Microangiopatia trombótica

Question 1

SHU

Answer 1

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy in which microthrombi, consisting primarily of platelets, form and occlude the arterioles and capillaries. These occlusions result in the simultaneous occurrence of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). HUS predominantly affects children and is caused by bacterial toxins, most commonly the Shiga-like toxin of enterohemorrhagic Escherichia coli (E. coli) O157:H7. If there is a strong suspicion of HUS based on clinical presentation and initial laboratory tests, treatment should begin immediately, as the condition may result in renal failure. Patients receive symptomatic treatment for renal symptoms, anemia, and complications affecting other organs, such as the brain and GI tract.
Thrombotic thrombocytopenic purpura (TTP), the other main type of thrombotic angiopathy, is discussed in the respective article.

Hematológico:
Hemolytic markers
↓ Hemoglobin 
↓ Haptoglobin
↑ Indirect bilirubin
↑ Reticulocytes
↑ LDH
↑ Schistocytes on blood smear (up to 10% of RBCs) 
Coagulation profile
↓ Platelets 
Normal/slightly elevated prothrombin time (PT) and activated partial thromboplastin time (aPTT) in contrast to DIC (see “Differential diagnoses” below)
Normal/slightly elevated Fibrin degradation products and D-dimer levels
↑ WBC count 
Negative Coombs test
Serum chemistry: ↑ BUN and ↑ creatinine (impaired renal function)
Urinalysis: hematuria, proteinuria

Question 2

TTP is a thrombotic microangiopathy, a condition in which microthrombi form and occlude the microvasculature. The other main thrombotic microangiopathy is hemolytic uremic syndrome (HUS). Although TTP and HUS share similarities in both pathophysiological findings and clinical features, these conditions differ in etiology; TTP, unlike HUS, is caused by a deficiency of ADAMTS13.
Autoantibodies or gene mutations → deficiency of ADAMTS13 (a metalloprotease that cleaves von Willebrand factor)
↓ Breakdown of vWF multimers → vWF multimers accumulate on endothelial cell surfaces
Platelet adhesion and microthrombosis
Microthrombi → fragmentation of RBCs with schistocyte formation → hemolytic anemia
Arteriolar and capillary microthrombosis → end-organ ischemia and damage, especially in the brain and kidneys (potentially resulting in acute kidney injury or stroke)

Answer 2

Hematology
↓ Platelets
↓ Hemoglobin
↑ Reticulocytes
↓ Haptoglobin
Normal or mildly prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT)
Normal or mildly elevated fibrin degradation products and D-dimer levels
Negative Coombs test
Peripheral blood smear
Large number of schistocytes (up to 10% of RBCs)
Low number of platelets
Serum chemistry
↑ LDH, ↑ indirect bilirubin (hemolytic anemia)
↑ BUN and ↑ creatinine (impaired renal function)
Urinalysis
Hematuria, proteinuria
ADAMTS13 activity and inhibitor testing
↓ ADAMTS13 activity
Not a routinely available test and should be used for confirmation only
Identification of secondary causes (e.g., tests for pregnancy, SLE, HIV, malignancy)