Rosen & Barkin's 5-Minute Emergency Medicine Consult (709 page)

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• Huang JH, Zager EL. Thoracic outlet syndrome.
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• Nichols AW. Diagnosis and management of thoracic outlet syndrome.
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• Ozoa G, Alves D, Fish DE. Thoracic outlet syndrome.
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Thank you to prior Authors Erin Horn, MD

See Also (Topic, Algorithm, Electronic Media Element)

www.ninds.nih.gov

CODES

353.0 Brachial plexus lesions

BASICS

• Thrombotic thrombocytopenic purpura (TTP) is a severe disorder of abnormal clotting affecting multiple organ systems.
  
• Classically characterized by pentad of:
  
  • Thrombocytopenia
    
  • Hemolytic anemia
    
  • Mild renal dysfunction
    
  • Neurologic signs
    
  • Fever
    
• Uncommon to see all 5 features in 1 patient; if present, severe end-organ damage or ischemia has likely taken place.
  
• Thrombocytopenia and hemolytic anemia are the most common features.
  
• Associated with acquired or congenital deficiency of plasma von Willebrand factor–cleaving protease (VWFcp)
  
• Patients who present with severe neurologic abnormalities with acute renal failure are best described by the comprehensive term TTP-HUS
  

• Acute onset
  
• Fulminant course lasting days to a few months
  
• Nearly always fatal without treatment:
  
  • >90% mortality without treatment
    
  • Reverses to >90% survival with modern treatment
    
• Clinical presentations include:
  
  • Idiopathic
    
  • Familial, chronic, or relapsing
    
  • Drug induced:
    
    • Allergic or immune mediated (quinine, ticlopidine, clopidogrel)
      
    • Dose-related toxicity (mitomycin C, cyclosporine)
      
  • Pregnancy, postpartum associated:
    
    • 10–25% of cases
      
  • Bone marrow transplantation associated
    
  • Infection
    
• More common in the 3rd–6th decades of life
  
• Uncommon in pediatric or geriatric populations
  
• Women affected about twice as frequently as men
  

• Unknown primary stimulant; possibly systemic endothelial cell damage results inactivation of coagulation pathway
  
• Platelet aggregation and fibrin deposition occurring in arterioles and capillaries leading to microthrombi and obstruction to blood flow
  
• Platelet aggregation leads to:
  
  • Consumption of platelets
    
  • Widespread microvascular hyaline thrombotic lesions
    
• Microvasculature obstruction with platelet aggregates leads to:
  
  • Red cell hemolysis
    
  • Accumulation of heme breakdown products
    
  • Anemia
    
• End-organ ischemia results from diffuse thrombosis in small vessels:
  
  • Most common in heart, brain, kidney, pancreas, and adrenal glands
    
• Deficiency of vWFcp causes failure of control of coagulation pathway.
  

• Some cases are genetic/familial.
  
• VWFcp was recently identified as new member of ADAMTS family and designated ADAMTS13.
  
• Mutations in ADAMTS13 gene cause autosomal recessive form of chronic relapsing TTP.
  

DIAGNOSIS

5 major clinical features: Classic pentad

• Thrombocytopenia:
  
  • Platelet count <20,000/mm
    ³
    
• Microangiopathic and hemolytic anemia:
  
  • Hb <10 g/dL (<6 g/dL in 40%)
    
• Neurologic symptoms:
  
  • Presenting complaint in 60%, occur in 90%
    
  • Typically fluctuating
    
  • Headache
    
  • Altered mentation (confusion, stupor, coma)
    
  • Behavioral or personality changes
    
  • Focal sensory or motor deficits or aphasia
    
  • Seizures
    
  • Spontaneous intracranial hemorrhage
    
• Renal insufficiency:
  
  • Usually mild
    
  • Creatinine <3 mg/dL
    
• Fever:
  
  • Occurs in acute episodes and prodromal syndromes
    
  • Fever is the least common feature
    
• Rare for all components of pentad to be present in the same individual
  

• General:
  
