PLASMIC score for thrombotic thrombocytopenic purpura (also searched as the Plasmic scoring system, ICD-10: M31.1) is an objective, seven-item clinical prediction instrument engineered to stratify the pre-test probability of severe ADAMTS13 deficiency (less than 10% enzymatic activity) among adult patients manifesting unexplained microangiopathic hemolytic anemia and thrombocytopenia^{1, 6}. By synthesizing readily available routine laboratory parameters and clinical history features into a concise point system, the PLASMIC score permits emergency clinicians and haematologists to rapidly identify patients harbouring immune thrombotic thrombocytopenic purpura (iTTP)—a catastrophic, life-threatening thrombotic microangiopathy—long before specialized, time-consuming functional protease assays return from reference laboratories^{2, 4}. Because untreated iTTP carries a mortality rate exceeding 90% within days of symptom onset due to multiorgan ischemia involving the central nervous system and myocardium, accurate risk stratification via the PLASMIC tool directly guides the immediate, time-critical initiation of therapeutic plasma exchange and targeted immunotherapy^{1, 5}.

Etiology & Risk Factors

Immune-Mediated Pathogenesis: Acquired, immune-mediated TTP (iTTP) is driven by neutralizing or clearance-inducing IgG autoantibodies directed against the spacer domain of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13)^{1, 4}.
Congenital Etiology (Upshaw-Schulman Syndrome): Inherited mutations in the ADAMTS13 gene on chromosome 9q34 lead to constitutional deficiency of the protease, typically manifesting in infancy, childhood, or during pregnancy, though distinct adult-onset presentations occur².
Precipitating Triggers & Secondary Associations: While the vast majority of iTTP cases arise sporadically in idiopathic contexts, recognized triggers and associations include pregnancy and the postpartum period, infections, autoimmune disorders (such as systemic lupus erythematosus), malignancies, and specific therapeutic agents (e.g., antiplatelet agents, chemotherapeutic drugs)^{3, 7}.
Demographic Predilections: iTTP demonstrates a pronounced predilection for adult females (exhibiting an approximate 2:1 to 3:1 female-to-male ratio) and occurs with higher incidence among individuals of African descent, who often present with more aggressive clinical phenotypes and higher autoantibody titers^{2, 7}.

Pathophysiology

ADAMTS13 functions as the dedicated plasma metalloproteinase responsible for cleaving ultra-large von Willebrand factor (UL-VWF) multimers released from activated endothelial cells into smaller, less adhesive functional units^{1, 4}. When ADAMTS13 activity is severely suppressed—falling below 10% of normal physiological levels due to autoimmune destruction or genetic mutation—uncleaved UL-VWF multimers accumulate excessively within the circulation^{1, 4}. These massive multimeric strands spontaneously bind circulating platelets via glycoprotein Ib-IX-V receptors under high shear stress conditions, precipitating the widespread formation of platelet-rich microvascular thrombi^{3, 4}. As erythrocytes traverse these partially occluded capillary and arteriolar networks, mechanical shearing occurs, destroying red blood cells and producing characteristic fragmented erythrocytes known as schistocytes alongside elevated serum lactate dehydrogenase (LDH) and indirect hyperbilirubinemia^{3, 5}. The resulting microvascular thrombosis induces severe tissue ischemia across multiple organ beds, prominently affecting the brain, heart, kidneys, and gastrointestinal tract, thereby generating the complex multiorgan clinical picture characteristic of the disease^{1, 7}.

Clinical Presentation & Classic Clinical Signs

History & Cardinal Symptoms: Patients frequently present with nonspecific prodromal complaints including profound generalized fatigue, weakness, low-grade fever, nausea, vomiting, abdominal pain, and petechial or purpuric skin eruptions reflecting severe peripheral thrombocytopenia^{3, 5}.
Physical Examination & Named Clinical Signs: The historically taught classic pentad of TTP—consisting of microangiopathic hemolytic anemia, thrombocytopenic purpura, fluctuating neurological deficits, renal insufficiency, and fever—is present in fewer than 10% of patients upon initial emergency department arrival^{1, 7}. Neurological manifestations range subtly from headache, confusion, lethargy, and transient aphasia to focal motor deficits, cranial nerve palsies, and generalized tonic-clonic seizures. Cardiovascular involvement may manifest as tachycardia, heart failure, arrhythmias, or myocardial infarction due to microthrombi within the coronary circulation^{1, 7}.

