ABSTRACT
Background: Haemostatic impact of SARS-CoV- 2 infection and multisystem inflammation syndrome (MIS-C) in children is still under consideration. Aim(s): To investigate COVID-19 coagulopathy in hospitalized children due to SARS-CoV- 2 infection. Method(s): A retrospective review on coagulation parameters of children with SARS-CoV- 2 infection and MIS-C hospitalized from August 2020 until December 2021 was conducted in our Haemostasis and Thrombosis Centre. Values of D-dimers, fibrinogen, antithrombin, protein C, PT, APTT and the respective coagulation factors were recorded at hospital admission, in multiple time points during hospitalization and upon hospital discharge. Statistical analysis was performed with Mann-Whitney test and t-test. Result(s): In total, 733 children (boys: 62.7%) of mean age 4.9 +/- 5.4 years (0-18) were investigated. Patients were categorized as follows: Patients with mild/moderate (87.6%) or severe COVID-19 (6.3%) and patients with MIS-C (6.1%). Severe, in comparison with mild/moderate patients, had significantly increased admission D-Dimer values (34.3 vs. 2.9 mug/ml), PT (25.2 vs. 14.3, sec), APTT (62.5 vs. 34.6, sec), fibrinogen (362.5 vs. 259.5, mg %), and factor VIII values (165.4 vs. 126.9, %). MIS-C children had significantly increased admission values of fibrinogen (501 mg %), factor VIII (200.3, %) and statistically decreased factor VII values (38.2 vs. 56.6, %), antithrombin values (81.5 vs. 98.1, %) and protein C values (52.4 vs. 63.3, %) in comparison with mild/ moderate patients. Interestingly, MIS-C children had markedly increased fibrinogen and factor VIII values even in comparison with severe patients. During hospitalization, PT, APTT, fibrinogen, factor VIII values were significantly decreased and factor VII values increased. Also, D-Dimers values were markedly decreased but without statistical significance. No child died and thrombosis was noticed in three children, one of which was suffered from MIS-C. Conclusion(s): Our COVID19 hospitalized children showed a mild deterioration of coagulation parameters. However, in children with MIS-C and severe COVID19, these coagulation parameters were found mainly affected.
ABSTRACT
Background: The polymorphism C>T substitution in position 677 (C677T) of the encoding gene of methylenetetrahydrofolate reductase (MTHFR), creates a thermolabile enzyme with reduced activity that may predispose to hyperhomocysteinemia , an established risk factor for arterial thrombosis and premature atherosclerosis and a probable risk factor for venous thromboembolic disease and its recurrence in the general population. There are conflicting results as to the role of the MTHFR C677T polymorphism as a risk factor for thrombosis. Although the homozygous substitution is often associated with hyperhomocysteinemia, mainly in folate deficiency, a clear association between this genetic marker and thrombosis has not yet been established. Aims: Primary aim was to evaluate the prevalence of mutant C677T MTHFR and its association with thrombosis in the Greek paediatric population. Secondary aim was to evaluate whether different MTHFR genotype is associated with evidence of activation of coagulation cascade through increased factor VIII activity. Methods: Data were retrospectively collected from children referred to our Haemostasis and Thrombosis Centre for laboratory screening of thrombophilia between 2018 and 2020. Some of them were checked due to history of thrombosis. Children were categorized according to MTHFR C677T genotype. FVIII Coagulant activity (%) was measured by One Stage Assay, away from acute thrombosis. The identification of mutations was based on polymerase chain reaction (PCR) and reverse- hybridization. Statistical analysis was performed with t-test and ANOVA. Results: A total of 688 children (boys: 49 %) of mean age 8.9± 8 years (0-18) were investigated. Twelve percent (81/688) of them had history of thrombosis, mainly venous thromboembolic disease. Children were categorized as follows: homozygous MTHFR C677T (15%), heterozygous (47%) and normal (38%). There was thrombosis history in 12% of homozygous MTHFR C677T, 11% heterozygous and 12 % of normal, fact showing that there is no association between MTHFR C677T genotype with thrombosis. Children with homozygosity MTHFR C677T, compared to children with heterozygosity and normal MTHFR C677T showed increased factor VIII values (132.8 vs 126.4 and 131.6, %, respectively), but without statistically significant difference. However, independently of MTHFR C677T genotype, mean factor VIII values were significantly increased in all children, with thrombosis history when they were compared to children without thrombosis history (161.3 vs 125.1, %, p<0.001). Interestingly, in children with thrombosis, mean factor VIII level was statistically increased in heterozygous and normal MTHFR C677T in contrast to children with MTHFR C677T homozygosity, in whom no statistically significant increase was found (166.9 vs 121.4, %-p<0.05, 160.2 vs 127.6, %-p<0.05 and 148.3 vs 130.6, %-p>0.05, respectively). Finally, it should be noticed that during the year 2020 mean factor VIII values were much increased in all children in comparison to the years 2018, 2019 and 2021 (137 vs 129, 123 and 127, %, respectively), probably reflecting the effects of unknown pandemic COVID-19 which initiated in 2020, and showing that factor VIII could be an evidence of stress condition. Summary/Conclusion: There is no probably association between MTHFR C677T genotype and thrombosis in our paediatric population. Moreover, it was not proved that different MTHFR genotypes affect factor VIII activity.
