scholarly journals Investigation of the Molecular Mechanism of Coagulopathy in Severe and Critical Patients With COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Daniel Elieh Ali Komi ◽  
Yaghoub Rahimi ◽  
Rahim Asghari ◽  
Reza Jafari ◽  
Javad Rasouli ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Protein C ◽  
Degradation Products ◽  
Protein S ◽  
Coagulation Factors ◽  
Fibrin Degradation Products ◽  
Significant Difference ◽  
Coagulation Tests ◽  
Critical Patients ◽  
D Dimer

Coagulopathy is a frequently reported finding in the pathology of coronavirus disease 2019 (COVID-19); however, the molecular mechanism, the involved coagulation factors, and the role of regulatory proteins in homeostasis are not fully investigated. We explored the dynamic changes of nine coagulation tests in patients and controls to propose a molecular mechanism for COVID-19-associated coagulopathy. Coagulation tests including prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen (FIB), lupus anticoagulant (LAC), proteins C and S, antithrombin III (ATIII), D-dimer, and fibrin degradation products (FDPs) were performed on plasma collected from 105 individuals (35 critical patients, 35 severe patients, and 35 healthy controls). There was a statically significant difference when the results of the critical (CRT) and/or severe (SVR) group for the following tests were compared to the control (CRL) group: PTCRT (15.014) and PTSVR (13.846) (PTCRL = 13.383, p < 0.001), PTTCRT (42.923) and PTTSVR (37.8) (PTTCRL = 36.494, p < 0.001), LACCRT (49.414) and LACSVR (47.046) (LACCRL = 40.763, p < 0.001), FIBCRT (537.66) and FIBSVR (480.29) (FIBCRL = 283.57, p < 0.001), ProCCRT (85.57%) and ProCSVR (99.34%) (ProCCRL = 94.31%, p = 0.04), ProSCRT (62.91%) and ProSSVR (65.06%) (ProSCRL = 75.03%, p < 0.001), D-dimer (p < 0.0001, χ2 = 34.812), and FDP (p < 0.002, χ2 = 15.205). No significant association was found in the ATIII results in groups (ATIIICRT = 95.71% and ATIIISVR = 99.63%; ATIIICRL = 98.74%, p = 0.321). D-dimer, FIB, PT, PTT, LAC, protein S, FDP, and protein C (ordered according to p-values) have significance in the prognosis of patients. Disruptions in homeostasis in protein C (and S), VIII/VIIIa and V/Va axes, probably play a role in COVID-19-associated coagulopathy.

scholarly journals Laboratory manifestations of COVID-19 associated with hemostatic abnormalities

2021 ◽  
Vol 4 (3) ◽  
pp. 423-427
Author(s):  
Ahmed Elhadi Elsadig ◽  
May Mohammed Ali ◽  
Alfatih Aboalbasher Yousif
Keyword(s):  
Disease Severity ◽  
Protein C ◽  
Degradation Products ◽  
Disease Outcome ◽  
Icu Patients ◽  
Fibrin Degradation Products ◽  
Laboratory Markers ◽  
Increased Risk ◽  
Coagulation Tests ◽  
D Dimer

Hemostatic abnormalities had been reported in COVID-19 patients, which may include disseminated intravascular coagulation (DIC), hypercoagulability, and alterations in platelets parameters. Articles that investigate the alterations of hemostatic abnormalities during the COVID-19 disease (2020-2021) and their predictive value of disease outcome have been thoroughly reviewed. Among the reviewed articles, thrombocytopenia is observed in 5.0-41.7% of COVID-19 patients, which is related to disease severity. Moreover, other platelets parameters, including Platelets/lymphocytes ratio (PLR), Mean platelets volume (MPV), and aggregation, may also be affected. On the other hand, findings of coagulation tests such as D dimer; fibrinogen, Antithrombin (AT), and Fibrin degradation products (FDP) are significantly elevated in COVID-19 patients, while in a single study, most of the patients had positive Lupus anticoagulants (LA) and normal protein C (PC). In the same perspective, these alterations showed significant correlations with disease severity. Overall, hemostatic laboratory markers are significant predictors of COVID-19 disease outcome as indicated by the increased risk of venous and arterial thrombotic events, especially in ICU patients.  

