ICI-associated immune thrombocytopenia
Also called: ITP · immune thrombocytopenia · immune-related thrombocytopenia · checkpoint inhibitor thrombocytopenia
One of the three commonest haematological irAEs, and the one most easily mistaken for something else — a low platelet count in a patient with cancer has many non-immune causes, so a baseline count and the exclusion of DIC come before the diagnosis. Median onset 41 days; managed as standard-of-care ITP with a steroid backbone.
Reported frequency
<1% — Overall haematological irAE frequency (ALL phenotypes, not ITP alone)
of 745 anti-PD-(L)1-treated patients in the prospective REISAMIC registry · Organ-level figure for all haem-irAEs, carried on this anchor card. No ITP-specific incidence is stated in any source held here
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Onset
SITC states a median time to onset for ITP of 41 days and a median time to resolve below grade 2 of 4 weeks. Stored in the units the source printed; 41 days is not converted to a weeks median.
Presentation
- · A fall in platelet count, often against a baseline established before ICI therapy
- · Bleeding or bruising in severe disease
- · Frequently asymptomatic and found on routine counts
Differential
- · Chemotherapy myelosuppression and other marrow-suppressing drugs
- · Disseminated intravascular coagulation — SITC puts DIC labs (PT/PTT/fibrinogen/d-dimer) in the work-up to exclude it
- · Cancer itself, radiation, infection, and pre-existing autoimmunity, which SITC lists as competing causes of thrombocytopenia in this population
- · Pseudothrombocytopenia, excluded on the blood smear
Work-up
CBC with differential, against a baseline platelet count · All patients
SITC advises a baseline count before ICI therapy so a later drop can be measured rather than guessed. The differential separates an isolated thrombocytopenia from a broader cytopenia.
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Blood smear evaluation · All patients
Confirms true thrombocytopenia and excludes pseudothrombocytopenia and a microangiopathic picture.
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DIC labs — PT, PTT, fibrinogen, d-dimer · All patients
SITC's exclusion of disseminated intravascular coagulation, a competing consumptive cause with a different treatment.
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LDH · All patients
Part of SITC's work-up; a marker of haemolysis or high cell turnover that points away from isolated ITP.
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Grade ladder
Grade 1
Hold the ICIOutpatientGrade 1 — ASCO's continue-at-grade-1 default names hematologic toxicity among its exceptions, so ITP is not automatically continued through. SITC's management is standard-of-care ITP: steroids at 1 mg/kg. The IVIG and rituximab escalations below are keyed to severity and steroid response, not to a CTCAE rung.
Corticosteroid 1 mg/kg/day (oral)
Taper within 6 weeks or longer, starting once: Not stated for this entity. SITC gives the 1 mg/kg dose and no taper; the ceiling shown is ASCO's cross-organ 'at least 4-6 weeks', a FLOOR in its own text, rendered open-ended.
No step size or interval is carried: the source guideline states a total window and a response marker, and does not specify a cadence.
Second line
- IVIG 0.5 g/kg/day for 5 days, in addition to steroids — Severe ITP.
- Rituximab — Steroid-refractory ITP — SITC notes it has been successfully managed this way.
- · Establish and track a baseline platelet count
- · Exclude DIC and other non-immune causes before attributing the drop to the ICI
Escalate when: Severe thrombocytopenia, bleeding, or no platelet recovery on steroids.
Grade 2
Hold the ICIOutpatientGrade 2 — ASCO may suspend the ICPi for most grade 2 toxicities. SITC's ITP management does not change by rung: standard-of-care steroids at 1 mg/kg, with IVIG for severe disease.
Corticosteroid 1 mg/kg/day (oral)
Taper within 6 weeks or longer, starting once: Not stated for this entity; the ceiling is ASCO's cross-organ minimum taper length.
No step size or interval is carried: the source guideline states a total window and a response marker, and does not specify a cadence.
Second line
- IVIG 0.5 g/kg/day for 5 days, in addition to steroids — Severe ITP.
- Rituximab — Steroid-refractory ITP.
- · Serial platelet counts against baseline
- · Haematology involvement for a count that does not recover
Escalate when: Progression to severe thrombocytopenia or bleeding.
Grade 3
Hold the ICIConsider admissionGrade 3 — ASCO suspends the ICPi and starts high-dose corticosteroids at grade 3. For ITP this is where 'severe' typically applies, and SITC adds IVIG at 0.5 g/kg/day for 5 days on top of steroids.
Corticosteroid 1 mg/kg/day (oral)
Taper within 6 weeks or longer, starting once: Not stated for this entity; the ceiling is ASCO's cross-organ minimum taper length.
No step size or interval is carried: the source guideline states a total window and a response marker, and does not specify a cadence.
Second line
- IVIG 0.5 g/kg/day for 5 days, in addition to steroids — Severe ITP — which grade 3 typically represents.
