Thrombotic Microangiopathy
Etiology (NEJM, 2014) [MEDLINE ]
Primary Thrombotic Microangiopathy
Hereditary Thrombotic Microangiopathy
Hereditary Thrombotic Thrombocytopenic Purpura (Hereditary TTP) (Upshaw–Schulman Syndrome) (see Thrombotic Thrombocytopenic Purpura-Hereditary , [[Thrombotic Thrombocytopenic Purpura-Hereditary]])
Epidemiology : typically presents in childhood (occasionally in adults)
Etiology : ADAMTS13 deficiency due to homozygous/compound ADAMTS13 mutations
Diagnosis : severely deficient ADAMTS13 (activity level <10%)
Clinical
Acute Kidney Injury (AKI) (see Acute Kidney Injury , [[Acute Kidney Injury]]): uncommon
Ischemic Organ Injury
Initial Treatment : fresh frozen plasma (FFP) (see Fresh Frozen Plasma , [[Fresh Frozen Plasma]])
Complement-Mediated Hemolytic-Uremic Syndrome (see Complement-Mediated Hemolytic-Uremic Syndrome , [[Complement-Mediated Hemolytic-Uremic Syndrome]])
Epidemiology : typically presents in childhood (occasionally in adults)
Etiology : mutations in CFH, CFI, CFB, C3, CD46, and other complement genes, resulting in uncontrolled activation of alternative complement pathway
Clinical : heterozygous mutations may be symptomatic
Initial Treatment : fresh frozen plasma (FFP) (see Fresh Frozen Plasma , [[Fresh Frozen Plasma]]), plasma exchange, anti-complement agent
Metabolism-Mediated Hemolytic-Uremic Syndrome
Epidemiology : typically presents in child <1 y/o (one case report in young adult with acute kidney injury and hypertension)
Etiology : homozygous mutations in MMACHC (encoding methylmalonic aciduria and homocystinuria type C protein)
Clinical : xxx
Initial Treatment
Vitamin B12 (see Vitamin B12 , [[Vitamin B12]])
Betaine
Folinic Acid
Coagulation-Mediated Hemolytic-Uremic Syndrome
Epidemiology : typically presents in child <1 y/o (with DGKE mutations)
Etiology : homozygous mutations in diacylglycerol kinase ε (DGKE) (mutations in plasminogen and thrombomodulin have also been implicated)
Clinical
Acute Kidney Injury (AKI) (see Acute Kidney Injury , [[Acute Kidney Injury]])
Initial Treatment : fresh frozen plasma (FFP) (see Fresh Frozen Plasma , [[Fresh Frozen Plasma]])
Acquired Thrombotic Microangiopathy
Acquired Thrombotic Thrombocytopenic Purpura (Acquired TTP) (see Thrombotic Thrombocytopenic Purpura-Acquired , [[Thrombotic Thrombocytopenic Purpura-Acquired]])
Epidemiology : initial presentation usually in adults
Etiology : autoantibody inhibition of ADAMTS13 activity
Diagnosis : detectable (Autoantibody) ADAMTS13 Inhibitor
Clinical
Acute Kidney Injury (AKI) (see Acute Kidney Injury , [[Acute Kidney Injury]]): uncommon
Ischemic Organ Injury
Initial Treatment : plasma exchange, immunosuppression
Shiga Toxin-Producing Escherichia Coli Hemolytic-Uremic Syndrome (see Shiga Toxin-Producing Escherichia Coli Hemolytic-Uremic Syndrome , [[Shiga Toxin-Producing Escherichia Coli Hemolytic-Uremic Syndrome]])
Epidemiology : initial presentation more common in young children
Most cases are sporadic (although large outbreaks may occur)
Etiology : enteric infection with a Shiga toxin–secreting strain of Escherichia Coli or Shigella Dysenteriae
Clinical
Initial Treatment : supportive care only
Drug-Induced Thrombotic Microangiopathy (see Drug-Induced Thrombotic Microangiopathy , [[Drug-Induced Thrombotic Microangiopathy]])
Immune Reaction Type : due to drug-dependent antibodies
Associated Drugs
Clinical: sudden onset of severe systemic symptoms with with anuric acute kidney injury (AKI) (see Acute Kidney Injury , [[Acute Kidney Injury]])
Initial Treatment: withdraw drug with supportive care
Toxic Dose-Related Reaction Type : multiple potential mechanisms
Associated Drugs
Bevacizumab (Avastin) (see Bevacizumab , [[Bevacizumab]]): VEGF inhibitor
Clinical: gradual onset of acute kidney injury (AKI) over weeks-months (see Acute Kidney Injury , [[Acute Kidney Injury]])
Initial Treatment: withdraw drug with supportive care
Complement-Mediated Hemolytic-Uremic Syndrome (see Complement-Mediated Hemolytic-Uremic Syndrome , [[Complement-Mediated Hemolytic-Uremic Syndrome]])
Epidemiology : initial presentation in children and adults
Etiology : antibody inhibition of complement factor H activity
Clinical
Initial Treatment : plasma exchange, immunosuppression, anti-complement agent
