Flip Side of the Same Coin

INTRODUCTION

Thrombotic microangiopathies (TMAs) comprise a heterogeneous group of disorders with varying etiologies and therapeutic management. Among them, thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uremic syndrome (aHUS) are particularly significant when considering diagnosis due to their specific treatments, which have an early impact on morbidity and mortality.

OBJECTIVES

To describe two cases of TMA with different clinical presentations and outcomes.

CASE 1

A 29-year-old woman with no significant medical history was referred to our hospital for thrombocytopenia and spontaneous bruising. Laboratory tests confirmed moderate thrombocytopenia (58x103/μL), elevated LDH (847 U/L) and schistocytes, without anaemia (Hb 14.3 g/dL). Given the TMA diagnosis of unclear etiology, plasmapheresis (PE) and corticosteroids (CS) were initiated. The patient had a favorable outcome, achieving complete response.

CASE 2

A 61-year-old man with a history of liver cirrhosis presented to the emergency department with abdominal pain, drowsiness and dysarthria. Laboratory tests revealed severe thrombocytopenia (7x103/μL), mild anaemia (10,8 g/dL) and signs of haemolysis (LDH 5215 U/L, total bilirubin 8,8 mg/dL, direct bilirubin 4,6 mg/dL) with schistocytes observed in the peripheral blood smear and signs of multiorgan failure (creatinine 2,78 mg/dL; ALT 58 U/L, AST 161 U/L, INR 1,6; APTT 31,1s; PT 18s; fibrinogen 222 mg/dL; D dimer 5405 ng/mL; CRP 2,15 mg/dL). He was admitted to the ICU with a suspected acute pancreatitis (lipase 1022 U/L, amylase 913 U/L). During the first 24 hours, his condition deteriorated and a haematology consultation was requested. Based on the TMA diagnosis, PE and CS were initiated. Despite the treatment, the patient's condition worsened, and he passed away 11 days after initiating treatment.

DISCUSSION

Would TTP had been suspected in any of these cases? According to the PLASMIC score, the probability of severe ADAMTS13 deficiency would be 6% and 0%, respectively. Nonetheless, ADAMTS13 levels were measured in both cases, yielding 0%. Thus, despite existing recommendations, we believe it is advisable to measure ADAMTS13 levels even in cases of low suspicion.

Given that TTP is an ultra-rare disease and the early initiation of treatment changes the prognosis drastically, it is crucial to have it under consideration when doing the differential diagnosis, even in patients with comorbidities who may seem to have a different diagnosis initially. For instance, case 2 illustrates how pre-existing (hepatic disease) or concomitant conditions (pancreatitis) should not lead to its exclusion, even if these conditions could potentially explain the cytopenias.

Additionally, the presentation can vary significantly depending on the disease's stage and this may also challenge the diagnostic process: in early stages (Case 1), anaemia may not be present, whereas in later stages (Case 2), multiorgan failure may result from TTP. This highlights the heterogeneity in TTP presentation and in these scenarios, predictive scores should support but not replace the clinical suspicion.

These two presented cases, each of them with opposite presentations and outcomes, reflect different aspects of the same condition.

Villegas:Agios: Consultancy.