LAUSR

Immune thrombocytopenic purpura (iTTP) is caused by a severe acquired deficiency in the metalloprotease ADAMTS13 and is one of several disease processes manifesting as a thrombotic microangiopathy (TMA). While therapeutic plasma exchange (TPE) has proven an effective therapy for iTTP, untreated cases can prove rapidly fatal and are associated with a mortality rate of up to 90%. Given its rarity, lethality and clinical urgency, iTTP continues to present even experienced physicians with important unanswered questions. As awareness of iTTP has risen in recent years, investigators have applied statistical methods to develop clinical scoring systems aimed at addressing various aspects of the disease, including evaluating the risk of severe ADAMTS13 deficiency in patients with TMA and assessing the risk of relapse and mortality in patients with known iTTP. However, a validated clinical scoring system to help identify patients at high risk for refractory disease has remained elusive. Such a score could be very useful in guiding the decision to use adjunctive immunosuppressive therapies such as rituximab. In this issue, Gui et al. report the development and validation of just such an instrument, called the AHC score (for age, haemoglobin and creatinine). Across 17 large academic medical centres in China, the investigators studied 134 patients with iTTP, of whom a total of 55 met their criteria for refractory disease, defined as a failure to double the platelet count within four days of starting TPE or recurrent thrombocytopenia with an elevated lactate dehydrogenase within 30 days of discontinuing TPE. These 134 patients were divided into derivation (n = 94) and validation (n = 40) cohorts. Refractory patients were significantly more likely to be admitted to the intensive care unit (ICU), have a longer length of hospital stay and die from the acute episode of iTTP. Using univariate logistic regression in the derivation cohort, the authors identified six variables present at admission that were associated with refractory disease: age, presence of fever, the presence of acute kidney injury, haemoglobin, creatinine and International Normalized Ratio (INR). When subjected to multivariate logistic regression, three of these six variables independently predicted refractoriness: age, haemoglobin and serum creatinine (hence, ‘AHC score’). The authors used the b coefficients from their multivariable logistic regression model to fashion the score (Table I), with higher point totals predictive of increased risk for refractory disease. Applying the AHC score to the validation cohort, the authors found that the AHC score correctly sorted 6/17 (35%) refractory patients into the high-risk category (>3 5 points) and only 1/17 (6%) were placed in the low risk category (<2 points), resulting in an area under the curve (AUC) of 0 87 [95% confidence interval (CI) 0 63–0 82]. Although externally validated, the validation cohort used in the study by Gui et al. was small and thus the 95% CI for the AUC estimate is wide (0 63–1 0). Notably, while the