Can infection also cause rheumatism? Recurrent blood clots should be vigilant!

The patient's serum creatinine was found to be elevated 8 years before admission, about 100μmol/L, and no special treatment
was given.

One year ago, the patient found that both lower limbs were edema, rest can be relieved, and the self-conscious anuria is reduced, the blood creatinine is about 200 μmol/L, the blood creatinine is about 300 μmol/L before July, and the biochemical albumin (ALB) is 38.
1g/L before March; Serum creatinine (Scr) 398 μmol/L, urea nitrogen (BUN) 22.
76mmol/L, HCO3-18.
6mmol/L, urine routine showed pro3+, residual negative, ^24-hour urine protein quantification 3.
2g /2150ml, in the past 2-3 months, the edema of both lower limbs of the patient has worsened compared with before, and there is still no decrease
in urine output.

20 days ago, the patient had no cause for cough, mainly dry cough at first, occasionally coughed up sputum, had blood sputum, coughed up sputum once in 3-5 days, with wheezing, could not lie flat, not accompanied by fever, visited Changping Hospital of Traditional Chinese Medicine, blood routine showed hemoglobin (HB) 110 g/L, WBC 9.
96*10⁹/L, NE% 87.
5%, CRP 73 mg/L, chest x-ray showed increased density of left middle and lower lung, increased cardiac shadow, and anti-infective treatment for 3 days
.

14 days ago, the patient underwent chest CT showed bilateral lung infection, increased cardiac shadow, pericardial effusion, bilateral pleural effusion, continued anti-infection treatment for 3 days, symptoms were not relieved, 2 days ago visited the emergency department of our hospital, temperature fluctuation was 37-37.
5 °C, CRP 459 mg/L, ALB 30 g/L, Scr 531 μmol/L, BUN 25.
3 g/L, procalcitonin (PCT) 0.
19 ng/ml, blood routine showed HB 80 g/L, to ertapenem anti-infection, Diuresis, phlegm and other symptomatic treatment, the patient's symptoms improved slightly, this morning there was hemoptysis sputum for further diagnosis and treatment into the Department of
Nephrology.

Anamnesis: The patient developed hearing loss more than 40 years ago and still has tinnitus; It was found that blood pressure increased for 11 years, the highest blood pressure was 170-180/90mmHg, and amlodipine besylate tablets 5 mg Bid treatment was regularly taken in the past 2 years, and the self-reported blood pressure was controlled at 130-150/80-90mmHg; Viral hepatitis C was diagnosed 12 years ago; 7 years ago, he suffered a cerebral hemorrhage and underwent surgery, the details of which are unknown
.

Physical examination indicates:

Body temperature 37.
2°C, pulse 89 times/min, breathing 32 times/min, blood pressure 153/92 mmHg, clear consciousness, correct answers, indifferent expression, acute appearance
.
Breath sounds in both lungs are coarse, dry rales and crackles can be heard, and there is no exception
.

Laboratory tests show:

● Blood routine: white blood cells 9.
9x10 9/L, neutrophil percentage 93%, HB 80 g/L, platelet count 285x10⁹/L;

● Urinalysis: urine protein ++, urine glucose-, urine occult blood +, urine RBC 23/ul;

● Biochemistry: alanine aminotransferase (ALT) 29 U/L, glutamyl aminotransferase (AST) 45 U/L, glutamyl transferase (GGT) 80U/L;

● ALB 30 g/L, SCr 517 μmol/L, uric acid 552 μmol/L, urea 25.
56 mmol/L，CRP 63.
81mg/L；

● PCT 0.
174 ng/ml;

● Coagulation test: prothrombin time (PT) 12.
8s, fibrin degradation product 6.
49 ug/ml, D dimer 733 ng/ml；

● Myocardial injury related examination: brain natriuretic peptide (BNP) 3442.
9 pg/ml (100 pg/ml), creatine kinase isoenzyme (CK-MB) 1.
9ng/ml (<6.
6 ng/ml), myoglobin (Mb) 206 ng/ml (<106ng/ml), high-sensitivity troponin l (hsTnl) 0.
429 ug/ml (< 0.
3ug/ml); negative ANAs, normal immunoglobulins and complement;

● Chest CT showed obvious bilateral patchy exudation
.

Half a day after admission, the patient's vital signs were unstable, shortness of breath and transferred to the ICU
.

Seeing this, it seems that this patient has nothing to do with rheumatic immunity Wow! Don't worry, let's continue to look down~

Dr.
Shi Lianjie introduced that after being transferred to the ICU (2017.
08.
25), the patient underwent right femoral vein catheterization
.
However, postoperative ultrasound showed thrombosis around the catheter of the right femoral vein and external iliac vein
.
After anticoagulation (2017.
09.
02), a blood clot
occurred in the left iliac vein.
Within three days, thrombus
was also found in the right external iliac artery, common femoral artery, and proximal end of the superficial femoral vein.

Interestingly, troponin I and D dimers also fluctuate considerably during the course of the patient's disease, and thrombocytopenia
also occurred during anticoagulation with low molecular weight heparin.

Recurrent arterial or venous thrombosis? Could it be heparin-induced thrombocytopenia (HIT)? Or do you think of antiphospholipid syndrome (APS)?

Sure enough, after multidisciplinary consultation, as a consultant in the rheumatology department, Dr.
Shi Lianjie believed that the patient could not rule out the possibility of APS, and stopped the anticoagulation treatment of low molecular weight heparin and tested for relevant antibodies:

ACL-IgG 104 CU，ACL-IgA 342 CU ; B2GPI-IgG 666 CU，B2GPI-IgA 333 CU； Lupus anticoagulant (LA) negative

It seems that the possibility of APS in patients cannot be ruled out! In the subsequent anticoagulation of rivaroxaban, the patient's blood clot continued to form, and the relevant antibodies were positive
.

Coincidentally, the patient's ECG also showed ST-segment elevation, suggesting myocardial infarction
.
Is it a coincidence, or is it a myocardial infarction caused by APS?

In this case, Dr.
Shi Lianjie gave anticoagulation and anti-infection treatment, plus prednisone 30mg gd, and the patient's vital signs stabilized after one month of treatment
.
Repeat chest CT showed that the patchy exudation of both lungs had largely dissipated
.

It is reported that pathogen infection can lead to an increase in the level of antiphospholipid antibodies in the body's serum, and some infections are accompanied by corresponding clinical symptoms of APS ^[1].

So, is the APS in this case the patient himself, or is APS triggered by infection?

The doctor retested the patient for APS-related antibodies before 1 month of admission, and the results showed that the APS-related antibodies before the patient were all negative
.
It appears that this should be a case of infection-related APS
.

According to Dr.
Shi Lianjie, APS is an autoimmune disease related to antiphospholipid antibodies, which bind to targeted phospholipid molecules through B2-GPI and/or lupus anticoagulants, resulting in recurrent miscarriage, thrombosis, thrombocytopenia, and symptoms
of the nervous, heart, and skin systems.

Among them, severe antiphospholipid antibody syndrome can appear in the whole body small blood vessels or large and small blood vessels within a few days to weeks of extensive thrombosis, causing ischemia and necrosis of multiple organs and systemic symptoms, also known as catastrophic antiphospholipid antibody syndrome (CAPS), its classification criteria include the following:

1) There is evidence of involvement of 3 or more organs or tissues;

2) Clinical symptoms appear at the same time or within 1 week;

3) Pathological histopathology confirms the occurrence of intravascular thrombosis in at least 1 organ or tissue;

4) Laboratory tests confirmed the presence of positive antiphospholipid antibodies (twice positive with an interval of more than 6 weeks).

brief summary

Finally, Dr.
Shi Lianjie made the following summary for us:

1.
Thrombocytopenia is very important for early diagnosis of APS, but be alert to HIT of heparin;

2.
Clinical diagnosis and classification criteria for APS should not be confused;

3.
The cornerstone of APS treatment is anticoagulation, but immune-related therapy may increase patient benefit;

4.
CAPS is dangerous, and early active management can help improve patient outcomes and outcomes
.

Professor Li Chun commented on this case:

Thank you Dr.
Lianjie Shi for sharing this wonderful case
.
The patient's first department of concern was nephrology, and APS is common
in rheumatology.
When APS is first seen in other departments, how to make a rapid and accurate diagnosis of patients is an important content that clinicians need to master, and the possibility
of APS should be considered for patients with thrombocytopenia.

APS caused by infection requires special attention
in clinical work.
Infectious triggers of APS include: parvovirus B19, varicella zoster virus, rubella virus, toxoplasmosis, streptococcal and staphylococcal infections, G-bacteria infection, Mycoplasma pneumoniae, tetanus toxoid, etc
.
For infection-related APS, rapid and accurate diagnosis, aggressive symptomatic treatment, and etiological treatment are critical
to prognosis.

In addition, the accurate diagnosis of this patient is inseparable from the specimen storage of previous patients, and in clinical work, the establishment of specimen storage and reasonable follow-up procedures is also helpful for the diagnosis, treatment and management
of patients.

It is worth noting that the positive rate of antiphospholipid antibodies in severe COVID-19 infection is as high as 52%, and the high titer of antiphospholipid antibodies is also as high as 40%.