The term thromobitic microangiopathy (TMA) encompasses a group of conditions that are defined by, or result from, a similar histopathological lesion. Hemolytic uremic syndrome HUS), thrombotic thrombocytopenic purpura (TTP) and several other conditions are assocaited with TMA. (Kplan, Pedian ephtrol (2008) 23: 1761-1767). Other notable causes for TMA iclude infection (e.g., bloody diarrhea associated with E. coli infection), medications (e.g., quinine, bevacizumab), connective tissue dsieases (e.g., systemic lupus erythematosus, antiphospholipid anitobdy syndrome, scleroderma), cancer, vasculitis, pregnancy, malignant hypertension, organ transplant and metabolic disorders. uraaemic syndrom (HUS) and thrombotic thrombocytopenic purpra (TT) are the clincial entitles comprising TMA, with predominantly renal manifestrations in the former, while the latter more often present with systemic and neurological findings. There are no standard laboratory values that define TMA, but the clinical traid of renal failure, thrmobocytopenia and microangiopathic haemolytic anaemia is considered the hallmark of TMA syndromes. Nephrol Dial Transplant (2006) 21: 3038-3045). 

Thrombotic microangiopathy (TMA) is a microvascular occlusive disorder characteried by preedominantly platelt thrombi in the renal and/or systemic circulations. Haemolytic 

Hemolytic Uremic Syndrome (HUS): See Kidney Diseases

Another major cause for TMA is atypical hemolytic uremic syndrome (aHUS), a discorder caused by dysregulation of a prt of the complement system. About 50% of aHUS pateints are found to have ither a genetic mutation in the complement system or an aut-antibody that inteeres with the reulation of complement. 

Hemolytic uremic syndrome (HUS) is characterized by the triad of thrombocytopenis, Coomb’s test negative microaniopathic hemolytic anemia, and acute renal failure. HUS is classified as eitehr D+ when it is associated with a preceding diarrhoeal illness, which in most people is caused by infection with E. coli 0157, or less commonly nondiarrhoeal associated (D_) (also called “atypical”). D- HUS may be sporadic or familial. Mutations have been reproted in the complement regulatory protein factor H in both sporadic and familial HUS. (Goodship, PNAS, 100(22), October 28, 2003). 

 Immune Thrombocytopenic Purpura (ITP)/ Thrombotic Thrombocytopenic Purpura (TTP): 

ITP refers to a rare disease characterized by microangiopathic hemolytic anemia, causing blood clots to form in small blood vessels throughout the body. These clots can cause serious problems if they block blood vessels and limit blood flow to the brain, kidneys or heart. Blood clots form when blood cells called platelets clump together. ITP is an autoimmune disease characterized by platelet clearance mediated by pathogenic platelet-specific antibodies. Autoantibody-coated platelets induce Fc receptor mediated phagocytosis by macrophages, primarily but not exclusively in the spleen. Thus the spleen is the key organ in the pathophysiology of ITP not only because platelet autoantibodies are formed in the white pulp but also because macrophages in the red pup destroy immunoglobulin coated platelets. If bone marrow megakaryocytes cannot increase production and matain a normal number of circulating platelets, thrombocytopenia and purpura develop. In the US, the annual incidence of chronic ITP is stimated to be about 6.6 cases per 100k persons. In adults, women are affectied about 3 times more frequently than men. Adults may be affected at any age, but most cases are diagnosed in women aged 30-40 years. Onset ina patient older than 60 years is uncommon, and a search for other causes of thrombocytopenia is warranted. The disease is characterized by reduced blood platelets, which cause visible skin blemishes from bleeding or brusing. Symptoms can include bleeding, red dots on the skin, red dots on the mouth membranes, purplish mouth membrane areas, bleeding nose, bleeding gum, digestive bleeding, urinary bleeding and brain bleeding. To establish a diagnosis of ITP, other causes of thrombocytopenia are excluded, such as leukemia.

Thrombotic thrombocytopenic purpura (TTP) is due to low activity of a protein called ADAMTS13. Some individuals are born with a mutation in the gene for ADAMTS13, although most affected pateitns have an acquired auto-antibody that blocks the activity of ADAMTS13. 

Causes/Pathophysiology:

Role of complement system:

(Hughes Am J Physiol Renal Physiol, 278: F747-F757, 2000) discloses that in an immune-meidated thromobtic microangiopathy model both CVF treatment and C6 deficiency reulsted in 10-25 fold reudction in the number of apoptotic cells. The results indicated that complement is the principal inducer of endothelial cell apoptosis in antibody-mediated glomerulenphritis and that this effect is mediated primarily by sublytic C5b-9. The data also strongly suggests that the C5b-9 membrane attack complext may play an important role in the induction of endothelial cell apoptosis in vivo, particularly in diseases associated with antiendothelial antibodies such as systemic lupus erhematosis, scleroderma, hemolytic uremic syndrome and the systemic vasculitides. 

Mutations have been reproted in the complement regulatory protein factor H in both sporadic and familial HUS with mutations identified in 10-20% of cases studied. (Goodship, PNAS, 100(22), October 28, 2003)