Coagulopathy in COVID-19 infection

2020 ◽  
Author(s):  
С.И. Кузнецов ◽  
Е.А. Шестаков ◽  
Е.Б. Жибурт
Keyword(s):  
Degradation Products ◽  
Activated Partial Thromboplastin Time ◽  
Low Molecular Weight ◽  
Time Data ◽  
Low Molecular Weight Heparins ◽  
Passive Immunotherapy ◽  
Fibrin Degradation Products ◽  
Pharmacological Thromboprophylaxis ◽  
D Dimer ◽  
Donor Plasma

Введение. Известно о коагулопатиях при инфекциях коронавирусами SARS и MERS. Цель исследования: изучить накопленную информацию о коагулопатии при инфекции COVID-19. Материалы и методы. В библиотеке PubMed провели поиск по ключевым словам «COVID-19», «coagulopathy». Обнаружили 15 публикаций, содержащих результаты оригинальных исследований. Результаты. При тяжелом течении заболевания наблюдают цитокиновый шторм, более высокие уровни Д-димера и продуктов деградации фибрина (ПДФ), более длительное протромбиновое время и активированное частичное тромбопластиновое время. Данные о частоте развития синдрома диссеминированного внутрисосудистого свертывания противоречивы. Заключение. У пациентов с COVID-19 с острой дыхательной недостаточностью наблюдается выраженная гиперкоагуляция. Всем госпитализированным пациентам с COVID-19 рекомендована фармакологическая тромбопрофилактика низкомолекулярными гепаринами или фондапаринуксом. Донорскую плазму для пассивной иммунотерапии нужно переливать только в рамках клинических исследований. Background. Coagulopathies are known for infections with SARS and MERS coronaviruses. Objectives: the reviewing the early accumulated information on coagulopathy in COVID-19. Patients / Methods. In PubMed Library with the keywords «COVID-19», «coagulopathy» we selected 15 publications containing the results of original studies. Results. In severe cases of the disease, a cytokine storm is observed, higher levels of D-dimer and fibrin degradation products (FDP), longer prothrombin time and activated partial thromboplastin time. Data about incidence of disseminated intravascular coagulation are contradictory. Conclusions. Patients with COVID-19 with acute respiratory failure exhibit severe hypercoagulation. Pharmacological thromboprophylaxis with low molecular weight heparins or fondaparinux is recommended for all hospitalized patients with COVID-19. Donor plasma for passive immunotherapy should be transfused only as part of clinical trials.

MONITORING OF DEEP VEIN THROMBOSIS BY D DIMER DETERMINATION. INFLUENCE OF HEPARIN REGIMEN

1987 ◽  
Author(s):  
C Soria ◽  
Mc Mirshahi ◽  
J Soria ◽  
M Mirshahi ◽  
R Faivre ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
No Reduction ◽  
Degradation Products ◽  
Low Molecular Weight ◽  
Dramatic Decrease ◽  
Vein Thrombosis ◽  
Non Invasive ◽  
Fibrin Degradation Products ◽  
Deep Vein ◽  
D Dimer

In 49 patients the level of plasma fibrin degradation products (FbDP) was measured during the first ten days of deep vein thrombosis (DVT) in order to determine whether FbDP may be used as a non invasive marker to follow the evolution of DVT. Plasma FbDP was measured precisely and reliably by Elisa using a personal anti D neo monoclonal antibody. Thrombus size was determined angiographically on day 0 and day 10 and expressed according to Marder score. Patients were treated by standard or by a very low molecular weight heparin (CY 222 from Choay Laboratory, Paris France).It is shown that before treatment, in 45 cases of DVT the level of FbDP was dramatically increased as compared to control and remained normal or slightly elevated in 4 cases of DVT. The correlation between thrombus size and FbDP level at day 0 was poor (p = 0.3). During the 10 days of treatment, FbDP determination may give some informations about the evolution of DVT. Three groups were defined :1 There was no reduction of thrombus size in patients who presented a normal or only slightly elevated FbDP level, leading to the evidence that thrombolysis was almost inexistant in these patients.2 Thrombolysis was almost complete in 10 days in patients presented both a high FbDP level before treatment and a dramatic decrease of FbDP after 10 days treatment. Taking into account the half life of FbDP, the decrease in FbDP level is related to the reduction in thrombus size.3 A partial or absence of recanalization was evidenced in patients presenting a high FbDP level throughout the 10 days on therapy. In cases without recanalization we have to assume that thrombolysis evidenced by plasma FbDP level was continuously counteract by a clotting process.Similar results were observed in patient treated by standard and CY 222.