Diagnostic Workup & Interpretation (Laboratory, Imaging & ECG/Pathology)

Diagnostic Modality / Test	Expected Clinical & Radiological / Laboratory Finding
Gold-Standard Investigation	Measurement of ADAMTS13 plasma proteolytic activity demonstrating severe deficiency (< 10%) accompanied by the presence of an inhibitory anti-ADAMTS13 IgG antibody^{1, 4}.
Laboratory Panel	Complete blood count showing profound thrombocytopenia (platelet count typically < 30,000/mcL) and Coombs-negative hemolytic anemia; peripheral blood smear revealing marked schistocytes (> 1% or numerous per high-power field); elevated serum lactate dehydrogenase (LDH, often > 500-1000 U/L); undetectable or severely depressed haptoglobin; elevated indirect bilirubin and reticulocytosis; and mild-to-moderate elevation in serum creatinine without heavy proteinuria^{1, 5, 7}.
Imaging / Radiology (X-ray, US, CT, MRI)	Brain magnetic resonance imaging (MRI) may demonstrate reversible posterior leukoencephalopathy syndrome (PRES) or ischemic microinfarcts during acute neurological deterioration; chest radiography and echocardiography assess cardiopulmonary status and rule out structural heart disease^{1, 7}.
ECG / Histopathology / Procedural	Electrocardiogram (ECG) performed routinely to screen for ischemic changes, ST-segment alterations, or arrhythmias secondary to myocardial microthrombi; tissue biopsy (rarely required) demonstrates hyaline thrombi within arterioles and capillaries without significant vessel wall inflammation or necrosis^{1, 7}.

Staging, Classification & Clinical Scoring Systems

Criterion / Stage / Score Component	Clinical Threshold, Points & Management Implication
Platelet Count	Platelet count < 30,000/mcL assigns 1 point in the PLASMIC algorithm, reflecting profound consumptive thrombocytopenia⁶.
Hemolysis Indicator	Presence of hemolysis (defined as reticulocyte count > 2.5%, undetectable haptoglobin, or indirect bilirubin > 2.0 mg/dL) assigns 1 point⁶.
Active Malignancy	Active cancer diagnosis within the previous year assigns 0 points if present (as malignancy shifts probability toward other microangiopathies), whereas absence of active cancer assigns 1 point⁶.
Previous Stem Cell or Organ Transplant	History of solid organ or hematopoietic stem cell transplant assigns 0 points if present, while absence of transplantation assigns 1 point⁶.
MCV Threshold	Mean corpuscular volume (MCV) < 100 fL assigns 1 point (helping differentiate TTP from megaloblastic or folate/B12 deficiency states), whereas MCV ≥ 100 fL assigns 0 points⁶.
INR Parameter	International Normalized Ratio (INR) < 1.5 assigns 1 point, reflecting preserved hepatic synthetic function and helping exclude disseminated intravascular coagulation (DIC)⁶.
Serum Creatinine	Serum creatinine < 2.0 mg/dL assigns 1 point, indicating the absence of severe acute kidney injury characteristic of hemolytic uremic syndrome, whereas creatinine ≥ 2.0 mg/dL assigns 0 points⁶.
PLASMIC Risk Stratification	Scores of 0-4 indicate low risk (predicted ADAMTS13 activity > 10%, alternative diagnosis likely); score of 5 indicates intermediate risk; scores of 6-7 indicate high risk (predicted ADAMTS13 activity < 10%, strongly warranting immediate therapeutic plasma exchange and diagnostic confirmation)^{4, 6}.

