
- Main complications skin rash, GI upset
• Goal of therapy is to maintain serum ferritin 500 ug/L
Second Line
• Myelodysplasia: PSA and RARS
• Treatment considerations as above, though no expected response to pyridoxine
• Some respond to combination of erythropoeitin (EPO) and granulocyte colony-stimulating factor (G-CSF) (1)[C]
• Chemotherapeutic agents may have a role.
SURGERY
• Splenectomy is contraindicated due to frequent postoperative thromboembolic complications (2)[B].
FOLLOW-UP
DISPOSITION
Admission Criteria
Generally managed in outpatient settings except for treatment of complications such as CHF, dysrhythmias.
Issues for Referral
• Hematology consultation is helpful for diagnosis and management, particularly if no reversible cause identified.
• Genetic counseling is important for patients with heritable cause of SA.
PROGNOSIS
• 75% of x-linked SA with ALAS-2 mutations are pyridoxine responsive (2)
• Prognosis better if iron overload prevented
• Aquired Idiopathic SA:
- RARS: 1- and 5-year cumulative risk of acute leukemia are 20% and 38%, respectively (1)
- When only the erythroid line is affected (PSA), course as in age-matched controls, transformation to leukemia not observed. (2)
- If SA follows treatment for malignancy, leukemic transformation is common.
COMPLICATIONS
• Iron overload causing organ damage
- Cardiac arrhythmia or CHF
- Hepatic dysfunction
• Transfusion complications
PATIENT MONITORING
• Yearly ferritin and transferrin saturation to monitor for Fe overload
• Follow response to treatment: Reticulocytosis within 2 weeks, improved hgb within 1-2 months of response to pyridoxine, and correction of nutritional deficiency or withdrawal of reversible cause.
REFERENCES
1. Alcindor T, Bridges KR. Sideroblastic anaemias. Br J Haematol. 2002;116:733-743.
2. Bottomley SS. Sideroblastic anemias. In: Greer JP, Foerster J, Lukens J, et al., eds. Wintrobe's Clinical Hematology, 11th ed. Philadelphia: Lippincott, Williams and Wilkins; 2004.
3. http://ghr.nlm.nih.gov/ghr/ accessed February 2006
4. Almhanna K, Khan P, Schaldenbrand M, Momin F. Sideroblastic anemia after bariatric surgery. Am J Hematol. 2006;81(2):155-156.
ADDITIONAL READING
• See http://www.genetests.org for counseling information on specific heritable SA syndromes and availability of testing.
• http://ghr.nlm.nih.gov/condition=xlinkedsideroblasticanemia