MONOCLONAL ANTIBODIES OF THE IgM AND IgG CLASS SPECIFIC FOR CROSSLINKED FIBRIN DEGRADATION PRODUCTS

1987 ◽  
Author(s):  
P J Gaffney ◽  
L J Creighton ◽  
A Curry ◽  
B MacMahon ◽  
R Thorpe
Keyword(s):  
Monoclonal Antibodies ◽  
Thrombolytic Therapy ◽  
Epitope Mapping ◽  
Degradation Products ◽  
Subcutaneous Route ◽  
Fibrin Degradation Products ◽  
Conformational Epitopes ◽  
Immunoglobulin Class Switching ◽  
Unique Specificity ◽  
D Dimer

Monoclonal antibodies (mabs) to crosslinked fibrin degradation products (XL-FDP) having the general formula D/Y[X]nY/D (known as X-oligomer) and D-D (known as D dimer) have been raised in balb/C mice by both a novel mtrasplenic and a conventional subcutaneous route of immunisation and by combinations of both these procedures. Mabs to X-oligomers (NIBn 52 and NIBn 123) obtained by an intrasplenic procedure have been demonstrated to crossreact only with X-oligomer in a 2-site ELISA procedure and not with D dimer or whole fibrinogen and have been shown to be of value m the examination of clinical material obtained from patients with various types of thrombosis and have also been useful in monitoring the efficacy of thrombolytic therapy. The X-oligomer mabs are immunoglobulins of the M class. It was demonstrated that their unique specificity for conformational epitopes on the large X-oligomer fragments does not reside in the IgM structure since alterative immunisation procedures have been used to generate mabs of the IgG class which have the same specificity. Using immunoglobulin class switching in culture rather than during immunisation was suggested by certain cell lines which produced both IgM and IgG specific for X-oligomer. This latter point needs rigorous validation.Immunoglobulin G type mabs to highly purified D dimer were raised by conventional subcutaneous immunisation of balb/C mice. One of these, NIBn-11, was found to crossreact with PVC-immobilised X-oligomer and D dimer but not with fibrinogen. However NIBn-11 did not bind to D dimer in a 2-site ELISA procedure while crossreactmg quite avidly with X-oligomer. This suggests that the D dimer epitope to which NIBn-11 is directed is expressed in some conformations and not m others and that these conformations are always expressed in the complex X-oligomer group of fragments. These mabs, whilst of value in measuring certain unique fibrin fragments m plasma, are useful in the epitope mapping of fibrinogen/fibrin and their plasmm-mediated

Primary prevention of venous thromboembolism

2012 ◽  
Vol 27 (2_suppl) ◽  
pp. 23-32 ◽  
Author(s):  
R S Figueiredo ◽  
G Stansby ◽  
V Bhattacharya
Keyword(s):  
Venous Thromboembolism ◽  
Arterial Disease ◽  
Low Molecular Weight ◽  
Compression Stockings ◽  
Low Molecular Weight Heparins ◽  
Pharmacological Prophylaxis ◽  
Risk Of Bleeding ◽  
Peripheral Arterial ◽  
Orally Active ◽  
Pharmacological Thromboprophylaxis

Venous thromboembolism (VTE) is the most common cause of preventable in-hospital mortality and all hospitalized patients should be VTE risk assessed. The VTE risk should be weighed up against risk of bleeding on an individualized basis to guide choice of prophylaxis. The most common method of mechanical thromboprophylaxis is graduated compression stockings, although others, such as intermittent pneumatic devices, are available. Stockings have the greatest benefit when used in combination with pharmacological prophylaxis. However, stockings are contraindicated in some patients, including those with stroke or peripheral arterial disease. Various options for pharmacological thromboprophylaxis are available. The most commonly used agents are the low-molecular-weight heparins, but newer orally active agents may play an increasing role in the future.

