Professor Wu Depei New stage, new concept, new pattern - the 2022 version of the guidelines leads a new era of TTP diagnosis and treatment

Thrombotic thrombocytopenic purpura (TTP) is a rare, severe thrombotic microangiopathy characterized by moderate to severe thrombocytopenia, microangiopathic hemolytic anemia (MAHA), ischemia, and extensive organ damage (especially the brain, kidneys, and heart), primarily caused
by severe deficiencies of von Willebrand factor (VWF) lyase (also known as ADAMTS13).
TTP can be divided into immune TTP (iTTP) and hereditary TTP (cTTP), of which iTTP accounts for the majority and was once called acquired TTP (aTTP).

In 2022, the Thrombosis and Hemostasis Group of the Hematology Branch of the Chinese Medical Association released the Chinese Guidelines for the Diagnosis and Treatment of Thrombotic Thrombocytopenic Purpura (2022 Edition), aiming to provide evidence-based basis for the clinical diagnosis and treatment of TTP in China and further standardize clinical diagnosis and treatment
.
Yimaitong specially invited Professor Wu Depei from the First Affiliated Hospital of Soochow University to interpret the disease status of TTP and the latest guidelines of TTP for readers!

Yimaitong: The Thrombosis and Hemostasis Group of the Hematology Branch of the Chinese Medical Association has released the "Chinese Guidelines for the Diagnosis and Treatment of Thrombotic Thrombocytopenic Purpura (2022 Edition)", can you please talk about the value of the formulation of this guideline for clinical practice?

In 2012, Academician Ruan Changgeng led and organized experts to write the first "Chinese Expert Consensus on the Diagnosis and Treatment of Thrombotrombotic Thrombocytopenic Purpura", which aims to standardize the clinical diagnosis and treatment of TTP, and elaborates on five parts: clinical manifestations, laboratory tests, key points of diagnosis, treatment plan and principles, and prognosis, to help domestic doctors understand TTP and gradually standardize the diagnosis and treatment
of TTP 。 However, it has been nearly 10 years since the publication of this consensus, and the examination methods, diagnostic methods and treatment plans of TTP have been updated at home and abroad, so domestic clinics need to keep up with the progress of international TTP diagnosis and treatment, and combine the actual situation in China to further improve the diagnosis and treatment level of domestic TTP, which is also the original intention
of the expert group to write this guideline.

Yimaitong: Compared with the previous guidelines, what important changes do you think have taken place in this guideline, and what is the basis for the update?

This guideline has been updated and supplemented accordingly from the aspects of pathogenesis, disease overview, laboratory tests, diagnosis and treatment procedures and treatment methods, mainly in the following aspects:

First, the guidelines have increased the PLASMA score
.
Although the lack of ADAMTS13 activity (<10%) is a specific diagnostic criterion for TTP, many hospitals in China cannot routinely carry out ADAMTS13 testing, or need to be sent to other testing centers for completion, which not only affects the timeliness of patient diagnosis, but also seriously interferes with the follow-up treatment<b11> of TTP patients.
Therefore, guidelines recommend a PLASMA score
for patients with suspected TTP.
Studies have confirmed that PLASMA score has high diagnostic value in Chinese TTP patients, and it has also been well verified
in domestic hospital studies.
The PLASMA score consists of 7 items, and the test results are available
within a short time after admission.
For patients with intermediate- to high-risk scores, plasma exchange should be performed quickly, which is valuable for early improvement
.

Second, this guideline adds a diagnostic flowchart
for TTP.
Unlike the diagnostic flowchart of other diseases, the diagnosis and treatment of patients with TTP are carried out
simultaneously.
In patients with suspected suspicion, plasma exchange and glucocorticoid therapy
can be started at the same time as ADAMTS13 activity, inhibitors, or IgG antibodies are sent.
Therefore, the flowchart is more in line with the diagnosis and treatment process of TTP and is conducive to guiding the actual work of
clinicians.