  • Weakness
    
  • Fatigue
    
  • Fever
    
  • Malaise
    
• Hemorrhage:
  
  • Easy bruising
    
  • Epistaxis
    
  • Menorrhagia
    
  • GI bleeding
    
  • Loss or change in vision
    
• GI complaints:
  
  • Anorexia
    
  • Diarrhea
    
  • Abdominal pain
    
• Neurologic:
  
  • Headache
    
  • Confusion
    
  • Seizure
    
  • Behavioral or personality changes
    
  • Focal sensory or motor deficits or aphasia
    

• Purpura
  
• GI hemorrhage
  
• Epistaxis
  
• Jaundice
  
• Shock
  
• Altered mental status
  
• Focal sensory or motor deficits
  
• Pulmonary infiltrates and edema
  
• Alteration of vision, retinal hemorrhage/detachment.
  
• Abnormalities of cardiac conduction
  

• Because of success of treatment, base diagnosis on:
  
  • Identification of 2 major findings:
    
    • Thrombocytopenia
      
    • Microangiopathic hemolytic anemia
      
  • Exclude other major differential diagnoses.
    
• Comprehensive history and physical exam with directed lab testing
  
• Identify possible drug-associated disease and avoid re-exposure.
  

• CBC/platelet count/reticulocyte count:
  
  • Anemia: Hemoglobin <10 g/dL
    
  • Thrombocytopenia <20,000/mm
    ³
    
  • Increased reticulocyte count
    
• Coagulation studies:
  
  • Normal
    
• Peripheral blood smear:
  
  • Macroangiopathic changes
    
  • Schistocytes
    
  • Helmet cells
    
  • Nucleated RBCs
    
• Coombs test:
  
  • Negative direct Coombs test
    
• Electrolytes, BUN, creatinine, glucose:
  
  • Mild elevation of BUN, creatinine
    
  • Hyperkalemia owing to RBC lysis
    
• Lactate dehydrogenase (LDH):
  
  • Elevated 5–10 times due to hemolysis and tissue ischemia
    
• Bilirubin:
  
  • Increased unconjugated bilirubin
    
• Urinalysis:
  
  • Hematuria (microscopic to gross)
    
• ADAMTS13 assay may be used to distinguish chronic recurring TTP, TTP secondary to presence of ADAMTS13 inhibitor, and hemolytic-uremic syndrome (HUS):
  
  • ADAMTS13 deficiency does not detect all patients who may respond to plasma exchange transfusions.
    

• CT head:
  
  • To rule out intracranial hemorrhage
    

• Biopsy:
  
  • Confirms diagnosis
    
  • Reveals hyaline lesions in small vessels
    
  • Contraindicated during fulminant presentation (hemorrhage risk)
    
• EEG:
  
  • To predict need for anticonvulsant therapy
    

• HUS:
  
  • Triad of thrombocytopenia, schistocytosis, and renal dysfunction
    
  • Neurologic symptoms unusual
    
  • Often preceded by infectious prodrome and diarrhea
    
• Disseminated intravascular coagulation (DIC):
  
  • Causes deposition of fibrin in microvasculature and not hyaline
    
  • Coagulation studies abnormal
    
• Idiopathic thrombocytopenic purpura (ITP):
  
  • No evidence of hemolysis
    
  • LDH and bilirubin normal
    
• Pregnancy-related thrombocytopenia:
  
  • Preeclampsia, eclampsia
    
  • Pregnancy-associated hemolysis
    
  • HELLP (hemolysis, elevated liver enzymes, and low platelets)
    
• Evans syndrome:
  
  • Autoimmune hemolytic anemia
    
  • Prominence of microspherocytes rather than schistocytes
    
  • Positive direct Coombs test
    
• Malignant hypertension
  
• Bacterial sepsis
  
• Subacute bacterial endocarditis
  
• Autoimmune disorders (e.g., systemic lupus erythematosus [SLE])
  
• Disseminated malignancy
  
• Heparin-associated thrombocytopenia
  
• Prosthetic valves or severely calcified aortic stenosis