scholarly journals D-dimer kit with a High FDP/D-Dimer Ratio is Useful for Diagnosing Thrombotic Diseases

2022 ◽  
Vol 28 ◽  
pp. 107602962110705
Author(s):  
Nozomi Ikeda ◽  
Hideo Wada ◽  
Yuhuko Ichikawa ◽  
Minoru Ezaki ◽  
Motoko Tanaka ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Critically Ill ◽  
Disseminated Intravascular Coagulation ◽  
Critically Ill Patients ◽  
Degradation Products ◽  
Intravascular Coagulation ◽  
Fibrin Degradation Products ◽  
Peripheral Arterial ◽  
Thrombotic Diseases ◽  
D Dimer

Introduction Although D-dimer is a useful biomarker of thrombosis, there are many D-dimer kits, with high and low fibrinogen and fibrin degradation products (FDP)/ D-dimer ratios. Methods Plasma D-dimer levels were measured using three different kits in critically ill patients to examine the usefulness of such measurements for detecting the thrombotic diseases and determining the correlation with the FDP and FDP/D-dimer ratio. Results Although three D-dimer kits showed marked utility for diagnosing disseminated intravascular coagulation (DIC) and peripheral arterial and venous thromboembolism (PAVTE), the D-dimer levels determined using the three kits varied among diseases. Indeed, one D-dimer kit showed a high FDP/D-dimer ratio, and another kit showed a low FDP/D-dimer ratio. D-dimer kit with low FDP/D-dimer ratio tended to have high cut-off values and low specificity for diagnosing DIC and PAVTE. In D-dimer kit with high FDP/D-dimer ratio, FDP/D-dimer ratios in patients with thrombosis was significantly higher than that in patients without thrombosis. Conclusion All three D-dimer kits show utility for detecting thrombotic diseases. However, the D-dimer levels determined using the kits varied due to differences in the FDP/D-dimer ratio. In combination with the FDP level, a D-dimer kit with a high FDP/D-dimer ratio may be useful.

New coronavirus infection, hemostasis and heparin dosing problems: It is important to say now

2020 ◽  
Author(s):  
А.Ю. Буланов ◽  
Е.В. Ройтман
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight ◽  
Evidence Based ◽  
Low Molecular Weight Heparins ◽  
Heparin Resistance ◽  
Hospital Patients ◽  
Expert’S Opinion ◽  
Coronavirus Infection ◽  
Based Medicine ◽  
D Dimer

В отсутствие достаточной базы доказательной медицины самым ценным становится мнение экспертов, опирающихся на свой опыт и опыт коллег. COVID-19-ассоциированная коагулопатия имеет характер тромбовоспаления. Назначение гепаринов — нефракционированного или, главным образом, низкомолекулярного (НМГ) призвано преодолеть его, поскольку гепарин обладает не только антикоагулянтным эффектом, но и оказывает непрямое и прямое противовоспалительное дейст вие. Поэтому назначение НМГ как минимум в профилактических дозах показано всем госпитализированным пациентам. Система гемостаза у пациентов с COVID-19, прежде всего у тяжелых, требует лабораторной оценки количества тромбоцитов, содержания Д-димера, протромбинового отношения или процентов протромбина по Квику и концентрации фибриногена. Анализ данных показал, что своеобразие коронавирусного гемостаза формирует гиперфибриногенемия, которая становится явным фактором гепаринорезистентности. Для преодоления последней назначение увеличенных (промежуточных или лечебных) доз НМГ выглядит перспективным решением. Достаточность назначения уместно определить либо по анти- Ха активности или (как экспресс-оценка) по тромбоэластрограмме. In the absence of a suffi cient base of evidence-based medicine, the most valuable becomes the expert’s opinion as a mirror of both personal and collegial experience. COVID-19-associated coagulopathy has a character of a thromboinfl ammation. The heparins — unfractionated or mainly low molecular weight heparins (LMWH) are intended to overcome it, since heparins have not only an anticoagulant effect but both an indirect and direct anti-infl ammatory effects as well. So that LMWH are indicated for all in-hospital patients. Patients with COVID-19, especially in severe cases, require laboratory testing of platelet count, D-dimer, prothrombin ratio or prothrombin percents by Quick and fi brinogen. Data analysis showed that a feature of coronavirus hemostasis is hyperfibrinogenemia that becomes an overt factor for heparin resistance. To overcome the latter, an adjusting doses of LMWH toward intermediate or therapeutic looks like a promising way. The suffi ciency of the adjusted LMWH dose is appropriate determining either with anti- Xa activity or thromboelastographically as express testing. Key words: hemostasis, COVID-19-associated coagulopathy, fibrinogen, low molecular weight heparins