PLASMA LEVELS OF FRAGMENT D-DIMER OF CROSSLINKED FIBRIN DURING THROMBOLYTIC THERAPY WITH RECOMBINANT TISSUE-TYPE PLASMINOGEN ACTIVATOR

1987 ◽  
Author(s):  
P Declerck ◽  
P Mombaerts ◽  
P Holvoet ◽  
D Collen
Keyword(s):  
Thrombolytic Therapy ◽  
Plasma Levels ◽  
Degradation Products ◽  
Fibrin Clot ◽  
Tissue Type ◽  
Fibrin Degradation Products ◽  
Type Plasminogen Activator ◽  
Rate Of Increase ◽  
Significant Difference ◽  
D Dimer

Plasma levels of crosslinked fibrin degradation products (XLDP) were measured before and at the end of the administration of rt-PA (40 to 100 mg over 1.5 to 8 hours) in healthy volunteers (n=5) and patients with deep venous thrombosis (DVT) (n=8), pulmonary embolism (PE) (n=16)and myocardial infarction(MI)(n=10). Determinations were performed using our newly developed ELISA, specific for crosslinked fibrin derivatives, based on two monoclonal antibodies (15C5 and 8D3H2) raised against purified human fragment D-dimer. All plasma samples were collected on citrate and trasylol. Results are expressed as mean and range of D-dimer equivalents (μg/ml).Baseline levels in patients with MI are only slightly elevated. The increased levels inDVT and PE are in agreement with previous studies. After infusion of rt-PA a small increase of XLDP is seen even innormal subjects. A very marked increasof XLDP is detected in patients with PE and DVT but not in patients with MI. This may reflect differences in the amounts of fibrin clot dissolved in these patient groups.No significant correlation was found between the increase of XLDP and success of therapy, although a significant difference in D-dimer levels was formed between the two groups with PE: successful (n=ll): 116 (range 61-192) vs. unsuccessful (n=5): 68 (36-155).Thus, XLDP are already elevated under baseline conditions in patients with DVT and PE and increase very markedly during thrombolytic therapy. The absolute levels after thrombolytic therapy do not strictly correlate with success of therapy. It could be useful to measure D-dimer levels during early stages of therapy, because the rate of increase of XLDP levels might correlate with the efficacy of thrombolytic treatment.

Haemostatic Studies in Carbohydrate-deficient Glycoprotein Syndrome Type I

1996 ◽  
Vol 76 (04) ◽  
pp. 502-504 ◽  
Author(s):  
A Fiumara ◽  
R Barone ◽  
P Buttitta ◽  
R Musso ◽  
L Pavone ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Protein C ◽  
Antithrombin Iii ◽  
Plasma Concentrations ◽  
Protein S ◽  
Coagulation Factors ◽  
Type I ◽  
Clotting Factors ◽  
Blood Coagulation Factors ◽  
D Dimer

SummaryCDG syndrome (CDGS) type I is the most frequent form of a group of metabolic disorders characterised by a defect of the carbohydrate moiety of glycoproteins. A large number of plasma glycoproteins, including clotting factors and inhibitors, are decreased and stroke-like episodes have been described in about half of the reported patients. We studied blood coagulation factors, inhibitors and D-dimer plasma levels in four subjects, aged 12-23 years, with CDGS type I. Factors VIII, XI, antithrombin III activity, antigen plasma levels of antithrombin III, free protein S and protein C were decreased whereas protein C as activity was normal. In addition two patients had reduction of factors II, V, VII, IX, X reflecting the phenotypic heterogeneity associated with CDGS type I. D-dimer plasma concentrations were elevated in all subjects. The hypercoagulable state as consequence of the combined deficiencies of coagulation inhibitors could contribute to the stroke-like phenomena in CDGS type I.

scholarly journals The cofactor role of protein S in the acceleration of whole blood clot lysis by activated protein C in vitro

Blood ◽  
1986 ◽  
Vol 67 (4) ◽  
pp. 1189-1192 ◽  
Author(s):  
NJ de Fouw ◽  
F Haverkate ◽  
RM Bertina ◽  
J Koopman ◽  
A van Wijngaarden ◽  
...  
Keyword(s):  
Whole Blood ◽  
Protein C ◽  
Degradation Products ◽  
Blood Clot ◽  
Activated Protein C ◽  
Protein S ◽  
Tissue Type ◽  
Clot Lysis ◽  
Fibrin Degradation Products