ABSTRACT
Background: Pulmonary embolism (PE) is reported in around2.6-8.9% of COVID-19 hospitalized adult patients, but it is very rare in children and adolescents with symptomatic infection from SARS-CoV-2. Aims: This is the case of a15-year-old male patient with COVID-19 complicated by deep vein thrombosis (DVT) who developed PE. Methods: The patient presented with fever and a four-day history of pain and swelling of the right lower limb, without any history of injury. It is notable that15 days before admission, he experienced diarrhea, vomiting and low-grade fever for 48 hours. The adolescent boy had short stature and was rather overweighted for his age and gender (body mass index:25.2 kg/m2), while over the last two years he was receiving anastrozole (aromatase inhibitor), for height increase. Results: On admission, due to pain, limited mobility of the right limb and edema of the ipsilateral knee, a triplex ultrasound was performed that revealed DVT extended from the right iliac to the popliteal vein. RT-PCR for SARS-CoV-2 was positive, while the rest of the laboratory results showed a prolongation in prothrombin time (16.3 seconds, normal values:10-14 sec), elevated d-dimers (10 mg/dl, n.v.: < 0.5 mg/dl), high levels of factor VIII (214 IU/dl, n.v: 50-150 IU/dl), low levels of antithrombin (36 IU/ml, n.v.: 80-120 IU/ml) and increased ferritin (346 μg/L, n.v.:10-150 μg/L). Initial management consisted of antibiotic therapy plus anticoagulation with subcutaneous low molecular weight heparin (LMWH) i.e. tinzaparin in therapeutic dose. Soon after admission the patient developed severe hypotension with low diastolic blood pressure, refractive to IV normal saline boluses while his oxygen saturation dropped to 94% few hours later. A CT pulmonary angiogram (CTPA) was performed revealing a big thrombus with longitudinal diameter of3 cm, in the left pulmonary artery, establishing the diagnosis of PE on the ground of DVT. After PE diagnosis, the patient was transferred to the intensive care unit (ICU) for 48 hours, and subsequently at the special SARS-CoV-2 ward for 4 weeks. He completed a ten-day course of intravenous dexamethasone and anticoagulation treatment was switched to oral warfarin, after completion of three weeks of LWMH. Apart from COVID-19 whose hypercoagulable physis is already well-established the patient had additional risk factors predisposing to thromboembolic episodes. More precisely, he was overweight and under aromatase inhibitor therapy (which can be procoagulant by increasing testosterone levels). Moreover, the preexisting symptoms from the gastrointestinal system, could have predisposed him to DVT in view of dehydration and increased viscosity. On top of it, it is noteworthy that the patient had excessive screen time for his tele-education the last three weeks prior to the onset of VTE, meaning there were long periods of immobilization. Additionally, during the course of COVID-19 infection he had low levels of antithrombin, a serious prothrombotic condition attributed to the disease. Summary/Conclusion: This case underlines the fact that pediatric patients with COVID-19, are predisposed to the development of thromboembolic events, especially in the presence of preexisting prothrombotic risk factors. Larger studies in pediatric population with SARS-CoV-2 infection are needed, for the establishment of recommendations regarding risk evaluation, hemostatic monitoring and application of anticoagulation in outpatient, as well as hospitalized patients.