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.

scholarly journals D-Dimer and Fibrin Degradation Products Impair Platelet Signaling: Plasma D-Dimer Is a Predictor and Mediator of Platelet Dysfunction During Trauma

2020 ◽  
Vol 5 (6) ◽  
pp. 1253-1264
Author(s):  
Christopher C Verni ◽  
Antonio Davila ◽  
Carrie A Sims ◽  
Scott L Diamond
Keyword(s):  
Degradation Products ◽  
Calcium Mobilization ◽  
Factor Xiiia ◽  
Platelet Glycoprotein ◽  
Trauma Patients ◽  
Platelet Dysfunction ◽  
Soluble Fibrin ◽  
Glycoprotein Vi ◽  
Fibrin Degradation Products ◽  
D Dimer

Abstract Background Platelet dysfunction often accompanies trauma-induced coagulopathy. Because soluble fibrin impairs platelet glycoprotein VI (GPVI) signaling and platelets of trauma patients can display impaired calcium mobilization, we explored the role of fibrinolysis on platelet dysfunction during trauma. Methods Convulxin-induced GPVI calcium mobilization was investigated in healthy platelet-rich plasma (PRP) pretreated with thrombin and tissue plasminogen activator (tPA). Blood samples from healthy participants (n = 7) and trauma patients (n = 22) were tested for platelet calcium mobilization, plasma D-dimer, platelet D-dimer binding (via flow cytometry), and platelet lumi-aggregometry. Results For healthy platelets, maximal platelet dysfunction was observed when cross-linked soluble fibrin (no tPA) or cross-linked fibrin degradation products (FDPs) were generated in suspension before convulxin stimulation. Lack of fibrin polymerization (inhibited by Gly-Pro-Arg-Pro [GPRP]) or lack of factor XIIIa cross-linking (T101-inhibited) restored GPVI signaling, whereas non–cross-linked FDPs only partially blocked signaling induced by convulxin. In addition, D-dimer added to healthy PRP impaired platelet aggregation and dense granule release induced by various agonists. Plasma D-dimer level was strongly correlated (R = 0.8236) with platelet dysfunction as measured by platelet calcium mobilization induced with various agonists. By 48 to 120 h after trauma, plasma D-dimer levels declined, and platelet function increased significantly but not to healthy levels. Trauma platelets displayed elevated D-dimer binding that was only partially reduced by αIIbβ3-inhibitor GR144053. After 60-minute incubation, washed healthy platelets resuspended in plasma from trauma patients captured approximately 10 000 D-dimer equivalents per platelet. Conclusions During trauma, D-dimer and FDPs inhibit platelets, potentially via GPVI and integrin αIIbβ3 engagement, contributing to a fibrinolysis-dependent platelet loss-of-function phenotype.

Identification of D-Dimer-E Complex in Disseminated Intravascular Coagulation (DIC)

1979 ◽  
Author(s):  
A.N. Whitaker ◽  
E.A. Rowe ◽  
P.P. Masci ◽  
P.J. Gaffney
Keyword(s):  
Gel Electrophoresis ◽  
Degradation Products ◽  
Polyacrylamide Gel Electrophoresis ◽  
Stable Complex ◽  
Fibrin Degradation Products ◽  
Pneumococcal Sepsis ◽  
D Antigen ◽  
D Dimer