Third, this guideline has made certain adjustments to the treatment plan, and gives corresponding recommendations
for the treatment options of relapsed iTTP, cTTP in remission and TTP in pregnancy.
For example, if patients in remission of iTTP need to become pregnant, ADAMTS13 activity should be checked before pregnancy; ADAMTS13 activity is less than 10%, and rituximab therapy is recommended first, and pregnancy is considered at least 6 months after the end of treatment; Patients with iTTP in pregnancy are advised to closely monitor ADAMTS13 activity and start plasma exchange
once below 10%.

In addition, some new terms have been added to the prognosis part of the guidelines, in addition to retaining the original concepts of clinical remission and clinical recurrence, the concept of ADAMTS13 remission and ADAMTS13 relapse is introduced for the first time, emphasizing the main role of ADAMTS13 measurement in efficacy assessment and prognosis evaluation, and also proposing the definition of refractory TTP for the first time to help such patients start adequate rituximab treatment
early.

Yimaitong: Can you talk about the current status of TTP and the current status of treatment, and what unmet needs exist?

Foreign data show that the annual incidence of TTP is 2~6/million, the ratio of women to men is about 2:1, and the peak age of onset is 30~50 years old
.
Most patients with TTP have a sudden onset and critical condition, and a small number of patients have an insidious onset and atypical
clinical manifestations.
Inflammation, infection, pregnancy, etc.
are common causes
of TTP.
As a life-threatening emergency, increased disease awareness, early diagnosis and adequate treatment are key to
saving patients' lives.

Although some progress has been made in the diagnosis and treatment of TTP, TTP still poses a great challenge
to medical institutions and patients.
Due to the rarity of TTP, most healthcare facilities have limited
experience in managing the disease.
In addition, TTP diagnostic methods such as ADAMTS13 measurement cannot be carried out in some hospitals, and need to be transferred to the corresponding institutions for testing, and some hospitals may have problems such as plasma shortages, and it is challenging
for patients to receive sufficient doses of plasma exchange in a timely manner.

Yimaitong: Based on the latest clinical guidelines and treatment progress, can you please talk about the treatment principles and treatment methods of TTP?

TTP is mostly acute onset, if it cannot be treated in time, the mortality rate is high, and clinically when the disease is moderately or highly suspected, relevant treatment
should be started as soon as possible.
Plasmapheresis is preferred for iTTP, with a combination of glucocorticoids as
appropriate.
cTTP is dominated
by alternative treatments.

Therapeutic plasmapheresis is indicated for the treatment of iTTP and for initial emergency treatment
when there is a high clinical suspicion of TTP.
Glucocorticoids can reduce inflammation, protect organ function, inhibit autoantibody production, and are mainly suitable for iTTP treatment
.
Rituximab effectively restores plasma ADAMTS13 activity
by selectively depleting B lymphocytes and reducing ADAMTS13 inhibitors or IgG antibody titers.
Caplacizumab can block the binding of VWF A1 region to platelet glycoprotein GP1b, prevent platelet interaction with VWF, prevent microthrombosis, reduce end-organ damage, and can be used in the early stages of TTP onset
.
A number of foreign studies have confirmed that Caplacizumab can reduce the mortality and recurrence rate of patients, while saving plasma dosage and reducing hospital stay, especially the number of days of stay in the ICU, the emergence of this new drug has brought new changes
to the treatment of TTP.
In addition, corresponding studies have confirmed the efficacy of bortezomib, recombinant ADAMTS13 and other drugs, and further clinical evidence
can be accumulated in the future.

Prof.
Depei Wu

• Director of the Department of Hematology, Chief Physician, Professor, Doctoral Supervisor, The First Affiliated Hospital of Soochow University

• Executive Deputy Director of the National Clinical Research Center for Hematological Diseases

• Deputy Director of Jiangsu Hematology Institute

• Director of the Institute of Hematopoietic Stem Cell Transplantation, Soochow University

• Member of the 13th National Committee of the Chinese People's Political Consultative Conference

• Chairman of the Hematology Branch of the Chinese Medical Association

• Vice President of Hematologist Branch of Chinese Medical Doctor Association

• Vice Chairman of the Expert Committee of China Hematopoietic Stem Cell Donor Database

• Editor-in-Chief of Chinese Journal of Hematology