LDH/AST ratio as a future tool for the differential diagnosis of thrombotic microangiopathy in pregnancy: an abstract

LDH/AST ratio as a future tool for the differential diagnosis of thrombotic microangiopathy in pregnancy: an abstract

The First Affiliated Hospital of Kunming Medical University can be translated in a single note

Critical Walker Translation Group

Thrombotic microangiopathies (TMAs) are a syndrome consisting of a heterogeneous set of symptoms with common pathological features, or more precisely, endothelial cell damage and microvascular thrombosis, as well as ischemic disorders characterized by thrombocytopenia, hemolytic anemia, and systemic multi-site (mainly but not limited to the kidneys and central nervous system). Thrombotic thrombocytopenic purpura (TTP), atypical hemolytic uremic syndrome (a-HUS), and classic disseminated intravascular coagulation (DIC) and antiphospholipid antibody syndrome. TMA is classified as primary and secondary. In primary TMA, the disease is defined as the presence of thrombotic microangiopathies, such as TTP due to a deficiency of ADAMTS13, a metalloproteinase that clears von Willebrand factor (v-WF), and α-HUS, which is characterized by complement dysregulation. On the other hand, in secondary TMA, it can manifest itself as an event in which TMA emerges as a complication of the underlying disease: pregnancy is one of the typical examples, but it can also be malignant hypertension, complications of preeclampsia or HELLP syndrome, drug-induced, kidney transplant or bone marrow transplant, systemic lupus erythematosus and tumors, among others. Due to the imbalance between the coagulation system, immune system, and complement system, TMA is a problematic disease. Pregnancy is associated with physiological changes in the balance of microcirculation and hemostasis, which may manifest as recessive congenital TMA, or it itself may be a trigger for secondary TMA. Mainly due to changes in hormone levels during pregnancy, it is necessary to protect the mother from bleeding complications during pregnancy, especially during childbirth and the postpartum period. As a result, there is an overall pattern of hypercoagulability and hypolysis during pregnancy, which also has a physiological state of "DIC", and TTP and a-HUS are not pathologies specific to pregnancy, but occur more frequently during or in connection with pregnancy. The incidence of these conditions in pregnancy is 1 in 20 for preeclampsia, 1 in 1000 for HELLP syndrome, 1 in 25000 for HUS, and 1 in 200000 for TTP. All TMAs are characterized by moderate thrombocytopenia (PLT 1%) and microangiopathic hemolytic anemia (elevated LDH and low haemoglobin and haptoglobin). Each pathology has a unique aspect: hypertension is a clinical feature of preeclampsia, gastrointestinal disorders (diarrhea, nausea and vomiting, right upper quadrant pain) are clinical features of HELLP syndrome, impaired renal function (elevated creatinine and decreased glomerular filtration rate) is a clinical feature of a-HUS, and neurological problems (confusion, headache, and visual disturbances) are clinical features of TTP. The difference between TTP and a-HUS lies primarily in the time stage of onset: 83% of TTP cases occur in the second and third trimesters, as a physiologic decrease in ADAMTS13 activity during pregnancy may precipitate the underlying pathology. In contrast, 78% of a-HUS occurs postpartum, which is thought to be due to activation and dysregulation of the complement system bypass pathway, due to inflammation secondary to delivery, release in fetal cell circulation, endothelial cell damage, and postpartum infection or hemorrhage. The differential diagnosis between these disorders is complex, both because of their overlapping clinical features and because they involve multiple disciplines (gynaecology, hematology, nephrology, etc.). They are usually diagnosed with HELLP syndrome or severe preeclampsia (PE-SF) during or after delivery. The reason for this confusion is that HELLP and PE-SF are more common pregnancy complications than the very rare complications TTP and HUS. In addition, clinical and laboratory manifestations can change rapidly over time, so it is essential to follow up with the mother on an ongoing basis, and early diagnosis and differentiation of the results is essential. There is a specific treatment for each syndrome, and if you can, you can use the Journal of Labor and Childbirth EXTENDED ABSTRACT 5th Annual Conference on Brain Disorders, Neurology and Therapeutics September 1415, 2020 | Tokyo, Japan 2018 | Volume 1 Issue 4, which can save the life of the mother and/or fetus. Therefore, given the high mortality and morbidity of these syndromes, the importance of their identification and early diagnosis is self-evident. The differential diagnosis between TMAs requires the detection of severe thrombocytopenia, particularly PLT < 5×109/L, assessment of blood pressure and proteinuria to make the differential diagnosis of preeclampsia, the presence of fragmented red blood cells in the peripheral blood smear, and these indicators of hemolysis, haptoglobin and hemoglobin, liver function, and gastrointestinal symptom assessment required to diagnose HELLP syndrome. If thrombocytopenia continues to worsen with LDH > 1000 IU/L and serum creatinine > 2 mg/dl (176.8 umol/L), ADAMTS13 activity is measured. If a 10% reference value is ADAMTS13>, it is strongly suggestive of aHUS, and if a 10% reference value is ADAMTS13<, the diagnosis is TTP. But one of the main problems of the Obstetrics and Gynecology Clinic of the University Hospital of Pisa, Italy, is the lack of ADAMTS13 testing, which is currently in the laboratory in Milan, so the waiting time is very long and unacceptable for a timely differential diagnosis. The authors hope that ADAMTS13 tests will also be carried out in local laboratories in Pisa in order to make increasingly accurate and rapid diagnoses. In addition, TMA mainly occurs in the perinatal period, and it is obvious that it is very difficult to make a detailed differential diagnosis at such a critical time, first of all, because the health of the mother and fetus can deteriorate rapidly, so it is not only necessary to try to put the diagnosis first, but also try to intervene in time to ensure the safety of the mother and fetus. Due to the very difficult nature of the differential diagnosis and timing of symptom onset, a study conducted by the Obstetrics and Gynecology Departments of Los Angeles and New York, Gupta and Feinberg in the United States showed that based on a systematic review of the literature in recent years, these authors in the United States developed a diagnostic algorithm to help address the differential diagnosis between TMAs. These authors highlight the significant differences between HELLP syndrome and a-HUS, which could help clinicians find their way between these two often subtle and confusing syndromes. In HELLP syndrome, the liver injury index increases more compared to the hemolysis index, whereas in a-HUS the opposite is true. This difference can be summarized as an LDH/AST ratio, which is always < 10 in HELLP syndrome and >10 in a-HUS. This report is a very useful tool for clinicians to guide the diagnosis and differentiation of HELLP syndrome and a-HUS, combined with laboratory results (ADAMTS13) and clinical presentation of patients after delivery.