Differential Diagnosis

Differential Condition	Distinguishing Clinical, Biochemical & Imaging Features
Hemolytic Uremic Syndrome (HUS)	Predominantly pediatric or Shiga toxin-associated (E. coli O157:H7); features prominent acute renal failure with elevated creatinine and minimal neurological involvement; normal ADAMTS13 activity (> 10%)³.
Disseminated Intravascular Coagulation (DIC)	Triggered by sepsis, trauma, or obstetrical emergencies; characterized by consumptive coagulopathy with prolonged prothrombin time (PT/INR), elevated activated partial thromboplastin time (aPTT), hypofibrinogenemia, and elevated D-dimer levels (unlike TTP, where coagulation parameters are typically normal)⁶.
Evans Syndrome	Autoimmune hemolytic anemia combined with immune thrombocytopenia; direct antiglobulin test (Coombs test) is strongly positive; absence of schistocytes on peripheral blood smear¹.
Heparin-Induced Thrombocytopenia (HIT)	Occurs in patients exposed to heparin; characterized by moderate-to-severe thrombocytopenia and high risk of arterial and venous thrombosis; positive anti-PF4 antibodies and functional platelet activation assays; lack of marked microangiopathic hemolytic anemia¹.

Management & Treatment Protocol

Initial Stabilization & Resuscitation: Suspected iTTP represents an immediate medical emergency requiring urgent hematology consultation and admission to an intensive care unit or specialized unit for continuous monitoring of neurological status, cardiac function, and fluid balance^{1, 4}.
First-Line Medical / Pharmacological Therapy (with exact adult dosing): Therapeutic plasma exchange (TPE) must be initiated within 6 hours of presentation, exchanging 1.5 plasma volumes daily using fresh frozen plasma (or solvent-detergent plasma) as replacement fluid until the platelet count normalizes (exceeding 150,000/mcL) for at least two consecutive days^{1, 4}. Adjunctive glucocorticoid therapy is administered concurrently, utilizing intravenous methylprednisolone at a dose of 1 mg/kg daily (or oral equivalent prednisone 1 mg/kg daily) until clinical remission is achieved^{1, 4}. Rituximab, an anti-CD20 monoclonal antibody, is recommended as part of frontline therapy at a standard adult dose of 375 mg/m² intravenously weekly for four consecutive doses to deplete B-lymphocytes producing anti-ADAMTS13 autoantibodies^{1, 4}. Caplacizumab, a bivalent anti-von Willebrand factor nanobody, is administered as a 10 mg intravenous loading bolus prior to the first plasma exchange, followed by daily subcutaneous injections of 10 mg throughout the duration of daily plasma exchange and for 30 days following cessation of TPE to actively prevent microvascular thrombosis and reduce exacerbation rates^{1, 4}.
Surgical / Interventional Indications: Indwelling central venous catheter placement (e.g., double-lumen dialysis catheter) under sterile ultrasound guidance is routinely performed to secure reliable, high-flow vascular access required for daily therapeutic plasma exchange sessions¹.

Complications & Prognosis

Acute Complications: Lifethreatening acute complications include ischemic stroke, intracerebral hemorrhage from profound thrombocytopenia, myocardial infarction, acute pulmonary edema, severe acute kidney injury, and fatal arrhythmia or cardiac arrest^{1, 2}.
Chronic Sequelae & Relapse: Survivors face significant risks of immune-mediated disease relapse (occurring in 20% to 40% of patients), long-term neurocognitive impairment, chronic hypertension, and secondary autoimmune disorders⁴.
Prognosis: With modern comprehensive management protocols incorporating prompt therapeutic plasma exchange, high-dose corticosteroids, rituximab, and caplacizumab, overall survival rates exceed 80% to 90%, transforming a previously universally fatal condition into a highly manageable and frequently curable disease entity^{1, 4}.

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PLASMIC score for thrombotic thrombocytopenic purpura