🩺What is ADAMTS13 Deficiency?
The PLASMIC score was developed by Bendapudi et al. and published in The Lancet Haematology in 2017. It was derived from a cohort of 214 patients with thrombotic microangiopathy (TMA) from three academic medical centers and externally validated in an independent cohort of 97 patients. The score incorporates seven clinical and laboratory variables: Platelet count <30 x10⁹/L, hemolysis (reticulocyte count >2.5%, undetectable haptoglobin, or indirect bilirubin >2 mg/dL), Active cancer (within 1 year), history of Solid organ or stem cell transplant, Mean corpuscular volume (MCV) <90 fL, International normalized ratio (INR) <1.5, and Creatinine <2.0 mg/dL (177 µmol/L). The acronym PLASMIC represents the seven variables: Platelets, hemolysis, Active cancer, Stem cell/solid organ transplant, MCV, INR, Creatinine. Two variables (active cancer and transplant) are negative predictors that subtract from the total score. The total score ranges from 0 to 7 after flooring negative values at 0. Risk stratification: 0-4 (low probability of severe ADAMTS13 deficiency <5%), 5 (intermediate probability 5-70%), and 6-7 (high probability >70%). The score has demonstrated excellent discrimination with a c-statistic of 0.94 for severe ADAMTS13 deficiency in the original validation cohort.
📊Clinical Assessment & Risk Scoring
Healthcare professionals use these validated clinical calculators, diagnostic scales, and risk scoring systems to assess the severity, prognosis, or therapeutic dosing requirements for ADAMTS13 Deficiency:
PLASMIC Score for TTP
The PLASMIC score is a validated clinical prediction tool for estimating the probability of severe ADAMTS13 deficiency (<10%) in patients presenting with thrombotic microangiopathy and suspected thrombotic thrombocytopenic purpura (TTP). It uses seven readily available clinical and laboratory variables to stratify patients into low, intermediate, and high probability categories, guiding urgent treatment decisions including plasma exchange initiation.
🧬Diagnostic Logic & Scoring Breakdown
The PLASMIC score is calculated by summing points from seven clinical variables. (1) Platelet count <30 x10⁹/L contributes +1 point. (2) Evidence of hemolysis — reticulocyte count >2.5%, undetectable haptoglobin, or indirect bilirubin >2 mg/dL — contributes +1 point. (3) Active cancer within the past year contributes -1 point (subtracts from the total). (4) History of solid organ or stem cell transplant contributes -1 point (subtracts from the total). (5) Mean corpuscular volume (MCV) <90 fL contributes +1 point. (6) INR <1.5 contributes +1 point. (7) Creatinine <2.0 mg/dL (177 µmol/L) contributes +1 point. If the score after adding all variables results in a negative value, it is floored at 0. The final score ranges from 0-7. Risk stratification: Low risk (score 0-4): <5% probability of severe ADAMTS13 deficiency — consider alternative TMA etiologies. Intermediate risk (score 5): 5-70% probability — send ADAMTS13 activity and consider initiating plasma exchange if clinical suspicion is high. High risk (score 6-7): >70% probability — start plasma exchange immediately and high-dose corticosteroids without waiting for ADAMTS13 results. The two negative predictors (active cancer and transplant) reflect that these conditions cause TMA through ADAMTS13-independent mechanisms (endothelial injury and complement dysregulation).
📢Clinical Significance & Implications
The PLASMIC score is the most validated clinical prediction tool for identifying patients with thrombotic microangiopathy who have severe ADAMTS13 deficiency (immune-mediated TTP). Its primary clinical impact is in guiding urgent decision-making about plasma exchange (PLEX) initiation. TTP is a medical emergency with mortality exceeding 90% if untreated, but PLEX reduces mortality to 10-20%. However, PLEX is resource-intensive, associated with procedural complications, and may be unnecessary for TMA patients who do not have TTP. The PLASMIC score enables early risk stratification at the bedside using readily available laboratory values, helping clinicians initiate PLEX promptly in high-probability patients while avoiding unnecessary PLEX in low-probability patients where alternative TMA etiologies (drug-induced TMA, complement-mediated HUS, DIC) should be pursued. The score's c-statistic of 0.94 for predicting severe ADAMTS13 deficiency demonstrates excellent discrimination. Key validation studies: The French TMA Reference Center validated the score in 550 patients, confirming its high negative predictive value (98.5% for low-risk category). A meta-analysis of 7 validation studies including 1,023 patients found pooled sensitivity of 91% and specificity of 89% for severe ADAMTS13 deficiency at the high-risk cutoff (score ≥6). Limitations include potential misclassification of patients with mild ADAMTS13 deficiency (10-50% activity) and reduced performance in cancer/transplant-associated TMA populations where the negative predictors may overcorrect.
