Evaluation of coagulation function by rotation thromboelastometry in critically ill patients with severe COVID-19 pneumonia

Critically ill patients with COVID-19 pneumonia suffered both high thrombotic and bleeding risk. The effect of SARS-CoV-2 on coagulation and fibrinolysis is not well known. We conducted a retrospective study of critically ill patients admitted to an intensive care unit (ICU) a cause of severe COVID-19 pneumonia and we evaluated coagulation function using rotational thromboelastometry (ROTEM) on day of admission (T0) and 5 (T5) and 10 (T10) days after admission to ICU. Coagulation standard parameters were also evaluated. Forty patients were enrolled into the study. The ICU and the hospital mortality were 10% and 12.5%, respectively. On ICU admission, prothrombin time was slightly reduced and it increased significantly at T10 (T0=65.1±9.8 vs T10=85.7±1.5, p=0.002), while activated partial thromboplastin time and fibrinogen values were higher at T0 than T10 (32.2±2.9 vs 27.2±2.1, p=0.017 and 895.1±110 vs 332.5±50, p= 0.002, respectively); moreover, whole blood thromboelastometry profiles were consistent with hypercoagulability characterized by an acceleration of the propagation phase of blood clot formation [i.e., CFT below the lower limit in INTEM 16/40 patients (40%) and EXTEM 20/40 patients (50%)] and significant higher clot strength [MCF above the upper limit in INTEM 20/40 patients (50%), in EXTEM 28/40 patients (70%) and in FIBTEM 29/40 patients (72.5%)]; however, this hypercoagulable state persists in the first five days, but it decreases ten day after, without returning to normal values. No sign of secondary hyperfibrinolysis or sepsis induced coagulopathy (SIC) were found during the study period. In six patients (15%) a deep vein thrombosis and in 2 patients (5%) a thromboembolic event, were found; 12 patients (30%) had a catheter-related thrombosis. ROTEM analysis confirms that patients with severe COVID-19 pneumonia had a hypercoagulation state that persisted over time.

Gestational diabetes mellitus is associated with antenatal hypercoagulability and secondary hyperfibrinolysis: a case control study of Chinese women

Background: To determine the relationship between gestational diabetes mellitus (GDM) and coagulation/fibrinolysis abnormality in antenatal Chinese women. Methods: Case control study. Fifty women had GDM and 132 did not (the NGDM group) grouping by the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Maternal plasma biochemistry and previous medical history were collected from perinatal health records. Antenatal coagulation/fibrinolysis activity(CFA) parameters was assessed using thromboelastography and routine CFA parameters respectively. Univariate and multiple regression analyses were used to evaluate the associations between GDM and CFA parameters. Results: The women with GDM were significantly older than those without GDM (30.3 vs. 28.6 years, P=0.012). Compared with the NGDM group, the GDM group had a significantly higher prevalence of cesarean delivery (56.0% vs. 37.9%, P=0.027) and higher values of fibrinogen (FIB) (4.7vs. 4.3 g/L P=0.001), activated partial thromboplastin time (APTT) (30.9 vs. 29.5 seconds P=0.010).There were no significant differences in the prevalence of maternal thrombotic events or neonatal events.GDM was significantly associated with higher APTT (β 1.41seconds, 95% CI 0.29–2.53), FIB (β 0.38g/L, 95% CI 0.14–0.61), and percentage reduction in clot lysis after 30 min(LY30)(β 1.14%, 95% CI 0.15–2.13) after adjustment for potential confounding factors. Conclusions: GDM is significantly associated with hypercoagulability and secondary hyperfibrinolysis in these antenatal Chinese women.

