Hematology, Oncology & Immunology · Topic 8 of 26

TTP & Thrombotic Microangiopathies

Hematology · thrombotic microangiopathy

TTP & Thrombotic Microangiopathies

Schistocytes plus low platelets is TTP until proven otherwise — score PLASMIC and start plasma exchange with steroids now.

Key numbers

TTP: ADAMTS13 activity below 10%ADAMTS13 < 10%

PLASMIC 6–7: high probability of TTPPLASMIC ≥ 6 = high

01 · Defined bySchistocytes plus low platelets = TMA

Thrombotic microangiopathy = thrombocytopenia plus Coombs-negative microangiopathic hemolytic anemia: schistocytes on the smear, high LDH and indirect bilirubin, high reticulocytes and low haptoglobin, often with organ ischemia.

02 · DoStart plasma exchange now

When TTP is suspected (unexplained thrombocytopenia with microangiopathic hemolysis), start therapeutic plasma exchange urgently; send ADAMTS13 activity and inhibitor but do not wait for results. Untreated TTP is over 90% fatal.

03 · CalculatePLASMIC 6–7: high probability of TTP

The PLASMIC score (7 points) estimates the chance of severe ADAMTS13 deficiency: 6–7 high — immediate plasma exchange; 5 intermediate — exchange if no other cause; 0–4 low — look for another diagnosis.

What it is

Core idea

TTP: ADAMTS13 activity below 10% must knowTTP is caused by severe ADAMTS13 deficiency (activity usually below 10%), most often an acquired autoantibody; uncleaved large von Willebrand multimers build platelet microthrombi in the brain, gut and kidneys.

Causes & risk factors

Why it happens

Drug-induced TMA: stop the drugDrug-induced TMA (quinine, cyclosporine, tacrolimus, gemcitabine, mitomycin) has normal ADAMTS13 and does not respond to plasma exchange, steroids, rituximab or complement inhibition — stop the drug.

Presentation

What you'll see

Neurologic signs; fever and severe AKI uncommonTTP causes multiorgan ischemia — confusion, seizures or coma, abdominal pain, arrhythmias; fever is usually absent and severe AKI is rare. Unexplained thrombocytopenia plus microangiopathic hemolysis alone justifies a presumptive diagnosis.

Diagnosis & monitoring

Work-up

PLASMIC: seven one-point itemsPLASMIC, 1 point each: platelets < 30,000/mcL; hemolysis; no active cancer; no organ or stem-cell transplant; MCV < 90 fL; INR < 1.5; creatinine < 2.0 mg/dL.

Exchange daily until platelets and LDH normalizeContinue plasma exchange daily until disease activity subsides, shown by a normal platelet count and LDH; with plasma exchange, steroids and rituximab, more than 95% of patients recover.

Do right now

In this order

First moves

Schistocytes plus low platelets = TMA

→

PLASMIC 6–7: high probability of TTPPLASMIC ≥ 6 = high

→

Start plasma exchange now

→

Add corticosteroids; consider rituximab and caplacizumab

Why each step

Schistocytes plus low platelets = TMAThrombotic microangiopathy = thrombocytopenia plus Coombs-negative microangiopathic hemolytic anemia: schistocytes on the smear, high LDH and indirect bilirubin, high reticulocytes and low haptoglobin, often with organ ischemia.

PLASMIC 6–7: high probability of TTPThe PLASMIC score (7 points) estimates the chance of severe ADAMTS13 deficiency: 6–7 high — immediate plasma exchange; 5 intermediate — exchange if no other cause; 0–4 low — look for another diagnosis.

Start plasma exchange nowWhen TTP is suspected (unexplained thrombocytopenia with microangiopathic hemolysis), start therapeutic plasma exchange urgently; send ADAMTS13 activity and inhibitor but do not wait for results. Untreated TTP is over 90% fatal.

Add corticosteroids; consider rituximab and caplacizumabFor immune TTP, add corticosteroids to plasma exchange (ISTH strong recommendation); rituximab and caplacizumab are conditionally recommended additions, for first episodes and relapses.

Management

Orders

Caplacizumab 11 mg with plasma exchangeCaplacizumab, an anti–von Willebrand factor nanobody, is given 11 mg IV before the first exchange, then 11 mg SC daily after each exchange; it speeds platelet recovery but raises bleeding risk.

