Thrombotic Microangiopathy

Anuja Java

General Principles

Thrombotic microangiopathy (TMA) is a pathologic process caused by thrombotic occlusion of the systemic microvasculature, leading to end-organ ischemia and infarction.
TMAs are characterized by thrombocytopenia (due to consumption), microangiopathic hemolytic anemia (MAHA; due to intravascular fragmentation), and variable degree of organ damage, with the kidney and the central nervous system being the most affected.
The histologic lesions of a TMA are seen in several clinically diverse disorders. The major TMAs include thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), and atypical hemolytic uremic syndrome (aHUS).

Definitions

The current diagnostic criteria for TTP include otherwise unexplained thrombocytopenia and MAHA. The classic pentad of thrombocytopenia, MAHA, fever, neurologic changes, and acute renal failure is seen in only 3% to 5% cases.

Most cases of TTP are acquired and occur in adults (due to an autoantibody to ADAMTS-13, the 13th member of a disintegrin and metalloprotease family with thrombospondin domains).
- Congenital TTP (Upshaw–Schulman syndrome) is a rare syndrome caused by deficiency of ADAMTS-13 due to homozygous or compound heterozygous mutations.
HUS is defined by the same criteria as TTP plus the presence of renal failure.
- Typical age of presentation is 1 to 5 years.
- In the United States and Europe, 90% of cases are caused by Shiga toxin–producing E. coli O157:H7.
aHUS (complement-mediated HUS) is a TMA resulting from an overactive complement system due to mutations in complement proteins.¹

Pathophysiology

Thrombotic thrombocytopenic purpura
- TTP is often idiopathic but may be familial or related to pregnancy, collagen vascular diseases such as SLE, malignancy, infections (HIV, parvovirus), bone marrow transplantation, or medications. Oral contraceptives, ticlopidine (and less commonly clopidogrel), mitomycin C, gemcitabine, and multiple other chemotherapeutics, calcineurin inhibitors, interferon-α, and quinine have all been associated with TTP.
- The pathogenesis of TTP is linked to inherited or acquired deficiencies of von Willebrand factor (vWF)-cleaving protease, which is normally responsible for cleaving and clearing large vWF multimers that promote platelet aggregation and microvascular thrombosis. An inhibitory autoantibody to vWF-cleaving protease has been found in patients with acquired TTP.
Hemolytic Uremic Syndrome: Classic childhood Shiga toxin–mediated HUS, or D+ HUS, is caused by certain E. coli strains (usually O157:H7) and Shigella. Transmission is from contaminated food (e.g., undercooked meat) or secondary person-to-person
contact. The Shiga toxin triggers the microangiopathic process by entering the circulation via inflamed colonic tissue and causing endothelial damage and platelet activation.

Only gold members can continue reading. Log In or Register to continue
Share this:
Related posts:

Assessment of Kidney Function Approach to Proteinuria and Hematuria Intrinsic Causes of Acute Kidney Injury Renal Diseases in Pregnancy Continuous and Prolonged Intermittent Renal Replacement Therapies Management of the Kidney Transplant Patient

Stay updated, free articles. Join our Telegram channel