ADDITIONAL READING
- Brantigan CO, Roos DB. Diagnosing thoracic outlet syndrome.
Hand Clin
. 2004;20(1):27–36.
- Huang JH, Zager EL. Thoracic outlet syndrome.
Neurosurgery
. 2004;55(4):897–902.
- Nichols AW. Diagnosis and management of thoracic outlet syndrome.
Curr Sports Med Rep
. 2009;8(5):240–249.
- Ozoa G, Alves D, Fish DE. Thoracic outlet syndrome.
Phys Med Rehabil Clin N Am.
2011;22(3):473–483.
- Povlsen B, Belzberg A, Hansson T, et al. Treatment for thoracic outlet syndrome.
Cochran Database Syst Rev
. 2010;(1):CD007218.
Thank you to prior Authors Erin Horn, MD
See Also (Topic, Algorithm, Electronic Media Element)
www.ninds.nih.gov
CODES
ICD9
353.0 Brachial plexus lesions
ICD10
G54.0 Brachial plexus disorders
THROMBOTIC THROMBOCYTOPENIC PURPURA
Hany Y. Atallah
BASICS
DESCRIPTION
- 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
Classic Course
- 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:
- 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
ETIOLOGY
- 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.
RISK FACTORS
Genetics
- 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
SIGNS AND SYMPTOMS
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
History
- 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
Physical-Exam
- 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
ESSENTIAL WORKUP
Clinical Diagnosis
- 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.
DIAGNOSIS TESTS & NTERPRETATION
Lab
- CBC/platelet count/reticulocyte count:
- Anemia: Hemoglobin <10 g/dL
- Thrombocytopenia <20,000/mm
3
- Increased reticulocyte count
- Coagulation studies:
- 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.
Imaging
- CT head:
- To rule out intracranial hemorrhage
Diagnostic Procedures/Surgery
- Biopsy:
- Confirms diagnosis
- Reveals hyaline lesions in small vessels
- Contraindicated during fulminant presentation (hemorrhage risk)
- EEG:
- To predict need for anticonvulsant therapy
DIFFERENTIAL DIAGNOSIS
- 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