- Rituximab — Steroid-refractory ITP.
- · IVIG alongside steroids for severe disease
- · Platelet transfusion for active bleeding, per haematological standard of care
Escalate when: Life-threatening bleeding or refractoriness to steroids and IVIG.
Grade 4
Discontinue permanentlyAdmitGrade 4 — ASCO's cross-organ rule is permanent discontinuation at grade 4, with an endocrine exception that does not apply. SITC's severe-disease management — steroids plus IVIG, with rituximab for refractory disease — is what fills the treatment side.
Corticosteroid 1 mg/kg/day (oral)
Taper within 6 weeks or longer, starting once: Not stated for this entity; the ceiling is ASCO's cross-organ minimum taper length.
No step size or interval is carried: the source guideline states a total window and a response marker, and does not specify a cadence.
Second line
- IVIG 0.5 g/kg/day for 5 days, in addition to steroids — Severe ITP.
- Rituximab — Steroid-refractory ITP.
- · Admission for severe or bleeding thrombocytopenia
- · Permanent discontinuation of the ICI
Escalate when: Already the top rung. Refractory ITP beyond steroids, IVIG and rituximab is outside what the chapters held here state.
Rechallenge
avoid
SITC states no ITP-specific rechallenge rule. The organ-level figure it does give — 43% recurrence when a small group with prior haem-irAEs was re-exposed (n=7) — is a caution rather than a recommendation, and is carried on this anchor card's citation. The stance is the conservative reading of a 43% recurrence signal and a phenotype whose severe form needs IVIG, not a documented protocol; the recurrence field is null because the 43% is an all-haem figure, not an ITP-specific one.
- · Platelet recovery and a haematology assessment before any re-exposure is contemplated
Deliberately not carried
- divergences — Empty because only ONE society chapter for this organ is held here. ASCO appears via its cross-organ ladder quoted from the abstract, which establishes no haematology chapter coverage — heme stays off ASCO's IRAE_GUIDELINE_ORGANS row.
- incidence — No ITP-specific incidence is stated in any source held here. The <1% carried is the organ-level frequency across all haem-irAEs, and its population field says so. The Delanoy cohort's '9 of 35 cases were ITP' is a composition of a grade-2-or-worse case series, not a rate, and is not entered as a framing.
- gradeThreePlus — Null. The Delanoy cohort was grade-2-or-worse by inclusion and 71% reached grade 4 — a figure shaped by the selection criterion, not a grade ≥3 rate of ITP, so it is described on the organ header rather than encoded as this entity's severity rate.
- mortality — Null. The two deaths in the Delanoy cohort were from febrile neutropenia, not ITP; attributing them here would misplace a neutropenia outcome. They are carried on the neutropenia card.
- onset.medianWeeks — SITC states the median in days (41). It is not converted to a weeks median; the note carries it in the published unit.
- ladder[].taper — SITC gives the 1 mg/kg dose and no taper for ITP. Every rung shows ASCO's cross-organ 'at least 4-6 weeks' as an open-ended ceiling labelled as ASCO's, with all three cadence fields null together.
- guidelinePmids — Left empty although ASCO and SITC are rows in guidelines.ts: their stored keyRecommendation strings are renal-scoped and would surface kidney dosing on a blood card.
Sources
- Brahmer JR, et al. (2021) Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse eventsCited for: That immune thrombocytopenia must be separated from the many non-immune causes of a low platelet count in cancer; the value of a baseline platelet count; the 41-day median onset and 4-week median resolution; the diagnostic work-up; and the graded management — steroids at 1 mg/kg, IVIG 0.5 g/kg/day for 5 days added for severe disease, and rituximab for steroid-refractory disease. This anchor citation also carries the organ-level context spans: the <1% frequency across 745 anti-PD-(L)1 patients, the 43% recurrence on rechallenge (n=7), and the 2-9 week typical resolution window.Supporting text: the full text
- Schneider BJ, et al. (2021) Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline UpdateCited for: That ASCO's continue-at-grade-1 default explicitly EXCLUDES some hematologic toxicities, and that permanent discontinuation is its grade 4 rule. Cited as the cross-organ ladder — no ASCO haematology chapter is held here.Supporting text: the PubMed abstract (checkable at the link above)
- Delanoy N, et al. (2019) Haematological immune-related adverse events induced by anti-PD-1 or anti-PD-L1 immunotherapy: a descriptive observational study.Cited for: The 0.5% frequency in the prospective registry; that neutropenia, autoimmune haemolytic anaemia and immune thrombocytopenia were the three commonest presentations at nine patients (26%) each; the grade skew (71% reaching grade 4); the two febrile-neutropenia deaths; and the 60% resolution. A cohort of 35 grade-2-or-worse cases assembled from three French pharmacovigilance databases.Supporting text: the PubMed abstract (checkable at the link above)