​Thrombocytopenia?

*Only for medical professionals to read for reference.
RA and thrombocytopenia, how do biological preparations take care of both? Rheumatoid arthritis (RA) is not only joint pain, but also affects multiple organs and systems throughout the body
.

When the blood system involved, the patient may anemia, thrombocytopenia occurred
.

Thrombocytopenia may cause severe bleeding
.

How should we diagnose and treat RA patients with thrombocytopenia in the clinic? In this issue, Dr.
Zhang Yingying from Zhejiang Provincial People's Hospital will introduce a related case to us.
Professor Li Yasong from Zhejiang Provincial People's Hospital commented on the diagnosis and treatment process
.

Case details Basic situation of the patient: female, 58 years old
.

Main complaint: Polyarthralgia of extremities for more than 10 years, worsening in April
.

History of present illness: The patient began to develop polyarthralgias in extremities with no obvious cause more than 10 years ago.
He visited the local hospital for many times.
He considered "rheumatoid arthritis" and was given long-term oral Chinese medicine treatment, but the effect was not good
.

Since 2015, thrombocytopenia has been found, and the progressive decline has occurred
.

In 2018, I went to a local hospital for hemoptysis, improved bone marrow and other related examinations, and considered "immune thrombocytopenia".
During this period, the treatment is unknown
.

In 2019, the platelet count dropped to 20,000 and improved after treatment with high-dose glucocorticoid (maximum methylprednisolone 48mg/d)
.

Glucocorticoids were discontinued in January 2021.
At present, there are about 37,000 platelets.
There are obvious swelling and pains in multiple joints of the limbs, accompanied by morning stiffness lasting for several hours, and limited activities
.

Admitted to hospital for further diagnosis and treatment
.

Past history: The patient has a history of "hypertension, diabetes"
.

Denied history of hematological diseases, heart disease, etc.
; denied history of infectious diseases such as hepatitis and tuberculosis; denied history of trauma; underwent cervical cancer surgery in 2006, preoperative chemotherapy, postoperative radiotherapy; history of blood transfusion, specific unknown, no transfusion reaction
.

Physical examination: body temperature: 36.
4℃, respiration: 19 beats/min, pulse: 95 beats/min, blood pressure: 132/82 mmHg, no obvious abnormalities in cardiopulmonary and abdominal examination
.

The lower limbs were not swollen, the metacarpophalangeal and toe joints on both sides were obviously swollen, and the joint movement of the upper limbs was limited
.

Auxiliary examination: blood routine + C-reactive protein (CRP): white blood cells and hemoglobin are normal, platelet count 30×109/L↓, CRP 21 mg/L↑, erythrocyte sedimentation rate (ESR) 68 mm/h↑; tumor markers rise High: CA125 55 U/ml, CA199 46 U/ml; anti-nuclear antibody (ANA), anti-neutrophil cytoplasmic antibody (ANCA), cardiolipin antibody (ACA), rheumatoid factor (RF, <20 IU/ ml), HLA-B27 negative, anti-mutant citrullinated vimentin (MCV)>1000 IU/ml, anti-cyclic citrullinated peptide antibody (CCP) 2372.
6 IU/ml, anti-perinuclear factor (APF) 1:40 ++, anti-keratin antibody (AKA) 1:40+++
.

Diagnosis: After treatment of RA, immune thrombocytopenia, diabetes, hypertension, and cervical cancer
.

Treatment: prednisone 25 mg qd + hydroxychloroquine (HCQ) 0.
1 g tid + abatacept 125 mg, once a week subcutaneous injection, supplemented with ricodine 20 mg tid to increase platelets, lower blood sugar, lower blood pressure, and anti-osteoporosis treatment
.

After discharge from the hospital, he continued to use abatacept + HCQ treatment, and so far, the hormone reduction has been smooth, and the dose is now reduced to 12.
5 mg/d
.

Efficacy evaluation: After treatment, the patient's joint swelling and pain, morning stiffness and other symptoms were basically relieved, CRP and ESR decreased to normal, and platelets stabilized above 70×109/L (Figure 1)
.

Figure 1: Changes in curative effects of patients after treatment.
Experts comment that thrombocytopenia is one of the common clinical manifestations of rheumatic immune diseases, which can lead to an increased risk of bleeding in patients.
In severe cases, it may be life-threatening
.

According to the recommendations of the 2020 "Consensus of Experts on the Diagnosis and Treatment of Thrombocytopenia in Adults in China", platelet count <100×109/L is defined as the criterion for thrombocytopenia
.

Immune factors and the consumption of thrombosis are the main mechanism of thrombocytopenia in diffuse connective tissue diseases.
For example, the most common cause of thrombocytopenia in patients with systemic lupus erythematosus (SLE) is increased platelet destruction and excessive consumption [1]
.

RA is an autoimmune disease.
The disorder of its immune function can lead to the occurrence of thrombocytopenia.
There may be some common immune mechanisms between the two.
For example, the abnormal activation of T cells is considered to be the central link in the development of RA.
Different subgroups of T cells play different roles in the pathogenesis of RA [2-3]; similarly, in the process of immune thrombocytopenia, T cells also play an important role-abnormal T cell response (especially the filtration of the spleen).
Vesicle helper T cells) can stimulate the proliferation and differentiation of self-reactive B cells, and the anti-platelet autoantibodies they produce help macrophages to swallow platelets; in addition, CD8+ T cells may increase platelet apoptosis and hinder The maturation of megakaryocytes destroys platelet production and promotes platelet reduction [4-5]
.