Give plasma if exchange is delayedIf plasma exchange cannot start immediately, give plasma infusion as a bridge, and manage the patient in a critical care unit with hematology and transfusion medicine.

Atypical HUS: complement inhibitor, meningococcal vaccineAtypical (complement-mediated) HUS lacks a diarrheal prodrome and usually has normal ADAMTS13 activity; treat with eculizumab or ravulizumab, and vaccinate against meningococcus because these drugs raise meningococcal infection risk.

Red flags & don'ts

Avoid harm

Avoid prophylactic platelet transfusion in TTP avoidAvoid prophylactic platelet transfusion in TTP — it has been associated with new thrombosis and sudden clinical deterioration; reserve platelets for life-threatening bleeding.

Relapse in about 40%: rituximab complicationAbout 40% of patients with autoantibody-mediated TTP relapse; recurrence after exchange is stopped, or a relapse, is treated with more intensive immunosuppression such as rituximab.

TTP or HUS?

Commonly confused

Mechanism	Severe ADAMTS13 deficiency (< 10%), usually an autoantibody
Prodrome	Not needed: low platelets plus MAHA suffice
Organs	Neurologic signs common; severe AKI rare
Treatment	Plasma exchange plus steroids, ± rituximab and caplacizumab

Commonly confused

Tell apart

Normal PT and fibrinogen separate TTP from DICTTP microthrombi are platelet–von Willebrand factor clots without fibrin, so PT/INR and fibrinogen are near normal (PLASMIC scores INR < 1.5); DIC shows prolonged PT and aPTT, low fibrinogen and high D-dimer.

ADAMTS13 ≥ 10%: look for another TMA causeADAMTS13 of 10% or more without an inhibitor makes TTP unlikely: consider DIC, sepsis, malignant hypertension, cancer, lupus, scleroderma, preeclampsia/HELLP and transplant-associated TMA.

More detail

Reference

Show 4 reference facts

Hereditary TTP (Upshaw–Schulman syndrome, congenital ADAMTS13 mutation) is treated with plasma infusion or recombinant ADAMTS13, not plasma exchange or immunosuppression; genetic testing is suggested when ADAMTS13 is low without an antibody.

Pregnancy can trigger TTP, which is often indistinguishable from severe preeclampsia or HELLP; US cohort data show a roughly 7-fold higher TTP risk in Black patients.

ISTH conditionally recommends rituximab for patients in clinical remission whose ADAMTS13 activity falls low again (outside pregnancy) and prophylactic plasma exchange during pregnancy.

Complement inhibitors given for Shiga toxin HUS needing dialysis or for atypical HUS can often reverse the kidney failure and may be stopped once disease activity resolves when no complement defect is found.

Pearl

Untreated TTP is over 90% fatal and treated TTP over 95% survivable — the difference is starting plasma exchange without waiting for ADAMTS13.

Sources · Merck Manual Professional — Thrombotic Thrombocytopenic Purpura (TTP) (Jun 2026) · Merck Manual Professional — Hemolytic-Uremic Syndrome (HUS) (Jun 2026) · Zheng XL et al. ISTH guidelines for treatment of thrombotic thrombocytopenic purpura. J Thromb Haemost 2020;18(10):2496–2502 (abstract via Europe PMC) · Zheng XL et al. ISTH guidelines for the diagnosis of thrombotic thrombocytopenic purpura. J Thromb Haemost 2020;18(10):2486–2495 (abstract via Europe PMC) · MDCalc — PLASMIC Score for TTP (Bendapudi PK et al., Lancet Haematol 2017) · Cablivi (caplacizumab-yhdp) prescribing information — DailyMed · Pène F, Russell L, Aubron C. Thrombocytopenia in the intensive care unit: diagnosis and management. Ann Intensive Care 2025;15:25 · Gauer RL, Whitaker DJ. Thrombocytopenia: Evaluation and Management (Table 5, thrombotic microangiopathies). Am Fam Physician 2022;106(3):288–298 · Merck Manual Professional — Overview of Platelet Disorders (peripheral smear findings) · Merck Manual Professional — Disseminated Intravascular Coagulation (DIC) · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).