Thrombotic Thrombocytopenic Purpura

Identify thrombotic microangiopathy from thrombocytopenia plus nonimmune microangiopathic hemolytic anemia: review the smear for schistocytes, and obtain LDH, indirect bilirubin, reticulocyte count, haptoglobin, creatinine, and coagulation studies. Typical TTP-associated findings include profound thrombocytopenia, schistocytes greater than 1%, elevated LDH and indirect bilirubin, low haptoglobin, reticulocytosis, a negative direct Coombs test except in some SLE-associated presentations, and coagulation tests that are not prolonged. PubMedPubMedThrombotic Thrombocytopenic Purpura Evaluation and Management - StatPearls - NCBI Bookshelf

Before therapeutic plasma exchange or plasma infusion, draw plasma for ADAMTS13 activity and for an inhibitor or anti-ADAMTS13 IgG assay whenever this does not delay treatment. ADAMTS13 activity below 10% in a patient with thrombocytopenia and hemolysis confirms TTP; severe sepsis can also be associated with activity below 10%, so interpret the result in the full clinical context. PubMed+2PubMedThrombotic Thrombocytopenic Purpura - StatPearls - NCBI BookshelfPubMedISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpuraPubMedThrombotic Thrombocytopenic Purpura Evaluation and Management - StatPearls - NCBI Bookshelf

If clinical probability is high, initiate empiric therapeutic plasma exchange while ADAMTS13 results are pending. This is a hematologic emergency: mortality remains approximately 10%-20% even with treatment, and ADAMTS13 results may not be available for several days at centers using referral laboratories. PubMed+2PubMedDiagnostic and treatment guidelines for thrombotic thrombocytopenic purpura (TTP) in Japan 2023PubMedThrombotic Thrombocytopenic Purpura Evaluation and Management - StatPearls - NCBI BookshelfPubMedUtilizing a PLASMIC score-based approach in the management of suspected immune thrombotic thrombocytopenic purpura: a cost minimization analysis within the Harvard TMA Research Collaborative

The PLASMIC score estimates the likelihood of severe ADAMTS13 deficiency in a patient with suspected thrombotic microangiopathy. Assign 1 point each for platelet count below 30 × 10^9/L, hemolysis, no active cancer, no solid-organ or stem-cell transplant history, MCV below 90 fL, INR below 1.5, and creatinine below 2.0 mg/dL. Peripheral schistocytes are required to apply the score. PubMed+2PubMedThrombotic Thrombocytopenic Purpura - StatPearls - NCBI BookshelfPubMedDiagnostic and treatment guidelines for thrombotic thrombocytopenic purpura (TTP) in Japan 2023PubMedKorean expert consensus on the management of thrombotic thrombocytopenic purpura

A score of 6-7 is high risk and supports empiric plasma exchange pending ADAMTS13 testing. A score of 5 is intermediate risk; one proposed approach considers plasma infusion at 30 mL/kg on day 1 then 15 mL/kg on days 2-4 while results are pending, at clinician discretion. A score of 0-4 should redirect the workup toward non-TTP causes of thrombotic microangiopathy. PubMed+1PubMedDiagnostic and treatment guidelines for thrombotic thrombocytopenic purpura (TTP) in Japan 2023PubMedUtilizing a PLASMIC score-based approach in the management of suspected immune thrombotic thrombocytopenic purpura: a cost minimization analysis within the Harvard TMA Research Collaborative

Use the score as a probability tool, not as a substitute for ADAMTS13 testing. The ISTH diagnostic guideline supports assessment of pretest probability by clinical judgment and/or PLASMIC or French scoring, with ADAMTS13 activity plus inhibitor or anti-ADAMTS13 testing central to the diagnostic pathway. PubMedPubMedISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura

Differentiate immune TTP from complement-mediated HUS and secondary thrombotic microangiopathies by integrating ADAMTS13 activity with context. Complement-mediated HUS, pregnancy, infection, malignancy, transplantation, endothelial-toxic drugs, and autoimmune disease can produce thrombocytopenia, hemolysis, and organ injury without immune TTP. A protocol describing complement-mediated HUS lists plasma therapy or eculizumab as treatment options, illustrating why confirmation of TTP materially changes therapy. cdn clinicaltrials+1cdn clinicaltrials[PDF] omeros - ClinicalTrials.govcdn clinicaltrialsEarly Intervention with Eculizumab to Treat Thrombotic ...