Abstract The effect of purified human activated protein C (APC) and protein S on fibrinolysis was studied by using an in vitro blood clot lysis technique. Blood clots were formed from citrated blood (supplemented with 125I-fibrinogen) by adding thrombin and Ca2+-ions; lysis of the clots was achieved by adding tissue-type plasminogen activator. The release of labeled fibrin degradation products from the clots into the supernatant was followed in time. We clearly demonstrated that APC accelerates whole blood clot lysis in vitro. The effect of APC was completely quenched by antiprotein C IgG, pretreatment of APC with diisopropylfluorophosphate, and preincubation of the blood with antiprotein S IgG. This demonstrates that both the active site of APC and the presence of the cofactor, protein S, are essential for the expression of the profibrinolytic properties. At present, the substrate of APC involved in the regulation of fibrinolysis is not yet known. Analysis of the radiolabeled fibrin degradation products demonstrated that APC had no effect on the fibrin cross-linking capacity of factor XIII.

scholarly journals Coagulation profile tests as a predictor for adult trauma patients’ mortality

2019 ◽  
Vol 7 (1) ◽  
pp. 1
Author(s):  
Ahmed Fawzy ◽  
Magdy Lolah ◽  
Samah Saad Ibrahim ◽  
Alaa Efat Hassan
Keyword(s):  
Partial Thromboplastin Time ◽  
Degradation Products ◽  
Characteristic Curve ◽  
P Value ◽  
Trauma Patients ◽  
Coagulation Profile ◽  
Fibrin Degradation Products ◽  
Trauma Induced Coagulopathy ◽  
Significant Difference ◽  
D Dimer

Background: Coagulopathy is commonly observed in poly-traumatized patients and is a known contributor to trauma mortality. Although, the incidence of coagulopathy is strongly associated with the severity of the injury, coagulopathy itself exerts an independent factor on mortality.Methods: This is a prospective, observational study on 100 trauma patients. All patients were evaluated using the modified shock index (MSI). Coagulation profile tests including platelet count, prothrombin time (PT), partial thromboplastin time (PTT), D-dimer and fibrinogen/fibrin degradation products (FDPs) were performed for all patients on admission and at 12 hours intervals. Statistically, a logistic regression analysis was performed of coagulation profile tests to determine the incidence of trauma induced coagulopathy (TIC) and its impact on 24 hours mortality. Correlation between clinical and laboratory status was done.Results: There was a statistically significant difference between the dead and the survived patients in the coagulation profile tests and MSI. The best cut-off point of each parameter of coagulation profile tests (PLT count, PT, PTT, d-dimer, FDPs) and MSI was calculated using receiver operating characteristic curve and were <173 × 109/l, >18.7 s, >31 s, >5 mg/l, > 321.5 mg/l and 1.6 respectively. Trauma induced coagulopathy in our study was defined by more than 2 of the following: PLT <173 × 109/l, PT >18.7 s, activated partial thromboplastin time (APTT) >31 s, D-dimer >5 mg/l and FDPs>321.5 mg/l with a p value 0.001 and associated with increased mortality.Conclusions: The incidence of trauma induced coagulopathy early after trauma is high and its severity is related to the injury itself. It is independent predictor of mortality. TIC was developed with presence of more than 2 of the coagulopathy parameters.

scholarly journals The cofactor role of protein S in the acceleration of whole blood clot lysis by activated protein C in vitro

Blood ◽  
1986 ◽  
Vol 67 (4) ◽  
pp. 1189-1192
Author(s):  
NJ de Fouw ◽  
F Haverkate ◽  
RM Bertina ◽  
J Koopman ◽  
A van Wijngaarden ◽  
...  
Keyword(s):  
Whole Blood ◽  
Protein C ◽  
Degradation Products ◽  
Blood Clot ◽  
Activated Protein C ◽  
Protein S ◽  
Tissue Type ◽  
Clot Lysis ◽  
Fibrin Degradation Products

The effect of purified human activated protein C (APC) and protein S on fibrinolysis was studied by using an in vitro blood clot lysis technique. Blood clots were formed from citrated blood (supplemented with 125I-fibrinogen) by adding thrombin and Ca2+-ions; lysis of the clots was achieved by adding tissue-type plasminogen activator. The release of labeled fibrin degradation products from the clots into the supernatant was followed in time. We clearly demonstrated that APC accelerates whole blood clot lysis in vitro. The effect of APC was completely quenched by antiprotein C IgG, pretreatment of APC with diisopropylfluorophosphate, and preincubation of the blood with antiprotein S IgG. This demonstrates that both the active site of APC and the presence of the cofactor, protein S, are essential for the expression of the profibrinolytic properties. At present, the substrate of APC involved in the regulation of fibrinolysis is not yet known. Analysis of the radiolabeled fibrin degradation products demonstrated that APC had no effect on the fibrin cross-linking capacity of factor XIII.

