Hypercoagulability of COVID-19 patients in Intensive Care Unit: A Report of Thromboelastography Findings and other Parameters of Hemostasis

BACKGROUND: The severe inflammatory state secondary to Covid-19 leads to a severe derangement of hemostasis that has been recently described as a state of disseminated intravascular coagulation (DIC) and consumption coagulopathy, defined as decreased platelet count, increased fibrin(ogen) degradation products such as D-dimer as well as low fibrinogen. AIMS: Whole blood from 24 patients admitted at the intensive care unit because of Covid-19 was collected and evaluated with thromboelastography by the TEG point-of-care device on a single occasion and six underwent repeated measurements on two consecutive days for a total of 30 observations. Plasma was evaluated for the other parameters of hemostasis. RESULTS: TEG parameters are consistent with a state of hypercoagulability as shown by decreased R and K values, and increased values of K angle and MA. Platelet count was normal or increased, prothrombin time and activated partial thromboplastin time were near(normal). Fibrinogen was increased and D-dimer was dramatically increased. C-reactive protein was increased. Factor VIII and von Willebrand factor (n=11) were increased. Antithrombin (n=11) was marginally decreased and protein C (n=11) was increased. CONCLUSION: The results of this cohort of patients with Covid-19 are not consistent with acute DIC, rather they support hypercoagulability together with a severe inflammatory state. These findings may explain the events of venous thromboembolism observed in some of these patients and support antithrombotic prophylaxis/treatment. Clinical trials are urgently needed to establish the type of drug, dosage and optimal duration of prophylaxis

Hypercoagulability in splenectomized thalassemic patients detected by whole-blood thromboelastometry, but not by thrombin generation in platelet-poor plasma

Background: The mechanisms responsible for the increased thrombotic risk associated with thalassemia are still unclear. They might be related to the effects of red blood cell or endothelial cell derangements, increased numbers of platelets as well as abnormal plasma coagulation. Design and Methods: To evaluate the relative role played by cells and plasma we investigated 169 patients with thalassemia by means of thromboelastometry and thrombin generation tests. Thromboelastometry measures indices of the viscoelastic properties of whole blood after activation of coagulation and is characterized by the clotting time, which may be considered as a conventional coagulation time, clot formation time, defined as the time needed for the clot to reach a fixed firmness, and the maximum clot firmness, defined as the maximal amplitude of the tracing. Results: All the thromboelastometry parameters determined in whole blood (including shortened clotting time and clot formation time, and increased maximum clot firmness), were consistent with hypercoagulability, especially in splenectomized patients. Conversely, thrombin generation as determined in platelet-poor plasma was not. Conclusions: These findings point to blood cells and/or platelets rather than to plasma abnormalities as the most important determinants of the thrombotic risk observed in thalassemic patients who had been splenectomized. These results might have important diagnostic and therapeutic implications

Misura della proteina S e della resistenza alla proteina C attivata. Risultati della Valutazione Esterna di Qualit\ue0 (VEQ)-CISMEL*

Background. One of the aims of the External Quality Assurance Scheme (EQAS) is to provide information useful to standardize laboratory methods and to help choosing the most appropriate laboratory strategy to investigate clinical conditions. Methods. We looked at the results coming from the EQAS in coagulation organized by the CISMEL group in three different exercises where participants analyzed three well characterized plasmas for protein S and activated protein C resistance. Results. Three consecutive exercises showed that the functional anticoagulant assay for protein S is affected by the presence of the factor V Leiden mutation and that the method for the measurement of activated protein C resistance based on prediluiton of test plasma in factor V deficient plasma is highly specific for factor V Leiden. Conclusions. EQAS exercises carried out across the country with samples unknown to the participants confirm two important findings that may be used to design a diagnostic strategy for the investigation of patients with thrombophilia

Standardization of Lupus Anticoagulant : The Lupus Anticoagulant Sensitivity Index (LASI)

Results for lupus anticoagulant (LA) are expressed as ratio of patient-to-normal clotting times (LA-ratio) according to the equation LA-ratio=(PatientClotting time/NormalClotting time). However, numerical results vary according to the method used for testing, thus making difficult the between-method and between-laboratory comparison of results. The hypothesis that the standardization model currently employed for the international normalized ratio for patients on warfarin is valid also for LA standardization has been taken into consideration. The model calls for the determination of a LA-sensitivity index (LASI) for each commercial method for LA detection against a common standard method. The LASI is then used to convert the LA-ratio into a scale called standardized LA-ratio (SLA-ratio) according to the equation SLA-ratio=(LA-ratio)LASI. The model proved effective in minimizing the between-method variability of results for LA detection. If implemented it could be a valuable tool to improve the comparability of results obtained in different laboratories, to quantify the LA potency and thus pave the way to the organization of collaborative clinical trials aimed at assessing whether the potency of LA is a risk factor for clinical events

Acquired coagulation disorders : revisited using global coagulation/anticoagulation test

Acquired coagulation defects are characterized by a decrease of both pro- and anti-coagulants. Because of this, we hypothesise that global tests, such as the prothrombin and partial thromboplastin times (PT and APTT), might be unsuitable for their investigation. Indeed, these tests are not good predictors of bleeding in acquired coagulopathies as they are in the congenital ones. This article discusses the possible reasons for this, using cirrhosis and the neonatal period as epitomes of acquired coagulation defects. Both display normal thrombin generation in the presence of thrombomodulin, in spite of prolonged PT and APTT. We surmise that, because of their design, the PT and APTT are responsive to thrombin generated as a function of pro-coagulants, but much less to thrombin inhibited by the anti-coagulants, especially protein C, which is activated to a limited extent in the absence of thrombomodulin. In conclusion, the PT and APTT can tell us whether or not a patient is deficient in one or more pro-coagulants, but not whether this deficiency is counterbalanced by a parallel deficiency of anti-coagulants. Thrombin generation assays are more suitable than PT and APTT for use in acquired coagulation defects