Thrombotic thrombocytopenic purpura causes

Thrombotic thrombocytopenic purpura Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Thrombotic thrombocytopenic purpura from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Study of Choice
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
Peripheral Smear
Direct Coombs Test
von Willebrand Factor-cleaving Protease Activity
X-ray
CT
MRI
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Thrombotic thrombocytopenic purpura causes On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Thrombotic thrombocytopenic purpura causes All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Thrombotic thrombocytopenic purpura causes
CDC on Thrombotic thrombocytopenic purpura causes
Thrombotic thrombocytopenic purpura causes in the news
Blogs on Thrombotic thrombocytopenic purpura causes
Directions to Hospitals Treating Thrombotic thrombocytopenic purpura
Risk calculators and risk factors for Thrombotic thrombocytopenic purpura causes

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sogand Goudarzi, MD [2]

Overview

TTP may be caused by decreasing function or amount of von Willebrand factor(vWF) cleaving protease ADAMTS13 .

Causes

Decrease function or amount of von Willebrand factor cleaving protease ADAMTS13 causes TTP.

Hereditary: Insertions, deletions, missense, nonsense point mutations and splice site mutations of both alleles of ADAMTS13 genes on chromosome 9q34 cause decrease in the amount or activity of the enzyme.

Acquried:

• Diseases: Lupus, cancer, HIV, and infections(influenza)
• Conditions: Pregnancy, surgery, blood and marrow stem cell transplant

• Drugs: Mitomycin, cyclosporin A, cisplatin, bleomycin, quinine, ticlopidine, clopidogrel, estrogen, HRT

ADAMTS13 is a zinc and calcium requiring 190,000 Dalton glycosylated protein that is encoded on chromosome 9q34. It is a disintegrin and a metalloprotease with 8 thrombospondin 1-like domains composed of an aminoterminal metalloprotease followed by a disintegrin domain; a thrombospondin 1-like domain; a cysteine-rich domain and an adjacent spacer portion; seven additional thrombospondin 1-like domains and 2 other different types of domains that resemble each other at the carboxyl-terminal end of the molecule. It cleaves a tyrosine 1605-1606 methionine peptide bond of VWF. This protease is 13 in a family of 19 distinct ADAMTS-type metalloprotease enzymes. It is produced predominantly in endothelial cells for slow, constitutive release into the circulation. Endothelial cells can be stimulated to secrete long vWF strings by inflammatory cytokines (TNF, IL8 & IL6, shiga toxins or estrogen). ADAMTS13 is inhibited by EDTA and therefore functional assays of the enzyme are usually performed using plasma anticoagulated with citrate (a weaker divalent cation binder than EDTA).

TTP, as with other microangiopathic hemolytic anemias (MAHAs), is caused by a spontaneous aggregation of platelets and activation of coagulation in the small blood vessels. When stimulated, endothelial cells secrete the ultra-large VWF multimers in long strips that remain anchored to the cell membrane. The long VWF multimeric strings are sticky to the glycoprotein Iba components of platelet GPIb-IX-V surface receptors. The initial adherence of platelets via the GPIb receptors to the long vWF strings and the subsequent coherence of additional platelets to each other (aggregation) via activated GPIIb/IIIa receptors produces potentially occlusive platelet thrombi. Platelets are consumed in the coagulation process, and bind fibrin, the end product of the coagulation pathway. These platelet fibrin complexes form microthrombi which circulate in the vasculature and cause shearing of red blood cells, resulting in hemolysis.