In SLE with thrombotic microangiopathy, do not attribute the syndrome automatically to lupus nephritis. Histologic thrombotic microangiopathy, microangiopathic hemolytic anemia, thrombocytopenia, or central nervous system involvement should trigger workup for TTP, complement-mediated HUS, and antiphospholipid syndrome nephropathy; low ADAMTS13 activity confirms TTP in this setting. ard eularard eularEULAR recommendations for the management of systemic lupus erythematosus with kidney involvement: 2025 update

If ADAMTS13 activity is below 10%, distinguish immune-mediated from congenital TTP through inhibitor or anti-ADAMTS13 IgG testing and clinical context. Acquired TTP results from autoantibodies that inhibit ADAMTS13 and/or accelerate its clearance, whereas congenital TTP is an inherited severe ADAMTS13-deficiency state. PubMed+1PubMedISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpuracdn clinicaltrials[PDF] For non-commercial use only - ClinicalTrials.gov

For high-probability immune TTP, start therapeutic plasma exchange empirically while ADAMTS13 activity is pending; a PLASMIC score of 6-7 is a practical trigger for this approach. In published management algorithms, high-risk patients are considered for empiric therapeutic plasma exchange, whereas low-risk patients are directed toward alternative thrombotic microangiopathy causes. PubMed+2PubMedDiagnostic and treatment guidelines for thrombotic thrombocytopenic purpura (TTP) in Japan 2023PubMedKorean expert consensus on the management of thrombotic thrombocytopenic purpuraPubMedUtilizing a PLASMIC score-based approach in the management of suspected immune thrombotic thrombocytopenic purpura: a cost minimization analysis within the Harvard TMA Research Collaborative

Caplacizumab dosing in the pivotal trial and U.S. label is a 10-mg intravenous loading bolus followed by 10 mg subcutaneously once daily during plasma exchange and for 30 days after plasma exchange. In the randomized trial, caplacizumab reduced recurrence during the overall treatment plus 28-day follow-up period from 38% with placebo to 13%; the DailyMed labeling reports major thromboembolic events in 8.5% and 8.2% of caplacizumab- and placebo-treated patients, respectively. dailymed nlm nih+1dailymed nlm nih[PDF] CABLIVI- caplacizumab - DailyMedNEJMCaplacizumab Treatment for Acquired Thrombotic ...

Caplacizumab selection depends on pretest probability and availability of timely ADAMTS13 testing. ISTH judges that the benefit-risk-cost balance does not support caplacizumab for intermediate- or low-suspicion TTP and recommends a positive ADAMTS13 activity result below 10 IU/dL or 10% before initiation in those settings. The guideline notes that ADAMTS13 testing was not required for enrollment in caplacizumab trials, creating a real-world tradeoff when assay turnaround is delayed and clinical suspicion is high. PubMedPubMedISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura

Escalate treatment intensity in refractory disease in conjunction with hematology. An ASH review describes twice-daily plasma exchange together with rituximab as a second-line strategy that usually leads to complete remission; the specific clinical threshold for refractory disease and agent sequencing should follow specialist-directed protocols. ASHASHThrombotic thrombocytopenic purpura | Blood - ASH Publications

Monitor ADAMTS13 activity during clinical remission because it is the most reliable biomarker cited for relapse prediction. One expert consensus summarizes ISTH-advised surveillance as monthly testing for the first 3 months, every 3 months during the first year, and then every 6-12 months. PubMedPubMedKorean expert consensus on the management of thrombotic thrombocytopenic purpura

Interpret late recurrent thrombocytopenia with repeat hemolysis testing and ADAMTS13 activity rather than assuming isolated thrombocytopenia is TTP relapse. In caplacizumab-treated patients who relapsed during post-treatment follow-up, ADAMTS13 activity was below 10% at the end of study treatment, linking unresolved severe deficiency to recurrence risk. dailymed nlm nihdailymed nlm nih[PDF] CABLIVI- caplacizumab - DailyMed

During follow-up, assess for neurologic, renal, and cardiac sequelae and for associated autoimmune disease. Long-term follow-up is necessary both to identify recurrence and to evaluate sequelae or additional autoimmune disorders. PubMedPubMedThrombotic Thrombocytopenic Purpura Evaluation and Management - StatPearls - NCBI Bookshelf