Systemic Disorders Associated with Microangiopathic Hemolytic Anemia (MAHA) and Thrombocytopenia (see Hemolytic Anemia , [[Hemolytic Anemia]] and Thrombocytopenia , [[Thrombocytopenia]])
Disseminated Intravascular Coagulation (DIC) (see Disseminated Intravascular Coagulation , [[Disseminated Intravascular Coagulation]])
Clinical : less severe than TTP usually
Hemolytic Anemia : variable
Thrombocytopenia (see Thrombocytopenia , [[Thrombocytopenia]])
Infection
Aspergillus (see Aspergillus , [[Aspergillus]])
Babesiosis (see Babesiosis , [[Babesiosis]])
Blastomycosis (see Blastomycosis , [[Blastomycosis]])
Borrelia (see Borrelia , [[Borrelia]])
Brucellosis (see Brucellosis , [[Brucellosis]])
Candida Albicans (see Candida , [[Candida]])
Chlamydia (see Chlamydia , [[Chlamydia]])
Clostridium Difficile (see Clostridium Difficile , [[Clostridium Difficile]])
Coxsackie Virus (see Coxsackie Virus , [[Coxsackie Virus]])
Cryptococcosis (see Cryptococcosis , [[Cryptococcosis]])
Cytomegalovirus (CMV) (see Cytomegalovirus , [[Cytomegalovirus]])
Dengue Virus (see Dengue Virus , [[Dengue Virus]])
Endocarditis (see Endocarditis , [[Endocarditis]])
Ehrlichiosis (see Ehrlichiosis , [[Ehrlichiosis]])
Epstein-Barr Virus (EBV) (see Epstein-Barr Virus , [[Epstein-Barr Virus]])
Hepatitis Viruses
Human Herpesvirus 6 (see Human Herpesvirus 6 , [[Human Herpesvirus 6]])
Human Immunodeficiency Virus (HIV) (see Human Immunodeficiency Virus , [[Human Immunodeficiency Virus]])
Influenza A (see Influenza Virus , [[Influenza Virus]])
Legionellosis (see Legionellosis , [[Legionellosis]])
Leptospirosis (see Leptospirosis , [[Leptospirosis]])
Malaria (see Malaria , [[Malaria]])
Mycobacteria (see Mycobacteria , [[Mycobacteria]])
Norovirus (see Norovirus , [[Norovirus]])
Parvovirus B19 (see Parvovirus B19 , [[Parvovirus B19]])
Rocky Mountain Spotted Fever (see Rocky Mountain Spotted Fever , [[Rocky Mountain Spotted Fever]])
Varicella-Zoster Virus (VZV) (see Varicella-Zoster Virus , [[Varicella-Zoster Virus]])
Malignant Hypertension (see Hypertension , [[Hypertension]])
Physiology : abnormal vessel wall -> damage to RBC
Clinical
Metastatic Carcinoma
Associated Malignancies
Multiple Pulmonary Metastases from Adenocarcinoma
Multiple Pulmonary Metastases from Lymphoma (see Lymphoma , [[Lymphoma]])
Physiology : due to activation of multifocal clotting -> hemolysis and thrombocytopenia
Pregnancy-Related Disorders
HELLP (Hemolysis, Elevated Liver Enzymes, and Low Platelets) Syndrome (see HELLP Syndrome , [[HELLP Syndrome]])
Severe Pre-Eclampsia/Eclampsia (see Pre-Eclampsia, Eclampsia , [[Pre-Eclampsia, Eclampsia]])
Rheumatologic Disease
Anti-Phospholipid Antibody Syndrome (see Anti-Phospholipid Antibody Syndrome , [[Anti-Phospholipid Antibody Syndrome]])
Clinical : thrombocytopenia
Scleroderma (see Scleroderma , [[Scleroderma]])
Clinical : mild thrombocytopenia
Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus , [[Systemic Lupus Erythematosus]])
Physiology : severe vasculitis -> fibrin deposition in vessels with damage to platelets and RBC
Clinical : thrombocytopenia (see Thrombocytopenia , [[Thrombocytopenia]])
Transplant-Related Disease
Bone Marrow Transplant/Stem Cell Transplant (see Bone Marrow Transplant , [[Bone Marrow Transplant]])
Renal Allograft Rejection (see Renal Allograft Rejection , [[Renal Allograft Rejection]])
Physiology : abnormal vessel wall -> damage to RBC
Clinical : mild thrombocytopenia (see Thrombocytopenia , [[Thrombocytopenia]])
Other
Adult-Onset Still’s Disease (see Adult-Onset Still’s Disease , [[Adult-Onset Stills Disease]])
Giant Hemangioma (Kasabach-Merritt Syndrome) (see Kasabach-Merritt Syndrome , [[Kasabach-Merritt Syndrome]])
Physiology : abnormal vessel wall -> damage to RBC
Clinical : mild thrombocytopenia
Severe Vitamin B12 Deficiency (see Vitamin B12 , [[Vitamin B12]])
Vasculitis (see Vasculitis , [[Vasculitis]])
Physiology
Pathologic Features
Arteriolar and Capillary Thrombosis with Characteristic Endothelial and Vessel Wall Abnormalities
Clinical Manifestations of Thrombotic Microangiopathies
Microangiopathic Hemolytic Anemia (MAHA) (see Hemolytic Anemia , [[Hemolytic Anemia]])
Thrombocytopenia (see Thrombocytopenia , [[Thrombocytopenia]])
Organ Injury
References
Syndromes of thrombotic microangiopathy. N Engl J Med. 2014 Aug 14;371(7):654-66. doi: 10.1056/NEJMra1312353 [MEDLINE ]
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