Objective: To evaluate the clinical approach, diagnostic approach, and most appropriate treatment management of thrombotic microangiopathy (TMA) in pregnancy, which remains a major killer in obstetrics today.

Materials and methods: An extensive review of the international literature and existing clinical studies was conducted to determine the state of the art in TMA during pregnancy. In view of this, 9 of the 152 cases of TMA from 2010 to 2019 were identified, analysed and re-discussed in the two maternity wards of O.O. U.U. 1 and 2 of the University Hospital of Pisa, where pregnant women were hospitalized and gave birth.

Results: Nine cases were rigorously reviewed and the diagnostic results were accurately analyzed by analyzing the diagnostic methods and medical records. Among them, 6 cases of thrombotic thrombocytopenic purpura (TTP), 2 cases of HELLP syndrome, and 1 case of atypical hemolytic uremic syndrome (aHUS) were diagnosed during pregnancy. By analyzing the medical records, diagnostic methods, and treatment management of these patients, the authors of this article questioned the previous diagnosis. From the point of view of the authors' analysis, these diagnoses were partially incompatible, with 4 cases having TTP and 5 cases possibly a-HUS.

Conclusions: Based on the history review of this article, in the Pisa obstetric clinic, the diagnosis of a-HUS cases may be lower compared with cases of TTP and HELLP syndrome due to the inability to detect ADAMTS13 and the unused LDH/AST ratio, which the authors of this article believe may represent a future resource for diagnostic approaches to thrombotic microangiopathy during pregnancy and beyond. The next commitment of the authors of this paper is to verify that the systemic vasculitis observed in COVID 19 can withstand clinical studies and pathophysiological tests in microangiopathy models (TTP and a-HUS, etc.) that can be prevented not only by low molecular weight heparin and glucocorticoids, but also by plasmapheresis and/or anti-complement drugs for more severe hospitalized patients. From this perspective, obstetrics science can be a beacon of relief from the deadly COVID 19 epidemic for humanity around the world.

文献来源：Battini Lorella, Mei Federica. Etal. LDH/AST Ratio: A Future Chance for Differential Diagnosis in Pregnancy Thrombotic Microangiopathies and Beyond. Abstract