Effects of Pentasaccharide (Fondaparinux) and Direct Thrombin Inhibitors on Coagulation Testing

2004 ◽  
Vol 128 (10) ◽  
pp. 1142-1145
Author(s):  
Robert C. Gosselin ◽  
Jeffrey H. King ◽  
Kim A. Janatpur ◽  
William H. Dager ◽  
Edward C. Larkin ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Protein C ◽  
Protein S ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Coagulation Tests ◽  
Von Willebrand ◽  
The Impact ◽  
Willebrand Factor ◽  
D Dimer

Abstract Context.—Direct thrombin inhibitors (DTIs) and fondaparinux represent a new class of anticoagulants. The effects of DTIs on activated partial thromboplastin time and prothrombin time measurements have been reported previously, but there are limited data on the impact of these anticoagulants on other coagulation tests. Objective.—To determine the effects of fondaparinux and 3 DTIs (argatroban, bivalirudin, and lepirudin) on miscellaneous coagulation tests. Design.—Bivalirudin, lepirudin, argatroban, and fondaparinux were added to pooled normal plasma and tested for fibrinogen, antithrombin (thrombin and Xa substrate methods), plasminogen, protein C (clot and chromogenic methods), protein S, von Willebrand factor, D-dimer, lupus anticoagulant testing (dilute Russell viper venom test [DRVVT] with ratio), and factors II, IX, and X activities. Results.—We found no drug interference on antithrombin, plasminogen, chromogenic protein C, von Willebrand factor, or D-dimer results. All DTIs falsely decreased fibrinogen values, while falsely increasing protein C and protein S levels. All DTIs prolonged the DRVVT, and only argatroban yielded DRVVT ratios less than 1.2. Lepirudin demonstrated no effect on factor II activity, and only argatroban demonstrated decreased factor X activity. All DTI samples demonstrated a linear, dose-dependent, false decrease of factor IX activity. Conclusions.—Using in vitro methods, we demonstrated DTI effects on numerous clot-based assays, but we found no interference with latex agglutination, chromogenic, or platelet aggregation methods. Fondaparinux only affected measurement of protein S activity. Caution must be used when interpreting coagulation test results on patients receiving these drugs.

Haemostatic reference intervals in pregnancy

2010 ◽  
Vol 103 (04) ◽  
pp. 718-727 ◽  
Author(s):  
Maja Jørgensen ◽  
Anna Klajnbard ◽  
Malene Andersen ◽  
Nina Colov ◽  
Steen Stender ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Gestational Age ◽  
Total Protein ◽  
Protein C ◽  
Protein S ◽  
Coagulation Factors ◽  
Reference Intervals ◽  
Specific Reference ◽  
D Dimer ◽  
Protein S Activity

SummaryHaemostatic reference intervals are generally based on samples from non-pregnant women. Thus, they may not be relevant to pregnant women, a problem that may hinder accurate diagnosis and treatment of haemostatic disorders during pregnancy. In this study, we establish gestational age-specific reference intervals for coagulation tests during normal pregnancy. Eight hundred one women with expected normal pregnancies were included in the study. Of these women, 391 had no complications during pregnancy, vaginal delivery, or postpartum period. Plasma samples were obtained at gestational weeks 13–20, 21–28, 29–34, 35–42, at active labor, and on postpartum days 1 and 2. Reference intervals for each gestational period using only the uncomplicated pregnancies were calculated in all 391 women for activated partial thromboplastin time (aPTT), fibrinogen, fibrin D-dimer, antithrombin, free protein S, and protein C and in a subgroup of 186 women in addition for prothrombin time (PT), Owren and Quick PT, protein S activity, and total protein S and coagulation factors II, V, VII, VIII, IX, X, XI, and XII. The level of coagulation factors II, V, X, XI, XII and antithrombin, protein C, aPTT, PT remained largely unchanged during pregnancy, delivery, and postpartum and were within non-pregnant reference intervals. However, levels of fibrinogen, D-dimer, and coagulation factors VII, VIII, and IX increased markedly. Protein S activity decreased substantially, while free protein S decreased slightly and total protein S was stable. Gestational age-specific reference values are essential for the accurate interpretation of a subset of haemostatic tests during pregnancy, delivery, and puerperium.

