Thrombotic thrombocytopenic purpura misdiagnosed as autoimmune cytopenia: Causes of diagnostic errors and consequence on outcome. Experience of the French thrombotic microangiopathies reference centre

Abstract

Thrombotic thrombocytopenic purpura (TTP) has a devastating prognosis without adapted management. Sources of misdiagnosis need to be identified to avoid delayed treatment. We studied 84 patients with a final diagnosis of severe (<10%) acquired ADAMTS13 deficiency-associated TTP from our National database that included 423 patients, who had an initial misdiagnosis (20% of all TTP). Main diagnostic errors were attributed to autoimmune thrombocytopenia, associated (51%) or not (37%) with autoimmune hemolytic anemia. At admission, misdiagnosed patients were more frequently females (P = .034) with a history of autoimmune disorder (P = .017) and had organ involvement in 67% of cases; they had more frequently antinuclear antibodies (P = .035), a low/undetectable schistocyte count (P = .001), a less profound anemia (P = .008), and a positive direct antiglobulin test (DAT) (P = .008). In multivariate analysis, female gender (P = .022), hemoglobin level (P = .028), a positive DAT (P = .004), and a low schistocytes count on diagnosis (P < .001) were retained as risk factors of misdiagnosis. Platelet count recovery was significantly longer in the misdiagnosed group (P = .041) without consequence on mortality, exacerbation and relapse. However, patients in the misdiagnosed group had a less severe disease than those in the accurately diagnosed group, as evidenced by less organ involvement at TTP diagnosis (P = .006). TTP is frequently misdiagnosed with autoimmune cytopenias. A low schistocyte count and a positive DAT should not systematically rule out TTP, especially when associated with organ failure.

Clinical presentation in thrombotic thrombocytopenic purpura: Real‐world data from two Mexican institutions

“…Diagnosing TTP can be challenging, especially when the presenting symptoms of the patient and initial laboratory findings are nonspecific . In these situations, TTP can be misdiagnosed as another disease, especially autoimmune thrombocytopenia, leading to delayed initiation of therapy and longer platelet recovery times . Despite the description of the “classic” clinical pentad, only a minority of patients with acute TTP present with it .…”

Thrombotic thrombocytopenic purpura: Toward targeted therapy and precision medicine

“…Consequently, the association of microangiopathic hemolytic anemia with peripheral thrombocytopenia should be enough to strongly suggest a diagnosis of TTP, before organ failure occurs. In line with this view, patients with an apparent diagnosis of immune thrombocytopenia (ITP) or Evan's syndrome who are not responding to the usual therapies should be investigated for schistocytes on repeated blood smears to revisit the diagnosis …”

“…Despite further improvements in the management of iTTP, including immunomodulation with rituximab, the last 20 years have seen only modest gains in survival . The two main causes of death are insufficient awareness of TTP diagnosis, leading to diagnostic delay, and the unmet need for new weapons for the management of the most severe cases, particularly early in the disease course. Another limitation of standard treatment is that TPE and catheter placement represent a cumbersome procedure associated with major complications including infection, bleeding, catheter‐associated thrombosis, toxicities of plasma infusion, and death .…”

Pediatric thrombotic thrombocytopenic purpura

“…However, a direct positive antiglobulin test or the absence of schistocytes on blood smears should not exclude the diagnosis of TTP, and 10% of TTP patients could display such atypical features, exposing them to diagnostic wandering . All these standard investigations are not specific for TTP in children and only a biological exploration of ADAMTS13 is able to confirm or to exclude the diagnosis.…”

“…47 Finally, other standard biological parameters are investigated: coagulation parameters, bacteriological analysis (cytobacteriological examination of the urine, blood culture, stool culture …), viral serology (HIV, HCV, HBV), and autoimmune investigations. However, a direct positive antiglobulin test or the absence of schistocytes on blood smears should not exclude the diagnosis of TTP, and 10% of TTP patients could display such atypical features,exposing them to diagnostic wandering 2,48. All these standard investigations are not specific for TTP in children and only a biological exploration of ADAMTS13 is able to confirm or to exclude the diagnosis.…”