Hubungan Kadar Awal D-Dimer Terhadap Mortalitas Pada Pasien Covid-19 di RSUP DR. Sardjito

ADAM ALQUSTAR, dr.Juni Kurniawaty,M.Sc,Sp.An,KAKV;dr.Yunita Widyastuti,M.Kes,Sp.An,KAP,Ph.D

2022 | Tesis-Spesialis | ANESTESIOLOGI DAN TERAPI INTENSIF

Latar belakang : Pasien COVID-19 berat memiliki respon imun berlebihan sehingga badai sitokin dan Systemic Inflammatory Response Syndrome (SIRS) dapat terjadi. Respon inflamasi sistemik berlebihan dapat menyebabkan terjadinya jejas endotel sistemik dan hiperkoagulasi sehingga terjadi makrotrombosis dan mikrotrombosis sistemik. D-dimer dilepaskan ketika plasmin dan enzim fibrinolitik memecah fibrin sebagai bentuk proses trombosis endovaskuler. Oleh karena itu, penilaian konsentrasi D-dimer dalam sirkulasi merupakan tes yang sensitif untuk mendiagnosis status trombosis (termasuk emboli paru dan disseminated intravascular coagulation (DIC)) serta prediksi terhadap kejadian mortalitas. Tujuan : Menilai hubungan kadar awal D-Dimer terhadap kejadian mortalitas pasien COVID-19. Metode : Metode studi observasional kohort retrospektif dilakukan dengan mengambil data sekunder dari rekam medis pasien terkonfirmasi COVID-19 yang dirawat di RSUP dr. Sardjito pada Maret-Desember 2020 yang dilakukan pemeriksaan D-Dimer selama perawatan. Data kadar D-dimer saat admisi dan kejadian mortalitas dikumpulkan untuk menghitung cut-off optimal menggunakan kurva ROC. Hubungan antara kadar D-dimer dengan mortalitas dianalisis menggunakan chi-square test. Analisis multivariat dilakukan dengan regresi logistik untuk mengontrol efek perancu variabel lain. Kaplan Meier dan Cox Regression digunakan untuk mengetahui kesintasan subjek berdasarkan nilai D-dimer. Pengujian dinyatakan signifikan apabila p < 0,05. Hasil : Berdasarkan kurva ROC, cut-off point D-dimer admisi senilai 669 ng/ml memiliki sensitivitas 71,2% dan spesifitas 62,2%. Pasien dengan D-dimer admisi > 669 ng/ml memiliki hubungan signifikan terhadap terjadinya mortalitas (p=0,000). Analisis multivariat menunjukkan bahwa D-dimer tetap memiliki hubungan signifikan terhadap mortalitas (OR 3,269;CI 1,655-6,457;p=0,001), dengan faktor perancu usia (p=0,000) dan indeks massa tubuh (p=0,017). Berdasarkan Kaplan Meier, didapatkan waktu kesintasan kelompok D-dimer admisi > 669 ng/ml lebih singkat (25,84 hari) dibandingkan D-dimer admisi <669 ng/ml (37,98 hari) (p = 0,000). Analisis cox regression menunjukkan D-dimer saat admisi merupakan variabel yang signifikan berpengaruh terhadap kesintasan pasien COVID-19 (p = 0,004; HR: 2,323; 95% CI: 1,301-4,147), dengan umur (p = 0,000) dan BMI (p=0,032) sebagai faktor perancu. Kesimpulan : Kadar awal D-dimer >669 ng/mL berhubungan positif dengan tingkat mortalitas. Tingkat mortalitas pasien COVID-19 dengan kadar D-dimer admisi > 669 ng/mL sebesar 3 kali lipat, dengan usia dan BMI sebagai faktor perancu.

Background : In severe COVID-19 infection, the immune response can be exaggerated and cause a systemic cytokine storm that triggers systemic inflammatory response syndrome (SIRS). Excessive systemic inflammatory response can lead to systemic endothelial injury (endotheliopathy) and a hypercoagulable state that increases the risk of systemic macrothrombosis and microthrombosis. D-dimers are released when plasmin, a fibrinolytic enzyme, breaks down fibrin and is a reflection of the endovascular thrombosis process. Assessment of circulating D-dimer concentrations is a sensitive test for diagnosing thrombotic status (including pulmonary embolism and DIC) and predicting mortality event in patient contracted with covid-19. Aim: Assessing D-Dimer levels on admission correlation towards mortality case in COVID-19 patients. Methods : The study was design used a retrospective cohort observational study method by taking secondary data from the medical records of COVID-19 confirmed patients treated at Dr. Sardjito from March to December 2020 who underwent D-Dimer testing during therapy. D-Dimer levels on admission and death events were collected to calculate the optimum cutoff using receiver operating characteristics curves (ROC). Using the chi-square test, we investigated the association between D-dimer levels and mortality A multivariate analysis with logistic regression was conducted to compensate for the confounding effects of other factors. In addition to Kaplan Meier and Cox Regression, the D-dimer value was analyzed to measure the subject's survival. Two-tailed P values <0.05 were considered statistically significant. Result : Based on the ROC curve, the D-dimer admission cut-off point of 669 ng/ml had a sensitivity of 71.2% and a specificity of 62.2%. Patients with D-dimer levels >669 ng/ml at admission had a higher risk of mortality (p=0,000). Despite the confounding effects of age (p=0,000) and body mass index (p=0.017), multivariate analysis revealed a significant association between D-dimer and mortality (OR 3,269; CI 1,651-6,457; p=0.001). According to Kaplan Meier, the D-dimer >669 ng/ml group had a shorter survival time (25.84 days) than the D-dimer < 669 ng/ml group (37.98 days) (p = 0.000). Cox regression analysis revealed that D-dimer at admission was a significant predictor of survival in COVID-19 patients (p = 0.004; HR: 2.323; 95% CI: 1.301-4,147), with age (p = 0.000) and BMI (p=0,032) as confounding variables Conclusion : Initial D-dimer level >669 ng/mL significantly related to mortality rate in patient contracted to Covid 19. D-dimer > 669 ng/mL increase three-fold to mortality level, with age and BMI as a counfounding factor.

Kata Kunci : COVID-19, D-Dimer, Koagulopati, Trombosis, Mortalitas