What is the PLASMIC score?
The PLASMIC score is a validated bedside prediction rule for hospitalized adults with suspected immune-mediated thrombotic thrombocytopenic purpura (TTP). It estimates the probability of severe ADAMTS13 deficiency (activity < 10%) using seven routinely available clinical and laboratory variables. The score was derived and externally validated to help clinicians decide whether to initiate therapeutic plasma exchange (TPE) while awaiting confirmatory ADAMTS-13 testing, which often requires days to return from reference laboratories.
The mnemonic PLASMIC reflects its components: Platelet count, hemolysis (L for laboratory evidence), absence of Active cancer, absence of solid-organ or stem-cell transplant history, MCV, INR, and serum Creatinine. The total ranges from 0 to 7, with higher scores indicating greater likelihood of severe ADAMTS13 deficiency and a management pathway favoring urgent plasma exchange when clinical suspicion for TTP remains high.
PLASMIC is a risk stratification and triage tool, not a substitute for hematology consultation, expert transfusion medicine support, or clinical judgment in a deteriorating patient.
Clinical context: TTP and thrombotic microangiopathy
Thrombotic thrombocytopenic purpura is a life-threatening form of thrombotic microangiopathy (TMA) characterized by microvascular platelet aggregation, consumptive thrombocytopenia, and microangiopathic hemolytic anemia (MAHA). The classic pentad (fever, neurologic symptoms, renal dysfunction, thrombocytopenia, and hemolytic anemia) is often incomplete at presentation; many patients present with thrombocytopenia and hemolysis alone.
Immune-mediated TTP is caused by autoantibodies that inhibit ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13), the von Willebrand factor-cleaving protease. When ADAMTS13 activity falls severely (typically < 10%), ultra-large von Willebrand factor multimers accumulate and drive platelet-rich microthrombi in the microcirculation. Without prompt TPE, mortality is high.
Not every TMA is TTP. Complement-mediated TMA (atypical HUS), drug-induced TMA, transplant-associated TMA, HELLP syndrome, disseminated intravascular coagulation (DIC), and other entities can present with overlapping thrombocytopenia and schistocytes. PLASMIC was designed specifically to distinguish patients in whom severe ADAMTS13 deficiency is likely enough to warrant early exchange in the inpatient setting.
Pathophysiology and the role of ADAMTS13 testing
Confirmatory diagnosis rests on demonstrating severely reduced ADAMTS13 activity, often with detectable ADAMTS13 inhibitor in immune-mediated disease. Turnaround time for send-out assays can delay definitive diagnosis. During that interval, clinicians must balance the morbidity of unnecessary plasma exchange against the risk of withholding treatment in true TTP.
PLASMIC integrates features that, in derivation cohorts, discriminated immune-mediated TTP from TMA mimics: severe thrombocytopenia, laboratory hemolysis, relatively preserved renal function and coagulation profile (low INR), and absence of cancer or transplant history (which point toward alternative TMA mechanisms). Low MCV may reflect microangiopathic red cell fragmentation patterns seen in classic presentations.
Patient population and when to apply the score
Use PLASMIC in hospitalized adult inpatients with suspected immune-mediated TTP who may benefit from early plasma exchange while ADAMTS-13 results are pending. Typical candidates have thrombocytopenia with evidence of hemolysis (schistocytes on peripheral smear, elevated LDH, low haptoglobin, elevated indirect bilirubin, or elevated reticulocyte count) and no clear alternative explanation for the cytopenias.
Do not apply PLASMIC after the patient has already undergone therapeutic plasma exchange, because exchange alters the laboratory and clinical variables the score was built upon. Do not use PLASMIC as the sole reason to withhold exchange in a patient who is clinically deteriorating with high suspicion for TTP; in that scenario, treat first and confirm later per institutional protocols.
Scoring variables (0–7 points)
Each criterion contributes 0 or 1 point. For cancer and transplant history, points are awarded when the risk factor is absent (favoring immune-mediated TTP). For all other items, points are awarded when the finding is present and meets the threshold below.
| Variable | Criteria | Points if met |
|---|---|---|
| Platelet count | < 30 × 109/L | +1 |
| ≥ 30 × 109/L | 0 | |
| Hemolysis | Reticulocytes > 2.5%, or haptoglobin undetectable, or indirect bilirubin > 2.0 mg/dL (34.2 µmol/L) | +1 |
| None of the above | 0 | |
| Active cancer | Cancer treated within the past year | 0 |
| No active cancer | +1 | |
| Transplant history | Prior solid-organ or stem-cell transplant | 0 |
| No transplant history | +1 | |
| MCV | < 90 fL | +1 |
| ≥ 90 fL | 0 | |
| INR | < 1.5 | +1 |
| ≥ 1.5 | 0 | |
| Creatinine | < 2.0 mg/dL (176.8 µmol/L) | +1 |
| ≥ 2.0 mg/dL | 0 |
Total PLASMIC score = sum of all seven items (range 0–7).
Rationale for individual criteria
- Severe thrombocytopenia (< 30 × 109/L): Profound platelet consumption is typical in TTP and supports MAHA in the appropriate context.
- Hemolysis: Any one of three laboratory surrogates (reticulocytosis, absent haptoglobin, or elevated indirect bilirubin) captures ongoing red cell fragmentation and destruction when a full smear review is pending.
- No active cancer: Malignancy and its treatment are more commonly associated with TMA mechanisms other than classic immune-mediated TTP; presence of active cancer reduces the score.
- No transplant history: Transplant-associated TMA is a distinct entity; absence of transplant favors immune-mediated TTP in the derivation framework.
- Low MCV: Fragmentation and microangiopathic changes can lower mean corpuscular volume in classic presentations.
