Usefulness of a Diagnostic Algorithm to Diagnose Thrombotic Microangiopathies in Pregnancy

Introduction Maternal mortality is an important indicator of a country level of development. Maternal death is considered as a death in pregnancy at any gestational age or up to 42 days postpartum, either by direct or indirect causes. The United Nations in its Millennium Development Goals proposed the reduction of the maternal mortality ratio by three quarters by 2015 in every country worldwide. Colombia has made great progress to reducing mortality from direct causes, but not in deaths from indirect causes. In part, the problem is the large knowledge gap in the incidence and characteristics of these diseases in middle-income countries such as Colombia, where very little is known and research is scant.

aHUS is defined as an ultra-rare disease, thus, it is not usually considered as a differential diagnosis. This disease often progresses to end stage renal disease despite standard treatment with plasma exchange, with a high mortality. In recent years, the role played by the complement system in the induction of endothelial damage in patients with aHUS has been established by characterizing multiple mutations and polymorphisms in genes encoding certain complement factors. Recently, treatment with Eculizumab (monoclonal antibody that inhibits the terminal moiety complement blocking complex formation membrane attack) in prospective studies in patients with aHUS has demonstrated rapid and sustained interruption of TMA, with a significant improvement of long-term renal function and a significant reduction in requirement of renal replacement therapy (RRT) or plasmapheresis.

The literature reports that the prevalence of aHUS is higher in adult women than in men, and that 21% of all cases in women occur related to pregnancy. However, the approach and treatment of this group represents a diagnostic and treatment challenge, because many of the clinical pictures are similar to other well-defined disorders in the obstetric population, with a high risk of misdiagnosis, especially with HELLP syndrome (hemolysis, elevated liver enzymes and low platelet).

Justification and Problem Statement The challenge of the clinician in obstetric patients is to identify and assess a differential diagnosis, with both non-specific symptomatology and laboratory results, resulting in a narrow line dividing the different TMAs, in this case, aHUS with other pathologies related to pregnancy such as HELLP syndrome, Acute Fatty Liver of Pregnancy (AFLP), sepsis and preeclampsia, as well as other microangiopathies that share many of clinical characteristics of aHUS and can consequently generate a diagnostic challenge for pregnant and postpartum women.

For this, a model or algorithm leading to an accurate diagnosis that minimizes the chances of incorrect identification of pathologies associated with TMA that can be triggered during pregnancy and postpartum is needed. This diagnostic algorithm for TMA in pregnant women will have an impact on improvements on health and could have a global health benefit. Currently, two consensus documents (from Spain and Colombia), present a systematic approach and a useful diagnostic flowchart for patients suspected with a TMA. The Colombian consensus flowchart was developed in December 2014 and published in August 2015. However, these diagnostic approaches have never been validated in the obstetric population. Therefore, the following research question is presented: