Pediatric patients with MPP complicated with thrombosis was rarely reported. Cases with mild pulmonary embolism(PE)may be asymptomatic, while severe cases may suffer from complex and diverse manifestations, difficult recognition and poor prognosis.All the children continued to have fever, and the imaging progress was consistent,despite the administration of appropriate macrolide antibiotics,with the diagnosis of refractory Mycoplasma pneumoniae pneumonia(RMPP). This suggests that RMPP is the most strongly associated risk factor for MPP-associated thrombosis. Attention should be paid to the manifestations of embolism in these children, so as to achieve early diagnosis, active treatment and improve the prognosis.
The mechanism underlying thrombosis due to MPP remains unknown. Narita, M proposed the pathological mechanism of extrapulmonary manifestations due to MP infection can be classified into three categories;the first is a direct type in which bacterial cell membrane lipoproteins induces inflammatory cytokines locally, the second is an indirect type which autoimmunity through the cross-reaction between MP bacterial components and human cells,and the third is a vascular occlusion type in which vasculitis and/or thrombosis with or without systemic hypercoagulable state induced by the bacterium15.Certain studies have demonstrated that patients of mycoplasma pneumoniae pneumonia associated thrombosis were positive for anticardiolipin antibodies, β2‑glycoprotein antibodies or lupus anticoagulant antibodies 16,17. Anticardiolipin antibody, β2‑glycoprotein antibody and lupus anticoagulant antibody are all antiphospholipid antibodies that react with phospholipids, phospholipid‑protein complexes and phospholipid‑binding proteins 18,19. The antiphospholipid antibodies contribute to thrombosis through protein phosphatase 2A activation via apolipoprotein E receptor 2, disabled‑2 and src homology domain‑containing transforming protein 1 complex formation in the endothelium20. These aforementioned antibodies were transient and became negative in certain patients 3‑6 months after initial disease onset16,17.
Thrombosis can occur in the vessels of any part of the body (see Table 1)16. All 14 patients developed Thrombosis on day 5‑22 and were hospitalized on day 5-18 from onset. Cerebral embolism and splenic artery embolism were found earlier, which were found on the 5th to 6th day of the course of disease.It is possible that these forms of thrombosis are often very symptomatic, so they could be diagnosed earlier that other forms.The main manifestations of pulmonary embolism are chest pain, hemoptysis, neck pain, dyspnea, etc. children with cerebral embolism mainly start with abnormal limb movement and paralysis. The manifestations of lower limb arterial embolism are weak arterial pulsation, reduced skin temperature, cyanosis, inflexible activity, etc.Due to the hidden onset of some patients, we should pay attention to the changes of children's condition. For those who have sudden chest pain, hemoptysis and sputum and whose condition has not recovered after active treatment, we should be alert to the possibility of thrombosis, and improve the imaging examination in time.
In this study, 14 children were accompanied by other complications except thrombosis.Among them, 13 children had small to medium amount of pleural effusion, 6 children had hepatic damage, and 3 children had rash.It is worth noting that 2 of them had no obvious embolism manifestations in the early stage , in the later stage of the disease,The pulmonary imaging showed necrosis in the consolidation of lobar lung, accompanied by multiple thin-walled or non walled cavities. Embolism was occasionally found by enhanced pulmonary CT.At present, the causes and mechanisms of NP are mainly believed to be related to pulmonary capillaries in the necrotic area are blocked by thrombus, which can cause pulmonary parenchymal ischemia and necrosis under the action of infammatory factors 21.Pulmonary parenchyma is ischemic, infarcted and necrotic, and a cavity is formed after the necrotic matter is discharged 22, 23.It is worth noting that the pulmonary embolism in this study is not consistent with the location of necrotizing pneumonia. It is considered that some children may have multiple vascular thrombotic occlusion except for large vessel embolism.
The peak value of venous blood CRP in 14 children increased significantly and LDH, FER,the percentage of neutrophils all increased significantly. It is considered that it is related to the serious systemic inflammatory response caused by mycoplasma pneumoniae infection.D-dimer increased in 14 children, suggesting hypercoagulable state 24.One patient had a slight increase in D-Dimer (0.5 mg / L), the reason is perhaps that we did not timely monitor its peak.The eighth child was examined for D-dimer of 0.5 mg /L on admission. On the second day of admission, he had neck pain, shortness of breath. The D-dimer increased to 11 mg / L. The cardiac ultrasound and pulmonary CTA were performed to find cardiac and pulmonary artery thrombosis.Therefore, for children at high risk of thrombosis, D-dimer should be dynamically monitored to guide diagnosis and treatment.D-dimer is the smallest fragment of fibrin degradation products. The increase of its level indicates the existence of hypercoagulable state and active fibrinolysis, which is of great significance for the early diagnosis of thrombotic diseases.D-dimer has high negative predictive value in the diagnosis of thrombotic diseases.Taking D-dimer < 0.5 mg/L as the boundary value and evaluating it in combination with clinical manifestations is an important auxiliary examination for evaluating patients with suspected pulmonary embolism 25. For pulmonary embolism, the detection sensitivity of plasma D-dimer can reach 92% ~ 100%26. Beijing Children's Hospital observed that mean D-dimer level of 43 children with MPP-associated thrombosis was 11.1 ± 12.4 mg/L16.
Angiography is the gold standard for the examination of deep venous thrombosis and pulmonary embolism, but its clinical application in children is limited due to its invasive and certain risk 27.CTA is a non-invasive method that can be applied to the examination of systemic blood vessels. Its trend to replace DSA as the gold standard is becoming more and more obvious.For children with cerebral infarction,MRI + MR angiography(MRA) can clearly show the abnormal signal shadow of intracranial and the development of vascular stenosis and occlusion, so as to guide clinical diagnosis and treatment.MRI is the first choice for children with cerebral infarction. MRA is helpful to clarify the responsible artery. Diffusion weighted imaging (DWI) sequence can indicate the acute infarct.Cases of splenic infarction can be clearly diagnosed by CTA.For children with limb arterial embolism, ultrasonography is the first choice, which can clarify the formation of lower limb arteriovenous thrombosis. If necessary, low tube voltage combined with low contrast CTA can better show the whole picture of limb vessels.
The major treatment for pediatric patients with acute PE is anticoagulant therapy.The American Society of Hematology (ASH) guideline panel recommends using anticoagulation rather than no anticoagulation in pediatric patients with symptomatic deep vein thrombosis (DVT) or PE. Either anticoagulation or no anticoagulation is recommended be used in pediatric patients with asymptomatic DVT or PE.The ASH guideline panel suggests against using thrombolysis followed by anticoagulation; rather, anticoagulation alone should be used in pediatric patients with DVT.The guideline panel also suggests against using thrombolysis followed by anticoagulation; rather, anticoagulation alone should be used in pediatric patients with submassive PE.It is suggested that thrombolysis followed by anticoagulation, rather than anticoagulation alone, in pediatric patients with PE with hemodynamic compromise should be given .The ASH guideline panel suggests against using thrombectomy followed by anticoagulation; rather, anticoagulation alone should be used in pediatric patients with symptomatic DVT or PE; Inferior vena cava (IVC) filter should not be used; anticoagulation alone should be used in pediatric patients with symptomatic DVT or PE.Anticoagulation should be used for ≤3 months rather than anticoagulation for >3 months in pediatric patients with provoked DVT or PE;Anticoagulation should be used for 6 to 12 months rather than anticoagulation for >6 to 12 months in pediatric patients with unprovoked DVT or PE28.
There is no unified standard for the treatment of MP pneumonia complicated with intracardiac thrombosis, mainly including anticoagulant therapy, thrombolytic therapy and surgical thrombectomy.Thrombolytic therapy of intracardiac thrombus in children is still inexperienced and needs further research.In this paper, only 2 of the 14 children with cardiac thrombosis were treated with urokinase thrombolysis. The other children were treated with low molecular weight heparin calcium anticoagulation and oral aspirin to inhibit platelet aggregation.The general course of treatment of heparin drugs is 5 ~ 10 days. Attention should be paid to monitoring APTT during medication. Vitamin K antagonists should be used after 12 ~ 48 hours of heparin treatment. The commonly used is oral warfarin, anticoagulant treatment ≤ 3 months. The international standardized ratio should be monitored during the period, which is generally maintained at 2 ~ 3 28, 29.Most patients with acute pulmonary embolism receive appropriate anticoagulant therapy and have a good prognosis, but we need to be vigilant about the loss of embolus during treatment.One case of pulmonary embolism complicated with right ventricular thrombosis had shoulder pain, irritability and other symptoms during treatment. Cardiac ultrasound showed that the thrombus attached to the wall of the heart fell off. The symptoms of the child improved for about 1 hour, without dyspnea, chest pain, hemoptysis and other manifestations, and the prognosis was good.For pulmonary embolism and cardiac thrombosis,The time of thrombus disappearance was followed up for 1 ~ 3 months.There is no clear data on the prognosis of pulmonary embolism. Canada's follow-up of 405 children with pulmonary embolism and deep venous thrombosis showed that the child mortality rate was 16% 30.Except 3 cases of external cerebral embolism with obvious sequelae, the other 11 cases had good curative effect, and no one died.
The clinical manifestations of Mycoplasma pneumoniae pneumonia complicated with thrombosis are diverse, which is easy to be misdiagnosed and missed. For such children, the blood inflammatory index and D-dimer level should be dynamically monitored, the relevant imaging examination should be improved in time, the diagnosis should be made clear, and anticoagulation, thrombolysis and other treatment should be carried out as early as possible, so as to improve the prognosis of children and reduce the mortality and disability rate.