Disturbances of coagulation in neonates with functionally univentricular physiology prior to the first stage of surgical reconstruction

2008 ◽  
Vol 18 (4) ◽  
pp. 397-401 ◽  
Author(s):  
Nina Hakacova ◽  
Zuzana Laluhova-Striezencova ◽  
Martin Zahorec
Keyword(s):  
Protein C ◽  
Complete Blood Count ◽  
Degradation Products ◽  
Protein S ◽  
Coagulation Factors ◽  
Surgical Reconstruction ◽  
Control Group ◽  
Increased Risk ◽  
Factor Ii ◽  
Cardiac Centre

AbstractBackgroundAltered levels of coagulation factors are reported in patients with functionally univentricular physiology before and following the second and third stages of reconstructive surgery. The aims of our study were to determine if such abnormalities are also present in newborns with this physiology prior to the first stage of surgical treatment.Patients and methodsWe studied 20 neonates with functionally univentricular physiology admitted to the Children’s Cardiac Centre in Slovakia, using 20 healthy neonates as age-matched controls. Demographic characteristics, and concentration of liver enzymes, serum albumin, and complete blood count, did not differ between the two groups. Concentrations of Factor II, V, VII, VIII, Protein C, Protein S and Antithrombin were compared between the groups, and assessed as variable factors for coagulation.ResultsIn those with functionally univentricular physiology, procoagulation Factor II (p < 0.001), VII (p < 0.001), VIII (p < 0.01), anticoagulation Protein C (p < 0.001), Protein S (p < 0.001) and Antitrombin III (p < 0.001) all were present in significantly lower values compared with findings in the control group. D-dimer (p < 0.0001) and Fibrin Degradation Products (p < 0.0001) were present at significantly higher levels, but the concentration of plasminogen was significantly lower (p < 0.0001). The activated partial thromboplastin time (p < 0.012), and the prothrombin time (p < 0.0001), was significantly prolonged in those with functionally univentricular physiology compared with their controls.ConclusionThe presence of abnormal coagulation factors, markers of thrombolysis in the plasma, and increased risk of bleeding, suggests activation of haemostasis, and consumption of factors responsible for coagulation, in those with functionally univentricular physiology. The question arises whether the reported abnormalities are predictive of the known abnormalities of coagulation occurring during the second and third stages of surgical repair for patients with functionally univentricular hearts.

APC Resistance and other Haemostatic Variables during Pregnancy and Puerperium

1999 ◽  
Vol 81 (04) ◽  
pp. 527-531 ◽  
Author(s):  
U. Kjellberg ◽  
N.-E. Andersson ◽  
S. Rosén ◽  
L. Tengborn ◽  
M. Hellgren
Keyword(s):  
Factor Viii ◽  
Plasminogen Activator ◽  
Protein C ◽  
Activated Protein C ◽  
Plasminogen Activator Inhibitor ◽  
Protein S ◽  
Reference Level ◽  
Soluble Fibrin ◽  
Prothrombin Fragment ◽  
D Dimer

SummaryForty-eight healthy pregnant women were studied prospectively and longitudinally. Blood sampling was performed at 10-15, 23-25, 32-34 and 38-40 weeks of gestation, within one week and at eight weeks postpartum. Classic and modified activated protein C ratio decreased as pregnancy progressed. In the third trimester 92% of the ratios measured with the classic test were above the lower reference level whereas all modified test ratios were normal. Slight activation of blood coagulation was shown with increased levels of prothrombin fragment 1+2, soluble fibrin and D-dimer. Fibrinogen, factor VIII and plasminogen activator inhibitor type 1 and type 2 increased. Protein S and tissue plasminogen activator activity decreased. Protein C remained unchanged. No correlation was found between the decrease in classic APC ratio and changes in factor VIII, fibrinogen, protein S, prothrombin fragment 1+2 or soluble fibrin, nor between the increase in soluble fibrin and changes in prothrombin fragment 1+2, fibrinogen and D-dimer.

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