For the treatment of thrombocytopenia, it is very important to clarify the cause
.

Detailed and targeted medical history inquiry and examination can help prompt the cause of thrombocytopenia
.

The principle of treatment is to treat the primary disease first.
After the primary disease is relieved, the factors that induce thrombocytopenia are controlled, and the count level will be improved [1]
.

Therefore, for thrombocytopenia secondary to autoimmune diseases, the primary disease should be treated first
.

However, it should be noted that drugs can also mediate drug-induced thrombocytopenia through immune or non-immune mechanisms.
As research reports have shown, tacrolimus [1], methotrexate [1], IL-6 inhibitors [ 6] May cause thrombocytopenia
.

Therefore, in clinical treatment, drugs should be selected reasonably, taking into account the treatment of the primary disease and the improvement of thrombocytopenia
.

In this case, the patient has a long course of RA and obvious symptoms such as joint swelling and pain.
In the past 5-6 years, the number of platelets has been gradually decreased
.

Through medical history, physical examination, and auxiliary examinations to diagnose the cause, it is determined that the cause of the patient's platelet decline is immune thrombocytopenia (secondary to RA)
.

In the treatment of drugs, hormones can be used for short-term treatment of RA and also the first-line treatment for thrombocytopenia; HCQ is a traditional synthetic disease-improving anti-rheumatic drug (csDMARD) commonly used in the treatment of RA, with good safety and tolerability; and The biological agent Abatacept is a selective T cell costimulatory regulator, which inhibits the activation of T cells by binding to CD80 and CD86 on antigen presenting cells
.

Research data at home and abroad have shown that abatacept can effectively improve the clinical symptoms of RA patients, control the disease activity, and improve the structure and function of the joints [7-9]
.

As a biological agent targeting T cells, in the treatment of this case, abatacept, as the patient's RA symptoms relieved, the number of platelets gradually increased, and the patient's hormone reduction was smooth during the treatment, and the thrombocytopenia did not repeat
.

During the follow-up, the patient did not develop infection
.

In addition, the patient has a history of "hypertension, diabetes" and is a high-risk population of cardiovascular disease.
Abatacept has the advantage of reducing the risk of cardiovascular disease in RA patients
.

The diagnosis and treatment of this case provides a new drug choice for the treatment of RA patients with immune thrombocytopenia in the clinic
.

 Expert profileProfessor Li Yasong Doctor of Medicine, Chief Physician, Master Tutor Director of Department of Rheumatology and Immunology, Zhejiang Provincial People's Hospital Chairman of Zhejiang Provincial Committee of Internal Medicine, Vice Chairman of Rheumatology Branch of Zhejiang Medical Association, Vice Chairman of Rheumatology Branch of Zhejiang Integrative Medicine Association, Vice Chairman of "Chinese General Practice" and other journals, Zhejiang Province "New Century 151" "Talent Project" training object: Dr.
Yingying Zhang, Attending Physician, Department of Rheumatology and Immunology, Zhejiang Provincial People's Hospital, and a postgraduate student, Youth Member of the Rheumatology and Immunology Branch of Zhejiang Medical Doctor Association, Orthopedics Specialty Committee of the Osteoporosis Branch of the Chinese Society of Gerontology and Geriatrics, Zhejiang Province Member references: [1] Chinese Medical Association Internal Medicine Branch.
Chinese Medical Association Internal Medicine Branch[J],2020,59(7):498-510.
[2]Cope AP,Schulze-Koops H,Aringer M.
The central role of T cells in rheumatoid arthritis[J].
Clin Exp Rheumatol,2007,25(5 Suppl 46):S4-11.
[3]Jiang Q,Yang G,Liu Q,et al.
Function and Role of Regulatory T Cells in Rheumatoid Arthritis[J].
Front Immunol,2021,12:626193.
[4]Ji X,Zhang L,Peng J,et al.
T cell immune abnormalities in immune thrombocytopenia[J].
J Hematol Oncol,2014,7 :72.
[5]Audia S,Mahévas M,Samson M,et al.
Pathogenesis of immune thrombocytopenia[J].
Autoimmun Rev,2017,16(6):620-632.
[6]Jung Sun Lee,Ji Seon Oh , Seokchan Hong, et al.
Tocilizumab-induced Thrombocytopenia in Patients with Rheumatoid Arthritis[J].
Journal of Rheumatic Diseases,2019,26(3):186-190.
[7]Schiff M,Keiserman M,Codding C,et al.
Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate[J].
Ann Rheum Dis,2008,67(8): 1096-1103.
[8]Weinblatt ME,Schiff M,Valente R,et al.
Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis:findings of a phase IIIb,multinational,prospective,randomized study[J].
Arthritis Rheum,2013,65(1):28-38.
[9]Schiff M,Weinblatt ME,Valente R,et al.
Head-to-head comparison of subcutaneous abatacept versus adalimumab for rheumatoid arthritis:two-year efficacy and safety findings from AMPLE trial[J].
Ann Rheum Dis,2014,73(1):86-94.
This article is only used to provide scientific information to medical and health professionals, and does not represent the platform's position
.