TTP PLASMIC Scoring System

Thrombotic thrombocytopenic purpura (TTP) is characterized by thrombocytopenia and microangiopathic hemolytic anemia, both resulting from microvascular platelet thrombi in terminal arteries and capillaries. Small vessel occlusion in various organs, notably the brain and kidney, is responsible for the clinical manifestations, which include fluctuating neurologic abnormalities and a variable degree of renal insufficiency. TTP can be fatal if not treated quickly by plasma exchange.

TTP is caused by a lack of ADAMTS13 activity, which normally cleaves the ultra-large von Willebrand factor multimers. Severe ADAMTS13 deficiency is defined as <10% of normal activity and has 90% sensitivity and 90% specificity for diagnosis of TTP.  Severe deficiency predicts good response to therapeutic plasma exchange. Approximately 80-90% of severely deficient patients respond to first-line therapies.

Unfortunately, most hospital laboratories do not perform the ADAMTS13 assay, but send a plasma sample to a reference laboratory. The result may not be available for 48 hours or more. A more rapid method to diagnose TTP is needed.  Recently, researchers at Massachusetts General Hospital developed a new diagnostic tool, referred to as the PLASMIC score. To develop this scoring system, researchers analyzed patients with a possible diagnosis of TTP between 2004 and 2015 and used univariate analysis to identify covariates for a logistic regression model predictive of severe ADAMTS13 deficiency (<10% activity). The factors most strongly associated with severe ADAMTS13 activity identified were platelet count, combined hemolysis variable, MCV, INR and serum creatinine. Together with the history of cancer in the preceding year and solid-organ or stem cell transplant, a final clinically predictive tool, the PLASMIC score, was developed. The PLASMIC score was validated for its diagnostic performances and also compared to the clinical assessment alone.

Variables Points*
Platelet count <30 x 109 per L 1
Hemolysis variable† 1
No active cancer 1
No history of solid-organ or stem-cell transplant 1
MCV <90 fL 1
INR <1.5 1
Creatinine <2.0 mg/dL 1
INR: International normalized ratio. MCV: Mean corpuscular volume.
†Reticulocyte count >2.5%, or haptoglobin undetectable, or indirect bilirubin >2.0 mg/dL.

 

When used in conjunction with clinical assessment, this score also provided significant discriminatory power to rule out other causes of microangiopathic hemolysis. The score is interpreted as follows:

Score Risk Category Risk of severe ADAMTS13 deficiency (≤ 10%)
0-4 Low 4.3%
5-6 Intermediate 56.8%
7 High 96.2%

 

Low (0-4) and high (7) PLASMIC scores are most useful clinically, correctly predicting the risk of severe ADAMTS13 deficiency in 96% of cases. Patients with low PLASMIC scores are likely to benefit from plasma exchange, while patients with high scores are not. An intermediate score is less helpful, only predicting a severe ADAMTS13 deficiency in 56% of patients.Pre-existing liver or renal disease may falsely lower the PLASMIC score due to baseline elevations in the international normalized ratio and/ or creatinine.

References

Bendapudi PK, et al. Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic microangiopathies: a cohort study. Lancet Hematology 2017;4:e157-64

Williams LA, Marques MB, Pathology Consultation of the Diagnosis of Thrombotic Microangiopathies (TMAs), Am J Clin Pathol February 2016;145:158-165 DOI: 10.1093/AJCP/AQV086

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