- Low INR (< 1.5): Coagulopathy with elevated INR suggests alternative diagnoses such as DIC or severe hepatic dysfunction rather than isolated TTP.
- Low creatinine (< 2.0 mg/dL): Renal-predominant TMA (for example some complement-mediated syndromes) may present with marked renal injury; relatively preserved creatinine favors TTP in this model.
Risk stratification and recommended actions
PLASMIC divides patients into three management-oriented risk categories. These thresholds match the CalcMD implementation and the original publication strata.
| PLASMIC score | Risk category | ADAMTS13 deficiency framing | Suggested clinical approach |
|---|---|---|---|
| 0–4 | Low risk | Unlikely severe ADAMTS13 deficiency | Consider alternative diagnoses (complement-mediated TMA, drug-induced TMA, DIC, other causes of thrombocytopenia and hemolysis). ADAMTS-13 testing may still be sent if clinical suspicion persists, but immediate plasma exchange is generally not indicated based on score alone. |
| 5 | Intermediate risk | Indeterminate | Send ADAMTS-13 activity testing, maintain close observation, obtain hematology consultation, and consider TPE if no alternative cause is identified while awaiting results. Do not delay exchange in a clinically worsening patient with high TTP suspicion. |
| 6–7 | High risk | High probability of severe ADAMTS13 deficiency | Send ADAMTS-13 testing, obtain urgent hematology consultation, and initiate immediate therapeutic plasma exchange. If exchange cannot be started promptly, plasma transfusion may be used per institutional protocol until TPE is available. |
Diagnostic performance in derivation and validation cohorts
In the original derivation cohort, a PLASMIC score ≤ 4 demonstrated 100% sensitivity for ADAMTS13 activity < 10%, supporting its use to identify patients in whom severe deficiency was unlikely. A score ≥ 6 had a positive predictive value (PPV) of approximately 62% for severe deficiency in derivation, rising to about 82% PPV at ≥ 6 in the external validation cohort. Sensitivity for severe deficiency at ≤ 4 was approximately 99% in external validation.
These statistics describe cohort-level performance. Individual patients may have severe ADAMTS13 deficiency at low scores or normal activity at high scores. PLASMIC should always be interpreted together with the full clinical picture, peripheral smear review, and expert input.
Therapeutic plasma exchange and supportive care
Therapeutic plasma exchange remains first-line treatment for confirmed or highly suspected immune-mediated TTP. Exchange removes ADAMTS13 inhibitors and ultra-large von Willebrand factor multimers while replacing functional ADAMTS13 from donor plasma. Daily exchange until platelet count recovery and clinical stabilization is standard at experienced centers.
Supportive measures include careful fluid management, avoidance of platelet transfusion unless life-threatening bleeding (platelet transfusion may worsen microvascular thrombosis in active TTP), treatment of concurrent infection if present, and monitoring for exchange-related complications. Corticosteroids and rituximab are commonly added for immune-mediated disease per hematology protocols but are adjuncts to TPE, not replacements for it in acute management.
When exchange cannot be initiated immediately in a high-risk patient, plasma infusion may serve as a bridge per local guidelines until apheresis capacity is available.
Differential diagnosis and mimics
Before anchoring on TTP, consider entities that share thrombocytopenia with schistocytes or hemolysis:
- Complement-mediated TMA (atypical HUS): Often prominent renal injury; eculizumab may be indicated when confirmed. PLASMIC may score low if creatinine is markedly elevated.
- Drug-induced TMA: Associated with quinine, ticlopidine, clopidogrel, calcineurin inhibitors, and other agents; requires drug withdrawal and targeted therapy.
- Transplant-associated TMA: Occurs in solid-organ and hematopoietic transplant recipients; management differs from immune-mediated TTP.
- DIC: Often elevated INR, low fibrinogen, and clinical context of sepsis, trauma, or malignancy.
- HELLP syndrome: Pregnant or postpartum patients; delivery may be definitive.
- Autoimmune cytopenias and other hemolytic anemias: May lack microangiopathic smear findings.
PLASMIC does not definitively separate all TMA subtypes. It prioritizes the decision to start exchange in suspected immune-mediated TTP while confirmatory testing is pending.
Important limitations and practice caveats
- Post-exchange use: Do not calculate PLASMIC after therapeutic plasma exchange has begun; laboratory values and clinical features change substantially.
- Clinical override: A low score does not exclude TTP in a patient with neurologic decline, cardiac ischemia, abdominal pain, or rising LDH with falling platelets. A high score does not replace ADAMTS-13 confirmation.
- Outpatient and pediatric populations: Validation focused on hospitalized adults; extrapolation to children or outpatients requires caution.
- Laboratory timing: Use the most contemporaneous values available at the time of decision-making; transfusion, dialysis, and acute kidney injury can shift creatinine and INR.
- Cancer and transplant definitions: Apply the original study definitions (active cancer treated within one year; any solid-organ or stem-cell transplant history) for consistency.
- Not a substitute for smear review: Schistocytes and MAHA on peripheral smear remain central to recognizing TMA even when PLASMIC hemolysis criteria are not yet fully met.
Documentation and workflow tips
When using PLASMIC in practice, document each criterion explicitly (platelet count, hemolysis source, cancer and transplant history, MCV, INR, creatinine) and the resulting total with risk category. Record the time ADAMTS-13 was sent and whether TPE was initiated, deferred, or bridged with plasma infusion. This audit trail supports quality review and handoffs between emergency, medicine, hematology, and apheresis teams.
Using this CalcMD calculator
Select yes or no for each of the seven criteria. The tool computes the PLASMIC total (0–7), assigns low (0–4), intermediate (5), or high (6–7) risk, and displays criterion-level points with management-oriented messaging aligned to the original score strata. Use the output for education, structured documentation, and shared decision-making alongside hematology consultation and institutional TTP pathways.