💡 Clinical Assessment Scenario Example
A 35-year-old woman presents with acute onset of confusion, petechiae, and mild jaundice. Laboratory findings: platelet count 18 x10⁹/L, hemoglobin 8.5 g/dL, reticulocyte count 4.2%, haptoglobin undetectable, indirect bilirubin 2.8 mg/dL, MCV 92 fL, INR 1.1, creatinine 1.2 mg/dL. No history of cancer or transplant. PLASMIC score: Platelets <30 (+1), Hemolysis — reticulocytes >2.5% (+1), Active cancer (-0), Transplant (-0), MCV <90 (92 fL, does not meet criteria, +0), INR <1.5 (+1), Creatinine <2.0 (+1) = Total Score 4/7 (Low risk, <5% probability of severe ADAMTS13 deficiency). Despite the low PLASMIC score, given the strong clinical suspicion for TTP (neurological involvement, severe thrombocytopenia, hemolysis), the clinician sends ADAMTS13 activity and initiates PLEX empirically due to the high mortality of missed TTP. ADAMTS13 results return at 35% activity (not severe deficiency), and the patient is diagnosed with complement-mediated HUS (aHUS), treated with eculizumab. This case illustrates the PLASMIC score's high negative predictive value — the low score correctly predicted absence of severe ADAMTS13 deficiency. However, clinical judgment remains critical in treatment decisions.
💊Common Medications & Interventions
The following pharmacological therapies and substances are commonly referenced or adjusted based on the clinical assessment of ADAMTS13 Deficiency:
⚠️Clinical Assessment Pitfalls
❌ Mistake: Applying the PLASMIC score to patients with established TTP diagnosis rather than undifferentiated TMA
✅ Correction: The PLASMIC score was designed for patients presenting with thrombotic microangiopathy (TMA) of unclear etiology — defined by microangiopathic hemolytic anemia (schistocytes on peripheral smear) and thrombocytopenia. It should not replace ADAMTS13 testing in patients with high clinical suspicion for TTP, nor should it be applied when the TMA etiology is already known.
❌ Mistake: Misinterpreting the negative predictors — thinking active cancer or transplant should exclude TTP entirely rather than reducing its probability
✅ Correction: Active cancer and transplant are negative predictors, each subtracting 1 point, but they do not rule out TTP. Patients with cancer or transplant can still develop immune-mediated TTP, though alternative TMA mechanisms (drug-induced, complement-mediated) are more likely. The score should be interpreted in clinical context — a cancer patient with high clinical suspicion still deserves ADAMTS13 testing.
🚑When to Seek Medical Attention
This reference supports clinical assessment of ADAMTS13 Deficiency; it does not replace urgent evaluation. Seek prompt in-person medical care if symptoms are severe, rapidly worsening, or life-threatening, or if you are unsure about a diagnosis or treatment plan. Patients should always consult their physician before starting or changing any therapy.
❓Frequently Asked Questions
Q: What is the PLASMIC score and when should it be used?
The PLASMIC score is a clinical prediction rule that estimates the probability of severe ADAMTS13 deficiency (<10%) in patients presenting with thrombotic microangiopathy (TMA) — defined by microangiopathic hemolytic anemia (schistocytes on peripheral smear, elevated LDH, low haptoglobin) and thrombocytopenia. It should be used in the emergency department or hospital setting when TTP is in the differential diagnosis to guide urgency of plasma exchange initiation. The score uses 7 variables: Platelet count <30 x10⁹/L, evidence of hemolysis, Active cancer within 1 year (negative predictor), history of Solid organ or stem cell transplant (negative predictor), MCV <90 fL, INR <1.5, and Creatinine <2.0 mg/dL. The score is not valid for patients with an established TMA etiology or those undergoing ADAMTS13 testing for known TTP.
Q: Should plasma exchange be started if the PLASMIC score is low (0-4)?
Not necessarily. A low PLASMIC score (0-4) indicates <5% probability of severe ADAMTS13 deficiency. In low-risk patients with alternative TMA etiologies (clear drug association, recent transplant, cancer, severe hypertension with TMA), plasma exchange is generally not indicated and the focus should be on treating the underlying cause. However, in patients with strong clinical suspicion for TTP despite a low PLASMIC score (e.g., neurological involvement with severe thrombocytopenia and microangiopathic hemolysis), ADAMTS13 activity should still be sent urgently, and empiric PLEX may be warranted given the high mortality of untreated TTP. Clinical judgment always supersedes the score — the PLASMIC score is a decision-support tool, not a replacement for clinical assessment.
📚Evidence-Based References
Medically Reviewed By
Dr. Mahmoud El-Sayed
MD | Hematology
Dr. Mahmoud El-Sayed is a hematology consultant with expertise in thrombotic microangiopathies and hemostasis.