Gestational diabetes mellitus is associated with antenatal hypercoagulability and secondary hyperfibrinolysis: a case control study of Chinese women

Background : To determine the relationship between gestational diabetes mellitus (GDM) and coagulation/fibrinolysis disorders in antenatal Chinese women . Methods: Case control study. Fifty women had GDM and 132 did not (the NGDM group). Maternal plasma biochemistry and previous medical history were collected from perinatal health records. Antenatal coagulation/fibrinolysis were assessed using thromboelastography and traditional measures, then the relationship between coagulation/fibrinolysis and GDM was analyzed by multiple regression analysis. Results: GDM was significantly associated with higher activated partial thromboplastin time (odds ratio [OR] 1.5, 95% confidence interval [CI] 0.4–2.6); fibrinogen (OR 0.3, 95% CI 0.1–0.6); and percentage reduction in clot lysis after 30 min (OR 1.2, 95% CI 0.2–2.2), after adjustment for potential confounding factors. Both the intraoperative (238.2±71.0 ml vs . 286.0±102.4 ml, P =0.003) and 24-hour after surgery (270.7±99.8 ml vs . 314.7±131.1 ml, P =0.033) blood loss were lower and the prevalence of cesarean delivery (56.0% vs . 37.9%, P =0.027) was higher in the GDM group. There were no significant differences in the prevalence of maternal thrombotic events or maternal body mass before delivery. Conclusions: GDM is significantly associated with hypercoagulability and secondary hyperfibrinolysis in these antenatal Chinese women.

Activation of the coagulation cascade after infusion of a factor XI concentrate in congenitally deficient patients

Virally inactivated, high-purity factor XI concentrates are available for treatment of patients with factor XI deficiency. However, preliminary experience indicates that some preparations may be thrombogenic. We evaluated whether a highly purified concentrate produced signs of activation of the coagulation cascade in two patients with severe factor XI deficiency infused before and after surgery. Signs of heightened enzymatic activity of the common pathway of coagulation (elevated plasma levels of prothrombin fragment 1 + 2 and fibrinopeptide A) developed in the early post-infusion period, accompanied by more delayed signs of fibrin formation with secondary hyperfibrinolysis (elevated D-dimer and plasmin-antiplasmin complex). These changes occurred in both patients, but were more severe in the older patient with breast cancer when she underwent surgery, being accompanied by fibrinogen and platelet consumption. There were no concomitant signs of heightened activity of the factor VII-tissue factor mechanism on the factor Xase complex (plasma levels of activated factor VII and of factor IX and X activation peptides did not increase). The observed changes in biochemical markers of coagulation activation indicate that concentrate infusions increased thrombin generation and activity and that such changes were magnified by malignancy and surgery. Because some factor XI concentrates may be thrombogenic, they should be used with caution, especially in patients with other risk factors for thrombosis.

Activation of the coagulation cascade after infusion of a factor XI concentrate in congenitally deficient patients

Virally inactivated, high-purity factor XI concentrates are available for treatment of patients with factor XI deficiency. However, preliminary experience indicates that some preparations may be thrombogenic. We evaluated whether a highly purified concentrate produced signs of activation of the coagulation cascade in two patients with severe factor XI deficiency infused before and after surgery. Signs of heightened enzymatic activity of the common pathway of coagulation (elevated plasma levels of prothrombin fragment 1 + 2 and fibrinopeptide A) developed in the early post-infusion period, accompanied by more delayed signs of fibrin formation with secondary hyperfibrinolysis (elevated D-dimer and plasmin-antiplasmin complex). These changes occurred in both patients, but were more severe in the older patient with breast cancer when she underwent surgery, being accompanied by fibrinogen and platelet consumption. There were no concomitant signs of heightened activity of the factor VII-tissue factor mechanism on the factor Xase complex (plasma levels of activated factor VII and of factor IX and X activation peptides did not increase). The observed changes in biochemical markers of coagulation activation indicate that concentrate infusions increased thrombin generation and activity and that such changes were magnified by malignancy and surgery. Because some factor XI concentrates may be thrombogenic, they should be used with caution, especially in patients with other risk factors for thrombosis.