D-dimer (D2), a product of the plasmin lysis of cross-linked (XL) fibrin, but not of non-XL fibrin or fibrinogen, has been identified in the plasma of patients with DIC due to amniotic fluid embolism. In vitro, D is involved with fragment E as a stable complex (D2-E) but D2 -E has not been identified in vivo before. Fibrin degradation products (FDP) were studied in a patient having fulminant postsplenectomy pneumococcal sepsis and DIC, by immunoprecipitation with anti-fibrinogen (f) and anti-fragment E and characterization by SDS polyacrylamide gel electrophoresis (PAGE). With both antisera soluble HMW fibrin complexes, D2 and E but no X, Y or D were obtained from serum. D2 and E were identified in the supernatant after removing partially XL HMW complexes and fibrinogen from plasma with 2.5 M β-alanine. The presence D antigen in the D2-E complex precipitated by monospecific anti-E was confirmed by crossed Ag-Ab electrophoresis. Crossed Ag-Ab electrophoresis of serum in agarose gave E peaks of slow mobility and no fast-moving free E was found. Thus, D2-E complex exists in vivo and its easy identification, proving the lysis of XL fibrin, would be of value in studying thrombosis. D2-E complex has been identified in other patients with sepsis but at lower concentrations than described above.

scholarly journals Fibrin fragment D-dimer and fibrinogen B beta peptides in plasma as markers of clot lysis during thrombolytic therapy in acute myocardial infarction

Blood ◽  
1990 ◽  
Vol 76 (7) ◽  
pp. 1341-1348 ◽  
Author(s):  
CM Lawler ◽  
EG Bovill ◽  
DC Stump ◽  
DJ Collen ◽  
KG Mann ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Degradation Product ◽  
Degradation Products ◽  
Tissue Type ◽  
Clot Lysis ◽  
Fibrin Degradation Product ◽  
Fibrin Degradation Products ◽  
Group 2 ◽  
D Dimer ◽  
Group 1

Abstract The validity of markers in plasma of in vitro thrombolysis was investigated in 12 patients with extensive fibrinogen breakdown (greater than 80%, group 1) and in 12 patients with minimal breakdown (less than 20%, group 2). The patients were treated with 100 mg of recombinant tissue-type plasminogen activator (rt-PA) in the “Thrombolysis in Myocardial Infarction II” (TIMI II) trial. Cross- linked fibrin degradation product levels were measured with two variant enzyme-linked immunosorbent assays (ELISAs), both using a fibrin fragment D-dimer specific capture antibody. In one instance, a tag antibody was used that cross-reacts with fibrinogen (pan-specific tag ELISA); in the other, the tag antibody was specific for fibrin fragment D (fibrin-specific tag ELISA). Apparent concentrations of cross-linked fibrin degradation products at baseline were within normal limits with both assays in most patients. At 8 hours after rt-PA infusion, the measured cross-linked fibrin degradation products were increased about twofold to fourfold in group 2 with both assays. However, in group 1, levels were significantly higher with the pan-specific tag ELISA (5.8 +/- 4.2 micrograms/mL) compared with the fibrin-specific tag ELISA (1.5 +/- 1.3 micrograms/mL). This observation was most likely a result of detection of fibrinogen degradation products in the pan-specific ELISA. Apparent levels of fibrinopeptide B beta 1–42, a marker of fragment X formation, increased during thrombolysis from 4.2 +/- 2.8 pmol/mL to 2,000 +/- 230 pmol/mL in group 1 and from 4.1 +/- 2.1 pmol/mL to 300 +/- 43 pmol/mL in group 2, and were correlated significantly with the extent of fibrinogen breakdown (r = -0.8). Fibrinopeptide beta 15–42 levels increased from 4.3 +/- 3 pmol/mL to 70 +/- 19 pmol/mL in group 1, but did not increase in group 2. The apparent increase in group 1 could be explained by cross-reactivity of fibrinopeptide B beta 1–42 in the fibrinopeptide beta 15–42 assay. We conclude that cross-linked fibrin degradation product levels as measured with a pan-specific tag ELISA and fibrinopeptide beta 15–42 levels as measured with certain monoclonal antibody-based ELISA are influenced by the extent of fibrinogen degradation. Fibrinopeptide B beta 1–42 is a marker specific for fibrinogen breakdown. Cross-linked fibrin degradation product levels, measured with a fibrin-specific tag ELISA, appear to be markers specific for thrombolysis. Consequently, assays similar to the fibrin- specific tag ELISA may provide more accurate information when correlated with clinical endpoints.

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