Related Experiment Video
Updated: Jul 8, 2026
08:50
Thrombus Profiling Assay: A Microfluidics-Based Platform for Comprehensively Characterizing Biomechanical Thrombogenesis
Published on: January 9, 2026
Pathogenesis of thrombotic microangiopathies
1Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia and The University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. zheng@email.chop.edu
Annual Review of Pathology
|January 25, 2008
Summary
Thrombotic microangiopathy, including TTP and HUS, involves low platelets and red blood cell destruction. Genetic factors and triggers like E. coli or complement issues often cause these serious blood disorders.
Area of Science:
- Hematology
- Genetics
- Pathophysiology
Background:
- Thrombotic microangiopathy (TMA) encompasses thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS).
- TTP is classified into congenital, idiopathic, and nonidiopathic forms, often linked to ADAMTS13 deficiency.
- HUS presents with renal failure, with diarrhea-associated HUS commonly caused by Shiga-toxin-producing E. coli.
Purpose of the Study:
- To delineate the underlying causes and classifications of TTP and HUS.
- To explore the genetic and immunological factors contributing to TMA.
- To highlight the role of precipitating events in TMA pathogenesis.
Main Methods:
- Review of existing literature on TTP and HUS.
- Analysis of genetic mutations in ADAMTS13 and complement regulatory genes.
- Investigation of autoantibodies affecting ADAMTS13 and complement factors.
Main Results:
- ADAMTS13 deficiency, due to gene mutations or autoantibodies, is central to TTP.
- Diarrhea-associated HUS is primarily infectious, while diarrhea-negative HUS involves complement dysregulation in up to 50% of cases.
- Mutations in complement genes (CFH, MCP, CFI, CFB) or anti-CFH antibodies are implicated in diarrhea-negative HUS.
Conclusions:
- TMA pathogenesis involves genetic predispositions, including ADAMTS13 and complement system abnormalities.
- Incomplete penetrance suggests that environmental triggers or secondary events are crucial for TMA development.
- Understanding these diverse etiologies is key for diagnosing and managing TTP and HUS.
Related Concept Videos
01:30Venous Thrombosis I: Introduction
Venous thrombosis, the most common disorder of the veins, involves the formation of a thrombus or blood clot associated with vein inflammation. It can be classified as either superficial vein thrombosis or deep vein thrombosis.Superficial Vein Thrombosis: This involves the formation of a thrombus in a superficial vein, usually the greater or lesser saphenous vein. Though less severe than deep vein thrombosis (DVT), SVT can lead to complications if untreated.Deep Vein Thrombosis (DVT): This...
01:30Anticoagulant Drugs: Low-Molecular-Weight Heparins
Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
01:24Disorders of Hemostasis
Hemostasis, the process that stops bleeding after a blood vessel injury, is crucial for maintaining the integrity of the circulatory system. However, disorders of hemostasis can disrupt this delicate balance, leading to either excessive clotting or bleeding. These disorders can be broadly classified into thromboembolic disorders and bleeding disorders.
Thromboembolic Disorders
Two factors primarily cause thromboembolic conditions.
Thromboembolic Disorders
Two factors primarily cause thromboembolic conditions.
01:16Clot Retraction and Fibrinolysis
After a fibrin clot is formed, the next step is clot retraction, a vital process facilitated by platelet contractile proteins, such as actin and myosin. These proteins pull the fibrin strands closer together and condense the clot. This action reduces the size of the clot, creating a smaller, denser structure that effectively seals off the damaged vessel. Clot retraction consolidates the clot and helps with wound healing by bringing the edges of the damaged blood vessel closer together.
01:15Ischemic Stroke ll: Pathophysiology
An ischemic stroke occurs when a cerebral blood vessel becomes obstructed, most often by a thrombus or embolus, interrupting the delivery of oxygen and glucose to brain tissue. Because neurons rely on continuous aerobic metabolism, energy failure begins within minutes of reduced perfusion. The region receiving the least blood flow becomes the infarct core, an area of irreversible cellular death. Surrounding this core lies the penumbra, a zone of hypoperfused but still viable tissue that is...
01:29Hemorrhagic Stroke ll: Pathophysiology
A hemorrhagic stroke develops when a cerebral blood vessel ruptures, allowing blood to escape into the surrounding brain tissue, as in intracerebral hemorrhage (ICH), or into the subarachnoid space, as in subarachnoid hemorrhage (SAH). Because the skull is a rigid compartment, the sudden presence of extravascular blood rapidly increases intracranial pressure and compresses adjacent neural structures, leading to immediate tissue injury and impaired cerebral perfusion.Mass Effect and Primary...