Definition of TMA and of the main conditions associated with features of TMA during pregnancy and postpartum
| Main conditions associated with features of TMA during pregnancy and postpartum . |
|---|
| Thrombotic microangiopathy (TMA) |
| TMA is defined by a pathological pattern1,3 ; endothelial cell swelling and detachment from the basement membrane, thrombi in the microcirculation and, in the kidney, “double contour” aspects of the glomerular basement membrane and a dissolution or attenuation of the mesangial matrix (mesangiolysis); it is however usually diagnosed based on a clinicopathological triad: |
| (a) peripheral thrombocytopenia (platelet count <100 × 109/L) |
| (b) mechanical hemolytic anemia (hemoglobin <10 g/dL, LDH >upper limit of normal, undetectable haptoglobin, schistocytes on blood smear) |
| (c) organ injury |
| Thrombotic thrombocytopenic purpura (TTP) |
| TMA with mainly hematological, neurological, and potentially cardiac involvement |
| Usually associated to a complete hereditary or immune deficiency in ADAMTS13 plasma activity |
| Hemolytic uremic syndrome (HUS) |
| TMA with mainly renal involvement and potentially neurological and cardiac involvement |
| May be linked to various types of endothelial cell injury1,107 |
| Atypical HUS is caused by a dysregulation of the complement alternative pathway1,107 |
| HUS can include extrarenal manifestations and TTP may be associated with significant renal disease, it may prove difficult to distinguish the 2 entities on clinical grounds alone |
| Preeclampsia/eclampsia (PE/E) and hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome |
| PE is defined as gestational hypertension (systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg) accompanied by ≥1 of the following new-onset conditions at ≥20 weeks’ gestation4 : |
| Proteinuria |
| Acute kidney injury (serum creatinine ≥90 μmol/L) |
| Alanine or aspartate aminotransferase >40 IU/L ± right upper quadrant or epigastric abdominal pain |
| Eclampsia, in addition to the criteria defining PE, is characterized by altered mental status, blindness, stroke, clonus, severe headaches, and persistent visual scotomata |
| Platelet count <100 g/L, disseminated intravascular coagulation, hemolysis |
| Fetal growth restriction, abnormal umbilical artery Doppler wave form analysis, or stillbirth |
| HELLP syndrome is considered part of PE/E4,5 (the most severe part of the spectrum of PE/E) |
| PE/E and HELLP syndrome are associated with an imbalance between angiogenic (placental growth factor) and antiangiogenic (soluble Flt1) factors |
| To date, PE/E and HELLP syndrome have not been linked to acquired or hereditary severe (<20%) deficiency in ADAMTS13 activity nor to a hereditary complement dysregulation |
| Catastrophic antiphospholipid syndrome (CAPS) |
| CAPS is defined by the occurrence of fulminant multiorgan damage (brain, kidney, lung, skin, etc) resulting from extensive small vessel thrombosis in the setting of persistent antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, and anti-b2GPI antibodies)7 ; it is usually associated with thrombocytopenia and mechanical hemolytic anemia |
| Main conditions associated with features of TMA during pregnancy and postpartum . |
|---|
| Thrombotic microangiopathy (TMA) |
| TMA is defined by a pathological pattern1,3 ; endothelial cell swelling and detachment from the basement membrane, thrombi in the microcirculation and, in the kidney, “double contour” aspects of the glomerular basement membrane and a dissolution or attenuation of the mesangial matrix (mesangiolysis); it is however usually diagnosed based on a clinicopathological triad: |
| (a) peripheral thrombocytopenia (platelet count <100 × 109/L) |
| (b) mechanical hemolytic anemia (hemoglobin <10 g/dL, LDH >upper limit of normal, undetectable haptoglobin, schistocytes on blood smear) |
| (c) organ injury |
| Thrombotic thrombocytopenic purpura (TTP) |
| TMA with mainly hematological, neurological, and potentially cardiac involvement |
| Usually associated to a complete hereditary or immune deficiency in ADAMTS13 plasma activity |
| Hemolytic uremic syndrome (HUS) |
| TMA with mainly renal involvement and potentially neurological and cardiac involvement |
| May be linked to various types of endothelial cell injury1,107 |
| Atypical HUS is caused by a dysregulation of the complement alternative pathway1,107 |
| HUS can include extrarenal manifestations and TTP may be associated with significant renal disease, it may prove difficult to distinguish the 2 entities on clinical grounds alone |
| Preeclampsia/eclampsia (PE/E) and hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome |
| PE is defined as gestational hypertension (systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg) accompanied by ≥1 of the following new-onset conditions at ≥20 weeks’ gestation4 : |
| Proteinuria |
| Acute kidney injury (serum creatinine ≥90 μmol/L) |
| Alanine or aspartate aminotransferase >40 IU/L ± right upper quadrant or epigastric abdominal pain |
| Eclampsia, in addition to the criteria defining PE, is characterized by altered mental status, blindness, stroke, clonus, severe headaches, and persistent visual scotomata |
| Platelet count <100 g/L, disseminated intravascular coagulation, hemolysis |
| Fetal growth restriction, abnormal umbilical artery Doppler wave form analysis, or stillbirth |
| HELLP syndrome is considered part of PE/E4,5 (the most severe part of the spectrum of PE/E) |
| PE/E and HELLP syndrome are associated with an imbalance between angiogenic (placental growth factor) and antiangiogenic (soluble Flt1) factors |
| To date, PE/E and HELLP syndrome have not been linked to acquired or hereditary severe (<20%) deficiency in ADAMTS13 activity nor to a hereditary complement dysregulation |
| Catastrophic antiphospholipid syndrome (CAPS) |
| CAPS is defined by the occurrence of fulminant multiorgan damage (brain, kidney, lung, skin, etc) resulting from extensive small vessel thrombosis in the setting of persistent antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, and anti-b2GPI antibodies)7 ; it is usually associated with thrombocytopenia and mechanical hemolytic anemia |
GPI, glycoprotein I.